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Epithelial fusion is a crucial process in embryonic development , and its failure underlies several clinically important birth defects . For example , failure of neural fold fusion during neurulation leads to open neural tube defects including spina bifida . Using mouse embryos , we show that cell protrusions emanating...	The neural tube is an embryonic structure that gives rise to the brain and spinal cord . It originates from a flat sheet of cells – the neural plate – that rolls up and fuses to form a tube during development . If this closure fails , it leads to birth defects such as spina bifida , a condition that causes severe disab...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "cell", "biology" ]	2016	Regulation of cell protrusions by small GTPases during fusion of the neural folds
Convergence and extension movements elongate tissues during development . Drosophila germ-band extension ( GBE ) is one example , which requires active cell rearrangements driven by Myosin II planar polarisation . Here , we develop novel computational methods to analyse the spatiotemporal dynamics of Myosin II during G...	Early in development , a growing embryo elongates to form its main body ( head–tail ) axis . This elongation is driven by a process called cell intercalation – when cells insert between each other . The mechanism that controls this coordinated cell movement is well understood on a small scale . However , it is not know...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "computational", "and", "systems", "biology" ]	2016	Unipolar distributions of junctional Myosin II identify cell stripe boundaries that drive cell intercalation throughout Drosophila axis extension
RNA editing by adenosine deamination alters genetic information from the genomic blueprint . When it recodes mRNAs , it gives organisms the option to express diverse , functionally distinct , protein isoforms . All eumetazoans , from cnidarians to humans , express RNA editing enzymes . However , transcriptome-wide scre...	For living cells to create a protein , a genetic code found in its DNA must first be ‘transcribed’ to create a corresponding molecule of messenger RNA ( mRNA ) . DNA and RNA are both made from smaller molecules called nucleotides that are linked together into long chains; the information in both DNA and RNA is containe...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "short", "report", "neuroscience", "genetics", "and", "genomics" ]	2015	The majority of transcripts in the squid nervous system are extensively recoded by A-to-I RNA editing
Autophagy is a catabolic process for bulk degradation of cytosolic materials mediated by double-membraned autophagosomes . The membrane determinant to initiate the formation of autophagosomes remains elusive . Here , we establish a cell-free assay based on LC3 lipidation to define the organelle membrane supporting earl...	Cells continually adapt their behavior to accommodate changes in their environment . For example , when nutrients are abundant , cells can grow or proliferate; in times of scarcity , however , they must conserve resources for essential tasks . In particular , during periods of starvation , cells can cannibalize themsel...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "cell", "biology" ]	2013	The ER–Golgi intermediate compartment is a key membrane source for the LC3 lipidation step of autophagosome biogenesis
Blood progenitors within the lymph gland , a larval organ that supports hematopoiesis in Drosophila melanogaster , are maintained by integrating signals emanating from niche-like cells and those from differentiating blood cells . We term the signal from differentiating cells the ‘equilibrium signal’ in order to disting...	Progenitor cells are cells that can either multiply to make new copies of themselves or mature into different specialized cell types—such as blood cells . In the fruit fly Drosophila , new blood cells are formed in several different locations , including in an organ called the lymph gland . In 2011 , researchers found ...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2014	Pvr expression regulators in equilibrium signal control and maintenance of Drosophila blood progenitors
Human cytomegalovirus ( hCMV ) immediate early 1 ( IE1 ) protein associates with condensed chromatin of the host cell during mitosis . We have determined the structure of the chromatin-tethering domain ( CTD ) of IE1 bound to the nucleosome core particle , and discovered that the specific interaction between IE1-CTD an...	Most of the DNA in a cell is tightly wrapped around groups of proteins called histones , which gives the impression of beads on a string . These bead-like structures are called nucleosomes , and interactions between histones in different nucleosomes can link one nucleosome to another , to package the DNA into a very co...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "short", "report", "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2016	Human cytomegalovirus IE1 protein alters the higher-order chromatin structure by targeting the acidic patch of the nucleosome
microRNA-1 ( miR-1 ) is an evolutionarily conserved , striated muscle-enriched miRNA . Most mammalian genomes contain two copies of miR-1 , and in mice , deletion of a single locus , miR-1-2 , causes incompletely penetrant lethality and subtle cardiac defects . Here , we report that deletion of miR-1-1 resulted in a ph...	MicroRNAs are tiny RNAs that do not encode proteins . Instead , they regulate the expression of genes by preventing protein-encoding messenger RNAs from being translated into protein . MicroRNAs are expressed throughout the body , including the heart , where the most abundant microRNA is called miR-1 . This is encoded ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "developmental", "biology" ]	2013	microRNA-1 regulates sarcomere formation and suppresses smooth muscle gene expression in the mammalian heart
Goal-directed behavior involves distributed neuronal circuits in the mammalian brain , including diverse regions of neocortex . However , the cellular basis of long-range cortico-cortical signaling during goal-directed behavior is poorly understood . Here , we recorded membrane potential of excitatory layer 2/3 pyramid...	Many animals can learn quickly to associate specific behaviors with rewards , such as food . Often , the animal’s senses of smell , taste , and touch trigger the behavior , and this allows an animal to respond favorably to changes in its environments . However , it is not clear exactly what happens in the animal’s brai...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "short", "report", "neuroscience" ]	2016	Target-specific membrane potential dynamics of neocortical projection neurons during goal-directed behavior
Recent genome analyses have identified recurrent mutations in the cohesin complex in a wide range of human cancers . Here we demonstrate that the most frequently mutated subunit of the cohesin complex , STAG2 , displays a strong synthetic lethal interaction with its paralog STAG1 . Mechanistically , STAG1 loss abrogate...	A big challenge for cancer research is to find drugs and treatments that kill cancer cells without harming the other cells of a patient . Cancer cells contain genetic mutations that cause them to grow and divide more rapidly than healthy cells . About half a million cancer patients worldwide have tumors that feature mu...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "short", "report", "cell", "biology", "cancer", "biology" ]	2017	Synthetic lethality between the cohesin subunits STAG1 and STAG2 in diverse cancer contexts
Transcription start-site ( TSS ) selection and alternative promoter ( AP ) usage contribute to gene expression complexity but little is known about their impact on translation . Here we performed TSS mapping of the translatome following energy stress . Assessing the contribution of cap-proximal TSS nucleotides , we fou...	The production of new proteins is a complex process that occurs in two steps known as transcription and translation . During transcription , the cell copies a section of DNA to make molecules of messenger ribonucleic acid ( or mRNA for short ) in the nucleus of the cell . The mRNA then leaves the nucleus and enters ano...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "biochemistry", "and", "chemical", "biology" ]	2017	Cap-proximal nucleotides via differential eIF4E binding and alternative promoter usage mediate translational response to energy stress
The cerebellum , a crucial center for motor coordination , is composed of a cortex and several nuclei . The main mode of interaction between these two parts is considered to be formed by the inhibitory control of the nuclei by cortical Purkinje neurons . We now amend this view by showing that inhibitory GABA-glycinergi...	The cerebellum is a region in the brain that plays a central role in controlling posture and movement . The cerebellum is composed of a cortex and several nuclei . The nuclei are thought to ‘compute’ the signals that are sent from the cerebellum to other parts of the brain to control posture and movement . They do this...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	A novel inhibitory nucleo-cortical circuit controls cerebellar Golgi cell activity
The SWI/SNF-family remodelers regulate chromatin structure by coupling the free energy from ATP hydrolysis to the repositioning and restructuring of nucleosomes , but how the ATPase activity of these enzymes drives the motion of DNA across the nucleosome remains unclear . Here , we used single-molecule FRET to monitor ...	Cells package their genetic information in a "complex” of proteins and DNA called chromatin . This complex is made of units called nucleosomes , each of which consist of a short stretch of DNA wrapped around proteins known as histones . These nucleosomes restrict access to the DNA wrapped around the histone proteins , ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology" ]	2016	Stepwise nucleosome translocation by RSC remodeling complexes
