December 2019

Research articles

    1. Developmental Biology
    2. Neuroscience

    Activity-dependent death of transient Cajal-Retzius neurons is required for functional cortical wiring

    Martina Riva et al.
    The complete elimination of a transient superficial population of neurons, and associated immature circuits, is required for the emergence of functional properties in the mature cerebral cortex.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Structural basis for the activation of PLC-γ isozymes by phosphorylation and cancer-associated mutations

    Nicole Hajicek et al.
    The high-resolution X-ray crystal structure of PLC-γ1 reveals a unifying model for the regulation of the PLC-γ isozymes.
    1. Chromosomes and Gene Expression

    Cdc7 activates replication checkpoint by phosphorylating the Chk1-binding domain of Claspin in human cells

    Chi-Chun Yang et al.
    Cdc7 and CK1g1 independently and additively phosphorylate the Chk1-binding domain of claspin to activate replication checkpoint with differential contribution of each kinase in different cell types.
    1. Epidemiology and Global Health

    Estimating effectiveness of case-area targeted response interventions against cholera in Haiti

    Edwige Michel et al.
    Case-area targeted interventions conducted by rapid response teams appeared significantly effective to mitigate and shorten local cholera outbreaks in the Centre department of Haiti in 2015-2017.
    1. Structural Biology and Molecular Biophysics

    Architecture of the chromatin remodeler RSC and insights into its nucleosome engagement

    Avinash B Patel et al.
    The structure of the yeast RSC complex, a member of the SWI/SNF chromatin remodeling family, determined by cryo-electron microscopy, reveals a conserved structural core and the mode of nucleosome engagement.
    1. Structural Biology and Molecular Biophysics

    The structure of the endogenous ESX-3 secretion system

    Nicole Poweleit et al.
    The structure of the endogenous ESX-3 secretion system reveals a highly coordinated inner membrane complex and suggests a mechanism for the regulated secretion of ESX substrates.
    1. Structural Biology and Molecular Biophysics

    Molecular basis of force-from-lipids gating in the mechanosensitive channel MscS

    Bharat Reddy et al.
    The structure of the mechanosensitive channel MscS embedded in a lipid bilayer redefines the nature, location and importance of lipid–protein interactions in the gating of mechanosensitive channels.
    1. Neuroscience

    High and asymmetric somato-dendritic coupling of V1 layer 5 neurons independent of visual stimulation and locomotion

    Valerio Francioni et al.
    Layer 5 neuron apical tuft in mouse visual cortex display widespread, highly correlated calcium signals, with a strong and asymmetric coupling to somatic signals, independent of visual stimulation and locomotion.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    The Ormdl genes regulate the sphingolipid synthesis pathway to ensure proper myelination and neurologic function in mice

    Benjamin A Clarke et al.
    The ORMDL proteins function to restrain the de novo sphingolipid biosynthetic pathway during myelination, when there is a high demand for sphingolipids to prevent excessive accumulation of metabolic intermediates.
    1. Human Biology and Medicine
    2. Neuroscience

    Spinal signalling of C-fiber mediated pleasant touch in humans

    Andrew G Marshall et al.
    Pleasant touch perception in humans is unaffected by spinothalamic disruption indicating integrated spinal processing of hedonic and discriminative tactile inputs rather than privileged C-tactile-lamina I-spinothalamic projections.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Subcellular drug targeting illuminates local kinase action

    Paula J Bucko et al.
    Genetically-encoded platforms direct kinase inhibitor drugs to organelles to reveal new dimensions of local kinase signaling.
    1. Cell Biology

    Unstructured regions in IRE1α specify BiP-mediated destabilisation of the luminal domain dimer and repression of the UPR

    Niko Amin-Wetzel et al.
    Client protein-driven reversal of endoplasmic reticulum chaperone (BiP) mediated-repression is revealed as a principal component of the regulation of the unfolded protein response transducer IRE1 in cells.
    1. Computational and Systems Biology
    2. Microbiology and Infectious Disease

    Human cytomegalovirus interactome analysis identifies degradation hubs, domain associations and viral protein functions

    Luis V Nobre et al.
    The human cytomegalovirus (HCMV) interactome systematically characterises high-confidence viral-viral and viral-host protein interactions in HCMV-infected cells, facilitating multiple novel insights into HCMV and herpesviral function.
    1. Cancer Biology

    Siglec1-expressing subcapsular sinus macrophages provide soil for melanoma lymph node metastasis

    Rohit Singh, Beom K Choi
    When pioneer metastatic cells enter a sentinel lymph node through afferent lymphatics subcapsular sinus, macrophages provide them soil to proliferate and colonize lymph node.
    1. Neuroscience

    A multilayer circuit architecture for the generation of distinct locomotor behaviors in Drosophila

    Aref Arzan Zarin et al.
    Generation of a premotor/motor neuron comprehensive TEM reconstruction, functional optogenetics, and recurrent network modeling reveals different phase relationships among a subset of Drosophila motor neurons in forward versus backward locomotion.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    C-mannosylation supports folding and enhances stability of thrombospondin repeats

    Aleksandra Shcherbakova et al.
    C-mannosylation supports native folding of thrombospondin type 1 repeats in the endoplasmic reticulum and stabilizes the folded proteins by modulating the dynamics of the tryptophan-arginine ladder.
    1. Neuroscience

    Relaxation of synaptic inhibitory events as a compensatory mechanism in fetal SOD spinal motor networks

