July 2015

Cover articles

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Research articles

    1. Genes and Chromosomes

    Resection is responsible for loss of transcription around a double-strand break in Saccharomyces cerevisiae

    Nicola Manfrini et al.
    The conversion of the ends of a double-strand break from double-stranded to single-stranded DNA, which is necessary to initiate homologous recombination, is responsible for loss of transcription and RNA polymerase occupancy around the double-strand break in Saccharomyces cerevisiae.
    1. Developmental Biology and Stem Cells

    miR-965 controls cell proliferation and migration during tissue morphogenesis in the Drosophila abdomen

    Pushpa Verma, Stephen M Cohen
    A microRNA-mediated mechanism coordinates cell proliferation with cell rearrangements during tissue morphogenesis.
    1. Biochemistry
    2. Biophysics and Structural Biology

    The enterococcal cytolysin synthetase has an unanticipated lipid kinase fold

    Shi-Hui Dong et al.
    The bacterial cytolysin synthetase CylM has a eukaryotic lipid kinase fold despite the absence of any clear sequence similarity, and contains adjacent phosphorylation and phosphate elimination active sites and an ordered activation loop in the absence of peptide substrate or regulatory proteins.
    1. Neuroscience

    Prefrontal dopamine regulates fear reinstatement through the downregulation of extinction circuits

    Natsuko Hitora-Imamura et al.
    Prefrontal dopamine regulates inhibition of fear extinction circuits in the infralimbic cortex and disinhibition of fear expression circuits in the amygdala, leading to fear reinstatement.
    1. Cell Biology

    Regulation of the PI3K pathway through a p85α monomer–homodimer equilibrium

    Lydia WT Cheung et al.
    The p85α homodimer plays a role in the PI3K pathway by regulating PTEN function.
    1. Cell Biology
    2. Developmental Biology and Stem Cells

    The Notch-mediated hyperplasia circuitry in Drosophila reveals a Src-JNK signaling axis

    Diana M Ho et al.
    A diverse group of modifier genes, including the proto-oncogene Src, cooperate with Notch specifically to control cell proliferation.
    1. Cell Biology
    2. Developmental Biology and Stem Cells

    First quantitative high-throughput screen in zebrafish identifies novel pathways for increasing pancreatic β-cell mass

    Guangliang Wang et al.
    A novel high-throughput, whole organism chemical screening platform was used to identify existing drugs that increase pancreatic beta-cell mass in zebrafish, implicating unique roles for the NF-κB and serotonergic signaling pathways in regulating pancreatic biology.
    1. Genes and Chromosomes

    The Ku subunit of telomerase binds Sir4 to recruit telomerase to lengthen telomeres in S. cerevisiae

    Evan P Hass, David C Zappulla
    In yeast, the secondary pathway for recruiting telomerase to chromosome ends requires a component of telomeric transcriptionally silent chromatin.
    1. Neuroscience

    Sleep deprivation suppresses aggression in Drosophila

    Matthew S Kayser et al.
    A single night of sleep deprivation suppresses fighting behaviors in male fruit flies, with consequent impairments in reproductive fitness.
    1. Developmental Biology and Stem Cells

    Endocrine remodelling of the adult intestine sustains reproduction in Drosophila

    Tobias Reiff et al.
    A hormone released after mating acts directly on adult intestinal progenitors and differentiated epithelial cells in Drosophila to change their homeostatic setpoint and maximise fecundity.
    1. Developmental Biology and Stem Cells
    2. Genomics and Evolutionary Biology

    Logics and properties of a genetic regulatory program that drives embryonic muscle development in an echinoderm

    Carmen Andrikou et al.
    A gene regulatory network model provides a simplified explanation of the molecular interactions that orchestrate muscle development in the sea urchin embryo.
    1. Ecology
    2. Epidemiology and Global Health

    Mycobacterium ulcerans dynamics in aquatic ecosystems are driven by a complex interplay of abiotic and biotic factors

