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There is evidence that lipids can be allosteric regulators of membrane protein structure and activation . However , there are no data showing how exactly the regulation emerges from specific lipid-protein interactions . Here we show in atomistic detail how the human β2-adrenergic receptor ( β2AR ) – a prototypical G pr...	Proteins known as G protein-coupled receptors , or GPCRs for short , detect and respond to hormones and other signaling molecules found outside cells . A signaling molecule activates a GPCR by binding to it and causing the receptor to change its shape . This triggers a cascade of signals inside the cell that leads to t...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics", "computational", "and", "systems", "biology" ]	2016	Mechanism of allosteric regulation of β2-adrenergic receptor by cholesterol
The Notch pathway is integrated into numerous developmental processes and therefore is fine-tuned on many levels , including receptor production , endocytosis , and degradation . Notch is further characterized by a twofold relationship with its Delta-Serrate ( DSL ) ligands , as ligands from opposing cells ( trans-liga...	Many biological processes require cells to send messages to one another . Typically , this is achieved when molecules are released from one cell and make contact with companion molecules on another cell . This triggers a chemical or biological reaction in the receiving cell . One of the most common examples of this is ...	[ "Abstract", "Main", "text", "Materials", "and", "methods" ]	[ "developmental", "biology", "short", "report", "cell", "biology" ]	2014	Cis-interactions between Notch and its ligands block ligand-independent Notch activity
The characterization of the transcriptome and proteome of Plasmodium falciparum has been a tremendous resource for the understanding of the molecular physiology of this parasite . However , the translational dynamics that link steady-state mRNA with protein levels are not well understood . In this study , we bridge thi...	The genome of an organism includes all of the genes or information necessary to build , maintain , and replicate that organism . However , cells with the same genome—such as a skin cell and a liver cell from the same person—can look and behave very differently depending on which of the genes in their genomes they expre...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "microbiology", "and", "infectious", "disease" ]	2014	Genome-wide regulatory dynamics of translation in the Plasmodium falciparum asexual blood stages
Crucial roles for T-box3 in development are evident by severe limb malformations and other birth defects caused by T-box3 mutations in humans . Mechanisms whereby T-box3 regulates limb development are poorly understood . We discovered requirements for T-box at multiple stages of mouse limb development and distinct mole...	Mutations in the gene that encodes a protein called T-box3 cause serious birth defects , including deformities of the hands and feet , via poorly understood mechanisms . Several other proteins are also important for ensuring that limbs develop correctly . These include the Sonic Hedgehog protein , which controls a sign...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2016	T-box3 is a ciliary protein and regulates stability of the Gli3 transcription factor to control digit number
Herd immunity , a process in which resistant individuals limit the spread of a pathogen among susceptible hosts has been extensively studied in eukaryotes . Even though bacteria have evolved multiple immune systems against their phage pathogens , herd immunity in bacteria remains unexplored . Here we experimentally dem...	When a disease spreads through a population , it encounters certain individuals it cannot infect . If there are enough of these individuals , the epidemic stops . This phenomenon is known as ‘herd immunity’ , and it occurs in many animals – for example , it plays an important role in human vaccination schemes . While b...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "ecology", "evolutionary", "biology" ]	2018	CRISPR-based herd immunity can limit phage epidemics in bacterial populations
Rhomboid proteases reside within cellular membranes , but the advantage of this unusual environment is unclear . We discovered membrane immersion allows substrates to be identified in a fundamentally-different way , based initially upon exposing ‘masked’ conformational dynamics of transmembrane segments rather than seq...	Proteases are enzymes that break the peptide bonds that hold proteins together , and have a central role in many physiological processes , including digestion , blood clotting and programmed cell death . An important characteristic of proteases is that they are highly selective , only cutting proteins that contain well...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology" ]	2012	Membrane immersion allows rhomboid proteases to achieve specificity by reading transmembrane segment dynamics
Carboxysomes are protein-based bacterial organelles encapsulating key enzymes of the Calvin-Benson-Bassham cycle . Previous work has implicated a ParA-like protein ( hereafter McdA ) as important for spatially organizing carboxysomes along the longitudinal axis of the model cyanobacterium Synechococcus elongatus PCC 79...	Cyanobacteria are tiny organisms that can harness the energy of the sun to power their cells . Many of the tools required for this complex photosynthetic process are packaged into small compartments inside the cell , the carboxysomes . In Synechococcus elongatus , a cyanobacterium that is shaped like a rod , the carbox...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "physics", "of", "living", "systems", "microbiology", "and", "infectious", "disease" ]	2018	Protein gradients on the nucleoid position the carbon-fixing organelles of cyanobacteria
The pervasive occurrence of sexual dimorphism demonstrates different adaptive strategies of males and females . While different reproductive strategies of the two sexes are well-characterized , very little is known about differential functional requirements of males and females in their natural habitats . Here , we stu...	Male and female animals of the same species sometimes differ in appearance and sexual behavior , a phenomenon known as sexual dimorphism . Both sexes share most of the same genes , but differences can emerge because of the way these are read by cells to create proteins – a process called gene expression . For instance ...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology", "genetics", "and", "genomics" ]	2020	Rapid sex-specific adaptation to high temperature in Drosophila
The motor cortex ( M1 ) is classically considered an agranular area , lacking a distinct layer 4 ( L4 ) . Here , we tested the idea that M1 , despite lacking a cytoarchitecturally visible L4 , nevertheless possesses its equivalent in the form of excitatory neurons with input–output circuits like those of the L4 neurons...	In 1909 , a German scientist called Korbinian Brodmann published the first map of the outer layer of the human brain . After staining neurons with a dye and studying the structures of the cells and how they were organized , he realized that he could divide the cortex into 43 numbered regions . Most Brodmann areas can b...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2014	A genuine layer 4 in motor cortex with prototypical synaptic circuit connectivity
Methylation of histone H3 at lysine 36 ( H3K36me ) , a widely-distributed chromatin mark , largely results from association of the lysine methyltransferase ( KMT ) SET-2 with RNA polymerase II ( RNAPII ) , but most eukaryotes also have additional H3K36me KMTs that act independently of RNAPII . These include the ortholo...	Not all genes in a cell’s DNA are active all the time . There are several ways to control this activity . One is by altering how the DNA is packaged into cells . DNA strands are wrapped around proteins called histones to form nucleosomes . Nucleosomes can then be packed together tightly , to restrict access to the DNA ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "genetics", "and", "genomics" ]	2018	ASH1-catalyzed H3K36 methylation drives gene repression and marks H3K27me2/3-competent chromatin
The mechanosensitive channel of large conductance , which serves as a model system for mechanosensitive channels , has previously been crystallized in the closed form , but not in the open form . Ensemble measurements and electrophysiological sieving experiments show that the open-diameter of the channel pore is >25 Å ...	Bacterial cells are full of fluid , and they will burst if they are not able to respond to a build up of pressure . Fortunately , the membrane of a bacterial cell contains channels that can detect the increased mechanical stress on the cell membrane and then open to relieve the pressure . In many bacterial cells , the ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics" ]	2014	Single molecule FRET reveals pore size and opening mechanism of a mechano-sensitive ion channel
Spontaneous fluctuations in neuronal activity emerge at many spatial and temporal scales in cortex . Population measures found these fluctuations to organize as scale-invariant neuronal avalanches , suggesting cortical dynamics to be critical . Macroscopic dynamics , though , depend on physiological states and are ambi...	Even when we are not engaged in any specific task , the brain shows coordinated patterns of spontaneous activity that can be monitored using electrodes placed on the scalp . This resting activity shapes the way that the brain responds to subsequent stimuli . Changes in resting activity patterns are seen in various neur...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	Irregular spiking of pyramidal neurons organizes as scale-invariant neuronal avalanches in the awake state
