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The neural fate commitment of pluripotent stem cells requires the repression of extrinsic inhibitory signals and the activation of intrinsic positive transcription factors . However , how these two events are integrated to ensure appropriate neural conversion remains unclear . In this study , we showed that Pou3f1 is e...	After an egg has been fertilized , it undergoes a series of divisions to produce a ball of cells known as a blastocyst . The cells within the blastocyst are pluripotent stem cells , which have the potential to become many different types of cell . After a few days , the stem cells organize into three layers—an innermos...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2014	The transcription factor Pou3f1 promotes neural fate commitment via activation of neural lineage genes and inhibition of external signaling pathways
Sperm-packaged DNA must undergo extensive reorganization to ensure its timely participation in embryonic mitosis . Whereas maternal control over this remodeling is well described , paternal contributions are virtually unknown . In this study , we show that Drosophila melanogaster males lacking Heterochromatin Protein 1...	The genetic information of cells is packaged into structures called chromosomes , which are made up of long strands of DNA that are wrapped around proteins to form a structure called chromatin . The cells of most animals contain two copies of every chromosome , but the egg and sperm cells contain only one copy . This m...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "cell", "biology" ]	2015	Mitotic fidelity requires transgenerational action of a testis-restricted HP1
The application of current channelrhodopsin-based optogenetic tools is limited by the lack of strict ion selectivity and the inability to extend the spectra sensitivity into the near-infrared ( NIR ) tissue transmissible range . Here we present an NIR-stimulable optogenetic platform ( termed 'Opto-CRAC' ) that selectiv...	Optogenetics is a technique that has been used to study nerve cells for several years . It involves genetically engineering these cells to produce proteins from light-sensitive bacteria , and results in nerve cells that will either send , or stop sending , nerve impulses when they are exposed to a particular color of l...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "cell", "biology", "tools", "and", "resources" ]	2015	Near-infrared photoactivatable control of Ca2+ signaling and optogenetic immunomodulation
Gamma activity in the subthalamic nucleus ( STN ) is widely viewed as a pro-kinetic rhythm . Here we test the hypothesis that rather than being specifically linked to movement execution , gamma activity reflects dynamic processing in this nucleus . We investigated the role of gamma during fast stopping and recorded sca...	Being able to stop walking to allow a car to pass is one example of how terminating a movement midway through can be essential for surviving in an ever-changing world . However , people with Parkinson’s disease sometimes struggle to stop performing a repetitive movement . Also , they may find themselves stopping despit...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2017	Subthalamic nucleus gamma activity increases not only during movement but also during movement inhibition
CHARGE syndrome is caused by heterozygous mutations in the chromatin remodeler , CHD7 , and is characterized by a set of malformations that , on clinical grounds , were historically postulated to arise from defects in neural crest formation during embryogenesis . To better delineate neural crest defects in CHARGE syndr...	CHARGE syndrome is a disease in which organs including the heart , eyes and ears may not develop properly . The cells that form the tissues affected by CHARGE syndrome develop in embryos from precursor cells called neural crest cells . Individuals with CHARGE syndrome also have mutations in a gene called CHD7 . However...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "medicine" ]	2017	CHARGE syndrome modeling using patient-iPSCs reveals defective migration of neural crest cells harboring CHD7 mutations
End-stage kidney disease ( ESKD ) patients are at high risk of severe COVID-19 . We measured 436 circulating proteins in serial blood samples from hospitalised and non-hospitalised ESKD patients with COVID-19 ( n = 256 samples from 55 patients ) . Comparison to 51 non-infected patients revealed 221 differentially expre...	COVID-19 varies from a mild illness in some people to fatal disease in others . Patients with severe disease tend to be older and have underlying medical problems . People with kidney failure have a particularly high risk of developing severe or fatal COVID-19 . Patients with severe COVID-19 have high levels of inflamm...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "medicine", "immunology", "and", "inflammation" ]	2021	Longitudinal proteomic profiling of dialysis patients with COVID-19 reveals markers of severity and predictors of death
The actin cortex plays a pivotal role in cell division , in generating and maintaining cell polarity and in motility . In all these contexts , the cortical network has to break symmetry to generate polar cytoskeletal dynamics . Despite extensive research , the mechanisms responsible for regulating cortical dynamics in ...	Cells are extremely complex because they have to perform a vast number of processes . However , this also makes it difficult for researchers to figure out how the individual parts of the cell work . There is interest , therefore , in developing simple artificial cells that can accurately mimic how specific parts of a c...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2014	Symmetry breaking in reconstituted actin cortices
Pif1 family helicases are conserved from bacteria to humans . Here , we report a novel DNA patrolling activity which may underlie Pif1’s diverse functions: a Pif1 monomer preferentially anchors itself to a 3′-tailed DNA junction and periodically reel in the 3′ tail with a step size of one nucleotide , extruding a loop ...	Helicases are enzymes that are best known for their ability to separate the two strands of DNA that make up the famous double-helix structure . Many important processes within cells—including the expression of genes as proteins , and the replication of DNA before cell division—rely on DNA molecules being separated in t...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics" ]	2014	Periodic DNA patrolling underlies diverse functions of Pif1 on R-loops and G-rich DNA
Oncogenic mutations in BRAF and NRAS occur in 70% of melanomas . In this study , we identify a microRNA , miR-146a , that is highly upregulated by oncogenic BRAF and NRAS . Expression of miR-146a increases the ability of human melanoma cells to proliferate in culture and form tumors in mice , whereas knockdown of miR-1...	Cancer is a leading cause of death worldwide , and although cancer can have many causes , mutations to a small number of genes are often responsible for a large number of cancer cases . For example , about 70% of cases of the deadliest form of skin cancer have mutations in two specific genes . Many cancer-causing genes...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2014	miR-146a promotes the initiation and progression of melanoma by activating Notch signaling
Bacterial factors favoring the unprecedented multidrug-resistant tuberculosis ( MDR-TB ) epidemic in the former Soviet Union remain unclear . We utilized whole genome sequencing and Bayesian statistics to analyze the evolutionary history , temporal emergence of resistance and transmission networks of MDR Mycobacterium ...	Multidrug-resistant tuberculosis , often shortened to MDR-TB , is a public health crisis with close to half a million patients falling ill each year globally . Some strains of the bacterium Mycobacterium tuberculosis , which causes tuberculosis disease , are resistant to the two most effective drugs used to treat the i...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology" ]	2018	Compensatory evolution drives multidrug-resistant tuberculosis in Central Asia
Bacteria often live in biofilms , which are microbial communities surrounded by a secreted extracellular matrix . Here , we demonstrate that hydrodynamic flow and matrix organization interact to shape competitive dynamics in Pseudomonas aeruginosa biofilms . Irrespective of initial frequency , in competition with matri...	Bacteria often live together – attached to surfaces like river rocks , water pipes , the lining of the gut and catheters – in communities called biofilms . These groups of bacteria are small-scale ecosystems in which cells cooperate and compete with one another to obtain resources , such as food and space to grow . Wit...	[ "Abstract", "Introduction", "Results/discussion", "Materials", "and", "methods" ]	[ "ecology", "short", "report", "microbiology", "and", "infectious", "disease" ]	2017	Flow environment and matrix structure interact to determine spatial competition in Pseudomonas aeruginosa biofilms
PP2C phosphatases control biological processes including stress responses , development , and cell division in all kingdoms of life . Diverse regulatory domains adapt PP2C phosphatases to specific functions , but how these domains control phosphatase activity was unknown . We present structures representing active and ...	To regulate the activity of proteins , cells often modify them by adding or removing chemical groups called phosphates . Therefore , the enzymes that add or remove these phosphate groups must be tightly regulated so that they are active at the right time and place . Enzymes known as phosphatases remove phosphate groups...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "microbiology", "and", "infectious", "disease" ]	2017	A widespread family of serine/threonine protein phosphatases shares a common regulatory switch with proteasomal proteases