    Andrés Garchitorena et al.
    Different transmission routes of Mycobacterium ulcerans to aquatic organisms may prevail depending on local physico-chemical conditions.
    1. Neuroscience

    Morphine disinhibits glutamatergic input to VTA dopamine neurons and promotes dopamine neuron excitation

    Ming Chen et al.
    Experiments examining the actions of morphine on single neurons from one of the brain's reward centers, the VTA, reveal the mechanism by which the drug exerts its hedonic effects.
    1. Neuroscience

    Spontaneous neurotransmission signals through store-driven Ca2+ transients to maintain synaptic homeostasis

    Austin L Reese, Ege T Kavalali
    Individual neurons can adjust the strength of their synapses by using spontaneous calcium influx through NMDA receptors to trigger the release of additional calcium from intracellular stores, which can in turn be used to regulate protein synthesis.
    1. Neuroscience

    Starvation promotes concerted modulation of appetitive olfactory behavior via parallel neuromodulatory circuits

    Kang I Ko et al.
    Starvation upregulates activity in certain sensory channels and downregulates it in others in what appears to be an optimization strategy that serves to increase the hedonic value of food odors.
    1. Biochemistry
    2. Biophysics and Structural Biology

    Tubulin cofactors and Arl2 are cage-like chaperones that regulate the soluble αβ-tubulin pool for microtubule dynamics

    Stanley Nithianantham et al.
    Soluble αβ-tubulin assembly is regulated by a cage-like molecular complex containing tubulin cofactors and Arl2.
    1. Ecology
    2. Plant Biology

    Seasonal shift in timing of vernalization as an adaptation to extreme winter

    Susan Duncan et al.
    An adaptation to extreme winter has involved a shift to autumn temperature monitoring.
    1. Developmental Biology and Stem Cells
    2. Human Biology and Medicine

    MicroRNA-203 represses selection and expansion of oncogenic Hras transformed tumor initiating cells

    Kent Riemondy et al.
    Inhibition of microRNA-203 by oncogenic HRas mutations promotes skin cancer initiation.
    1. Human Biology and Medicine

    Genomic variations of the mevalonate pathway in porokeratosis

    Zhenghua Zhang et al.
    Mutations in four members of the mevalonate pathway have been identified from 134 index porokeratosis patients, including some that correlate with specific clinical manifestations of the disease.
    1. Ecology
    2. Genomics and Evolutionary Biology

    Viral dark matter and virus–host interactions resolved from publicly available microbial genomes

    Simon Roux et al.
    From public microbial genomes, VirSorter revealed 12,498 viral genome sequences that expand the map of the global virosphere and whose analyses improve understanding of viral taxonomy, evolution and virus-host interactions.
    1. Developmental Biology and Stem Cells
    2. Genes and Chromosomes

    Cancer-associated TERT promoter mutations abrogate telomerase silencing

    Kunitoshi Chiba et al.
    TERT promoter mutations impair TERT silencing upon cellular differentiation and are sufficient to facilitate cellular immortalization without additional tumor selected changes, explaining why they are associated with a very specific tumor spectrum.
    1. Cell Biology
    2. Genes and Chromosomes

    Lipid-mediated regulation of SKN-1/Nrf in response to germ cell absence

    Michael J Steinbaugh et al.
    Germ cell ablation delays C. elegans aging, in part, because unconsumed fat triggers activation of the detoxification factor SKN-1/Nrf, which is regulated by lipid signals and maintains lipid homeostasis.
    1. Genomics and Evolutionary Biology
    2. Plant Biology

    Stress induced gene expression drives transient DNA methylation changes at adjacent repetitive elements

    David Secco et al.
    Phosphate starvation in rice induces widespread, but transient, modulation of DNA methylation near stress responsive genes that is independent from the RNA-directed DNA methylation pathway.
    1. Neuroscience