    Pascal Branchereau et al.
    Electrophysiological and simulation approaches show that a chloride-related longer relaxation of the inhibitory synaptic events partially compensates the early defect in the chloride homeostasis detected in fetal SOD spinal motoneurons.
    1. Cell Biology
    2. Immunology and Inflammation

    A role for phagocytosis in inducing cell death during thymocyte negative selection

    Nadia S Kurd et al.
    Self-reactive thymocyte death is most efficient when peptide-presenting cells are phagocytic, and blocking phagocytosis inhibits self-reactive thymocyte death, suggesting that phagocytes play central roles during thymocyte negative selection.
    1. Neuroscience

    Homeostatic regulation of perisynaptic matrix metalloproteinase 9 (MMP9) activity in the amblyopic visual cortex

    Sachiko Murase et al.
    Dark exposure lowers the MMP9 activation threshold, and subsequent light stimulation to an amblyopic eye is sufficient to induce proteolysis at thalamo-cortical synapses in deprived mouse visual cortex.
    1. Computational and Systems Biology
    2. Neuroscience

    From single neurons to behavior in the jellyfish Aurelia aurita

    Fabian Pallasdies et al.
    A multiscale computational nerve net model describes how the activity of individual neurons controls the swimming motion of a jellyfish in its hydrodynamic environment.
    1. Neuroscience

    Acute cerebellar knockdown of Sgce reproduces salient features of myoclonus-dystonia (DYT11) in mice

    Samantha Washburn et al.
    Acute knock down of Sgce that is mutated in Myoclonus Dystonia (DYT11), in the cerebellum of mice, leads to dystonia and myoclonus-like motor signs that like patients improve with alcohol.
    1. Structural Biology and Molecular Biophysics

    Activation of a nucleotide-dependent RCK domain requires binding of a cation cofactor to a conserved site

    Celso M Teixeira-Duarte et al.
    Cations are essential cofactors in the ATP activation mechanism of the KtrAB cation channel and appear to be cofactors of many other nucleotide-dependent RCK domains.
    1. Developmental Biology
    2. Evolutionary Biology

    Resolving homology in the face of shifting germ layer origins: Lessons from a major skull vault boundary

    Camilla S Teng et al.
    Homology of vertebrate skull structures should be based on evolutionary continuity and an appreciation of germ layer origins and inductive signaling in the embryonic head.
    1. Developmental Biology

    VEGF/VEGFR2 signaling regulates hippocampal axon branching during development

    Robert Luck et al.
    Hippocampal axon branching, required for the formation of functional neuronal networks, is regulated by VEGF/VEGFR2 signaling during development.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Robust cullin-RING ligase function is established by a multiplicity of poly-ubiquitylation pathways

    Spencer Hill et al.
    Human cullin-RING ligases are buffered to a much greater extent than had been previously appreciated, and the roles of ubiquitin chain extension enzymes are far more nuanced at physiological concentrations.
    1. Cell Biology
    2. Computational and Systems Biology

    Development, calibration, and validation of a novel human ventricular myocyte model in health, disease, and drug block

    Jakub Tomek et al.
    A computer model of human cardiomyocyte was produced and validated on independent datasets, overcoming shortcomings of its predecessors, also yielding broadly relevant insights and results on major ionic currents.
    1. Cell Biology
    2. Developmental Biology

    Metabolic modulation regulates cardiac wall morphogenesis in zebrafish

    Ryuichi Fukuda et al.
    3D single cell imaging and genetic analyses reveal a new role of cardiac metabolism in cardiac wall morphogenesis.
    1. Neuroscience
    2. Stem Cells and Regenerative Medicine

    Aberrant calcium channel splicing drives defects in cortical differentiation in Timothy syndrome

    Georgia Panagiotakos et al.
    The Timothy syndrome mutation in Cav1.2 gives rise to defects in neuronal differentiation by preventing a developmental switch in channel splicing and elevating calcium signaling in differentiating cells.
    1. Cancer Biology
    2. Developmental Biology

    Regulation of zebrafish melanocyte development by ligand-dependent BMP signaling

    Alec K Gramann et al.
    The oncogenic role ligand-dependent BMP signaling plays in suppressing differentiation in melanoma is a reiteration of its physiological roles during melanocyte development.
    1. Evolutionary Biology
    2. Structural Biology and Molecular Biophysics

    Indirect sexual selection drives rapid sperm protein evolution in abalone

    Damien Beau Wilburn et al.
    An NMR-based structural study of sperm proteins reveals a novel protein packaging/dispersion system embedded in a coevolutionary arms race.
    1. Developmental Biology
    2. Neuroscience

    EphrinB2 regulates VEGFR2 during dendritogenesis and hippocampal circuitry development

    Eva Harde et al.
    The internalization of the angiogenic receptor VEGFR2 expressed in neurons is controlled by ephrinB2 and is required for neuronal dendritic arborization, spine morphogenesis and circuitry development in the hippocampus.
    1. Cell Biology
    2. Neuroscience

    Sensing of nutrients by CPT1C regulates late endosome/lysosome anterograde transport and axon growth

    Marta Palomo-Guerrero et al.
    The pseudoenzyme CPT1C is able to sense changes in intracellular malonyl-CoA levels caused by nutrients or energy stress and regulate late endosomes/lysosomes anterograde transport, necessary for proper axon growth.
    1. Neuroscience
    2. Structural Biology and Molecular Biophysics

    MeCP2 nuclear dynamics in live neurons results from low and high affinity chromatin interactions

    Francesco M Piccolo et al.
    Single molecular imaging of MeCP2 at high spatial/temporal resolution identifies distinct structural domains contributing to its dynamic behaviors and chromatin interactions in live neurons.
    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    Single-cell analysis uncovers that metabolic reprogramming by ErbB2 signaling is essential for cardiomyocyte proliferation in the regenerating heart

