November 2018

Cover articles

    1. Stem Cells and Regenerative Medicine

    Insulin mutations, beta cells and diabetes

    Diego Balboa, Jonna Saarimäki-Vire ... Timo Otonkoski
    1. Developmental Biology
    2. Physics of Living Systems

    Modeling morphology

    Silas Boye Nissen, Steven Rønhild ... Kim Sneppen
    1. Chromosomes and Gene Expression
    2. Microbiology and Infectious Disease

    Viral gene restriction

    Joseph M Cabral, Hyung Suk Oh, David M Knipe

Highlights controls:

Research articles

    1. Cancer Biology

    Rejection of immunogenic tumor clones is limited by clonal fraction

    Ron S Gejman, Aaron Y Chang ... David A Scheinberg
    A new, high-throughput in vivo MHC-I peptide minigene library platform shows that the naive immune system cannot eliminate cells presenting immunogenic antigens found at low frequencies within a growing tumor.
    1. Developmental Biology
    2. Evolutionary Biology

    A novel enhancer near the Pitx1 gene influences development and evolution of pelvic appendages in vertebrates

    Abbey C Thompson, Terence D Capellini ... David M Kingsley
    Regulatory sequences downstream of a key limb identity gene are required for normal sizes of leg bones, and are changed in wild species with dramatic alterations in pelvic structures.
    1. Cell Biology

    The spatial separation of processing and transport functions to the interior and periphery of the Golgi stack

    Hieng Chiong Tie, Alexander Ludwig ... Lei Lu
    Transport machinery localizes at the cisternal rim while modification machinery localizes at the interior.
    1. Evolutionary Biology
    2. Structural Biology and Molecular Biophysics

    Evolutionary pathways of repeat protein topology in bacterial outer membrane proteins

    Meghan Whitney Franklin, Sergey Nepomnyachyi ... Joanna SG Slusky
    There is a strand-based evolutionary mechanism for the diversification of outer membrane proteins, which has implications for how repeat proteins are created and for how outer membrane proteins fold.
    1. Cancer Biology

    The SERM/SERD bazedoxifene disrupts ESR1 helix 12 to overcome acquired hormone resistance in breast cancer cells

    Sean W Fanning, Rinath Jeselsohn ... Geoffrey L Greene
    Bazedoxifene's SERD activities enable it to resist the impact of activating ESR1 mutations in breast cancer.
    1. Neuroscience

    Neural activity related to volitional regulation of cortical excitability

    Kathy Ruddy, Joshua Balsters ... Nicole Wenderoth
    Changing brain state using feedback from transcranial magnetic stimulation, by training participants to increase or decrease how excitable their motor pathways are.
    1. Ecology

    Plant diversity maintains multiple soil functions in future environments

    Nico Eisenhauer, Jes Hines ... Peter B Reich
    Empirical evidence shows that conserving local plant diversity is a robust strategy to maintain multiple valuable ecosystem services provided by soils in both present and future environmental conditions.
    1. Structural Biology and Molecular Biophysics

    The hydrophobic nature of a novel membrane interface regulates the enzyme activity of a voltage-sensing phosphatase

    Akira Kawanabe, Masaki Hashimoto ... Yasushi Okamura
    Electrophysiological and fluorometric studies of Ci-VSP expressed in Xenopus oocyte revealed two states of the enzyme region with distinct enzyme activity and distinct coupling to the voltage sensor.
    1. Immunology and Inflammation

    TAPBPR mediates peptide dissociation from MHC class I using a leucine lever

    F Tudor Ilca, Andreas Neerincx ... Louise H Boyle
    Immunopeptidomics in combination with novel cell-based assays that assess peptide exchange reveal a critical role for the K22-D35 loop of TAPBPR in mediating peptide dissociation and peptide selection on MHC I.
    1. Neuroscience

    Neural dynamics at successive stages of the ventral visual stream are consistent with hierarchical error signals

    Elias B Issa, Charles F Cadieu, James J DiCarlo
    Neural spiking responses in the visual cortex carry both an explicit representation of the presence of a face and a late-arriving, explicit encoding of errors in face estimation.
    1. Chromosomes and Gene Expression

    Pericentromeric hypomethylation elicits an interferon response in an animal model of ICF syndrome

    Srivarsha Rajshekar, Jun Yao ... Mary Goll
    Derepression of transcripts from hypomethylated pericentromeric repeats triggers an innate immune response in an animal model of Immunodeficency, Centromere and Facial anomalies (ICF) syndrome.
    1. Developmental Biology
    2. Neuroscience

    Human-specific ARHGAP11B induces hallmarks of neocortical expansion in developing ferret neocortex