Mechanisms enabling positional identity re-establishment are likely critical for tissue regeneration . Planarians use Wnt/beta-catenin signaling to polarize the termini of their anteroposterior axis , but little is known about how regeneration signaling restores regionalization along body or organ axes . We identify th...	Some animals can regrow tissues that have been amputated . A group of flatworms called planarians are often used as a model to study the regeneration process because they are able to restore any lost tissue or even an entire animal from even tiny pieces of the body . For regeneration to be successful , it is critical t...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "stem", "cells", "and", "regenerative", "medicine", "short", "report" ]	2016	Wnt, Ptk7, and FGFRL expression gradients control trunk positional identity in planarian regeneration
Estimating local surface orientation ( slant and tilt ) is fundamental to recovering the three-dimensional structure of the environment . It is unknown how well humans perform this task in natural scenes . Here , with a database of natural stereo-images having groundtruth surface orientation at each pixel , we find dra...	The ability to assess how tilted a surface is , or its ‘surface orientation’ , is critical for interacting productively with the environment . For example , it helps organisms to determine whether a particular surface is better suited for walking or climbing . Humans and other animals estimate 3-dimensional ( 3D ) surf...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2018	The lawful imprecision of human surface tilt estimation in natural scenes
Annual changes in the environment threaten survival , and numerous biological processes in mammals adjust to this challenge via seasonal encoding by the suprachiasmatic nucleus ( SCN ) . To tune behavior according to day length , SCN neurons display unified rhythms with synchronous phasing when days are short , but wil...	In winter , as the days become shorter , millions of people find that their mood and energy levels start to drop . They crave carbohydrates , struggle with their weight , and find it harder to get out of bed in the mornings . These individuals are suffering from the ‘winter blues’ or seasonal affective disorder ( SAD )...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2019	Seasonal plasticity in GABAA signaling is necessary for restoring phase synchrony in the master circadian clock network
Sodium/proton antiporters maintain intracellular pH and sodium levels . Detailed structures of antiporters with bound substrate ions are essential for understanding how they work . We have resolved the substrate ion in the dimeric , electroneutral sodium/proton antiporter PaNhaP from Pyrococcus abyssi at 3 . 2 Å , and ...	Although the membrane that surrounds a cell is effective at separating the inside of a cell from the outside environment , certain molecules must enter or leave the cell for it to work correctly . One way this transport can occur is via proteins embedded in the cell membrane , called transporters . Transporters that ar...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2014	Structure and substrate ion binding in the sodium/proton antiporter PaNhaP
The ability of a neuron to regenerate its axon after injury depends in part on its intrinsic regenerative potential . Here , we identify novel intrinsic regulators of axon regeneration: poly ( ADP-ribose ) glycohodrolases ( PARGs ) and poly ( ADP-ribose ) polymerases ( PARPs ) . PARGs , which remove poly ( ADP-ribose )...	Neurons carry information around the body along slender projections known as axons . An injury that crushes or cuts an axon can lead to permanent disability if the axon fails to regenerate . While some damaged neurons in the body can repair themselves , typically those present in the brain and spinal cord cannot regene...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "short", "report", "neuroscience" ]	2016	Inhibiting poly(ADP-ribosylation) improves axon regeneration
The nonsense-mediated mRNA decay ( NMD ) pathway detects aberrant transcripts containing premature termination codons ( PTCs ) and regulates expression of 5–10% of non-aberrant human mRNAs . To date , most proteins involved in NMD have been identified by genetic screens in model organisms; however , the increased compl...	The DNA in our cells contains the hereditary information that makes each of us unique . Molecules called mRNAs are copies of this information and are used as templates for making proteins . When a strand of incorrectly copied mRNA , or one including errors from the original DNA template , is recognized , our cells dest...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "biochemistry", "and", "chemical", "biology" ]	2018	ICE1 promotes the link between splicing and nonsense-mediated mRNA decay
Retinal ganglion cell ( RGC ) axons of binocular animals cross the midline at the optic chiasm ( OC ) to grow toward their synaptic targets in the contralateral brain . Ventral anterior homeobox 1 ( Vax1 ) plays an essential role in the development of the OC by regulating RGC axon growth in a non-cell autonomous manner...	We see the world around us when light bounces off of objects and hits the retina at the back of our eyes . This triggers electrical signals in neurons called retinal ganglion cells ( RGCs ) , which have long structures called axons that extend out from the retina and into the parts of the brain where the signals are in...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "neuroscience" ]	2014	Regulation of retinal axon growth by secreted Vax1 homeodomain protein
Inflammation-induced release of prostaglandin E2 ( PGE2 ) changes breathing patterns and the response to CO2 levels . This may have fatal consequences in newborn babies and result in sudden infant death . To elucidate the underlying mechanisms , we present a novel breathing brainstem organotypic culture that generates ...	Humans and other mammals breathe air to absorb oxygen into the body and to remove carbon dioxide . We know that in a part of the brain called the brainstem , several regions work together to create breaths , but it is not clear precisely how this works . These regions adjust our breathing to the demands placed on the b...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology", "neuroscience" ]	2016	CO2-evoked release of PGE2 modulates sighs and inspiration as demonstrated in brainstem organotypic culture
Assessing the danger of transition of HIV transmission from a concentrated to a generalized epidemic is of major importance for public health . In this study , we develop a phylogeny-based statistical approach to address this question . As a case study , we use this to investigate the trends and determinants of HIV tra...	In epidemiology , the “basic reproductive number” describes how efficiently a disease is transmitted , and represents the average number of new infections that an infected individual causes . If this number is less than one , many people do not infect anybody and hence the transmission chains die out . On the other han...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "epidemiology", "and", "global", "health", "microbiology", "and", "infectious", "disease" ]	2017	Assessing the danger of self-sustained HIV epidemics in heterosexuals by population based phylogenetic cluster analysis
Biosensors for small molecules can be used in applications that range from metabolic engineering to orthogonal control of transcription . Here , we produce biosensors based on a ligand-binding domain ( LBD ) by using a method that , in principle , can be applied to any target molecule . The LBD is fused to either a flu...	Small molecules play essential roles in organisms , and so methods to sense these molecules within living cells could have wide-ranging uses in both biology and biotechnology . However , current methods for making new “biosensors” are limited and only a narrow range of small molecules can be detected . One approach to ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2015	A general strategy to construct small molecule biosensors in eukaryotes
Ecdysis ( moulting ) is the defining character of Ecdysoza ( arthropods , nematodes and related phyla ) . Despite superficial similarities , the signalling cascade underlying moulting differs between Panarthropoda and the remaining ecdysozoans . Here , we reconstruct the evolution of major components of the ecdysis pat...	Animals such as insects , crabs and spiders belong to one of the most species-rich animal groups , called the arthropods . These animals have exoskeletons , which are hard , external coverings that support their bodies . Arthropods shed their exoskeletons as they grow , a process called ecdysis or moulting , and this b...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology", "short", "report", "genetics", "and", "genomics" ]	2019	Ancient origins of arthropod moulting pathway components
Neuropeptides are essential for the regulation of appetite . Here we show that neuropeptides could regulate feeding in mutants that lack neurotransmission from the motor neurons that stimulate feeding muscles . We identified nlp-24 by an RNAi screen of 115 neuropeptide genes , testing whether they affected growth . NLP...	When and how much an animal eats is controlled by a complex web of signals that are produced by the animal's body and brain . Molecules called opioid neuropeptides are among these signals , and act to control eating in mammals by binding to receptors in the brain and body . These receptors can also bind to similar mole...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	An opioid-like system regulating feeding behavior in C. elegans
The circuit structure and function underlying post-coital male behaviors remain poorly understood . Using mutant analysis , laser ablation , optogenetics , and Ca2+ imaging , we observed that following C . elegans male copulation , the duration of post-coital lethargy is coupled to cellular events involved in ejaculati...	The nematode worm , C . elegans , is roughly 1 mm long , made up of around 1000 cells and has two sexes: male and hermaphrodite . Hermaphrodite worms produce both eggs and sperm and can self-fertilize to generate around 300 offspring each time . Fertilization by a male , on the other hand , results in three times as ma...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2014	Caenorhabditis elegans male sensory-motor neurons and dopaminergic support cells couple ejaculation and post-ejaculatory behaviors