Primary cilia are vital signaling organelles that extend from most types of cells , including neurons and glia . These structures are essential for development of many tissues and organs; however , their function in adult tissues , particularly neurons in the brain , remains largely unknown . Tau tubulin kinase 2 ( TTB...	Many mammalian cells have a single hair-like structure , known as the primary cilium that projects away from the surface of the cell . This small projection from the membrane regulates many signaling pathways , particularly during embryonic development . However , most of the neurons in the adult brain also have primar...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "neuroscience" ]	2020	TTBK2 and primary cilia are essential for the connectivity and survival of cerebellar Purkinje neurons
Evaluation of sepsis-induced immunoparalysis has highlighted how decreased lymphocyte number/function contribute to worsened infection/cancer . Yet , an interesting contrast exists with autoimmune disease development , wherein diminishing pathogenic effectors may benefit the post-septic host . Within this framework , t...	Sepsis is a life-threatening condition that can happen when the immune system overreacts to an infection and begins to damage tissues and organs in the body . It causes an extreme immune reaction called a cytokine storm , where the body releases uncontrolled levels of cytokines , proteins that are involved in coordinat...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "immunology", "and", "inflammation" ]	2020	Sepsis impedes EAE disease development and diminishes autoantigen-specific naive CD4 T cells
Colorectal cancer ( CRC ) organoids can be derived from almost all CRC patients and therefore capture the genetic diversity of this disease . We assembled a panel of CRC organoids carrying either wild-type or mutant RAS , as well as normal organoids and tumor organoids with a CRISPR-introduced oncogenic KRAS mutation ....	Recent technical advances mean that miniature replicas of many tissues can be grown in the laboratory . These so-called organoids provide scientists with model systems that are not as limited as simple , two-dimensional sheets of cells growing in a petri dish , and less labor and resource intensive than studies using l...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "cancer", "biology" ]	2016	Targeting mutant RAS in patient-derived colorectal cancer organoids by combinatorial drug screening
Adaptive immunity vitally depends on major histocompatibility complex class I ( MHC I ) molecules loaded with peptides . Selective loading of peptides onto MHC I , referred to as peptide editing , is catalyzed by tapasin and the tapasin-related TAPBPR . An important catalytic role has been ascribed to a structural feat...	Cells in the body keep the immune system informed about their health by showing it fragments of the proteins they have been making . They display these fragments , called peptides , on MHC molecules for passing immune cells to inspect . That way , if a cell becomes infected and starts to make virus proteins , or if it ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "immunology", "and", "inflammation" ]	2020	A loop structure allows TAPBPR to exert its dual function as MHC I chaperone and peptide editor
The hologenome concept proposes that microbes and their host organism are an independent unit of selection . Motivated by this concept , we hypothesized that thermal acclimation in poikilothermic organisms , owing to their inability to maintain their body temperature , is connected to their microbiome composition . To ...	Animals and plants host diverse microbial communities that are vital for their survival . In fact , the host organisms and their associated ‘microbiome’ are so closely linked that they are often described as a single entity: the holobiont unit . This suggests that when the host adapts to cope with stressful conditions ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "microbiology", "and", "infectious", "disease" ]	2018	Host genetic selection for cold tolerance shapes microbiome composition and modulates its response to temperature
The spindle- and kinetochore-associated ( Ska ) complex is essential for normal anaphase onset in mitosis . The C-terminal domain ( CTD ) of Ska1 binds microtubules and was proposed to facilitate kinetochore movement on depolymerizing spindle microtubules . Here , we show that Ska complex recruits protein phosphatase 1...	When one cell divides into two daughter cells it is critical that both new cells inherit an entire copy of the genetic material . This process is called mitosis , and it involves the duplicated chromosomes lining up in the middle of the cell before being pulled apart into the two newly forming cells . Many different pr...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "cell", "biology" ]	2016	The human SKA complex drives the metaphase-anaphase cell cycle transition by recruiting protein phosphatase 1 to kinetochores
Cyclic G/AMP synthase ( cGAS ) initiates type-1 interferon responses against cytosolic double-stranded ( ds ) DNA , which range from antiviral gene expression to apoptosis . The mechanism by which cGAS shapes this diverse signaling landscape remains poorly defined . We find that substrate-binding and dsDNA length-depen...	The human immune system protects the body from various threats such as damaged cells or invading microbes . Many of these threats can move molecules of DNA , which are usually only found within a central compartment in the cell known as the nucleus , to the surrounding area , the cytoplasm . An enzyme called cGAS searc...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "immunology", "and", "inflammation" ]	2018	The allosteric activation of cGAS underpins its dynamic signaling landscape
Multidimensional landscapes of regulatory genes in neuronal phenotypes at whole-brain levels in the vertebrate remain elusive . We generated single-cell transcriptomes of ~67 , 000 region- and neurotransmitter/neuromodulator-identifiable cells from larval zebrafish brains . Hierarchical clustering based on effector gen...	The brain harbors an astounding diversity of interconnected cells . Each cell contains the same basic set of genetic instructions , but only a fraction of the genome is used in each cell to assemble proteins . This selective gene expression gives rise to each cell’s characteristic properties , such as their shape and l...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "tools", "and", "resources", "neuroscience" ]	2021	The landscape of regulatory genes in brain-wide neuronal phenotypes of a vertebrate brain
Locomotion of tetrapods on land adapted to different environments and needs resulting in a variety of different gait styles . However , comparative analyses reveal common principles of limb movement control . Here , we report that a kinematic synergy involving the planar covariation of limb segment motion holds in 54 d...	Animals have evolved very different body shapes and styles of movement that are adapted to their needs in the habitats they live in . For example , mice , lions and many other animals use four limbs to walk , while humans and birds only use two limbs . The styles animals use to walk also differ in terms of how long eac...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology", "neuroscience" ]	2018	A kinematic synergy for terrestrial locomotion shared by mammals and birds
The neuronal DNA-/RNA-binding protein Pur-alpha is a transcription regulator and core factor for mRNA localization . Pur-alpha-deficient mice die after birth with pleiotropic neuronal defects . Here , we report the crystal structure of the DNA-/RNA-binding domain of Pur-alpha in complex with ssDNA . It reveals base-spe...	Some proteins perform several different tasks inside cells . This is the case for a protein called Pur-alpha , which is essential for neurons to work correctly . For example , Pur-alpha can bind to DNA to regulate gene activity . It also binds to RNA molecules , which are copies of a gene , and helps to distribute them...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2016	Structural basis of nucleic-acid recognition and double-strand unwinding by the essential neuronal protein Pur-alpha
The mTOR complex 1 ( mTORC1 ) and endoplasmic reticulum ( ER ) stress pathways are critical regulators of intestinal inflammation and colon cancer growth . Sestrins are stress-inducible proteins , which suppress both mTORC1 and ER stress; however , the role of Sestrins in colon physiology and tumorigenesis has been elu...	An organ that is inflamed has an increased risk of developing cancer . Inflammation can be elicited in various ways; and intestinal inflammation and colon cancer development are often associated with a protein complex – called mTORC1 – being overactive in the tissue . This protein complex has been studied in other cont...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "cancer", "biology" ]	2016	Tumor suppressive role of sestrin2 during colitis and colon carcinogenesis
C4 photosynthesis represents a most remarkable case of convergent evolution of a complex trait , which includes the reprogramming of the expression patterns of thousands of genes . Anatomical , physiological , and phylogenetic and analyses as well as computational modeling indicate that the establishment of a photoresp...	Environmental pressures sometimes cause different organisms to independently evolve the same traits . A dramatic example of this phenomenon , which is called convergent evolution , can be seen in the modes used by plants to convert carbon dioxide from the air into starch during photosynthesis . Early plants existed in ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology", "evolutionary", "biology" ]	2014	The role of photorespiration during the evolution of C4 photosynthesis in the genus Flaveria