    Nereo Kalebic, Carlotta Gilardi ... Wieland B Huttner
    Expression of human-specific gene ARHGAP11B in the developing ferret neocortex leads to an increase in abundance of neural progenitor cells, which results in neocortex expansion.
    1. Neuroscience

    Rat behavior and dopamine release are modulated by conspecific distress

    Nina T Lichtenberg, Brian Lee ... Matthew R Roesch
    Rat behavior and dopamine release are preferentially modulated by subjective rather than objective evaluation of outcomes in a social setting.
    1. Developmental Biology

    Spatiotemporally controlled genetic perturbation for efficient large-scale studies of cell non-autonomous effects

    Andrea Chai, Ana M Mateus ... Rita Sousa-Nunes
    A novel genetic strategy for induction of reproducible neural tumors (or any other deleterious phenotype) in a single Drosophila stock (applicable to other organisms).
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Molecular basis for activation of lecithin:cholesterol acyltransferase by a compound that increases HDL cholesterol

    Kelly A Manthei, Shyh-Ming Yang ... John JG Tesmer
    Structure of lecithin:cholesterol acyltransferase with a covalent acyl-intermediate mimic and a small molecule activator reveals an active conformation and that the enzyme can be activated via its membrane binding domain.
    1. Biochemistry and Chemical Biology

    Selective agonist of TRPML2 reveals direct role in chemokine release from innate immune cells

    Eva Plesch, Cheng-Chang Chen ... Christian Grimm
    Direct and selective activation of TRPML2 promotes macrophage migration through release of CCL2.
    1. Biochemistry and Chemical Biology

    Translation attenuation by minocycline enhances longevity and proteostasis in old post-stress-responsive organisms

    Gregory M Solis, Rozina Kardakaris ... Michael Petrascheck
    Directly targeting the ribosome to attenuate translation partly mimics the integrated stress response, increasing lifespan and preserving protein folding capacity even in older individuals with dysfunctional stress response signaling.
    1. Genetics and Genomics

    Natural variation in sugar tolerance associates with changes in signaling and mitochondrial ribosome biogenesis

    Richard G Melvin, Nicole Lamichane ... Ville Hietakangas
    The optimal macronutrient composition, macronutrient space, varies strongly between closely related species and is determined by genetic changes in regulatory genes that globally reprogram gene expression profiles of metabolic pathways.
    1. Neuroscience

    Variance adaptation in navigational decision making

    Ruben Gepner, Jason Wolk ... Marc Gershow
    Fruit fly larvae adapt their decision-making process to the variability of the environment, illuminating the structure of adaptation in the underlying neural substrates.
    1. Neuroscience

    Augmented reality powers a cognitive assistant for the blind

    Yang Liu, Noelle RB Stiles, Markus Meister
    A non-invasive cognitive assistant for blind people endows objects in the environment with voices, allowing users to explore the scene, localize objects, and navigate through a building with minimal training.
    1. Structural Biology and Molecular Biophysics

    Piezo’s membrane footprint and its contribution to mechanosensitivity

    Christoph A Haselwandter, Roderick MacKinnon
    Membrane mechanics predict that the ion channel Piezo recruits the surrounding membrane to amplify its sensitivity to changes in membrane tension, with greatest sensitivity in the low-tension regime.
    1. Developmental Biology
    2. Physics of Living Systems

    Theoretical tool bridging cell polarities with development of robust morphologies

    Silas Boye Nissen, Steven Rønhild ... Kim Sneppen
    Biological shapes and morphological transitions can emerge from combining directed interactions between cells with apical-basal and planar cell polarity.
    1. Cancer Biology

    FoxA1 and FoxA2 drive gastric differentiation and suppress squamous identity in NKX2-1-negative lung cancer

    Soledad A Camolotto, Shrivatsav Pattabiraman ... Eric L Snyder
    Lineage specifiers FoxA1 and FoxA2 control lung cancer growth and identity by activating gastric differentiation and suppressing squamous cell carcinoma transdifferentiation.
    1. Cancer Biology

    Hyperactivation of ERK by multiple mechanisms is toxic to RTK-RAS mutation-driven lung adenocarcinoma cells

    Arun M Unni, Bryant Harbourne ... Harold Varmus
    Cancer cells driven by mutations in KRAS or EGFR are dependent on DUSP6 to prevent ERK-induced cell death, creating a novel vulnerability for targeted therapy.
    1. Structural Biology and Molecular Biophysics

    Translational initiation factor eIF5 replaces eIF1 on the 40S ribosomal subunit to promote start-codon recognition

