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The AP2 clathrin adaptor complex links protein cargo to the endocytic machinery but it is unclear how AP2 is activated on the plasma membrane . Here we demonstrate that the membrane-associated proteins FCHo and SGIP1 convert AP2 into an open , active conformation . We screened for Caenorhabditis elegans mutants that ph...	All cells are enveloped by a plasma membrane . To interact with the outside world , cells constantly recycle the molecules found in , or on , this barrier . This is accomplished by drawing in small patches of the membrane containing these ‘cargo’ molecules via a process called endocytosis . The predominant method of en...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2014	The membrane-associated proteins FCHo and SGIP are allosteric activators of the AP2 clathrin adaptor complex
The diversity of cutaneous sensory afferents has been studied by many investigators using behavioral , physiologic , molecular , and genetic approaches . Largely missing , thus far , is an analysis of the complete morphologies of individual afferent arbors . Here we present a survey of cutaneous sensory arbor morpholog...	Sensory neurons carry information from sensory cells in the eyes , ears and other sensory organs to the brain and spinal cord so that they can coordinate the body's response to its environment and various stimuli . The sensory organs responsible for four of the traditional senses—vision , hearing , smell and taste—are ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "neuroscience" ]	2012	Morphologic diversity of cutaneous sensory afferents revealed by genetically directed sparse labeling
Selection for a promiscuous enzyme activity provides substantial opportunity for competition between endogenous and newly-encountered substrates to influence the evolutionary trajectory , an aspect that is often overlooked in laboratory directed evolution studies . We selected the Escherichia coli nitro/quinone reducta...	In the cell , most tasks are performed by big molecules called proteins , which behave like molecular machines . Although proteins are often described as having one job each , this is not always true , and many proteins can perform different roles . Enzymes are a type of protein that facilitate chemical reactions . The...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology", "biochemistry", "and", "chemical", "biology" ]	2020	Intracellular complexities of acquiring a new enzymatic function revealed by mass-randomisation of active-site residues
Maintaining attention at a task-relevant spatial location while making eye-movements necessitates a rapid , saccade-synchronized shift of attentional modulation from the neuronal population representing the task-relevant location before the saccade to the one representing it after the saccade . Currently , the precise ...	When we look at a scene , our gaze does not move continuously across it . Instead , our eyes move discontinuously , shifting gaze rapidly from point to point to focus on different locations in the scene . These eye movements are known as saccades , and during them the brain temporarily and selectively stops processing ...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "short", "report", "neuroscience" ]	2016	Visual attention is available at a task-relevant location rapidly after a saccade
Duplication of the yeast centrosome ( called the spindle pole body , SPB ) is thought to occur through a series of discrete steps that culminate in insertion of the new SPB into the nuclear envelope ( NE ) . To better understand this process , we developed a novel two-color structured illumination microscopy with singl...	Cells divide to produce two new daughter cells that each contain the same genetic material . First , the DNA of the parent cell is copied , then it must be physically separated into the daughter cells by a structure made of filaments called microtubules . To ensure that the DNA is separated into two equal parts , the m...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "cell", "biology" ]	2015	Structured illumination with particle averaging reveals novel roles for yeast centrosome components during duplication
Complexins play activating and inhibitory functions in neurotransmitter release . The complexin accessory helix inhibits release and was proposed to insert into SNARE complexes to prevent their full assembly . This model was supported by ‘superclamp’ and ‘poor-clamp’ mutations that enhanced or decreased the complexin-I...	The instructions sent to , from and within the brain are rapidly transmitted along neurons in the form of electrical signals . These signals cannot pass across the small gaps—called synapses—that separate neighboring neurons . Instead , neurons release chemicals called neurotransmitters into the synapses , and these re...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics", "neuroscience" ]	2014	Re-examining how complexin inhibits neurotransmitter release
Chromatin accessibility mapping is a powerful approach to identify potential regulatory elements . A popular example is ATAC-seq , whereby Tn5 transposase inserts sequencing adapters into accessible DNA ( ‘tagmentation’ ) . CUT&Tag is a tagmentation-based epigenomic profiling method in which antibody tethering of Tn5 t...	Cells keep their DNA tidy by wrapping it into structures called nucleosomes . Each of these structures contains a short section of DNA wound around a cluster of proteins called histones . Not only do nucleosomes keep the genetic code organized , they also control whether the proteins that can switch genes on or off hav...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "tools", "and", "resources" ]	2020	Efficient chromatin accessibility mapping in situ by nucleosome-tethered tagmentation
The transmembrane chemokines CX3CL1/fractalkine and CXCL16 are widely expressed in different types of tumors , often without an appropriate expression of their classical receptors . We observed that receptor-negative cancer cells could be stimulated by the soluble chemokines . Searching for alternative receptors we det...	The cells that make up an animal need to communicate with each other for a variety of purposes , including controlling the growth and repair of tissues . Commonly , such signaling involves ‘ligand’ molecules binding to specific ‘receptor’ proteins embedded in the cell membrane . When a ligand docks to the right recepto...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2016	Transmembrane chemokines act as receptors in a novel mechanism termed inverse signaling
Epidemiological evidence suggests that social interactions and especially bonding between couples influence tumorigenesis , yet whether this is due to lifestyle changes , homogamy ( likelihood of individuals to marry people of similar health ) , or directly associated with host-induced effects in tumors remains debatab...	People’s social interactions could influence their risk of developing various diseases , including cancer , according to population-level studies . In particular , studies have identified a so-called widowhood effect where a person’s risk of disease increases following the loss of a spouse . However , the cause of the ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "short", "report", "cancer", "biology" ]	2021	Persistent effects of pair bonding in lung cancer cell growth in monogamous Peromyscus californicus
Chromosome segregation during mitosis depends upon Kinesin-5 motors , which display a conserved , bipolar homotetrameric organization consisting of two motor dimers at opposite ends of a central rod . Kinesin-5 motors crosslink adjacent microtubules to drive or constrain their sliding apart , but the structural basis o...	Successful cell division requires copies of the chromosomes containing the genetic material of a cell to be accurately copied and then separated so that when a cell divides , each new daughter cell contains exactly one copy of each chromosome . If this does not happen , the cell may malfunction or die . To separate the...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2014	Structural basis for the assembly of the mitotic motor Kinesin-5 into bipolar tetramers
Adaptation is a salient property of sensory processing . All adaptational or gain control mechanisms face the challenge of obtaining a reliable estimate of the property of the input to be adapted to and obtaining this estimate sufficiently rapidly to be useful . Here , we explore how the primate retina balances the nee...	To process the sights and sounds around us , our senses must be attuned to a huge range of signals: from barely audible whispers to deafening rock concerts , and from dim glimmers of light to bright spotlights . Sensory neurons face the challenge of encoding this huge range of inputs within their much more restricted r...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2013	Controlling gain one photon at a time
Selective elimination of unwanted synapses is vital for the precise formation of neuronal circuits during development , but the underlying mechanisms remain unclear . Using inositol 1 , 4 , 5-trisphosphate receptor type 2 knockout ( Itpr2−/− ) mice to specifically disturb somatic Ca2+ signaling in astrocytes , we showe...	Neighbouring neurons connect to each other and share information through structures known as synapses . As the brain develops , many synapses turn out to be redundant . Just like trees in a garden that need to be trimmed , these redundant synapses must be pruned in order to form the right pattern of connections between...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Astrocytes contribute to synapse elimination via type 2 inositol 1,4,5-trisphosphate receptor-dependent release of ATP
Statistical analysis of evolutionary-related protein sequences provides information about their structure , function , and history . We show that Restricted Boltzmann Machines ( RBM ) , designed to learn complex high-dimensional data and their statistical features , can efficiently model protein families from sequence ...	Almost every process that keeps a cell alive depends on the activities of several proteins . All proteins are made from chains of smaller molecules called amino acids , and the specific sequence of amino acids determines the protein’s overall shape , which in turn controls what the protein can do . Yet , the relationsh...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology", "physics", "of", "living", "systems", "tools", "and", "resources" ]	2019	Learning protein constitutive motifs from sequence data
