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By analyzing and simulating inactive conformations of the highly homologous dopamine D2 and D3 receptors ( D2R and D3R ) , we find that eticlopride binds D2R in a pose very similar to that in the D3R/eticlopride structure but incompatible with the D2R/risperidone structure . In addition , risperidone occupies a sub-poc...	Almost a third of prescribed drugs work by acting on a group of proteins known as GPCRs ( short for G-protein coupled receptors ) , which help to transmit messages across the cell’s outer barrier . The neurotransmitter dopamine , for instance , can act in the brain and body by attaching to dopamine receptors , a sub-fa...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2020	Distinct inactive conformations of the dopamine D2 and D3 receptors correspond to different extents of inverse agonism
Neoblasts are adult stem cells ( ASCs ) in planarians that sustain cell replacement during homeostasis and regeneration of any missing tissue . While numerous studies have examined genes underlying neoblast pluripotency , molecular pathways driving postmitotic fates remain poorly defined . In this study , we used trans...	Adult tissues constantly replace the millions of cells they lose on a daily basis . This is made possible by adult stem cells . But how is a stable population of stem cells maintained throughout the life of the organism with constant cell division ? One way this can be accomplished is if at every stem cell division , o...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "stem", "cells", "and", "regenerative", "medicine" ]	2015	A mex3 homolog is required for differentiation during planarian stem cell lineage development
Angiogenesis is coordinated by VEGF and Notch signaling . DLL4-induced Notch signaling inhibits tip cell formation and vessel branching . To ensure proper Notch signaling , receptors and ligands are clustered at adherens junctions . However , little is known about factors that control Notch activity by influencing the ...	Blood vessels transport oxygen and nutrients to all our organs and also remove waste products . New blood vessels form – in a process called angiogenesis – when a tissue is not receiving enough oxygen . This happens during normal development and wound healing , but also during tumor growth . Cells at the tip of a branc...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cancer", "biology" ]	2018	MPDZ promotes DLL4-induced Notch signaling during angiogenesis
MKLP2 , a kinesin-6 , has critical roles during the metaphase-anaphase transition and cytokinesis . Its motor domain contains conserved nucleotide binding motifs , but is divergent in sequence ( ~35% identity ) and size ( ~40% larger ) compared to other kinesins . Using cryo-electron microscopy and biophysical assays ,...	Cells constantly replicate to provide new cells for growing tissues , and to replace ageing or defective cells around the body . Each new cell needs a copy of the genetic material , and a cellular structure called the mitotic spindle makes sure that this material is shared correctly when a cell divides in two . The spi...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics" ]	2017	The divergent mitotic kinesin MKLP2 exhibits atypical structure and mechanochemistry
Rheumatoid arthritis ( RA ) is a prevalent systemic autoimmune disease , caused by a combination of genetic and environmental factors . Animal models suggest a role for intestinal bacteria in supporting the systemic immune response required for joint inflammation . Here we performed 16S sequencing on 114 stool samples ...	We share our bodies with a diverse set of microorganisms , known collectively as the human microbiome . Indeed , estimates suggest that our bodies contain 10 times as many microbial cells as human cells . Our stomach and intestines alone are home to many hundreds and possibly thousands of microbial species that break d...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "immunology", "and", "inflammation" ]	2013	Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis
The existence of abnormal connectivity patterns between resting state networks in neuropsychiatric disorders , including Autism Spectrum Disorder ( ASD ) , has been well established . Traditional treatment methods in ASD are limited , and do not address the aberrant network structure . Using real-time fMRI neurofeedbac...	Even when we are at rest , our brains are always active . For example , areas of the brain involved in vision remain active in complete darkness . Different brain regions that connect together to perform a given task often show coordinated activity at rest . Past studies have shown that these resting connections are di...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2017	Direct modulation of aberrant brain network connectivity through real-time NeuroFeedback
Extensive transcriptional alterations are observed in cancer , many of which activate core biological processes established in unicellular organisms or suppress differentiation pathways formed in metazoans . Through rigorous , integrative analysis of genomics data from a range of solid tumors , we show many transcripti...	Cancers arise when harmful changes happen in the genetic information of certain cells . These ‘mutations’ are different from person to person , but overall , they disrupt healthy cells in similar ways . In particular , cancer cells tend to lose features that help cells work together in the body . Researchers have sugge...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology", "cancer", "biology" ]	2019	Somatic mutations in early metazoan genes disrupt regulatory links between unicellular and multicellular genes in cancer
Early mouse development is accompanied by dynamic changes in chromatin modifications , including G9a-mediated histone H3 lysine 9 dimethylation ( H3K9me2 ) , which is essential for embryonic development . Here we show that genome-wide accumulation of H3K9me2 is crucial for postimplantation development , and coincides w...	The genome contains full instructions for the development of the whole organism . The genes within the genome encode for all the proteins , but specific genes are selected to be active at the appropriate time . For this reason , there are mechanisms that can turn the genes on and off as and when required . One such mec...	[ "Abstract", "Introduction", "Results", "Discussion" ]	[ "chromosomes", "and", "gene", "expression", "developmental", "biology" ]	2015	Chromatin dynamics and the role of G9a in gene regulation and enhancer silencing during early mouse development
Aicardi–Goutières syndrome ( AGS ) is a severe childhood inflammatory disorder that shows clinical and genetic overlap with systemic lupus erythematosus ( SLE ) . AGS is thought to arise from the accumulation of incompletely metabolized endogenous nucleic acid species owing to mutations in nucleic acid-degrading enzyme...	The immune system protects the body from attack by bacteria , viruses , and other microbes . A key feature of this system is the ability to discriminate between the body's own cells and potential foreign invaders . Occasionally , this process can go wrong and the immune system starts attacking its own tissues , which c...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "genetics", "and", "genomics" ]	2015	Genome-wide DNA hypomethylation and RNA:DNA hybrid accumulation in Aicardi–Goutières syndrome
We present a 3D-fluorescence imaging and classification tool for high throughput analysis of microbial eukaryotes in environmental samples . It entails high-content feature extraction that permits accurate automated taxonomic classification and quantitative data about organism ultrastructures and interactions . Using p...	Our planet’s ecosystems – from its oceans to its forests – are teeming with microbes . DNA analysis of environmental samples shows that many of these microbes belong to a group known as protists . This group consists of single-celled organisms that are close relatives of fungi , plants and animals . Though protists are...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "ecology", "cell", "biology", "tools", "and", "resources" ]	2017	Quantitative 3D-imaging for cell biology and ecology of environmental microbial eukaryotes
Type III CRISPR systems detect foreign RNA and activate the cyclase domain of the Cas10 subunit , generating cyclic oligoadenylate ( cOA ) molecules that act as a second messenger to signal infection , activating nucleases that degrade the nucleic acid of both invader and host . This can lead to dormancy or cell death;...	Bacteria protect themselves from infections using a system called CRISPR-Cas , which helps the cells to detect and destroy invading threats . The type III CRISPR-Cas system , in particular , is one of the most widespread and efficient at killing viruses . When a bacterium is infected , the CRISPR-Cas system takes a fra...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology" ]	2020	Tetramerisation of the CRISPR ring nuclease Crn3/Csx3 facilitates cyclic oligoadenylate cleavage
Aurora B kinase , a key regulator of cell division , localizes to specific cellular locations , but the regulatory mechanisms responsible for phosphorylation of substrates located remotely from kinase enrichment sites are unclear . Here , we provide evidence that this activity at a distance depends on both sites of hig...	Cell division is a highly organized process that involves a series of major changes . First , the cell’s chromosomes are copied and arranged at the middle of the cell . Then , the pairs of copied chromosomes are separated and pulled towards opposite ends of the cell and , finally , the cell splits in two . These steps ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "computational", "and", "systems", "biology" ]	2016	Bistability of a coupled Aurora B kinase-phosphatase system in cell division
