α = 0.05. There \nare no correlations between the statements “The courses \nabout art and design had contents that were able to teach \nme artistic design principles both theoretically and \npractically” and “I don’t think we have received sufficient \neducation about the significance and necessity that \nesthetic values should bear the characteristics of our \nculture”. Correlations \n \n \n \n2-4 \n3-6 \nSpearman's rho \n2_4 Correlation Coefficient 1.000 \n-.053 \nSig. (2-tailed) \n. .558 \nN \n126 \n126 \n3_6 Correlation Coefficient -.053 \n1.000 \nSig. (2-tailed) \n.558 \n. N \n126 \n126 Correlations \n \n \n \n2-4 \n3-6 \nSpearman's rho \n2_4 Correlation Coefficient 1.000 \n-.053 \nSig. (2-tailed) \n. .558 \nN \n126 \n126 \n3_6 Correlation Coefficient -.053 \n1.000 \nSig. (2-tailed) \n.558 \n. Tataroglu N \n126 \n126 A conflict was identified between the positive attitudes \nof the majority of the students about course contents \n(Table 13) and negative attitudes of almost half of the \nstudents about esthetic value education (Table 41). Section Item 4- II. Section Item 6 contents of education program”. Such a correlation was \nabout 41%. contents of education program”. Such a correlation was \nabout 41%. H0: There are no correlations between the statements “I \ndon’t think we have received sufficient education about \nthe significance and necessity that esthetic values should \nbear the characteristics of our culture” and “I don’t think \nesthetic and meta-esthetic topics were sufficiently placed \nin course contents of education program”. Student attitudes about the insufficiency of esthetic \nvalue education (50.8%) (Table 14) and insufficiency of \nesthetic and meta-esthetic content of the programs (42%) \n(Table 14) were considered as conflicting opinions. In this \ncase, 58% was thinking that esthetic and meta esthetic \ncourses were sufficiently placed in educational programs. On the other hand, they were also thinking that esthetic \nvalue education was not sufficiently placed in contents \n(Table 42). H1: There is a correlation between the statements “I don’t \nthink we have received sufficient education about the \nsignificance and necessity that esthetic values should \nbear the characteristics of our culture” and “I don’t think \nesthetic and meta-esthetic topics were sufficiently placed \nin course contents of education program”. Section Item 1 - II. Section Item 4 H0: There are no correlations between the statements \n“The courses about art and design had contents that \nwere able to teach me artistic design principles both \ntheoretically and practically” and “I don’t think we have \nreceived sufficient education about the significance and \nnecessity \nthat \nesthetic \nvalues \nshould \nbear \nthe \ncharacteristics of our culture”. H1: There is a correlation between the statements “The \ncourses about art and design had contents that are able \nto teach me artistic design principles both theoretically \nand practically” and “The art education courses did not \nhave contents in which I can use my creativity and \ncomposition knowledge”. H1: There is a correlation between the statements “The \ncourses about art and design had contents that were able \nto teach me artistic design principles both theoretically \nand practically” and “I don’t think we have received \nsufficient education about the significance and necessity H0 was not rejected since P = 0.062 > α = 0.05. There are \nno correlations between the statements “The courses \nabout art and design had contents able to teach me \nartistic design principles both theoretically and practically” 927 Section Item 6 - IV. Section Item 1 H0 was rejected since P = 0.000 < α = 0.05. There is a \ncorrelation between the statements “I don’t think we have \nreceived sufficient education about the significance and \nnecessity that esthetic values should bear the charac-\nteristics of our culture” and “I don’t think esthetic and \nmeta esthetic topics were sufficiently placed in course H0: There are no correlations between the statements “I \ndon’t think esthetic and meta esthetic topics were \nsufficiently placed into course contents of education \nprogram” and “I hear the concept of “meta esthetics” for \nthe first time”. Educ. Res. Rev. 928 Table 43. Correlations between the statements “I don’t think esthetic and meta \nesthetic topics were sufficiently placed into course contents of education program” \nand “I hear the concept of “meta esthetics” for the first time Table 43. Correlations between the statements “I don’t think esthetic and meta \nesthetic topics were sufficiently placed into course contents of education program” \nand “I hear the concept of “meta esthetics” for the first time Correlations \n \n \n \n 2-6 4-1 \nSpearman's rho 2_6 Correlation Coefficient 1.000 \n-.146 \nSig. (2-tailed) \n. .104 \nN \n126 \n126 \n4_1 Correlation Coefficient -.146 \n1.000 \nSig. (2-tailed) \n.104 \n. N \n126 \n126 Table 44. Correlations between the statements “I don’t think \nwe have received sufficient education about the significance \nand necessity that esthetic values should bear the \ncharacteristics of our culture” and “I hear the concept of \n“meta esthetics” for the first time. the significance and necessity that esthetic values should \nbear the characteristics of our culture” and “I hear the \nconcept of “meta esthetics” for the first time”. H1: There is a correlation between the statements “I don’t \nthink we have received sufficient education about the \nsignificance and necessity that esthetic values should \nbear the characteristics of our culture” and “I hear the \nconcept of “meta esthetics” for the first time”. Correlations \n \n \n \n2-4 \n4-1 \nSpearman's rho 2_4 Correlation Coefficient 1.000 .030 \nSig. (2-tailed) \n. .739 \nN \n126 \n126 \n4_1 Correlation Coefficient .030 1.000\nSig. (2-tailed) \n.739 . N \n126 \n126 p\nH0 was not rejected since P = 0,739 > α = 0,05. There are \nno correlations between the statements “I don’t think we \nhave received sufficient education about the significance \nand necessity that esthetic values should bear the \ncharacteristics of our culture” and “I hear the concept of \n“meta esthetics” for the first time”. Section Item 6 - IV. Section Item 1 In Table 14, while 49.2% of the students was indicating \ninsufficiency of education about esthetic values, 56.4% \nindicated that they heard about the concept of meta \nesthetics for the first time. However, 50.8% found the \nesthetic value education sufficient. Such a case again is \nconflicting (Table 44). H1: There is a correlation between the statements “I don’t \nthink esthetic and meta esthetic topics were sufficiently \nplaced into course contents of education program” and “I \nhear the concept of “meta esthetics” for the first time”. H0 \nwas rejected since P = 0.104 < α = 0.05. There is a \ncorrelation between the statements “I don’t think esthetic \nand meta esthetic topics were sufficiently placed into \ncourse contents of education program” and “I hear the \nconcept of “meta esthetics” for the first time”. Such a \ncorrelation was about 14%. H1: There is a correlation between the statements “I don’t \nthink esthetic and meta esthetic topics were sufficiently \nplaced into course contents of education program” and “I \nhear the concept of “meta esthetics” for the first time”. H0 \nwas rejected since P = 0.104 < α = 0.05. There is a \ncorrelation between the statements “I don’t think esthetic \nand meta esthetic topics were sufficiently placed into \ncourse contents of education program” and “I hear the \nconcept of “meta esthetics” for the first time”. Such a \ncorrelation was about 14%. Section Item 1 - III. Section Item 2 H0: There are no correlations between the statements “I \ndon’t feel uncomfortable buying products for which \nadvertisement is made by exaggerating or distorting their \ncharacteristics although they are “nice” according to my \nsenses” and “Appearance of a product to be purchased is \nmore important than its functions”. In Table 16, 58% was thinking that esthetic and meta-\nesthetic topics were included in course contents \nsufficiently. Besides, in Table 23, 56.4% indicated they \nhave heard the concept of meta esthetics for the first \ntime. Such a correlation was in negative direction and it is \na contradictory correlation (Table 43). H1: There is a correlation between the statements “I don’t \nfeel uncomfortable buying products for which advertise-\nment is made by exaggerating or distorting their \ncharacteristics although they are “nice” according to my \nsenses” and “Appearance of a product to be purchased is \nmore important than its functions”. Section Item 2 - IV. Section Item 3 H0: There are no correlations between the statements “I \nthink esthetic appearance and functionality are equally \nand highly important in design of every use intended \nproduct” and “In a product produced to express myself, I \ndon’t care about the interests and needs of the crowd \nwith which I share that product”. Correlations Correlations \n \n \n \n3-1 \n3-2 \nSpearman's rho 3_1 Correlation Coefficient 1.000 .108 \nSig. (2-tailed) \n. .230 \nN \n126 \n126 \n3_2 Correlation Coefficient .108 1.000\nSig. (2-tailed) \n.230 . N \n126 \n126 *. Correlation is significant at the 0.05 level (2-tailed). ment is made by exaggerating or distorting their \ncharacteristics although they are “nice” according to my \nsenses” and “Appearance of a product to be purchased is \nmore important than its functions”. product however 52.4% found the institutions providing \nbasic art/design education and raising artist/designer are \ninsufficient in raising conscious art consumers. About half \nof the remaining students thought contrarily. That \nexplains the significant relationship between the items \n(Table 46). In Table 17, 51.2% of the students indicated that they \ndon’t feel uncomfortable buying products for which \nadvertisement is made by exaggerating or distorting their \ncharacteristics although they “nice” according to my \nsenses. Besides, in Table 18, 40.07% indicated the \nsignificance of functions of a product. Such opinions are \nalso conflicting (Table 45). Section Item 4 - IV. Section Item 1 p\nH0 was not rejected since P = 0.230 > α = 0.05. There \naren’t any correlations between the statements “I don’t \nfeel uncomfortable buying products for which advertise- H0: There are no correlations between the statements “I \ndon’t think we have received sufficient education about 929 Tataroglu Table 46. Because of art and design education I received, I \nlook for initially the esthetic integrity and uniqueness in a \nproduct I purchase” and “I think the institutions providing \nbasic art/design education and raising artists/designers are \ninsufficient in raising conscious art consumers. Table 45. Correlations between the statements “I don’t feel \nuncomfortable buying products for which advertisement is \nmade by exaggerating or distorting their characteristics \nalthough they are “nice” according to my senses” and \n“Appearance of a product to be purchased is more important \nthan its functions. Correlations \n \n \n \n3-5 \n3-6 \nSpearman's rho 3_5 Correlation Coefficient 1.000 .210*\nSig. (2-tailed) \n. .018 \nN \n126 \n126 \n3_6 Correlation Coefficient .210* 1.000\nSig. (2-tailed) \n.018 . N \n126 \n126 \n \n*. Correlation is significant at the 0.05 level (2-tailed). Correlations \n \n \n \n3-5 \n3-6 \nSpearman's rho 3_5 Correlation Coefficient 1.000 .210*\nSig. (2-tailed) \n. .018 \nN \n126 \n126 \n3_6 Correlation Coefficient .210* 1.000\nSig. (2-tailed) \n.018 . N \n126 \n126 \n \n*. Correlation is significant at the 0.05 level (2-tailed). Correlations \n \n \n \n3-1 \n3-2 \nSpearman's rho 3_1 Correlation Coefficient 1.000 .108 \nSig. (2-tailed) \n. .230 \nN \n126 \n126 \n3_2 Correlation Coefficient .108 1.000\nSig. (2-tailed) \n.230 . N \n126 \n126 Section Item 5 - III. Section Item 6 H0: There are no correlations between the statements \n“Because of art and design education I received, I look \nfor initially the esthetic integrity and uniqueness in a \nproduct I purchase” and “I think the institutions providing \nbasic art/design education and raising artists/designers \nare insufficient in raising conscious art consumers”. H1: There is a correlation between the statements “I think \nesthetic appearance and functionality are equally and \nhighly important in design of every intended use product” \nand “In a product produced to express myself, I don’t \ncare about the interests and needs of the crowd with \nwhich I share that product”. H1: There is a correlation between the statements \n“Because of art and design education I received, I look \nfor initially the esthetic integrity and uniqueness in a \nproduct I purchase” and “I think the institutions providing \nbasic art/design education and raising artists/designers \nare insufficient in raising conscious art consumers”. H0 was not rejected since P = 0.128 > α = 0.05. There \naren’t any correlations between the statements “I think \nesthetic appearance and functionality are equally and \nhighly important in design of every intended use product” \nand “In a product produced to express myself, I don’t \ncare about the interests and needs of the mass with \nwhich I share that product”. g\nH0 was rejected since P = 0.018 < α = 0.05. There is a \ncorrelation between the statements “Because of art and \ndesign education I received, I look for initially the esthetic \nintegrity and uniqueness in a product I purchase” and “I \nthink the institutions providing basic art/design education \nand raising artists/designers are insufficient in raising \nconscious art consumers”. Such a correlation was about \n21%. In Table 24, 76.2% of the students preferred \nappearance over functions. On the other hand in Table \n25, 42.8 of the students indicated that they didn’t care \nabout the functions in production. It was expected that \nthis item should have higher rates as parallel to the \nprevious item. Student attitudes were also found \nconflicting here (Table 47). In Table 21, 78.2% great majority indicated that they \nprioritized esthetic integrity and specificity in purchasing a 930 Educ. Res. Rev. Table 48. Correlations between the statements “It is possible \nto direct people without being noticed and to impose the \nelements of a culture on them” and “I think that creating a \nneed for anything requires creativity of people as well. Table 47. Section Item 5 - V. Section Item 2 H0: There are no correlations between the statements “It \nis possible to direct people without being noticed and to \nimpose the elements of a culture on them” and “I think \nknowledge of metaesthetics by creative individuals is \nboth necessary and significant in culture transfer”. H1: There is a correlation between the statements “It is \npossible to direct people without being noticed and to \nimpose the elements of a culture on them” and “I think \nknowledge of metaesthetics by creative individuals is \nboth necessary and significant in culture transfer”. H0: There are no correlations between the statements “It \nis possible to direct people without being noticed and to \nimpose the elements of a culture on them” and “I think \nknowledge of metaesthetics by creative individuals is \nboth necessary and significant in culture transfer”. Section Item 5 - V. Section Item 1 H0: There are no correlations between the statements “It \nis possible to direct people without being noticed and to \nimpose the elements of a culture on them” and “I think \nthat creating a need for anything requires creativity of \npeople as well”. Correlations \n \n \n \n4-5 \n5-2 \nSpearman's rho 4_5 Correlation Coefficient 1.000 .126 \nSig. (2-tailed) \n. .159 \nN \n126 \n126 \n5_2 Correlation Coefficient .126 1.000\nSig. (2-tailed) \n.159 . N \n126 \n126 H1: There is a correlation between the statements “It is \npossible to direct people without being noticed and to \nimpose the elements of a culture on them” and “I think \ncreating a need for anything requires creativity of people \nas well”. H0 was rejected since P = 0.000 < α = 0.05. There is a \ncorrelation between the statements “It is possible to direct \npeople without being noticed and to impose the elements \nof a culture on them” and “I think that creating a need for \nanything requires creativity of people as well.” Such a \ncorrelation was about 39%. H0 was not rejected since P = 0,159 > α = 0.05. There are \nno correlations between the statements “It is possible to \ndirect people without being noticed and to impose the \nelements of a culture on them” and “I think knowledge of \nmetaesthetics by creative individuals is both necessary \nand significant in culture transfer”. Of the participant students, 85.4% approved the \nesthetic characteristic of meta esthetics to purchaser \n(Table 27) and 84.1% indicated that creativeness was \neffective in manipulations toward the human needs. Therefore, the correlation between them was significant \n(Table 48). Of the participant students, 85.4% indicated that it was \npossible to direct people without being noticed and to \nimpose the elements of a culture on them (Table 27) and \n70.7% indicated that knowledge of metaesthetics by \ncreative individuals was both necessary and significant in \nculture transfer (Table 30). These two statements indi-\ncated the same opinions and they were accepted \nindependently by the majority of the students (Table 49). Section Item 5 - III. Section Item 6 Correlations between the statements “I think \nesthetic appearance and functionality are equally and highly \nimportant in design of every use intended product” and “In a \nproduct produced to express myself, I don’t care about the \ninterests and needs of the crowd with which I share that \nproduct. Correlations \n \n \n \n4-5 \n5-1 \nSpearman's rho 4_5 Correlation Coefficient 1.000 .395**\nSig. (2-tailed) \n. .000 \nN \n126 \n126 \n5_1 Correlation Coefficient .395** 1.000\nSig. (2-tailed) \n.000 . N \n126 \n126 \n \n**. Correlation is significant at the 0.01 level (2-tailed). Correlations Correlations \n \n \n \n4-2 \n4-3 \nSpearman's rho 4_2 Correlation Coefficient 1.000 -.136\nSig. (2-tailed) \n. .128 \nN \n126 \n126 \n4_3 Correlation Coefficient -.136 1.000\nSig. (2-tailed) \n.128 . N \n126 \n126 **. Correlation is significant at the 0.01 level (2-tailed). Table 49. It is possible to direct people without being noticed \nand to impose the elements of a culture on them” and “I think \nknowledge of metaesthetics by creative individuals is both \nnecessary and significant in culture transfer Section Item 4 - V. Section Item 5 H1: There is a correlation between the statements “It is \npossible to direct people without being noticed and to \nimpose the elements of a culture on them” and “I think \nknowledge of metaesthetics by creative individuals is \nboth necessary and significant in culture transfer”. H0: There are no correlations between the statements “I \nthink the material value assigned to an artwork \ncommoditizes the art” and “The objective of making 931 Tataroglu Table 50. Correlations between the statements “I think the \nmaterial value assigned to an artwork commoditizes the art” \nand “The objective of making money draws the artist away \nfrom artistic creativity \n \nCorrelations \n \n \n \n5-4 \n5-5 \nSpearman's rho 5_4 Correlation Coefficient 1.000 .066 \nSig. (2-tailed) \n. .461 \nN \n126 \n126 \n5_5 Correlation Coefficient .066 1.000\nSig. (2-tailed) \n.461 . N \n126 \n126 Table 50. Correlations between the statements “I think the \nmaterial value assigned to an artwork commoditizes the art” \nand “The objective of making money draws the artist away \nfrom artistic creativity conflicting results in many tables. Accordingly, it was \ndetermined that the students agreed on the matters of the \nspecificity of art or design product, multiplication of \ndesign product and advertising; however despite all the \nrecognized knowledge, they developed an attitude to \nbring themselves forward or to disregard all ethical values \nfor the sake of making money. Correlations \n \n \n \n5-4 \n5-5 \nSpearman's rho 5_4 Correlation Coefficient 1.000 .066 \nSig. (2-tailed) \n. .461 \nN \n126 \n126 \n5_5 Correlation Coefficient .066 1.000\nSig. (2-tailed) \n.461 . N \n126 \n126 g\ny\nOne of the striking conclusions has shown itself in \njudgments of university students about art educators. While the students’ responses were not consistent about \nwhether art educators were adequately sensitive and \nsincere in teaching art, substantial majority, ended with \nnegative response (Table-14). In this case, unsatisfied \nexpectations of the students can be considered as a \nnegative attitude. The failure of faculty members to \nexpress their sincerity to the students was mainly \nbecause of heavy course loads and time limitations. Decreasing the course loads or increasing working hours \nmay result in more effective relationships between the \nstudents and the faculty members. money draws the artist away from artistic creativity”. H1: There is a correlation between the statements “I think \nthe material value assigned to an artwork commoditizes \nthe art” and “The objective of making money draws the \nartist away from artistic creativity”. Section Item 4 - V. Section Item 5 Art students still have doubts about the nature of art \ncourses (Table-12). Thus, majority of them expressed the \ninstable nature of art courses and the rest were in \ndilemma about the sufficiency of art courses. Thus, art \neducation curriculum should be rearranged. y\ny\nH0 was not rejected since P = 0.461 > α = 0.05. There \naren’t any correlations between the statements “I think \nthe material value assigned to an artwork commoditizes \nthe art” and “The objective of making money draws the \nartist away from artistic creativity”. Such outcomes brought forward initially the respon-\nsibility of higher educational institutes with regard to \nquality and practical characteristics of the education they \nprovided and ultimately the responsibility of families in \nevery case affecting the students. Of the participant students, 54.8% indicated that the \nmaterial value assigned to an artwork commoditizes the \nart (Table 32) and 59.6% indicated that the objective of \nmaking money draws the artists away from artistic \ncreativity (Table 33). Considering student opinions about \nmoney-meta-art relationship, they exhibited different and \neven conflicting attitudes from each other (Table 50). The student failures in esthetic and art history classes \nsupplementing art/design education should also be \ncarefully evaluated and relevant measures should be \ntaken. Negative attitudes toward the instructors and \ncourse contents might definitely be effective in such \noutcomes, but considering the age group of the students, \nthey were mostly between 22-25 years of age. They were \nat ages to be able to mentally synthesize the theoretical \nknowledge however their attitudes putting the ethics \nbehind the publicity and money is daunting. A value \ntraining starting from the lowest levels should be provided \non this matter. Higher educational institutes of art and \ndesign faculties providing sensitivity education should \nfocus more on esthetics, esthetic values, art history and \ncritical theories. Otherwise, future instructors, artists, \ndesigners and even parents will turn into ethically- \ncrippled generations and they will put exchange value of \nitems over any values in time. CONCLUSION AND SUGGESTIONS The following conclusions can be drawn from the state-\nments provided by the students about attitude scales: Majority of the participant students were females of ages \nbetween 22-25 years and most of them were enrolled in \nfreshman (1st class) year at Interior Architecture and \nEnvironmental Design Department (Tables 1, 2, 3 and 4). With regard to educational levels of parents, while fathers \nmostly had undergraduate and graduate level education, \nmothers mostly had high school education (Tables 5 and \n6). Physical and technological equipment to provide \npractical \nopportunities \nto \nstudents, \nand \ninstructor \nattitudes, controlled, liberal, and cooperative and solid \neducation and training methods will be crucial and \nmandatory for raising conscious youths. It is thought that \ninner happiness and sensual satisfaction of instructors \nfrom their professions is the primary effect and later on \nfinding, discovering and using modern ways of aware-\nness and protection and transfer to other generations of )\nThe courses in which the students were the least suc-\ncessful were in order: English, Esthetics, and Art History. The place of the two of four disciplines of art/design \neducation such as Esthetic and Art History is extremely \nstriking and this has characteristic to affect all results. It was determined that most of the students agreed on \nmost items almost as polarized and this situation led to Educ. Res. Rev. 932 Haug WF (1997). Criticism of Meta-Esthetics (Translated by: Ayşe Gul). (1\nst Issue) İstanbul: Spartakus Publications. (Original work was \npublished in 1986). national values will enable satisfaction of instructors \nsecondarily. There are several internal and international \npublications on this issue. The common denominator of \nall these works is happiness, transformation, adaptation \nand motivation. This basic pattern is regarded as \ncomponents to bring success to instructors; and it is \nsuggested that providing these can be achieved only by a \nconscious programming and classification. Peşkersoy E (2009). Effects Of Demographic Characteristics and Art \nEducation On Student Consciousness About Meta Esthetics, \nAnkara/TR: Unpublished Ph.D thesis, Gazi University, Institute of \nEducational Sciences. Ranciére J (2001). Esthetic Unconsciousness. (Translated by: Kenan \nSarialioglu) (1st Edition). Izmir: ARA-lik Publishing Robinson K (2008). Creativity Overcome the Limits of Mind. (Translated \nby: Nihal Geydan Koldaş) (2nd Edition). İstanbul: Kitap Publications. Boydaş N (2006). Introduction to Art Criticism. (1\nst Issue) Ankara: \nGunduz Education and Publication. CONCLUSION AND SUGGESTIONS A higher education, which is conscious about cultural \nmatters, and producing and consuming consciously, and \nwhich can control the entire media and most importantly \ncan adapt their own self values and customs and make \ngeneralization, is the right of all youngsters. To achieve \nthis, the present study and similar studies will illuminate \nus, and provide comparison opportunity and will allow us \nto make an evaluation and will open new ways. A \ncomparison of this study and the doctorate thesis study, \nwhich was done previously and unpublished, will be \nmade. It is hoped that new doors and study areas will be \nopened to youngsters in meta esthetic and objectivation \nmatters. Read H (1978). Art And Industry. (Translated by: Dr. Nigan Bayazit). (O\n19 2) Read H (1978). Art And Industry. (Translated by: Dr. Nigan Baya\nIstanbul: ITU Press. (Original work was published in 1952). Istanbul: ITU Press. (Original work was published in 1952). Tdk, Great Turkish Dictionary, Web: http//www.tdk.gov.tr \nth ,\ny,\np\ng\nTunali I (1998). Esthetics. (5\nth Edition) Istanbul: Remzi Publishing. d Tunali I (1998). Esthetics. (5\nth Edition) Istanbul: Remzi Pu\nrd Tunali I (2003). Marxist Esthetics. (3\nrd Edition) Istanbul: Analiz \nPublishing. d Tunali I (2009). Design Philosophy. (3\nrd Issue) Istanbul: Yem Publishing. Yildirim A, Simsek H (2000). Qualitative Research Methods in Social \nSciences. (2\nnd Edition) Ankara: Seckin Publishing."}}},{"rowIdx":12590,"cells":{"identifier":{"kind":"string","value":"https://openalex.org/W2093356898"},"pdf_url":{"kind":"string","value":"https://jm.copernicus.org/articles/16/109/1997/jm-16-109-1997.pdf"},"lang":{"kind":"string","value":"English"},"error":{"kind":"null"},"title":{"kind":"string","value":"&lt;i&gt;Axelheibergella&lt;/i&gt; (Ostracoda, Crustacea), a new genus of marginally septate cladocopid ostracods from the central Arctic Ocean"},"source_name":{"kind":"string","value":"Journal of micropalaeontology"},"publication_year":{"kind":"number","value":1997,"string":"1,997"},"license":{"kind":"string","value":"cc-by"},"word_count":{"kind":"number","value":12854,"string":"12,854"},"text":{"kind":"string","value":"INTRODUCTION Fig. 1. Locality map of Arctic Ocean showing the two study areas,\nbathymetry, physiography and surface currents. Large clear and black\narrows denote input of North Pacific and North Atlantic water,\nrespectively; small clear arrows denote Beaufort Gyre; large black\nfishtail arrows denote Transpolar Drift (TPD) and export of water via\nFram Strait, and smaller black arrows denote Siberian branch of TPD. This study is based on an examination of the ostracods present \nin the top CL1 cm section of two bottom sediment samples from \nthe central Arctic Ocean CAO (Fig. 1), one from the Alpha \nRidge (CESAR 83-211, at a present-day water depth (PDWD) \nof 1730 m) and the other from the continental margin off Axel \nHeiberg Island (AH 87200-009, 1150m PDWD). g\n(\n,\n)\nThe two samples were collected by personnel of the \nGeological Survey of Canada from drifting ice islands during \nproject CESAR over the Alpha Ridge (Jackson & Mudie, 1984; \nJackson et al., 1985), and during the Canadian Ice Island Project \nISIS along the margin of the Canada Basin off Axel Heiberg \nIsland (Mungall, 1984; Jackson, 1986). Each 0-lcm sample \ncontained specimens of two new species of a new genus of \ncladocopid ostracod characterized by well-developed, radially \naligned septa between the outer lamella of the shell and the \ninfold along the free margin of the shell. Table 1 lists the \npodocopid and cladocopid ostracod taxa present in the two \nsamples. p\nThe new genus Axelheibergella is established to accommodate \ncladocopid ostracods with marginally septate shells. Although Axelheibergella is rare in bottom-surface samples \nfrom the two CESAR and Axel Heiberg sites discussed here \n(Fig. 1 and Table l), an ongoing investigation by the present \nauthor and T. M. Cronin of core top and downcore samples \nfrom 18 box cores collected from the Arctic Ocean by the joint \nCanada--United States Expedition to the Arctic Ocean, 1994, \nand referred to as the Arctic Ocean Section 1994 (AOS’94), has \nproduced 3048 specimens of A. arctica (2030) and A . punctata \n(1018) from eight of the box cores. The eight AOS’94 box cores \ncontaining ostracod assemblages that include the two species of \nAxelheibergella are from deep-water (1 020-2400 m PDWD) \nridge and slope sites in the Amerasian Basin (=Canada and \nMakarov Basins; Fig. 1) of the Arctic Ocean. Fig. 1. Locality map of Arctic Ocean showing the two study areas, \nbathymetry, physiography and surface currents. Axelheibergella (Ostracoda, Crustacea), a new genus of marginally septate cladocopid ostracods from \nthe central Arctic Ocean WILLIAM M. BRIGGS, Jr \nearch (INSTAAR), University of Colorado, Campus Box 450, Boulder, CO 80309-0450, USA. WILLIAM M. BRIGGS, Jr \nInstitute of Arctic and Alpine Research (INSTAAR), University of Colorado, Campus Box 450 WILLIAM M. BRIGGS, Jr \nInstitute of Arctic and Alpine Research (INSTAAR), University of Colorado, Campus Box 450, Boulder, CO 80309-0450, USA. ABSTRACT - The genus Axelheibergella is established for cladocopid ostracods with well-developed, \nradially aligned septa between the outer lamella and the relatively wide, free-margin infold parts of the \nshell. Two deep-water species of the genus are described from the Holocene of the Alpha Ridge rise and \nAxel Heiberg slope, central Arctic Ocean (CAO). Two other species are present in the warmer, shallower \nwaters of the Mediterranean region. Presumably the septa are designed to strengthen the free margin of the \nshell. The relationship of the camerae (interseptal chambers) to marginal pore canals in extant ostracods, \nincluding the Punciacopina, and to the marginal shell glands of cladocopids and halocypridid \nmyodocopids is discussed. Cladocopid and podocopid (podocopine) shell ultrastructure is discussed, \nand new terms are defined. The septate frill and its function in the enigmatic Punciacopina are discussed in \nthe light of recent discoveries of the radically different lifestyle of Manawa, and presumably of Puncia and \nPromunawa, from other non-punciacean ostracods. It is suggested that the frill of the Punciacopina is \nhomologous to the ala of some cytheracean (cytherurid) podocopid ostracods. Two unnamed species of \nPuncia from the New Zealand Pleistocene are illustrated, and complement the discussion of septa and \ncamerae in Axelheibergella. J. Micropalueontol. 16(2): 10S120, October 1997. 0262-821X3/97 $10.00 0 \n1997 British Micropalaeontological Society. 0262-821X3/97 $10.00 0 \n1997 British Micropalaeontological Society. Journal of Micropalaeontology, 1 6 109-1 20. Axelheibergella (Ostracoda, Crustacea), a new genus of marginally septate cladocopid ostracods from \nthe central Arctic Ocean PREVIOUS WORK Previous detailed work on the taxonomy and distribution of the \nmodern ostracods of the CAO is limited to a single study by Joy \n& Clark (1977). This study was based on an examination of the \n6 3 c m section of the tops of gravity cores retrieved in water \ndepths of 135 1 3812 m from the Alpha Cordillera, Charlie Gap, \nChukchi Rise and the Canada Basin, following the drift tract of \nIce Island T-3 (Fletcher's Ice Island), which served as a platform \nfor sample retrieval. Joy & Clark (1977) identified eight species \nof cladocopids assignable to Polycope (Family Polycopidae), \nrepresenting 42% of the total fauna of 19 species recorded from \n33 core tops in their study area. None of the species of \ncladocopids identified by Joy & Clark (1977) contain septa. More recently, some of the ostracod taxa dealt with by Joy & \nClark (1 977) have been recorded from the Pleistocene sections of \ncores retrieved from the CAO (Clark et al., 1990; Pak et al., \n1992). Additional studies by Cronin et al. (1994, 1995), and \nanother by Briggs & Mudie (in preparation), on the late \nQuaternary ostracods of the Arctic Ocean, emphasize the use of \nostracods as proxy indicators of Arctic Ocean palaeoceano- \ngraphic and palaeoclimatic history. Several intermediate-depth CESAR and Axel Heiberg slope ostracod taxa CESAR and Axel Heiberg slope ostracod taxa Argilloecia cylindrica Sars, 1866 g\ny\n,\nAustraloecia minuta (Joy & Clark, g\ny\n,\nAustraloecia minuta (Joy & Clark, 1977) (\ny\nBythocytherid gen. et sp. nov. y\ny\ng\np\nCytheropteron alatum Sars, 1866 y\np\n,\nCytheropteron arcticum Neale & Howe, 1973 y\np\n,\nCytheropteron arcticum Neale & Howe, 1973 y\np\n,\nCytheropteron bronwynae Joy & Clark, 1977 y\np\n,\nCytheropteron bronwynae Joy & Clark, 1977 y\np\ny\ny\n,\nCytheropteron carolinae Whatley & Coles, 1987 y\np\ny\nCytheropteron hamatum Sars, 1869 y\np\ny\nCytheropteron hamatum Sars, 1869 y\np\n,\nCytheropteron ex gr. hamatwn Sars, 1869 y\np\ng\n,\nCyrheropteron porterae Whatley & Coles, 1987 y\np\np\ny\n,\nCytheropteron pseudoinflaturn Whatley & Eynon, 1996 y\np\np\ny\n,\nCytheropteron pseudoinflaturn Whatley & Eynon, 1996 y\np\np\nf\ny\ny\n,\nCytheropteron scoresbyi Whatley & Eynon, 1996 y\np\ny\ny\nCytheropteron testudo Sars, 1869 y\np\ny\ny\nCytheropteron testudo Sars, 1869 y\np\nEucytherura sp. y\np\nHenryhowella dasyderma (Brady, 1880) y\ny\n(\ny,\n)\nKrithe glacialis Brady, Crosskey & Robertson, 1874 g\ny,\ny\n,\nMicrocythere medistriata (Joy & Clark, 1977) y\np\nParacytherois chukchiensis Joy & Clark, 1977 y\ny\n,\nPedicythere neofluitans Joy & Clark, 1977 y\nf\nPropontocypris sp. p\nyp\np\nPseudocythere caudata Sars, 1866 y\nSclerochilus sp. Swainocythere nanseni (Joy & Clark, 1981) Number of species Number of species p\nNumber of specimens Number of specimens able 1. Counts of cladocopid and podocopid ostracod species from CESAR and Axel Heiberg sites. Table 1. Counts of cladocopid and podocopid ostracod species from CESAR and Axel Heiberg sites to deeper-water ostracod species that are common in the \nassemblages of the Amerasian and Eurasian Basins have been \ndescribed as new by Whatley & Eynon (1996) from deep-water \nsites in the Greenland Sea area of the North Atlantic Ocean. Two of these taxa are present in assemblages containing \nAxelheibergella from the CESAR and Axel Heiberg sites \n(Table 1). INTRODUCTION Large clear and black \narrows denote input of North Pacific and North Atlantic water, \nrespectively; small clear arrows denote Beaufort Gyre; large black \nfishtail arrows denote Transpolar Drift (TPD) and export of water via \nFram Strait, and smaller black arrows denote Siberian branch of TPD. The presence of Axelheibergella in the Arctic Ocean and the \nMediterranean Sea is one more piece of evidence linking the \ncladocopid and podocopid ostracods of these two widely \nseparated regions (Cronin et al., 1994, 1995). 109 Briggs Briggs CESAR and Axel Heiberg slope ostracod taxa \nAH 87200-009 \nCESAR 83-21 1 \n1150m PDWD \n1730m PDWD \nArchypolycope archys (Joy & Clark, 1977) \nArchypolycope semipunctata (Joy & Clark, 1977) \nAxelheibergella arctica gen. et sp. nov. Axelheibergella punctata gen. et sp. nov. Polycope bireticulata Joy & Clark, 1977 \nPolycope bispinosa Joy & Clark, 1977 \nPolycope inornata Joy & Clark, 1977 \nPolycope punctata Sars, 1870 \nPolycope orbicularis Sars, 1866 \nPontopolycope moenia (Joy & Clark, 1977) \nAcetabulastoma arcticum Shornikov, 1970 \nArgilloecia cylindrica Sars, 1866 \nAustraloecia minuta (Joy & Clark, 1977) \nBythocytherid gen. et sp. nov. Cytheropteron alatum Sars, 1866 \nCytheropteron arcticum Neale & Howe, 1973 \nCytheropteron bronwynae Joy & Clark, 1977 \nCytheropteron carolinae Whatley & Coles, 1987 \nCytheropteron hamatum Sars, 1869 \nCytheropteron ex gr. hamatwn Sars, 1869 \nCyrheropteron porterae Whatley & Coles, 1987 \nCytheropteron pseudoinflaturn Whatley & Eynon, 1996 \nCytheropteron scoresbyi Whatley & Eynon, 1996 \nCytheropteron testudo Sars, 1869 \nEucytherura sp. Henryhowella dasyderma (Brady, 1880) \nKrithe glacialis Brady, Crosskey & Robertson, 1874 \nMicrocythere medistriata (Joy & Clark, 1977) \nMicrocythere sp. Paracytherois chukchiensis Joy & Clark, 1977 \nPedicythere neofluitans Joy & Clark, 1977 \nPropontocypris sp. Pseudocythere caudata Sars, 1866 \nSclerochilus sp. Swainocythere nanseni (Joy & Clark, 1981) \nNumber of species \nNumber of specimens \n4 \n1 \n13 \n1 \n50 \n296 \n8 \n46 \n23 \n4 \n11 \n8 \n11 \n1 \n28 \n28 \n12 \n7 \n1 \n53 \n20 \n10 \n8 \n108 \n8 \n10 \n20 \n4 \n12 \n1 \n7 \n31 \n814 \n9 \n27 \n2 \n5 \n83 \n1 \n123 \n63 \n13 \n3 \n12 \n15 \n3 \n12 \n1 \n3 \n9 \n2 \n1 \n11 \n2 \n14 \n14 \n23 \n438 \nTable 1. Counts of cladocopid and podocopid ostracod species from CESAR and Axel Heiberg sites. CESAR and Axel Heiberg slope ostracod taxa Water masses The three-layered division of the water masses in the CAO based \non temperature and salinity consists of (1) Arctic surface water \n(ASW) (surface to 200m): cold, low salinity water; (2) Arctic \nintermediate water (AIW) = Atlantic layer (200-900m): rela- \ntively warm >O°C, high salinity water; and (3) (ABW) Arctic \nbottom water ( > 900 m): < O°C, high salinity water (Coachman \n& Aagaard, 1974). Aagaard et al. (1985) place the lower \nboundary of AIW in the Canada Basin at c. 1300m, and refer to \nthe ABW in this area of the CAO as Canada Basin Deep Water \n(CBDW). I10 Axelheibergella, a new genus of cladocopid ostracod samples of Shakespeare Cliff Siltstone and Tainui Shellbed are \nrecorded as NZMS 260 Sheet and Metric Fossil Record File No. R22/f6627 and R22/f6628, respectively. The 1970 recollections \nfrom these two units bear the same fossil record file numbers as \nthe 1965 collections. Shakespeare Cliff Siltstone lies immediately \nabove Tainui Shellbed stratigraphically, and both units lie \nwithin oxygen isotope stage 11 (Beu & Edwards, 1984; Beu et al., \n1987). samples of Shakespeare Cliff Siltstone and Tainui Shellbed are \nrecorded as NZMS 260 Sheet and Metric Fossil Record File No. R22/f6627 and R22/f6628, respectively. The 1970 recollections \nfrom these two units bear the same fossil record file numbers as \nthe 1965 collections. Shakespeare Cliff Siltstone lies immediately \nabove Tainui Shellbed stratigraphically, and both units lie \nwithin oxygen isotope stage 11 (Beu & Edwards, 1984; Beu et al., \n1987). The CESAR site at a depth of 1730m is within the upper part \nof the CBDW, with bottom temperatures and salinities around \n-0.5\"C and 34.9% respectively. The Axel Heiberg slope site at a \ndepth of 1150m may lie within the uppermost part of CBDW, \nbut the presence of Cytheropteron porterae, C. pseudoinjlatum \nand C. testudo (Table 1) suggests lowermost AIW. Briggs & \nMudie (in preparation) present evidence that suggests the AIW/ \nCBDW boundary could be as deep as c. 1200-1300m, based on \na semi-quantitative analysis of ostracod assemblages from \nCESAR and Axel Heiberg shelf/slope sites. Reflected light photography of the holotype specimen (Pl. 1, \nfig. 1) of Axelheibergella arctica utilized a 16mm Zeiss Luminar \nlens with the aperture set at fl5, and a bellows draw that resulted \nin an initial magnification on the film of 40x. The light source \nused was electronic flash from a single unit in the upper left field \nof view. Water masses The 35mm camera shutter was locked open and the \nelectronic flash was triggered manually by electric cable twice to \nproduce the best image density on Kodak TMAX 100 \nphotographic film. The transparent specimen was photographed \nin a single-cell microfaunal slide against the black background \nof the slide, which resulted in maximum contrast between shell \nstructures and background. Transmitted light photography of \nspecimens (Fig. 2, figs 1-3) of Axelheibergellu utilized either an \nOlympus Vanox compound microscope with automatic expo- \nsure features or a Leitz compound microscope with a manual \nexposure meter, using Kodak Technical Pan film and tungsten \nlight source. The specimens were photographed in a single-cavity \nglass slide using immersion oil with an RI of 1.5. Both types of \nfilm were developed for an exposure index (ASA/ISO) of 50/18\". The transmitted light photograph of Puncia sp. B (Fig. 2, fig. 4) \nwas taken in late 1968 at Victoria University of Wellington, \nusing a Leitz compound microscope, tungsten light source and \ngreen Wratten filter, with the specimen in the same type of glass \ncavity slide and immersed in clove oil, and using Kodak \n(Microfile) High Contrast Copy film. The film, which is no \nlonger manufactured, was exposed and processed in such a way \nin Kodak Microdol-X developer that the ASA value of 64 was \nreduced to an approximate effective value of ASA 6. Age of the ostracod fauna g\nBecause sedimentation rates are low in the CAO, some of the \nspecimens of the two species on which AxelheibergeZZa is based \nfrom the Axel Heiberg and CESAR sites may date from 1 ka BP \nand the earliest Holocene, respectively. Unfortunately, the two \n&l cm surface samples were not treated with a protoplasm- \nspecific stain. Most of the 1252 specimens listed in Table 1 from \nthe two sites are disarticulated valves and none contain \nappendages. Some support for the relict nature of the ostracod \nfauna comes from studies of the benthic foraminifera in surface \nsediments on the Axel Heiberg Shelf by Schroder-Adams et al. (1 990a, b). Rose Bengal staining revealed that living specimens \nof foraminifera make up less than 3% of the surface population, \nsuggesting that the surface fauna is largely subfossil or residual. The same may be true of the ostracods. Specimens selected for SEM photography were mounted on \ntwo stubs following the method described by Finch (1974). Given the rarity, small size and the fragility of the specimens, it \nwas decided not to remove the paratype (Pl. 1, fig. 2) of \nAxelheibergella arctica, or the holotype (Pl. 1, fig. 6) and shell \nfragment (Pl. 1, fig. 12) of Axelheibergella punctata from the \nSEM stubs. Figured and unfigured specimens of both species of \nAxelheibergella are deposited in the Specimen Repository at the \nGeological Survey of Canada, Ottawa, Ontario, Canada. Specimens are referred to by a GSC (Geological Survey of \nCanada) catalogue number in the main body of text and in the \nplate and text-figure explanations for illustrated specimens. Specimens of the two species of Puncia are deposited in the \nostracod collections of the Institute of Geological & Nuclear \nSciences (IGNS), Ltd. (formerly the New Zealand Geological \nSurvey), Lower Hutt, New Zealand, and are referred to by \nIGNS preceding their catalogue numbers. Sedimentation rates Sedimentation rates in the nearly perennial ice-covered CAO \nduring the latest Pleistocene-Holocene are on the order of \n1-3 mm ka-' and are based on magneto-stratigraphic, accel- \nerator mass spectrometry I4C dating (to the limit of the method), \nand stable isotope studies (Clark et al., 1980, 1986; Witte & \nKent, 1988; Morris, 1988). Aksu (1985), Aksu & Mudie (1985) \nand Scott et al. (1989) determined sedimentation rates of about \n1 mm ka- ' (maximum 1.5-3 mm ka-I) in CESAR cores from the \nAlpha Ridge, and Van Wagoner et al. (1989) have suggested an \naccumulation rate of 0.8-3.9cmka-' on the Axel Heiberg shelf. MATERIAL AND METHODS The Arctic Ocean bottom sediments (Fig. 1) were collected by \nsampling devices lowered to the ocean floor through holes that \npenetrated the thickness of the ice islands. CESAR 83-21 1 is the \n0-1 cm section from the top of a 46 cm-long Benthos gravity \ncore retrieved from the Alpha Ridge graben, 1730m PDWD, at \n85'43.9'N, 108'51.9' W. (Jackson et al., 1985). Axel Heiberg AH \n87200-009 is the 0-1 cm section from the top surface of sediment \nretrieved by a Dietz-LaFond grab from the upper slope, 11 50 m \nPDWD, at 82'09.62\", \n102'33.87'W. For each of the samples \nused for microfossil analysis, about 35 ml of wet sediment were \nprocessed and washed on a 63 pm screen by personnel from the \nBedford Institute of Oceanography. The two illustrated species of Puncia are from samples \ncollected at an exposure of Shakespeare Cliff Siltstone and \nTainui Shellbed, Castlecliff coastal section, Wanganui Basin, \nNorth Island, New Zealand, which the author collected on 12 \nNovember 1965, with Alan Beu and Philip Maxwell, and which I \nsubsequently recollected on 25 September 1970. The 1965 The shell terminology used follows closely that proposed by \nKornicker (1969). Axial zone as used in this report refers to the \narea of the shell between outer lamella and infold, including the \nvestibule; it is delimited distally by the edge of the shell and \nproximally by the inner margin of the infold. Kornicker's (1969) \nuse of the term excluded the vestibule. Although a rostrum is not 11 1 Briggs Briggs Plate 1 Plate 1 112 112 Axelheibergella, a new genus of cladocopid ostracod Fig. 2. Transmitted light photographs. figs 1-2. Axelheibergellu arctica gen. et sp. nov. Paratype, RV A: fig. 1. interior lateral view, x348, fig. 2. detail \nof septa, larger arrows point to larger-diameter openings, and smaller arrow points to smaller diameter opening in the outer lamella of the axial zone, \nX858, GSC 115785; fig. 3. Axelheibergellu puncraru gen. et sp. nov. Paratype, RV A, exterior lateral view (a rectangular-shaped hole occurs in the \nshell), x220, GSC 115793; locality: Axel Heiberg, AH 87200-009, 1150m PDWD. fig. 4. Puncia sp. B (60 camerae are present, but this species \n(although the specimen is missing part of its shell dorsally) lacks the two subdorsal ponticulate carinae of Puncia sp. Fig. 1. Reflected light photograph. Figs 2-13. Scanning electron microscope photographs. Figs 1-5,7-11. Axelheibergellu urctica gen. et sp. nov.: fig. \n1, Holotype, RV A, exterior lateral view, x207, GSC 115780; fig. 2, Paratype, RV A, exterior lateral view, x211, GSC 11 5781; figs 3,7-8, Paratype, \nLV A: fig. 3, interior lateral view, x211, fig. 7, detail of hinge, x558, fig. 8, detail of muscle scars, x2160, GSC 115782; figs 4, 9-11, RV A: fig. 4, \ninterior lateral view of broken specimen (arrow points to nick point in section of shell shown in fig. 9), x238, fig. 9, detail of infold of ventral margin \nof specimen shown in fig. 4 (arrow points to enlargement of shell wall shown in fig. ll), x895, fig. 10, detail of posterior hinge of specimen shown in \nfig. 4, x 1018, fig. 11, ultrastructure of outer lamella showing the two layers of endocuticle of specimen shown in fig. 4. Note the hummocky inner \nsurface of the outer layer of the shell. The inner surface of the shell is shown top right and a sliver of the outer surface is visible in bottom right half of \nphotograph, ~5200, GSC 115783; fig. 5, LV A, interior lateral view of broken specimen exposing two camera1 septa between outer lamella and \nbroken away part of infold, x235, GSC 11 5784; locality: Axel Heiberg, AH 87200-009, 1150m PDWD. Figs 6,12. Axelheibergeflupuncrata gen. et sp. \nnov.: fig. 6, Holotype, LV-A, exterior lateral view, x232, GSC 115791; fig. 12, LV-A, interior lateral view, detail of septa of an incompletely calcified \nadult shell (arrows point to two smaller-diameter pores in the outer lamella of the axial zone), x353. Note the interior expression of the puncta of this \nspecies, which indicates that calcification of the shell ceased shortly after the protoostracum stage in this specimen. GSC 115792; locality: Alpha \nRidge, CESAR 83-211, 1730m PDWD. Fig. 13. Puncia sp. A (possibly Puncia sp. A of Swanson (1991) with c. 60 camerae and two subdorsal \nponticulate carinae), RV A, exterior lateral view, x84, IGNS OP1157, Tainui Shellbed, Wanganui Coastal Section, North Island, New Zealand; New \nZealand Metric Fossil Record File number R22/f6628 (1970 recollection), Pleistocene. MATERIAL AND METHODS A; the black areas of the camerae \nare entrapped air bubbles in the oil of cloves), RV A, exterior lateral view, x97, IGNS OP1156, Shakespeare Cliff Siltstone, Wanganui Coastal \nSection, North Island, New Zealand; New Zealand Metric Fossil Record File number R22/f6627 (1965 original collection), Pleistocene. Fig. 2. Transmitted light photographs. figs 1-2. Axelheibergellu arctica gen. et sp. nov. Paratype, RV A: fig. 1. interior lateral view, x348, fig. 2. detail \nof septa, larger arrows point to larger-diameter openings, and smaller arrow points to smaller diameter opening in the outer lamella of the axial zone, \nX858, GSC 115785; fig. 3. Axelheibergellu puncraru gen. et sp. nov. Paratype, RV A, exterior lateral view (a rectangular-shaped hole occurs in the \nshell), x220, GSC 115793; locality: Axel Heiberg, AH 87200-009, 1150m PDWD. fig. 4. Puncia sp. B (60 camerae are present, but this species \n(although the specimen is missing part of its shell dorsally) lacks the two subdorsal ponticulate carinae of Puncia sp. A; the black areas of the camerae \nare entrapped air bubbles in the oil of cloves), RV A, exterior lateral view, x97, IGNS OP1156, Shakespeare Cliff Siltstone, Wanganui Coastal \nSection, North Island, New Zealand; New Zealand Metric Fossil Record File number R22/f6627 (1965 original collection), Pleistocene. uated in units of 20 pm at a magnification of x80. All \ndimensions are maximum ones and are given as length \n(L) x height (H) in millimetres. A- 1 and A-2 refer to penultimate \nand antepenultimate instars, respectively. Specimen counts \n(Table 1) include valves and carapaces of adult and juvenile \ninstars. By convention, one disarticulated valve or one \narticulated (bivalve) carapace counts as one specimen. present in cladocopids, the author uses the term ‘rostra1 incisure’ \nto indicate a barely perceptible inflection in the curvature of the \noutline of the shell margin which helps to identify the anterior \nend of the shell from the posterior end. Shell and valve are used \ninterchangeably throughout the text. g\ny\ng\nRV and LV refer to right and left valves, respectively. Measurements were made with an eyepiece micrometer grad- Explanation of Plate I Fig. 1. Reflected light photograph. Figs 2-13. Scanning electron microscope photographs. Figs 1-5,7-11. Axelheibergellu urctica gen. et sp. nov.: fig. 1, Holotype, RV A, exterior lateral view, x207, GSC 115780; fig. 2, Paratype, RV A, exterior lateral view, x211, GSC 11 5781; figs 3,7-8, Paratype, \nLV A: fig. 3, interior lateral view, x211, fig. Fig. 1. Reflected light photograph. Figs 2-13. Scanning electron microscope photographs. Figs 1-5,7-11. Axelheibergellu urctica gen. et sp. nov.: fig. \n1, Holotype, RV A, exterior lateral view, x207, GSC 115780; fig. 2, Paratype, RV A, exterior lateral view, x211, GSC 11 5781; figs 3,7-8, Paratype, \nLV A: fig. 3, interior lateral view, x211, fig. 7, detail of hinge, x558, fig. 8, detail of muscle scars, x2160, GSC 115782; figs 4, 9-11, RV A: fig. 4, \ninterior lateral view of broken specimen (arrow points to nick point in section of shell shown in fig. 9), x238, fig. 9, detail of infold of ventral margin \nof specimen shown in fig. 4 (arrow points to enlargement of shell wall shown in fig. ll), x895, fig. 10, detail of posterior hinge of specimen shown in \nfig. 4, x 1018, fig. 11, ultrastructure of outer lamella showing the two layers of endocuticle of specimen shown in fig. 4. Note the hummocky inner \nsurface of the outer layer of the shell. The inner surface of the shell is shown top right and a sliver of the outer surface is visible in bottom right half of \nphotograph, ~5200, GSC 115783; fig. 5, LV A, interior lateral view of broken specimen exposing two camera1 septa between outer lamella and \nbroken away part of infold, x235, GSC 11 5784; locality: Axel Heiberg, AH 87200-009, 1150m PDWD. Figs 6,12. Axelheibergeflupuncrata gen. et sp. \nnov.: fig. 6, Holotype, LV-A, exterior lateral view, x232, GSC 115791; fig. 12, LV-A, interior lateral view, detail of septa of an incompletely calcified \nadult shell (arrows point to two smaller-diameter pores in the outer lamella of the axial zone), x353. Note the interior expression of the puncta of this \nspecies, which indicates that calcification of the shell ceased shortly after the protoostracum stage in this specimen. GSC 115792; locality: Alpha \nRidge, CESAR 83-211, 1730m PDWD. Fig. 13. Puncia sp. A (possibly Puncia sp. A of Swanson (1991) with c. 60 camerae and two subdorsal \nponticulate carinae), RV A, exterior lateral view, x84, IGNS OP1157, Tainui Shellbed, Wanganui Coastal Section, North Island, New Zealand; New \nZealand Metric Fossil Record File number R22/f6628 (1970 recollection), Pleistocene. MATERIAL AND METHODS 7, detail of hinge, x558, fig. 8, detail of muscle scars, x2160, GSC 115782; figs 4, 9-11, RV A: fig. 4, \ninterior lateral view of broken specimen (arrow points to nick point in section of shell shown in fig. 9), x238, fig. 9, detail of infold of ventral margin \nof specimen shown in fig. 4 (arrow points to enlargement of shell wall shown in fig. ll), x895, fig. 10, detail of posterior hinge of specimen shown in \nfig. 4, x 1018, fig. 11, ultrastructure of outer lamella showing the two layers of endocuticle of specimen shown in fig. 4. Note the hummocky inner \nsurface of the outer layer of the shell. The inner surface of the shell is shown top right and a sliver of the outer surface is visible in bottom right half of \nphotograph, ~5200, GSC 115783; fig. 5, LV A, interior lateral view of broken specimen exposing two camera1 septa between outer lamella and \nbroken away part of infold, x235, GSC 11 5784; locality: Axel Heiberg, AH 87200-009, 1150m PDWD. Figs 6,12. Axelheibergeflupuncrata gen. et sp. nov.: fig. 6, Holotype, LV-A, exterior lateral view, x232, GSC 115791; fig. 12, LV-A, interior lateral view, detail of septa of an incompletely calcified \nadult shell (arrows point to two smaller-diameter pores in the outer lamella of the axial zone), x353. Note the interior expression of the puncta of this \nspecies, which indicates that calcification of the shell ceased shortly after the protoostracum stage in this specimen. GSC 115792; locality: Alpha \nRidge, CESAR 83-211, 1730m PDWD. Fig. 13. Puncia sp. A (possibly Puncia sp. A of Swanson (1991) with c. 60 camerae and two subdorsal \nponticulate carinae), RV A, exterior lateral view, x84, IGNS OP1157, Tainui Shellbed, Wanganui Coastal Section, North Island, New Zealand; New \nZealand Metric Fossil Record File number R22/f6628 (1970 recollection), Pleistocene. 113 Briggs Briggs the marginally septate cypridacean podocopids listed above, \ncould be the conduits through which epidermal cells and sensory \ncells (sensilla) are extended to the proximity of the outer shell \nmargin, where the setae egress the shell through relatively short \ncanals and marginal pores. It has also been suggested that the \ncamerae and septa are in some way connected to the presence of \nthe so-called marginal shell glands described in some polycopids. Marginal shell glands and their associated canals and pores will \nbe discussed in greater detail below. Septa and camerae The presence of septa between infold and outer lamella along the \nfree margin of four species of cladocopids is a radical departure \nfrom the conservative nature of the shell architecture in the \norder. This is particularly demonstrable in the polycopaceans, \nfor example, in which the dome-shaped architecture of the shell \nexhibits perhaps the simplest known type of carapace design, as \nexemplified in Metapolycope by Benson (1 98 1). Presumably the \nsepta present in Axelheibergella act as buttresses which give \nadded strength to the thinly calcified and fragile carapace along \nits periphery. Camerae (camera, sing., cameral, adj.) are defined herein as \nthe interseptal chambers that result from the formation of septa \nbetween outer lamella and infold along the free margin of each \nvalve. Camerae are much wider structures than the combined \nwidths of the adjacent radial septa that form their sides. The \ncamerae in the two Arctic species of Axelheibergella are open to \nthe interior of the valve cavity proximally (Pl. 1, figs 1, 3-5, 9, \n12; Fig. 2, figs 1-3) and open to the exterior environment distally \n(Fig. 2, figs 1-3). Camerae are the morphological equivalent of \nthe interseptal ‘chambers’ and the ‘chamberlets’ or ‘compart- \nments’ used by Hornibrook (1949, 1963) to describe the \ninterseptal areas of the punciid frill (Pl. 1, fig. 13; Fig. 2, fig. 4), and of the ‘lunettes’ used to describe the interseptal areas in \nthe frill of Manawa by McKenzie & Neil (1983). The ‘hollow’ in \nthe frill of Promanawa between the ‘radial canals’ described by \nMcKenzie & Neil (1983) is apparently a camera. Functional morphology of the septate punciid frill \nIt has been suggested by Swanson (1991) that the septate punciid \nfrill (Pl. 1, fig. 13; Fig. 2, fig. 4) may serve a dual role, \nfunctioning both as benthic support structure and gas-filled \nbuoyancy device in Puncia and Promanuwa; but, as Swanson \npointed out, the true function of this structure must await the \ndiscovery of live specimens of these genera. Swanson (1989a, b, 1991) observed live specimens of Manawa \nstaceyi in the laboratory and found this punciid’s ontogeny to be \nunique amongst all known living ostracods. In this species, the \nearliest juveniles were found to have single, dome-shaped \n(univalve) carapaces, whilst older juveniles and adults have \nbivalve carapaces, in which the valves of their instars are fully \nextended laterally to nearly 180” during locomotion. MATERIAL AND METHODS The illustrations of the microfossils were produced by digital \nimagery techniques (Scott, 1995). SEM and light microscope \nphotographs were first made on glossy bromide paper, using \nconventional photographic methods. Each photograph was \nsubsequently scanned at a resolution of 320 dpi and imported \ninto Adobe Photoshop, where the images were enhanced and \nrearranged to compose Plate 1 and Fig. 2, and the files saved in \nRGB format. A Fujix Pictrography 3000 colour printer was used \nwith the same software to produce the black and white \nphotographs (by the mixing of colours) at a resolution of 320 \ndpi on glossy paper. All of the digital imagery was done on a \nMacintosh platform. g\nSepta are present in the enigmatic and extant Superfamily \nPunciacea Hornibrook, 1949. This taxon has been regarded as a \nwayward orphan by ostracod taxonomists, following description \nof Puncia and Manawa by Hornibrook (1949) and Promanawa \nby McKenzie & Neil (1983): first, having been regarded as a \npalaeocopid and, then, as podocopid (podocopine or platyco- \npine, or something intermediate between these two suborders). Although the debate continues, current opinion has come full \ncircle and the Punciacea are once again regarded as the only \nliving representatives of the predominately Palaeozoic Order \nPalaeocopida, but the relationship of this superfamily to the \nextinct Superfamily Kirkbyacea remains a subject of vigorous \ndebate (e.g. Becker & Swanson, 1992). Swanson (1985) pointed \nout that the septa in the punciid frill (Fig. 2, fig. 4) which were \nidentified correctly by Hornibrook (1949) have subsequently \nbeen referred to incorrectly as marginal pore canals. The \ncamerae in the frill of Puncia and Promanawa are normally \nclosed distally, and Swanson (1991) attributes the cause of \npartially open to fully open camerae in some specimens of \nPuncia to incomplete calcification of the frill. Some of the \ncamerae in the specimen of Puncia shown on PI. 1, fig. 13 are also \nopen distally. Moreover, there is evidence to suggest that the \ncamerae are closed off from the carapace interior (domicilium) \nproximally by a thin calcareous membrane (Swanson, 1985, \n1991). Shell (exocrine) glands, shell gland canals and ducts Unequivocal \nmarginal pore canals (randstundige Porenkunale) with setae \nwere found by Hartmann (1959) in the infold of the attached \nmargin of Polycope duplidentata Hartmann, 1959, where they \nare restricted to the area around the hinge bar. Kornicker & Van \nMorkhoven (1976) do not discuss marginal pore canals per se in \ntheir treatment of Metapolycope, but they do, however, illustrate \nsimple and noded pores along the valve edge of three species of \nMetapolycope that may be marginal pores. Moreover, Benson \n(1981) illustrated (his Fig. 3B) a marginal pore canal containing \na seta in M . hartrnanni, but Benson’s Fig. 3D showing a \nmarginal pore and seta appears to be the same as one he used \nearlier (Benson, 1975), which is an adaptation of a figure used by \nKesling (1951) to show the shell morphology of Cypridopsis. Kornicker & Iliffe (1989) illustrate several hairs on the \nanterodorsal margin of Polycopissa anax which exit through \npores on the exterior (outer lamella) surface of the shell. Most of \nthese hairs, however, are located within inner and outer shell \nmargins, i.e. in the axial zone, the area of the shell between the \ninfold and the outer lamella. The few marginal pore canals \npresent in the infold along both free margin and attached margin \nareas are connected to shell glands, and some of these canals exit \nto the outer lamella shell surface short of the outer margin, while \nthe remaining ones traverse the axial zone. The slender, short- \ncropped and closely spaced hairs that adorn the anteroventral, \nventral and posteroventral margins of this species are attached \nto the selvage, and they appear to be non-sensory in function. K M S\nd S H E\nh\nh h\nth\nth (\n)\ny\np\ny\np\nKornicker & Iliffe (1989) illustrated shell glands (‘glandular \nmasses’) between shell outer lamella and vestment of Polycopissa \nanax Kornicker & Iliffe. The shell (exocrine) glands are largely \nconcentrated along the inner margin of the infold, and most \nhave canals that open through presumed exocrine pores on the \nouter surface of the shell as normal pore canals. However, a few \nof the canals that begin in the axial zone near the inner margin \nopen to presumed exocrine pores on the outer surface of the \nshell within the axial zone, while fewer still pass through the \naxial zone to the valve margin. Shell (exocrine) glands, shell gland canals and ducts Shell (exocrine) glands, shell gland canals and ducts \nMarginal shell glands, the function of which is unclear, and \nmarginal canals presumably occupied by these glands (Kanule \nder Schalenranddrusen) are present in some species of Polycope, \nas reported by Hartmann (1954, 1955, 1963, 1965). Shell glands \nare present in Polycope onkophora Hartmann, 1954, and \nHartmann (1954) described and illustrated structures in the \ninfold area of the left valve of Polycope longipes Hartmann, \n1954, which he referred to as marginal shell gland canals. The \nmarginal structures illustrated in P. longipes by Hartmann \n(1954) are the septa1 and camera1 structures described herein for \nAxelheibergella. Subsequently, Hartmann (1 955) described and \nillustrated shell glands with nucleated cells that penetrate the \naxial zone of the infold of P. cancellea Hartmann, 1954, as seen \nin an oblique section through the (uncalcified?) shell margin. However, Hartmann (1955) acknowledged that the relationship \nbetween shell glands and the presumed canals and pores \nassociated with them is anything but clear. y\np\nInformation on marginal (radial) pore canals and marginal \npores in cladocopids is scarce and often contradictory. Accord- \ning to Hartmann (1955), Van Morkhoven (1963) and Pokorny \n(1 9654, sensillum-type marginal pores, as defined by Okada \n(1983), and their attendant canals are present in polycopids, but \ntheir numbers are few, and not much is known about them in \ndetail. Hartmann (1963, 1965, 1975) subsequently rejected the \nexistence of sensillum-type marginal canals in polycopids, noting \ninstead that the marginal canals and/or marginal pores present \nin some species of Polycope, e.g. Hartmann (1954, 1955), are \nassociated with the marginal shell glands. In a comprehensive \ntreatment on the classification of ostracods by Hartmann & Pun \n(1974), there was no mention of the presence in cladocopids of \nnormal or marginal pore canals, including those tied to shell \nglands. y\ng\nChavtur (1981) transferred Hartmann’s (1954) two species \nPolycope onkophora and P. longipes to Eupolycope Chavtur, \n198 1 and Polycopiella Chavtur, 198 1, respectively, retaining only \nHartmann’s (1954) Polycope cancellea in Polycope. g\nMarginal setae or hair presumably associated with marginal \npore canals have been reported by Hartmann (1954, 1955) from \nseveral species of Polycope he described from the Amphioxus- \nsands, near Banyuls-Sur-Mer, Mediterranean France, in 1954. In P. limbata and P. microdispar, setae are located on anterior \nand posteroventral margins, respectively, while in P. cancellea \nthey are mostly confined to the hinge area. Shell (exocrine) glands, shell gland canals and ducts Two of the latter canals open to \nexocrine pores containing extrusions of an unspecified sub- \nstance, with