    The active-zone protein Munc13 controls the use-dependence of presynaptic voltage-gated calcium channels

    Nathaniel Calloway et al.
    Munc13, a protein that is essential for exocytosis, controls the behavior of voltage gated calcium channels and shapes synaptic plasticity on fast time scales.
    1. Plant Biology

    Calcium specificity signaling mechanisms in abscisic acid signal transduction in Arabidopsis guard cells

    Benjamin Brandt et al.
    The calcium-dependent signaling pathway during ABA-dependent stomatal closure requires the calcium-independent pathway, and calcium signaling specificity is mediated by PP2C protein phosphatases.
    1. Immunology

    A pain-mediated neural signal induces relapse in murine autoimmune encephalomyelitis, a multiple sclerosis model

    Yasunobu Arima et al.
    Pain sensation induces relapse in a mouse model of multiple sclerosis via a sensory-sympathetic signaling pathway.
    1. Human Biology and Medicine

    Functional evidence implicating chromosome 7q22 haploinsufficiency in myelodysplastic syndrome pathogenesis

    Jasmine C Wong et al.
    Immature hematopoietic cells from mice with a large segmental deletion found in human myeloid malignancies exhibit cardinal features of myelodysplastic syndrome.
    1. Biophysics and Structural Biology

    Contacts-based prediction of binding affinity in protein–protein complexes

    Anna Vangone, Alexandre MJJ Bonvin
    The number of contacts at the interface of a protein–protein complex, together with the properties of the surface, provides a simple, but well-performing predictor of binding affinity.
    1. Developmental Biology and Stem Cells

    Neuron hemilineages provide the functional ground plan for the Drosophila ventral nervous system

    Robin M Harris et al.
    Hemilineages link neuronal stem cells to behavioral functions by providing a conserved ground plan of neuronal types that evolution then uses to sculpt different types of walking and flight behaviors.
    1. Cell Biology
    2. Developmental Biology and Stem Cells

    Transdifferentiation mediated tumor suppression by the endoplasmic reticulum stress sensor IRE-1 in C. elegans

    Mor Levi-Ferber et al.
    IRE-1 manipulates tumor cell identity to restore apoptosis sensitivity and suppress an aggressive germline tumor in C. elegans.
    1. Biophysics and Structural Biology
    2. Cell Biology

    STIL binding to Polo-box 3 of PLK4 regulates centriole duplication

    Christian Arquint et al.
    Binding of STIL to PLK4's characteristic Polo-box 3 links PLK4 kinase activation to STIL self-association and is a crucial regulatory step for the localized recruitment of downstream factors in centriole duplication.
    1. Cell Biology

    The equatorial position of the metaphase plate ensures symmetric cell divisions

    Chia Huei Tan et al.
    Human cells center the position of the metaphase plate before anaphase onset to ensure the formation of equal-sized daughter cells.
    1. Developmental Biology and Stem Cells
    2. Neuroscience

    Robo2 acts in trans to inhibit Slit-Robo1 repulsion in pre-crossing commissural axons

    Timothy A Evans et al.
    The Roundabout2 receptor acts non-autonomously to promote commissural axons to cross the midline by antagonizing Slit-dependent axon repulsion.
    1. Biochemistry
    2. Cell Biology

    The deca-GX3 proteins Yae1-Lto1 function as adaptors recruiting the ABC protein Rli1 for iron-sulfur cluster insertion

    Viktoria Désirée Paul et al.
    Two newly identified assembly factors for the ribosome-associated iron-sulfur protein Rli1 reveal a general mechanism for how the cytosolic iron-sulfur protein assembly (CIA) machinery recruits apoproteins.
    1. Cell Biology

    Dopamine receptors reveal an essential role of IFT-B, KIF17, and Rab23 in delivering specific receptors to primary cilia