It is currently unknown whether the molecular steps of large dense-core vesicle ( LDCV ) docking and priming are identical to the corresponding reactions in synaptic vesicle ( SV ) exocytosis . Munc13s are essential for SV docking and priming , and we systematically analyzed their role in LDCV exocytosis using chromaff...	Mammals have adrenal glands , which secrete the stress hormone adrenaline as well as other hormones into the bloodstream . These molecules are produced in chromaffin cells , where they are packaged into compartments called large dense-core vesicles ( LDCVs ) . To release the hormones into the bloodstream , the vesicles...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	Identification of a Munc13-sensitive step in chromaffin cell large dense-core vesicle exocytosis
The innervation of the mammary gland is controlled by brain-derived neurotrophic factor ( BDNF ) , and sexually dimorphic sequestering of BDNF by the truncated form of TrkB ( TrkB . T1 ) directs male-specific axonal pruning in mice . It is unknown whether other cues modulate these processes . We detected specific , non...	Almost every action an animal can perform in its life will rely on its nervous system being wired correctly . Before the animal is born , nerve cells next to the spinal cord send out long fibers – called axons – to connect with different parts of its body . These nerves will help relay sensations to the brain . The end...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2019	Balance between BDNF and Semaphorins gates the innervation of the mammary gland
Myelin is best known for its role in increasing the conduction velocity and metabolic efficiency of long-range excitatory axons . Accordingly , the myelin observed in neocortical gray matter is thought to mostly ensheath excitatory axons connecting to subcortical regions and distant cortical areas . Using independent a...	The brain is far away from the muscles that it controls . In humans , for example , the brain must be able to trigger the contraction of muscles that are more than a meter away . This task falls to specialized motor neurons that stretch from the brain to the spinal cord , and from the spinal cord to the muscles . Neuro...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	A large fraction of neocortical myelin ensheathes axons of local inhibitory neurons
Hair cells , the receptors of the inner ear , detect sounds by transducing mechanical vibrations into electrical signals . From the top surface of each hair cell protrudes a mechanical antenna , the hair bundle , which the cell uses to detect and amplify auditory stimuli , thus sharpening frequency selectivity and prov...	The sense of hearing relies on specialized sensory cells in the inner ear . Each of these hair cells converts sounds into electrical signals that the brain can interpret . The hair cell takes its name from the bundle of rod-like structures that protrude from its top surface , which resemble hairs under the microscope ....	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "physics", "of", "living", "systems", "tools", "and", "resources", "neuroscience" ]	2021	Rapid mechanical stimulation of inner-ear hair cells by photonic pressure
Tonic pain after injury characterises a behavioural state that prioritises recovery . Although generally suppressing cognition and attention , tonic pain needs to allow effective relief learning to reduce the cause of the pain . Here , we describe a central learning circuit that supports learning of relief and concurre...	Chronic pain lasting longer than three months is a common problem that affects about 1 in 5 people at some point in their lives . The lack of effective treatments has led to widespread use of a group of drugs called opioids – the best-known example is morphine . Opioids work by activating the brain’s natural painkillin...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2018	The control of tonic pain by active relief learning
Antimicrobial peptides ( AMPs ) are small cationic molecules best known as mediators of the innate defence against microbial infection . While in vitro and ex vivo evidence suggest AMPs’ capacity to kill cancer cells , in vivo demonstration of an anti-tumour role of endogenous AMPs is lacking . Using a Drosophila model...	Animals have a natural defence system – the immune system – that is needed to fight off disease-causing microbes , known as pathogens . One way the immune system attacks pathogens is by producing small microbe-killing molecules called antimicrobial peptides . These antimicrobial peptides carry a positive charge , which...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "cancer", "biology" ]	2019	The antimicrobial peptide defensin cooperates with tumour necrosis factor to drive tumour cell death in Drosophila
Memory reconsolidation is a fundamental plasticity process in the brain that allows established memories to be changed or erased . However , certain boundary conditions limit the parameters under which memories can be made plastic . Strong memories do not destabilize , for instance , although why they are resilient is ...	New memories must go through a period of consolidation to become stable and long-lasting in the brain . Recalling memories can make them unstable again , so that they need reconsolidating . Treatments in which the reconsolidation process is interrupted have been used to help weaken traumatic fear memories . However , m...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2020	Noradrenergic projections from the locus coeruleus to the amygdala constrain fear memory reconsolidation
The amyloid precursor protein ( APP ) , whose mutations cause familial Alzheimer’s disease , interacts with the synaptic release machinery , suggesting a role in neurotransmission . Here we mapped this interaction to the NH2-terminal region of the APP intracellular domain . A peptide encompassing this binding domain -n...	Alzheimer’s disease has been linked to mutations in a gene encoding the amyloid precursor protein ( APP ) . Mutations in this gene cause early onset Alzheimer’s disease in some families . Studies in animals suggest this mutant form of the protein may interfere with the messages sent between brain cells . But it remains...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	APP and APLP2 interact with the synaptic release machinery and facilitate transmitter release at hippocampal synapses
The activity of sensory neural populations carries information about the environment . This may be extracted from neural activity using different strategies . In the auditory brainstem , a recent theory proposes that sound location in the horizontal plane is decoded from the relative summed activity of two populations ...	Having two ears allows animals to localize the source of a sound . For example , barn owls can snatch their prey in complete darkness by relying on sound alone . It has been known for a long time that this ability depends on tiny differences in the sounds that arrive at each ear , including differences in the time of a...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2013	Decoding neural responses to temporal cues for sound localization
Motor skill learning is characterized by improved performance and reduced motor variability . The neural mechanisms that couple skill level and variability , however , are not known . The zebra finch , a songbird , presents a unique opportunity to address this question because production of learned song and induction o...	‘Practice makes perfect’ captures the essence of how we learn new skills . When learning to play a musical instrument , for example , it often takes hours of practice before we can play a single piece of music properly for the first time . And as we get better , the variability in our performance—which is an advantage ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2014	A neural circuit mechanism for regulating vocal variability during song learning in zebra finches
A network of brain regions have been linked with episodic memory retrieval , but limited progress has been made in identifying the contributions of distinct parts of the network . Here , we utilized continuous measures of retrieval to dissociate three components of episodic memory: retrieval success , precision , and v...	Remembering is something we do countless times each day . The detail and vividness with which we can remember is part of what makes memories so precious . Given the significance and complexity of memories , it is perhaps unsurprising that several parts of the brain are needed for us to experience them . Indeed , the br...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Distinct neural mechanisms underlie the success, precision, and vividness of episodic memory
Flexibility in the bilateral coordination of muscle contraction underpins variable locomotor movements or gaits . While the locomotor rhythm is generated by ipsilateral excitatory interneurons , less is known about the commissural excitatory interneurons . Here we examined how the activity of the V0v interneurons – an ...	During movements such as swimming and walking , the left and right sides of the body are kept coordinated by specific neurons in the spinal cord . Some of these neurons – called V0 neurons – can either excite or inhibit neurons on the opposite side of the spinal cord . In mice , the inhibitory V0 neurons are responsibl...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Functional diversity of excitatory commissural interneurons in adult zebrafish
Polarised mRNA transport is a prevalent mechanism for spatial control of protein synthesis . However , the composition of transported ribonucleoprotein particles ( RNPs ) and the regulation of their movement are poorly understood . We have reconstituted microtubule minus end-directed transport of mRNAs using purified c...	In our cells , tiny molecular motors transport the components necessary for life’s biological processes from one location to another . They do so by loading their cargo , and burning up chemical fuel to carry it along pathways made of filaments . For example , one such motor , called dynein , can move molecules of mess...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2018	RNA-directed activation of cytoplasmic dynein-1 in reconstituted transport RNPs