Protein output from synonymous codons is thought to be equivalent if appropriate tRNAs are sufficiently abundant . Here we show that mRNAs encoding iterated lysine codons , AAA or AAG , differentially impact protein synthesis: insertion of iterated AAA codons into an ORF diminishes protein expression more than insertio...	Genes provide the instructions to assemble proteins from smaller molecules called amino acids . When a gene is ‘switched on’ , the DNA that makes up the gene is copied into messenger ribonucleic acid ( or mRNA ) molecules , composed of building blocks called nucleotides . There are four types of nucleotides in mRNA mol...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology" ]	2015	Ribosomes slide on lysine-encoding homopolymeric A stretches
Linear Ubiquitin chain Assembly Complex ( LUBAC ) is an E3 ligase complex that generates linear ubiquitin chains and is important for tumour necrosis factor ( TNF ) signaling activation . Mice lacking Sharpin , a critical subunit of LUBAC , spontaneously develop inflammatory lesions in the skin and other organs . Here ...	In response to an injury or an infection , areas of the body can become inflamed as the immune system attempts to repair the damage and/or destroy any microbes or toxins that have entered the body . At the level of individual cells inflammation can involve cells being programmed to die in one of two ways: apoptosis and...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "immunology", "and", "inflammation" ]	2014	Sharpin prevents skin inflammation by inhibiting TNFR1-induced keratinocyte apoptosis
Synaptic membrane-remodeling events such as endocytosis require force-generating actin assembly . The endocytic machinery that regulates these actin and membrane dynamics localizes at high concentrations to large areas of the presynaptic membrane , but actin assembly and productive endocytosis are far more restricted i...	Neurons constantly talk to each other by sending chemical signals across the tiny gap , or ‘synapse’ , that separates two cells . While inside the emitting cell , these molecules are safely packaged into small , membrane-bound vessels . Upon the right signal , the vesicles fuse with the external membrane of the neuron ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "neuroscience" ]	2021	An autoinhibitory clamp of actin assembly constrains and directs synaptic endocytosis
T cell self-tolerance is thought to involve peripheral tolerance and negative selection , involving apoptosis of autoreactive thymocytes . However , evidence supporting an essential role for negative selection is limited . Loss of Bim , a Bcl-2 BH3-only protein essential for thymocyte apoptosis , rarely results in auto...	Our immune system protects us from disease by recognizing and mounting a defence against harmful pathogens that enter our bodies . T cells , a type of white blood cell , play a key role in this process . Each T cell has a unique protein called a T cell receptor on its surface that is able to recognize particular pieces...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "immunology", "and", "inflammation" ]	2014	T cell-specific inhibition of multiple apoptotic pathways blocks negative selection and causes autoimmunity
One manifestation of individualization is a progressively differential response of individuals to the non-shared components of the same environment . Individualization has practical implications in the clinical setting , where subtle differences between patients are often decisive for the success of an intervention , y...	Even identical twins who share genetics and the same environment develop individual traits . But how individuality emerges and the biological mechanisms behind it are not clear . It is hard to study people for a long time , so scientists turn to animal studies to answer such questions . One way to study the respective ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2018	Selective increases in inter-individual variability in response to environmental enrichment in female mice
With experience we become accustomed to the types of environments that we normally encounter as we navigate in the world . But how does this fundamental knowledge develop in the first place and what brain regions are involved ? To examine de novo environmental learning , we created an ‘alien’ virtual reality world popu...	Throughout our lives , we encounter novel environments that we must learn to find our way around , from a new office to a new city . Studies of brain activity in humans and rodents have revealed that many brain regions are involved in navigation , most notably the hippocampus . However , these experiments have typicall...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	A central role for the retrosplenial cortex in de novo environmental learning
Neurotrophin-3 ( Ntf3 ) and brain derived neurotrophic factor ( Bdnf ) are critical for sensory neuron survival and establishment of neuronal projections to sensory epithelia in the embryonic inner ear , but their postnatal functions remain poorly understood . Using cell-specific inducible gene recombination in mice we...	Noise-induced hearing loss is common , and can result from prolonged exposure to moderate levels of noise that are not perceived as painful or even unpleasant . Some hearing loss can be attributed to the death of hair cells in a part of the inner ear called the cochlea . When sound waves hit the cochlea , they cause th...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2014	Neurotrophin-3 regulates ribbon synapse density in the cochlea and induces synapse regeneration after acoustic trauma
The Hedgehog ( Hh ) signal is transduced across the membrane by the heptahelical protein Smoothened ( Smo ) , a developmental regulator , oncoprotein and drug target in oncology . We present the 2 . 3 Å crystal structure of the extracellular cysteine rich domain ( CRD ) of vertebrate Smo and show that it binds to oxyst...	Just over 30 years ago , researchers identified a new signaling molecule with an important role in the development of fruit flies . Embryos lacking this molecule were thought to resemble a hedgehog , eventually leading to this cell–cell communication system being designated the “Hedgehog” pathway . This pathway has sub...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2013	Structure and function of the Smoothened extracellular domain in vertebrate Hedgehog signaling
Primaquine is the only drug available to prevent relapse in vivax malaria . The main adverse effect of primaquine is erythrocyte age and dose-dependent acute haemolytic anaemia in individuals with glucose-6-phosphate dehydrogenase deficiency ( G6PDd ) . As testing for G6PDd is often unavailable , this limits the use of...	Malaria is the most important parasitic disease that affects humans . Over half of the malaria cases in Asia and South America are caused by a species of malaria parasite called Plasmodium vivax ( known as vivax malaria ) . This form of malaria results in repeated illness because dormant parasites in the liver wake at ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "epidemiology", "and", "global", "health", "computational", "and", "systems", "biology" ]	2017	Modelling primaquine-induced haemolysis in G6PD deficiency
Transcription is a highly stochastic process . To infer transcription kinetics for a gene-of-interest , researchers commonly compare the distribution of mRNA copy-number to the prediction of a theoretical model . However , the reliability of this procedure is limited because the measured mRNA numbers represent integrat...	Scientific investigation requires researchers to use experimental observations to understand the biological process that resulted in these observations . One example is a cellular process called transcription , where the DNA of a gene is copied many times to make molecules of messenger RNA ( mRNA ) , which are later us...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "short", "report", "computational", "and", "systems", "biology" ]	2016	Single-cell analysis of transcription kinetics across the cell cycle
Lethal mutagenesis has emerged as a novel potential therapeutic approach to treat viral infections . Several studies have demonstrated that increases in the high mutation rates inherent to RNA viruses lead to viral extinction in cell culture , but evidence during infections in vivo is limited . In this study , we show ...	Viruses can infect , take control of and replicate themselves inside the living cells of other organisms . Some viral diseases can be treated with antiviral drugs , which stop viral infections either by making it more difficult for viruses to enter cells or by preventing the virus replicating once inside . As antiviral...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "microbiology", "and", "infectious", "disease" ]	2014	Favipiravir elicits antiviral mutagenesis during virus replication in vivo
Nonsense-mediated mRNA decay ( NMD ) is a translation-dependent RNA quality-control pathway targeting transcripts such as messenger RNAs harboring premature stop-codons or short upstream open reading frame ( uORFs ) . Our transcription start sites ( TSSs ) analysis of Saccharomyces cerevisiae cells deficient for RNA de...	Eukaryotes such as animals , plants and fungi store their DNA within the nucleus of each of their cells . Genes within this DNA contain the instructions needed to make molecules of RNA; some of which can leave the nucleus and be decoded to build proteins . However , not all of the DNA that is copied into RNA actually c...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "genetics", "and", "genomics" ]	2015	Quality control of transcription start site selection by nonsense-mediated-mRNA decay