Evolution has often copied and repurposed the mitogen-activated protein kinase ( MAPK ) signaling module . Understanding how connections form during evolution , in disease and across individuals requires knowledge of the basic tenets that govern kinase-substrate interactions . We identify criteria sufficient for establ...	Nature has evolved a number of ways to link signals from a cell’s environment , like the concentration of a hormone , to the behavior of that cell . These new connections often form by reusing certain common signaling components , such as mitogen-activated protein kinases . These enzymes – referred to as MAPKs for shor...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "computational", "and", "systems", "biology" ]	2016	Rewiring MAP kinases in Saccharomyces cerevisiae to regulate novel targets through ubiquitination
Most amino acids can be encoded by several synonymous codons , which are used at unequal frequencies . The significance of unequal codon usage remains unclear . One hypothesis is that frequent codons are translated relatively rapidly . However , there is little direct , in vivo , evidence regarding codon-specific trans...	Genes contain the instructions for making proteins from molecules called amino acids . These instructions are encoded in the order of the four building blocks that make up DNA , which are symbolized by the letters A , T , C , and G . The DNA of a gene is first copied to make a molecule of RNA , and then the letters in ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology" ]	2014	Measurement of average decoding rates of the 61 sense codons in vivo
Social relationships have profound effects on health in humans and other primates , but the mechanisms that explain this relationship are not well understood . Using shotgun metagenomic data from wild baboons , we found that social group membership and social network relationships predicted both the taxonomic structure...	The digestive system is home to a complex community of microbes—known as the gut microbiome—that contributes to our health and wellbeing by digesting food , producing essential vitamins , and preventing the growth of harmful bacteria . The recent development of rapid genome sequencing techniques has made it much easier...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "ecology", "genetics", "and", "genomics" ]	2015	Social networks predict gut microbiome composition in wild baboons
Neuroimaging has been used to examine developmental changes of the brain . While PET studies revealed maturation-related changes , maturation of metabolic connectivity of the brain is not yet understood . Here , we show that rat brain metabolism is reconfigured to achieve long-distance connections with higher energy ef...	The brain consumes a great deal of a sugar called glucose , which is delivered to the brain through blood vessels . Active regions of the brain need more glucose , and so the brain has a metabolic network that controls when and where glucose is metabolized . Yet precisely how this metabolic network changes during brain...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	Maturation of metabolic connectivity of the adolescent rat brain
Much of the vertebrate skeleton develops from cartilage templates that are progressively remodeled into bone . Lineage tracing studies in mouse suggest that chondrocytes within these templates persist and become osteoblasts , yet the underlying mechanisms of this process and whether chondrocytes can generate other deri...	Our adult bones are made of a fatty tissue , called marrow , wrapped inside a hard outer layer produced by bone cells . They may appear stiff and unyielding , but our bones are actually dynamic structures . Early in life , most bones start as small ‘templates’ made of another , flexible tissue called cartilage . As the...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "stem", "cells", "and", "regenerative", "medicine", "developmental", "biology" ]	2019	Programmed conversion of hypertrophic chondrocytes into osteoblasts and marrow adipocytes within zebrafish bones
Interoception , the sensitivity to visceral sensations , plays an important role in homeostasis and guiding motivated behaviour . It is also considered to be fundamental to self-awareness . Despite its importance , the developmental origins of interoceptive sensitivity remain unexplored . We here provide the first evid...	From the beginning till the end of a person’s life , parts of the body continuously send signals to the brain . Most of this happens without the person even being aware of it , yet people can become aware of the signals under certain circumstances . For example , we can feel our racing heart rate or the “butterflies in...	[ "Abstract", "Materials", "and", "methods" ]	[ "short", "report", "neuroscience" ]	2017	Neurobehavioral evidence of interoceptive sensitivity in early infancy
Assembly , maintenance and function of synaptic junctions depend on extracellular matrix ( ECM ) proteins and their receptors . Here we report that Tenectin ( Tnc ) , a Mucin-type protein with RGD motifs , is an ECM component required for the structural and functional integrity of synaptic specializations at the neurom...	Nerve cells or neurons can communicate with each other by releasing chemical messengers into the gap between them , the synapse . Both neurons and synapses are surrounded by a network of proteins called the extracellular matrix , which anchors , protects and supports the synapse . The matrix also helps to regulate the ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "neuroscience" ]	2018	Tenectin recruits integrin to stabilize bouton architecture and regulate vesicle release at the Drosophila neuromuscular junction
SNARE proteins play a crucial role in intracellular trafficking by catalyzing membrane fusion , but assigning SNAREs to specific intracellular transport routes is challenging with current techniques . We developed a novel Förster resonance energy transfer-fluorescence lifetime imaging microscopy ( FRET-FLIM ) -based te...	Many processes in living cells involve membranes coming together and fusing . For example , white blood cells known as dendritic cells rely on membrane fusion to fight off infections . When a dendritic cell detects a bacterial infection , it releases signaling molecules called cytokines to recruit other immune cells th...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics", "immunology", "and", "inflammation" ]	2017	Fluorescence Lifetime Imaging Microscopy reveals rerouting of SNARE trafficking driving dendritic cell activation
The evolutionarily conserved Crumbs protein is required for epithelial polarity and morphogenesis . Here we identify a novel role of Crumbs as a negative regulator of actomyosin dynamics during dorsal closure in the Drosophila embryo . Embryos carrying a mutation in the FERM ( protein 4 . 1/ezrin/radixin/moesin ) domai...	A layer of epithelial cells covers the body surface of animals . Epithelial cells have a property known as polarity; this means that they have two different poles , one of which is in contact with the environment . Midway through embryonic development , the Drosophila embryo is covered by two kinds of epithelial sheets...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]	[ "cell", "biology" ]	2015	Crumbs is an essential regulator of cytoskeletal dynamics and cell-cell adhesion during dorsal closure in Drosophila
Zona pellucida ( ZP ) , the extracellular matrix sheltering mammalian oocytes and embryos , is composed by 3 to 4 proteins . The roles of the three proteins present in mice have been elucidated by KO models , but the function of the fourth component ( ZP4 ) , present in all other eutherian mammals studied so far , has ...	The egg cells of mammals , called oocytes , are encased in a protective layer called the zona pellucida . This layer is made from proteins called ZP1 to 4 . Most studies of the zona pellucida use mice , which do not have ZP4 . This means that the research community have limited knowledge of what ZP4 does in humans and ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2019	ZP4 confers structural properties to the zona pellucida essential for embryo development
Microtubule asters - radial arrays of microtubules organized by centrosomes - play a fundamental role in the spatial coordination of animal cells . The standard model of aster growth assumes a fixed number of microtubules originating from the centrosomes . However , aster morphology in this model does not scale with ce...	Cells must carefully organize their contents in order to work effectively . Protein filaments called microtubules often play important roles in this organization , as well as giving structure to the cell . Many cells contain structures called asters that are formed of microtubules that radiate out from a central point ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "physics", "of", "living", "systems" ]	2016	Physical basis of large microtubule aster growth
The haptoglobin-haemoglobin receptor of the African trypanosome species , Trypanosoma brucei , is expressed when the parasite is in the bloodstream of the mammalian host , allowing it to acquire haem through the uptake of haptoglobin-haemoglobin complexes . Here we show that in Trypanosoma congolense this receptor is i...	Trypanosomes are single-celled parasites that infect a range of animal hosts . These parasites need a molecule called haem to grow properly and are mostly spread by insects that feed on the blood of mammals . Most haem in mammals is found in red blood cells and is bound to a protein called haemoglobin . When it is rele...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology", "microbiology", "and", "infectious", "disease" ]	2016	Evolutionary diversification of the trypanosome haptoglobin-haemoglobin receptor from an ancestral haemoglobin receptor