Skeletal integrity is maintained by the co-ordinated activity of osteoblasts , the bone-forming cells , and osteoclasts , the bone-resorbing cells . In this study , we show that mice overexpressing galectin-8 , a secreted mammalian lectin of the galectins family , exhibit accelerated osteoclasts activity and bone turno...	The forces applied to the body during daily activities cause bones to be constantly remodeled , which is essential for keeping them healthy . In most adult organisms , new bone is created at the same rate at which old bone is destroyed . This means that overall bone mass remains the same . But , in diseases such as ost...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2015	The mammalian lectin galectin-8 induces RANKL expression, osteoclastogenesis, and bone mass reduction in mice
The transcriptional coactivator Yes-associated protein ( Yap ) promotes proliferation and inhibits apoptosis , suggesting that Yap functions as an oncogene . Most oncogenes , however , require a combination of at least two signals to promote proliferation . In this study , we present evidence that Yap activation is ins...	As we grow up , the organs in our body tend to stop growing and then remain roughly the same size for the rest of our lives . This is possible because of control systems that determine how often the cells within the organ can divide and when they should die . If these controls fail , the cells may divide rapidly and no...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2015	Two-signal requirement for growth-promoting function of Yap in hepatocytes
Fields as diverse as human genetics and sociology are increasingly using polygenic scores based on genome-wide association studies ( GWAS ) for phenotypic prediction . However , recent work has shown that polygenic scores have limited portability across groups of different genetic ancestries , restricting the contexts ...	Complex diseases like cancer and heart disease are caused by the interplay of many factors: the variants of genes we inherit , the lifestyles we lead and the environments we inhabit , plus the interaction of all these factors . In fact , almost every trait , even how many years we will spend studying , is influenced bo...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "genetics", "and", "genomics" ]	2020	Variable prediction accuracy of polygenic scores within an ancestry group
Little is known about the density and function of dendritic spines on midbrain dopamine neurons , or the relative contribution of spine and shaft synapses to excitability . Using Ca2+ imaging , glutamate uncaging , fluorescence recovery after photobleaching and transgenic mice expressing labeled PSD-95 , we comparative...	When a nerve cell is viewed under the microscope , its structure looks a little like that of a tree . Each nerve cell , or neuron , has an array of ‘branches’ known as dendrites , which receive chemical messages from other cells . These messages are converted into electrical signals in the cell body and then travel dow...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Electrical and Ca2+ signaling in dendritic spines of substantia nigra dopaminergic neurons
The cell decision between lytic and lysogenic infection is strongly influenced by dynamics of DNA injection into a cell from a phage population , as phages compete for limited resources and progeny . However , what controls the timing of viral DNA ejection events was not understood . This in vitro study reveals that DN...	Viruses are tiny ‘parasites’ that smuggle their genetic material inside a cell and then hijack its resources for their own benefit . A viral infection can either be lytic or latent . In a lytic cycle , viruses make their host produce many copies of themselves , ultimately killing the cell . In contrast , during a laten...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics", "microbiology", "and", "infectious", "disease" ]	2018	The mobility of packaged phage genome controls ejection dynamics
The success of fMRI places constraints on the nature of the neural code . The fact that researchers can infer similarities between neural representations , despite fMRI’s limitations , implies that certain neural coding schemes are more likely than others . For fMRI to succeed given its low temporal and spatial resolut...	We can appreciate that a cat is more similar to a dog than to a truck . The combined activity of millions of neurons in the brain somehow captures these everyday similarities , and this activity can be measured using imaging techniques such as functional magnetic resonance imaging ( fMRI ) . However , fMRI scanners are...	[ "Abstract", "Introduction", "Smoothness", "and", "the", "neural", "code", "Model", "Deep", "learning", "networks", "Discussion" ]	[ "neuroscience" ]	2017	What the success of brain imaging implies about the neural code
The adaptive prokaryotic immune system CRISPR-Cas provides RNA-mediated protection from invading genetic elements . The fundamental basis of the system is the ability to capture small pieces of foreign DNA for incorporation into the genome at the CRISPR locus , a process known as Adaptation , which is dependent on the ...	In most animals , the adaptive immune system creates specialized cells that adapt to efficiently fight off any viruses or other pathogens that have invaded . Bacteria ( and another group of single-celled organisms called archaea ) also have an adaptive immune system , known as CRISPR-Cas , that combats viral invaders ....	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology" ]	2015	Intrinsic sequence specificity of the Cas1 integrase directs new spacer acquisition
The Spike protein of SARS-CoV-2 , its receptor-binding domain ( RBD ) , and its primary receptor ACE2 are extensively glycosylated . The impact of this post-translational modification on viral entry is yet unestablished . We expressed different glycoforms of the Spike-protein and ACE2 in CRISPR-Cas9 glycoengineered cel...	COVID-19 is an infectious disease caused by the virus SARS-CoV-2 . To access the internal machinery necessary for its replication , the virus needs to latch onto and then enter host cells . Such processes rely on specific ‘glycoproteins’ that carry complex sugar molecules ( or glycans ) , and can be found at the surfac...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "microbiology", "and", "infectious", "disease" ]	2020	Inhibition of SARS-CoV-2 viral entry upon blocking N- and O-glycan elaboration
Virus assembly and maturation proceed through the programmed operation of molecular switches , which trigger both local and global structural rearrangements to produce infectious particles . HIV-1 contains an assembly and maturation switch that spans the C-terminal domain ( CTD ) of the capsid ( CA ) region and the fir...	Viruses like HIV must undergo a process called maturation in order to successfully infect cells . Maturation involves a dramatic rearrangement in the architecture of the virus . That is to say , the virus’s internal protein coat – called the capsid – must change from an immature sphere into a mature cone-shaped coat . ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2016	Crystal structure of an HIV assembly and maturation switch
The function of a neural circuit is shaped by the computations performed by its interneurons , which in many cases are not easily accessible to experimental investigation . Here , we elucidate the transformation of visual signals flowing from the input to the output of the primate retina , using a combination of large-...	Light that enters the eye begins the process of vision by activating two types of photoreceptors: rods , which support vision under low light levels , and cones , which are responsible for fine detail and color vision . Activation of either type of photoreceptor triggers responses in bipolar cells , which activate the ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology", "neuroscience" ]	2015	Mapping nonlinear receptive field structure in primate retina at single cone resolution
Besides cardiomyocytes ( CM ) , the heart contains numerous interstitial cell types which play key roles in heart repair , regeneration and disease , including fibroblast , vascular and immune cells . However , a comprehensive understanding of this interactive cell community is lacking . We performed single-cell RNA-se...	In our bodies , heart attacks lead to cell death and inflammation . This is then followed by a healing phase where the organ repairs itself . There are many types of heart cells , from muscle and pacemaker cells that help to create the beating motion , to so-called fibroblasts that act as a supporting network . Yet , i...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "computational", "and", "systems", "biology" ]	2019	Single-cell expression profiling reveals dynamic flux of cardiac stromal, vascular and immune cells in health and injury
There is currently a need for proxy measures of the HIV rebound competent reservoir ( RCR ) that can predict viral rebound after combined antiretroviral treatment ( cART ) interruption . In this study , macaques infected with a barcoded SIVmac239 virus received cART beginning between 4- and 27 days post-infection , lea...	Several drugs are available to control HIV , but they do not completely eliminate the virus from the body . Instead , these treatments stop the virus from multiplying , but unless a person is treated very soon after infection , inactive HIV can hide inside cells , and the infection is not completely cleared . Once trea...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "microbiology", "and", "infectious", "disease" ]	2019	Predictors of SIV recrudescence following antiretroviral treatment interruption
Like many behaviors , Caenorhabditis elegans egg laying alternates between inactive and active states . To understand how the underlying neural circuit turns the behavior on and off , we optically recorded circuit activity in behaving animals while manipulating circuit function using mutations , optogenetics , and drug...	It has been said that if the human brain were so simple that we could understand it , we would be so simple that we couldn’t . This quote neatly captures the challenge of working out how 80 billion neurons collectively generate our thoughts and behavior . Fortunately , the nervous system is also organized into simpler ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Activity of the C. elegans egg-laying behavior circuit is controlled by competing activation and feedback inhibition