Rapid and stable control of pupil size in response to light is critical for vision , but the neural coding mechanisms remain unclear . Here , we investigated the neural basis of pupil control by monitoring pupil size across time while manipulating each photoreceptor input or neurotransmitter output of intrinsically pho...	The retina is the part of our eye that detects light and sends visual information to the brain . There are several different types of light-sensitive cell in the retina that perform different roles . For example , retinal cells called intrinsically photosensitive retinal ganglion cells ( or ipRGCs for short ) rapidly r...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	A visual circuit uses complementary mechanisms to support transient and sustained pupil constriction
The circadian transcriptional repressors cryptochrome 1 ( Cry1 ) and 2 ( Cry2 ) evolved from photolyases , bacterial light-activated DNA repair enzymes . In this study , we report that while they have lost DNA repair activity , Cry1/2 adapted to protect genomic integrity by responding to DNA damage through posttranslat...	Many aspects of our physiology and behavior , most notably our patterns of sleep and wakefulness , are synchronized with the day–night cycle . These circadian rhythms are generated and maintained by the circadian clock , which consists of positive and negative feedback loops formed by a large number of genes and protei...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "neuroscience" ]	2015	DNA damage shifts circadian clock time via Hausp-dependent Cry1 stabilization
Starch , as the major nutritional component of our staple crops and a feedstock for industry , is a vital plant product . It is composed of glucose polymers that form massive semi-crystalline granules . Its precise structure and composition determine its functionality and thus applications; however , there is no versat...	Most plants and algae produce a carbohydrate called starch , which provides the plant with a dense store of energy . Starch is also the main carbohydrate in our diet and its unusual physical properties mean that it has many industrial uses . It is made of two different sugar-based molecules known as glucans and forms l...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology", "biochemistry", "and", "chemical", "biology" ]	2016	Recreating the synthesis of starch granules in yeast
Human cytomegalovirus ( HCMV ) is a highly prevalent pathogen that induces life-long infections notably through the establishment of latency in hematopoietic stem cells ( HSC ) . Bouts of reactivation are normally controlled by the immune system , but can be fatal in immuno-compromised individuals such as organ transpl...	Human cytomegalovirus ( HCMV ) is an extremely common virus that causes life-long infections in humans . Most individuals are exposed to HCMV during childhood , and the infection rarely causes any symptoms of disease in healthy individuals . However , in people with weaker immune systems—for example , newborn babies , ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "microbiology", "and", "infectious", "disease" ]	2015	Release of human cytomegalovirus from latency by a KAP1/TRIM28 phosphorylation switch
While Cre-dependent viral systems permit the manipulation of many neuron types , some cell populations cannot be targeted by a single DNA recombinase . Although the combined use of Flp and Cre recombinases can overcome this limitation , insufficient recombinase activity can reduce the efficacy of existing Cre+Flp-depen...	The brain contains hundreds of types of neurons , which differ in size , shape and behavior . But neuroscientists often wish to study individual neuronal types in isolation . They are able to do this with the aid of a toolkit made up of two parts: viral vectors and genetically modified mice . Viral vectors are viruses ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "medicine", "tools", "and", "resources", "neuroscience" ]	2021	tTARGIT AAVs mediate the sensitive and flexible manipulation of intersectional neuronal populations in mice
Social interactions are often powerful drivers of learning . In female mice , mating creates a long-lasting sensory memory for the pheromones of the stud male that alters neuroendocrine responses to his chemosignals for many weeks . The cellular and synaptic correlates of pheromonal learning , however , remain unclear ...	To navigate social situations , humans and other animals need to remember who they have interacted with and how it went , and adjust their behavior in future encounters accordingly . For example , your physical actions , and even your body’s physiological responses , will be very different when you encounter the last p...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2017	Neural mechanisms of social learning in the female mouse
For decades , the mechanism of skeletal patterning along a proximal-distal axis has been an area of intense inquiry . Here , we examine the development of the ribs , simple structures that in most terrestrial vertebrates consist of two skeletal elements—a proximal bone and a distal cartilage portion . While the ribs ha...	During animal development , the ribs grow from the back of the embryo around towards the chest . In fish , these bones simply terminate . Yet in land animals , cartilage forms at the end of the rib where it connects to the breastbone , or sternum . This encloses the chest cavity . Fogel , Lakeland et al . have now aske...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2017	A minimally sufficient model for rib proximal-distal patterning based on genetic analysis and agent-based simulations
Bioluminescence imaging ( BLI ) is ubiquitous in scientific research for the sensitive tracking of biological processes in small animal models . However , due to the attenuation of visible light by tissue , and the limited set of near-infrared bioluminescent enzymes , BLI is largely restricted to monitoring single proc...	Fireflies and some other insects glow to attract mates or prey . This so-called bioluminescence occurs when an enzyme called luciferase modifies the molecule luciferin , which can then emit bright yellow-green light . The gene that encodes the luciferase enzyme has been introduced into cells from mammals , including ca...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2019	Near-infrared dual bioluminescence imaging in mouse models of cancer using infraluciferin
Human visual recognition activates a dense network of overlapping feedforward and recurrent neuronal processes , making it hard to disentangle processing in the feedforward from the feedback direction . Here , we used ultra-rapid serial visual presentation to suppress sustained activity that blurs the boundaries of pro...	The human brain can interpret the visual world in less than the blink of an eye . Specialized brain regions process different aspects of visual objects . These regions form a hierarchy . Areas at the base of the hierarchy process simple features such as lines and angles . They then pass this information onto areas abov...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2018	Ultra-Rapid serial visual presentation reveals dynamics of feedforward and feedback processes in the ventral visual pathway
Mycobacterium tuberculosis ( Mtb ) expresses a broad-spectrum β-lactamase ( BlaC ) that mediates resistance to one of the highly effective antibacterials , β-lactams . Nonetheless , β-lactams showed mycobactericidal activity in combination with β-lactamase inhibitor , clavulanate ( Clav ) . However , the mechanistic as...	A bacterium called Mycobacterium tuberculosis causes tuberculosis in humans . Multiple antibiotics are available to treat this infection , yet around one million people still die from tuberculosis each year . One of the reasons that the number of deaths is so high is because many M . tuberculosis cells have become resi...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "microbiology", "and", "infectious", "disease" ]	2017	Efficacy of β-lactam/β-lactamase inhibitor combination is linked to WhiB4-mediated changes in redox physiology of Mycobacterium tuberculosis
Epithelioid hemangioendothelioma ( EHE ) is a vascular sarcoma that metastasizes early in its clinical course and lacks an effective medical therapy . The TAZ-CAMTA1 and YAP-TFE3 fusion proteins are chimeric transcription factors and initiating oncogenic drivers of EHE . A combined proteomic/genetic screen in human cel...	The proliferation of human cells is tightly regulated to ensure that enough cells are made to build and repair organs and tissues , while at the same time stopping cells from dividing uncontrollably and damaging the body . To get the right balance , cells rely on physical and chemical cues from their environment that t...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "cancer", "biology" ]	2021	TAZ-CAMTA1 and YAP-TFE3 alter the TAZ/YAP transcriptome by recruiting the ATAC histone acetyltransferase complex
Local and cross-border importation remain major challenges to malaria elimination and are difficult to measure using traditional surveillance data . To address this challenge , we systematically collected parasite genetic data and travel history from thousands of malaria cases across northeastern Namibia and estimated ...	The number of malaria cases has dropped in some Southern Africa countries , but others still remain seriously affected . When people travel within and between countries , they can bring the parasites that cause the disease to different areas . This can fuel local transmission or even lead to outbreaks in a malaria-free...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "epidemiology", "and", "global", "health" ]	2019	Using parasite genetic and human mobility data to infer local and cross-border malaria connectivity in Southern Africa
From humans to vinegar flies , exposure to diets rich in sugar and fat lowers taste sensation , changes food choices , and promotes feeding . However , how these peripheral alterations influence eating is unknown . Here we used the genetically tractable organism D . melanogaster to define the neural mechanisms through ...	Obesity is a major health problem affecting over 650 million adults worldwide . It is typically caused by overeating high-energy foods , which often contain a lot of sugar . Consuming sugary foods triggers the production of a reward signal called dopamine in the brains of insects and mammals , which reinforces sugar-co...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2020	Dietary sugar inhibits satiation by decreasing the central processing of sweet taste