The spindle position checkpoint ( SPOC ) is a spindle pole body ( SPB , equivalent of mammalian centrosome ) associated surveillance mechanism that halts mitotic exit upon spindle mis-orientation . Here , we monitored the interaction between SPB proteins and the SPOC component Bfa1 by FRET microscopy . We show that Bfa...	A cell must duplicate its genetic material and then separate the two copies before it divides . This process is carefully controlled so that each new cell receives an identical set of chromosomes after cell division . In budding yeast , new daughter cells grow as a bud on the side a larger mother cell and are eventuall...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2016	A FRET-based study reveals site-specific regulation of spindle position checkpoint proteins at yeast centrosomes
Hydroxychloroquine and chloroquine are used extensively in malaria and rheumatological conditions , and now in COVID-19 prevention and treatment . Although generally safe they are potentially lethal in overdose . In-vitro data suggest that high concentrations and thus high doses are needed for COVID-19 infections , but...	Hydroxychloroquine and chloroquine are closely-related drugs used for the treatment of malaria and rheumatological conditions , such as lupus . Laboratory tests have indicated that these drugs could also be used against the virus that causes COVID-19 . Given the urgent need , these drugs have been fast-tracked into lar...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "medicine" ]	2020	Concentration-dependent mortality of chloroquine in overdose
The Ciona notochord displays planar cell polarity ( PCP ) , with anterior localization of Prickle ( Pk ) and Strabismus ( Stbm ) . We report that a myosin is polarized anteriorly in these cells and strongly colocalizes with Stbm . Disruption of the actin/myosin machinery with cytochalasin or blebbistatin disrupts polar...	Animal cells that form flat layers of a tissue , such as the skin or the lining of internal cavities , are often orientated in the same direction . The same is true for structures such as hairs or feathers , which are attached to the skin . This phenomenon is known as ‘planar cell polarity’ ( or ‘PCP’ for short ) . Man...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2015	Reciprocal and dynamic polarization of planar cell polarity core components and myosin
The ventricular-subventricular zone ( V-SVZ ) , on the walls of the lateral ventricles , harbors the largest neurogenic niche in the adult mouse brain . Previous work has shown that neural stem/progenitor cells ( NSPCs ) in different locations within the V-SVZ produce different subtypes of new neurons for the olfactory...	Nerve cells , or neurons , are the central building blocks of brain circuits . Their damage , death or loss of function leads to cognitive decline . Neural stem/progenitor cells ( NSPCs ) first appear during embryo development , generating most of the neurons found in the nervous system . However , the adult brain reta...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "stem", "cells", "and", "regenerative", "medicine", "neuroscience" ]	2021	Single-cell analysis of the ventricular-subventricular zone reveals signatures of dorsal and ventral adult neurogenesis
Cancer develops and progresses often by inactivating p53 . Here , we unveil nerve growth factor receptor ( NGFR , p75NTR or CD271 ) as a novel p53 inactivator . p53 activates NGFR transcription , whereas NGFR inactivates p53 by promoting its MDM2-mediated ubiquitin-dependent proteolysis and by directly binding to its c...	Cancer often develops as a result of alterations to “tumor suppressor” genes within cells . This results in the cells growing and dividing too much , which causes a tumor to form . One of the most important tumor suppressor genes produces a protein called p53 , which is lost or mutated in roughly half of all human canc...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "cancer", "biology" ]	2016	Nerve growth factor receptor negates the tumor suppressor p53 as a feedback regulator
The HIV-1 protein Rev controls a critical step in viral replication by mediating the nuclear export of unspliced and singly-spliced viral mRNAs . Multiple Rev subunits assemble on the Rev Response Element ( RRE ) , a structured region present in these RNAs , and direct their export through the Crm1 pathway . Rev-RRE as...	To be able to multiply , viruses have to first infect a host cell and then hijack the host's molecular machinery to make viral proteins . One stage of this process takes place in the nucleus of the host cell and involves the viral DNA being transcribed to make RNA molecules . These RNA molecules must then be exported f...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "microbiology", "and", "infectious", "disease" ]	2014	RNA-directed remodeling of the HIV-1 protein Rev orchestrates assembly of the Rev–Rev response element complex
Replicate populations of natural and experimental organisms often show evidence of parallel genetic evolution , but the causes are unclear . The wrinkly spreader morph of Pseudomonas fluorescens arises repeatedly during experimental evolution . The mutational causes reside exclusively within three pathways . By elimina...	Different living things often develop similar strategies to adapt to the environments in which they live . Sometimes two species that share a common ancestor independently evolve the same trait by changing the exact same genes . This is called ‘parallel evolution’ , and it has led some scientists to ask: are there cert...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology" ]	2015	Experimental evolution reveals hidden diversity in evolutionary pathways
The proteostasis network has evolved to support protein folding under normal conditions and to expand this capacity in response to proteotoxic stresses . Nevertheless , many pathogenic states are associated with protein misfolding , revealing in vivo limitations on quality control mechanisms . One contributor to these ...	Proteins must fold into specific shapes to work inside cells , and the misfolding of proteins is associated with a growing number of diseases . For example , prions are misfolded proteins that form insoluble aggregates called amyloids . These aggregates are not easily destroyed and can cause other nearby proteins to mi...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2014	Spatial quality control bypasses cell-based limitations on proteostasis to promote prion curing
Neurons rely on translation of synaptic mRNAs in order to generate activity-dependent changes in plasticity . Here , we develop a strategy combining compartment-specific crosslinking immunoprecipitation ( CLIP ) and translating ribosome affinity purification ( TRAP ) in conditionally tagged mice to precisely define the...	The brain has over 100 billion neurons that together form vast networks to relay electrical signals . A neuron receives electrical signals from other neurons via branch-like structures known as dendrites . The signals then travel into the cell body of the neuron . If their sum reaches a threshold , they fire a new sign...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience", "genetics", "and", "genomics" ]	2021	FMRP regulates mRNAs encoding distinct functions in the cell body and dendrites of CA1 pyramidal neurons
Due to the uniform cyto-architecture of the cerebellar cortex , its overall physiological characteristics have traditionally been considered to be homogeneous . In this study , we show in awake mice at rest that spiking activity of Purkinje cells , the sole output cells of the cerebellar cortex , differs between cerebe...	The cerebellum , located at the back of the brain underneath the cerebral hemispheres , is best known for its role in the control of movement . Despite its small size , the cerebellum contains more than half of the brain's neurons . These are organized in a repeating pattern in which cells called Purkinje cells receive...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2014	Cerebellar modules operate at different frequencies
A large group of bacterial virulence autotransporters including AIDA-I from diffusely adhering E . coli ( DAEC ) and TibA from enterotoxigenic E . coli ( ETEC ) require hyperglycosylation for functioning . Here we demonstrate that TibC from ETEC harbors a heptosyltransferase activity on TibA and AIDA-I , defining a lar...	Bacteria release proteins known as virulence factors to help them infect host cells . Many bacteria are surrounded by two membranes , so virulence factors must be able to pass through both of these membranes . Autotransporters are a group of virulence factors that pass through the inner membrane and anchor themselves i...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics", "microbiology", "and", "infectious", "disease" ]	2014	A structural mechanism for bacterial autotransporter glycosylation by a dodecameric heptosyltransferase family
The synaptonemal complex ( SC ) is an ultrastructurally conserved proteinaceous structure that holds homologous chromosomes together and is required for the stabilization of pairing interactions and the completion of crossover ( CO ) formation between homologs during meiosis I . Here , we identify a novel role for a ce...	The majority of DNA in animal cells is stored in structures called chromosomes . Most cells contain two sets of chromosomes , one inherited from the mother and one from the father . Sperm and egg cells , however , contain only a single set of chromosomes . A specialized type of cell division called meiosis generates th...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "cell", "biology" ]	2017	Polo-like kinase-dependent phosphorylation of the synaptonemal complex protein SYP-4 regulates double-strand break formation through a negative feedback loop.
