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Reversible lysine acetylation is one of the most important protein posttranslational modifications that plays essential roles in both prokaryotes and eukaryotes . However , only a few lysine deacetylases ( KDACs ) have been identified in prokaryotes , perhaps in part due to their limited sequence homology . Herein , we...
After proteins have been made , they can be modified in several ways . For example , chemical tags called acetyl groups may be added to ( and later removed from ) the protein to regulate cell activities such as aging and metabolism . Enzymes are proteins that help catalyze the reactions that add or remove the acetyl ta...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "biochemistry", "and", "chemical", "biology" ]
2015
YcgC represents a new protein deacetylase family in prokaryotes
CLC secondary active transporters exchange Cl- for H+ . Crystal structures have suggested that the conformational change from occluded to outward-facing states is unusually simple , involving only the rotation of a conserved glutamate ( Gluex ) upon its protonation . Using 19F NMR , we show that as [H+] is increased to...
Cells have transporter proteins on their surface to carry molecules in and out of the cell . For example , the CLC family of transporters move two chloride ions in one direction at the same time as moving one hydrogen ion in the opposite direction . To be able to move these ions in opposite directions , transporters ha...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "structural", "biology", "and", "molecular", "biophysics" ]
2016
Revealing an outward-facing open conformational state in a CLC Cl–/H+ exchange transporter
Autophagy is a conserved cellular process involved in the elimination of proteins and organelles . It is also used to combat infection with pathogenic microbes . The intracellular pathogen Legionella pneumophila manipulates autophagy by delivering the effector protein RavZ to deconjugate Atg8/LC3 proteins coupled to ph...
Organisms have to fight bacteria and other disease-causing microbes on a daily basis . To stay on top of the game , cells use many ways to defend themselves . Autophagy , for example , is a process that breaks down unwanted or damaged molecules inside cells , which has also been linked to fighting infections caused by ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]
2017
Elucidation of the anti-autophagy mechanism of the Legionella effector RavZ using semisynthetic LC3 proteins
Long Interspersed Nuclear Element-1 ( LINE-1 , L1 ) is a mobile genetic element active in human genomes . L1-encoded ORF1 and ORF2 proteins bind L1 RNAs , forming ribonucleoproteins ( RNPs ) . These RNPs interact with diverse host proteins , some repressive and others required for the L1 lifecycle . Using differential ...
Our genome consists of about two percent genes , while around 60 to 70 percent are made up of hundreds of thousands of copies of very similar DNA sequences . These repeats have accumulated over time due to specific genetic elements called transposons . Transposons are often referred to as ‘jumping genes’ , as they can ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "biochemistry", "and", "chemical", "biology", "computational", "and", "systems", "biology" ]
2018
Dissection of affinity captured LINE-1 macromolecular complexes
Fibroblast growth factor-21 ( FGF21 ) is a hormone secreted by the liver during fasting that elicits diverse aspects of the adaptive starvation response . Among its effects , FGF21 induces hepatic fatty acid oxidation and ketogenesis , increases insulin sensitivity , blocks somatic growth and causes bone loss . Here we...
In 1934 , in a famous experiment at Cornell University , it was discovered that laboratory mice could live twice as long as expected if they were fed a low-calorie diet that included enough nutrients to avoid malnutrition . This phenomenon has since been observed in species ranging from worms to primates , but not in h...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "chromosomes", "and", "gene", "expression" ]
2012
The starvation hormone, fibroblast growth factor-21, extends lifespan in mice
The ability to decrypt volatile plant signals is essential if herbivorous insects are to optimize their choice of host plants for their offspring . Green leaf volatiles ( GLVs ) constitute a widespread group of defensive plant volatiles that convey a herbivory-specific message via their isomeric composition: feeding of...
Plants have developed a variety of strategies to defend themselves against herbivorous animals , particularly insects . In addition to mechanical defences such as thorns and spines , plants also produce compounds known as secondary metabolites that keep insects and other herbivores at bay by acting as repellents or tox...
[ "Abstract", "Introduction", "Results", "Discussion", "Material", "and", "methods" ]
[ "ecology", "neuroscience" ]
2013
Feeding-induced rearrangement of green leaf volatiles reduces moth oviposition
In eukaryotes , most integral membrane proteins are synthesized , integrated into the membrane , and folded properly in the endoplasmic reticulum ( ER ) . We screened the mutants affecting rhabdomeric expression of rhodopsin 1 ( Rh1 ) in the Drosophila photoreceptors and found that dPob/EMC3 , EMC1 , and EMC8/9 , Droso...
The membranes that surround cells contain many proteins , and those that span the entire width of the membrane are known as transmembrane proteins . Rhodopsin is one such transmembrane protein that is found in the light-sensitive ‘photoreceptor’ cells of the eye , where it plays an essential role in vision . Transmembr...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "biology" ]
2015
dPob/EMC is essential for biosynthesis of rhodopsin and other multi-pass membrane proteins in Drosophila photoreceptors
Parkinson’s disease ( PD ) is a common neurodegenerative disorder without effective disease-modifying therapeutics . Here , we establish a chemogenetic dopamine ( DA ) neuron ablation model in larval zebrafish with mitochondrial dysfunction and robustness suitable for high-content screening . We use this system to cond...
Parkinson’s disease is caused by the slow death and deterioration of brain cells , in particular of the neurons that produce a chemical messenger known as dopamine . Certain drugs can mitigate the resulting drop in dopamine levels and help to manage symptoms , but they cause dangerous side-effects . There is no treatme...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience", "genetics", "and", "genomics" ]
2021
A zebrafish screen reveals Renin-angiotensin system inhibitors as neuroprotective via mitochondrial restoration in dopamine neurons
The most frequent missense mutations in familial Parkinson’s disease ( PD ) occur in the highly conserved LRRK2/PARK8 gene with G2019S mutation . We previously established a fly model of PD carrying the LRRK2-G2019S mutation that exhibited the parkinsonism-like phenotypes . An herbal medicine , Gastrodia elata Blume ( ...
Parkinson’s disease is a brain disorder that leads to tremors and difficulties with balance and coordination . These symptoms are caused by the loss of neurons which release a chemical messenger that is needed to regulate movement called dopamine . Most treatments for this disease work by boosting levels of dopamine in...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2021
Glial Nrf2 signaling mediates the neuroprotection exerted by Gastrodia elata Blume in Lrrk2-G2019S Parkinson’s disease
Leaf senescence is an essential part of the plant lifecycle during which nutrients are re-allocated to other tissues . The regulation of leaf senescence is a complex process . However , the underlying mechanism is poorly understood . Here , we uncovered a novel and the pivotal role of Arabidopsis HDA9 ( a RPD3-like his...
The leaves of many plants turn yellow in the fall as nutrients are recycled to prepare for the winter months . However , if leaves age and yellow too early , it can limit how much energy the plant can harvest from light . Thus , it is crucial for plants to know when they should start the leaf aging process . This is al...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "chromosomes", "and", "gene", "expression", "plant", "biology" ]
2016
POWERDRESS interacts with HISTONE DEACETYLASE 9 to promote aging in Arabidopsis
Cell behavior is controlled through spatio-temporally localized protein activity . Despite unique and often contradictory roles played by Src-family-kinases ( SFKs ) in regulating cell physiology , activity patterns of individual SFKs have remained elusive . Here , we report a biosensor for specifically visualizing act...
Cells contain networks of signaling proteins that can respond to a variety of cues from the surrounding environment . Often the cell’s response to these cues is not just controlled by the level of protein , but by changing the activity of signaling proteins . For example , a signaling protein in humans and other mammal...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "biochemistry", "and", "chemical", "biology", "cell", "biology" ]
2020
A Fyn biosensor reveals pulsatile, spatially localized kinase activity and signaling crosstalk in live mammalian cells
Planarian neoblasts are pluripotent , adult somatic stem cells and lineage-primed progenitors that are required for the production and maintenance of all differentiated cell types , including the germline . Neoblasts , originally defined as undifferentiated cells residing in the adult parenchyma , are frequently compar...
Flatworms are masters of regeneration . If virtually any piece of a flatworm is cut off , a new fully functional individual will grow from it within two weeks . This is no simple task since flatworms contain a wide variety of organ systems , including a brain , nervous system , eyes , kidneys , gut , muscle and skin . ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "stem", "cells", "and", "regenerative", "medicine" ]
2017
Embryonic origin of adult stem cells required for tissue homeostasis and regeneration
The evolutionary origins of the hypoxia-sensitive cells that trigger amniote respiratory reflexes – carotid body glomus cells , and ‘pulmonary neuroendocrine cells’ ( PNECs ) - are obscure . Homology has been proposed between glomus cells , which are neural crest-derived , and the hypoxia-sensitive ‘neuroepithelial cel...