Microglial dysfunction is a key pathological feature of Alzheimer's disease ( AD ) , but little is known about proteome-wide changes in microglia during the course of AD and their functional consequences . Here , we performed an in-depth and time-resolved proteomic characterization of microglia in two mouse models of a...	Alzheimer’s disease is a progressive , irreversible brain disorder . Patients with Alzheimer’s have problems with memory and other mental skills , which lead to more severe cognitive decline and , eventually , premature death . This is due to increasing numbers of nerve cells in the brain dying over time . A distinctiv...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "tools", "and", "resources", "neuroscience" ]	2020	Fibrillar Aβ triggers microglial proteome alterations and dysfunction in Alzheimer mouse models
The pupil is primarily regulated by prevailing light levels but is also modulated by perceptual and attentional factors . We measured pupil-size in typical adult humans viewing a bistable-rotating cylinder , constructed so the luminance of the front surface changes with perceived direction of rotation . In some partici...	The pupils control how much light reaches the eye . They become smaller in bright light and larger in darkness to let more light in . Other factors can also affect pupil size . For example , the pupils slightly constrict when a person focuses on brighter objects and they enlarge when focusing on a darker object . Track...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2018	Pupillometry reveals perceptual differences that are tightly linked to autistic traits in typical adults
The spatial organization of gut microbiota influences both microbial abundances and host-microbe interactions , but the underlying rules relating bacterial dynamics to large-scale structure remain unclear . To this end , we studied experimentally and theoretically the formation of three-dimensional bacterial clusters ,...	The human gut is home to vast numbers of bacteria that grow , compete and cooperate in a dynamic , densely packed space . The spatial arrangement of organisms – for example , if they are clumped together or broadly dispersed – plays a major role in all ecosystems; but how bacteria are organized in the human gut remains...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "physics", "of", "living", "systems", "microbiology", "and", "infectious", "disease" ]	2021	Gut bacterial aggregates as living gels
Although combinatorial regulation is a common feature in gene regulatory networks , how it evolves and affects network structure and function is not well understood . In S . cerevisiae , the phosphate starvation ( PHO ) responsive transcription factors Pho4 and Pho2 are required for gene induction and survival during p...	The diversity of life on Earth has intrigued generations of scientists and nature lovers alike . Research over recent decades has revealed that much of the diversity we can see did not require the invention of new genes . Instead , living forms diversified mostly by using old genes in new ways – for example , by changi...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology", "microbiology", "and", "infectious", "disease" ]	2017	Evolution of reduced co-activator dependence led to target expansion of a starvation response pathway
The brain is sensitive to the dose of MeCP2 such that small fluctuations in protein quantity lead to neuropsychiatric disease . Despite the importance of MeCP2 levels to brain function , little is known about its regulation . In this study , we report eleven individuals with neuropsychiatric disease and copy-number var...	The X-chromosome carries a number of genes that are involved in a child's intellectual development . One of these genes encodes a protein called MeCP2 , which is important for brain function after birth . Mutations in the MECP2 gene cause a disorder known as Rett syndrome . At around 18 months of age , affected childre...	[ "Abstract", "Main", "text", "Materials", "and", "methods" ]	[ "short", "report", "neuroscience" ]	2015	NUDT21-spanning CNVs lead to neuropsychiatric disease and altered MeCP2 abundance via alternative polyadenylation
Primary cilia are sensory organelles crucial for cell signaling during development and organ homeostasis . Cilia arise from centrosomes and their formation and function is governed by numerous factors . Through our studies on Townes-Brocks Syndrome ( TBS ) , a rare disease linked to abnormal cilia formation in human fi...	Primary cilia are the ‘antennae’ of animal cells: these small , flexible protrusions emerge from the surface of cells , where they help to sense and relay external signals . Cilia are assembled with the help of the cytoskeleton , a dynamic network of mesh-like filaments that spans the interior of the cell and controls ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "cell", "biology" ]	2020	LUZP1, a novel regulator of primary cilia and the actin cytoskeleton, is a contributing factor in Townes-Brocks Syndrome
The Insulin signaling pathway couples growth , development and lifespan to nutritional conditions . Here , we demonstrate a function for the Drosophila lipoprotein LTP in conveying information about dietary lipid composition to the brain to regulate Insulin signaling . When yeast lipids are present in the diet , free c...	How does an animal sense if it is well nourished or not , and then regulate its metabolism appropriately ? This process largely relies on the animal's body deciphering signals that that are transmitted between different organs in the form of molecules and hormones . Many animals—ranging from insects to mammals ( includ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "neuroscience" ]	2014	Delivery of circulating lipoproteins to specific neurons in the Drosophila brain regulates systemic insulin signaling
A key challenge in antibiotic stewardship is figuring out how to use antibiotics therapeutically without promoting the evolution of antibiotic resistance . Here , we demonstrate proof of concept for an adjunctive therapy that allows intravenous antibiotic treatment without driving the evolution and onward transmission ...	Antibiotics are essential for treating infections . But their use can inadvertently lead to the emergence of antibiotic-resistant bacteria that do not respond to antibiotic drugs , making infections with these bacteria difficult or impossible to treat . Finding ways to prevent antibiotic resistance is critical to prese...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology" ]	2020	An adjunctive therapy administered with an antibiotic prevents enrichment of antibiotic-resistant clones of a colonizing opportunistic pathogen
Transposable elements ( TEs ) , the movement of which can damage the genome , are epigenetically silenced in eukaryotes . Intriguingly , TEs are activated in the sperm companion cell – vegetative cell ( VC ) – of the flowering plant Arabidopsis thaliana . However , the extent and mechanism of this activation are unknow...	In most organisms , the genetic information contains DNA segments called transposable elements which are able to move around in the genome . When transposable elements insert themselves in a new location , this can lead to negative outcomes such as cell death or cancer . Animals , plants and other organisms have evolve...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "plant", "biology" ]	2019	Natural depletion of histone H1 in sex cells causes DNA demethylation, heterochromatin decondensation and transposon activation
Parvalbumin-positive ( PV+ ) γ-aminobutyric acid ( GABA ) interneurons are critically involved in producing rapid network oscillations and cortical microcircuit computations , but the significance of PV+ axon myelination to the temporal features of inhibition remains elusive . Here , using toxic and genetic mouse model...	The brain contains billions of neurons that connect with each other via cable-like structures called axons . Axons transmit electrical impulses and are often wrapped in a fatty substance called myelin . This insulation increases the speed of nerve impulses and reduces the energy lost over long distances . Loss or damag...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2022	Myelination synchronizes cortical oscillations by consolidating parvalbumin-mediated phasic inhibition
RasGRP1 and SOS are Ras-specific nucleotide exchange factors that have distinct roles in lymphocyte development . RasGRP1 is important in some cancers and autoimmune diseases but , in contrast to SOS , its regulatory mechanisms are poorly understood . Activating signals lead to the membrane recruitment of RasGRP1 and R...	Individual cells within the human body must grow , divide or specialize to perform the tasks required of them . The fates of these cells are often directed by proteins in the Ras family , which detect signals from elsewhere in the body and orchestrate responses within each cell . The activities of these proteins must b...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics" ]	2013	Structural analysis of autoinhibition in the Ras-specific exchange factor RasGRP1
Tumors are composed of many different cell types including cancer cells , fibroblasts , and immune cells . Dissecting functional metabolic differences between cell types within a mixed population can be challenging due to the rapid turnover of metabolites relative to the time needed to isolate cells . To overcome this ...	Tumors contain a mixture of many different types of cells , including cancer cells and non-cancer cells . The interactions between these two groups of cells affect how the cancer cells use nutrients , which , in turn , affects how fast these cells grow and divide . Furthermore , different cell types may use nutrients i...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cancer", "biology" ]	2020	Dissecting cell-type-specific metabolism in pancreatic ductal adenocarcinoma