The nematode Caenorhabditis elegans possesses a simple embryonic nervous system with few enough neurons that the growth of each cell could be followed to provide a systems-level view of development . However , studies of single cell development have largely been conducted in fixed or pre-twitching live embryos , becaus...	Understanding how the brain and nervous system develops from a few cells into complex , interconnected networks is a key goal for neuroscientists . Although researchers have identified many of the genes involved in this process , how these work together to form an entire brain remains unknown . A simple worm called Cae...	[ "Abstract", "Introduction", "Results", "Discussion", "M" ]	[ "computational", "and", "systems", "biology", "developmental", "biology", "tools", "and", "resources" ]	2015	Untwisting the Caenorhabditis elegans embryo
To generate energy efficiently , the cell is uniquely challenged to co-ordinate the abundance of electron transport chain protein subunits expressed from both nuclear and mitochondrial genomes . How an effective stoichiometry of this many constituent subunits is co-ordinated post-transcriptionally remains poorly unders...	Animal cells generate over 90% of the energy they need within small structures called mitochondria . Converting food into energy requires many different proteins and cells control the relative amounts of the proteins in mitochondria to ensure this process is efficient . To make more of a given protein , the cell must c...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "genetics", "and", "genomics" ]	2019	The long non-coding RNA Cerox1 is a post transcriptional regulator of mitochondrial complex I catalytic activity
Chronic itch remains a highly prevalent disorder with limited treatment options . Most chronic itch diseases are thought to be driven by both the nervous and immune systems , but the fundamental molecular and cellular interactions that trigger the development of itch and the acute-to-chronic itch transition remain unkn...	Chronic itch is a debilitating disorder that can last for months or years . Eczema , or atopic dermatitis , is the most common cause for chronic itch , affecting one in ten people worldwide . Many treatments for the condition are ineffective , and the exact cause of the disease is unknown , but many different types of ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience", "immunology", "and", "inflammation" ]	2019	Neutrophils promote CXCR3-dependent itch in the development of atopic dermatitis
It has been suggested that Staufen ( Stau ) is key in controlling the variability of the posterior boundary of the Hb anterior domain ( xHb ) . However , the mechanism that underlies this control is elusive . Here , we quantified the dynamic 3D expression of segmentation genes in Drosophila embryos . With improved cont...	Broadly speaking , all individuals of any animal species share a highly consistent shape and structure . Despite this , the activity of the genes that control these body patterns can vary significantly . There are currently two models that have been proposed for how noisy systems of genes , and the proteins they code ,...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "computational", "and", "systems", "biology" ]	2020	The dynamic transmission of positional information in stau- mutants during Drosophila embryogenesis
PapC ushers are outer-membrane proteins enabling assembly and secretion of P pili in uropathogenic E . coli . Their translocation domain is a large β-barrel occluded by a plug domain , which is displaced to allow the translocation of pilus subunits across the membrane . Previous studies suggested that this gating mecha...	Escherichia coli is a bacterium that commonly lives in the intestines of mammals , including humans , where it is usually harmless and can even be beneficial to its host . However , some types of E . coli produce hair-like filaments called P pili that allow the bacteria to attach to the human urinary tract and cause di...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics" ]	2014	Allosteric signalling in the outer membrane translocation domain of PapC usher
The brainstem plays a crucial role in sleep-wake regulation . However , the ensemble dynamics underlying sleep regulation remain poorly understood . Here , we show slow , state-predictive brainstem ensemble dynamics and state-dependent interactions between the brainstem and the hippocampus in mice . On a timescale of s...	Though almost all animals sleep , its exact purpose remains an enigma . This is particularly true for the period of sleep where people dream most vividly , which is known as rapid eye movement sleep or REM sleep for short . In addition to the eye movements that give it its name , during this phase of sleep , the pupils...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2020	State-dependent brainstem ensemble dynamics and their interactions with hippocampus across sleep states
Understanding how the brain captures transient experience and converts it into long lasting changes in neural circuits requires the identification and investigation of the specific ensembles of neurons that are responsible for the encoding of each experience . We have developed a Robust Activity Marking ( RAM ) system ...	Every experience – be it a sight , a sound or a memorable event – activates a unique set of neurons within the brain that together are known as a neuronal ensemble . Identifying these ensembles is key to deciphering how the brain represents experiences and stores them in memory . The most commonly used method for doing...	[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]	[ "tools", "and", "resources", "neuroscience" ]	2016	A robust activity marking system for exploring active neuronal ensembles
Molecular tension sensors have contributed to a growing understanding of mechanobiology . However , the limited dynamic range and inability to specify the mechanical sensitivity of these sensors has hindered their widespread use in diverse contexts . Here , we systematically examine the components of tension sensors th...	Cells must sense signals from their surroundings to play their roles within the body . These signals can be biochemical , such as growth-promoting substances , or mechanical , for example the stiffness or softness of the environment . Mechanical signals can be detected by load-bearing proteins , which stretch like tiny...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2018	Tunable molecular tension sensors reveal extension-based control of vinculin loading
A great deal of interest has been focused recently on the habenula and its critical role in aversion , negative-reward and drug dependence . Using a conditional mouse model of the ACh-synthesizing enzyme choline acetyltransferase ( Chat ) , we report that local elimination of acetylcholine ( ACh ) in medial habenula ( ...	Neuroscientists are making progress in understanding the brain regions and neural circuits that are involved in reward and addiction . One such region , called the habenula , is found near the center of the brain and sends nerves to another brain region called the interpeduncular nucleus ( or IPN for short ) ; this cre...	[ "Abstract", "Introduction", "Results", "Discussion", "Material", "and", "methods" ]	[ "neuroscience" ]	2015	An essential role of acetylcholine-glutamate synergy at habenular synapses in nicotine dependence
Microtubules control different aspects of cell polarization . In cells with a radial microtubule system , a pivotal role in setting up asymmetry is attributed to the relative positioning of the centrosome and the nucleus . Here , we show that centrosome loss had no effect on the ability of endothelial cells to polarize...	Networks of blood vessels grow like trees . Sprouts appear on existing vessels , stretching out to form new branches in a process called angiogenesis . The cells responsible are the same cells that line the finished vessels . These “endothelial cells” start the process by reorganizing themselves to face the direction o...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2018	Control of endothelial cell polarity and sprouting angiogenesis by non-centrosomal microtubules
The host–pathogen interactions induced by Salmonella Typhi and Salmonella Paratyphi A during enteric fever are poorly understood . This knowledge gap , and the human restricted nature of these bacteria , limit our understanding of the disease and impede the development of new diagnostic approaches . To investigate meta...	Enteric fever is estimated to affect over 37 million people every year . Although treatable with antimicrobial drugs , a slow and/or incorrect diagnosis can result in serious and often life-threatening complications . Enteric fever is the combined name for typhoid fever and paratyphoid fever . While the symptoms of the...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "epidemiology", "and", "global", "health", "microbiology", "and", "infectious", "disease" ]	2014	Salmonella Typhi and Salmonella Paratyphi A elaborate distinct systemic metabolite signatures during enteric fever
There is a continuing need for driver strains to enable cell-type-specific manipulation in the nervous system . Each cell type expresses a unique set of genes , and recapitulating expression of marker genes by BAC transgenesis or knock-in has generated useful transgenic mouse lines . However , since genes are often exp...	Scientists can track and even alter the activity of different kinds of neurons , as well as the connections between neurons , by manipulating their genes . However , most genes are active in many different kinds of cells in many different places in the brain , making it difficult to track or target only a particular ne...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "tools", "and", "resources", "neuroscience" ]	2016	A Mammalian enhancer trap resource for discovering and manipulating neuronal cell types
