December 2016

Research articles

    1. Structural Biology and Molecular Biophysics

    Measuring the sequence-affinity landscape of antibodies with massively parallel titration curves

    Rhys M Adams, Thierry Mora ... Justin B Kinney
    The absolute affinities of thousands of variant antibodies are measured in parallel using a combination of cell sorting and high-throughput DNA sequencing.
    1. Computational and Systems Biology
    2. Immunology and Inflammation

    Adequate immune response ensured by binary IL-2 and graded CD25 expression in a murine transfer model

    Franziska Fuhrmann, Timo Lischke ... Ria Baumgrass
    A murine adoptive transfer model shows that binary IL-2 and graded CD25 expression tailor the T helper cell response to the antigen amount in vivo.
    1. Computational and Systems Biology
    2. Neuroscience

    Dendritic trafficking faces physiologically critical speed-precision tradeoffs

    Alex H Williams, Cian O'Donnell ... Timothy O'Leary
    A simple model of active transport in neurons allows intracellular cargo to find sites of demand using only local signals, but predicts long delays in distributing cargo throughout a dendritic tree.
    1. Immunology and Inflammation
    2. Neuroscience

    Peripherally administered orexin improves survival of mice with endotoxin shock

    Yasuhiro Ogawa, Yoko Irukayama-Tomobe ... Masashi Yanagisawa
    When the neuropeptide orexin is peripherally administered in mice with septic shock, it penetrates the blood-brain barrier and acts in the brain to improve survival through multiple autonomic and neuroendocrine pathways.
    1. Neuroscience

    Perceptually relevant remapping of human somatotopy in 24 hours

    James Kolasinski, Tamar R Makin ... Heidi Johansen-Berg
    A combination of 7 tesla fMRI and psychophysics revealed the reorganisation of the human somatosensory cortex and changes in tactile perceptual abilities after just 24 hours of altered hand use.
    1. Cell Biology
    2. Developmental Biology

    Drosophila non-muscle myosin II motor activity determines the rate of tissue folding

    Claudia G Vasquez, Sarah M Heissler ... Adam C Martin
    The rate of cell and tissue contraction scales with the motor activity of myosin 2.
    1. Neuroscience

    Binocular matching of thalamocortical and intracortical circuits in the mouse visual cortex

    Yu Gu, Jianhua Cang
    The binocular matching of thalamic inputs to layer 4 cortical neurons initiates before that of intracortical inputs.
    1. Biochemistry and Chemical Biology
    2. Chromosomes and Gene Expression

    The Chd1 chromatin remodeler shifts hexasomes unidirectionally

    Robert F Levendosky, Anton Sabantsev ... Gregory D Bowman
    Oriented hexasomes can be generated using the Widom 601 positioning sequence, which enables straightforward production of nucleosomes with asymmetrically modified H2A/H2B dimers.
    1. Neuroscience

    Visual projection neurons in the Drosophila lobula link feature detection to distinct behavioral programs

    Ming Wu, Aljoscha Nern ... Gerald M Rubin
    Neurons called lobula columnar cells help fruit flies respond appropriately to specific visual cues, such as those signaling an approaching predator.
    1. Neuroscience

    SUMOylation of NaV1.2 channels mediates the early response to acute hypoxia in central neurons

    Leigh D Plant, Jeremy D Marks, Steve AN Goldstein
    The immediate response of the brain to a sudden, harmful drop in oxygen supply is the addition of SUMO proteins to sodium ion channels in neurons, increasing their activity.
    1. Ecology

    Harbouring public good mutants within a pathogen population can increase both fitness and virulence

    Richard J Lindsay, Michael J Kershaw ... Ivana Gudelj
    Cooperation theory and a novel synthetic infection system provides a mechanistic understanding of why a seemingly successful disease management strategy can have devastating consequences for infected hosts.
    1. Neuroscience

    Activity-dependent switch of GABAergic inhibition into glutamatergic excitation in astrocyte-neuron networks

    Gertrudis Perea, Ricardo Gómez ... Alfonso Araque
    Astrocytes decode temporal interneuron activity and transform inhibitory into excitatory signals that impact excitatory synaptic strength and neuronal circuit function.
    1. Cell Biology
    2. Microbiology and Infectious Disease

    EMC1-dependent stabilization drives membrane penetration of a partially destabilized non-enveloped virus

    Parikshit Bagchi, Takamasa Inoue, Billy Tsai
    Biochemical and cell-based analyses reveal how a non-enveloped virus exploits the chaperone activity of an ER transmembrane protein to penetrate the ER membrane required for successful virus infection.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Molecular basis of outer kinetochore assembly on CENP-T