    Hessel Honkoop et al.
    Single-cell RNA sequencing reveals Nrg1/ErbB2-induced metabolic reprogramming as a pivotal event for cardiomyocyte proliferation during heart regeneration.
    1. Neuroscience

    Pathway-, layer- and cell-type-specific thalamic input to mouse barrel cortex

    B Semihcan Sermet et al.
    Two distinct thalamocortical pathways were found to provide differential excitatory synaptic input to distinct cell-types across layers of mouse primary somatosensory barrel cortex.
    1. Neuroscience

    FMRP has a cell-type-specific role in CA1 pyramidal neurons to regulate autism-related transcripts and circadian memory

    Kirsty Sawicka et al.
    Identifying FMRP-bound mRNAs in hippocampal CA1 pyramidal neurons reveals cell-type specific regulation of autism-candidate and circadian mRNAs and FMRP-mediated control of memory across the circadian cycle.
    1. Cell Biology
    2. Microbiology and Infectious Disease

    Length-dependent disassembly maintains four different flagellar lengths in Giardia

    Shane G McInally et al.
    Giardia, a multi-ciliated parasitic protist, maintains four different flagellar lengths by balancing flagellar length-independent IFT-mediated assembly with length-dependent kinesin-13 mediated disassembly.
    1. Neuroscience

    Uncovering the functional anatomy of the human insula during speech

    Oscar Woolnough et al.
    Direct insular recordings in humans reveal that contrary to several prominent models of speech production, it is not engaged in pre-articulatory planning, but in auditory and somatosensory components of speech.
    1. Cancer Biology

    TLE3 loss confers AR inhibitor resistance by facilitating GR-mediated human prostate cancer cell growth

    Sander AL Palit et al.
    A mechanistic link between TLE3 loss and glucocorticoid receptor-mediated androgen receptor inhibitor resistance supports the rationale to target GR during anti-hormonal treatment in castrate-resistant prostate cancer.
    1. Structural Biology and Molecular Biophysics

    De novo design of a homo-trimeric amantadine-binding protein

    Jooyoung Park et al.
    The first successful de novo design of a homo-trimeric protein that binds a C3 symmetric small molecule larger than a metal ion is an advance for computational protein design.
    1. Chromosomes and Gene Expression

    The Fml1-MHF complex suppresses inter-fork strand annealing in fission yeast

    Io Nam Wong et al.
    Genomic deletions formed from inter-fork strand annealing associated with a collapsed replication fork are suppressed by the FANCM-related DNA helicase Fml1 in conjunction with its partner proteins Mhf1 and Mhf2.
    1. Chromosomes and Gene Expression

    GC content shapes mRNA storage and decay in human cells

    Maïté Courel et al.
    The GC content of human mRNAs is key to P-body localization and protein yield, and has a major impact on their post-transcriptional control.
    1. Computational and Systems Biology
    2. Structural Biology and Molecular Biophysics

    Common activation mechanism of class A GPCRs

    Qingtong Zhou et al.
    Contrary to previous findings, class A GPCRs share a common activation pathway that directly links ligand binding to G-protein activation, as revealed by novel quantitative analysis.
    1. Cell Biology
    2. Physics of Living Systems

    Single-molecule turnover dynamics of actin and membrane coat proteins in clathrin-mediated endocytosis

    Michael M Lacy et al.
    The main proteins of clathrin-mediated endocytosis bind and unbind rapidly, continuously turning over about five times during the formation of an endocytic vesicle in yeast.
    1. Structural Biology and Molecular Biophysics

    Large-scale state-dependent membrane remodeling by a transporter protein

    Wenchang Zhou et al.
    The conformational mechanism of a transporter protein is found to have profound and energetically costly effects on the morphology of the surrounding membrane.
    1. Neuroscience

    Catecholaminergic modulation of meta-learning

    Jennifer L Cook et al.
    A human psychopharmacology study reveals that a drug that affects the dopamine and noradrenaline systems enhances people's ability to adapt their learning rate to suit the volatility of the environment.
    1. Neuroscience

    Inferring synaptic inputs from spikes with a conductance-based neural encoding model

    Kenneth W Latimer et al.
    The conductance-based encoding model creates a new bridge between statistical models and biophysical models of neurons, and infers visually-evoked excitatory and inhibitory synaptic conductances from spike trains in macaque retina.
    1. Structural Biology and Molecular Biophysics

    HIV restriction factor APOBEC3G binds in multiple steps and conformations to search and deaminate single-stranded DNA

    Michael Morse et al.
    APOBEC3G, an anti-viral protein with the capability to inhibit HiV-1 infectivity, binds single stranded DNA in multiple physical conformations, enabling complex interactions that allow APOBEC3G to perform multiple diverse functions.
    1. Stem Cells and Regenerative Medicine

    The follicle epithelium in the Drosophila ovary is maintained by a small number of stem cells

    Jocelyne Fadiga, Todd G Nystul
    Just 2-4 follicle stem cells maintain each follicle epithelium in the Drosophila ovary, and they reside within a single ring at the anterior edge of the tissue.
    1. Developmental Biology

    Primary cilia deficiency in neural crest cells models anterior segment dysgenesis in mouse

    Céline Portal et al.
    Primary cilia of neural crest-derived cells mediate Indian hedgehog-induced signal transduction in the periocular mesenchyme and are required for normal anterior segment development.
    1. Ecology
    2. Epidemiology and Global Health