Microbial communities feature an immense diversity of species and this diversity is linked to outcomes ranging from ecosystem stability to medical prognoses . Yet the mechanisms underlying microbial diversity are under debate . While simple resource-competition models don't allow for coexistence of a large number of sp...	In most environments , organisms compete for limited resources . The number and relative abundance of species that an ecosystem can host is referred to as ‘species diversity’ . The competitive-exclusion principle is a hypothesis which proposes that , in an ecosystem , competition for resources results in decreased dive...	[ "Abstract", "Introduction", "Results", "Discussion" ]	[ "ecology", "physics", "of", "living", "systems" ]	2020	Nutrient levels and trade-offs control diversity in a serial dilution ecosystem
Restoration of touch after hand amputation is a desirable feature of ideal prostheses . Here , we show that texture discrimination can be artificially provided in human subjects by implementing a neuromorphic real-time mechano-neuro-transduction ( MNT ) , which emulates to some extent the firing dynamics of SA1 cutaneo...	Our hands provide us with a wide variety of information about our surroundings , enabling us to detect pain , temperature and pressure . Our sense of touch also allows us to interact with objects by feeling their texture and solidity . However , completely reproducing a sense of touch in artificial or prosthetic hands ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Intraneural stimulation elicits discrimination of textural features by artificial fingertip in intact and amputee humans
Superfast muscles ( SFMs ) are extremely fast synchronous muscles capable of contraction rates up to 250 Hz , enabling precise motor execution at the millisecond time scale . SFM phenotypes have been discovered in most major vertebrate lineages , but it remains unknown whether all SFMs share excitation-contraction coup...	Across animals , different muscle types have evolved to perform vastly different tasks at different speeds . For example , tortoise leg muscles move slowly over several seconds , while the flight muscles of a hummingbird move quickly dozens of times per second . The speed record holders among vertebrates are the so-cal...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics", "neuroscience" ]	2017	Fundamental constraints in synchronous muscle limit superfast motor control in vertebrates
Multicellular organisms evolved via repeated functional divergence of transcriptionally related sister cell types , but the mechanisms underlying sister cell type divergence are not well understood . Here , we study a canonical pair of sister cell types , retinal photoreceptors and bipolar cells , to identify the key c...	Humans see the world through a light-sensitive tissue at the back of the eye called the retina , which is made up of three layers that each contain specific cell types . The layers form a circuit , with light-sensing photoreceptor cells in the outermost layer connected to bipolar cells in the middle layer , which conne...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "genetics", "and", "genomics" ]	2019	Cis-regulatory basis of sister cell type divergence in the vertebrate retina
The current epidemic of artemisinin resistant Plasmodium falciparum in Southeast Asia is the result of a soft selective sweep involving at least 20 independent kelch13 mutations . In a large global survey , we find that kelch13 mutations which cause resistance in Southeast Asia are present at low frequency in Africa . ...	Malaria is an infectious disease caused by a microscopic parasite called Plasmodium , which is transferred between humans by mosquitos . One species of malaria parasite called Plasmodium falciparum can cause particularly severe and life-threatening forms of the disease . Currently , the most widely used treatment for P...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "epidemiology", "and", "global", "health", "microbiology", "and", "infectious", "disease" ]	2016	Genomic epidemiology of artemisinin resistant malaria
The basal ganglia are known to be involved in the planning , execution and control of gripping force and movement vigour . Here we aim to define the nature of the basal ganglia control signal for force and to decode gripping force based on local field potential ( LFP ) activities recorded from the subthalamic nucleus (...	The basal ganglia are a group of structures deep within the brain . Alongside its many other roles , it is thought to be able to control the vigour of movements , including how quickly we move and how much force we use to grip objects . Some of the best evidence for this comes from patients with Parkinson’s disease , w...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Decoding gripping force based on local field potentials recorded from subthalamic nucleus in humans
Proteolytic cleavage and release from the cell surface of membrane-tethered ligands is an important mechanism of regulating intercellular signalling . TACE is a major shedding protease , responsible for the liberation of the inflammatory cytokine TNFα and ligands of the epidermal growth factor receptor . iRhoms , catal...	Injury or infection can cause tissues in the body to become inflamed . The immune system triggers this inflammation to help repair the injury or fight the infection . A signal molecule known as TNF – which is produced by immune cells called macrophages – triggers inflammation . This protein is normally attached to the ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "cell", "biology" ]	2017	Phosphorylation of iRhom2 at the plasma membrane controls mammalian TACE-dependent inflammatory and growth factor signalling
Deep-sea anglerfishes are relatively abundant and diverse , but their luminescent bacterial symbionts remain enigmatic . The genomes of two symbiont species have qualities common to vertically transmitted , host-dependent bacteria . However , a number of traits suggest that these symbionts may be environmentally acquir...	The deep sea is home to many different species of anglerfish , a group of animals in which females often display a dangling lure on the top of their heads . This organ shelters bacteria that make light , a partnership ( known as symbiosis ) that benefits both parties . The bacteria get a safe environment in which to gr...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "ecology", "evolutionary", "biology" ]	2019	Diverse deep-sea anglerfishes share a genetically reduced luminous symbiont that is acquired from the environment
Thermodynamic models of gene regulation can predict transcriptional regulation in bacteria , but in eukaryotes , chromatin accessibility and energy expenditure may call for a different framework . Here , we systematically tested the predictive power of models of DNA accessibility based on the Monod-Wyman-Changeux ( MWC...	Cells in the brain , liver and skin , as well as many other organs , all contain the same DNA , yet behave in very different ways . This is because before a gene can produce its corresponding protein , it must first be transcribed into messenger RNA . As an organism grows , the transcription of certain genes is switche...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "physics", "of", "living", "systems" ]	2020	Quantitative dissection of transcription in development yields evidence for transcription-factor-driven chromatin accessibility
Cannabinoid type one receptor ( CB1R ) is only stably surface expressed in axons , where it downregulates neurotransmitter release . How this tightly regulated axonal surface polarity is established and maintained is unclear . To address this question , we used time-resolved imaging to determine the trafficking of CB1R...	The brain contains around 100 billion neurons that are in constant communication with one another . Each consists of a cell body , plus two components specialized for exchanging information . These are the axon , which delivers information , and the dendrites , which receive it . This exchange takes place at contact po...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2019	The C-terminal helix 9 motif in rat cannabinoid receptor type 1 regulates axonal trafficking and surface expression
How generalist parasites with wide host ranges can evolve is a central question in parasite evolution . Albugo candida is an obligate biotrophic parasite that consists of many physiological races that each specialize on distinct Brassicaceae host species . By analyzing genome sequence assemblies of five isolates , we s...	Many microorganisms live as parasites inside another living organism , and gain nutrients at their host's expense . Plants and animals have immune systems that serve to protect against this kind of exploitation , but successful parasites have evolved ways to avoid detection by their hosts' immune systems , and/or to su...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology", "genetics", "and", "genomics" ]	2015	Evidence for suppression of immunity as a driver for genomic introgressions and host range expansion in races of Albugo candida, a generalist parasite
The mechanism for Myc-induced genetic instability is not well understood . Here we show that sublethal activation of Caspase-3 plays an essential , facilitative role in Myc-induced genomic instability and oncogenic transformation . Overexpression of Myc resulted in increased numbers of chromosome aberrations and γH2AX ...	Healthy cells can become cancerous if their DNA is damaged and not repaired properly , leading to changes in the DNA known as mutations . The cells tend to accumulate more and more mutations – a phenomenon known as genomic instability – as they transition into cancer cells . A protein called Myc is known to promote gen...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "cancer", "biology" ]	2017	Essential roles of Caspase-3 in facilitating Myc-induced genetic instability and carcinogenesis