    Pim J Huis in 't Veld, Sadasivam Jeganathan ... Andrea Musacchio
    The centromeric protein CENP-T assembles the microtubule-binding interface of kinetochores through direct recruitment of two Ndc80 complexes and indirect recruitment of a third one through the Mis12 complex.
    1. Developmental Biology
    2. Chromosomes and Gene Expression

    Spatiotemporal coupling and decoupling of gene transcription with DNA replication origins during embryogenesis in C. elegans

    Ehsan Pourkarimi, James M Bellush, Iestyn Whitehouse
    Replication origins are fundamental organizers and regulators of gene activity through embryonic development.
    1. Structural Biology and Molecular Biophysics
    2. Chromosomes and Gene Expression

    Structural snapshots of Xer recombination reveal activation by synaptic complex remodeling and DNA bending

    Aleksandra Bebel, Ezgi Karaca ... Orsolya Barabas
    DNA-bound crystal structures of an essential Xer site-specific recombinase from the bacterium Helicobacter pylori reveal how large conformational changes initiate the untangling of chromosomes upon cell division.
    1. Neuroscience

    Translational control of auditory imprinting and structural plasticity by eIF2α

    Gervasio Batista, Jennifer Leigh Johnson ... Jose L Pena
    Behavioral pharmacology and molecular biology reveal a translational control mechanism underlying auditory imprinting and structural plasticity that can be pharmacologically manipulated to reopen the critical period.
    1. Cell Biology

    Functional dichotomy and distinct nanoscale assemblies of a cell cycle-controlled bipolar zinc-finger regulator

    Johann Mignolet, Seamus Holden ... Patrick H Viollier
    Forward genetics and super-resolution microscopy identifies ZitP as a conserved multifunctional regulator that accumulates at both cell extremities in distinct macromolecular structures to perform different functions in the asymmetric model bacterium Caulobacter crescentus.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Ric-8A, a G protein chaperone with nucleotide exchange activity induces long-range secondary structure changes in Gα

    Ravi Kant, Baisen Zeng ... Stephen R Sprang
    Hydrogen-Deuterium exchange experiments show that Ric-8A induces similar dynamic changes in the structure of Gα as G protein-coupled receptors, yet protects a larger surface of the nucleotide-binding Ras domain.
    1. Biochemistry and Chemical Biology
    2. Microbiology and Infectious Disease

    Translation initiation by the hepatitis C virus IRES requires eIF1A and ribosomal complex remodeling

    Zane A Jaafar, Akihiro Oguro ... Jeffrey S Kieft
    The hepatitis C virus IRES binds and remodels preassembled eukaryotic translation preinitiation complexes, using specific initiation factor protein within a "bacterial-like" mode of initiation that can function in both stressed and unstressed cells.
    1. Plant Biology

    Pathogen effectors and plant immunity determine specialization of the blast fungus to rice subspecies

    Jingjing Liao, Huichuan Huang ... Jean-Benoit Morel
    Specialized fungal pathogen populations infect rice varieties with contrasting immune systems co-cultivated in a traditional agro-system, indicating the relevance of crop diversity to restricting epidemics in the landscape.
    1. Cell Biology
    2. Chromosomes and Gene Expression

    Modularity and determinants of a (bi-)polarization control system from free-living and obligate intracellular bacteria

    Matthieu Bergé, Sébastien Campagne ... Patrick H Viollier
    Common ancestries, activities and structural determinants of a modular (bi-)polarization control system encoded in free-living and obligate intracellular α-proteobacteria, including the rickettsial pathogens, are described.
    1. Computational and Systems Biology
    2. Neuroscience

    Interneuronal mechanisms of hippocampal theta oscillations in a full-scale model of the rodent CA1 circuit

    Marianne J Bezaire, Ivan Raikov ... Ivan Soltesz
    Spontaneous theta oscillations and interneuron-specific phase preferences emerge spontaneously in a full-scale model of the isolated hippocampal CA1 subfield, corroborating and extending recent experimental findings.
    1. Structural Biology and Molecular Biophysics
    2. Microbiology and Infectious Disease

    Structural basis for the inhibition of RecBCD by Gam and its synergistic antibacterial effect with quinolones

    Martin Wilkinson, Luca A Troman ... Dale B Wigley
    Building on previous work (Wilkinson et al, 2016), it is shown that inhibition of RecBCD-induced DNA break repair can be used as a co-antibacterial strategy with quinolones.
    1. Plant Biology

    Dormancy-specific imprinting underlies maternal inheritance of seed dormancy in Arabidopsis thaliana

    Urszula Piskurewicz, Mayumi Iwasaki ... Luis Lopez-Molina
    A genomic imprinting program in the endosperm of Arabidopsis mature seeds is dynamically adjusted according to seed dormancy levels and regulates germination.
    1. Neuroscience