    Jose Luis Llácer, Tanweer Hussain ... V Ramakrishnan
    The N-terminal domain (NTD) of the initiation factor eIF5 bound to the 40S subunit at the precise location vacated by eIF1 promotes tRNAi accommodation at AUG codons.
    1. Developmental Biology

    ppargc1a controls nephron segmentation during zebrafish embryonic kidney ontogeny

    Joseph M Chambers, Shahram Jevin Poureetezadi ... Rebecca A Wingert
    The transcriptional coactivator ppargc1a regulates the renal progenitor patterning to delineate boundary formation of differentiated segment populations during nephrogenesis.
    1. Neuroscience

    Response to short-term deprivation of the human adult visual cortex measured with 7T BOLD

    Paola Binda, Jan W Kurzawski ... Maria Concetta Morrone
    Two hour deprivation of vision in one eye transiently boosts the representation of the deprived eye (suppressing the non-deprived eye) in adult human V1 and along the ventral pathway.
    1. Cell Biology
    2. Developmental Biology

    Mechanical force regulates tendon extracellular matrix organization and tenocyte morphogenesis through TGFbeta signaling

    Arul Subramanian, Lauren Fallon Kanzaki ... Thomas Friedrich Schilling
    Perturbation of mechanical force at muscle attachments and its effects on tendon morphogenesis provides insights into the mechanisms underlying cellular responses to tensional force and resulting extracellular matrix production.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    The shape of the bacterial ribosome exit tunnel affects cotranslational protein folding

    Renuka Kudva, Pengfei Tian ... Gunnar von Heijne
    Proteins can fold deeper inside ribosomes with an enlarged exit tunnel.
    1. Neuroscience

    Endocytosis at the Drosophila blood–brain barrier as a function for sleep

    Gregory Artiushin, Shirley L Zhang ... Amita Sehgal
    Endocytosis through the Drosophila blood–brain barrier influences and depends upon sleep.
    1. Cell Biology

    Splicing factors Sf3A2 and Prp31 have direct roles in mitotic chromosome segregation

    Claudia Pellacani, Elisabetta Bucciarelli ... Maria Patrizia Somma
    Extensive cytological and biochemical analyses show that the conserved Sf3A2 and Prp31 splicing factors bind microtubules and the Ndc80 complex, playing direct mitotic functions in both Drosophila and human mitosis.
    1. Cancer Biology
    2. Genetics and Genomics

    Targets and genomic constraints of ectopic Dnmt3b expression

    Yingying Zhang, Jocelyn Charlton ... Alexander Meissner
    Ectopic expression of Dnmt3b leads to wide-spread CpG island hypermethylation that is largely defined by chromatin state and has some distinct features when compared to the cancer methylome.
    1. Neuroscience

    Decision and navigation in mouse parietal cortex

    Michael Krumin, Julie J Lee ... Matteo Carandini
    When mice use vision to choose their trajectories, a large fraction of parietal cortex activity can be precisely predicted from navigational attributes such as spatial position and heading.
    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    ASH1-catalyzed H3K36 methylation drives gene repression and marks H3K27me2/3-competent chromatin

    Vincent T Bicocca, Tereza Ormsby ... Eric U Selker
    While SET-2 methylates histone H3K36 during transcription, ASH1 methylates this residue in repressed regions, is important for silencing, and can both positively and negatively influence methylation of histone H3K27.
    1. Chromosomes and Gene Expression
    2. Microbiology and Infectious Disease

    ATRX promotes maintenance of herpes simplex virus heterochromatin during chromatin stress

    Joseph M Cabral, Hyung Suk Oh, David M Knipe
    Epigenetic restriction of herpes simplex virus occurs in a biphasic manner, in which ATRX maintains viral heterochromatin after an initial phase of chromatin deposition.
    1. Neuroscience

    A time-stamp mechanism may provide temporal information necessary for egocentric to allocentric spatial transformations

    Avner Wallach, Erik Harvey-Girard ... Len Maler
    A novel neural mechanism for precise, unbiased estimation of time intervals in the thalamus of electric fish is likely used for computing distance between object encounters.
    1. Evolutionary Biology
    2. Neuroscience

    Metazoan evolution of glutamate receptors reveals unreported phylogenetic groups and divergent lineage-specific events

    David Ramos-Vicente, Jie Ji ... Àlex Bayés
    The animal phylogeny of glutamate receptors indicates that vertebrate types do not account for all receptor classes originated during evolution, neither are they the pinnacle of a linear evolutive process.
    1. Chromosomes and Gene Expression

    Multi-protein bridging factor 1(Mbf1), Rps3 and Asc1 prevent stalled ribosomes from frameshifting

    Jiyu Wang, Jie Zhou ... Elizabeth J Grayhack
    An eukaryotic specific system cooperates with the ribosome quality control pathway to maintain the reading frame during translation of slowly translated sequences.
    1. Neuroscience

