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Skeletal muscle myoblasts ( iMyoblasts ) were generated from human induced pluripotent stem cells ( iPSCs ) using an efficient and reliable transgene-free induction and stem cell selection protocol . Immunofluorescence , flow cytometry , qPCR , digital RNA expression profiling , and scRNA-Seq studies identify iMyoblast...	Muscular dystrophies are a group of inherited genetic diseases characterised by progressive muscle weakness . They lead to disability or even death , and no cure exists against these conditions . Advances in genome sequencing have identified many mutations that underly muscular dystrophies , opening the door to new the...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "stem", "cells", "and", "regenerative", "medicine", "developmental", "biology", "tools", "and", "resources" ]	2022	iMyoblasts for ex vivo and in vivo investigations of human myogenesis and disease modeling
In amyotrophic lateral sclerosis ( ALS ) the large motoneurons that innervate the fast-contracting muscle fibers ( F-type motoneurons ) are vulnerable and degenerate in adulthood . In contrast , the small motoneurons that innervate the slow-contracting fibers ( S-type motoneurons ) are resistant and do not degenerate ....	Amyotrophic lateral sclerosis ( ALS ) , which is also known as Lou Gherig's disease or motoneuron disease , is a neurodegenerative disorder in which muscles throughout the body gradually waste away due to the death of the neurons that control their activity . The disease often begins with weakness of the arms or legs ,...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2014	Early intrinsic hyperexcitability does not contribute to motoneuron degeneration in amyotrophic lateral sclerosis
Birds and other vertebrates display stunning variation in pigmentation patterning , yet the genes controlling this diversity remain largely unknown . Rock pigeons ( Columba livia ) are fundamentally one of four color pattern phenotypes , in decreasing order of melanism: T-check , checker , bar ( ancestral ) , or barles...	The rock pigeon is a familiar sight in urban settings all over the world . Domesticated thousands of years ago and still raised by hobbyists , there are now more than 350 breeds of pigeon . These breeds have a spectacular variation in anatomy , feather color and behavior . Color patterns are important for birds in spec...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "genetics", "and", "genomics" ]	2018	Introgression of regulatory alleles and a missense coding mutation drive plumage pattern diversity in the rock pigeon
Membrane transporters that clear the neurotransmitter glutamate from synapses are driven by symport of sodium ions and counter-transport of a potassium ion . Previous crystal structures of a homologous archaeal sodium and aspartate symporter showed that a dedicated transport domain carries the substrate and ions across...	Molecules of glutamate can carry messages between cells in the brain , and these signals are essential for thought and memory . Glutamate molecules can also act as signals to build new connections between brain cells and to prune away unnecessary ones . However , too much glutamate outside of the cells kills the brain ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics", "neuroscience" ]	2014	Coupled ion binding and structural transitions along the transport cycle of glutamate transporters
TCF/LEF factors are ancient context-dependent enhancer-binding proteins that are activated by β-catenin following Wnt signaling . They control embryonic development and adult stem cell compartments , and their dysregulation often causes cancer . β-catenin-dependent transcription relies on the NPF motif of Pygo proteins...	In animals , cells have to be able to communicate with neighboring cells in order to generate and maintain the different tissues and organs . One ancient method of cell communication that is used in all animals is the Wnt signaling pathway . In this pathway , a cell secretes a protein called Wnt , which binds to a Wnt ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2015	An ancient Pygo-dependent Wnt enhanceosome integrated by Chip/LDB-SSDP
Adaptation is a key component of efficient coding in sensory neurons . However , it remains unclear how neurons can provide a stable representation of external stimuli given their history-dependent responses . Here we show that a stable representation is maintained if efficiency is optimized by a population of neurons ...	Humans see , hear , feel , taste and smell the world as spiking electrical signals in the brain encoded by sensory neurons . Sensory neurons learn from experience to adjust their activity when exposed repeatedly to the same stimuli . A loud noise or that strange taste in your mouth might be alarming at first but soon s...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology", "neuroscience" ]	2019	Population adaptation in efficient balanced networks
When females mate with more than one male , the males’ paternity share is affected by biases in sperm use . These competitive interactions occur while female and male molecules and cells work interdependently to optimize fertility , including modifying the female’s physiology through interactions with male seminal flui...	When fruit flies and other animals reproduce , a compatible male and a female mate , allowing sperm from the male to swim to and fuse with the female’s egg cells . The males also produce proteins known as seminal proteins that travel with the sperm . These proteins increase the likelihood of sperm meeting an egg and in...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology", "genetics", "and", "genomics" ]	2020	Drosophila seminal sex peptide associates with rival as well as own sperm, providing SP function in polyandrous females
Development and function of highly polarized cells such as neurons depend on microtubule-associated intracellular transport , but little is known about contributions of specific molecular motors to the establishment of synaptic connections . In this study , we investigated the function of the Kinesin I heavy chain Kif5...	Different regions of a neuron have distinct structures and roles . For example , each neuron has a cable-like structure called the axon that extends out of the body of the cell and carries electrical signals away from the cell body . To pass these messages on to neighboring cells , branches on the axon form connections...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	Deletion of a kinesin I motor unmasks a mechanism of homeostatic branching control by neurotrophin-3
Several neurodegenerative diseases are driven by the toxic gain-of-function of specific proteins within the brain . Elevated levels of alpha-synuclein ( α-Syn ) appear to drive neurotoxicity in Parkinson's disease ( PD ) ; neuronal accumulation of tau is a hallmark of Alzheimer's disease ( AD ) ; and their increased le...	Behind many neurodegenerative diseases are specific proteins that abnormally accumulate inside neurons and damage the cells . In Parkinson’s disease , the protein alpha-synuclein accumulates; in Alzheimer’s disease , the protein tau is one of the toxic culprits; and in other neurodegenerative diseases , alpha-synuclein...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	TRIM28 regulates the nuclear accumulation and toxicity of both alpha-synuclein and tau
During development internal models of the sensory world must be acquired which have to be continuously adapted later . We used event-related potentials ( ERP ) to test the hypothesis that infants extract crossmodal statistics implicitly while adults learn them when task relevant . Participants were passively exposed to...	On a crowded city street , we automatically attribute the sounds of cars to the cars we see driving past , and not to the motorcycles or trucks on the same road . Similarly , we assign the voices we hear to the pedestrians around us , and not to the dogs those pedestrians are walking . As adults , we cope with these ev...	[ "Abstract", "Introduction", "Results", "Discussion" ]	[ "neuroscience" ]	2017	Infants are superior in implicit crossmodal learning and use other learning mechanisms than adults
When relatively sated , people ( and rodents ) are still easily tempted to consume calorie-dense foods , particularly those containing fat and sugar . Consumption of such foods while calorically replete likely contributes to obesity . The nucleus accumbens ( NAc ) opioid system has long been viewed as a critical substr...	Imagine that you have just finished Thanksgiving dinner . You are completely full , having eaten large portions of turkey , green beans and mashed potatoes . Yet , despite feeling full , you still find yourself tempted by a slice of pie for dessert , maybe even with ice cream on top . Why is it that in such a state of ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2018	Endogenous opioids in the nucleus accumbens promote approach to high-fat food in the absence of caloric need
Understanding how climate-mediated biotic interactions shape thermal niche width is critical in an era of global change . Yet , most previous work on thermal niches has ignored detailed mechanistic information about the relationship between temperature and organismal performance , which can be described by a thermal pe...	Insects , reptiles and many other animals are often referred to as being ‘cold-blooded’ because , unlike mammals and birds , their body temperature fluctuates with the temperature of their surrounding environment . As a result , many cold-blooded animals are very sensitive to changes in local climate . Environmental fa...	[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "Discussion" ]	[ "ecology" ]	2020	Antagonistic effects of intraspecific cooperation and interspecific competition on thermal performance
