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Retinol plays a vital role in the immune response to infection , yet proteins that mediate retinol transport during infection have not been identified . Serum amyloid A ( SAA ) proteins are strongly induced in the liver by systemic infection and in the intestine by bacterial colonization , but their exact functions rem...	Vitamins are nutrients that organisms require in order to survive and grow . If an organism is unable to synthesize a vitamin in sufficient quantities , it is essential that it obtain the vitamin through its diet instead . Vitamin A is found in foods such as eggs , animal liver and carrots , and a diet that is lacking ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics", "immunology", "and", "inflammation" ]	2014	Serum amyloid A is a retinol binding protein that transports retinol during bacterial infection
The unfolded protein response ( UPR ) is an essential cell signaling system that detects the accumulation of misfolded proteins within the endoplasmic reticulum ( ER ) and initiates a cellular response in order to maintain homeostasis . How cells detect the accumulation of misfolded proteins remains unclear . In this s...	Proteins perform many essential tasks in cells , but to be able to work they first have to correctly fold into a specific three-dimensional shape . Within the cell , many proteins are folded with the help of ‘chaperone’ proteins . If any proteins fold incorrectly , the normal workings of the cell can be disturbed , whi...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2015	Noncanonical binding of BiP ATPase domain to Ire1 and Perk is dissociated by unfolded protein CH1 to initiate ER stress signaling
Histone modifiers play essential roles in controlling transcription and organizing eukaryotic genomes into functional domains . Here , we show that Set1 , the catalytic subunit of the highly conserved Set1C/COMPASS complex responsible for histone H3K4 methylation ( H3K4me ) , behaves as a repressor of the transcriptome...	Genes can be turned on or off at different times in an organism's life . In humans , yeast and other eukaryotes , this is mainly controlled by the way DNA is packaged with proteins—known as histones—in a structure called chromatin . Genes that are switched on , or only temporarily switched off , are associated with are...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "genetics", "and", "genomics" ]	2014	Heterochromatin assembly and transcriptome repression by Set1 in coordination with a class II histone deacetylase
Traumatic brain injury ( TBI ) is a major cause of death and disability worldwide . Unfavorable TBI outcomes result from primary mechanical injuries to the brain and ensuing secondary non-mechanical injuries that are not limited to the brain . Our genome-wide association study of Drosophila melanogaster revealed that t...	Traumatic brain injury ( TBI ) caused by a violent blow to the head or body and the resultant collision of the brain against the skull is a major cause of disability and death in humans . Primary injury to the brain triggers secondary injuries that further damage the brain and other organs , generating many of the detr...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "neuroscience" ]	2015	Death following traumatic brain injury in Drosophila is associated with intestinal barrier dysfunction
Conflict over parental investment between parent and offspring is predicted to lead to selection on genes expressed in offspring for traits influencing maternal investment , and on parentally expressed genes affecting offspring behaviour . However , the specific genetic variants that indirectly modify maternal or offsp...	Genes encode instructions that can influence the behaviour and physical traits of the individual that carries them . Individuals of the same species can carry different versions ( or variants ) of the same gene , leading to a variety of traits in the population . However , a gene expressed in one individual can also al...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "genetics", "and", "genomics" ]	2015	Genetic variation in offspring indirectly influences the quality of maternal behaviour in mice
Selective transcription of individual protein coding genes does not occur in trypanosomes and the cellular copy number of each mRNA must be determined post-transcriptionally . Here , we provide evidence that codon choice directs the levels of constitutively expressed mRNAs . First , a novel codon usage metric , the gen...	Genes are made up of DNA and contain the instructions to make molecules called proteins . This information is stored as a genetic code consisting of four bases: adenine ( A ) , cytosine ( C ) , guanine ( G ) and thymine ( T ) . The order of these bases and their different combinations serves as a blueprint for making t...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "microbiology", "and", "infectious", "disease" ]	2018	Codon choice directs constitutive mRNA levels in trypanosomes
Context-dependent changes in genetic interactions are an important feature of cellular pathways and their varying responses under different environmental conditions . However , methodological frameworks to investigate the plasticity of genetic interaction networks over time or in response to external stresses are large...	Within a cell , communication routes that involve many different genes work to control how the cell responds to the environment . Although different communication routes – so called signaling pathways – control different cell activities , they do not work in isolation . Instead , they form part of larger regulatory net...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "research", "communication", "computational", "and", "systems", "biology", "genetics", "and", "genomics" ]	2018	Time-resolved mapping of genetic interactions to model rewiring of signaling pathways
A central problem in infection biology is understanding why two individuals exposed to identical infections have different outcomes . We have developed an experimental model where genetically identical , co-housed Drosophila given identical systemic infections experience different outcomes , with some individuals succu...	Sick individuals do not all respond to an infection in the same way . One individual may experience mild symptoms and recover easily , while another may suffer devastating illness or even death . A number of factors are often assumed to account for these differences , including the sex , age and genes of the individual...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "microbiology", "and", "infectious", "disease" ]	2017	Stochastic variation in the initial phase of bacterial infection predicts the probability of survival in D. melanogaster
CRISPR-based homing gene drives have sparked both enthusiasm and deep concerns due to their potential for genetically altering entire species . This raises the question about our ability to prevent the unintended spread of such drives from the laboratory into a natural population . Here , we experimentally demonstrate ...	Gene drives are a new genome editing technology where artificial gene packages are designed to create a mutation that will quickly spread within a population . These packages target a specific sequence in a genome , where they could potentially add , remove or deactivate a gene . They also trigger a process known as dr...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "short", "report", "genetics", "and", "genomics" ]	2019	Molecular safeguarding of CRISPR gene drive experiments
Motoneurons ( MNs ) control muscle contractions , and their recruitment by premotor circuits is tuned to produce accurate motor behaviours . To understand how these circuits coordinate movement across and between joints , it is necessary to understand whether spinal neurons pre-synaptic to motor pools have divergent pr...	We are able to walk , run and move our bodies in other ways thanks to circuits of neurons in the spinal cord that control how and when our muscles contract and relax . Neurons known as premotor neurons receive information from other parts of the central nervous system and control the activities of groups ( known as poo...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2021	Proximal and distal spinal neurons innervating multiple synergist and antagonist motor pools
Visual pigments can be spontaneously activated by internal thermal energy , generating noise that interferes with real-light detection . Recently , we developed a physicochemical theory that successfully predicts the rate of spontaneous activity of representative rod and cone pigments from their peak-absorption wavelen...	At the back of our eyes is a thin layer of cells that contain light-absorbing pigment molecules . These cells convert light energy into electrical signals that the brain then interprets to allow us to see . In this cell layer , the so-called cone cells work in bright light and provide us with the sense of color , where...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "short", "report", "neuroscience" ]	2017	Spontaneous activation of visual pigments in relation to openness/closedness of chromophore-binding pocket
Cytoplasmic dynein powers intracellular movement of cargo toward the microtubule minus end . The first step in a variety of dynein transport events is the targeting of dynein to the dynamic microtubule plus end , but the molecular mechanism underlying this spatial regulation is not understood . Here , we reconstitute d...	Eukaryotic cells use transport systems to efficiently move materials from one location to another . Much transport in the cell interior is achieved using molecular motors , which carry cargoes along tracks called microtubules . Unlike roads of human construction , microtubules are very dynamic . One of their ends ( the...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2014	Reconstitution of dynein transport to the microtubule plus end by kinesin