Motor-skill learning can be accompanied by both increases and decreases in brain activity . Increases may indicate neural recruitment , while decreases may imply that a region became unimportant or developed a more efficient representation of the skill . These overlapping mechanisms make interpreting learning-related c...	Functional magnetic resonance imaging ( fMRI ) is a widely used technique that makes it possible to observe changes in a person’s brain activity as they perform specific tasks while lying in a scanner . These could range from listening to music or looking at images , to recalling words or imagining a scene , and each w...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2013	Skill learning strengthens cortical representations of motor sequences
The segregation of the trophectoderm ( TE ) from the inner cell mass ( ICM ) in the mouse blastocyst is determined by position-dependent Hippo signaling . However , the window of responsiveness to Hippo signaling , the exact timing of lineage commitment and the overall relationship between cell commitment and global ge...	In female mammals , conception is a complex process that involves several stages . First , an egg is released from the ovary and travels along a tube called the oviduct , where sperm from a male may fertilize it . If the egg is fertilized , the newly formed embryo moves into the womb , where it will then implant into t...	[ "Abstract", "Introduction", "Results", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2017	Position- and Hippo signaling-dependent plasticity during lineage segregation in the early mouse embryo
Regulated nuclear translocation of the PER/CRY repressor complex is critical for negative feedback regulation of the circadian clock of mammals . However , the precise molecular mechanism is not fully understood . Here , we report that KPNB1 , an importin β component of the ncRNA repressor of nuclear factor of activate...	Most organisms have an internal clock—known as the circadian clock—that regulates many aspects of their biology and behavior in roughly 24-hr long cycles . In animals , the core of the circadian clock is made of two ‘activator’ proteins and two ‘repressor’ proteins that inhibit the activators so that the levels of all ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "genetics", "and", "genomics" ]	2015	KPNB1 mediates PER/CRY nuclear translocation and circadian clock function
Dephosphorylation of eukaryotic translation initiation factor 2a ( eIF2a ) restores protein synthesis at the waning of stress responses and requires a PP1 catalytic subunit and a regulatory subunit , PPP1R15A/GADD34 or PPP1R15B/CReP . Surprisingly , PPP1R15-PP1 binary complexes reconstituted in vitro lacked substrate s...	For a cell to build a protein , it must first copy the instructions contained within a gene . A complex molecular machine called a ribosome then reads these instructions and translates them into a protein . This translation process involves a number of steps . Proteins called eukaryotic translation initiation factors (...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2015	G-actin provides substrate-specificity to eukaryotic initiation factor 2α holophosphatases
Centrosome structure , function , and number are finely regulated at the cellular level to ensure normal mammalian development . Here , we characterize PPP1R35 as a novel bona fide centrosomal protein and demonstrate that it is critical for centriole elongation . Using quantitative super-resolution microscopy mapping a...	Most animal cells contain a structure called the centrosome , which plays a vital role in helping cells to divide for producing new cells . Early in the cell division process , cells make a copy of their centrosome . Each centrosome includes two cylindrical structures called centrioles encased in a complex web of other...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2018	PPP1R35 is a novel centrosomal protein that regulates centriole length in concert with the microcephaly protein RTTN
We present in vivo single-cell FRET measurements in the Escherichia coli chemotaxis system that reveal pervasive signaling variability , both across cells in isogenic populations and within individual cells over time . We quantify cell-to-cell variability of adaptation , ligand response , as well as steady-state output...	Many sophisticated computer programs use random number generators to help solve challenging problems . These problems range from achieving secure communication across the Internet to deciding how best to invest in the stock market . Much research in recent years has found that randomness is also widespread in living ce...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology" ]	2017	Phenotypic diversity and temporal variability in a bacterial signaling network revealed by single-cell FRET
Recent phylogenetic analyses indicate that RNA virus populations carry a significant deleterious mutation load . This mutation load has the potential to shape patterns of adaptive evolution via genetic linkage to beneficial mutations . Here , we examine the effect of deleterious mutations on patterns of influenza A sub...	Each year , up to 15% of the world's population experience symptoms of an influenza infection , also commonly known as flu . The most common culprit is a strain of the virus called influenza type A subtype H3N2 . One reason that so many people become infected each year is that this virus evolves rapidly . Within a few ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "epidemiology", "and", "global", "health" ]	2015	The effects of a deleterious mutation load on patterns of influenza A/H3N2's antigenic evolution in humans
The number of children born since the origin of Assisted Reproductive Technologies ( ART ) exceeds 5 million . The majority seem healthy , but a higher frequency of defects has been reported among ART-conceived infants , suggesting an epigenetic cost . We report the first whole-genome DNA methylation datasets from sing...	Infertility has become more common in many countries , particularly those where many people delay having children until later in life . To help individuals experiencing infertility conceive a child , scientists have developed treatments called assisted reproductive technologies ( or ARTs for short ) . So far , more tha...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2017	DNA methylation and gene expression changes derived from assisted reproductive technologies can be decreased by reproductive fluids
Protein-protein interactions involving intrinsically disordered proteins are important for cellular function and common in all organisms . However , it is not clear how such interactions emerge and evolve on a molecular level . We performed phylogenetic reconstruction , resurrection and biophysical characterization of ...	Proteins are an important building block of life and are vital for almost every process that keeps cells alive . These molecules are made from chains of smaller molecules called amino acids linked together . The specific order of amino acids in a protein determines its shape and structure , which in turn controls what ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics", "computational", "and", "systems", "biology" ]	2017	Emergence and evolution of an interaction between intrinsically disordered proteins
Acquisition of distinct neuronal identities during development is critical for the assembly of diverse functional neural circuits in the brain . In both vertebrates and invertebrates , intrinsic determinants are thought to act in neural progenitors to specify their identity and the identity of their neuronal progeny . ...	The cells in the brain—including the neurons that transmit information—work together in groups called neural circuits . These cells develop from precursor cells called neuroblasts . Each neuroblast can produce many cells , and it is likely that cells that develop from the same neuroblast work together in the adult brai...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "neuroscience" ]	2014	Genetic transformation of structural and functional circuitry rewires the Drosophila brain
Sterol homeostasis is essential for the function of cellular membranes and requires feedback inhibition of HMGR , a rate-limiting enzyme of the mevalonate pathway . As HMGR acts at the beginning of the pathway , its regulation affects the synthesis of sterols and of other essential mevalonate-derived metabolites , such...	All cells are enclosed by a membrane that is made up of fatty molecules called lipids and is studded with proteins . This membrane allows cells to detect and react to outside events . Since external conditions , such as temperature , can vary dramatically , membranes need to be able to adjust their properties . For exa...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "cell", "biology" ]	2013	Sterol homeostasis requires regulated degradation of squalene monooxygenase by the ubiquitin ligase Doa10/Teb4
Planarian flatworms regenerate every organ after amputation . Adult pluripotent stem cells drive this ability , but how injury activates and directs stem cells into the appropriate lineages is unclear . Here we describe a single-organ regeneration assay in which ejection of the planarian pharynx is selectively induced ...	Some animals can regrow whole limbs or organs after amputation . Flatworms called planaria , for example , can regenerate their whole body from small pieces . This remarkable ability depends on neoblasts—a type of stem cell found in planaria that can detect damaged or lost organs , migrate to the site of damage , produ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "stem", "cells", "and", "regenerative", "medicine" ]	2014	Selective amputation of the pharynx identifies a FoxA-dependent regeneration program in planaria
The human visual system is tasked with recovering the different physical sources of optical structure that generate our retinal images . Separate research has focused on understanding how the visual system estimates ( a ) environmental sources of image structure and ( b ) blur induced by the eye’s limited focal range ,...	We perceive the visual world as made of objects of different shapes , sizes and colors . Some may be smooth , shiny and reflective , whereas others are rough and uneven; some may be in shadow , while others are brightly lit . The brain must identify and distinguish all of these different features to build an accurate ,...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2019	The perception and misperception of optical defocus, shading, and shape