The TAM receptor tyrosine kinases Tyro3 , Axl , and Mer regulate key features of cellular physiology , yet the differential activities of the TAM ligands Gas6 and Protein S are poorly understood . We have used biochemical and genetic analyses to delineate the rules for TAM receptor–ligand engagement and find that the T...	Cells send out and receive signals to communicate with other cells . Detecting these signals is largely carried out by proteins called receptors that span the cell surface membrane . These proteins typically have extracellular domains outside of the cell that can bind to specific signaling molecules and an intracellula...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "immunology", "and", "inflammation" ]	2014	Differential TAM receptor–ligand–phospholipid interactions delimit differential TAM bioactivities
The loss of previously adaptive traits is typically linked to relaxation in selection , yet the molecular steps leading to such repeated losses are rarely known . Molecular studies of loss have tended to focus on gene sequences alone , but overlooking other aspects of protein expression might underestimate phenotypic d...	Bats are famous for using their hearing to explore their environments , yet fewer people are aware that these flying mammals have both good night and daylight vision . Some bats can even see in color thanks to two light-sensitive proteins at the back of their eyes: S-opsin which detects blue and ultraviolet light and L...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology" ]	2018	Multifactorial processes underlie parallel opsin loss in neotropical bats
Cells can , in principle , control their size by growing to a specified size before commencing cell division . How any cell actually senses its own size remains poorly understood . The fission yeast Schizosaccharomyces pombe are rod-shaped cells that grow to ∼14 µm in length before entering mitosis . In this study , we...	Although different types of cells come in a variety of shapes and sizes , most cells are able to maintain a fairly consistent size and shape as they grow and divide . For example , the rod-shaped cells of the fission yeast S . pombe grow to be 14 microns long before dividing in the middle to form two new cells . This p...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2014	Cortical regulation of cell size by a sizer cdr2p
Plant meristems carry pools of continuously active stem cells , whose activity is controlled by developmental and environmental signals . After stem cell division , daughter cells that exit the stem cell domain acquire transit amplifying cell identity before they are incorporated into organs and differentiate . In this...	Unlike animals , plants continuously generate new organs that make up their body . At the core of this amazing capacity lie tissues called meristems , which are found at the growing tips of all plants . Meristems contain dividing stem cells . The daughters of these stem cells pass through nearby regions called transiti...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology", "developmental", "biology" ]	2017	Control of plant cell fate transitions by transcriptional and hormonal signals
Spontaneous slow oscillation-associated slow wave activity represents an internally generated state which is characterized by alternations of network quiescence and stereotypical episodes of neuronal activity - slow wave events . However , it remains unclear which macroscopic signal is related to these active periods o...	When a person is in a deep non-dreaming sleep , neurons in their brain alternate slowly between periods of silence and periods of activity . This gives rise to low-frequency brain rhythms called slow waves , which are thought to help stabilize memories . Slow wave activity can be detected on multiple scales , from the ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2017	Cortex-wide BOLD fMRI activity reflects locally-recorded slow oscillation-associated calcium waves
Laetoli is a well-known palaeontological locality in northern Tanzania whose outstanding record includes the earliest hominin footprints in the world ( 3 . 66 million years old ) , discovered in 1978 at Site G and attributed to Australopithecus afarensis . Here , we report hominin tracks unearthed in the new Site S at ...	Fossil footprints are extremely useful tools in the palaeontological record . Their physical features can help to identify their makers , but can also be used to infer biological information . How did the track-maker move ? How large was it ? How fast was it going ? Footprints of hominins ( namely the group to which hu...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology" ]	2016	New footprints from Laetoli (Tanzania) provide evidence for marked body size variation in early hominins
Arbuscular mycorrhiza ( AM ) symbioses contribute to global carbon cycles as plant hosts divert up to 20% of photosynthate to the obligate biotrophic fungi . Previous studies suggested carbohydrates as the only form of carbon transferred to the fungi . However , de novo fatty acid ( FA ) synthesis has not been observed...	Most land plants are able to form partnerships with certain fungi – known as arbuscular mycorrhiza fungi – that live in the soil . These fungi supply the plant with mineral nutrients , especially phosphate and nitrogen , in return for receiving carbon-based food from the plant . To exchange nutrients , the fungi grow i...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology" ]	2017	Lipid transfer from plants to arbuscular mycorrhiza fungi
Morphogenesis and physiology of tissues and organs requires planar cell polarity ( PCP ) systems that orient and coordinate cells and their behaviors , but the relationship between PCP systems has been controversial . We have characterized how the Frizzled and Dachsous-Fat PCP systems are connected through the Spiny-le...	Animals have many asymmetric organs . Wings , for example , are aerodynamically shaped and have a clear front , back , top and bottom , and even additions to these organs , such as feathers on the wing , often need to be oriented in a specific manner . This kind of orientation arises when cells divide and grow asymmetr...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "cell", "biology" ]	2015	Coordination of planar cell polarity pathways through Spiny-legs
In response to proteasome dysfunction , mammalian cells upregulate proteasome gene expression by activating Nrf1 . Nrf1 is an endoplasmic reticulum-resident transcription factor that is continually retrotranslocated and degraded by the proteasome . Upon proteasome inhibition , Nrf1 escapes degradation and is cleaved to...	The proteasome is a machine that destroys unnecessary or damaged proteins inside cells . This role of the proteasome is essential for cell survival , and so when the proteasome is inhibited , cells produce new proteasomes to compensate . Upon proteasome inhibition , a protein called Nrf1 is activated and executes this ...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "short", "report" ]	2016	The aspartyl protease DDI2 activates Nrf1 to compensate for proteasome dysfunction
Intelligence and education are predictive of better physical and mental health , socioeconomic position ( SEP ) , and longevity . However , these associations are insufficient to prove that intelligence and/or education cause these outcomes . Intelligence and education are phenotypically and genetically correlated , wh...	Highly educated people tend to be healthier and have higher incomes than those with less schooling . This might be because education helps people adopt a healthier lifestyle , as well as qualifying them for better-paid jobs . But , on average , highly educated people also score more highly on cognitive tests . This may...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "epidemiology", "and", "global", "health" ]	2019	Multivariable two-sample Mendelian randomization estimates of the effects of intelligence and education on health
Emerging evidence suggests that dopamine may modulate learning and memory with important implications for understanding the neurobiology of memory and future therapeutic targeting . An influential hypothesis posits that dopamine biases reinforcement learning . More recent data also suggest an influence during both cons...	Brain cells release a naturally occurring chemical called dopamine . The release of this chemical affects how people respond to their ever-changing environment , including how they learn from rewards and punishments . Parkinson’s disease is a condition where the brain cells that make dopamine start to die , and so the ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2017	Effects of dopamine on reinforcement learning and consolidation in Parkinson’s disease
Axis elongation is a conserved process in which the head-to-tail or anterior-posterior ( AP ) axis of an embryo extends . In Drosophila , cellular rearrangements drive axis elongation . Cells exchange neighbours by converging into transient multicellular vertices which resolve through the assembly of new cell interface...	Tissues and organs form certain shapes that allow them to perform particular roles in the body . For example , the lungs form sacs that accommodate large volumes of air , while the skin forms a sheet to cover and protect our internal organs . One way to shape a tissue is for cells to swap places with their neighbours ....	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "cell", "biology" ]	2016	Local mechanical forces promote polarized junctional assembly and axis elongation in Drosophila
To understand how long-range patterning gradients are interpreted at the cellular level , we investigate how a gradient of expression of the Four-jointed kinase specifies planar polarised distributions of the cadherins Fat and Dachsous in the Drosophila wing . We use computational modelling to test different scenarios ...	Epithelial cells form sheets that line the body surfaces and internal cavities of animals—such as the skin and the lining of the gut . Certain structures on the surface of epithelial cell sheets—for example scales , hair , and feathers—are often all orientated in a particular direction . Epithelial cells with structure...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2015	Cellular interpretation of the long-range gradient of Four-jointed activity in the Drosophila wing