Despite the central role that antibodies play in the adaptive immune system and in biotechnology , much remains unknown about the quantitative relationship between an antibody’s amino acid sequence and its antigen binding affinity . Here we describe a new experimental approach , called Tite-Seq , that is capable of mea...	Antibodies are proteins produced by cells of the immune system to tag or neutralize potential threats to the body , such as foreign substances and disease-causing microbes . Antibodies do this by binding to target molecules called antigens . An antibody’s ability to bind to an antigen depends on the sequence of amino a...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics" ]	2016	Measuring the sequence-affinity landscape of antibodies with massively parallel titration curves
The Ccr4-Not complex removes mRNA poly ( A ) tails to regulate eukaryotic mRNA stability and translation . RNA-binding proteins contribute to specificity by interacting with both Ccr4-Not and target mRNAs , but this is not fully understood . Here , we reconstitute accelerated and selective deadenylation of RNAs contain...	When a cell needs to make a particular protein , it first copies the instructions from the matching gene into a molecule known as a messenger RNA ( or an mRNA for short ) . The more mRNA copies it makes , the more protein it can produce . A simple way to control protein production is to raise or lower the number of the...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology" ]	2019	RNA-binding proteins distinguish between similar sequence motifs to promote targeted deadenylation by Ccr4-Not
Carotenoids are essential in oxygenic photosynthesis: they stabilize the pigment–protein complexes , are active in harvesting sunlight and in photoprotection . In plants , they are present as carotenes and their oxygenated derivatives , xanthophylls . While mutant plants lacking xanthophylls are capable of photoautotro...	Most life on Earth depends on photosynthesis , the process used by plants and many other organisms to store energy from sunlight and produce oxygen . The first steps of photosynthesis , the capture and conversion of sunlight into chemical energy , happen in large assemblies of proteins containing many pigment molecules...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "plant", "biology" ]	2020	Photosynthesis without β-carotene
Individual recognition ( IR ) is essential for maintaining various social interactions in a group , and face recognition is one of the most specialised cognitive abilities in IR . We used both a mating preference system and an electric shock conditioning experiment to test IR ability in medaka , and found that signals ...	Being able to recognize each other is crucial for social interactions in humans , as well as many other animals . To humans , faces are the most important body part to differentiate between one another . Humans read the face as a whole , rather than look at parts of the face , which is why it is harder to recognise a f...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "ecology", "neuroscience" ]	2017	Individual recognition and the ‘face inversion effect’ in medaka fish (Oryzias latipes)
Peptide transport plays an important role in cellular homeostasis as a key route for nitrogen acquisition in mammalian cells . PepT1 and PepT2 , the mammalian proton coupled peptide transporters ( POTs ) , function to assimilate and retain diet-derived peptides and play important roles in drug pharmacokinetics . A key ...	The cell membrane encases cells and functions as a protective barrier . Although this has the benefit of preventing harmful substances from entering a cell , it also keeps beneficial molecules out . The cell membrane therefore contains a system of different ‘gates’ , called transporters , through which selected supplie...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology" ]	2014	Thermodynamic evidence for a dual transport mechanism in a POT peptide transporter
The 96-nm axonemal repeat includes dynein motors and accessory structures as the foundation for motility of eukaryotic flagella and cilia . However , high-resolution 3D axoneme structures are unavailable for organisms among the Excavates , which include pathogens of medical and economic importance . Here we report cryo...	The parasites that cause African sleeping sickness , known as trypanosomes , propel themselves forward using a structure called a flagellum , a bit like the tail of a human sperm . But rather than connect to the body of the cell just at the base , like in a sperm , the parasite flagellum runs along the side of the cell...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "microbiology", "and", "infectious", "disease" ]	2019	Cryo electron tomography with volta phase plate reveals novel structural foundations of the 96-nm axonemal repeat in the pathogen Trypanosoma brucei
Canine transmissible venereal tumour ( CTVT ) is a clonally transmissible cancer that originated approximately 11 , 000 years ago and affects dogs worldwide . Despite the clonal origin of the CTVT nuclear genome , CTVT mitochondrial genomes ( mtDNAs ) have been acquired by periodic capture from transient hosts . We seq...	A unique cancer called canine transmissible venereal tumour ( CTVT ) causes ugly tumours to form on the genitals of dogs . Unlike most other cancers , CTVT is contagious: the cancer cells can be directly transferred from one dog to another when they mate . The disease originated from the cancer cells of one individual ...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "short", "report", "cancer", "biology" ]	2016	Mitochondrial genetic diversity, selection and recombination in a canine transmissible cancer
Neurons are sensitive to low oxygen ( hypoxia ) and employ a conserved pathway to combat its effects . Here , we show that p38 MAP Kinase ( MAPK ) modulates this hypoxia response pathway in C . elegans . Mutants lacking p38 MAPK components pmk-1 or sek-1 resemble mutants lacking the hypoxia response component and proly...	The brain accounts for 2% of our body weight , but consumes about 20% of our oxygen intake . This oxygen gluttony is due to the tremendous appetite of brain cells for energy , which neurons satisfy through oxygen-dependent ( aerobic ) metabolism . As a result , the loss of oxygen to the brain during a stroke , heart at...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "neuroscience" ]	2016	The p38 MAP kinase pathway modulates the hypoxia response and glutamate receptor trafficking in aging neurons
Small GTPases of the Rab family not only regulate target recognition in membrane traffic but also control other cellular functions such as cytoskeletal transport and autophagy . Here we show that Rab26 is specifically associated with clusters of synaptic vesicles in neurites . Overexpression of active but not of GDP-pr...	Our brain contains billions of cells called neurons that form an extensive network through which information is readily exchanged . These cells connect to each other via junctions called synapses . Our developing brain starts off with far more synapses than it needs , but the excess synapses are destroyed as the brain ...	[ "Abstract", "Introduction", "Results", "Discussion", "Material", "and", "methods" ]	[ "neuroscience" ]	2015	The GTPase Rab26 links synaptic vesicles to the autophagy pathway
The population genetics of most range expansions is thought to be shaped by the competition between Darwinian selection and random genetic drift at the range margins . Here , we show that the evolutionary dynamics during range expansions is highly sensitive to additional fluctuations induced by environmental heterogene...	Throughout evolution , countless populations have expanded their territories by invading new areas . This invasion can happen on the scale of kilometers and millennia – such as when humans migrated out of Africa – or millimeters and months , such as the growth of a population of cells in a solid tumor . During this exp...	[ "Abstract", "Introduction", "Results", "Discussion" ]	[ "evolutionary", "biology", "physics", "of", "living", "systems" ]	2019	Environmental heterogeneity can tip the population genetics of range expansions
Liver metabolism follows diurnal fluctuations through the modulation of molecular clock genes . Disruption of this molecular clock can result in metabolic disease but its potential regulation by immune cells remains unexplored . Here , we demonstrated that in steady state , neutrophils infiltrated the mouse liver follo...	Every day , the body's biological processes work to an internal clock known as the circadian rhythm . This rhythm is controlled by ‘clock genes’ that are switched on or off by daily physical and environmental cues , such as changes in light levels . These daily rhythms are very finely tuned , and disturbances can lead ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "immunology", "and", "inflammation" ]	2020	Neutrophil infiltration regulates clock-gene expression to organize daily hepatic metabolism
CRISPR-Cas systems provide sequence-specific immunity against phages and mobile genetic elements using CRISPR-associated nucleases guided by short CRISPR RNAs ( crRNAs ) . Type III systems exhibit a robust immune response that can lead to the extinction of a phage population , a feat coordinated by a multi-subunit effe...	Just as humans are susceptible to viruses , bacteria have their own viruses to contend with . These viruses – known as phages – attach to the surface of bacterial cells , inject their genetic material , and use the cells’ enzymes to multiply while destroying their hosts . To defend against a phage attack , bacteria hav...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "microbiology", "and", "infectious", "disease" ]	2019	A type III-A CRISPR-Cas system employs degradosome nucleases to ensure robust immunity
Crimean-Congo hemorrhagic fever ( CCHF ) is the most widely distributed tick-borne viral infection in the world . Strikingly , reported mortality rates for CCHF are extremely variable , ranging from 5% to 80% ( Whitehouse , 2004 ) . CCHF virus ( CCHFV , Nairoviridae ) exhibits extensive genomic sequence diversity acros...	Crimean-Congo hemorrhagic fever ( CCHF ) is caused by infection with a virus spread by ticks in Europe , Africa and Asia . It can cause severe disease in humans , including high fevers and bleeding . How deadly CCHF is varies with between 5% to 80% of those infected dying . Scientists suspect genetic differences in var...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "microbiology", "and", "infectious", "disease" ]	2020	A single mutation in Crimean-Congo hemorrhagic fever virus discovered in ticks impairs infectivity in human cells