Hygrosensation is an essential sensory modality that is used to find sources of moisture . Hygroreception allows animals to avoid desiccation , an existential threat that is increasing with climate change . Humidity response , however , remains poorly understood . Here we find that humidity-detecting sensilla in the Dr...	Some insects have a sense – called hygroreception – that allows them to detect changing levels of moisture in the air . These insects use this sense to avoid becoming too dry , or to find food or places to lay their eggs . In many species , including the fruit fly Drosophila melanogaster , the antennae are important fo...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2018	Humidity response depends on the small soluble protein Obp59a in Drosophila
Positional information is essential for coordinating the development of multicellular organisms . In plants , positional information provided by the hormone auxin regulates rhythmic organ production at the shoot apex , but the spatio-temporal dynamics of auxin gradients is unknown . We used quantitative imaging to demo...	Plants , like animals and many other multicellular organisms , control their body architecture by creating organized patterns of cells . These patterns are generally defined by signal molecules whose levels differ across the tissue and change over time . This tells the cells where they are located in the tissue and the...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology", "developmental", "biology" ]	2020	Temporal integration of auxin information for the regulation of patterning
Most research on neurodegenerative diseases has focused on neurons , yet glia help form and maintain the synapses whose loss is so prominent in these conditions . To investigate the contributions of glia to Huntington's disease ( HD ) , we profiled the gene expression alterations of Drosophila expressing human mutant H...	When a neuron dies , through injury or disease , the body loses all communication that passes through it . The brain compensates by rerouting the flow of information through other neurons in the network . Eventually , if the loss of neurons becomes too great , compensation becomes impossible . This process happens in A...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology", "genetics", "and", "genomics" ]	2021	Downregulation of glial genes involved in synaptic function mitigates Huntington's disease pathogenesis
Arrhythmogenesis from aberrant electrical remodeling is a primary cause of death among patients with heart disease . Amongst a multitude of remodeling events , reduced expression of the ion channel subunit KChIP2 is consistently observed in numerous cardiac pathologies . However , it remains unknown if KChIP2 loss is m...	The heart pumps blood throughout the body to provide oxygen and nourishment . To do so , proteins in the heart create electrical signals that tell the heart muscles to contract in a coordinated manner . Heart disease can cause cells to lose control of the production or activity of these proteins , creating disorganized...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2017	KChIP2 is a core transcriptional regulator of cardiac excitability
Anxiety disorders affect approximately 1 in 5 ( 18% ) Americans within a given 1 year period , placing a substantial burden on the national health care system . Therefore , there is a critical need to understand the neural mechanisms mediating anxiety symptoms . We used unbiased , multimodal , data-driven , whole-brain...	Anxiety disorders affect around one in five Americans , and in many cases people experience anxiety so intensely that they have difficulties performing day-to-day activities . To help these people , it is important to understand how anxiety works . Current research suggests that anxiety disorders are caused when the co...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2017	Threat of shock increases excitability and connectivity of the intraparietal sulcus
Climate change is accelerating plant developmental transitions coordinated with the seasons in temperate environments . To understand the importance of these timing advances for a stable life history strategy , we constructed a full life cycle model of Arabidopsis thaliana . Modelling and field data reveal that a crypt...	Plants adjust when they grow , develop flowers and produce , or ‘set’ , seeds in response to changes in temperature and day length . It is therefore unsurprising that climate change alters the timing of these important events in plants' lives; for example , many plants are adapting to rising temperatures by flowering e...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology" ]	2015	Flowering time and seed dormancy control use external coincidence to generate life history strategy
The mammalian suprachiasmatic nucleus ( SCN ) drives daily rhythmic behavior and physiology , yet a detailed understanding of its coordinated transcriptional programmes is lacking . To reveal the finer details of circadian variation in the mammalian SCN transcriptome we combined laser-capture microdissection ( LCM ) an...	The daily cycles of life in mammals are driven by a small region of the brain called the suprachiasmatic nucleus ( or SCN ) . The SCN receives signals from sunlight and other environmental factors to help coordinate most aspects of daily biological activity and behaviour . To work correctly , it is essential that the S...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "neuroscience", "tools", "and", "resources", "genetics", "and", "genomics" ]	2015	Temporal transcriptomics suggest that twin-peaking genes reset the clock
Voltage-sensing domains ( VSDs ) underlie the movement of voltage-gated ion channels , as well as the voltage-sensitive fluorescent responses observed from a common class of genetically encoded voltage indicators ( GEVIs ) . Despite the widespread use and potential utility of these GEVIs , the biophysical underpinnings...	Nerve cells , or neurons , transmit information using changes in the voltage across their cell membranes . In the brain , these neurons work together in complex networks , and so understanding how the brain processes information will require neuroscientists to analyze voltage changes in many neurons at the same time . ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics", "neuroscience" ]	2015	Single-molecule fluorimetry and gating currents inspire an improved optical voltage indicator
Cells must appropriately sense and integrate multiple metabolic resources to commit to proliferation . Here , we report that S . cerevisiae cells regulate carbon and nitrogen metabolic homeostasis through tRNA U34-thiolation . Despite amino acid sufficiency , tRNA-thiolation deficient cells appear amino acid starved . ...	The building blocks of all cells are made from a handful of chemical elements , including carbon , nitrogen , sulfur and phosphorus . To grow optimally , cells need to regulate their metabolism – in other words , the biochemical reactions that keep them alive – based on the availability of these elements . As a result ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "genetics", "and", "genomics" ]	2019	A tRNA modification balances carbon and nitrogen metabolism by regulating phosphate homeostasis
Eukaryotes and prokaryotes last shared a common ancestor ~2 billion years ago , and while many present-day genes in these lineages predate this divergence , the extent to which these genes still perform their ancestral functions is largely unknown . To test principles governing retention of ancient function , we asked ...	All life on Earth – from bacteria to human beings – can be traced back to a common ancestor that lived over three billion years ago . As a result , modern-day organisms share many essential parts of life’s molecular machinery , such as certain genes and proteins . Yet there are also vital differences that allow scienti...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology", "computational", "and", "systems", "biology" ]	2017	Systematic bacterialization of yeast genes identifies a near-universally swappable pathway
Phase transitions of linear multivalent proteins control the reversible formation of many intracellular membraneless bodies . Specific non-covalent crosslinks involving domains/motifs lead to system-spanning networks referred to as gels . Gelation transitions can occur with or without phase separation . In gelation dri...	Our cells contain a variety of structures called organelles that perform specific roles within a cell . Some organelles are surrounded by a membrane , while others float inside the cell as spherical droplets made of proteins . These proteins contain several sticky regions , which are connected by flexible linker protei...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "computational", "and", "systems", "biology" ]	2017	Intrinsically disordered linkers determine the interplay between phase separation and gelation in multivalent proteins
Upon fertilization , the genome of animal embryos remains transcriptionally inactive until the maternal-to-zygotic transition . At this time , the embryo takes control of its development and transcription begins . How the onset of zygotic transcription is regulated remains unclear . Here , we show that a dynamic compet...	The DNA in a fertilized egg contains all the information required to form an animal’s body . In order for the animal to develop properly , particular genes encoded in the DNA are only active at specific times . The DNA is wrapped around proteins called histones , which allows the DNA to be tightly packed inside the cel...	[ "Abstract", "Introduction", "Results", "Discussion", "M" ]	[ "chromosomes", "and", "gene", "expression", "developmental", "biology" ]	2017	Competition between histone and transcription factor binding regulates the onset of transcription in zebrafish embryos
Maintenance of connective tissue integrity is fundamental to sustain function , requiring protein turnover to repair damaged tissue . However , connective tissue proteome dynamics remain largely undefined , as do differences in turnover rates of individual proteins in the collagen and glycoprotein phases of connective ...	Muscles are anchored to bones through specialized tissues called tendons . Made of bundles of fibers ( or fascicles ) linked together by an ‘interfascicular’ matrix , healthy tendons are required for organisms to move properly . Yet , these structures are constantly exposed to damage: the interfascicular matrix , in pa...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2020	Heterogeneity of proteome dynamics between connective tissue phases of adult tendon