Neurons of the cerebellar nuclei ( CbN ) transmit cerebellar signals to premotor areas . The cerebellum expresses several autism-linked genes , including GABRB3 , which encodes GABAA receptor β3 subunits and is among the maternal alleles deleted in Angelman syndrome . We tested how this Gabrb3 m-/p+ mutation affects Cb...	The cerebellum is a part of the brain that plays a role in controlling movement , coordination and balance . It also contributes to cognitive processes that do not relate to movement . Changes in the cerebellum are often seen in individuals with autism spectrum disorders , and many genes implicated in autism are active...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Sex differences in cerebellar synaptic transmission and sex-specific responses to autism-linked Gabrb3 mutations in mice
The nematodes C . elegans and P . pacificus populate diverse habitats and display distinct patterns of behavior . To understand how their nervous systems have diverged , we undertook a detailed examination of the neuroanatomy of the chemosensory system of P . pacificus . Using independent features such as cell body pos...	Nerve cells , also called neurons , are responsible both for sensing signals from the environment and for determining how organisms react . This means that the unique features of an animal’s nervous system underpin its characteristic behaviors . Comparing the anatomy of the nervous systems in different animals could th...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2019	Evolution of neuronal anatomy and circuitry in two highly divergent nematode species
Polarized epithelial morphogenesis is an essential process in animal development . While this process is mostly attributed to directional cell intercalation , it can also be induced by other mechanisms . Using live-imaging analysis and a three-dimensional vertex model , we identified ‘cell sliding , ’ a novel mechanism...	Many organs arise from simple sheets and tubes of cells . During development these sheets bend and deform into the more complex shape of the final organ . This can be seen , for example , in the hindgut of fruit flies , which is an organ that is equivalent to our intestines . Initially , the hindgut is a simple tube of...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2018	Chiral cell sliding drives left-right asymmetric organ twisting
The bacteriophage population is large , dynamic , ancient , and genetically diverse . Limited genomic information shows that phage genomes are mosaic , and the genetic architecture of phage populations remains ill-defined . To understand the population structure of phages infecting a single host strain , we isolated , ...	Viruses are unable to replicate independently . To generate copies of itself , a virus must instead invade a target cell and commandeer that cell's replication machinery . Different viruses are able to invade different types of cell , and a group of viruses known as bacteriophages ( or phages for short ) replicate with...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "microbiology", "and", "infectious", "disease", "genetics", "and", "genomics" ]	2015	Whole genome comparison of a large collection of mycobacteriophages reveals a continuum of phage genetic diversity
Life history strategies for optimizing individual fitness fall on a spectrum between maximizing reproductive efforts and maintaining physical health over time . Strategies across this spectrum are viable and different suites of personality traits evolved to support these strategies . Using data from 538 captive chimpan...	Like humans , animals have distinct personalities . Our close evolutionary cousins chimpanzees even display the same five major personality traits that we do – extraversion , neuroticism , conscientiousness , openness , and agreeableness – as well as a distinct trait , for dominance . How did these distinct personality...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "ecology", "epidemiology", "and", "global", "health" ]	2018	Personality links with lifespan in chimpanzees
The eradication of tumor cells requires communication to and signaling by cells of the immune system . Natural killer ( NK ) cells are essential tumor-killing effector cells of the innate immune system; however , little is known about whether or how other immune cells recognize tumor cells to assist NK cells . Here , w...	When cells in the body grow and divide uncontrollably , cancerous tumors can form . An individual's likelihood of recovering from cancer is highly variable and often depends on the type of cancer and the extent of the disease at the start of treatment . Researchers are therefore interested in discovering how the body r...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "immunology", "and", "inflammation" ]	2014	Recognition of tumor cells by Dectin-1 orchestrates innate immune cells for anti-tumor responses
In mammals , hepatic lipid catabolism is essential for the newborns to efficiently use milk fat as an energy source . However , it is unclear how this critical trait is acquired and regulated . We demonstrate that under the control of PPARα , the genes required for lipid catabolism are transcribed before birth so that ...	Birth is a highly stressful and critical event . In the womb , babies rely on the supply of oxygen and nutrients provided by the placenta . However , once they are born they need to breathe for themselves and gain all their nutrients from suckling milk . The placenta provides a sugar-rich diet , while milk is richer in...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2016	Glucocorticoid receptor-PPARα axis in fetal mouse liver prepares neonates for milk lipid catabolism
Control of the COVID-19 pandemic will rely on SARS-CoV-2 vaccine-elicited antibodies to protect against emerging and future variants; an understanding of the unique features of the humoral responses to infection and vaccination , including different vaccine platforms , is needed to achieve this goal . The epitopes and ...	When SARS-CoV-2 – the virus that causes COVID-19 – infects our bodies , our immune system reacts by producing small molecules called antibodies that stick to a part of the virus called the spike protein . Vaccines are thought to work by triggering the production of similar antibodies without causing disease . Some of t...	[ "Abstract", "Introduction", "Results", "Discussion" ]	[ "microbiology", "and", "infectious", "disease", "immunology", "and", "inflammation" ]	2022	Comprehensive characterization of the antibody responses to SARS-CoV-2 Spike protein finds additional vaccine-induced epitopes beyond those for mild infection
C . elegans SET-9 and SET-26 are highly homologous paralogs that share redundant functions in germline development , but SET-26 alone plays a key role in longevity and heat stress response . Whereas SET-26 is broadly expressed , SET-9 is only detectable in the germline , which likely accounts for their different biolog...	Cells keep their DNA organized by wrapping it around groups of proteins called histones . These structures not only keep the genetic code tidy , they also affect how and when a cell uses its genes . This is because small chemical groups that are added to histones , such as a methyl group added to the fourth position of...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "developmental", "biology" ]	2018	SET-9 and SET-26 are H3K4me3 readers and play critical roles in germline development and longevity
Whole-organism chemical screening can circumvent bottlenecks that impede drug discovery . However , in vivo screens have not attained throughput capacities possible with in vitro assays . We therefore developed a method enabling in vivo high-throughput screening ( HTS ) in zebrafish , termed automated reporter quantifi...	Type 1 diabetes is caused by the body incorrectly destroying the cells in the pancreas—known as β cells—that produce insulin and so control the amount of sugar found in the bloodstream . Drugs that increase the rate at which new β cells form could therefore help to treat this disease . High-throughput screening is a te...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "cell", "biology" ]	2015	First quantitative high-throughput screen in zebrafish identifies novel pathways for increasing pancreatic β-cell mass
Host immune and physical barriers protect against pathogens but also impede the establishment of essential symbiotic partnerships . To reveal mechanisms by which beneficial organisms adapt to circumvent host defenses , we experimentally evolved ecologically distinct bioluminescent Vibrio fischeri by colonization and gr...	Most bacteria that associate with animals do not cause harm , and many are essential to health or provide other benefits . An animal’s immune system must permit these beneficial associations and at the same time block harmful microbes . This ultimately means that even beneficial bacteria must adapt to the immune barrie...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "microbiology", "and", "infectious", "disease", "genetics", "and", "genomics" ]	2017	Host-selected mutations converging on a global regulator drive an adaptive leap towards symbiosis in bacteria
To protect against aneuploidy , chromosomes must attach to microtubules from opposite poles ( ‘biorientation’ ) prior to their segregation during mitosis . Biorientation relies on the correction of erroneous attachments by the aurora B kinase , which destabilizes kinetochore-microtubule attachments that lack tension . ...	When a cell divides to create two new daughter cells , it must produce a copy of each of its chromosomes . It is important that each daughter cell gets just one copy of each chromosome . If an error occurs and one cell gets two copies of a single chromosome , it can lead to cancer or birth defects . Fortunately , there...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "cell", "biology" ]	2014	Shugoshin biases chromosomes for biorientation through condensin recruitment to the pericentromere