    Sensorimotor pathway controlling stopping behavior during chemotaxis in the Drosophila melanogaster larva

    Ibrahim Tastekin, Avinash Khandelwal ... Matthieu Louis
    The reconstruction of a sensorimotor pathway from the olfactory-sensory neurons down to the pre-motor system reveals a descending neuron that plays a critical role in the organization of larval chemotaxis.
    1. Biochemistry and Chemical Biology

    Random-sequence genetic oligomer pools display an innate potential for ligation and recombination

    Hannes Mutschler, Alexander I Taylor ... Philipp Holliger
    Random sequence RNA pools display an innate capacity for ligation and recombination, enabling them to “bootstrap” themselves towards higher compositional, informational and structural complexity.
    1. Neuroscience

    Macro-connectomics and microstructure predict dynamic plasticity patterns in the non-human primate brain

    Sean Froudist-Walsh, Philip GF Browning ... Paula L Croxson
    Brain recovery after injury can be predicted based on its activity and structure, which may allow us to understand why some brain injuries lead to permanent loss of cognitive function, while others do not.
    1. Microbiology and Infectious Disease

    Rotavirus VP3 targets MAVS for degradation to inhibit type III interferon expression in intestinal epithelial cells

    Siyuan Ding, Shu Zhu ... Harry B Greenberg
    Rotavirus infection induces phosphorylation and proteasomal degradation of MAVS to suppress host antiviral interferon signaling.
    1. Structural Biology and Molecular Biophysics

    The CryoEM structure of the Saccharomyces cerevisiae ribosome maturation factor Rea1

    Piotr Sosnowski, Linas Urnavicius ... Helgo Schmidt
    The high-resolution structure of Rea1, an essential ribosome maturation factor in Saccharomyces cerevisiae, explains how the ATPase domain is regulated and reveals the linker domain, the mechanical element carrying out ribosome remodeling.
    1. Neuroscience

    Expanded genetic screening in Caenorhabditis elegans identifies new regulators and an inhibitory role for NAD+ in axon regeneration

    Kyung Won Kim, Ngang Heok Tang ... Yishi Jin
    A function-based genetic screen using the Caenorhabditis elegans axotomy model identifies new regulators and an inhibitory role for NAD+ in axon regeneration, expanding the understanding of axon injury responses and regeneration.
    1. Neuroscience

    Bright multicolor labeling of neuronal circuits with fluorescent proteins and chemical tags

    Richi Sakaguchi, Marcus N Leiwe, Takeshi Imai
    A bright and stochastic multicolor labeling method, Tetbow, facilitates millimeters-scale reconstructions of neuronal circuits at a large scale using tissue clearing.
    1. Cell Biology
    2. Neuroscience

    Proteolytically released Lasso/teneurin-2 induces axonal attraction by interacting with latrophilin-1 on axonal growth cones

    Nickolai V Vysokov, John-Paul Silva ... Yuri A Ushkaryov
    Lasso and latrophilin-1 interact across the synapse, while shed Lasso binds latrophilin-1 on distant growth cones and attracts them, providing a universal mechanism for short- and long-range axonal guidance.
    1. Ecology
    2. Evolutionary Biology

    Reconstructing the functions of endosymbiotic Mollicutes in fungus-growing ants

    Panagiotis Sapountzis, Mariya Zhukova ... Jacobus J Boomsma
    Domestication of endosymbiotic Mollicutes may have resolved nitrogen-recycling challenges for attine ants and enabled the evolutionary derived leaf-cutting ants to fully exploit their herbivorous niches.
    1. Chromosomes and Gene Expression
    2. Computational and Systems Biology

    Genome-wide Estrogen Receptor-α activation is sustained, not cyclical

    Andrew N Holding, Amy E Cullen, Florian Markowetz
    Activation of the Estrogen Receptor by estra-2-diol results in sustained binding and the previously described cyclical response kinetics are likely an artefact of observing a highly variable process without replicates.
    1. Ecology

    The lost world of Cuatro Ciénegas Basin, a relictual bacterial niche in a desert oasis

    Valeria Souza, Alejandra Moreno-Letelier ... Luis Enrique Eguiarte
    At Cuatro Ciénegas, the ancestral niche conditions of the ancient shores of Laurentia persisted along with its microbial communities that have been coevolving for a very long time.
    1. Structural Biology and Molecular Biophysics

    CryoEM structures of open dimers of gyrase A in complex with DNA illuminate mechanism of strand passage