Assembly of mitochondrial iron-sulfur ( Fe/S ) proteins is a key process of cells , and defects cause many rare diseases . In the first phase of this pathway , ten Fe/S cluster ( ISC ) assembly components synthesize and insert [2Fe-2S] clusters . The second phase is dedicated to the assembly of [4Fe-4S] proteins , yet ...	Proteins perform almost all the tasks necessary for cells to survive . However , some proteins , especially enzymes involved in metabolism and energy production , need to contain extra molecules called co-factors to work properly . In human , yeast and other eukaryotic cells , co-factors called iron-sulfur clusters are...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "cancer", "biology" ]	2016	Mitochondrial Bol1 and Bol3 function as assembly factors for specific iron-sulfur proteins
Dynamic changes in protein S-palmitoylation are critical for regulating protein localization and signaling . Only two enzymes - the acyl-protein thioesterases APT1 and APT2 – are known to catalyze palmitate removal from cytosolic cysteine residues . It is unclear if these enzymes act constitutively on all palmitoylated...	Proteins play important roles in many processes in cells . Some of these proteins can be modified by the addition of a molecule called palmitate . This process , termed “palmitoylation” , helps direct these proteins to the compartments within the cell where they are needed to carry out their roles . One target of palmi...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "short", "report", "biochemistry", "and", "chemical", "biology" ]	2015	ABHD17 proteins are novel protein depalmitoylases that regulate N-Ras palmitate turnover and subcellular localization
Notch signaling regulates cell fate selection during development in multiple organs including the lung . Previous studies on the role of Notch in the lung focused mostly on Notch pathway core components or receptor-specific functions . It is unclear , however , how Jagged or Delta-like ligands collectively or individua...	Cells communicate with each other by sending messages through a range of signaling pathways . One of the ways cells signal to each other is through a well-studied pathway known as Notch . In this pathway , cells display molecules on their surface , known as Notch ligands , that can activate Notch receptor proteins on t...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2019	Jagged and Delta-like ligands control distinct events during airway progenitor cell differentiation
PDZ domain scaffold proteins are molecular modules orchestrating cellular signalling in space and time . Here , we investigate assembly of PDZ scaffolds using supported cell membrane sheets , a unique experimental setup enabling direct access to the intracellular face of the cell membrane . Our data demonstrate how mul...	Inside a cell , many different signals carry information that is essential for the cell to remain healthy and perform its role in the body . It is , therefore , very important that the signals are sent to the right places at the right times . Scaffold proteins play an essential role in organizing these signals by bring...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology" ]	2019	Mechanisms of PDZ domain scaffold assembly illuminated by use of supported cell membrane sheets
The extent to which brain structure is influenced by sensory input during development is a critical but controversial question . A paradigmatic system for studying this is the mammalian visual cortex . Maps of orientation preference ( OP ) and ocular dominance ( OD ) in the primary visual cortex of ferrets , cats and m...	The structure of the brain results from a combination of nature ( genes ) and nurture ( environment ) . The brain’s ability to adapt to changes in the environment is known as plasticity , and the young brain is especially plastic . An animal’s sensory experiences in early life help to determine how its brain will proce...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Sensory experience modifies feature map relationships in visual cortex
Treatment for medulloblastoma , the most common malignant brain tumor in children , remains limited to surgical resection , radiation , and traditional chemotherapy; with long-term survival as low as 50–60% for Sonic Hedgehog ( Shh ) -type medulloblastoma . We have shown that the transcription factor Atonal homologue 1...	Medulloblastoma is the most common solid brain tumor that develops in children , with more than five hundred new cases diagnosed in the United States every year . There are four broad types of medulloblastoma . One of these is called the “Sonic Hedgehog” subtype , named after the biological pathway that becomes re-acti...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "short", "report", "cancer", "biology" ]	2017	Jak2-mediated phosphorylation of Atoh1 is critical for medulloblastoma growth
Neurons regulate ionic fluxes across their plasma membrane to maintain their excitable properties under varying environmental conditions . However , the mechanisms that regulate ion channels abundance remain poorly understood . Here we show that pickpocket 29 ( ppk29 ) , a gene that encodes a Drosophila degenerin/epith...	Neurons communicate with one another via electrical signals known as action potentials . These signals are generated when a stimulus causes sodium and potassium ion channels in the cell membrane to open , leading to an influx of sodium ions , followed by an efflux of potassium ions . Changes in temperature affect the r...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "neuroscience" ]	2014	Natural antisense transcripts regulate the neuronal stress response and excitability
Out of millions of ejaculated sperm , a few reach the fertilization site in mammals . Flagellar Ca2+ signaling nanodomains , organized by multi-subunit CatSper calcium channel complexes , are pivotal for sperm migration in the female tract , implicating CatSper-dependent mechanisms in sperm selection . Here using bioch...	When mammals mate , males ejaculate millions of sperm cells into the females’ reproductive tract . But as the sperm travel up the tract , only a handful of the ‘fittest’ sperm will actually manage to reach the egg . This process of elimination prevents the egg from being fertilized by multiple sperm cells and stops the...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2020	3D in situ imaging of the female reproductive tract reveals molecular signatures of fertilizing spermatozoa in mice
Lipid droplets ( LDs ) are ubiquitous organelles that store neutral lipids , such as triacylglycerol ( TG ) , as reservoirs of metabolic energy and membrane precursors . The Arf1/COPI protein machinery , known for its role in vesicle trafficking , regulates LD morphology , targeting of specific proteins to LDs and lipo...	Just like the body contains organs that perform different jobs , the cells within the body contain organelles that carry out different tasks . The endoplasmic reticulum , for example , makes proteins that are sent to other organelles or to destinations outside the cell . Each organelle is typically sealed within a memb...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "cell", "biology" ]	2014	Arf1/COPI machinery acts directly on lipid droplets and enables their connection to the ER for protein targeting
Eukaryotes have evolved various quality control mechanisms to promote proteostasis in the endoplasmic reticulum ( ER ) . Selective removal of certain ER domains via autophagy ( termed as ER-phagy ) has emerged as a major quality control mechanism . However , the degree to which ER-phagy is employed by other branches of...	For cells to survive they need to be able to remove faulty or damaged components . The ability to recycle faulty parts is so crucial that some of the molecular machinery responsible is the same across the plant and animal kingdoms . One of the major recycling pathways cells use is autophagy , which labels damaged prote...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology", "cell", "biology" ]	2020	A cross-kingdom conserved ER-phagy receptor maintains endoplasmic reticulum homeostasis during stress
Homeostatic signaling stabilizes synaptic transmission at the neuromuscular junction ( NMJ ) of Drosophila , mice , and human . It is believed that homeostatic signaling at the NMJ is bi-directional and considerable progress has been made identifying mechanisms underlying the homeostatic potentiation of neurotransmitte...	Neurons are organised into networks via junctions called synapses . The arrival of an electrical signal , called an action potential , at a neuronal synapse causes an influx of calcium ions into the cell . This in turn causes packages of chemicals called neurotransmitters that are stored inside the cell to fuse with th...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	Homeostatic synaptic depression is achieved through a regulated decrease in presynaptic calcium channel abundance
HIV encodes Tat , a small protein that facilitates viral transcription by binding an RNA structure ( trans-activating RNA [TAR] ) formed on nascent viral pre-messenger RNAs . Besides this well-characterized mechanism , Tat appears to modulate cellular transcription , but the target genes and molecular mechanisms remain...	The human immunodeficiency virus ( HIV ) reproduces and spreads throughout the body by hijacking human immune cells and causing them to copy the virus’s genetic information . As the virus multiplies , it also causes the death of the immune system cells that help the human body recognize and eliminate viruses . This all...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression" ]	2015	HIV Tat controls RNA Polymerase II and the epigenetic landscape to transcriptionally reprogram target immune cells