As countries in the Greater Mekong Sub-region ( GMS ) increasingly focus their malaria control and elimination efforts on reducing forest-related transmission , greater understanding of the relationship between deforestation and malaria incidence will be essential for programs to assess and meet their 2030 elimination ...	Biting mosquitos spread the malaria parasite to humans . Along the Mekong River in Southeast Asia , spending time in the surrounding forest increases a person's risk of malaria . This has led to a debate about whether deforestation in this area , which is called the Greater Mekong Sub-region ( GMS ) , will increase or ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "epidemiology", "and", "global", "health" ]	2021	Spatio-temporal associations between deforestation and malaria incidence in Lao PDR
Multisite modification is a basic way of conferring functionality to proteins and a key component of post-translational modification networks . Additional interest in multisite modification stems from its capability of acting as complex information processors . In this paper , we connect two seemingly disparate themes:...	Proteins help our cells perform the chemical reactions necessary for life . Once proteins are made , they can also be modified in different ways . This can simply change their activity , or otherwise make them better suited for their specific jobs within the cell . Biological ‘catalysts’ called enzymes carry out protei...	[ "Abstract", "Introduction", "Results", "Discussion" ]	[ "physics", "of", "living", "systems" ]	2021	Symmetry breaking meets multisite modification
Fluctuations in organelle abundance can profoundly limit the precision of cell biological processes from secretion to metabolism . We modeled the dynamics of organelle biogenesis and predicted that organelle abundance fluctuations depend strongly on the specific mechanisms that increase or decrease the number of a give...	Any cell that has a nucleus also contains various other organelles , such as the mitochondria that generate energy inside the cells . Like the nucleus , most of these organelles are enclosed within a membrane . Unlike the nucleus , however , there can be two or more copies of other types of organelles in a healthy cell...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2014	Mechanisms of organelle biogenesis govern stochastic fluctuations in organelle abundance
About 60% of emerging infectious diseases in humans are of zoonotic origin . Their increasing number requires the development of new methods for early detection and monitoring of infectious agents in wildlife . Here , we investigated whether blood meals from hematophagous flies could be used to identify the infectious ...	About 60% of new infectious diseases in humans come from animals . Their increasing number and rapid spread are linked to increasing levels of contact between humans and wildlife , as recently highlighted by the epidemics of Zika in Brazil or Ebola in West Africa . To anticipate and prevent similar outbreaks in the fut...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "ecology", "epidemiology", "and", "global", "health", "tools", "and", "resources" ]	2017	Tracking zoonotic pathogens using blood-sucking flies as 'flying syringes'
Voltage-gated ion channels mediate electrical dynamics in excitable tissues and are an important class of drug targets . Channels can gate in sub-millisecond timescales , show complex manifolds of conformational states , and often show state-dependent pharmacology . Mechanistic studies of ion channels typically involve...	Ion channels are specialized proteins that span the cell membrane . When activated , these channels allow ions to pass through them , which can produce electrical spikes that carry information in nerve cells and regulate the beating of the heart . Researchers interested in understanding how ion channels behave often us...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "tools", "and", "resources", "neuroscience" ]	2016	Optical electrophysiology for probing function and pharmacology of voltage-gated ion channels
Rod and cone photoreceptors are coupled by gap junctions ( GJs ) , relatively large channels able to mediate both electrical and molecular communication . Despite their critical location in our visual system and evidence that they are dynamically gated for dark/light adaptation , the full impact that rod–cone GJs can h...	People can see in a range of light levels—from dim moonlight to bright midday sun—because our eyes contain two types of light-sensitive cells: rods and cones . Rods are more plentiful than cones , and while they are sensitive at low light levels , rods can only provide grey-scale vision . Further , bright light can rap...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2014	Mouse rods signal through gap junctions with cones
Comparative genomics studies in primates are restricted due to our limited access to samples . In order to gain better insight into the genetic processes that underlie variation in complex phenotypes in primates , we must have access to faithful model systems for a wide range of cell types . To facilitate this , we gen...	Comparing the genomes of different species can reveal how they are related to one another . Such comparative studies can also reveal how genomes are modified in species-specific ways to regulate gene activity . The genomes of humans and chimpanzees are very similar in sequence . It is therefore likely that differing pa...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "stem", "cells", "and", "regenerative", "medicine", "tools", "and", "resources", "genetics", "and", "genomics" ]	2015	A panel of induced pluripotent stem cells from chimpanzees: a resource for comparative functional genomics
Early life adversity can affect an individual’s health , survival , and fertility for many years after the adverse experience . Whether early life adversity also imposes intergenerational effects on the exposed individual’s offspring is not well understood . We fill this gap by leveraging prospective , longitudinal dat...	Experiences early in life can have lasting effects on the health and survival of humans and other creatures . Whether early hardships can also influence the wellbeing of the next generation is less clear . One previous study with captive hamsters suggested that adversity early in the life of a mother may indeed shorten...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "ecology", "evolutionary", "biology" ]	2019	Intergenerational effects of early adversity on survival in wild baboons
Biophysical mechanisms underlying collective cell migration of eukaryotic cells have been studied extensively in recent years . One mechanism that induces cells to correlate their motions is contact inhibition of locomotion , by which cells migrating away from the contact site . Here , we report that tail-following beh...	The cells of animals and many other living things are able to migrate together in groups . This collective cell migration plays crucial roles in many processes in animals such as forming organs and limbs , and healing wounds . A soil-dwelling amoeba called Dictyostelium discoideum – or just Dicty for short – is commonl...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "physics", "of", "living", "systems" ]	2020	Polar pattern formation induced by contact following locomotion in a multicellular system
Cell fate decisions are critical for life , yet little is known about how their reliability is achieved when signals are noisy and fluctuating with time . In this study , we show that in budding yeast , the decision of cell cycle commitment ( Start ) is determined by the time integration of its triggering signal Cln3 ....	Budding yeast and other single-celled organisms can reproduce by dividing to produce two daughter cells . The timing of the cell division is critical because if the cell is still small when it divides , the resulting daughter cells may not be big enough to survive . In budding yeast , the irreversible decision to divid...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2015	Reliable cell cycle commitment in budding yeast is ensured by signal integration
Nuclear Pore Complexes ( NPCs ) are key cellular transporter that control nucleocytoplasmic transport in eukaryotic cells , but its transport mechanism is still not understood . The centerpiece of NPC transport is the assembly of intrinsically disordered polypeptides , known as FG nucleoporins , lining its passageway ....	Animal , plant and fungal cells contain a structure called the nucleus , inside which the genetic material of the cell is stored . For the cell to work properly , certain proteins and other molecules need to be able to enter and exit the nucleus . This transport is carried out by pore-like molecular “devices” known as ...	[ "Abstract", "Introduction", "Mathematical", "model", "Results", "Discussion" ]	[ "physics", "of", "living", "systems", "computational", "and", "systems", "biology" ]	2016	Simple biophysics underpins collective conformations of the intrinsically disordered proteins of the Nuclear Pore Complex
Humans perform saccadic eye movements two to three times per second . When doing so , the nervous system strongly suppresses sensory feedback for extended periods of time in comparison to movement time . Why does the brain discard so much visual information ? Here we suggest that perceptual suppression may arise from e...	Although we have the impression that our eyes move smoothly from place to place , we in fact perform rapid eye movements called saccades several times per second . Experiments have shown that our ability to perceive contrast and flashes decreases before and during each saccade . This phenomenon is known as saccadic sup...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology", "neuroscience" ]	2017	Saccadic suppression as a perceptual consequence of efficient sensorimotor estimation
Chunking is a key mechanism for sequence processing . Studies on speech sequences have suggested low-frequency cortical activity tracks spoken phrases , that is , chunks of words defined by tacit linguistic knowledge . Here , we investigate whether low-frequency cortical activity reflects a general mechanism for sequen...	From digital personal assistants like Siri and Alexa to customer service chatbots , computers are slowly learning to talk to us . But as anyone who has interacted with them will appreciate , the results are often imperfect . Each time we speak or write , we use grammatical rules to combine words in a specific order . T...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2020	Low-frequency neural activity reflects rule-based chunking during speech listening