    Katarzyna M Soczek, Tim Grant ... Alfonso Mondragón
    CryoEM structures of open gyrase A dimers and DNA in two states representing steps either prior to or after passage through the DNA-gate, show where a putative T-segment is found.
    1. Microbiology and Infectious Disease

    Host genetic selection for cold tolerance shapes microbiome composition and modulates its response to temperature

    Fotini Kokou, Goor Sasson ... Itzhak Mizrahi
    Microbiome and transcriptomic profiling of genetically selected tropical fish with high and low tolerance to cold exposure revealed host control over microbiome composition and response to temperature changes.
    1. Developmental Biology

    The Toll pathway inhibits tissue growth and regulates cell fitness in an infection-dependent manner

    Federico Germani, Daniel Hain ... Konrad Basler
    Toll pathway inactivation enhances tissue growth and cell fitness when the environment in which animals develop is not deprived of pathogens.
    1. Developmental Biology

    Unique morphogenetic signatures define mammalian neck muscles and associated connective tissues

    Eglantine Heude, Marketa Tesarova ... Shahragim Tajbakhsh
    Genetic studies in the mouse provide a blueprint of the embryonic origins of neck muscles originating from cranial and somitic mesoderm, as well as associated connective tissue.
    1. Cell Biology
    2. Structural Biology and Molecular Biophysics

    Lipidation-independent vacuolar functions of Atg8 rely on its noncanonical interaction with a vacuole membrane protein

    Xiao-Man Liu, Akinori Yamasaki ... Li-Lin Du
    The core autophagy protein Atg8 plays non-autophagy roles through binding to an integral membrane protein Hfl1, which harbors an unusual Atg8-interacting motif.
    1. Neuroscience

    Sucrose intensity coding and decision-making in rat gustatory cortices

    Esmeralda Fonseca, Victor de Lafuente ... Ranier Gutierrez
    The neural representation of perceived sucrose intensity was contained in the firing rate and spike-timing of a 'small' population of neurons distributed across the Insula and Orbitofrontal taste cortices.
    1. Neuroscience

    Hedonic processing in humans is mediated by an opioidergic mechanism in a mesocorticolimbic system

    Christian Buchel, Stephan Miedl, Christian Sprenger
    The pleasure of rewards in humans is mediated by an opioidergic mechanism.
    1. Cell Biology
    2. Developmental Biology

    Angiopoietin-4-dependent venous maturation and fluid drainage in the peripheral retina

    Harri Elamaa, Minna Kihlström ... Lauri Eklund
    Identification of importance of Angiopoietin-4 (Angpt4) as a first growth factor that initiates venous specification in the peripheral retina, and Angpt4-dependent mechanism for fluid clearance in the mouse retina.
    1. Biochemistry and Chemical Biology
    2. Microbiology and Infectious Disease

    Mycobacterium tuberculosis induces decelerated bioenergetic metabolism in human macrophages

    Bridgette M Cumming, Kelvin W Addicott ... Adrie JC Steyn
    Quantifiable bioenergetic parameters, determined from extracellular flux analyses, are distinct between macrophages infected with Mycobacteriumtuberculosis or vaccine strain M. bovis BCG, enabling assessment of future vaccine and drug efficacy.
    1. Biochemistry and Chemical Biology
    2. Cancer Biology

    Targeted degradation of BRD9 reverses oncogenic gene expression in synovial sarcoma

    Gerard L Brien, David Remillard ... Scott A Armstrong
    BRD9 provides the first actionable therapeutic target in synovial sarcoma tumours that is both biochemically and functionally linked to the SS18-SSX fusion protein which drives disease development.
    1. Stem Cells and Regenerative Medicine

    Long-term live imaging of the Drosophila adult midgut reveals real-time dynamics of division, differentiation and loss

    Judy Lisette Martin, Erin Nicole Sanders ... Lucy Erin O'Brien
    A new platform for imaging live Drosophila adults yields vivid movies of the midgut over prolonged time scales, opening the door to the real-time study of organ renewal dynamics in a near-native context.
    1. Cell Biology
    2. Developmental Biology

    Shear-induced damped oscillations in an epithelium depend on actomyosin contraction and E-cadherin cell adhesion

    Ehsan Sadeghipour, Miguel A Garcia ... Beth L Pruitt
    Cell movement toward and away from the midline of an epithelium over tens of hours are caused by spontaneous or externally-applied shear forces to eliminate force imbalances within the tissue.
    1. Microbiology and Infectious Disease

    High-resolution mapping of fluoroquinolones in TB rabbit lesions reveals specific distribution in immune cell types

    Landry Blanc, Isaac B Daudelin ... Véronique Dartois
    Penetration of the fluoroquinolones in tuberculosis lesions is heterogeneous even in fully cellular areas, is driven by macrophage content and decreases as the distance from lesion outer rim increases.
    1. Neuroscience