one of the extrusions partly coiled. According to \nKornicker & Iliffe (1989), the extruded substance is never \npresent on the outer surface of the shell, where many of the shell \ngland (exocrine) pores are located. Another important feature of exocrine pores that open on the \nouter lamella of the shell of cladocopids is the apparent lack of \nthe finger-like (core-catcher like) projections that surround and \nsometimes cover the opening in cytheracean podocopids, as \nshown by Okada (1982, 1983) and Hanai (1988). Shell glands are very common along the free margin in the \nnon-calcified to slightly calcified shells of the mostly pelagic \nhalocypridacean myodocopids. Some glands open into a \ncommon pore along the free margin, as shown by Muller \n(1894, 1908, 1912) and Skogsberg (1920), and especially in \nAIacia belgicae (Muller, 1906), as shown by Kock (1992), but the \nreal function of the marginal shell glands in this superfamily \nand, by implication, in cladocopids, is not known, according to \na summary and discussion of these glands by Hartmann (1955) \nof past theories on their functional use. Septa and camerae If Puncia \nand Promanawa eventually turn out to share with Manawa the \nsame, radically different lifestyle, it is entirely plausible that the \npunciid frill may have been an early evolutionary innovation in \nthe palaeocopids of a structure analogous to alae in podocopids. The hydrodynamic cross-sectional shape of the frill of Puncia, \nfor example, with its curved sole, is ideally suited for the ease of \nmovement of a wide-gaped, thinly-calcified, delicate carapace \neither over or within the coarse biogenic sands (as described for \nManuwa), depending on whether species of the genus are \nepifaunal or infaunal, respectively (\n)\npp\ny\nThe septa in the relatively wide axial plane between shell \ninfold and outer lamella along the free margin of the shell of \nAxelheibergella are unique to this genus among the cladocopid \nostracods. They are absent in myodocopids, podocopid platy- \ncopines, and in nearly all other podocopids, except for the \nfreshwater cypridacean genera Stenocypris (Triebel, 1953, 1958; \nMcKenzie, 1977), Strandesia (Triebel, 1958), Heterocypris \n(Triebel, 1953), Cypretta (Muller, 1894; Pokorny, 1965; \nMcKenzie, 1977), and Bradycypris and Paracypretta (McKen- \nzie, 1977). These freshwater genera show varying degrees of \nsepta1 development in the area of the free-margin infold, with \nthe septa particularly well-developed along the anterior and \nanteroventral margins of Cypretta, Heterocypris and Stenocy- \npris. In some taxa, the septa are confined to one valve only (e.g. McKenzie, 1977). The camerae of Axelheibergella, like the cameral structures of 114 Axelheibergella, a new genus of cladocopid ostracod Axelheibergella, a new genus of cladocopid ostracod Axelheibergella, a new genus of cladocopid ostracod present along the free margin of these taxa. Marginal pore canals, pores and setae present along the free margin of these taxa. g\np\np\nA detailed histological and morphological study by Okada \n(1982) of normal and marginal pores bearing setae (sensillum \npores) using light, scanning and transmission microscopy \ntechniques has shown that, except for the canals being narrower \nand longer, marginal pores have an internal morphology \nessentially the same as normal pores. Conclusion g\ny pp\ny\nK. M. Swanson and S. H. Eagar have each shown the author \nscanning electron microscope (SEM) photographs of a modem \nspecies of Polycope and one of the myodocopid Ancohenia, \nrespectively, from New Zealand, which clearly show setae More research on the nature and extent of sensilla and exocrine \ntypes of marginal pore canals in cladocopids is needed, but the \nlimited data available indicate the presence of one or the other 115 Briggs fig. 4) exposed by the breakage has a hummocky topography (PI. 1, fig. 11). Ventrally, the two endocuticle layers continue to the \nshell margin, but they then merge to become one layer along the \nless thick infolded part of the shell wall, which appears to be \nfinely laminated (Pl. 1, fig. 9). Dorsally, in the region of the \ninfolded part of the shell that forms the hinge, the integrity of \nthe two endocuticle layers is maintained and both are distinctly \nlaminated (Pl. 1, fig. 10). Dissolution and attendant differential \netching of the endocuticle and the exposure of its organic matrix \nhas occurred in the shell possibly prior to, and certainly \nfollowing, the major break in the shell wall, greatly enhancing \ndetection of the endocuticle laminae and their geometry. I have \nused the effects of naturally occurring dissolution and breaks in \nthe ostracod shell to full advantage in studies of the \nultrastructure of hemicytherid and trachyleberidid cytheracean \npodocopids from New Zealand. or both types of pore canals in some taxa, although these \nstructures are not known in any great detail. Furthermore, the \nsensilla-type pores of cladocopids may not serve the same \nfunction as those present in podocopids (K. M. Swanson, \nwritten comm.). )\nThere is ample evidence to suggest that shell glands, \nparticularly the marginal type of gland, do not occur uncom- \nmonly in cladocopid ostracods, based on Hartmann’s (1 954, \n1955) and Kornicker & Iliffe’s (1989) studies. There is no \nevidence, however, to suggest that the septa and camerae present \nin the axial zone of the infold of Axelheibergella are a \nconsequence of these marginal shell glands. SHELL ULTRASTRUCTURE The shell ultrastructure of Polycope and Metapolycope was \ninvestigated by Sohn & Kornicker (1988). In both genera the \nendocuticle is formed of a relatively thick outer fine granular \nlayer capped on its exterior side by a thin epicuticle layer, and a \nthinner inner columnar layer. The epicuticle is the outermost \ncuticular layer of the ostracod exoskeleton that does not become \ncalcified. It is the template on which calcification of the \nendocuticle layer of the shell fist takes place, and the finest of \nornamental structures of the epicuticle such as puncta and \nfoveolae are replicated in this incipient stage of shell calcifica- \ntion. I have referred to this first-formed and thus outermost \nmineralized layer of the ostracod shell as the protoostracum and \nthis first step of mineralization of the cuticle the protoostracum \nstage of shell calcification. Sohn & Kornicker (1988) have shown \nthe relationship between puncta in the epicuticle and the \nunderlying calcified endocuticle in an unnamed species of \nPolycope. This relationship is also shown in P1. I , fig. 12 of \nthe inner side of a fragment of the shell of Axelheibergella \npunctata, where the convex surfaces of numerous puncta are \nvisible. The photograph also shows that shell calcification \nadvanced very little beyond the protoostracum stage before \nthe ostracod died, and that the wide infold and septa were in \nplace at this earliest stage of shell calcification. The ultrastructure of the shell of Axelheibergella differs in \nseveral ways from the ultrastructure of Polycope and Metapo- \nlycope. The laminate ultrastructure of the endocuticle in the \ninfold of Axelheibergella is apparently absent in the infold of \nPolycope and Metapolycope, and perhaps in other cladocopid \ngenera. It is most like that described in the infold of some \nmyodocopid genera. Additional studies need to be carried out \non cladocopid ultrastructure before any significance can be \nattached to the laminate nature of the infold of Axelheibergella. SYSTEMATIC DESCRIPTIONS Class Ostracoda Latreille, 1806 \nO d\nC\ni\nS\n1866 Order Cladocopida Sars, 1866 Remarks. Ostracod classification at the ordinal level and above \nis in a state of flux. Kornicker & Iliffe (1989) recognize the \nSuperorder Myodocopa Sars, 1866, which contains the orders \nMyodocopida Sars and Halocyprida Dana, 1853. The Halocy- \nprida comprise the suborders Halocypridina Dana and the \nCladocopina, Sars, 1866. In this paper, and for convenience \nonly, I regard the Cladocopida and Myodocopida as orders, and \nthe halocyprids are given family-group status within the \nM yodocopida. p\ng\nThe broken shell of Axelheibergella arctica shown on PI. I , fig. 4 consists of two distinct layers, which are shown in greater \ndetail in oblique views of the shell on P1. I, figs 9-1 1. The two \nlayers shown in the broken section of the shell running from the \ndorsum to the venter are of about equal thickness, but their \nultrastructure appears to be quite different. The separation of \nthe shell into two layers may be due to weak bonding between \ntwo layers differing slightly in composition, and it probably \noccurred contemporaneously with, and as a result of, the \nbreakage of the shell. The epicuticle layer is not discernible in \nthe outer shell layer of the section. Because the two layers are \nnearly equal in thickness, they are assumed to be the endocuticle\ncomponent of the shell, exclusive of any epicuticle layer that \nmay be present in the outermost layer. Slightly below midheight \nand near the nick point caused by the offset of the outer shell \nlayer across a small break that affects this layer only (arrow, PI. 1, figs 4, 9), the combined thicknesses of the layers of the shell \nwall are c. 3.7pm (Pl. 1, fig.11). The outer of the two layers (Pi. 1, fig.1 I) is fine granular, relative to the coarse granular nature \nof the inner layer. Both layers in this region of the shell have a \nweak but nevertheless discernible columnar (linear) component. Moreover, the inner, lateral surface of the outer shell layer (PI. 1, Suborder Cladocopina Sars, 1866 \nSuperfamily Polycopacea Sars, 1866 \nFamily Polycopidae Sars, 1866 \nRemarks. As understood herein, the Polycopidae comprise 17 \nliving genera distributed amongst two subfamilies: Polycopinae \nSars, 1866 (15) and Polycopsisinae Chavtur, 1981 (2). Remarks. As understood herein, the Polycopidae comprise 17 \nliving genera distributed amongst two subfamilies: Polycopinae \nSars, 1866 (15) and Polycopsisinae Chavtur, 1981 (2). SYSTEMATIC DESCRIPTIONS Internally, infold well \ndeveloped, relatively wide ventrally, tapering gradually toward \nfree-margin extremities (Pl. 1, figs 1, 3-5); septa radially aligned, \ndouble-walled, hairpin-shaped structures, with bend of hairpin \ncoincident with inner margin of infold proximally, and with each \nleg of the hairpin structure bending away from fold axis distally \nto form, overall, about 17 inverted Y-shaped septal structures \n(Pl. 1, fig. 1; Fig. 2, figs 1-2); interseptal chambers (camerae) \narched distally, arch formed of adjacent bent legs of Y-shaped \nseptal structures; camerae open to shell interior proximally, and \nto shell exterior distally through much smaller diameter opening; \neach opening leading to canal opening to outside through crest \n(?) between adjacent flutes. Posterior-most and ventral scar of \nthree adductor scars wedge-shape (Pl. 1, fig. 8), with thin edge of \nscar directed anteriorly, upper two scars polygonal. Attached \nmargin depressed below dorsum; hinge element of left valve (PI. 1, fig. 7) the sloped edge of the attached margin infold which fits \ninto a well-defined groove in the infold of the attached margin of \nthe right valve (Pl. 1, fig. 4). Sexual dimorphism not observed. Dimensions (mm). described in this report from the CAO and two species from the \nMediterranean Sea. The Mediterranean Sea species include \nPolycope longipes Hartmann (Hartmann, 1954, p. 91, p1.30, figs \n6a-f; pl. 34, figs 6g-i), \nbased on three specimens from \nAmphioxus-Sands near Banyuls, Gulf of Lion, southern France, \nand Polycope sp. B, from the Limski Channel, Adriatic Sea, \ndescribed from seven specimens by Uffenorde (1972, p. 50, pl. 1, \nfig. 3). The Gulf of Lion and the Adriatic Sea species are larger \n(320 and 230pm L, respectively) than the two CAO species \n(200pm L). The two CAO species of Axelheibergella are \namongst the smallest of the 71 modern cladocopids ranked by \nlength size by Neale (1983). The Mediterranean species also \ndiffer from the CAO species by having an infold containing \nmore than 20 septa. Hartmann (1954), as noted above, referred \nto the septa as canals opening from glands in the proximity of \nthe shell margin, while Uffenorde (1972) simply referred to them \nas cone shaped structures. Septa are present in the earliest instars of both Arctic Ocean \nspecies of Axelheibergellu, based on an examination of the \njuveniles in the more than 3000 specimens of the two species in \nthe AOS'94 box cores from the Amerasian Basin. The soft-part anatomy of Polycope longipes was described by \nHartmann (1954). SYSTEMATIC DESCRIPTIONS Genus Axelheibergella nov. Type species. Axelheibergella arctica sp. nov. Derivation of name. Axel Heiberg Island, Canadian Arctic \nArchipelago. Diagnosis. Small (L<320 pm), subcircular to subelliptical \nlateral-outline cladocopids with a well-developed, free-margin \ninfold, with axial zone between infold and outer lamella \ncontaining up to 20 or more radially aligned septa and inter- \nsepta1 chambers (camerae) open to the interior of the shell \nproximally, and to the exterior of the shell marginally. Stratigraphic range. Quaternary. Remarks. The genus at present contains the two species Genus Axelheibergella nov. Type species. Axelheibergella arctica sp. nov. Derivation of name. Axel Heiberg Island, Canadian Arctic \nArchipelago. Diagnosis. Small (L<320 pm), subcircular to subelliptical \nlateral-outline cladocopids with a well-developed, free-margin \ninfold, with axial zone between infold and outer lamella \ncontaining up to 20 or more radially aligned septa and inter- \nsepta1 chambers (camerae) open to the interior of the shell \nproximally, and to the exterior of the shell marginally. St\nti\nhi\nQ\nt Stratigraphic range. Quaternary. Remarks. The genus at present contains the two species 116 Axelheibergellu, a new genus of cladocopid ostracod described in this report from the CAO and two species from the \nMediterranean Sea. The Mediterranean Sea species include \nPolycope longipes Hartmann (Hartmann, 1954, p. 91, p1.30, figs \n6a-f; pl. 34, figs 6g-i), \nbased on three specimens from \nAmphioxus-Sands near Banyuls, Gulf of Lion, southern France, \nand Polycope sp. B, from the Limski Channel, Adriatic Sea, \ndescribed from seven specimens by Uffenorde (1972, p. 50, pl. 1, \nfig. 3). The Gulf of Lion and the Adriatic Sea species are larger \n(320 and 230pm L, respectively) than the two CAO species \n(200pm L). The two CAO species of Axelheibergella are \namongst the smallest of the 71 modern cladocopids ranked by \nlength size by Neale (1983). The Mediterranean species also \ndiffer from the CAO species by having an infold containing \nmore than 20 septa. Hartmann (1954), as noted above, referred \nto the septa as canals opening from glands in the proximity of \nthe shell margin, while Uffenorde (1972) simply referred to them \nas cone shaped structures. scattered, about 2S30 in number, with one centrally located \npore containing two ducts (Pl. 1, fig. 2: centre white spot). Narrow flange surrounds most of free margin; the outer lamella \nshell margin adjacent to flange is fluted (scallop shaped), \nparticularly along anterior and anteroventral margins. Crests \nare present between adjacent flutes. SYSTEMATIC DESCRIPTIONS L\nH Holotype: RV A \nGSC 115780 Locality A H 87200-009 \n0.19x0.17 \nParatype: \nRV A GSC 115781 Locality AH 87200-009 \n0.20x0.16 \nParatype: \nLV A \nGSC 115782 Locality A H 87200-009 \n0.20x0.16 \nParatype: \nRV A \nGSC 115785 Locality AH 87200-009 \n0.20x0.17 \nParatype: \nRV A \nGSC 115786 Locality AH 87200-009 \n0.19x0.16 \nParatype: \nRV A \nGSC 115787 Locality A H 87200-009 \n0.20x0.17 \nParatype: \nRV A \nGSC 115788 Locality A H 87200-009 \n0.19x0.16 \nParatype: \nRV A \nGSC 115789 Locality A H 87200-009 \n0.19x0.16 \nParatype: \nRV A \nGSC 115790 Locality CESAR 83-211 0.20x0.16 \nRemarks. Other openings of canals that lead to the outer or \nexternal surface of the shell are present in the axial zone between \nshell outer lamella and infold in this species (arrow, PI. 1, fig. 5; \nlarger arrows Fig. 2, fig. 2). These openings are of similar size to \nthe normal pores scattered over the valve, as described above. They are also similar to openings described by Kornicker & Iliffe \n(1 989) in the axial zone of the shell of Polycopissu unux, a species \ncontaining numerous shell glands. According to Kornicker & \nIliffe (1989) the openings connect pore canals (? chitinous tubule \nextensions) leading from the glands, which are located between \nvestment and shell, to the outer surface of the shell by way of the \naxial zone. A third type of axial zone canal opening, with a \nsmaller diameter than the ones described above, occurs at the \ndistal end of some of the septa, within the inverted Y-shaped \narea (smaller arrow, Fig. 2, fig. 2). The function of the canals \nleading from these openings to the outside of the shell is not \nknown, nor is the geometry of the openings and their proximity \nto the septa understood\nL\nH Holotype: RV A \nGSC 115780 Locality A H 87200-009 \n0.19x0.17 \nParatype: \nRV A GSC 115781 Locality AH 87200-009 \n0.20x0.16 \nParatype: \nLV A \nGSC 115782 Locality A H 87200-009 \n0.20x0.16 \nParatype: \nRV A \nGSC 115785 Locality AH 87200-009 \n0.20x0.17 \nParatype: \nRV A \nGSC 115786 Locality AH 87200-009 \n0.19x0.16 \nParatype: \nRV A \nGSC 115787 Locality A H 87200-009 \n0.20x0.17 \nParatype: \nRV A \nGSC 115788 Locality A H 87200-009 \n0.19x0.16 \nParatype: \nRV A \nGSC 115789 Locality A H 87200-009 \n0.19x0.16 \nParatype: \nRV A \nGSC 115790 Locality CESAR 83-211 0.20x0.16 \nL\nH SYSTEMATIC DESCRIPTIONS Chavtur (1981) included this species and \nseveral others in the genus Polycopiellu which was established at \nthe same time. No details of the ecology of Polycope Iongipes were given by \nHartmann (1954). Uffenorde (1972) reported Polycope sp. B \nfrom five stations in the Limski Channel, in water depths \nbetween 32 and 37m, bottom temperatures between 13 and \n20°C, and salinity of c. 38%. Holotype: RV A \nGSC 115780 Locality A H 87200-009 \n0.19x0.17 \nParatype: \nRV A GSC 115781 Locality AH 87200-009 \n0.20x0.16 \nParatype: \nLV A \nGSC 115782 Locality A H 87200-009 \n0.20x0.16 \nParatype: \nRV A \nGSC 115785 Locality AH 87200-009 \n0.20x0.17 \nParatype: \nRV A \nGSC 115786 Locality AH 87200-009 \n0.19x0.16 \nParatype: \nRV A \nGSC 115787 Locality A H 87200-009 \n0.20x0.17 \nParatype: \nRV A \nGSC 115788 Locality A H 87200-009 \n0.19x0.16 \nParatype: \nRV A \nGSC 115789 Locality A H 87200-009 \n0.19x0.16 \nParatype: \nRV A \nGSC 115790 Locality CESAR 83-211 0.20x0.16 \nRemarks. Other openings of canals that lead to the outer or \nexternal surface of the shell are present in the axial zone between \nshell outer lamella and infold in this species (arrow, PI. 1, fig. 5; \nlarger arrows Fig. 2, fig. 2). These openings are of similar size to \nthe normal pores scattered over the valve, as described above. They are also similar to openings described by Kornicker & Iliffe \n(1 989) in the axial zone of the shell of Polycopissu unux, a species \ncontaining numerous shell glands. According to Kornicker & \nIliffe (1989) the openings connect pore canals (? chitinous tubule \nextensions) leading from the glands, which are located between \nvestment and shell, to the outer surface of the shell by way of the \naxial zone. A third type of axial zone canal opening, with a \nsmaller diameter than the ones described above, occurs at the \ndistal end of some of the septa, within the inverted Y-shaped \narea (smaller arrow, Fig. 2, fig. 2). The function of the canals \nleading from these openings to the outside of the shell is not \nknown, nor is the geometry of the openings and their proximity \nto the septa understood. Axelheibergella arctica sp. nov. (Pl. 1, figs 1-5, 7-11; Fig. 2, figs 1-2) (Pl. 1, figs 1-5, 7-11; Fig. 2, figs 1-2) \nDerivation of name. With reference to the geographic locale of \nthis taxon, the Arctic Ocean. y\nParatype: \nRV A \nGSC 115790 Locality CESAR 83-211 0.20x0.16 \nRemarks. Other openings of canals that lead to the outer or \nexternal surface of the shell are present in the axial zone between \nshell outer lamella and infold in this species (arrow, PI. 1, fig. 5; \nlarger arrows Fig. 2, fig. 2). These openings are of similar size to \nthe normal pores scattered over the valve, as described above. They are also similar to openings described by Kornicker & Iliffe \n(1 989) in the axial zone of the shell of Polycopissu unux, a species \ncontaining numerous shell glands. According to Kornicker & \nIliffe (1989) the openings connect pore canals (? chitinous tubule \nextensions) leading from the glands, which are located between \nvestment and shell, to the outer surface of the shell by way of the \naxial zone. A third type of axial zone canal opening, with a \nsmaller diameter than the ones described above, occurs at the \ndistal end of some of the septa, within the inverted Y-shaped \narea (smaller arrow, Fig. 2, fig. 2). The function of the canals \nleading from these openings to the outside of the shell is not \nknown, nor is the geometry of the openings and their proximity \nto the septa understood. Diagnosis. Carapace small, nearly circular in lateral outline, \nsurface smooth except for faint pattern of punctate, mostly \nzigzag furrows arranged in two to three poorly defined \nconcentric ellipses; 2S30 widely spaced normal pores; about \nI7 free-margin septa. g\np\nHolotype. RV A GSC 115780. Material. Fifteen adult valves, nine entire, six broken. In \naddition, one LV adult specimen was lost from the tip of the \npicking brush during transfer to a single-cell cavity slide, and \none RV A-1 or A-2 juvenile disintegrated during manipulation \nwith the picking brush; both specimens were from Axel Heiberg \nlocality AH 872000-009. y\nLocality and horizon. Axel Heiberg upper slope, CAO. Locality \nAH 87200-009, Lat. 82O09.62'N; Long. 102O33.87'W. Dietz- \nLaFond grab, top CL1 cm, 1150m PDWD. Holocene. Present \nalso at Alpha Ridge, CAO. CESAR locality 83-211, Lat. 85O43.9\"; \nLong. 108\"51.9'W. Gravity core, top &I cm, \n1730 m PDWD. Holocene. Description. Axelheibergella arctica sp. nov. John Andrews, \nDonnie Barber, Wendy Cunningham, John Hollin, Rolf Kihl, \nVera Markgraf, Mark Meier, Susan Short, Kerstin Williams \n(INSTAAR), Rich Harding (Molecular, Cellular and Develop- \nmental Biology), and Doug Wray (Engineering), all of the \nUniversity of Colorado, provided various amenities, including \nsupplies, use of equipment, services and encouragement. John \nHollin, Nancy Weiner and Kerstin Williams offered suggestions \non how to improve the manuscript. Thomas Cronin, U.S. Geological Survey, Reston, provided the Arctic’91 sample \ncontaining Axelheibergella arctica. Ursula Grigg and Qadeer \nSiddiqui, Saint Mary’s University, Halifax and Elisabeth \nBrouwers, US. Geological Survey, Denver, provided copies of \nsome of the more inaccessible references. Kjell Sandved, \nSmithsonian Institution, and Bob Grover, Grover Instruments \nCorporation, custom built the bellows camera stand and loaned \nthe Zeiss Luminar lens, respectively. P.-N. Webb (Ohio State \nUniversity) provided the SEM photograph of Punciu sp. A, \nwhile with the New Zealand Geological Survey, 1970. George \nScott (Institute of Geological & Nuclear Sciences, Ltd., New \nZealand) and David Underwood (University of Colorado) \nprovided advice and services, respectively, for the digital \nimagery techniques used to produce the illustrations. Christina \nCallicott, Teresa Nettleton, Nina Seevers and Travers Ichinose \n(University of Colorado) provided invaluable assistance in the \nprocessing of the AOS’94 box core samples. Axelheibergella punctata sp. nov. Axelheibergella punctata sp. nov. (\ng\ng\ng\n)\nDerivation of name. With reference to the punctate surface of \nthis taxon. (\ng\ng\ng\n)\nDerivation of name. With reference to the punctate surface of \nthis taxon. Diagnosis. Carapace small, subelliptical in lateral outline; \nsurface punctate; about 40 widely spaced normal pores; about \n20 free-margin septa. Several saw-tooth denticles present along \nantero- and posteroventral margins. Diagnosis. Carapace small, subelliptical in lateral outline; \nsurface punctate; about 40 widely spaced normal pores; about \n20 free-margin septa. Several saw-tooth denticles present along \nantero- and posteroventral margins. p\nHolotype. LV A GSC 11 5791. Material. Six adult and juvenile valves, only four of which are \nunbroken. Locality and horizon. Alpha Ridge, CAO, CESAR locality 83- \n211, Lat. 85’43.9”; \nLong. 108’51.9’W. Gravity core, top & \n1 cm, 1730m PDWD. Holocene. Present also on the Axel \nHeiberg upper slope, CAO. Locality AH 87200-009, Lat. 82’09.62’ N; Long. 102O33.87’W. Dietz-LaFond grab, top 0- \n1 cm, 1150m PDWD. Holocene. Description. Axelheibergella arctica sp. nov. Carapace small (L5200 pm), subelliptical in lateral \noutline, highest at anterior cardinal angle; rostra1 incisure slight; \nsurface punctate except for a smooth, relatively narrow, \ncontinuous marginal strip, highly sinuous on its inner side, \nrunning from anterodorsal margin along dorsum to poster- \noventral margin, and a smooth circular area in centre of valve; \nabout 40 widely spaced normal pores; about 20 free-margin \nsepta. The same type of marginal flange and adjacent fluted \nstructures present in the type-species are also present in this \nspecies. The crests between adjacent flutes appear to be aligned \nwith the cameral openings present between the bent legs of \nadjacent double-walled septa1 elements. About 8-10 saw-tooth \ndenticles are present along the anteroventral margin (Pl. 1, fig. 12), with each denticle positioned opposite a cameral opening \n(Fig. 2, fig. 3). Although it is unclear, the canals leading from the \ncameral openings most likely open to the outside of the shell \nthrough the crests rather than through the denticles. Somewhat \nsmaller and fewer denticles are present along the posteroventral \nmargin. All of the taxa illustrated in this report were presented at an \ninformal talk given at the Friends of the Ostracodes meeting \n(predecessor of The North American Research Group on \nOstracoda), 1 November 1989, at the Denver Annual Meeting \nof the Geological Society of America. I thank Jean Berdan, \nSmithsonian Institution, and R. Lundin, University of Arizona, \nfor comments and a discussion of functional morphology \nfollowing the presentation. Finally, I thank Stephen Eagar, Victoria University of \nWellington, and Kerry Swanson, University of Canterbury, \nChristchurch, New Zealand, for discussions via electronic mail \nof cladocopid, myodocopid and punciacopine morphology and \ntaxonomy, and the exchange of scanning electron microscope \nphotographs. g\nDimensions (mm). Holotype: LV A \nGSC 115791 Locality CESAR 83-211 0.20x0.16 \nParatype: \nRV A \nGSC 115793 Locality AH 87200-009 \n0.20x0.17 \nParatype: \nRV A \nGSC 115794 Locality CESAR 83-211 0.19x0.15 \nParatype: \nLV A-1 GSC 115795 Locality CESAR 83-211 0.15x0.13 Partial support for this project was provided by National \nScience Foundation (ARCSS/OPP) Grant No. OPP-9400255. Remarks. The muscle scars, their arrangement and details of the \nhinge were not observed in this species. The configuration and \narrangement of the septa and camerae are the same as described\nfor A. urctica. Septa are Present in the A-1, possibly A-2,\njuvenile. Some of the larger diameter pores present in the outer \nlamella of the axial zone of the type-species are also present in \nthis species (arrows, P1. Axelheibergella arctica sp. nov. 1, fig. 12), but the smaller diameter pores \npresent at the ends of the inverted Y-shaped septa in the type- \nspecies were not observed. A surface pore similar in size and \nlocation to the two-duct pore of the type-species occurs in the \ncentre of the smooth central area of the shell (Pl. 1, fig. 6), but it \nappears to have one duct only. Manuscript received July 1993 Manuscript received July 1993 Manuscript accepted November 1996 Axelheibergella arctica sp. nov. Carapace small (L5200 pm), nearly circular in \nlateral outline; rostra1 incisure barely perceptible; dorsum of \nright valve slightly deflated laterally along attached margin. Lateral surface nearly smooth except for faint, zigzag pattern of \npunctate shallow furrows arranged in two to three poorly \ndefined concentric ellipses; normal pores widely spaced, Description. Carapace small (L5200 pm), nearly circular in \nlateral outline; rostra1 incisure barely perceptible; dorsum of \nright valve slightly deflated laterally along attached margin. Lateral surface nearly smooth except for faint, zigzag pattern of \npunctate shallow furrows arranged in two to three poorly \ndefined concentric ellipses; normal pores widely spaced, One adult LV specimen of this species (dimensions, mm: \n0.19x0.18) is present in Arctic'91 Polurstern sample PS2186-5 \n(GKG), Lomonosov Ridge, 88\"3 1 .2'N, 140°9.6'E, 1996 m \nPDWD, in the interval lCLllcm downcore (T. M. Cronin, \npers. comm.). A lithological description of the box-core \nsediments is recorded in Fiitterer (1992). 117 Briggs Briggs phy, for providing the samples and locality data. John Andrews, \nDonnie Barber, Wendy Cunningham, John Hollin, Rolf Kihl, \nVera Markgraf, Mark Meier, Susan Short, Kerstin Williams \n(INSTAAR), Rich Harding (Molecular, Cellular and Develop- \nmental Biology), and Doug Wray (Engineering), all of the \nUniversity of Colorado, provided various amenities, including \nsupplies, use of equipment, services and encouragement. John \nHollin, Nancy Weiner and Kerstin Williams offered suggestions \non how to improve the manuscript. Thomas Cronin, U.S. Geological Survey, Reston, provided the Arctic’91 sample \ncontaining Axelheibergella arctica. Ursula Grigg and Qadeer \nSiddiqui, Saint Mary’s University, Halifax and Elisabeth \nBrouwers, US. Geological Survey, Denver, provided copies of \nsome of the more inaccessible references. Kjell Sandved, \nSmithsonian Institution, and Bob Grover, Grover Instruments \nCorporation, custom built the bellows camera stand and loaned \nthe Zeiss Luminar lens, respectively. P.-N. Webb (Ohio State \nUniversity) provided the SEM photograph of Punciu sp. A, \nwhile with the New Zealand Geological Survey, 1970. George \nScott (Institute of Geological & Nuclear Sciences, Ltd., New \nZealand) and David Underwood (University of Colorado) \nprovided advice and services, respectively, for the digital \nimagery techniques used to produce the illustrations. Christina \nCallicott, Teresa Nettleton, Nina Seevers and Travers Ichinose \n(University of Colorado) provided invaluable assistance in the \nprocessing of the AOS’94 box core samples. phy, for providing the samples and locality data. REFERENCES Aagaard, K., Swift, J. H. & Carmack, E. C. 1985. Thermohaline \ncirculation in the Arctic Mediterranean Seas. Journal of Geophysical \nResearch, 90: 48334846. Aksu, A. E. 1985. Paleomagnetic stratigraphy of the CESAR cores. In \nJackson, H. R., Mudie, P. J. & Blasco, S. M. (Eds.) 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Late Pleistocene \nstratigraphy and micropaleontology of a part of the Eurasian Basin y\nPak, D. L., Clark, D. L. & Blasco, S. M. 1992. Late Pleistocene \nstratigraphy and micropaleontology of a part of the Eurasian Basin \n(= Fram Basin), central Arctic Ocean. Marine Micropaleontology, 2 0 \nI--22. f f\ng\ny\nf\ng,\nHartmann, G. 1965. Neontological and paleontological classification of \nOstracoda. Pubblicarioni a'ella stazione zoologica di Napoli, Naples, 33 \nSuppl., (1964): 5%-587. (= Fram Basin), central Arctic Ocean. Marine Micropaleontology, 2 0 \nI--22. pp , (\n)\nHartmann, G. 1975. Ostracoda. In Gruner, H.-E. (Ed.) Dr. H . G. Bronns \nKlassen und Ordnungen des Tierreichs. 5 Arthropoda, Abt. 1 \nCrustacea, Buch 2, Teil 4, Lieferung 4, 569-786. Gustav Fischer, Jena. Pokorny, V. 1965. Principles of Zoological Micropalaeontology, 2, Neale, \nJ. ACKNOWLEDGEMENTS Becker, G. & Swanson, K. M. 1992. Are the Kirkbyacea extinct \npalaeocopine ostracods or close relatives of the extant Punciacea? Senckenbergiana lethaea, 72: 121-128. 118 Axelheibergella, a new genus of cladocopid ostracod Axelheibergella, a new genus of cladocopid ostracod W. (Ed.) 465 p. Pergamon Press, Oxford. y,\np\nf\ng\np\ngy, ,\n,\nJ. W. (Ed.) 465 p. Pergamon Press, Oxford. Schroder-Adams, C . J., Cole, F. E., Medioli, F. S., Mudie, P. J., Scott, \nD. B. & Dobbin, L. 1990a. Recent Arctic shelf foraminifera: \nseasonally ice covered vs. perennially ice covered areas. Journal of \nForaminifera1 Research, 2 0 8-36. (\n)\np\ng\n,\nSchroder-Adams, C . J., Cole, F. E., Medioli, F. S., Mudie, P. J., Scott, g\nHartmann, G. & Pun, H. S. 1974. Summary of neontological and \npaleontological classification of Ostracoda. Mitteilungen aus dem \nHamburgischen Zoologischen Museum und Institut, I 0 7-73. ,\n,\n,\n,\n,\n,\n,\n,\n,\nD. B. & Dobbin, L. 1990a. Recent Arctic shelf foraminifera: \nseasonally ice covered vs. perennially ice covered areas. Journal of \nForaminifera1 Research, 2 0 8-36. g\ng\nHornibrook, N. de B. 1949. A new family of living Ostracoda with \nstriking resemblances to some Palaeozoic Beyrichidae. Transactions of \nthe Royal Society of New Zealand, 11: 469471. f\n,\nSchroder-Adams, C. J., Mudie, P. J., Cole, F. E. & Medioli, F. S. 1990b. Late Holocene benthic foraminifera beneath perennial sea ice on an \nArctic continental shelf. Marine Geology, 93: 221-242. y\ny\nf\n,\nHornibrook, N. de B. 1963. The New Zealand ostracode family \nPunciidae. Micropaleontology, 9: 3 18-320. gy\nScott, D. B., Mudie, P. J., Baki, V., MacKinnon, K. D. & Cole, F. E. 1989. Biostratigraphy and late Cenozoic paleoceanography of the p\ngy,\nJackson, R. 1986. Ice island lab shows petroleum potential. Geos, 15: 1- 119 Briggs Briggs Arctic Ocean: foraminiferal, lithostratigraphic, and isotopic evidence. Geological Socie ty of America Bulletin, 101: 260-271. Triebel, E. 1958. Spezielle Arbeitsgebiete der Mikropalaontologie 2. Ostracoden. In Freund, H. (Ed.) Handbuch der Mikroskopie in der \nTechnik, 8: 193-236, Umschau Verlag, Frankfurt. g\ny f\n,\nScott, G. 1995. Digital imagery for making plates. Journal of \nMicropalaentology, 14 118. ,\n,\ng,\nUffenorde, H. 1972. Okologie und jahreszeitliche Verteilung rezenter \nbenthonischer Ostracoden des Limski Kana1 bei Rovinj (nordliche \nAdria). GGttinger Arbeiten zur Geologie und Palaontologie, 13: 1-121. p\ngy,\nSkogsberg, T. 1920. Studies on marine Ostracoda. Pt.1. (cyprinids, \nhalocyprids, and polycopids). Zoologbche Beitrage a m Uppsala, 1 \n(Suppl.): 1-787. Stockholm. )\ng\nz\ng\ng ,\nVan Morkhoven, F. P. C. M. 1962. Post-Palaeozoic Ostracoda, their \nMorphology, Taxonomy, and Economic Use, 1, 204 pp. Elsevier, \nAmsterdam. Axelheibergella, a new genus of cladocopid ostracod (\npp )\nSohn, I. G. & Kornicker, L. S. 1988. Ultrastructure of myodocopid \nshells (Ostracoda). In Hanai, T., Ikeya, N. & Ishizaki, K. (Eds.), \nEvolutionary Biology of Ostracoda, 243-258. Kodansha Ltd., Tokyo. Van Morkhoven, F. P. C. M . 1963. Post-Palaeozoic Ostracoda. their \nMorphology, Taxonomy, and Economic Use, 2, 418 pp. Elsevier, \nAmsterdam. y\ngy f\n,\n,\ny\nSwanson, K. M. 1985. The discovery of living punciid ostracodes in New \nZealand. New Zealand Geological Survey Record, 9 87-89. Lower \nHutt. Van Wagoner, N. A., Mudie, P. J., Cole, F. E. & Daborn, G. 1989. Siliceous sponge communities, biological zonation, and Recent sea- \nlevel change on the Arctic margin: Ice Island results. Canadian Journal \nof Earth Science, 2 6 2341-2355. Swanson, K. M. 1989a. Ostracod phylogeny and evolution - a manawan \nperspective. Courier Forschungsinstitut Senckenberg, 113: 1 1-20. p\np\ng\ng,\nSwanson, K. M. 1989b. Manawa staceyi n. sp. (Punciidae, Ostracoda): \nsoft anatomy and ontogeny. Courier Forschungsinstitut Senckenberg, \n113: 235249. f\n,\nWhatley, R. & Eynon, M. P. 1996. Four new Arctic deepwater ostracod \nspecies from East Greenland. In Keen, M. C. (Ed.) Proceedings of the \n2nd European Ostracodologists Meeting, University of Glasgow 1993, \n195200. Swanson, K. M. 1991. Distribution, affinities and origin of the Punciidae \n(Crustacea: Ostracoda). Memoirs of the Queensland Museum, 31: 77- \n92. Witte, W. K. & Kent, D. V. 1988. Revised magnetostratigraphies \nconfirm low sedimentation rates in Arctic Ocean cores. Quaternary \nResearch, 2 9 43-53. Triebel, E. 1953. Genotypus und Schalen-Merkmale der Ostracoden- \nGattung Stenocypris. Senckenbergiana, 34: 514. 120"}}},{"rowIdx":12591,"cells":{"identifier":{"kind":"string","value":"https://openalex.org/W4231846140"},"pdf_url":{"kind":"string","value":"http://eprints.whiterose.ac.uk/121041/1/Green%20Open%20Access%20CSFB%208.1.pdf"},"lang":{"kind":"string","value":"English"},"error":{"kind":"null"},"title":{"kind":"string","value":"A look at ‘fishy drag’ and androgynous fashion: Exploring the border spaces beyond gender-normative deviance for the straight, cisgendered woman"},"source_name":{"kind":"string","value":"Critical studies in fashion & beauty"},"publication_year":{"kind":"number","value":2017,"string":"2,017"},"license":{"kind":"string","value":"cc-by"},"word_count":{"kind":"number","value":12186,"string":"12,186"},"text":{"kind":"string","value":"Reuse Items deposited in White Rose Research Online are protected by copyright, with all rights reserved unless \nindicated otherwise. They may be downloaded and/or printed for private study, or other acts as permitted by \nnational copyright laws. The publisher or other rights holders may allow further reproduction and re-use of \nthe full text version. This is indicated by the licence information on the White Rose Research Online record \nfor the item. Article: Article:\nWillson, JM orcid.org/0000-0002-1988-1683 and McCartney, N (2017) A look at ‘fishy drag’\nand androgynous fashion: Exploring the border spaces beyond gender-normative \ndeviance for the straight, cisgendered woman. Critical Studies in Fashion and Beauty, 8 \n(1). pp. 99-122. ISSN 2040-4417 https://doi.org/10.1386/csfb.8.1.99_1 https://doi.org/10.1386/csfb.8.1.99_1 (c) 2017, Intellect Ltd. This is an author produced version of a paper published in Critical \nStudies in Fashion and Beauty. Uploaded in accordance with the publisher's self-archiving \npolicy. This is a repository copy of A look at ‘fishy drag’ and androgynous fashion: Exploring the \nborder spaces beyond gender-normative deviance for the straight, cisgendered woman. White Rose Research Online URL for this paper:\nhttp://eprints.whiterose.ac.uk/121041/ White Rose Research Online URL for this paper:\nhttp://eprints.whiterose.ac.uk/121041/ Version: Accepted Version Version: Accepted Version Takedown If you consider content in White Rose Research Online to be in breach of UK law, please notify us by \nemailing eprints@whiterose.ac.uk including the URL of the record and the reason for the withdrawal request. eprints@whiterose.ac.uk\nhttps://eprints.whiterose.ac.uk/ eprints@whiterose.ac.uk\nhttps://eprints.whiterose.ac.uk/ eprints@whiterose.ac.uk\nhttps://eprints.whiterose.ac.uk/ 1 1 NICOLA McCARTNEY University of the Arts, London and University of London University of the Arts, London and University of London Abstract This article seeks to re-explore and critique the current trend of androgyny in fashion and \npopular culture and the potential it may hold for gender deviant dress and politics. In order to \ndo this, it will discuss the way in which a popular version of male drag has monopolized a \nvision of gender subversion that has marginalized ‘straight’ cisgendered women’s \ntransgressive challenge to gender norms. Although not misogynistic in itself, RuPaul’s Drag \nRace (Logo 2009-2017) brings to the surface the misogyny inherent in femininity – the \nperformance underscores deeper asymmetrical power imbalances which are embedded in \nwomen’s daily lives. Recent unisex fashion collections with their subsequent campaigns have \nsought to address this imbalance; however, this is not a problem with an easy fix. This article \nlooks at the way in which particular performers such as Grace Jones and Harnaam Kaur have \nad(dressed) their gender resistance without camouflaging and thus losing sight of a feminist \nhistory of gender inequality which still strongly resonates. This article seeks to re-explore and critique the current trend of androgyny in fashion and \npopular culture and the potential it may hold for gender deviant dress and politics. In order to \ndo this, it will discuss the way in which a popular version of male drag has monopolized a \nvision of gender subversion that has marginalized ‘straight’ cisgendered women’s transgressive challenge to gender norms. Although not misogynistic in itself, RuPaul’s Drag \nRace (Logo 2009-2017) brings to the surface the misogyny inherent in femininity – the \nperformance underscores deeper asymmetrical power imbalances which are embedded in \nwomen’s daily lives. Recent unisex fashion collections with their subsequent campaigns have \nsought to address this imbalance; however, this is not a problem with an easy fix. This article \nlooks at the way in which particular performers such as Grace Jones and Harnaam Kaur have \nad(dressed) their gender resistance without camouflaging and thus losing sight of a feminist \nhistory of gender inequality which still strongly resonates. Keywords 2 2 cisgender \nstraight women \ngender-deviance \nmisogyny Introduction It has become fashionable to challenge gender binaries. The popularization of drag, of terms \nsuch as ‘gender fluid’ and the commodification of unisex or androgynous clothing, It has become fashionable to challenge gender binaries. The popularization of drag, of terms \nsuch as ‘gender fluid’ and the commodification of unisex or androgynous clothing, \ndemonstrate this. There are now 58+ gender options on Facebook. Younger generations are \nmore informed about the complexities of gender, sex and sexuality than ever before and are \nusing clothes as part of their protest. However, there is a danger that the current trends of \ndrag and androgyny are celebrated unwittingly. For these methodologies of gender-normative \ndeviance have been traversed before and continue to marginalize the straight, cisgendered \nwoman. Where is she within this discourse, and can she hold her own agency? This article seeks to re-explore and critique the methodologies of drag and androgyny \nas means of gender-normative dissonance, given their current popularity in fashion. It will \ndiscuss this trend in relation to a specific oversaturated identity – the ‘straight’ biologically-\nborn woman. It will contend that the mainstreaming of male drag has monopolized a vision \nof gender subversion that has overshadowed biologically-born women’s heterosexual \nresistance. It will also discuss the way in which this has come about. The television show, \nRuPaul’s Drag Race (RPDR), for example, arguably does this by putting a particular \nsubversive ‘queer’ male performance of female bodies and femininity centre stage. Within \nthis parodic performance, a saturated and privileged ideal of cisgendered visibility becomes a \nvehicle for performing marginalized identities otherwise. However, as Katie R. Horowitz \n(2013) argues in ‘The trouble with “queerness”’, male drag performers focus predominantly 3 on the glitz of celebrity and a socio-economic privilege of white femininity and \nheteronormative female subjectivity in order to reflect and perform their own material \nconditions as marginalized gay, or queer, men. The Drag Queen’s subversion of gender, \nsexuality, class and race is thus contingent on their own set of economic and social \ndeterminants and disadvantages. Male-to-female drag creates a distance yet also an ironic affiliation between ‘straight’ \nbiologically-born women and gay men. It highlights the parodic, subversive and indeed \nentertaining qualities of the masquerade of femininity; however, it does so, we want to argue, \nby reappropriating heteronormative and heterosexist misogyny as a frame for the \nflamboyantly defiant retort of its own group’s interests. Another method of deviance is androgynous or unisex clothing. Introduction Through three case \nstudies, this article will explore and problematize commodified unisex fashion. These case \nstudies demonstrate that unisex clothing is not always as visually exciting as their potential \nfor politics of gender-deviance might suggest, and nor do their marketing campaigns truly \nseek to create a space for a third sex. Similarly, the unisex trend is problematic for the \ncisgendered woman’s deviance, as she is, as in drag, taken for granted and marginalized. A ‘straight’ female scholar, who desires to assert her own resistance and indeed her \nsolidarity with queer resistance, yet also believes it important and necessary to challenge such \nstereotypical and limiting heteronormative gender assumptions, can find herself cast into a \ndifficult position. Positioned as already having too much privilege, therefore as not being \nmarginalized, not being disadvantaged, such a female scholar can find herself perceived as at \nthe centre of normalcy, not deviant at all, and thus without any legitimate claim to resistance \nor critique. If such female scholars recognize themselves in the ‘queer’ performances they \nwrite about and want to endorse the political resistance and assertions that these present, what \nare they to do? 4 It is clear that some feel a guilty need to qualify their own identities. Postscripts or \ndefensive footnotes have been included in essays as an attempt to disarm this accusation, \nwhich undermines any claim to resistance by white or cisidentified women and their self-\nrecognition as also not ‘normal’. Halla Beloff (2001), in her essay on ‘Lesbian masks’, for \ninstance, wrote at the end of her argument: ‘I must admit that I am a straight woman […] I \nhave wanted to emphasize my sameness not my difference, which does not come in a spirit of \ncolonising nor romanticizing, but comes of solidarity, because I recognize myself in “others”’ \n(Beloff 2001: 71). Similarly, in a recent article which explored ‘trans-’ visibilities by way of \nblack, lesbian and transsexual Montreal-based artists, the authors Marie-Claude G. Olivier \nand Audrey Laurin felt the need to disclose their identity as a side note: [w]e want to mention that we are both white ciswomen. While transwomen and non-white individuals \nare always marked as the ‘other’, we want to recognize that white cisgender identity is a political \nidentity, and, in this case, a privileged one. Introduction (Olivier and Laurin 2016: 111) Cisgender is a term that refers to people who feel their gender identity matches their \nsex as assigned at birth. This article would like to explore a particular idea of ‘queerness’ in \nrelation to the material conditions and consequences of living in a heterosexual, biologically-\nborn female’s body. This is not a side note but is our focus as we consider the current trend \nand interest in drag and androgynous fashion. We want to understand what this specific \n‘deviance’ might mean. This article would therefore like to open up new ways of reading \ngender-normative deviant dress which allow for other resistant female identities to emerge. ‘Fish/Fishing’ (RPDR) We have recently seen a rise in the celebration of a third gender coming from within fashion \nthat articulates a reaction or response to gender binaries. In popular culture, television shows 5 5 such as RuPaul’s Drag Race are a visible example of this, serving to popularize gender \ndeviation, but also, we maintain, needing a deeper interrogation to really evaluate its agency \nfor women. At a superficial level, the show uses fashion, make-up and performance to \nproblematize heteronormative gender constructs in a humorous and accessible way; this \nseemingly celebrates a third gender. However, mainstream presentations of drag highlight \nstill-present misogynist and asymmetrical notions of ‘woman’, which are dominated by men \nand continue to bar women’s own resistance. RPDR premiered on Feb 2nd 2009 on Logo TV in the US; Season 9 began 24th March \n2017 on VH1. It is an exuberant parody of America’s Next Top Model contest but with Drag \nQueens – who are predominantly of black, Hispanic or Latino American origins and gay. RPDR premiered on Feb 2nd 2009 on Logo TV in the US; Season 9 began 24th March \n2017 on VH1. It is an exuberant parody of America’s Next Top Model contest but with Drag \nQueens – who are predominantly of black, Hispanic or Latino American origins and gay. Contestants are given tasks such as creating their own DIY costumes out of junk, \nchoreographing and styling their own girl band, or transforming themselves, dolls or veteran \ngay men into Drag Queens. At the end of each show, contestants undertake a catwalk to \nimpress the panel of celebrity judges and one is eliminated after a lip-sync battle – ‘sing for \nyour life’. This popular show has forwarded a challenge to restrictive ways of viewing gender \nand sexuality through dress and has legitimized as mainstream an important intersectional \ndefiance However, notions of ‘feminine’ dress and the flamboyant celebration of key terms \nwithin the Drag Queen arena, such as ‘bitchy’, ‘fishy’ and ‘cunty’, are also problematic from \na feminist perspective. To be ‘fishy’ or ‘serve fish’ is a compliment reserved for those Drag \nQueens who have ‘passed’ as a beautiful, biological woman. The term is, of course, also a \nderogatory informal adjective used to describe the smell of a woman’s vagina. For this \nreason, the term can feel incendiary and insulting to women when appropriated within drag \ndiscourse. ‘Fish/Fishing’ (RPDR) The gender deviance performed in RPDR – albeit playful and humorous – \nultimately relies on a perpetuation of misogynist stereotypes. 6 RPDR’s gender deviance is complex – it is an incisive parody but also a camp \ncelebration of America’s Next Top Model. It idolizes a particular ‘successful’ RPDR’s gender deviance is complex – it is an incisive parody but also a camp \ncelebration of America’s Next Top Model. It idolizes a particular ‘successful’ \nheteronormative femininity, thus perpetuating and reiterating limiting stereotypes, and yet it \nalso imagines these identities otherwise by inserting other male, gay, black or Hispanic, \nsocially and economically excluded bodies into this framework. ‘Passing’ as a beautiful \nbiological woman is the aim of the contest. Figure 1: Manilla Luzon, who featured in Season 3 of RuPaul’s Drag Race, photographed at \nthe Nashville ‘Queens for the Cure’ drag show 2017 by Patrick Finnegan on Flickr. Uploaded \n22 March 2017. Creative Commons licence (CC BY 2.0). If we think through Judith Butler’s ideas of performativity, then the contest on this \nshow is still reliant on the enactment of culturally gendered identities; one could therefore \nargue that RuPaul’s drag deviance sits within a traditional understanding of gender. (Rupaul’s \nfull name is Rupaul Andre Charles. He rose to fame as a drag queen, recording artist and later \nbecame the first male model for MAC Cosmetics. He is a recognised television personality, \nthe host and main judge of RPDR). Indeed, the contestants always appear dressed as men \nbefore the drag tasks take place, reasserting their transition, and RuPaul’s own regular \nappearance as a ‘man’ in a suit allows for the audience to feel assured of his standing as a \n‘real’ man who is dressing up as a woman for the purpose of entertainment. In one episode, \nwhen this ‘real’ man, workroom Ru, is parodied by the contestant ‘Milk’, some of the judges \nare insulted, declaring this drag not ‘drag’, which underscores the clearly expected rules of \nthe game (Season 6, Episode 5). When in drag the male-sexed body is camouflaged – the penis is ‘tucked’ down with \ntape or held between the thighs; if the sex is ‘unveiled’, then the contestant is exposed to 7 comic, humiliating or vulgar effect. ‘Fish/Fishing’ (RPDR) It does this by bringing \nsocial and cultural stereotypes and perceptions about the female body and about femininity as \nan interior experience into both the various characters or personas enacted in the show and in \ncomments from judges. Words that are commonly used derogatively or as expletives about \nwomen are translated into terms of endearment: for instance – ‘C.U.N.T.’ (Charisma, \nUniqueness, Nerve and Talent) and B.I.T.C.H. (Being in Total Control of Herself). Thus, \ncultural appropriation becomes a way of distancing these ‘bitches’ over here from those \n‘bitches’ over there. RPDR is therefore also a parody of the policing of women by women \nand the stigma of failing femininity or indeed losing what is coveted (Tseëlon 1995: 88). Women are pitted against each other and we see this echoing in childhood tales – for \ninstance, stepmother against stepdaughter in Snow White (Akass and McCabe 2004: 178–79). And this subsequently plays itself out by way of insecurity, bitchiness and rivalry between \nwomen, as very clearly dealt with in the popular mainstream film Mean Girls (2004: Dir. Mark Waters). is a transgender woman contestant – ‘Monica Beverley Hill’); and pointed politics through \nHIV and AIDS awareness. The Drag Race performs a different conception of an embodied \nperformance of being a feminine ‘woman’ in a male-born body. It does this by bringing \nsocial and cultural stereotypes and perceptions about the female body and about femininity as \nan interior experience into both the various characters or personas enacted in the show and in \ncomments from judges. Words that are commonly used derogatively or as expletives about \nwomen are translated into terms of endearment: for instance – ‘C.U.N.T.’ (Charisma, \nUniqueness, Nerve and Talent) and B.I.T.C.H. (Being in Total Control of Herself). Thus, \ncultural appropriation becomes a way of distancing these ‘bitches’ over here from those \n‘bitches’ over there. RPDR is therefore also a parody of the policing of women by women \nand the stigma of failing femininity or indeed losing what is coveted (Tseëlon 1995: 88). Women are pitted against each other and we see this echoing in childhood tales – for \ninstance, stepmother against stepdaughter in Snow White (Akass and McCabe 2004: 178–79). And this subsequently plays itself out by way of insecurity, bitchiness and rivalry between \nwomen, as very clearly dealt with in the popular mainstream film Mean Girls (2004: Dir. Mark Waters). ‘Fish/Fishing’ (RPDR) For example, RuPaul exclaimed with a wry smile in \nregard to one contestant whose ‘tuck’ was not discreet enough that he had never before seen \nsuch a ‘beautiful woman’ with such a ‘big cock’ (Season 1, Episode 3). This comment about \nits unwieldy size continued into the next episode as an ongoing problem – ‘still a lot of \nsnakes’. Similarly, the judges criticized the contestant ‘Nina Flowers’ when her costume \nrevealed too much of her manly chest and arms, which ‘gives away the man’ (Season 1, \nEpisode 4). However, the reference to a large penis on a beautiful woman does radically \nchallenge and destabilize gender-sex-sexuality assumptions and opens the possibility of \ngender being reimagined. Discussing the shocking disclosure of the penis in the film The \nCrying Game (1992: Dir. Neil Jordan), van Lenning et al. (2001) argue that even with this \nunveiling, ‘the feminine appearance’ continues to be ‘fully respected’ and not a figure of fun, \nunlike traditional Hollywood transvestite plots such as Tootsie (1982: Dir. Sydney Pollack) \nand Mrs Doubtfire (1993: Dir. Chris Columbus) (2001: 89–90). For van Lenning et al. (2001), humour and notions of the grotesque have been used within the Hollywood canon to \ndefuse and thus sanitize any potential subversion. The more traditional plotlines develop \nexpectantly to the climax – ‘the coming out’, reveal or abandonment of disguise – which \nclearly resolves any apparent gendered confusion and thus confrontation. However, the subversion in RPDR comes sharply dressed in wit but never pretends to \nbe safe. It is both popular and radical because it deals with very knowable mainstream \naspects of the feminine masquerade. While we might understand this with reference to \nRiviere’s (1929) ‘Womanliness as a masquerade’, in which the cisgendered woman performs \nfemininity to appease and transgress the borders of patriarchy, RPDR demonstrates a more \nobvious play with femininity, acting out stereotypes of the ‘housewife’ or embracing the \nperceived glamour and theatricality of women like Cher or Joan Collins. This is combined \nwith quite dangerous sexualities; deviantly gendered bodies (for instance, by Season 5 there 8 is a transgender woman contestant – ‘Monica Beverley Hill’); and pointed politics through \nHIV and AIDS awareness. The Drag Race performs a different conception of an embodied \nperformance of being a feminine ‘woman’ in a male-born body. ‘Fish/Fishing’ (RPDR) Some of \nthese favourite models themselves appear to have let their own masks slip, sometimes \ntragically, revealing heterosexual love trauma, loss, addiction and the pathos of becoming, in \nsome instances, caricatures of what successful womanhood is supposed to be. The straight women; for instance, Courtney Love or Liza Minnelli. What is it about these women \nthat appeals? Perhaps it is precisely because of their vulnerability and their apparent failure to \nachieve the happy ending that successful femininity is ‘supposed’ to guarantee. Some of \nthese favourite models themselves appear to have let their own masks slip, sometimes tragically, revealing heterosexual love trauma, loss, addiction and the pathos of becoming, in \nsome instances, caricatures of what successful womanhood is supposed to be. The masquerade or mask of womanliness donned by the drag acts can also therefore register the \nfalse promise of happiness offered by fairy tales of the ‘straight’ heterosexual world, as played out in the stories of such celebrity victims. The drag performances link into the drag \nperformer’s own situation as outsider with their own need for love and recognition. This is \nsupported at the end of each show by RuPaul’s mantra – ‘If you can’t love yourself, then how \nthe hell you gonna love somebody else’. This is a drag version that uses the aggression \ninherent in misogynistic language that is aimed at women and the violent stigma inherent in \nthe feminine masquerade as a weapon to fire back in relation to its own group’s parallel but \ndifferent inequalities such as homophobia, racism and HIV and AIDS intolerance. RPDR is therefore not misogynist and drag is not misogyny. One could say that this \nembodied stylization of ‘womanhood’ is not about women at all – it is, on the whole, about \ngay men’s own intersectional subversion of gender-sex-sexuality assumptions, hierarchies \nand privileges, as well as their own life-affirming performance in the face of HIV and AIDS. However, what male drag does demonstrate is that even within subversive discourse the \nperformance of femininity cannot help but reveal its own failure in relation to gender and sex \nresistance, for it preserves within itself traces of misogyny. ‘Fish/Fishing’ (RPDR) RuPaul’s catchphrases that kick-start the contest and tasks each week – ‘Let the best \nwoman win’ and ‘Don’t fuck it up’ – grow out of this female culture. However, the use of \nparticular terminology by male drag is linked into the criteria or judgements operated within \ndrag culture regarding participants’ representations of ‘womanliness’ and the ‘authenticity’ of \ntheir performance. It is part of the ‘catty’ pecking order where the girls ‘throw shade’ on each \nother within their own staging of man-to-woman drag in this ‘beauty’ contest. The contestants in RPDR often model themselves on women who are inspirational to \nthem, such as black celebrity host Oprah Winfrey or the model Tyra Banks. Yet there are \nother favoured role models that might well appear problematical or even uninspiring to many 9 straight women; for instance, Courtney Love or Liza Minnelli. What is it about these women \nthat appeals? Perhaps it is precisely because of their vulnerability and their apparent failure to \nachieve the happy ending that successful femininity is ‘supposed’ to guarantee. Some of \nthese favourite models themselves appear to have let their own masks slip, sometimes \ntragically, revealing heterosexual love trauma, loss, addiction and the pathos of becoming, in \nsome instances, caricatures of what successful womanhood is supposed to be. The \nmasquerade or mask of womanliness donned by the drag acts can also therefore register the \nfalse promise of happiness offered by fairy tales of the ‘straight’ heterosexual world, as \nplayed out in the stories of such celebrity victims. The drag performances link into the drag \nperformer’s own situation as outsider with their own need for love and recognition. This is \nsupported at the end of each show by RuPaul’s mantra – ‘If you can’t love yourself, then how \nthe hell you gonna love somebody else’. This is a drag version that uses the aggression \ninherent in misogynistic language that is aimed at women and the violent stigma inherent in \nthe feminine masquerade as a weapon to fire back in relation to its own group’s parallel but \ndifferent inequalities such as homophobia, racism and HIV and AIDS intolerance. straight women; for instance, Courtney Love or Liza Minnelli. What is it about these women \nthat appeals? Perhaps it is precisely because of their vulnerability and their apparent failure to \nachieve the happy ending that successful femininity is ‘supposed’ to guarantee. ‘Drag Kinging’ What are the options, then, for the cisgendered woman to deviate from the suffocating What are the options, then, for the cisgendered woman to deviate from the suffocating 10 demands of rigid binary dress norms? We have a legacy of cultural icons and artists who \nhave offered us some alternatives in relation to drag kinging. These are not limited to but \ninclude a spectrum of women – straight, lesbian, queer and genderfluid – who have used \ntraditional male dress to denote their own sociological and cultural subversion, from Frida \nKahlo to Hannah Gluck, Claude Cahun, Patti Smith and Lady Gaga. However, we could \nargue that drag kinging equally perpetuates notions of gendered dress, much like some of the\ncontestants on RPDR. A Drag King is a performer who makes masculinity into his or her act (yes, there can be male Drag \nKings). The Drag King may make costume into the whole performance, or s/he may lip sync or play air \nguitar or tell crude jokes about ‘girlies’ and ‘homos.’ S\\he often sports facial hair: sideburns, \nmoustaches or even a goatee and s/he’ll wear slick-backed hair or a pompadour or a short back-and-\nsides or some kind of hat. (Halberstam and Del LaGrace 1999: 36). Drag kinging has since become popularized, or at least more, visible and thus slightly less \ntaboo. In 1995, London hosted its first Drag King competition. From a feminist perspective, \ndeliberately masquerading as a man is an inherently critical act. As Tseëlon argues, masquerade ‘calls attention to such fundamental issues as the nature of identity, the truth of \nidentity, the stability of identity categories and the relationship between the supposed identity \nand its outward manifestations (or essence and appearance)’ (2001: 3). Drag acts and \ncompetitions are largely staged among the queer community. While they are a source of \nentertainment, they are also, as we have argued, a means of disrupting gender. What is \nproblematic about the Drag King, however, is that it perpetuates myths of masculinity in the \nsame way that RPDR does with femininity. Competitions might involve categories such as \n‘YMCA construction worker’ or ‘Hispanic Soul Daddy’, for example, much like the \nstereotyping tropes of the ‘Banjee Girl’ in RPDR. ‘Drag Kinging’ Perhaps we can think of Gaga as the clown or jester, a central role in the subversive carnival; \nso outlandish might her fashion-sculptures be considered that they detract from gender \naltogether. Indeed, faced with the problem of merely perpetuating gender norms through the \nuse of ‘drag’, Joshua Williams presents ‘transspecies drag’ as an alternate solution. ‘Transspecies drag is the performative face of simian feminism, the practice by which women \nartists test the limits imposed on their political selves by moving ‘crabwise’ across categories \nof gender, race and species’ (2016: 70). He suggests that for feminists to get ‘around’ the \nproblematics of drag we might first move sideways (Williams uses the animal pun of the \ncrab) by adopting the dress of an alternate species rather than gender before moving be appropriating. A contemporary example we might analyse for her elaborate use of dress is \nLady Gaga. From adorning herself with several Kermit the Frogs to clothing herself in meat, \nLady Gaga’s own dress, or performance art, could be read as an employment of the grotesque \nas defined by Bakhtin. Her ‘meat dress’ was visceral and a reminder of the common body as \nmatter: ‘something universal, representing all the people’ (Bakhtin 1984: 19). Bakhtin \nconceives of the grotesque and the carnival as ways of puncturing authoritarian structures. Perhaps we can think of Gaga as the clown or jester, a central role in the subversive carnival; \nso outlandish might her fashion-sculptures be considered that they detract from gender \naltogether. Indeed, faced with the problem of merely perpetuating gender norms through the \nuse of ‘drag’, Joshua Williams presents ‘transspecies drag’ as an alternate solution. ‘Transspecies drag is the performative face of simian feminism, the practice by which women \nartists test the limits imposed on their political selves by moving ‘crabwise’ across categories \nof gender, race and species’ (2016: 70). He suggests that for feminists to get ‘around’ the \nproblematics of drag we might first move sideways (Williams uses the animal pun of the \ncrab) by adopting the dress of an alternate species rather than gender, before moving \n‘forward’. Gaga’s Kermit the Frogs costume is thus far more than comedy – not only does she \nwear another animal, it is a fictional male one. Her deviance is to question fashion, beauty \nand gender. ‘Drag Kinging’ The Drag King category of ‘sissy boy’, for 11 11 example, complicates the predominantly butch/male drag performance but, while we must \nnot forget that drag competitions are also about having fun, there is room for more nuanced \nacts that address the complex and undefinable nature of gender, as opposed to creating more \ncategories or boundaries. Female celebrities such as Demi Moore and Natalie Portman have since appeared in \ndrag, sporting facial hair for mainstream publications, and we have seen a rise in women \nembodying masculinity – Playgirls with ‘dicks’. More often than not, however, these acts are \nsuperficial media stunts or they conform to sexualized ideas of women with penis envy. The \nmasculinity supposedly portrayed in these ‘acceptable’ media images is considered \n‘palatable’, deliberately superficial and not too jarring, least of all really subversive. More \nshocking, perhaps, was the genuine growth of bodily hair by actress Julia Roberts, \nphotographed in 1999, presented as a ‘true life’ phenomenon. Throughout the twenty-first century, the hairless body has come to connote perfected \nfemininity, yet, as Anneke Smelik argues, it simultaneously betrays a cultural (and \npatriarchal) fear of adult female sexuality (Smelik 2015: 233). So, while Drag Kings have \nbeen featured in mainstream popular culture, and there is certainly a historical legacy of \nrepresentations of women in male attire, the Drag King is still largely met with fear, disgust \nor confusion in comparison to the humour and warmth offered to the Drag Queen. As such, \nthe Drag Queen, or queer male, is still able to dress with more agency than the cisgendered \nwoman. Figure 2: Lady Gaga at the GMA (Good Morning America) Concert 2011, New York, by TJ \nSengel on Flickr. Uploaded 27 May 2011. Creative Commons licence (CC BY 2.0). In light of this, perhaps it is not ‘male’ fashion that the gender-deviant woman should 12 be appropriating. A contemporary example we might analyse for her elaborate use of dress is \nLady Gaga. From adorning herself with several Kermit the Frogs to clothing herself in meat, \nLady Gaga’s own dress, or performance art, could be read as an employment of the grotesque \nas defined by Bakhtin. Her ‘meat dress’ was visceral and a reminder of the common body as \nmatter: ‘something universal, representing all the people’ (Bakhtin 1984: 19). Bakhtin \nconceives of the grotesque and the carnival as ways of puncturing authoritarian structures. ‘Drag Kinging’ However, while dressing as an animal might be a provocative statement and a \nuseful tool for performance artists, it is not an everyday practical solution for the layperson. Gaga’s androgynous appeal is undeniably a large part of her success and continues to attract \nmore ‘Monsters’, the term she uses for her fans. Ironically, her least imaginative attempt to \nsubvert gender norms was her 2011 Drag King performance as Jo Calderone at the MTV \nVideo Music Awards, where she embodied stereotypical male traits and physiology, from \nquiffed hair and sideburns to a blazer and holding poses and a gait that would imply a large 13 penis. penis. The problem with some of these much celebrated subversive icons is that they have \nbeen almost fetishized – desired or worshiped, sometimes sexually, for their difference – \nfurther marginalizing them from the ‘norm’. What makes their deviance standout has \nremained relatively unique and thus Other. For example, while artists like Kahlo or Cahun \nhave been posthumously embraced, they remain a part of the subaltern – social outsiders – \nunable to speak for themselves (Spivak 1988). Similarly, while Lady Gaga is considered a \nmainstream icon of popular culture, her use of the grotesque renders her almost monstrous, as \ncelebrated by her ‘monsters’, her exuberant performances dismissed as flamboyant and as \njust that – a performance. What cisgendered women need, therefore, in order to challenge \nheteronormative dress, is a line of clothing that sits somewhere in between the ‘masculine’ \nDrag King and the exaggerated performances reserved for pop-music arenas. We need a \nlifestyle change. It is partly this call which has motivated the turn towards current trends in \nunisex fashion and androgynous styles. These are attractive solutions precisely because they \nvisually eliminate the unequal status attributed to a female, sexed body, which has become \ningrained within its symbolic presentation of the feminine. Unisex fashion trends: Commodifying safe androgyny A cultural turn towards this desire to visually eliminate gendered difference is commodified \nin recent contemporary unisex fashion trends with Selfridges’s Agender collection; Rad \nHourani’s Unisex range; and Diesel’s 2015 gender-neutral advert. How though can we \nconceive of and read unisex clothing, androgyny and dress beyond binaries in new ways \nwhen these articulations only result, as Francette Pacteau argues, in the inevitable unveiling \nof difference? To quote Pacteau on the androgyne: ‘[i]t can only exist in the shadow area of \nthe image; once unveiled, once we throw a light on it, it becomes a woman or man’ (Pacteau 14 14 1986: 78) Rick Owen’s Sphinx show in 2015 also emerged from the same desire to visualize \nnew ways of imaging fashion beyond binaries by provocatively sending ‘feminine’-looking \nmen down the catwalk whilst displaying their penises. The male models were feminized in \nthe way that their bodies were presented as passive and vulnerable. The unveiling of a sexed \nyet feminine man on the runway may have revealed an anatomical difference but, as Alison Rick Owen’s Sphinx show in 2015 also emerged from the same desire to visualize \nnew ways of imaging fashion beyond binaries by provocatively sending ‘feminine’-looking \nmen down the catwalk whilst displaying their penises. The male models were feminized in \nthe way that their bodies were presented as passive and vulnerable. The unveiling of a sexed \nyet feminine man on the runway may have revealed an anatomical difference but, as Alison \nBancroft argues, this did not succeed in moving fashion beyond binaries. Regardless of how \nmany male bodies and penises you send down the runway, fashion will automatically default \nto the feminine, for the culture of fashion always feminizes the object of its desiring gaze \n(Bancroft 2016: 2). Historically, the submissive position of being looked at has been female. Fashion does not operate in a vacuum. The show provoked a strong reaction – not simply \nbecause the penis is rarely seen, whereas the sight of a naked female body on the runway is \ntaken for granted – but because to display the male body in such a feminized manner is to \ntake a step down in terms of power hierarchies. It did not dislodge male privilege but \ncemented the asymmetrical material realities of living in a male- or a female-sexed body. Unisex fashion trends: Commodifying safe androgyny This display was seen as ridiculous, funny and silly, with Owens himself stating afterwards \nthat it was ‘puerile’ (Bancroft 2016: 20). Giving the male body the same submissive status as \na female body was to undermine or at least highlight in quite a startling manner its privilege. How therefore can fashion move beyond this impasse to allow the sexed body the validity to \nexpress a full range of gender attributes and positioning? Do current unisex fashion brands \ncreate a space for women to deviate from rigid, normative, gendered presumptions? Selfridge’s Agender fashion line claims gender neutrality as its concept – ‘fashion \nwithout definition’. The promotional film ‘He, She, Me’ (2015) is described by Kathryn \nFerguson (co-director with Alex Turvey) as ‘a subtle push and pull between masculinity and \nfemininity’, with the film coming ‘at a time when important conversations about gender 15 fluidity and non-binary ways of being are finally getting a lot of attention’.1 Indeed, the film, \ncampaign and collection situate themselves firmly within a burgeoning move towards \nopenness as regards transsexual and transgender rights and visibility. The years 2015 and \n2016 in particular saw an explosive interest, from within both popular culture and academia, \nin all ideas relating to ‘trans-’ ‘androgyny’ and unisex (for instance, the fascination with \nCaitlyn Jenner, the press accounts of transphobia in prisons and hospitals, The Danish Girl \n[2015: Dir. Tom Hooper], Jo B. Paoletti’s Sex and Unisex [2015] and the On \nTrans/Performance [2016, 21: 5] edition of Performance Research edited by Amelia Jones). Also noticeable at this time was the proliferation of young male fashion students at Central \nSaint Martins in London (a leading global fashion brand in itself), fashioning themselves in \ndresses and skirts. The Agender campaign situated itself therefore within a clear desire for change. The \npromotional film – ‘He, She, Me’ – images a wide spectrum of body types and \ngendered/queer variations as the lead transgender character moves from room to room \ndancing with and around these differently gendered bodies to a soundtrack written by \nDevonte Hynes and Neneh Cherry. Although a valiant effort has been put into \nchoreographing an inclusive array of fashioned identities and non-normative looks, what the \nfilm ends up doing is fetishizing the subaltern in much the same way as was discussed in \nrelation to Lady Gaga’s ‘monstrosity’. Unisex fashion trends: Commodifying safe androgyny This is a tableau which features queer identities and \ntaut muscular male bodies but offers up a limited palette for the cisgendered woman. The \nfilm ends up emphasizing non-normative difference rather than agendered non-difference. These are ‘the unwanted’ of patriarchal norms – which include a disabled woman, an old \nwoman, a large woman, a lesbian ‘femme’ and the queer, fetishized and trans-body. By \nrevealing what is usually culturally hidden or undesired – the excess, the grotesque, the \ndebauched or strange – the film only emphasizes and reiterates their outsider status as non- 16 16 normative ‘Other’. From a feminist perspective, we already understand the problems of creating an \nalternative or parallel herstory. For example, in the art world, the ambition to reinstate the \nvisibility of women artists initially resulted in a series of decontextualized and gendered \nmonographs and encyclopaedias: ‘[i]n the attempt to make art history take notice of women \nartists, we have submerged them once again in a slightly reformed but still traditional notion \nof history’ (Parker and Pollock 1981: 45). This separation or highlighting of ‘woman’ only \nsets her further apart. It also fails to critique the infrastructures that defined women as such, \nbecause it employs the same language and historical methodologies that once wrote women \nout of history. This is a principle we can apply to any minority. A different approach is demonstrated in the Unisex range by Rad Hourani,2 which is a \nrichly executed and thoughtful collaboration of photography, staging and design. This \nimagery hints towards a promise of androgyny; however, the binaries still remain intact. There are masculine dioramas equating to the public domain with models of both sexes \ndressed in sharply tailored suits and concomitant attitude. In these images the young female \nmodels sit in traditional male poses with legs open and muscles protruding. The garments are \nexquisitely tailored in blacks and greys, with the models set against windows looking out \ntowards urban backdrops. And then there are feminine dioramas equating to the private world \nof emotion and passivity, where young male and female models recline in domestic, windowless backdrops. Both sexes are draped in soft white lines, arms wrapped around each \nother, with ethereal long-haired beauty foregrounded. However, although these images push \ntowards immersing both sexes in both genders they are not challenging, for they still reiterate \nthe cultural significance of each binary code. Unisex fashion trends: Commodifying safe androgyny The imagery continues to naturalize the \nmaterial realities of gendered difference and therefore the sexed, embodied, sociopolitical \nimplications of that inequality for the female or male citizen. 17 Both the Agender and Unisex campaigns set about creating aesthetic sartorial \nsolutions to the social and cultural problems presented by gendered difference. But they also \nhit upon the same problem, a problem that has been consistently associated with androgyny. The desire to harness both male ‘andro’ and female ‘gyne’ powers was put forward by \nVirginia Woolf in A Room of One’s Own (1929) as a way for women to widen their scope for \n‘being’. To this end, Carolyn G. Heilbrun in her 1973 text, Toward a Recognition of \nAndrogyny, held Woolf up as an icon for her own age in its push for a freer androgynous \nimagination. However, Woolf’s stance on androgyny has been criticized – her aesthetics of \nempowerment seen by some to represent a ‘male-humanist concept of an essential human \nidentity’ (Moi 1985: 9), which was predicated on the repression of the female body (Rado \n1997: 150). In a focused discussion of Woolf’s Orlando (1928), Lisa Rado argued that there \nis ‘an elaborate series of veils which serve to distract and deflect our attention from Orlando’s \nbiological sex in order to preserve his/her androgynous subject-position from the imposition \nof patriarchal norms’ (Rado 1997: 153). Both the Agender and Unisex campaigns set about creating aesthetic sartorial \nsolutions to the social and cultural problems presented by gendered difference. But they also \nhit upon the same problem, a problem that has been consistently associated with androgyny. The desire to harness both male ‘andro’ and female ‘gyne’ powers was put forward by \nVirginia Woolf in A Room of One’s Own (1929) as a way for women to widen their scope for \n‘being’. To this end, Carolyn G. Heilbrun in her 1973 text, Toward a Recognition of Androgyny, held Woolf up as an icon for her own age in its push for a freer androgynous \nimagination. However, Woolf’s stance on androgyny has been criticized – her aesthetics of \nempowerment seen by some to represent a ‘male-humanist concept of an essential human \nidentity’ (Moi 1985: 9), which was predicated on the repression of the female body (Rado \n1997: 150). Unisex fashion trends: Commodifying safe androgyny In a focused discussion of Woolf’s Orlando (1928), Lisa Rado argued that there \nis ‘an elaborate series of veils which serve to distract and deflect our attention from Orlando’s \nbiological sex in order to preserve his/her androgynous subject-position from the imposition \nof patriarchal norms’ (Rado 1997: 153). The push to ‘be’ more fully a woman or a man beyond limited sex roles through \ngender play is indeed undermined when one’s sex is revealed. For that sexed body is situated \nwithin a patriarchal culture which insists on imposing heteronormative hierarchies, binaries \nand inequalities of status on that body, regardless of what that particular subject desires. Unisex fashions cover up the sexed body in order to strengthen the assertion of its androgyny, \nbut its androgynous aesthetic is steeped in masculinist systems which reiterate \nheteronormative binary rules. The extent to which androgynously spirited expression is \nundermined or indeed reappropriated reveals a certain dread that androgyny may contaminate \nsafe, assured heteronormative masculinity or femininity for the cisgendered woman and man. ‘Gender-bending’ fears are averted, suppressed or depoliticized in fashion imagery by either \nmaintaining feminine sex appeal (an example being the iconic fashion image of Natalie The push to ‘be’ more fully a woman or a man beyond limited sex roles through \ngender play is indeed undermined when one’s sex is revealed. For that sexed body is situated \nwithin a patriarchal culture which insists on imposing heteronormative hierarchies, binaries \nand inequalities of status on that body, regardless of what that particular subject desires. 18 Portman in a suit with her hair slicked back, accessorized with a moustache, that appeared on \nthe Jan/Feb 2008 cover of Flash Art) or by ridiculing, humiliating and stressing the \n‘funniness’ of transvestite behaviour for men. All of this indicates that Mary Ann Doane’s \noft-quoted point from 1982 still holds true in some quarters: ‘[m]ale transvestitism is an \noccasion for laughter; female transvestitism only another occasion for desire’ (Doane 1982: \n81) Portman in a suit with her hair slicked back, accessorized with a moustache, that appeared on \nthe Jan/Feb 2008 cover of Flash Art) or by ridiculing, humiliating and stressing the \n‘funniness’ of transvestite behaviour for men. Unisex fashion trends: Commodifying safe androgyny All of this indicates that Mary Ann Doane’s \noft-quoted point from 1982 still holds true in some quarters: ‘[m]ale transvestitism is an \noccasion for laughter; female transvestitism only another occasion for desire’ (Doane 1982: \n81) 81) Similarly, the threat to heterosexual norms is averted in RuPaul’s Drag Race as the \nidea of being ‘gay’ is constantly referred to (although ‘drag’ is not necessarily synonymous \nwith ‘gay’). Male muscular models often appear on the show, with RuPaul and the idea of being ‘gay’ is constantly referred to (although ‘drag’ is not necessarily synonymous \nwith ‘gay’). Male muscular models often appear on the show, with RuPaul and the \ncontestants making the size of the penis an exciting point of reference. However, as well as \nassuaging the fear of ‘drag’ being linked to heterosexual men, the persistent reference to the \n‘tuck’ is the assurance for a mainstream audience that this is a man in drag and he will return \nto masculinity after the show. Drag kinging, because of the imposition of patriarchal norms \non a female body, is possibly more threatening to the status quo – especially if the performers \nare not lesbian themselves. Historically, women who have rebelliously cross-dressed, such as \nGreta Garbo and Marlene Dietrich (adding to those discussed above), have also been \nassertively assigned a lesbian identity as exotic ‘Other’ in film and popular cultural histories, \ndistancing this subversive sartorial behaviour from their heterosexual counterparts. This \ntherefore neutralizes or directs attention away from the feasibility that heterosexual women \nmay also offer up radical alternative gestures. The apolitical aesthetic of androgyny – its camp potential – is not a threat, but the \nembodied material application of this androgynous desire – its political potential – is \ndangerous. This moves the discussion on to the third example of the unisex fashion trend – \nDiesel’s Gender Neutral advert,3 which presents another aspect of the problems that have \narisen in current unisex trends. Diesel’s Gender Neutral advertisement images a young male 19 and female model holding onto each other and staring directly into the camera – hair shorn \nshort, wearing the same jeans and khaki-styled jumpers and sporting nude make-up. There is \na catchphrase to the side which reads ‘this ad is gender neutral’. However, this uniformity \nbetrays its purpose as the khaki styling is modelled on a predominantly male military form of \ncamouflage. Therefore the ‘neutrality’ of this advert needs to be explored further. Unisex fashion trends: Commodifying safe androgyny The symbolic presentation of equality and ‘neutrality’ \nfails to acknowledge women’s actual, embodied, material conditions and situated-ness as \nregards the surveilling gaze; it masks both the pleasure of femininity as a signifier of sexual \nattraction and neoliberal capitalism’s continual need for gender inequality in relation to the \nhome and care economies. Consequently, it once more ends up in an unsatisfactory impasse. to, them. The campaign did not increase awareness as to the gender-binary master narrative; \nit just made female clients angry at the perceived policing of how a feminist should dress. Like the short-lived unisex trends in the politically tumultuous 1960s and early 1970s, camouflaging the feminine is not a failsafe way of extricating oneself from all the hallmarks \nof that mask. To disavow femininity and disguise the female body is just a superficial and \nineffectual papering over of the cracks. The symbolic presentation of equality and ‘neutrality’ \nfails to acknowledge women’s actual, embodied, material conditions and situated-ness as \nregards the surveilling gaze; it masks both the pleasure of femininity as a signifier of sexual \nattraction and neoliberal capitalism’s continual need for gender inequality in relation to the \nhome and care economies. Consequently, it once more ends up in an unsatisfactory impasse. How, therefore, can gender disruption and androgyny become an enabler that \narticulates and accounts for ‘straight’ cisgendered women’s desire to play with femininity in \nrelation to self-presentation and the rituals of sexuality, whilst giving them leverage to \ncritically resist patriarchal oppression and inequality? Is there another way of looking at \ngendered positions which challenges masculine and male-dominated binaries and positions? The last section will seek to explore this dilemma further in order to come to a clearer \nunderstanding of our position vis-à-vis androgynous dress and gender-deviant border spaces. Unisex fashion trends: Commodifying safe androgyny Jo Paoletti has pointed out in Sex and Unisex (2015: 6) that for the United States in \nthe late 1960s and early 1970s, ‘“unisex” meant more masculine clothing for girls and \nwomen. Attempts to feminize men’s appearance turned out to be particularly short-lived’. Unisex clothing was appealing for women during this brief time because, as Joan K. Peters \nargues, ‘gender blending was twinned with sexual equality’ (Peters 2004: 67). This feminist \nexcitement in the political potential and idyll of androgyny and unisex soon faded with the \nonset of economic austerity, when high inflation and high unemployment made the symbolic \nimpetus for social change within unisex fashions look dated. The actual material economic \nand social realities increased the working day for men and left women with all the home- and \nchild-care as well as a 50+ hours job. Women therefore had a choice between the male role of \nwork or adding this role on top of their traditional female role as housewife/mother. Unisex \nideals were therefore shown to be a political illusion. To camouflage woman under \nmasculinity was not to become equally free but actually masked real material inequality via \nan illusion of equal non-difference. Sybil Goldfinger (2011; 96), CEO of feminist fashion brand Comme Il Faut, has \nargued that in considering gender subversion in fashion one needs to take into account both \nthe ‘symbolic’ and the material ‘pragmatic’ realities. Her company’s 2010 campaign, which \nsought to challenge gender binaries by way of androgyny, failed both in terms of its \nsubversion and its appeal, because the advertisement featuring masculine female models and \nfeminine male models alienated their target audience who felt that this did not speak for, or 20 to, them. The campaign did not increase awareness as to the gender-binary master narrative; \nit just made female clients angry at the perceived policing of how a feminist should dress. Like the short-lived unisex trends in the politically tumultuous 1960s and early 1970s, \ncamouflaging the feminine is not a failsafe way of extricating oneself from all the hallmarks \nof that mask. To disavow femininity and disguise the female body is just a superficial and \nineffectual papering over of the cracks. Androgyny as enabler This article does not pose a resolution to the trappings of gender. We have examined the \npossibilities of drag and unisex clothing, but this has only opened up further questions and so \nwe do not conceive such a resolution as being possible. What we do pose, however, is a \nfashioning of androgyny that acknowledges the impossibility of overcoming heteronormative \nbinaries and which complicates these through image and body-image. We believe the \nfollowing case studies serve as examples of an androgyny where the body or dress have been 21 problematized as part of their imaging. They are self-conscious examples of gender resistance \n– knowing and witty. They literally wear or embody a history of gender deviance and its \ntrappings, and as such, their fashioned bodies are empowered and their imaging empowering. The model and musician Grace Jones is often celebrated for her confrontational \npersona and androgynous fashioning. Historically, her role as being one of few black models \nin high fashion has meant that she has been styled and directed in problematic sets and \nshoots, performing and perpetuating the trope of blackness as aggressive or primitive, or \nhomogenizing what it is to be black. Today, she is more autonomous and less of a muse, \nperforming her own music and representing herself in interviews. Her body is used less as a \ntool for others and more as a means of resisting another bar placed on women: age. In \nDecember 2016, Billboard magazine ranked her as the 40th most-successful dance artist of \nall time. She released a compilation album in 2015; continues to perform at festivals; and \nwears suitably outlandish costumes as part of her own masquerade. Significantly, this is not a \nmasquerade of womanliness, but rather an exaggeration of all attributes – loud, proud and \noften controversial for the sake of it – demonstrating that she is as defiant and subversive as \never, if not more so, now that she works for herself. Figure 3: Grace Jones at Carriageworks, Sydney, as part of Vivid Festival, 1 June 2015, by \nBruce kingArthur_Aus on Flickr. Uploaded 1 June 2015. Creative Commons licence (CC BY \n2.0). 2.0). 2.0). However, there is no denying that her experience of modelling means she is better \nable to view her body as a tool or device, rather like a hanger that serves a purpose, and less \npreciously than those of us whose bodies have not been publicly displayed or utilized. Androgyny as enabler As \nsuch, Jones is better able to play with dress and androgyny, casting aside embodied notions of 22 gender, because she has spent a career distancing herself from the material body. Her body is \na blank canvas, a site for contestation. At 68, she remains muscular and keeps her hair short. Moreover, she almost dismisses gender codes with her flippant irreverence about undressing \nin public, literally discarding any trappings of gender. The artist has come a long way since her first single in 1975 titled ‘I Need a Man’. Her album covers perhaps demonstrate a third-gender trajectory. Nightclubbing (1981) \nconcentrates on Jones as confrontational, her gaze meeting the viewer with suspicion, while \nher chiselled features and haircut defy a reading of either sex. The blazer reveals a flat-\nchested torso while the powerful shoulder-padding tapers into a suggested waist, only to \naccentuate her square shoulders. Slave to the Rhythm (1985) addresses Jones as aggressive: \nthis person has to be reckoned with. The collaged effect emphasizes her open mouth as if \nscreaming, and her hair, still with short back-and-sides, is higher than before, also suggestive \nof power. Bulletproof Heart (1989) presents the artist as otherworldly – her eyes are yellow \nand her skin tone ambiguous – and here gender is forsaken altogether. In Warm Leatherette \n(1980), Jones wears what appears to be a wrestling costume, where the body’s contours are \ngiven a genderless silhouette. In 2016, her touring poster takes dress-up to another level. Gender is forsaken for fashion: a silver glittering bowler hat and cosmic make-up dominate \nthe picture. Her metallic eyebrow is painted on in a straight line, to defy the arching of a \nfemale brow, as is her cropped-out neck, so we cannot use the (absence of an) Adam’s apple \nas an index. This leaves a shaved head and, once again, a confrontational, reciprocated gaze. Jones is often seen publicly wearing flamboyant fashions, altering the silhouette of her figure \nand, much like Lady Gaga, this overshadows the otherwise prevalent fascination with her \nandrogyny or sex and sexuality. The fact that Jones invariably acknowledges the camera and reflects our gaze The artist has come a long way since her first single in 1975 titled ‘I Need a Man’. Her album covers perhaps demonstrate a third-gender trajectory. Androgyny as enabler Nightclubbing (1981) \nconcentrates on Jones as confrontational, her gaze meeting the viewer with suspicion, while \nher chiselled features and haircut defy a reading of either sex. The blazer reveals a flat-\nchested torso while the powerful shoulder-padding tapers into a suggested waist, only to \naccentuate her square shoulders. Slave to the Rhythm (1985) addresses Jones as aggressive: \nthis person has to be reckoned with. The collaged effect emphasizes her open mouth as if \nscreaming, and her hair, still with short back-and-sides, is higher than before, also suggestive \nof power. Bulletproof Heart (1989) presents the artist as otherworldly – her eyes are yellow \nand her skin tone ambiguous – and here gender is forsaken altogether. In Warm Leatherette \n(1980), Jones wears what appears to be a wrestling costume, where the body’s contours are \ngiven a genderless silhouette. In 2016, her touring poster takes dress-up to another level. Gender is forsaken for fashion: a silver glittering bowler hat and cosmic make-up dominate \nthe pict re Her metallic e ebro\nis painted on in a straight line to def the arching of a accentuate her square shoulders. Slave to the Rhythm (1985) addresses Jones as aggressive: \nthis person has to be reckoned with. The collaged effect emphasizes her open mouth as if \nscreaming, and her hair, still with short back-and-sides, is higher than before, also suggestive \nof power. Bulletproof Heart (1989) presents the artist as otherworldly – her eyes are yellow \nand her skin tone ambiguous – and here gender is forsaken altogether. In Warm Leatherette \n(1980), Jones wears what appears to be a wrestling costume, where the body’s contours are \ngiven a genderless silhouette. In 2016, her touring poster takes dress-up to another level. Gender is forsaken for fashion: a silver glittering bowler hat and cosmic make-up dominate \nthe picture. Her metallic eyebrow is painted on in a straight line, to defy the arching of a \nfemale brow, as is her cropped-out neck, so we cannot use the (absence of an) Adam’s apple \nas an index. This leaves a shaved head and, once again, a confrontational, reciprocated gaze. Jones is often seen publicly wearing flamboyant fashions, altering the silhouette of her figure \nand, much like Lady Gaga, this overshadows the otherwise prevalent fascination with her \nandrogyny or sex and sexuality. The fact that Jones invariably acknowledges the camera and reflects our gaze \nempowers her gender-normative dissonance. Androgyny as enabler Being highly staged and photographed, Jones’s 23 album-cover portraits demonstrate a knowingness that this is performance. It is an imaging of \nan ambiguous border space which is aware of its position as trans and playful. Her gaze is \nself-conscious and challenging – why is Jones’s gender-ambivalent image or persona \nprovocative, if it does not merely emphasize how misogynist other portrayals are? While we have included Grace Jones as an example of androgyny, this implies a \ncombination of both sexes. It might be more useful to think of it as a defiance of both, while \nrecognizing how these are historically represented. As Jackie Stacey points out, there are \n‘failures of feminist and queer language to articulate the nuances of affective registers; \nandrogyne, butch, tomboy, trans, and genderqueer designate styles of gendered and sexual \nembodiment, but these do not extend satisfactorily to aesthetic moods and atmospheres’ \n(Stacey 2015: 243). Jones’s imaging is nothing if not an aesthetic, which she has continued to \nfashion on and off-stage. It might be more useful, then, to consider Stacey’s proposed term of \n‘off-gender’ when considering historically understood images of androgyny, which we \nbelieve inherently recognize their own problematic hybridity and temporal nature. ‘To be off-\ngender would be less the in-between-ness of androgyny and more the capacity to move \nacross, to embody the mobility of temporal flux’ (Stacey 2015: 267). On the other hand, we have another mode of androgyny that embraces the indexical \ntraces of the traditionally gendered body through hair. With a long beard, West Londoner \nHarnaam Kaur wears her facial hair with pride. This is different from Stacey’s sense of ‘off-\ngender’, because it plays, less ambiguously and more directly, with gendered bodily tropes. This is still considered provocative, startling, which may be why she was chosen to walk the \nrunway and open the show for Marianna Harutunian at the Royal Fashion Day Show in \nLondon in February 2016. She has since established a successful (‘verified’ with a blue tick) \nsocial media profile and works on body-positive imaging. Kaur does not blur the lines of \ngender or sit within its border spaces; instead, she knowingly occupies both its ends. Her 24 beard is silky and groomed, and very long by any gender standards. Androgyny as enabler This contrasts with her \noften colourful, otherwise ‘femme’ outfits, or traditional cultural attire – Kaur is Sikh and \nsometimes wears a turban; her Instagram account @harnaamkaur often depicts her in lavish \ntraditional dress. Figure 4: Harnaam Kaur’s Fixers ITV broadcast shoot. By Fixer UK on Flickr. Uploaded 20 \nMay 2015. Creative Commons licence (CC BY 2.0). Her beard is only problematic to the extent that it was not originally intended; she has \nhad polycystic ovaries since a teenager, a condition which changes hormones and usually \nresults in women having more body hair than ‘normal’. That she now chooses not to conform \nto societal pressures on women to render their bodily hair invisible is what makes her \npersonal circumstances and choices political. Because she is a woman, this can be seen to \nmake her more transgressive than the facial hair of Tom Neuwirth, for instance, who won the \n2014 Eurovision Song Contest in his drag persona of Conchita Wurst. Moreover, her beard is \nreal – unlike Demi Moore’s or Natalie Portman’s, who wore deliberately artificial facial hair; \nits ‘removablity’ and therefore status as ‘drag’ was encoded as part of the image. In the case \nof Moore and Portman, any ‘hair-fear’ – the fear of this hair contaminating safe, assured, \nheteronormative masculinity or femininity for the cisgendered woman and man – was \nneutralized. Kaur, like Grace Jones, takes control of her image but through her online profile of \nselfies and self-fashioned images. She reciprocates her own gaze in the act of photographing \nherself (the extended arm and mirrored camera-phone) and edits her own image, output and \ncommunication, thus subverting the traditional surveilling gaze or pleasures of femininity \noffered as signifiers of sexual attraction. The selfie is an inherently knowing genre of self- 25 portraiture that, in this case, generates an added political potency to Kaur’s confronting gaze \nand androgynous self-consciousness. Kaur has subsequently been recognized by Guinness \nWorld Records (March 2016) and embraced for her Otherness. What is progressive about her \nbody-image is in danger of becoming fetishized, and what was political about Grace Jones’s \nimage still remains, leaving us asking whether enough has changed. Conclusion The current popularization and mainstreaming of drag and androgyny as a means of defying \nheteronormative dress is problematic because it assumes a culture of gender progress or \nmission accomplished. It was therefore important to traverse examples of these assumed \nchallenges to gender and fashion – from RuPaul’s Drag Race to Diesel's marketing campaign \n– to demonstrate that the cisgendered, straight woman is still marginalized. These are not \nviable methodologies of dress for her resistance to society’s inherent misogyny. Her sexuality \nand womanliness are taken for granted and assumed as privileged yet she is parodied, \nmocked and left redundant, still searching for her own battleground within which to \nchallenge gender-norms. As we have demonstrated, there are various pitfalls to the act of drag. While it is an \nimportant component of gender deviance and an inherently subversive political act, often also \nserving as fantastic entertainment, binaries and stereotypes ironically remain largely intact. More extreme and challenging versions of drag are possible and potentially more successful, \nsuch as carnivalesque or transspecies performances. But these become fetishized and \nmonstrous, they are one-offs and often render the artist as an Other, as marginalized or as a \nsuperstar. They are not really an affordable or practical vehicle for resistance. The recent turn \nto asexual or unisex clothing is promising because it indicates a re-emerging interest in \ncisgendered feminist dress, but it is not particularly progressive because, as we have argued, 26 either gender binaries remain evident or the models are exoticized and thus further \nmarginalized. These campaigns also posit a sense of resolution, that the problem has been \nsolved, which is not true and does not register the significant and ongoing struggle for gender \nequality – an integral part of progression. It is understandable that several women, or any minority group that has fought to be \nheard or seen, should embrace their inclusion without the caveat of being named by their \ngender or what previously rendered them invisible and unheard. Several women artists or \nwomen writers do not want to be categorized as such, or patronized by being included in \nwomen-only shows and anthologies; they want to be considered artists and writers on a par \nwith dominant, hegemonic (and heteronormative) groups. Conclusion However, regarding the \ncisgendered, dissidently fashioned body, it seems essential to recognize one’s otherness or to \nclaim the bodily epithet and its problematic historical fashioning because, in this special case, \nthe content is also the form. As Nancy Miller argues, it is important to emphasize the \ndifferences produced by the ‘asymmetrical demands generated by different writing identities, \nmale and female, or, perhaps more usefully, canonical or hegemonic and noncanonical or \nmarginal’ (Miller 1986: 105). Here, it is important for the woman to recognize her \ncomplicated sex and gender, her position as an ‘asymmetrical’ or ‘noncanonical’ subject, or \nelse she may be in danger of camouflaging the problem, and thereby perpetuating and \nrepeating it, rather than achieving desired change. We have discussed a few cases where we think gender deviance has been \nproblematized and acknowledged through androgyny, and others where the body or dress is \nflawed but open-ended because it does not pretend that the long history of gendered \nstereotyping and heteronormative positioning has been overcome and is past. We appreciate \nthat gender-washing might just be another marketing strategy that employs androgyny for the \npurpose of commodification. But knowledge is power for change and that must be reflected 27 in attempts at resistance. We cannot expect every straight cisgendered woman to dress in a \nway that will both embody and resist the cumulative weight of historical discourses of sex, \ngender, sexuality – for who can wear a moustache, ironic femme attire and unisex clothing all \nat once? But we contend that for gender-deviant dress to retain agency it must reflect self-\nawareness and conscious decisions and choices that make resistance visible. This is the only \nway history can be addressed and redressed. Butler, Judith (1990) Gender Trouble: Feminism and the Subversion of Identity. New York, \nUSA and Oxon, UK: Routledge. Doane, Mary Ann (1982), ‘Film and the masquerade: Theorizing the female spectator’, \nScreen, 23:3–4, pp. 74–87. References Akass, Kim and McCabe, Janet (2004), ‘Ms Parker and the vicious circle: Female narrative \nand humour in Sex and the City’, in Kim Akass and Janet McCabe (eds), Reading Sex and the \nCity, London and New York: I.B. Tauris, pp. 177-198. 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Butler, Judith (1990) Gender Trouble: Feminism and the Subversion of Identity. New York, \nUSA and Oxon, UK: Routledge. 28 28 Doane, Mary Ann (1982), ‘Film and the masquerade: Theorizing the female spectator’, \nScreen, 23:3–4, pp. 74–87. Goldfinger, Sybil (2011), ‘Comme il faut – where ethics is not just a brand image but a brand \nessence’, Critical Studies in Fashion and Beauty, 2:1–2, pp. 83–116. Goldfinger, Sybil (2011), ‘Comme il faut – where ethics is not just a brand image but a brand \nessence’, Critical Studies in Fashion and Beauty, 2:1–2, pp. 83–116. Halberstam, Judith and Del LaGrace, Volcano (1999), The Drag King Book, London: \nSerpent’s Tale. Heilbrun, Carolyn G. (1973), Toward a Recognition of Androgyny. New York: Harper \nColophon Books. Horowitz, Katie R. (2013), ‘The trouble with “queerness”: Drag and the making of two \ncultures’, Signs, 38:2, pp. 303–26. van Lenning, Alkeline, Maas, Saskia and Leeks, Wendy (2001), ‘Is womanliness anything \nbut a masquerade? An analysis of The Crying Game’, in Efrat Tseëlon (ed.), Masquerade and \nIdentities: Essays on Gender, Sexuality and Marginality, London and New York: Routledge, \npp. 83–100. van Lenning, Alkeline, Maas, Saskia and Leeks, Wendy (2001), ‘Is womanliness anything \nbut a masquerade? An analysis of The Crying Game’, in Efrat Tseëlon (ed.), Masquerade and \nIdentities: Essays on Gender, Sexuality and Marginality, London and New York: Routledge, \npp. 83–100. References Tseëlon, Efrat (1995), The Masque of Femininity: The Presentation of Woman in Everyday \nLife, London: Sage. __ (ed.) (2001), Masquerade and Identities, London: Taylor and Francis. Williams, Joshua (2016), ‘Going ape: Simian feminism and transspecies drag’, Performance \nResearch: A Journal of the Performing Arts, ‘On trans/performance’, special issue, 21:5, pp. 68–77. References van Lenning, Alkeline, Maas, Saskia and Leeks, Wendy (2001), ‘Is womanliness anything \nbut a masquerade? 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Olivier, Marie-Claude G. and Laurin, Audrey (2016), ‘Trans time: Time for trans visibility in \ncontemporary art’, Performance Research: A Journal for the Performing Arts, ‘On \ntrans/performance’, special issue, 21:5, pp. 111–13. Pacteau, Francette (1986), ‘The impossible referent: Representations of the androgyne’, in \nVictor Burgin, James Donald and Cora Kaplan (eds), Formations of Fantasy, London: \nMethuen, pp. 62–84. Parker, Rozsika and Pollock, Griselda (1981), Old Mistresses: Women, Art and Ideology, \nLondon: Pandora. Paoletti, Jo B. (2015), Sex and Unisex: Fashion, Feminism and the Sexual Revolution, \nBloomington: Indiana University Press. Paoletti, Jo B. (2015), Sex and Unisex: Fashion, Feminism and the Sexual Revolution, Bloomington: Indiana University Press. Peters, Joan K. (2004), ‘Gender remembered: The ghost of “unisex” past, present and future’, \nWomen’s Studies, 31:1, pp. 67–83. 30 Rado, Lisa (1997), ‘Would the real Virginia Woolf please stand up? Feminist criticism, the \nandrogyny debates, and Orlando’, Women’s Studies, 26:2, pp. 147–69. Rado, Lisa (1997), ‘Would the real Virginia Woolf please stand up? Feminist criticism, the \nandrogyny debates, and Orlando’, Women’s Studies, 26:2, pp. 147–69. Riviere, Joan (1929), ‘Womanliness as a masquerade’, International Journal of \nPsychoanalysis, 10, pp. 303–13. Spivak, Gayatri (1988), ‘Can the subaltern speak?’, in Carry Nelson (ed.), Marxism and the \nInterpretation of Culture, Macmillan Education, Basingstoke, pp. 271–313. Stacey, Jackie (2015), ‘Crossing over with Tilda Swinton – the mistress of “flat affect”’, \nInternational Journal of Political Cultural Sociology, 28, pp. 243–71. Smelik, Anneke (2015), ‘A close shave: The taboo on female body hair’, Critical Studies in \nFashion and Beauty, 6:2, pp. 233–51. Contributor details 31 Jacki Willson is university academic fellow in performance and culture at the University of \nLeeds. She holds a Ph.D. from Loughborough University on women’s explicit performance \npractice in relation to the artist-artiste-activist triad. She has written two monographs: The \nHappy Stripper: Pleasures and Politics of New Burlesque (2008) and Being Gorgeous: \nFeminism, Sexuality and the Pleasures of the Visual (2015) both published by I.B.Tauris. Current research areas include bawdiness and feminine style, as well as the naked flâneuse \nand citizenship. She is co-organizing Revisiting the Gaze: Feminism, Fashion and the Female\nBody, a conference which is taking place at Chelsea College of the Arts, London, 28–29 June \n2017. She is currently working on her third book. Jacki Willson is university academic fellow in performance and culture at the University of \nLeeds. She holds a Ph.D. from Loughborough University on women’s explicit performance \npractice in relation to the artist-artiste-activist triad. She has written two monographs: The \nHappy Stripper: Pleasures and Politics of New Burlesque (2008) and Being Gorgeous: \nFeminism, Sexuality and the Pleasures of the Visual (2015) both published by I.B.Tauris. Current research areas include bawdiness and feminine style, as well as the naked flâneuse \nand citizenship. She is co-organizing Revisiting the Gaze: Feminism, Fashion and the Female\nBody, a conference which is taking place at Chelsea College of the Arts, London, 28–29 June \n2017. She is currently working on her third book. Jacki Willson is university academic fellow in performance and culture at the University of \nLeeds. She holds a Ph.D. from Loughborough University on women’s explicit performance \npractice in relation to the artist-artiste-activist triad. She has written two monographs: The \nHappy Stripper: Pleasures and Politics of New Burlesque (2008) and Being Gorgeous: \nFeminism, Sexuality and the Pleasures of the Visual (2015) both published by I.B.Tauris. Current research areas include bawdiness and feminine style, as well as the naked flâneuse Jacki Willson is university academic fellow in performance and culture at the University of \nLeeds. She holds a Ph.D. from Loughborough University on women’s explicit performance \npractice in relation to the artist-artiste-activist triad. She has written two monographs: The \nHappy Stripper: Pleasures and Politics of New Burlesque (2008) and Being Gorgeous: Central Saint Martins, University of the Arts Central Saint Martins, University of the Arts 1 Granary Square London, N1C 4AA 1 ‘He, She, Me’, http://www.selfridges.com/GB/en/content/agender-film/?cm_sp=Campaign-_-\nAgenderLandingPage-_-TheFilm. Accessed 18th April, 2017. \n2 http://www.radhourani.com. Accessed 18th April, 2017. \n3 http://cdn.emgn.com/wp-content/uploads/2015/12/Diesel-gender-neutral-ad.jpg Contact: j.m.willson@leeds.ac.uk School of Performance and Cultural Industries, School of Performance and Cultural Industries, Faculty of Arts, Humanities and Cultures, Faculty of Arts, Humanities and Cultures, University of Leeds. Nicola McCartney is an artist and educator (www.nicolamccartney.co.uk). She has \nundertaken residencies overseas and in the United Kingdom, including last year at Yinka \nShonibare MBE’s studio. She is a lecturer in cultural studies for fashion/textile and jewellery \nprogrammes at Central Saint Martins, University of the Arts, London, and is currently \nassociate research fellow at Birkbeck, History of Art Department, University of London, \nwhere she completed her Ph.D. researching artistic identity and authorship. Her monograph, \nDeath of the Artist: Art World Dissidents and Their Alternative Identities (I.B. Tauris) is out \nlater this year. She is interested in gender, ageing, celebrity culture, performance, authorship \nand modes of documentation/artistic historiography. Contact: n.mccartney@csm.arts.ac.uk Contact: n.mccartney@csm.arts.ac.uk Room L202, Cultural Studies 32 g\ng\ng _\np\n2 http://www.radhourani.com. Accessed 18th April, 2017. \n3 3 http://cdn.emgn.com/wp-content/uploads/2015/12/Diesel-gender-neutral-ad.jpg AgenderLandingPage-_-TheFilm. Accessed 18th April, 2017. 1 ‘He, She, Me’, http://www.selfridges.com/GB/en/content/agender-film/?cm_sp=Campaign-_-\nth"}}},{"rowIdx":12592,"cells":{"identifier":{"kind":"string","value":"https://openalex.org/W2000608815"},"pdf_url":{"kind":"string","value":"https://europepmc.org/articles/pmc4054613?pdf=render"},"lang":{"kind":"string","value":"English"},"error":{"kind":"null"},"title":{"kind":"string","value":"Body Pigmentation as a Risk Factor for the Formation of Intracranial Aneurysms"},"source_name":{"kind":"string","value":"BioMed research international"},"publication_year":{"kind":"number","value":2014,"string":"2,014"},"license":{"kind":"string","value":"cc-by"},"word_count":{"kind":"number","value":7903,"string":"7,903"},"text":{"kind":"string","value":"Günter Schulter,1 Klaus Leber,2 Elke Kronawetter,1 Viktoria R. Rübenbauer,1\nPeter Konstantiniuk,3 and Ilona Papousek1\n1 Department of Psychology, Biological Psychology Unit, Karl-Franzens-University, Universit¨atsplatz 2/III, 8010 Graz, A\n2 Department of Neurosurgery Medical University Auenbruggerplatz 2 8036 Graz Austria 1 Department of Psychology, Biological Psychology Unit, Karl-Franzens-University, Universit¨atsplatz 2/III, 8010 Graz, Austria\n2 Department of Neurosurgery, Medical University, Auenbruggerplatz 2, 8036 Graz, Austria\n3 Department of Surgery, Division of Vascular Surgery, Medical University, Auenbruggerplatz 2, 8036 Graz, Austria Correspondence should be addressed to G¨unter Schulter; guenter.schulter@uni-graz.at Received 20 February 2014; Revised 6 May 2014; Accepted 9 May 2014; Published 22 May 2014 Copyright © 2014 G¨unter Schulter et al. This is an open access article distributed under the Creative Commons Attribution License,\nwhich permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Recent studies demonstrated pigmented cells both in the murine heart, in pulmonary veins, and in brain arteries. Moreover, a role\nfor melanocytes in the downregulation of inflammatory processes was suggested. As there is increasing evidence that inflammation\nis contributing significantly to the pathogenesis of intracranial aneurysms, melanocyte-like cells may be relevant in preventing age-\nrelated impairment of vessels. As pigmentation of the heart reflects that of coat color, aspects of body pigmentation might be\nassociated with the incidence of intracranial aneurysms. We performed a case-control study to evaluate associations between the\npigmentation of hair and eyes and the formation of aneurysms. In addition to hair and eye color, constitutive and facultative skin\npigmentation were assessed in a replication study as well as individual handedness which can be seen as a neurophysiological\ncorrelate of developmental pigmentation processes. Hair pigmentation was highly associated with intracranial aneurysms in\nboth samples, whereas eye pigmentation was not. In the replication cohort, facultative but not constitutive skin pigmentation\nproved significant. The strongest association was observed for individual handedness. Results indicate a significant association\nof intracranial aneurysms with particular aspects of body pigmentation as well as handedness, and imply clinical usefulness for\nscreening of aneurysms and possible interventions. Hindawi Publishing Corporation\nBioMed Research International\nVolume 2014, Article ID 301631, 9 pages\nhttp://dx.doi.org/10.1155/2014/301631 Hindawi Publishing Corporation\nBioMed Research International\nVolume 2014, Article ID 301631, 9 pages\nhttp://dx.doi.org/10.1155/2014/301631 Hindawi Publishing Corporation\nBioMed Research International\nVolume 2014, Article ID 301631, 9 pages\nhttp://dx.doi.org/10.1155/2014/301631 2. Materials and Methods The study was designed as a case-control study. Patients\nwith a diagnosed intracranial aneurysm were compared with\nhealthy controls with respect to degree of pigmentation of\nhair and eyes. 2.1. Study Population. We collected data in a sample of 53\nconsecutive adult patients of the same ethnic group (white\nEuropeans) within a period of six months. The only selection\ncriterion was at least one diagnosed intracranial aneurysm;\nthat is, there were no further restrictions regarding, for\ninstance, age, sex, smoking status, or rupture. There was an\nincidence of rupture/subarachnoid hemorrhage in 29 out of\n53 cases. Patients were met at their follow-up check at the\noutpatient clinic of the Department of Neurosurgery of the\nMedical University of Graz during the time of waiting for\ntheir medical examination, about six months after they had\nundergone successful treatment. A total of 136 adult controls\nwere recruited by advertisements in a local newspaper, with\nreference to an ongoing study on human pigmentation in\na quite different setting (i.e., in a study at the University\nof Natural Sciences), so that patients and controls were\nvery probably unrelated although both came from the same\nlocal area. An even distribution of men and women was\nrealized. Controls were also white Europeans, were paid for\ntheir participation, and were without any currently existing\nhealth problems or long-term medication according to their\nown statements and with no known intracranial aneurysm. Assuming an average prevalence of 2-3% for an asymptomatic\nintracranial aneurysm [25], three or four individuals out of\n136 controls may have had an incidental cerebral aneurysm,\nwhich is statistically neglectable. Moreover, any assimilation\nof controls to patients will increase the odds against detecting\nstatistically significant differences. Detailed sample charac-\nteristics are given in Table 1. Therefore, individual differences in the melanocortin\nsystem (determined, inter alia, by single nucleotide poly-\nmorphisms in the MC1R gene) should be correlated with\nindividual differences in the regulation of inflammatory\nprocesses and, consequently, with a different disposition\ntowards the formation of intracranial aneurysms. As the\nindividual level of pigmentation in the heart is correlated with\nthe individual coat color in animals [21], we assumed that\nindividual differences in the quantity and/or functionality\nof neural crest-derived pigment cells in hair follicles and\niris may mirror individual differences in the number and/or\nfunctioning of neural crest-derived nonclassical melanocytes\nand/or in the functioning of melanocortin 1 receptors in\nvascular and cardiovascular tissues. 1. Introduction several unfavorable conditions (e.g., smoking, oxidative and\nhemodynamic stress, and others) result in serious inflam-\nmatory responses and, consequently, in aneurysm forma-\ntion, but in the vast majority of individuals they do not. Therefore, any new perspective in aneurysm research may\nhelp to increase the understanding of etiological processes\nand, consequently, may improve screening methods and\ntherapeutic interventions. One such new and possibly fruitful\napproach relates to recent studies investigating the distri-\nbution and function of “non-classical” melanocytes, that\nis, pigmented cells which are not located in the skin and\nare not involved in skin pigmentation. Such nonclassical\nmelanocytes are located in sites as different as the eye, inner\near, bones, and meninges. Additionally, recent evidence exists\nthat there is also a consistent distribution of pigmented cells\nin several structures of the mouse heart [8, 9]. Moreover, The pathogenesis of intracranial aneurysm formation and\nrupture remains mostly unknown. Current evidence favors\nan interaction of multiple environmental [1, 2] and genetic\nfactors [3, 4] in the initiation and progression of intracranial\naneurysms. However, there is a growing body of evidence that\ninflammation is contributing significantly to the pathogen-\nesis of intracranial aneurysms. Starting with an endothelial\ndysfunction, an increasing inflammatory response results in\na modulation of vascular smooth muscle cells and, finally, in\nan apoptotic degradation of the vascular wall giving rise to\naneurysmal dilation and progression [5–7]. Nevertheless, the various results on the involvement\nof inflammation in aneurysm formation raise another still\nunresolved issue, in particular why only in some individuals BioMed Research International 2 the Circle of Willis) have also been shown to originate\nexclusively from such (cephalic) neural crest progenitor cells\n[22]. As in neural crest lineage segregation melanocytic and\nmyofibroblastic precursors develop from common interme-\ndiate pluripotent neural crest cells and only then differen-\ntiate to either melanocytes or pericytes and smooth muscle\ncells, respectively [23], a significant association between\nindividual hair and eye pigmentation and the disposition\nand functionality of intracranial vasculature was hypothe-\nsized. Moreover, as a majority of intracranial aneurysms are\nlocalized at the anterior part of the Circle of Willis [24],\nempirical evidence for such an association may be of special\nimportance for etiological models of intracranial aneurysm\nformation. 1. Introduction there is also evidence for the existence of melanocyte-like\ncells in murine and human vessels, that is, cells populating\nthe endothelium of pulmonary veins, expressing both the\nmelanin synthesis enzyme dopachrome tautomerase (Dct)\nand melanoblast markers, and some of them even containing\nmature melanosomes [10]. Finally, and most importantly\nfor the present study, the presence of melanocytes was also\nverified in murine brain arteries, with a particularly high\nconcentration of melanocytes observed in the wall of middle\ncerebral arteries and in several of their branches on the basal\nbrain surface. The melanocytes were mainly multipolar and\noften formed a plexus around blood vessels [11]. t\np\nFunctionally, such “non-classical” melanocytes in the\nheart, for instance, may be involved in atrioventricular valve\ndevelopment, but a recent study also demonstrated that the\nmechanical properties along the leaflet vary with the degree\nof pigmentation; that is, the viscoelastic properties of the\nvalves and their proper functioning were affected by the\npresence of melanocytes [12]. Furthermore, a Dct-dependent\nintermediate of the melanin synthesis was already established\nas a potent hydroxyl radical-scavenging agent [13], indicating\na possible role for melanocytes in murine and human vessels\nin the regulation of antioxidation processes, too. As long-\nlasting (mitochondrial) oxidative stress is causing deleterious\nchanges in vascular walls [14], Dct-expressing cells, therefore,\nmay also be relevant in preventing age-related impairment\nof vessels such as the formation of aneurysms. Of particular\nimportance, however, are various anti-inflammatory and\nimmunomodulatory properties of the melanocortin system. A lot of recent studies have demonstrated potent anti-\ninflammatory effects of alpha-melanocyte-stimulating hor-\nmone (𝛼-MSH) mediated by melanocortin receptors of dif-\nferent subtypes (MC1R to MC5R). Although 𝛼-MSH/MC1R\ninteractions primarily contribute to the regulation of skin\nphysiology, MC1 receptor functions extend well beyond the\nregulation of melanogenesis as it is expressed in a variety\nof cells, especially in cells of the immune system, that\nis, macrophage/monocytic cells, lymphocytes with antigen-\npresenting and cytotoxic functions, neutrophils, and also\nperipheral blood-derived dendritic cells, downregulating the\nproduction of specific proinflammatory cytokines [15–17]. Moreover, and most important for the present study, MC1\nreceptors are also expressed in endothelial cells [18–20]. 3. Results Multivariate logistic regression was done on the three global\ngroups of hair and eye color, respectively. Respective analyses\nshowed different results for hair and eye pigmentation, with\nodds ratios adjusted for age, smoking, and sex (Table 2). Hair\ncolor showed a pronounced effect in predicting the occur-\nrence of intracranial aneurysms, indicating an increasing\ndegree of association with decreasing pigmentation of hair (𝑃\nfor trend <0.001). Compared to dark colored hair, blond hair\nand very light hair were highly associated with intracranial\naneurysm (odds ratio: 23.50; 95% confidence interval [CI]:\n3.99 to 138.24). By contrast, the regression with pigmentation\nlevels of eyes as explanatory variable showed no significant\neffect (Table 2). 2.2. Hair Color. Pigmentation levels were objectively deter-\nmined by comparing patient’s hair with seven natural hair\nsamples selected from standard hair color swatches, a collec-\ntion routinely used in physical anthropology and medicine\n(Fischer and Saller color standards; DKSH, Z¨urich, Switzer-\nland). Pigmentation was classified on a numeric scale from\n1 (strong pigmentation, that is, dark brown) to 7 (weak\npigmentation, that is, strawberry blonde/red-haired; red\nhair contains greater contents of pheomelanin relative to\neumelanin, but both pigments are on a low level) [26]. In\nfour/two patients/controls with greyed hair and in two/five\npatients/controls with dyed hair, either inspection was done\nclose to the scalp or—if whitening/coloring was comprising\nthe whole hair shaft—original hair color was estimated by\nthe color of the eyebrows and by the participant him-/herself. To further optimize reliability of ratings and to facilitate a\nstraightforward interpretation of results, the seven grading\nvalues were pooled into three global color groups: dark brown\nto brown, light brown to dark blond, and blond to light blond\nor strawberry blonde/red-haired. 2. Materials and Methods Moreover, pericytes and\nsmooth muscle cells of the ventral/anterior compartment of\nblood vessels in the brain (including the anterior part of Written informed consent was obtained from all partic-\nipants, and the study protocol was approved by the Insti-\ntutional Review Board of the Medical University of Graz. After recording participants’ date of birth and smoking status\n(smoker or ex-smoker versus nonsmoker), hair and eye\npigmentation was assessed. BioMed Research International 3 Table 1: Summary of sample characteristics. Patients\nControls\n𝑛(%)\n𝑛(%)\nSample I\n53\n136\nSex\nMales\n16 (30.2)\n68 (50.0)\nFemales\n37 (69.8)\n68 (50.0)\nSmoking status\nSmokers\n34 (64.2)\n80 (58.8)\nNonsmokers\n19 (35.8)\n56 (41.2)\nAge (mean/SD)\n55.9 ± 13.2\n32.7 ± 8.7\nSample II\n58\n38\nSex\nMales\n17 (29.3)\n25 (65.8)\nFemales\n41 (70.7)\n13 (34.2)\nSmoking status\nSmokers\n41 (70.7)\n22 (57.9)\nNonsmokers\n17 (29.3)\n16 (42.1)\nAge (mean/SD)\n49.9 ± 11.5\n69.9 ± 9.7 Table 1: Summary of sample characteristics. intracranial aneurysms. Owing to the collinearity of the dif-\nferent facets of pigmentation, the effect of each pigmentation\nvariable on the risk of aneurysm formation was evaluated in\nseparate multivariate models. Each model was adjusted for\nage (treated as a continuous variable), smoking, and sex to\ncorrect for possible effects of these variables on pigmentation. Odds ratios were calculated for particular subgroups of pig-\nmentation to facilitate interpretation of odds ratios associated\nwith a respective subtype. Moreover, to evaluate trends in\nodds, ordinal variables were modeled as single, continuous,\nand independent variables. Additionally, an estimation (by\nNagelkerke 𝑅2 coefficient) of the percentage of variation\nexplained by the developed model is presented, but we only\nreported the amount of explained variance which is added\nby the relevant pigmentation variable (or by handedness)\nin our stepwise logistic regression model, excluding the\ncontributions by the covariates (see last column: 𝑅2+ in\nTables 2, 3, and 4). Analyses were done using SPSS 18 (IBM\nCorporation, Somers, NY, USA). 2.4. Statistical Analysis. Multivariate logistic regression was\nused to estimate odds ratios in predicting the occurrence of 4. Replication Study: Materials and Methods In view of these inconsistent results, we conducted a replica-\ntion study, because replication is strongly recommended by\nstatisticians as the best validation strategy [27]. For this pur-\npose, another independent sample of patients with diagnosed\nintracranial aneurysms was tested. The same methods and\nstatistical analyses were applied in both samples. However,\nthe control group of Sample II differed from Sample I in\nso far as in all participants it was angiographically ensured\nthat there was no incidence of an intracranial aneurysm. Furthermore, in addition to the assessment of hair and eye\ncolor, constitutive and facultative skin pigmentation were\ndetermined. Moreover, for the common variance between\nbrain lateralization and body pigmentation (both presum-\nably mirroring characteristics and common pathways in the\ndevelopment of the cephalic neural crest), handedness was\nassessed.i 2.3. Eye Color. The patient’s eye color was objectively deter-\nmined by comparing it with ten images of natural eyes\nrepresenting the whole spectrum of eye colors. Eye pig-\nmentation was classified on a numeric scale from 1 (strong\npigmentation, that is, dark brown) to 10 (weak pigmentation,\nthat is, light blue). Ratings were always done under identical\nlight conditions. To optimize reliability, the ten grading values\nwere also pooled into three global eye color groups: dark color\n(shades of brown), mixed color (blue or green with admixture\nof brown pigment), and light color (shades of blue or gray). Body pigmentation is associated with specific functional\ncharacteristics of the central nervous system. In the visual\nsystem, for instance, a misrouting of the optic nerves in\nhuman albinism, that is, an abnormal projection of the 2.4. Statistical Analysis. Multivariate logistic regression was\nused to estimate odds ratios in predicting the occurrence of 4 BioMed Research International Table 2: Results of logistic regression in Sample I. Table 2: Results of logistic regression in Sample I. Table 2: Results of logistic regression in Sample I. 4. Replication Study: Materials and Methods Explanatory variables\nPatients\n𝑛(%)\nControls\n𝑛(%)\nAdjusted odds ratio†\n(95% CI)\n𝑃# (𝑅2+)\n§\nSample I\n53\n136\nHair color\nDark brown to brown\n12 (22.6)\n60 (44.1)\n1.0\n0.001 (5.60)\nLight brown to dark blond\n20 (37.8)\n64 (47.1)\n3.11 (0.86–11.27)\nBlond to strawberry blonde/red\n21 (39.6)\n12 (8.8)\n23.50∗∗∗(3.99–138.24)\nEye color\nDark color\n21 (39.6)\n56 (41.2)\n1.0\n0.40 (0.30)\nMixed color\n10 (18.8)\n31 (22.8)\n1.07 (0.29–3.96)\nLight color\n22 (41.6)\n49 (36.0)\n0.59 (0.18–1.96)\n†Odds ratios were adjusted for age, sex, and smoking (𝑃values for these covariates were 0.001, 0.040, and 0.114, resp.); #𝑃for trend; §explained variance (%)\nby the respective variable (Nagelkerke 𝑅2+); ∗significance for odds ratios: ∗∗∗𝑃< 0.001. †Odds ratios were adjusted for age, sex, and smoking (𝑃values for these covariates were 0.001, 0.040, and 0.114, resp.); #𝑃for trend; §explained variance (%)\nby the respective variable (Nagelkerke 𝑅2+); ∗significance for odds ratios: ∗∗∗𝑃< 0.001. Table 3: Results of logistic regression in Sample II. Table 3: Results of logistic regression in Sample II. Explanatory variables\nPatients\n𝑛(%)\nControls\n𝑛(%)\nAdjusted odds ratio†\n(95% CI)\n𝑃# (𝑅2+)\n§\nSample II\n58\n38\nHair color\nDark brown to brown\n12 (20.7)\n25 (65.8)\n1.00\n0.001 (8.10)\nLight brown to dark blond\n23 (39.7)\n10 (26.3)\n2.36 (0.44–12.78)\nBlond to strawberry blonde/red\n23 (39.6)\n3 (7.9)\n29.11∗∗∗(3.78–224.32)\nEye color\nDark color\n14 (24.1)\n13 (34.2)\n1.00\n0.58 (0.09)\nMixed color\n17 (29.3)\n6 (15.8)\n2.06 (0.30–14.19)\nLight color\n27 (46.6)\n19 (50.0)\n1.70 (0.35–8.32)\nSkin color\nDark\n15 (25.9)\n17 (44.7)\n1.00\n0.68 (0.02)\nMedium\n19 (32.8)\n13 (34.2)\n1.43 (0.30–6.82)\nLight\n24 (41.3)\n8 (21.1)\n1.43 (0.28–7.41)\nSkin phototype\nRarely/never burns, tans profusely (V + VI)\n6 (10.3)\n22 (57.9)\n1.00\n0.04 (0.48)\nBurns moderately/minimally, tans moderately (III + IV)\n19 (32.8)\n12 (31.6)\n2.08 (0.43–10.05)\nBurns easily, tans never/minimally (I + II)\n33 (56.9)\n4 (10.5)\n6.08∗(1.11–33.45)\nHandedness\nPronounced right-handed\n8 (14.0)\n24 (63.2)\n1.00\n0.001 (11.40)\nModerate right-handed\n20 (35.1)\n11 (28.9)\n22.36∗∗(2.64–189.32)\nBimanual or left-handed\n29 (50.9)\n3 (7.9)\n64.09∗∗∗(5.40–760.69)\n†Odds ratios were adjusted for age, sex, and smoking (𝑃values for these covariates were 0.001, 0.009, and 0.558, resp.); #𝑃for trend; §explained variance (%)\nby the respective variable (Nagelkerke 𝑅2+); ∗significance for odds ratios: ∗𝑃< 0.05, ∗∗𝑃< 0.01, and ∗∗∗𝑃< 0.001. motor lateralization, was observed in subjects with light\npigmentation of their hair. temporal retina to the contralateral hemisphere, is well doc-\numented [28]. 