The carotid bodies are small glands found in either side of our neck , near the carotid artery . When the level of oxygen in our blood drops , specialized cells in the carotid bodies signal to the brain to increase our heart rate and make us breathe more rapidly and deeply . As a result , more oxygen is delivered to ou...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "developmental", "biology" ]
2017
Evolution of the hypoxia-sensitive cells involved in amniote respiratory reflexes
Communication between pre- and postsynaptic cells promotes the initial organization of synaptic specializations , but subsequent synaptic stabilization requires transcriptional regulation . Here we show that fibroblast growth factor 22 ( FGF22 ) , a target-derived presynaptic organizer in the mouse hippocampus , induce...
Nerve cells in the developing brain must organize themselves into complex networks by forming appropriate connections with one another . These connections are known as synapses , and they assemble via two critical stages . First , a new synapse forms , and then it stabilizes . This first stage is a localized event that...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "developmental", "biology", "neuroscience" ]
2016
Retrograde fibroblast growth factor 22 (FGF22) signaling regulates insulin-like growth factor 2 (IGF2) expression for activity-dependent synapse stabilization in the mammalian brain
Transcription is tightly regulated to maintain energy homeostasis during periods of feeding or fasting , but the molecular factors that control these alternating gene programs are incompletely understood . Here , we find that the B cell lymphoma 6 ( BCL6 ) repressor is enriched in the fed state and converges genome-wid...
Obesity has nearly tripled worldwide since the 1970s . A major health concern related to obesity is that excess fat can spill into organs such as the liver . This can lead to fatty liver disease or even liver cancer . Therefore , it is important to fully understand the mechanisms that lead to fat accumulation in the li...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "chromosomes", "and", "gene", "expression" ]
2019
Dynamic repression by BCL6 controls the genome-wide liver response to fasting and steatosis
Polo-like kinases ( PLK ) are eukaryotic regulators of cell cycle progression , mitosis and cytokinesis; PLK4 is a master regulator of centriole duplication . Here , we demonstrate that the SCL/TAL1 interrupting locus ( STIL ) protein interacts via its coiled-coil region ( STIL-CC ) with PLK4 in vivo . STIL-CC is the f...
Centrioles are structures that organize the molecular scaffolding inside cells , which is important for a cell's shape and activity , as well as the segregation of duplicated chromosomes during cell division . Centrioles also form part of the base of the antenna-like structures called cilia , which project out from the...
[ "Abstract", "Introduction", "Results", "Discussion" ]
[ "cell", "biology", "structural", "biology", "and", "molecular", "biophysics" ]
2015
STIL binding to Polo-box 3 of PLK4 regulates centriole duplication
Digital signaling enhances robustness of cellular decisions in noisy environments , but it is unclear how digital systems transmit temporal information about a stimulus . To understand how temporal input information is encoded and decoded by the NF-κB system , we studied transcription factor dynamics and gene regulatio...
Cells have communication systems called signaling pathways that enable them to detect and respond to changes in their surrounding environment . For example , in humans and other animals , a signaling pathway called NF-κB signaling is part of the immune system and regulates the inflammation that is caused by damage to c...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "computational", "and", "systems", "biology", "immunology", "and", "inflammation" ]
2015
Digital signaling decouples activation probability and population heterogeneity
The Eph receptor tyrosine kinase ( RTK ) family is the largest subfamily of RTKs playing critical roles in many developmental processes such as tissue patterning , neurogenesis and neuronal circuit formation , angiogenesis , etc . How the 14 Eph proteins , via their highly similar cytoplasmic domains , can transmit div...
As an animal’s body develops , its cells need to find their way to the right place to form its tissues and organs . On top of this , nerve cells need to set up connections as they grow . A family of receptors called Eph receptors help to make this happen . They sit across cell membranes , waiting for signals from molec...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "structural", "biology", "and", "molecular", "biophysics" ]
2018
Specific Eph receptor-cytoplasmic effector signaling mediated by SAM–SAM domain interactions
Porcine reproductive and respiratory syndrome virus ( PRRSV ) and transmissible gastroenteritis virus ( TGEV ) are two highly infectious and lethal viruses causing major economic losses to pig production . Here , we report generation of double-gene-knockout ( DKO ) pigs harboring edited knockout alleles for known recep...
Pig epidemics are the biggest threat to the pork industry . In 2019 alone , hundreds of billions of dollars worldwide were lost due to various pig diseases , many of them caused by viruses . The porcine reproductive and respiratory virus ( PRRS virus for short ) , for instance , leads to reproductive disorders such as ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "microbiology", "and", "infectious", "disease" ]
2020
CD163 and pAPN double-knockout pigs are resistant to PRRSV and TGEV and exhibit decreased susceptibility to PDCoV while maintaining normal production performance
The Firmicutes are a phylum of bacteria that dominate numerous polymicrobial habitats of importance to human health and industry . Although these communities are often densely colonized , a broadly distributed contact-dependent mechanism of interbacterial antagonism utilized by Firmicutes has not been elucidated . Here...
Most bacteria live in densely colonized environments , such as the human gut , in which they must constantly compete with other microbes for space and nutrients . As a result , bacteria have evolved a wide array of strategies to directly fight their neighbors . For example , some bacteria release antimicrobial compound...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "microbiology", "and", "infectious", "disease" ]
2017
A broadly distributed toxin family mediates contact-dependent antagonism between gram-positive bacteria
Alternative splicing of mRNA precursors represents a key gene expression regulatory step and permits the generation of distinct protein products with diverse functions . In a genome-scale expression screen for inducers of the epithelial-to-mesenchymal transition ( EMT ) , we found a striking enrichment of RNA-binding p...
As the human body develops , countless cells change from one state into another . Two important cell states are known as epithelial and mesenchymal . Cells in the epithelial state tend to be tightly connected and form barriers , like skin cells . Mesenchymal state cells are loosely organized , move around more and make...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "biology", "cancer", "biology" ]
2018
An alternative splicing switch in FLNB promotes the mesenchymal cell state in human breast cancer
Myocardial infarction ( MI ) promotes a range of systemic effects , many of which are unknown . Here , we investigated the alterations associated with MI progression in heart and other metabolically active tissues ( liver , skeletal muscle , and adipose ) in a mouse model of MI ( induced by ligating the left ascending ...
The human body is like a state-of-the-art car , where each part must work together with all the others . When a car breaks down , most of the time the problem is not isolated to only one part , as it is an interconnected system . Diseases in the human body can also have systemic effects , so it is important to study th...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "medicine", "computational", "and", "systems", "biology" ]
2021
Integrative transcriptomic analysis of tissue-specific metabolic crosstalk after myocardial infarction
Inducible epigenetic changes in eukaryotes are believed to enable rapid adaptation to environmental fluctuations . We have found distinct regions of the Arabidopsis genome that are susceptible to DNA ( de ) methylation in response to hyperosmotic stress . The stress-induced epigenetic changes are associated with condit...
Most plants spend their entire lives in one fixed spot and so must be able to quickly adapt to any changes in their surroundings . For example , high levels of salt in the soil – which can be toxic to cells – triggers stress responses in plants that help them to mitigate any damage . Once the stress has passed , plants...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "computational", "and", "systems", "biology", "genetics", "and", "genomics" ]
2016
Hyperosmotic stress memory in Arabidopsis is mediated by distinct epigenetically labile sites in the genome and is restricted in the male germline by DNA glycosylase activity
Non-rapid eye movement ( NREM ) sleep , characterized by slow-wave electrophysiological activity , underlies several critical functions , including learning and memory . However , NREM sleep is heterogeneous , varying in duration , depth , and spatially across the cortex . While these NREM sleep features are thought to...
Sleep has many roles , from strengthening new memories to regulating mood and appetite . While we might instinctively think of sleep as a uniform state of reduced brain activity , the reality is more complex . First , over the course of the night , we cycle between a number of different sleep stages , which reflect dif...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2021
Cortical astrocytes independently regulate sleep depth and duration via separate GPCR pathways
The developmental potential of early embryos is mainly dictated by the quality of the oocyte . Here , we explore the utility of the maternal spindle transfer ( MST ) technique as a reproductive approach to enhance oocyte developmental competence . Our proof-of-concept experiments show that replacement of the entire cyt...