In our dynamic world , decisions about noisy stimuli can require temporal accumulation of evidence to identify steady signals , differentiation to detect unpredictable changes in those signals , or both . Normative models can account for learning in these environments but have not yet been applied to faster decision pr...	Organisms gather information from their surroundings to make decisions . Traditionally , neuroscientists have investigated decision-making by first asking what would be optimal for the animal , and then seeing whether and how the brain implements the optimal process . This approach has assumed that the environment cons...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	Normative evidence accumulation in unpredictable environments
Elucidating cardiac evolution has been frustrated by lack of fossils . One celebrated enigma in cardiac evolution involves the transition from a cardiac outflow tract dominated by a multi-valved conus arteriosus in basal actinopterygians , to an outflow tract commanded by the non-valved , elastic , bulbus arteriosus in...	Modern research has majorly advanced our understanding of how the heart works , and has led to new therapies for cardiac diseases . However , little is known about how the heart has evolved throughout the history of animals with backbones – a group that is collectively referred to as vertebrates . This is partly becaus...	[ "Abstract", "Introduction", "Results", "Discussion", "Material", "and", "methods" ]	[ "ecology", "evolutionary", "biology" ]	2016	Heart fossilization is possible and informs the evolution of cardiac outflow tract in vertebrates
Organisms need to adapt to the ecological constraints in their habitat . How specific processes reflect such adaptations are difficult to model experimentally . We tested whether environmental shifts in oxygen tension lead to events in the adult newt brain that share features with processes occurring during neuronal re...	During the winter , red-spotted newts remain active in water that is covered by ice . The oxygen levels under the ice tend to drop and so the newts adjust their metabolism to cope with these conditions . However , when oxygen levels return to normal , this may result in the newts producing larger amounts of chemically ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "stem", "cells", "and", "regenerative", "medicine", "cell", "biology" ]	2015	Environmental changes in oxygen tension reveal ROS-dependent neurogenesis and regeneration in the adult newt brain
Gaining insights into the regulatory mechanisms that underlie the transcriptional variation observed between individual cells necessitates the development of methods that measure chromatin organization in single cells . Here I adapted Nucleosome Occupancy and Methylome-sequencing ( NOMe-seq ) to measure chromatin acces...	DNA contains all the information and instructions needed to build an organism and enables its cells to fulfil their role . There are many different cell types in animals , and each type only needs a small portion of the information found in the DNA to do its job . Hence , only the sections – also known as genes – speci...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "tools", "and", "resources", "genetics", "and", "genomics" ]	2017	Simultaneous measurement of chromatin accessibility, DNA methylation, and nucleosome phasing in single cells
Although shape perception is considered a function of the ventral visual pathway , evidence suggests that the dorsal pathway also derives shape-based representations . In two psychophysics and neuroimaging experiments , we characterized the response properties , topographical organization and perceptual relevance of th...	We rely on our sense of vision to perceive the world around us and the objects within it . We also use vision to guide our interactions with objects . One of the most influential theories in cognitive neuroscience is the idea that separate pathways within the brain support these two processes . The ventral pathway is i...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2017	The large-scale organization of shape processing in the ventral and dorsal pathways
Particulate matter ( PM ) air pollution causes cardiopulmonary mortality via macrophage-driven lung inflammation; however , the mechanisms are incompletely understood . RNA-sequencing demonstrated Acod1 ( Aconitate decarboxylase 1 ) as one of the top genes induced by PM in macrophages . Acod1 encodes a mitochondrial en...	Air pollution is a major global health problem that causes around 4 . 2 million deaths each year . Once inhaled , pollution particles can remain in the lungs , where they cause inflammation , tissue damage , and ultimately chronic disease . Macrophages , a population of immune cells in the lungs , are involved in this ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "immunology", "and", "inflammation" ]	2020	Endogenous itaconate is not required for particulate matter-induced NRF2 expression or inflammatory response
Developmental programs sculpt plant morphology to meet environmental challenges , and these same programs have been manipulated to increase agricultural productivity ( Doebley et al . , 1997; Khush , 2001 ) . Hormones coordinate these programs , creating chemical circuitry ( Vanstraelen and Benková , 2012 ) that has be...	The genetic information of plants contains sets of instructions that shape a growing seedling . These ‘developmental programs’ are under the control of a range of hormones , such as auxin . Typically , the information from the hormones is relayed to the genetic material through proteins called transcription factors , w...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "plant", "biology", "tools", "and", "resources" ]	2018	Synthetic hormone-responsive transcription factors can monitor and re-program plant development
The beating of motile cilia generates fluid flow over epithelia in brain ventricles , airways , and Fallopian tubes . Here , we patch clamp single motile cilia of mammalian ependymal cells and examine their potential function as a calcium signaling compartment . Resting motile cilia calcium concentration ( [Ca2+] ~170 ...	Certain specialized cells in the brain , airways and Fallopian tubes have large numbers of hair-like structures called motile cilia on their surface . By beating in a synchronized manner , these cilia help to move fluids across the surface of the cells: for example , cilia on lung cells beat to clear mucus away , while...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2015	Ion channels and calcium signaling in motile cilia
Mammalian cardiomyocytes become post-mitotic shortly after birth . Understanding how this occurs is highly relevant to cardiac regenerative therapy . Yet , how cardiomyocytes achieve and maintain a post-mitotic state is unknown . Here , we show that cardiomyocyte centrosome integrity is lost shortly after birth . This ...	Muscle cells in the heart contract in regular rhythms to pump blood around the body . In humans , rats and other mammals , the vast majority of heart muscle cells lose the ability to divide shortly after birth . Therefore , the heart is unable to replace cells that are lost over the life of the individual , for example...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "short", "report", "cell", "biology" ]	2015	Developmental alterations in centrosome integrity contribute to the post-mitotic state of mammalian cardiomyocytes
Antimicrobial peptides ( AMPs ) are broad spectrum antibiotics that selectively target bacteria . Here we investigate the activity of human AMP LL37 against Escherichia coli by integrating quantitative , population and single-cell level experiments with theoretical modeling . We observe an unexpected , rapid absorption...	Many organisms use molecules called antimicrobial peptides as a first line of defense against harmful bacteria . For example , in humans , these natural antibiotics are found in the airways , on the skin and in the urinary tract . Because antimicrobial peptides are positively charged , they function in a different way ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology", "microbiology", "and", "infectious", "disease" ]	2018	Heterogeneous absorption of antimicrobial peptide LL37 in Escherichia coli cells enhances population survivability
Truncating mutations in the giant sarcomeric protein Titin result in dilated cardiomyopathy and skeletal myopathy . The most severely affected dilated cardiomyopathy patients harbor Titin truncations in the C-terminal two-thirds of the protein , suggesting that mutation position might influence disease mechanism . Usin...	The heart is able to beat partly because of a large protein called Titin that helps to give heart muscle its elasticity . Mutations that shorten the gene that encodes Titin can cause part of the heart to become enlarged and weakened , a condition called dilated cardiomyopathy . Some people with shortened copies of this...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "genetics", "and", "genomics" ]	2015	An internal promoter underlies the difference in disease severity between N- and C-terminal truncation mutations of Titin in zebrafish
Mammalian cerebral cortex is accepted as being critical for voluntary motor control , but what functions depend on cortex is still unclear . Here we used rapid , reversible optogenetic inhibition to test the role of cortex during a head-fixed task in which mice reach , grab , and eat a food pellet . Sudden cortical inh...	Many of the movements that humans and other animals make every day are deceptively complex and only appear easy because of extensive practice . For example , picking up an object involves several steps that must be precisely controlled , including reaching towards the item and holding it using the right amount of press...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	Cortex commands the performance of skilled movement