4. Replication Study: Materials and Methods Moreover, there is evidence for a significant\nrelationship between the extent of such deviant functional\nbrain lateralization and the individual degree of hair and eye\npigmentation [29]. Similar associations have been shown for\nthe albino auditory system [30] and also for the motor system\nin humans without distinct features of albinism [31]. A higher\nfrequency of non-right-handedness, that is, an anomalous 4.1. Study Population. Half a year after finishing data collec-\ntion for Study I, we started data collection in an independent\nsample of 58 consecutive white European patients, also within\na period of six months and following the same procedure\nand selection criteria as in Study I. There was an incidence BioMed Research International BioMed Research International 5 Table 4: Results of logistic regression in data combined from Samples I and II. Explanatory variables\nPatients\n𝑛(%)\nControls\n𝑛(%)\nAdjusted odds ratio†\n(95% CI)\n𝑃# (𝑅2+)\n§\nSamples I + II\n111\n174\nHair color\nDark brown to brown\n24 (21.6)\n85 (48.9)\n1.0\n0.001 (13.40)\nLight brown to dark blond\n43 (38.7)\n74 (42.5)\n2.84∗∗(1.45–5.58)\nBlond to strawberry blonde/red\n44 (39.6)\n15 (8.6)\n10.82∗∗∗(4.71–24.87)\nEye color\nDark color\n35 (31.5)\n69 (39.7)\n1.0\n0.55 (0.20)\nMixed color\n27 (24.3)\n37 (21.3)\n1.73 (0.85–3.56)\nLight color\n49 (44.1)\n68 (39.1)\n1.22 (0.66–2.25)\n†Odds ratios were adjusted for age, sex, and smoking (𝑃values for these covariates were 0.001, 0.001, and 0.018, resp.); #𝑃for trend; §explained variance (%)\nby the respective variable (Nagelkerke 𝑅2+); ∗significance for odds ratios: ∗∗𝑃< 0.01, ∗∗∗𝑃< 0.001. Table 4: Results of logistic regression in data combined from Samples I and II. †Odds ratios were adjusted for age, sex, and smoking (𝑃values for these covariates were 0.001, 0.001, and 0.018, resp.); #𝑃for trend; §explained variance (%)\nby the respective variable (Nagelkerke 𝑅2+); ∗significance for odds ratios: ∗∗𝑃< 0.01, ∗∗∗𝑃< 0.001. into three subgroups of photosensitivity: rarely/never burns,\ntans profusely (PSPT V + VI), burns moderately/minimally,\ntans moderately (PSPT III + IV), and burns easily, tans\nnever/minimally (PSPT I + II). into three subgroups of photosensitivity: rarely/never burns,\ntans profusely (PSPT V + VI), burns moderately/minimally,\ntans moderately (PSPT III + IV), and burns easily, tans\nnever/minimally (PSPT I + II). of rupture/subarachnoid hemorrhage in 34 out of 58 cases. Deviating from Study I, however, controls were recruited at\nthe Department of Surgery, Division of Vascular Surgery of\nthe Medical University of Graz. 5. Replication Study: Results 4.2. Skin Color. To objectively determine constitutive skin\npigmentation [32], the surface of a scanner (CanoScan Lide\n90, Colour Image Scanner) was covered by a sheet of paper\nwith a squared area of 5 × 7 cm left open. The inner surface\nof the left and right upper arm was scanned about 5 cm\nproximally to the crook of the arm. The resulting image was\nstandardized to a size of 800 × 570 pixels with a 24-bit color\nresolution (using Microsoft Picture Manager). To each of the\nthree color components “Red,” “Green,” and “Blue,” intensity\nvalues (RGB values, ranging from 0 = no color to 255 = bright\ncolor) were then assigned (using Adobe Photoshop software). Averaging the RGB values of all pixels and both arms resulted\nin a basic score of skin pigmentation. Statistical analysis\nwas then based on terciles of these mean scores, defining\nsubgroups of dark, medium, and light skin pigmentation. The same statistical methods were applied as in Study I. One aneurysm patient with a handedness score of 𝑧> 3.5\n(unrealistically extreme left-handedness) was excluded from\nthe respective analysis, reducing the number of cases to\n57. Multivariate logistic regression was done on the three\nglobal groups of hair and eye color, as well as on the three\nsubgroups of photosensitivity. Results of case-control com-\nparisons are shown in Table 3. The analysis of hair color\nyielded virtually identical results as in Sample I (𝑃for trend =\n0.001). Compared to dark pigmented hair, light pigmentation\nwas highly associated with intracranial aneurysm (odds ratio:\n29.11; 95% CI: 3.78 to 224.32). While positive findings for\nhair color were fully replicated, associations between eye\npigmentation and aneurysms were again nonsignificant. Skin phototype as an explanatory variable proved signif-\nicant, while skin color did not. The odds ratio for subjects\nreporting easy burning and minimal/no tanning was 6.08\n(95% CI: 1.11 to 33.45) in comparison to rarely/never burning\nand profusely tanning participants, with a 𝑃for trend of\n0.04. The strongest association was observed for individual\nhandedness. Compared to subjects with pronounced right-\nhandedness, the odds of an intracranial aneurysm were\n22.36 (95% CI: 2.64 to 189.32) for subjects with moderate 4.3. Skin Phototype. Whereas constitutive skin color desig-\nnates a genetically determined level of cutaneous melanin,\nfacultative pigmentation designates the ability to adjust\nmelanization of epidermal cells after sunlight exposure. 4. Replication Study: Materials and Methods They were 38 white European\npatients who were medically examined and treated for carotid\nstenosis and, therefore, possible intracranial aneurysms were\nreliably excluded by the use of intracranial angiography. Control patients were tested during their in-patient stay at the\nsecond postoperative day after having given written informed\nconsent. The protocol was approved by the Institutional\nReview Board of the Medical University of Graz. Detailed\nsample characteristics are given in Table 1. 4.4. Handedness. Handedness was assessed by an objective\nand standardized paper and pencil test [34] consisting of tasks\nwhich had to be performed with the left and the right hand as\nquickly as possible. A laterality coefficient [(𝐿−𝑅)/(𝐿+ 𝑅) ∗\n100] was calculated as a measure of degree of handedness,\nwith positive values indicating left-handedness. Statistical\nanalysis was based on terciles of laterality coefficients, defin-\ning subgroups of pronounced right-handed, moderate right-\nhanded, and bimanual or left-handed subjects. 4.4. Handedness. Handedness was assessed by an objective\nand standardized paper and pencil test [34] consisting of tasks\nwhich had to be performed with the left and the right hand as\nquickly as possible. A laterality coefficient [(𝐿−𝑅)/(𝐿+ 𝑅) ∗\n100] was calculated as a measure of degree of handedness,\nwith positive values indicating left-handedness. Statistical\nanalysis was based on terciles of laterality coefficients, defin-\ning subgroups of pronounced right-handed, moderate right-\nhanded, and bimanual or left-handed subjects. Date of birth, smoking status, and hair and eye pigmen-\ntation were determined using the same methods as in Study\nI. Additionally, constitutive and facultative skin pigmentation\nwere assessed as well as direction and extent of handedness. 5. Replication Study: Results Some variants of the MC1R gene are\nstrongly associated with light pigmentation and especially\nwith red hair color in humans (i.e., the RHC alleles), and\nmelanocytes with such MC1R mutations were recently shown\nto have diminished ability to cope with oxidative stress [43]. Therefore, lighter compared to darker pigmented individuals\nshould be more susceptible to oxidative stress and, conse-\nquently, to the formation of intracranial aneurysms. Addi-\ntionally, there is recent evidence of a general vulnerability of\nvessels in individuals with MC1R variants. Red- compared to\ndark-haired volunteers reported significantly more bruising,\nbut without significant differences in a series of coagulation\ntests, that is, with no abnormalities in hemostasis [44]. Similarly, the usually stronger pigmentation of the anogenital\nregion and areolae compared to the surrounding skin may be\nattributed to protective functions of these areas. In a forensic\nsexual assault examination in women after consensual sexual\nintercourse, for instance, anogenital injury prevalence and\nfrequency varied by the extent of pigmentation; that is,\nlighter skin color rather than race was a strong predictor for\nincreased external anogenital injuries [45].l Finally, we combined the data from both samples and\ncalculated two logistic regressions to get a more reliable\nestimation of odds ratios and, especially, their confidence\nlimits. A combination was possible for the variables of hair\nand eye color determined in both samples, resulting in a\ndata set of 111 patients and 174 controls. Results of these\nregression analyses are given in Table 4 and reveal remarkable\nfacts in comparison to the results reported in Tables 2 and 3. Firstly, even the odds ratio for the particular state “light\nbrown to dark blond hair” reaches significance in comparison\nwith “dark brown to brown hair”; that is, even a modest\nreduction in dye intensity is associated with a small but\nsignificant increase in the risk of aneurysm formation: the\nmost conservative estimation of the particular odds ratio, that\nis, the lower confidence limit, is still 1.45 for individuals with\nlight brown to dark blond hair compared to those with dark\nbrown or brown hair. This is also supported by the significant\ntrend observed already in separate analyses of Samples I and\nII (𝑃< 0.001). Secondly, the odds ratio for the particular\nstate “blond to strawberry blonde/red hair” and the respective\nconfidence limits are substantially reduced indicating a lower\nerror of measurement. 5. Replication Study: Results The “Physician-diagnosed Skin Photo-Type” system (PSPT)\n[33] was used, asking for the participants’ skin responses\nafter a first average sun exposure. Subjects were categorized 6 BioMed Research International 6 right-handedness and increased to 64.09 (95% CI: 5.40 to\n760.69) for bimanual or left-handed subjects. The degree of\nassociation increased with an increasing shift from right- to\nleft-handedness (𝑃for trend = 0.001). various anomalies in brain lateralization, such as in the\nmotor system manifested as ambidexterity or left-handedness\n[28–31]. Brain lateralization in turn is clearly associated\nwith several immune functions, as was shown in a series\nof studies in animals and humans, using various methods\n(e.g., handedness tests, resections of the cortex, transcranial\nmagnetic stimulation, and EEG analyses) and concerning\nparameters and processes of both the humoral and cellular\nimmune system (e.g., S-IgA, B and T cells, and natural\nkiller cells) [35–40]. Additionally, a relationship between\ndifferent levels of specific proinflammatory cytokines (inter-\nleukin 1𝛽and interleukin 6) in left versus right cortices and\nmotor lateralization has also been demonstrated [41, 42]. Consequently, the strong association between handedness\nand aneurysm formation observed in the present study may\nresult from different dispositions between left- and right-\nhanders to regulate inflammation in brain arteries, though\nwe cannot, however, explain in detail the immunological\nprocesses behind this observation. t\nTo give a rough estimate of their predictive power as a\nscreening tool, a logistic regression was additionally cal-\nculated with a combination of those independent variables\nin the data set of Study II which had revealed significant\nassociations with case-control status, that is, hair color,\nskin photosensitivity, and handedness. For this purpose, the\nrespective global group values for each variable were averaged\nfor each individual and modeled as single, continuous, and\nindependent variable and case-control status was modeled as\nthe dependent variable. Logistic regression showed a highly\nsignificant result (Wald statistic = 12.3, df = 1, and 𝑃< 0.000),\nwith the following classification parameters: sensitivity =\n94.7% and specificity = 86.8%; that is, 94.7% and 86.8% of\npatients and controls, respectively, were classified correctly. Accordingly, the false positive/negative rates were 13.2 and 5.3\npercent. One possible explanation relates to an important func-\ntional characteristic of melanocytes: recent evidence indi-\ncated distinct differences in the antioxidative efficiency of the\nmelanocyte system between individuals. These differences\nare caused by the melanocortin 1 receptor which is highly\npolymorphic and a major contributor to the diversity of\nhuman pigmentation. 5. Replication Study: Results Moreover, the lower confidence limit\nstill amounts to about 4, that is, a remarkable value which is\nbased on both data sets and therefore a more valid parameter. Beyond that, the importance of inflammatory processes\nin intracranial aneurysm formation is further substantiated\nby the results of recent studies showing that frequent use\nof acetylsalicylic acid both attenuates inflammation in the\nwalls of human cerebral aneurysms [46] and, thereby, may\nalso reduce the risk of intracranial aneurysm rupture [47]. However, several successful attempts have already been\nreported targeting the melanocortin receptors themselves as\na novel strategy to control inflammation [48]. The thera-\npeutic potential of 𝛼-MSH and other receptor ligands was\ndemonstrated, for instance, in proteinuria [49], uveitis [50],\nand skin inflammation [51]. Treatment effects concerning\ndisordered vasculature are, however, the most important for 6. Discussion A synthetic MC1R agonist (BMS-470539),\nfor instance, was demonstrated to inhibit leucocyte traffick-\ning in the inflamed vasculature [52], and the natural agonist\n𝛼-melanocyte-stimulating hormone was shown to regulate\nvascular NO availability and to protect against endothelial\ndysfunction [53]. Agonists of the melanocortin system, therefore, may\nprospectively be seen as efficient therapeutic strategies to\nfight against developing inflammation in brain arteries and,\nmost importantly, to prevent aneurysm rupture. The logic\nbehind such a strategy, however, requires empirical evidence\nthat particular aspects of body pigmentation, that is, specific\nprocesses and functions of the melanocortin system, are\nsignificantly associated with the incidence of intracranial\naneurysms. Such associations were documented for the first\ntime by the present study which, therefore, adds some\nnew aspects to etiological models of intracranial aneurysm\nformation. With respect to the genetic characteristics of the various\naspects of body pigmentation, the present results also add\nsome information concerning possible genetic determinants\nof the observed association: the anti-inflammatory properties\nof melanocytes arise mainly from the 𝛼-MSH hormone which\nis mediated by the MC1R receptor. The MC1R receptor\nand its genetic mutations, again, are the main source of\nindividual variation in hair and skin pigmentation, a fact\nwell documented in the literature (e.g., [54, 55]). However, in\nmost genetic studies, no association of MC1R with eye color\nwas observed [56–58]. Remarkably, this distinction is also\nreflected in the results of the present study: significant effects\nfor hair color, but not even a trend in the data concerning\neye color. Consequently, the common underlying cause of\nboth lighter pigmentation and an increased susceptibility to\naneurysm formation may be seen (among others) in par-\nticular polymorphisms of the MC1R gene. Such pleiotropic\neffects, however, must be demonstrated directly by analyzing\nthe specific genetic variations in patients with intracranial\naneurysms in future studies. Conflict of Interests The authors declare that there is no conflict of interests\nregarding the publication of this paper. There are several limitations of the present study. The\nmain sources of imprecision result from the relatively small\nsample size, especially in Study II. First, this fact specifi-\ncally concerns facultative and constitutive skin pigmentation. Whereas one of the estimated odds ratios for skin phototype\nreached significance, logistic regression failed to show an 7. Conclusions A significant association between particular aspects of body\npigmentation and the incidence of intracranial aneurysms\nwas demonstrated in the present study. Odds ratios increased\nwith a decreased pigmentation of hair and a reduced ability to\nadjust melanization of epidermal cells after sunlight exposure\n(“skin photo-type”). Results for hair color were validated\nin a second independent sample of cases and controls,\nand the replication study yielded virtually identical results. In addition, individual handedness as a neurophysiological\ncorrelate of developmental pigmentation processes was also\nstrongly associated with aneurysm formation; that is, the\ndegree of association increased with an increasing shift from\nright- to left-handedness. y\nBased on the data of Sample II, a rough estimate of\nthe predictive power was finally done with those variables\nwhich had proven to be significant in the logistic regression. This analysis resulted in estimations of about 95% and 87%\nfor sensitivity and specificity, respectively. These figures are\nquite comparable with or even higher than those of other\nprocedures widely used in clinical screening, for instance,\nfaecal occult blood tests for the detection of colorectal\ncancer in an average-risk screening population (estimated\nsensitivities ranging from 6% to 83% and specificities ranging\nfrom 65% to 99%) [59]. Despite a preliminary and very\nrough estimation, results indicate that these variables, that\nis, certain facets of pigmentation and individual handedness,\nmay also have a role as part of clinical screening procedures\nin detecting intracranial aneurysms in the future.hh 6. Discussion Intracranial aneurysms were clearly associated with particu-\nlar aspects of body pigmentation, and the strongest associa-\ntion with aneurysm formation was observed for individual\nhandedness. As for handedness, it is an essential indicator\nof direction and degree of individual brain lateralization,\nwhich in turn is correlated with several aspects of body pig-\nmentation: aberrant and limited migration of cephalic neural\ncrest cells, defective/reduced melanin production, and/or\ndysfunctional melanocortin receptors, for instance, may be\nconsidered as a common basis of two different but related\nmanifestations, that is, reduced pigmentation/albinism and BioMed Research International 7 effect for skin color, although a (nonsignificant) trend in the\nfrequency distributions for the three categories of skin color\ncan be observed in the expected direction (distribution in\npatients opposed to that in controls). However, confidence\nlimits for both skin pigmentation variables are unrealistically\nhigh indicating a large portion of error variance caused by\nthe small sample size. This is especially true for the effect\nof handedness: the highly significant odds ratios for both\nhandedness categories as well as the significant overall trend\nindicate fundamental importance of this variable. The actual\nfigures, however, appear highly implausible. Future studies\ndetermined on a much larger data base will provide more\nrealistic estimates for the common variance between brain\nlateralization, body pigmentation (both mirroring charac-\nteristics and common pathways in the development of the\ncephalic neural crest), and the formation of intracranial\naneurysms. Secondly, a further source of imprecision relates\nto the quantification of pigmentary traits. With the exception\nof skin color, pigmentation variables have been based on\nsubjective phenotypes using categorical scales in estimating\nthe level of pigmentation. In future studies, objective and\nquantitative measures of skin, hair, and eye color should\nbe collected by using, for instance, reflectance or digital\nspectroscopy and, thereby, excluding a further source of error\nvariance. Finally, our study provides only indirect evidence\nof an association between the melanocyte system and the\nformation of aneurysms. As already mentioned above, effects\nof the melanocyte system on aneurysm formation should be\ndemonstrated directly by analyzing specific genetic variations\nin patients and controls. the present study. A synthetic MC1R agonist (BMS-470539),\nfor instance, was demonstrated to inhibit leucocyte traffick-\ning in the inflamed vasculature [52], and the natural agonist\n𝛼-melanocyte-stimulating hormone was shown to regulate\nvascular NO availability and to protect against endothelial\ndysfunction [53]. the present study. References [17] C. Maaser, K. Kannengiesser, and T. 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Marston See next page for additional authors Follow this and additional works at: https://newprairiepress.org/kaesrr Part of the Other Animal Sciences Commons ansas Agricultural Experiment Station Research Reports \nansas Agricultural Experiment Station Research Reports ansas Agricultural Experiment Station Research Reports \nansas Agricultural Experiment Station Research Reports Volume 0 \nIssue 1 Cattleman's Day (1993-2014) Volume 0 \nIssue 1 Cattleman's Day (1993-2014) Article 251 Recommended Citation \nRecommended Citation Marston, T.T.; Llewellyn, Donald A.; Homm, J.W.; and Hollis, Larry C. (2003) \"Effects of castration age and \na growth implant during suckling on weaning and preconditioned weights (2003),\" Kansas Agricultural \nExperiment Station Research Reports: Vol. 0: Iss. 1. https://doi.org/10.4148/2378-5977.1654 This report is brought to you for free and open access by New \nPrairie Press. It has been accepted for inclusion in Kansas \nAgricultural Experiment Station Research Reports by an \nauthorized administrator of New Prairie Press. Copyright 2003 \nthe Author(s). Contents of this publication may be freely \nreproduced for educational purposes. All other rights reserved. Brand names appearing in this publication are for product \nidentification purposes only. No endorsement is intended, nor \nis criticism implied of similar products not mentioned. K-State \nResearch and Extension is an equal opportunity provider and \nemployer. This research report is available in Kansas Agricultural Experiment Station Research Reports: \nhttps://newprairiepress.org/kaesrr/vol0/iss1/251 Effects of castration age and a growth implant during suckling on weaning and \nEffects of castration age and a growth implant during suckling on weaning and \npreconditioned weights (2003) \npreconditioned weights (2003) Authors \nAuthors \nT.T. Marston, Donald A. Llewellyn, J.W. Homm, and Larry C. Hollis Experimental Procedures One hundred forty-one spring-born (aver-\nage birth date = March 4), Angus crossbred \ncalves were used in this experiment. Calves \nwere blocked by dam age and then randomly \nassigned to treatments. The three treatments \nwere: 1) castrated in early June with no im-\nplant, 2) castrated in early June and implanted \nwith Synovex C (Fort Dodge), and 3) cas-\ntrated mid-October on the day of weaning. Calves in the early castrated/ no implant and \nearly castrated/ implanted treatments were ap-\nproximately 90 days of age when castrated, \nwhereas late castrated calves averaged 226 \ndays of age at time of castration. Dates of cas-\ntration were used to simulate typical branding \nand weaning ages of the calves. Calves were \nallowed to freely nurse their dams throughout \nthe summer with no creep feed. Three weeks \nprior to weaning, all calves were weighed and \ninjected with Cattlemaster 4 (Pfizer) and For-\ntress 7 (Pfizer). Calves were weighed, re-\nceived a booster vaccination of Cattlemaster 4, \nand were treated with Dectomax Pour-on \n(Pfizer) on the day of weaning. After wean-\ning, calves were fed round bales of brome hay \nfree choice and hand-fed 5 pounds/day of a \npelleted, commercial starter feed for 28 days. During the first 5 days after weaning, the Summary calves to be held for 30 to 45 days after wean-\ning. The timing of castration and implementa-\ntion of an implant program may affect selling \nweight. Therefore, the objective of this trial \nwas to determine the effect of different castra-\ntion ages in combination with a growth im-\nplant on calf weights at weaning and after pre-\nconditioning. Crossbred Angus calves (n=141) were \nused to determine the effect of castration age \nand implant on weaning and preconditioned \nweights. Calf treatments consisted of: early \ncastration at 90 days of age with no growth \nimplant, early castration with a growth im-\nplant (Synovex C) at 90 days of age, or late \ncastration at weaning (226 days of age). All \ncalves completed a preconditioning program \nthat consisted of timely vaccinations (21 days \nprior and at weaning) and a 28-day, post-\nweaning feeding period. Steers that were \nearly \ncastrated/implanted \nhad \nweaning \nweights similar to those of bull calves, and \nboth groups weighed 15 lb more than their \nearly castrated/no implant contemporaries. However, 28 days after weaning the early cas-\ntrated/implanted steers weighed 20 lb more \nthan either the early castrate/no implant or late \ncastrated steers. Our data indicate that early \ncastration in combination with a suckling \nphase implant produces the greatest amount of \nsaleable weight along with the most flexibility \nin marketing options. Authors \nAuthors Cattlemen’s Day 2003 Introduction Cow/calf producers have several options \nfor selling their calves. Traditionally, calves \nhave been sold either at weaning, after a grow-\ning period, or retained until slaughter. The \ninitiation of a preconditioning program can \ncreate a new marketing opportunity. Most \npreconditioning programs require vaccinations \nand boosters for bovine respiratory diseases, \nclostridials, treatment for internal and external \nparasites, as well as dehorning and castration. The more stringent programs will also require 69 hand-fed supplement was top dressed with \nAueromycin (Alpharma) at a rate of 5 grams \nchlortetracycline per calf daily. planted and late castrated calves would have \nhad greater pay weights than their early cas-\ntrated/ no implant contemporaries. Previous \nreports suggest that the price of bull calves \nwould be $5 to $6/cwt less than of comparable \nsteer mates. These price discounts would \nhave made our late castrated calves the least \nvaluable at weaning time. Market prices \nwould dictate the necessary price adjustments \ncow/calf producers would need to compensate \nfor the weight difference between early cas-\ntrated/ no implant and early castrated/ im-\nplanted calves (See Table 2). Results and Discussion Descriptions of the calves and results are \nsummarized in Table 1. Summer health of the \ncalves was excellent and was reflected by their \nsummer weight gains. Between the June and \nSeptember weigh dates the average calf gain \nof all calves was 2.46 lb/day. The early cas-\ntrated/ no implant calves gained slower \n(P<0.01) while suckling their mothers than did \nearly castrated/ implanted and late castrated \ncalves (2.37 lb/day, 2.53 lb/day, and 2.53 \nlb/day, respectively). Our data indicates that a \nsingle implant given during the suckling phase \nwill produce a positive weight gain response \nwhen compared to non-implanted steer calves \nand that the weight gain of castrated, im-\nplanted calves will mirror intact bull calf per-\nformance. The weather following weaning was cool, \ndamp, and cloudy for the first 2-week period. All calves readily ate the commercial starter \nfeed by the third day. At 28 days after wean-\ning, early castrated/ implanted steers weighed \nmore than either early castrated/ no implant or \nlate castrated steers. Average daily gains dur-\ning the post-weaning period were similar \n(P=0.22) between early castrated/ implanted \n(1.72 lb/day) and early castrated/ no implant \n(1.52 lb/day) steers and both were greater \n(P<0.01) than late castrated (1.16 lb/day). This difference in rate of gain erased any \nweight advantage late castrated calves had \nover their contemporaries at weaning time. Average gain of all calves (1.61 lb/day) \nduring the 21 days from first vaccination to \nweaning dates was less than the previous \nsummer period. This is probably the result of \nseveral factors, including decreasing dam milk \nproduction and maturing forages. Regardless, \nno differences in rate of gain were noted be-\ntween treatments (P>0.94) during this short \nperiod of time. If calves were to be marketed \ndirectly off their dams, early castrated/ im- Cow/calf producers that desire marketing \nflexibility should consider early castration and \nimplanting suckling calves if maximum \npounds of saleable product are desirable. 70 Table 1. Description of Calves Table 1. Description of Calves Treatments Treatments \n \nEarly Castration \nLate \nItem: \nNo implant \nImplant \nCastration \nNo. Results and Discussion of calves \n60 \n40 \n41 \nAverage birth date \nMarch 9 \nMarch 2 \nMarch 2 \nAverage castration age, days \n87 ± 18 \n94 ± 19 \n226 ± 16 \nWeight, lb \n \n \n \nJune \n304 ± 38 \n311 ± 37 \n317 ± 42 \nSeptember 2 \n530 ± 3 \n545 ± 4 \n544 ± 4 \nOctober 15 \n564 ± 5 \n580 ± 5 \n578 ± 5 \nNovember 12 \n606 ± 4 \n628 ± 4 \n611 ± 4 Table 2. Market Price Adjustments Needed to Compensate for Differences in Weaning \nWeight or Weight 28 Days After Weaning Between Early Castrated/No Implant and Early \nCastrated/Implanted Steer Calves \n \nPrice Adjustmenta, $/cwt \nAnticipated market price \nSell at Weaning \nSell after Preconditioning \n$105/cwt \n+2.90 \n+3.79 \n$100/cwt \n+2.76 \n+3.50 \n$95/cwt \n+2.62 \n+3.33 \n$90/cwt \n+2.48 \n+3.15 \n$85/cwt \n+2.34 \n+2.98 \n$80/cwt \n+2.21 \n+2.80 \naThe additional price that would need to be received to justify not implanting early-castrated \ncalves. aThe additional price that would need to be received to justify not implanting early-castrated \ncalves. 71 71"}}},{"rowIdx":12594,"cells":{"identifier":{"kind":"string","value":"https://openalex.org/W4306816490"},"pdf_url":{"kind":"string","value":"https://mediatum.ub.tum.de/doc/1693552/document.pdf"},"lang":{"kind":"string","value":"English"},"error":{"kind":"null"},"title":{"kind":"string","value":"Quantification of oxidative stress in Saccharomyces pastorianus propagation: Gene expression analysis using quantitative reverse transcription polymerase chain reaction and flow cytometry"},"source_name":{"kind":"string","value":"Frontiers in chemical engineering"},"publication_year":{"kind":"number","value":2022,"string":"2,022"},"license":{"kind":"string","value":"cc-by"},"word_count":{"kind":"number","value":6709,"string":"6,709"},"text":{"kind":"string","value":"COPYRIGHT COPYRIGHT\n© 2022 Beugholt, Büchner, Geier and\nBecker. This is an open-access article\ndistributed under the terms of the\nCreative Commons Attribution License\n(CC BY). The use, distribution or\nreproduction in other forums is\npermitted, provided the original\nauthor(s) and the copyright owner(s) are\ncredited and that the original\npublication in this journal is cited, in\naccordance with accepted academic\npractice. No use, distribution or\nreproduction is permitted which does\nnot comply with these terms. KEYWORDS\naeration, flow cytometry, oxidative stress, yeast propagation, reactive oxygen (ROS),\nqPCR, Saccharomyces TYPE Original Research\nPUBLISHED 19 October 2022\nDOI 10.3389/fceng.2022.1035348 TYPE Original Research\nPUBLISHED 19 October 2022\nDOI 10.3389/fceng.2022.1035348 TYPE Original Research\nPUBLISHED 19 October 2022\nDOI 10.3389/fceng.2022.1035348 Quantification of oxidative stress\nin Saccharomyces pastorianus\npropagation: Gene expression\nanalysis using quantitative\nreverse transcription polymerase\nchain reaction and flow\ncytometry Quantification of oxidative stress\nin Saccharomyces pastorianus\npropagation: Gene expression\nanalysis using quantitative\nreverse transcription polymerase\nchain reaction and flow\ncytometry OPEN ACCESS\nEDITED BY\nVasudeo Zambare,\nUniversity of Technology Malaysia,\nMalaysia\nREVIEWED BY\nLuis H. Reyes,\nUniversity of Los Andes, Colombia,\nColombia\nBhupendra Gopalbhai Prajapati,\nGanpat University, India\n*CORRESPONDENCE\nDominik Ulrich Geier,\nDominik.geier@tum.de\nSPECIALTY SECTION\nThis article was submitted to\nBiochemical Engineering,\na section of the journal\nFrontiers in Chemical Engineering\nRECEIVED 02 September 2022\nACCEPTED 03 October 2022\nPUBLISHED 19 October 2022\nCITATION\nBeugholt A, Büchner K, Geier DU and\nBecker T (2022), Quantification of\noxidative stress in Saccharomyces\npastorianus propagation: Gene\nexpression analysis using quantitative\nreverse transcription polymerase chain\nreaction and flow cytometry. Front. Chem. Eng. 4:1035348. doi: 10.3389/fceng.2022.1035348 Alexander Beugholt, Kai Büchner, Dominik Ulrich Geier* and\nThomas Becker Chair of Brewing and Beverage Technology, Technical University of Munich, Munich, Germany When confronted with environmental stress, yeast cell reacts, among others, by\nmodifying the expression of specific genes. In this study, gene expression was\nanalyzed via RT-qPCR to quantify the oxidative stress of Saccharomyces\npastorianus during yeast propagation as a reaction to different aeration\nlevels. Target genes were identified, and a reference gene system was\ndeveloped. Fermentation experiments were conducted in shaking flasks,\napplying different shaking speeds to generate various aeration efficiencies. The cells were sampled at different propagation stages and, additionally to\nthe expression\nstudy,\nanalyzed\nby flow\ncytometry\nafter staining with\ndihydroethidium (DHE) to quantify reactive oxygen species (ROS) inside the\ncells. The results indicate that high oxygen fermentation conditions led to an\nincreased expression of the catalase-A gene CTA1 during propagation. Furthermore, the determination of cell internal ROS shows increasing\noxidative\nstress\nover\nthe\nprocess\nin\naccordance\nwith\nthe\nRT-qPCR\nmeasurements. Beugholt A, Büchner K, Geier DU and\nBecker T (2022), Quantification of\noxidative stress in Saccharomyces\npastorianus propagation: Gene\nexpression analysis using quantitative\nreverse transcription polymerase chain\nreaction and flow cytometry. Front. Chem. Eng. 4:1035348. doi: 10.3389/fceng.2022.1035348 1 Introduction Saccharomyces pastorianus is a facultative anaerobic organism that can alternate its\nmetabolism between respiration and fermentation. Since the oxidative pathway yields\nmore ATP, this yeast requires the presence of oxygen in the cultivation medium for\noptimal growth conditions (Alexander & Jeffries, 1990). During multistage metabolic\nprocesses, such as respiration, steroidogenesis, and β-oxidation of fatty acids, various 01 Frontiers in Chemical Engineering Frontiers in Chemical Engineering frontiersin.org 10.3389/fceng.2022.1035348 Beugholt et al. glutathione is a quintessential member of the nonenzymatic\nclass of antioxidants. The redox-active sulphydryl group of\nglutathione reacts directly with oxidants and reduces them to\nless harmful molecules (Moradas-Ferreira et al., 1996). One\nsignificant enzymatic way to control the ROS level in the cell\nutilizes metal-dependent enzymes like catalases. Catalase is an\niron-containing enzyme with a haem group in its active site. S. cerevisiae\ncontains\ntwo\ncatalases:\ncytosolic\nCTT1\nand\nperoxisomal\ncatalase\nCTA1. Catalase\nreduces\nhydrogen\nperoxide to water and oxygen using a dismutation mechanism\n(Toledano et al., 2003). Adequate aeration and low ROS\nconcentrations must be balanced for good aerobic growth\nconditions. Thus, the oxygen supply for yeast propagation is\ncrucial due to the versatile function of oxygen in yeast cell\nmetabolism and its essential role in enhancing unsaturated\nfatty acids and ergosterol biosynthesis, both vital molecules\nfor cell growth (Verbelen et al., 2009). S. pastorianus, a hybrid\nof S. cerevisiae and S. eubayanus, is one of the industrially most\nrelevant yeasts (Monerawela & Bond, 2018). Despite this,\nknowledge about the organism is mainly derived from the\napparent similarity to S. cerevisiae. For industrial brewing\napplications, yeast is cultivated in propagator vessels in\npreparation for the following beer fermentation. Cell counts\nincrease 10-fold up to 100·106 cells during this aerobic\nprocess. This work aims to evaluate the response of S. pastorianus to ROS during brewer’s yeast propagation. The\nexpression of catalases as the primary protection mechanism\nagainst hydrogen peroxide was monitored using RT-qPCR\nmeasurements. Furthermore, the ROS content was estimated\nusing fluorescence dye as a reference method. partially reduced forms of molecular oxygen are formed as by-\nproducts (i.e., hydrogen peroxide, hydroxyl radicals, and\nsuperoxide anions) (Jamieson, 1995; Jamieson, 1998). These\nintermediates are called reactive oxygen species (ROS). ROS\ncan react with various intracellular molecules and affect the\nwhole organism by damaging DNA, lipid structures, and\nproteins, even triggering apoptosis. (Bayir, 2005; Dickinson &\nSchweizer, 2005; Perrone et al., 2008). 1 Introduction Reactive oxidants can\ncause damage to DNA and nucleoproteins through base and\nsugar alterations, the introduction of abasic sites and strand\nbreaks, and DNA-protein cross-links (Moradas-Ferreira et al.,\n1996). One of the main reactions forming ROS is the iron-\ncatalyzed Haber-Weiss and Fenton reaction, with hydrogen\nperoxide as a key molecule and the highly reactive hydroxyl\nradical as a product that can directly interact with DNA\n(Frankenberg et al., 1993; Baynes & Dominiczak, 2019). High\nconcentrations of hydrogen peroxide lead to lipid peroxidation\nand affect the structural integrity of membranes by increasing\nmembrane fluidity and shortening fatty acyl chains (Steels et al.,\n1994). Increased membrane fluidity was shown to correlate with\nhigher stress susceptibility (Ishmayana et al., 2017). ROS, and\nespecially hydroxyl radical exposure, result in huge damage due\nto reactions with the alpha carbon and the amino acid side chains\non the protein side. The radical reaction promotes chain\nreactions or cleavage of the protein backbone (Toledano et al.,\n2003). Most ROS are generated in the mitochondrial respiratory\nchain, where 85%–90% of the available oxygen is consumed\n(Halliwell & Gutteridge, 2005). Consequently,\naerobically\ngrowing\nbrewer’s\nyeast\nis\npermanently exposed to reactive oxygen species (Lushchak &\nGospodaryov, 2005). Given the omnipresent character of ROS,\nyeasts have developed protection for their cellular components\nagainst reactive oxidants (Jamieson, 1998). Under normal\nconditions, there is a balance between reactive oxidants,\nantioxidant\nbuffering\ncapacity,\nand\ndefense\nmechanisms\ncapable of maintaining homeostasis. 2.2.1 RNA extraction and cDNA synthesis 2.2.1 RNA extraction and cDNA synthesis\nSampling was conducted according to literature (Dragosits\net al., 2011). The Monarch Total RNA Miniprep Kit (New\nEngland Biolabs, Ipswich, United States) was used for RNA\nextraction. RNA purity and integrity were controlled by\ndenaturing\nagarose\ngel\nelectrophoresis\nand\ncapillary\nelectrophoresis\n(Bioanalyzer;\nAgilent\nTechnologies). The\ndenaturation of 5 µl RNA was carried out using a buffer\nconsisting of 2 µl MOPS ×10 buffer (200 mM MOPS, 50 mM\nsodium acetate trihydrate, 10 mM EDTA Quantification), 10 µl\nDimethylformamid at a temperature of 65°C for 10 min. The\nelectrophoresis was performed at 70 V/cm in ×1 MOPS buffer. Additional\nquality\ncontrol\nwas\nevaluated\nusing\nspectrophotometry\n(NanoDrop;\nThermo\nScientific). The\nvisibility of clear 28S and 18S rRNA bands on the gel was\nused to indicate minor RNA degradation. Additionally, the\nRNA integrity number (RIN) was evaluated. cDNA synthesis 2.2.2 Primers Table 1 shows the primer set for the selected target gene\nCTA1. According to the literature, possible reference genes were\nselected from different metabolic pathways, as displayed in\nTable 2, to minimize possible coregulation [25, 28, 29]. The\nSaccharomyces genome was taken from the Saccharomyces\ngenome database due to the hybrid genetic character of S. pastorianus (Cherry et al., 2012). Primers were designed using\nClone Manager nine software (Sci Ed Software) and synthesized\nusing TIB Molbiol Syntheselabor GmbH (Berlin). Primer\nefficiencies were determined using a 1:5 cDNA dilution series\nof five steps (Rasmussen, 2001). A no-template control (NTC)\nwas also measured for each primer pair. All dilutions and NTCs\nwere determined in triplicate. For known pseudogenes, primers\nwere chosen according to the alignment results between genes\nand pseudogenes. In this direction, the primers were unique to\nthe genes of interest. The secondary structure of the amplicons\nwas analyzed with a Mfold using the criteria −3 < dG. intended for combination with the shaker used (PreSens\nPrecision Sensing GmbH, 2022). 2.1 Fermentation Fermentations were performed with S. pastorianus TUM 34/\n70 in 500 ml baffled shake flasks at 28°C. The initial filling volume\nwas 40 ml of fresh wort in addition to 10 ml preculture, resulting\nin an initial cell count of 2.1·107 ± 8.7·106 cells. In the brewing\nindustry, “extract” and “free amino nitrogen (FAN)” are\nterminologies for carbon and nitrogen sources available for\nthe yeast. The wort used for this study had an extract content\nof 11.28 ± 0.11 °P, 197.6 ± 3.69 mg/L FAN, and a pH of 5.14 ±\n0.036. The hopped wort was provided by an industrial brewery\nduring knockout. Cultures were grown at 100 rpm, 150 rpm,\n200 rpm, and 250 rpm shaking speeds for different aeration\nlevels, resulting in kLa values ranging from 51 to 180 h−1. Samples were taken after 0 h, 4 h, 24 h, 48 h, and 72 h. Dissolved Oxygen (DO) in shake flasks was measured with a\nnoninvasive optical sensor (SFR Vario, PreSens Precision Sensing\nGmbH, Regensburg). The kLa values were calculated using the\nkLa calculator from PreSens Precision Sensing GmbH, which is The two parts of the cellular reaction to oxidants are primary\ndefense mechanisms that neutralize ROS, while secondary\nmechanisms repair oxidation damage. In the case of exceeding\nROS levels compared to antioxidants, the cell experiences\noxidative stress (Moradas-Ferreira et al., 1996). Next to by-\nproducts of oxidative phosphorylation, oxidative stress can\ndirectly be caused by the take-up of dissolved oxygen (DO)\nfrom\nthe\nmedium. Yeast\ncells\ndeploy\ndifferent\ndefense\nmechanisms depending on ROS dose (Temple et al., 2005). Lower amounts of ROS cause adaptation, leading to more\nrobust cells against further oxidative stress (Jamieson, 1992). Significant exposure induces the expression of antioxidants and\ndelays the cell cycle, while even higher concentrations initiate\napoptosis in parts of the culture or lead to necrosis (Lee et al.,\n1996; Perrone et al., 2008). To constantly maintain a low ROS\nconcentration, yeast relies on enzymatic and nonenzymatic\nantioxidant\ndefense\nmechanisms. The\nradical\nscavenger Frontiers in Chemical Engineering Frontiers in Chemical Engineering 02 frontiersin.org 10.3389/fceng.2022.1035348 Beugholt et al. TABLE 1 The target primer set used for RT-qPCR amplification\n(Verbelen et al., 2009). TABLE 1 The target primer set used for RT-qPCR amplification\n(Verbelen et al., 2009). was conducted according to New England Biolabs (New England\nBiolabs, Ipswich, United States) first-strand cDNA synthesis\nprotocol (NEB#M0368). 2.2.3 qPCR and analysis of expression stability qPCR measurements were conducted in a final volume of 10-\nμl containing 1 μl of DNA template, 0.4 μl of each respective\nprimer, 5 μl of SybrGreen (Biozym, Germany), and 3.2 μl of\nRNase-free water. Gene expression was measured by real-time RT-qPCR, and\nthe expression stabilities were evaluated by the M and V values\nbased on the geNorm algorithm using the software qBase+\n(Biogazelle, Gent, Belgium) (Vandesompele et al., 2002). The TABLE 2 Primer sets used for RT-qPCR amplification as possible reference genes. TABLE 2 Primer sets used for RT-qPCR amplification as possible reference genes. Gene\nDirection\nPrimer sequence (59-39)\nFunction\nUBC6\nReverse\nTTGTTCAGCGCGTATTCTGTC\nUbiquitin-conjugating enzyme\nForward\nATGCGGCAAATACAGGTGATG\nTAF10\nReverse\nCACCGTCAGAACAACTTTGC\nSubunit of TFIID and SAGA complexes\nForward\nTAACAACAGTCAGGCGAGAG\nALG9\nReverse\nCTCTCGGAGGTACAACTG\nMannosyltransferase\nForward\nCACTAAATCAAGGTGGTGTGAAG\nTFC1\nReverse\nTCGTCTGGCTCTTCAGTTATGG\nSubunit of RNA polymerase III transcription initiation factor complex\nForward\nTGGATGCAGGTAGTCAAATGTC\nPGK1\nReverse\nTTCGTCTAACAAAGCCTTAGTACC\n3-phosphoglycerate kinase\nForward\nCTAGAAAGTTGTTTGCTGCTACTG\nKRE11\nReverse\nCTCTCGGAGGTACAACTG\nComponent of transport protein particle complex II\nForward\nATTCGCCCTTGACACTGG\nPFK1\nReverse\nAACCTTAGCGTCAGTGTTTGG\nα-subunit of heterooctameric phosphofructokinase\nForward\nCATGTTCAACAAGGTGGTGTTC\nYRB1\nReverse\nCTGCTTCACCTTCTGCAATATC\nRan GTPase binding protein\nForward\nCCACATCATTGCTCCAGAATAC 03 Frontiers in Chemical Engineering frontiersin.org Beugholt et al. 10.3389/fceng.2022.1035348 ^fh(x) \u0002 1\nnh \u0001\nnh\nn\nK (x −xi)\nh\nKernel density estimation\n(1)\nKi \u0002\n⎧\n⎪\n⎨\n⎪\n⎩\n3\n4 \u00071 −x2\b\n0\nEpanechikov −Kernel\n(2)\nh \u0002 0.9 min\t^σ, IQR\n1.34\nn−1/5 SilvermanMethod\n(3) Cq values from RT-qPCR were imported into qBase Plus\nsoftware (Biogazelle). Normalized relative quantities were\ncalculated using the modified Pfafflmethod with multiple\nreference genes (Hellemans et al., 2007). (1) (2) 2.3 Determination of reactive oxygen\nspecies (3) x = independent and identically distributed samples, IQR =\ninterquartile range. A Cytoflex flow cytometer (Beckman Coulter GmbH,\nKrefeld) equipped with an argon-ion laser operating at\n488 nm was used in the experiments. The cytometer was\nfitted with four sensors for front and side scatter detection of\ngreen (525 nm, channel 1), yellow (585 nm, channel 2),\norange (610 nm, channel 3), and red (780 nm, channel 4)\nfluorescence. The cells harvested simultaneously for PCR\nanalysis were washed three times in a Ringer solution, and\nthe optical density was set to 0.1. The staining of the cells was\nconducted with dihydroethidium (DHE), according to\nLandolfo et al. (Landolfo et al., 2008). The fluorescence\nwas detected at 610 nm, and at least 2·105 cells were\nanalyzed in each experiment. Further data analysis and\nvisualization\nwere\nperformed\nwith\nMATLAB\n(The\nMathWorks, Natick, United States). The typical evaluation\nof flow cytometry data is the calculation of histograms with\nan event count over logarithmically scaled fluorescence. One\nsignificant disadvantage of this technique is the artificial\ncategorization of continuous data. Here, the choice of\nintervals has a decisive influence on the representation\nand possible evaluation based on the histograms. A more\nelegant method is the use of so-called Kernel density\nestimates. These enable a continuous estimation of an\nunknown\ndistribution\nof\ndata\npoints. Calculating\nthe\nprobability density function enables discretization of the\ndata and a more accurate and independent display of the\nresults by creating continuous data. The estimate calculation\nwas based on Eq. 1 shown below, where n = sample size, h =\nbandwidth, and K = Kernel function. Usually, the first step\nwould be to choose the best fitting Kernel function between\nGauß-, rectangular-, triangular-, and Epanechikov-Kernel. In the case of flow cytometry, the vast amount of evaluated\ndata points makes the difference in the resulting estimation\nnegligible. In this study, the Epanechikov-Kernel (Eq. 2) was\nused. However, the bandwidth choice for the density\nfunction\ndistribution\ncalculation\nmakes\na\nsignificant\ndifference. The larger the bandwidth, the smoother the\nfunction,\nand\nthe\npoorly\nrepresented\nthe\nactual\ndistribution. Various methods exist for calculating the\noptimal bandwidth, whereby the method, according to the\nEq. 3 by Silverman, is used here (Silverman, 2018). This\nmethod is a fast, sufficiently good approximation of the\noptimal bandwidth and depends on the standard deviation\nof the data sets and the interquartile range. 2.3 Determination of reactive oxygen\nspecies ^σ = standard deviation, h = bandwidth, K = kernel, \u000b\nfh(x) =\nkernel density estimation. 3.1 Oxygen saturation during propagation DO concentration during yeast propagation in shake flasks\nwas measured using noninvasive optical online sensors. The\nresulting concentrations for all four tested shaking speeds are\nshown in Figure 1. During the first hour post-inoculation, the\noxygen content of the medium increased rapidly. The maximum\nof each curve depends on the respective kLa, generated through\ndifferent shaking speeds. As the duration of the process increases,\nso do the cell count and the associated oxygen uptake rate. The\nlower the speed of the shaker, the less the increased oxygen\ndemand of the cultures can be met. A rapid decline to nearly zero\nwas shown after 30 h, especially in the oxygen saturation at\n100 rpm shaking speed. The oxygen saturation of the medium\nwas coupled with the shaking speed of the flasks. Therefore,\noxygen saturation provided a reasonable basis for the following\nexperiments. 3.2.1 Melting curve analysis and determination of\nPCR amplification efficiency The quality checks performed before gene expression\nanalysis are shown in Figure 2. After extraction, RNA quality\nwas tested using capillary gel electrophoresis (Figure 2A). The\nformation of two distinct bands (28S and 18S RNA) in the upper\npart of the gel indicated good RNA quality. Degradation of RNA\nwould come with a significant band at the bottom of the gel and\nthe absence or low intensity of the 28S and 18S bands. The\ncapillary gel electrophoresis shows RIN values between 7.3 and\n8.6, indicating reliable RNA quality and minor degradation\n(Schroeder et al., 2006). This quality is necessary for the\nfollowing experiments. After testing the integrity of the RNA,\nall primers were tested by checking the specific primer bonding\nusing agarose gel electrophoresis of the resulting amplicons. A\nrepresentative gel of the primers tested is shown in Figure 2B. Frontiers in Chemical Engineering Frontiers in Chemical Engineering 04 frontiersin.org Beugholt et al. 10.3389/fceng.2022.1035348 FIGURE 1\nO2 Saturations in the medium during yeast propagation. The different shaking speeds correspond to the following kLa values: 100 rpm: 51.7 s−1,\n150 rpm: 85.1 s−1, 200 rpm: 123.3 s−1, 250 rpm: 179.8 s−1. FIGURE 1\nO2 Saturations in the medium during yeast propagation. The different shaking speeds correspond to the following kLa values: 100 rpm: 51.7 s−1,\n150 rpm: 85.1 s−1, 200 rpm: 123.3 s−1, 250 rpm: 179.8 s−1. There was just one band indicating one size of amplicons per\nprimer pair and a lack of bands for the NTC. As the last step, the\namplicons were checked by melting curve analysis. The melting\ncurve peaks are characteristic of a particular PCR product. The\nmelting curve analysis served as a qualitative evaluation of the\nPCR product. The curve helps to compare and differentiate\ndifferent PCR products concerning their melting behavior. All\ncurves had a unimodal distribution proving specific primer\nbinding to the target gene (Figure 2C) (Ririe et al., 1997). based on the geometric averaging of multiple logarithmically\ntransformed reference genes and their standard deviations\nduring pairwise variation. In this method, the lowest M value\ncorrelates with the highest stability. Since the reference selection\nis based on non-coregulated genes, stepwise exclusion of the most\nunstable gene results in two reference genes with the most stable\nexpression. Stably expressed reference genes show M values\nlower than 0.5 for homogeneous samples. The last three tested\nreference gene candidates met these criteria (Vandesompele\net al., 2002). 3.2.1 Melting curve analysis and determination of\nPCR amplification efficiency The amplification efficiencies (E) for the eight candidate\nreference genes ranged from 1.75 to 2.36, and standard errors\n(SD) were between 0.027 and 0.170 (Table 3). Agarose gel\nelectrophoresis of all reference gene amplicons showed one\nsingle band, and the additional melting curve analysis revealed\nthe presence of a single peak, indicating the specificity of the\nprimers used. No signal was detected in the negative controls for\nall eight reference genes. Normalization by multiple reference genes is required to\nincrease measurement stability under different experimental\nconditions. The\nbest\nreference\ngene\ncombination\nalways\ncompromises\naccuracy\nand\npractical\nconsiderations. The\npairwise variation is calculated between the two consecutive\nnormalization factors NFn and NFn+1 to assess whether the\ninclusion\nof\nmore\ngenes\nis\nhelpful\nfor\nnormalization. Reference genes are added until the (n+1)th gene has no\nsignificant effect on the recalculated normalization factor. The\nvalue of V3/4, displayed in Figure 3, is already under the threshold\nof 0.15 suggested by Vandesompele et al., below which the\ninclusion\nof\nadditional\nreference\ngenes\nis\nnot\nrequired\n(Vandesompele et al., 2002). In the shown case, the inclusion\nof a fourth reference gene had no significant effect on\nnormalization. Together with the M values shown in Figure 4,\nthe resulting reference gene system for the following gene\nexpression experiments consists of the genes KRE11, UBC6,\nand TAF10. Both quality criteria, the M value, and the V Frontiers in Chemical Engineering 3.2.2 Reference gene system for S. pastorianus The built-in geNorm algorithm of qBase Plus was used to\ncalculate the M and V values and to evaluate the average\nexpression stability of the reference genes. The M value is a\nmeasure used to determine the expression stability of control\ngenes based on non-normalized expression levels. Unlike ideal\nreference genes, real genes are not consistently expressed under\nall experimental conditions. Variations in expression ratios\nindicate unstable expression of reference gene candidates. The\nM value defines the expression stability of all reference genes Frontiers in Chemical Engineering Frontiers in Chemical Engineering 05 frontiersin.org Beugholt et al. 10.3389/fceng.2022.1035348 FIGURE 2\n(A) Capillary gel electrophoresis of six representative RNA samples. The leftmost sample shows the ladder. Two distinct bands (28S and 18S RNA)\nindicate intact RNA samples and good RNA quality after extraction. (B) Agarose gel electrophoresis of three representative primers and one no-\ntemplate control with a 100 bp ladder leftmost. One single DNA band indicates specific primer bonding and the suitability of the primers. (C) Melting\ncurve analysis of the PCR amplicons. FIGURE 2\n(A) Capillary gel electrophoresis of six representative RNA samples. The leftmost sample shows the ladder. Two distinct bands (28S and 18S RNA)\nindicate intact RNA samples and good RNA quality after extraction. (B) Agarose gel electrophoresis of three representative primers and one no-\ntemplate control with a 100 bp ladder leftmost. One single DNA band indicates specific primer bonding and the suitability of the primers. (C) Melting\ncurve analysis of the PCR amplicons. value,\nare\nbelow\nthe\nminima\nsuggested\nby\nliterature\n(Vandesompele\net\nal.,\n2002),\nrendering\nthe\ndeveloped\nreference gene system suitable for the following analysis. preculture was treated the same way for every sample, the 0- and 4-h\nsamples were expected to be analogous. The 48-h samples showed a\ntwo- to 3-fold increase in expression compared to the 0-h sample. After 72 h, the 100 rpm sample had an even higher expression. The\nCTA1 gene tested in this experiment was responsible for the catalase\nproduction of the cell. This metal-dependent enzyme is part of the\nprimary defense mechanisms against ROS. Catalase reduces the\nhydrogen peroxide content in the cell by reducing it using the\ndismutase mechanism (Toledano et al., 2003). Hydrogen peroxide is\na product of oxygen reduction built as a by-product of cellular\nrespiration. It enables the formation of other radicals in cells and is\nan essential part of reactive oxygen species. 3.2.2 Reference gene system for S. pastorianus Due to the relationship\nbetween catalase and ROS, CTA1 expression should directly 3.2.3 Influence of aeration on relative gene\nexpression The results of the CTA1 gene expression analysis for four\ndifferent kLa over the experimental time of 72 h relative to the\ndeveloped reference gene system are shown in Figure 5: Relative\nexpression of CTA1 gene during yeast propagation in shake flasks,\nincluding the 95% confidence interval. The data show increased\nexpression of the CTA1 gene after 48 h. For the first 24 h, there was a\nlow expression for all tested samples and shaking speeds. Since the Frontiers in Chemical Engineering 06 frontiersin.org Beugholt et al. 10.3389/fceng.2022.1035348 TABLE 3 Amplification efficiencies and standard errors of designed\nprimers. Gene\nBase for exponential\namplification E\nStandard error\nYRB1\n2.106\n0.027\nPGK1\n1.954\n0.027\nALG9\n1.754\n0.172\nPFK1\n2.340\n0.080\nTFC1\n2.122\n0.038\nTAF10\n2.158\n0.041\nUBC6\n1.833\n0.046\nKRE11\n1.880\n0.041\nCTA1\n2.364\n0.154\nFIGURE 3\ngeNorm V analysis for optimal reference gene number\ndetermination. Pairwise variation was used to determine the\nminimum number of reference genes for normalization. According to Vandesompele et al. (2002) variations below the\ncut-off value of 0.15, displayed as a dashed horizontal line, indicate\nno significant contribution of an additional control gene to the\nnormalization factor. Beugholt et al. TABLE 3 Amplification efficiencies and standard errors of designed\nprimers. FIGURE 4\ngeNorm M analysis for analysis of reference gene stability. More stably expressed genes were positioned on the right side of\nthe diagram and less stably expressed on the left side. Reference\ngenes with mean stability values below 0.5 are considered to\nbe stably expressed. Gene\nBase for exponential\namplification E\nStandard error\nYRB1\n2.106\n0.027\nPGK1\n1.954\n0.027\nALG9\n1.754\n0.172\nPFK1\n2.340\n0.080\nTFC1\n2.122\n0.038\nTAF10\n2.158\n0.041\nUBC6\n1.833\n0.046\nKRE11\n1.880\n0.041\nCTA1\n2.364\n0.154 FIGURE 3\ngeNorm V analysis for optimal reference gene number\ndetermination. Pairwise variation was used to determine the\nminimum number of reference genes for normalization. According to Vandesompele et al. (2002) variations below the\ncut-off value of 0.15, displayed as a dashed horizontal line, indicate\nno significant contribution of an additional control gene to the\nnormalization factor. FIGURE 4\ngeNorm M analysis for analysis of reference gene stability. More stably expressed genes were positioned on the right side of\nthe diagram and less stably expressed on the left side. Reference\ngenes with mean stability values below 0.5 are considered to\nbe stably expressed. samples of the 200 rpm experiment over time. 3.2.3 Influence of aeration on relative gene\nexpression The 200 rpm samples\nwere chosen because of their representative character for the other\nexperiments that showed similar results. Dihydroethidium is\noxidized in the cell by ROS superoxide and hydrogen peroxide. As a result, fluorescence can be measured at 610 nm. Fluorescence\ncorrelates directly with the amount of ROS in the cell. At the\nbeginning of each experiment, the main portion of the investigated\ncells had a fluorescence below 104 procedure-defined units (p.d.u.). After 4 h, a trimodal distribution formed with peaks at 105 p.d.u. and\napproximately 5·106 p.d.u. After 24 h, there was a huge shift toward a\nfluorescence of 106. After 48 h, the fluorescence decreased again\nbelow 106. After 72 h, the fluorescence was still decreasing. geNorm V analysis for optimal reference gene number\ndetermination. Pairwise variation was used to determine the\nminimum number of reference genes for normalization. According to Vandesompele et al. (2002) variations below the\ncut-off value of 0.15, displayed as a dashed horizontal line, indicate\nno significant contribution of an additional control gene to the\nnormalization factor. geNorm V analysis for optimal reference gene number\ndetermination. Pairwise variation was used to determine the\nminimum number of reference genes for normalization. According to Vandesompele et al. (2002) variations below the\ncut-off value of 0.15, displayed as a dashed horizontal line, indicate\nno significant contribution of an additional control gene to the\nnormalization factor. The logarithmic fluorescence of DHE for the 24-h samples of all\ntested shaking speeds is shown in Figure 7. The displayed samples are\nrepresentative selections. The first measurement after inoculation was\nadded as a comparative value with the fluorescence of approximately\n104 p.d.u. The prominent peaks of the resulting graphs are around a\nvalue of 106 p.d.u. The 150 rpm and 200 rpm graphs had a unimodal\ndistribution. At 100 rpm and 250 rpm, there was a bimodal\ndistribution. For 100 rpm and 250 rpm, the distribution has a\nportion of cells with a fluorescence of 104 p.d.u., which is the\nreference value of the 0-h sample. This suggests that this portion\nof the cells did not react with the dye and could be excluded from\nfurther analysis. In this case, the remaining. correlate with oxidative stress in the cell. Overall, there seems to be a\ntrend in increasing CTA1 expression after 48 h, although there was\nno significant difference between the samples under different\nexperimental conditions. 4 Discussion mRNA was successfully extracted from\nthe cells and the subsequent quality check using capillary gel\nelectrophoresis showed two distinct bands of 28S and 18S RNA\nand the absence of a strong lower band. The resulting bands\nindicate minor degradation of the extracted RNA. Additionally,\ncapillary gel electrophoresis was utilized to determine the quality\nof the RNA. RIN values between 7.3 and 8.6 indicate suitable\nRNA quality for the following steps. Agarose gel electrophoresis\nwas used to test specific primer bonding. The absence of multiple\nbands and a negative NTC prove the reliability of the synthesized\ncDNA. The unimodal form of the melting curves also indicates\nthe specific primer bonding. The reference gene system was\ndeveloped by using the geNorm algorithm. In a first step, all\npotential reference genes were sorted by stability calculating the\ngeNorm M value. In a second step, the geNorm V value calculates\nthe optimal number of reference genes. The three most stably expressed genes were successfully utilized as reference for the\ntranscription analysis of the CTA1 target gene in yeast samples\npropagated in lager beer wort. The CTA1 gene, coding for the\nenzyme catalase, that plays a major role in ROS degradation, was\nused to indicate oxidative stress in S. pastorianus cells under\ndifferent aeration conditions. Intracellular reactive oxygen\nspecies\nwere\nmeasured\nusing\nflow\ncytometry\nwith\ndihydroethidium\nstaining. The\nresulting\nfluorescence\nat\n610 nm correlates directly with the amount of ROS in the\ncells. In conjunction with the CTA1 transcription analysis,\nthis measurement enabled a time-resolved insight into the\nbuild-up of oxidative stress and the cellular stress response. Comparing the results from the expression analysis with the\nresults of the ROS determination, the ROS build-up took 24 h. The expression of CTA1 as a reaction of the cell to the increasing\nROS content increased after 48 h. The higher CTA1 expression\nmight be a reason for the decreasing ROS content, since catalase\ncatalyzed ROS degradation; the genes expression appears to\nfollow the increasing ROS content of the cell in a delayed\nfashion. Cells cultivated under low aerobic conditions showed\na similar fluorescence behavior as those cultivated under the\nhigher aeration efficiencies. Contrary to intuitive assumptions,\nthe ROS built up independently of the shaking speed for the\ninvestigated conditions. This phenomenon follows the results of\nthe gene expression analysis. In these experiments, increased\nCTA1 expression was shown after 48 h. 4 Discussion Applying the equations described in 2.3 to the flow cytometry\ndata results in the graphs shown in Figure 6. It shows the triplicate Saccharomyces is one of the most important industrially used\nyeasts and therefore needs to be supplied in a sufficient quantity Frontiers in Chemical Engineering 07 frontiersin.org Beugholt et al. 10.3389/fceng.2022.1035348 FIGURE 5\nRelative expression of CTA1 gene during yeast propagation in shake flasks, including the 95% confidence interval. The data show increased\nexpression of the CTA1 gene after 48 h. FIGURE 5\nRelative expression of CTA1 gene during yeast propagation in shake flasks, including the 95% confidence interval. The data show increased\nexpression of the CTA1 gene after 48 h. FIGURE 6\nProbability density function (PDF) of dihydroethidium fluorescence data from flow cytometry measurements. The data from the 200 rpm\npropagations was representative of the other experiments. FIGURE 6\nProbability density function (PDF) of dihydroethidium fluorescence data from flow cytometry measurements. The data from the 200 rpm\npropagations was representative of the other experiments. 