Platelet-neutrophil interactions are important for innate immunity , but also contribute to the pathogenesis of deep vein thrombosis , myocardial infarction and stroke . Here we report that , under flow , von Willebrand factor/glycoprotein Ibα-dependent platelet ‘priming’ induces integrin αIIbβ3 activation that , in tu...	Platelets in our blood form clots over sites of injury to stop us from bleeding . Blood clots can also occur in places where they are not needed , such as deep veins in our legs or other regions of the body . Developing such clots – also known as deep vein thrombosis ( or DVT for short ) – is one of the most common car...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2020	Activated αIIbβ3 on platelets mediates flow-dependent NETosis via SLC44A2
Information about nutrient availability is assessed via largely unknown mechanisms to drive developmental decisions , including the choice of Caenorhabditis elegans larvae to enter into the reproductive cycle or the dauer stage . In this study , we show that CMK-1 CaMKI regulates the dauer decision as a function of fee...	Living organisms have the remarkable ability to adapt to changes in their external environment . For example , when conditions are favorable , the larvae of the tiny roundworm C . elegans rapidly mature into adults and reproduce . However , when faced with starvation , over-crowding or other adverse conditions , they c...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "neuroscience" ]	2015	Feeding state-dependent regulation of developmental plasticity via CaMKI and neuroendocrine signaling
EAG-like ( ELK ) voltage-gated potassium channels are abundantly expressed in the brain . These channels exhibit a behavior called voltage-dependent potentiation ( VDP ) , which appears to be a specialization to dampen the hyperexitability of neurons . VDP manifests as a potentiation of current amplitude , hyperpolariz...	In humans and other animals , electrical signals trigger the heart to beat and carry information around the brain and nervous system . Particular cells can generate these signals by regulating the flow of ions into and out of the cell via proteins called ion channels . These proteins sit in the membrane that surrounds ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics", "neuroscience" ]	2017	Molecular mechanism of voltage-dependent potentiation of KCNH potassium channels
The field of tissue engineering entered a new era with the development of human pluripotent stem cells ( hPSCs ) , which are capable of unlimited expansion whilst retaining the potential to differentiate into all mature cell populations . However , these cells harbor significant risks , including tumor formation upon t...	The development of ‘human pluripotent stem cells’ has the potential to revolutionize the future of medicine . This is because these cells can both replicate themselves indefinitely ( i . e . , they can self-renew ) and develop into any of the cell types found in the human body ( a process that is referred to as differe...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "stem", "cells", "and", "regenerative", "medicine" ]	2015	Generation of an expandable intermediate mesoderm restricted progenitor cell line from human pluripotent stem cells
We report a draft assembly of the genome of Hi5 cells from the lepidopteran insect pest , Trichoplusia ni , assigning 90 . 6% of bases to one of 28 chromosomes and predicting 14 , 037 protein-coding genes . Chemoreception and detoxification gene families reveal T . ni-specific gene expansions that may explain its wides...	A common moth called the cabbage looper is becoming increasingly relevant to the scientific community . Its caterpillars are a serious threat to cabbage , broccoli and cauliflower crops , and they have started to resist the pesticides normally used to control them . Moreover , the insect’s germline cells – the ones tha...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "genetics", "and", "genomics" ]	2018	The genome of the Hi5 germ cell line from Trichoplusia ni, an agricultural pest and novel model for small RNA biology
Understanding allostery in enzymes and tools to identify it offer promising alternative strategies to inhibitor development . Through a combination of equilibrium and nonequilibrium molecular dynamics simulations , we identify allosteric effects and communication pathways in two prototypical class A β-lactamases , TEM-...	Antibiotics are crucial drugs for treating and preventing bacterial infections , but some bacteria are evolving ways to resist their effects . This ‘antibiotic resistance’ threatens lives and livelihoods worldwide . β-lactam antibiotics , like penicillin , are some of the most commonly used , but some bacteria can now ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "medicine", "structural", "biology", "and", "molecular", "biophysics" ]	2021	Allosteric communication in class A β-lactamases occurs via cooperative coupling of loop dynamics
Given a sample of genome sequences from an asexual population , can one predict its evolutionary future ? Here we demonstrate that the branching patterns of reconstructed genealogical trees contains information about the relative fitness of the sampled sequences and that this information can be used to predict successf...	When viruses multiply , they copy their genetic material to make clones of themselves . However , the genetic material in the clone is often slightly different from the genetic material in the original virus . These mutations can be caused by mistakes made during copying or by radiation or chemicals . Further mutations...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology", "physics", "of", "living", "systems" ]	2014	Predicting evolution from the shape of genealogical trees
Glutamate receptors are divided in two unrelated families: ionotropic ( iGluR ) , driving synaptic transmission , and metabotropic ( mGluR ) , which modulate synaptic strength . The present classification of GluRs is based on vertebrate proteins and has remained unchanged for over two decades . Here we report an exhaus...	Nerve cells or neurons communicate with each other by releasing specific molecules in the gap between them , the synapses . The sending neuron passes on messages through packets of chemicals called neurotransmitters , which are picked up by the receiving cell with the help of receptors on its surface . Neurons use diff...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology", "neuroscience" ]	2018	Metazoan evolution of glutamate receptors reveals unreported phylogenetic groups and divergent lineage-specific events
When complexed with antigenic peptides , human leukocyte antigen ( HLA ) class I ( HLA-I ) molecules initiate CD8+ T cell responses via interaction with the T cell receptor ( TCR ) and co-receptor CD8 . Peptides are generally critical for the stable cell surface expression of HLA-I molecules . However , for HLA-I allel...	The immune system keeps tabs on everything that happens in our body , looking for potential signs of threat . To alert it to any problems , almost every cell produces specific proteins on its surface called human leukocyte antigens class I , or HLA-I for short . These HLA-I molecules are bound to small protein fragment...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "immunology", "and", "inflammation" ]	2018	Empty conformers of HLA-B preferentially bind CD8 and regulate CD8+ T cell function
Determining the adaptive potential of foundation species , such as reef-building corals , is urgent as the oceans warm and coral populations decline . Theory predicts that corals may adapt to climate change via selection on standing genetic variation . Yet , corals face not only rising temperatures but also novel disea...	The staghorn coral was once prevalent throughout the Florida Reef Tract . However , the last few decades have seen a substantial reduction in the coral population because of disease outbreaks and increasing ocean temperatures . The staghorn coral shows no evidence of natural recovery , and so has been the focus of rest...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "ecology" ]	2018	Bleaching causes loss of disease resistance within the threatened coral species Acropora cervicornis
Psychological theories of suicide suggest that certain traits may reduce aversion to physical threat and increase the probability of transitioning from suicidal ideation to action . Here , we investigated whether blunted sensitivity to bodily signals is associated with suicidal action by comparing individuals with a hi...	The human brain closely monitors body signals essential for our survival , including our heartbeat , our breathing and even the temperature of our skin . This mostly unconscious process is called interoception . It helps people perceive potential or actual threats and helps them to respond appropriately . For example ,...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2020	Diminished responses to bodily threat and blunted interoception in suicide attempters
We present a reanalysis of the stochastic model of organelle production and show that the equilibrium distributions for the organelle numbers predicted by this model can be readily calculated in three different scenarios . These three distributions can be identified as standard distributions , and the corresponding exa...	Any cell that has a nucleus also contains a number of subcellular structures called organelles . The number of organelles inside a cell increases when new organelles are made from scratch ( a process known as de novo synthesis ) , or when an existing organelle divides to produce two organelles in a process called fissi...	[ "Abstract", "Introduction", "Analysis", "Discussion", "Materials", "and", "methods" ]	[ "short", "report", "cell", "biology", "computational", "and", "systems", "biology" ]	2016	Evaluation of predictions of the stochastic model of organelle production based on exact distributions