TRPV1 channels in sensory neurons are integrators of painful stimuli and heat , yet how they integrate diverse stimuli and sense temperature remains elusive . Here , we show that external sodium ions stabilize the TRPV1 channel in a closed state , such that removing the external ion leads to channel activation . In stu...	Humans and other mammals sense elevated heat and other painful stimuli via a sensory ion channel protein called TRPV1 . Ion channels create pores in the outer membrane of cells and act as gates that open and close to regulate the flow of ions into and out of cells . This flow of ions generates electrical signals that s...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics" ]	2016	An external sodium ion binding site controls allosteric gating in TRPV1 channels
In contrast to the complex acoustic environments we encounter everyday , most studies of auditory segregation have used relatively simple signals . Here , we synthesized a new stimulus to examine the detection of coherent patterns ( ‘figures’ ) from overlapping ‘background’ signals . In a series of experiments , we dem...	Even when seated in the middle of a crowded restaurant , we are still able to distinguish the speech of the person sitting opposite us from the conversations of fellow diners and a host of other background noise . While we generally perform this task almost effortlessly , it is unclear how the brain solves what is in r...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2013	Segregation of complex acoustic scenes based on temporal coherence
The swimming larvae of many marine animals identify a location on the sea floor to undergo metamorphosis based on the presence of specific bacteria . Although this microbe–animal interaction is critical for the life cycles of diverse marine animals , what types of biochemical cues from bacteria that induce metamorphosi...	Many marine animals , including corals and tubeworms , begin life as larvae swimming in open water before transforming into adults that anchor themselves to the seabed . These transformations , known as metamorphoses , are often triggered by certain types of bacteria that form friendly relationships ( or “symbioses” ) ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "short", "report", "structural", "biology", "and", "molecular", "biophysics", "microbiology", "and", "infectious", "disease" ]	2019	A contractile injection system stimulates tubeworm metamorphosis by translocating a proteinaceous effector
3D imaging data necessitate 3D reference atlases for accurate quantitative interpretation . Existing computational methods to generate 3D atlases from 2D-derived atlases result in extensive artifacts , while manual curation approaches are labor-intensive . We present a computational approach for 3D atlas construction t...	The research community needs precise , reliable 3D atlases of organs to pinpoint where biological structures and processes are located . For instance , these maps are essential to understand where specific genes are turned on or off , or the spatial organization of various groups of cells over time . For centuries , at...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology", "developmental", "biology", "tools", "and", "resources" ]	2021	Constructing and optimizing 3D atlases from 2D data with application to the developing mouse brain
Animals have a carefully orchestrated relationship with oxygen . When exposed to low environmental oxygen concentrations , and during periods of increased energy expenditure , animals maintain cellular oxygen homeostasis by enhancing internal oxygen delivery , and by enabling the anaerobic production of ATP . These low...	Almost all animals need oxygen to live . This is because they use oxygen to release much of the energy locked up in their diets . Oxygen may have also played a crucial role in the early evolution of animal life . Animals evolved from single-celled ancestors in the ocean over 800 million years ago . Before then , it is ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology" ]	2018	The last common ancestor of animals lacked the HIF pathway and respired in low-oxygen environments
The RhoGTPases are characterized as membrane-associated molecular switches that cycle between active , GTP-bound and inactive , GDP-bound states . However , 90–95% of RhoGTPases are maintained in a soluble form by RhoGDI , which is generally viewed as a passive shuttle for inactive RhoGTPases . Our current understandin...	Organisms rely on many signaling molecules to control how their cells grow , divide and heal . For example , when the cell membrane is damaged , two signaling proteins , Rho and Cdc42 , are recruited to wounds and activated to promote repair . Active Rho and active Cdc42 form two concentric rings at the membrane to dir...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "cell", "biology" ]	2019	Extraction of active RhoGTPases by RhoGDI regulates spatiotemporal patterning of RhoGTPases
The microtubule ( MT ) -associated motor protein kinesin utilizes its conserved ATPase head to achieve diverse motility characteristics . Despite considerable knowledge about how its ATPase activity and MT binding are coupled to the motility cycle , the atomic mechanism of the core events remain to be found . To obtain...	Motor proteins called kinesins perform a number of different roles inside cells , including transporting cargo and organizing filaments called microtubules to generate the force needed for a cell to divide . Kinesins move along the microtubules , with different kinesins moving in different ways: some ‘walk’ , some jump...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics", "computational", "and", "systems", "biology" ]	2017	Kinesin motility is driven by subdomain dynamics
Zebrafish Gdf3 ( Dvr1 ) is a member of the TGFβ superfamily of cell signaling ligands that includes Xenopus Vg1 and mammalian Gdf1/3 . Surprisingly , engineered homozygous mutants in zebrafish have no apparent phenotype . Elimination of Gdf3 in oocytes of maternal-zygotic mutants results in embryonic lethality that can...	All vertebrates – animals with backbones like fish and humans – have body plans with three clear axes: head-to-tail , back-to-front and left-to-right . Animals lay down these plans as embryos , when signaling molecules bind to receptors on the surface of their cells . These signaling molecules include related proteins ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2017	Maternal Gdf3 is an obligatory cofactor in Nodal signaling for embryonic axis formation in zebrafish
A detailed understanding of tRNA/mRNA translocation requires measurement of the forces generated by the ribosome during this movement . Such measurements have so far remained elusive and , thus , little is known about the relation between force and translocation and how this reflects on its mechanism and regulation . H...	Producing a protein first requires its gene to be transcribed into a long molecule called a messenger RNA ( mRNA ) . A complex molecular machine called the ribosome then translates the mRNA code by reading it three letters at a time . Each triplet of letters—known as a codon—tells the ribosome which amino acid to add n...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "physics", "of", "living", "systems" ]	2014	Direct measurement of the mechanical work during translocation by the ribosome
In mammals , the carboxy-terminal domain ( CTD ) of RNA polymerase ( Pol ) II consists of 52 conserved heptapeptide repeats containing the consensus sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7 . Post-translational modifications of the CTD coordinate the transcription cycle and various steps of mRNA maturation . Here we...	When a gene is expressed , the DNA is first transcribed to produce an intermediate molecule called a messenger RNA ( mRNA ) , which is then translated to produce a protein . RNA Polymerase II is an enzyme that makes mRNA molecules in organisms as diverse as plants , animals , and yeast . RNA Polymerase II is a complex ...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Material", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "short", "report" ]	2014	Tyrosine phosphorylation of RNA polymerase II CTD is associated with antisense promoter transcription and active enhancers in mammalian cells
Phytoplankton-bacteria interactions drive the surface ocean sulfur cycle and local climatic processes through the production and exchange of a key compound: dimethylsulfoniopropionate ( DMSP ) . Despite their large-scale implications , these interactions remain unquantified at the cellular-scale . Here we use secondary...	Sulfur is an essential element for many organisms and environmental processes . Every year , organisms including microalgae produce more than one billion tons of a sulfur-containing compound called DMSP . Some of this DMSP is released into seawater , where it acts as a key nutrient for microscopic organisms and as a fo...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "ecology", "short", "report", "microbiology", "and", "infectious", "disease" ]	2017	Subcellular tracking reveals the location of dimethylsulfoniopropionate in microalgae and visualises its uptake by marine bacteria
DYT1 is a debilitating movement disorder caused by loss-of-function mutations in torsinA . How these mutations cause dystonia remains unknown . Mouse models which have embryonically targeted torsinA have failed to recapitulate the dystonia seen in patients , possibly due to differential developmental compensation betwe...	Dystonia is the third most common type of movement disorder after Parkinson’s disease and tremor . Patients with dystonia experience prolonged involuntary contractions of their muscles , often causing uncontrollable postures or repetitive movements . Almost thirty years ago , genetic studies revealed that a mutation in...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2017	A role for cerebellum in the hereditary dystonia DYT1