Infertility is a growing problem that affects millions of people worldwide . Medical procedures known as in vitro fertilization ( IVF ) help many individuals experiencing infertility to have children . Typically in IVF , a woman’s egg cells are collected , fertilized with sperm from a chosen male and grown for a few da...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "developmental", "biology", "cell", "biology" ]
2020
Maternal spindle transfer overcomes embryo developmental arrest caused by ooplasmic defects in mice
Many biological features are conserved and thus considered to be resistant to evolutionary change . While rapid genetic adaptation following the removal of conserved genes has been observed , we often lack a mechanistic understanding of how adaptation happens . We used the budding yeast , Saccharomyces cerevisiae , to ...
All plants , animals and fungi share a common ancestor , and though they have evolved to become very distinct over billions of years , they all share the essential machinery needed for cells to grow and divide . At the heart of this is the complex interaction of proteins involved in DNA replication , the process of dup...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "evolutionary", "biology", "genetics", "and", "genomics" ]
2020
The evolutionary plasticity of chromosome metabolism allows adaptation to constitutive DNA replication stress
Intrinsically disordered proteins ( IDPs ) present a functional paradox because they lack stable tertiary structure , but nonetheless play a central role in signaling , utilizing a process known as allostery . Historically , allostery in structured proteins has been interpreted in terms of propagated structural changes...
Proteins carry out most of the key tasks inside cells . To perform these roles , proteins must fold up to form complex three-dimensional structures . Researchers used to think that the useful parts of proteins all had set structures . However , we now know that ‘disordered’ proteins with variable structures are common ...
[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]
[ "structural", "biology", "and", "molecular", "biophysics" ]
2017
Genetically tunable frustration controls allostery in an intrinsically disordered transcription factor
Astrocytes have emerged as integral partners with neurons in regulating synapse formation and function , but the mechanisms that mediate these interactions are not well understood . Here , we show that Sonic hedgehog ( Shh ) signaling in mature astrocytes is required for establishing structural organization and remodel...
A central system of neurons in the spinal cord and brain coordinate most of our body’s actions , ranging from regulating our heart rate to controlling our movement and thoughts . As the brain develops , neurons form specialized contacts with one another known as synapses . If the number of synapses is not properly regu...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2019
Sonic hedgehog signaling in astrocytes mediates cell type-specific synaptic organization
Most kinesins transport cargoes bound to their C-termini and use N-terminal motor domains to move along microtubules . We report here a novel function for KIF1C: it transports Rab6A-vesicles and can influence Golgi complex organization . These activities correlate with KIF1C's capacity to bind the Golgi protein Rab6A d...
Within our cells there are many compartments that play important roles . Small bubble-like packages called vesicles carry proteins and other molecules between these compartments . These vesicles can be driven around cells by a family of motor proteins called kinesins , which move along a network of filaments called mic...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "biochemistry", "and", "chemical", "biology", "cell", "biology" ]
2015
The Rab6-regulated KIF1C kinesin motor domain contributes to Golgi organization
Most DNA in the genomes of higher organisms does not code for proteins . RNA Polymerase II ( Pol II ) transcribes non-coding DNA into long non-coding RNAs ( lncRNAs ) , but biological roles of lncRNA are unclear . We find that mutations in the yeast lncRNA CUT60 result in poor growth . Defective termination of CUT60 tr...
Genes are made up of DNA and contain the information to make proteins , which carry out a variety of roles in the cell and the body . First , the information found on DNA needs to be transcribed into RNA molecules , which then act as a template to build the actual proteins . However , the vast majority of DNA does not ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "chromosomes", "and", "gene", "expression", "genetics", "and", "genomics" ]
2018
Efficient termination of nuclear lncRNA transcription promotes mitochondrial genome maintenance
Within the confines of tissues , cancer cells can use blebs to migrate . Eps8 is an actin bundling and capping protein whose capping activity is inhibited by Erk , a key MAP kinase that is activated by oncogenic signaling . We tested the hypothesis that Eps8 acts as an Erk effector to modulate actin cortex mechanics an...
Cells within an animal have to be able to move both during development and later stages of life . For example , white blood cells have to move around the body and into tissues to fight off infections . Normally , cell movement is heavily controlled and will only happen when it is necessary to keep an animal healthy . H...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "biology" ]
2015
Erk regulation of actin capping and bundling by Eps8 promotes cortex tension and leader bleb-based migration
Cystic kidney diseases ( CKDs ) affect millions of people worldwide . The defining pathological features are fluid-filled cysts developing from nephric tubules due to defective flow sensing , cell proliferation and differentiation . The underlying molecular mechanisms , however , remain poorly understood , and the deri...
Millions of people around the world are affected by cystic kidney diseases , which are amongst the most common inherited genetic disorders . Throughout their life , people with these diseases develop fluid-filled cysts in their kidneys , which stop these organs from working properly and can eventually lead to organ fai...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "stem", "cells", "and", "regenerative", "medicine" ]
2015
Stem cells and fluid flow drive cyst formation in an invertebrate excretory organ
Clathrin-mediated endocytosis is an essential process that forms vesicles from the plasma membrane . Although most of the protein components of the endocytic protein machinery have been thoroughly characterized , their organization at the endocytic site is poorly understood . We developed a fluorescence microscopy meth...
Cells take up proteins and other useful material ( called cargo ) from their external environment through a process known as endocytosis . To start with , the cargo accumulates in a patch on the surface of the cell . On the inner side of the cell's membrane , a protein called clathrin gathers around the patch of cargo ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "biology", "structural", "biology", "and", "molecular", "biophysics" ]
2015
Visualizing the functional architecture of the endocytic machinery
Breathing is a vital rhythmic behavior generated by hindbrain neuronal circuitry , including the preBötzinger complex network ( preBötC ) that controls inspiration . The emergence of preBötC network activity during prenatal development has been described , but little is known regarding inspiratory neurons expressing pa...
Babies need to start breathing immediately when they are born . Researchers have detected rhythmic movements in the fetus that are related to breathing , which supports the idea that the nervous system circuits needed for breathing are still being established and refined shortly before birth . Neurons in a part of the ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2016
Development of pacemaker properties and rhythmogenic mechanisms in the mouse embryonic respiratory network
Organismal phenotypes frequently involve multiple organ systems . Histology is a powerful way to detect cellular and tissue phenotypes , but is largely descriptive and subjective . To determine how synchrotron-based X-ray micro-tomography ( micro-CT ) can yield 3-dimensional whole-organism images suitable for quantitat...
Diagnosing diseases , such as cancer , requires scientists and doctors to understand how cells respond to different medical conditions . A common way of studying these microscopic cell changes is by an approach called histology: thin slices of centimeter-sized samples of tissues are taken from patients , stained to dis...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "developmental", "biology", "tools", "and", "resources" ]
2019
Computational 3D histological phenotyping of whole zebrafish by X-ray histotomography
Non-centrosomal microtubule organizing centers ( MTOCs ) are important for microtubule organization in many cell types . In fission yeast Schizosaccharomyces pombe , the protein Mto1 , together with partner protein Mto2 ( Mto1/2 complex ) , recruits the γ-tubulin complex to multiple non-centrosomal MTOCs , including th...
Nearly all cells contain networks of filaments called microtubules that play many different roles . They provide internal structure; they serve as ‘tracks’ for transporting materials from one region of the cell to another; and they help to separate chromosomes during cell division . To understand how microtubules work ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "biology" ]
2018
Exportin Crm1 is repurposed as a docking protein to generate microtubule organizing centers at the nuclear pore
Glycosylphosphatidylinositol ( GPI ) anchors attach nearly 150 proteins to the cell membrane . Patients with pathogenic variants in GPI biosynthesis genes develop diverse phenotypes including seizures , dysmorphic facial features and cleft palate through an unknown mechanism . We identified a novel mouse mutant ( cleft...
Many of the proteins that cells produce have sugar molecules attached to them . These additions , called glycosylations , often help to deliver proteins to the parts of the cell where they are needed . In some genetic disorders , individuals have gene mutations that prevent glycosylation from occurring properly . This ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "developmental", "biology" ]
2019
Glycosylphosphatidylinositol biosynthesis and remodeling are required for neural tube closure, heart development, and cranial neural crest cell survival
While most animals thermotax only to regulate their temperature , female mosquitoes are attracted to human body heat during pursuit of a blood meal . Here we elucidate the basic rules of Aedes aegypti thermotaxis and test the function of candidate thermoreceptors in this important behavior . We show that host-seeking m...