The rate of protein synthesis in the adult heart is one of the lowest in mammalian tissues , but it increases substantially in response to stress and hypertrophic stimuli through largely obscure mechanisms . Here , we demonstrate that regulated expression of cytosolic poly ( A ) -binding protein 1 ( PABPC1 ) modulates ...	Hundreds of thousands of different proteins are needed to build and maintain the cells in the human body . All proteins are produced when copies of genetic information in the form of molecules of messenger RNA ( mRNAs ) are translated by the ribosome . The rate at which proteins are made varies widely between different...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "biochemistry", "and", "chemical", "biology" ]	2017	Poly(A) tail length regulates PABPC1 expression to tune translation in the heart
A polyubiquitin comprises multiple covalently linked ubiquitins and recognizes myriad targets . Free or bound to ligands , polyubiquitins are found in different arrangements of ubiquitin subunits . To understand the structural basis for polyubiquitin quaternary plasticity and to explore the target recognition mechanism...	Proteins can be tagged with other molecules that indicate what the cell should do with that protein . For example , proteins tagged with a small protein called ubiquitin—which is linked to other ubiquitin molecules to form ‘polyubiquitin’—may be destroyed or relocated within a cell . Like all proteins , a ubiquitin is ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics" ]	2015	Lys63-linked ubiquitin chain adopts multiple conformational states for specific target recognition
In mammals , the neocortical layout consists of few modality-specific primary sensory areas and a multitude of higher order ones . Abnormal layout of cortical areas may disrupt sensory function and behavior . Developmental genetic mechanisms specify primary areas , but mechanisms influencing higher order area propertie...	The neocortex is the most recently evolved part of the human brain . It is associated with higher thought processes , including language and the processing of information from our senses . Anatomically , the neocortex is organised into different regions called ‘primary areas’ and ‘higher order areas’ , and perturbation...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "neuroscience" ]	2015	Genetic mechanisms control the linear scaling between related cortical primary and higher order sensory areas
Combinatorial cis-regulatory networks encoded in animal genomes represent the foundational gene expression mechanism for directing cell-fate commitment and maintenance of cell identity by transcription factors ( TFs ) . However , the 3D spatial organization of cis-elements and how such sub-nuclear structures influence ...	Stem cells in an embryo have the potential to become any type of cell in the body . When a cell begins to specialize , it loses this ability and can only become a limited number of cell types . These transitions are caused by changes in gene expression . Proteins called transcription factors bind to DNA to switch diffe...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "structural", "biology", "and", "molecular", "biophysics" ]	2014	3D imaging of Sox2 enhancer clusters in embryonic stem cells
Listeria monocytogenes hijacks host actin to promote its intracellular motility and intercellular spread . While L . monocytogenes virulence hinges on cell-to-cell spread , little is known about the dynamics of bacterial spread in epithelia at a population level . Here , we use live microscopy and statistical modeling ...	Eating food that has been contaminated with bacteria called Listeria monocytogenes can result in life-threatening infections . The bacteria first invade the epithelial cells that line the small intestine . After this , L . monocytogenes can move from one host cell to another , which allows the infection to reach other ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "research", "communication", "cell", "biology", "microbiology", "and", "infectious", "disease" ]	2019	Listeria monocytogenes cell-to-cell spread in epithelia is heterogeneous and dominated by rare pioneer bacteria
Intracellular protein gradients are significant determinants of spatial organization . However , little is known about how protein patterns are established , and how their positional information directs downstream processes . We have accomplished the reconstitution of a protein concentration gradient that directs the a...	When a cell divides , it is important that its contents are separated in the right place to make sure that both daughter cells have everything that they need to survive . To do this , the molecular ‘machinery’ that physically divides the cell needs to know where to assemble . In the bacterium E . coli , the location of...	[ "Abstract", "Introduction", "Results", "Discussion", "Material", "and", "methods" ]	[ "cell", "biology" ]	2014	Reconstitution of self-organizing protein gradients as spatial cues in cell-free systems
In plants , a complex mixture of solutes and macromolecules is transported by the phloem . Here , we examined how solutes and macromolecules are separated when they exit the phloem during the unloading process . We used a combination of approaches ( non-invasive imaging , 3D-electron microscopy , and mathematical model...	A mechanism called photosynthesis allows plants to use energy from sunlight to make sugars from carbon dioxide gas and water . These sugars can then be used as fuel , or as building blocks for wood and other plant structures . Every part of the plant requires sugars , but most photosynthesis happens in the leaves and s...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology" ]	2017	Phloem unloading in Arabidopsis roots is convective and regulated by the phloem-pole pericycle
KATP channels are metabolic sensors that couple cell energetics to membrane excitability . In pancreatic β-cells , channels formed by SUR1 and Kir6 . 2 regulate insulin secretion and are the targets of antidiabetic sulfonylureas . Here , we used cryo-EM to elucidate structural basis of channel assembly and gating . The...	The hormone insulin reduces blood sugar levels by encouraging fat , muscle and other body cells to take up sugar . When blood sugar levels rise following a meal , cells within the pancreas known as beta cells should release insulin . In people with diabetes , the beta cells fail to release insulin , meaning that the hi...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics" ]	2017	Cryo-EM structure of the ATP-sensitive potassium channel illuminates mechanisms of assembly and gating
Comparing the impact of the COVID-19 pandemic between countries or across time is difficult because the reported numbers of cases and deaths can be strongly affected by testing capacity and reporting policy . Excess mortality , defined as the increase in all-cause mortality relative to the expected mortality , is widel...	Countries around the world reported 4 . 2 million deaths from SARS-CoV-2 ( the virus that causes COVID-19 ) from the beginning of pandemic until the end of July 2021 , but the actual number of deaths is likely higher . While some countries may have imperfect systems for counting deaths , others may have intentionally u...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "epidemiology", "and", "global", "health", "tools", "and", "resources" ]	2021	Tracking excess mortality across countries during the COVID-19 pandemic with the World Mortality Dataset
Enhancers play a central role in cell-type-specific gene expression and are marked by H3K4me1/2 . Active enhancers are further marked by H3K27ac . However , the methyltransferases responsible for H3K4me1/2 on enhancers remain elusive . Furthermore , how these enzymes function on enhancers to regulate cell-type-specific...	Almost every cell in a human body carries the same genes , but not every cell will express all of these genes as proteins . As different types of cells , such as brain , liver , fat or muscle cells , develop , they will express different genes; or they will express the same genes , but at different times and in differe...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "cell", "biology" ]	2013	H3K4 mono- and di-methyltransferase MLL4 is required for enhancer activation during cell differentiation
Nuclear pore complexes ( NPCs ) form a selective filter that allows the rapid passage of transport factors ( TFs ) and their cargoes across the nuclear envelope , while blocking the passage of other macromolecules . Intrinsically disordered proteins ( IDPs ) containing phenylalanyl-glycyl ( FG ) -rich repeats line the ...	Eukaryotic cells have a nucleus that contains most of the organism's genetic material . Two layers of membrane form an envelope around the nucleus and protect its contents from the rest of the cell's interior . However , this protective barrier must also allow certain proteins and nucleic acids ( collectively called ‘c...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2015	The molecular mechanism of nuclear transport revealed by atomic-scale measurements
Human perception is invariably accompanied by a graded feeling of confidence that guides metacognitive awareness and decision-making . It is often assumed that this arises solely from the feed-forward encoding of the strength or precision of sensory inputs . In contrast , interoceptive inference models suggest that con...	As you read the words on this page , you might also notice a growing feeling of confidence that you understand their meaning . Every day we make decisions based on ambiguous information and in response to factors over which we have little or no control . Yet rather than being constantly paralysed by doubt , we generall...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Unexpected arousal modulates the influence of sensory noise on confidence
The brain has evolved an internal model of gravity to cope with life in the Earth's gravitational environment . How this internal model benefits the implementation of skilled movement has remained unsolved . One prevailing theory has assumed that this internal model is used to compensate for gravity's mechanical effect...	Many of the activities of humans and other animals require the limbs to be moved in a coordinated manner . For a movement to be successful , the brain must generate muscle contractions that take into account factors in the environment that might affect the movement . One such prominent environmental feature is gravity ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology", "neuroscience" ]	2016	Direction-dependent arm kinematics reveal optimal integration of gravity cues