    Antagonism between parasites within snail hosts impacts the transmission of human schistosomiasis

    Martina R Laidemitt et al.
    Interactions among parasites in snails create cascading effects on their transmission and highlight that biodiversity has complex, context-dependent and important effects on human schistosomiasis transmission dynamics.
    1. Epidemiology and Global Health
    2. Microbiology and Infectious Disease

    Combining genomics and epidemiology to analyse bi-directional transmission of Mycobacterium bovis in a multi-host system

    Joseph Crispell et al.
    Analyses combining genomic and epidemiological data of Mycobacterium bovis, which causes bovine tuberculosis, revealed evidence of transmission within and between cattle and badger populations.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Cell-based HTS identifies a chemical chaperone for preventing ER protein aggregation and proteotoxicity

    Keisuke Kitakaze et al.
    Cell-based high-throughput screening identifies IBT21 as a chemical chaperone, that inhibits ER protein aggregation and prevents the cell death caused by a proteotoxin, the aggregation-prone prion protein.
    1. Neuroscience

    Invariant representations of mass in the human brain

    Sarah Schwettmann et al.
    A network of brain regions implicated in physical inference represents abstract, generalizable variables used as inputs to physics engines.
    1. Computational and Systems Biology
    2. Human Biology and Medicine

    Single-cell modeling of routine clinical blood tests reveals transient dynamics of human response to blood loss

    Anwesha Chaudhury et al.
    Unsteady state modeling of blood cell populations reveals that blood loss triggers a cellular clearance delay and a cellular production increase, and modeling provides earlier detection and individualized patient characterization.
    1. Plant Biology

    Compensatory sequence variation between trans-species small RNAs and their target sites

    Nathan R Johnson et al.
    Superfamilies of trans-species small RNAs from the parasitic plant Cuscuta have sequence variation that correspond to synonymous site variation in host plant target mRNAs.
    1. Cancer Biology

    Replication Study: Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis

    Mee Rie Sheen et al.
    Editors' Summary: This Replication Study has reproduced some parts of the original paper but other parts could not be interpreted.
    1. Chromosomes and Gene Expression

    Crl activates transcription by stabilizing active conformation of the master stress transcription initiation factor

    Juncao Xu et al.
    The cryo-EM structure of Escherichia coli Crl–TAC reveals the mechanism of DNA-contact-independent transcription activation.
    1. Human Biology and Medicine
    2. Neuroscience

    Default mode-visual network hypoconnectivity in an autism subtype with pronounced social visual engagement difficulties

    Michael V Lombardo et al.
    Functional hypoconnectivity between ‘social brain’ default mode circuitry and visual association cortex underpins a subtype of autistic toddlers with a strong preference to attend to the non-social visual world.
    1. Physics of Living Systems
    2. Structural Biology and Molecular Biophysics

    Efficient conversion of chemical energy into mechanical work by Hsp70 chaperones

    Salvatore Assenza et al.
    A multiscale modeling approach reveals how the energy from ATP hydrolysis is used by Hsp70 chaperones to remodel the conformation of their substrates through a novel force-generating mechanism.
    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    Har-P, a short P-element variant, weaponizes P-transposase to severely impair Drosophila development

    Satyam P Srivastav et al.
    A female fertility syndrome in Drosophila called gonadal dysgenesis is caused by the P-transposase actively mobilizing a very short P-element variant that has been named the Har-P.
    1. Neuroscience

    Navigating the garden of forking paths for data exclusions in fear conditioning research

    Tina B Lonsdorf et al.
    Exclusion of participants in tasks with a learning element can introduce substantial bias and needs to be carefully considered and transparently reported and justified.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    E. coli TraR allosterically regulates transcription initiation by altering RNA polymerase conformation

    James Chen et al.
    Cryo-electron microscopy structures, combined with biochemical experiments, show how the E. coli F element-encoded TraR protein regulates transcription initiation by altering RNA polymerase conformation and conformational heterogeneity.
    1. Immunology and Inflammation

    Ribosome biogenesis restricts innate immune responses to virus infection and DNA

    Christopher Bianco, Ian Mohr
    Ribosome production is unexpectedly integrated into innate cell-intrinsic responses that regulate double strand DNA-sensing and inflammatory cytokine induction in infected and uninfected cells.
    1. Ecology

    Tritrophic metabolism of plant chemical defenses and its effects on herbivore and predator performance

    Ruo Sun et al.
    Genetic manipulation demonstrates the costs and benefits of detoxifying glucosinolate plant defenses in a pest insect and its predator.
    1. Immunology and Inflammation

    Tissue-specific shaping of the TCR repertoire and antigen specificity of iNKT cells

    Rebeca Jimeno et al.
    The tissue environment shapes the lipid recognition capacity of natural killer T cells.
    1. Neuroscience

    Opioids modulate an emergent rhythmogenic process to depress breathing

    Xiaolu Sun et al.
    Inspiratory rhythmogenesis is mediated by an emergent mechanism independent of bursts associated with motor output and is modulated by opioids, pointing to strategies for ameliorating opioid-induced respiratory depression.
    1. Cancer Biology
    2. Human Biology and Medicine

    PCK1 and DHODH drive colorectal cancer liver metastatic colonization and hypoxic growth by promoting nucleotide synthesis

    Norihiro Yamaguchi et al.
    The gluconeogenic enzyme PCK1 and pyrimidine nucleotide biosynthetic enzyme DHODH drive hypoxic pyrimidine nucleotide biosynthesis and liver metastatic colonization in colorectal cancer, which is therapeutically exploitable by DHODH pharmacologic inhibition.
    1. Cell Biology
    2. Developmental Biology