Temperature can vary considerably in an environment . Living organisms have evolved sensory systems to detect and avoid excessive heat or cold: a behavior that is termed ‘thermotaxis’ . In rare cases , animals use this ability to locate food sources in their environment . One example of such an adaptation is the female...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials" ]
[ "neuroscience" ]
2015
The cation channel TRPA1 tunes mosquito thermotaxis to host temperatures
In the Drosophila circadian clock , Period ( PER ) and Timeless ( TIM ) proteins inhibit Clock-mediated transcription of per and tim genes until PER is degraded by Doubletime/CK1 ( DBT ) -mediated phosphorylation , establishing a negative feedback loop . Multiple regulatory delays within this feedback loop ensure ~24 h...
Many behaviors , such as when we fall asleep or wake up , follow the rhythm of day and night . This is regulated in part by our ‘circadian clock’ , which controls biological processes through the timed activation of hundreds of genes over the 24-hour day . In fruit flies , the proteins that form the core of the circadi...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "biochemistry", "and", "chemical", "biology", "neuroscience" ]
2018
CK1/Doubletime activity delays transcription activation in the circadian clock
Plant trait diversity is known to influence population yield , but the scale at which this happens remains unknown: divergent individuals might change yields of immediate neighbors ( neighbor scale ) or of plants across a population ( population scale ) . We use Nicotiana attenuata plants silenced in mitogen-activated ...
Whether on farmland or in a forest , plants do not grow in isolation . Plants compete with their neighbors over limited space and resources , and individual plants respond to this competition in different ways by changing how much they grow and how they use resources . The efficiency with which crop plants use water , ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "ecology", "plant", "biology" ]
2020
Determining the scale at which variation in a single gene changes population yields
Diet plays a significant role in maintaining lifelong health . In particular , lowering the dietary protein: carbohydrate ratio can improve lifespan . This has been interpreted as a direct effect of these macronutrients on physiology . Using Drosophila melanogaster , we show that the role of protein and carbohydrate on...
For the past fifteen years , animal studies have consistently shown that a low-protein , high-carbohydrate ( ‘carbs’ ) diet can extend the lifespan of many organisms , but at the cost of the number of offspring an individual can produce . Yet , it is still unclear what the best dietary balance is , and how these effect...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "evolutionary", "biology", "medicine" ]
2021
A dietary sterol trade-off determines lifespan responses to dietary restriction in Drosophila melanogaster females
SCP1 as a nuclear transcriptional regulator acts globally to silence neuronal genes and to affect the dephosphorylation of RNA Pol ll . However , we report the first finding and description of SCP1 as a plasma membrane-localized protein in various cancer cells using EGFP- or other epitope-fused SCP1 . Membrane-located ...
Cancerous tumors are the leading cause of death worldwide . Tumors cannot grow beyond a couple of millimeters in diameter unless they are supplied with nutrients and oxygen . To receive these , tumors connect to the body’s blood supply by stimulating the growth of new blood vessels . Drugs that reduce the ability of ne...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "biology", "cancer", "biology" ]
2017
Palmitoylated SCP1 is targeted to the plasma membrane and negatively regulates angiogenesis
The risk of developing cancer is correlated with body size and lifespan within species . Between species , however , there is no correlation between cancer and either body size or lifespan , indicating that large , long-lived species have evolved enhanced cancer protection mechanisms . Elephants and their relatives ( P...
From the gigantic blue whale to the minuscule bumblebee bat , animals come in all shapes and sizes . Any species can develop cancer , but some are more at risk than others . In theory , if every cell has the same probability of becoming cancerous , then bigger animals should get cancer more often since they have more c...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "evolutionary", "biology", "cancer", "biology" ]
2021
Pervasive duplication of tumor suppressors in Afrotherians during the evolution of large bodies and reduced cancer risk
Many neurodegenerative diseases are linked to amyloid aggregation . In Huntington’s disease ( HD ) , neurotoxicity correlates with an increased aggregation propensity of a polyglutamine ( polyQ ) expansion in exon 1 of mutant huntingtin protein ( mHtt ) . Here we establish how the domains flanking the polyQ tract shape...
Huntington’s disease is a neurodegenerative disorder in which misshapen proteins accumulate in the brain and kill neurons . The misshapen proteins form as a result of specific mutations in the gene that encodes a protein called huntingtin . These mutations result in a region of the protein called the polyQ tract being ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "biochemistry", "and", "chemical", "biology", "cell", "biology" ]
2016
Control of the structural landscape and neuronal proteotoxicity of mutant Huntingtin by domains flanking the polyQ tract
The dynamics of local climates make development of agricultural strategies challenging . Yield improvement has progressed slowly , especially in drought-prone regions where annual crop production suffers from episodic aridity . Underlying drought responses are circadian and diel control of gene expression that regulate...
Around 60% of the food produced worldwide relies entirely on rain for its water supply . However , in the decades ahead global climate change is predicted to cause droughts to happen more often and become more severe in many regions . Therefore , in order to sustain our food supply we need to better understand how plan...
[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]
[ "plant", "biology" ]
2017
Temporal network analysis identifies early physiological and transcriptomic indicators of mild drought in Brassica rapa
Evaluation of preclinical evidence prior to initiating early-phase clinical studies has typically been performed by selecting individual studies in a non-systematic process that may introduce bias . Thus , in preparation for a first-in-human trial of mesenchymal stromal cells ( MSCs ) for septic shock , we applied syst...
Most attempts to transform exciting findings from laboratories into clinical treatments are unsuccessful . One reason for this may be the failure to consider all of the laboratory work that has been performed before deciding to test a treatment on patients for the first time . In particular , negative findings ( that s...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "epidemiology", "and", "global", "health", "medicine" ]
2016
Evaluating mesenchymal stem cell therapy for sepsis with preclinical meta-analyses prior to initiating a first-in-human trial
Emiliania huxleyi is a model coccolithophore micro-alga that generates vast blooms in the ocean . Bacteria are not considered among the major factors influencing coccolithophore physiology . Here we show through a laboratory model system that the bacterium Phaeobacter inhibens , a well-studied member of the Roseobacter...
Microscopic algae that live in the ocean release countless tons of oxygen into the atmosphere each year . Widespread algae – known as coccolithophores – surround their little plant-like body with a mineral shell made of a material similar to chalk . These microscopic algae form seasonal blooms . Over several weeks in e...
[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]
[ "ecology" ]
2016
Dynamic metabolic exchange governs a marine algal-bacterial interaction
Birds display remarkable diversity in the distribution and morphology of scales and feathers on their feet , yet the genetic and developmental mechanisms governing this diversity remain unknown . Domestic pigeons have striking variation in foot feathering within a single species , providing a tractable model to investi...
Animals ranging from fish to birds display dramatic diversity within and among species; yet remarkably little is known about the genetic and developmental mechanisms that underlie this variation . In birds and their extinct dinosaur relatives , the distribution of scales and feathers on the feet is a highly variable tr...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "developmental", "biology", "genetics", "and", "genomics" ]
2016
Molecular shifts in limb identity underlie development of feathered feet in two domestic avian species
Reduced cardiac contractility during heart failure ( HF ) is linked to impaired Ca2+ release from Ryanodine Receptors ( RyRs ) . We investigated whether this deficit can be traced to nanoscale RyR reorganization . Using super-resolution imaging , we observed dispersion of RyR clusters in cardiomyocytes from post-infarc...
The muscle cells of the heart coordinate how they contract and relax in order to produce the heartbeat . During heart failure , these cells become less able to contract . As a result the heart becomes inefficient , pumping less blood around the body . For the cardiac muscle cells to contract , the levels of calcium ion...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "biology" ]
2018
Ryanodine receptor dispersion disrupts Ca2+ release in failing cardiac myocytes
Apical constriction is a widely utilized cell shape change linked to folding , bending and invagination of polarized epithelia . It remains unclear how apical constriction is regulated spatiotemporally during tissue invagination and how this cellular process contributes to tube formation in different developmental cont...
Many organs in the human body – like the kidneys , lungs , and salivary glands – are organized as a single layer of cells that surround a hollow tube . There are a number of ways that cells can achieve this particular arrangement . In one mechanism , a small group of cells bud out of a single cell layer to become the e...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "developmental", "biology", "cell", "biology" ]
2017
Uncoupling apical constriction from tissue invagination
Dengue virus is a growing global health threat . Dengue and other flaviviruses commandeer the host cell’s RNA degradation machinery to generate the small flaviviral RNA ( sfRNA ) , a noncoding RNA that induces cytopathicity and pathogenesis . Host cell exonuclease Xrn1 likely loads on the 5′ end of viral genomic RNA an...