    Immediate perception of a reward is distinct from the reward’s long-term salience

    John P McGinnis, Huoqing Jiang ... Kausik Si
    The experiences that are most rewarding at the time are not necessarily those that are remembered long-term.
    1. Neuroscience

    Response repetition biases in human perceptual decisions are explained by activity decay in competitive attractor models

    James J Bonaiuto, Archy de Berker, Sven Bestmann
    Residual activity from previous trials in a biophysical decision network model causes biases in choice behavior such that a previous response is more likely to be repeated.
    1. Developmental Biology

    Angiopoietin receptor Tie2 is required for vein specification and maintenance via regulating COUP-TFII

    Man Chu, Taotao Li ... Yulong He
    Analyses with genetically engineered mouse models in combination with biochemical approaches reveal a crucial role of the receptor tyrosine kinase Tie2 mediated signals in venogenesis via an Akt mediated regulation of COUP-TFII protein stabilization.
    1. Developmental Biology

    Functional evolution of a morphogenetic gradient

    Chun Wai Kwan, Jackie Gavin-Smyth ... Urs Schmidt-Ott
    BMP guides the evolution of extraembryonic tissue complexity in fly embryos through changes in the control of a positive feedback circuit.
    1. Structural Biology and Molecular Biophysics
    2. Microbiology and Infectious Disease

    Coincidence detection and bi-directional transmembrane signaling control a bacterial second messenger receptor

    Richard B Cooley, John P O’Donnell, Holger Sondermann
    Building on previous work (Chatterjee et al., 2014), the mechanism of coincidence detection in bacterial second messenger signaling across membranes is revealed at a molecular level, providing insight into the regulation of a conserved transmembrane receptor.
    1. Cell Biology

    A microRNA negative feedback loop downregulates vesicle transport and inhibits fear memory

    Rebecca S Mathew, Antonis Tatarakis ... Danesh Moazed
    A fear conditioning-induced miRNA acts in a negative feedback loop that targets vesicle exocytosis and neurotransmitter receptor trafficking, and inhibits memory formation.
    1. Structural Biology and Molecular Biophysics

    Cryo-EM structures of the autoinhibited E. coli ATP synthase in three rotational states

    Meghna Sobti, Callum Smits ... Alastair G Stewart
    A molecular model that provides a framework for interpreting the wealth of functional information obtained on the E. coli F-ATP synthase has been generated using cryo-electron microscopy.
    1. Cell Biology

    Hypoxic mitophagy regulates mitochondrial quality and platelet activation and determines severity of I/R heart injury

    Weilin Zhang, He Ren ... Quan Chen
    Mitophagy regulates mitochondrial quality and mediates extensive mitochondrial degradation in (patho-)physiological settings and is one of the key components of hypoxic preconditioning which protects the heart from ischemia/reperfusion injury.
    1. Genetics and Genomics

    Comparative genetic screens in human cells reveal new regulatory mechanisms in WNT signaling

    Andres M Lebensohn, Ramin Dubey ... Rajat Rohatgi
    A systematic genetic analysis comprising seven genome-wide screens in haploid human cells uncovered new regulatory mechanisms at most levels in the WNT signaling pathway.
    1. Neuroscience

    Early dysfunction and progressive degeneration of the subthalamic nucleus in mouse models of Huntington's disease

    Jeremy F Atherton, Eileen L McIver ... Mark D Bevan
    In mouse models of Huntington's disease, the subthalamic nucleus, which suppresses movements, also exhibits impaired glutamate homeostasis, NMDA receptor-dependent mitochondrial oxidant stress, firing disruption, and 30% neuronal loss.
    1. Neuroscience

    CCR5 is a suppressor for cortical plasticity and hippocampal learning and memory

    Miou Zhou, Stuart Greenhill ... Alcino J Silva
    Repression of the G protein-coupled chemokine receptor CCR5 enhances MAPK/CREB signaling, long-term potentiation, somatosensory cortical plasticity, and learning and memory, while CCR5 over-activation by viral proteins may contribute to HIV-associated cognitive deficits.
    1. Ecology

    Carbon recovery dynamics following disturbance by selective logging in Amazonian forests

    Camille Piponiot, Plinio Sist ... Bruno Hérault
    Carbon recovery in Amazonian forests disturbed by selective logging is higher in the Guiana Shield and in the west, and is mainly shaped by the carbon gain of trees that survived the disturbance.
    1. Cancer Biology
    2. Cell Biology

    Sam68/KHDRBS1-dependent NF-κB activation confers radioprotection to the colon epithelium in γ-irradiated mice