Exophilin-8 has been reported to play a role in anchoring secretory granules within the actin cortex , due to its direct binding activities to Rab27 on the granule membrane and to F-actin and its motor protein , myosin-Va . Here , we show that exophilin-8 accumulates granules in the cortical F-actin network not by dire...	The human body contains trillions of cells with hundreds of different jobs that must cooperate with each other . Many cells communicate using hormones and other chemical messengers that they release into the blood or tissues . These messengers are stored in containers called secretory granules , which are held just und...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "neuroscience" ]	2017	Exophilin-8 assembles secretory granules for exocytosis in the actin cortex via interaction with RIM-BP2 and myosin-VIIa
The subthalamic nucleus ( STN ) is a small almond-shaped subcortical structure classically known for its role in motor inhibition through the indirect pathway within the basal ganglia . Little is known about the role of the STN in mediating cognitive functions in humans . Here , we explore the role of the STN in human ...	Deep brain stimulation , or DBS for short , is used to treat movement disorders like Parkinson’s disease in patients who are responding inadequately to medications . It requires implanting an electrode into the brain and using electrical stimulation aimed at a specific cluster of brain cells to reduce unwanted symptoms...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2018	Intermittent subthalamic nucleus deep brain stimulation induces risk-aversive behavior in human subjects
Exosomes are extracellular vesicles that are released when endosomes fuse with the plasma membrane . They have been implicated in various functions in both health and disease , including intercellular communication , antigen presentation , prion transmission , and tumour cell metastasis . Here we show that inactivating...	Cells generally communicate with each other over short distances by direct contact , and over long distances by releasing chemicals such as hormones . But there is also a third way that is less well understood – small capsules or “vesicles” called exosomes can transfer molecules from one cell to another . Exosomes are ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2016	Tetherin is an exosomal tether
Uromodulin is the most abundant protein in the urine . It is exclusively produced by renal epithelial cells and it plays key roles in kidney function and disease . Uromodulin mainly exerts its function as an extracellular matrix whose assembly depends on a conserved , specific proteolytic cleavage leading to conformati...	Several proteins in humans and other animals contain a region called a 'zona pellucida domain' . This domain enables these proteins to associate with each other and form long filaments . Uromodulin is one such protein that was first identified more than fifty years ago . This protein is known to play a role in human di...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "cell", "biology" ]	2015	The serine protease hepsin mediates urinary secretion and polymerisation of Zona Pellucida domain protein uromodulin
Tarantula toxins that bind to voltage-sensing domains of voltage-activated ion channels are thought to partition into the membrane and bind to the channel within the bilayer . While no structures of a voltage-sensor toxin bound to a channel have been solved , a structural homolog , psalmotoxin ( PcTx1 ) , was recently ...	Venomous animals like tarantulas or scorpions inject their prey with toxins to disable them . Some of these toxins work by altering the activity of proteins called ion channels , which are found within membranes in cells . These channels can allow potassium ions and/or other ions to pass through the membrane and have m...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics" ]	2015	Tarantula toxins use common surfaces for interacting with Kv and ASIC ion channels
Genome sequences diverge more rapidly in mammals than in other animal lineages , such as birds or insects . However , the effect of this rapid divergence on transcriptional evolution remains unclear . Recent reports have indicated a faster divergence of transcription factor binding in mammals than in insects , but othe...	The genetic information that makes each individual unique is encoded in DNA molecules . Cells read this molecular instruction manual by a process called transcription , in which proteins called transcription factors bind to DNA in specific places and regulate which sections of the DNA will be expressed . These 'transcr...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology", "short", "report", "computational", "and", "systems", "biology" ]	2015	Evidence for a common evolutionary rate in metazoan transcriptional networks
Genetic variants identified by genome-wide association studies explain only a modest proportion of heritability , suggesting that meaningful associations lie 'hidden' below current thresholds . Here , we integrate information from association studies with epigenomic maps to demonstrate that enhancers significantly over...	Most complex traits are governed by a large number of genetic contributors , each playing only a modest effect . This makes it difficult to identify the genetic variants that increase disease risk , hindering the discovery of new drug targets and the development of new therapeutics . To overcome this limitation in disc...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "genetics", "and", "genomics" ]	2016	Discovery and validation of sub-threshold genome-wide association study loci using epigenomic signatures
Resistance to targeted cancer therapies is an important clinical problem . The discovery of anti-resistance drug combinations is challenging as resistance can arise by diverse escape mechanisms . To address this challenge , we improved and applied the experimental-computational perturbation biology method . Using stati...	Drugs that target the activity of specific genes could potentially form precise cancer therapies . Some cancers , including the aggressive skin cancer called melanoma , initially respond well to such treatments . However , resistance to drugs develops quickly , leading to the rapid regrowth of the tumors . Resistance c...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "computational", "and", "systems", "biology" ]	2015	Perturbation biology nominates upstream–downstream drug combinations in RAF inhibitor resistant melanoma cells
Atoh1-null mice die at birth from respiratory failure , but the precise cause has remained elusive . Loss of Atoh1 from various components of the respiratory circuitry ( e . g . the retrotrapezoid nucleus ( RTN ) ) has so far produced at most 50% neonatal lethality . To identify other Atoh1-lineage neurons that contrib...	Breathing seems very simple: humans and other animals do it all the time without even thinking about it . Yet , many different cell types coordinate rhythmic breathing movements . Some cells set the breathing rhythm , motor neurons control the muscles , and other cells sense blood oxygen and carbon dioxide levels . Inf...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "neuroscience" ]	2018	Loss of Atoh1 from neurons regulating hypoxic and hypercapnic chemoresponses causes neonatal respiratory failure in mice
Paternal environmental conditions can influence phenotypes in future generations , but it is unclear whether offspring phenotypes represent specific responses to particular aspects of the paternal exposure history , or a generic response to paternal ‘quality of life’ . Here , we establish a paternal effect model based ...	Until recently , it seemed impossible that the conditions a person or animal experiences during their lifetime might affect the health of their offspring and future generations . Research over the past decade , however , has shown that a parent’s environment can cause changes that can be passed to future generations . ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression" ]	2017	Paternal nicotine exposure alters hepatic xenobiotic metabolism in offspring
Transcription activator-like effectors ( TALEs ) bind DNA through an array of tandem 34-residue repeats . How TALE repeat domains wrap around DNA , often extending more than 1 . 5 helical turns , without using external energy is not well understood . Here , we examine the kinetics of DNA binding of TALE arrays with var...	The DNA contains all the information needed to build an organism . It is made up of two strands that wind around each other like a twisted ladder to form the double helix . The strands consist of sugar and phosphate molecules , which attach to one of for bases . Genes are built from DNA , and contain specific sequences...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2019	Functional instability allows access to DNA in longer transcription Activator-Like effector (TALE) arrays
Distributed neural activity patterns are widely proposed to underlie object identification and categorization in the brain . In the olfactory domain , pattern-based representations of odor objects are encoded in piriform cortex . This region receives both afferent and associative inputs , though their relative contribu...	Imagine bringing your groceries home and tucking them into the refrigerator . You’ll probably organize the items by categories: lemons and oranges into the fruit drawer , carrots and cauliflower into the vegetable drawer . Categorization is essential , allowing us to interact with the world in the most efficient way po...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	The role of piriform associative connections in odor categorization
Mammalian visual behaviors , as well as responses in the neural systems underlying these behaviors , are driven by luminance and color contrast . With constantly improving tools for measuring activity in cell-type-specific populations in the mouse during visual behavior , it is important to define the extent of luminan...	Color is a key part of our visual experience . Humans can distinguish between colors thanks to light-sensitive cells at the back of the eye called cones . Our eyes contain three types of cones , most simply named red , green and blue . When light enters the eye , it activates each cone type to a different degree . The ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2018	Mouse color and wavelength-specific luminance contrast sensitivity are non-uniform across visual space