The cross-talk between dynamic microtubules and integrin-based adhesions to the extracellular matrix plays a crucial role in cell polarity and migration . Microtubules regulate the turnover of adhesion sites , and , in turn , focal adhesions promote the cortical microtubule capture and stabilization in their vicinity ,...	Animal cells are organized into tissues and organs . A scaffold-like framework outside of the cells called the extracellular matrix provides support to the cells and helps to hold them in place . Cells attach to the extracellular matrix via structures called focal adhesions on the cell surface; these structures contain...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2016	Talin-KANK1 interaction controls the recruitment of cortical microtubule stabilizing complexes to focal adhesions
Vestibular hair cells in the inner ear encode head movements and mediate the sense of balance . These cells undergo cell death and replacement ( turnover ) throughout life in non-mammalian vertebrates . However , there is no definitive evidence that this process occurs in mammals . We used fate-mapping and other method...	Cells in the inner ear called hair cells sense sound waves and head movements , allowing us to hear and maintain balance . In non-mammals such as birds and fish , the hair cells responsible for balance die and are replaced ( in a process known as turnover ) throughout life . However , it is largely assumed that no new ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "neuroscience" ]	2017	Supporting cells remove and replace sensory receptor hair cells in a balance organ of adult mice
Chromatin assembly involves the combined action of ATP-dependent motor proteins and histone chaperones . Because motor proteins in chromatin assembly also function as chromatin remodeling factors , we investigated the relationship between ATP-driven chromatin assembly and chromatin remodeling in the generation of perio...	In many cells , genomic DNA is wrapped around proteins known as histones to produce particles called nucleosomes . These particles then join together—like beads on a string—to form a highly periodic structure called chromatin . In the nucleus , chromatin is further folded and condensed into chromosomes . However , many...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "biochemistry", "and", "chemical", "biology" ]	2013	ATP-dependent chromatin assembly is functionally distinct from chromatin remodeling
Antimicrobial peptides ( AMPs ) are host-encoded antibiotics that combat invading microorganisms . These short , cationic peptides have been implicated in many biological processes , primarily involving innate immunity . In vitro studies have shown AMPs kill bacteria and fungi at physiological concentrations , but litt...	All animals – from humans to mice , jellyfish to fruit flies – are armed with an immune system to defend against infections . The immune system’s first line of defence often involves a group of short proteins called antimicrobial peptides . These proteins are found anywhere that germs and microbes come into contact wit...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "immunology", "and", "inflammation" ]	2019	Synergy and remarkable specificity of antimicrobial peptides in vivo using a systematic knockout approach
Signal recognition particles ( SRPs ) are universal ribonucleoprotein complexes found in all three domains of life that direct the cellular traffic and secretion of proteins . These complexes consist of SRP proteins and a single , highly structured SRP RNA . Canonical SRP RNA genes have not been identified for some The...	Cells make many proteins that are eventually released outside the cell or inserted into the cell’s membrane . As these proteins are still being made , they are captured by a “signal recognition particle” ( or SRP ) ; this molecular machine then guides the newly forming protein to the cell’s membrane . SRPs are found in...	[ "Abstract", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "short", "report" ]	2015	Circularization restores signal recognition particle RNA functionality in Thermoproteus
We report that Histone Deacetylase 7 ( HDAC7 ) controls the thymic effector programming of Natural Killer T ( NKT ) cells , and that interference with this function contributes to tissue-specific autoimmunity . Gain of HDAC7 function in thymocytes blocks both negative selection and NKT development , and diverts Vα14/Jα...	To protect us , our immune system must walk a narrow line: while it eliminates all external threats , it also has to refrain from attacking the healthy tissues of our body . When such misdirected attacks do take place , they can result in life-threatening autoimmune diseases . T cells are a highly diverse population of...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "immunology", "and", "inflammation" ]	2018	Histone Deacetylase 7 mediates tissue-specific autoimmunity via control of innate effector function in invariant Natural Killer T Cells
Ribonucleotide reductase ( RNR ) converts ribonucleotides to deoxyribonucleotides , a reaction that is essential for DNA biosynthesis and repair . This enzyme is responsible for reducing all four ribonucleotide substrates , with specificity regulated by the binding of an effector to a distal allosteric site . In all ch...	DNA contains the instructions required to make proteins and other molecules in cells . DNA is made of four building blocks called deoxyribonucleotides , which are in turn made from molecules called ribonucleotides by enzymes known as ribonucleotide reductases ( RNRs for short ) . RNR enzymes are responsible for maintai...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2016	Molecular basis for allosteric specificity regulation in class Ia ribonucleotide reductase from Escherichia coli
The glycosyltransferase EOGT transfers O-GlcNAc to a consensus site in epidermal growth factor-like ( EGF ) repeats of a limited number of secreted and membrane proteins , including Notch receptors . In EOGT-deficient cells , the binding of DLL1 and DLL4 , but not JAG1 , canonical Notch ligands was reduced , and ligand...	As an embryo develops , its cells undergo a series of divisions and transformations until they specialize to form distinct cell types . These transformations are regulated by many molecules and signaling pathways . Often one cell will release signaling molecules that are then recognized by specialized receptor proteins...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "biochemistry", "and", "chemical", "biology" ]	2017	O-GlcNAc on NOTCH1 EGF repeats regulates ligand-induced Notch signaling and vascular development in mammals
Mitochondrial calcium ( Ca2+ ) import is a well-described phenomenon regulating cell survival and ATP production . Of multiple pathways allowing such entry , the mitochondrial Ca2+ uniporter is a highly Ca2+-selective channel complex encoded by several recently-discovered genes . However , the identity of the pore-form...	Mitochondria are tiny organelles , less than a micrometre across , found inside almost all eukaryotic cells . Their main function is to act as the ‘power plant’ of the cell , generating adenosine triphosphate or ATP , which is the source of chemical energy for cellular processes . Beyond generating ATP , mitochondria p...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "cell", "biology" ]	2013	MCU encodes the pore conducting mitochondrial calcium currents
Defining mechanisms of direct-acting antivirals facilitates drug development and our understanding of virus function . Heteroaryldihydropyrimidines ( HAPs ) inappropriately activate assembly of hepatitis B virus ( HBV ) core protein ( Cp ) , suppressing formation of virions . We examined a fluorophore-labeled HAP , HAP...	Viruses are simple structures formed of genetic information wrapped inside a shell . For the hepatitis B virus , this casing looks like a soccer ball . It is composed of 240 copies of the same protein , arranged in a pattern of pentagons and hexagons . These proteins form a protective shield for the virus’ genetic info...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "microbiology", "and", "infectious", "disease" ]	2018	Hepatitis B virus core protein allosteric modulators can distort and disrupt intact capsids
Anxiety results in sub-optimal motor learning , but the precise mechanisms through which this effect occurs remain unknown . Using a motor sequence learning paradigm with separate phases for initial exploration and reward-based learning , we show that anxiety states in humans impair learning by attenuating the update o...	Feeling anxious can hinder how well someone performs a task , a phenomenon that is sometimes called “choking under pressure” . Anxiety may also impair a person’s ability to learn a new manual task , like juggling or playing the piano; however , it remains unclear exactly how this happens . People learn manual tasks mor...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2020	Alterations in the amplitude and burst rate of beta oscillations impair reward-dependent motor learning in anxiety
Heat shock factor 1 ( HSF1 ) , a key regulator of transcriptional responses to proteotoxic stress , was linked to estrogen ( E2 ) signaling through estrogen receptor α ( ERα ) . We found that an HSF1 deficiency may decrease ERα level , attenuate the mitogenic action of E2 , counteract E2-stimulated cell scattering , an...	About 70% of breast cancers rely on supplies of a hormone called estrogen – which is the main hormone responsible for female physical characteristics – to grow . Breast cancer cells that are sensitive to estrogen possess proteins known as estrogen receptors and are classified as estrogen-receptor positive . When estrog...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "cancer", "biology" ]	2021	Heat shock factor 1 (HSF1) cooperates with estrogen receptor α (ERα) in the regulation of estrogen action in breast cancer cells
Predicting neurological recovery after spinal cord injury ( SCI ) is challenging . Using topological data analysis , we have previously shown that mean arterial pressure ( MAP ) during SCI surgery predicts long-term functional recovery in rodent models , motivating the present multicenter study in patients . Intra-oper...	Spinal cord injury is a devastating condition that involves damage to the nerve fibers connecting the brain with the spinal cord , often leading to permanent changes in strength , sensation and body functions , and in severe cases paralysis . Scientists around the world work hard to find ways to treat or even repair sp...	[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "computational", "and", "systems", "biology" ]	2021	Topological network analysis of patient similarity for precision management of acute blood pressure in spinal cord injury