    Telophase correction refines division orientation in stratified epithelia

    Kendall J Lough et al.
    Telophase reorientation corrects errors in spindle orientation that persist after imprecise initial spindle positioning during early mitosis, and contributes to balancing self-renewal with differentiation during epidermal development.
    1. Cancer Biology
    2. Cell Biology

    Axon-like protrusions promote small cell lung cancer migration and metastasis

    Dian Yang et al.
    In small cell lung cancer, the transition from a neuroendocrine state to a more neuronal state endows these cancer cells with increased migration and metastatic potential.
    1. Genetics and Genomics
    2. Human Biology and Medicine

    Single cell transcriptional signatures of the human placenta in term and preterm parturition

    Roger Pique-Regi et al.
    Parturition gene regulation across multiple cell-types and placental compartments is deciphered at single cell resolution, highlighting the common role of the NFKB pathway in both term and preterm birth.
    1. Human Biology and Medicine

    Straightjacket/α2δ3 deregulation is associated with cardiac conduction defects in myotonic dystrophy type 1

    Emilie Auxerre-Plantié et al.
    Drosophila DM1 models suggest that elevated cardiac expression of straightjacket/α2δ3, a regulatory subunit of voltage-gated calcium channel, contributes to cardiac conduction defects in DM1.
    1. Developmental Biology

    Developmentally regulated Tcf7l2 splice variants mediate transcriptional repressor functions during eye formation

    Rodrigo M Young et al.
    The inclusion of a new alternatively spliced exon in Tcf7l2 can switch its function to repress transcription of Wnt target genes.
    1. Cell Biology

    Direct comparison of clathrin-mediated endocytosis in budding and fission yeast reveals conserved and evolvable features

    Yidi Sun et al.
    Quantitative comparison of clathrin-mediated endocytosis in budding and fission yeast identified conserved mechanisms and species-specific adaptations with broad implications that extend from yeast to humans.
    1. Cell Biology

    Magnetic resonance measurements of cellular and sub-cellular membrane structures in live and fixed neural tissue

    Nathan H Williamson et al.
    Low-field single-sided magnetic resonance diffusion methods detect and measure permeability of sub-micron compartments which likely include cell processes, organelles, and cellular vesicles within ex vivo mouse spinal cords.
    1. Neuroscience

    Essential role for InSyn1 in dystroglycan complex integrity and cognitive behaviors in mice

    Akiyoshi Uezu et al.
    InSyn1 is a new inhibitory post-synaptic protein that is essential for the dystroglycan complex, neuronal activity in vitro and in vivo, and cognitive behavior.
    1. Cell Biology
    2. Physics of Living Systems

    Rod nuclear architecture determines contrast transmission of the retina and behavioral sensitivity in mice

    Kaushikaram Subramanian et al.
    Establishing retinal contrast transmission as a novel determinant of mammalian fitness, this research adds functional significance to a prominent exception of nuclear organization, previously described in nocturnal rod photoreceptor cells.
    1. Neuroscience

    The recovery of standing and locomotion after spinal cord injury does not require task-specific training

    Jonathan Harnie et al.
    Restoring locomotion after complete spinal cord injury does not require locomotor training, only the return of sufficient excitability within neurons of the spinal cord.
    1. Neuroscience

    Axon TRAP reveals learning-associated alterations in cortical axonal mRNAs in the lateral amgydala

    Linnaea E Ostroff et al.
    A diverse assortment of mRNAs are present in projection axons in the adult forebrain and their translation is associated with new memory formation.
    1. Neuroscience

    Agonist-specific voltage-dependent gating of lysosomal two-pore Na+ channels

    Xiaoli Zhang et al.
    Tricyclic antidepressants activate lysosomal two-pore Na+ channels in a voltage-dependent manner.
    1. Neuroscience

    The computation of directional selectivity in the Drosophila OFF motion pathway

    Eyal Gruntman et al.
    ON and OFF visual motion is computed with the same algorithm despite differences in circuit architecture.
    1. Neuroscience

    MouseBytes, an open-access high-throughput pipeline and database for rodent touchscreen-based cognitive assessment

    Flavio H Beraldo et al.
    Comprehensive dataset of high-level cognitive assessment in mouse models of neurodegeneration, accompanied by an open-access database/repository to change the paradigm of how cognitive studies in animal models can be shared/re-used.
    1. Genetics and Genomics

    Diversification of the Caenorhabditis heat shock response by Helitron transposable elements

    Jacob M Garrigues et al.
    Helitron transposable elements, by providing high density transcription factor binding sites upstream of host genes, have diversified the heat shock response within and among Caenorhabditis species.
    1. Evolutionary Biology
    2. Neuroscience

    A novel lineage of candidate pheromone receptors for sex communication in moths

    Lucie Bastin-Héline et al.
    In moths, male receptors tuned to type I female pheromones may not have a monophyletic origin.
    1. Evolutionary Biology

    Retinal oxygen supply shaped the functional evolution of the vertebrate eye

    Christian Damsgaard et al.
    Multiple respiratory and vascular mechanisms have recurrently evolved across the vertebrates to alleviate the oxygen diffusion limitations inherent to the morphology of the retina.
    1. Neuroscience

    mTORC1 in the orbitofrontal cortex promotes habitual alcohol seeking

    Nadege Morisot et al.
    In the orbitofrontal cortex, mTORC1, a multiprotein complex centered around the kinase mTOR, contributes to the development and/or maintenance of habitual alcohol seeking.
    1. Computational and Systems Biology
    2. Epidemiology and Global Health