    Decoding hierarchical control of sequential behavior in oscillatory EEG activity

    Atsushi Kikumoto, Ulrich Mayr
    Mental codes that track our position within complex, behavioral sequences, have been hard to pin down empirically, but can be identified and traced over time using oscillatory EEG activity.
    1. Chromosomes and Gene Expression

    A whole lifespan mouse multi-tissue DNA methylation clock

    Margarita V Meer, Dmitriy I Podolskiy ... Vadim N Gladyshev
    A robust mouse multi-tissue age predictor is presented that can be used to assess the DNA methylation age of mouse tissues and test the effects of longevity interventions.
    1. Neuroscience

    Oxytocin-mediated social enrichment promotes longer telomeres and novelty seeking

    Jamshid Faraji, Mitra Karimi ... Gerlinde AS Metz
    Social enrichment supports longevity.
    1. Cell Biology

    Comment on ‘Orthogonal lipid sensors identify transbilayer asymmetry of plasma membrane cholesterol’

    Kevin C Courtney, Karen YY Fung ... Xiaohui Zha
    We challenge a recent report that most of the cholesterol in the plasma membrane of mammalian cells is in the exofacial leaflet.
    1. Chromosomes and Gene Expression

    Translesion polymerase kappa-dependent DNA synthesis underlies replication fork recovery

    Peter Tonzi, Yandong Yin ... Tony T Huang
    Translesion polymerase kappa promotes replication fork restart to maintain genome stability during conditions of nucleotide deprivation.
    1. Neuroscience

    Dopamine neurons drive fear extinction learning by signaling the omission of expected aversive outcomes

    Ximena I Salinas-Hernández, Pascal Vogel ... Sevil Duvarci
    Dopamine signaling is necessary for normal fear extinction learning.
    1. Cell Biology
    2. Neuroscience

    Rescue of cognitive function following fractionated brain irradiation in a novel preclinical glioma model

    Xi Feng, Sharon Liu ... Nalin Gupta
    Whole-brain radiotherapy, but not glioma growth in distal region from the hippocampus, results in impaired recognition memory, which can be prevented by CSF-1R inhibitor-mediated microglia depletion.
    1. Neuroscience

    Molecular mechanisms that stabilize short term synaptic plasticity during presynaptic homeostatic plasticity

    Jennifer M Ortega, Özgür Genç, Graeme W Davis
    Genetic and electrophysiological experiments define how homeostatic signaling stabilizes both the gain and short-term dynamic properties of neurotransmitter release, ensuring that synaptic information transfer remains robust to external perturbation.
    1. Cell Biology
    2. Structural Biology and Molecular Biophysics

    Structural basis of tubulin recruitment and assembly by microtubule polymerases with tumor overexpressed gene (TOG) domain arrays

    Stanley Nithianantham, Brian D Cook ... Jawdat Al-Bassam
    TOG (tumor overexpressed gene) domains organize then polymerize tubulins at microtubule plus ends.
    1. Computational and Systems Biology
    2. Developmental Biology

    A stochastic epigenetic switch controls the dynamics of T-cell lineage commitment

    Kenneth KH Ng, Mary A Yui ... Hao Yuan Kueh
    The timing and outcome of mammalian cell lineage decisions can be controlled by slow, stochastic events on individual regulatory gene loci.
    1. Cancer Biology

    Targeting MYC dependency in ovarian cancer through inhibition of CDK7 and CDK12/13

    Mei Zeng, Nicholas P Kwiatkowski ... Nathanael S Gray
    A multi-transcriptional CDKs inhibitor suppresses MYC and induces regression of ovarian tumors, indicating that targeting CDK7, 12, 13 with THZ1 may be an effective approach for treating MYC-dependent malignancies.
    1. Ecology

    Meta-analysis challenges a textbook example of status signalling and demonstrates publication bias

    Alfredo Sánchez-Tójar, Shinichi Nakagawa ... Julia Schroeder
    Meta-analysis takes down a textbook example in behavioural and evolutionary ecology, and demonstrates the existence of biases in the current scientific publishing culture.
    1. Neuroscience

    TrpV1 receptor activation rescues neuronal function and network gamma oscillations from Aβ-induced impairment in mouse hippocampus in vitro

    Hugo Balleza-Tapia, Sophie Crux ... André Fisahn
    TrpV1 receptor activation rescues cognition-relevant network dynamics in mouse hippocampus in an acute Alzheimer disease model providing a novel therapeutic target.
    1. Neuroscience