The ascidian embryo is an ideal system to investigate how cell position is determined during embryogenesis . Using 3D timelapse imaging and computational methods we analyzed the planar cell divisions in ascidian early embryos and found that spindles in every cell tend to align at metaphase in the long length of the api...	The position of cells within an embryo early in development determines what type of cells they will become in the fully formed embryo . The embryos of ascidians , commonly known as sea squirts , are ideal for studying what influences cell positioning . These embryos consist of a small number of cells that divide accord...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2017	The invariant cleavage pattern displayed by ascidian embryos depends on spindle positioning along the cell's longest axis in the apical plane and relies on asynchronous cell divisions
Stem cells fuel the development and maintenance of tissues . Many studies have addressed how local signals from neighboring niche cells regulate stem cell identity and their proliferative potential . However , the regulation of stem cells by tissue-extrinsic signals in response to environmental cues remains poorly unde...	Stem cells have the unique ability to mature into the various , specialized groups of cells required for organisms to work properly . Local signals released by the tissues immediately surrounding stem cells usually trigger this specialization process . However , recent studies have revealed that external signals , such...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2020	Neuronal octopamine signaling regulates mating-induced germline stem cell increase in female Drosophila melanogaster
Kinetochore fibers ( K-fibers ) of the mitotic spindle are force-generating units that power chromosome movement during mitosis . K-fibers are composed of many microtubules that are held together throughout their length . Here , we show , using 3D electron microscopy , that K-fiber microtubules ( MTs ) are connected by...	Before a cell divides , its genetic material must be copied and then equally distributed between the newly formed daughter cells . In the cells of plants , animals , and fungi , a structure known as the spindle pulls the two copies of the chromosomes apart . The spindle is made up of a network of long , protein filamen...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2015	The mesh is a network of microtubule connectors that stabilizes individual kinetochore fibers of the mitotic spindle
The mechanisms linking systems-level programs of gene expression to discrete cell biological processes in vivo remain poorly understood . In this study , we have defined such a program for multi-ciliated epithelial cells ( MCCs ) , a cell type critical for proper development and homeostasis of the airway , brain and re...	Cells that have hundreds of tiny hair-like structures called cilia on their surface have important roles in our airways and also in the brain and reproductive system . By beating in a coordinated manner , the cilia cause fluid to flow in a particular direction . The development of these multiciliated cells is a complex...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "cell", "biology" ]	2014	Coordinated genomic control of ciliogenesis and cell movement by RFX2
Can limb regeneration be induced ? Few have pursued this question , and an evolutionarily conserved strategy has yet to emerge . This study reports a strategy for inducing regenerative response in appendages , which works across three species that span the animal phylogeny . In Cnidaria , the frequency of appendage reg...	The ability of animals to replace damaged or lost tissue ( or ‘regenerate’ ) is a sliding scale , with some animals able to regenerate whole limbs , while others can only scar . But why some animals can regenerate while others have more limited capabilities has puzzled the scientific community for many years . The like...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "stem", "cells", "and", "regenerative", "medicine", "evolutionary", "biology" ]	2021	A conserved strategy for inducing appendage regeneration in moon jellyfish, Drosophila, and mice
DNA polymerase θ ( Polθ ) promotes insertion mutations during alternative end-joining ( alt-EJ ) by an unknown mechanism . Here , we discover that mammalian Polθ transfers nucleotides to the 3’ terminus of DNA during alt-EJ in vitro and in vivo by oscillating between three different modes of terminal transferase activi...	DNA polymerases are enzymes that replicate DNA by using single-stranded DNA as a template . DNA replication is needed to duplicate an organism’s genome , and repair it if it is damaged . For example , when DNA double-strand breaks occur in the genome , DNA polymerases help repair these potentially lethal DNA breaks . I...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "biochemistry", "and", "chemical", "biology" ]	2016	Polymerase θ is a robust terminal transferase that oscillates between three different mechanisms during end-joining
Zolpidem produces paradoxical recovery of speech , cognitive and motor functions in select subjects with severe brain injury but underlying mechanisms remain unknown . In three diverse patients with known zolpidem responses we identify a distinctive pattern of EEG dynamics that suggests a mechanistic model . In the abs...	Some individuals who experience severe brain damage are left with disorders of consciousness . While they can appear to be awake , these individuals lack awareness of their surroundings and cannot respond to events going on around them . Few treatments are available , but a minority of patients show striking improvemen...	[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine", "neuroscience" ]	2013	Common resting brain dynamics indicate a possible mechanism underlying zolpidem response in severe brain injury
Natural product screening programs have uncovered molecules from diverse natural sources with various biological activities and unique structures . However , much is yet underexplored and additional information is hidden in these exceptional collections . We applied untargeted mass spectrometry approaches to capture th...	Cyanobacteria and algae are found in all oceans around the globe . Like plants , they can use sunlight as a source of energy in a process called photosynthesis . As a result , these organisms are important sources of oxygen and another vital nutrient called nitrogen for other marine organisms . Many of these organisms ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "ecology" ]	2017	Digitizing mass spectrometry data to explore the chemical diversity and distribution of marine cyanobacteria and algae
Oncogenic stress provokes tumor suppression by p53 but the extent to which this regulatory axis is conserved remains unknown . Using a biosensor to visualize p53 action , we find that Drosophila p53 is selectively active in gonadal stem cells after exposure to stressors that destabilize the genome . Similar p53 activit...	The most common genetic change seen in cancer patients produces a faulty version of the p53 protein , which normally restricts tissue growth . This change promotes cancer because cells can now divide faster and fail to die when they should . Much remains to be learned about how p53 functions to restrain growth . As p53...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2014	p53 activity is selectively licensed in the Drosophila stem cell compartment
The phylum Apicomplexa comprises human pathogens such as Plasmodium but is also an under-explored hotspot of evolutionary diversity central to understanding the origins of parasitism and non-photosynthetic plastids . We generated single-cell transcriptomes for all major apicomplexan groups lacking large-scale sequence ...	Microscopic parasites known collectively as apicomplexans are responsible for several infectious diseases in humans including malaria and toxoplasmosis . The cells of the malaria parasite and many other apicomplexans contain compartments known as cryptic chloroplasts that produce molecules the parasites need to survive...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology", "microbiology", "and", "infectious", "disease" ]	2019	Apicomplexan-like parasites are polyphyletic and widely but selectively dependent on cryptic plastid organelles
The target of rapamycin complex I ( TORC1 ) regulates cell growth and metabolism in eukaryotes . Previous studies have shown that nitrogen and amino acid signals activate TORC1 via the small GTPases , Gtr1/2 . However , little is known about the way that other nutrient signals are transmitted to TORC1 . Here we report ...	In humans , yeast and other eukaryotes , a group of proteins called the Target of Rapamycin Complex I ( TORC1 ) promote cell growth and increase metabolic activity when nutrients are plentiful . Previous studies have shown how molecules that contain the nutrient nitrogen – which is needed to make proteins – activate TO...	[ "Abstract", "Introduction", "Results", "Discussion" ]	[ "biochemistry", "and", "chemical", "biology", "computational", "and", "systems", "biology" ]	2015	Snf1/AMPK promotes the formation of Kog1/Raptor-bodies to increase the activation threshold of TORC1 in budding yeast
Macrophage activation/polarization to distinct functional states is critically supported by metabolic shifts . How polarizing signals coordinate metabolic and functional reprogramming , and the potential implications for control of macrophage activation , remains poorly understood . Here we show that IL-4 signaling co-...	Macrophages are immune cells that are found in most of the tissues of the body . Exactly what the macrophages do depends on which tissue they are in , and the state of the tissue . For example , M2 macrophages can multiply in numbers , heal wounds or help to fight off parasites depending on the signals they receive fro...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "immunology", "and", "inflammation" ]	2016	Akt-mTORC1 signaling regulates Acly to integrate metabolic input to control of macrophage activation
The zebrafish was used to assess the impact of social isolation on behaviour and brain function . As in humans and other social species , early social deprivation reduced social preference in juvenile zebrafish . Whole-brain functional maps of anti-social isolated ( lonely ) fish were distinct from anti-social ( loner ...	Socialising is good for people’s mental health and wellbeing . The connections and relationships that we form can make us more resilient and healthier . Researchers also know that prolonged periods of social isolation , and feeling lonely , can be detrimental to our health , especially in early childhood . The paradox ...	[ "Abstract", "Introduction", "Materials", "and", "methods" ]	[ "short", "report", "neuroscience" ]	2020	Whole-brain mapping of socially isolated zebrafish reveals that lonely fish are not loners