It is well established that learning can occur without external feedback , yet normative reinforcement learning theories have difficulties explaining such instances of learning . Here , we propose that human observers are capable of generating their own feedback signals by monitoring internal decision variables . We in...	Much of our behavior is shaped by feedback from the environment . We repeat behaviors that previously led to rewards and avoid those with negative outcomes . At the same time , we can learn in many situations without such feedback . Our ability to perceive sensory stimuli , for example , improves with training even in ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Mesolimbic confidence signals guide perceptual learning in the absence of external feedback
Bacterial H-NS forms nucleoprotein filaments that spread on DNA and bridge distant DNA sites . H-NS filaments co-localize with sites of Rho-dependent termination in Escherichia coli , but their direct effects on transcriptional pausing and termination are untested . In this study , we report that bridged H-NS filaments...	Genes—which are made of DNA—contain the genetic blueprint of an organism . Different genes are switched on ( expressed ) at various points in an organism's life when they are needed . When a gene is switched on or ‘expressed’ , the DNA is copied using molecules of ribonucleic acid ( RNA ) that can then be used as templ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "biochemistry", "and", "chemical", "biology" ]	2015	Bridged filaments of histone-like nucleoid structuring protein pause RNA polymerase and aid termination in bacteria
α-Synuclein is a presynaptic protein that is implicated in Parkinson's and other neurodegenerative diseases . Physiologically , native α-synuclein promotes presynaptic SNARE-complex assembly , but its molecular mechanism of action remains unknown . Here , we found that native α-synuclein promotes clustering of synaptic...	The central nervous system coordinates many different activities by sending instructions to large numbers of cells and , simultaneously , processing all the signals that are sent back to the brain . All these messages are carried by electrical pulses that travel along chains of neurons , with neurotransmitter molecules...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics", "neuroscience" ]	2013	Native α-synuclein induces clustering of synaptic-vesicle mimics via binding to phospholipids and synaptobrevin-2/VAMP2
Epicardial cells on the heart’s surface give rise to coronary artery smooth muscle cells ( caSMCs ) located deep in the myocardium . However , the differentiation steps between epicardial cells and caSMCs are unknown as are the final maturation signals at coronary arteries . Here , we use clonal analysis and lineage tr...	The heart is a complex organ composed of several different cell types . Muscle cells of walls of the heart contract to pump blood around the body . These muscle cells are themselves supplied with blood from the coronary arteries that penetrate deep into this muscle tissue . The lining of the coronary arteries is made o...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2015	Pericytes are progenitors for coronary artery smooth muscle
Lymph nodes ( LNs ) contain innate-like lymphocytes that survey the subcapsular sinus ( SCS ) and associated macrophages for pathogen entry . The factors promoting this surveillance behavior have not been defined . Here , we report that IL7RhiCcr6+ lymphocytes in mouse LNs rapidly produce IL17 upon bacterial and fungal...	The lymphatic system is a network of vessels and a vital part of our immune system . Amongst other things , the lymphatic system carries microbes that have entered the body – for example via to a cut or mosquito bite – to small , oval-shaped organs called lymph nodes . The lymph nodes are packed with immune cells that ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "immunology", "and", "inflammation" ]	2016	Migratory and adhesive cues controlling innate-like lymphocyte surveillance of the pathogen-exposed surface of the lymph node
Activation of the integrated stress response ( ISR ) or the ribosome-associated quality control ( RQC ) pathway stimulates regulatory ribosomal ubiquitylation ( RRub ) on distinct 40S ribosomal proteins , yet the cellular role and fate of ubiquitylated proteins remain unclear . We demonstrate that uS10 and uS5 ubiquity...	Ribosomes are cellular machines that build proteins by latching on and then reading template molecules known as mRNAs . Several ribosomes may be moving along the same piece of mRNA at the same time , each making their own copy of the same protein . Damage to an mRNA or other problems may cause a ribosome to stall , lea...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2020	Distinct regulatory ribosomal ubiquitylation events are reversible and hierarchically organized
In response to proteotoxic stress , chloroplasts communicate with the nuclear gene expression system through a chloroplast unfolded protein response ( cpUPR ) . We isolated Chlamydomonas reinhardtii mutants that disrupt cpUPR signaling and identified a gene encoding a previously uncharacterized cytoplasmic protein kina...	Life on Earth crucially depends on photosynthesis , the process by which energy stored in sunlight is harnessed to convert carbon dioxide into sugars and oxygen . In plants and algae , photosynthesis occurs in specialized cellular compartments called chloroplasts . Inside chloroplasts , complex molecular machines absor...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "genetics", "and", "genomics" ]	2019	The Mars1 kinase confers photoprotection through signaling in the chloroplast unfolded protein response
Nervous systems distinguish between self- and other-generated movements by monitoring discrepancies between planned and performed actions . To do so , corollary discharges are conveyed to sensory areas and gate expected reafference . Such gating is observed in neonatal rats during wake-related movements . In contrast ,...	Many parts of our body twitch while we are asleep and these movements are especially common in babies . Unlike the movements we make while awake , twitches during sleep are brief , staccato-like movements that appear to be aimless – but they are not , as traditionally believed , mere remnants of dreams . Rather , it is...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "short", "report", "neuroscience" ]	2016	Gating of reafference in the external cuneate nucleus during self-generated movements in wake but not sleep
Targeted sequencing of sixteen SLE risk loci among 1349 Caucasian cases and controls produced a comprehensive dataset of the variations causing susceptibility to systemic lupus erythematosus ( SLE ) . Two independent disease association signals in the HLA-D region identified two regulatory regions containing 3562 polym...	The human immune system defends the body against microbes and other threats . However , if this process goes wrong the immune system can attack the body’s own healthy cells , which can lead to serious autoimmune diseases . Systemic lupus erythematosus ( SLE ) is an autoimmune disease in which immune cells often attack ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "genetics", "and", "genomics" ]	2016	Regulatory polymorphisms modulate the expression of HLA class II molecules and promote autoimmunity
As superfamily 2 ( SF2 ) -type translocases , chromatin remodelers are expected to use an inchworm-type mechanism to walk along DNA . Yet how they move DNA around the histone core has not been clear . Here we show that a remodeler ATPase motor can shift large segments of DNA by changing the twist and length of nucleoso...	DNA is shaped like a spiral staircase , twisting around itself to create a double helix . This results in a long string-like molecule that needs to be carefully packaged to fit inside the cells of organisms as diverse as fungi or humans . This packaging process starts when a portion of DNA tightly wraps around a spool-...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "biochemistry", "and", "chemical", "biology" ]	2018	A twist defect mechanism for ATP-dependent translocation of nucleosomal DNA
The essential functions required for mitotic spindle assembly and chromosome biorientation and segregation are not fully understood , despite extensive study . To illuminate the combinations of ingredients most important to align and segregate chromosomes and simultaneously assemble a bipolar spindle , we developed a c...	Before a cell divides , it must make a copy of its genetic material and then promptly split in two . This process , called mitosis , is coordinated by many different molecular machines . The DNA is copied , then the duplicated chromosomes line up at the middle of the cell . Next , an apparatus called the mitotic spindl...	[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "Discussion" ]	[ "cell", "biology", "computational", "and", "systems", "biology" ]	2020	Mechanisms of chromosome biorientation and bipolar spindle assembly analyzed by computational modeling
In post-industrial settings , apolipoprotein E4 ( APOE4 ) is associated with increased cardiovascular and neurological disease risk . However , the majority of human evolutionary history occurred in environments with higher pathogenic diversity and low cardiovascular risk . We hypothesize that in high-pathogen and ener...	Genes contain the instructions needed for a cell to make molecules called proteins , which perform various roles in the body . Different variants of a gene can affect how the protein works , and in some cases , can increase a person’s risk to develop certain diseases . For example , people who carry a version of the ap...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology", "medicine" ]	2021	APOE4 is associated with elevated blood lipids and lower levels of innate immune biomarkers in a tropical Amerindian subsistence population
The haptoglobin-haemoglobin receptor ( HpHbR ) of African trypanosomes allows acquisition of haem and provides an uptake route for trypanolytic factor-1 , a mediator of innate immunity against trypanosome infection . In this study , we report the structure of Trypanosoma brucei HpHbR in complex with human haptoglobin-h...	African Trypanosomes are a group of single-celled parasites that are a major concern for livestock farmers in sub-Saharan Africa . They are carried by the tsetse fly and can cause disease in domestic livestock that diminishes productivity through reduced growth , and may ultimately lead to death . The parasites are coa...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics", "microbiology", "and", "infectious", "disease" ]	2014	Structural basis for ligand and innate immunity factor uptake by the trypanosome haptoglobin-haemoglobin receptor