HIV replication requires nuclear export of unspliced and singly spliced viral transcripts . Although a unique RNA structure has been proposed for the Rev-response element ( RRE ) responsible for viral mRNA export , how it recruits multiple HIV Rev proteins to form an export complex has been unclear . We show here that ...	HIV is a virus that causes the immune system of an infected person to gradually fail , which can eventually result in AIDS . The virus consists of an RNA molecule—which encodes its genetic information—surrounded by coats of proteins . Once HIV enters a host cell , its RNA genome is converted into a DNA molecule , which...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2014	RNA-guided assembly of Rev-RRE nuclear export complexes
The mammalian circadian clock drives daily oscillations in physiology and behavior through an autoregulatory transcription feedback loop present in central and peripheral cells . Ablation of the core clock within the endocrine pancreas of adult animals impairs the transcription and splicing of genes involved in hormone...	Circadian rhythms – ‘inbuilt’ 24-hour cycles – control many aspects of behaviour and physiology . In mammals , they operate in nearly all tissues , including those involved in glucose metabolism . Recent studies have shown that mice with faulty genes involved in circadian rhythms , the core clock genes , can develop di...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2022	P2Y1 purinergic receptor identified as a diabetes target in a small-molecule screen to reverse circadian β-cell failure
Over the last 50 years , anatomical models of memory have repeatedly highlighted the hippocampal inputs to the mammillary bodies via the postcommissural fornix . Such models downplay other projections to the mammillary bodies , leaving them largely ignored . The present study challenged this dominant view by removing ,...	The hippocampus is a seahorse-shaped structure in the brain and its role in memory has been recognized since the 1950s . However , much less is known about two small structures called the mammillary bodies that are found near the hippocampus . These bodies are part of the limbic system—a network of brain regions that a...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2013	Dismantling the Papez circuit for memory in rats
A substantial fraction of the metazoan transcriptome undergoes circadian oscillations in many cells and tissues . Based on the transcription feedback loops important for circadian timekeeping , it is commonly assumed that this mRNA cycling reflects widespread transcriptional regulation . To address this issue , we dire...	Many biological processes oscillate with a period of roughly 24 hr , and the ability of organisms as diverse as bacteria and humans to maintain such circadian rhythms , even under conditions of continuous darkness , influences a range of phenomena , including sleep , migration and reproduction . One characteristic of c...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "genetics", "and", "genomics" ]	2012	Nascent-Seq reveals novel features of mouse circadian transcriptional regulation
The functional repertoire of surface ion channels is sustained by dynamic processes of trafficking , sorting , and degradation . Dysregulation of these processes underlies diverse ion channelopathies including cardiac arrhythmias and cystic fibrosis . Ubiquitination powerfully regulates multiple steps in the channel li...	Cells are surrounded by a membrane that separates the outside of the cell from its inside . Proteins called ion channels are embedded within this membrane and allow charged ions to move in and out of the cell . The movement of ions generates electrical currents that are essential for many processes that keep us alive ,...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "structural", "biology", "and", "molecular", "biophysics", "tools", "and", "resources" ]	2017	Sculpting ion channel functional expression with engineered ubiquitin ligases
We lack detailed knowledge about the spatio-temporal physiological signatures of REM sleep , especially in humans . By analyzing intracranial electrode data from humans , we demonstrate for the first time that there are prominent beta ( 15–35 Hz ) and theta ( 4–8 Hz ) oscillations in both the anterior cingulate cortex ...	Over the course of a night we cycle through several different stages of sleep . During one of these stages , our eyes move rapidly from side to side behind our closed eyelids . This movement gives this stage its name: rapid eye movement sleep , or REM sleep for short . Most other muscles are paralyzed during REM sleep ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2017	Frontal beta-theta network during REM sleep
Sleep deprivation has marked effects on food intake , shifting food choices toward energy-dense options . Here we test the hypothesis that neural processing in central olfactory circuits , in tandem with the endocannabinoid system ( ECS ) , plays a key role in mediating this relationship . We combined a partial sleep-d...	People who do not get enough sleep often start to favor sweet and fatty foods , which contributes to weight gain . While the exact mechanisms are still unknown , lack of sleep seems to change food preferences by influencing the levels of molecules that regulate food intake . In particular , it could have an effect on t...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2019	Olfactory connectivity mediates sleep-dependent food choices in humans
A major feature of embryogenesis is the specification of stem cell systems , but in contrast to the situation in most animals , plant stem cells remain quiescent until the postembryonic phase of development . Here , we dissect how light and metabolic signals are integrated to overcome stem cell dormancy at the shoot ap...	Plants are able to grow and develop throughout their lives thanks to groups of stem cells at the tips of their shoots and roots , which can constantly divide to produce new cells . Energy captured from sunlight during a process called photosynthesis is the main source of energy for most plants . Therefore , the amount ...	[ "Abstract", "Introduction", "Results", "Discussion", "Material", "and", "methods" ]	[ "plant", "biology", "developmental", "biology" ]	2016	Integration of light and metabolic signals for stem cell activation at the shoot apical meristem
The detection of foreign antigens in vivo has relied on fluorescent conjugation or indirect read-outs such as antigen presentation . In our studies , we found that these widely used techniques had several technical limitations that have precluded a complete picture of antigen trafficking or retention across lymph node ...	The lymphatic system is a network of ducts that transports fluid , proteins , and immune cells from different organs around the body . Lymph nodes provide pit stops at hundreds of points along this network where immune cells reside , and lymph fluid can be filtered and cleaned . When pathogens , such as viruses or bact...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "tools", "and", "resources", "immunology", "and", "inflammation" ]	2021	Molecular tracking devices quantify antigen distribution and archiving in the murine lymph node
As exome sequencing gives way to genome sequencing , the need to interpret the function of regulatory DNA becomes increasingly important . To test whether evolutionary conservation of cis-regulatory modules ( CRMs ) gives insight into human gene regulation , we determined transcription factor ( TF ) binding locations o...	Stretches of DNA called cis-regulatory modules ( or CRMs for short ) could help researchers to identify the regions of DNA that are most important for controlling genes . CRMs are regions where multiple transcription factors—proteins that control when and how genes are expressed—bind to DNA . As important biological pa...	[ "Abstract", "Introduction", "Results", "Discussion" ]	[ "genetics", "and", "genomics" ]	2014	Multi-species, multi-transcription factor binding highlights conserved control of tissue-specific biological pathways
Genomic sequencing has implicated large numbers of genes and de novo mutations as potential disease risk factors . A high throughput in vivo model system is needed to validate gene associations with pathology . We developed a Drosophila-based functional system to screen candidate disease genes identified from Congenita...	Around one in 100 children are born with heart defects caused by congenital heart disease . Studying the genetic sequences of people with congenital heart disease has revealed many genes that may play a role in causing the condition , but few of these findings have been confirmed experimentally in animal model systems ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2017	High throughput in vivo functional validation of candidate congenital heart disease genes in Drosophila
High-speed atomic force microscopy was employed to observe structural changes in actin filaments induced by cofilin binding . Consistent with previous electron and fluorescence microscopic studies , cofilin formed clusters along actin filaments , where the filaments were 2-nm thicker and the helical pitch was ∼25% shor...	Actin is one of the most abundant proteins found inside all eukaryotic cells including plant , animal , and fungal cells . This protein is involved in a wide range of biological processes that are essential for an organism's survival . Actin proteins form long filaments that help cells to maintain their shape and also ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2015	Cofilin-induced unidirectional cooperative conformational changes in actin filaments revealed by high-speed atomic force microscopy
Large social insect colonies exhibit a remarkable ability for recognizing group members via colony-specific cuticular pheromonal signatures . Previous work suggested that in some ant species , colony-specific pheromonal profiles are generated through a mechanism involving the transfer and homogenization of cuticular hy...	Honey bees are social insects that live in large groups called colonies , within structures known as hives . The young adult bees stay within the hive to build nests and care for the young , while the older bees leave the hive to forage for food . Honey bees store food and other valuable resources in their hives , so t...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "ecology" ]	2019	The cuticular hydrocarbon profiles of honey bee workers develop via a socially-modulated innate process