Many studies of visual processing are conducted in constrained conditions such as head- and gaze-fixation , and therefore less is known about how animals actively acquire visual information in natural contexts . To determine how mice target their gaze during natural behavior , we measured head and bilateral eye movemen...	As you read this sentence , your eyes will move automatically from one word to the next , while your head remains still . Moving your eyes enables you to view each word using your central – as opposed to peripheral – vision . Central vision allows you to see objects in fine detail . It relies on a specialized area of t...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2020	Dynamics of gaze control during prey capture in freely moving mice
Prdm14 is a sequence-specific transcriptional regulator of embryonic stem cell ( ESC ) pluripotency and primordial germ cell ( PGC ) formation . It exerts its function , at least in part , through repressing genes associated with epigenetic modification and cell differentiation . Here , we show that this repressive fun...	In animals , there are many different types of cells that perform different roles . For example , stem cells divide to produce new cells that may then become other types of cells such as muscle or skin cells . Most stem cells can only produce a limited range of other cell types , except for a subset known as ‘pluripote...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "stem", "cells", "and", "regenerative", "medicine", "structural", "biology", "and", "molecular", "biophysics" ]	2015	ETO family protein Mtgr1 mediates Prdm14 functions in stem cell maintenance and primordial germ cell formation
Plants react to seasonal change in day length through altering physiology and development . Factors that function to harmonize growth with photoperiod are poorly understood . Here we characterize a new protein that associates with both circadian clock and photoreceptor components , named PHOTOPERIODIC CONTROL OF HYPOCO...	Most living things possess an internal “circadian” clock that synchronizes many behaviors , such as eating , resting or growing , with the day-night cycle . With the help of proteins that can detect light , known as photoreceptors , the clock also coordinates these behaviors as the number of daylight hours changes duri...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology" ]	2016	PCH1 integrates circadian and light-signaling pathways to control photoperiod-responsive growth in Arabidopsis
Gut enzymes can metabolize plant defense compounds and thereby affect the growth and fitness of insect herbivores . Whether these enzymes also influence feeding preference is largely unknown . We studied the metabolization of taraxinic acid β-D-glucopyranosyl ester ( TA-G ) , a sesquiterpene lactone of the common dande...	Plants produce certain substances to fend off attackers like plant-feeding insects . To stop these compounds from damaging their own cells , plants often attach sugar molecules to them . When an insect tries to eat the plant , the plant removes the stabilizing sugar , ‘activating’ the compounds and making them toxic or...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "ecology" ]	2021	A beta-glucosidase of an insect herbivore determines both toxicity and deterrence of a dandelion defense metabolite
ApoE , ApoE receptors and APP cooperate in the pathogenesis of Alzheimer’s disease . Intriguingly , the ApoE receptor LRP4 and APP are also required for normal formation and function of the neuromuscular junction ( NMJ ) . In this study , we show that APP interacts with LRP4 , an obligate co-receptor for muscle-specifi...	One of the hallmarks of Alzheimer’s disease is the formation of plaques in the brain by a protein called β-amyloid . This protein is generated by the cleavage of a precursor protein , and mutations in the gene that encodes amyloid precursor protein greatly increase the risk of developing a familial , early-onset form o...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "neuroscience" ]	2013	APP interacts with LRP4 and agrin to coordinate the development of the neuromuscular junction in mice
Olfactory receptor usage is highly heterogeneous , with some receptor types being orders of magnitude more abundant than others . We propose an explanation for this striking fact: the receptor distribution is tuned to maximally represent information about the olfactory environment in a regime of efficient coding that i...	A mouse’s nose contains over 10 million receptor neurons divided into about 1 , 000 different types , which detect airborne chemicals – called odorants – that make up smells . Each odorant activates many different receptor types . And each receptor type responds to many different odorants . To identify a smell , the br...	[ "Abstract", "Introduction", "Discussion", "Materials", "and", "methods" ]	[ "physics", "of", "living", "systems" ]	2019	Adaptation of olfactory receptor abundances for efficient coding
An outstanding challenge has been to understand the mechanism whereby proteins associate . We report here the results of exhaustively sampling the conformational space in protein–protein association using a physics-based energy function . The agreement between experimental intermolecular paramagnetic relaxation enhance...	Proteins rarely act alone . Instead , they tend to bind to other proteins to form structures known as complexes . When two proteins come together to form a complex , they twist and turn through a series of intermediate states before they form the actual complex . These intermediate states are difficult to study because...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics" ]	2014	Encounter complexes and dimensionality reduction in protein–protein association
Delineating the basic cellular components of cortical inhibitory circuits remains a fundamental issue in order to understand their specific contributions to microcircuit function . It is still unclear how current classifications of cortical interneuron subtypes relate to biological processes such as their developmental...	Our brain contains over a 100 billion nerve cells or neurons , and each of them is thought to connect to over 1 , 000 other neurons . Together , these cells form a complex network to convey information from our surroundings or transmit messages to designated destinations . This circuitry forms the basis of our unique c...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2018	Neurogliaform cortical interneurons derive from cells in the preoptic area
Neuregulin 1 ( NRG1 ) and the γ-secretase subunit APH1B have been previously implicated as genetic risk factors for schizophrenia and schizophrenia relevant deficits have been observed in rodent models with loss of function mutations in either gene . Here we show that the Aph1b-γ-secretase is selectively involved in Nr...	Schizophrenia affects around 1% of the world's population , with symptoms including hallucinations and delusions , apathy and cognitive impairments . Multiple genes and environmental factors interact to increase the risk of schizophrenia , making the causes of the disease—which can differ between individuals—difficult ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2014	Cell autonomous regulation of hippocampal circuitry via Aph1b-γ-secretase/neuregulin 1 signalling
The histone variant H2A . Z is a universal mark of gene promoters , enhancers , and regulatory elements in eukaryotic chromatin . The chromatin remodeler SWR1 mediates site-specific incorporation of H2A . Z by a multi-step histone replacement reaction , evicting histone H2A-H2B from the canonical nucleosome and deposit...	A DNA molecule can be several meters long and to fit this length inside a cell , it is wrapped around proteins called histones . This compacts the DNA to form a structure known as chromatin; complexes of DNA and histones , called nucleosomes , serve as the building blocks of chromatin . Cells regulate the organization ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods", "Supplemental", "information" ]	[ "chromosomes", "and", "gene", "expression", "short", "report", "biochemistry", "and", "chemical", "biology" ]	2015	H2A histone-fold and DNA elements in nucleosome activate SWR1-mediated H2A.Z replacement in budding yeast
Most behaviors such as making tea are not stereotypical but have an obvious structure . However , analytical methods to objectively extract structure from non-stereotyped behaviors are immature . In this study , we analyze the locomotion of fruit flies and show that this non-stereotyped behavior is well-described by a ...	Many behaviors that we perform everyday , including something as familiar as making a peanut-butter sandwich , consist of a sequence of recognizable acts . These acts may include , for example , holding a knife and opening a jar . Yet often neither the sequence nor the individual acts are always performed in the exact ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2019	Statistical structure of locomotion and its modulation by odors
Neurophysiological studies in humans and nonhuman primates have revealed movement representations in both the contralateral and ipsilateral hemispheres . Inspired by clinical observations , we ask if this bilateral representation differs for the left and right hemispheres . Electrocorticography was recorded in human pa...	The brain is split into two hemispheres , each playing the leading role in coordinating movement for the opposite side of the body: lesions on the left hemisphere therefore often result in difficulties moving the right arm or leg , and vice versa . In fact , very few anatomical connections exist between a given hemisph...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2022	Left hemisphere dominance for bilateral kinematic encoding in the human brain