Reaction times ( RTs ) are assumed to reflect the underlying computations required for making decisions and preparing actions . Recent work , however , has shown that movements can be initiated earlier than typically expressed without affecting performance; hence , the RT may be modulated by factors other than computat...	Often , we need to make split-second decisions , be it to avoid an accident , outwit someone in an argument or to win a game . The time that it takes to respond to a signal , i . e . , the reaction time , might be the crucial factor to help us succeed or even survive . Many people assume that the reaction time represen...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2017	Reaction times can reflect habits rather than computations
β- and γ-cytoplasmic actins are ubiquitously expressed in every cell type and are nearly identical at the amino acid level but play vastly different roles in vivo . Their essential roles in embryogenesis and mesenchymal cell migration critically depend on the nucleotide sequences of their genes , rather than their amin...	Most mammalian cells make both β- and γ-actin , two proteins which shape the cell’s internal skeleton and its ability to migrate . The molecules share over 99% of their sequence , yet they play distinct roles . In fact , deleting the β-actin gene in mice causes death in the womb , while the animals can survive with com...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2021	Different translation dynamics of β- and γ-actin regulates cell migration
Neuropathic pain following peripheral nerve injury is associated with hyperexcitability in damaged myelinated sensory axons , which begins to normalise over time . We investigated the composition and distribution of shaker-type-potassium channels ( Kv1 channels ) within the nodal complex of myelinated axons following i...	Around 20% of the world’s population experiences long-lasting “chronic” pain , which often results in poor sleep , depression and anxiety . One of the most disabling forms of chronic pain is called neuropathic pain , which results from injuries to sensory nerves . Pain or discomfort is felt in response to touches that ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Altered potassium channel distribution and composition in myelinated axons suppresses hyperexcitability following injury
The origins and functions of kidney macrophages in the adult have been explored , but their roles during development remain largely unknown . Here we characterise macrophage arrival , localisation , heterogeneity , and functions during kidney organogenesis . Using genetic approaches to ablate macrophages , we identify ...	The kidneys clean our blood by filtering out waste products while ensuring that useful components , like nutrients , remain in the bloodstream . Blood enters the kidneys through a network of intricately arranged blood vessels , which associate closely with the ‘cleaning tubes’ that carry out filtration . Human kidneys ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2019	Macrophages restrict the nephrogenic field and promote endothelial connections during kidney development
A 3 . 3 MDa macromolecular cage between two Escherichia coli proteins with seemingly incompatible symmetries–the hexameric AAA+ ATPase RavA and the decameric inducible lysine decarboxylase LdcI–is reconstructed by cryo-electron microscopy to 11 Å resolution . Combined with a 7 . 5 Å resolution reconstruction of the min...	Bacteria inhabit most habitats on Earth , ranging from our bodies to the deepest depths of oceans . In order to thrive in these diverse surroundings , bacteria have developed sophisticated systems that enable them to adapt to changes in their environment . For instance , the bacteria that live in our stomach are expose...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "physics", "of", "living", "systems" ]	2014	Assembly principles of a unique cage formed by hexameric and decameric E. coli proteins
RecQ helicases promote genomic stability through their unique ability to suppress illegitimate recombination and resolve recombination intermediates . These DNA structure-specific activities of RecQ helicases are mediated by the helicase-and-RNAseD like C-terminal ( HRDC ) domain , via unknown mechanisms . Here , emplo...	Molecules of DNA carry instructions for all of the biological processes that happen in cells . Therefore , it is very important that cells maintain their DNA and quickly repair any damage . DNA molecules are made of two strands that twist together to form a double helix . The most reliable way to repair damage affectin...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2019	Homology sensing via non-linear amplification of sequence-dependent pausing by RecQ helicase
Photosynthetic starch reserves that accumulate in Arabidopsis leaves during the day decrease approximately linearly with time at night to support metabolism and growth . We find that the rate of decrease is adjusted to accommodate variation in the time of onset of darkness and starch content , such that reserves last a...	Many organisms build up reserves of food when it is available so that metabolism and growth can continue when food is no longer available . Plants , for example , use energy from the sun to produce starch during the day , which is then used as a source of energy during the night . In some plants the amount of starch in...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology" ]	2013	Arabidopsis plants perform arithmetic division to prevent starvation at night
Aggregation of Cu–Zn superoxide dismutase ( SOD1 ) is implicated in the motor neuron disease , amyotrophic lateral sclerosis ( ALS ) . Although more than 140 disease mutations of SOD1 are available , their stability or aggregation behaviors in membrane environment are not correlated with disease pathophysiology . Here ...	Amyotrophic lateral sclerosis , or ALS , is an incurable neurodegenerative disease in which a person slowly loses specialized nerve cells that control voluntary movement . It is not fully understood what causes this fatal disease . However , it is suspected that clumps , or aggregates , of a protein called SOD1 in nerv...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics" ]	2021	The metal cofactor zinc and interacting membranes modulate SOD1 conformation-aggregation landscape in an in vitro ALS model
miR-128 , a brain-enriched microRNA , has been implicated in the control of neurogenesis and synaptogenesis but its potential roles in intervening processes have not been addressed . We show that post-transcriptional mechanisms restrict miR-128 accumulation to post-mitotic neurons during mouse corticogenesis and in adu...	The unique capabilities of the mammalian brain depend on the patterns formed by spatial arrangements and connections between millions ( sometimes billions ) of electrically active cells called neurons , and on the connections between these neurons . During the development of the cortex , the largest part of the brain ,...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "cell", "biology" ]	2015	miR-128 regulates neuronal migration, outgrowth and intrinsic excitability via the intellectual disability gene Phf6
We describe the physical context of the Dinaledi Chamber within the Rising Star cave , South Africa , which contains the fossils of Homo naledi . Approximately 1550 specimens of hominin remains have been recovered from at least 15 individuals , representing a small portion of the total fossil content . Macro-vertebrate...	Modern humans , or Homo sapiens , are now the only living species in their genus . But as recently as 20 , 000 years ago there were other species that belonged to the genus Homo . Together with modern humans , these extinct human species , our immediate ancestors and their close relatives are collectively referred to a...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology" ]	2015	Geological and taphonomic context for the new hominin species Homo naledi from the Dinaledi Chamber, South Africa
Males and females typically pursue divergent reproductive strategies and accordingly require different dietary compositions to maximise their fitness . Here we move from identifying sex-specific optimal diets to understanding the molecular mechanisms that underlie male and female responses to dietary variation in Droso...	"You are what you eat" is a popular saying that can often make scientific sense . Everything an animal eats gets broken down into smaller molecules that fuel the many biological processes required to survive , move and reproduce . However , the food that the sexes need to maximize their fertility may not be exactly the...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology", "genetics", "and", "genomics" ]	2019	Sex-specific transcriptomic responses to changes in the nutritional environment
In mouse embryo gastrulation , epiblast cells delaminate at the primitive streak to form mesoderm and definitive endoderm , through an epithelial-mesenchymal transition . Mosaic expression of a membrane reporter in nascent mesoderm enabled recording cell shape and trajectory through live imaging . Upon leaving the stre...	As an embryo develops , its cells divide and specialize to form different tissues and organs . Early in development the cells arrange into so-called germ layers , which each produce particular types of tissue . One of these layers , called the mesoderm , develops into the muscles , bones and circulatory system of the e...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2019	Distinct mesoderm migration phenotypes in extra-embryonic and embryonic regions of the early mouse embryo