Escherichia coli single-stranded DNA ( ssDNA ) binding protein ( SSB ) is the defining bacterial member of ssDNA binding proteins essential for DNA maintenance . SSB binds ssDNA with a variable footprint of ∼30–70 nucleotides , reflecting partial or full wrapping of ssDNA around a tetramer of SSB . We directly imaged s...	Chromosomes consist of two strands of DNA that are intertwined as a helix . These strands can peal apart to form single-stranded DNA before the DNA is copied and for other processes in cells . Single-stranded DNA can also form if double-stranded DNA is damaged by harmful radiation or chemicals so that only one strand c...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology" ]	2015	Imaging and energetics of single SSB-ssDNA molecules reveal intramolecular condensation and insight into RecOR function
SWELL1 ( LRRC8A ) is the only essential subunit of the Volume Regulated Anion Channel ( VRAC ) , which regulates cellular volume homeostasis and is activated by hypotonic solutions . SWELL1 , together with four other LRRC8 family members , potentially forms a vastly heterogeneous cohort of VRAC channels with different ...	Every cell needs to regulate its internal volume or it will burst . Most of a cell’s volume is a watery mixture of salts , proteins and other molecules . A cell can take in more water from its surroundings , diluting this mixture and causing the cell to expand . If a cell starts to take up too much water , it will open...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics" ]	2018	Structure of the human volume regulated anion channel
Imprinted gene expression occurs during seed development in plants and is associated with differential DNA methylation of parental alleles , particularly at proximal transposable elements ( TEs ) . Imprinting variability could contribute to observed parent-of-origin effects on seed development . We investigated intrasp...	When animals or plants reproduce sexually , the DNA in a sperm or pollen is combined with that in an egg cell to generate an offspring that inherits two copies of each gene , one from each parent . For a very small number of genes , the copy from one of the parents is consistently turned off . This process—called impri...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology", "genetics", "and", "genomics" ]	2014	Natural epigenetic polymorphisms lead to intraspecific variation in Arabidopsis gene imprinting
Adjunctive dexamethasone reduces mortality from tuberculous meningitis ( TBM ) but not disability , which is associated with brain infarction . We hypothesised that aspirin prevents TBM-related brain infarction through its anti-thrombotic , anti-inflammatory , and pro-resolution properties . We conducted a randomised c...	The deadliest form of tuberculosis is tuberculosis meningitis ( TBM ) , which causes inflammation in the brain . Even with the best treatment available , about half of patients with TBM become disabled or die , often because they have a stroke . Strokes are caused by blood clots or other blockages in blood vessels in t...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "medicine", "microbiology", "and", "infectious", "disease" ]	2018	A randomised double blind placebo controlled phase 2 trial of adjunctive aspirin for tuberculous meningitis in HIV-uninfected adults
Monocytes are circulating short-lived macrophage precursors that are recruited on demand from the blood to sites of inflammation and challenge . In steady state , classical monocytes give rise to vasculature-resident cells that patrol the luminal side of the endothelium . In addition , classical monocytes feed macropha...	Macrophage cells play a crucial role in keeping the body free of disease-causing microbes and debris . They surveille the tissues , detect and clear infections , and tidy up dead cells . Most internal organs contain a population of macrophages that move into the organ during development and then persist throughout an o...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "immunology", "and", "inflammation" ]	2020	Defining murine monocyte differentiation into colonic and ileal macrophages
The bivalent hypothesis posits that genes encoding developmental regulators required for early lineage decisions are poised in stem/progenitor cells by the balance between a repressor histone modification ( H3K27me3 ) , mediated by the Polycomb Repressor Complex 2 ( PRC2 ) , and an activator modification ( H3K4me3 ) . ...	When an embryo is developing , genes are switched on or off at different times , for many different reasons . Many of these genes are switched off , or repressed , by making the DNA inaccessible to the various proteins and molecules that control gene activity . This is achieved by altering the way that the DNA is packa...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "developmental", "biology" ]	2014	Polycomb- and REST-associated histone deacetylases are independent pathways toward a mature neuronal phenotype
Working memory and conscious perception are thought to share similar brain mechanisms , yet recent reports of non-conscious working memory challenge this view . Combining visual masking with magnetoencephalography , we investigate the reality of non-conscious working memory and dissect its neural mechanisms . In a spat...	Many everyday activities require you to store information in your brain for immediate use . For example , imagine that you are cooking a meal: You have to remember the ingredients , add them in the correct order , and operate the stove . This ability is called working memory . Researchers have long believed that , when...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2017	A theory of working memory without consciousness or sustained activity
The Golgi complex is the central sorting compartment of eukaryotic cells . Arf guanine nucleotide exchange factors ( Arf-GEFs ) regulate virtually all traffic through the Golgi by activating Arf GTPase trafficking pathways . The Golgi Arf-GEFs contain multiple autoregulatory domains , but the precise mechanisms underly...	The cells of plants , animals and other eukaryotes are subdivided into different membrane-bound compartments . One of these compartments – called the Golgi complex – has been likened to the 'Grand Central Station' of the eukaryotic cell , because it serves as the cell’s centralized sorting compartment . Small , spheric...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2016	The Sec7 N-terminal regulatory domains facilitate membrane-proximal activation of the Arf1 GTPase
ADP-ribosylation ( ADPr ) is a posttranslational modification ( PTM ) of proteins that controls many cellular processes , including DNA repair , transcription , chromatin regulation and mitosis . A number of proteins catalyse the transfer and hydrolysis of ADPr , and also specify how and when the modification is conjug...	Inside cells , genetic information is stored within molecules of DNA . If any of the DNA becomes damaged , the cell has a suite of proteins that can help to repair the DNA . Many of these proteins act as signals that alert the cell to the presence of damaged DNA . One such signal involves adding a molecule called ADPr ...	[ "Abstract", "Introduction", "Results", "Discussion", "Material", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology" ]	2017	Serine ADP-ribosylation reversal by the hydrolase ARH3
Neural connectomics has begun producing massive amounts of data , necessitating new analysis methods to discover the biological and computational structure . It has long been assumed that discovering neuron types and their relation to microcircuitry is crucial to understanding neural function . Here we developed a non-...	The human brain is made up of billions of neurons , which are organised into networks via trillions of connections . The study of the nature of these connections will be central to understanding how the brain works . In recent years , a number of new methods for imaging the brain have made it possible to visualise and ...	[ "Abstract", "Introduction", "Model", "Results", "Discussion", "Methods" ]	[ "tools", "and", "resources", "neuroscience" ]	2015	Automatic discovery of cell types and microcircuitry from neural connectomics
Reward perception guides all aspects of animal behavior . However , the relationship between the perceived value of a reward , the latent value of a reward , and the behavioral response remains unclear . Here we report that , given a choice between two sweet and chemically similar sugars—L- and D-arabinose—Drosophila m...	We often remember experiences that are rewarding in some way . However , not every rewarding experience is stored in memory , and the particular experiences we remember are not always those we would expect to remember . Why is it that some experiences generate long-term memories whereas others do not ? Fruit flies feed...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "short", "report", "neuroscience" ]	2016	Immediate perception of a reward is distinct from the reward’s long-term salience
During low arousal states such as drowsiness and sleep , cortical neurons exhibit rhythmic slow wave activity associated with periods of neuronal silence . Slow waves are locally regulated , and local slow wave dynamics are important for memory , cognition , and behaviour . While several brainstem structures for contro...	We usually think of sleep as a global state: that the entire brain is either asleep or awake . However , recent evidence has suggested that smaller regions of the brain can show sleep-like activity while the rest of the brain remains awake . It is not clear why or how these sleep-like patterns of brain activity appear ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	Thalamic reticular nucleus induces fast and local modulation of arousal state
Influenza virus infections have a significant impact on global human health . Individuals with suppressed immunity , or suffering from chronic inflammatory conditions such as COPD , are particularly susceptible to influenza . Here we show that suppressor of cytokine signaling ( SOCS ) five has a pivotal role in restric...	Influenza , commonly referred to as the flu , is a highly contagious disease caused by a virus . When an infected person coughs or sneezes , droplets containing the virus are released into the air . Other individuals nearby may breathe in the virus , which then enters the cells lining the lungs and multiplies . Some pe...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "microbiology", "and", "infectious", "disease" ]	2017	Suppressor of cytokine signaling (SOCS)5 ameliorates influenza infection via inhibition of EGFR signaling