    Linking glycemic dysregulation in diabetes to symptoms, comorbidities, and genetics through EHR data mining

    Isa Kristina Kirk et al.
    Text mining of complete EHRs for 14,017 diabetes patients and subsequent clustering led to phenotypically deep clusters, showing distinct glycemic profiles, comorbidities, and SNP association patterns.
    1. Neuroscience

    Local cortical desynchronization and pupil-linked arousal differentially shape brain states for optimal sensory performance

    Leonhard Waschke et al.
    The momentary levels of local cortical desynchronization and pupil-linked arousal pose dissociable influences not only on the processing of sensory information but also on human perceptual performance.
    1. Biochemistry and Chemical Biology

    Long-lived metabolic enzymes in the crystalline lens identified by pulse-labeling of mice and mass spectrometry

    Pan Liu et al.
    By performing 15N pulse-labeling of mice, the turnover of hundreds of proteins in eye tissues was measured by mass spectrometry that revealed long-lived metabolic enzymes in the lens.
    1. Human Biology and Medicine
    2. Neuroscience

    Neural ensemble dynamics in dorsal motor cortex during speech in people with paralysis

    Sergey D Stavisky et al.
    Neurons in human dorsal motor cortex, an area involved in controlling arm and hand movements, are also active – and show similar ensemble dynamics – during speaking.
    1. Cell Biology
    2. Developmental Biology

    Dzip1 and Fam92 form a ciliary transition zone complex with cell type specific roles in Drosophila

    Jean-André Lapart et al.
    Genetic analyses in Drosophila establish the functional hierarchy of the ciliary transition zone module, Dzip1/Fam92/Cby, and reveal tissue specific variations in basal body anchoring pathways in fly ciliated tissues.
    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    Broadly neutralizing human antibodies against dengue virus identified by single B cell transcriptomics

    Natasha D Durham et al.
    Identification of viral and host determinants of broadly neutralizing antibodies targeting a new epitope on dengue virus that can be used to guide vaccine design.
    1. Cell Biology
    2. Chromosomes and Gene Expression

    Vasohibin1, a new mouse cardiomyocyte IRES trans-acting factor that regulates translation in early hypoxia

    Fransky Hantelys et al.
    In mouse cardiomyocytes, (lymph)angiogenic growth factors are induced during early hypoxia by a translational mechanism involving a new IRES trans-acting factor, vasohibin-1.
    1. Evolutionary Biology
    2. Genetics and Genomics

    Mutations that improve efficiency of a weak-link enzyme are rare compared to adaptive mutations elsewhere in the genome

    Andrew B Morgenthaler et al.
    Mutations elsewhere in the genome play critical roles in improving fitness during amplification and divergence of a gene encoding a weak-link enzyme whose inefficiency limits growth rate.
    1. Cell Biology
    2. Immunology and Inflammation

    B cells extract antigens at Arp2/3-generated actin foci interspersed with linear filaments

    Sophie I Roper et al.
    Two modes of actin polymerization, branched and linear, cooperate in B cells to extract antigens from surfaces of presenting cells.
    1. Neuroscience

    Amyloid and tau accumulate across distinct spatial networks and are differentially associated with brain connectivity

    Joana B Pereira et al.
    The amyloid patterns overlap with the default-mode network, whereas the tau patterns overlap with distinct functional networks and are associated with a loss of anatomical connectivity and multiple cognitive functions.
    1. Neuroscience

    Calpain fosters the hyperexcitability of motoneurons after spinal cord injury and leads to spasticity

    Vanessa Plantier et al.
    Calpain is a promising therapeutic target to reduce spasticity after a spinal cord injury.
    1. Genetics and Genomics
    2. Neuroscience

    Probe-Seq enables transcriptional profiling of specific cell types from heterogeneous tissue by RNA-based isolation

    Ryoji Amamoto et al.
    Probe-Seq is a cell type specific bulk RNA sequencing method that can be applied to a wide-ranging tissue types from both vertebrates and invertebrates without genetic labeling.
    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    Repressive H3K9me2 protects lifespan against the transgenerational burden of COMPASS activity in C. elegans

    Teresa Wei-sy Lee et al.
    The transgenerational inheritance of lifespan is facilitated by the accumulation of repressive chromatin across generations.
    1. Developmental Biology
    2. Neuroscience

    Sequential phosphorylation of NDEL1 by the DYRK2-GSK3β complex is critical for neuronal morphogenesis

    Youngsik Woo et al.
    Sequential phosphorylation of NDEL1 Ser336/Ser332 by DYRK2 and GSK3β is a novel regulatory step for actin dynamics that contributes to the neurite outgrowth and neuronal arborization in the developing brain.
    1. Neuroscience
    2. Structural Biology and Molecular Biophysics

    Two new polymorphic structures of human full-length alpha-synuclein fibrils solved by cryo-electron microscopy

    Ricardo Guerrero-Ferreira et al.
    Two new polymorphic structures of recombinant human alpha-synuclein fibrils show striking differences to previous structures, while familial PD mutation sites remain crucial for protofilament interaction and fibril stability.
    1. Structural Biology and Molecular Biophysics

    Molecular structures of the human Slo1 K+ channel in complex with β4

    Xiao Tao, Roderick MacKinnon
    The structures of Slo1 in complex with b4 imply that the auxiliary beta subunits modulate the channel's gating properties through stabilizing ‘pre-existing’ conformations rather than creating new ones.
    1. Microbiology and Infectious Disease