    Kai Fu, Xin Sun ... Fengyi Wan
    Building on previous work (Fu et al., 2016), we demonstrate the critical role of Sam68 in orchestrating genotoxic stress-initiated NF-κB signaling in the colon and the pathophysiological relevance of Sam68-dependent NF-κB activation in colonic cell survival/recovery from extrinsic DNA damage.
    1. Developmental Biology

    Prostaglandin signaling regulates nephron segment patterning of renal progenitors during zebrafish kidney development

    Shahram Jevin Poureetezadi, Christina N Cheng ... Rebecca A Wingert
    Prostaglandin synthesis and PGE2 receptor activity are essential for mediating segmentation of renal progenitors during pronephros formation in the zebrafish.
    1. Cell Biology

    IRBIT controls apoptosis by interacting with the Bcl-2 homolog, Bcl2l10, and by promoting ER-mitochondria contact

    Benjamin Bonneau, Hideaki Ando ... Katsuhiko Mikoshiba
    IRBIT and the Bcl-2 homolog Bcl2l10 form a complex at the endoplasmic reticulum that controls Ca2+ signaling, however IRBIT turns into an apoptosis facilitator following stress and inhibits anti-apoptotic activity of Bcl2l10.
    1. Developmental Biology

    Transcriptional signatures of somatic neoblasts and germline cells in Macrostomum lignano

    Magda Grudniewska, Stijn Mouton ... Eugene Berezikov
    De novo transcriptome assembly and comprehensive characterization of gene expression in proliferating cells of regeneration-capable flatworm Macrostomum lignano advance this organism as a powerful model for stem cell research.
    1. Structural Biology and Molecular Biophysics
    2. Neuroscience

    Neurodegenerative disease mutations in TREM2 reveal a functional surface and distinct loss-of-function mechanisms

    Daniel L Kober, Jennifer M Alexander-Brett ... Thomas J Brett
    Structural, biophysical, and functional analyses reveal that mutations in TREM2 trigger either misfolding or reduced binding to cell-surface glycosaminoglycans, which segregate with neurodegenerative disease link and highlight a functional surface linked to the pathogenesis of Alzheimer's disease.
    1. Neuroscience

    Semi-intact ex vivo approach to investigate spinal somatosensory circuits

    Junichi Hachisuka, Kyle M Baumbauer ... Sarah E Ross
    A new spinal somatosensory preparation is described which enables fine control of sensory input and the ability to manipulate spinal interneurons while recording from spinal projection neurons.
    1. Cell Biology
    2. Neuroscience

    Mitochondrial support of persistent presynaptic vesicle mobilization with age-dependent synaptic growth after LTP

    Heather L Smith, Jennifer N Bourne ... Kristen M Harris
    Three-dimensional electron microscopy (3DEM) demonstrates the dependence on presynaptic mitochondria for vesicle mobilization as dendritic spines are silently added at P15 or synapses are silently enlarged in adults after long-term potentiation.
    1. Structural Biology and Molecular Biophysics

    Epithelial magnesium transport by TRPM6 is essential for prenatal development and adult survival

    Vladimir Chubanov, Silvia Ferioli ... Thomas Gudermann
    Mice deficient in the TRPM6 channel suffer from impaired prenatal development, shortened lifespan, growth deficit and disturbed energy balance due to a defect in epithelial Mg2+ uptake, thus highlighting a pivotal role of TRPM6 in organismal Mg2+ homeostasis.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Relief of autoinhibition by conformational switch explains enzyme activation by a catalytically dead paralog

    Oleg A Volkov, Lisa Kinch ... Margaret A Phillips
    A catalytically dead paralog activates its cognate enzyme through an allosteric mechanism that combined structural and phylogenomic analysis indicates arose through acquisition of a dimerization domain, suggesting a general model for how complex allostery evolves.
    1. Neuroscience

    Spinal microcircuits comprising dI3 interneurons are necessary for motor functional recovery following spinal cord transection

    Tuan V Bui, Nicolas Stifani ... Robert M Brownstone
    A genetically-defined population of spinal interneurons is reciprocally connected with spinal locomotor circuits and mediates recovery of locomotor function following spinal cord transection.
    1. Developmental Biology
    2. Neuroscience

    Stereotyped responses of Drosophila peptidergic neuronal ensemble depend on downstream neuromodulators

    Wilson Mena, Sören Diegelmann ... John Ewer
    The response of the peptidergic neurons that control a stereotyped behavior depends on the actions of a triggering neuropeptide, downstream neuropeptides and GABA inhibitory influences.
    1. Genetics and Genomics

    Genetic and environmental influences on adult human height across birth cohorts from 1886 to 1994

    Aline Jelenkovic, Yoon-Mi Hur ... Karri Silventoinen
    Genetic variance of adult human height shows a generally increasing trend across the birth-year cohorts but heritability estimates do not present any clear pattern of secular changes over a century.
    1. Evolutionary Biology