The T cell receptor ( TCR ) repertoire encodes immune exposure history through the dynamic formation of immunological memory . Statistical analysis of repertoire sequencing data has the potential to decode disease associations from large cohorts with measured phenotypes . However , the repertoire perturbation induced b...	The immune system has two major ways of clearing up an infection . A rapid , first line of defense buys time while the second ‘adaptive’ response disposes of the threat with precision . The adaptive response takes longer to develop but once it has dealt with a disease , it remembers: the next time the body encounters t...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology", "immunology", "and", "inflammation" ]	2018	Human T cell receptor occurrence patterns encode immune history, genetic background, and receptor specificity
We read jubmled wrods effortlessly , but the neural correlates of this remarkable ability remain poorly understood . We hypothesized that viewing a jumbled word activates a visual representation that is compared to known words . To test this hypothesis , we devised a purely visual model in which neurons tuned to letter...	“Aoccdrnig to a rseearch at Cmabridge Uinervtisy , it deos not mttaer in what oredr the ltteers in a wrod are , the olny iprmoatnt tihng is taht the frist and lsat ltteer be in the rghit pclae . ” The above text is an example of the so-called “Cambridge University effect” , a meme that often circulates on the Internet ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2020	A compositional neural code in high-level visual cortex can explain jumbled word reading
Maintenance of epigenetic modifiers is of utmost importance to preserve the epigenome and consequently appropriate cellular functioning . Here , we analyzed Polycomb group protein ( PcG ) complex integrity in response to heat shock ( HS ) . Upon HS , various Polycomb Repressive Complex ( PRC ) 1 and PRC2 subunits , inc...	All cells in our bodies contain the same sequence of DNA , hence the same genes , in a compartment called the nucleus . Yet different sets of genes are switched on in different types of cells . Cells achieve this by a process called epigenetic regulation . Proteins known as epigenetic regulators modify DNA and its asso...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "biochemistry", "and", "chemical", "biology" ]	2019	Protein quality control in the nucleolus safeguards recovery of epigenetic regulators after heat shock
Polycomb Repressive Complex 2 ( PRC2 ) is essential for gene silencing , establishing transcriptional repression of specific genes by tri-methylating Lysine 27 of histone H3 , a process mediated by cofactors such as AEBP2 . In spite of its biological importance , little is known about PRC2 architecture and subunit orga...	Protein complexes—stable structures that contain two or more proteins—have an important role in the biochemical processes that are associated with the expression of genes . Some help to silence genes , whereas others are involved in the activation of genes . The importance of such complexes is emphasized by the fact th...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics" ]	2012	Molecular architecture of human polycomb repressive complex 2
Most glucose is processed in muscle , for energy or glycogen stores . Malignant Hyperthermia Susceptibility ( MHS ) exemplifies muscle conditions that increase [Ca2+]cytosol . 42% of MHS patients have hyperglycemia . We show that phosphorylated glycogen phosphorylase ( GPa ) , glycogen synthase ( GSa ) – respectively a...	Animals and humans move by contracting the skeletal muscles attached to their bones . These muscles take up a type of sugar called glucose from food and use it to fuel contractions or store it for later in the form of glycogen . If muscles fail to use glucose it can lead to excessive sugar levels in the blood and a con...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics" ]	2020	Intracellular calcium leak lowers glucose storage in human muscle, promoting hyperglycemia and diabetes
GIRK channels control spike frequency in atrial pacemaker cells and inhibitory potentials in neurons . By directly responding to G proteins , PIP2 and Na+ , GIRK is under the control of multiple signaling pathways . In this study , the mammalian GIRK2 channel has been purified and reconstituted in planar lipid membrane...	Though every cell in the body is surrounded by a membrane , there are a number of ways that molecules can pass through this membrane to either enter or leave the cell . Proteins from the GIRK family form channels in the membranes of mammalian cells , and when open these channels allow potassium ions to flow through the...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2014	Quantitative analysis of mammalian GIRK2 channel regulation by G proteins, the signaling lipid PIP2 and Na+ in a reconstituted system
In many mouse models of skin cancer , only a few tumors typically form even though many cells competent for tumorigenesis receive the same oncogenic stimuli . These observations suggest an active selection process for tumor-initiating cells . Here , we use quantitative mRNA- and miR-Seq to determine the impact of HrasG...	DNA mutations occur and accumulate during an individual's lifetime . Often these changes are harmless . But some mutations—called driver mutations—can trigger the formation of tumors . This is often because these mutations allow the cells to grow faster than normal cells . Mutations in genes in the Ras gene family are ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "cancer", "biology" ]	2015	MicroRNA-203 represses selection and expansion of oncogenic Hras transformed tumor initiating cells
Most mammalian transcription factors ( TFs ) and cofactors occupy thousands of genomic sites and modulate the expression of large gene networks to implement their biological functions . In this study , we describe an exception to this paradigm . TRIM33 is identified here as a lineage dependency in B cell neoplasms and ...	The DNA inside every cell in a human body is the same , and yet the activities that occur within different types of cells can vary greatly . White blood cells , for example , are different from skin cells or liver cells because different genes are active in each type of cell . Molecules called transcription factors and...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "short", "report" ]	2015	The transcriptional cofactor TRIM33 prevents apoptosis in B lymphoblastic leukemia by deactivating a single enhancer
We recently implemented a bioinformatics pipeline that can uncover novel , but rare , riboswitch candidates as well as other noncoding RNA structures in bacteria . A prominent candidate revealed by our initial search efforts was called the ‘thiS motif’ because of its frequent association with a gene coding for the ThiS...	Many bacteria use small genetic devices called riboswitches to sense molecules that are essential for life and regulate the genes necessary to make , break or move these molecules . Riboswitches are made of molecules of RNA and appear to have ancient origins that predate the evolution of bacteria and other lifeforms ma...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology" ]	2019	A bacterial riboswitch class for the thiamin precursor HMP-PP employs a terminator-embedded aptamer
Human vestibular sensory epithelia in explant culture were incubated in gentamicin to ablate hair cells . Subsequent transduction of supporting cells with ATOH1 using an Ad-2 viral vector resulted in generation of highly significant numbers of cells expressing the hair cell marker protein myosin VIIa . Cells expressing...	The inner ear contains our balance system ( the vestibular system ) and our hearing organ ( the cochlea ) . Their sensing units , the hair cells , detect movement or sound waves . A loss of hair cells is a major cause of inner ear disorders , such as dizziness , imbalance and deafness . When hair cells die , supporting...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2018	Regenerating hair cells in vestibular sensory epithelia from humans
The mammalian target of rapamycin complex 1 ( mTORC1 ) is the key signaling hub that regulates cellular protein homeostasis , growth , and proliferation in health and disease . As a prerequisite for activation of mTORC1 by hormones and mitogens , there first has to be an available pool of intracellular amino acids . Ar...	Cells need to be able to sense and respond to signals from their environment . A group ( or complex ) of conserved proteins called mTORC1 acts a key signaling hub that regulates cell growth and many other processes . This complex can be activated by many different signals from outside the cell . However , mTORC1 can on...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2016	Control of TSC2-Rheb signaling axis by arginine regulates mTORC1 activity
The origin of animal multicellularity may be reconstructed by comparing animals with one of their closest living relatives , the choanoflagellate Salpingoeca rosetta . Just as animals develop from a single cell–the zygote–multicellular rosettes of S . rosetta develop from a founding cell . To investigate rosette develo...	All animals descended from a common ancestor that made the leap from living as a single cell to becoming more complicated , with many cells working together . At first , such a creature would likely have been made from clusters of cells that all had the same function . Eventually , different cells took on different rol...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "genetics", "and", "genomics" ]	2014	The rosetteless gene controls development in the choanoflagellate S. rosetta