    Alison Leaf, Mark Von Zastrow
    The mechanism of signaling receptor delivery to primary cilia involves a specific cellular role of a Rab protein that is critical for vertebrate development.
    1. Genes and Chromosomes
    2. Genomics and Evolutionary Biology

    Genome-wide DNA hypomethylation and RNA:DNA hybrid accumulation in Aicardi–Goutières syndrome

    Yoong Wearn Lim et al.
    Global epigenetic perturbations and accumulation of RNA:DNA hybrids are two novel hallmarks of the lupus-like inflammatory disorder Aicardi-Goutières syndrome.
    1. Genomics and Evolutionary Biology
    2. Microbiology and Infectious Disease

    Chromerid genomes reveal the evolutionary path from photosynthetic algae to obligate intracellular parasites

    Yong H Woo et al.
    Analysis of chromerid algal genomes reveals how apicomplexans have evolved from free-living algae into successful eukaryotic parasites via massive losses and re-inventing functional roles of genes.
    1. Biochemistry
    2. Microbiology and Infectious Disease

    Deconvoluting heme biosynthesis to target blood-stage malaria parasites

    Paul A Sigala et al.
    Insights into the basic metabolic architecture and adaptations of malaria parasites for growth within human erythrocytes exemplify how incisive knowledge of biochemical pathways and mechanisms may be leveraged to develop new therapies.
    1. Cell Biology
    2. Human Biology and Medicine

    Nur77 prevents excessive osteoclastogenesis by inducing ubiquitin ligase Cbl-b to mediate NFATc1 self-limitation

    Xiaoxiao Li et al.
    Orphan nuclear receptor Nur77 protects bone by enabling a timely termination of osteoclast differentiation.
    1. Cell Biology
    2. Genes and Chromosomes

    LXRs link metabolism to inflammation through Abca1-dependent regulation of membrane composition and TLR signaling

    Ayaka Ito et al.
    The cholesterol-sensing nuclear receptor LXR regulates inflammatory responses by altering the lipid composition of cell membranes.
    1. Biochemistry
    2. Microbiology and Infectious Disease

    Phytotoxin production in Aspergillus terreus is regulated by independent environmental signals

    Markus Gressler et al.
    Elevated methionine levels, or a shortage of nitrogen or iron, induce terrein production in the fungus Aspergillus terreus.
    1. Immunology

    Self-recognition drives the preferential accumulation of promiscuous CD4+ T-cells in aged mice

    Neha R Deshpande et al.
    Higher affinity for self-pMHC complexes and broader promiscuity for foreign-pMHC complexes imparts a fitness advantage within the CD4+ T cell compartment in older mice.
    1. Developmental Biology and Stem Cells

    Paracrine Met signaling triggers epithelial–mesenchymal transition in mammary luminal progenitors, affecting their fate

    Amandine Di-Cicco et al.
    Mammary progenitors identified by a new marker, ICAM-1, undergo epithelial-mesenchymal transition and luminal-to-basal switch in response to paracrine Met activation.
    1. Cell Biology
    2. Neuroscience

    VCP-dependent muscle degeneration is linked to defects in a dynamic tubular lysosomal network in vivo

    Alyssa E Johnson et al.
    The AAA-ATPase VCP sustains sarcoplasmic proteostasis, in part, by controlling autophagosome-lysosome fusion and the integrity of a dynamic tubular lysosomal network.
    1. Cell Biology
    2. Immunology

    Immune surveillance of the lung by migrating tissue monocytes

    Mathieu P Rodero et al.
    Monocytes display distinct migratory and functional activity compared to dendritic cells and alveolar macrophages in the lungs.
    1. Biophysics and Structural Biology
    2. Genes and Chromosomes

    MutS/MutL crystal structure reveals that the MutS sliding clamp loads MutL onto DNA

    Flora S Groothuizen et al.
    Visualization of the sliding clamp in DNA mismatch repair shows how a transient complex is activated.
    1. Cell Biology