To understand the neural origins of rhythmic behavior one must characterize the central pattern generator circuit and quantify the population size needed to sustain functionality . Breathing-related interneurons of the brainstem pre-Bötzinger complex ( preBötC ) that putatively comprise the core respiratory rhythm gene...	Our first breath , moments after we are born , is the result of a pattern of activity in our brain that started in the embryo and will continue almost effortlessly until we die . Like other rhythmic activities , such as walking and swimming , breathing originates from circuits of neurons in the brain that generate patt...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2014	Laser ablation of Dbx1 neurons in the pre-Bötzinger complex stops inspiratory rhythm and impairs output in neonatal mice
We recently reported that the C2AB portion of Synaptotagmin 1 ( Syt1 ) could self-assemble into Ca2+-sensitive ring-like oligomers on membranes , which could potentially regulate neurotransmitter release . Here we report that analogous ring-like oligomers assemble from the C2AB domains of other Syt isoforms ( Syt2 , Sy...	Reliable communication between neurons is essential for the brain to work properly . This is accomplished by tightly controlling how chemical messengers , called neurotransmitters , move between neurons . Neurotransmitters are typically packaged into bubble-like structures called synaptic vesicles and are released only...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics", "neuroscience" ]	2016	Ring-like oligomers of Synaptotagmins and related C2 domain proteins
COPI coated vesicles carry material between Golgi compartments , but the role of COPI in the secretory pathway has been ambiguous . Previous studies of thermosensitive yeast COPI mutants yielded the surprising conclusion that COPI was dispensable both for the secretion of certain proteins and for Golgi cisternal matura...	Proteins play many important roles for cells , and these roles often require the proteins to be in particular locations in or around the cells . A set of cell compartments called the Golgi packages certain proteins into bubble-like structures called vesicles to enable the proteins to be used elsewhere in the cell or re...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2015	COPI selectively drives maturation of the early Golgi
Ethylene plays critical roles in plant development and biotic stress response , but the mechanism of ethylene in host antiviral response remains unclear . Here , we report that Rice dwarf virus ( RDV ) triggers ethylene production by stimulating the activity of S-adenosyl-L-methionine synthetase ( SAMS ) , a key compon...	Rice provides food for billions of people all over the world , but diseases caused by plant-infecting viruses cause serious risks to the production of rice . As a result , there is an urgent demand for developing new and impactful ways to help defend rice plants from harmful viruses . Toward this goal , it will be impo...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology" ]	2017	A viral protein promotes host SAMS1 activity and ethylene production for the benefit of virus infection
Matrix stiffening with downstream activation of mechanosensitive pathways is strongly implicated in progressive fibrosis; however , pathologic changes in extracellular matrix ( ECM ) that initiate mechano-homeostasis dysregulation are not defined in human disease . By integrated multiscale biomechanical and biological ...	Idiopathic pulmonary fibrosis ( IPF ) is a devastating disease of the lung , which scars the tissue and gradually destroys the organ , ultimately leading to death . It is still unclear what exactly causes this scarring , but it is thought that increasing amounts of proteins in the space surrounding the cells of the lun...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2018	Nanoscale dysregulation of collagen structure-function disrupts mechano-homeostasis and mediates pulmonary fibrosis
Across the animal kingdom , environmental light cues are widely involved in regulating gamete release , but the molecular and cellular bases of the photoresponsive mechanisms are poorly understood . In hydrozoan jellyfish , spawning is triggered by dark-light or light-dark transitions acting on the gonad , and is media...	Many animals living in the sea reproduce by releasing sperm and egg cells at the same time into the surrounding water . Animals often use changes in ambient light at dawn and dusk as reliable daily cues to coordinate this spawning behavior between individuals . For example , jellyfish of the species Clytia hemisphaeric...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2018	A gonad-expressed opsin mediates light-induced spawning in the jellyfish Clytia
Sensory systems sequentially extract increasingly complex features . ON and OFF pathways , for example , encode increases or decreases of a stimulus from a common input . This ON/OFF pathway split is thought to occur at individual synaptic connections through a sign-inverting synapse in one of the pathways . Here , we ...	We rely on our senses to capture information about the world around us . Sense organs convert sensory information – such as light or sound waves – into patterns of neuronal activity . In the mammalian retina , for example , specialized neurons called photoreceptors detect individual photons of light as they hit the bac...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2019	ON selectivity in the Drosophila visual system is a multisynaptic process involving both glutamatergic and GABAergic inhibition
Reverse replay of hippocampal place cells occurs frequently at rewarded locations , suggesting its contribution to goal-directed path learning . Symmetric spike-timing dependent plasticity ( STDP ) in CA3 likely potentiates recurrent synapses for both forward ( start to goal ) and reverse ( goal to start ) replays duri...	To find their way around , animals – including humans – rely on an area of the brain called the hippocampus . Studies in rodents have shown that certain neurons in the hippocampus called place cells become active when an animal passes through specific locations . At each position , a different set of place cells fires ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2018	Recurrent network model for learning goal-directed sequences through reverse replay
Social insects frequently engage in oral fluid exchange – trophallaxis – between adults , and between adults and larvae . Although trophallaxis is widely considered a food-sharing mechanism , we hypothesized that endogenous components of this fluid might underlie a novel means of chemical communication between colony m...	Ants , bees and other social insects live in large colonies where all the individuals work together to gather food , rear young and defend the colony . This level of cooperation requires the insects in the colony to be able to communicate with each other . Most social insects share fluid mouth-to-mouth with other indiv...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology", "genetics", "and", "genomics" ]	2016	Oral transfer of chemical cues, growth proteins and hormones in social insects
Hypoxia and ischemia are linked to oxidative stress , which can activate the oxidant-sensitive transient receptor potential ankyrin 1 ( TRPA1 ) channel in cerebral artery endothelial cells , leading to vasodilation . We hypothesized that TRPA1 channels in endothelial cells are activated by hypoxia-derived reactive oxyg...	A stroke can cause long-lasting physical and mental disabilities in patients including loss of mobility , speech defects and confusion . Most strokes happen when the blood supply to part of the brain is cut off due to blood clots or clumps of fat blocking blood vessels called arteries . To prevent a blocked blood vesse...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2018	Neuroprotective effects of TRPA1 channels in the cerebral endothelium following ischemic stroke
Primate evolution has been argued to result , in part , from changes in how genes are regulated . However , we still know little about gene regulation in natural primate populations . We conducted an RNA sequencing ( RNA-seq ) -based study of baboons from an intensively studied wild population . We performed complement...	Our genes contain the instructions needed to make all aspects of the body . These instructions can be changed by altering the sequence of the DNA that makes up the genes , which can account for many of the different characteristics found in humans and other animals . However , our characteristics can also be altered by...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology" ]	2015	The genetic architecture of gene expression levels in wild baboons
Tumor suppressor p53 prevents early death due to cancer development . However , the role of p53 in aging process and longevity has not been well-established . In humans , single nucleotide polymorphism ( SNP ) with either arginine ( R72 ) or proline ( P72 ) at codon 72 influences p53 activity; the P72 allele has a weak...	How long most animals live depends on the balance between the biological processes that allow them to regenerate their tissues when damaged and those that prevent them from developing cancer . Regeneration relies mostly on cells , in particular stem cells , dividing to make new cells , while cancer occurs when cell div...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cancer", "biology" ]	2018	A polymorphism in the tumor suppressor p53 affects aging and longevity in mouse models
PAK1 inhibitors are known to markedly improve social and cognitive function in several animal models of brain disorders , including autism , but the underlying mechanisms remain elusive . We show here that disruption of PAK1 in mice suppresses inhibitory neurotransmission through an increase in tonic , but not phasic ,...	Brain cells communicate by sending chemical signals that activate or excite neighbouring cells . However , too much signalling can be harmful . As such the brain has systems in place to inhibit brain signals , and healthy brain activity relies striking a proper balance between excitation and inhibition . In some brain ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	p21-activated kinase 1 restricts tonic endocannabinoid signaling in the hippocampus