Optogenetics is a powerful technique to control cellular activity by light . The light-gated Channelrhodopsin has been widely used to study and manipulate neuronal activity in vivo , whereas optogenetic control of second messengers in vivo has not been examined in depth . In this study , we present a transgenic mouse m...	Tiny hair-like structures called cilia on the outside of cells play many important roles , including detecting physical and chemical signals from the environment . Special cilia—called flagella—help cells to move around and perhaps the most well-known of these are sperm flagella , which propel sperm in their quest to f...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2015	Controlling fertilization and cAMP signaling in sperm by optogenetics
The cohesin complex topologically encircles DNA to promote sister chromatid cohesion . Alternatively , cohesin extrudes DNA loops , thought to reflect chromatin domain formation . Here , we propose a structure-based model explaining both activities . ATP and DNA binding promote cohesin conformational changes that guide...	When a cell divides , it has to ensure that each of its daughter cells inherits one copy of its genetic information . It does this by duplicating its chromosomes ( the DNA molecules that encode the genome ) and distributing one copy of each to its daughter cells . Once a cell duplicates a chromosome , the two identical...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "computational", "and", "systems", "biology" ]	2021	A Brownian ratchet model for DNA loop extrusion by the cohesin complex
Perceptual learning is often orientation and location specific , which may indicate neuronal plasticity in early visual areas . However , learning specificity diminishes with additional exposure of the transfer orientation or location via irrelevant tasks , suggesting that the specificity is related to untrained condit...	People can become more sensitive to small changes in what they are seeing – such as detecting a slight change in the angle of a particular line – with practice . This process is called perceptual learning , but the improvement is often specific such that it is typically lost if the line moves to a new place , or a diff...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Bottom-up and top-down influences at untrained conditions determine perceptual learning specificity and transfer
The capacity to remember temporal relationships between different events is essential to episodic memory , but little is currently known about its underlying mechanisms . We performed time-lapse imaging of thousands of neurons over weeks in the hippocampal CA1 of mice as they repeatedly visited two distinct environment...	The ability to recall the timing of events is an important feature of long-term memory . Episodic memory , the mental account of “what” happened , “where” and “when” , depends on a region of a brain called the hippocampus . Certain neurons in the hippocampus , called place-cells , are known to capture information about...	[ "Abstract", "Materials", "and", "methods" ]	[ "short", "report", "neuroscience" ]	2015	Hippocampal ensemble dynamics timestamp events in long-term memory
Chromosome alignment in the middle of the bipolar spindle is a hallmark of metazoan cell divisions . When we offset the metaphase plate position by creating an asymmetric centriole distribution on each pole , we find that metaphase plates relocate to the middle of the spindle before anaphase . The spindle assembly chec...	The genetic information of a cell is stored in the form of chromosomes . Before a cell divides , its entire set of chromosomes is duplicated so that the two newly formed daughter cells receive a full set . In animal cells , the chromosomes line up in the center of the cell . The two sets of chromosomes are then separat...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2015	The equatorial position of the metaphase plate ensures symmetric cell divisions
Bridging brain-scale circuit dynamics and organism-scale behavior is a central challenge in neuroscience . It requires the concurrent development of minimal behavioral and neural circuit models that can quantitatively capture basic sensorimotor operations . Here , we focus on light-seeking navigation in zebrafish larva...	All animals with the ability to move use sensory signals to help them navigate towards areas that seem better than their current location . Such areas might contain desirable things like food and mates , or they might allow an animal to escape from threats such as predators . But how the brain gives rise to this naviga...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology", "neuroscience" ]	2020	From behavior to circuit modeling of light-seeking navigation in zebrafish larvae
Starvation induces sustained increase in locomotion , which facilitates food localization and acquisition and hence composes an important aspect of food-seeking behavior . We investigated how nutritional states modulated starvation-induced hyperactivity in adult Drosophila . The receptor of the adipokinetic hormone ( A...	Animals can be thought of as tightly controlled eating machines . An animal’s brain senses if it is hungry via signals from the nervous system or hormones , and then alters the animal’s behavior to obtain a supply of food . These behaviors include looking for food and eating it; and regulating both food seeking and foo...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Regulation of starvation-induced hyperactivity by insulin and glucagon signaling in adult Drosophila
PKMζ is a persistently active PKC isoform proposed to maintain late-LTP and long-term memory . But late-LTP and memory are maintained without PKMζ in PKMζ-null mice . Two hypotheses can account for these findings . First , PKMζ is unimportant for LTP or memory . Second , PKMζ is essential for late-LTP and long-term mem...	How are long-term memories stored in the brain ? The formation of memories is believed to depend on the strengthening of connections between neurons . During learning , neurons produce an enzyme called PKMzeta ( or PKMζ ) , which is thought to be responsible for maintaining the newly strengthened connections . Inhibito...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Compensation for PKMζ in long-term potentiation and spatial long-term memory in mutant mice
Humans can run without falling down , usually despite uneven terrain or occasional pushes . Even without such external perturbations , intrinsic sources like sensorimotor noise perturb the running motion incessantly , making each step variable . Here , using simple and generalizable models , we show that even such smal...	Running at a constant speed seems like a series of repetitive , identical strides , but it is not . There are small variations in each stride . Self-inflicted errors in the forces generated by the muscles , or misperceptions from the senses , may cause these tiny imperfections . Uneven terrain or other outside forces ,...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology" ]	2019	Step-to-step variations in human running reveal how humans run without falling
Natural Killer ( NK ) cells confer protection from tumors and infections by releasing cytotoxic granules and pro-inflammatory cytokines upon recognition of diseased cells . The responsiveness of NK cells to acute stimulation is dynamically tuned by steady-state receptor-ligand interactions of an NK cell with its cellul...	White blood cells called “natural killer cells” are part of the first line of immune defense . Often called NK cells for short , one job of these cells is to help prevent cancer by killing tumor cells . If an NK cell spots a tumor cell , it must become energized so that it can deliver the killing blow , which comes in ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "immunology", "and", "inflammation", "cancer", "biology" ]	2017	Endothelial cells express NKG2D ligands and desensitize antitumor NK responses
Our ability to rapidly detect threats is thought to be subserved by a subcortical pathway that quickly conveys visual information to the amygdala . This neural shortcut has been demonstrated in animals but has rarely been shown in the human brain . Importantly , it remains unclear whether such a pathway might influence...	Being able to quickly detect and respond to potential threats is essential for survival . Fear and threat trigger a range of responses in the body , which are controlled by different regions in the brain . For example , a structure located deep within the brain called the amygdala is connected to other parts of the bra...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "research", "communication", "neuroscience" ]	2019	An afferent white matter pathway from the pulvinar to the amygdala facilitates fear recognition
Faced with potential harm , individuals must estimate the probability of threat and initiate an appropriate fear response . In the prevailing view , threat probability estimates are relayed to the ventrolateral periaqueductal gray ( vlPAG ) to organize fear output . A straightforward prediction is that vlPAG single-uni...	The brain is hard-wired to detect and respond to threats . Catching sight of a spider or a snake , or hearing an unfamiliar sound in the house at night , can make you freeze momentarily . Multiple regions of the brain contribute to this process . According to the textbook view of threat detection , the amygdala and pre...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2019	Ventrolateral periaqueductal gray neurons prioritize threat probability over fear output
The secretory pathway of eukaryotic cells packages cargo proteins into COPII-coated vesicles for transport from the endoplasmic reticulum ( ER ) to the Golgi . We now report that complete genetic deficiency for the COPII component SEC24A is compatible with normal survival and development in the mouse , despite the fund...	The endoplasmic reticulum ( ER ) is a structure that performs a variety of functions within eukaryotic cells . It can be divided into two regions: the surface of the rough ER is coated with ribosomes that manufacture various proteins , while the smooth ER is involved in activities such as lipid synthesis and carbohydra...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "cell", "biology" ]	2013	SEC24A deficiency lowers plasma cholesterol through reduced PCSK9 secretion

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