The transport receptor Crm1 mediates the export of diverse cargos containing leucine-rich nuclear export signals ( NESs ) through complex formation with RanGTP . To ensure efficient cargo release in the cytoplasm , NESs have evolved to display low affinity for Crm1 . However , mechanisms that overcome low affinity to a...	Plants , fungi , and animals store their genetic material within the nucleus of each of their cells . This structure is surrounded by a double layer of membrane that prevents the contents of the nucleus from mixing with the contents of the rest of the cell ( namely the cytoplasm ) . Exchange of material between the nuc...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "cell", "biology" ]	2015	A non-canonical mechanism for Crm1-export cargo complex assembly
Herbivore-induced defenses are widespread , rapidly evolving and relevant for plant fitness . Such induced defenses are often mediated by early defense signaling ( EDS ) rapidly activated by the perception of herbivore associated elicitors ( HAE ) that includes transient accumulations of jasmonic acid ( JA ) . Analyzin...	A variety of different insects feed on plants and these insects often produce molecules known as elicitors that the plants can recognize . This triggers a sophisticated suite of defenses in the plant that can either deter feeding by the insects , or help the plants endure the attack . The elicitors stimulate the rapid ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology", "evolutionary", "biology" ]	2016	Evolution of herbivore-induced early defense signaling was shaped by genome-wide duplications in Nicotiana
The dynamics of host-parasite interactions are highly temperature-dependent and may be modified by increasing frequency and intensity of climate-driven heat events . Here , we show that altered patterns of temperature variance lead to an almost order-of-magnitude shift in thermal performance of host and pathogen life-h...	Global warming is increasing average temperatures and causing extreme temperature fluctuations and heatwaves . These changes may affect when , where , and how often infectious disease outbreaks occur . This could have profound impacts on agriculture , human health , and wildlife . Studying how extreme temperatures or t...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "ecology", "short", "report", "microbiology", "and", "infectious", "disease" ]	2022	Alternate patterns of temperature variation bring about very different disease outcomes at different mean temperatures
While a first pregnancy before age 22 lowers breast cancer risk , a pregnancy after age 35 significantly increases life-long breast cancer risk . Pregnancy causes several changes to the normal breast that raise barriers to transformation , but how pregnancy can also increase cancer risk remains unclear . We show in mic...	Pregnancy changes the probability that a woman will later develop breast cancer . If a woman’s first pregnancy occurs before her 22nd birthday , the chances of developing breast cancer are reduced . However , if the first pregnancy occurs after her 35th birthday , there is an increased risk of breast cancer . It is not...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2013	Mechanism and preclinical prevention of increased breast cancer risk caused by pregnancy
Many driver mutations in cancer are specific in that they occur at significantly higher rates than – presumably – functionally alternative mutations . For example , V600E in the BRAF hydrophobic activation segment ( AS ) pocket accounts for >95% of all kinase mutations . While many hypotheses tried to explain such sign...	Mutations in the gene that encodes a protein called BRAF are commonly found in certain cancers , such as melanomas . The same BRAF mutation is found in nearly all of these cancers . This mutation causes the 600th amino acid in the BRAF protein – an amino acid called a valine – to be replaced with another amino acid , a...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Conclusions", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics", "computational", "and", "systems", "biology" ]	2016	The yin–yang of kinase activation and unfolding explains the peculiarity of Val600 in the activation segment of BRAF
KCNQ channels are critical determinants of neuronal excitability , thus emerging as a novel target of anti-epileptic drugs . To date , the mechanisms of KCNQ channel modulation have been mostly characterized to be inhibitory via Gq-coupled receptors , Ca2+/CaM , and protein kinase C . Here we demonstrate that methylati...	In the brain , cells called neurons transmit information along their length in the form of electrical signals . To generate electrical signals , ions move into and out of neurons through ion channel proteins – such as the KCNQ channel – in the surface of these cells , which open and close to control the electrical resp...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Protein arginine methylation facilitates KCNQ channel-PIP2 interaction leading to seizure suppression
The centromere , responsible for chromosome segregation during mitosis , is epigenetically defined by CENP-A containing chromatin . The amount of centromeric CENP-A has direct implications for both the architecture and epigenetic inheritance of centromeres . Using complementary strategies , we determined that typical h...	The genetic information in a cell is packed into structures called chromosomes . These contain strands of DNA wrapped around proteins called histones , which helps the long DNA chains to fit inside the relatively small nucleus of the cell . When a cell divides , it is important that both of the new cells contain all of...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2014	The quantitative architecture of centromeric chromatin
Centrioles are composed of long-lived microtubules arranged in nine triplets . However , the contribution of triplet microtubules to mammalian centriole formation and stability is unknown . Little is known of the mechanism of triplet microtubule formation , but experiments in unicellular eukaryotes indicate that delta-...	Most structures inside a cell have a short lifespan and are continually replaced . Centrioles – specialized structures that help cells divide , and send and receive signals – are among the few exceptions and can persist through many cell generations . Centrioles are cylindrical structures that are made up of protein tu...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2017	Centriole triplet microtubules are required for stable centriole formation and inheritance in human cells
Stress is a potent modulator of the mammalian brain . The highly conserved stress hormone response influences many brain regions , particularly the hippocampus , a region important for memory function . The effect of acute stress on the unique population of adult neural stem/progenitor cells ( NPCs ) that resides in th...	A little stress can be good for you . Just over 100 years ago , psychologists Robert Yerkes and John Dodson suggested that cognitive performance improves as stress increases , although it falls off again if stress levels continue to rise . The hippocampus is a key brain region for both memory and the regulation of emot...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2013	Acute stress enhances adult rat hippocampal neurogenesis and activation of newborn neurons via secreted astrocytic FGF2
Enhancers and silencers often depend on the same transcription factors ( TFs ) and are conflated in genomic assays of TF binding or chromatin state . To identify sequence features that distinguish enhancers and silencers , we assayed massively parallel reporter libraries of genomic sequences targeted by the photorecept...	Different cell types are established by activating and repressing the activity of specific sets of genes , a process controlled by proteins called transcription factors . Transcription factors work by recognizing and binding short stretches of DNA in parts of the genome called cis-regulatory sequences . A cis-regulator...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology", "genetics", "and", "genomics" ]	2021	Information content differentiates enhancers from silencers in mouse photoreceptors
Sensory cilia are populated by a select group of signaling proteins that detect environmental stimuli . How these molecules are delivered to the sensory cilium and whether they rely on one another for specific transport remains poorly understood . Here , we investigated whether the visual pigment , rhodopsin , is criti...	Our vision begins with light being captured by the rod and cone photoreceptor cells of the retina at the back of the eye . Photoreceptors have large antennae , termed outer segments , which contain specialized proteins that produce electrical signals when stimulated by light . However , it remains mostly unknown how th...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	Guanylate cyclase 1 relies on rhodopsin for intracellular stability and ciliary trafficking
Microtubule dynamics facilitate neurite growth and establish morphology , but the role of minus-end binding proteins in these processes is largely unexplored . CAMSAP homologs associate with microtubule minus-ends , and are important for the stability of epithelial cell adhesions . In this study , we report morphologic...	Microtubules are tiny tubular structures made from many copies of proteins called tubulins . Microtubules have a number of important roles inside cells: they are part of the cytoskeleton that provides structural support for the cell; they help to pull chromosomes apart during cell division; and they guide the trafficki...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]	[ "cell", "biology", "neuroscience" ]	2014	The Caenorhabditis elegans microtubule minus-end binding homolog PTRN-1 stabilizes synapses and neurites