    New footprints from Laetoli (Tanzania) provide evidence for marked body size variation in early hominins

    Fidelis T Masao, Elgidius B Ichumbaki ... Giorgio Manzi
    Bipedal footprints made 3.66 million years ago provide the clearest available evidence to date of the occurrence of marked body size variation in Australopithecus afarensis..
    1. Plant Biology

    Multiple alleles at a single locus control seed dormancy in Swedish Arabidopsis

    Envel Kerdaffrec, Danièle L Filiault ... Magnus Nordborg
    Natural variation for an adaptively important life history trait is largely due to variation at a single, major-effect locus with multiple alleles, demonstrating that not all complex traits are massively polygenic.
    1. Cell Biology
    2. Developmental Biology

    Fine-tuning of Notch signaling sets the boundary of the organ of Corti and establishes sensory cell fates

    Martin L Basch, Rogers M Brown II ... Andrew K Groves
    The cochlea deploys two Fringe proteins at exactly the same time and position to regulate a novel mode of Notch signaling that sets the boundary of the organ of Corti, the ear's hearing organ.
    1. Developmental Biology

    Clec11a/osteolectin is an osteogenic growth factor that promotes the maintenance of the adult skeleton

    Rui Yue, Bo Shen, Sean J Morrison
    A C-type lectin domain protein is an anabolic growth factor that promotes mesenchymal progenitors in the bone marrow to differentiate into bone cells to maintain skeletal bone mass throughout adult life.
    1. Developmental Biology
    2. Microbiology and Infectious Disease

    A conserved bacterial protein induces pancreatic beta cell expansion during zebrafish development

    Jennifer Hampton Hill, Eric A Franzosa ... Karen Guillemin
    A previously undescribed protein produced by certain resident intestinal bacteria induces zebrafish pancreatic beta cell expansion.
    1. Cell Biology
    2. Neuroscience

    An alternative splicing switch shapes neurexin repertoires in principal neurons versus interneurons in the mouse hippocampus

    Thi-Minh Nguyen, Dietmar Schreiner ... Peter Scheiffele
    Interneuron-specific alternative splice variants of the synaptic receptor neurexin are critical for hippocampal network activity and short-term memory.
    1. Neuroscience

    Acetylated tubulin is essential for touch sensation in mice

    Shane J Morley, Yanmei Qi ... Paul A Heppenstall
    Increased stiffness of sensory neurons in the absence of microtubule acetylation renders mice profoundly insensitive to touch and pain.
    1. Neuroscience

    eIF2α-mediated translational control regulates the persistence of cocaine-induced LTP in midbrain dopamine neurons

    Andon N Placzek, Gonzalo Viana Di Prisco ... Mauro Costa-Mattioli
    Building on previous work (Huang et al., 2016), we show that translational control by p-eIF2α is a defense mechanism that prevents persistent cocaine-induced synaptic synaptic potentiation underlying compulsive drug seeking.
    1. Cell Biology

    A plasma membrane template for macropinocytic cups

    Douwe M Veltman, Thomas D Williams ... Robert R Kay
    Rings of actin polymerisation that form around PIP3/Ras patches in the cell membrane drive the formation of macropinocytic cups.
    1. Structural Biology and Molecular Biophysics
    2. Microbiology and Infectious Disease

    Regulation of signaling directionality revealed by 3D snapshots of a kinase:regulator complex in action

    Felipe Trajtenberg, Juan A Imelio ... Alejandro Buschiazzo
    The molecular mechanism of switching between phosphotransferase- and phosphatase-competent states in histidine-kinases has been uncovered, through direct crystallographic observation of bona fide complexes between a histidine-kinase and its response regulator from Bacillus subtilise.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Cellular encoding of Cy dyes for single-molecule imaging

    Lilia Leisle, Rahul Chadda ... Christopher A Ahern
    Cyanine fluorophores are encoded as non-canonical amino acids to produce functional proteins in cell-free translation systems and live cells for single-molecule imaging.
    1. Cell Biology

    Akt1-Inhibitor of DNA binding2 is essential for growth cone formation and axon growth and promotes central nervous system axon regeneration

    Hyo Rim Ko, Il-Sun Kwon ... Jee-Yin Ahn
    Akt mediated S14 phosphorylation of Id2 augments its protein stability and growth cone localization, promoting growth cone formation and axon growth in the developing neuron and contributing to axon regeneration in the damaged hippocampus slice.
    1. Chromosomes and Gene Expression
    2. Plant Biology

    Biogenesis of phased siRNAs on membrane-bound polysomes in Arabidopsis

    Shengben Li, Brandon Le ... Xuemei Chen
    Arabidopsis microRNAs and their effector protein ARGONAUTE1 associate with and act on polysomes on the rough endoplasmic reticulum.
    1. Cell Biology