More than 40% of people around the globe are at risk of being bitten by mosquitoes infected with the virus that causes Dengue fever . Every year , more than 100 million of these individuals are infected . Many develop severe headaches , pain , and fever , but some develop a life-threatening condition where tiny blood v...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "biochemistry", "and", "chemical", "biology", "microbiology", "and", "infectious", "disease" ]
2014
RNA structures that resist degradation by Xrn1 produce a pathogenic Dengue virus RNA
Although many high-risk mucosal and cutaneous human papillomaviruses ( HPVs ) theoretically have the potential to synthesize L1 isoforms differing in length , previous seroepidemiological studies only focused on the short L1 variants , co-assembling with L2 to infectious virions . Using the multimammate mouse Mastomys ...
Cancer is not one disease but rather a collection of disorders . As such there are many reasons why someone may develop cancer during their lifetime , including the individual’s family history , lifestyle and habits . Infections with certain viruses can also lead to cancer and human papillomaviruses are viruses that es...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "microbiology", "and", "infectious", "disease" ]
2020
Expression of different L1 isoforms of Mastomys natalensis papillomavirus as mechanism to circumvent adaptive immunity
Out-of-plane tissue deformations are key morphogenetic events during plant and animal development that generate 3D shapes , such as flowers or limbs . However , the mechanisms by which spatiotemporal patterns of gene expression modify cellular behaviours to generate such deformations remain to be established . We use t...
Plant and animal organs come in many different shapes , from pitcher-shaped leaves and butterfly wings , to orchid flowers and the convoluted shape of the brain . Unlike pottery or sculpture , no external hand guides the formation of these biological structures; they arise on their own , through sheets of cells develop...
[ "Abstract", "Introduction", "Results", "Discussion", "Material", "and", "methods" ]
[ "plant", "biology", "developmental", "biology" ]
2017
Generation of shape complexity through tissue conflict resolution
The Ras-superfamily GTPases are central controllers of cell proliferation and morphology . Ras signaling is mediated by a system of interacting molecules: upstream enzymes ( GEF/GAP ) regulate Ras’s ability to recruit multiple competing downstream effectors . We developed a multiplexed , multi-turnover assay for measur...
Cells sense and respond to the world around them using signaling “circuits” made of proteins and other molecules , and when an important cell circuit breaks , diseases like cancer may arise . Much like with electrical circuits , a given set of molecular components can be used to build different signaling circuits that ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "biochemistry", "and", "chemical", "biology", "computational", "and", "systems", "biology" ]
2016
Mapping the functional versatility and fragility of Ras GTPase signaling circuits through in vitro network reconstitution
Neuropeptides play a key role in the regulation of behaviors and physiological responses including alertness , social recognition , and hunger , yet , their mechanism of action is poorly understood . Here , we focus on the endocrine control ecdysis behavior , which is used by arthropods to shed their cuticle at the end...
Most behaviors occur only under specific circumstances: we eat when we are hungry , for example . But how does the nervous system decide when to start or stop a particular behavior ? Molecules called neuropeptides are thought to play a key role in these decisions . Neuropeptides are produced by organs throughout the bo...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "developmental", "biology", "neuroscience" ]
2016
Stereotyped responses of Drosophila peptidergic neuronal ensemble depend on downstream neuromodulators
Unesterified cholesterol accumulation in the late endosomal/lysosomal ( LE/LY ) compartment is the cellular hallmark of Niemann-Pick C ( NPC ) disease , caused by defects in the genes encoding NPC1 or NPC2 . We previously reported the dramatic stimulation of NPC2 cholesterol transport rates to and from model membranes ...
Cholesterol is a type of fat that is essential for many processes in the body , such as repairing damaged cells and producing certain hormones . Normally , cholesterol enters cells from the bloodstream and is then moved to the parts of the cell that need it via a process known as ‘trafficking’ . When cholesterol traffi...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "biochemistry", "and", "chemical", "biology", "cell", "biology" ]
2019
Intracellular cholesterol trafficking is dependent upon NPC2 interaction with lysobisphosphatidic acid
Disorders of consciousness are a heterogeneous mixture of different diseases or injuries . Although some indicators and models have been proposed for prognostication , any single method when used alone carries a high risk of false prediction . This study aimed to develop a multidomain prognostic model that combines res...
Severe brain injury can lead to disorders of consciousness ( DOC ) , such as a coma . Some patients regain consciousness after injury , while others do not . Those who do not recover are unable to communicate or move in purposeful ways , and need long-term care . It can be difficult for physicians to predict which pati...
[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "Discussion" ]
[ "medicine", "neuroscience" ]
2018
Prognostication of chronic disorders of consciousness using brain functional networks and clinical characteristics
Viruses like influenza are infamous for their ability to adapt to new hosts . Retrospective studies of natural zoonoses and passaging in the lab have identified a modest number of host-adaptive mutations . However , it is unclear if these mutations represent all ways that influenza can adapt to a new host . Here we tak...
Viruses copy themselves by hijacking the cells of an infected host , but this comes with some limitations . Cells from different species have different molecular machinery and so viruses often have to specialize to a narrow group of species . This specialization consists largely of fine-tuning the way that viral protei...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "epidemiology", "and", "global", "health", "microbiology", "and", "infectious", "disease" ]
2019
Comprehensive mapping of adaptation of the avian influenza polymerase protein PB2 to humans
Dedifferentiation of acini to duct-like cells occurs during the physiologic damage response in the pancreas , but this process can be co-opted by oncogenic Kras to drive carcinogenesis . Myeloid cells infiltrate the pancreas during the onset of pancreatic cancer , and promote carcinogenesis . Here , we show that the fu...
The pancreas contains many types of highly specialized cells . For example , the acinar cells produce enzymes that help to digest food , and the ductal cells build the ducts to transport these enzymes to the gut . When the pancreas gets injured , the acinar cells start to transform into duct-like cells . The cells can ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cancer", "biology" ]
2017
Epithelial-Myeloid cell crosstalk regulates acinar cell plasticity and pancreatic remodeling in mice
Appropriate physiological signaling by primary cilia depends on the specific targeting of particular receptors to the ciliary membrane , but how this occurs remains poorly understood . In this study , we show that D1-type dopaminergic receptors are delivered to cilia from the extra-ciliary plasma membrane by a mechanis...
Slender structures called primary cilia protrude from the outer membrane of nearly every human cell . Each cell generally has one cilium , which helps the cell to sense its environment and respond to the signaling molecules sent to the cell to influence its behavior . Proteins called receptors , which are embedded in t...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "biology" ]
2015
Dopamine receptors reveal an essential role of IFT-B, KIF17, and Rab23 in delivering specific receptors to primary cilia
Agouti-related-peptide ( AgRP ) neurons—interoceptive neurons in the arcuate nucleus of the hypothalamus ( ARC ) —are both necessary and sufficient for driving feeding behavior . To better understand the functional roles of AgRP neurons , we performed optetrode electrophysiological recordings from AgRP neurons in awake...
Appetite is controlled in part by the opposing actions of the ‘hunger hormone’ ( called ghrelin ) and the ‘satiety hormone’ ( called leptin ) . Ghrelin is released by the stomach when empty and stimulates appetite , whereas leptin is released by fat stores and induces feelings of fullness . Both hormones travel via the...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2015
Arcuate hypothalamic AgRP and putative POMC neurons show opposite changes in spiking across multiple timescales
Trimethylamine-oxide ( TMAO ) is present in seafood which is considered to be beneficial for health . Deep-water animals accumulate TMAO to protect proteins , such as lactate dehydrogenase ( LDH ) , against hydrostatic pressure stress ( HPS ) . We hypothesized that TMAO exerts beneficial effects on the circulatory syst...
Heart failure is a common cause of death in industrialized countries with aging populations . Japan , however , has lower rates of heart failure and fewer deaths linked to this disease than the United States or Europe , despite having the highest proportion of elderly people in the world . Dietary differences between t...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "medicine" ]
2020
TMAO, a seafood-derived molecule, produces diuresis and reduces mortality in heart failure rats
The emergence of multicellularity in Animalia is associated with increase in ROS and expansion of tRNA-isodecoders . tRNA expansion leads to misselection resulting in a critical error of L-Ala mischarged onto tRNAThr , which is proofread by Animalia-specific-tRNA Deacylase ( ATD ) in vitro . Here we show that in additi...