Alternative splicing ( AS ) programs are primarily controlled by regulatory RNA-binding proteins ( RBPs ) . It has been proposed that a small number of master splicing regulators might control cell-specific splicing networks and that these RBPs could be identified by proximity of their genes to transcriptional super-en...	All the cells in our body contain the same genetic information , but they only switch on the genes that they need to fulfill their specific role in the organism . Genetic sequences known as enhancers can turn on the genes that are required by a particular cell to perform its tasks . Once a gene is activated , its seque...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression" ]	2019	Identification of RBPMS as a mammalian smooth muscle master splicing regulator via proximity of its gene with super-enhancers
Long-range cis-regulatory elements such as enhancers coordinate cell-specific transcriptional programmes by engaging in DNA looping interactions with target promoters . Deciphering the interplay between the promoter connectivity and activity of cis-regulatory elements during lineage commitment is crucial for understand...	Virtually every cell in the body contains the same set of DNA , which encodes thousands of genes . The activities of these genes vary between different types of cells and at different points in time . As a result , our DNA contains a complex array of molecular switches that instruct genes to switch on and off at the ri...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "stem", "cells", "and", "regenerative", "medicine", "chromosomes", "and", "gene", "expression", "tools", "and", "resources" ]	2017	Global reorganisation of cis-regulatory units upon lineage commitment of human embryonic stem cells
Innate immunity is the first immunological defence against pathogens . During virus infection detection of nucleic acids is crucial for the inflammatory response . Here we identify DNA-dependent protein kinase ( DNA-PK ) as a DNA sensor that activates innate immunity . We show that DNA-PK acts as a pattern recognition ...	For multicellular organisms , the innate immune system is the first immunological defence against infection , rapidly recognizing and responding to the presence of any pathogen . Many different cell types contribute to the innate immunity , including fibroblasts , epithelial cells , dendritic cells and macrophages . On...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "microbiology", "and", "infectious", "disease", "immunology", "and", "inflammation" ]	2012	DNA-PK is a DNA sensor for IRF-3-dependent innate immunity
Animals discriminate stimuli , learn their predictive value and use this knowledge to modify their behavior . In Drosophila , the mushroom body ( MB ) plays a key role in these processes . Sensory stimuli are sparsely represented by ∼2000 Kenyon cells , which converge onto 34 output neurons ( MBONs ) of 21 types . We s...	An animal's survival depends on its ability to respond appropriately to its environment , approaching stimuli that signal rewards and avoiding any that warn of potential threats . In fruit flies , this behavior requires activity in a region of the brain called the mushroom body , which processes sensory information and...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2014	Mushroom body output neurons encode valence and guide memory-based action selection in Drosophila
Phylogenetic relationships among extinct hominoids ( apes and humans ) are controversial due to pervasive homoplasy and the incompleteness of the fossil record . The bony labyrinth might contribute to this debate , as it displays strong phylogenetic signal among other mammals . However , the potential of the vestibular...	Humans , gorillas , chimpanzees , orangutans and gibbons all belong to a group known as the hominoids . This ‘superfamily’ also includes the immediate ancestors and close relatives of these species , however in many instances the evolutionary relationships between these extinct ape species remain controversial . While ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology" ]	2020	The evolution of the vestibular apparatus in apes and humans
Mammals articulate their jaws using a novel joint between the dentary and squamosal bones . In eutherian mammals , this joint forms in the embryo , supporting feeding and vocalisation from birth . In contrast , marsupials and monotremes exhibit extreme altriciality and are born before the bones of the novel mammalian j...	The defining feature of all mammals is how the jaw works . Fish , reptiles and other animals with backbones have a lower jaw made of many bones fused together , one of which connects to the upper jaw . The lower jaw in mammals , however , is made of a single bone that connects with the upper jaw using a completely uniq...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "evolutionary", "biology" ]	2020	Transient role of the middle ear as a lower jaw support across mammals
Nutritional regulation by ants emerges from a distributed process: food is collected by a small fraction of workers , stored within the crops of individuals , and spread via local ant-to-ant interactions . The precise individual-level underpinnings of this collective regulation have remained unclear mainly due to diffi...	In an ant society , a small group of workers , called foragers , feeds the rest of the colony . Each forager goes out of the nest to find food; any liquid food she collects is stored in her ‘crop’ , a pouch located just upstream of her stomach . When a forager goes back to the nest , she unloads this liquid by mouth-to...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "ecology", "computational", "and", "systems", "biology" ]	2018	Individual crop loads provide local control for collective food intake in ant colonies
Image-based cell classification has become a common tool to identify phenotypic changes in cell populations . However , this methodology is limited to organisms possessing well-characterized species-specific reagents ( e . g . , antibodies ) that allow cell identification , clustering , and convolutional neural network...	Cells are the building blocks of all living organisms . They come in many types , each with a different role . Understanding the composition of cells , i . e . , how many cells and which types of cells are present inside an organ can indicate what that organ does . It can also reveal how that organ changes under differ...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "tools", "and", "resources" ]	2021	Image3C, a multimodal image-based and label-independent integrative method for single-cell analysis
To evolve and to be maintained , seasonal migration , despite its risks , has to yield fitness benefits compared with year-round residency . Empirical data supporting this prediction have remained elusive in the bird literature . To test fitness related benefits of migration , we studied a partial migratory population ...	Winter is one of the most challenging seasons for many animals . Cold temperatures , bad weather , short days , long nights and a shortage of food can impose a deadly threat . To avoid these inhospitable conditions , some animals migrate to warmer climes during the winter . These animals include many songbirds , which ...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "ecology", "short", "report" ]	2017	Migration confers winter survival benefits in a partially migratory songbird
Bovines have evolved a subset of antibodies with ultra-long heavy chain complementarity determining regions that harbour cysteine-rich knob domains . To produce high-affinity peptides , we previously isolated autonomous 3–6 kDa knob domains from bovine antibodies . Here , we show that binding of four knob domain peptid...	Antibodies are proteins produced by the immune system that can selectively bind to other molecules and modify their behaviour . Cows are highly equipped at fighting-off disease-causing microbes due to the unique shape of some of their antibodies . Unlike other jawed vertebrates , cows’ antibodies contain an ultra-long ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics", "immunology", "and", "inflammation" ]	2021	The allosteric modulation of complement C5 by knob domain peptides
PD-1 blockade therapy has revolutionized cancer treatments . However , a substantial population of patients is unresponsive . To rescue unresponsive patients , the mechanism of unresponsiveness to PD-1 blockade therapy must be elucidated . Using a ‘bilateral tumor model’ where responsive and unresponsive tumors were in...	Immunotherapy is a fast-emerging treatment area that turns the body’s own immune system against cancer . One powerful group of treatments are the PD-1 blockers . PD-1 is an inducible protein that is sometimes found on healthy immune cells called T cells and normally acts to stop T cells mistakenly attacking healthy cel...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "immunology", "and", "inflammation" ]	2020	Tumors attenuating the mitochondrial activity in T cells escape from PD-1 blockade therapy
Variability within isogenic T cell populations yields heterogeneous ‘local’ signaling responses to shared antigenic stimuli , but responding clones may communicate ‘global’ antigen load through paracrine messengers , such as cytokines . Such coordination of individual cell responses within multicellular populations is ...	The cells of the immune system face the challenge of removing viruses and other pathogens without endangering healthy tissues . Cells called T cells plays a variety of roles in the immune response: some T cells directly destroy infected cells , some recruit other cells called phagocytes to the site of infection , and s...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "immunology", "and", "inflammation" ]	2014	T cells translate individual, quantal activation into collective, analog cytokine responses via time-integrated feedbacks
Mammalian genomes typically contain hundreds of thousands of endogenous retroviruses ( ERVs ) , derived from ancient retroviral infections . Using this molecular 'fossil' record , we reconstructed the natural history of a specific retrovirus lineage ( ERV-Fc ) that disseminated widely between ~33 and ~15 million years ...	Viruses have been with us for billions of years , and exist everywhere in nature that life is found . Viruses therefore have had a significant impact on the evolution of all organisms , from bacteria to humans . Unfortunately , viruses do not leave fossils , and so we know very little about how viruses originate and ev...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology", "microbiology", "and", "infectious", "disease" ]	2016	Tracking interspecies transmission and long-term evolution of an ancient retrovirus using the genomes of modern mammals