The CRISPR system for prokaryotic adaptive immunity provides RNA-mediated protection from viruses and mobile genetic elements . When viral RNA transcripts are detected , type III systems adopt an activated state that licenses DNA interference and synthesis of cyclic oligoadenylate ( cOA ) . cOA activates nucleases and ...	The gene editing tool often known simply as CRISPR has become well known in recent years . Its potential applications are wide ranging , including uses in research , healthcare and agriculture . Yet , the CRISPR system originated in microbes where it helps to protect them from viral infections . Viruses infect by inser...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology" ]	2018	Control of cyclic oligoadenylate synthesis in a type III CRISPR system
Platelets are anucleate cells in blood whose principal function is to stop bleeding by forming aggregates for hemostatic reactions . In addition to their participation in physiological hemostasis , platelet aggregates are also involved in pathological thrombosis and play an important role in inflammation , atherosclero...	Platelets are small cells in the blood that primarily help stop bleeding after an injury by sticking together with other blood cells to form a clot that seals the broken blood vessel . Blood clots , however , can sometimes cause harm . For example , if a clot blocks the blood flow to the heart or the brain , it can res...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "short", "report", "cell", "biology" ]	2020	Intelligent classification of platelet aggregates by agonist type
Environmental stress during early development can impact adult phenotypes via programmed changes in gene expression . C . elegans larvae respond to environmental stress by entering the stress-resistant dauer diapause pathway and resume development once conditions improve ( postdauers ) . Here we show that the osm-9 TRP...	Increasing evidence suggests that experiencing stressful environments early on in life can have profound effects on the health and behavior of adults . For example , stressful conditions in the womb have been linked to adult depression and metabolic disorders . These effects are thought to be the result of changes in t...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "neuroscience" ]	2016	Developmental programming modulates olfactory behavior in C. elegans via endogenous RNAi pathways
Neural progenitors undergo temporal patterning to generate diverse neurons in a chronological order . This process is well-studied in the developing Drosophila brain and conserved in mammals . During larval stages , intermediate neural progenitors ( INPs ) serially express Dichaete ( D ) , grainyhead ( Grh ) and eyeles...	The brain consists of billions of neurons that come in a range of shapes and sizes , with different types of neurons specialized to perform different tasks . Despite their diversity , all of these neurons originate from a single population known as neural stem cells . As the brain develops , each neural stem cell divid...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "neuroscience" ]	2019	The transcription factor odd-paired regulates temporal identity in transit-amplifying neural progenitors via an incoherent feed-forward loop
The microtubule cytoskeleton is critical for muscle cell differentiation and undergoes reorganisation into an array of paraxial microtubules , which serves as template for contractile sarcomere formation . In this study , we identify a previously uncharacterised isoform of microtubule-associated protein MAP4 , oMAP4 , ...	Skeletal muscles—which enable animals to move—are made up of large elongated muscle cells that span the entire length of the muscle . These cells contain stacks of structures called sarcomeres that enable the cells to contract and generate the force required for movement . Cells called myoblasts elongate and fuse toget...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2015	A novel isoform of MAP4 organises the paraxial microtubule array required for muscle cell differentiation
Eukaryotic cells rapidly reduce protein synthesis in response to various stress conditions . This can be achieved by the phosphorylation-mediated inactivation of a key translation initiation factor , eukaryotic initiation factor 2 ( eIF2 ) . However , the persistent translation of certain mRNAs is required for deployme...	Proteins carry out essential tasks for living cells and genes contain the instructions to make proteins within their DNA . These instructions are copied to make a molecule of mRNA , and a molecular machine known as a ribosome then reads and translates the mRNA to build the protein . The first step in the translation pr...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology" ]	2015	Translation of 5′ leaders is pervasive in genes resistant to eIF2 repression
Developed areas are thought to have low species diversity , low animal abundance , few native predators , and thus low resilience and ecological function . Working with citizen scientist volunteers to survey mammals at 1427 sites across two development gradients ( wild-rural-exurban-suburban-urban ) and four plot types...	Humans transform natural ecosystems worldwide into towns and cities , replacing natural habitat with human-built surfaces . This loss of habitat and increase in human activity make suburban areas difficult for some species to survive in , raising concerns that developed areas become ecologically unbalanced as they lose...	[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "and", "discussion" ]	[ "ecology", "short", "report" ]	2018	Mammal communities are larger and more diverse in moderately developed areas
The only true living endothermic vertebrates are birds and mammals , which produce and regulate their internal temperature quite independently from their surroundings . For mammal ancestors , anatomical clues suggest that endothermy originated during the Permian or Triassic . Here we investigate the origin of mammalian...	School textbooks often refer to “cold-blooded” and “warm-blooded” animals , but these terms are misleading . Rather than being cold , animals like reptiles have body temperatures that are mostly determined by their external environment and can actually achieve high body temperatures , for example , by basking in the su...	[ "Abstract", "Introduction", "Results", "Discussion", "Material", "and", "methods" ]	[ "ecology" ]	2017	Oxygen isotopes suggest elevated thermometabolism within multiple Permo-Triassic therapsid clades
Management of salivary gland hypofunction caused by irradiation ( IR ) therapy for head and neck cancer remains lack of effective treatments . Salivary glands , especially the parotid gland , actively uptake dietary nitrate and secrete it into saliva . Here , we investigated the effect of dietary nitrate on the prevent...	Head and neck cancers are commonly treated using radiotherapy , where a beam of high-energy radiation is targeted at the tumour . This often severely damages the surrounding salivary glands , leading to chronic dry mouth and impairing a patient’s sense of taste , nutrient intake , speech and immune system . Despite thi...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2021	Dietary nitrate supplementation prevents radiotherapy-induced xerostomia
Both proteins and RNAs can misfold into non-functional conformations . Protein chaperones promote native folding of nascent polypeptides and refolding of misfolded species , thereby buffering mutations that compromise protein structure and function . Here , we show that RNA chaperones can also act as mutation buffers t...	Stretches of DNA known as genes contain the instructions to make the proteins and RNA molecules that are essential for life . The DNA sequence of the gene is first copied to make a strand of RNA , which may subsequently be ‘translated’ to make a protein . To carry out their tasks , proteins and many RNA molecules must ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology" ]	2015	RNA chaperones buffer deleterious mutations in E. coli
Antibody class switching is a feature of the adaptive immune system which enables diversification of the effector properties of antibodies . Even though class switching is essential for mounting a protective response to pathogens , the in vivo patterns and lineage characteristics of antibody class switching have remain...	The human immune system comprises cells and processes that protect the body against infection and disease . B cells are immune cells that once activated produce antibodies , or proteins that help identify and neutralize infectious microbes and diseased host cells . Antibodies fall into one of ten different classes , an...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology", "immunology", "and", "inflammation" ]	2016	Lineage tracing of human B cells reveals the in vivo landscape of human antibody class switching
How genetic changes are linked to morphological novelties and developmental constraints remains elusive . Here , we investigate genetic apparatuses that distinguish fish fins from tetrapod limbs by analyzing transcriptomes and open-chromatin regions ( OCRs ) . Specifically , we compared mouse forelimb buds with the pec...	Animals come in all shapes and sizes . This diversity arose through genetic mutations during evolution , but it is unclear exactly how these variations led to the formation of new shapes . There is increasing evidence to suggest that not all shapes are possible and that variability between animals is limited by a pheno...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "evolutionary", "biology" ]	2021	Developmental hourglass and heterochronic shifts in fin and limb development
During awake consciousness , the brain intrinsically maintains a dynamical state in which it can coordinate complex responses to sensory input . How the brain reaches this state spontaneously is not known . General anesthesia provides a unique opportunity to examine how the human brain recovers its functional capabilit...	General anesthesia is essential to modern medicine . It allows physicians to temporarily keep people in an unconscious state . When infusions of the anesthetic drug stop , patients gradually recover consciousness and awaken , a process called emergence . Previous studies using recordings of electrical activity in the b...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2018	A transient cortical state with sleep-like sensory responses precedes emergence from general anesthesia in humans