The first animals evolved around 750 million years ago from single-celled ancestors that were most similar to modern-day organisms called the Choanoflagellates . As animals evolved they developed more complex body plans consisting of multiple cells organized into larger structures known as tissues and organs . Over tim...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "biochemistry", "and", "chemical", "biology", "cell", "biology" ]
2020
Genomic innovation of ATD alleviates mistranslation associated with multicellularity in Animalia
The sequence of events that initiates T cell signaling is dictated by the specificities and order of activation of the tyrosine kinases that signal downstream of the T cell receptor . Using a platform that combines exhaustive point-mutagenesis of peptide substrates , bacterial surface-display , cell sorting , and deep ...
A class of enzymes known as tyrosine kinases relay signals in cells by adding phosphate groups onto specific sites ( called 'tyrosine residues' ) in other proteins . Most tyrosine kinases can phosphorylate many targets ( or 'substrates' ) ; they can also phosphorylate and thereby activate themselves , when given the ri...
[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]
[ "structural", "biology", "and", "molecular", "biophysics", "immunology", "and", "inflammation" ]
2016
An electrostatic selection mechanism controls sequential kinase signaling downstream of the T cell receptor
Bicuspid aortic valve ( BAV ) is the most common congenital cardiovascular disease in general population and is frequently associated with the development of thoracic aortic aneurysm ( TAA ) . There is no effective strategy to intervene with TAA progression due to an incomplete understanding of the pathogenesis . Insuf...
To function properly , the heart must remain a one-way system , pumping out oxygenated blood into the aorta – the largest artery in the body – so it can be distributed across the organism . The aortic valve , which sits at the entrance of the aorta , is a key component of this system . Its three flaps ( or ‘cusps’ ) ar...
[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "Discussion" ]
[ "medicine" ]
2021
Aorta smooth muscle-on-a-chip reveals impaired mitochondrial dynamics as a therapeutic target for aortic aneurysm in bicuspid aortic valve disease
There is an urgent requirement for safe , oral and cost-effective drugs for the treatment of visceral leishmaniasis ( VL ) . We report that delamanid ( OPC-67683 ) , an approved drug for multi-drug resistant tuberculosis , is a potent inhibitor of Leishmania donovani both in vitro and in vivo . Twice-daily oral dosing ...
Better , safer , oral drugs are desperately needed for the treatment of visceral leishmaniasis , a parasitic infectious disease that causes an estimated 40 , 000 deaths a year , predominantly in South America , East Africa and the Indian subcontinent . The parasite that causes visceral leishmaniasis is transmitted betw...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "microbiology", "and", "infectious", "disease" ]
2016
The anti-tubercular drug delamanid as a potential oral treatment for visceral leishmaniasis
Electrophysiological methods , that is M/EEG , provide unique views into brain health . Yet , when building predictive models from brain data , it is often unclear how electrophysiology should be combined with other neuroimaging methods . Information can be redundant , useful common representations of multimodal data m...
How old are you ? What about your body , and your brain ? People are used to answering this question by counting the years since birth . However , biological age could also be measured by looking at the integrity of the DNA in cells or by measuring the levels of proteins in the blood . Whether one goes by chronological...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "tools", "and", "resources", "neuroscience" ]
2020
Combining magnetoencephalography with magnetic resonance imaging enhances learning of surrogate-biomarkers
We do not know how or why multicellularity evolved . We used the budding yeast , Saccharomyces cerevisiae , to ask whether nutrients that must be digested extracellularly select for the evolution of undifferentiated multicellularity . Because yeast use invertase to hydrolyze sucrose extracellularly and import the resul...
Life first appeared on Earth more than 3 billion years ago in the form of single-celled microorganisms . The diverse array of complex life forms that we see today evolved from these humble beginnings , but it is not clear what triggered the evolution of multicellular organisms from single cells . One of the simplest mu...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "evolutionary", "biology" ]
2013
Improved use of a public good selects for the evolution of undifferentiated multicellularity
The permeability barrier of nuclear pore complexes ( NPCs ) controls bulk nucleocytoplasmic exchange . It consists of nucleoporin domains rich in phenylalanine-glycine motifs ( FG domains ) . As a bottom-up nanoscale model for the permeability barrier , we have used planar films produced with three different end-grafte...
The cells of animals , plants and other eukaryotic organisms contain a compartment called the nucleus that contains most of the cell's genetic material . Proteins and other molecules – collectively known as cargos – can enter and exit the nucleus via tiny channels in the membrane that surrounds and protects it . Recept...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "physics", "of", "living", "systems" ]
2016
A physical model describing the interaction of nuclear transport receptors with FG nucleoporin domain assemblies
Overproduced yeast ribosomal protein ( RP ) Rpl26 fails to assemble into ribosomes and is degraded in the nucleus/nucleolus by a ubiquitin-proteasome system quality control pathway comprising the E2 enzymes Ubc4/Ubc5 and the ubiquitin ligase Tom1 . tom1 cells show reduced ubiquitination of multiple RPs , exceptional ac...
Ribosomes are the molecular machines in cells that produce proteins . The ribosomes themselves are composed of almost 80 different proteins that are held together by scaffolds made from molecules of RNA . Each protein is present in one copy , and so equal numbers of all proteins are needed to assemble a ribosome . Howe...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "biochemistry", "and", "chemical", "biology", "cell", "biology" ]
2016
A conserved quality-control pathway that mediates degradation of unassembled ribosomal proteins
How organ-shaping mechanical imbalances are generated is a central question of morphogenesis , with existing paradigms focusing on asymmetric force generation within cells . We show here that organs can be sculpted instead by patterning anisotropic resistance within their extracellular matrix ( ECM ) . Using direct bio...
All organs have specific shapes and architectures that are necessary for them to work properly . Many different factors are responsible for arranging the right cells into the correct positions to make an organ . These include physical forces that act within and around cells to pull them into the right shape and locatio...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "developmental", "biology", "cell", "biology" ]
2017
Organ sculpting by patterned extracellular matrix stiffness
NMDA receptor ( NMDAR ) -dependent forms of synaptic plasticity are thought to underlie the assembly of developing neuronal circuits and to play a crucial role in learning and memory . It remains unclear how NMDAR might contribute to the wiring of adult-born granule cells ( GCs ) . Here we demonstrate that nascent GCs ...
The brain contains billions of cells called neurons . Although most neurons have already formed by the time we are born , part of the brain called the hippocampus produces new neurons throughout our life . These new neurons are thought to be important for learning and forming new memories . Neurons send signals to each...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2015
Distinct roles of NMDA receptors at different stages of granule cell development in the adult brain
Humans and other animals often violate economic principles when choosing between multiple alternatives , but the underlying neurocognitive mechanisms remain elusive . A robust finding is that adding a third option can alter the relative preference for the original alternatives , but studies disagree on whether the thir...
A man in a restaurant is offered a choice between apple or blueberry pie , and chooses apple . The waiter then returns a few moments later and tells him they also have cherry pie available . “In that case” , replies the man , “I’ll have blueberry” . This well-known anecdote illustrates a principle in economics and psyc...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2018
Value-based attentional capture affects multi-alternative decision making
Sarcoidosis is a complex systemic granulomatous disease of unknown etiology characterized by the presence of activated macrophages and Th1/Th17 effector cells . Data mining of our RNA-Seq analysis of CD14+monocytes showed enrichment for metabolic and hypoxia inducible factor ( HIF ) pathways in sarcoidosis . Further in...
Sarcoidosis is a rare disease that is characterized by the formation of small lumps known as granulomas inside the body . These lumps are made up of clusters of immune cells , and are commonly found in the skin , lung or eye . Other organs of the body can also be affected , and symptoms will vary depending on where in ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "medicine", "immunology", "and", "inflammation" ]
2019
HIF-1α regulates IL-1β and IL-17 in sarcoidosis
Although critical for brain function , the physiological values of cerebral oxygen concentration have remained elusive because high-resolution measurements have only been performed during anesthesia , which affects two major parameters modulating tissue oxygenation: neuronal activity and blood flow . Using measurements...
Brain cells need a constant supply of oxygen to fuel their activities . This oxygen is delivered by the flow of blood through the vessels in the brain . If the blood flow to brain tissue is cut off as happens in stroke , or if an individual stops breathing , the brain becomes deprived of oxygen and brain cells will be ...