Experimental study of the role of disorder in protein function is challenging . It has been proposed that proteins utilize disordered regions in the adaptive recognition of their various binding partners . However apart from a few exceptions , defining the importance of disorder in promiscuous binding interactions has ...	Proteins are made from long chains of smaller molecules , called amino acids , that twist and fold into complex three-dimensional shapes . Folding into the correct shape is crucial for a protein to function properly because many proteins work by binding to certain other proteins or molecules , like a key fitting into a...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2014	Super Spy variants implicate flexibility in chaperone action
The endodermis represents the main barrier to extracellular diffusion in plant roots , and it is central to current models of plant nutrient uptake . Despite this , little is known about the genes setting up this endodermal barrier . In this study , we report the identification and characterization of a strong barrier ...	Plant roots forage in the soil for minerals and water , but they must also provide a barrier that stops these nutrients leaking back out of the plant and stops microbes invading and causing disease . The endodermis—an inner layer of cells that surrounds the veins that run along the middle of a root—acts as such a barri...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology", "cell", "biology" ]	2014	A receptor-like kinase mutant with absent endodermal diffusion barrier displays selective nutrient homeostasis defects
Models based in differential expansion of elastic material , axonal constraints , directed growth , or multi-phasic combinations have been proposed to explain brain folding . However , the cellular and physical processes present during folding have not been defined . We used the murine cerebellum to challenge folding m...	The human brain has a characteristic pattern of ridges and grooves that make up its folded shape . Folds in the outer layer of the brain , known as the cortex , increase the surface area and make more space for cells to connect and form complex circuitries . Different models have been put forward to explain how these f...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "physics", "of", "living", "systems" ]	2019	Cerebellar folding is initiated by mechanical constraints on a fluid-like layer without a cellular pre-pattern
During meiosis , a single round of DNA replication is followed by two consecutive rounds of nuclear divisions called meiosis I and meiosis II . In meiosis I , homologous chromosomes segregate , while sister chromatids remain together . Determining how this unusual chromosome segregation behavior is established is centr...	Diploid organisms contain two sets of chromosomes , one set inherited from the mother and the other from the father . Humans , for example , have 23 pairs of chromosomes , and the chromosomes within each pair are said to be homologous because they are similar to each other in a number of ways , including length and sha...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "cell", "biology" ]	2012	Meiosis I chromosome segregation is established through regulation of microtubule–kinetochore interactions
Calcium-activated chloride channel regulator 1 ( CLCA1 ) activates calcium-dependent chloride currents; neither the target , nor mechanism , is known . We demonstrate that secreted CLCA1 activates calcium-dependent chloride currents in HEK293T cells in a paracrine fashion , and endogenous TMEM16A/Anoctamin1 conducts th...	Many biological processes that are important for our health involve the movement of ions into , and out of , our cells . For example , the flow of chloride ions out of cells controls the production of the sticky mucus that lines our windpipe and other airways . This mucus helps trap pollution and other foreign particle...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2015	Secreted CLCA1 modulates TMEM16A to activate Ca2+-dependent chloride currents in human cells
Conductance-based models of neural activity produce large amounts of data that can be hard to visualize and interpret . We introduce visualization methods to display the dynamics of the ionic currents and to display the models’ response to perturbations . To visualize the currents’ dynamics , we compute the percent con...	The nervous system contains networks of neurons that generate electrical signals to communicate with each other and the rest of the body . Such electrical signals are due to the flow of ions into or out of the neurons via proteins known as ion channels . Neurons have many different kinds of ion channels that only allow...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "tools", "and", "resources", "neuroscience" ]	2019	Visualization of currents in neural models with similar behavior and different conductance densities
In many cell types , lateral diffusion barriers compartmentalize the plasma membrane and , at least in budding yeast , the endoplasmic reticulum ( ER ) . However , the molecular nature of these barriers , their mode of action and their cellular functions are unclear . Here , we show that misfolded proteins of the ER re...	Cell division isn't always about splitting a cell into two identical parts . The diversity of many of our own cells relies on asymmetric cell divisions . The yeast used to make bread rely on a process called ‘budding’ that involves a small daughter cell emerging from the surface of the mother cell . Mother cells can on...	[ "Abstract", "Introduction", "Results", "Discussion", "Material", "and", "methods" ]	[ "cell", "biology" ]	2014	A sphingolipid-dependent diffusion barrier confines ER stress to the yeast mother cell
Although it is currently understood that the exon junction complex ( EJC ) is recruited on spliced mRNA by a specific interaction between its central protein , eIF4AIII , and splicing factor CWC22 , we found that eIF4AIII and the other EJC core proteins Y14 and MAGO bind the nascent transcripts of not only intron-conta...	Cells and organisms survive and thrive in large part due to the activities of thousands of proteins . The instructions for making these proteins are found in the DNA sequences of genes . However , these genes also tend to contain large sections called introns that do not encode protein . To make a protein , the gene’s ...	[ "Abstract", "Introduction", "Results", "Discussion", "Material", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression" ]	2016	Exon junction complex proteins bind nascent transcripts independently of pre-mRNA splicing in Drosophila melanogaster
Fireflies and their luminous courtships have inspired centuries of scientific study . Today firefly luciferase is widely used in biotechnology , but the evolutionary origin of bioluminescence within beetles remains unclear . To shed light on this long-standing question , we sequenced the genomes of two firefly species ...	Glowing fireflies dancing in the dark are one of the most enchanting sights of a warm summer night . Their light signals are ‘love messages’ that help the insects find a mate – yet , they also warn a potential predator that these beetles have powerful chemical defenses . The light comes from a specialized organ of the ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "genetics", "and", "genomics" ]	2018	Firefly genomes illuminate parallel origins of bioluminescence in beetles
Paranoia is the belief that harm is intended by others . It may arise from selective pressures to infer and avoid social threats , particularly in ambiguous or changing circumstances . We propose that uncertainty may be sufficient to elicit learning differences in paranoid individuals , without social threat . We used ...	Everyone has had fleeting concerns that others might be against them at some point in their lives . Sometimes these concerns can escalate into paranoia and become debilitating . Paranoia is a common symptom in serious mental illnesses like schizophrenia . It can cause extreme distress and is linked with an increased ri...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2020	Paranoia as a deficit in non-social belief updating
Viruses interact with hundreds to thousands of proteins in mammals , yet adaptation against viruses has only been studied in a few proteins specialized in antiviral defense . Whether adaptation to viruses typically involves only specialized antiviral proteins or affects a broad array of virus-interacting proteins is un...	When an environmental change occurs , species are able to adapt in response due to mutations in their DNA . Although these mutations occur randomly , by chance some of them make the organism better suited to their new environment . These are known as adaptive mutations . In the past ten years , evolutionary biologists ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Mmethods" ]	[ "evolutionary", "biology", "computational", "and", "systems", "biology" ]	2016	Viruses are a dominant driver of protein adaptation in mammals
Formation of the Drosophila adult abdomen involves a process of tissue replacement in which larval epidermal cells are replaced by adult cells . The progenitors of the adult epidermis are specified during embryogenesis and , unlike the imaginal discs that make up the thoracic and head segments , they remain quiescent d...	Tissues in living organisms are shaped via complex processes that are collectively called ‘morphogenesis’ . Many researchers have used the fruit fly Drosophila as a model to understand morphogenesis , which occurs both during the development of a Drosophila embryo and during metamorphosis ( when the pupa changes to bec...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2015	miR-965 controls cell proliferation and migration during tissue morphogenesis in the Drosophila abdomen