    Erk regulation of actin capping and bundling by Eps8 promotes cortex tension and leader bleb-based migration

    Jeremy S Logue et al.
    Eps8, a specific effector of oncogenic signaling, organizes the cortical actin cytoskeleton of cancer cells to promote mechanical properties that favor a newly identified mode of confined, adhesion-independent cell migration.
    1. Neuroscience

    Differential inhibition onto developing and mature granule cells generates high-frequency filters with variable gain

    María Belén Pardi et al.
    Immature and mature granule cells in the hippocampal dentate gyrus show differing responses to physiologically relevant stimuli, with immature cells better at encoding stimulus frequency and mature cells better at encoding stimulus onset.
    1. Epidemiology and Global Health
    2. Microbiology and Infectious Disease

    Integrating between-host transmission and within-host immunity to analyze the impact of varicella vaccination on zoster

    Benson Ogunjimi et al.
    An individual-based model estimates exogenous boosting of immunity following re-exposure to chickenpox is limited to 2 years after re-exposure, but an increase in herpes zoster incidence is still expected to occur following universal varicella vaccination.
    1. Biochemistry
    2. Biophysics and Structural Biology

    A composite double-/single-stranded RNA-binding region in protein Prp3 supports tri-snRNP stability and splicing

    Sunbin Liu et al.
    Structural and functional analyses show how the spliceosomal Prp3 protein concomitantly binds double- and single- stranded regions in U4/U6 di-snRNAs and serves to stabilize the U4/U6•U5 tri-snRNP for splicing.
    1. Neuroscience

    Arcuate hypothalamic AgRP and putative POMC neurons show opposite changes in spiking across multiple timescales

    Yael Mandelblat-Cerf et al.
    Gradual changes in the firing of specific hypothalamic neurons over many hours signal falling energy levels, while short-lived changes over seconds and minutes signal the availability of food.
    1. Neuroscience

    Slit2 as a β-catenin/Ctnnb1-dependent retrograde signal for presynaptic differentiation

    Haitao Wu et al.
    A novel retrograde signal is involved in nerve terminal differentiation at mouse neuromuscular junctions.
    1. Biochemistry
    2. Biophysics and Structural Biology

    Structures of the scanning and engaged states of the mammalian SRP-ribosome complex

    Rebecca M Voorhees, Ramanujan S Hegde
    Structures of the signal recognition particle before and after it captures a transmembrane domain suggest how it chooses, engages, and shields its clients during membrane protein targeting to the endoplasmic reticulum.
    1. Biophysics and Structural Biology
    2. Developmental Biology and Stem Cells

    Structure and functional properties of Norrin mimic Wnt for signalling with Frizzled4, Lrp5/6, and proteoglycan

    Tao-Hsin Chang et al.
    The crystal structure of Norrie Disease Protein in complex with the extracellular cysteine-rich domain of Frizzled4 receptor and sucrose octasulfate reveals binding sites for Frizzled4, low density lipoprotein receptor related protein 5/6, and proteoglycan.
    1. Neuroscience

    Cerebellar associative sensory learning defects in five mouse autism models

    Alexander D Kloth et al.
    Five mouse models of autism show deficits in delay eyeblink conditioning, a form of split-second sensory learning that involves the cerebellum, a frequent site of disruption in autistic brains.
    1. Developmental Biology and Stem Cells
    2. Immunology

    Identification of polarized macrophage subsets in zebrafish

    Mai Nguyen-Chi et al.
    The discovery of evolutionarily conserved macrophage subsets in zebrafish paves the way for a comprehensive study of macrophage behaviour and function.
    1. Computational and Systems Biology
    2. Immunology

    An open-source computational and data resource to analyze digital maps of immunopeptidomes

    Etienne Caron et al.
    A community-based international effort generates standardized HLA allele-specific peptide assay libraries and enables the analysis of the human immunopeptidome by SWATH mass spectrometry.
    1. Neuroscience