The mechanisms that underlie directional cell migration are incompletely understood . Eph receptors usually guide migrations of cells by exclusion from regions expressing Ephrin . In sea urchin embryos , pigmented immunocytes are specified in vegetal epithelium , transition to mesenchyme , migrate , and re-enter ectode...	During animal development , numerous cells move around the embryo to form and shape the growing tissues . As these cells move , they are guided to their destination by molecular cues . The embryo’s tissues produce these cues and the cues can either repel or attract migrating cells . Ephrins are a large and well-studied...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[]	2016	Eph and Ephrin function in dispersal and epithelial insertion of pigmented immunocytes in sea urchin embryos
Sex differences and social context independently contribute to the development of stress-related disorders . However , less is known about how their interplay might influence behavior and physiology . Here we focused on social hierarchy status , a major component of the social environment in mice , and whether it influ...	Most people experience chronic stress at some point in their life , which may increase their chances of developing depression or anxiety . There is evidence that chronic stress may more negatively impact the well-being of women , placing them as higher risk of developing these mental health conditions . The biological ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2020	Social dominance mediates behavioral adaptation to chronic stress in a sex-specific manner
Although cell cycle control is an ancient , conserved , and essential process , some core animal and fungal cell cycle regulators share no more sequence identity than non-homologous proteins . Here , we show that evolution along the fungal lineage was punctuated by the early acquisition and entrainment of the SBF trans...	Living cells grow and divide with remarkable precision to ensure that their genetic material is faithfully duplicated and distributed equally to the newly formed daughter cells . This precision is achieved through a series of steps known as the cell cycle . The cell cycle is ancient and conserved across all Eukaryotes ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology", "computational", "and", "systems", "biology" ]	2016	Punctuated evolution and transitional hybrid network in an ancestral cell cycle of fungi
Weight loss and anorexia are common symptoms in cancer patients that occur prior to initiation of cancer therapy . Inflammation in the brain is a driver of these symptoms , yet cellular sources of neuroinflammation during malignancy are unknown . In a mouse model of pancreatic ductal adenocarcinoma ( PDAC ) , we observ...	Weight loss , decreased appetite and fatigue are symptoms of a wasting disorder known as cachexia , which is common in several serious diseases such as AIDS , chronic lung disease and heart failure . Up to 80 percent of people with advanced cancer also develop cachexia , and there are no effective treatments . It is no...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience", "immunology", "and", "inflammation" ]	2020	Circulating myeloid cells invade the central nervous system to mediate cachexia during pancreatic cancer
Heme is required for survival of all cells , and in most eukaryotes , is produced through a series of eight enzymatic reactions . Although heme production is critical for many cellular processes , how it is coupled to cellular differentiation is unknown . Here , using zebrafish , murine , and human models , we show tha...	Heme is an iron-containing compound that is important for all living things , from bacteria to humans . Our red blood cells use heme to carry oxygen and deliver it throughout the body . The amount of heme that is produced must be tightly regulated . Too little or too much heme in a person’s red blood cells can lead to ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2017	Erythropoietin signaling regulates heme biosynthesis
Nucleation promoting factors ( NPFs ) initiate branched actin network assembly by activating Arp2/3 complex , a branched actin filament nucleator . Cellular actin networks contain multiple NPFs , but how they coordinately regulate Arp2/3 complex is unclear . Cortactin is an NPF that activates Arp2/3 complex weakly on i...	Cells constantly sense , and react to , their environments . They can monitor or alter their surroundings by taking up or secreting various substances , and may also migrate toward food supplies , or toward signaling molecules—for example , to clot blood or heal wounds . These actions depend on the cytoskeleton , a pro...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2013	Mechanism of synergistic activation of Arp2/3 complex by cortactin and N-WASP
The TMPRSS2:ERG gene fusion is common in androgen receptor ( AR ) positive prostate cancers , yet its function remains poorly understood . From a screen for functionally relevant ERG interactors , we identify the arginine methyltransferase PRMT5 . ERG recruits PRMT5 to AR-target genes , where PRMT5 methylates AR on arg...	Prostate cancers are among the most common types of cancer in men , which , like other cancers , are driven by genetic mutations . Roughly half of all prostate cancers contain a genetic change that incorrectly fuses two genes together , causing the cells to produce abnormally high levels of a protein called ERG . ERG i...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "short", "report", "cell", "biology", "cancer", "biology" ]	2016	ERG signaling in prostate cancer is driven through PRMT5-dependent methylation of the Androgen Receptor
Cell-to-cell viral infection , in which viruses spread through contact of infected cell with surrounding uninfected cells , has been considered as a critical mode of virus infection . However , since it is technically difficult to experimentally discriminate the two modes of viral infection , namely cell-free infection...	Viruses such as HIV-1 replicate by invading and hijacking cells , forcing the cells to make new copies of the virus . These copies then leave the cell and continue the infection by invading and hijacking new cells . There are two ways that viruses may move between cells , which are known as ‘cell-free’ and ‘cell-to-cel...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology", "microbiology", "and", "infectious", "disease" ]	2015	Cell-to-cell infection by HIV contributes over half of virus infection
Cross-synaptic synchrony—correlations in transmitter release across output synapses of a single neuron—is a key determinant of how signal and noise traverse neural circuits . The anatomical connectivity between rod bipolar and A17 amacrine cells in the mammalian retina , specifically that neighboring A17s often receive...	The human eye is capable of detecting a single photon of starlight . This level of sensitivity is made possible by the high sensitivity of photoreceptors called rods . There are around 120 million rods in the retina , and they support vision in levels of light that are too low to activate the photoreceptors called cone...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2014	Cross-synaptic synchrony and transmission of signal and noise across the mouse retina
Gamma rhythms are known to contribute to the process of memory encoding . However , little is known about the underlying mechanisms at the molecular , cellular and network levels . Using local field potential recording in awake behaving mice and concomitant field potential and whole-cell recordings in slice preparation...	Changes in the strength of synapses – the connections between neurons – form the basis of learning and memory . This process , which is known as synaptic plasticity , incorporates transient experiences into persistent memory traces . However , a single synapse should not be viewed in isolation . Neurons typically belon...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Cell-specific synaptic plasticity induced by network oscillations
Adolescent synaptic pruning is thought to enable optimal cognition because it is disrupted in certain neuropathologies , yet the initiator of this process is unknown . One factor not yet considered is the α4βδ GABAA receptor ( GABAR ) , an extrasynaptic inhibitory receptor which first emerges on dendritic spines at pub...	Memories are formed at structures in the brain known as dendritic spines . These structures receive connections from other brain cells through regions called synapses . In humans , the number of these brain connections increases dramatically from birth to childhood , reflecting a period of rapid learning . However , th...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "neuroscience" ]	2016	Synaptic pruning in the female hippocampus is triggered at puberty by extrasynaptic GABAA receptors on dendritic spines
To understand complex regulatory processes in multicellular organisms , it is critical to be able to quantitatively analyze protein movement and protein-protein interactions in time and space . During Arabidopsis development , the intercellular movement of SHORTROOT ( SHR ) and subsequent interaction with its downstrea...	Stem cells are a specific type of cell found in both plants and animals . These cells can divide to produce daughter cells that can take on the role of any of the different tissues and organs within the plant or animal . A plant known as Arabidopsis is often used as a model in scientific research . In Arabidopsis , two...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology", "developmental", "biology" ]	2016	Tracking transcription factor mobility and interaction in Arabidopsis roots with fluorescence correlation spectroscopy
In higher eukaryotes , the endoplasmic reticulum ( ER ) contains a network of membrane tubules , which transitions into sheets during mitosis . Network formation involves curvature-stabilizing proteins , including the reticulons ( Rtns ) , as well as the membrane-fusing GTPase atlastin ( ATL ) and the lunapark protein ...	The endoplasmic reticulum is a compartment within the cells of plants , animals and other eukaryotes . This compartment plays a number of roles within cells , for example , serving as the site where many proteins and fat molecules are built . Most often the endoplasmic reticulum exists as a network of thin tubules . Ho...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2016	Cooperation of the ER-shaping proteins atlastin, lunapark, and reticulons to generate a tubular membrane network