Pore-blocking toxins inhibit voltage-dependent K+ channels ( Kv channels ) by plugging the ion-conduction pathway . We have solved the crystal structure of paddle chimera , a Kv channel in complex with charybdotoxin ( CTX ) , a pore-blocking toxin . The toxin binds to the extracellular pore entryway without producing d...	The deadly toxins produced by many creatures , including spiders , snakes , and scorpions , work by blocking the ion channels that are essential for the normal operation of many different types of cells . Ion channels are proteins and , as their name suggests , they allow ions—usually sodium , potassium , or calcium io...	[ "Abstract", "Introduction", "Results", "Discussion" ]	[ "structural", "biology", "and", "molecular", "biophysics", "neuroscience" ]	2013	Structure of a pore-blocking toxin in complex with a eukaryotic voltage-dependent K+ channel
Soluble N-ethylmaleimide-sensitive factor attachment protein receptors ( SNAREs ) are evolutionarily conserved machines that couple their folding/assembly to membrane fusion . However , it is unclear how these processes are regulated and function . To determine these mechanisms , we characterized the folding energy and...	Many processes in living things need molecules to be transported within , or between , cells . For example , damaged or waste molecules are transported within a cell to structures that can break the molecules down , while nerve impulses are transmitted from one neuron to the next via the release of signaling molecules ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2014	Common intermediates and kinetics, but different energetics, in the assembly of SNARE proteins
To investigate the phenomic and genomic traits that allow green algae to survive in deserts , we characterized a ubiquitous species , Chloroidium sp . UTEX 3007 , which we isolated from multiple locations in the United Arab Emirates ( UAE ) . Metabolomic analyses of Chloroidium sp . UTEX 3007 indicated that the alga ac...	Single-celled green algae , also known as green microalgae , play an important role for the world’s ecosystems , in part , because they can harness energy from sunlight to produce carbon-rich compounds . Microalgae are also important for biotechnology and people have harnessed them to make food , fuel and medicines . G...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology", "genetics", "and", "genomics" ]	2017	The genome and phenome of the green alga Chloroidium sp. UTEX 3007 reveal adaptive traits for desert acclimatization
Evolutionary origin of muscle is a central question when discussing mesoderm evolution . Developmental mechanisms underlying somatic muscle development have mostly been studied in vertebrates and fly where multiple signals and hierarchic genetic regulatory cascades selectively specify myoblasts from a pool of naive mes...	Muscles , bones , and blood vessels all develop from a tissue called the mesoderm , which forms early on in the development of an embryo . Networks of genes control which parts of the mesoderm transform into different cell types . The gene networks that control the development of muscle cells from the mesoderm have so ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "evolutionary", "biology" ]	2015	Logics and properties of a genetic regulatory program that drives embryonic muscle development in an echinoderm
Retinal prostheses are promising tools for recovering visual functions in blind patients but , unfortunately , with still poor gains in visual acuity . Improving their resolution is thus a key challenge that warrants understanding its origin through appropriate animal models . Here , we provide a systematic comparison ...	One of the most common causes of blindness is a disorder called retinitis pigmentosa . In a healthy eye , the surface at the back of the eye – called the retina – contains cells called photoreceptors that detect light and convert it into electrical signals for the brain to process . In people with retinitis pigmentosa ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Probing the functional impact of sub-retinal prosthesis
The phosphoinositide 3-kinase ( PI3K ) -Akt network is tightly controlled by feedback mechanisms that regulate signal flow and ensure signal fidelity . A rapid overshoot in insulin-stimulated recruitment of Akt to the plasma membrane has previously been reported , which is indicative of negative feedback operating on a...	For the body to work properly , cells must constantly ‘talk’ to each other using signalling molecules . Receiving a chemical signal triggers a series of molecular events in a cell , a so-called ‘signal transduction pathway’ that connects a signal with a precise outcome . Disturbing cell signalling can trigger disease ,...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "computational", "and", "systems", "biology" ]	2021	Akt phosphorylates insulin receptor substrate to limit PI3K-mediated PIP3 synthesis
Secretory and endolysosomal fusion events are driven by SNAREs and cofactors , including Sec17/α-SNAP , Sec18/NSF , and Sec1/Munc18 ( SM ) proteins . SMs are essential for fusion in vivo , but the basis of this requirement is enigmatic . We now report that , in addition to their established roles as fusion accelerators...	Eukaryotic organisms , from single-celled yeast to humans , divide their cells into membrane-bound compartments ( organelles ) of distinct function . To move from one compartment to another , or to enter or exit a cell , large molecules like proteins are packaged into small membrane sacs called vesicles . To release it...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "cell", "biology" ]	2014	SM proteins Sly1 and Vps33 co-assemble with Sec17 and SNARE complexes to oppose SNARE disassembly by Sec18
Rhythmic behaviors vary across individuals . We investigated the sources of this output variability across a motor system , from the central pattern generator ( CPG ) to the motor plant . In the bilaterally symmetric leech heartbeat system , the CPG orchestrates two coordinations in the bilateral hearts with different ...	Many of our everyday behaviors are rhythmic actions , such as walking , breathing and chewing . Networks of neurons called Central Pattern Generators , or CPGs , are in charge of rhythmic behaviors . CPGs send instructions to cells called motor neurons , which in turn tell muscles to contract in a particular sequence t...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2018	Output variability across animals and levels in a motor system
The ability to computationally predict whether a compound treats a disease would improve the economy and success rate of drug approval . This study describes Project Rephetio to systematically model drug efficacy based on 755 existing treatments . First , we constructed Hetionet ( neo4j . het . io ) , an integrative ne...	Of all the data in the world today , 90% was created in the last two years . However , taking advantage of this data in order to advance our knowledge is restricted by how quickly we can access it and analyze it in a proper context . In biomedical research , data is largely fragmented and stored in databases that typic...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology" ]	2017	Systematic integration of biomedical knowledge prioritizes drugs for repurposing
While small molecule inhibitors of the bacterial ribosome have been instrumental in understanding protein translation , no such probes exist to study ribosome biogenesis . We screened a diverse chemical collection that included previously approved drugs for compounds that induced cold sensitive growth inhibition in the...	Inside cells , molecular machines called ribosomes make proteins from instructions that are provided by genes . The ribosomes themselves are made up of about 50 proteins and three RNA molecules that need to be assembled like a 3-D jigsaw . In bacteria , a group of proteins called ribosome biogenesis factors help to ass...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "microbiology", "and", "infectious", "disease" ]	2014	Discovery of a small molecule that inhibits bacterial ribosome biogenesis
Cellular senescence is a crucial tumor suppressor mechanism . We discovered a CAPERα/TBX3 repressor complex required to prevent senescence in primary cells and mouse embryos . Critical , previously unknown roles for CAPERα in controlling cell proliferation are manifest in an obligatory interaction with TBX3 to regulate...	Cell division and growth are essential for survival . But it is equally important that cells can stop dividing , because failing to do so can lead to the uncontrolled tumor growth seen in cancer . One such quality control mechanism is called senescence , which stops the growth and multiplication of cells that are old ,...	[ "Abstract", "Introduction", "Results", "Discussion", "Material", "and", "methods" ]	[ "developmental", "biology", "cell", "biology" ]	2014	Coordinated control of senescence by lncRNA and a novel T-box3 co-repressor complex
Every DNA segment in a eukaryotic genome normally replicates once and only once per cell cycle to maintain genome stability . We show here that this restriction can be bypassed through alternative transposition , a transposition reaction that utilizes the termini of two separate , nearby transposable elements ( TEs ) ....	To make accurate copies of its genome , a cell takes precautions to make sure each section of DNA is only duplicated once in every round of copying . However , there are some sections of DNA called transposons that can avoid these restrictions and be duplicated more often . Transposons are mobile pieces of DNA: they ca...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "plant", "biology" ]	2014	Transposition-mediated DNA re-replication in maize
Heat shock factor ( Hsf1 ) regulates the expression of molecular chaperones to maintain protein homeostasis . Despite its central role in stress resistance , disease and aging , the mechanisms that control Hsf1 activity remain unresolved . Here we show that in budding yeast , Hsf1 basally associates with the chaperone ...	Proteins are strings of amino acids that carry out crucial activities inside cells , such as harvesting energy and generating the building blocks that cells need to grow . In order to carry out their specific roles inside the cell , the proteins need to “fold” into precise three-dimensional shapes . Protein folding is ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "computational", "and", "systems", "biology" ]	2016	Dynamic control of Hsf1 during heat shock by a chaperone switch and phosphorylation