    Cerebellar learning using perturbations

    Guy Bouvier, Johnatan Aljadeff ... Boris Barbour
    A proposal for a complete cellular/network implementation of trial-and-error motor learning in the olivo-cerebellar system.
    1. Ecology

    Global warming reduces leaf-out and flowering synchrony among individuals

    Constantin M Zohner, Lidong Mo, Susanne S Renner
    Individuals differ in how their leaf-out and flowering are regulated by abiotic stimuli and, under climate warming, this leads to reduced within-population phenological synchrony, impacting mutualistic and antagonistic community interactions.
    1. Computational and Systems Biology
    2. Neuroscience

    Subunit exchange enhances information retention by CaMKII in dendritic spines

    Dilawar Singh, Upinder Singh Bhalla
    Due to subunit-exchange, CaMKII can store information at diverse time-scales and might play a central role in the memory maintenance.
    1. Structural Biology and Molecular Biophysics

    New tools for automated high-resolution cryo-EM structure determination in RELION-3

    Jasenko Zivanov, Takanori Nakane ... Sjors HW Scheres
    RELION-3 calculates single-particle reconstructions to higher resolution and with less user-interactions than previously available versions.
    1. Cancer Biology
    2. Stem Cells and Regenerative Medicine

    T-ALL leukemia stem cell 'stemness' is epigenetically controlled by the master regulator SPI1

    Haichuan Zhu, Liuzhen Zhang ... Hong Wu
    The identification of key determinants of LSC “stemness” and LSC differentiation that is reversible through an epigenetic mechanism may have considerable implications in understanding leukemia and designing effective therapies.
    1. Cell Biology
    2. Genetics and Genomics

    Inhibition of mTORC1 by ER stress impairs neonatal β-cell expansion and predisposes to diabetes in the Akita mouse

    Yael Riahi, Tal Israeli ... Gil Leibowitz
    mTORC1 inhibition by perinatal ER stress induces beta-cell growth arrest with subsequent development of diabetes.
    1. Stem Cells and Regenerative Medicine

    Insulin mutations impair beta-cell development in a patient-derived iPSC model of neonatal diabetes

    Diego Balboa, Jonna Saarimäki-Vire ... Timo Otonkoski
    Mutations causing proinsulin misfolding trigger unfolded protein response and lead to impaired proliferation and reduced mTORC1 signalling of developing beta-cells in a patient-derived induced pluripotent stem cell disease model.
    1. Computational and Systems Biology
    2. Developmental Biology

    Tuned polymerization of the transcription factor Yan limits off-DNA sequestration to confer context-specific repression

    C Matthew Hope, Jemma L Webber ... Ilaria Rebay
    Tuned protein–protein interaction affinity optimizes the repressive function of the ETS family transcription factor Yan in order to contribute specificity and robustness to cell fate specification in the developing Drosophila eye.
    1. Cell Biology
    2. Neuroscience

    CRELD1 is an evolutionarily-conserved maturational enhancer of ionotropic acetylcholine receptors

    Manuela D'Alessandro, Magali Richard ... Jean-Louis Bessereau
    The protein disulphide isomerase CRELD1 controls the biosynthesis of nicotinic acetylcholine receptors in nematode and mouse muscle.
    1. Neuroscience

    Light-dependent pathways for dopaminergic amacrine cell development and function

    Teona Munteanu, Katelyn J Noronha ... Tiffany M Schmidt
    Rods, not ipRGCs, are the major retinal photoreceptor impacting development of dopaminergic signaling in the retina.
    1. Structural Biology and Molecular Biophysics

    Germline VRC01 antibody recognition of a modified clade C HIV-1 envelope trimer and a glycosylated HIV-1 gp120 core

    Andrew J Borst, Connor E Weidle ... David Veesler
    An integrative structural and biophysical workflow indicates engagement of VRC01 germline antibodies can occur with a gp120 426c core construct containing all wild-type N-linked glycosylation sites, including the Asn276 glycan.
    1. Cell Biology
    2. Neuroscience

    The insulin/IGF signaling cascade modulates SUMOylation to regulate aging and proteostasis in Caenorhabditis elegans

    Lorna Moll, Noa Roitenberg ... Ehud Cohen
    By controlling the SUMOylation of the protein CAR-1, the aging-regulating pathways downstream of the Insulin/IGF signaling cascade and of the germ cells of the nematode Caenorhabditis elegans are integrated.
    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    A bacterial immunomodulatory protein with lipocalin-like domains facilitates host–bacteria mutualism in larval zebrafish

    Annah S Rolig, Emily Goers Sweeney ... Karen Guillemin
    Discovery of a secreted protein from resident gut bacteria that reduced intestinal innate immune responses which would otherwise simultaneously compromise both bacterial and host survival.
    1. Cell Biology