    Homeostatic control of cell wall hydrolysis by the WalRK two-component signaling pathway in Bacillus subtilis

    Genevieve S Dobihal et al.
    Molecular genetic analyses define the first homeostatic control pathway that maintains cell wall remodeling activity during bacterial growth.
    1. Cell Biology

    Kinetochores attached to microtubule-ends are stabilised by Astrin bound PP1 to ensure proper chromosome segregation

    Duccio Conti et al.
    Human chromosome-microtubule attachments are stabilised by Astrin-mediated dynamic delivery of PP1 phosphatase to the attachment site, which ensures the normal segregation of chromosomes.
    1. Immunology and Inflammation

    Tight nuclear tethering of cGAS is essential for preventing autoreactivity

    Hannah E Volkman et al.
    Tight nuclear tethering of the cGAS DNA sensor maintains it in its resting state and prevents activation by self-DNA.
    1. Developmental Biology
    2. Human Biology and Medicine

    Spatiotemporal dynamics and heterogeneity of renal lymphatics in mammalian development and cystic kidney disease

    Daniyal J Jafree et al.
    Three-dimensional imaging was used to identify structural and quantitative features of developing lymphatics in the kidneys of mice, humans and in a genetic mouse model of polycystic kidney disease.
    1. Cell Biology
    2. Physics of Living Systems

    Bridging the gap between single-cell migration and collective dynamics

    Florian Thüroff et al.
    A computational model, based on single-cell features like contractility and polarizability, quantitatively describes cellular dynamics from the single cell level up to small cohorts and confluent tissues.
    1. Plant Biology

    Homeostasis of branched-chain amino acids is critical for the activity of TOR signaling in Arabidopsis

    Pengfei Cao et al.
    Despite BCAAs being de novo-synthesized in chloroplasts, TOR activation by BCAAs is conserved in plants and triggers a re-organization of actin and actin-associated endomembranes.
    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    Distinct roles for S. cerevisiae H2A copies in recombination and repeat stability, with a role for H2A.1 threonine 126

    Nealia CM House et al.
    Despite differing by only one amino acid in the C-terminal tail, copy 1 of yeast histone 2A has a repair-specific role not shared by copy 2.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Mechanistic basis of the inhibition of SLC11/NRAMP-mediated metal ion transport by bis-isothiourea substituted compounds

    Cristina Manatschal et al.
    The structural and mechanistic characterization of competitive inhibition of human DMT1 offers a promising route for the development of compounds for the treatment of iron overload disorders.
    1. Developmental Biology
    2. Neuroscience

    Gradient-independent Wnt signaling instructs asymmetric neurite pruning in C. elegans

    Menghao Lu, Kota Mizumoto
    Genetic analyses revealed the critical role of local Wnt in neuronal patterning by instructing neurite pruning.
    1. Neuroscience

    Insights into the dynamic control of breathing revealed through cell-type-specific responses to substance P

    Nathan A Baertsch, Jan-Marino Ramirez
    The neuromodulator substance P enhances mechanisms of recurrent excitation between breaths to control breathing frequency and stability.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Molecular determinants of the Ska-Ndc80 interaction and their influence on microtubule tracking and force-coupling

    Pim J Huis in 't Veld et al.
    Binding of two macromolecular complexes allows kinetochores to capture force produced by the depolymerising ends of microtubules, allowing chromosomes to be transmitted from a mother cell to its two daughters.
    1. Neuroscience

    The representational space of observed actions

    Raffaele Tucciarelli et al.
    Representational similarity analysis of human functional magnetic resonance imaging data demonstrates that the lateral occipitotemporal cortex represents action knowledge along dimensions that are in accordance with behavioural judgements.
    1. Biochemistry and Chemical Biology
    2. Genetics and Genomics

    Interferon-β-induced miR-1 alleviates toxic protein accumulation by controlling autophagy

    Camilla Nehammer et al.
    A microRNA prevents the accumulation of toxic proteins by inducing autophagy.
    1. Computational and Systems Biology
    2. Plant Biology

    Evolution of C4 photosynthesis predicted by constraint-based modelling

    Mary-Ann Blätke, Andrea Bräutigam
    Constraint-based modelling predicts C4 photosynthesis evolves under resource limitation from an ancestral ground state of C3 photosynthesis and attributes divergent metabolic routes in extant C4 subtypes to light.
    1. Biochemistry and Chemical Biology

    Exchange of water for sterol underlies sterol egress from a StARkin domain

    George Khelashvili et al.
    The capture and export of a hydrophobic sterol molecule from the binding pocket of a Lam/GramD1 sterol-binding protein is unexpectedly mediated by water.
    1. Developmental Biology
    2. Plant Biology

    Coordination of tissue cell polarity by auxin transport and signaling

    Carla Verna et al.
    GNOM controls both auxin transport and auxin signaling to coordinate tissue cell polarity during vein patterning in plants.
    1. Cancer Biology
    2. Cell Biology

    Junction Mapper is a novel computer vision tool to decipher cell–cell contact phenotypes

    Helena Brezovjakova et al.
    Junction Mapper is a powerful new semi-automated software that provides a fingerprint of cell–cell contact morphometry and receptor density alterations.
    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    An integrin/MFG-E8 shuttle loads HIV-1 viral-like particles onto follicular dendritic cells in mouse lymph node

    Chung Park, John H Kehrl
    Intravital imaging with HIV-1 viral-like particle in mouse model reveals a mechanism for HIV-1 uptake by subcapsular sinus macrophages that facilitates HIV-1 spreading tofollicular dendritic and B cells.
    1. Evolutionary Biology
    2. Genetics and Genomics