Without transposon-silencing Piwi-interacting RNAs ( piRNAs ) , transposition causes an ovarian atrophy syndrome in Drosophila called gonadal dysgenesis ( GD ) . Harwich ( Har ) strains with P-elements cause severe GD in F1 daughters when Har fathers mate with mothers lacking P-element-piRNAs ( i . e . ISO1 strain ) . ...	DNA provides the instructions needed for life , a role that relies on it being a very stable and organized molecule . However , some sections of DNA are able to move from one place in the genome to another . When these “mobile genetic elements” move they may disrupt other genes and cause disease . For example , a mobil...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "genetics", "and", "genomics" ]	2019	Har-P, a short P-element variant, weaponizes P-transposase to severely impair Drosophila development
The ability to detect and/or manipulate specific cell populations based upon the presence of intracellular protein epitopes would enable many types of studies and applications . Protein binders such as nanobodies ( Nbs ) can target untagged proteins ( antigens ) in the intracellular environment . However , genetically ...	Biologists often wish to study the role of a particular cell type within an organism , but such studies are often not possible due to the lack of reagents that allow one to gain control of the cell type of interest . One method that can be used to detect and manipulate the cells that express specific proteins uses mole...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "neuroscience" ]	2016	Detection and manipulation of live antigen-expressing cells using conditionally stable nanobodies
Cell migration and polarization is controlled by signals in the environment . Migrating cells typically form filopodia that extend from the cell surface , but the precise function of these structures in cell polarization and guided migration is poorly understood . Using the in vivo model of zebrafish primordial germ ce...	Some of the cells in an animal embryo have to migrate long distances to reach their final positions; that is to say , to reach the locations where they will participate in the formation of tissues and organs . The migration of cells is also important throughout the entire lifespan of an animal . White blood cells , for...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2015	Dynamic filopodia are required for chemokine-dependent intracellular polarization during guided cell migration in vivo
Cells of multi-cellular organisms evolve toward uni-cellularity in the form of cancer and , if humans intervene , continue to evolve in cell culture . During this process , gene dosage relationships may evolve in novel ways to cope with the new environment and may regress back to the ancestral uni-cellular state . In t...	Multicellular life relies on a group of cells working together for a common interest . To study these cells , researchers take them out of the organism and grow them in the laboratory . Instead of growing as part of organs and tissues , the cells normally have a free-living lifestyle . Because multicellular life evolve...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology" ]	2017	Free-living human cells reconfigure their chromosomes in the evolution back to uni-cellularity
Senescent cells accumulate in fat with aging . We previously found genetic clearance of senescent cells from progeroid INK-ATTAC mice prevents lipodystrophy . Here we show that primary human senescent fat progenitors secrete activin A and directly inhibit adipogenesis in non-senescent progenitors . Blocking activin A p...	The likelihood of developing metabolic diseases such as diabetes increases with age . This is , in part , because the cells within fat and other tissues become less sensitive to the hormone insulin as people and other animals get older . Also , the stem cells that give rise to new , insulin-responsive fat cells become ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2015	Targeting senescent cells enhances adipogenesis and metabolic function in old age
The ability to form cooperative societies may explain why humans and social insects have come to dominate the earth . Here we examine the ecological consequences of cooperation by quantifying the fitness of cooperative ( large groups ) and non-cooperative ( small groups ) phenotypes in burying beetles ( Nicrophorus nep...	The ability to live and work together in groups likely helped the earliest humans to leave their savannah homes in Africa and successfully settle around the globe . In doing so , humans shifted from being savannah specialists to generalists able to cope with a range of different environments . Cooperation is also belie...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "ecology" ]	2014	Climate-mediated cooperation promotes niche expansion in burying beetles
Recycling of synaptic vesicles ( SVs ) is a fundamental step in the process of neurotransmission . Endocytosed SV can travel directly into the recycling pool or recycle through endosomes but little is known about the molecular actors regulating the switch between these SV recycling routes . ADP ribosylation factor 6 ( ...	Communication between neurons takes place at cell-to-cell contacts called synapses . Each synapse is formed between one neuron that sends the message , and another neuron that receives it . The neuron before the synapse – called the presynaptic neuron – contains packets called synaptic vesicles , which are full of chem...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Arf6 regulates the cycling and the readily releasable pool of synaptic vesicles at hippocampal synapse
A guiding principle in self-assembly is that , for high production yield , nucleation of structures must be significantly slower than their growth . However , details of the mechanism that impedes nucleation are broadly considered irrelevant . Here , we analyze self-assembly into finite-sized target structures employin...	The self-assembly of a large biological molecule from small building blocks is like finishing a puzzle of magnetic pieces by shaking the box . Even though each piece of the puzzle is attracted to its correct neighbours , the limited control makes it very hard to finish the puzzle in a short amount of time . The problem...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "physics", "of", "living", "systems" ]	2020	Stochastic yield catastrophes and robustness in self-assembly
Biofilms are communities of microorganisms attached to a surface or each other . Biofilm-associated cells are the etiologic agents of recurrent Staphylococcus aureus infections . Infected human tissues are hypoxic or anoxic . S . aureus increases biofilm formation in response to hypoxia , but how this occurs is unknown...	Millions of bacteria live on the human body . Generally these bacteria co-exist with us peacefully , but sometimes certain bacteria may enter the body and cause infections , such as gum disease or a bone infection called osteomyelitis . Many of these infections are thought to occur when the bacteria become able to form...	[ "Abstract", "Introduction", "Results", "Discussion", "Material", "and", "methods" ]	[ "microbiology", "and", "infectious", "disease" ]	2017	Impaired respiration elicits SrrAB-dependent programmed cell lysis and biofilm formation in Staphylococcus aureus
Energy conservation in microorganisms is classically categorized into respiration and fermentation; however , recent work shows some species can use mixed or alternative bioenergetic strategies . We explored the use of extracellular electron transfer for energy conservation in diverse lactic acid bacteria ( LAB ) , mic...	Bacteria produce the energy they need to live through two processes , respiration and fermentation . While respiration is often more energetically efficient , many bacteria rely on fermentation as their sole means of energy production . Respiration normally depends on the presence of small soluble molecules , such as o...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "microbiology", "and", "infectious", "disease" ]	2022	Extracellular electron transfer increases fermentation in lactic acid bacteria via a hybrid metabolism
Integrins are transmembrane receptors composed of α and β subunits . Although most integrins contain β1 , canonical activation mechanisms are based on studies of the platelet integrin , αIIbβ3 . Its inactive conformation is characterized by the association of the αIIb transmembrane and cytosolic domain ( TM/CT ) with a...	Proteins called integrins span the membranes of most human cells , and help our cells to interact with their surroundings , enabling them to organise , communicate and to form a variety of structures . Cells in different parts of the body typically produce different integrins so that they can specifically connect with ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "cell", "biology" ]	2016	Implications of the differing roles of the β1 and β3 transmembrane and cytoplasmic domains for integrin function
Mechanical load of the skeleton system is essential for the development , growth , and maintenance of bone . However , the molecular mechanism by which mechanical stimuli are converted into osteogenesis and bone formation remains unclear . Here we report that Piezo1 , a bona fide mechanotransducer that is critical for ...	The bones in our skeletons are constantly exposed to mechanical forces , including those exerted by our muscles and also Earth’s gravity . These forces normally help osteoblasts , the cells which build new bone tissue , ensure that bones grow correctly and remain strong . Removing mechanical loads from bones , however ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2019	The mechanosensitive Piezo1 channel is required for bone formation
Obesity produces a chronic inflammatory state involving the NFκB pathway , resulting in persistent elevation of the noncanonical IκB kinases IKKε and TBK1 . In this study , we report that these kinases attenuate β-adrenergic signaling in white adipose tissue . Treatment of 3T3-L1 adipocytes with specific inhibitors of ...	Obesity is a complex metabolic disorder that is caused by increased food intake and decreased expenditure of energy . Obesity also increases the risk of developing type 2 diabetes , heart disease , stroke , arthritis , and certain cancers . There is considerable evidence to suggest that adipose tissue becomes less sens...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2013	Inflammation produces catecholamine resistance in obesity via activation of PDE3B by the protein kinases IKKε and TBK1