08 Frontiers in Chemical Engineering frontiersin.org frontiersin.org Beugholt et al. 10.3389/fceng.2022.1035348 FIGURE 7\nProbability density function of dihydroethidium fluorescence data from cytometry measurements after 24 h. The peak location indicates the\nprobability that a cell will fluoresce at a certain level. The course of the graph indicates the distribution of fluorescence in the cell population. FIGURE 7\nProbability density function of dihydroethidium fluorescence data from cytometry measurements after 24 h. The peak location indicates the\nprobability that a cell will fluoresce at a certain level. The course of the graph indicates the distribution of fluorescence in the cell population. and vitality. One of the key factors to efficient yeast propagation\nis oxygen supply to avoid growth limitations. Brewer´s yeast S. pastorianus is a genetic hybrid of S. cerevisiae and S. eubayanus\nthat shows high phenotypic and genomic similarities to S. cerevisiae and is highly relevant to industrial beer production. The presented study investigated the effect of aeration levels on\noxidative stress response during the propagation of brewing\nyeast. For that purpose, a reference gene system for RT-qPCR\nanalysis of S. pastorianus was developed: primers for an array of\npotential reference genes were screened for amplification\nefficiency\nand\ntarget\nexpression\nstability\nunder\ndifferent\naeration conditions. Frontiers in Chemical Engineering Funding This Project (ZF4025035SK9) was part of the “ZIM”\n(Zentrales\nInnovationsprogramm\nMittelstand)\nfunding\nprogram and supported by the Federal Ministry for Economic\nAffairs and Climate Action (BMWK) on the basis of a decision by\nthe German Bundestag. Conflict of interest The authors declare that the research was conducted in the\nabsence of any commercial or financial relationships that could\nbe construed as a potential conflict of interest. Author contributions AB. Data collection and drafted the article, Conception or\ndesign of the work KB. Conception or design of the work DG. Publisher’s note All claims expressed in this article are solely those of the authors\nand do not necessarily represent those of their affiliated organizations,\nor those of the publisher, the editors and the reviewers. Any product\nthat may be evaluated in this article, or claim that may be made by its\nmanufacturer, is not guaranteed or endorsed by the publisher. Data availability statement The original contributions presented in the study are\nincluded\nin\nthe\narticle/supplementary\nmaterial,\nfurther\ninquiries can be directed to the corresponding authors. 4 Discussion The expression, however,\nlike the fluorescence values, was independent of the cultivation and vitality. One of the key factors to efficient yeast propagation\nis oxygen supply to avoid growth limitations. Brewer´s yeast S. pastorianus is a genetic hybrid of S. cerevisiae and S. eubayanus\nthat shows high phenotypic and genomic similarities to S. cerevisiae and is highly relevant to industrial beer production. Frontiers in Chemical Engineering Frontiers in Chemical Engineering 09 frontiersin.org Beugholt et al. 10.3389/fceng.2022.1035348 conditions. The presented data of gene expression analysis as an\nindicator for the cellular defence reaction of Saccharomyces yeast\nto higher aeration rates in combination with flow cytometry\nanalysis as an indicator for the overall cell reaction can give useful\ninformation for later applications. An overall similar trend\nemerges between different samples propagated at different kLa\nvalues. This indicates that the aeration efficiency in the tested\nrange does not provoke a cellular reaction. The tested oxygen\nsupply conditions cover kLa values of industrial relevance;\ntherefore, these results indicate the possible usage of higher\noxygen concentrations in industrial yeast propagation. With\nthis\ndata,\nthe\nstudy\nlays\nthe\nfoundation\nfor\nfurther\ninvestigation and optimization of industrially relevant yeast\npropagation processes on a molecular level. Critical revision of the article TB. Final approval of the version to\nbe published. References Jamieson, D. J. (1998). Oxidative stress responses of the yeast Saccharomyces\ncerevisiae. Yeast 14 (16), 1511–1527. doi:10.1002/(SICI)1097-0061.14:16<1511::\nAID-YEA356>3.0.CO;2-S Jamieson, D. J. (1998). Oxidative stress responses of the yeast Saccharomyces\ncerevisiae. Yeast 14 (16), 1511–1527. doi:10.1002/(SICI)1097-0061.14:16<1511::\nAID-YEA356>3.0.CO;2-S Alexander, M. A., and Jeffries, T. W. (1990). Respiratory efficiency and metabolite\npartitioning as regulatory phenomena in yeasts. Enzyme Microb. Technol. 12 (1),\n2–19. doi:10.1016/0141-0229(90)90173-N Bayir, H. (2005). Reactive oxygen species. Crit. Care Med. 33 (12 Suppl. l),\nS498–S501. doi:10.1097/01.CCM.0000186787.64500.12 Jamieson, D. J. (1992). Saccharomyces cerevisiae has distinct adaptive responses to\nboth hydrogen peroxide and menadione. J. Bacteriol. 174 (20), 6678–6681. doi:10. 1128/jb.174.20.6678-6681.1992 Baynes, J. W., and Dominiczak, M. H. (2019). Medical biochemistry. 5th edition. Amsterdam, Netherlands: Elsevier. Available at: https://ebookcentral.proquest. com/lib/kxp/detail.action?docID=5493083. Baynes, J. W., and Dominiczak, M. H. (2019). Medical biochemistry. 5th edition. Amsterdam, Netherlands: Elsevier. Available at: https://ebookcentral.proquest. com/lib/kxp/detail.action?docID=5493083. Jamieson, D. J. (1995). The effect of oxidative stress on Saccharomyces cerevisiae. Redox Rep. 1 (2), 89–95. doi:10.1080/13510002.1995.11746964 Jamieson, D. J. (1995). The effect of oxidative stress on Saccharomyces cerevisiae. Redox Rep. 1 (2), 89–95. doi:10.1080/13510002.1995.11746964 Cherry, J. M., Hong, E. L., Amundsen, C., Balakrishnan, R., Binkley, G., Chan, E. T., et al. (2012). Saccharomyces Genome Database: The genomics resource of\nbudding yeast. Nucleic Acids Res. 40, D700–D705. doi:10.1093/nar/gkr1029 J. R. Dickinson and M. Schweizer (Editors) (2005). The metabolism and molecular\nphysiology of Saccharomyces cerevisiae. Second edition (Boca Raton, Florida: CRC\nPress). Available\nat:\nhttps://ebookcentral.proquest.com/lib/kxp/detail.action? docID=5850754. Dragosits, M., Mattanovich, D., and Gasser, B. (2011). Induction and\nmeasurement of UPR and osmotic stress in the yeast Pichia pastoris. Methods\nEnzymol. 489, 165–188. doi:10.1016/B978-0-12-385116-1.00010-8 Landolfo, S., Politi, H., Angelozzi, D., and Mannazzu, I. (2008). Ros accumulation\nand oxidative damage to cell structures in Saccharomyces cerevisiae wine strains\nduring fermentation of high-sugar-containing medium. Biochimica Biophysica Acta\n- General Subj. 1780 (6), 892–898. doi:10.1016/j.bbagen.2008.03.008 Landolfo, S., Politi, H., Angelozzi, D., and Mannazzu, I. (2008). Ros accumulation\nand oxidative damage to cell structures in Saccharomyces cerevisiae wine strains\nduring fermentation of high-sugar-containing medium. Biochimica Biophysica Acta\n- General Subj. 1780 (6), 892–898. doi:10.1016/j.bbagen.2008.03.008 Frankenberg,\nD.,\nFrankenberg-Schwager,\nM.,\nand\nHarbich,\nR. (1993). Mechanisms of oxygen radiosensitization in irradiated yeast. I. Dna double-\nstrand\nbreakage. Int. J. Radiat. Biol. 64\n(5),\n511–521. doi:10.1080/\n09553009314551721 Lee, J., Romeo, A., and Kosman, D. J. (1996). Transcriptional remodeling and\nG1 arrest in dioxygen stress in Saccharomyces cerevisiae. J. Biol. Chem. 271 (40),\n24885–24893. doi:10.1074/jbc.271.40.24885 Lee, J., Romeo, A., and Kosman, D. J. (1996). Moradas-Ferreira, P., Costa, V., Piper, P., and Mager, W. (1996). The molecular\ndefences against reactive oxygen species in yeast. Mol. Microbiol. 19 (4), 651–658.\ndoi:10.1046/j.1365-2958.1996.403940.x References Transcriptional remodeling and\nG1 arrest in dioxygen stress in Saccharomyces cerevisiae. J. Biol. Chem. 271 (40),\n24885–24893. doi:10.1074/jbc.271.40.24885 Halliwell, B., and Gutteridge, J. M. C. (2005). Free radicals in biology and\nmedicine. Oxford, UK: Oxford science publications. Oxford Univ. Press, 3. Lushchak, V. I., and Gospodaryov, D. V. (2005). Catalases protect cellular\nproteins from oxidative modification in. Cell Biol. Int. 29 (3), 187–192. doi:10. 1016/j.cellbi.2004.11.001 Lushchak, V. I., and Gospodaryov, D. V. (2005). Catalases protect cellular\nproteins from oxidative modification in. Cell Biol. Int. 29 (3), 187–192. doi:10. 1016/j.cellbi.2004.11.001 Hellemans, J., Mortier, G., Paepe, A. de, Speleman, F., and Vandesompele, J. (2007). Qbase relative quantification framework and software for management and\nautomated analysis of real-time quantitative PCR data. Genome Biol. 8 (2), R19. doi:10.1186/gb-2007-8-2-r19 Monerawela, C., and Bond, U. (2018). The hybrid genomes of Saccharomyces\npastorianus: A current perspective. Yeast (Chichester, Engl. 35 (1), 39–50. doi:10. 1002/yea.3250 Monerawela, C., and Bond, U. (2018). The hybrid genomes of Saccharomyces\npastorianus: A current perspective. Yeast (Chichester, Engl. 35 (1), 39–50. doi:10. 1002/yea.3250 Ishmayana, S., Kennedy, U. J., and Learmonth, R. P. (2017). Further investigation\nof relationships between membrane fluidity and ethanol tolerance in Saccharomyces\ncerevisiae. World J. Microbiol. Biotechnol. 33 (12), 218. doi:10.1007/s11274-017-\n2380-9 Moradas-Ferreira, P., Costa, V., Piper, P., and Mager, W. (1996). The molecular\ndefences against reactive oxygen species in yeast. Mol. Microbiol. 19 (4), 651–658. doi:10.1046/j.1365-2958.1996.403940.x 10 Frontiers in Chemical Engineering frontiersin.org Beugholt et al. Beugholt et al. 10.3389/fceng.2022.1035348 Perrone, G. G., Tan, S.-X., and Dawes, I. W. (2008). Reactive oxygen species and\nyeast apoptosis. Biochimica Biophysica Acta - Mol. Cell Res. 1783 (7), 1354–1368. doi:10.1016/j.bbamcr.2008.01.023 Perrone, G. G., Tan, S.-X., and Dawes, I. W. (2008). Reactive oxygen species and\nyeast apoptosis. Biochimica Biophysica Acta - Mol. Cell Res. 1783 (7), 1354–1368. doi:10.1016/j.bbamcr.2008.01.023 Steels, E. L., Learmonth, R. P., and Watson, K. (1994). Stress tolerance and\nmembrane lipid unsaturation in Saccharomyces cerevisiae grown aerobically or\nanaerobically. Microbiology 140 (Pt 3), 569–576. doi:10.1099/00221287-140-3-569 Temple, M. D., Perrone, G. G., and Dawes, I. W. (2005). Complex cellular\nresponses to reactive oxygen species. Trends Cell Biol. 15 (6), 319–326. doi:10.1016/\nj.tcb.2005.04.003 PreSens Precision Sensing GmbH (2022). kla-calculator. Available at: https://\nwww.presens.de/support-services/kla-calculator. PreSens Precision Sensing GmbH (2022). kla-calculator. Available at: https://\nwww.presens.de/support-services/kla-calculator. Rasmussen, R. (2001). “Quantification on the LightCycler,” in Rapid cycle\nreal-time PCR. Editors S. Meuer, C. Wittwer, and K.-I. Nakagawara (Springer\nBerlin Heidelberg), 21–34. doi:10.1007/978-3-642-59524-0_3 Toledano, M. References B., Delaunay, A., Biteau, B., Spector, D., and Azevedo, D. (2003). “Oxidative stress responses in yeast,” in Topics in current genetics. Yeast stress\nresponses. Editors S. Hohmann and W. H. Mager (Springer Berlin Heidelberg), 1,\n241–303. doi:10.1007/3-540-45611-2_6 Ririe, K. M., Rasmussen, R. P., and Wittwer, C. T. (1997). Product differentiation\nby analysis of DNA melting curves during the polymerase chain reaction. Anal. Biochem. 245 (2), 154–160. doi:10.1006/abio.1996.9916 Vandesompele, J., Preter, K. de, Pattyn, F., Poppe, B., Roy, N., Paepe, A. de, et al. (2002). Accurate normalization of real-time quantitative RT-PCR data by geometric\naveraging of multiple internal control genes. Genome Biol. 3, RESEARCH0034.1. doi:10.1186/gb-2002-3-7-research0034 Schroeder, A., Mueller, O., Stocker, S., Salowsky, R., Leiber, M., Gassmann, M.,\net al. (2006). The RIN: An RNA integrity number for assigning integrity values to\nRNA measurements. BMC Mol. Biol. 7, 3. doi:10.1186/1471-2199-7-3 Verbelen, P. J., Depraetere, S. A., Winderickx, J., Delvaux, F. R., and Delvaux, F. (2009). The influence of yeast oxygenation prior to brewery fermentation on yeast\nmetabolism and the oxidative stress response. FEMS Yeast Res. 9 (2), 226–239. doi:10.1111/j.1567-1364.2008.00476.x Silverman, B. W. (2018). Density estimation for statistics and data analysis. Chapman Hall/CRC Monogr. Statistics Appl. Probab. 26 Routledge. Available at:\nhttps://ebookcentral.proquest.com/lib/kxp/detail.action?docID=5475481. 11 frontiersin.org Frontiers in Chemical Engineering"}}},{"rowIdx":12595,"cells":{"identifier":{"kind":"string","value":"https://openalex.org/W4244115734"},"pdf_url":{"kind":"string","value":"https://www.scielo.br/j/rbee/a/vzkQ9frsmTWwftWBCbh4QTM/?lang=pt&format=pdf"},"lang":{"kind":"string","value":"Portuguese"},"error":{"kind":"null"},"title":{"kind":"string","value":"Editorial"},"source_name":{"kind":"string","value":"Revista brasileira de educação especial"},"publication_year":{"kind":"number","value":2006,"string":"2,006"},"license":{"kind":"string","value":"cc-by"},"word_count":{"kind":"number","value":754,"string":"754"},"text":{"kind":"string","value":"Rev. Bras. Ed. Esp., Marília, Mai.-Ago. 2006, v.12, n.2, p.147-148 Editorial Editorial EDITORIAL Prezados sócios da ABPEE e leitores da Revista Brasileira de Educação Prezados sócios da ABPEE e leitores da Revista Brasileira de Educação\nEspecial. Especial. Informamos a todos que conseguimos atingir mais uma das metas para\na divulgação da ABPEE: a partir de agora, todos os números da Revista Brasileira\nde Educação Especial, desde 1992 ao número 1 de 2006, poderão ser acessados na\nnossa homepage, que foi atualizada - www.marilia.unesp.br/abpee. Esse novo\nempreendimento permitirá que os pesquisadores possam acessar as revistas esgo-\ntadas e usá-las como fonte de referência. O número 2, volume 12, de 2006, da Revista Brasileira de Educação\nEspecial apresenta sete relatos de pesquisa. Como o leitor poderá verificar, os artigos\npublicados relatam pesquisas sobre deficiência visual, mental, auditiva, física e\nmúltipla deficiência. O primeiro artigo apresenta pesquisa sobre o ensino de física, mais\nespecificamente a termologia. Os autores, durante um curso de licenciatura em\nfísica, analisam as produções dos formandos sobre suas idéias para a adaptação\ncurricular para o ensino de alunos com deficiência visual. Por meio de uma\nabordagem qualitativa, as categorias identificadas poderão ser de ajuda para futuros\npesquisadores para nortear a análise em pesquisa qualitativa. O segundo artigo teve como meta investigar as práticas educativas\nescolares e os procedimentos utilizados pelo educador para promover a\naprendizagem de um aluno com dismotria cerebral ontogenética. O estudo ocorreu\nem sala de aula e no ambiente escolar. A metodologia contou com a coleta de\ndados por meio de observações, entrevista e análise de documentos do aluno, como\nredação, provas, atividades acadêmicas. Os resultados, segundo os autores,\nindicaram que, do ponto de vista de aprendizagem, não houve inclusão educacional,\nas práticas educativas observadas não contemplaram a especificidade curricular e\nde aprendizagem a fim de atender às necessidades do aluno. O terceiro artigo trata de um tema importante e com poucas pesquisas\nna área de educação especial: política de atendimento aos alunos com necessidades\neducacionais especiais. O campo de pesquisa foi a Rede Municipal de Ensino de\nSão Paulo e focalizou as ações direcionadas ao aluno com deficiência mental nas\nSalas de Atendimento aos Portadores de Necessidades Especiais (SAPNE). Os\nautores indicam a necessidade de investimentos nos serviços que deveriam ser\ngarantidos por uma política que vise ações inclusivas. 147 Rev. Bras. Ed. Esp., Marília, Mai.-Ago. Rev. Bras. Ed. Esp., Marília, Mai.-Ago. 2006, v.12, n.2, p.147-148 Editorial 2006, v.12, n.2, p.147-148 O quarto estudo se refere ao processo de normatização e validação da\nsegunda versão do Teste de Nomeação de Figuras por Escolha, destinado à pessoas\nsurdas. O teste avalia o desenvolvimento da competência de leitura e analisa a\nparticipação de processos quirêmicos, ortográficos e semânticos envolvidos na\nescolha de palavras escritas para nomear figuras que representam conceitos\nconhecidos (em especial, objetos ou animais) da população escolar no Ensino\nFundamental. Trata-se de mais um instrumento que poderá auxiliar pesquisadores\ne educadores. Os dois outros artigos que seguem tratam da problemática da\nprofissionalização e trabalho da pessoa com deficiência. O primeiro estudo dentro\ndesse tema descreve o processo de planejamento, desenvolvimento, implementação\ne avaliação de diversos serviços relativos à formação do deficiente mental para o\ntrabalho. O segundo estudo apresenta uma descrição das práticas que vêm sendo\nadotadas para inclusão de pessoa com deficiência no mercado de trabalho e as\neventuais dificuldades encontradas nesse processo. A investigação incide sobre as\nempresas que empregam jovens e adultos com necessidades especiais e as\ninstituições que promovem a profissionalização desses usuários. O sétimo artigo se refere à avaliação do benefício proporcionado pelo\naparelho de amplificação sonora individual (AASI). A coleta de dados foi realizada\npor questionários de auto-avaliação aplicados a crianças e adolescentes usuários\nde AASI na faixa etária de 7 a 14 anos. Os resultados indicam os ambientes,\nmomentos, tempo de uso do AASI e os benefícios, segundo a percepção dos alunos\nsurdos, fornecidos pelo aparelho. O último artigo apresenta importante estudo na área de comunicação\nalternativa sobre enunciados de um aluno não-falante usuário de recurso\nsuplementar de comunicação durante a construção de histórias. O artigo apresenta\nvários exemplos de narrativa que foram construídos por meio de recursos para\nauxiliar a comunicação. Fechando o volume 12, número 2, são apresentadas as resenhas de dois\nlivros: Inclusão e avaliação na escola de alunos com necessidades educacionais especiais,\nde Hugo Otto Beyer e Inclusão Social: formação do deficiente mental para o trabalho,\norganizado por Celso Goyos e Eliane Araújo. Eduardo José Manzini\nEditor 148 Rev. Bras. Ed. Esp., Marília, Mai.-Ago. 2006, v.12, n.2, p.147-148"}}},{"rowIdx":12596,"cells":{"identifier":{"kind":"string","value":"https://openalex.org/W2884134084"},"pdf_url":{"kind":"string","value":"https://www.scielo.br/j/abmvz/a/cnZ48SPtSzpYbLgdzKyg76d/?lang=pt&format=pdf"},"lang":{"kind":"string","value":"Portuguese"},"error":{"kind":"null"},"title":{"kind":"string","value":"Parâmetros fisiológicos de vacas F1 Holandês x Zebu criadas em ambientes com e sem sombreamento"},"source_name":{"kind":"string","value":"Arquivo Brasileiro de Medicina Veterinária e Zootecnia/Arquivo brasileiro de medicina veterinária e zootecnia"},"publication_year":{"kind":"number","value":2018,"string":"2,018"},"license":{"kind":"string","value":"cc-by"},"word_count":{"kind":"number","value":5340,"string":"5,340"},"text":{"kind":"string","value":"RESUMO Objetivou-se, com este estudo, caracterizar o efeito do microclima proporcionado por dois ambientes \ndistintos, sobre as respostas fisiológicas de vacas F1 HxZ em fase de lactação, durante o verão. Foram \navaliadas 34 vacas oriundas de quatro diferentes grupos genéticos F1 HxZ. Durante o período \nexperimental, foram feitas medições diárias das variáveis ambientais: temperatura do ar, umidade relativa \ndo ar e temperatura de globo negro, para cálculo dos valores de ITGU. Os parâmetros fisiológicos \nfrequência respiratória, batimento cardíaco, temperatura de superfície corporal, temperatura retal e taxa de \nsudação foram obtidos às 7h e às 14 horas. A pesagem do leite foi feita semanalmente. Os animais F1 \navaliados não apresentaram alterações fisiológicas, e não houve redução na produção láctea em função \ndos ambientes de criação. O ITGU atingiu valores considerados estressantes (87,7), porém os ambientes \nde criação não proporcionaram estresse nem redução na produção dos animais. Palavras-chave: ambiência, bem-estar animal, bovino leiteiro, estresse térmico, heterose [Physiological parameters of F1 Holstein X Zebu cows raised in environments with and without shading] A.L.O. Castro, C.C.S. Carvalho*, J.R.M. Ruas, K.C.B. Pereira, G.C.C. Menezes, M.D. Costa Universidade Estadual de Montes Claros ˗ Janaúba, MG Universidade Estadual de Montes Claros ˗ Janaúba, MG http://dx.doi.org/10.1590/1678-4162-9305 Arq. Bras. Med. Vet. Zootec., v.70, n.3, p.722-730, 2018 Keywords: ambience, animal welfare, bovine, heat stress, heterosis Keywords: ambience, animal welfare, bovine, heat stress, heterosis Recebido em 15 de julho de 2016 \nAceito em 28 de setembro de 2017 \n*Autor para correspondência (corresponding author) \nE-mail: cinara.carvalho@unimontes.br ABSTRACT The objective of this study was to characterize the effect of microclimate provided by two distinct \nenvironments on the physiological responses of F1 HxZ cows lactating during the summer, where 34 \ncows were evaluated originating from 4 different genetic groups F1 HxZ. During the trial period, daily \nmeasurements of environmental variables were determined: dry bulb temperature, relative humidity and \nblack globe temperature, to calculate the BGT values. The physiological parameters respiratory rate, \nheart rate, body surface temperature, rectal temperature, and sweat rate were obtained at 07:00 and \n14:00h. Weighing of milk was done weekly. The F1 animals evaluated did not present physiological \nchanges, nor was there a reduction in milk production as a function of breeding environments. The BGT \nreached levels considered stressful (87.7), but the breeding environments provided no stress or reduced \nproduction of animals. INTRODUÇÃO ao \nconjunto \nde \nfatores \nambientais \nque \ncaracterizam o sistema de produção da região, \npodendo esses ser favoráveis a alguns genótipos \ne desfavoráveis a outros (Mcmanus et al., 2008). Portanto, para aperfeiçoar a produção leiteira, é \nimportante \nidentificar \nos \ngenótipos \nmais \nconvenientes a cada região. Nos países de clima tropical, o aumento na \nprodução leiteira é limitado pelos baixos níveis \nprodutivos das raças nativas e pelas dificuldades \nadaptativas das raças de origem europeia \n(Vasconcellos et al., 2003). Como uma alternativa viável para o aumento da \neficiência produtiva, utiliza-se o cruzamento A eficácia produtiva e reprodutiva dos animais \nestá relacionada à adaptação dos seus genótipos Parâmetros fisiológicos... genético envolvendo raças de origem indiana \n(zebuínos) e raças de origem europeia (taurinos), \nconciliando, assim, o potencial produtivo das \nraças taurinas com a rusticidade e resistência ao \nclima tropical das raças zebuínas, por meio \nda \nheterose. A \nheterose \nconfere \nmaior \nadaptabilidade \naos \nanimais, \ncontudo \ncom \nrespostas produtivas baseadas nos efeitos do \nambiente em que estão inseridos. sombra), sobre as respostas fisiológicas de vacas \nF1 HxZ na fase de lactação, durante o verão. MATERIAL E MÉTODOS O presente estudo foi submetido e aprovado pelo \nComitê de Ética em Experimentação e Bem-\nEstar animal da Universidade Estadual de \nMontes Claros (Processo n° 083/2015). Animais criados a pasto ficam expostos a \nvariações climáticas, radiação solar direta e \nintempéries, que podem vir a influenciar, de \nforma negativa, no sistema termorregulatório \ndeles. Considera-se que a maior influência do \nestresse pelo calor sobre a produção de leite é \nexercida \nvia \ndiminuição \ndo \nconsumo \nde \nalimentos e consequente redução da ingestão de \nenergia metabolizável. Temperaturas diárias \nmédias e máximas têm efeitos variáveis sobre a \ningestão de alimentos e, consequentemente, \nsobre a produção de leite, dependendo da \numidade relativa do ar e do tempo em que as \nvacas ficam em temperaturas capazes de \nprovocar estresse (Azevêdo et al., 2005). O experimento foi conduzido durante os meses \nde fevereiro a abril (verão), com o propósito \nde \ncaracterizar \no \nefeito \ndo \nmicroclima \nproporcionado por dois ambientes distintos sobre \nas respostas fisiológicas de 34 vacas F1 em terço \nfinal de lactação. A área experimental está \nlocalizada a uma latitude de 18° 43’ 52’’ S, \nlongitude de 44° 52’ 33’’ W e com altitude de \n628 metros. O clima é do tipo Aw, segundo a \nclassificação de Köppen (tropical com estação \nseca). O índice pluviométrico anual é de \n1118,9mm, com temperaturas médias anuais de \n22,6°C. Os animais avaliados são provenientes do \ncruzamento de touro Holandês com vacas de \nquatro bases maternas zebuínas distintas, com \n100% de heterose, sendo eles: oito animais \nHolandês (50%) x Nelore (50%); 10 animais \nHolandês (50%) x Gir (50%); 10 animais \nHolandês (50%) x Nelore (25%) x Gir (50%); \nseis animais Holandês (50%) x Guzerá (25%) x \nNelore (25%). A Tab. 1 ilustra a caracterização \nfísica e produtiva do lote estudado. O uso de sombreamento natural com árvores \nisoladas ou bosques, bem como sombrites, são \nestratégias adotadas no sistema de criação a \npasto, para proporcionar conforto, manter a \nhomeotermia e a produção. Nesse contexto, objetivou-se, com este estudo, \ncaracterizar \no \nefeito \ndo \nmicroclima \nproporcionado por dois ambientes distintos (sol e Tabela 1. MATERIAL E MÉTODOS Médias da ordem de partos e do período de lactação (dias), dos grupamentos genéticos, de \nacordo com o ambiente experimental \nGrupamentos \ngenéticos \nAmbiente 1 \nAmbiente 2 \nOrdem de partos \nPeríodo de lactação \nOrdem de partos \nPeríodo de lactação \nH x Gir \n5,4 \n246 \n3,6 \n216 \nH x Nelogir \n4,4 \n204 \n4,4 \n264 \nH x Guzonel \n2,3 \n90 \n2,0 \n50 \nH x Nelore \n3,2 \n142 \n2,0 \n100 . Médias da ordem de partos e do período de lactação (dias), dos grupamentos genéticos, de \nom o ambiente experimental divididos em piquetes de 1 hectare, onde os \nanimais permaneciam pelo período de um dia \n(pastejo rotacionado). A distância deste pasto até \no curral de manejo era de 450 metros. As 34 vacas foram subdivididas em dois grupos \nde 17 animais. Esse número era composto por \nanimais de todos os grupos genéticos, de forma \nque os dois grupos possuíam a mesma \nquantidade de animais de cada grupo genético. Os animais foram alojados em dois ambientes \ndistintos, denominados ambientes 1 e 2. O \nambiente 1 era provido de pastagem sem \nsombreamento, \ncomposto \npor 18 \nhectares O ambiente 2 era composto por 8 hectares, dos \nquais, \naproximadamente, \n2 \nhectares \neram \nprovidos com sombreamento natural, formado \npor bosques de árvores nativas. 723 Arq. Bras. Med. Vet. Zootec., v.70, n.3, p.722-730, 2018 Castro et al. Castro et al. Este pasto possuía uma região de aguada \nutilizada como bebedouro para os animais. A \ndistância do pasto sombreado até o curral de \nmanejo era de 810 metros. posteriormente, \ndeterminada \na \nfrequência \ncardíaca por minuto. A temperatura retal foi registrada por meio do \nuso de um termômetro clínico digital, inserido \ndiretamente no reto do animal. Durante o período experimental, foram feitas \nmedições diárias das variáveis ambientais: \ntemperatura do ar, umidade relativa do ar e \ntemperatura de globo negro, com início às sete e \ntérmino às 16 horas. Para tal, foram utilizados \nquatro termômetros digitais, programados para \ncoletar as variáveis a cada 10 minutos, sendo \ndois dispostos no piquete ao sol e dois em \nsombra, a fim de se caracterizar com maior \nprecisão o local de permanência dos animais. A temperatura de superfície corporal foi medida \nna fronte, no dorso, na canela posterior e no \núbere do animal, por meio de termômetro de \ninfravermelho \ndigital \nportátil. A \nmédia \nponderada foi calculada atribuindo-se peso de \n10% para a fronte, 70% para o dorso, 12% para a \ncanela e 8% para o úbere, de acordo com a \nmetodologia descrita por Pinheiro et al. (2005): TSC = 0,10 x T.fronte + 0,7 x T.dorso + 0,12 x \nT.canela + 0,08 x T.úbere \neq 2 Esses instrumentos específicos para coleta das \nvariáveis climáticas foram instalados a 1,60m do \nsolo. em que: em que: \nTSC = temperatura de superfície corporal \nT = temperatura (°C). Com base nos dados coletados, foi calculado o \níndice de temperatura de globo negro e umidade \n(ITGU), por meio da equação proposta por \nBuffington et al. (1981), obtido com a seguinte \nexpressão: A taxa de sudação foi realizada conforme \nmetodologia descrita por Schleger e Turner \n(1965) e calculada, então pela seguinte fórmula: ITGU = Tgn + 0,36 x Tpo + 41,5 eq. 1, \nem que: S = (22x3600) / (2,06t) = 38446,6/t, g.m-2.h-1 \n eq. 3. S = (22x3600) / (2,06t) = 38446,6/t, g.m-2.h-1 Tpo = temperatura do ponto de orvalho (°C) RESULTADOS E DISCUSSÃO equação de regressão mostra que, a cada hora, \nocorria um aumento de 1,77ºC na temperatura do \nar (Tab. 2). A temperatura do ar foi crescente ao longo do dia \nno ambiente 1 (pasto sem sombreamento) e, a \npartir das 10h da manhã, os animais foram \nexpostos a temperaturas superiores à zona de \ntermoneutralidade fixada para animais zebuínos, \nque é de até 29ºC (Fig. 1 e Tab. 2). A elevação da temperatura do ar é justificada \npela maior radiação solar incidente durante o \nverão, situação rotineira em quase todo território \nnacional que se encontra na faixa tropical \n(Baccari Júnior, 2001). No período da tarde, às 15h, verificou-se o maior \nvalor médio de temperatura do ar, 37,3ºC. A Figura 1. Valores médios de temperatura do ar, umidade relativa do ar e ITGU ao longo do dia, nos pastos \nsem sombreamento e com sombreamento natural. Figura 1. Valores médios de temperatura do ar, umidade relativa do ar e ITGU ao longo do dia, nos past\nsem sombreamento e com sombreamento natural. Tabela 2. Modelos de regressão em função das variáveis climáticas para os dois ambientes experimentais \nVariáveis \nclimáticas \nRegressão \nAmbiente 1 \nAmbiente 2 \nTar (°C) \nŶ=11,59 + 1,77x \nR²=0,97 \nŶ=7,29 + 2,76x - 0, \n086x² \nR²=0,97 \nUR (%) \nŶ=110,09 – 3,96x \nR²=0,97 \nŶ=110,09 – 3, 96x \nR²=0,97 \nITGU \nŶ=53,93 + 4,25x – 0,15x² \nR²=0,98 \nŶ=53,93 + 4, 25x – \n0,15x² \nR²=0,98 Tabela 2. Modelos de regressão em função das variáveis climáticas para os dois ambientes experimentai No ambiente 2 (pasto sombreado), a temperatura \ndo ar foi crescente ao longo do dia, porém não \nultrapassou \na \nzona \nde \ntermoneutralidade \nconsiderável para bovinos, mesmo no período da \ntarde, quando a temperatura geralmente é mais \nelevada (Fig. 1). A arborização da pastagem \ncontribui para a diminuição da temperatura do ar; \nem condições tropicais, a temperatura sob a copa \ndas árvores é cerca de 2 a 3°C menor que sob céu \naberto, havendo registro de reduções de até 9°C \n(Martin, 2002). foram superiores a 70% e, a partir das 13h, \nestiveram abaixo de 55%. À medida que ocorria \na elevação da temperatura do ar, ocorria redução \nda umidade do ar. foram superiores a 70% e, a partir das 13h, \nestiveram abaixo de 55%. À medida que ocorria \na elevação da temperatura do ar, ocorria redução \nda umidade do ar. No ambiente com sombreamento natural, a \numidade relativa do ar média verificada foi de \n69,7%. Tgn = temperatura do globo negro (°C). Tgn = temperatura do globo negro (°C). A pesagem do leite para se determinar a média \nde produção dos animais foi feita semanalmente. A pesagem do leite para se determinar a média \nde produção dos animais foi feita semanalmente. Os \nparâmetros \nfisiológicos: \nfrequência \nrespiratória (FR), batimento cardíaco (BC), \ntemperatura de superfície corporal (TSC) e \ntemperatura retal (TR) foram mensurados às sete \ne às 14 horas. A taxa de sudação (TS) foi feita \nem \n16 \nanimais \ndiariamente, \ntomados \naleatoriamente dos quatro diferentes grupos \ngenéticos estudados. A coleta foi realizada no \ntronco localizado no curral, durante 15 dias. Utilizou-se o delineamento inteiramente ao \nacaso, inicialmente no esquema fatorial 4 x 2 x 2 \n(quatro grupos genéticos, dois ambientes e dois \nhorários) com 34 repetições. Uma segunda \nanálise \nfoi \nfeita \npara \ncada \nambiente \nseparadamente, eliminando-se o grupo genético \ndo modelo e avaliando-se apenas o efeito dos \ndois horários no comportamento animal. Foi \ncalculada a correlação entre os parâmetros \nfisiológicos e as variáveis ambientais, bem como \no efeito dos ambientes em função dos horários na \nprodução de leite. Com o objetivo de se verificar \no comportamento das variáveis climáticas no \ndecorrer do dia, foi feita análise de regressão. As \nvariáveis foram submetidas à análise de \nvariância, utilizando-se o pacote estatístico SAS \n(Statistical Analysis System) e, quando o teste F \nfoi \nsignificativo, \ntiveram \nas \nmédias \ndos \ntratamentos comparadas pelo teste de Tukey a \n5% de significância. A frequência respiratória foi determinada por \nmeio de avaliação visual, observando-se os \nmovimentos do flanco por 15 segundos, \nmultiplicados por quatro para se determinarem os \nmovimentos por minuto. A mensuração da frequência cardíaca ocorreu \npor meio de auscultação, com o uso de \nestetoscópio, no lado esquerdo do animal, entre o \nterceiro e quinto espaços intercostais. A \nauscultação foi feita por 15 segundos e, 724 Arq. Bras. Med. Vet. Zootec., v.70, n.3, p.722-730, 2018 Parâmetros fisiológicos... RESULTADOS E DISCUSSÃO Os maiores valores foram observados nas \nprimeiras horas, com diminuição gradativa ao \nlongo do dia (Fig. 1). O microclima formado pela arborização e pela \naguada existente na pastagem contribuiu para \nque a umidade no local ficasse próxima aos \nvalores \nconsiderados \nideais \npara \nbovinos \n(Ferreira et al., 2006). Os valores de umidade relativa do ar foram \ndecrescentes no ambiente 1, ocorrendo acentuada \nredução ao longo do dia (Fig. 1). A equação \nlinear foi a que melhor se ajustou, mostrando \numa diminuição de 3,96% a cada hora do dia \n(Tab. 2). Porém, verificou-se que, no período da \nmanhã, os valores de umidade relativa do ar Diante da elevação da temperatura e da redução \nda umidade relativa do ar, calcularam-se os 725 Arq. Bras. Med. Vet. Zootec., v.70, n.3, p.722-730, 2018 Castro et al. Os valores dos parâmetros fisiológicos FR, TR, \nBC, TSC e TS e produção de leite dos grupos \ngenéticos estudados (Tab. 3) apresentaram \nvalores semelhantes, tanto nos animais do \nambiente 1 quanto do ambiente 2, logo, os \ngrupamentos \nnão \napresentaram \ndiferença \nestatística entre si (P>0,05), e todos os valores se \napresentaram dentro da faixa de normalidade \npara a espécie. Os valores dos parâmetros fisiológicos FR, TR, \nBC, TSC e TS e produção de leite dos grupos \ngenéticos estudados (Tab. 3) apresentaram \nvalores semelhantes, tanto nos animais do \nambiente 1 quanto do ambiente 2, logo, os \ngrupamentos \nnão \napresentaram \ndiferença \nestatística entre si (P>0,05), e todos os valores se \napresentaram dentro da faixa de normalidade \npara a espécie. valores de ITGU, que foram crescentes ao longo \ndo dia. De acordo com Buffington et al. (1981), \nvalores de ITGU até 74 definem conforto, de 74 \na 78 é sinal de alerta, de 79 a 84 é sinal de perigo \ne, acima de 84, é considerado sinal de \nemergência para bovinos. valores de ITGU, que foram crescentes ao longo \ndo dia. De acordo com Buffington et al. (1981), \nvalores de ITGU até 74 definem conforto, de 74 \na 78 é sinal de alerta, de 79 a 84 é sinal de perigo \ne, acima de 84, é considerado sinal de \nemergência para bovinos. Ao serem avaliados os valores propostos pelo \nautor, observou-se que, no ambiente 1, os \nanimais estiveram em situação de perigo até às \nnove horas e em situação de emergência a partir \ndas 10h. Duperez (2000) fixou valores de 38 a 39,3ºC \ncomo temperatura retal normal para animais \nleiteiros. RESULTADOS E DISCUSSÃO A frequência respiratória indicativa de \ninício de estresse é de 70 a 75 mov.min.-1 (Pires e \nCampos, 2004; Ávila et al., 2005). O batimento \ncardíaco normal de vacas leiteiras varia de 60 a \n80 pulsações por minuto (Nääs e Arcaro Júnior, \n2001). No ambiente sombreado, o ITGU foi menor \ntambém na parte da manhã; ao longo do dia, os \nvalores foram crescentes, o que foi ocasionado \npelo aumento gradativo da temperatura do ar e \npela diminuição da umidade relativa do ar (Fig. 1). Ao se analisarem os valores propostos por \nBuffington et al. (1981), os animais estavam em \nsituação de conforto no ambiente sombreado \nentre às sete e às nove horas, e, a partir das 10h, \nos animais ficariam expostos a um ambiente de \ndesconforto térmico, por este ser classificado \ncomo situação de alerta. Martello et al. (2004) afirmou que a temperatura \nde superfície corporal de vacas pode variar de \n31,6 a 34,7ºC em ambiente climatizado. Tabela 3. Médias de frequência respiratória (FR), temperatura retal (TR), batimento cardíaco (BC), \ntemperatura de superfície corporal (TSC), taxa de sudação (TS) e produção de leite (PL) dos diferentes \ngrupos genéticos grupos genéticos \nCruzamento \nFR \n(mov.min.-1) \nBC \n(bat.min.-1) \nTSC \n(ºC) \nTR \n(ºC) \nTS \n(g.m2.h-1) \nPL \n(litros. vaca. dia-1) \nAmbiente 1 – Pasto sem sombreamento \n1 - H x G \n36,90 ±7,1 \n72,74±6,8 \n35,0±3,3 \n38,30±0,4 \n1949,01±364,0 \n5,63±2,4 \n2 - H x NG \n38,42±7,7 \n74,82±8,2 \n35,34±3,4 \n38,34±0,5 \n1984,28±359,5 \n5,87±1,6 \n3 - H x GN \n39,42±8,5 \n76,26±5,9 \n34,59±4,2 \n38,40±0,6 \n1767,82±355,08 \n5,70±1,7 \n4 - H x N \n39,70±6,8 \n71,50±8,1 \n35,28±3,7 \n38,25±0,5 \n2203,61±264,72 \n5,33±1,7 \nAmbiente 2 – Pasto com sombreamento natural \n1 - H x G \n37,70±8,0 \n82,90±8,0 \n35,60±2,4 \n38,52±0,5 \n1650,56±139,8 \n5,91±1,7 \n2 - H x NG \n44,21±7,5 \n77,43±4,8 \n35,74±2,3 \n38,48±0,4 \n2111,56±248,8 \n5,27±2,5 \n3 - H x GN \n42,04±8,2 \n82,53±8,4 \n35,32±2,1 \n38,59±0,3 \n1836,38±304,5 \n5,73±2,2 \n4 - H x N \n46,76±6,7 \n77,86±7,3 \n35,41±2,5 \n38,53±0,4 \n1818,62±406,9 \n4,58±1,8 \n \nPode-se observar que os valores encontrados no\nque\na\ncomposição\ngenética\ninfluencia\nna Pode-se observar que os valores encontrados no \nexperimento (Tab. 3) estão dentro dos valores \npadrão para parâmetros fisiológicos, o que indica \nque os animais F1, criados em ambientes com e \nsem sombreamento, não necessitaram utilizar \ntrocas latentes para realizar a termorregulação. Na Tab. 4, estão dispostos os valores médios de \nFR, BC, TR, TSC e TS dos animais criados no \npasto sem sombreamento e com sombreamento \nnatural, diante da comparação entre os horários \nde ordenha. RESULTADOS E DISCUSSÃO A base materna não teve efeito sobre a produção \nde leite (Tab. 3). Resultados diferentes aos \nencontrados neste experimento foram descritos \npor Vasconcelos et al. (2003), que afirmaram Houve \ndiferença \nestatística \n(P<0,05) \nna \nfrequência respiratória dos animais criados no \npasto sem sombreamento ao se compararem os 726 Arq. Bras. Med. Vet. Zootec., v.70, n.3, p.722-730, 2018 Parâmetros fisiológicos... manhã, porém o valor calculado esteve acima da \ncondição de conforto sugerido por Buffington et \nal. (1981). horários de ordenha, visto que os menores \nvalores foram verificados no período da manhã. O ITGU, utilizado para caracterizar a condição \nde conforto térmico, foi menor no período da Tabela 4. Valores médios de frequência respiratória (FR), batimentos cardíacos (BC), temperatura retal \n(TR), temperatura de superfície corporal (TSC) e taxa de sudação (TS) dos animais criados nos pastos \nsem sombreamento e com sombreamento natural \nHorário \nFR \n(mov.min.-1) \nBC \n(bat.min.-1) \nTSC \n(ºC) \nTR \n(ºC) \nTS \n(g.m2.h-1) \nAmbiente 1 – Pasto sem sombreamento \n07:00 \n31,5±3,2 A \n68,0±7,5 A \n31,6±1,1 A \n37,8±0,2 A \n2022,6±602,5NS \n14:00 \n45,3±6,0 B \n79,3±5,8 B \n38,5±0,5 B \n38,7±0,2 B \n1927,5±259,6NS \nAmbiente 2 – Pasto com sombreamento natural \n07:00 \n37,0±5,0 A \n75,0±7,1 A \n33,3±0,5 A \n38,1±0,2 A \n1915,5±384,7NS \n14:00 \n45,3±7,2 B \n85,0±6,0 B \n37,7±0,4 B \n38,8±0,2 B \n1719,6 K±162,6NS \n*Médias seguidas por letras distintas maiúsculas nas colunas diferem entre si pelo teste Tukey a 5% de probabilidade. *NS- Não significativo. Tabela 4. Valores médios de frequência respiratória (FR), batimentos cardíacos (BC), temperatura ret\n(TR), temperatura de superfície corporal (TSC) e taxa de sudação (TS) dos animais criados nos past\nsem sombreamento e com sombreamento natural 0.06853, indicando que o ambiente climático não \ninfluenciou de forma negativa. 0.06853, indicando que o ambiente climático não \ninfluenciou de forma negativa. No período da tarde, a frequência respiratória foi \nmaior (P<0,05), em virtude do menor tempo de \ndescanso entre as ordenhas e do ITGU elevado. De acordo com Buffington et al. (1981), o ITGU \ncalculado acima de 84 indica situação de \nemergência para a criação de bovinos. No \nentanto, embora a frequência respiratória dos \nanimais tenha apresentado correlação positiva \ncom o ITGU, ela foi baixa (0,1995), ou seja, \nmesmo com o ITGU indicando o ambiente \nclimático como perigoso e de emergência, este \nnão elevou a FR a valores prejudiciais ou \nestressantes para os animais. Na Tab. Arq. Bras. Med. Vet. Zootec., v.70, n.3, p.722-730, 2018 Castro et al. Castro et al. correlação positiva, porém baixa, com o ITGU \nde 0, 05851, o que indica que o ambiente não \nteve forte efeito sobre a TR. mais elevado (Tab. 1), que leva a um acúmulo de \ncalor no organismo no animal e, assim, a uma \nelevação de seus parâmetros fisiológicos. Os \nanimais \nacomodados \nno \npasto \ncom \nsombreamento natural percorriam uma distância \nde 810 metros até chagarem ao curral de manejo. Essa distância, associada aos altos valores de \nITGU no período da tarde, contribuiu para o \naumento nos valores de batimento cardíaco dos \nanimais. Contudo, a ultrapassagem do valor \npadrão de batimento cardíaco não expõe os \nanimais a estresse térmico. O tipo de glândula e o ambiente térmico em que \nestão os animais são importantes para eficiência \nda sudorese (Silva, 1999; Gebremedhin e Wu, \n2002). Dessa forma, verificou-se que não houve \ndiferença (P>0,05) da taxa de sudação para os \nanimais entre os dois horários de coleta (Tab. 4). O sistema termorregulatório dos animais F1 foi \neficiente no sentido de manter a homeotermia \ndurante o verão, quando são verificados valores \nelevados de temperatura do ar e umidade relativa \ndevido às chuvas. Dessa forma, os animais F1, \nquando expostos a ambientes com ITGU \nvariando de 76 a 85,3, não expressam \ndesconforto térmico. Uma vez que ocorre acréscimo nos valores dessa \nvariável fisiológica, isso é reflexo de falha ou \nesgotamento nos mecanismo de perda de calor \n(Rocha et al., 2012). Neste trabalho, pôde-se \nobservar, então, que os animais utilizaram os \nmecanismos de perda de calor de forma eficiente, \npois \nos \nparâmetros \nfisiológicos \nnão \ndemonstraram alteração acima da normalidade. Essas \nrespostas \nfisiológicas \nexpressam \na \nadaptabilidade dos F1 em razão da heterose dos \ncruzamentos. Para os animais do pasto com sombreamento \nnatural, houve diferença significativa (P<0,05) \nentre os valores de frequência respiratória \nverificados nos períodos da manhã e da tarde \n(Tab. 4). Os maiores valores foram verificados \nno período da tarde, quando a temperatura do ar \nfoi maior e a umidade relativa do ar mais baixa, \nocasionando maiores valores de ITGU. Os valores de taxa de sudação dos animais não \nmostraram \ndiferença \nsignificativa \n(P>0,05) \nquando comparados os períodos da manhã e da \ntarde (Tab. 4), o que confirma que a \ntermorregulação dos animais F1 foi eficiente no \npropósito de manter a homeotermia. Arq. Bras. Med. Vet. Zootec., v.70, n.3, p.722-730, 2018 Arq. Bras. Med. Vet. Zootec., v.70, n.3, p.722-730, 2018 RESULTADOS E DISCUSSÃO 4, observa-se que os valores de \ntemperatura de superfície corporal dos animais \nforam maiores (P<0,05) no período da tarde, \nquando se verificaram valores médios de 38,5°C, \nenquanto no período da manhã, a TSC média foi \nde 31,6°C. O ITGU mais elevado no período da \ntarde contribuiu para o aumento da carga de calor \nsobre os animais, que acabava sendo acumulado \nsobre sua superfície, e resultou em maior média \nde temperatura dos animais nesse horário. A \ntemperatura \nde \nsuperfície \ncorporal \nteve \ncorrelação positiva de 0,32607 com o ITGU, \nporém baixa. Em todos os tratamentos, os animais não \ndemonstraram sinal de estresse térmico, estando \nesses valores dentro da normalidade mesmo \nquando os valores de temperatura e umidade não \nestavam \nideais. Pires \ne \nCampos \n(2008) \nevidenciaram que, com 23 mov.min-1, os animais \nnão \nsofrem \nestresse \ne, \nem \ncondições \ntermoneutras, a frequência respiratória varia de \n24 a 36 movimentos por minuto (Baccari Jr., \n2001). A temperatura retal foi menor (P<0,05) na \nprimeira ordenha do dia, às sete horas (Tab. 3), \nvisto que o clima da manhã é mais ameno, como \nse pode verificar pelo valor de ITGU (Tab. 2). Esse resultado corrobora dados encontrados por \nRezende et al. (2015), que observaram que a \ntemperatura retal média da tarde é, em geral, \nmais elevada que a da manhã, podendo chegar de \n0,5 a 1,5ºC de elevação. Neste trabalho, tanto os \nvalores da manhã quanto os da tarde não \nultrapassaram os valores normais de temperatura \nretal para bovinos, de 38,0 a 39,3ºC (Duperez, \n2000), mesmo quando o ITGU indicou o \nambiente climático como perigoso e emergente. O valor de batimento cardíaco (Tab. 4) dos \nanimais seguiu o mesmo padrão da frequência \nrespiratória. O período da manhã mostrou-se, \nnovamente, mais confortável (P<0,05) para os \nanimais, \ncom \nmédia \nde \n68 \nbat.min-1, \nproporcionando \nmenor \nbatimento \ncardíaco \nquando comparado com o período da tarde, com \nmédia de 79,3 bat.min-1. No presente trabalho, a \ncorrelação entre os valores de BC e ITGU foi de Esse comportamento indica a adaptação dos \nanimais F1 HxZ a ambiente em que o ITGU \nchega a atingir 87,2. A temperatura retal teve 727 Arq. Bras. Med. Vet. Zootec., v.70, n.3, p.722-730, 2018 REFERÊNCIAS Houve correlação negativa de -0,28798 da \nprodução de leite com o ITGU, assim, com o \naumento do ITGU, a produção de leite diminuiu. O ITGU teve tendência de elevação ao longo do \ndia, sendo maior no período da tarde, mas não \npode ser apontado como causa total da \ndiminuição da produção, uma vez que os animais \nque são ordenhados mais de uma vez no dia \ntendem a diminuir a produção na segunda \nordenha. Houve correlação negativa de -0,28798 da \nprodução de leite com o ITGU, assim, com o \naumento do ITGU, a produção de leite diminuiu. O ITGU teve tendência de elevação ao longo do \ndia, sendo maior no período da tarde, mas não \npode ser apontado como causa total da \ndiminuição da produção, uma vez que os animais \nque são ordenhados mais de uma vez no dia \ntendem a diminuir a produção na segunda \nordenha. ÁVILA, A.S.; JÁCOME, I.M.T.D.; FACCENDA, A.; \nLANA, A.M.Q. et al. Estimativa de níveis críticos \nsuperiores do índice de temperatura e umidade \npara vacas leiteiras 1/2, 3/4, 7/8 Holandês-Zebu \nem lactação. Rev. Bras. Zootec., v.34, p.2000-\n2008, 2005. AZEVEDO, M.; PIRES, M.F.A.; SATURNINO, \nH.M. et al. Estimativas de níveis críticos \nsuperiores do índice de temperatura e umidade \npara vacas leiteiras 1/2, 3/4 e 7/8 Holandês-Zebú, \nem lactação. Rev. Soc. Bras. Zootec., v.34, \np.2000-2008, 2005. Silva et al. (2002) afirmam que a resistência e a \nadaptação dos animais ao clima quente é o \nmotivo do resultado, considerando que, em casos \nde animais adaptados ao calor e de baixa \nprodução, o efeito do sombreamento sobre a \nprodução láctea é inexistente. BACCARI JUNIOR, F. Manejo ambiental da \nvaca leiteira em climas quentes. Londrina: UEL, \n2001. 141p. A superioridade genética dos animais F1 H x Z \n(100% de heterose) utilizados neste experimento \nfez com que a produção de leite não fosse \nalterada pela disponibilidade ou não de sombra, \njá que os animais são adaptados ao ambiente \nquente e têm comportamento diferenciado \nquando se trata dos efeitos do clima sobre o seu \nbem- estar. BUFFINGTON, D.E.; COLLAZO-AROCHO, \nA.; CANTON, G.H. et al. Black globe humidity \nindex (BGHI) as comfort equation for dairy \ncows. Trans. Am. Soc. Agricult. Eng., v.24, \np.711-714, 1981. DU \nPREEZ, \nJ.H. Parameters \nfor \nthe \ndetermination and evaluation of heat stress in \ndairy cattle in South Africa. J. Vet. Res. v.67, \np.263-271, 2000. CONCLUSÃO GEBREMEDHIN, K.G.; WU, B. Simulation of \nsensible and latent heat losses from wet-skin \nsurface and fur layer J. Ther. Biol., v.27, p.291-\n297, 2002. Animais F1 criados em pasto sem sombreamento \ne com sombreamento natural não sofrem \nalteração nos padrões fisiológicos indicativos de \nestresse e não reduzem a produção láctea. O \níndice de temperatura do globo e a umidade \natingiram valores considerados estressantes, \nporém \nos \nambientes \nde \ncriação \nnão \nproporcionaram estresse e redução na produção \ndos animais. MARTELLO, L.S. et al. Respostas fisiológicas e \nprodutivas de vacas holandesas em lactação \nsubmetidas a diferentes ambientes. Rev. Bras. Zootec., v.33, p.181-191, 2004. MARTIN, G.O. Mantenga la sombra en sus \npotreros y reduzca el estrés animal. Rev. Prod., \n2002. Disponíble en: <http://www.ecampo.com/ \nsections/news/print.php/uuid.582F356F-2996-\n417A- 8D93D1A411F549BD>. Acceso en 07 \nmar. 2016. REFERÊNCIAS Dessa forma, o conceito de zona de conforto para \nvacas F1 H x Z necessita de melhor avaliação, \nvisto que os padrões fisiológicos indicativos de \nestresse diferem dos preconizados para o gado \neuropeu. FERREIRA, F.; PIRES, M.F.A.; MARTINEZ, \nM.L.; \nCOELHO, \nS.G. et al. Parâmetros \nfisiológicos de bovinos cruzados submetidos ao \nestresse calórico. Arq. Bras. Med. Vet. Zootec., \nv.58, p.732-738, 2006. Castro et al. Nesse \nsentido, os animais F1, quando expostos a \nambientes com variáveis climáticas por vezes \nacima dos limites de termoneutralidade, não \ndemonstraram sinal de estresse térmico. No ambiente 2, os valores de frequência \nrespiratória ficaram dentro dos padrões de \nnormalidade, indicando que os animais não \npassaram por estresse, mesmo com valores das \nvariáveis climáticas elevados no período da \ntarde. A Tab. 5 ilustra a média da produção de leite \ndiária dos animais em função dos horários e do \nambiente em que estavam alojados. Os valores de batimento cardíaco e temperatura \nde superfície corporal dos animais também foram \ndiferentes (P<0,05) entre os horários da manhã e \nda tarde (Tab. 4). Ao se comparar a produção de leite entre os \nperíodos, verificou-se que, na primeira ordenha \ndo dia (sete horas), a produção de leite foi maior \n(P<0,05) quando comparada com a ordenha das \n14h. Nääs e Arcaro Jr. (2001) fixam valores de 60 a \n80 batimentos por minuto como normais para a \nespécie bovina. No período da tarde, os animais \nultrapassaram esse valor, em razão do ITGU Tabela 5. Média de produção de leite diária (litros. vaca. dia-1) dos animais criados em pastos se\nsombreamento e com sombreamento natural Tabela 5. Média de produção de leite diária (litros. vaca. dia 1) dos animais criados em pastos sem \nsombreamento e com sombreamento natural \nHorários de ordenha \nPasto sem sombreamento \nPasto com sombreamento natural \n7h \n7,0±1,7 A \n7,0±2,7 A \n14h \n4,3±0,9 B \n3,2±1,1 B \n*Médias seguidas por letras distintas maiúsculas nas colunas diferem entre si pelo teste de Tukey a 5% de \nprobabilidade. 728 Arq. Bras. Med. Vet. Zootec., v.70, n.3, p.722-730, 2018 Parâmetros fisiológicos... Arq. Bras. Med. Vet. Zootec., v.70, n.3, p.722-730, 2018 Arq. Bras. Med. Vet. Zootec., v.70, n.3, p.722-730, 2018 AGRADECIMENTOS À Fapemig, à Capes, ao CNPq, à Epamig, à \nUnimontes, à Finep e ao MCTI, pelo apoio \nfinanceiro ao projeto nº1334/13. 729 Arq. Bras. Med. Vet. Zootec., v.70, n.3, p.722-730, 2018 Castro et al. MCMANUS, C.; TEIXEIRA, A.R.; DIAS, L.T.; \nLOUVANDINI, \nH. et \nal. Características \nprodutivas e reprodutivas de vacas Holandesas e \nmestiças Holandês × Gir no Planalto Central. Rev. Bras. Zootec., v.37, p.819-823, 2008. ROCHA, D.R.; SALLES, M.G.F.; MOURA, \nA.A.A.N.; ARAÚJO, A.A. Índices de tolerância \nao calor de vacas leiteiras no período chuvoso e \nseco no Ceará. Rev. Acad. Ciênc. Agrar. Amb., \nv.10, p.335-343, 2012. NAAS, I.A.; ARCARO JÚNIOR, I. Influência \nde ventilação e aspersão em sistemas de \nsombreamento artificial para vacas em lactação \nem condições de calor. Rev.Bras. Eng. Agrar. Amb. v.5, p.139-42. 2001. SCHLEGER, A.; TURNER, H.G. Swetting rates \nof cattle in field and their reaction to diurnal and \nseasonal changes. Austr. J. Agric. Res., v.16, \np.92-106, 1965. SILVA, I.J.O.; PANDORFI, H.; ACARARO \nJUNIOR, I.; PIEDADE, S.M.S.; MOURA, D.J. Efeitos da climatização do curral de espera na \nprodução de leite de vacas Holandesas. Rev. Bras. Zootec., v.31, p.2036-2042, 2002. PINHEIRO, M.G.; NOGUEIRA, J.R.; LIMA, \nM.L.P. et al. Efeito do ambiente pré-ordenha \n(sala de espera) sobre a temperatura da pele, a \ntemperatura retal e a produção de leite de \nbovinos da raça Jersey. Rev. Port. Zootec., v.12, \np.37-43, 2005. SILVA, R.G. Estimativa do balanço térmico por \nradiação em vacas Holandesas expostas ao sol e \nà sombra em ambiente tropical. Rev. Bras. Zootec., v.28, p.1403-1411, 1999. PIRES, M.F.A.; CAMPOS, A.T. Conforto \nanimal para maior produção de leite. Viçosa: \nCentro de Produções Técnicas, 2008. 254p. VASCONCELOS, \nB.F.; \nPÁDUA, \nJ.T.; \nMUÑOZ, \nC.F.M.; \nTONHATI, \nH. Efeitos \ngenéticos e ambientais sobre a produção de leite, \no intervalo de partos e a duração da lactação em \num rebanho leiteiro com animais mestiços no \nBrasil. Rev.Univ. Rural S. Ciênc. Vida, v.23, \np.39-45, 2003. PIRES, M.F.A.; CAMPOS, A.T. Modificações \nambientais para reduzir o estresse calórico em \ngado de leite. Juiz de Fora: EMBRAPA, 2004. p.1-6. (Comunicado técnico 42). Disponível em: \n<http://www.cnpgl.embrapa.br>. Acessado em \n12 de dezembro de 2015. REZENDE, S.R.; MUNHOZ, S.K.; NASCIMENTO, \nM.R.B.M. GUIMARÃES, J.L.N. Características de \ntermorregulação em vacas leiteiras em ambiente \ntropical: revisão. Vet. Notícia, v.21, p.18-29, \n2015. 730"}}},{"rowIdx":12597,"cells":{"identifier":{"kind":"string","value":"https://openalex.org/W2784122645"},"pdf_url":{"kind":"string","value":"https://revistes.uab.cat/dea/article/download/v4-deventura/85-pdf-it"},"lang":{"kind":"string","value":"Italian"},"error":{"kind":"null"},"title":{"kind":"string","value":"“Donne mi parver, non da ballo sciolte”: appunti su danza e pericorsi tra gli spiriti sapienti"},"source_name":{"kind":"string","value":"Dante e l'arte"},"publication_year":{"kind":"number","value":2017,"string":"2,017"},"license":{"kind":"string","value":"cc-by"},"word_count":{"kind":"number","value":5766,"string":"5,766"},"text":{"kind":"string","value":"Dante e l’arte 4, 2017 125-136 Dante e l’arte 4, 2017 125-136 Abstract Sorprendentemente, gli spiriti sapienti nel cielo del Sole sono appaiono come donne dan\nzanti. Forse perché nella Bibbia Sapientia è una fanciulla che danza. Ma soprattutto perché \nmovimento eterno di danza circolare, e danza nuziale, è la pericoresi trinitaria. Si potrebbe \ncosì cogliere la coerenza teologica di Paradiso X, che lega le donne danzanti al proemio \ntrinitario e ai versi conclusivi che descrivono la Sposa che canta una mattinata allo sposo \nperché l’ami. Parole chiave: danza; Sapienza; pericoresi; mattinata. “Donne mi parver, non da ballo sciolte”: \nappunti su danza e pericoresi tra gli spiriti sapienti Paolo De Ventura\nItalian Studies, University of Birmingham\np.deventura@bham.ac.uk ISSN 2385-5355 (digital), ISSN 2385-7269 (paper) Keywords: dance; Sapientia; perichoresis; aubade. Abstract Surprisingly, in the Heaven of the Sun, the Wise Spirits appear as dancing women. Arguably \nbecause Sapientia appears in the Bible like a dancing girl; but, first and foremost, because \nthe divine perichoresis is an eternal and circular movement of dance, a nuptial dance. One \ncould thus appreciate the theological and narrative coherence in the narrative of Paradise X, \nbeginning with a solemn Trinitarian proem, and ending with the Bride singing an aubade \nto the groom, so that He may love Her. Keywords: dance; Sapientia; perichoresis; aubade. 126 Dante e l’arte 4, 2017 Paolo De Ventura S\nuperato l’ultimo possibile cono d’ombra e arrivato al cielo del Sole, dove \nseppure per un istante si eclissa persino lo splendore degli occhi di Beatrice, \nDante viene inondato di nuova luce, viene anzi circondato da luci che si sta\ngliano sulla luce, da fulgori vivi e vincenti che danzano e cantano «più dolci \nin voce che in vista lucenti», in un’armonia che supera in musicale dolcezza \nl’intensità dei loro fulgori. La narrazione prosegue: S Poi, sì cantando, quelli ardenti soli\nsi fuor girati intorno a noi tre volte,\ncome stelle vicine a’ fermi poli,\n\t\ndonne mi parver, non da ballo sciolte [...] \n(Pd. X, 76-79)1 Poi, sì cantando, quelli ardenti soli si fuor girati intorno a noi tre volte, come stelle vicine a’ fermi poli, Chi sono queste donne danzanti, questi ardenti soli nel cielo del Sole? Il novo peregrin d’amore farà presto la loro conoscenza e – possiamo sup\nporre con la massima sopresa – apprenderà trattarsi nientemento che delle \nanime dei più illustri profeti e dottori della chiesa di tutti i tempi.2 p\np\np\nCome nel Purgatorio Stazio aveva incontrato la fonte prima del suo poetare \ne del suo essere cristiano, ora, nel suo paradiso, è Dante che incontra – e a noi \npotremmo partecipare all’evento con un simile lampeggiar di riso – nienteme\nno che l’ombra, anzi la luce, di fra Tommaso (non ancora santo in quel 1300). 1.\t\nCito il testo dantesco, secondo l’edizione Petrocchi, dal sito Dante online, con la consulenza \nscientifica della Società Dantesca Italiana, e disponibile in rete all’indirizzo: https://www.\ndanteonline.it. 2.\t Per un puntuale e aggiornato identikit di questi spiriti sapienti si vedano gli studi di Paolo \nFalzone 2015, 2016a e 2016b. 5.\t Mi permetterei di riportare estesamente il commento di Ravasi: «La sapienza dice: io sono la \nrealtà più preziosa della forza di Dio, ma anche la prima delle realtà create, perché le tengo \ninsieme. La sapienza quindi è di Dio ed è anche nostra: c’è Dio il sapiente e c’è l’uomo \nsapiente. La stessa cosa è ripresa nella parte finale. Riprendo due particolari. «Io ero con il \nSignore come architetto». Abbiamo il vocabolo ebraico ‘amon che ricorre una volta sola nella \nBibbia. Secondo la filologia comparata questo termine significa «architetto». [...]. D’altra \nparte è possibile con altre argomentazioni tradurre questo vocabolo con «fanciullo» e allora \nabbiamo un’immagine ancora più suggestiva che viene sviluppata in tutto ciò che segue. 3.\t Sull’atteggiamento dei Padri nei confronti della danza, segnalo, tra gli altri, Petrini 2001, \nLugaresi 2008, Sinibaldi 2009, Resta 2015. Sulla dottrina ufficiale della Chiesa cattolica, \nun recente pronunciamento in materia è in Sacra Congregazione pro Culto Divino 1975. \nAlla possibilità della danza di farsi preghiera è dedicato il bel libro autobiografico della nota \ndanzatrice di balletto classico Mireille Nègre (1984).\n4.\t Sulla vitalità del motivo dell’armonia delle sfere celesti in ambito medievale, si veda Knäble 4.\t Sulla vitalità del motivo dell’armonia delle sfere celesti in ambito medievale, si veda Knäbl\n2014. Abstract Nella sua infiammata cortesia e nel suo discreto latino, prima di magnificare \nle lodi degli amanti Francesco e Povertà, Tommaso presenta i suoi compagni \nnella corona degli Spiriti Sapienti, quasi materializzando davanti a Dante la \nsumma delle summae della scienza, che si era incarnata storicamente nella vita \ne nelle opere di personaggi come Alberto Magno, maestro di Tommaso; Fran\ncesco Graziano, fondatore del diritto canonico; Pietro Lombardo, vittorino \ne professore a Parigi. La sequenza dei nomi si arresta per enfatizzare, accen\ntuandone il significato simbolico e le implicazioni generali, la presenza di re \nSalomone, che Dante può ora certificare essere in paradiso, nonostante, a tacer \nd’altro (e se la Bibbia non sbaglia il conto – se ‘l vero è vero), le 700 mogli e \n300 concubine: La quinta luce, ch’è tra noi più bella,\nspira di tale amor, che tutto ‘l mondo\nlà giù ne gola di saper novella:\n\t\nentro v’è l’alta mente u’ sì profondo\nsaver fu messo, che, se ‘l vero è vero,\na veder tanto non surse il secondo. (Pd. X, 109-114) La quinta luce, ch’è tra noi più bella,\nspira di tale amor, che tutto ‘l mondo\nlà giù ne gola di saper novella:\n\t\nentro v’è l’alta mente u’ sì profondo\nsaver fu messo, che, se ‘l vero è vero,\na veder tanto non surse il secondo. (Pd. X, 109-114) La quinta luce, ch’è tra noi più bella, là giù ne gola di saper novella: entro v’è l’alta mente u’ sì profondo saver fu messo, che, se ‘l vero è vero, a veder tanto non surse il secondo. 1. Cito il testo dantesco, secondo l’edizione Petrocchi, dal sito Dante online, con la consulenza \nscientifica della Società Dantesca Italiana, e disponibile in rete all’indirizzo: https://www. danteonline.it. 1. Cito il testo dantesco, secondo l’edizione Petrocchi, dal sito Dante online, con la consulenza \nscientifica della Società Dantesca Italiana, e disponibile in rete all’indirizzo: https://www. danteonline.it. l\nd\nk\nd\nd\nl\nd d\nl 2. Per un puntuale e aggiornato identikit di questi spiriti sapienti si vedano gli studi di Paolo \nFalzone 2015, 2016a e 2016b. 2. Per un puntuale e aggiornato identikit di questi spiriti sapienti si vedano gli studi di Paol\nFalzone 2015, 2016a e 2016b. Abstract “Donne mi parver, non da ballo sciolte”: Appunti su danza e pericoresi\t\nDante e l’arte 4, 2017 127 “Donne mi parver, non da ballo sciolte”: Appunti su danza e pericoresi Dante e l’arte 4, 2017 127 Peccatore e profeta, scriba Dei dei Libri Sapienziali e del Cantico dei Cantici, \nSalomone – ora sappiamo – è salvato dal misericordiare di Dio, lo stesso che \naveva infuso nella sua mente la sapienza del suo spirito d’amore, il suo sì \nprofondo saver. La presentazione degli Spiriti Sapienti continua con Dionigi \nl’Areopagita, discepolo di san Paolo, fonte da Dante privilegiata su Grego\nrio in tema di angeologia; Paolo Orosio, discepolo di sant’Agostino e autore \ndegli Historiarum libri VII adversus paganos; Severino Boezio, l’autore del De \nconsolatione philosophie; Isidoro di Siviglia, l’autore degli enciclopedici Etymo\nlogiarum libri; il Venerabile Beda; Riccardo di San Vittore, e infine Sigieri di \nBrabante, professore alla Sorbona, avversato in vita da Tommaso ma ora vicino \nin armoniosa concordia al suo fianco. Finite le presentazioni, la danza continua, e la gloriosa rota torna a muo\nversi e render voce a voce. L’immagine dei Padri sapienti come donne danzanti \ngiunge indubbiamente inattesa, a tutta prima sorprendente, “bizarre or at lest \nundignified”, come osserva per esempio Freccero (1986: 228), che immagina \nsenz’altro “the reader’s sense of shock in reading these lines”. Tanto più quan\ndo si pensi che non era sempre tenero lo sguardo dei Padri nei confronti della \ndanza, e che, allora come ora, la danza era osteggiata nell’uso liturgico.3 Come mai allora dottori di tal sorta appaiono addirittura danzare? Per Freccero la risposta è da trovarsi nella persistenza, nel contesto dante\nsco, della vitalità dell’immagine platonica della danza delle stelle, riflessa nella \n«zodiacal dance» dei dodici sapienti. Certamente si deve concedere che l’onda lunga della mitopoiesi di ascen\ndenza platonica arrivasse alle soglie dell’officina dantesca,4 combinandosi e \ntrasformandosi nella nuova costruzione cristiana. Ma se rivolgessimo la do\nmanda ad un teologo, probabilmente la risposta immediata sarebbe che gli \nspiriti sapienti appaiono come donne danzanti perché, come osserva il card. Ravasi commentando il Libro dei Proverbi, «La sapienza potrebbe essere rap\npresentata come una fanciulla che danza».5 128 Dante e l’arte 4, 2017 Paolo De Ventura Nei Proverbi, Salomone (che ora Dante ci presenta come una delle donne \nimpegnate in un ballo), canta di Sapienza, che si presenta in prima persona \ncome una creatura primigenia, giocosamente ludens (nella Vulgata) all’alba dei \ntempi. Michelangelo, nella Cappella Sistina, rappresentando la creazione, raffigura la sapienza come \nun giovane meraviglioso ed armonioso che sta giocando nell’atelier immenso del cosmo. Dio \nè rappresentato come colui che gioca. Il gioco puro e creativo è, forse, il simbolo più alto per \nparlare di Dio [...]. La sapienza potrebbe essere rappresentata come una fanciulla che danza. \nLa danza è il segno più alto dell’armonia e del gioco e non per nulla le grandi liturgie antiche \nhanno sempre avuto nel loro interno degli elementi che comprendevano la danza. Pensiamo \nalla danza mirabile dei Dervisci islamici, che è armonia con la danza del Creatore. Infatti, \nle espressioni che seguono, che sono state tradotte con delizia e dilettandomi, si riferiscono \nad un vocabolo ebraico molto più suggestivo. È il termine che è stato usato per festeggiare \nDavide vincitore contro Golia; per descrivere Davide che porta l’arca a Gerusalemme e \ndanza davanti ad essa; è il termine usato da Zaccaria per descrivere i ragazzi che giocano \nnelle piazze della Gerusalemme del futuro. Le espressioni, quindi, vogliono rappresentare \nla creazione come un’opera artistica, come un gioco supremo; architetto e fanciullo, quindi, \nsi incontrano nello stesso significato. È per questo che la teologia, in epoca recente, come \nin passato, ha tentato di esprimere l’atto creativo proprio ricorrendo all’immagine del riso, \ndel gioco» (Ravasi 2016: 12). 6.\t Il passo del libro dei Proverbi (8, 26-31) è citato nell’edizione CEI, disponibile in rete all’in\ndirizzo: http://www.vatican.va/archive/ITA0001/_INDEX.HTM. Abstract Ed è, come ricordiamo, un Davide addirittura tre\nscante7 quello che viene intagliato nel marmo della prima cornice purgatoriale \na beneficio delle anime una volta superbe: Lì precedeva al benedetto vaso,\ntrescando alzato, l’umile salmista,\ne più e men che re era in quel caso. (Pg. X, 64-66) Lì precedeva al benedetto vaso,\ntrescando alzato, l’umile salmista,\ne più e men che re era in quel caso. (Pg. X, 64-66) trescando alzato, l’umile salmista, Nella Bibbia (2 Sam 6,21) la danza di Davide è immediata ed entusiastica ri\nsposta al messaggio divino, gioia spirituale di gratitudine ed espressione fisica \ndella sua esultanza di fronte all’arca della nuova alleanza con il Dio. Di fronte \na tanta grazia, il re non disdegna di mettersi a saltare, o come Dante caratteriz\nza, a trescare sollevandosi i panni come un popolano qualsiasi. Nel suo danzare \nsi riflettono divinità e umanità, dignità regale e umiltà, sapienza e prudenza, \ngratuità e rendimento di grazie. L’«umile salmista», proprio nel suo effondere \nin danza la propria esultanza, si umilia ad un tempo e si eleva al cospetto di \nDio, e si fa veramente «più e men che re».8 Così, umili e sublimi, come donne danzanti ci appaiono gli spiriti sapien\nti. È certamente un’invenzione poetica che coglie l’essenza della concezione \ncristiana della sapientia, sulla quale sono state scritte pagine molto illuminanti.9 p\nq\np g\nMa forse c’è di più. Nell’armonia del movimento di danza, nel suo es\nsere risposta di immediata accoglienza, di compartecipazione gioiosamente \nluminosa della giocosità creatrice di Sapienza, si potrebbe cogliere il progetto \ncostruttivo del canto X del Paradiso, che si apre con un solenne proemio che \ndescrive l’attività trinitaria: Guardando nel suo Figlio con l’Amore\nche l’uno e l’altro etternalmente spira,\nlo primo e ineffabile Valore\n\t\nquanto per mente e per loco si gira\ncon tant’ordine fé, ch’esser non puote\nsanza gustar di lui chi ciò rimira. (Pd. X, 1-6) Guardando nel suo Figlio con l’Amore quanto per mente e per loco si gira sanza gustar di lui chi ciò rimira. 