    A pathway for Parkinson’s Disease LRRK2 kinase to block primary cilia and Sonic hedgehog signaling in the brain

    Herschel S Dhekne, Izumi Yanatori ... Suzanne R Pfeffer
    Pathogenic LRRK2kinase requires Rab10 and RILPL1 to block primary cilia formation, shortening cilia on cholinergic neurons needed for a hedgehog driven circuit that supports dopaminergic neurons in mouse brain.
    1. Ecology
    2. Microbiology and Infectious Disease

    Immune-mediated hookworm clearance and survival of a marine mammal decrease with warmer ocean temperatures

    Mauricio Seguel, Felipe Montalva ... Nicole Gottdenker
    In years with colder ocean temperatures, fur seal pups receive more maternal care and have a better energy balance, clearing hookworm infection earlier, which increases their chances of survival.
    1. Neuroscience

    Value-based attentional capture affects multi-alternative decision making

    Sebastian Gluth, Mikhail S Spektor, Jörg Rieskamp
    Speeded value-based decisions between two options can be affected by a third, high-value distractor that captures attention and slows down the choice process.
    1. Developmental Biology

    A novel mechanism of gland formation in zebrafish involving transdifferentiation of renal epithelial cells and live cell extrusion

    Richard W Naylor, Hao-Han G Chang ... Alan J Davidson
    A rare example of direct transdifferentiation is discovered in zebrafish in which kidney epithelial cells change into an endocrine gland and undergo live-cell extrusion from the renal tubule.
    1. Neuroscience

    Current and future goals are represented in opposite patterns in object-selective cortex

    Anouk Mariette van Loon, Katya Olmos-Solis ... Christian NL Olivers
    Multivoxel pattern of fMRI data reveals how the brain distinguishes between relevant and irrelevant representations as representations adapt to the order in which they are required in multiple task sequences.
    1. Neuroscience

    CA2 neuronal activity controls hippocampal low gamma and ripple oscillations

    Georgia M Alexander, Logan Y Brown ... Serena M Dudek
    Hippocampal area CA2 controls low gamma and ripple oscillations, brain waves known to be impaired in schizophrenia, implicating this important brain region in cognition.
    1. Evolutionary Biology
    2. Neuroscience

    Recalibrating timing behavior via expected covariance between temporal cues

    Benjamin J De Corte, Rebecca R Della Valle, Matthew S Matell
    Rats act as if they expect that the delays associated with temporal cues will covary due to a common causal factor.
    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    Plasmodium-specific atypical memory B cells are short-lived activated B cells

    Damián Pérez-Mazliah, Peter J Gardner ... Jean Langhorne
    Plasmodium-specific atypical memory B cells generated to naturally (mosquito) transmitted rodent malaria infection are short-lived activated B cells, and do not prevent resolution of infection or generation of long-lived memory.
    1. Neuroscience

    Altered hippocampal interneuron activity precedes ictal onset

    Mitra L Miri, Martin Vinck ... Jessica A Cardin
    GABAergic interneuron populations in the hippocampus exhibit cell-type-specific patterns of disruption in advance of seizure onset.
    1. Evolutionary Biology
    2. Structural Biology and Molecular Biophysics

    OSCA/TMEM63 are an evolutionarily conserved family of mechanically activated ion channels

    Swetha E Murthy, Adrienne E Dubin ... Ardem Patapoutian
    A family of proteins (OSCA/TMEM63) that encode mechanosensitive ion channels has been characterized in plants, flies, and mammals.
    1. Neuroscience

    A resource for the Drosophila antennal lobe provided by the connectome of glomerulus VA1v

    Jane Anne Horne, Carlie Langille ... Ian A Meinertzhagen
    FIB-SEM is used to identify comprehensively and reconstruct 192 neurons and their complete connectome for glomerulus VA1v of the Drosophila antennal lobe, in particular to reconstruct its local interneurons.
    1. Neuroscience

    Deletion of KCNQ2/3 potassium channels from PV+ interneurons leads to homeostatic potentiation of excitatory transmission

    Heun Soh, Suhyeorn Park ... Anastasios V Tzingounis
    Loss of potassium channel activity from fast-spiking interneurons increases their excitability leading to unexpectedly increased fast excitatory transmission and seizure susceptibility.
    1. Structural Biology and Molecular Biophysics

    Cryo-EM structure of the mechanically activated ion channel OSCA1.2

    Sebastian Jojoa-Cruz, Kei Saotome ... Andrew B Ward
    Structures of OSCA1.2, a member of a newly characterized family of mechanically activated ion channels, provide insights into mechanism of channel gating by membrane tension.