    The number of olfactory stimuli that humans can discriminate is still unknown

    Richard C Gerkin, Jason B Castro
    The recent claim that humans can discriminate more than one trillion odors is shown to be unwarranted.
    1. Neuroscience

    Irregular spiking of pyramidal neurons organizes as scale-invariant neuronal avalanches in the awake state

    Timothy Bellay et al.
    Spontaneous, irregular spiking in single cortical pyramidal neurons assembles as neuronal avalanches at the group level identifying a robust scale-invariant organization of resting activity in the awake state.
    1. Developmental Biology and Stem Cells
    2. Human Biology and Medicine

    The acinar differentiation determinant PTF1A inhibits initiation of pancreatic ductal adenocarcinoma

    Nathan M Krah et al.
    By regulating acinar cell differentiation, the transcription factor PTF1A acts as a novel class of tumor suppressor in pancreatic cancer.
    1. Cell Biology
    2. Genes and Chromosomes

    Mitotic fidelity requires transgenerational action of a testis-restricted HP1

    Mia T Levine et al.
    Analysis of a spermiogenesis protein reveals a new chromatin requirement for synchrony between maternal DNA packaged in the egg and sperm-packaged paternal DNA in the first embryonic mitosis in Drosophila melanogaster.
    1. Computational and Systems Biology
    2. Neuroscience

    On the dimensionality of odor space

    Markus Meister
    A recent claim that humans can discriminate 1 trillion odors is found to be unwarranted, and further analysis offers insights into the dimensionality of olfactory perception.
    1. Computational and Systems Biology
    2. Neuroscience

    Noise promotes independent control of gamma oscillations and grid firing within recurrent attractor networks

    Lukas Solanka et al.
    Random fluctuations in neuronal firing may enable a single brain region, the medial entorhinal cortex, to perform distinct roles in cognition (by generating gamma waves) and spatial navigation (by producing a grid cell map).
    1. Developmental Biology and Stem Cells

    NKX2-5 mutations causative for congenital heart disease retain functionality and are directed to hundreds of targets

    Romaric Bouveret et al.
    Some NKX2-5 mutations that cause congenital heart disease retain transcriptional activity and can bind to many off-target genes, in part through their interactions with cofactors.
    1. Neuroscience

    Functional effects of distinct innervation styles of pyramidal cells by fast spiking cortical interneurons

    Yoshiyuki Kubota et al.
    Cortical interneurons inhibit pyramidal cells to a greater degree when they form synapses with the pyramidal cell body than when they form synapses with dendrites.
    1. Neuroscience

    Optogenetic feedback control of neural activity

    Jonathan P Newman et al.
    The 'Optoclamp' is a feedback control technology that enables precise, continuously updated, closed-loop optical control of neural firing both in vitro and in vivo.
    1. Neuroscience

    Quantitative and functional interrogation of parent-of-origin allelic expression biases in the brain

    Julio D Perez et al.
    A subset of genes in the mouse brain show dynamically regulated and unequal expression of maternally and paternally derived variants, with implications for brain development and function.
    1. Developmental Biology and Stem Cells
    2. Neuroscience

    Protocadherin-dependent dendritic self-avoidance regulates neural connectivity and circuit function

    Dimitar Kostadinov, Joshua R Sanes
    Patterning of dendrites by protocadherin-dependent self-avoidance and self/non-self discrimination is required for proper function of a retinal circuit that computes the direction of motion.
    1. Genes and Chromosomes

    The β-hairpin of 40S exit channel protein Rps5/uS7 promotes efficient and accurate translation initiation in vivo

    Jyothsna Visweswaraiah et al.
    A structural element of mRNA exit channel protein Rps5 performs a critical role in start codon recognition during translation initiation by stabilizing initiator tRNA binding to the pre-initiation complex.

Magazine

  1. Research: Theory, models and biology

    Wenying Shou et al.