Caspase-3 carries out the executioner phase of apoptosis , however under special circumstances , cells can survive its activity . To document systematically where and when cells survive caspase-3 activation in vivo , we designed a system , CasExpress , which drives fluorescent protein expression , transiently or perman...	Every day , individual cells in our body actively decide whether to live or die . There are enzymes called executioner caspases that help cells to die in a carefully controlled process called apoptosis . Although the activation of executioner caspases generally leads to apoptosis , there are some circumstances in which...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "cell", "biology" ]	2016	CasExpress reveals widespread and diverse patterns of cell survival of caspase-3 activation during development in vivo
A number of TP53-MDM2 inhibitors are currently under investigation as therapeutic agents in a variety of clinical trials in patients with TP53 wild type tumors . Not all wild type TP53 tumors are sensitive to such inhibitors . In an attempt to improve selection of patients with TP53 wild type tumors , an mRNA expressio...	Damaged cells in the human body can develop into tumors if left unchecked . TP53 ( also called p53 ) is a protein that normally helps to repair or eliminate these damaged cells and prevent tumors from forming . About half of all cancerous tumors have mutations that prevent TP53 from working . In tumors with normal TP53...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "short", "report", "computational", "and", "systems", "biology", "cancer", "biology" ]	2015	Expression signature based on TP53 target genes doesn't predict response to TP53-MDM2 inhibitor in wild type TP53 tumors
Tau pathology first appears in the transentorhinal and anterolateral entorhinal cortex ( alEC ) in the aging brain . The transition to Alzheimer’s disease ( AD ) is hypothesized to involve amyloid-β ( Aβ ) facilitated tau spread through neural connections . We contrasted functional connectivity ( FC ) of alEC and poste...	The changes in the brain that cause Alzheimer's disease begin up to 25 years before the first symptoms appear . During this long incubation period , two proteins accumulate in brain tissue: amyloid-β and tau . Amyloid-β forms clumps known as plaques , while tau forms structures called tangles . But whereas amyloid plaq...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2019	Cortical tau deposition follows patterns of entorhinal functional connectivity in aging
Different types of neurons in the retina are organized vertically into layers and horizontally in a mosaic pattern that helps ensure proper neural network formation and information processing throughout the visual field . The vertebrate Dscams ( DSCAM and DSCAML1 ) are cell adhesion molecules that support the developme...	Neurons in a part of the eye called the retina detect light and convert it into electrical signals that are sent to the brain . Different types of neurons in the retina are arranged vertically into layers and horizontally in a mosaic pattern so that two neurons of the same type are not next to each other . To establish...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Replacing the PDZ-interacting C-termini of DSCAM and DSCAML1 with epitope tags causes different phenotypic severity in different cell populations
LINE-1 ( L1 ) retrotransposons represent approximately one sixth of the human genome , but only the human-specific L1HS-Ta subfamily acts as an endogenous mutagen in modern humans , reshaping both somatic and germline genomes . Due to their high levels of sequence identity and the existence of many polymorphic insertio...	Retrotransposons , also known as jumping genes , have invaded the genomes of most living organisms . These fragments of DNA have the ability to move or copy themselves from one location of a chromosome to another . Depending on where they insert themselves , retrotransposons can modify the sequence of nearby genes , wh...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "genetics", "and", "genomics" ]	2016	Activation of individual L1 retrotransposon instances is restricted to cell-type dependent permissive loci
Several genes positively influence final leaf size in Arabidopsis when mutated or overexpressed . The connections between these growth regulators are still poorly understood although such knowledge would further contribute to understand the processes driving leaf growth . In this study , we performed a combinatorial sc...	Different individuals of the same species are not usually identical . Humans , for example , have a range of different values for various traits , such as height and weight , and similar variations are seen in other animals and plants . Some of this variation can be explained by the individual animals or plants inherit...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology" ]	2014	Combining growth-promoting genes leads to positive epistasis in Arabidopsis thaliana
The delta-protocadherins ( δ-Pcdhs ) play key roles in neural development , and expression studies suggest they are expressed in combination within neurons . The extent of this combinatorial diversity , and how these combinations influence cell adhesion , is poorly understood . We show that individual mouse olfactory s...	Multicellular life depends on cells being able to stick together . The human body , for example , consists of trillions of cells grouped into tissues and organs . The brain alone contains some 87 billion neurons organized into complex networks . To stay together , cells use proteins on their surface called cell adhesio...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "neuroscience" ]	2018	Tuning of delta-protocadherin adhesion through combinatorial diversity
Initiation of transcription is a primary means for controlling gene expression . In bacteria , the RNA polymerase ( RNAP ) holoenzyme binds and unwinds promoter DNA , forming the transcription bubble of the open promoter complex ( RPo ) . We have determined crystal structures , refined to 4 . 14 Å-resolution , of RPo c...	Inside cells , molecules of double-stranded DNA encode the instructions needed to make proteins . To make a protein , the two strands of DNA that make up a gene are separated and one strand acts as a template to make molecules of messenger ribonucleic acid ( or mRNA for short ) . This process is called transcription . ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2015	Structure of a bacterial RNA polymerase holoenzyme open promoter complex
In animals , microtubules and centrosomes direct the migration of gamete pronuclei for fertilization . By contrast , flowering plants have lost essential components of the centrosome , raising the question of how flowering plants control gamete nuclei migration during fertilization . Here , we use Arabidopsis thaliana ...	Sexual reproduction involves combining the genetic material from two parents to create an offspring . The genetic material in the male sperm cell and the female egg cell is contained in the nucleus of each cell . Once these two cells fuse at fertilization , their nuclei must then navigate towards each other and fuse . ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology" ]	2014	Dynamic F-actin movement is essential for fertilization in Arabidopsis thaliana
Natural selection of variants within the Arabidopsis thaliana circadian clock can be attributed to adaptation to varying environments . To define a basis for such variation , we examined clock speed in a reporter-modified Bay-0 x Shakdara recombinant inbred line and localized heritable variation . Extensive variation l...	Life on Earth tends to follow a daily rhythm: some animals are awake during the day and asleep at night , whilst others are more active at night , or during the twilight around dawn and dusk . For many living things , these cycles of activity are driven by an internal body clock that helps the organism to adapt to the ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology", "cell", "biology" ]	2014	Natural variation reveals that intracellular distribution of ELF3 protein is associated with function in the circadian clock
Engineering light-sensitivity into proteins has wide ranging applications in molecular studies and neuroscience . Commonly used tethered photoswitchable ligands , however , require solvent-accessible protein labeling , face structural constrains , and are bulky . Here , we designed a set of optocontrollable NMDA recept...	Nerve cells communicate with each other by releasing chemicals , also known as neurotransmitters , from one cell to the next . Once released , these neurotransmitters bind to specific docking stations , called receptors , which are located on the surface of the neighboring cell . Due to changes in neurotransmitter rele...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "tools", "and", "resources", "neuroscience" ]	2017	Optocontrol of glutamate receptor activity by single side-chain photoisomerization
Numerous brain regions have been shown to have neural correlates of gradually accumulating evidence for decision-making , but the causal roles of these regions in decisions driven by accumulation of evidence have yet to be determined . Here , in rats performing an auditory evidence accumulation task , we inactivated th...	Imagine that you have to buy a computer before the start of the school year . You have a few options , such as a laptop or a desktop , each with its own advantages and disadvantages . A laptop is relatively light and portable , whereas a desktop has more memory and is cheaper . You will gradually accumulate evidence fo...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	Distinct effects of prefrontal and parietal cortex inactivations on an accumulation of evidence task in the rat

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