    Deep sampling of Hawaiian Caenorhabditis elegans reveals high genetic diversity and admixture with global populations

    Tim A Crombie et al.
    Hawaiian Caenorhabditis elegans harbor high levels of genetic diversity that might represent the complex patterns of ancestral diversity in the species prior to human influence.
    1. Ecology

    Biophysical and physiological processes causing oxygen loss from coral reefs

    Cynthia B Silveira et al.
    Coral reef heterotrophic bacteria and fleshy macroalgae cause oxygen loss from reef systems through microbial biomass accumulation and ebullition from algae surfaces.
    1. Cell Biology
    2. Human Biology and Medicine

    Impaired lysosomal acidification triggers iron deficiency and inflammation in vivo

    King Faisal Yambire et al.
    Impaired lysosomal acidification results in retention of iron inside lysosomes, triggering functional iron deficiency, dysfunctional mitochondria (especially mtDNA loss), and inflammation in vivo in a mouse model of lysosomal disease.
    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    Dynamic regulation of chromatin accessibility by pluripotency transcription factors across the cell cycle

    Elias T Friman et al.
    OCT4 and SOX2 display partially independent activity to regulate chromatin accessibility, and highly dynamic activity of OCT4 is required throughout the cell cycle to maintain pluripotency enhancer accessibility.
    1. Epidemiology and Global Health
    2. Microbiology and Infectious Disease

    Transmission dynamics and control of multidrug-resistant Klebsiella pneumoniae in neonates in a developing country

    Thomas Crellen et al.
    Colonisation with resistant Klebsiella pneumoniae in a Cambodian neonatal unit is driven by person-to-person transmission, transmissibility varies by sequence type, and antibiotic consumption generally increases the risk of acquisition.
    1. Developmental Biology
    2. Microbiology and Infectious Disease

    High fat diet induces microbiota-dependent silencing of enteroendocrine cells

    Lihua Ye et al.
    Enteroendocrine cells sense nutrients in the gut and regulate digestive physiology but are rendered insensitive following fat ingestion due to alteration of gut microbiota.
    1. Human Biology and Medicine
    2. Neuroscience

    Tight junction protein occludin regulates progenitor Self-Renewal and survival in developing cortex

    Raphael M Bendriem et al.
    That early cortical neural progenitor divisions strictly require OCLN isoform expression is a paradigm shift in the functional consideration of this protein best known for promoting between-cell barrier functions.
    1. Computational and Systems Biology
    2. Neuroscience

    Differences in topological progression profile among neurodegenerative diseases from imaging data

    Sara Garbarino et al.
    Computational-driven, imaging-based topological profiles of neurodegeneration differ substantially in different neurodegenerative conditions, suggesting distinct modes of dependence of the pathological spread on the underlying connectivity.
    1. Human Biology and Medicine
    2. Immunology and Inflammation

    Chronic muscle weakness and mitochondrial dysfunction in the absence of sustained atrophy in a preclinical sepsis model

    Allison M Owen et al.
    Sepsis-induced long-term muscle weakness was reproduced using a refined murine model, which was accompanied by mitochondrial dysfunction in the absence of sustained atrophy, suggesting the promise of mitochondria-targeted post-sepsis therapies.
    1. Neuroscience
    2. Physics of Living Systems

    Analysis of stochastic fluctuations in responsiveness is a critical step toward personalized anesthesia

    Andrew R McKinstry-Wu et al.
    Responses to anesthetics differ among individuals and fluctuate stochastically despite constant drug concentration, however, the amount of noise driving transitions between the responsive and the unresponsive state is conserved.
    1. Genetics and Genomics
    2. Plant Biology

    The MADS-box transcription factor PHERES1 controls imprinting in the endosperm by binding to domesticated transposons

    Rita A Batista et al.
    Jumping of transposable elements provides DNA-binding sites for the MADS-box transcription factor PHERES1, allowing the regulation of imprinted genes and other key endosperm development genes.
    1. Genetics and Genomics
    2. Microbiology and Infectious Disease

    Herpesviral lytic gene functions render the viral genome susceptible to novel editing by CRISPR/Cas9

    Hyung Suk Oh et al.
    CRISPR genome editing technology can efficiently introduce mutations into lytic and latent HSV genomes to block lytic replication and reactivation of latent herpes simplex virus genome though differential mechanisms.
    1. Cell Biology
    2. Neuroscience

    Neurotrophins induce fission of mitochondria along embryonic sensory axons

    Lorena Armijo-Weingart et al.
    Induction of the fission of mitochondria-populating sensory axons is shown to be a novel biological action of neurotrophins.
    1. Chromosomes and Gene Expression

    An mRNA-binding channel in the ES6S region of the translation 48S-PIC promotes RNA unwinding and scanning

    Irene Díaz-López et al.
    The ES6S region of the small subunit ribosome makes a place for the threading and secondary structure unwinding of mRNA, which regulates genome-wide translation.
    1. Developmental Biology

    Coronary arterial development is regulated by a Dll4-Jag1-EphrinB2 signaling cascade

    Stanislao Igor Travisano et al.
    Notch ligands Jag1 and Dll4 and their effector Ephb2 are required in sinus venosus endocardium for primitive coronary vasculature formation and later for arterial differentiation and maturation of coronary endothelium.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Modulating FOXO3 transcriptional activity by small, DBD-binding molecules

    Judith Hagenbuchner et al.
    The mode of binding and cellular effect of the first FOXO3-DNA-binding-domain targeting small compound discovered by a combined pharmacophore-based/biochemical screening approach is reported.