The influence of biomechanics on the tempo and mode of morphological evolution is unresolved , yet is fundamental to organismal diversification . Across multiple four-bar linkage systems in animals , we discovered that rapid morphological evolution ( tempo ) is associated with mechanical sensitivity ( strong correlatio...	Imagine going for a swim on a shallow reef . You might see mantis shrimp striking at fish or snails , and reef fish gulping down smaller fish and plankton . Despite how different these movements are , rapid mantis shrimp strikes and fish suction are guided by the same mechanics: four-bar linkages . These shared mechani...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "ecology" ]	2018	Strong biomechanical relationships bias the tempo and mode of morphological evolution
Growth factor signaling is essential for pattern formation , growth , differentiation , and maintenance of stem cell pluripotency . Nodal-related signaling factors are required for axis formation and germ layer specification from sea urchins to mammals . Maternal transcripts of the zebrafish Nodal factor , Squint ( Sqt...	In many organisms , embryonic development is controlled in part by RNAs that are deposited into the egg as it forms inside the mother . These ‘maternal RNAs’ may localize to particular regions of the egg or embryo , where they are then exclusively translated into protein and carry out their specific function . This hel...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2013	An essential role for maternal control of Nodal signaling
When epithelia become too crowded , some cells are extruded that later die . To extrude , a cell produces the lipid , Sphingosine 1-Phosphate ( S1P ) , which activates S1P2 receptors in neighboring cells that seamlessly squeeze the cell out of the epithelium . Here , we find that extrusion defects can contribute to car...	Epithelial cells cover the surface of our bodies , line our lungs , stomach and intestines and serve as a protective layer around other organs . If too many epithelial cells die and are not replaced , this protective layer may erode and lead to organ damage . However , if too many new cells grow , tumors can form . One...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "cancer", "biology" ]	2015	Defective apical extrusion signaling contributes to aggressive tumor hallmarks
Mechanical force and Wnt signaling activate β-catenin-mediated transcription to promote proliferation and tissue expansion . However , it is unknown whether mechanical force and Wnt signaling act independently or synergize to activate β-catenin signaling and cell division . We show that mechanical strain induced Src-de...	Tissues and organs can both produce and respond to physical forces . For example , the lungs expand and contract; the heart pumps blood; and bones and muscles grow or shrink depending on how much they are used . These responses are possible because cells contain proteins that can respond to physical forces . One of the...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2016	Increasing β-catenin/Wnt3A activity levels drive mechanical strain-induced cell cycle progression through mitosis
Evolutionary innovations that enable organisms to colonize new ecological niches are rare compared to gradual evolutionary changes in existing traits . We discovered that key mutations in the gltA gene , which encodes citrate synthase ( CS ) , occurred both before and after Escherichia coli gained the ability to grow a...	Bacteria and other organisms are constantly under pressure to survive in the face of ever-changing environmental challenges . They generally adapt to these challenges through genetic mutations that modify features they already have . However , occasionally a species may acquire an entirely new characteristic – known as...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology" ]	2015	Fine-tuning citrate synthase flux potentiates and refines metabolic innovation in the Lenski evolution experiment
In Heliconius butterflies , wing colour pattern diversity and scale types are controlled by a few genes of large effect that regulate colour pattern switches between morphs and species across a large mimetic radiation . One of these genes , cortex , has been repeatedly associated with colour pattern evolution in butter...	Heliconius butterflies have bright patterns on their wings that tell potential predators that they are toxic . As a result , predators learn to avoid eating them . Over time , unrelated species of butterflies have evolved similar patterns to avoid predation through a process known as Müllerian mimicry . Worldwide , the...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "evolutionary", "biology" ]	2021	Cortex cis-regulatory switches establish scale colour identity and pattern diversity in Heliconius
Eliminating malaria from a defined region involves draining the endemic parasite reservoir and minimizing local malaria transmission around imported malaria infections . In the last phases of malaria elimination , as universal interventions reap diminishing marginal returns , national resources must become increasingly...	Swaziland has set a national goal of eliminating malaria transmission in the very short term , which would make it the first country in sub-Saharan Africa to do so . More than half of the cases of malaria that are observed in Swaziland are caused by infections picked up by travelers while they were in other countries w...	[ "Abstract", "Introduction", "Discussion", "Methods" ]	[ "epidemiology", "and", "global", "health", "medicine" ]	2015	Mapping residual transmission for malaria elimination
Decision-makers often arrive at different choices when faced with repeated presentations of the same evidence . Variability of behavior is commonly attributed to noise in the brain’s decision-making machinery . We hypothesized that phasic responses of brainstem arousal systems are a significant source of this variabili...	When asked to make repeated decisions we will often choose differently each time even when we are given the same information to inform our choice . A stock trader , for example , will typically be more inclined to buy on some days and sell on others even if the financial markets remain unchanged . Fluctuations in the b...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2017	Dynamic modulation of decision biases by brainstem arousal systems
Optogenetic techniques enable precise excitation and inhibition of firing in specified neuronal populations and artifact-free recording of firing activity . Several studies have suggested that optical stimulation provides the precision and dynamic range requisite for closed-loop neuronal control , but no approach yet p...	Cells called neurons use electrical signals to rapidly carry information around the body . When a neuron is activated , it generates ( or ‘fires’ ) a short electrical impulse that travels along the cell to relay a message to other neurons , muscles or organs . Optogenetics is a technique that allows scientists to genet...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	Optogenetic feedback control of neural activity
The gradient of Decapentaplegic ( Dpp ) in the Drosophila wing has served as a paradigm to characterize the role of morphogens in regulating patterning . However , the role of this gradient in regulating tissue size is a topic of intense debate as proliferative growth is homogenous . Here , we combined the Gal4/UAS sys...	From the wings of a butterfly to the fingers of a human hand , living tissues often have complex and intricate patterns . Developmental biologists have long been fascinated by the signals – called morphogens – that guide how these kinds of pattern develop . Morphogens are substances that are produced by groups of cells...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2017	Boundary Dpp promotes growth of medial and lateral regions of the Drosophila wing
Protein folding homeostasis in the endoplasmic reticulum ( ER ) requires efficient protein thiol oxidation , but also relies on a parallel reductive process to edit disulfides during the maturation or degradation of secreted proteins . To critically examine the widely held assumption that reduced ER glutathione fuels d...	Proteins are basically strings of amino acids that have folded into a specific three-dimensional shape , and this shape is often important for the protein's function . Some proteins have bonds between pairs of cysteines—an amino acid that contains sulfur—in different parts of the protein to maintain its correct shape ....	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2014	Intact protein folding in the glutathione-depleted endoplasmic reticulum implicates alternative protein thiol reductants
Oriented cell division is one mechanism progenitor cells use during development and to maintain tissue homeostasis . Common to most cell types is the asymmetric establishment and regulation of cortical NuMA-dynein complexes that position the mitotic spindle . Here , we discover that HMMR acts at centrosomes in a PLK1-d...	As an embryo develops , its cells divide , grow and change into many different types of cells that eventually build our body . When cells divide , they first need to duplicate their genetic material . A structure called the spindle then distributes the two copies of the genetic information between the new cells . Cells...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "cell", "biology" ]	2017	HMMR acts in the PLK1-dependent spindle positioning pathway and supports neural development
Small nucleolar RNAs ( snoRNAs ) are a diverse group of non-coding RNAs that direct chemical modifications at specific residues on other RNA molecules , primarily on ribosomal RNA ( rRNA ) . SnoRNAs are altered in several cancers; however , their role in cell homeostasis as well as in cellular transformation remains po...	Ribosomes are cellular machines responsible for translating the genetic code into proteins . Research has shown that changes in ribosome activity can contribute to healthy cells becoming cancerous . Ribosomes consist of proteins and other molecules known as ribosomal RNAs ( or rRNAs for short ) . Before they can become...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "cancer", "biology" ]	2019	A single H/ACA small nucleolar RNA mediates tumor suppression downstream of oncogenic RAS