[ "Abstract", "Introduction", "Results", "Discussion" ]
[ "neuroscience" ]
2016
Mapping oxygen concentration in the awake mouse brain
Cell surface reception of Sonic hedgehog ( Shh ) must ensure that the graded morphogenic signal is interpreted accordingly in neighboring cells to specify tissue patterns during development . Here , we report endocytic sorting signals for the receptor Patched1 ( Ptch1 ) , comprising two ‘PPXY’ motifs , that direct it t...
Sonic hedgehog protein fulfils many vital roles in establishing the body plan of multicellular organisms during development . And in adult organisms it regulates the stem cells that maintain organs and tissues . In the embryo , Sonic hedgehog is secreted by certain cells to create a concentration gradient; cells then m...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "developmental", "biology" ]
2014
Requirement of Smurf-mediated endocytosis of Patched1 in sonic hedgehog signal reception
The roundworm C . elegans is a mainstay of aging research due to its short lifespan and easily manipulable genetics . Current , widely used methods for long-term measurement of C . elegans are limited by low throughput and the difficulty of performing longitudinal monitoring of aging phenotypes . Here we describe the W...
Aging affects almost all living things , yet little is known about the biological changes that occur as we get older . Scientists often study aging in the microscopic roundworm Caenorhabditis elegans because it reproduces quickly and its lifespan is short ( about 2–3 weeks on average ) . To date , investigations have h...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "chromosomes", "and", "gene", "expression", "tools", "and", "resources", "neuroscience" ]
2017
Longitudinal imaging of Caenorhabditis elegans in a microfabricated device reveals variation in behavioral decline during aging
It has been postulated that a proneural factor , neurogenin 1 ( Ngn1 ) , simultaneously activates the neurogenic program and inhibits the alternative astrogliogenic program when specifying the neuronal fate . While Ngn1 substantially suppresses the activation of the astrogliogenic Jak-Stat pathway , the underlying mole...
The brain processes information from all over the body through a complex network of cells called neurons . Other brain cells—including star-shaped cells called astrocytes—support this network . Both neurons and astrocytes originate from the same group of stem cells , which first give rise to neurons in a process called...
[ "Abstract", "Main", "text", "Materials", "and", "methods" ]
[ "developmental", "biology", "short", "report", "neuroscience" ]
2015
Ngn1 inhibits astrogliogenesis through induction of miR-9 during neuronal fate specification
How long neural information is stored in a local brain area reflects functions of that region and is often estimated by the magnitude of the autocorrelation of intrinsic neural signals in the area . Here , we investigated such intrinsic neural timescales in high-functioning adults with autism and examined whether local...
Autism is a brain disorder that affects how people interact with others . It occupies a spectrum , with severe autism at one end and high-functioning autism at the other . People with severe autism usually have intellectual impairments and little spoken language . Those with high-functioning autism have average or abov...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2019
Atypical intrinsic neural timescale in autism
Despite the high burden of pain experienced by hospitalised neonates , there are few analgesics with proven efficacy . Testing analgesics in neonates is experimentally and ethically challenging and minimising the number of neonates required to demonstrate efficacy is essential . EEG ( electroencephalography ) -derived ...
Hospitalized newborns often undergo medical procedures , like blood tests , without pain relief . This can cause the baby to experience short-term distress that may have negative consequences later in life . However , testing the effects of pain relief in newborns is challenging because , unlike adults , they cannot re...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "medicine", "neuroscience" ]
2021
Quantifying noxious-evoked baseline sensitivity in neonates to optimise analgesic trials
Seasonal migration is a taxonomically widespread behaviour that integrates across many traits . The European blackcap exhibits enormous variation in migration and is renowned for research on its evolution and genetic basis . We assembled a reference genome for blackcaps and obtained whole genome resequencing data from ...
Every year as the seasons change , thousands of animals migrate huge distances in search of food or better climates . As far as migrations go , there might be none so impressive as the trans-oceanic flights made by small migrating songbirds . These birds can weigh as little as three grams and travel up to 15 , 000 kilo...
[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]
[ "evolutionary", "biology", "genetics", "and", "genomics" ]
2020
The evolutionary history and genomics of European blackcap migration
An emerging theme in cellular logistics is the close connection between mRNA and membrane trafficking . A prominent example is the microtubule-dependent transport of mRNAs and associated ribosomes on endosomes . This coordinated process is crucial for correct septin filamentation and efficient growth of polarised cells...
DNA contains the instructions to build proteins . These instructions are first copied to make a molecule of messenger RNA ( or mRNA for short ) . A large machine called the ribosome then reads the mRNA molecule and translates it to build a protein . Many proteins must get to particular locations in a cell to carry out ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "biology", "microbiology", "and", "infectious", "disease" ]
2015
A FYVE zinc finger domain protein specifically links mRNA transport to endosome trafficking
We have discovered a new mechanism of monoallelic gene expression that links antigenic variation , cell cycle , and development in the model parasite Trypanosoma brucei . African trypanosomes possess hundreds of variant surface glycoprotein ( VSG ) genes , but only one is expressed from a telomeric expression site ( ES...
African sleeping sickness is a potentially lethal disease that is caused by a parasite called T . brucei and spread by tsetse flies . Like many of the parasites that cause tropical diseases , T . brucei employs genetic trickery to evade the immune systems of humans and other mammals . This involves changing the variant...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "chromosomes", "and", "gene", "expression", "cell", "biology" ]
2014
Expression site attenuation mechanistically links antigenic variation and development in Trypanosoma brucei
The prion protein ( PrPC ) is highly expressed in the nervous system and critically involved in prion diseases where it misfolds into pathogenic PrPSc . Moreover , it has been suggested as a receptor mediating neurotoxicity in common neurodegenerative proteinopathies such as Alzheimer's disease . PrPC is shed at the pl...
Prion proteins are anchored to the surface of brain cells called neurons . Normally , prion proteins are folded into a specific three-dimensional shape that enables them to carry out their normal roles in the brain . However , they can be misfolded into a different shape known as PrPSc , which can cause Creutzfeldt-Jak...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience", "microbiology", "and", "infectious", "disease" ]
2015
The sheddase ADAM10 is a potent modulator of prion disease
Synaptotagmin-1 ( Syt1 ) acts as a Ca2+ sensor for neurotransmitter release through its C2 domains . It has been proposed that Syt1 promotes SNARE-dependent fusion mainly through its C2B domain , but the underlying mechanism is poorly understood . In this study , we show that the C2B domain interacts simultaneously wit...
Information travels around the nervous system along cells called neurons , which communicate with each other via connections called synapses . When a signal travelling along one neuron reaches a synapse , it triggers the release of molecules known as neurotransmitters . These molecules are then taken up by the next neu...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "structural", "biology", "and", "molecular", "biophysics", "neuroscience" ]
2016
Synaptotagmin-1 C2B domain interacts simultaneously with SNAREs and membranes to promote membrane fusion
IFIT ( interferon-induced with tetratricopeptide repeats ) proteins are critical mediators of mammalian innate antiviral immunity . Mouse IFIT1 selectively inhibits viruses that lack 2'O-methylation of their mRNA 5' caps . Surprisingly , human IFIT1 does not share this antiviral specificity . Here , we resolve this dis...
When a virus is detected in the body , hundreds of different proteins in the immune system are rapidly produced as a first line of defense to limit the ability of the virus to multiply and spread . Many of these ‘innate’ immunity proteins have rapidly evolved in mammals in escalating molecular 'arms races' with the vir...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "microbiology", "and", "infectious", "disease" ]
2016
Evolution-guided functional analyses reveal diverse antiviral specificities encoded by IFIT1 genes in mammals
Replication checkpoint is essential for maintaining genome integrity in response to various replication stresses as well as during the normal growth . The evolutionally conserved ATR-Claspin-Chk1 pathway is induced during replication checkpoint activation . Cdc7 kinase , required for initiation of DNA replication at re...
It takes a human cell between six and eight hours to copy all three billion letters of its genome . During this time , any interruption to the process can lead to genetic errors , putting the cell in danger of developing disease . To guard against this , cells use a checkpoint system , testing their own health before ,...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "chromosomes", "and", "gene", "expression" ]
2019
Cdc7 activates replication checkpoint by phosphorylating the Chk1-binding domain of Claspin in human cells
In diverse organisms , nanostructures that coherently scatter light create structural color , but how such structures are built remains mysterious . We investigate the evolution and genetic regulation of butterfly scale laminae , which are simple photonic nanostructures . In a lineage of buckeye butterflies artificiall...