The hemispheric , bi-layered optic cup forms from an oval optic vesicle during early vertebrate eye development through major morphological transformations . The overall basal surface , facing the developing lens , is increasing , while , at the same time , the space basally occupied by individual cells is decreasing ....	The eye is our most important organ for sensing and recognizing our environment . In humans and other vertebrates , the eye forms from an outgrowth of the brain as the embryo develops . This outgrowth is called the optic vesicle and it is rapidly transformed into a cup-shaped structure known as the optic cup . Defects ...	[ "Abstract", "Main", "Text", "Materials", "and", "methods" ]	[ "developmental", "biology", "short", "report", "neuroscience" ]	2015	Eye morphogenesis driven by epithelial flow into the optic cup facilitated by modulation of bone morphogenetic protein
The C-cluster of the enzyme carbon monoxide dehydrogenase ( CODH ) is a structurally distinctive Ni-Fe-S cluster employed to catalyze the reduction of CO2 to CO as part of the Wood-Ljungdahl carbon fixation pathway . Using X-ray crystallography , we have observed unprecedented conformational dynamics in the C-cluster o...	Life relies on countless chemical reactions , almost all of which need to be sped up by enzymes . About half of all enzymes carry metal ions that expand the range of the reactions that they can catalyze . In some enzymes these metal ions assemble with sulfur ions to form so-called metalloclusters . These structures can...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "short", "report", "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2018	Redox-dependent rearrangements of the NiFeS cluster of carbon monoxide dehydrogenase
Ankyrins together with their spectrin partners are the master organizers of micron-scale membrane domains in diverse tissues . The 24 ankyrin ( ANK ) repeats of ankyrins bind to numerous membrane proteins , linking them to spectrin-based cytoskeletons at specific membrane microdomains . The accessibility of the target ...	The membrane that surrounds the cells of animals is organized into regions known as microdomains . Different microdomains have different roles; for example , one microdomain may strengthen the cell while another may contain the apparatus used by cells to signal to each other . A family of proteins called the ankyrins p...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics" ]	2017	Autoinhibition of ankyrin-B/G membrane target bindings by intrinsically disordered segments from the tail regions
Shifting attention among visual stimuli at different locations modulates neuronal responses in heterogeneous ways , depending on where those stimuli lie within the receptive fields of neurons . Yet how attention interacts with the receptive-field structure of cortical neurons remains unclear . We measured neuronal resp...	At any moment , our brain receives an enormous amount of information from our senses . However , we are not aware of all of this information; only the information we decide to focus on is perceived in detail . This ability to focus our attention is important for survival . The neurons involved in vision respond best to...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Attention operates uniformly throughout the classical receptive field and the surround
The process of cell fate determination has been depicted intuitively as cells travelling and resting on a rugged landscape , which has been probed by various theoretical studies . However , few studies have experimentally demonstrated how underlying gene regulatory networks shape the landscape and hence orchestrate cel...	Cells in animals use a process called differentiation to specialize into specific cell types such as skin cells and liver cells . Proteins called transcription factors drive particular steps in differentiation by controlling the activity of specific genes . Many transcription factors interact with each other to form co...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology" ]	2017	Engineering of a synthetic quadrastable gene network to approach Waddington landscape and cell fate determination
A major challenge in biology is identifying distinct cell classes and mapping their interactions in vivo . Tissue-dissociative technologies enable deep single cell molecular profiling but do not provide spatial information . We developed a proximity ligation in situ hybridization technology ( PLISH ) with exceptional s...	The human body contains several hundred types of specialized cells that have different roles . The cells form tissues , and each tissue can only work if it has the right cells and if they are correctly organized and distributed to build working structures . This is how the same body parts , e . g . lungs , brains , hea...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "tools", "and", "resources" ]	2018	Automated cell-type classification in intact tissues by single-cell molecular profiling
Active flight requires the ability to efficiently fuel bursts of costly locomotion while maximizing energy conservation during non-flying times . We took a multi-faceted approach to estimate how fruit-eating bats ( Uroderma bilobatum ) manage a high-energy lifestyle fueled primarily by fig juice . Miniaturized heart ra...	To survive , all animals have to balance how much energy they take in and how much they use . They must find enough food to fuel the chemical processes that keep them alive – known as their metabolism – and store leftover fuel to use when food is not available . Bats , for example , have a fast metabolism and powerful ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "ecology" ]	2017	Cyclic bouts of extreme bradycardia counteract the high metabolism of frugivorous bats
Serum amyloid A ( SAA ) is an evolutionally conserved enigmatic biomarker of inflammation . In acute inflammation , SAA plasma levels increase ~1 , 000 fold , suggesting that this protein family has a vital beneficial role . SAA increases simultaneously with secretory phospholipase A2 ( sPLA2 ) , compelling us to deter...	Cell boundaries are made up of fatty substances known as lipids . When cells get severely damaged , their lipid membranes break apart . These broken fragments of membrane become highly toxic , and must be removed as soon as possible to allow the tissue to heal . A small protein called serum amyloid A , SAA for short , ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "immunology", "and", "inflammation" ]	2019	Synergy between serum amyloid A and secretory phospholipase A2
Experience governs neurogenesis from radial-glial neural stem cells ( RGLs ) in the adult hippocampus to support memory . Transcription factors ( TFs ) in RGLs integrate physiological signals to dictate self-renewal division mode . Whereas asymmetric RGL divisions drive neurogenesis during favorable conditions , symmet...	In humans and other mammals , a region of the brain known as the hippocampus plays important roles in memory . New experiences guide cells in the hippocampus known as radial-glial neural stem cells ( RGLs ) to divide to make new neurons and other types of cells involved in forming memories . Each time an RGL divides , ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "stem", "cells", "and", "regenerative", "medicine", "neuroscience" ]	2022	Transcriptional regulation of neural stem cell expansion in the adult hippocampus
Many small endotherms use torpor to reduce metabolic rate and manage daily energy balance . However , the physiological ‘rules’ that govern torpor use are unclear . We tracked torpor use and body composition in ruby-throated hummingbirds ( Archilochus colubris ) , a long-distance migrant , throughout the summer using r...	Torpor is an energy-saving strategy used by warm-blooded animals , including birds and small mammals . Similar to hibernation , although shorter in duration , torpor is a state of minimal activity , low body temperatures and reduced metabolism that helps animals conserve energy in unfavorable conditions . Some animals ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "ecology", "short", "report", "evolutionary", "biology" ]	2021	Reversal of the adipostat control of torpor during migration in hummingbirds
Hox genes are essential regulators of embryonic development . Their step-wise transcriptional activation follows their genomic topology and the various states of activation are subsequently memorized into domains of progressively overlapping gene products . We have analyzed the 3D chromatin organization of Hox clusters...	Most animals are symmetrical about an imaginary line that runs from the head to the tail . A family of genes called the Hox family ensures that the cells in an animal embryo develop into the correct body parts along this head-to-tail axis . Hox genes—which are found in animals as diverse as flies and humans—are often c...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression" ]	2014	Temporal dynamics and developmental memory of 3D chromatin architecture at Hox gene loci
Recent studies suggest de novo mutations may involve the pathogenesis of autism and attention-deficit/hyperactivity disorder ( ADHD ) . Based on the evidence that excessive alcohol consumption may be associated with an increased rate of de novo mutations in germ cells ( sperms or eggs ) , we examine here whether the ri...	Children learn to talk , manage their emotions , and control their behavior in a period when the brain is developing rapidly . The first signs of several developmental disorders , such as autism and attention-deficit/hyperactivity disorder ( ADHD ) , may also emerge during this period . Children with autism may have di...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "short", "report", "epidemiology", "and", "global", "health" ]	2014	Autism and attention-deficit/hyperactivity disorder among individuals with a family history of alcohol use disorders