The neurophysiological processes underlying non-invasive brain activity measurements are incompletely understood . Here , we developed a connectome-based brain network model that integrates individual structural and functional data with neural population dynamics to support multi-scale neurophysiological inference . Si...	Neuroscientists can use various techniques to measure activity within the brain without opening up the skull . One of the most common is electroencephalography , or EEG for short . A net of electrodes is attached to the scalp and reveals the patterns of electrical activity occurring in brain tissue . But while EEG is g...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology", "neuroscience" ]	2018	Inferring multi-scale neural mechanisms with brain network modelling
N-myristoylation is a ubiquitous class of protein lipidation across eukaryotes and N-myristoyl transferase ( NMT ) has been proposed as an attractive drug target in several pathogens . Myristoylation often primes for subsequent palmitoylation and stable membrane attachment , however , growing evidence suggests addition...	A microscopic parasite known as Toxoplasma gondii infects around 30% of the human population . Most infections remain asymptomatic , but in people with a compromised immune system , developing fetuses and people infected with particular virulent strains of the parasite , infection can be fatal . T . gondii is closely r...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "microbiology", "and", "infectious", "disease" ]	2020	Profiling of myristoylation in Toxoplasma gondii reveals an N-myristoylated protein important for host cell penetration
Bats host virulent zoonotic viruses without experiencing disease . A mechanistic understanding of the impact of bats’ virus hosting capacities , including uniquely constitutive immune pathways , on cellular-scale viral dynamics is needed to elucidate zoonotic emergence . We carried out virus infectivity assays on bat c...	Bats can carry viruses that are deadly to other mammals without themselves showing serious symptoms . In fact , bats are natural reservoirs for viruses that have some of the highest fatality rates of any viruses that people acquire from wild animals – including rabies , Ebola and the SARS coronavirus . Bats have a suit...	[ "Abstract", "Introduction", "Results", "Discussion" ]	[ "ecology", "epidemiology", "and", "global", "health" ]	2020	Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence
The coordination of movement across the body is a fundamental , yet poorly understood aspect of motor control . Mutant mice with cerebellar circuit defects exhibit characteristic impairments in locomotor coordination; however , the fundamental features of this gait ataxia have not been effectively isolated . Here we de...	Though it seems simple , walking is a complex activity . The arms , legs , body , and head all need to work together . A part of the brain called the cerebellum helps to coordinate the movements of different body parts allowing both simple and complex tasks to be carried out smoothly . But it is not known exactly how t...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	A quantitative framework for whole-body coordination reveals specific deficits in freely walking ataxic mice
Metastasis is a major cause of cancer mortality . We generated an autochthonous transgenic mouse model whereby conditional expression of MYC and Twist1 enables hepatocellular carcinoma ( HCC ) to metastasize in >90% of mice . MYC and Twist1 cooperate and their sustained expression is required to elicit a transcriptiona...	Cancer develops when cells in the body gain mutations that allow them to grow and divide rapidly and uncontrollably . As the disease progresses these cancer cells develop the ability to spread around the body . This process of spreading , called metastasis , is responsible for most cancer-related deaths in humans , but...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cancer", "biology" ]	2020	MYC and Twist1 cooperate to drive metastasis by eliciting crosstalk between cancer and innate immunity
Plants produce many different specialized ( secondary ) metabolites that function in solving ecological challenges; few are known to function in growth or other primary processes . 17-Hydroxygeranylinalool diterpene glycosides ( DTGs ) are abundant herbivory-induced , structurally diverse and commonly malonylated defen...	Plants produce tens of thousands of molecules called secondary metabolites that are thought to help them cope with threats from their environment , such as attack by insects or ultraviolet radiation from the sun . Wild coyote tobacco plants produce large amounts of a particular class of secondary metabolite known as DT...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "ecology", "plant", "biology" ]	2018	The decoration of specialized metabolites influences stylar development
During embryonic development , cells of the green alga Oophila amblystomatis enter cells of the salamander Ambystoma maculatum forming an endosymbiosis . Here , using de novo dual-RNA seq , we compared the host salamander cells that harbored intracellular algae to those without algae and the algae inside the animal cel...	Throughout the natural world , when different species form a close association , it is known as a symbiosis . One species can depend on another for food , defense against predators or even for reproduction . Corals , for example , incorporate single-celled algae into their own cells . The algae photosynthesize , harnes...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "ecology" ]	2017	Transcriptome analysis illuminates the nature of the intracellular interaction in a vertebrate-algal symbiosis
Production of healthy gametes in meiosis relies on the quality control and proper distribution of both nuclear and cytoplasmic contents . Meiotic differentiation naturally eliminates age-induced cellular damage by an unknown mechanism . Using time-lapse fluorescence microscopy in budding yeast , we found that nuclear s...	The cells of living organisms accumulate damage as they age . Some of this age-associated damage is found around the organism’s DNA . However , when genetic material is passed on during sexual reproduction , newly born offspring avoid inheriting this age-induced damage . This ensures that the progeny are ‘re-set’ with ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2019	Meiotic cellular rejuvenation is coupled to nuclear remodeling in budding yeast
The molecular codes underpinning the functions of plant NLR immune receptors are poorly understood . We used in vitro Mu transposition to generate a random truncation library and identify the minimal functional region of NLRs . We applied this method to NRC4—a helper NLR that functions with multiple sensor NLRs within ...	Just like humans , plants get sick . They can be infected by parasites as diverse as fungi , bacteria , viruses , nematode worms and insects . But , also like humans , plants have an immune system that helps them defend against disease . Their first line of defence are disease resistance genes . Many of these genes enc...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology" ]	2019	An N-terminal motif in NLR immune receptors is functionally conserved across distantly related plant species
Diarrheal illness is a leading cause of antibiotic use for children in low- and middle-income countries . Determination of diarrhea etiology at the point-of-care without reliance on laboratory testing has the potential to reduce inappropriate antibiotic use . This prospective observational study aimed to develop and ex...	Diarrhea is one of the most common illnesses among children worldwide . In low- and middle-income countries with limited health care resources , it can be deadly . Diarrhea can be caused by infections with viruses or bacteria . Antibiotics can treat bacterial infections , but they are not effective against viral infect...	[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "Discussion" ]	[ "epidemiology", "and", "global", "health", "medicine" ]	2022	External validation of a mobile clinical decision support system for diarrhea etiology prediction in children: A multicenter study in Bangladesh and Mali
The age of large-scale genome-wide association studies ( GWAS ) has provided us with an unprecedented opportunity to evaluate the genetic liability of complex disease using polygenic risk scores ( PRS ) . In this study , we have analysed 162 PRS ( p<5×10−05 ) derived from GWAS and 551 heritable traits from the UK Bioba...	An individual’s risk of developing many diseases , including heart disease and schizophrenia , is influenced by a complex combination of lifestyle factors and the genes they inherit at birth . The total number of genetic variants that an individual has that increases their risk of developing a particular disease can be...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "tools", "and", "resources", "genetics", "and", "genomics" ]	2019	An atlas of polygenic risk score associations to highlight putative causal relationships across the human phenome
In the heart , reliable activation of Ca2+ release from the sarcoplasmic reticulum during the plateau of the ventricular action potential requires synchronous opening of multiple CaV1 . 2 channels . Yet the mechanisms that coordinate this simultaneous opening during every heartbeat are unclear . Here , we demonstrate t...	To pump blood around the body , the muscle cells within the heart must contract and relax together with a regular rhythm . A contraction begins when proteins called CaV1 . 2 channels embedded in the cell membranes of heart cells open to allow calcium ions to enter the cells . The calcium ions that enter through these C...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics" ]	2015	Graded Ca2+/calmodulin-dependent coupling of voltage-gated CaV1.2 channels

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