    Experimental reconstitution of chronic ER stress in the liver reveals feedback suppression of BiP mRNA expression

    Javier A Gomez, D Thomas Rutkowski
    Feedback mechanisms that contribute to the deactivation of the unfolded protein response lead to the dysregulation of mRNA expression during chronic stress in the liver, including that of the critical endoplasmic reticulum chaperone BiP.
    1. Structural Biology and Molecular Biophysics
    2. Computational and Systems Biology

    Transient protein-protein interactions perturb E. coli metabolome and cause gene dosage toxicity

    Sanchari Bhattacharyya, Shimon Bershtein ... Eugene I Shakhnovich
    Weak yet highly species-specific protein-protein interactions enhance the activity of metabolically related enzymes in bacteria at endogenous conditions, but also mean that overexpression of one partner leads to permanent non-physiological complexes and gene dosage toxicity.
    1. Neuroscience

    Distinct memory engrams in the infralimbic cortex of rats control opposing environmental actions on a learned behavior

    Nobuyoshi Suto, Amanda Laque ... Friedbert Weiss
    Current findings help reconcile the contradictory reports regarding the role of infralimbic cortex in the environmental control of appetitive behavior.
    1. Chromosomes and Gene Expression

    RNase H enables efficient repair of R-loop induced DNA damage

    Jeremy D Amon, Douglas Koshland
    In addition to causing DNA damage, R-loops cause genomic instability by interfering with DNA repair.
    1. Developmental Biology
    2. Neuroscience

    Thalamo-cortical axons regulate the radial dispersion of neocortical GABAergic interneurons

    Sabrina Zechel, Yasushi Nakagawa, Carlos F Ibáñez
    Glutamate derived from thalamo-cortical axons regulates the radial dispersion of interneurons in the developing mouse neocortex by limiting the level of expression of the K/Cl co-transporter KCC2.
    1. Neuroscience

    Optimal compensation for neuron loss

    David GT Barrett, Sophie Denève, Christian K Machens
    Spiking networks compensate the loss of neurons instantaneously, when restoration of excitatory/inhibitory balance becomes equivalent to restoration of functionality.
    1. Cell Biology
    2. Immunology and Inflammation

    Regulation of B cell fate by chronic activity of the IgE B cell receptor

    Zhiyong Yang, Marcus J Robinson ... Christopher D C Allen
    The immunoglobulin E (IgE) B cell receptor promotes plasma cell differentiation in the absence of cognate antigen and limits the competitive fitness of IgE+ B cells in germinal centers.
    1. Cancer Biology

    Assessing the mechanism and therapeutic potential of modulators of the human Mediator complex-associated protein kinases

    Paul A Clarke, Maria-Jesus Ortiz-Ruiz ... Dirk Wienke
    Detailed molecular profiling investigations alongside antitumor testing and tolerability studies in animals suggest caution when considering the clinical development of inhibitors of CDK8 and CDK19, since a clear therapeutic window could not be demonstrated with two structurally distinct, potent and selective prototype drugs.
    1. Structural Biology and Molecular Biophysics
    2. Neuroscience

    Structural basis for subtype-specific inhibition of the P2X7 receptor

    Akira Karasawa, Toshimitsu Kawate
    Crystal structures of a mammalian P2X7 receptor and structure-based functional studies reveal a novel drug-binding site and subtype-specific conformational rearrangements required for channel opening.
    1. Structural Biology and Molecular Biophysics
    2. Immunology and Inflammation

    Structure of the transporter associated with antigen processing trapped by herpes simplex virus

    Michael L Oldham, Nikolaus Grigorieff, Jue Chen
    Herpes simplex virus evades the immune response by inhibiting the TAP transporter with a peptide inhibitor ICP47 that has an extensive interface at the peptide translocation cavity and locks the transporter in an inactive state.
    1. Neuroscience

    Genome-wide identification of neuronal activity-regulated genes in Drosophila

    Xiao Chen, Reazur Rahman ... Michael Rosbash
    Activity-regulated genes in Drosophila neurons differ from the well-characterized situation in mammals, and these genes provided a strategy to construct reporters for monitoring neuronal activity in fly brains.
    1. Structural Biology and Molecular Biophysics
    2. Cell Biology

    Labeling proteins inside living cells using external fluorophores for microscopy

    Kai Wen Teng, Yuji Ishitsuka ... Paul R Selvin
    A toxin is used to introduce an otherwise cell-impermeant fluorophore-antibody (or some thing which is equally specific) to bind to an intracellular protein which allows for super resolution imaging and single particle tracking inside the living cell.
    1. Computational and Systems Biology
    2. Neuroscience