Defensive behaviors reflect underlying emotion states , such as fear . The hypothalamus plays a role in such behaviors , but prevailing textbook views depict it as an effector of upstream emotion centers , such as the amygdala , rather than as an emotion center itself . We used optogenetic manipulations to probe the fu...	Animals have evolved a large number of ‘defensive behaviors’ to deal with the threat of predators . Examples include reptiles camouflaging themselves to avoid discovery , fish and birds swarming to confuse predators , insects releasing toxic chemicals , and humans readying themselves to fight or flee . In mammals , def...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	Ventromedial hypothalamic neurons control a defensive emotion state
Stu2p/XMAP215 proteins are essential microtubule polymerases that use multiple αβ-tubulin-interacting TOG domains to bind microtubule plus ends and catalyze fast microtubule growth . We report here the structure of the TOG2 domain from Stu2p bound to yeast αβ-tubulin . Like TOG1 , TOG2 binds selectively to a fully ‘cur...	Dynamic filaments of proteins , called microtubules , have several important roles inside cells . Microtubules provide structural support for the cell; they help to pull chromosomes apart during cell division; and they guide the trafficking of proteins and molecules across the cell . The building blocks of microtubules...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2014	A tethered delivery mechanism explains the catalytic action of a microtubule polymerase
Amyloid protein aggregates are associated with dozens of devastating diseases including Alzheimer’s , Parkinson’s , ALS , and diabetes type 2 . While structure-based discovery of compounds has been effective in combating numerous infectious and metabolic diseases , ignorance of amyloid structure has hindered similar ap...	Alzheimer’s disease is the most common form of dementia , estimated to affect roughly five million people in the United States , and its incidence is steadily increasing as the population ages . A pathological hallmark of Alzheimer’s disease is the presence in the brain of aggregates of two proteins: tangles of a prote...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics" ]	2013	Structure-based discovery of fiber-binding compounds that reduce the cytotoxicity of amyloid beta
Protein kinases have evolved diverse specificities to enable cellular information processing . To gain insight into the mechanisms underlying kinase diversification , we studied the CMGC protein kinases using ancestral reconstruction . Within this group , the cyclin dependent kinases ( CDKs ) and mitogen activated prot...	All living things have enzymes called protein kinases that transfer chemical tags called phosphates onto other proteins . Adding a phosphate to a protein can change the protein's activity—for example , by switching it on or off—and many biological processes involve large networks of kinases that phosphorylate hundreds ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology", "biochemistry", "and", "chemical", "biology" ]	2014	Ancestral resurrection reveals evolutionary mechanisms of kinase plasticity
Phosphorylation of the α-subunit of initiation factor 2 ( eIF2 ) controls protein synthesis by a conserved mechanism . In metazoa , distinct stress conditions activate different eIF2α kinases ( PERK , PKR , GCN2 , and HRI ) that converge on phosphorylating a unique serine in eIF2α . This collection of signaling pathway...	The synthesis of proteins is an essential step in many biological processes , including memory , and drugs that inhibit protein synthesis are known to impair memory in rodents . It is thought that the brain needs these proteins to convert short-term memories into long-term memories through a process known as consolidat...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "neuroscience" ]	2013	Pharmacological brake-release of mRNA translation enhances cognitive memory
Acquired therapeutic resistance by tumors is a substantial impediment to reducing the morbidity and mortality that are attributable to human malignancies . The mechanisms responsible for the dramatic shift between chemosensitivity and chemoresistance in colorectal carcinoma have not been defined . Here , we report that...	Most chemotherapy drugs kill cancer cells by damaging their DNA . The cells have systems to combat this damage and help them to survive , and in some cells these systems work effectively enough to make the cancer effectively resistant to the treatment . For example , a protein called NF-κB can turn on various genes tha...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "cancer", "biology" ]	2017	Blockade of the LRP16-PKR-NF-κB signaling axis sensitizes colorectal carcinoma cells to DNA-damaging cytotoxic therapy
The striatum is an input structure of the basal ganglia implicated in several time-dependent functions including reinforcement learning , decision making , and interval timing . To determine whether striatal ensembles drive subjects' judgments of duration , we manipulated and recorded from striatal neurons in rats perf...	You know someone is a good cook from their rice - grains must be well cooked , but not to the point of being mushy . Despite consistently using the same pot and stove , we , however , will sometimes overcook it . It is as if our inner sense of time itself is variable . What is it about the brain that explains this vari...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	Striatal dynamics explain duration judgments
In many species , males can make rapid adjustments to ejaculate performance in response to sperm competition risk; however , the mechanisms behind these changes are not understood . Here , we manipulate male social status in an externally fertilising fish , chinook salmon ( Oncorhynchus tshawytscha ) , and find that in...	Males of many animal species fight to establish social dominance and control access to females so that they have more opportunities to reproduce than their competitors . Males with lower social status will struggle to directly compete for mates , thus they attempt to mate with females by stealth . This often leads to m...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology" ]	2017	Sperm competition risk drives rapid ejaculate adjustments mediated by seminal fluid
Human calcium-sensing receptor ( CaSR ) is a G-protein-coupled receptor ( GPCR ) that maintains extracellular Ca2+ homeostasis through the regulation of parathyroid hormone secretion . It functions as a disulfide-tethered homodimer composed of three main domains , the Venus Flytrap module , cysteine-rich domain , and s...	Calcium ions regulate many processes in the human body . The calcium-sensing receptor , called CaSR , is responsible for maintaining a stable level of calcium ions in the blood . This receptor can detect small changes in the concentration of calcium ions , and activates signalling events within the cell to restore the ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2016	Structural mechanism of ligand activation in human calcium-sensing receptor
The light environment greatly impacts human alertness , mood , and cognition by both acute regulation of physiology and indirect alignment of circadian rhythms . These processes require the melanopsin-expressing intrinsically photosensitive retinal ganglion cells ( ipRGCs ) , but the relevant downstream brain areas inv...	Light , whether natural or artificial , affects our everyday lives in several ways . Exposure to light impacts on our health and well-being . It plays a crucial but indirect role in helping to align our internal body clock with the 24-hour cycle of day and night , and a burst of bright light in the middle of the night ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2019	Distinct ipRGC subpopulations mediate light’s acute and circadian effects on body temperature and sleep
Endoplasmic reticulum ( ER ) stress is implicated in many chronic diseases , but very little is known about how the unfolded protein response ( UPR ) responds to persistent ER stress in vivo . Here , we experimentally reconstituted chronic ER stress in the mouse liver , using repeated injection of a low dose of the ER ...	Toxic chemicals , extreme temperatures and other abnormal environmental conditions can cause the cells in our bodies to become stressed . Several kinds of stresses overwhelm a compartment in the cell called the endoplasmic reticulum , which is critical for processing new proteins so that they can work correctly . Endop...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2016	Experimental reconstitution of chronic ER stress in the liver reveals feedback suppression of BiP mRNA expression
To understand the function of eukaryotic cells , it is critical to understand the role of protein-protein interactions and protein localization . Currently , we do not know the importance of global protein localization nor do we understand to what extent the cell is permissive for new protein associations – a key requi...	Our actions often depend on who we interact with: parents , teachers , friends , colleagues . So it is for proteins in the cell: their function depends on which other proteins they work with . If a protein interacts with new partners or ends up in a new neighborhood of the cell , it can perform an entirely unexpected r...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "tools", "and", "resources" ]	2016	Synthetic protein interactions reveal a functional map of the cell
Mobile integrons are widespread genetic platforms that allow bacteria to modulate the expression of antibiotic resistance cassettes by shuffling their position from a common promoter . Antibiotic stress induces the expression of an integrase that excises and integrates cassettes , and this unique recombination and expr...	From urinary tract infections to bacterial pneumonia , many diseases can now be treated through a course of antibiotics . Yet bacteria have evolved to respond to this threat , gaining new antibiotic resistance genes that allow them to evade the drugs . Addressing this growing issue requires to either discover new antib...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology", "microbiology", "and", "infectious", "disease" ]	2021	Integron activity accelerates the evolution of antibiotic resistance

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