From iridescent blues to vibrant purples , many butterflies display dazzling ‘structural colors’ created not by pigments but by microscopic structures that interfere with light . For instance , the scales that coat their wings can contain thin films of chitin , the substance that normally makes the external skeleton of...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "evolutionary", "biology" ]
2020
Structural color in Junonia butterflies evolves by tuning scale lamina thickness
Odor attraction in walking Drosophila melanogaster is commonly used to relate neural function to behavior , but the algorithms underlying attraction are unclear . Here , we develop a high-throughput assay to measure olfactory behavior in response to well-controlled sensory stimuli . We show that odor evokes two behavio...
All kinds of animals use their sense of smell to find things . Doing this is difficult because odors in air travel as plumes , which meander downwind and break apart . Scientists are interested in learning the rules that animals use to decipher these odor signals and trace them back to their source . For example , do a...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2018
Elementary sensory-motor transformations underlying olfactory navigation in walking fruit-flies
Bile is an important component of the human gastrointestinal tract with an essential role in food absorption and antimicrobial activities . Enteric bacterial pathogens have developed strategies to sense bile as an environmental cue to regulate virulence genes during infection . We discovered that Vibrio parahaemolyticu...
When we eat a meal , bile salts in the intestine help the body to absorb molecules of fat . Certain bacteria that cause food poisoning in humans , such as Vibrio parahaemolyticus , can also detect bile salts and use them to sense that they have reached the intestine of a suitable host . The bacteria then produce toxins...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "structural", "biology", "and", "molecular", "biophysics", "microbiology", "and", "infectious", "disease" ]
2016
Bile salt receptor complex activates a pathogenic type III secretion system
Phytochromes are photoreceptors regulating growth and development in plants . Using the model plant Arabidopsis , we identified a novel signalling pathway downstream of the far-red light-sensing phytochrome , phyA , that depends on the highly conserved CCR4-NOT complex . CCR4-NOT is integral to RNA metabolism in yeast ...
Place a seedling on a windowsill , and soon you will notice the fragile stem bending towards the glass to soak in the sun and optimize its growth . Plants can ‘sense’ light thanks to specialized photoreceptor molecules: for instance , the phytochrome A is responsible for detecting weak and ‘far-red’ light from the very...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "plant", "biology" ]
2021
Uncovering a novel function of the CCR4-NOT complex in phytochrome A-mediated light signalling in plants
Diverse clustered protocadherins are thought to function in neurite morphogenesis and neuronal connectivity in the brain . Here , we report that the protocadherin alpha ( Pcdha ) gene cluster regulates neuronal migration during cortical development and cytoskeletal dynamics in primary cortical culture through the WAVE ...
There are hundreds of billions of neurons in a human brain , and each one can form several thousand connections with other neurons . This complex network determines our thoughts , memories , personality , and behavior , but how does it form ? During brain development , specific areas give rise to new neurons , which th...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2018
Alpha protocadherins and Pyk2 kinase regulate cortical neuron migration and cytoskeletal dynamics via Rac1 GTPase and WAVE complex in mice
Hippocampal place cells fire at different rates when a rodent runs through a given location on its way to different destinations . However , it is unclear whether such firing represents the animal’s intended destination or the execution of a specific trajectory . To distinguish between these possibilities , Lister Hood...
How does the brain represent the outside world ? One way of answering this question is to study the brains of rats , because the basic plan of a rodent’s brain is similar to that of other mammals , such as humans . For example , the brains of rodents and humans both contain a structure called the hippocampus , which pl...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2016
Place cells on a maze encode routes rather than destinations
Embryonal Rhabdomyosarcoma ( ERMS ) and Undifferentiated Pleomorphic Sarcoma ( UPS ) are distinct sarcoma subtypes . Here we investigate the relevance of the satellite cell ( SC ) niche in sarcoma development by using Hepatocyte Growth Factor ( HGF ) to perturb the niche microenvironment . In a Pax7 wild type backgroun...
Soft tissue sarcomas are rare cancers that originate in tissues such as muscles , tendons , cartilage and fat . These cancers are further classified into subtypes based on their appearance . For example , rhabdomyosarcoma cells resemble the cells that normally develop into muscle , while other soft tissue tumors that d...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "developmental", "biology", "cell", "biology" ]
2016
Hepatocyte Growth Factor-mediated satellite cells niche perturbation promotes development of distinct sarcoma subtypes
Cell-cell interactions influence all aspects of development , homeostasis , and disease . In cancer , interactions between cancer cells and stromal cells play a major role in nearly every step of carcinogenesis . Thus , the ability to record cell-cell interactions would facilitate mechanistic delineation of the role of...
It takes the coordinated effort of more than 40 trillion cells to build and maintain a human body . This intricate process relies on cells being able to communicate across long distances , but also with their immediate neighbors . Interactions between cells in close contact are key in both health and disease , yet trac...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "biology", "tools", "and", "resources", "cancer", "biology" ]
2020
A versatile system to record cell-cell interactions
Generating recombinant monoclonal antibodies ( R-mAbs ) from mAb-producing hybridomas offers numerous advantages that increase the effectiveness , reproducibility , and transparent reporting of research . We report here the generation of a novel resource in the form of a library of recombinant R-mAbs validated for neur...
The immune system fights off disease-causing microbes using antibodies: Y-shaped proteins that each bind to a specific foreign molecule . Indeed , these proteins bind so tightly and so specifically that they can pick out a single target in a complex mixture of different molecules . This property also makes them useful ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "tools", "and", "resources", "neuroscience" ]
2019
A toolbox of IgG subclass-switched recombinant monoclonal antibodies for enhanced multiplex immunolabeling of brain
Chemosensory neurons extract information about chemical cues from the environment . How is the activity in these sensory neurons transformed into behavior ? Using Caenorhabditis elegans , we map a novel sensory neuron circuit motif that encodes odor concentration . Primary neurons , AWCON and AWA , directly detect the ...
A sense of smell can help animals to find food and detect danger . Odor molecules activate so-called olfactory neurons that relay signals to the brain in the form of nerve impulses . This information is then processed , and the appropriate response is triggered; for example , an animal might move towards the smell of f...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2015
Circuit mechanisms encoding odors and driving aging-associated behavioral declines in Caenorhabditis elegans
Genetic variants regulating RNA splicing and transcript usage have been implicated in both common and rare diseases . Although transcript usage quantitative trait loci ( tuQTLs ) have been mapped across multiple cell types and contexts , it is challenging to distinguish between the main molecular mechanisms controlling...
Genes contain all instructions needed to build an organism in form of DNA . Humans share around 99 . 5% of DNA , but it is the remaining 0 . 5% that contain the small genetic variations that make us unique . Subtle differences in genes can , for example , influence the color of our hair or eyes . To build gene products...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "computational", "and", "systems", "biology", "genetics", "and", "genomics" ]
2019
Genetic effects on promoter usage are highly context-specific and contribute to complex traits
BST2/tetherin , an antiviral restriction factor , inhibits the release of enveloped viruses from the cell surface . Human immunodeficiency virus-1 ( HIV-1 ) antagonizes BST2 through viral protein u ( Vpu ) , which downregulates BST2 from the cell surface . We report the crystal structure of a protein complex containing...
HIV is a retrovirus that attacks the immune system , making the body increasingly susceptible to opportunistic infections and disease and eventually leading to AIDS . While antiretroviral drugs have allowed people with AIDS to live longer , there is no cure or vaccine for HIV . Two types of HIV exist , with HIV-1 being...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "structural", "biology", "and", "molecular", "biophysics", "microbiology", "and", "infectious", "disease" ]
2014
Structural basis of HIV-1 Vpu-mediated BST2 antagonism via hijacking of the clathrin adaptor protein complex 1
The molecular machinery responsible for DNA expression , recombination , and compaction has been difficult to visualize as functionally complete entities due to their combinatorial and structural complexity . We report here the structure of the intact functional assembly responsible for regulating and executing a site-...
Some viruses can remain dormant inside an infected cell and only become active when conditions are right to multiply and infect other cells . Bacteriophage λ is a much-studied model virus that adopts this lifecycle by inserting its genetic information into the chromosome of a bacterium called Escherichia coli . Certain...
[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]
[ "chromosomes", "and", "gene", "expression", "structural", "biology", "and", "molecular", "biophysics" ]
2016
Structure of a Holliday junction complex reveals mechanisms governing a highly regulated DNA transaction