    Flexible theta sequence compression mediated via phase precessing interneurons

    Angus Chadwick, Mark CW van Rossum, Matthew F Nolan
    A new model for phase precession accounts for theta sequence generation, suggests critical roles for interneurons, and predicts circuit properties to optimise memory storage.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Implications of the differing roles of the β1 and β3 transmembrane and cytoplasmic domains for integrin function

    Zhenwei Lu, Sijo Mathew ... Roy Zent
    Diverse biophysical properties of β1 and β3 integrin transmembrane and cytoplasmic domains result in distinct mechanisms of integrin activation and function.
    1. Structural Biology and Molecular Biophysics

    The angiopoietin-like protein ANGPTL4 catalyzes unfolding of the hydrolase domain in lipoprotein lipase and the endothelial membrane protein GPIHBP1 counteracts this unfolding

    Simon Mysling, Kristian Kølby Kristensen ... Michael Ploug
    Building on previous work (Mysling et al., 2016), it is shown that angiopoietin-like protein 4 (ANGPTL4) inhibits lipoprotein lipase activity by catalyzing the unfolding of its hydrolase domain.
    1. Neuroscience

    Stimulus-dependent recruitment of lateral inhibition underlies retinal direction selectivity

    Qiang Chen, Zhe Pei ... Wei Wei
    Synapse-specific genetic manipulations show that distinct GABAergic inputs are differentially recruited to encode motion direction in the retina in a stimulus-dependent manner.
    1. Biochemistry and Chemical Biology

    Prefabrication of a ribosomal protein subcomplex essential for eukaryotic ribosome formation

    Cohue Peña, Sabina Schütz ... Vikram G Panse
    The ATPase Fap7 prefabricates a uS11:eS26 ribosomal protein complex for ribosome assembly.
    1. Cancer Biology
    2. Immunology and Inflammation

    Tumor-induced MDSC act via remote control to inhibit L-selectin-dependent adaptive immunity in lymph nodes

    Amy W Ku, Jason B Muhitch ... Sharon S Evans
    Tumor-induced myeloid-derived suppressor cells exert systemic suppression of adaptive immunity by limiting L-selectin-directed trafficking of T cells at vascular checkpoints in lymph nodes.
    1. Neuroscience

    On cross-frequency phase-phase coupling between theta and gamma oscillations in the hippocampus

    Robson Scheffer-Teixeira, Adriano BL Tort
    Phase-locking of hippocampal theta and gamma waves has been proposed to support memory formation, but an analysis using robust statistical methods finds no convincing evidence for the phenomenon.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Multiple selection filters ensure accurate tail-anchored membrane protein targeting

    Meera Rao, Voytek Okreglak ... Shu-ou Shan
    Biochemical dissections show that the Guided Entry of Tail Anchored proteins (GET) pathway selects ER-destined tail-anchored proteins using at least two distinct molecular mechanisms, each recognizing a distinct physicochemical feature in the substrate.
    1. Neuroscience

    Inhibitory control of correlated intrinsic variability in cortical networks

    Carsen Stringer, Marius Pachitariu ... Nicholas A Lesica
    A new cortical network model fit directly to multi-neuron recordings reveals that local inhibitory feedback can control neural dynamics, modulate brain state and enhance sensory processing.
    1. Cell Biology

    Calcium-mediated actin reset (CaAR) mediates acute cell adaptations

    Pauline Wales, Christian E Schuberth ... Roland Wedlich-Söldner
    Calcium influx during acute cell stimulation triggers a global actin reset in mammalian cells, which is linked to plasma membrane repair and transcription and has implications for our understanding of cell migration, cancer, inflammation and cell stress response.
    1. Chromosomes and Gene Expression

    Direct screening for chromatin status on DNA barcodes in yeast delineates the regulome of H3K79 methylation by Dot1

    Hanneke Vlaming, Thom M Molenaar ... Fred van Leeuwen
    The interrogation of histone modifications on DNA barcodes enables efficient and direct screening for epigenetic regulators in thousands of mutants in parallel.
    1. Neuroscience

    The CNS connectome of a tadpole larva of Ciona intestinalis (L.) highlights sidedness in the brain of a chordate sibling

    Kerrianne Ryan, Zhiyuan Lu, Ian A Meinertzhagen
    Serial-section EM analysis uncovers the CNS connectome of a Ciona larva, the second of any entire nervous system, and exposes left-right asymmetries in its synaptic circuits.
    1. Developmental Biology

    Drosophila neprilysins control insulin signaling and food intake via cleavage of regulatory peptides

    Benjamin Hallier, Ronja Schiemann ... Heiko Meyer
    The catalytic activity of a Drosophila neprilysin is critical to proper insulin expression and food intake by regulating homeostasis of distinct signaling peptides.
    1. Neuroscience