7. Come osserva Andrea Battistini, «il Landino chiosa «idest danzando colla sua cithara et \nalzato ne’ panni per essere più espedito “. Il passo è la traduzione del biblico “ David \nsaltabat totis viribus ante Dominum “ (II Reg. 6, 14)». Come sostantivo, tresca «compare \nsolo in If. Abstract Rileggiamone alcuni versetti: Quando ancora non aveva fatto la terra e i campi\nné le prime zolle del mondo;\nquando egli fissava i cieli, io ero là; \nquando tracciava un cerchio sull’abisso; \nquando condensava le nubi in alto, \nquando fissava le sorgenti dell’abisso; \nquando stabiliva al mare i suoi limiti, \nsicché le acque non ne oltrepassassero la spiaggia;\nquando disponeva le fondamenta della terra,\nallora io ero con lui come architetto \ned ero la sua delizia ogni giorno, \ndilettandomi davanti a lui in ogni istante; \ndilettandomi sul globo terrestre, \nponendo le mie delizie tra i figli dell’uomo».6 Quando ancora non aveva fatto la terra e i campi, Quando ancora non aveva fatto la terra e i camp\nné le prime zolle del mondo;\nquando egli fissava i cieli, io ero là; \nquando tracciava un cerchio sull’abisso; \nquando condensava le nubi in alto, \nquando fissava le sorgenti dell’abisso; \nquando stabiliva al mare i suoi limiti, \nsicché le acque non ne oltrepassassero la spiaggia\nquando disponeva le fondamenta della terra,\nallora io ero con lui come architetto \ned ero la sua delizia ogni giorno, \ndilettandomi davanti a lui in ogni istante; \ndilettandomi sul globo terrestre, \nponendo le mie delizie tra i figli dell’uomo».6 quando tracciava un cerchio sull’abisso; quando condensava le nubi in alto, q\nsicché le acque non ne oltrepassassero la spiaggia; Il concetto teologico di Sapientia, come insegna il magistero di von Balthasar, \nè modello analogico del rapporto di Dio con il creato, dono di grazia per co\nnoscere il mistero della bellezza di Dio nel creato e nelle creature. Nel libro dei \nProverbi, Sapienza personificata è insieme architetto e fanciulla, il suo dilettarsi \n(ludere nella Vulgata) è un danzare, espressione di gioiosa armonia e di umile \nsemplicità, di ilare creativa e di gioco, risposta felice alla stessa giocosità cre\natrice di Dio. Se oggi le analisi linguistiche sugli originali ebraici consentono \ndi ricostruire filologicamente il danzare di Sapienza, Dante non avrà avuto \nbisogno di ricorrere alle concordanze bibliche per riflettere sulla consonanza \ntematica di questi versetti con i passi che raccontano di Davide e della sua Donne mi parver, non da ballo sciolte”: Appunti su danza e pericoresi\t\nDante e l’arte 4, 2017 129 “Donne mi parver, non da ballo sciolte”: Appunti su danza e pericoresi esultanza che si fa danza. p\n8.\t Un’attenta analisi sul significato delle analogie tra la danza dei sapienti e la tresca di Davide, \ntra i canti X di Purgatorio e Paradiso è in Catelli 2008. 7.\t Come osserva Andrea Battistini, «il Landino chiosa «idest danzando colla sua cithara et \nalzato ne’ panni per essere più espedito “. Il passo è la traduzione del biblico “ David \nsaltabat totis viribus ante Dominum “ (II Reg. 6, 14)». Come sostantivo, tresca «compare \nsolo in If. XIV 40: Sanza riposo mai era la tresca / de le misere mani, con il valore metaforico \ndi “movimento affannoso e frenetico”. Il passaggio dal senso proprio di “ ballo” a quello \ntraslato è spiegato dal Boccaccio: “È la tresca una maniera di ballare la quale si fa di mani e \ndi piedi; a similitudine della quale vuole qui l’autore che noi intendiamo i peccatori quivi le \nmane menare» (si vedano rispettivamente le voci Trescare e Tresca in Enciclopedia Dantesca, \n1970-78, vol. V, p. 715a).. 9.\t Tra gli studi più recenti, ricorderei almeno Bausi 2009. 10.\t Tra gli studi sull’icona di Rublëv, si veda Ange 1999. Segnalo inoltre, per chiarezza e sintesi, \nla descrizione e il commento di Faccin 2006.\n11.\t Sulla necessità del gustare inteso come partecipazione esistenziale al mistero divino, tratto \ncaratterizzante della spiritualità vittorina, si leggano le osservazioni di Vincenzo Placella: \n«L’itinerario cristiano dalle creature al Creatore, peraltro, non è qui proposto da Dante in \nuna dimensione meramente intellettualistica [...]: il contesto, invece, è di carattere esperien\nziale, come s’è visto commentando il «gustar» (6), il «vagheggiar» (10) e quel «preliba» (23), \nquel «lieto» (24), quel «ti ciba» (25). È un tipo d’itinerario proposto in maniera sistematica \nin un’opera celeberrima (a cui fa riferimento l’autore dell’Epistola a Cangrande), un’opera, \nil De Gratia Contemplationis o Beniamin Maior, scritta da un personaggio (Riccardo da San \nVittore) che Dante incontra nel Cielo del Sole, all’interno dell aprima Ghirlanda di Beati, \nnel canto X» (Placella 2013: 264). Sul ruolo della spiritualità vittorina nella costruzione della \nCommedia, si veda in particolare Mirocan 2012. 10.\t Tra gli studi sull’icona di Rublëv, si veda Ange 1999. Segnalo inoltre, per chiarezza e sintesi, \nla descrizione e il commento di Faccin 2006. 12.\t «Creare non est proprium alicui Personae, sed commune toti Trinitati. Sed tamen divinae \nPersonae secundum rationem suae processionis habent causalitatem respectu creationis re-\nrum; creare est proprie causare sive producere esse rerum. [...] Ut enim supra [q. 14 a. 8; q. 19 \na. 4] ostensum est, cum de Dei scientia [= il Figlio] et voluntate [= lo Spirito Santo] agere\ntur, Deus est causarerum per suum intellectum [ancora il Figlio] et voluntatem [ancora lo \nSpirito Santo], sicut artifex rerum artificiatarum. Artifex autem per verbum in intellectu \nconceptum, et per amorem suae voluntatis ad aliquid relatum, operatur. Unde et Deus pater \noperatus est creaturam per suum verbum, quod est filius; et per suum amorem, qui est spiritus \nsanctus. Et secundum hoc processiones personarum suntrationes productionis creaturarum, \ninquantum includunt essentialia attributa, quaesunt scientia et voluntas» (Summa theologiae\nIª q. 45 a. 6co.). Grande l’affinità di questo brano con i primi sei versi del Canto che stiamo \nesaminando: quella di Dante sembra quasi una traduzione» (Placella 2013: 253, nota 2). 3.\t Segnalo tuttavia una buona definizione di pericoresi e un aggiornato quadro d’insieme in \nArtemi 2017. Abstract XIV 40: Sanza riposo mai era la tresca / de le misere mani, con il valore metaforico \ndi “movimento affannoso e frenetico”. Il passaggio dal senso proprio di “ ballo” a quello \ntraslato è spiegato dal Boccaccio: “È la tresca una maniera di ballare la quale si fa di mani e \ndi piedi; a similitudine della quale vuole qui l’autore che noi intendiamo i peccatori quivi le \nmane menare» (si vedano rispettivamente le voci Trescare e Tresca in Enciclopedia Dantesca, \n1970-78, vol. V, p. 715a).. 130 Dante e l’arte 4, 2017 Paolo De Ventura L’esordio di Pd. X potrebbe fungere da didascalia alla famosa icona di Andrey \nRublëv [Fig. 1], che raffigura il ritmo della vita trinitaria, movimento che si \nfa danza, e «danza nuziale» (Faccin 2006). Lì, in una circolare e dinamica \ncorrispondenza di sguardi, appaiono le tre ipostasi della Trinità con il Figlio \nal centro che incontra gli occhi del Padre (a sinistra) entrambi in dialogo con \nla figura dello Spirito, in una prospettiva aperta verso l’esterno, incentrata sul \ndono del calice nuziale.10 È un dono rivolto all’uomo, perché, come dice Dante, possa «gustar di lui \nchi ciò rimira».11 La Sapienza architetto creativo e fanciulla danzante partecipa dell’attività \ncreatrice della Trinità,12 Trinità che nella distinzione di relazione tra le ipostasi \ndel Padre, del Figlio e dello Spirito vive e vivifica in un eterno movimento \ncircolare, in una processione che nel linguaggio teologico è detta pericoresi. Per definizione inconoscibile da mente umana, il mistero trinitario della \nreciproca inabitazione e il movimento di co-inerenza delle persone divine è \nanche naturalmente impossibile da esporre in queste brevi pagine, come pure \nè impensabile poter fornire una pur essenziale bibliografia per il problema dei \nproblemi che ha arrovellato i pensatori cristiani di tutti i tempi.13 Con tutte \nle cautele del caso, e levandomi i calzari di fronte al roveto ardente della teo\nlogia trinitaria, mi permetterei di indicare con la massima sintesi alcuni nodi 11. Sulla necessità del gustare inteso come partecipazione esistenziale al mistero divino, tratto \ncaratterizzante della spiritualità vittorina, si leggano le osservazioni di Vincenzo Placella: \n«L’itinerario cristiano dalle creature al Creatore, peraltro, non è qui proposto da Dante in \nuna dimensione meramente intellettualistica [...]: il contesto, invece, è di carattere esperien\nziale, come s’è visto commentando il «gustar» (6), il «vagheggiar» (10) e quel «preliba» (23), \nquel «lieto» (24), quel «ti ciba» (25). Abstract È un tipo d’itinerario proposto in maniera sistematica \nin un’opera celeberrima (a cui fa riferimento l’autore dell’Epistola a Cangrande), un’opera, \nil De Gratia Contemplationis o Beniamin Maior, scritta da un personaggio (Riccardo da San \nVittore) che Dante incontra nel Cielo del Sole, all’interno dell aprima Ghirlanda di Beati, \nnel canto X» (Placella 2013: 264). Sul ruolo della spiritualità vittorina nella costruzione della \nCommedia, si veda in particolare Mirocan 2012. 12. «Creare non est proprium alicui Personae, sed commune toti Trinitati. Sed tamen divinae \nPersonae secundum rationem suae processionis habent causalitatem respectu creationis re-\nrum; creare est proprie causare sive producere esse rerum. [...] Ut enim supra [q. 14 a. 8; q. 19 \na. 4] ostensum est, cum de Dei scientia [= il Figlio] et voluntate [= lo Spirito Santo] agere\ntur, Deus est causarerum per suum intellectum [ancora il Figlio] et voluntatem [ancora lo \nSpirito Santo], sicut artifex rerum artificiatarum. Artifex autem per verbum in intellectu \nconceptum, et per amorem suae voluntatis ad aliquid relatum, operatur. Unde et Deus pater \noperatus est creaturam per suum verbum, quod est filius; et per suum amorem, qui est spiritus \nsanctus. Et secundum hoc processiones personarum suntrationes productionis creaturarum, \ninquantum includunt essentialia attributa, quaesunt scientia et voluntas» (Summa theologiae\nIª q. 45 a. 6co.). Grande l’affinità di questo brano con i primi sei versi del Canto che stiamo \nesaminando: quella di Dante sembra quasi una traduzione» (Placella 2013: 253, nota 2). 13. Segnalo tuttavia una buona definizione di pericoresi e un aggiornato quadro d’insieme in \nArtemi 2017. Donne mi parver, non da ballo sciolte”: Appunti su danza e pericoresi\t\nDante e l’arte 4, 2017 131 “Donne mi parver, non da ballo sciolte”: Appunti su danza e pericoresi fondamentali delle implicazioni legate al concetto di pericoresi. Desunto dagli \nantichi Stoici e in particolare da Anassagora, περιχώρησις,“pericóresis” (com\nposto della preposizione περὶ, “attorno”, e del verbo χωρέω, “aver luogo”, “far \nposto”), il termine viene usato già nel quarto secolo da Gregorio Nazianzeno \nper indicare il rapporto di relazione in Cristo delle distinte nature umana e \ndivina. Abstract Tradotto dai Padri latini come circuminsessio e circumincessio (compo\nsti entrambi della preposizione circum, “attorno” con il verbo insidere, “stare \ndentro”, o, in un senso più dinamico, con il verbo incedere, “avanzare”), il \nconcetto di pericoresi si espande a coinvolgere l’intera Trinità, caratterizzando \nl’essenza del dio triuno, in cui ogni persona sta e si muove verso le altre in \nun rapporto di reciproca e dinamica immanenza. Il ciclico ed eterno “girare \nattorno” spinto dall’amore dello Spirito si espande poi, creativamente e analo\ngicamente, all’universo intero e al movimento delle sue rote, postulando così \nuna trinitaria pericoresi cosmica. Movimento primo ed energia d’amore, per i teologi la pericoresi è già \ndanza. Per Klaus Hemmerle (1998: 39), «pericoresi è originariamente il nome di \nuna danza: uno danza intorno all’altro, l’altro danza intorno a lui, e così tutto \nfluisce in maniera reciproca, l’uno nell’altro». Per Robert Cheaib (2013: 110): Il concetto di perichóresis (circumincessio) si fonda sulle affermazioni di \nGesù: «Io sono nel Padre e il Padre è in me» (Gv 14,10.11); «Il Padre è in \nme e io nel Padre» (Gv 10,38; 17,21). A partire da questi versetti, viene svi\nluppata una riflessione sulla reciprocainabitazione delle persone trinitarie. pp\np\np\nL’immagine che rende meglio il concetto è quella della danza. Pensiamo \nad esempio al quadro La danza di Henri Matisse. Nella danza raffigurata vi \nè una comunione di persone che danzano in cerchio. Il movimento volon\ntario e trascinante della danza le rende uno. La bellezza del balletto si fonda \nsul loro libero corrispondere al movimento e al ritmo della coreografia. La \nriuscita del ballo si fonda sul fatto che ognuno si muove facendo spazio \nall’altro e, contemporaneamente, entrando nello spazio lasciato proprio a \nlui dall’altro. Così possiamo pensare per analogia alla Trinità: la vita di Dio non \nè stasi, ma è estasi, è un dinamismo d’amore, di donazione e di risposta \nall’amore e nell’amore. È in una parola una danza dell’amore. Anche per Battista Mondin (2010: 35), il ritmo della vita trinitaria è movimen\nto di danza, danza d’amore, moto vivificante ed energia creatrice: Sulla scorta di Riccardo da San Vittore, noi preferiamo seguire l’analogia \nagapica, la quale concepisce la Trinita’ come uno stupendo incontro di Tre \nEterni Amanti che felicemente danzano la beatificante danza dell’amore: \nAmore sorgivo del Padre, Amore recettivo del Figlio e Amore reciproco \ndello Spirito Santo. Abstract Sulla scorta di Riccardo da San Vittore, noi preferiamo seguire l’analogia \nagapica, la quale concepisce la Trinita’ come uno stupendo incontro di Tre \nEterni Amanti che felicemente danzano la beatificante danza dell’amore: \nAmore sorgivo del Padre, Amore recettivo del Figlio e Amore reciproco \ndello Spirito Santo. In una prospettiva pericoretica, la danza dei sapienti appare dunque qualcosa \ndi più di una semplice «coreografia», e sicuramente dovrebbe essere rivista e \nattenuata la definizione di «command performance» coniata da John Freccero. 132 Dante e l’arte 4, 2017 Paolo De Ventura La danza pericoretica è emanazione di amore e di sapientia, armonia creatrice \nche muove e vivica il divenire del creato in un movimento ciclico analogico \ncon il ritmo trinitario. Allora hanno certamente ragione Paolo Cherchi e Sele\nne Sarteschi (2011: 325) nel trarre le logiche conseguenze dal concetto teologico \ndi pericoresi applicato alla danza dei sapienti nel cielo del Sole: I teologi ruotano in danza lungo il tracciato ideale di una circonferenza, ciò \nche fa sì che ogni danzatore venga ad occupare il luogo lasciato libero da \nun altro danzatore il quale a sua volta occupa il posto di un altro, e così per \ntutta la durata della danza. Lo scambio di spazi è perfetto e lo scambio di \nvoci è altrettanto perfetto. Nella danza ogni partecipante “entra” nel ruolo \ndi un altro mentre cede il proprio. Si può dire che nella danza i partecipanti \nsi “intuano”, si integrano negli altri in un processo che arricchisce tutti \ne produce un bene comune che è la Sapientia. In questo modo la danza \nriproduce la perichoresis divina. Emanazione e operazione dello Spirito, il movimento pericoretico si estende \nnella creazione e si apre all’uomo, che viene chiamato a partecipare, unione \nnella distinzione, all’abbraccio del dio triuno, arrivando a deificarsi nell’eterno \ndivenire dello Spirito che è amore. La danza pericoretica della Trinità informa \ndi sé analogicamente l’amore umano, che viene pertanto a definirsi come vera \ne propria «danza nuziale».14 Dopo l’esordio solenne con lo sguardo rivolto al guardare della Trinità, \ndopo l’invito dello scriba al suo lettore affinché possa gustare l’armonia delle \nrote, e dopo la rassegna degli spiriti sapienti, teologicamente coerente è la con\nclusione del canto, che dal tempo si apre all’eterno nell’immagine della danza \nnuziale della Sposa, che unica può rendere possibile ai cristiani il partecipare \ndella pericoresi trinitaria. (\np\np\n15.\t Sulla meccanica di questo orologio, segnalo Rizzardi 2000. 14.\t Danza nuziale viene oggi comunemente definito nella pastorale cattolica l’amore coniugale \ne il sacramento del matrimonio (si veda, per esempio Pilloni 2002). q\ng\n16.\t Si veda, tra gli altri, Zupan 1990. 5\nq\ng\ng\n16.\t Si veda, tra gli altri, Zupan 1990. e il sacramento del matrimonio (si veda, per esempio Pilloni 2002).\n15.\t Sulla meccanica di questo orologio, segnalo Rizzardi 2000.\n16.\t Si veda, tra gli altri, Zupan 1990. Abstract Con una audace similitudine, l’armonia dei movimenti di danza viene \nparagonata alla maravigliosa modernissima invenzione dell’orologio di torre, il \ncui meccanismo era costituito da ruote dentate azionate da un sistema di pesi \ne contrappesi (penso ai ruoli di Tommaso e di Sigieri, per esempio), congegna\nti con un dispositivo di suoneria con martelletti e campanelle.15 Suggerendo \nuna percezione insieme visiva e acustica, le rote dell’orologio del tempo terreno \ne misurabile contemplano i traguardi della scientia umana (ed un esempio del \nprogresso tecnologico medievale di cui, com’è noto, questi versi costituiscono \nuna delle prime attestazioni). Ma c’è di più. L’orologio che fa tin tin sonando, \nsuona l’ora dell’amore, l’ora mattutina in cui l’amante canta i suoi versi all’a\nmata perché l’ami. Il riferimento esplicito è al genere erotico della mattinata,16 “Donne mi parver, non da ballo sciolte”: Appunti su danza e pericoresi “Donne mi parver, non da ballo sciolte”: Appunti su danza e pericoresi\t\nDante e l’arte 4, 2017 133 133 che preclude con il canto all’incontro amoroso. Rileggiamo i versi finali di \nParadiso X: Indi, come orologio che ne chiami\nne l’ora che la sposa di Dio surge\na mattinar lo sposo perché l’ami,\n\t\nche l’una parte e l’altra tira e urge,\ntin tin sonando con sì dolce nota,\nche ‘l ben disposto spirto d’amor turge;\n\t\ncosì vid’ïo la gloriosa rota\nmuoversi e render voce a voce in tempra\ne in dolcezza ch’esser non pò nota\t \n\t\nse non colà dove gioir s’insempra. (Pd. X, 139-148) Il gioire, quel jauzir che per i trovatori era tecnicismo specifico per significare \nil culminare, agognato, del piacere sensuale, diventa slancio di una gioia che \nsi eterna. Diventa slancio anagogico, incontro d’amore, danza nuziale, istante \nche si schiude e si apre all’eterno, jauzir che s’insempra, osculum aeternitatis. In conclusione, a margine dei molti e validi interventi tesi a chiarire la \nstruttura stilistica e la coerenza narrativa dei canti del cielo del Sole, nell’im\nmagine dei sapienti come donne danzanti si potrà forse cogliere anche la \nprofonda coerenza teologica del poeta cristiano, che non può descrivere con \nparole umane l’esperienza del suo trasumanare, ma che invita il lettore a fare \nqualcosa di più di leggere: lo invita a gustare e cibarsi da sé, a mirare i giri delle \neterne rote, a lasciarsi trasportare in alto, a prendere parte, anagogicamente, \nal movimento dal tempo all’eterno, a partecipare alla danza mistica della pe\nricoresi divina. Fig. 1. Andrej Rublëv, 1425, Icona della Trinità, tempera su legno, Galleria Tret’jakov, Mosca. Abstract Paolo De Ventura 134 Dante e l’arte 4, 2017 “Donne mi parver, non da ballo sciolte”: Appunti su danza e pericoresi “Donne mi parver, non da ballo sciolte”: Appunti su danza e pericoresi\t\nDante e l’arte 4, 2017 135 Dante e l’arte 4, 2017 135 Bibliografia Ange, D., 1999, Dalla Trinità all’eucaristia. L’icona della Trinità di Rublëv (Tra arte \nteologia), Milano, Ancora edizioni. Ange, D., 1999, Dalla Trinità all eucaristia. Licona della Trinità di Rublëv (Tra arte e \nteologia), Milano, Ancora edizioni. Artemi, E., 2017, «The Term Perichoresis from Cappadocian Fathers to Maximus teologia), Milano, Ancora edizioni. Artemi, E., 2017, «The Term Perichoresis from Cappadocian Fathers to Maximus \nConfessor» International Journal of European Studies vol 1 n 1 pp 21-29 g\nArtemi, E., 2017, «The Term Perichoresis from Cappadocian Fathers to Maximu\nConfessor», International Journal of European Studies, vol. 1, n. 1, pp. 21-29. Battistini, A., 1970-1978, Tresca e Trescare, in Enciclopedia Dantesca, Roma, Istituto \ndell’Enciclopedia Italiana, vol. V, p. 715a (l’opera è oggi disponibile in rete all’in\ndirizzo http://www.treccani.it/enciclopedia). Bausi, F., 2009, Dante fra scienza e sapienza: esegesi del canto XII del “Paradiso”, Firenze, \nOlschki. Catelli, N., 2008, «Coreografie paradisiache. Le danze dei sapienti (Par. X-XIV)», \nL’Alighieri, 32, pp. 119-138. g\npp\nCheaib, R., 2013, Un Dio umano. Primi passi nella fede cristiana, Roma, Edizioni \nPaoline. Cherchi, P. – Sarteschi, S., 2011, «Per una lettura della Commedia a “lunghe campa\nte”», Critica del testo [Dante, oggi/2], XIV/2, pp. 311-332. Faccin, G., 2006, L’icona della Trinità: una danza nuziale [omelia tenuta presso la \nCattedrale di Udine all’apertura dell’Anno pastorale 2006-7], disponibile in rete \nall’indirizzo: http://www.webdiocesi.chiesacattolica.it/cci_new/documenti_dioce\nsi/213/2006-09/11-39/Trinita-Cattedrale-sito1.pdf. Falzone, P., 2015, «Canto X. Dante nel sole», in Lectura Dantis Romana. Cento canti \nper cento anni. III. Paradiso. 1. Canti I-XVII, Roma, Salerno, pp. 279-314. Falzone, P., 2016a, «Il sole dei sapienti: Paradiso X (I)»), Bollettino di Italianistica, n.s., \nXIII/1, pp. 5-30. Falzone, P., 2016b, «Il sole dei sapienti: Paradiso X (II)», Bollettino di Italianistica, n.s., \nXIII/2, pp. 5-23. pp\nFreccero, J., 1986, The Dance of the Stars: Paradiso X, in Id., Dante: The Poetics of \nConversion, Cambridge, Harvard University Press, pp. 221-244. Hemmerle, K., 1998, Partire dall’unità. La Trinità come stile di vita e forma di pensiero, \na cura di Peter Blättler, prefazione e trad. di V. de Marco, Roma, Città Nuova (ed. orig. 1995) Knäble, P., 2014, «L’harmonie des sphères et la danse dans le contexte clérical a\nMoyen Âge», Médiévales, vol. 1, n. 66, pp. 65-80. y\ng\npp\nLugaresi, L., 2008, Il teatro di Dio. Il problema degli spettacoli nel cristianesimo antic\n(II-IV secolo), Brescia, Morcelliana. Mirocan, M., 2012, L’Arca della mente. Riccardo di San Vittore nella «Commedia» d\nDante, Firenze, Leo S. Olschki. Sinibaldi, C., 2009, «Quando la filosofia illumina la danza come pensiero dell’essere \ned esperienza del divino», Danza e Ricerca. Laboratorio di studi, scritture, visioni, \nanno I, numero 0, pp. 79-105. Sacra Congregazione pro Culto Divino, 1975, «La Danza nella Liturgia», Notitiae, 2, \npp. 202-205. pp\nZupan, P., 1990, «The New Dantean “Alba”: A Note on Paradiso X, 139-148», Lectura \nDantis, 6, pp. 92-99. Bibliografia Mondin, B., 2010, La Trinità mistero d’amore: Trattato di teologia trinitaria [second\nedizione riveduta], Bologna, Edizioni Studio Domenicano. g\nNègre, M., 1984, Danzerò per te, Roma, Edizioni Paoline. l\nl\nl\nd Pietrini, S., 2001, Spettacoli e immaginario teatrale nel Medioevo, Roma, Bulzoni. Pilloni, F., 2002, Danza nuziale. Itinerario teologico e catechismo per coppie e famigli\nTorino, Cantalupa. p\nPlacella, V., 2013, «Paradiso X», Studi Danteschi, LXXVIII, pp. 251-284. Ravasi, G., 2016, Il libro della Sapienza, Bologna, Edizioni Dehoniane. Resta, M., 2015, «Saltationes sceleratissimorum: la musica e la danza nei canoni conci\nliari e nelle epistole pontificie (iv-vii secolo)», Synesis, 7, 1, pp. 116-123. p\np\ny\npp\nRizzardi, S., 2000, «Dante e l’orologio», Studi e problemi di critica testuale, 60, pp. 51-70 p\np\ny\npp\nRizzardi, S., 2000, «Dante e l’orologio», Studi e problemi di critica testuale, 60, pp. 51-70. 136 Dante e l’arte 4, 2017 Paolo De Ventura Sinibaldi, C., 2009, «Quando la filosofia illumina la danza come pensiero dell’essere \ned esperienza del divino», Danza e Ricerca. Laboratorio di studi, scritture, visioni, \nanno I, numero 0, pp. 79-105. pp 79\n5\nZupan, P., 1990, «The New Dantean “Alba”: A Note on Paradiso X, 139-148», Lectura \nDantis, 6, pp. 92-99."}}},{"rowIdx":12598,"cells":{"identifier":{"kind":"string","value":"https://openalex.org/W4285086200"},"pdf_url":{"kind":"string","value":"https://www.researchsquare.com/article/rs-1781226/latest.pdf"},"lang":{"kind":"string","value":"English"},"error":{"kind":"null"},"title":{"kind":"string","value":"Umbilical cord plasma Lysophospholipids and Triacylglycerols Associated with Birthweight Percentiles"},"source_name":{"kind":"string","value":"Research Square (Research Square)"},"publication_year":{"kind":"number","value":2022,"string":"2,022"},"license":{"kind":"string","value":"cc-by"},"word_count":{"kind":"number","value":7800,"string":"7,800"},"text":{"kind":"string","value":"Umbilical cord plasma Lysophospholipids and Triacylglycerols Associated\nwith Birthweight Percentiles Gerard Wong Kok Hian Tan \nKK Women's and Children's Hospital (KKH) Fabian Yap \nKK Women's and Children's Hospital (KKH) Fabian Yap \nKK Women's and Children's Hospital (KKH) Lynette P Shek \nSingapore Institute for Clinical Sciences (SICS) Lynette P Shek \nSingapore Institute for Clinical Sciences (SICS) Yap Seng Chong \nSingapore Institute for Clinical Sciences (SICS) Yap Seng Chong \nSingapore Institute for Clinical Sciences (SICS) Peter Gluckman \nSingapore Institute for Clinical Sciences (SICS) Peter Gluckman \nSingapore Institute for Clinical Sciences (SICS) Introduction Maternal glycemia has been strongly correlated with offspring birthweight as a continuum across the glycemia spectrum 1. Further, there have been reports\nshowing associations between well-controlled gestational diabetes (GDM) and fetal overgrowth or macrosomia, indicating that factors other than glucose\nmay actively contribute to fetal growth 2,3. For example, in pregnant women with well-controlled GDM, maternal circulating free fatty acids were positively\ncorrelated with neonatal adiposity at birth 4. This observation has led to the hypothesis that dysregulated maternal to fetal lipid transfer and placental lipid\nmetabolism may also be critical drivers in the regulation of fetal size, independently of maternal glycemia 5. However, the mechanisms remain poorly\nunderstood. The transplacental supply of glucose and key amino acids are known to influence fetal growth but the specific lipid species involved remain\nunknown. Lipids not only form components of cellular structures and serve as substrates for energy and metabolism, but they have wide-ranging bioactive\nproperties of their own 6. It is believed that fatty acids are transferred in unesterified forms across the maternal-placental and placental-fetal interfaces but\nthere is now evidence that lipids such as lysophospholipids may also cross the placental syncytiotrophoblast barrier through plasma membrane transporters\n7. It is clear that fatty acids and lipids derived from the mother undergo extensive metabolism in the placenta before export to the fetus 8 for nutritive purposes\nand also as biological signalling compounds. In addition to transplacental transfer, fetal fatty acids and lipids can also be synthesised from glucose by fetal\ntissues de novo, except the long chain polyunsaturated fatty acids (LC-PUFA) due to the lack of specific desaturase expression in fetal-placental tissue. However, the full range of fatty acids and the predominant lipid forms in which fatty acids are transported across the placental interfaces are not well-\ncharacterized. An understanding of the key lipid species involved in regulating fetal size and the role of placental lipid metabolism and transfer are essential in\nforming the basis for developing novel strategies in the management of pathological conditions such as gestational diabetes, maternal obesity and\nuteroplacental insufficiency. New strategies, including the modulation of placental lipid metabolism and transplacental lipid supply, are required since present\napproaches aimed at improving maternal glycemic regulation and the control of gestational weight gain, have not shown consistent efficacy in optimizing\nfetal growth. We hypothesized that specific lipid species in the fetal circulation are associated with fetal growth. Article eywords: Umbilical cord blood, Lysophosphatidylcholine, Triacylglycerol, Lipidomics, Fetal growth, GUSTO License:\n\n\nThis work is licensed under a Creative Commons Attribution 4.0 International\nLicense. Read Full License Page 1/12 Page 1/12 Page 1/12 Introduction With increasing maternal glycemia, we\npostulate that there is altered transplacental lipid supply and changes in the fetal metabolism of lipids, which collectively alter the concentration of specific\nlipid species in the fetal circulation that are associated with fetal size. To address present knowledge gaps, we aimed to describe the relationship between\nmaternal glycemia and the concentrations of specific lipid species in umbilical cord plasma, identify lipid species in umbilical cord plasma which are most\nassociated with birthweight, and assess alongside each specific lipid species, the particular effect estimate of maternal glycemia on birthweight. Association of cord blood lipid species with maternal glucose Although 78 lipid species demonstrated an uncorrected p-value<0.05 (filtered results shown in Table 2), after correcting for false discovery none of the 404\ncord blood lipid species’ concentrations was associated with fasting glucose after adjustment for maternal age, maternal BMI, mode of delivery, assisted\nconception, and insulin treatment. The filtered (uncorrected p<0.05) results for the association of cord blood lipid species concentration with 2h post-load glucose adjusted for similar covariates\nas for fasting glucose, included 83 lipid species (Table 3). Following FDR correction, increasing 2h-glucose was significantly associated with only one lipid\nspecies: ceramide (Cer) d18:1/C33:1 (β 0.36 SDs of log10 relative concentration per mmol/L increase; 95% CI 0.21, 0.51; FDR corrected p= 4.93 E-03). Abstract Dysregulated transplacental lipid transfer and fetal-placental lipid metabolism affect birthweight, as does maternal hyperglycemia. As the mechanisms are\nunclear, we aimed to identify the lipids in umbilical cord plasma that were most associated with birthweight. Seventy-five Chinese women with singleton\npregnancies recruited into the GUSTO mother-offspring cohort were selected from across the glycemic range based on a mid-gestation 75g oral glucose\ntolerance test, excluding pre-existing diabetes. Cord plasma were analysed using targeted liquid-chromatography tandem mass-spectrometry to determine\nrelative concentrations of 404 lipid species across 17 lipid classes. Birthweights were standardized for sex and gestational age by local references, and\nregression analyses adjusted for maternal age, BMI, parity, mode of delivery, insulin treatment, and fasting/2h glucose, with false discovery-corrected p<0.05\nconsidered significant. Ten lysophosphatidylcholines (LPC) and two lysophosphatidylethanolamines were positively associated with birthweight percentiles,\nwhile twenty-four triacylglycerols negatively associated with birthweight percentiles. The topmost associated lipid was LPC 20:2 [21.28 (95%CI 12.70, 29.87)\npercentile increase in standardized birthweight with each SD-unit increase in log10-transformed relative concentration]. Within these same regression models,\nmaternal glycemia did not significantly associate with birthweight percentile. Specific fetal circulating lysophospholipids and triacylglycerols associate with\nbirthweight independently of maternal glycemia, but a causal relationship remains to be established. Maternal subject characteristics Fasting and 2h post-load glucose measurements at a mid-gestation 75g oral glucose tolerance test (OGTT) defining the four glycemia quartile groups were\nsignificantly different as expected (Table 1). Fifteen women (20%) had GDM and three of them received insulin treatment. The groups had similar maternal\nage, pre-pregnancy BMI, infant sex, gestational age at birth, and mode of delivery, with a small minority of cases of assisted conception in all groups. Standardized birthweight percentiles were different between glycemia groups with the lowest and highest glycemia quartile groups having the lowest and\nhighest mean birthweight percentiles, respectively. Discussion This study identified specific LPC and LPE species to be positively associated with birthweight, along with specific TAG species to be negatively associated\nwith birthweight, independently of maternal glycemia. The cord plasma lipidome encapsulates maternal metabolism, placental metabolism, transfer across\nthe maternal-placental-fetal axis and fetal metabolism, to provide valuable insights into the availability of nutrients for the fetus and the state of fetal\nmetabolism as well as the presence of bioactive lipid signalling compounds circulating in the fetus. Novel aspects of our study are the identification of the\nrange of specific lipid species that could be potentially involved in the regulation of fetal size, and that individually they appear to have a greater influence on\nbirthweight than maternal glycemia. Our results on LPC lipid species strongly concur with a population-based observational study of predominantly White Caucasians in Germany 9 that also\nreported positive associations between cord blood LPC 16:1, LPC 18:1 and LPC 20:3 with birthweight. Similarly, a UK study of pregnant women with obesity\n(UPBEAT cohort) also found positive correlations between cord blood LPC 16:1 and LPC 18:1 with birthweight 10 using targeted metabolomics panels which\ntested only a restricted number of lipids. This suggests that such associations transcend ethnicity. In addition, with our more extensive analytical method we\nhave made novel identifications of several other LPC species, including LPC 18:3, LPC 20:0, LPC 20:2, and LPC 22:5, that were positively associated with\nbirthweight that have not previously been reported. The high representation of LPCs containing monounsaturated fatty acids (MUFAs) such as LPC 16:1, LPC 18:1, LPC 20:1 and LPE 18:1, as among the most\npositively associated lipids with birthweight percentiles is interesting. Stearoyl-Coenzyme A desaturase-1 (SCD1) is a rate-limiting enzyme that converts\nsaturated fatty acids to mono-unsaturated fatty acids and is involved in the development of obesity-promoting lipogenesis 11. Our results suggest that\nenhanced SCD1 activity, perhaps within the fetal-placental unit, may have a role in promoting fetal growth. Increased lipogenesis possibly results in greater\nfetal fat accretion and consequently higher birthweight. The main source of LPCs in the fetal circulation is unknown. A study has suggested the occurrence of placental to fetal transfer of LPCs through plasma\nmembrane transporters like MFSD2A 7 but endogenous fetal LPC synthesis is also likely. Association of cord blood lipid species with standardized birthweight percentiles After adjusting for maternal age, pre-pregnancy BMI, parity, mode of delivery, assisted conception, fasting glucose, 2hr glucose and insulin treatment, only 36\nlipid species from 3 lipid classes were identified to be significantly associated (FDR-corrected p-value<0.05) with standardized birthweight percentiles: Page 2/12 specifically, lysophosphatidylcholine (LPC; 10 species), lysophosphatidylethanolamines (LPE; 2 species) and triacylglycerols (TAG; 24 species) (Table 4). LPC\nand LPE lipid species were all positively associated while TAGs were all negatively associated with standardized birthweight percentiles. specifically, lysophosphatidylcholine (LPC; 10 species), lysophosphatidylethanolamines (LPE; 2 species) and triacylglycerols (TAG; 24 species) (Table 4). LPC\nand LPE lipid species were all positively associated while TAGs were all negatively associated with standardized birthweight percentiles. The LPC species containing eicosadienoic acid (LPC 20:2) displayed the largest magnitude of association and most statistically significant result with\nstandardized birthweight percentile. Each SD-unit increase in the log10-transformed relative concentration of LPC 20:2 was associated with a 21.28 (95%CI\n12.70, 29.87) percentile increase in standardized birthweight. Lysophospholipids containing mono- and poly-unsaturated fatty acids of 18-carbon and 20-\ncarbon chain lengths also featured prominently: LPC 18:1, LPC 18:2, LPC 18:3, LPC 20:0p/20:1e, LPC 20:1, LPC 20:2, LPC 20:3 and LPC 20:4. The\nlysophospholipids containing the long chain polyunsaturated fatty acids (LC-PUFA) arachidonic acid (LPC 20:4), docosapentaenoic acid (DPA; LPC 22:5), as\nwell as containing a common monounsaturated fatty acid (LPC 16:1) were also identified. Of note, none of the identified LPCs or LPEs contained saturated\nfatty acids. Generally, TAGs displayed a similar magnitude of association with standardized birthweight percentile (range: -12.11 to -27.67% per-SD increase log10-\ntransformed relative lipid concentration) compared with the lysophospholipids (13.19 to 21.28 % per-SD log10 relative lipid), but the associations were in the\nopposite direction (Table 4). The lipid species with the strongest negative association was TAG 50:2 (β -27.67 % [-41.81, -13.52] per-SD log10 lipid). The fatty\nacid triplet composition of many of these TAGs (total carbon range from 48-58) comprised predominantly long-chain fatty acids (≥14 carbon length), and\n83.3% of them contained at least one mono-unsaturated or poly-unsaturated fatty acid combined with one or two long-chain saturated fatty acids. Interestingly, 20.8% of the TAGs (TAG 53:1, TAG 55:3, TAG 57:3, TAG 53:3, TAG 53:0) included at least one odd chain fatty acid. Sensitivity Analyses In the first sensivity analysis, which excluded subjects treated with insulin (Table S1; n=72), and in the second sensivity analysis, which excluded participants\nwith diabetes in pregnancy (possibly undiagnosed pre-existing diabetes defined by fasting glucose ≥7.0 and/or 2h glucose ≥7.8 mmol/L in a mid-gestation\n75g OGTT; Table S2; n=72), the list of lipid species most associated with standardized birthweight percentiles, and the magnitude of effect size, were very\nsimilar to the list obtained in the main analyses of the complete set of subjects. The list still comprised of only LPCs, LPEs and TAGs with almost similar\nrankings even though there was overall less significant p-values which are likely a reflection of reduced statistical power from the smaller sample sizes. The\nthird sensivity analysis, which excluded participants with possible placental insufficiency or hypertensive disorders of pregnancy (Table S3), reduced the\nsample size considerably to 55, but still showed largely similar results. In all three sensitivity analyses, LPC 20:2 remained the topmost significantly\nassociated with standardized birthweight percentile, with a similar magnitude of association across all analyses (beta coefficient range 17.17 – 21.81 % per-\nSD log10 relative lipid). Association of cord blood lipid species with standardized birthweight percentiles Within the same linear regression models incorporating each of the 36 significant lipid species, we also documented the estimated effect of maternal\nglycemia with standardized birthweight, and found that the corresponding covariates of fasting and 2h glucose measurements were both not associated with\nstandardized birthweight percentiles following FDR-correction (Table 4). This suggests that maternal glycemia did not significantly influence birthweight\npercentile, unlike the corresponding lipid species in each model. Discussion We postulate that the negative correlation between cord blood TAGs and birthweight may be partly attributed to lower endothelial lipoprotein lipase (LPL)\nactivity in adipose tissue of smaller fetuses, leading to reduced hydrolysis of circulating TAG-rich lipoproteins 4,18,19, which is required to release fatty acids for\nlocal cellular uptake. The expression of local LPL is known to strongly associate with adipose tissue development 20. Consistent with the notion of impaired\nlipid uptake and utilization by adipose tissue, Holtrop et al. 21 showed that TAGs were elevated in extremely low birthweight infants receiving lipid emulsions. However, the fact that there are particular TAG species that are more negatively associated with birthweight than others suggest more specific functions\nplayed by individual TAGs over and above the supply of energy and substrates for growth. These roles remain speculative at present and may involve\ndifferential fatty-acid-composition-dependent substrate preferences of various tissue-specific lipases during development, which have implications for fetal\ngrowth. Within the regression models for each of the lipid species associated with birthweight, the influence of maternal glycemia on birthweight was limited. This is\nconsistent with the postulation that fetal growth can also be significantly influenced by altered lipid supply and metabolism, and not just by maternal\nglycemia 5. Nonetheless we had investigated if maternal glycemia associated with any cord plasma lipid concentrations. Comparisons of our results with other studies\nthat had used targeted metabolomics methods that included a much narrower range of lipid species showed some consistency. Like our study, one reported\nno association between cord lipids and maternal fasting glycaemia 22 but unlike our results, another study found a positive association between maternal\nfasting glycemia and cord LPC 16:1 concentration 10. Our finding of an association between maternal 2h post-glucose load and cord Cer d18:1/C33:1 is novel,\nbut needs to be replicated in an independent cohort. In general, ceramides are sphingolipids that form structural components of the plasma membrane as well\nas act as bioactive agents involved in regulating cell viability, oxygen sensing, and have been associated with changes in maternal insulin resistance\nperipartum 23 and in adults, 24 and implicated in hepatic insulin resistance 25 Either altered transplacental passage or modified fetal synthesis of ceramides\ncould plausibly underlie the ceramide association with maternal glycemia, but in our study the ceramides did not associate with birthweight percentile and the\nclinical significance of this glycemia-ceramide association is unknown. Discussion LPC as a lipid class is known to be related to regulation of\ninflammatory processes 12,13 and LPC-DHA (docosahexaenoic acid) is important for brain growth 14 but their role in fetal metabolism, growth and adiposity is\nnot understood. Lysophospholipids comprise only a very small fraction of total circulating fetal lipids thus they are unlikely to be significant contributors to Page 3/12 Page 3/12 energy supply and cellular structures required for bodily growth, and more likely to act as important biological signals regulating fetal growth. For example,\nLPCs were found to activate adipocyte glucose uptake thereby lowering blood glucose in animal models of diabetes 15. energy supply and cellular structures required for bodily growth, and more likely to act as important biological signals regulating fetal growth. For example,\nLPCs were found to activate adipocyte glucose uptake thereby lowering blood glucose in animal models of diabetes 15. The most significant lipid species observed in every linear regression model, including all sensitivity analyses, was consistently LPC 20:2, which affirms the\nrobustness of our results. The magnitude of association of LPC 20:2 with birthweight is clinically significant; a twenty-one percentile increase in standardized\nbirthweight with every SD increase in log10-transformed relative concentration. The potential mechanism by which LPC 20:2 could regulate growth, however,\nremains elusive. Our cord lipidomic profiling also showed that the TAG lipid species were negatively associated with standardized birthweight percentiles. The measurement of\ncord blood total TAGs in general using clinically validated instruments has been previously performed in several European studies 4,10,16 which also reported\nthat total TAGs negatively associated with birthweight. They found that TAG concentrations were significantly higher in small-for-gestational-age (SGA)\nneonates compared with appropriately grown and large-for-gestational-age (LGA) neonates. Unlike these studies, our study examined in greater depth what the\nspecific TAG species were that associated with birthweight, which is a novel contribution of our work. The fatty acid triplet composition of the 24 identified\nTAG species showed the predominance of combinations of long-chain mono-unsaturated fatty acids with long-chain saturated fatty acids. Furthermore, about\na fifth of these TAGs contained one odd chain fatty acid (C15 or C17) which are of very low abundance in the human circulation. The C17:0 fatty acid has\nbeen linked with glucose intolerance in adults, 17 thus its role as a metabolic modulator and growth regulator in the fetus is plausible. Discussion Even though our findings are largely concordant with other similar studies, our study has several limitations that may reduce generalizability. Our selected\nsubsample only included subjects of Chinese ethnicity, of predominantly non-obese mothers, and with fairly uniform numbers selected from each glycemia\nquartile, which increases representation at both ends of the glycemic spectrum and therefore does not represent normal distribution within a general obstetric\npopulation. Nevertheless, the GDM rate of 20% among this subsample is similar to the overall GDM incidence among Chinese women in the whole GUSTO\ncohort 26. There was a higher proportion of SGA and LGA neonates, as well as rates of hypertensive disorders, more than would be expected from a\nrepresentative sample of the population, although these criteria were not used in the selection process. However, exclusion of the extreme cases of\nhyperglycemia and of SGA and hypertension cases in sensitivity analyses did not materially alter our results. Our expanded findings of lipid species\nassociated with birthweight can largely be attributed to a more comprehensive analytical lipid profiling platform that covered over 400 lipid species distributed\nacross 17 lipid classes. This allowed the novel identification of specific lipid species that are independently and significantly associated with standardized\nbirthweight percentiles. However, it is important to replicate our findings in a larger sample to confirm these associations. In conclusion, our results demonstrate that birthweight is positively associated with specific fetal circulating lysophospholipids and negatively associated with\nspecific TAGs, independently of maternal glycemia. We suggest that specific lysophospholipids may act as biological signals in promoting fetal growth, while\ncirculating concentrations of specific TAGs are changed as a consequence of altered metabolism and consumption by developing fetal tissues. Further\nstudies to understand the mechanistic relationships between these specific lipid species and in utero growth could lead to new approaches in optimizing fetal\nsize, including the modulation of transplacental lipid supply, which is urgently needed in an era of rising incidences of fetal macrosomia, maternal obesity and\ndiabetes. Cord blood plasma lipidomic analysis Thawed cord plasma samples were spiked with known amounts of lipid internal standards and lipids were extracted using a modified Bligh & Dyer method\n28. The lipidomic profile of the cord plasma samples were determined with targeted lipid analysis using liquid chromatography multiple reaction monitoring\nmass spectrometry (LC-MS/MS). The quantification of phospholipids, sphingolipids, glycolipids were determined by an Agilent 1290 HPLC system paired with\nan Agilent 6460 triple quadrupole mass spectrometer. The quantification of neutral lipid species diacylglycerols (DAG) and triacylglycerols (TAG) was\ndetermined by a Shimadzu LC-10/20 system paired with an ABI 3200 triple quadrupole mass spectrometer. In total, the relative concentrations of 404 lipid\nspecies from 17 lipid classes were determined. The 17 lipid classes included TAG, DAG, lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE),\nceramide (Cer), dihydroceramide (DHCer), monohexosyl ceramide (MHCer), phosphatidylcholine (PC), oddPC, alkyl-phosphatidylcholine [PC(O)], alkenyl-\nphosphatidylcholine [PC(P)], phosphatidylethanolamine (PE), alkyl-PE [PE(O)], alkenyl-PE [PE(P)], phosphatidylinositol (PI), phosphatidylserine (PS),\nand sphingomyelin (SM). Cord blood collection and sample selection Umbilical venous cord blood was collected at delivery in EDTA tubes, centrifuged and the plasma stored frozen with trasylol until batch analysis. For this\nsubstudy, cord blood plasma samples were confined to those from neonates with homogenous Chinese parentage (the largest ethnic group in GUSTO) 27 and\ndelivered at term by non-smoking mothers, excluding known cases of pre-existing maternal diabetes, to minimize confounding by these factors. Samples\n(n=75) were then selected to cover the entire maternal glycemic spectrum in GUSTO, thus, approximately equal numbers from each of the 4 quartiles of the\nmaternal fasting glycemic range based on a mid-gestation (mean ~26 weeks at time of testing) two time-point 75g oral glucose tolerance test (OGTT) were\nchosen. Selected cases also had 2h glycemia values in the same quartiles as their fasting glycemia. Gestational Diabetes Mellitus (GDM) was defined using\nthe World Health Organisation (WHO) 1999 criteria (fasting glucose ≥7.0 and/or 2h glucose ≥7.8 mmol/L), which was the criteria in use at the time of the\nstudy. Statistical Analysis Sex-specific birthweight-for-gestational age percentile was derived based on GUSTO data according to published methods 29. The relative concentrations\nof lipid species were log10 transformed and standardized to z-scores to minimise skewness in their distribution and to faciltiate comparison between lipid\nspecies with often very different levels of concentration. Multiple linear regression was applied for each and every lipid species analyzed in cord blood plasma\nto determine its association with maternal glycemia or standardized birthweight percentile. Adjustments were made for maternal age, maternal BMI, parity,\nmode of delivery (vaginal, non-labour cesarean, intrapartum cesarean), conception by assisted reproductive techniques, insulin treatment, fasting glucose\nand/or 2h post-load glucose. The p-values were false-discovery rate (FDR) corrected using the Benjamini-Hochberg approach 30. Statistical significance was\nset at FDR <0.05. We also conducted a series of sensitivity analyses to assess the robustness of our results. Three sub-analyses were performed to ensure results were not\nsignificantly changed: i) exclusion of those treated with insulin, ii) exclusion of those with diabetes in pregnancy as determined by fasting glucose ≥7.0\nand/or 2h glucose ≥11.1 mmol/L, iii) exclusion of possible placental insufficiency suggested by a birthweight percentile below 10, or the presence of pre-\neclampsia or pregnancy-induced hypertension. All statistical analyses were performed using MATLAB R2017b. Materials And Methods The GUSTO Study Page 4/12 This work is part of The Growing Up in Singapore Towards Healthy Outcomes (GUSTO) study, a prospective mother-offspring cohort study in Singapore\ndesigned to investigate the effect of early-life events on the risk of developing metabolic diseases later in life 27. This study was approved by the Centralised\nInstitutional Review Board of the KK Women's and Children's Hospital (KKH) and the Domain-Specific Review Board of the National University Hospital (NUH). Informed written consent was obtained from all participants upon recruitment and all methods were performed in accordance with the relevant guidelines and\nregulations. Study participants of 18 years of age and older were recruited (n=1450) from among pregnant women attending antenatal care (between 10 to 14\nweeks of gestation) between June 2009 and September 2010 at the two largest public maternity units in Singapore, KKH and NUH. Eligible participants were\nof Chinese, Malay or Indian ethnicity, Singapore residents with intention to reside in Singapore for at least five years post-delivery, and willing to donate bio-\nsamples. Women receiving chemotherapy, psychotropic drugs or with type 1 diabetes mellitus were excluded. Demographic data including maternal age,\nethnicity, self-reported pre-pregnancy body mass index (BMI), and history of assisted conception were obtained by interviewer administered questionnaires,\nand details of mode of delivery, infant sex, gestational age at birth and birthweight were obtained from medical records. Acknowledgements: The authors thank the GUSTO study group, which includes Allan Sheppard, Amutha Chinnadurai, Anne Eng Neo Goh, Anne Rifkin-Graboi, Anqi Qiu, Arijit\nBiswas, Bee Wah Lee, Birit F.P. Broekman, Boon Long Quah, Borys Shuter, Chai Kiat Chng, Cheryl Ngo, Choon Looi Bong, Christiani Jeyakumar Henry, Cornelia\nYin Ing Chee, Yam Thiam Daniel Goh, Doris Fok, George Seow Heong Yeo, Helen Chen, Hugo P S van Bever, Iliana Magiati, Inez Bik Yun Wong, Ivy Yee-Man\nLau, Jeevesh Kapur, Jenny L. Richmond, Jerry Kok Yen Chan, Joanna D. Holbrook, Joshua J. Gooley, Kenneth Kwek, Krishnamoorthy Niduvaje, Leher Singh, Lin\nLin Su, Lourdes Mary Daniel, Mark Hanson, Mary Foong-Fong Chong, Mary Rauff, Mei Chien Chua, Michael Meaney, Ngee Lek, Oon Hoe Teoh, P. C. Wong,\nPratibha Agarwal, Rob M. van Dam, Salome A. Rebello, Seang-Mei Saw, Shang Chee Chong, Shirong Cai, Shu-E Soh, Sok Bee Lim, Chin-Ying Stephen Hsu,\nVictor Samuel Rajadurai, Walter Stunkel, Wee Meng Han, Wei Wei Pang, Yin Bun Cheung, and Yiong Huak Chan. Authorship Page 5/12 References 1. Group, H. S. C. R. et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 358, 1991–2002, doi:10.1056/NEJMoa0707943 (2008). 2. Kc, K., Shakya, S. & Zhang, H. Gestational diabetes mellitus and macrosomia: a literature review. Ann Nutr Metab 66 Suppl 2, 14–20,\ndoi:10 1159/000371628 (2015) 1. Group, H. S. C. R. et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 358, 1991–2002, doi:10 1. Group, H. S. C. R. et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 358, 1991 2002, doi:10.1056/NEJMoa0707943 (2008). 2. Kc, K., Shakya, S. & Zhang, H. Gestational diabetes mellitus and macrosomia: a literature review. Ann Nutr Metab 66 Suppl 2, 14–20,\ndoi:10.1159/000371628 (2015). 2. Kc, K., Shakya, S. & Zhang, H. Gestational diabetes mellitus and macrosomia: a literature review. Ann Nutr Metab 66 Suppl 2, 14–20,\ndoi:10.1159/000371628 (2015). 3. Ladfors, L. et al. Fetal overgrowth in women with type 1 and type 2 diabetes mellitus. PLoS One 12, e0187917, doi:10.1371/journal.pone.0187917 (2017). 4. Schaefer-Graf, U. M. et al. Maternal lipids as strong determinants of fetal environment and growth in pregnancies with gestational diabetes mellitus. Diabetes Care 31, 1858–1863, doi:10.2337/dc08-0039 (2008). 3. Ladfors, L. et al. Fetal overgrowth in women with type 1 and type 2 diabetes mellitus. PLoS One 12, e01879 3. Ladfors, L. et al. Fetal overgrowth in women with type 1 and type 2 diabetes mellitus. PLoS One 12, e0187917, doi:10.1371/journal.pone.0187917 (2017). 4. Schaefer-Graf, U. M. et al. Maternal lipids as strong determinants of fetal environment and growth in pregnancies with gestational diabetes mellitus. 3. Ladfors, L. et al. Fetal overgrowth in women with type 1 and type 2 diabetes mellitus. PLoS One 12, e0187917, doi:10.1371/journal.pone.0187917 (2017 3. Ladfors, L. et al. Fetal overgrowth in women with type 1 and type 2 diabetes mellitus. PLoS One 12, e0187917, doi:10.1371/journal.pone.0187917 (2017). 4. Schaefer-Graf, U. M. et al. Maternal lipids as strong determinants of fetal environment and growth in pregnancies with gestational diabetes mellitus. Diabetes Care 31, 1858–1863, doi:10.2337/dc08-0039 (2008). 4. Schaefer-Graf, U. M. et al. Maternal lipids as strong determinants of fetal environment and growth in pregnancies with gestational diabetes mellitus. Diabetes Care 31, 1858–1863, doi:10.2337/dc08-0039 (2008). 5. Herrera, E. & Ortega-Senovilla, H. Implications of Lipids in Neonatal Body Weight and Fat Mass in Gestational Diabetic Mothers and Non-Diabetic\nControls. Curr Diab Rep 18, 7, doi:10.1007/s11892-018-0978-4 (2018). 5. Herrera, E. & Ortega-Senovilla, H. Data availability The results from the lipidomics analyses in this study are fully presented both in the main manuscript as well as in the supplementary tables. Clinical data and\nlipidomics data are not publicly available but could be obtained from the corresponding author upon reasonable request and subject to appropriate approvals,\nincluding from the GUSTO cohort’s Executive Committee. Role of the Funder/Sponsor The funders had no role in the design and conduct of the study; collection, management, analysis, and interpret\napproval of the manuscript; and decision to submit the manuscript for publication. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or\napproval of the manuscript; and decision to submit the manuscript for publication. Page 5/12 SYC conceived and designed this study together with MW and NK, who co-supervised the main analyses of samples and data analyses performed by WFC,\nGW and KN. SN, IA, SES SLL and AB contributed to data used in the analyses. KHT, FY, LS, YSC, PD, KMG and YSL SYC conceived and designed this study together with MW and NK, who co-supervised the main analyses of samples and data analyses performed by WFC,\nGW and KN. SN, IA, SES SLL and AB contributed to data used in the analyses. KHT, FY, LS, YSC, PD, KMG and YSL were involved in the design and supervision of the overall GUSTO cohort study. GW, KN, NK and SYC were responsible for drafting the manuscript. All authors\nprovided feedback on interpretation of results, and edition of the manuscript. The first two authors and the last two authors had full access to all the data in\nthe study and takes responsibility for the integrity of the data and the accuracy of the data analysis. SYC is the guarantor of this work. Competing interest SYC, YSC, YSL and KMG have received reimbursement for speaking at conferences sponsored by companies selling nutritional products. YSC, KMG, NK, and\nSYC are part of an academic consortium that has received research funding from Abbott Nutrition, Nestle S.A, Danone and Benevolent AI for work unrelated to\nthis manuscript. The other authors have no financial or personal conflict of interest to declare. Funding/Support: This research is supported by the Singapore National Research Foundation under its Translational and Clinical Research (TCR) Flagship Programme and\nadministered by the Singapore Ministry of Health’s National Medical Research Council (NMRC), Singapore - NMRC/TCR/004-NUS/2008; NMRC/TCR/004-\nNUS/2008. The Singapore Lipidomics Incubator receives funding from the Life Sciences Institute, the National University of Singapore Yong Loo Lin School of\nMedicine, and the National Research Foundation (grant number NRFI2015-05). This research is also supported by a Clinician Scientist Award to SYC from the\nSingapore National Medical Research Council (NMRC/CSA-INV/0010/2016; MOH-CSAINV19nov-0002). KMG is supported by the UK Medical Research Council\n(MC_UU_12011/4), the National Institute for Health Research (NIHR Senior Investigator (NF-SI-0515-10042) and the NIHR Southampton Biomedical Research\nCentre) and the European Union (Erasmus+ Programme ImpENSA 598488-EPP-1-2018-1-DE-EPPKA2-CBHE-JP). Additional funding is provided by the\nSingapore Institute for Clinical Sciences (SICS), Agency for Science Technology and Research (A*STAR). References Implications of Lipids in Neonatal Body Weight and Fat Mass in Gestational Diabetic Mothers and Non-Diabetic\nControls. Curr Diab Rep 18, 7, doi:10.1007/s11892-018-0978-4 (2018). 6. Phillips, R., Ursell, T., Wiggins, P. & Sens, P. Emerging roles for lipids in shaping membrane-protein function. Nature 459, 379–385,\ndoi:10.1038/nature08147 (2009). 6. Phillips, R., Ursell, T., Wiggins, P. & Sens, P. Emerging roles for lipids in shaping membrane-protein function. Nature 459, 379–385,\ndoi:10.1038/nature08147 (2009). 7. Ferchaud-Roucher, V. et al. A potential role for lysophosphatidylcholine in the delivery of long chain polyunsaturated fatty acids to the fetal circulation. Biochim Biophys Acta Mol Cell Biol Lipids 1864, 394–402, doi:10.1016/j.bbalip.2018.12.007 (2019). 7. Ferchaud-Roucher, V. et al. A potential role for lysophosphatidylcholine in the delivery of long chain polyunsaturated fatty acids to the fetal circulation. Biochim Biophys Acta Mol Cell Biol Lipids 1864, 394–402, doi:10.1016/j.bbalip.2018.12.007 (2019). 7. Ferchaud-Roucher, V. et al. A potential role for lysophosphatidylcholine in the delivery of long chain polyunsaturated fatty acids to the fetal circulation. Biochim Biophys Acta Mol Cell Biol Lipids 1864, 394–402, doi:10.1016/j.bbalip.2018.12.007 (2019). 8. Perazzolo, S. et al. The influence of placental metabolism on fatty acid transfer to the fetus. J Lipid Res 58 9. Hellmuth, C. et al. Cord Blood Metabolome Is Highly Associated with Birth Weight, but Less Predictive for Later Weight Development. Obes Facts 10, 85–\n100, doi:10.1159/000453001 (2017). 9. Hellmuth, C. et al. Cord Blood Metabolome Is Highly Associated with Birth Weight, but Less Predictive for Later Weight Development. Obes Facts 10, 85–\n100, doi:10.1159/000453001 (2017). 10. Patel, N. et al. Cord Metabolic Profiles in Obese Pregnant Women: Insights Into Offspring Growth and Body Composition. J Clin Endocrinol Metab 103,\n346–355, doi:10.1210/jc.2017-00876 (2018). 11. Paton, C. M. & Ntambi, J. M. Biochemical and physiological function of stearoyl-CoA desaturase. Am J Physiol Endocrinol Metab 297, E28-37,\ndoi:10.1152/ajpendo.90897.2008 (2009). 11. Paton, C. M. & Ntambi, J. M. Biochemical and physiological function of stearoyl-CoA desaturase. Am J Physiol Endocrinol Metab 297, E28-37,\ndoi:10.1152/ajpendo.90897.2008 (2009). 12. Aiyar, N. et al. Lysophosphatidylcholine induces inflammatory activation of human coronary artery smooth muscle cells. Mol Cell Biochem 295, 113–120,\ndoi:10.1007/s11010-006-9280-x (2007). 12. Aiyar, N. et al. Lysophosphatidylcholine induces inflammatory activation of human coronary artery smooth muscle cells. Mol Cell Biochem 295, 113–120\ndoi:10.1007/s11010-006-9280-x (2007). 13. Sevastou, I., Kaffe, E., Mouratis, M. A. & Aidinis, V. Lysoglycerophospholipids in chronic inflammatory disorders: the PLA(2)/LPC and ATX/LPA axes. Biochim Biophys Acta 1831, 42–60, doi:10.1016/j.bbalip.2012.07.019 (2013). 13. 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A global reference for fetal-weight and birthweight percentiles. Lancet 377, 1855–1861, doi:10.1016/S0140-6736(11)60364-4\n(2011). 30. Benjamini Y, H. Y. Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing. Journal of the Royal Statistical Society. Series B (Methodological) 57 (1995). 30. Benjamini Y, H. Y. Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing. Journal of the Royal Statistical Society. Series B (Methodological) 57 (1995). References Sevastou, I., Kaffe, E., Mouratis, M. A. & Aidinis, V. Lysoglycerophospholipids in chronic inflammatory disorders: the PLA(2)/LPC and ATX/LPA axes. Biochim Biophys Acta 1831, 42–60, doi:10.1016/j.bbalip.2012.07.019 (2013). Page 6/12 14. Nguyen, L. N. et al. Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid. Nature 509, 503–506, doi:10.1038/nature13241\n(2014). 15. Yea, K. et al. 