mRNA translation decodes nucleotide into amino acid sequences . However , translation has also been shown to affect mRNA stability depending on codon composition in model organisms , although universality of this mechanism remains unclear . Here , using three independent approaches to measure exogenous and endogenous m...	Proteins are made by joining together building blocks called amino acids into strings . The proteins are ‘translated’ from genetic sequences called mRNA molecules . These sequences can be thought of as series of ‘letters’ , which are read in groups of three known as codons . Molecules called tRNAs recognize the codons ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression" ]	2019	Translation affects mRNA stability in a codon-dependent manner in human cells
Heritability of human lifespan is 23–33% as evident from twin studies . Genome-wide association studies explored this question by linking particular alleles to lifespan traits . However , genetic variants identified so far can explain only a small fraction of lifespan heritability in humans . Here , we report that the ...	Most living things undergo biological changes as they get older , a process that we generally refer to as aging . Despite being a widespread phenomenon , scientists do not fully understand why we age , though it appears that a combination of genetics and lifestyle factors , such as diet , play a role in influencing lif...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "genetics", "and", "genomics" ]	2020	Germline burden of rare damaging variants negatively affects human healthspan and lifespan
Clustering of proteins into micrometer-sized structures at membranes is observed in many signaling pathways . Most models of clustering are specific to particular systems , and relationships between physical properties of the clusters and their molecular components are not well understood . We report biochemical recons...	The membrane that surrounds a cell is made up of a mixture of lipid molecules and proteins . Membrane proteins perform a wide range of roles , including transmitting signals into , and out of , cells and helping neighboring cells to stick together . To perform these tasks , these proteins commonly need to bind to other...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "physics", "of", "living", "systems" ]	2014	Phase transitions of multivalent proteins can promote clustering of membrane receptors
Transposable elements ( TEs ) are widespread genomic parasites , and their evolution has remained a critical question in evolutionary genomics . Here , we study the relatively unexplored epigenetic impacts of TEs and provide the first genome-wide quantification of such effects in D . melanogaster and D . simulans . Sur...	The DNA inside an organism encodes all the instructions needed for the organism to develop and work properly . Organisms carefully organize and maintain their DNA ( collectively known as the genome ) so that the genetic information remains intact and the cell can understand the instructions . However , there are some p...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "genetics", "and", "genomics" ]	2017	Pervasive epigenetic effects of Drosophila euchromatic transposable elements impact their evolution
Understanding the relationships between different properties of data , such as whether a genome or connectome has information about disease status , is increasingly important . While existing approaches can test whether two properties are related , they may require unfeasibly large sample sizes and often are not interp...	If you want to estimate whether height is related to weight in humans , what would you do ? You could measure the height and weight of a large number of people , and then run a statistical test . Such ‘independence tests’ can be thought of as a screening procedure: if the two properties ( height and weight ) are not re...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology", "tools", "and", "resources", "neuroscience" ]	2019	Discovering and deciphering relationships across disparate data modalities
Intracellular lipopolysaccharide ( LPS ) triggers the non-canonical inflammasome pathway , resulting in pyroptosis of innate immune cells . In addition to its well-known proinflammatory role , LPS can directly cause regression of some tumors , although the underlying mechanism has remained unknown . Here we show that s...	Inflammation serves to kill invading bacteria and viruses . Certain molecules on the surface of the microbes can trigger an inflammatory cascade , and one example of such a molecule is lipopolysaccharide ( LPS ) . Cells can react to LPS by triggering a process called pyroptosis that causes the cell to burst and die . T...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "immunology", "and", "inflammation" ]	2018	A novel pathway of LPS uptake through syndecan-1 leading to pyroptotic cell death
Epithelial morphogenesis and stability are essential for normal development and organ homeostasis . The mouse neural plate is a cuboidal epithelium that remodels into a columnar pseudostratified epithelium over the course of 24 hr . Here we show that the transition to a columnar epithelium fails in mutant embryos that ...	In mammals , the brain and spinal cord develop from a flat sheet of cells called the neural plate , which bends around to create a structure known as the neural tube . This bending process occurs through a complex sequence of cell shape changes . The cells in the neural plate are initially short and wide , but transfor...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "cell", "biology" ]	2016	The tumor suppressor PTEN and the PDK1 kinase regulate formation of the columnar neural epithelium
How left-right patterning drives asymmetric morphogenesis is unclear . Here , we have quantified shape changes during mouse heart looping , from 3D reconstructions by HREM . In combination with cell labelling and computer simulations , we propose a novel model of heart looping . Buckling , when the cardiac tube grows b...	The heart is an organ that pumps blood throughout the body to supply oxygen and to remove carbon dioxide and waste products . Its left and right side are shaped differently to circulate blood through two pathways: to the lungs and to all other organs . As the heart develops inside the embryo , it transforms from a simp...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2017	A predictive model of asymmetric morphogenesis from 3D reconstructions of mouse heart looping dynamics
Transcription occurs in stochastic bursts . Early models based upon RNA hybridisation studies suggest bursting dynamics arise from alternating inactive and permissive states . Here we investigate bursting mechanism in live cells by quantitative imaging of actin gene transcription , combined with molecular genetics , st...	Understanding how gene activity is regulated relies on accurate measurements of the output of genes . Proteins are generated from genes via a multi-step process . In the first step , called transcription , the DNA of a gene is copied by complex cell machinery to create molecules of mRNA . Subsequently , these mRNA mole...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "computational", "and", "systems", "biology" ]	2016	A continuum model of transcriptional bursting
Nuclear speckles ( NS ) are among the most prominent biomolecular condensates . Despite their prevalence , research on the function of NS is virtually restricted to colocalization analyses , since an organizing core , without which NS cannot form , remains unidentified . The monoclonal antibody SC35 , raised against a ...	Most cells store their genetic material inside a compartment called the nucleus , which helps to separate DNA from other molecules in the cell . Inside the nucleus , DNA is tightly packed together with proteins that can read the cell’s genetic code and convert into the RNA molecules needed to build proteins . However ,...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "cell", "biology" ]	2020	SON and SRRM2 are essential for nuclear speckle formation
A major goal of cancer genomics is to identify all genes that play critical roles in carcinogenesis . Most approaches focused on genes positively selected for mutations that drive carcinogenesis and neglected the role of negative selection . Some studies have actually concluded that negative selection has no role in ca...	The DNA in the cells of the human body is usually copied correctly when a cell divides . However , errors ( mutations ) are sometimes introduced during the copying process . Although the majority of mutations have no major impact on cells , many mutations are harmful: they decrease the ability of cells to survive . The...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cancer", "biology" ]	2021	Use of signals of positive and negative selection to distinguish cancer genes and passenger genes
The ellipsoid body ( EB ) in the Drosophila brain is a central complex ( CX ) substructure that harbors circumferentially laminated ring ( R ) neuron axons and mediates multifaceted sensory integration and motor coordination functions . However , what regulates R axon lamination and how lamination affects R neuron func...	The human brain contains around one hundred billion nerve cells , or neurons , which are interconnected and organized into distinct layers within different brain regions . Electrical impulses pass along a cable-like part of each neuron , known as the axon , to reach other neurons in different layers of various brain st...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "neuroscience" ]	2017	The laminar organization of the Drosophila ellipsoid body is semaphorin-dependent and prevents the formation of ectopic synaptic connections

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