    New learning while consolidating memory during sleep is actively blocked by a protein synthesis dependent process

    Roi Levy, David Levitan, Abraham J Susswein
    The brain inhibits the formation of new memories just after waking to safeguard the ongoing stabilization of existing memories during sleep.
    1. Neuroscience

    Chemogenetic inhibition of the medial prefrontal cortex reverses the effects of REM sleep loss on sucrose consumption

    Kristopher McEown, Yohko Takata ... Michael Lazarus
    Loss of REM sleep increases sucrose and fat consumption in mice; and inhibiting the prefrontal cortex reverses the increased consumption of sucrose, but not fat, following REM sleep loss.
    1. Structural Biology and Molecular Biophysics

    RETRACTED: The structure of SV40 large T hexameric helicase in complex with AT-rich origin DNA

    Dahai Gai, Damian Wang ... Xiaojiang S Chen
    A structural study reveals how the simian virus 40 Large-T hexamer helicase interacts with its origin DNA and partially melts the origin double-stranded DNA within the hexamer channel.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Assembling the Tat protein translocase

    Felicity Alcock, Phillip J Stansfeld ... Ben C Berks
    Evolutionary bioinformatics and experimentation are applied to the components of the Tat protein transport system to elucidate the structure of the membrane-bound receptor complex and to deduce a molecular description for its substrate-triggered activation.
    1. Cell Biology
    2. Developmental Biology

    Spatial patterning of P granules by RNA-induced phase separation of the intrinsically-disordered protein MEG-3

    Jarrett Smith, Deepika Calidas ... Geraldine Seydoux
    A competition for RNA drives the localized assembly of RNA granules in the C. elegans embryo.
    1. Cell Biology
    2. Neuroscience

    Filamin, a synaptic organizer in Drosophila, determines glutamate receptor composition and membrane growth

    GaYoung Lee, Thomas L Schwarz
    Filamin, by recruiting a signaling complex to the postsynapse, orchestrates the correct formation and growth of postsynaptic membranes and localization of glutamate receptor subunits.
    1. Neuroscience

    Young adult born neurons enhance hippocampal dependent performance via influences on bilateral networks

    Jia-Min Zhuo, Hua-an Tseng ... Xue Han
    Adult neurogenesis, although happening at a slow rate in the adult brain, plays an important role in learning and memory and has the ability to powerfully modulate large scale neural networks.
    1. Neuroscience

    Targeted deletion of AKAP7 in dentate granule cells impairs spatial discrimination

    Brian W Jones, Jennifer Deem ... G Stanley McKnight
    The PKA anchoring protein, AKAP7, localizes PKA in dentate granule mossy fibers and this localization plays an important role in contextual discrimination and cAMP-induced synaptic plasticity.
    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    Population scale mapping of transposable element diversity reveals links to gene regulation and epigenomic variation

    Tim Stuart, Steven R Eichten ... Ryan Lister
    Fine mapping of transposable element presence/absence variation amongst 216 Arabidopsis strains uncovers widespread novel genetic diversity that underlies differences in transcription and DNA methylation patterns.
    1. Structural Biology and Molecular Biophysics
    2. Microbiology and Infectious Disease

    Malaria parasite CelTOS targets the inner leaflet of cell membranes for pore-dependent disruption

    John R Jimah, Nichole D Salinas ... Niraj H Tolia
    The structure, function and mechanism of the malaria vaccine candidate CelTOS reveal a unique pore-forming and membrane-disrupting protein with specificity for the inner leaflet of host and vector cells.
    1. Cell Biology

    Two subunits of human ORC are dispensable for DNA replication and proliferation

    Etsuko Shibata, Manjari Kiran ... Anindya Dutta
    Human cell lines replicate and proliferate without ORC1 or ORC2, two subunits of the replication initiator protein complex ORC, which has till now been considered essential for DNA replication.
    1. Cell Biology
    2. Developmental Biology

    BRAF activates PAX3 to control muscle precursor cell migration during forelimb muscle development

    Jaeyoung Shin, Shuichi Watanabe ... Thomas Braun
    Genetic and biochemical approaches identify a new component of the cellular signaling machinery driving migration of limb muscle precursor cells during mouse embryogenesis and reveal the underlying molecular mechanism.
    1. Developmental Biology
    2. Evolutionary Biology

    The evolutionary origin of bilaterian smooth and striated myocytes

    Thibaut Brunet, Antje HL Fischer ... Detlev Arendt
    Molecular profiling of annelid myocytes reveals that the last common protostome-deuterostome ancestor already possessed a dual musculature, with visceral smooth muscles ensuring digestion and somatic striated muscles ensuring locomotion.