Intraflagellar transport ( IFT ) is essential for the elongation and maintenance of eukaryotic cilia and flagella . Due to the traffic jam of multiple trains at the ciliary tip , how IFT trains are remodeled in these turnaround zones cannot be determined by conventional imaging . Using PhotoGate , we visualized the ful...	Cilia and flagella are hair-like structures that protrude from nearly every human cell and play a number of roles including transmitting signals and enabling cells to move . These structures lengthen when new material is deposited at their tip by a process called intraflagellar transport ( IFT ) . In this process , pro...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2017	Dynamics of the IFT machinery at the ciliary tip
A leading theory holds that neurodevelopmental brain disorders arise from imbalances in excitatory and inhibitory ( E/I ) brain circuitry . However , it is unclear whether this one-dimensional model is rich enough to capture the multiple neural circuit alterations underlying brain disorders . Here , we combined computa...	In many brain disorders , from autism to schizophrenia , the anatomy of the brain appears remarkably unchanged . This implies that the problem may reside in how neurons communicate with one another . Unfortunately , neuroscientists know little about how brain activity might differ from normal in these disorders , or ho...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2017	Beyond excitation/inhibition imbalance in multidimensional models of neural circuit changes in brain disorders
Recent studies , partly based on murine models , suggest childhood immunization and vitamin A supplements may confer protection against malaria infection , although strong evidence to support these theories in humans has so far been lacking . We analyzed national survey data from children aged 6–59 months in four sub-S...	More than half of the world's population is at risk of malaria , with an estimated 198 million clinical cases each year . A vaccine that fully prevents it has not yet been discovered . Most cases of malaria occur among children living in sub-Saharan Africa , a region where many receive routine vaccinations designed to ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "epidemiology", "and", "global", "health" ]	2015	Vitamin A supplements, routine immunization, and the subsequent risk of Plasmodium infection among children under 5 years in sub-Saharan Africa
Varicella-zoster virus ( VZV ) causes chickenpox and reactivation of latent VZV causes herpes zoster ( HZ ) . VZV reactivation is subject to the opposing mechanisms of declining and boosted VZV-specific cellular mediated immunity ( CMI ) . A reduction in exogenous re-exposure ‘opportunities’ through universal chickenpo...	The itchy-scratchy misery of a chickenpox was until recently a rite of passage for children around the world . The varicella-zoster virus causes chickenpox infections . This virus persists in small numbers in nerve cells for many years after infection , and can reactivate from these cells . Often this reactivation caus...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "epidemiology", "and", "global", "health", "microbiology", "and", "infectious", "disease" ]	2015	Integrating between-host transmission and within-host immunity to analyze the impact of varicella vaccination on zoster
During neural circuit assembly , axonal growth cones are exposed to multiple guidance signals at trajectory choice points . While axonal responses to individual guidance cues have been extensively studied , less is known about responses to combination of signals and underlying molecular mechanisms . Here , we studied t...	The ability of animals to walk and perform skilled movements depends on particular groups of muscles contracting in a coordinated manner . Muscles are activated by nerve cells called motor neurons found in the spinal cord . The connections between the motor neurons and muscles are established in the developing embryo ....	[ "Abstract", "Introduction", "Results", "Discussion", "Experimental", "procedures" ]	[ "developmental", "biology", "neuroscience" ]	2015	Synergistic integration of Netrin and ephrin axon guidance signals by spinal motor neurons
In animal locomotion a tradeoff exists between stereotypy and flexibility: fast long-distance travelling ( LDT ) requires coherent regular motions , while local sampling and area-restricted search ( ARS ) rely on flexible movements . We report here on a posture control system in C . elegans that coordinates these needs...	Animals navigate through their environment using different strategies according to their current needs . For example , when the goal is to travel long distances , they move quickly and in an efficient way by employing regular , repetitive movements . However , when the aim is to explore the nearby area – to search for ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Regulation of two motor patterns enables the gradual adjustment of locomotion strategy in Caenorhabditis elegans
Selective autophagy is mediated by cargo receptors that link the cargo to the isolation membrane via interactions with Atg8 proteins . Atg8 proteins are localized to the membrane in an ubiquitin-like conjugation reaction , but how this conjugation is coupled to the presence of the cargo is unclear . Here we show that t...	A living cell must remove unhealthy or excess material from its interior in order to remain healthy and operational . Cells pack this waste into membrane-bound compartments named autophagosomes in a process called autophagy . So-called autophagy proteins make sure that only the unwanted material is eliminated . However...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology" ]	2016	Mechanism of cargo-directed Atg8 conjugation during selective autophagy
Cnidarians possess remarkable powers of regeneration , but the cellular and molecular mechanisms underlying this capability are unclear . Studying the hydrozoan Hydractinia echinata we show that a burst of stem cell proliferation occurs following decapitation , forming a blastema at the oral pole within 24 hr . This pr...	Although all animals are capable of regenerating damaged tissue to some extent , a few—including jellyfish , coral , and their relatives—are able to regenerate entire lost body parts . Closely related species may have very different regeneration capabilities . This has led some researchers to propose that higher animal...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "stem", "cells", "and", "regenerative", "medicine" ]	2015	Distinct mechanisms underlie oral vs aboral regeneration in the cnidarian Hydractinia echinata
The eukaryotic translation initiation factor 2α ( eIF2α ) kinase GCN2 is activated by amino acid starvation to elicit a rectifying physiological program known as the Integrated Stress Response ( ISR ) . A role for uncharged tRNAs as activating ligands of yeast GCN2 is supported experimentally . However , mouse GCN2 act...	Often thought of as “workhorse” molecules , proteins take part in almost every structure and activity in a living cell . They are constructed from smaller building blocks called amino acids by molecular machines called ribosomes . Each cell needs a constant supply of amino acids to make new proteins . If cells are runn...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "genetics", "and", "genomics" ]	2019	The ribosomal P-stalk couples amino acid starvation to GCN2 activation in mammalian cells
Sensory stimuli have varying statistics influenced by both the environment and by active sensing behaviors that rapidly and globally change the sensory input . Consequently , sensory systems often adjust their neural code to the expected statistics of their sensory input to transmit novel sensory information . Here , w...	To see an object , light must travel from it and be focused onto the retina at the back of the eye . The image projected onto each retina is then processed by neurons known as ganglion cells , which transmit a processed version of the image to the brain . Each ganglion cell responds to a specific section of the retinal...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	Synchronized amplification of local information transmission by peripheral retinal input
As species face rapid environmental change , we can build resilient populations through restoration projects that incorporate predicted future climates into seed sourcing decisions . Eucalyptus melliodora is a foundation species of a critically endangered community in Australia that is a target for restoration . We exa...	Yellow box , or Eucalyptus melliodora , is an emblematic Australian tree that is essential to many native ecosystems . Some of these environments are now critically endangered , and replanting yellow box trees is one of the first steps to try to restore them . However , it can be difficult for reforestation practitione...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology" ]	2018	Landscape genomic prediction for restoration of a Eucalyptus foundation species under climate change
The ring-like ATPase complexes in the AAA+ family perform diverse cellular functions that require coordination between the conformational transitions of their individual ATPase subunits ( Erzberger and Berger , 2006; Puchades et al . , 2020 ) . How the energy from ATP hydrolysis is captured to perform mechanical work b...	In cells , many biological processes are carried out by large complexes made up of different proteins . These macromolecules act like miniature machines , flexing and moving their various parts to perform their cellular roles . One such complex is the 26S proteasome , which is responsible for recycling other proteins i...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics", "physics", "of", "living", "systems" ]	2022	An empirical energy landscape reveals mechanism of proteasome in polypeptide translocation

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