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Tables Table 1: Characteristics of subjects across the four glycemia quartiles used for case selection Page 7/12 Page 7/12 Q1\nQ2\nQ3\nQ4\nn\n19\n21\n17\n18\nMaternal age (years)\n30.18 (5.58)\n32.51 (4.38)\n31.40 (5.33)\n33.51 (3.97)\nPre-pregnancy BMI (kg/m2) \n20.09 (4.61)\n22.32 (2.92)\n21.48 (3.36)\n23.20 (4.60)\nSpontaneous conception \n19 (100.0)\n19 (90.5)\n16 (94.1)\n15 (83.3)\nFasting glucose (median [IQR])Ϯ\n3.90 [3.80, 4.00]\n4.20 [4.20, 4.30]\n4.40 [4.40, 4.50]\n4.90 [4.80, 5.10]\n2 hour glucose (median [IQR])Ϯ\n4.90 [4.60, 5.05]\n6.20 [5.80, 6.40]\n6.80 [6.70, 7.00]\n8.65 [7.95, 9.30]\nGestational diabetes \n0 (0.0)\n0 (0.0)\n0 (0.0)\n15 (83.3)\nHypertensive disorders of pregnancy $\n\n\n\n\n PE\n1 (5.3)\n0 (0.0)\n0 (0.0)\n1 (5.6)\n PIH\n2 (10.5)\n2 (9.5)\n0 (0.0)\n2 (11.1)\nFemale neonate \n8 (42.1)\n9 (42.9)\n14 (82.4)\n7 (38.9)\nGestational age at delivery (weeks) \n39.19 (0.78)\n39.04 (1.05)\n39.39 (0.93)\n39.01 (1.09)\nMode of delivery \n\n\n\n\nVaginal\n13 (68.4)\n16 (76.2)\n12 (70.6)\n10 (55.6)\nIntrapartum Caesarean section\n2 (10.5)\n3 (14.3)\n2 (11.8)\n3 (16.7)\nNon-labour Caesarean section\n4 (21.1)\n2 (9.5)\n3 (17.6)\n5 (27.8)\nStandardized birthweight percentile (mean %) #\n37.14 (33.51)\n62.70 (36.58)\n46.49 (29.44)\n66.86 (32.35)\nSize at birth§\n\n\n\n\n Small for gestational age (<10th percentile)\n6 (31.6)\n5 (23.8)\n2 (11.8)\n1 (5.6)\n Large for gestational age (>90th percentile)\n2 (10.5)\n6 (28.6)\n2 (11.8)\n6 (33.3) (standard deviation) or number (%) unless otherwise stated. Data presented as mean (standard deviation) or number (%) unless otherwise stated. Ϯ Results from 2-time point 75g oral glucose tolerance test conducted at ~26 weeks’ gestation. Ϯ Results from 2-time point 75g oral glucose tolerance test conducted at ~26 weeks’ gestation. § By WHO 1999 criteria (fasting glucose ≥7.0 and/or 2h glucose ≥7.8 mmol/L)\n$Pre-eclampsia (PE) and pregnancy-induced hypertension (PIH)\n#Standardized for sex and gestational age using a local population reference calculated using methods described by Mikolajczyk et.al., 2011.29\nAbbreviations: BMI, body mass index; IVF, in vitro fertilization\nTable 2. Cord blood lipid species and their association with fasting glucose § By WHO 1999 criteria (fasting glucose ≥7.0 and/or 2h glucose ≥7.8 mmol/L) #Standardized for sex and gestational age using a local population reference calculated using methods described by Mikolajczyk et.al., 2011.29 Standardized for sex and gestational age using a local population reference calculated using methods described by Mikolajczyk et.al., 2011. Abbreviations: BMI, body mass index; IVF, in vitro fertilization Table 2. ϮZ-score standardized relative log lipid concentration per mmol/L increase in maternal fasting glucose concentration at ~26 weeks’ gestation. Adjusted for\nmaternal age, maternal BMI, mode of delivery, assisted conception, and insulin treatment. FDR: false discovery rate. Table 3. Cord blood lipid species and their association with 2-hour post-load glucose Table 3. Cord blood lipid species and their association with 2-hour post-load glucose g p\np\ng g\naternal age, maternal BMI, mode of delivery, assisted conception, and insulin treatment. FDR: false discovery rate -score standardized relative log lipid concentration per mmol/L increase in maternal fasting glucose concentratio\nl\nl\nd\nf d li\ni\nd\ni\nd i\nli\nf l\ndi ϮZ-score standardized relative log lipid concentration per mmol/L increase in maternal fasting glucose concentr\nmaternal age, maternal BMI, mode of delivery, assisted conception, and insulin treatment. FDR: false discovery ssociation with 2-hour post-load glucose ϮZ-score standardized relative lipid concentration per mmol/L increase in 2h maternal glucose concentration in a 75g oral glucose tolerance test conducted at\n~26 weeks’ gestation. Adjusted for maternal age, maternal BMI, mode of delivery, assisted conception, and insulin treatment. Statistical significance set at p <\n5.00E-02. ipids associated with birthweight and the relative influence of the covariates of fasting and 2h maternal glucose Table 4. Cord blood lipids associated with birthweight and the relative influence of the covariates of fasting and 2h maternal glucose able 4. Cord blood lipids associated with birthweight and the relative influence of the covariates of fasting and 2h FDR: false discovery rate. Tables Cord blood lipid species and their association with fasting glucose Page 8/12 Cord Blood \n Lipid\nBeta Coefficient \n (SD log10 lipid per mmol/L glucose) Ϯ \nLower \n Bound\nUpper \n Bound\np-value\nFDR \n corrected p\nDAG38:3\n0.64\n0.26\n1.02\n1.48E-03\n2.13E-01\nPC(O-36:2)\n0.59\n0.23\n0.95\n2.17E-03\n2.13E-01\nPC(P-36:1)\n0.59\n0.23\n0.95\n2.17E-03\n2.13E-01\noddPC 35:2\n0.56\n0.20\n0.93\n3.49E-03\n2.13E-01\nDAG37:4\n0.55\n0.19\n0.91\n3.72E-03\n2.13E-01\nDAG38:2\n0.55\n0.19\n0.92\n3.99E-03\n2.13E-01\nSM d18:1/18:0\n0.58\n0.20\n0.96\n4.27E-03\n2.13E-01\nDAG43:4\n0.56\n0.18\n0.93\n4.83E-03\n2.13E-01\nPC(P-38:1)\n0.58\n0.19\n0.97\n4.93E-03\n2.13E-01\nDAG42:4\n0.52\n0.16\n0.88\n5.98E-03\n2.13E-01\nPC 32:2\n0.55\n0.17\n0.93\n6.16E-03\n2.13E-01\nDAG46:5\n0.51\n0.15\n0.87\n6.73E-03\n2.13E-01\nDAG37:3\n0.53\n0.15\n0.91\n7.37E-03\n2.13E-01\nSM d18:1/20:1\n0.53\n0.16\n0.91\n7.37E-03\n2.13E-01\nSM d18:1/18:1\n0.53\n0.15\n0.91\n8.15E-03\n2.19E-01\nPS 38:3\n0.53\n0.14\n0.93\n9.63E-03\n2.22E-01\nDAG39:1\n0.50\n0.12\n0.88\n1.19E-02\n2.22E-01\nDAG42:3\n0.47\n0.11\n0.83\n1.21E-02\n2.22E-01\nDAG43:5\n0.48\n0.11\n0.85\n1.42E-02\n2.22E-01\nMHCer d18:2/C22:0\n0.48\n0.11\n0.86\n1.46E-02\n2.22E-01\nMHCer d18:1/C20:0\n0.51\n0.11\n0.91\n1.47E-02\n2.22E-01\nDAG38:4\n0.51\n0.11\n0.91\n1.47E-02\n2.22E-01\nCer d17:0/C23:1\n0.51\n0.11\n0.91\n1.48E-02\n2.22E-01\nCer d18:1/C26:1\n0.51\n0.11\n0.91\n1.50E-02\n2.22E-01\nSM d18:1/22:0\n0.48\n0.10\n0.86\n1.53E-02\n2.22E-01 Table 3. Cord blood lipid species and their association with 2-hour post-load glucose Page 9/12 Cord Blood \n Lipid\nBeta Coefficient \n (SD log10 lipid per mmol/L glucose) Ϯ\nLower \n Bound\nUpper \n Bound\np-value\nFDR \n corrected p\nCer d18:1/C33:1\n0.36\n0.21\n0.51\n1.22E-05\n4.93E-03\nCer d18:2/C16:0\n0.30\n0.14\n0.45\n3.27E-04\n6.61E-02\nCer d19:0/C15:2\n0.28\n0.13\n0.44\n7.25E-04\n7.26E-02\nPC 36:3\n0.26\n0.11\n0.41\n1.24E-03\n7.26E-02\nPC(O-36:2)\n0.25\n0.10\n0.39\n1.48E-03\n7.26E-02\nPC(P-36:1)\n0.25\n0.10\n0.39\n1.48E-03\n7.26E-02\nLPC 14:0\n0.25\n0.10\n0.40\n1.57E-03\n7.26E-02\nDAG47:6\n0.24\n0.10\n0.38\n1.60E-03\n7.26E-02\nCer d18:1/C33:0\n0.27\n0.11\n0.43\n1.76E-03\n7.26E-02\nLPC 16:1\n0.24\n0.10\n0.39\n1.80E-03\n7.26E-02\nPC(P-38:1)\n0.25\n0.10\n0.41\n2.17E-03\n7.96E-02\nLPC 20:2\n0.23\n0.09\n0.37\n2.45E-03\n8.07E-02\nPE(P-18:0/22:5)\n0.24\n0.09\n0.39\n2.71E-03\n8.07E-02\nDAG43:4\n0.24\n0.09\n0.39\n2.80E-03\n8.07E-02\noddPC 35:2\n0.22\n0.07\n0.37\n4.54E-03\n1.22E-01\nPC 38:3\n0.23\n0.07\n0.38\n5.33E-03\n1.35E-01\nLPC 16:0\n0.22\n0.07\n0.38\n6.20E-03\n1.44E-01\nPE(O-18:2/20:3)\n0.22\n0.07\n0.37\n6.44E-03\n1.44E-01\nPE(O-40:6)\n0.21\n0.06\n0.37\n7.76E-03\n1.51E-01\nPE(P-16:0/20:4)\n0.22\n0.06\n0.38\n8.21E-03\n1.51E-01\nPE(P-36:4)\n0.22\n0.06\n0.38\n8.21E-03\n1.51E-01\nCer d18:1/C26:0\n0.23\n0.06\n0.39\n8.23E-03\n1.51E-01\nDAG46:6\n0.20\n0.05\n0.35\n9.16E-03\n1.61E-01\nDAG47:5\n0.20\n0.05\n0.34\n1.01E-02\n1.71E-01\nCer d18:1/C28:0\n0.21\n0.05\n0.37\n1.16E-02\n1.78E-01 FDR: false discovery rate. Tables Page 10/12 Association between lipid\nand standardized birthweight percentile †\nFasting glucose influence on standardized\nbirthweight percentile †\n2h glucose influence on standardized\nbirthweight percentile †\nLipid\nspecies\n(predictor)\nBeta\nCoefficient\n(BW%/SD\nlog10\nlipid) ††\nLipid\nLower\nBound\nLipid\nUpper\nBound\nFDR\ncorrected\np value\nBeta\nCoefficient\n(BW%/\nmmol/L) †††\nLipid\nLower\nBound\nLipid\nUpper\nBound\nFDR\ncorrected\np value\nBeta\nCoefficient\n(BW%/\nmmol/L) †††\nLipid\nLower\nBound\nLipid\nUpper\nBound\nFDR\ncorrected\np value\nLPC 20:2\n21.28\n12.70\n29.87\n2.25E-03\n11.19\n-6.87\n29.25\n4.51E-01\n-3.86\n-11.42\n3.70\n9.79E-01\nLPC 18:1\n18.99\n11.00\n26.99\n2.25E-03\n9.55\n-8.71\n27.81\n4.51E-01\n-1.84\n-9.33\n5.64\n9.79E-01\nLPC 16:1\n18.38\n9.38\n27.38\n7.07E-03\n11.95\n-6.96\n30.85\n4.51E-01\n-3.66\n-11.62\n4.31\n9.79E-01\nLPC 18:2\n16.42\n8.29\n24.55\n7.07E-03\n11.38\n-7.56\n30.32\n4.51E-01\n-2.49\n-10.34\n5.36\n9.79E-01\nLPE 18:1\n16.15\n8.15\n24.15\n7.07E-03\n4.34\n-14.85\n23.54\n6.61E-01\n3.18\n-4.58\n10.94\n9.79E-01\nLPC 20:3\n15.87\n7.14\n24.60\n1.51E-02\n10.32\n-8.98\n29.62\n4.51E-01\n-1.94\n-9.90\n6.03\n9.79E-01\nLPC 18:3\n15.61\n6.32\n24.90\n2.43E-02\n17.93\n-2.08\n37.93\n4.51E-01\n-4.00\n-12.43\n4.42\n9.79E-01\nLPC 22:5\n14.71\n6.14\n23.27\n2.23E-02\n10.66\n-8.81\n30.14\n4.51E-01\n-1.24\n-9.23\n6.74\n9.79E-01\nLPC 20:1\n13.35\n5.03\n21.67\n3.28E-02\n5.52\n-14.40\n25.44\n5.92E-01\n0.39\n-7.58\n8.36\n9.79E-01\nLPE 18:2\n13.35\n5.30\n21.40\n2.66E-02\n7.78\n-11.87\n27.43\n4.64E-01\n0.41\n-7.53\n8.34\n9.79E-01\nLPC\n20:0p/20:1e\n13.32\n5.49\n21.15\n2.31E-02\n12.88\n-6.67\n32.42\n4.51E-01\n-1.58\n-9.61\n6.45\n9.79E-01\nLPC 20:4\n13.19\n4.53\n21.85\n4.61E-02\n12.45\n-7.38\n32.27\n4.51E-01\n-1.37\n-9.52\n6.78\n9.79E-01\nTAG50:2\n-27.67\n-41.81\n-13.52\n8.57E-03\n9.16\n-9.91\n28.22\n4.51E-01\n-0.05\n-7.78\n7.68\n9.97E-01\nTAG50:4\n-25.47\n-36.70\n-14.24\n2.39E-03\n10.39\n-8.08\n28.85\n4.51E-01\n0.67\n-6.81\n8.15\n9.79E-01\nTAG54:3\n-20.27\n-31.31\n-9.24\n1.47E-02\n12.73\n-6.57\n32.02\n4.51E-01\n-0.20\n-8.02\n7.63\n9.87E-01\nTAG50:3\n-19.96\n-30.18\n-9.74\n8.57E-03\n11.29\n-7.77\n30.35\n4.51E-01\n0.01\n-7.73\n7.74\n9.99E-01\nTAG54:1\n-19.93\n-29.07\n-10.79\n3.76E-03\n13.77\n-4.91\n32.46\n4.51E-01\n-1.04\n-8.64\n6.56\n9.79E-01\nTAG52:3\n-18.81\n-27.00\n-10.61\n2.38E-03\n13.80\n-4.66\n32.27\n4.51E-01\n-0.51\n-7.99\n6.97\n9.79E-01\nTAG58:1\n-18.60\n-28.21\n-8.99\n8.93E-03\n8.91\n-10.20\n28.02\n4.51E-01\n0.54\n-7.20\n8.28\n9.79E-01\nTAG52:2\n-18.48\n-26.14\n-10.83\n2.25E-03\n10.66\n-7.52\n28.85\n4.51E-01\n-0.64\n-8.03\n6.76\n9.79E-01\nTAG56:0\n-17.37\n-24.81\n-9.93\n2.28E-03\n12.84\n-5.52\n31.21\n4.51E-01\n-0.02\n-7.46\n7.42\n9.98E-01\nTAG54:2\n-16.76\n-24.76\n-8.76\n5.90E-03\n14.93\n-3.98\n33.83\n4.51E-01\n-1.20\n-8.87\n6.48\n9.79E-01\nTAG58:2\n-16.31\n-25.29\n-7.33\n1.51E-02\n9.00\n-10.32\n28.33\n4.51E-01\n0.79\n-7.03\n8.62\n9.79E-01\nTAG52:1\n-16.31\n-24.87\n-7.74\n1.03E-02\n11.94\n-7.21\n31.10\n4.51E-01\n-0.80\n-8.60\n7.01\n9.79E-01\nTAG52:4\n-16.03\n-24.22\n-7.85\n8.57E-03\n12.01\n-7.04\n31.07\n4.51E-01\n0.33\n-7.39\n8.05\n9.80E-01\nTAG53:0\n-16.02\n-25.53\n-6.50\n2.43E-02\n10.61\n-8.92\n30.14\n4.51E-01\n-0.67\n-8.63\n7.30\n9.79E-01\nTAG54:0\n-14.87\n-23.12\n-6.62\n1.55E-02\n8.63\n-10.73\n27.99\n4.51E-01\n0.66\n-7.17\n8.49\n9.79E-01\nTAG53:1\n-14.76\n-23.34\n-6.19\n2.23E-02\n10.41\n-9.06\n29.87\n4.51E-01\n0.17\n-7.73\n8.07\n9.87E-01\nTAG55:3\n-14.73\n-23.32\n-6.14\n2.23E-02\n7.46\n-12.10\n27.03\n4.73E-01\n0.99\n-6.90\n8.89\n9.79E-01\nTAG57:3\n-14.66\n-23.71\n-5.61\n3.10E-02\n9.83\n-9.81\n29.48\n4.51E-01\n0.17\n-7.79\n8.14\n9.87E-01\nTAG53:3\n-14.30\n-23.07\n-5.54\n3.00E-02\n8.02\n-11.67\n27.70\n4.63E-01\n0.77\n-7.18\n8.71\n9.79E-01\nTAG48:3\n-14.27\n-22.59\n-5.94\n2.23E-02\n11.15\n-8.33\n30.63\n4.51E-01\n0.82\n-7.08\n8.71\n9.79E-01\nTAG48:2\n-13.24\n-21.86\n-4.62\n4.61E-02\n9.99\n-9.79\n29.77\n4.51E-01\n0.90\n-7.11\n8.91\n9.79E-01\nTAG52:0\n-12.62\n-20.93\n-4.32\n4.61E-02\n7.93\n-11.95\n27.81\n4.64E-01\n0.92\n-7.10\n8.94\n9.79E-01\nTAG58:3\n-12.40\n-20.57\n-4.24\n4.61E-02\n8.18\n-11.69\n28.05\n4.62E-01\n0.58\n-7.45\n8.60\n9.79E-01\nTAG56:1\n-12.11\n-20.08\n-4.15\n4.61E-02\n8.47\n-11.38\n28.32\n4.53E-01\n0.56\n-7.46\n8.58\n9.79E-01\n†Standardized for sex and gestational age using a local population reference calculated using methods described by Mikolajczyk, et al. Page 11/12 Standardized birthweight percentile change for each SD increase in z-score standardized log10 relative lipid conce ††Standardized birthweight percentile change for each SD increase in z-score standardized log10 relative lipid concentration Page 11/12 Page 11/12 †Standardized for sex and gestational age using a local population reference calculated using methods describ Page 11/12 Tables 2011.29 †††Standardized birthweight percentile change per mmol/L increase in maternal glucose concentration (fasting and 2-hour) determined in a 75g oral glucose\ntolerance test conducted at ~26 weeks’ gestation. Regression model: BW percentile as outcome, Cord Blood Lipid Concentration as predictor, adjusted for these covariates: maternal age, maternal BMI, parity,\nmode of delivery, assisted conception, fasting glucose, 2hr Post-Load Glucose, insulin treatment. Statistical significance set at p < 5.00E-02. Abbreviations:\nBW%, standardized birthweight percentile; FDR, false discovery rate. SupplementaryTables.docx Supplementary Files This is a list of supplementary files associated with this preprint. Click to download. SupplementaryTables.docx Page 12/12"}}},{"rowIdx":12599,"cells":{"identifier":{"kind":"string","value":"https://openalex.org/W1994056886"},"pdf_url":{"kind":"string","value":"https://dash.harvard.edu/bitstream/1/14169380/1/74446175.pdf"},"lang":{"kind":"string","value":"English"},"error":{"kind":"null"},"title":{"kind":"string","value":"Systematic Investigation on Interactions for HIV Drug Resistance and Cross-Resistance among Protease Inhibitors"},"source_name":{"kind":"string","value":"Journal of proteome science and computational biology"},"publication_year":{"kind":"number","value":2012,"string":"2,012"},"license":{"kind":"string","value":"cc-by"},"word_count":{"kind":"number","value":7946,"string":"7,946"},"text":{"kind":"string","value":"Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available \nunder the terms and conditions applicable to Other Posted Material, as set forth at http://\nnrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA Permanent link http://nrs.harvard.edu/urn-3:HUL.InstRepos:14169380 Published Version\ndoi:10.7243/2050-2273-1-2 ub s ed e s o\ndoi:10.7243/2050-2273-1-2 Citation Zhang, Jing, Tingjun Hou, Yang Liu, Gang Chen, Xiao Yang, Jun S Liu, and Wei Wang. 2012. “Systematic Investigation on Interactions for HIV Drug Resistance and Cross-Resistance \nAmong Protease Inhibitors.” Journal of Proteome Science and Computational Biology 1 (1): 2. doi:10.7243/2050-2273-1-2. Published Version\ndoi:10.7243/2050-2273-1-2 Journal of Proteome Science\nComputational Biology\n& Open Access Abstract We systematically investigate the interactions for HIV drug resistance and cross-resistance of three protease inhibitors. Using Bayesian \nprobabilistic models, we first detect mutation combinations related to drug resistance in the HIV-1 protease or reverse transcriptase \n(RT) of patients with single, double and triple drug treatments respectively, and then infer detailed interaction structures of these \nmutations. Moreover, we compare the resistance patterns of single-drug treatments and multiple-drug treatments and study the \nselection patterns of mutations from single-drug treatments and multiple-drug treatments, using molecular dynamics simulation and \nfree energy calculations, in order to draw inference for giving advice on the design of multiple-drug treatments. Systematic Investigation on Interactions for HIV Drug Resistance and \nCross-Resistance among Protease Inhibitors Jing Zhang1†*, Tingjun Hou3†, Yang Liu1, Gang Chen1, Xiao Yang1, Jun S. Liu4 and Wei Wang2* © 2012 Zhang & Wang et al; licensee Herbert Publications Ltd. This is an open access article distributed under the terms of Creative Commons Attribution License \n(http://creativecommons.org/licenses/by/3.0),This permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Introduction seven nucleoside/nucleotide reverse transcription (RT) inhibitors \n(NRTI), six protease inhibitors (PIs), and three nonnucleoside RT \ninhibitors (NNRTI) [11-12]. Yet previous studies provide little insight \non this issue and often give inconsistent results when analyzing the \nsame input mutation data [5,10]. HIV drug-resistance, which is caused by mutations of viral proteins \nthat disrupt the drugs’ binding, enables the virus to survive and \nreproduce in the presence of antiretroviral drugs, hence substantially \ndiminishes the efficacy of HIV drug therapy [1-3]. Furthermore, HIV \ndrug-resistance induced by the genetic variation in virus replication \nis preserved and flourished by selection pressure during therapy \n[3-5]. Although it has been shown that physicians with access to drug \nresistance data can provide better-responded therapy to patients, \nthe complicated mutation patterns and unequal importance of the \nviral protein mutations make it hard for genotypic data to be helpful \nin designing therapeutic regimen[7-9]. In this study, we proposed a systematic procedure to apply BVP \nand RMS on the data of single, double and triple treatments of three \nPIs: IDV, NFV and SQV from Stanford HIVdb database to detect the \nmultiple-drug treatment effects and compare them to the single-drug \ntreatment effects. We then use Molecular Dynamic (MD) Simulations \nand Free Energy Calculations to explore the selection pattern of \ndrug-resistance effects from single-drug profile to multiple-drug \nprofile. We find that only a few mutation positions of single-drug \ntreatment showing up in multiple-drug treatment, and that the \nexistence of these mutations depends on the competing outcome \nof the interaction effects on the drugs. Zhang [13] proposed an innovative method for investigating \nmutation interactions of HIV induced by a certain drug treatment [13]. In this study, the Bayesian variable partition (BVP) model is applied \nto the data of three different drug treatments (Indinavir, zidovudine, \nand nevirapine) respectively to select mutations associated with drug \nresistance, and then the recursive model selection (RMS) procedure is \nemployed to infer the dependence structure among the interacting \nmutation positions found by the BVP model. This paper rediscovers \nthe majority of known resistant mutations to the aforementioned \nthree drugs [8] and uncovers several interacting structures for these \nmutations. In particular, a conditional independence structure among \nthe mutations M46I, I54V and V82A agrees with previous experimental \nresults. Share Your Story The Harvard community has made this article openly available. Please share how this access benefits you. Submit a story . Accessibility Journal of Journal of © 2012 Zhang & Wang et al; licensee Herbert Publications Ltd. This is an open access article distributed under the terms of Cr\n(http://creativecommons.org/licenses/by/3.0),This permits unrestricted use, distribution, and reproduction in any medium, provid *correspondence: jing.zhang.jz349@yale.edu\n1Department of Statistics, Yale University, \n24 Hillhouse Avenue, New Haven, CT. \nFull list of Author’s information is available at the end of the article Materials and methods\nUsing BVP and RMS for cross-resistance for multiple drug Here we first used the Bayesian variable partition (BVP) model [13,14] \nto search for the mutation positions (1 to 99) associated with the \ncross-resistance of IDV, NFV and SQV interactively. After detecting the \ninteraction mutation positions, we applied Recursive Model Selection \n[13] (RMS) to infer the detailed dependence structure among the \ninteracting positions. However, combinations of drugs from more than one drug classes, \nwhich are believed to be able to prolong virus suppression and \nimmunologic reconstitution, lead to the problem of cross-resistance, \ni.e.,drug resistance of the HIV virus when two or more drugs are used \nin the therapy for the same patient [11-15]. Currently there are sixteen \nantiretroviral drugs that have been approved for the HIV-1 infection: BVP and RMS are both designed to explore mutations for single-\ndrug resistance rather than cross-resistance for multiple drugs. We now \nshow our procedure of using BVP and RMS to study cross-resistance. We applied them sequentially to the data from single-drug treated, \ndouble-drug treated and triple-drug treated patients respectively. From Stanford database, we collected 4146 untreated patients’ \nsequences, and single-drug treated sequences (949 IDV-treated, 714 \nNFV-treated, 240 SQV-treated), double-drug treated sequences (280 \nIDV-NFV, 143 IDV-SQV, 96 NFV-SQV), and finally triple-drug treated \npatients (201 IDV-NFV-SQV). *correspondence: jing.zhang.jz349@yale.edu\n1Department of Statistics, Yale University, \n24 Hillhouse Avenue, New Haven, CT. Full list of Author’s information is available at the end of the article Zhang & Wang et al. Journal of Proteome Science & Computational Biology 2012, \nhttp://www.hoajonline.com/journals/jpscb/content/pdf/volume/2/2.pdf 2 First we applied BVP to all single-drug-treated datasets (IDV, NFV and \nSQV) versus 4146 untreated dataset, and searched for interactively \nassociated mutation positions (see Figure 1 for results). Then RMS was \nused to figure out the dependence structure among the interacting \npositions (see Figure 2). These are just single-drug resistance results. Interactions for single-drug resistance of IDV, NFV and SQV\nZhang [13] proposed a systematic approach for detecting and \nunderstanding combinatorial mutation patterns responsible for \nHIV single-drug resistance. In order to find interaction pattern for \ndrug resistance of IDV, Zhang [13] applied Bayesian variable partition \n(BVP) and Recursive Model Selection (RMS) on HIV-1 type B protease \nsequence data - 4146 sequences from untreated patients and 949 \nsequences from IDV-treated patients. Similarly, we applied BVP and \nRMS on HIV-1 type B protease sequence data, from NFV-treated \npatients (714 sequences) and SQV-treated patients (240 sequences). Materials and methods\nUsing BVP and RMS for cross-resistance for multiple drug Figure 1 and Figure 2 show the interacting positions detected by BVP \nand the dependence structure inferred by RMS for IDV, NFV and SQV. Interestingly, even from this single-drug resistance results we can \nsee there are some positions associated with more than one drug \ntreatments. 54, 82 and 90 (in red circles in Figure 1) are associated \nwith all of the three drugs, and 10, 71 and 73 are associated with \nIDV and SQV (but not NFV), while 88 associated with NFV and SQV \n(but not IDV). Totally, there are 10 positions interactively associated \nwith IDV, 6 with NFV, and12 with SQV. Second, we applied BVP and RMS to 3 double-drug datasets \nindividually (Figure 4 shows the results for IDV-NFV, Figure S1 and \nS2 in Supplementary Materials show the results for IDV-SQV, NFV-\nSQV). Comparing this result with the single-drug resistance results, \nwe can see how the resistant mutation interactions change when \ntwo of the three protease inhibitors were used. Third, we applied BVP and RMS to triple-drug dataset. Figure 3 \nshows the result. Results We downloaded the data from Stanford HIVdb database (http://www. hivdb.stanford.edu). Among all protease inhibitors (PI), NRTI, NNRTI, \nonly several PIs and RTs have sufficient sample sizes, namely IDV, \nNFV, SQV, AZT and NVP. Since we are interested in cross-resistance \nwithin drug classes, we also need good sample sizes for multiple-\ndrug treatments. Only IDV, NFV and SQV have large enough sample \nsizes for all single-drug treatments (949 IDV-treated sequences, 714 \nNFV-treated, 240 SQV-treated), double-drug treated sequences \n(280 IDV-NFV, 143 IDV-SQV, 96 NFV-SQV), and triple-drug treated \npatients (201 IDV-NFV-SQV). Hence we focus our investigation on \nthese three PIs, with the understanding that given enough data, \nthe same methods can be applied to other PIs and NRTI, NNRTI, etc. Dependent structures for IDV, NFV and SQV The \ndetailed structure inside the last group was ambiguous. mutation interactions from one drug will not affect the one from \nanother drug in the same treatment, then we would expect to see \nmost of the mutation interactions in single-drug treatments show \nup in multiple-drug treatment. For example, there are 10 mutation \npositions involved in resistant interactions of IDV treatment and \n6 positions involved in NFV treatment (Figure 1 and 2A), totally \n13 non-redundant positions forming about 4 interaction groups \n(one for 30 and 88, one for 10 and 71, one for 73, 90 and 20, one \nfor 54, 82 and others) for IDV and NFV. Based on the independent \nassumption, if we apply BVP and RMS to double-drug treatment \nof IDV and NFV, we would expect to see about 13 positions for \nmutation interactions and 4 interaction groups either from IDV \nor NFV. Similar arguments could also be applied for double-drug \ntreatments of IDV-SQV and NFV-SQV. Finally, in triple-drug treatment one contains 48, 54 and 82, the other containing 71, 73, 79 and 90. It is interesting to see that the group of 54 and 82 are associated \nwith all of the drugs. The group of 90 is interacting with 73 for IDV \nand SQV, but with 20 for NFV. The interacting group of 30 and 88 \nis drug-specific for NFV. Dependent structures for IDV, NFV and SQV In (a), totally eight \npositions are interactively associated: 24, 30, 46, 54, 73, 82, 88 and 90. In (b), three inde-\npendent interaction groups were inferred: 30 and 88; 73 and 90; 24, 46, 54 and 82. The \ndetailed structure inside the last group was ambiguous. Figure 2. The inference of detailed dependence structure \nfor IDV (a), NFV (b) and SQV (c) using RMS. The result \nof IDV was reported in Zhang [13]. For NFV (b), three \nindependent interaction groups were inferred with high \nposterior probabilities (>0.9): 54 and 82, 20 and 90, 30 and \n88. For SQV (c), two independent interation groups were \ninferred with high posterior probability (>0.9): 48, 54 and \n82; 71, 73, 79 and 90, although other details of the struc-\nture were not able to inferred with high confidence. Figure.3 The posterior probabilities (a) of each position of mutation to be associ-\nated interactively with triple-drug treatment (IDV, NFV and SQV, applying BVP to \ntriple-drug treated dataset) and the inferred detail dependence structure (b) among \ninteracting positions (applying RMS to triple-drug treated dataset). In (a), totally eight \npositions are interactively associated: 24, 30, 46, 54, 73, 82, 88 and 90. In (b), three inde-\npendent interaction groups were inferred: 30 and 88; 73 and 90; 24, 46, 54 and 82. The \ndetailed structure inside the last group was ambiguous. Figure.3 The posterior probabilities (a) of each position of mutation to be associ-\nated interactively with triple-drug treatment (IDV, NFV and SQV, applying BVP to \ntriple-drug treated dataset) and the inferred detail dependence structure (b) among \ninteracting positions (applying RMS to triple-drug treated dataset). In (a), totally eight \npositions are interactively associated: 24, 30, 46, 54, 73, 82, 88 and 90. In (b), three inde-\npendent interaction groups were inferred: 30 and 88; 73 and 90; 24, 46, 54 and 82. The \ndetailed structure inside the last group was ambiguous. Figure.3 The posterior probabilities (a) of each position of mutation to be associ-\nated interactively with triple-drug treatment (IDV, NFV and SQV, applying BVP to \ntriple-drug treated dataset) and the inferred detail dependence structure (b) among \ninteracting positions (applying RMS to triple-drug treated dataset). In (a), totally eight \npositions are interactively associated: 24, 30, 46, 54, 73, 82, 88 and 90. In (b), three inde-\npendent interaction groups were inferred: 30 and 88; 73 and 90; 24, 46, 54 and 82. Dependent structures for IDV, NFV and SQV After applying RMS, we were able to figure out some of the dependent \nstructures among the interacting positions. Zhang [13] identified two \nindependent groups: one is composed of 46, 54 and 82, the other \ncomposed of 73 and 90 (Figure 2a). In Figure 2b and 2c, there are \nthree independent groups identified for NFV: 54 and 82, 20 and 90, \n30 and 88. While for SQV, two independent groups were identified: Figure 1. The posterior probabilities of each position of mutation to be associated interactively with IDV, NFV and \nSQV treatments respectively (applying BVP to single-drug treated datasets). Red circles show the positions interac-\ntively associated with all of the three drugs (i.e. 54, 82, 90). Blue circles show the positions interactively associated \nwith IDV and SQV, but not NFV (i.e. 10, 71 and 73). Green circles show the positions interactively associated with \nNFV and SQV, but not IDV (i.e. 88). Figure 1. The posterior probabilities of each position of mutation to be associated interactively with IDV, NFV and \nSQV treatments respectively (applying BVP to single-drug treated datasets). Red circles show the positions interac-\ntively associated with all of the three drugs (i.e. 54, 82, 90). Blue circles show the positions interactively associated \nwith IDV and SQV, but not NFV (i.e. 10, 71 and 73). Green circles show the positions interactively associated with \nNFV and SQV, but not IDV (i.e. 88). 3 Zhang & Wang et al. Journal of Proteome Science & Computational Biology 2012, \nhttp://www.hoajonline.com/journals/jpscb/content/pdf/volume/2/2.pdf Zhang & Wang et al. Journal of Proteome Science & Computational Biology 2012, \nhttp://www.hoajonline.com/journals/jpscb/content/pdf/volume/2/2.pdf Figure 2. The inference of detailed dependence structure \nfor IDV (a), NFV (b) and SQV (c) using RMS. The result \nof IDV was reported in Zhang [13]. For NFV (b), three \nindependent interaction groups were inferred with high \nposterior probabilities (>0.9): 54 and 82, 20 and 90, 30 and \n88. For SQV (c), two independent interation groups were \ninferred with high posterior probability (>0.9): 48, 54 and \n82; 71, 73, 79 and 90, although other details of the struc-\nture were not able to inferred with high confidence. Figure.3 The posterior probabilities (a) of each position of mutation to be associ-\nated interactively with triple-drug treatment (IDV, NFV and SQV, applying BVP to \ntriple-drug treated dataset) and the inferred detail dependence structure (b) among \ninteracting positions (applying RMS to triple-drug treated dataset). Conjecture of drug-resistance mutation interaction profiles \nfor multiple-drug treatments based on profiles from single-\ndrug treatments Figure 1 and Figure 2 are the drug-resistant mutation interaction \nprofiles for IDV, NFV and SQV based on single-drug treatment \ndata. Currently, the state of art in cross-resistance is based on \nsingle-drug resistance profiles. If the drug-resistant effects in a \nmultiple-drug treatment are simply additive (independent), i.e. Zhang & Wang et al. Journal of Proteome Science & Computational Biology 2012, \nhttp://www.hoajonline.com/journals/jpscb/content/pdf/volume/2/2.pdf Zhang & Wang et al. Journal of Proteome Science & Computational Biology 2012, \nhttp://www.hoajonline.com/journals/jpscb/content/pdf/volume/2/2.pdf 4 of IDV-NFV-SQV, we would expect to see totally 18 non-redundant \npositions for resistant interactions. Similar things happen to the dependent structure of double-drug \nresistance inferred by RMS. For IDV-NFV double-drug treatment, \nwe found three resistant interaction groups: 24, 54 and 82 are from \none independent interaction group in IDV resistance [13], while 73 \nand 90 are from another independent group of IDV [13]; 30 and \n88 are from NFV independent group. All of these independence \nstructures remain the same for double-drug resistance. However, we \ndid not see the conditional independence of 46, 54 and 82 (which \nwas observed in IDV drug resistance) in IDV-NFV treatment. In NFV \nsingle-drug treatment, 90 is in the group of 20, but in IDV-NFV \ndouble-drug treatment, 20 is not even detected by BVP (Figure 4). So again comparing with our conjecture from single-drug profiles, \nthe group of 10 and 71 from IDV disappeared. Interactions for double-drug resistance of IDV, NFV and SQV\nIn order to study the interaction patterns for double-drug resistance \nof three PIs, we applied BVP and RMS to sequences from double-\nPI treatments: 280 from IDV-NFV treatment, 143 from IDV-SQV \ntreatment, 96 from NFV-SQV treatment. Figure 4 shows the results \nfor IDV-NFV data, while Figure S1 and S2 in the Supplementary \nMaterials show those for IDV-SQV data and NFV-SQV data. For IDV-\nNFV treatment, in Figure 4, all of the 7 positions BVP detected are \neither from IDV single drug resistance [13], or from NFV single drug \nresistance (see Figure 1). For example, 54, 82 and 90 are interactively \nassociated with both IDV and NFV treatments, while 24 and 73 are \nonly associated with IDV treatment, 30 and 88 from NFV treatment. But there are only 7 mutation positions (Figure 4), instead of 13, as \nconjectured, from single-drug treatments of IDV and NFV. In other \nwords, 6 positions (10, 20, 32, 46, 47, 71) disappeared comparing \nwith single-drug treatment profiles. Conjecture of drug-resistance mutation interaction profiles \nfor multiple-drug treatments based on profiles from single-\ndrug treatments As for IDV-SQV data, we observed similar results (Figure S1): most \nof the positions detected are from IDV or SQV single-drug resistance, \nand two independent groups (46, 54, 82, and 73, 90) are also the \nsame as the ones from IDV single-drug resistance. However, due to \nthe small sample size (143 sequences), we were not able to infer the \ndetails of each group. 20, 36, 61, 63 are not in single-drug profiles Figure 4. The posterior probabilities (a) of each position of mutation to be \nassociated interactively with double-drug treatment (IDV and NFV, using \nBVP) and the inferred detail dependence structure (b) among interacting \npositions (using RMS). In (a), totally seven positions are interactively asso-\nciated: 24, 30, 54, 73, 82, 88 and 90. In (b), three independent interaction \ngroups were inferred: 30 and 88; 73 and 90; 24, 54 and 82. The detailed \nstructure inside the last group was ambiguous. Figure S1. The posterior probabilities (a) of each position of mutation to \nbe associated interactively with double-drug treatment (IDV and SQV, \nusing BVP) and the inferred detail dependence structure (b) among \ninteracting positions (using RMS). In (a), totally twelve positions are in-\nteractively associated: 20, 32, 36, 46, 54, 61, 26, 63, 71, 73, 82, 88 and 90. In (b), three independent interaction groups were inferred: 61 and 71; 73 \nand 90; 46, 54 and 82. The other details of the structure were ambiguous. Figure S1. The posterior probabilities (a) of each position of mutation to \nbe associated interactively with double-drug treatment (IDV and SQV, \nusing BVP) and the inferred detail dependence structure (b) among \ninteracting positions (using RMS). In (a), totally twelve positions are in-\nteractively associated: 20, 32, 36, 46, 54, 61, 26, 63, 71, 73, 82, 88 and 90. In (b), three independent interaction groups were inferred: 61 and 71; 73 \nand 90; 46, 54 and 82. The other details of the structure were ambiguous. Figure 4. The posterior probabilities (a) of each position of mutation to be \nassociated interactively with double-drug treatment (IDV and NFV, using \nBVP) and the inferred detail dependence structure (b) among interacting \npositions (using RMS). In (a), totally seven positions are interactively asso-\nciated: 24, 30, 54, 73, 82, 88 and 90. In (b), three independent interaction \ngroups were inferred: 30 and 88; 73 and 90; 24, 54 and 82. The detailed \nstructure inside the last group was ambiguous. Figure 4. Interactions for triple-drug resistance of IDV, NFV and SQV Interactions for triple-drug resistance of IDV, NFV and SQV\nWe also studied triple-drug resistance of the three drugs by applying \nBVP and RMS to 201 sequences from three PI treated patients (note \nthat this sample size is even larger than double-drug treatments \nof IDV-SQV and NFV-SQV). Figure 3 shows the associated positions \nand the detailed dependent structure. The results are very similar \nto double-drug IDV-NFV resistance (Figure 4) except that 46 is \nobserved again. However, only 8 positions are involved in resistant \ninteractions, much smaller than what we conjectured from single-drug \nprofiles:18. It seems that only the ones repetitively detected in single-\ndrug, double-drug profiles are detected in triple-drug profile. In \nFigure 3b, three independent interaction groups were inferred: 30 \nand 88; 73 and 90; 24, 46, 54 and 82. The detailed structure inside \nthe last group (24, 46, 54 and 82) was ambiguous due to the small \nsample size. These interaction groups are also showing up repetitively \nin single- and double- drug profiles. The interaction group of 30 and 88 behaves very differently from \n54 and 82, since there are two possible mutations at 88: 88D or 88S. The interaction effect is most evident when we compare 30N/88D \nwith 30N/88S in NFV: neither 30N nor 88S has individual resistance \nto NFV, but 88D does; more importantly, 30N/88D has intermediate \nresistance but 30N/88S is more susceptible to NFV than the wild \ntype. This strong interaction effect is the main reason that 30 and \n88 are detected in any single-, double- and triple-drug treatment \nwhere NFV is involved. Figure 5 shows the difference between the drug-protease residue \ninteractions of D30N/N88S and those of D30N/N88D for (a) IDV, (b) \nSQV and (c) NFV. It is quite clear that for IDV, there is very minimum \ndifference; for SQV, some intermediate level of difference were \nobserved; however, for NFV, very strong difference were observed \nat positions 50 and 50’. This observation is consistent with our \nstatistical inference for IDV, SQV and NFV. Figure 6 shows the structural \ndistributions of important residues labeled in Figure 5b for SQV and \nFigure 5c for NFV. The D30N/N88S HIV-1 protease mutant is shown \nas blue strand and SQV or NFV is shown as green stick. Multiple-drug treatment effect Observing the results of double-drug treatments and triple-drug \ntreatment, we see they are very different from what we conjectured \nfrom single-drug resistance profiles. In double-drug IDV-NFV \ntreatment profile, there are only 7 mutation positions (Figure 4) in \ninteractions, not 13 as conjectured from single-drug treatments of \nIDV and NFV. In triple-drug IDV-NFV-SQV treatment profile, only 8 are \nin Figure 3, not 18, as conjectured from single-drug profiles. Thus in \nmultiple-drug treatment, the resistance profile is not simply additive \nfrom single-drug profiles. There are some multi-drug treatment \neffects that select mutation interactions from single-drug profiles. In order to figure out what is this selection effect, we further did \nMolecular Dynamic (MD) Simulations and Free Energy Calculations of \ntwo interaction groups: 54 and 82; 30 and 88 (since it is well-known \nthat the resistance caused by 73 and 90 cannot be explained by the \nbinding free energy analysis [13], so we did not do MD simulation or \nfree energy analysis on this group). Both are repetitively detected \nin single-, double- and triple-drug resistance profiles. We hope to \nfigure out what makes them selected in multiple-drug profiles from \nsingle-drug profile. Figure S2. The posterior probabilities (a) of each position of mutation to \nbe associated interactively with double-drug treatment (NFV and SQV, \nusing BVP) and the inferred detail dependence structure (b) among inter-\nacting positions (using RMS).In (a), totally ten positions are interactively \nassociated: 10, 30, 48, 54, 73, 74, 82, 84, 88 and 90. In (b), the details of the \ndependence structure were ambiguous. Interactions for triple-drug resistance of IDV, NFV and SQV The favorable \nresidues to the binding of SQV or NFV to the D30N/N88S mutant are \nshown as the yellow CPK model, those of the unfavorable residues \nare the red CPK model, and the residues at positions 30 and 88 are \nthe green CPK model. In both cases of SQV (Figure 6a) and NFV \n(Figure 6b), the distributions of favorable and unfavorable residues \nare very unbalanced. Conjecture of drug-resistance mutation interaction profiles \nfor multiple-drug treatments based on profiles from single-\ndrug treatments The posterior probabilities (a) of each position of mutation to be \nassociated interactively with double-drug treatment (IDV and NFV, using \nBVP) and the inferred detail dependence structure (b) among interacting \npositions (using RMS). In (a), totally seven positions are interactively asso-\nciated: 24, 30, 54, 73, 82, 88 and 90. In (b), three independent interaction \ngroups were inferred: 30 and 88; 73 and 90; 24, 54 and 82. The detailed \nstructure inside the last group was ambiguous. Figure S1. The posterior probabilities (a) of each position of mutation to \nbe associated interactively with double-drug treatment (IDV and SQV, \nusing BVP) and the inferred detail dependence structure (b) among \ninteracting positions (using RMS). In (a), totally twelve positions are in-\nteractively associated: 20, 32, 36, 46, 54, 61, 26, 63, 71, 73, 82, 88 and 90. In (b), three independent interaction groups were inferred: 61 and 71; 73 \nand 90; 46, 54 and 82. The other details of the structure were ambiguous. 5 Zhang & Wang et al. Journal of Proteome Science & Computational Biology 2012, \nhttp://www.hoajonline.com/journals/jpscb/content/pdf/volume/2/2.pdf of IDV or SQV, but in double-drug treatment profile of IDV-SQV. 10, \n22, 23, 48, 79 and 84 are in single-drug profiles but not double-drug \nprofile. For NFV-SQV (Figure S2), again the sample size is too small \n(96 sequences), so the posterior probabilities shown in Figure S2a \nare very moderate, thus the details of the dependence structure \ncannot be inferred (Figure S2b). which we can see that the interaction effects of 54V/82A in all of \nthe three drugs are very strong but in different directions: 54V has \nindividual resistance in neither IDV nor NFV but it amplifies the \none from 82A in IDV while neutralizes 82A in NFV; in SQV 54V does \nhave some intermediate resistance but 82A does not (even more \nsusceptible than the wild type), so 82A actually neutralizes 54V for \n54V/82A. Because the interaction effects are strong in all the drugs, \nthe interaction group of 54 and 82 are detected in all single-, double- \nand triple-drug treatments. Figure S5 shows the difference between \nthe drug-protease residue interactions of the wild-type complex \nand those of the L82A mutated complex for (a) IDV, (b) NFV and (c) \nSQV. Figure S6 shows the structure alignment of the wild-type and \nthe L82A mutated complexes of IDV and the structural distributions \nof eight important residues labeled in Figure S5a. Molecular Basis of Interacting Mutations Revealed by MD \nSimulations and Free Energy Calculations From above statistical analysis we can see the three independent \ninteraction groups: 54 and 82; 30 and 88; 73 and 90, repeatedly being \ndetected in single-, double- and triple-drug resistance. To further \ninvestigate the molecular implications of the mutation interactions \nwithin the three groups across three different PIs, we conducted MD \nsimulations to analyze the binding free energies of the protease/\nIDV/NFV/SQV complexes. The results are shown in Table1, from Figure S2. The posterior probabilities (a) of each position of mutation to \nbe associated interactively with double-drug treatment (NFV and SQV, \nusing BVP) and the inferred detail dependence structure (b) among inter-\nacting positions (using RMS).In (a), totally ten positions are interactively \nassociated: 10, 30, 48, 54, 73, 74, 82, 84, 88 and 90. In (b), the details of the \ndependence structure were ambiguous. Figure S2. The posterior probabilities (a) of each position of mutation to \nbe associated interactively with double-drug treatment (NFV and SQV, \nusing BVP) and the inferred detail dependence structure (b) among inter-\nacting positions (using RMS).In (a), totally ten positions are interactively \nassociated: 10, 30, 48, 54, 73, 74, 82, 84, 88 and 90. In (b), the details of the \ndependence structure were ambiguous. Zhang & Wang et al. Journal of Proteome Science & Computational Biology 2012, \nhttp://www.hoajonline.com/journals/jpscb/content/pdf/volume/2/2.pdf 6 ∆Evdw\n∆Eele\n∆GGB\n∆GSA\n∆Eele+∆GGB\n∆Evdw+∆GSA\n∆Gcal. ∆∆Gcal. Molecular Basis of Interacting Mutations Revealed by MD \nSimulations and Free Energy Calculations IDV\nWild\n-80.00 0.16b\n-25.59 0.35\n33.97 0.35\n-9.87 0.06\n8.37 0.00\n-89.87 0.22\n-81.50 0.46\n0\n30N\n-76.40 0.76\n-24.30 1.10\n29.67 1.02\n-10.14 0.01\n5.37 0.08\n-86.54 0.77\n-81.17 0.85\n0.33\n54V\n-82.99 0.26\n-25.38 0.21\n36.13 0.16\n-9.25 0.57\n10.74 0.37\n-92.24 0.83\n-81.50 0.46\n0\n73S\n-78.79 0.50\n-24.76 0.51\n33.26 0.14\n-10.36 0.67\n8.50 0.37\n-89.15 0.17\n-80.65 0.54\n0.85\n82A\n-75.98 1.27\n-24.67 0.10\n34.54 0.13\n-9.56 0.00\n9.87 0.23\n-85.54 1.27\n-75.67 1.50\n5.83\n88S\n-76.60 1.25\n-24.69 2.04\n30.74 1.20\n-10.59 0.56\n6.05 0.84\n-87.19 1.81\n-81.14 0.97\n0.36\n88D\n-74.67 0.81\n-25.63 0.03\n31.01 0.02\n-9.90 0.02\n5.38 0.05\n-84.57 0.82\n-79.18 0.77\n2.32\n90M\n-80.56 0.32\n-27.13 0.33\n35.59 0.06\n-9.78 0.06\n8.46 0.39\n-90.33 0.38\n-81.87 0.00\n-0.37\n30N/88S\n-74.97 0.28\n-24.53 0.02\n29.26 0.05\n-9.95 0.00\n4.73 0.07\n-84.92 0.29\n-80.19 0.35\n1.31\n30N/88D\n-74.64 1.41\n-25.20 0.87\n29.93 0.59\n-10.49 0.50\n4.74 0.28\n-85.12 1.91\n-80.39 2.20\n1.11\n54V/82A\n-71.84 0.64\n-19.62 0.92\n31.08 1.06\n-9.82 0.01\n11.46 0.13\n-81.66 0.63\n-70.20 0.77\n11.3\n73S/90M\n-81.31 0.37\n-22.89 0.19\n33.01 0.05\n-9.80 0.00\n10.12 0.24\n-91.11 0.38\n-80.99 0.14\n0.51\nSQV\nWild\n-74.44 .78\n-18.38 .35\n26.67 0.08\n-10.01 0.02\n8.29 0.27\n-84.45 .81\n-76.16 1.08\n0\n30N\n-69.55 1.10\n-20.9 1.49\n25.68 0.38\n-9.92 0.12\n5.59 1.11\n-79.47 1.22\n-73.88 0.11\n2.28\n54V\n-79.12 1.36\n-8.42 0.39\n22.17 0.11\n-9.57 0.61\n13.75 0.50\n-88.69 0.74\n-74.94 0.25\n1.22\n73S\n-77.92 0.85\n-17.16 0.53\n24.52 0.55\n-10.22 0.06\n7.36 0.02\n-88.14 0.79\n-80.78 0.77\n-4.62\n82A\n-72.26 0.00\n-31.67 1.07\n34.85 1.11\n-9.34 0.58\n3.18 0.03\n-81.59 0.58\n-78.41 0.54\n-2.25\n88S\n-71.66 0.95\n-16.16 0.72\n25.84 0.73\n-9.83 0.16\n9.67 0.01\n-81.48 1.11\n-71.81 1.10\n4.35\n88D\n-77.23 0.60\n-17.82 1.94\n26.89 1.69\n-9.43 0.68\n9.07 0.26\n-86.66 1.28\n-77.59 1.54\n-1.43\n90M\n-73.44 1.64\n-23.66 5.89\n29.87 3.53\n-10.18 0.10\n6.21 2.36\n-83.62 1.73\n-77.41 0.63\n-1.25\n30N/88S\n-73.97 3.00\n-20.42 1.50\n27.25 0.57\n-9.93 0.03\n6.83 2.08\n-83.90 3.03\n-77.07 0.96\n-0.91\n30N/88D\n-74.06 2.14\n-14.13 0.20\n23.11 0.19\n-10.01 1.07\n8.99 0.40\n-84.07 1.08\n-75.09 0.68\n1.07\n54V/82A\n-75.15 1.31\n-18.86 2.01\n27.30 2.19\n-9.760 .05\n8.44 0.19\n-84.91 1.36\n-76.47 1.17\n-0.31\n73S/90M\n-69.29 0.14\n-24.12 1.12\n30.02 0.18\n-10.53 0.02\n5.91 0.93\n-79.82 0.12\n-73.91 0.81\n2.25\nNFV\nWild\n-67.48 0.50\n-24.48 2.65\n27.91 2.21\n-9.48 0.47\n3.43 0.44\n-73.76 0.97\n-73.53 0.53\n0\n30N\n-69.98 0.44\n-18.81 0.11\n24.11 0.09\n-9.69 0.66\n5.30 0.20\n-78.66 1.10\n-73.36 0.90\n0.17\n54V\n-66.93 0.58\n-23.04 2.18\n26.84 2.24\n-10.24 0.06\n3.80 0.06\n-77.17 .64\n-73.37 0.58\n0.16\n73S\n-69.49 0.59\n-20.31 0.74\n25.30 0.91\n-8.33 0.53\n4.99 0.16\n-77.82 1.12\n-72.83 1.28\n0.7\n82A\n-65.83 0.81\n-20.65 0.44\n-24.94 1.6\n-8.43 0.65\n4.29 0.28\n-74.26 1.46\n-69.97 1.74\n3.56\n88S\n-70.93 1.19\n-14.67 0.72\n21.91 0.01\n-9.15 0.16\n7.24 0.71\n-80.09 1.36\n-72.85 2.07\n0.68\n88D\n-67.13 0.27\n-23.34 0.62\n29.71 1.01\n-9.53 0.50\n6.37 0.39\n-76.66 0.77\n-70.29 0.38\n3.24\n90M\n-69.03 0.64\n-21.81 0.45\n26.54 0.80\n-8.53 0.63\n4.73 0.35\n-77.56 0.01\n-72.83 0.36\n0.7\n30N/88S\n-71.18 1.05\n18.62 0.16\n23.78 0.38\n-8.57 0.59\n5.16 0.22\n-79.74 0.46\n-74.59 0.24\n-1.06\n30N/88D\n-69.37 0.91\n-18.88 0.06\n23.71 0.25\n-7.12 0.56\n4.82 0.31\n-76.50 0.35\n-71.67 0.03\n1.86\n54V/82A\n-66.79 1.73\n-24.07 1.31\n28.09 0.36\n-10.07 0.17\n4.03 0.95\n-76.86 1.90\n-72.84 0.95\n0.69\n73S/90M\n-69.12 2.10\n-19.79 0.33\n24.27 0.09\n-8.48 0.60\n4.49 0.25\n-77.60 1.51\n-73.12 1.26\n0.41\nTable 1. Molecular Basis of Interacting Mutations Revealed by MD \nSimulations and Free Energy Calculations The difference between the drug-protease residue \ninteractions of the wild-type complex and those of the N88S \nmutated complex for (a) IDV, (b) NFV and (c) SQV. The residues \nwith absolute value larger than 1.00 kcal/mol are labeled. (∆G dif-\nference equals to the interactions between drug and the wile-type \nprotease minus those between drug and the mutant). Figure S5. The difference between the drug-protease residue interac-\ntions of the wild-type complex and those of the L82A mutated complex \nfor (a) IDV, (b) NFV and (c) SQV. The residues with absolute value \nlarger than 1.00 kcal/mol are labeled. (∆G difference equals to the inter-\nactions between drug and the wile-type protease minus those between \ndrug and the mutant). Figure S4. The difference between the drug-protease residue \ninteractions of the wild-type complex and those of the N88S \nmutated complex for (a) IDV, (b) NFV and (c) SQV. The residues \nwith absolute value larger than 1.00 kcal/mol are labeled. (∆G dif-\nference equals to the interactions between drug and the wile-type \nprotease minus those between drug and the mutant). Figure S4. The difference between the drug-protease residue \ninteractions of the wild-type complex and those of the N88S \nmutated complex for (a) IDV, (b) NFV and (c) SQV. The residues \nwith absolute value larger than 1.00 kcal/mol are labeled. (∆G dif-\nference equals to the interactions between drug and the wile-type \nprotease minus those between drug and the mutant). Figure S5. The difference between the drug-protease residue interac-\ntions of the wild-type complex and those of the L82A mutated complex \nfor (a) IDV, (b) NFV and (c) SQV. The residues with absolute value \nlarger than 1.00 kcal/mol are labeled. (∆G difference equals to the inter-\nactions between drug and the wile-type protease minus those between \ndrug and the mutant). Figure S6. Structure alignment of the wild-type and the L82A mutated \ncomplexes of IDV and the structural distributions of eight important resi-\ndues labeled in Figure S5a. The wild-type complex is shown as red strand, \nthe mutated complex as green strand and IDV is shown as red or green \nstick. The favorable residues to the binding of IDV with the wild-type \nprotease are shown as the red CPK model, and the unfavorable residue as \nthe green CPK model. The structures are averaged from0.5 to 3 ns. Molecular Basis of Interacting Mutations Revealed by MD \nSimulations and Free Energy Calculations The \nroot mean square deviation (RMSD) of the main-chain atoms for the two \naveraged structures after structure alignment is 0.97 Å. Figure S4 shows the difference between the drug-protease residue \ninteractions of the wild-type complex and those of the N88S mutated \ncomplex for (a) IDV, (b) NFV and (c) SQV. More positions are affected \nin SQV compared with IDV and NFV by N88S single mutation. The results suggest that if the interaction effect is strong to one \nof the drugs, and intermediate or weak to some other drugs in the \nsame treatment, it has more chance to be selected in multiple-drug \ntreatment, like 30 and 88 in NFV. But the drug-resistant effects in a multiple-drug treatment \nare not simply additive (independent), thus the state of art in \ncross-resistance based on single-drug resistance profiles (which \nignores the epistasis effect in multiple-drug treatment) is very \ninaccurate, and multiple-drug resistance profile should be built \nbased on multiple-drug treatment data equipped with advanced \nstatistical inference. Figure S6. Structure alignment of the wild-type and the L82A mutated \ncomplexes of IDV and the structural distributions of eight important resi-\ndues labeled in Figure S5a. The wild-type complex is shown as red strand, \nthe mutated complex as green strand and IDV is shown as red or green \nstick. The favorable residues to the binding of IDV with the wild-type \nprotease are shown as the red CPK model, and the unfavorable residue as \nthe green CPK model. The structures are averaged from0.5 to 3 ns. The \nroot mean square deviation (RMSD) of the main-chain atoms for the two \naveraged structures after structure alignment is 0.97 Å. Figure S6. Structure alignment of the wild-type and the L82A mutated \ncomplexes of IDV and the structural distributions of eight important resi-\ndues labeled in Figure S5a. The wild-type complex is shown as red strand, \nthe mutated complex as green strand and IDV is shown as red or green \nstick. The favorable residues to the binding of IDV with the wild-type \nprotease are shown as the red CPK model, and the unfavorable residue as \nthe green CPK model. The structures are averaged from0.5 to 3 ns. The \nroot mean square deviation (RMSD) of the main-chain atoms for the two \naveraged structures after structure alignment is 0.97 Å. Molecular Basis of Interacting Mutations Revealed by MD \nSimulations and Free Energy Calculations The binding free energies and the energy components calculated by MM/GBSA (kcal/mol)\na∆∆Gcal is the difference between the binding free energy of the mutated complex and that of the wild-type (WT). bStandard deviations were estimated from two block average values. The binding free energies and the energy components calculated by MM/GBSA (kcal/mol) Figure 6. Structural distributions of important residues labeled in (a) Figure 5b and \n(b) Figure 5c. The D30N/N88S HIV-1 protease mutant is shown as blue strand and \nSQV (a) or NFV (b) is shown as green stick. The favorable residues to the binding \nof SQV to the D30N/N88S mutant are shown as the yellow CPK model, those of the \nunfavorable residues as the red CPK model, and the residues at positions 30 and 88 as \nthe green CPK mode. Figure 5. The difference \nbetween the drug-protease \nresidue interactions of \nD30N/N88S and those of \nD30N/N88D for (a) IDV, \n(b) SQV and (c) NFV. The \nresidues with absolute value \nlarger than 1.00 kcal/mol are \nlabeled. (ΔΔG equals to the \ninteractions between drug \nand the D30N/N88S protease \nmutant minus those between \ndrug and the D30N/N88D \nprotease mutant). Figure 5. The difference \nbetween the drug-protease \nresidue interactions of \nD30N/N88S and those of \nD30N/N88D for (a) IDV, \n(b) SQV and (c) NFV. The \nresidues with absolute value \nlarger than 1.00 kcal/mol are \nlabeled. (ΔΔG equals to the \ninteractions between drug \nand the D30N/N88S protease \nmutant minus those between \ndrug and the D30N/N88D \nprotease mutant). Figure 6. Structural distributions of important residues labeled in (a) Figure 5b and \n(b) Figure 5c. The D30N/N88S HIV-1 protease mutant is shown as blue strand and \nSQV (a) or NFV (b) is shown as green stick. The favorable residues to the binding \nof SQV to the D30N/N88S mutant are shown as the yellow CPK model, those of the \nunfavorable residues as the red CPK model, and the residues at positions 30 and 88 as\nthe green CPK mode. 7 Zhang & Wang et al. Journal of Proteome Science & Computational Biology 2012, \nhttp://www.hoajonline.com/journals/jpscb/content/pdf/volume/2/2.pdf g\ng\np\ngy\nhttp://www.hoajonline.com/journals/jpscb/content/pdf/volume/2/2.pdf\nFigure S4 shows the difference between the drug-protease residue \ninteractions of the wild-type complex and those of the N88S mutated \ncomplex for (a) IDV, (b) NFV and (c) SQV. More positions are affected \nin SQV compared with IDV and NFV by N88S single mutation. Molecular Basis of Interacting Mutations Revealed by MD \nSimulations and Free Energy Calculations The results suggest that if the interaction effect is strong to one \nof the drugs, and intermediate or weak to some other drugs in the \nsame treatment, it has more chance to be selected in multiple-drug \ntreatment, like 30 and 88 in NFV. But the drug-resistant effects in a multiple-drug treatment \nare not simply additive (independent), thus the state of art in \ncross-resistance based on single-drug resistance profiles (which \nignores the epistasis effect in multiple-drug treatment) is very \ninaccurate, and multiple-drug resistance profile should be built \nbased on multiple-drug treatment data equipped with advanced \nstatistical inference. Discussion\nUtilizing the pioneering method proposed by Zhang [13], which \nintegrates Bayesian statistical modeling with molecular dynamic \nFigure S5. The difference between the drug-protease residue interac-\ntions of the wild-type complex and those of the L82A mutated complex \nfor (a) IDV, (b) NFV and (c) SQV. The residues with absolute value \nlarger than 1.00 kcal/mol are labeled. (∆G difference equals to the inter-\nactions between drug and the wile-type protease minus those between \ndrug and the mutant). Figure S6. Structure alignment of the wild-type and the L82A mutated \ncomplexes of IDV and the structural distributions of eight important resi-\ndues labeled in Figure S5a. The wild-type complex is shown as red strand, \nthe mutated complex as green strand and IDV is shown as red or green \nstick. The favorable residues to the binding of IDV with the wild-type \nprotease are shown as the red CPK model, and the unfavorable residue as \nthe green CPK model. The structures are averaged from0.5 to 3 ns. The \nroot mean square deviation (RMSD) of the main-chain atoms for the two \naveraged structures after structure alignment is 0.97 Å. Figure S4. The difference between the drug-protease residue \ninteractions of the wild-type complex and those of the N88S \nmutated complex for (a) IDV, (b) NFV and (c) SQV. The residues \nwith absolute value larger than 1.00 kcal/mol are labeled. (∆G dif-\nference equals to the interactions between drug and the wile-type \nprotease minus those between drug and the mutant). http://www.hoajonline.com/journals/jpscb/content/pdf/volume/2/2.pdf\nFigure S5. The difference between the drug-protease residue interac-\ntions of the wild-type complex and those of the L82A mutated complex \nfor (a) IDV, (b) NFV and (c) SQV. The residues with absolute value \nlarger than 1.00 kcal/mol are labeled. (∆G difference equals to the inter-\nFigure S4. References 1. Beerenwinkel N, Schmidt B, Walter H, Kaiser R, Lengauer T, Hoffmann \nD, et al.: Diversity and complexity of HIV-1 drug resistance: a bioin-\nformatics approach to predicting phenotype from genotype. Proc \nNatl Acad Sci U S A 2002; 99;(12.);8271-6. | Article | PubMed Abstract | \nPubMed Full text 2. Condra JH, Schleif WA, Blahy OM, Gabryelski LJ, Graham DJ, Quintero \nJC, et al.: In vivo emergence of HIV-1 variants resistant to multiple \nprotease inhibitors. Nature 1995; 374;(6522.);569-71. | Article | \nPubMed 3. Condra JH, Holder DJ, Schleif WA, Blahy OM, Danovich RM, Gabryelski \nLJ, et al.: Genetic correlates of in vivo viral resistance to indinavir, \na human immunodeficiency virus type 1 protease inhibitor. J Virol \n1996; 70;(12.);8270-6. | Article | PubMed Abstract | Pubmed Full text 4. Johnson VA, Brun-Vezinet F, Clotet B, Gunthard HF, Kuritzkes DR, Pillay \nD, et al.: Update of the drug resistance mutations in HIV-1: Spring \n2008. Top HIV Med 2008; 16;(1.);62-8. | Article | PubMed q\ng\nThere are, admittedly, many complexities not addressed in this \npaper. For example, the HIV data from Stanford HIV db are collected \nfrom a global sample and thus multiple subpopulations in both \ntreated and untreated population are possible, which may render \nour inference biased. Another issue may lie in the quasi-species \nnature of HIV-1. The HIV-1 population within an individual consists of \ninnumerable variants and minor variants that often go undetected \nand hence there exists the possibility that our data underrepresent \nthose variants. Furthermore, HIV-1 drug resistance can be not only \nacquired (developing in a person receiving antiretroviral treatment) \nbut also transmitted (occurring because a virus with drug-resistance \nmutations was transmitted to a drug-naive person). In recent years, \nthe transmitted resistance occurrence has been increasing due to \nscaled-up antiretroviral treatments. In Europe, North America, and \nBrazil, it has been reported that the prevalence of drug resistance \nranges from 5–15% in newly diagnosed individuals. Because our \nuntreated sequence data were collected from 1982 to 2005, it is \npossible that there are several transmitted drug resistant sequences \nin the untreated group that may affect both the sensitivity of our \nBVP algorithm and the power of our Bayesian model structure \ninference method. Because there are many antiretroviral drugs, \ncross-resistance is a severe and practical problem. 5. Liu TF, Shafer RW: Web resources for HIV type 1 genotypic-resis-\ntance test interpretation. Clin Infect Dis 2006; 42;(11.);1608-18. Discussion Utilizing the pioneering method proposed by Zhang [13], which \nintegrates Bayesian statistical modeling with molecular dynamic 8 Zhang & Wang et al. Journal of Proteome Science & Computational Biology 2012, \nhttp://www.hoajonline.com/journals/jpscb/content/pdf/volume/2/2.pdf simulations, we were able to detect and analyze, beyond the single-\ndrug level, the complex interactions of drug resistance mutations \nand cross-mutations of the HIV-1 protease and reverse transcriptase. Most significantly, we applied the said method to all possible \ncombinations of single-, double-, and triple-drug treatment data \non IDV, NFV and SQV from the Stanford HIV-1db database to study \nthe problem of cross-resistance, revealing the selection pattern of \nthe puzzled problem of multiple-drug treatment effects. We find \nthat in general, the interactions effect is likely to be strengthened \nwhen it has strong interaction with at least one other drug in the \nsame treatment. Hence it seems that simultaneous multi-drug \ntreatment is more effective than sequential multi-drug treatment. Acknowledgement g\nJ Zhang was supported by start-up funding and Sesseel Award \nfrom Yale University. The computation was done with the help \nfrom the Yale University Biomedical High Performance Computing \nCenter, which was supported by the NIH grant RR19895. 14. Zhang Y, Liu JS: Bayesian inference of epistatic interactions in case-\ncontrol studies. Nat Genet 2007; 39;(9.);1167-73. | Article | Pubmed 14. Zhang Y, Liu JS: Bayesian inference of epistatic interactions in case-\ncontrol studies. Nat Genet 2007; 39;(9.);1167-73. | Article | Pubmed 15. Zhang YM, Imamichi H, Imamichi T, Lane HC, Falloon J, Vasudevachari \nMB, et al.: Drug resistance during indinavir therapy is caused by \nmutations in the protease gene and in its Gag substrate cleav-\nage sites. J Virol 1997; 71;(9.);6662-70. | Article | Pubmed Abstract | \nPubmed Full text 15. Zhang YM, Imamichi H, Imamichi T, Lane HC, Falloon J, Vasudevachari \nMB, et al.: Drug resistance during indinavir therapy is caused by \nmutations in the protease gene and in its Gag substrate cleav-\nage sites. J Virol 1997; 71;(9.);6662-70. | Article | Pubmed Abstract | \nPubmed Full text Author information UCSD, 9500 Gilman Drive La Jolla, CA 92093-0359. 4Department of Statistics, Harvard University, 1 References | \nArticle | Pubmed Abstract | Pubmed Full text 6. Marchini J, Donnelly P, Cardon LR: Genome-wide strategies for \ndetecting multiple loci that influence complex diseases. Nat Genet \n2005; 37;(4.);413-7. | Article | Pubmed 7. Ravela J, Betts BJ, Brun-Vezinet F, Vandamme AM, Descamps D, van \nLaethem K, et al.: HIV-1 protease and reverse transcriptase mutation \npatterns responsible for discordances between genotypic drug \nresistance interpretation algorithms. J Acquir Immune Defic Syndr \n2003; 33;(1.);8-14. | Article | Pubmed Abstract | Pubmed Full text 8. Rhee SY, Taylor J, Wadhera G, Ben-Hur A, Brutlag DL, Shafer RW: Ge-\nnotypic predictors of human immunodeficiency virus type 1 drug \nresistance. Proc Natl Acad Sci U S A 2006; 103;(46.);17355-60. | Article | \nPubmed Abstract | Pubmed Full text 9. Rhee SY, Gonzales MJ, Kantor R, Betts BJ, Ravela J, Shafer RW: Human \nimmunodeficiency virus reverse transcriptase and protease \nsequence database. Nucleic Acids Res 2003; 31;(1.);298-303. | Article | \nPubmed Abstract | Pubmed Full text 10. Ritchie MD, Hahn LW, Roodi N, Bailey LR, Dupont WD, Parl FF, et al.: \nMultifactor-dimensionality reduction reveals high-order interac-\ntions among estrogen-metabolism genes in sporadic breast can-\ncer. Am J Hum Genet 2001; 69;(1.);138-47. | Article | Pubmed Abstract | \nPubmed Full text 11. Shafer RW: Genotypic testing for human immunodeficiency virus \ntype 1 drug resistance. Clin Microbiol Rev 2002; 15;(2.);247-77. | Article\n| Pubmed Abstract | Pubmed Full text Despite all the possibilities that may emerge, this study has verified \nthe original findings of HIV drug resistance and demonstrated the \nlong-puzzled selection pattern of HIV multiple drug treatment \neffects. We are positive that the method and results presented here \nwill enlighten new and more accurate ways to decipher the myths \nbehind drug resistance of HIV and other related diseases. 12. Shafer RW, Rhee SY, Pillay D, Miller V, Sandstrom P, Schapiro JM, et \nal.: HIV-1 protease and reverse transcriptase mutations for drug \nresistance surveillance. AIDS 2007; 21;(2.);215-23. | Pubmed Abstract \n| Pubmed Full text 13. Zhang J, Hou T, Wang W, Liu JS: Detecting and understanding com-\nbinatorial mutation patterns responsible for HIV drug resistance. Proc Natl Acad Sci U S A 2010; 107;(4.);1321-6. | Article | Pubmed \nAbstract | Pubmed Full text Competing interests\nThe authors declare that they have no compting interests. Article history Article history \nEditor: Hongyu Miao, University of Rochester School of Medicine, USA. Received: 03-Mar-2012 Revised: 20-Apr-2012 \nAccepted: 03-May-2012 Published: 23-May-2012"}}}],"truncated":false,"partial":true},"paginationData":{"pageIndex":125,"numItemsPerPage":100,"numTotalItems":93470,"offset":12500,"length":100}},"jwt":"eyJhbGciOiJFZERTQSIsImtpZCI6IjVHZDBvd0g5MTM2eDZjc1FvbE1zcktNWUZoRVFoUm5PVVVybEpjOUhaUEEifQ.eyJyZWFkIjp0cnVlLCJwZXJtaXNzaW9ucyI6eyJyZXBvLmNvbnRlbnQucmVhZCI6dHJ1ZX0sImlhdCI6MTc4NjM3MTYyOSwianRpIjoiMDFmYjQ4YzgtOTFjOC00ZWVhLWFiZDctODg4ZTNlMzFjMGI0Iiwic3ViIjoiL2RhdGFzZXRzL0xMTURIL09wZW5TY2llbmNlIiwiZXhwIjoxNzg2Mzc1MjI5LCJpc3MiOiJodHRwczovL2h1Z2dpbmdmYWNlLmNvIn0.Jnw2a9ku9_gfWNEwR7cmLnjyt7kYqeq9aMoJQQ7hf-7ffvEqQws59WBLmdYWHlwbTY6lphLIvLy2vv8IEglQCg","displayUrls":true,"splitSizeSummaries":[{"config":"default","split":"train","numRows":93470,"numBytesParquet":2772077973}]},"discussionsStats":{"closed":0,"open":1,"total":1},"fullWidth":true,"hasGatedAccess":true,"hasFullAccess":true,"isEmbedded":false,"savedQueries":{"community":[],"user":[]}}">
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https://openalex.org/W2019005849 | https://jyx.jyu.fi/bitstream/123456789/40695/1/opportunity%20discovery%20and%20creation%20in%20cloud%20computing.pdf | English | null | Opportunity Discovery and Creation in Cloud Computing | null | 2,013 | public-domain | 7,579 | 1. Introduction Over the last decade, increasing scholarly
attention has been paid to cloud computing and
software-as-a-service (SaaS). It has been shown that
cloud computing and related services can bring about
important technical benefits and business advantages
[5, 6, 17, 20, 34]. The studies in question have ... |
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doi:10.1017/jfm.2014.619
Numerical simulation of turbulent flow through
Schiller’s wavy pipe
G. Daschiel1, V. Krieger2, J. Jovanović2,† and A. Delgado2
1Institut für Strömungsmechanik, Karlsruher Institut für Technologie, Kaiserstraße 10,
D-76131 ... |
W4288345795.txt | https://zenodo.org/records/6322372/files/D8.2.pdf | de | Ageing@Work Web Portal | Zenodo (CERN European Organization for Nuclear Research) | 2,019 | cc-by | 1,869 | Ref. Ares(2019)3530087 - 30/05/2019
GA #826299
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Ageing@Work
Smart, Personalized and Adaptive ICT Solutions for Active, Healthy and
Productive Ageing with enhanced Workability
No 826299
3 years (starting 1 January 2019)
Deliverable D8.2
Ageing@Wor... | |
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Ideas | Approaches | Accessibility | Availability Dr. Henry Garrett
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TRENDS OF DISTANCE LEARNING TRAINING (PJJ) BEFORE AND
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Lueschow, Shiloh R
McElroy, Steven J UC Davis
UC Davis Previously Published Works
Title
The Paneth Cell: The Curator and Defender of the Immature Small Intestine
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Publication Date
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DOI
10.3389/fimmu.2020... |
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multipartite entangled optical
beams with a correlated noisy
channel received: 29 June 2016
accepted: 09 February 2017
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Erica Reeve
(
ereeve@deakin.edu.au
)
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) Identifying opportunities to strengthen school food
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https://openalex.org/W2085818617 | https://europepmc.org/articles/pmc3528711?pdf=render | English | null | Rescue of Murine F508del CFTR Activity in Native Intestine by Low Temperature and Proteasome Inhibitors | PloS one | 2,012 | cc-by | 11,917 | Abstract This is an open-access article distributed under the terms of the Creative Commons Attr
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by grants from the EU (grant QLG1-CT-2001-01005), the Cystic Fibrosis Fo... |
https://openalex.org/W4319336044 | https://www.thieme-connect.de/products/ejournals/pdf/10.1055/s-0043-1761206.pdf | English | null | null | European journal of pediatric surgery reports | 2,023 | cc-by | 2,598 | Abstract Introduction
Cloacal malformations comprise a heterogeneous group of anomalies
that are considered the most complex anorectal malformations (ARMs) in females. Precise evaluation to identify the unique anatomy prior to reconstruction with
collaboration between colorectal surgeons, urologists, and gynecologists ... |
https://openalex.org/W2159763003 | https://tspace.library.utoronto.ca/bitstream/1807/86115/1/13059_2006_Article_1374.pdf | English | null | Analysis of the Saccharomyces cerevisiae proteome with PeptideAtlas. | GenomeBiology.com | 2,006 | cc-by | 11,564 | Open Access Open Access Open Access Open Access
2006
King
et al.