Most motile bacteria sense and respond to their environment through a transmembrane chemoreceptor array whose structure and function have been well-studied , but many species also contain an additional cluster of chemoreceptors in their cytoplasm . Although the cytoplasmic cluster is essential for normal chemotaxis in ...	Many bacteria swim through water by rotating tiny hair-like structures called flagella . In E . coli , if all the flagella on the surface of a bacterium rotate in a counterclockwise fashion , then it will swim in a particular direction , but if the flagella all rotate in an clockwise fashion , then the bacterium will s...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics", "microbiology", "and", "infectious", "disease" ]	2014	Structure of bacterial cytoplasmic chemoreceptor arrays and implications for chemotactic signaling
Plexins are cell surface receptors that bind semaphorins and transduce signals for regulating neuronal axon guidance and other processes . Plexin signaling depends on their cytoplasmic GTPase activating protein ( GAP ) domain , which specifically inactivates the Ras homolog Rap through an ill-defined non-canonical cata...	A key question in neurobiology is how the brain becomes wired up . How do axons—the ‘wires’ along which neural signals flow—know in which direction to grow to reach their intended targets ? A family of signalling proteins called semaphorins contribute to this process by acting as stop signals for axons that are heading...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2013	Structural basis for activation and non-canonical catalysis of the Rap GTPase activating protein domain of plexin
Internal ribosome entry sites ( IRESs ) are powerful model systems to understand how the translation machinery can be manipulated by structured RNAs and for exploring inherent features of ribosome function . The intergenic region ( IGR ) IRESs from the Dicistroviridae family of viruses are structured RNAs that bind dir...	Many viruses store their genetic information in the form of strands of ribonucleic acid ( RNA ) , which contain building blocks called nucleotides . Once inside an infected cell , the virus hijacks the cellular structures that build proteins ( called ribosomes ) , which forces the cell to start making viral proteins . ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology" ]	2015	A dynamic RNA loop in an IRES affects multiple steps of elongation factor-mediated translation initiation
The standard reference Caenorhabditis elegans strain , N2 , has evolved marked behavioral changes in social feeding behavior since its isolation from the wild . We show that the causal , laboratory-derived mutations in two genes , npr-1 and glb-5 , confer large fitness advantages in standard laboratory conditions . Usi...	Why do humans walk on two feet ? And what makes us smarter than our ape ancestors ? The answers to these questions , and countless others about the particular traits of any number of species , is often said to be natural selection – a process where genes that ensure the survival of a species are favored of others . But...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology" ]	2018	Changes to social feeding behaviors are not sufficient for fitness gains of the Caenorhabditis elegans N2 reference strain
Renal medullary carcinoma ( RMC ) is a rare and deadly kidney cancer in patients of African descent with sickle cell trait . We have developed faithful patient-derived RMC models and using whole-genome sequencing , we identified loss-of-function intronic fusion events in one SMARCB1 allele with concurrent loss of the o...	Renal medullary carcinoma ( RMC for short ) is a rare type of kidney cancer that affects teenagers and young adults . These patients are usually of African descent and carry one of the two genetic changes that cause sickle cell anemia . RMC is an aggressive disease without effective treatments and patients survive , on...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cancer", "biology" ]	2019	Renal medullary carcinomas depend upon SMARCB1 loss and are sensitive to proteasome inhibition
Many organisms in nature have evolved mechanisms to tolerate severe hypoxia or ischemia , including the hibernation-capable Arctic ground squirrel ( AGS ) . Although hypoxic or ischemia tolerance in AGS involves physiological adaptations , little is known about the critical cellular mechanisms underlying intrinsic AGS ...	When animals hibernate , they lower their body temperature and metabolism to conserve the energy they need to withstand cold harsh winters . One such animal is the Arctic ground squirrel , an extreme hibernator that can drop its body temperatures to below 0°C . This hibernation ability means the cells of Arctic ground ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "genetics", "and", "genomics" ]	2020	Cytoprotection by a naturally occurring variant of ATP5G1 in Arctic ground squirrel neural progenitor cells
The Dna2 nuclease-helicase maintains genomic integrity by processing DNA double-strand breaks , Okazaki fragments and stalled replication forks . Dna2 requires ssDNA ends , and is dependent on the ssDNA-binding protein Rpa , which controls cleavage polarity . Here we present the 2 . 3 Å structure of intact mouse Dna2 b...	DNA carries the genetic information that is essential for organisms to survive and reproduce . It is made of two strands that twist together to form a double helix . However , these strands can be damaged when the DNA is copied before a cell divides , or by exposure to radiation or hazardous chemicals . To prevent this...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Conclusions", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "structural", "biology", "and", "molecular", "biophysics" ]	2015	Dna2 nuclease-helicase structure, mechanism and regulation by Rpa
Here , we present a method for in-depth human plasma proteome analysis based on high-resolution isoelectric focusing HiRIEF LC-MS/MS , demonstrating high proteome coverage , reproducibility and the potential for liquid biopsy protein profiling . By integrating genomic sequence information to the MS-based plasma proteom...	Blood cells travel through the blood vessels in a soupy mixture of proteins called plasma . Most of these proteins are plasma-specific , yet small amounts of proteins can leak into the plasma from other body parts and may provide hints about what is going on elsewhere in the body . This could allow doctors to use plasm...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology", "tools", "and", "resources" ]	2019	In-depth human plasma proteome analysis captures tissue proteins and transfer of protein variants across the placenta
Despite the crucial role of bacterial capsules in pathogenesis , it is still unknown if systemic cues such as the cell cycle can control capsule biogenesis . In this study , we show that the capsule of the synchronizable model bacterium Caulobacter crescentus is cell cycle regulated and we unearth a bacterial transglut...	Many bacteria have a tough outer coating known as capsule that protects them from untoward environmental conditions . This capsule also prevents viruses called bacteriophages from invading the bacterial cells , and it shields those bacteria that can infect humans from attack by our immune system . External conditions—s...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "microbiology", "and", "infectious", "disease" ]	2014	Cell cycle constraints on capsulation and bacteriophage susceptibility
How cells sense their mechanical environment and transduce forces into biochemical signals is a crucial yet unresolved question in mechanobiology . Platelets use receptor glycoprotein Ib ( GPIb ) , specifically its α subunit ( GPIbα ) , to signal as they tether and translocate on von Willebrand factor ( VWF ) of injure...	Platelets – the blood clotting cells – have the ability to detect , interpret and respond to mechanical forces , such as those generated by the flow of blood . The magnitude and duration of the forces detected by the platelets influences whether they form a blood clot . Understanding how the platelets respond to mechan...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics" ]	2016	Cooperative unfolding of distinctive mechanoreceptor domains transduces force into signals
Transmission reduction is a key component of global efforts to control and eliminate malaria; yet , it is unclear how the density of transmission stages ( gametocytes ) influences infection ( proportion of mosquitoes infected ) . Human to mosquito transmission was assessed using 171 direct mosquito feeding assays condu...	Malaria is one of the world’s most deadly infectious diseases . The most severe form is caused by the parasite Plasmodium falciparum , which can reside within red blood cells and thus evade the human immune system . Plasmodium is transmitted between humans by mosquitoes . When a mosquito takes a blood meal from an indi...	[ "Abstract", "Introduction", "Results", "Discussion", "Material", "and", "methods" ]	[ "epidemiology", "and", "global", "health" ]	2013	Predicting mosquito infection from Plasmodium falciparum gametocyte density and estimating the reservoir of infection
Skilled performance is characterized by precise and flexible control of movement sequences in space and time . Recent theories suggest that integrated spatio-temporal trajectories are generated by intrinsic dynamics of motor and premotor networks . This contrasts with behavioural advantages that emerge when a trained s...	Once a pianist has learned to play a song , he or she can nearly effortlessly reproduce the sequence of finger movements needed to play the song with a particular rhythm . A skilled pianist can also improvise , pairing the same keystrokes with a different rhythm or playing the same rhythm with a slightly different sequ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2014	Human premotor areas parse sequences into their spatial and temporal features
The outer membrane ( OM ) of Gram-negative bacteria serves as a selective permeability barrier that allows entry of essential nutrients while excluding toxic compounds , including antibiotics . The OM is asymmetric and contains an outer leaflet of lipopolysaccharides ( LPS ) or lipooligosaccharides ( LOS ) and an inner...	Gram-negative bacteria are a large group of single-celled organisms that share a typical external envelope . This casing is formed of an inner and an outer membrane , which have different structures and properties . The outer membrane lets nutrients penetrate inside the cell , but blocks out other compounds , such as a...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "microbiology", "and", "infectious", "disease" ]	2019	The Acinetobacter baumannii Mla system and glycerophospholipid transport to the outer membrane