Volume 7, Issue 11, Article R106
Method
Analysis of the Saccharomyces cerevisiae proteome with
PeptideAtlas
Nichole L King*, Eric W Deutsch*, Jeffrey A Ranish*, Alexey I Nesvizhskii†,
James S Eddes*, Parag Mallick‡, Jimmy Eng*§, Frank Desiere¶, Mark Flo... |
https://openalex.org/W289622549 | https://journals.iucr.org/e/issues/2008/08/00/is2312/is2312.pdf | Latin | null | (<i>E</i>)-3-(2-Chlorophenyl)-1-(2-furyl)prop-2-en-1-one | Acta crystallographica. Section E | 2,008 | cc-by | 3,314 | organic compounds Acta Crystallographica Section E
Structure Reports
Online
ISSN 1600-5368 Data collection
Bruker SMART APEXII CCD
area-detector diffractometer
Absorption correction: multi-scan
(SADABS; Bruker, 2005)
Tmin = 0.865, Tmax = 0.952 30354 measured reflections
3902 independent reflections
3738 reflections with I... |
https://openalex.org/W2906711994 | https://europepmc.org/articles/pmc6359514?pdf=render | English | null | Chitosan-Based Mucoadhesive Vaginal Tablets for Controlled Release of the Anti-HIV Drug Tenofovir | Pharmaceutics | 2,019 | cc-by | 13,293 | Received: 22 November 2018; Accepted: 28 December 2018; Published: 5 January 2019 Abstract: Vaginal microbicides have the potential to give women at high risk of contracting HIV
the option of self-protection by preventing the sexual transmission of the virus. In this paper,
mucoadhesive vaginal tablets based on chitosa... |
https://openalex.org/W2055539671 | https://vtechworks.lib.vt.edu/bitstream/10919/95839/1/AllamEffect.pdf | English | null | The Effect of Social Support Features and Gamification on a Web-Based Intervention for Rheumatoid Arthritis Patients: Randomized Controlled Trial | JMIR. Journal of medical internet research/Journal of medical internet research | 2,015 | cc-by | 14,023 | Abstract Background: Rheumatoid arthritis (RA) is chronic systematic disease that affects people during the most productive period of
their lives. Web-based health interventions have been effective in many studies; however, there is little evidence and few studies
showing the effectiveness of online social support and ... |
https://openalex.org/W2316354594 | http://www.scielo.br/pdf/csp/v31n12/en_0102-311X-csp-31-12-2523.pdf | English | null | Transtorno do estresse pós-traumático no puerpério em uma maternidade de alto risco fetal no Município do Rio de Janeiro, Brasil | Cadernos de Saúde Pública | 2,015 | cc-by | 7,428 | 1
ARTIGO ARTICLE 1
ARTIGO ARTICLE 1
ARTIGO ARTICLE 1 Universidade do Estado do
Rio de Janeiro, Rio de Janeiro,
Brasil.
2 Universidade Estácio de Sá,
Rio de Janeiro, Brasil.
3 Instituto Nacional de Saúde
da Mulher, da Criança e
do Adolescente Fernandes
Figueira, Fundação Oswaldo
Cruz, Rio de Janeiro, Brasil... |
https://openalex.org/W2811097641 | http://jfqhc.ssu.ac.ir/files/site1/user_files_f703af/edstojkovic-A-10-644-2-c380c3f.pdf | English | null | Increased Health Impact of Aflatoxins Due to Climate Change: Prospective Risk Management Strategies | Journal of food quality and hazards control | 2,018 | cc-by | 1,224 | Acronyms and abbreviations
AF=Aflatoxin Acronyms and abbreviations
AF=Aflatoxin Naturally occurring mycotoxins are an important
challenge since they are present in many kinds of
foodstuffs. Various types of agricultural products,
especially ones with rich carbohydrates, are vulnerable to
fungi growth and their im... |
https://openalex.org/W2986708966 | https://revistaenfermagematual.com.br/index.php/revista/article/download/349/232 | Portuguese | null | Metodologia da problematização como estratégia de ensino e aprendizagem na enfermagem | Revista Enfermagem Atual In Derme | 2,019 | cc-by | 3,783 | RESUMO Objetiva-se descrever a experiência vivenciada por acadêmicos do curso de enfermagem a partir da implementação
da metodologia problematizadora no decorrer do estágio supervisionado em uma Estratégia de Saúde da Família
de um município da região Noroeste do Estado do Rio Grande do Sul. Trata-se de um estudo des... |
https://openalex.org/W4312108872 | https://seer.ufu.br/index.php/biosciencejournal/article/download/47967/31749 | English | null | Classification of the sperm chromatin compaction alterations in bulls (Bos taurus) and its correlation with the efficiency of the in vitro production of embryos | DOAJ (DOAJ: Directory of Open Access Journals) | 2,021 | cc-by | 6,625 | Abstract This paper proposes to classify the sperm chromatin compaction alterations in bulls, according to the
affected area location and its objective is evaluating the correlation of the intensity, the heterogeneity and
these kinds of chromatin decompaction with the rates of cleavage and the formation of blastocyst... |
W4287666534.txt | https://zenodo.org/records/4105946/files/10.pdf | en | ASSESS THE INCIDENCE OF DENTAL CARIES AMONG PEDIATRIC POPULATION IN DENTAL OUTPATIENT DEPARTMENT AT GOVERNMENT RAJAJI HOSPITAL, MADURAI | Zenodo (CERN European Organization for Nuclear Research) | 2,020 | cc-by | 2,613 | ISSN: 2320-5407
Int. J. Adv. Res. 8(09), 181-188
Journal Homepage: -www.journalijar.com
Article DOI:10.21474/IJAR01/11648
DOI URL: http://dx.doi.org/10.21474/IJAR01/11648
RESEARCH ARTICLE
ASSESS THE INCIDENCE OF DENTAL CARIES AMONG PEDIATRIC POPULATION IN DENTAL
OUTPATIENT DEPARTMENT AT GOVERNMENT RAJAJI HOSPITAL, M... | |
https://openalex.org/W4382775744 | https://www.mdpi.com/1996-1073/16/13/5053/pdf?version=1688034783 | English | null | Silver-Nanoparticle-Decorated Fused Carbon Sphere Composite as a Catalyst for Hydrogen Generation | Energies | 2,023 | cc-by | 8,483 | Keywords: silver nanoparticles; fused carbon spheres; hydrogen production; hydrogen feedstock; catalyst Citation: Biehler, E.; Quach, Q.;
Abdel-Fattah, T.M. Silver-
Nanoparticle-Decorated Fused
Carbon Sphere Composite as a
Catalyst for Hydrogen Generation. Energies 2023, 16, 5053. https://
doi.org/10.3390/en16135053 Ar... |
https://openalex.org/W4366078339 | https://hsr-journal.com/index.php/journal/article/download/552/270 | Ukrainian | null | Вплив спеціально спрямованих вправ на рівень підготовленості до змагань гандболістів 13-14 років | Zdorov'â, sport, reabìlìtacìâ | 2,016 | cc-by | 3,423 | Харківська державна академія фізичної культури Анотація. У статті наведені результати досліджень, що свідчать про позитивний вплив вправ
координаційної спрямованості, що виконувались сполученим методом на рівень фізичної, спеціальної
технічної підготовленості та передстартових станів гандболістів 13-14 років. Підвище... |
https://openalex.org/W2593435690 | https://hal.science/hal-03065681/file/%5B15200477%20-%20Bulletin%20of%20the%20American%20Meteorological%20Society%5D%20The%20Global%20Aerosol%20Synthesis%20and%20Science%20Project%20%28GASSP%29%20Measurements%20and%20Modeling%20to%20Reduce%20Uncertainty.pdf | English | null | The Global Aerosol Synthesis and Science Project (GASSP): Measurements and Modeling to Reduce Uncertainty | Bulletin of the American Meteorological Society | 2,017 | cc-by | 13,679 | The Global Aerosol Synthesis and Science Project
(GASSP): Measurements and Modeling to Reduce
Uncertainty
C. Reddington, K. Carslaw, P. Stier, N. Schutgens, H. Coe, D. Liu, J. Allan,
J. Browse, K. Pringle, L. Lee, et al.
To cite this version:
C. Reddington, K. Carslaw, P. Stier, N. Schutgens, H. Coe, et al.. The Global... |
https://openalex.org/W2161471522 | https://europepmc.org/articles/pmc4105781?pdf=render | English | null | Predictive factors of self-medicated analgesic use in Spanish adults: a cross-sectional national study | BMC pharmacology & toxicology | 2,014 | cc-by | 7,580 | Abstract Background: Analgesics are among the most commonly consumed drugs by the world populations. Within the
broader context of self-medication, pain relief occupies a prominent position. Our study was to ascertain the
prevalence of self-medication with analgesics among the Spanish population and to identify predict... |
https://openalex.org/W4309921285 | https://pure.eur.nl/ws/files/77368318/1_s2.0_S0022199622001258_main.pdf | English | null | Trade intermediation by producers | Journal of international economics | 2,023 | cc-by | 11,209 | a r t i c l e
i n f o Article history:
Received 16 April 2022
Received in revised form 12 September 2022
Accepted 8 November 2022
Available online 24 November 2022
Dataset
link:
https://data.mendeley.com/
datasets/fhfpn7drw3
JEL classifications:
F12
F14
L2
Keywords:
Trade intermediation
Intermediaries
Carry-along trade
... |
https://openalex.org/W2167162102 | https://jmedicalcasereports.biomedcentral.com/counter/pdf/10.1186/1752-1947-4-196 | English | null | Recurrent furunculosis as a cause of isolated penile lymphedema: a case report | Journal of medical case reports | 2,010 | cc-by | 2,367 | CASE REPORT Open Access Open Access Introduction Although peno-scrotal lymphedema is common, isolated
penile lymphedema is extremely rare [1]. A literature
review for the last 30 years revealed only two cases of iso-
lated penile involvement. In the first, chronic lymphatic
edema occurred due to long term usage of a pe... |
https://openalex.org/W4286899946 | https://zenodo.org/records/5579261/files/V1I70034.pdf | Russian | null | РАЗРАБОТКА МАХРОВЫХ ТКАНЕЙ НА СОВРЕМЕННЫХ ТКАЦКИХ СТАНКАХ | Zenodo (CERN European Organization for Nuclear Research) | 2,021 | cc-by | 2,740 | РАЗРАБОТКА МАХРОВЫХ ТКАНЕЙ НА СОВРЕМЕННЫХ
ТКАЦКИХ СТАНКАХ Юсупова Н.Б.1, Содиқова Н.Р.2, Хурсандова Ф.М.3, Жураева Д.М4
1 Доцент, Ташкентский институт текстильной и легкой
промышленности (Кафедра технология текстильных полотен)
2Доцент, Ташкентский институт текстильной и легкой
промышленности (Кафедра технология... |
https://openalex.org/W4379517828 | https://www.researchsquare.com/article/rs-2797218/latest.pdf | English | null | Distribution characteristics of non-point source pollution and identification of key source areas in Nanyi Lake(China) Basin: Based on InVEST model and source list method | Research Square (Research Square) | 2,023 | cc-by | 15,980 | Distribution characteristics of non-point source
pollution and identi¦cation of key source areas in
Nanyi Lake(China) Basin: Based on InVEST model
and source list method Lei Ding ( dinglei@stu.ahjzu.edu.cn )
anhui jianzhu university
Cui-cui QI
Anhui Provincial Environmental Science Research Institute
Wei-qing Zhang... |
https://openalex.org/W3193292964 | https://digital.csic.es/bitstream/10261/249361/1/Zurro-2021-Fishing%20during%20the%20early%20human%20occupations%20of%20the%20Atacama%20Desert%20coast.pdf | English | null | Fishing during the early human occupations of the Atacama Desert coast: what if we standardize the data? | Archaeological and anthropological sciences | 2,021 | cc-by | 12,780 | Abstract The Atacama Desert coast (18–30° S) presents one of the earliest chronologies in the South America region, whose first
occupations date from ~ 13,000 cal BP. Since that time, coastal and marine resources have been a common component at
sites along the littoral zone. Fish species have been particularly import... |
https://openalex.org/W2045860606 | https://boundaryvalueproblems.springeropen.com/counter/pdf/10.1186/1687-2770-2013-253 | English | null | Fourier-Hankel solution of the Robin problem for the Helmholtz equation in supershaped annular domains | Boundary value problems | 2,013 | cc-by | 7,404 | R ES EARCH Open Access ©2013 Caratelli et al.; licensee Springer. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction
in any medium, provided the original work ... |
https://openalex.org/W200733635 | https://univoak.eu/islandora/object/islandora%3A86354/datastream/PDF/view | English | null | Nonaqueous capillary electrophoretic behavior of 2-aryl propionic acids in the presence of an achiral ionic liquid | Journal of chromatography A/Journal of chromatography | 2,007 | cc-by | 6,770 | NONAQUEOUS CAPILLARY ELECTROPHORETIC BEHAVIOR OF 2-ARYL
1
PROPIONIC ACIDS IN THE PRESENCE OF AN ACHIRAL IONIC LIQUID.
2
A CHEMOMETRIC APPROACH
3
4
Yannis François1, Anne Varenne1, Emilie Juillerat1, Anne-Catherine Servais2, Patrice Chiap2,
5
Pierre Gareil1*
6
7
8
1 Laboratory of Electrochemistry and... |
https://openalex.org/W2940663307 | http://www.aaejournal.com/pdf-102461-33946?filename=Analysis of selected.pdf | English | null | Analysis of selected methodological problems regarding the examination of traffic events at road intersections | Archiwum Motoryzacji/The Archives of Automotive Engineering | 2,018 | cc-by | 5,214 | 77 77 The Archives of Automotive Engineering – Archiwum Motoryzacji Vol. 82, No. 4, 2018 ANALYSIS OF SELECTED METHODOLOGICAL
PROBLEMS REGARDING THE EXAMINATION
OF TRAFFIC EVENTS AT ROAD
INTERSECTIONS ANDRZEJ METELSKI1
Opole University of Technology Summary The planning of statistical examining of population within t... |
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https://doi.org/10.1007/s12119-023-10076-0 Sexuality & Culture (2023) 27:1504–1526
https://doi.org/10.1007/s12119-023-10076-0 ORIGINAL ARTICLE Changes and Forms of Sexual Behaviour in old age: A
Qualitative Study of Older People in Southeastern Nigeria Stephen Sunday Ede1,2,3
·... |
https://openalex.org/W2906230554 | https://europepmc.org/articles/pmc6323505?pdf=render | English | null | Characterization of a Microalgal UV Mutant for CO<sub>2</sub> Biofixation and Biomass Production | BioMed research international | 2,018 | cc-by | 6,826 | Hindawi
BioMed Research International
Volume 2018, Article ID 4375170, 8 pages
https://doi.org/10.1155/2018/4375170 Hindawi
BioMed Research International
Volume 2018, Article ID 4375170, 8 pages
https://doi.org/10.1155/2018/4375170 Feng Qi
,1,2,3,4 Daoji Wu
,1 Ruimin Mu,1,4 Shuo Zhang,2,5 and Xinyi Xu6 1School of Munic... |
https://openalex.org/W4297688892 | http://www.jmlr.org/papers/volume20/17-153/17-153.pdf | English | null | Matched bipartite block model with covariates | arXiv (Cornell University) | 2,017 | cc-by | 66,321 | Matched Bipartite Block Model with Covariates Zahra S. Razaee
Arash A. Amini
Jingyi Jessica Li
University of California, Los Angeles
Department of Statistics
8125 Math Sciences Bldg., Box 951554
Los Angeles, CA 90095-1554, USA Zahra S. Razaee
Arash A. Amini
Jingyi Jessica Li razaee@ucla.edu
aaamini@stat.ucla.edu
jli@st... |
https://openalex.org/W4255144558 | https://zenodo.org/record/1521830/files/article.pdf | German | null | Sichtbilder zur Pflanzengeographie und Biologie | Feddes repertorium specierum novarum regni vegetabilis | 1,916 | public-domain | 1,314 | F. Fedde. F. Fedde. 364 LXII. $hofeffor Dr. f. febbe,
EietbiIber 3ur PfiangengeograpQie nnb 23iologie.
81.-85. 8eihe (nr. 401-415) 6. Xarftenl),
Ha li f o rn i f4e Xo n i f e r en.
(Xalifornien I.-111.) LXII. $hofeffor Dr. f. febbe,
EietbiIber 3ur PfiangengeograpQie nnb 23iologie. 81.-85. 8eihe (nr. 401-415) 6. Xa... |
https://openalex.org/W2530940254 | http://ejournal.upi.edu/index.php/japanedu/article/download/3292/2279 | Japanese | null | PENGGUNAAN DIALEK KANSAI DALAM ANIME DETECTIVE CONAN EPISODE 651 | Japanedu/Jurnal Japanedu | 2,016 | cc-by-sa | 2,845 | Aulia Raversa, Ahmad Dahidi1, Noviyanti Aneros2 aulia.raversa@gmail.com Kata kunci: Bahasa Jepang standar, dialek Kansai, miskomunikasi Raversa, Dahidi, Aneros, The Use of Dialect Kansai Raversa, Dahidi, Aneros, The Use of Dialect Kansai PENGGUNAAN DIALEK KANSAI DALAM ANIME DETECTIVE CONAN
EPISODE 651 Aulia Raversa, A... |
https://openalex.org/W2235807029 | https://europepmc.org/articles/pmc4738947?pdf=render | English | null | The Function of Naringin in Inducing Secretion of Osteoprotegerin and Inhibiting Formation of Osteoclasts | Evidence-based complementary and alternative medicine | 2,016 | cc-by | 5,257 | Hindawi Publishing Corporation
Evidence-Based Complementary and Alternative Medicine
Volume 2016, Article ID 8981650, 7 pages
http://dx.doi.org/10.1155/2016/8981650 Hindawi Publishing Corporation
Evidence-Based Complementary and Alternative Medicine
Volume 2016, Article ID 8981650, 7 pages
http://dx.doi.org/10.1155/201... |
https://openalex.org/W2474475767 | https://www.frontiersin.org/articles/10.3389/fpls.2016.00931/pdf | English | null | De Novo Transcriptional Analysis of Alfalfa in Response to Saline-Alkaline Stress | Frontiers in plant science | 2,016 | cc-by | 10,758 | ORIGINAL RESEARCH
published: 04 July 2016
doi: 10.3389/fpls.2016.00931 De Novo Transcriptional Analysis of
Alfalfa in Response to Saline-Alkaline
Stress
Yi-Min An, Li-Li Song, Ying-Rui Liu, Yong-Jun Shu and Chang-Hong Guo*
State Key Laboratory of Molecular Genetics, Harbin Normal University, Harbin, China Saline-alkali... |
https://openalex.org/W1011938423 | https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1004358&type=printable | English | null | Dynamic Allostery of the Catabolite Activator Protein Revealed by Interatomic Forces | PLOS computational biology/PLoS computational biology | 2,015 | cc-by | 9,852 | Editor: Qiang Cui, University of Wisconsin-Madison,
UNITED STATES Editor: Qiang Cui, University of Wisconsin-Madison,
UNITED STATES Received: November 18, 2014
Accepted: May 28, 2015
Published: August 5, 2015 Received: November 18, 2014
Accepted: May 28, 2015
Published: August 5, 2015 Copyright: © 2015 Louet et al. Thi... |
https://openalex.org/W2969358405 | https://europepmc.org/articles/pmc6702247?pdf=render | English | null | Incidence and impact of sepsis on long-term outcomes after subarachnoid hemorrhage: a prospective observational study | Annals of intensive care | 2,019 | cc-by | 5,790 | Abstract Background: Aneurysmal subarachnoid hemorrhage (SAH) is an acute cerebrovascular disease associated with high
mortality and long-term functional impairment among survivors. Systemic inflammatory responses after acute injury
and nosocomial infections are frequent complications, making the management of these... |
https://openalex.org/W1996480372 | https://zenodo.org/records/1809768/files/article.pdf | English | null | The Determination of Total, Fixed and Volatile Acids in Wines. | The journal of industrial and engineering chemistry/Journal of industrial and engineering chemistry | 1,909 | public-domain | 9,403 | T H E JOURNAL OF INDLJSTRIAL A N D ENGINEERING CHEMISTRY. T H E JOURNAL OF INDLJSTRIAL A N D ENGINEERING CHEMISTRY. 31 Polymerization with Fuming Nitric A cid.-The
method of Burton' cannot be recommended, be-
ing very dangerous, exceedingly trying and time-
consuming and, at best, not at all accurate. His
detai... |
https://openalex.org/W4391558498 | https://www.pjms.org.pk/index.php/pjms/article/download/8271/2109 | English | null | Unveiling the spectrum: A cross-sectional exploration of hirsutism causes in women | Pakistan journal of medical sciences | 2,024 | cc-by | 3,945 | INTRODUCTION Pak J Med Sci March - April 20
1. Rana Tabassum Ansari, FCPS. Fellow Endocrine
2. Uneeba Syed, FCPS. Assistant Professor, Consultant Endocrinologist,
Allama Iqbal Medical College,
Jinnah hospital, Lahore, Pakistan. 3. Musarrat Riaz, FCPS. Department of Medicine, Associate Professor,
Consultan... |
https://openalex.org/W2901670094 | http://e-journal.president.ac.id/presunivojs/index.php/EXPOSE/article/download/369/249 | Indonesian | null | FILM DOKUMENTER GEROMBOLAN PEMBURU BATU MENGGANA (Mengapresiasi Tinggalan Leluhur Dengan Talenta) | Expose | 2,018 | cc-by | 1,937 | LATAR BELAKANG memberikan media literasi kebudayaan bagi
masyarakat. Dengan memberikan pengertian
kepada
masyarakat
cara
mengapresiasi nilai
melalui
media
literasi,
maka
diharapkan
masyarakat
memiliki
kemampuan
berpikir
menyaring dan kritis atas informasi yang diterima. Banyak media cetak atau elektroni... |
https://openalex.org/W2616334262 | https://europepmc.org/articles/pmc5471714?pdf=render | English | null | Corneal ulcerative disease in dogs under primary veterinary care in England: epidemiology and clinical management | Canine genetics and epidemiology | 2,017 | cc-by | 9,895 | © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original au... |
https://openalex.org/W3088866792 | https://eresearch.qmu.ac.uk/bitstream/handle/20.500.12289/10911/10911.pdf | English | null | Evaluating impact from research: A methodological framework | Research policy | 2,021 | cc-by | 18,602 | A B S T R A C T i Our guidance enables impact evaluation design to be tailored to the aims and context of the evaluation, for example choosing a design to establish a body of research
as a necessary (e.g. a significant contributing factor amongst many) or sufficient (e.g. sole, direct) cause of impact, and choosing th... |
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International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original au... |
https://openalex.org/W4389393911 | https://link.springer.com/content/pdf/10.1007/s10238-023-01252-5.pdf | English | null | Correction to: Reduced regulatory effects of bone marrow-derived mesenchymal stem cells on activated T lymphocytes and Th1/Th2 cytokine secretion in children with aplastic anemia | Clinical and Experimental Medicine | 2,023 | cc-by | 758 | Xiaoping Guo1 · Wenwen Weng1 · Yuwen Wang1 · Jin Pan2 · Sisi Li3 · Yuanyuan Chen1 · Hua Song1 · Jingying Zhang1 ·
Weiqun Xu1 · Xiaojun Xu1 · Yongmin Tang1 Xiaoping Guo1 · Wenwen Weng1 · Yuwen Wang1 · Jin Pan2 · Sisi Li3 · Yuanyuan Chen1 · Hua Song1 · Jingying Zhang1 ·
Weiqun Xu1 · Xiaojun Xu1 · Yongmin Tang1 Xiaoping... |
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Postpartum depression
(postpartum) anxiety
Risk factors
Early detection Background: Depression and anxiety occur frequently postpartum, calling for early detection and treatment. Evidence on risk factors may support early detection, but is inconclusive. Our aim was to identify risk ... |
https://openalex.org/W2017110838 | https://ccsenet.org/journal/index.php/ijc/article/download/6165/5774 | English | null | One-pot Preparation of ?–amino Carbonyl Compounds by Mannich Reaction Using MgO/ZrO2 as Effective and Reusable Catalyst | International journal of chemistry | 2,010 | cc-by | 2,172 | One-pot Preparation of β–amino Carbonyl Compounds by Mannich
Reaction Using MgO/ZrO2 as Effective and Reusable Catalyst Deepak.M. Nagrik (Corresponding author)
Department of Chemistry, PLIT and MS
Buldana-443001, M.S., India
E-mail: dmnagrik@rediffmail.com D.M.Ambhore
P.G.Department of Chemistry, Jijamata Mahavid... |
https://openalex.org/W2073561414 | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0080961&type=printable | English | null | De Novo Assembly of the Transcriptome of the Non-Model Plant Streptocarpus rexii Employing a Novel Heuristic to Recover Locus-Specific Transcript Clusters | PloS one | 2,013 | cc-by | 9,580 | Introduction anisocotyly, the unequal development of cotyledons after germi-
nation whereby the first phyllomorph is derived from the
continued growth of one of the two cotyledons to form the
macrocotyledon (cotyledonary phyllomorph), from the activity of
the basal meristem [3]. The molecular mechanisms that underlie t... |
https://openalex.org/W4321845751 | https://bulmed.md/bulmed/article/download/3462/3465 | Kirghiz, Kyrgyz | null | Pediatric tuberculosis in relation to the immune system | Buletinul Academiei de Ştiinţe a Moldovei: Ştiinţe Medicale | 2,022 | cc-by | 3,493 | Științe Medicale Științe Medicale 29 CZU: [616.24-002.5+612.017]-053.2
https://doi.org/10.52692/1857-0011.2022.3-74.04 TUBERCULOZA PEDIATRICĂ ÎN RAPORT CU SISTEMUL IMUN
(Reviul literaturii) Stela KULCIȚKAIA1, dr. în șt. med., conf. univ.,
Constantin IAVORSCHI1,3, dr. hab. în șt. med., prof. cercet., acad. al AȘMM,
Al... |
https://openalex.org/W4237208221 | https://www.researchsquare.com/article/rs-4833/v2.pdf?c=1631844541000 | English | null | A feasibility study of a WhatsApp-delivered transtheoretical model-based intervention to promote healthy eating knowledge and habits for firefighters in Hong Kong: A cluster randomized controlled trial | Research Square (Research Square) | 2,019 | cc-by | 9,170 | A feasibility study of a WhatsApp-delivered
transtheoretical model-based intervention to
promote healthy eating knowledge and habits for
firefighters in Hong Kong: A cluster randomized
controlled trial Winnie WM NG
(
winnie.wm.ng@connect.polyu.hk
)
Hong Kong Polytechnic University
https://orcid.org/0000-0002-8357-5... |
https://openalex.org/W1978379449 | https://digitalcommons.wustl.edu/cgi/viewcontent.cgi?article=1504&context=open_access_pubs | English | null | Ancestral Genes Can Control the Ability of Horizontally Acquired Loci to Confer New Traits | PLOS genetics | 2,011 | cc-by | 12,801 | Ancestral genes can control the ability of horizontally acquired
Ancestral genes can control the ability of horizontally acquired
loci to confer new traits
loci to confer new traits H. Deborah Chen
Washington University School of Medicine in St. Louis
Mollie W. Jewett
Washington University School of Medicine in S... |
W2097876175.txt | https://www.scielo.br/j/spmj/a/GxnG5LBz3v7xGZDMHghTjcf/?lang=en&format=pdf | en | Thromboembolism in chronic Chagas' heart disease | São Paulo medical journal | 1,995 | cc-by | 2,720 | Joao Carlos Braga, Andre Labrunie, Fabio Villac;a,
Ezilaine do Nascimento, Luiz Quijada
Thromboembolism in chronic Chagas' heart disease
Heart Institute of Mart1ia, Faculdade de Medicina de
Mart1ia. Sao Paulo, Brazil
Thromboembolic episodes are particularly important in chronic Chagas' heart disease. Systemic and pul... | |
https://openalex.org/W2134703690 | https://ccsenet.org/journal/index.php/ies/article/download/33229/20055 | English | null | Modeling the Relations among Parental Involvement, School Engagement and Academic Performance of High School Students | International education studies | 2,014 | cc-by | 6,320 | 1. Introduction School engagement is considered one of the most important factors that affect students’ learning and academic
success. Specifically, it is considered the main model for understanding and predicting graduation of students
from high school (Fall & Roberts, 2012). Previous studies have found that student... |
https://openalex.org/W4324265022 | https://www.scielo.br/j/rpp/a/mfd7dVXMvDYYCytgQnNByQP/?lang=en&format=pdf | English | null | Content validation of a questionnaire to assess the knowledge of pediatricians, family, and community physicians on obesity | Revista Paulista de Pediatria | 2,023 | cc-by | 5,225 | ABSTRACT Objective: The aim of this study was to validate the content of
a questionnaire in order to assess the attitudes and practices in
childcare consultations, knowledge on overweight and obesity, their
risk factors, and barriers in addressing the issue by pediatricians
and family physicians. Objetivo: Validar ... |
https://openalex.org/W2918014542 | https://escholarship.org/content/qt3n4271zj/qt3n4271zj.pdf?t=qalin6 | English | null | Evolution and Diversification of FRUITFULL Genes in Solanaceae | Frontiers in plant science | 2,019 | cc-by | 19,159 | Keywords: dry fruit, fleshy fruit, fruit development, fruit evolution, FRUITFULL, gene duplication, MADS-box
transcription factors, Solanaceae Powered by the California Digital Library
University of California eScholarship.org ORIGINAL RESEARCH
published: 21 February 2019
doi: 10.3389/fpls.2019.00043 ORIGINAL RESEARCH
... |
https://openalex.org/W4200016634 | https://pure.eur.nl/files/80800248/Physical_activity_dimensions_after_stroke.pdf | English | null | Physical activity dimensions after stroke: patterns and relation with lower limb motor function | Journal of neuroengineering and rehabilitation | 2,021 | cc-by | 7,177 | Abstract Background: Stroke survivors show deteriorated physical functioning and physical activity levels. Physical activity
levels of stroke survivors are generally low. It is increasingly recognized that physical activity is a multidimensional
construct that cannot be captured in a single outcome. In-depth insight... |
https://openalex.org/W1751417315 | https://aricjournal.biomedcentral.com/counter/pdf/10.1186/2047-2994-4-S1-P3 | English | null | A surveillance and control of Ebola Outbreak Disease at Télimélé, Guinea Conakry 2014 | Antimicrobial resistance and infection control | 2,015 | cc-by | 750 | Introduction The Global Outbreak Alert and Response Network
(GOARN) have been involved in infectious diseases out-
break response low-resource settings for many years. The current Ebola Virus Disease (EVD) outbreak in
West Africa, originated in Conakry Guinea. Burial
rituals, traditional healer practices, illegal healt... |
https://openalex.org/W4255860320 | https://bmcpregnancychildbirth.biomedcentral.com/counter/pdf/10.1186/s12884-021-03696-7 | English | null | Design and Psychometric Evaluation of the Fathers' Fear of Childbirth Scale: A Mixed Method Study | Research Square (Research Square) | 2,020 | cc-by | 7,115 | © The Author(s). 2021, corrected publication 2021. Open Access This article is licensed under a Creative Commons Attribution
4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as
long as you give appropriate credit to the original author(s) and the ... |
https://openalex.org/W4282939461 | https://file.techscience.com/ueditor/files/csse/TSP_CSSE-44-2/TSP_CSSE_28755/TSP_CSSE_28755.pdf | English | null | Intelligent Student Mental Health Assessment Model on Learning Management System | Computer systems science and engineering | 2,023 | cc-by | 7,087 | Nasser Ali Aljarallah1,2, Ashit Kumar Dutta3,*, Majed Alsanea4 and Abdul Rahaman Wahab Sait5 asser Ali Aljarallah1,2, Ashit Kumar Dutta3,*, Majed Alsanea4 and Abdul Rahaman W 1AlMaarefa University, Ad Diriyah, Riyadh, 13713, Kingdom of Saudi Arabia
2Department of Business Administration, Majmaah University, AlMajmaah, ... |
W4380629729.txt | https://ejournal.uinsaizu.ac.id/index.php/yinyang/article/download/8044/3147 | en | Konsep Hijab Dalam Pemikiran Fatima Mernissi | Yinyang | 2,023 | cc-by-sa | 0 | ||
https://openalex.org/W3037166995 | https://www.mdpi.com/2073-4352/10/6/540/pdf?version=1593482376 | English | null | Material Properties of Zr–Cu–Ni–Al Thin Films as Diffusion Barrier Layer | Crystals | 2,020 | cc-by | 14,110 | Received: 8 June 2020; Accepted: 22 June 2020; Published: 24 June 2020 Abstract: Due to the rapid increase in current density encountered in new chips, the phenomena
of thermomigration and electromigration in the solder bump become a serious reliability issue. Currently, Ni or TiN, as a barrier layer, is widely academi... |
https://openalex.org/W2593934310 | https://newprairiepress.org/cgi/viewcontent.cgi?article=1678&context=fgr | English | null | Improved techniques for assayinq protein concentration in geminating Neurospora conidia. | Fungal genetics reports | 1,980 | cc-by-sa | 1,090 | Improved techniques for assayinq protein concentration in
Improved techniques for assayinq protein concentration in
geminating Neurospora conidia.
geminating Neurospora conidia. R. L. Christensen
D. Wolens
J. C. Schmit Follow this and additional works at: https://newprairiepress.org/fgr This work is licensed unde... |
https://openalex.org/W4234348789 | https://backend.orbit.dtu.dk/ws/files/239473081/wes_6_111_2021.pdf | English | null | Model-free Estimation of Available Power using Deep Learning | null | 2,019 | cc-by | 15,589 | Downloaded from orbit.dtu.dk on: Oct 24, 2024 Downloaded from orbit.dtu.dk on: Oct 24, 2024 Downloaded from orbit.dtu.dk on: Oct 24, 2024 Citation (APA):
Göçmen, T., Meseguer Urban, A., Liew, J. Y., & Lio, A. W. H. (2021). Model-free estimation of available power
using deep learning. Wind Energy Science, 6(1), 111-129.... |
https://openalex.org/W4221062573 | https://zenodo.org/record/5813929/files/5-1368-Article%20Text-5582-1-6-20211210-CE.pdf | Indonesian | null | Evaluasi Program Pembelajaran PJOK Kurikulum 2013 secara Daring saat Pandemi Covid-19 pada SMP Negeri se-Kecamatan Kuta Tahun 2021 | Zenodo (CERN European Organization for Nuclear Research) | 2,022 | cc-by | 7,087 | P-ISSN 2337-9561
E-ISSN 2580-1430 P-ISSN 2337-9561
E-ISSN 2580-1430 P-ISSN 2337-9561
E-ISSN 2580-1430 Jurnal Pendidikan Kesehatan Rekreasi
Vol. 8, No. 1, Hal. 40-55, Januari 2022 ABSTRAK Penelitian bertujuan untuk mengetahui pelaksanaan program pembelajaran PJOK Kurikulum
2013 secara daring pada SMP Negeri se-Kec... |
https://openalex.org/W2419841160 | https://www.scielo.br/j/cagro/a/ndwjB4DxQZfkwydymTXXXVJ/?lang=en&format=pdf | English | null | Cassava starch edible coating incorporated with propolis on bioactive compounds in strawberries | Ciência e Agrotecnologia | 2,016 | cc-by | 6,339 | RESUMO O morango é um fruto muito apreciado em todo o mundo por apresentar atributos de qualidade atrativos para o consumidor e destaca-
se por seu alto conteúdo de compostos fenólicos, contribuindo, positivamente, para propriedades biológicas de interesse nutricional. Objetivou-se, neste estudo, avaliar o efeito de co... |
https://openalex.org/W2096272680 | https://nutritionj.biomedcentral.com/counter/pdf/10.1186/1475-2891-12-65 | English | null | Ethnic differences in grains consumption and their contribution to intake of B-vitamins: results of the Multiethnic Cohort Study | Nutrition journal | 2,013 | cc-by | 8,450 | Sharma et al. Nutrition Journal 2013, 12:65
http://www.nutritionj.com/content/12/1/65 * Correspondence: gita.sharma@ualberta.ca
1Department of Medicine, Aboriginal and Global Health Research Group,
University of Alberta, 5-10 University Terrace, 8303 112 Street, Edmonton,
Alberta T6G 2T4, Canada
Full list of author inf... |
https://openalex.org/W4285318001 | https://revistas.pucsp.br/index.php/risus/article/download/56956/38661 | English | null | SOCIAL REPRESENTATION OF THE INNOVATION CONCEPT: CROSS-COUNTRY IN BOLIVIA, BRAZIL, INDIA AND MEXICO | RISUS - Revista de Inovação e Sustentabilidade | 2,021 | cc-by | 13,457 | SOCIAL REPRESENTATION OF THE INNOVATION CONCEPT: CROSS-COUNTRY
IN BOLIVIA, BRAZIL, INDIA AND MEXICO
Ì Rodrigo Franklin Frogeri1, Pedro dos Santos Portugal Júnior1, Fabrício Pelloso Piurcosky1, Meenu Bhardwaj2,
Juan-Carlos González-Islas3, Juan Carlos Arroyo Mendizábal4
1UNIS Educational Group, Varginha – Brazil, 2C... |
https://openalex.org/W2800485751 | https://europepmc.org/articles/pmc5938413?pdf=render | English | null | Challenges in Reproducibility, Replicability, and Comparability of Computational Models and Tools for Neuronal and Glial Networks, Cells, and Subcellular Structures | Frontiers in neuroinformatics | 2,018 | cc-by | 23,877 | Challenges in Reproducibility,
Replicability, and Comparability of
Computational Models and Tools for
Neuronal and Glial Networks, Cells,
and Subcellular Structures Tiina Manninen 1,2*, Jugoslava A ´cimovi ´c 1,2*, Riikka Havela 1,2, Heidi Teppola 1,2 and
Marja-Leena Linne 1,2* 1 Computational Neuroscience Group, BioMe... |
https://openalex.org/W4306784196 | https://wcd.copernicus.org/articles/4/115/2023/wcd-4-115-2023.pdf | English | null | Replies to all reviewer comments, wcd-2022-35 | null | 2,022 | cc-by | 14,743 | Cloud-radiative impact on the dynamics and predictability of an
idealized extratropical cyclone Behrooz Keshtgar1, Aiko Voigt2, Corinna Hoose1, Michael Riemer3, and Bernhard Mayer4
1Institute of Meteorology and Climate Research – Department Troposphere Research,
Karlsruhe Institute of Technology, Karlsruhe, Germany
2De... |
https://openalex.org/W2287153317 | https://europepmc.org/articles/pmc4735710?pdf=render | English | null | The Shine-Dalgarno sequence of riboswitch-regulated single mRNAs shows ligand-dependent accessibility bursts | Nature communications | 2,016 | cc-by | 14,210 | ARTICLE Received 18 Sep 2015 | Accepted 21 Oct 2015 | Published 19 Jan 2016 Received 18 Sep 2015 | Accepted 21 Oct 2015 | Published 19 Jan 2016 1 Single Molecule Analysis Group, Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA. 2 Program in Chemical Biology,
University of Michigan, Ann Ar... |
https://openalex.org/W2142630149 | https://gutpathogens.biomedcentral.com/counter/pdf/10.1186/1757-4749-5-13 | English | null | Uropathogenic specific protein gene, highly distributed in extraintestinal uropathogenic Escherichia coli, encodes a new member of H-N-H nuclease superfamily | Gut pathogens | 2,013 | cc-by | 7,687 | © 2013 Zaw et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.... |
https://openalex.org/W3196647328 | https://jurnal.ugm.ac.id/kawistara/article/download/63587/32079 | Indonesian | null | Peran Kepemimpinan dalam Sinergi antar Dinas di Pemerintahan Daerah: Studi Program Percepatan Peningkatan Status Kemajuan dan Kemandirian Desa di Provinsi Kalimantan Barat | Kawistara : Jurnal Ilmiah Sosial dan Humaniora/Kawistara | 2,021 | cc-by-sa | 7,399 | *Corresponding author: sitifatmawati@mail.ugml.ac.id.
Copyright© 2021 THE AUTHOR (S). This article is distributed under a Creative Commons Attribution-Share Alike
4.0 International license. Jurnal Kawistara is published by the Graduate School of Universitas Gadjah Mada JURNAL KAWISTARA Halaman 115—128 VOLUME 11 VOLUME ... |
https://openalex.org/W4313005146 | https://www.matec-conferences.org/articles/matecconf/pdf/2022/15/matecconf_newtech22_01014.pdf | English | null | Management of tools in digital manufacturing - A case study | MATEC web of conferences | 2,022 | cc-by | 4,383 | Management of tools in digital manufacturing - A case
study Vojin Vukadinović1, Jovan Živković1, Dragan Đurđanović2, Vidosav Majstorović3*
[ 0000-0001-9534-8461 ] Vojin Vukadinović1, Jovan Živković1, Dragan Đurđanović2, Vidosav Majstorović3*
[ 0000-0001-9534-8461 ] 1 Company Metalac, Gornji Milanovac, Serb... |
https://openalex.org/W2789946978 | https://research-repository.st-andrews.ac.uk/bitstream/10023/16665/1/Varela_2018_ACIE_Opticalstructure_CC.pdf | English | null | Optical Structural Analysis of Individual α‐Synuclein Oligomers | Angewandte Chemie | 2,018 | cc-by | 5,318 | Protein Aggregates Optical Structural Analysis of Individual a-Synuclein Oligomers
Juan A. Varela, Margarida Rodrigues, Suman De, Patrick Flagmeier, Sonia Gandhi,
Christopher M. Dobson, David Klenerman,* and Steven F. Lee* Abstract: Small aggregates of misfolded proteins play a key
role in neurodegenerative disorders. ... |
https://openalex.org/W4385769910 | http://anapub.co.ke/journals/jbsha/jbsha_pdf/2023/jbsha_volume_3-issue_2/JBSHA202303010.pdf | English | null | A Comprehensive Review on Healthcare Data Analytics | Journal of biomedical and sustainable healthcare applications | 2,023 | cc-by | 8,759 | ISSN: 2790-0088 ISSN: 2790-0088 Journal of Biomedical and Sustainable Healthcare Applications 3(2)(2023) Published by AnaPub Publications Abstract – Healthcare data can be collected from various sources, including sensors, and conventional electronic records, photographs,
data from clinical notes/biological literature... |
https://openalex.org/W2265447742 | http://bura.brunel.ac.uk/bitstream/2438/12390/4/Fulltext.pdf | English | null | Searches for a heavy scalar boson H decaying to a pair of 125 GeV Higgs bosons hh or for a heavy pseudoscalar boson A decaying to Zh, in the final states with h →ττ | Physics letters. B | 2,016 | cc-by | 20,324 | a b s t r a c t Article history:
Received 5 October 2015
Received in revised form 10 January 2016
Accepted 26 January 2016
Available online 9 February 2016
Editor: M. Doser
Keywords:
CMS
Physics
MSSM
τ
Higgs A search for a heavy scalar boson H decaying into a pair of lighter standard-model-like 125 GeV Higgs
bosons hh... |
https://openalex.org/W2778194714 | https://bop.unibe.ch/linguistik-online/article/download/4179/6275 | English | null | The risk of metacommunication to manage interactional trouble in online chat counseling | Linguistik online | 2,017 | cc-by | 12,317 | Abstract The main handbook on online counseling used in the Netherlands recommends counselors to
use metacommunication, i. e. to state what happens during the interaction, in case of interac-
tional trouble. The aim of this study was to explore this interactional strategy by describing
how counselors may use metacomm... |
https://openalex.org/W4385572905 | https://aclanthology.org/2022.emnlp-main.73.pdf | English | null | Zero-Shot Text Classification with Self-Training | null | 2,022 | cc-by | 8,822 | ∗These authors contributed equally to this work. Zero-Shot Text Classification with Self-Training
Ariel Gera∗, Alon Halfon∗, Eyal Shnarch∗, Yotam Perlitz∗,
Liat Ein-Dor, Noam Slonim IBM Research
{ariel.gera1, yotam.perlitz}@ibm.com,
{alonhal, eyals, liate, noams}@il.ibm.com In their pioneering work on more general-
pur... |
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materials
ISSN 1996-1944
www.mdpi.com/journal/materials
Article
Prosthetic Meshes for Repair of Hernia and Pelvic Organ
Prolapse: Comparison of Biomechanical Properties
Manfred M. Maurer 1,*, Barbara Röhrnbauer 1, Andrew Feola 2, Jan Deprest 2 and
Edoardo M... |
https://openalex.org/W4392977392 | https://www.researchsquare.com/article/rs-4113874/latest.pdf | English | null | Compassionate use of cefiderocol in a complex case of extensively drug-resistant Acinetobacter baumannii fracture-related infection: a comprehensive approach and multidisciplinary management | Research Square (Research Square) | 2,024 | cc-by | 4,341 | Compassionate use of ce¦derocol in a complex
case of extensively drug-resistant Acinetobacter
baumannii fracture-related infection: a
comprehensive approach and multidisciplinary
management Petrucci Flavia Sapienza University of Rome
Perciballi Beatrice
Sapienza University of Rome
Rivano Capparuccia Marco
Sapienza Un... |
https://openalex.org/W3186609544 | https://www.revistas.usp.br/rmrp/article/download/173234/174125 | English | null | Repercussões cardiovasculares em usuários de cocaína: uma revisão integrativa | Medicina | 2,021 | cc-by | 9,761 | ORIGINAL ARTICLE ORIGINAL ARTICLE Cardiovascular repercussions in cocaine users:
an integrative review egina Pereira Pantaleão1
, André da Silveira Ribeiro Lins1
, Manoel Marques de Souto Nóbrega Filho1 ABSTRACT Introduction: The use of cocaine is considered an important health problem. An increasing number of patie... |
https://openalex.org/W4380415521 | https://zenodo.org/records/8030054/files/Relat%C3%B3rio%20T%C3%A9cnico%20-%20Estudo%20de%20Caso%201.pdf | Portuguese | null | Safety ArtISt - Relatório Técnico de Pesquisa - Desenvolvimento do Estudo de Caso de Sistema de Detecção de Arritmias Cardíacas por Aprendizado Supervisionado Profundo | Zenodo (CERN European Organization for Nuclear Research) | 2,023 | cc-by | 320,583 | Desenvolvimento do Estudo de Caso de Sistema
de Detecção de Arritmias Cardíacas por
Aprendizado Supervisionado Profundo Autor: Antonio Vieira da Silva Neto
Revisor: Paulo Sérgio Cugnasca Revisão 3 – 12/06/2023 Título:
RELATÓRIO TÉCNICO DE PESQUISA – DESENVOLVIMENTO DO ESTUDO DE
CASO DE SISTEMA DE DETECÇÃO DE ARRIT... |
https://openalex.org/W2465793971 | https://academicjournals.org/journal/ERR/article-full-text-pdf/CF33ADE51931.pdf | English | null | Effects of art/design education on meta-esthetics consciousness of fine arts students | Educational research and reviews | 2,015 | cc-by | 12,405 | Full Length Research Paper
Effects of art/design education on meta-esthetics
consciousness of fine arts students Eylem TATAROGLU Eylem TATAROGLU
Baskent University, Fine Arts Design and Architecture Faculty, Baglica Campus, Eskisehir Yolu 20. Km, 06870
Etimesgut, Ankara, Turkey. Received 17 November, 2014; Accept... |
https://openalex.org/W2093356898 | https://jm.copernicus.org/articles/16/109/1997/jm-16-109-1997.pdf | English | null | &lt;i&gt;Axelheibergella&lt;/i&gt; (Ostracoda, Crustacea), a new genus of marginally septate cladocopid ostracods from the central Arctic Ocean | Journal of micropalaeontology | 1,997 | cc-by | 12,854 | INTRODUCTION Fig. 1. Locality map of Arctic Ocean showing the two study areas,
bathymetry, physiography and surface currents. Large clear and black
arrows denote input of North Pacific and North Atlantic water,
respectively; small clear arrows denote Beaufort Gyre; large black
fishtail arrows denote Transpolar Drift (T... |
https://openalex.org/W4231846140 | http://eprints.whiterose.ac.uk/121041/1/Green%20Open%20Access%20CSFB%208.1.pdf | English | null | A look at ‘fishy drag’ and androgynous fashion: Exploring the border spaces beyond gender-normative deviance for the straight, cisgendered woman | Critical studies in fashion & beauty | 2,017 | cc-by | 12,186 | Reuse Items deposited in White Rose Research Online are protected by copyright, with all rights reserved unless
indicated otherwise. They may be downloaded and/or printed for private study, or other acts as permitted by
national copyright laws. The publisher or other rights holders may allow further reproduction and ... |
https://openalex.org/W2000608815 | https://europepmc.org/articles/pmc4054613?pdf=render | English | null | Body Pigmentation as a Risk Factor for the Formation of Intracranial Aneurysms | BioMed research international | 2,014 | cc-by | 7,903 | Günter Schulter,1 Klaus Leber,2 Elke Kronawetter,1 Viktoria R. Rübenbauer,1
Peter Konstantiniuk,3 and Ilona Papousek1
1 Department of Psychology, Biological Psychology Unit, Karl-Franzens-University, Universit¨atsplatz 2/III, 8010 Graz, A
2 Department of Neurosurgery Medical University Auenbruggerplatz 2 8036 Graz Aust... |
https://openalex.org/W2297508794 | https://newprairiepress.org/cgi/viewcontent.cgi?article=1654&context=kaesrr | English | null | Effects of castration age and a growth implant during suckling on weaning and preconditioned weights | Kansas Agricultural Experiment Station research reports | 2,003 | cc-by | 1,402 | Effects of castration age and a growth implant during suckling on
Effects of castration age and a growth implant during suckling on
weaning and preconditioned weights (2003)
weaning and preconditioned weights (2003) T.T. Marston See next page for additional authors Follow this and additional works at: https://newpra... |
https://openalex.org/W4306816490 | https://mediatum.ub.tum.de/doc/1693552/document.pdf | English | null | Quantification of oxidative stress in Saccharomyces pastorianus propagation: Gene expression analysis using quantitative reverse transcription polymerase chain reaction and flow cytometry | Frontiers in chemical engineering | 2,022 | cc-by | 6,709 | COPYRIGHT COPYRIGHT
© 2022 Beugholt, Büchner, Geier and
Becker. This is an open-access article
distributed under the terms of the
Creative Commons Attribution License
(CC BY). The use, distribution or
reproduction in other forums is
permitted, provided the original
author(s) and the copyright owner(s) are
credited and ... |
https://openalex.org/W4244115734 | https://www.scielo.br/j/rbee/a/vzkQ9frsmTWwftWBCbh4QTM/?lang=pt&format=pdf | Portuguese | null | Editorial | Revista brasileira de educação especial | 2,006 | cc-by | 754 | Rev. Bras. Ed. Esp., Marília, Mai.-Ago. 2006, v.12, n.2, p.147-148 Editorial Editorial EDITORIAL Prezados sócios da ABPEE e leitores da Revista Brasileira de Educação Prezados sócios da ABPEE e leitores da Revista Brasileira de Educação
Especial. Especial. Informamos a todos que conseguimos atingir mais uma das metas p... |
https://openalex.org/W2884134084 | https://www.scielo.br/j/abmvz/a/cnZ48SPtSzpYbLgdzKyg76d/?lang=pt&format=pdf | Portuguese | null | Parâmetros fisiológicos de vacas F1 Holandês x Zebu criadas em ambientes com e sem sombreamento | Arquivo Brasileiro de Medicina Veterinária e Zootecnia/Arquivo brasileiro de medicina veterinária e zootecnia | 2,018 | cc-by | 5,340 | RESUMO Objetivou-se, com este estudo, caracterizar o efeito do microclima proporcionado por dois ambientes
distintos, sobre as respostas fisiológicas de vacas F1 HxZ em fase de lactação, durante o verão. Foram
avaliadas 34 vacas oriundas de quatro diferentes grupos genéticos F1 HxZ. Durante o período
experimental, ... |
https://openalex.org/W2784122645 | https://revistes.uab.cat/dea/article/download/v4-deventura/85-pdf-it | Italian | null | “Donne mi parver, non da ballo sciolte”: appunti su danza e pericorsi tra gli spiriti sapienti | Dante e l'arte | 2,017 | cc-by | 5,766 | Dante e l’arte 4, 2017 125-136 Dante e l’arte 4, 2017 125-136 Abstract Sorprendentemente, gli spiriti sapienti nel cielo del Sole sono appaiono come donne dan
zanti. Forse perché nella Bibbia Sapientia è una fanciulla che danza. Ma soprattutto perché
movimento eterno di danza circolare, e danza nuziale, è la pe... |
https://openalex.org/W4285086200 | https://www.researchsquare.com/article/rs-1781226/latest.pdf | English | null | Umbilical cord plasma Lysophospholipids and Triacylglycerols Associated with Birthweight Percentiles | Research Square (Research Square) | 2,022 | cc-by | 7,800 | Umbilical cord plasma Lysophospholipids and Triacylglycerols Associated
with Birthweight Percentiles Gerard Wong Kok Hian Tan
KK Women's and Children's Hospital (KKH) Fabian Yap
KK Women's and Children's Hospital (KKH) Fabian Yap
KK Women's and Children's Hospital (KKH) Lynette P Shek
Singapore Institute for Clinic... |
https://openalex.org/W1994056886 | https://dash.harvard.edu/bitstream/1/14169380/1/74446175.pdf | English | null | Systematic Investigation on Interactions for HIV Drug Resistance and Cross-Resistance among Protease Inhibitors | Journal of proteome science and computational biology | 2,012 | cc-by | 7,946 | Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available
under the terms and conditions applicable to Other Posted Material, as set forth at http://
nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA Permanent link http://nrs.harvard.edu/urn-3:HUL.InstRep... |
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