In order to assess the contribution of a central clock in the hypothalamic suprachiasmatic nucleus ( SCN ) to circadian behavior and the organization of peripheral clocks , we generated forebrain/SCN-specific Bmal1 knockout mice by using floxed Bmal1 and pan-neuronal Cre lines . The forebrain knockout mice showed >90% ...	Jet lag is a common experience when flying long distance . This disorientating phenomenon occurs when our internal ‘body clock’ remains set to the time zone where the plane departed and fails to reset to the new local time . Our internal clock actually consists of a series of clocks—each of which is based upon groups o...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2014	Differential effects of light and feeding on circadian organization of peripheral clocks in a forebrain Bmal1 mutant
Across many studies , animals with enhanced synaptic plasticity exhibit either enhanced or impaired learning , raising a conceptual puzzle: how enhanced plasticity can yield opposite learning outcomes ? Here , we show that the recent history of experience can determine whether mice with enhanced plasticity exhibit enha...	All animals can learn from their experiences . One of the main ideas for how learning occurs is that it involves changes in the strength of the connections between neurons , known as synapses . The ability of synapses to become stronger or weaker is referred to as synaptic plasticity . High levels of synaptic plasticit...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2017	A saturation hypothesis to explain both enhanced and impaired learning with enhanced plasticity
Many bacteria communicate with kin and coordinate group behaviors through a form of cell-cell signaling called acyl-homoserine lactone ( AHL ) quorum sensing ( QS ) . In these systems , a signal synthase produces an AHL to which its paired receptor selectively responds . Selectivity is fundamental to cell signaling . D...	Communication is vital in any community and it is no different for bacteria . Some of the microbes living in bacterial communities are closely related to one another and can help each other survive and grow . They do this by releasing chemical signals that coordinate their behaviors , including those that are damaging ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology", "microbiology", "and", "infectious", "disease" ]	2021	A covariation analysis reveals elements of selectivity in quorum sensing systems
The precise pattern of motor neuron ( MN ) activation is essential for the execution of motor actions; however , the molecular mechanisms that give rise to specific patterns of MN activity are largely unknown . Phrenic MNs integrate multiple inputs to mediate inspiratory activity during breathing and are constrained to...	In mammals , air is moved in and out of the lungs by a sheet of muscle called the diaphragm . When this muscle contracts air gets drawn into the lungs and as the muscle relaxes this pushes air back out . Movement of the diaphragm is controlled by a group of nerve cells called motor neurons which are part of the phrenic...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "neuroscience" ]	2020	Phrenic-specific transcriptional programs shape respiratory motor output
Reproductive synchrony generally occurs in various group-living animals . However , the underlying mechanisms remain largely unexplored . The migratory locust , Locusta migratoria , a worldwide agricultural pest species , displays synchronous maturation and oviposition when forms huge swarm . The reproductive synchrony...	Since 2019 , a plague of flying insects known as migratory locusts has been causing extensive damage to crops in East Africa . Migratory locusts sometimes live a solitary lifestyle but , if environmental conditions allow , they form large groups containing millions of individuals known as swarms that are responsible fo...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "ecology", "biochemistry", "and", "chemical", "biology" ]	2022	Aggregation pheromone 4-vinylanisole promotes the synchrony of sexual maturation in female locusts
Paired fins are a defining feature of the jawed vertebrate body plan , but their evolutionary origin remains unresolved . Gegenbaur proposed that paired fins evolved as gill arch serial homologues , but this hypothesis is now widely discounted , owing largely to the presumed distinct embryonic origins of these structur...	A common way to evolve new body parts is to copy existing ones and to remodel them . In insects for example , the antennae , mouth parts and legs all follow the same basic body plan , with modifications that adapt them for different uses . In the late 19th century , anatomist Karl Gegenbaur noticed a similar pattern in...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "evolutionary", "biology" ]	2020	Embryonic origin and serial homology of gill arches and paired fins in the skate, Leucoraja erinacea
Schistosomes infect hundreds of millions of people in the developing world . Transmission of these parasites relies on a stem cell-driven , clonal expansion of larvae inside a molluscan intermediate host . How this novel asexual reproductive strategy relates to current models of stem cell maintenance and germline speci...	Schistosomiasis—a disease caused by parasitic flatworms known as schistosomes—affects more than 200 million people worldwide , mainly in tropical regions , and in public health importance is second only to malaria ( according to the World Health Organization ) . Chronic infection leads to damage to internal organs , an...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "stem", "cells", "and", "regenerative", "medicine", "microbiology", "and", "infectious", "disease" ]	2013	Functional genomic characterization of neoblast-like stem cells in larval Schistosoma mansoni
T follicular helper cells ( Tfh ) are critical for the longevity and quality of antibody-mediated protection against infection . Yet few signaling pathways have been identified to be unique solely to Tfh development . ROQUIN is a post-transcriptional repressor of T cells , acting through its ROQ domain to destabilize m...	The immune system protects the body from invading microbes like bacteria and viruses . Upon recognizing the presence of these microbes , cells in the immune system are activated to destroy the foreign threat and clear it from the body . A type of immune cell called T follicular helper cells ( or Tfh for short ) are for...	[ "Abstract", "Introduction", "Results", "Materials", "and", "methods" ]	[ "cell", "biology", "immunology", "and", "inflammation" ]	2015	Attenuation of AMPK signaling by ROQUIN promotes T follicular helper cell formation
It was recently proposed ( Bushdid et al . , 2014 ) that humans can discriminate between at least a trillion olfactory stimuli . Here we show that this claim is the result of a fragile estimation framework capable of producing nearly any result from the reported data , including values tens of orders of magnitude large...	Scientists are interested in the number of colors , sounds and smells we can distinguish because this information can shed light onto how our brains process these senses both in health and disease . It is relatively straightforward to determine how many colors we can see or sounds we can hear because these stimuli are ...	[ "Abstract", "Introduction", "Building", "the", "stimulus", "space" ]	[ "neuroscience" ]	2015	The number of olfactory stimuli that humans can discriminate is still unknown
Signals delivered by costimulatory molecules are implicated in driving T cell expansion . The requirements for these signals , however , vary from dispensable to essential in different infections . We examined the underlying mechanisms of this differential T cell costimulation dependence and found that the viral contex...	When the immune system detects a virus in the body it mounts a response to eliminate it . Immune cells called CD8+ T cells detect fragments of virus proteins that are presented on the surface of other immune cells . The CD8+ T cells then rapidly divide to form populations that roam the body to kill cells that are infec...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "microbiology", "and", "infectious", "disease", "immunology", "and", "inflammation" ]	2015	The viral context instructs the redundancy of costimulatory pathways in driving CD8+ T cell expansion
Sexual selection is generally predicted to act more strongly on males than on females . The Darwin-Bateman paradigm predicts that this should also hold for hermaphrodites . However , measuring this strength of selection is less straightforward when both sexual functions are performed throughout the organism’s lifetime ...	Many factors affect an organism’s ability to survive and reproduce . These factors are often called “selection pressures” and include the availability of food and shelter , conditions in the environment such as temperature , and the presence of diseases and predators . Males and females experience different selection p...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "ecology" ]	2017	Sexual selection gradients change over time in a simultaneous hermaphrodite
The vascular pathogen Verticillium dahliae infects the roots of plants to cause Verticillium wilt . The molecular mechanisms underlying V . dahliae virulence and host resistance remain elusive . Here , we demonstrate that a secretory protein , VdSCP41 , functions as an intracellular effector that promotes V . dahliae v...	Like animals , plants have an immune system to protect themselves from disease . When a plant detects a disease-causing microbe , proteins that serve as master regulators of its immune system activate defense-related genes . Yet some microbes can overcome these defenses and successfully infect plants . Verticillium dah...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology", "microbiology", "and", "infectious", "disease" ]	2018	The plant-specific transcription factors CBP60g and SARD1 are targeted by a Verticillium secretory protein VdSCP41 to modulate immunity
In amyotrophic lateral sclerosis ( ALS ) and animal models of ALS , including SOD1-G93A mice , disassembly of the neuromuscular synapse precedes motor neuron loss and is sufficient to cause a decline in motor function that culminates in lethal respiratory paralysis . We treated SOD1-G93A mice with an agonist antibody t...	Amyotrophic lateral sclerosis – often shortened to ALS – is a disease that starts with difficulties moving and progresses to paralysis of many muscles , including those used for breathing . The disease is usually lethal , with patients rarely surviving more than a few years after diagnosis . There is no cure or effecti...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2018	Preserving neuromuscular synapses in ALS by stimulating MuSK with a therapeutic agonist antibody

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