November 2016

Cover articles

Research articles

    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Structural basis for the disaggregase activity and regulation of Hsp104

    Alexander Heuck, Sonja Schitter-Sollner ... Tim Clausen
    Protein disaggregases employ two mechanically-linked ATPase rings that are under steric control by a wrapped-around coiled-coil belt.
    1. Cell Biology
    2. Developmental Biology

    Differentiation alters stem cell nuclear architecture, mechanics, and mechano-sensitivity

    Su-Jin Heo, Tristan P Driscoll ... Robert L Mauck
    Nuclear reorganization and stiffening accompanies mesenchymal stem cell differentiation, resulting in increased sensitivity to mechanical perturbation.
    1. Neuroscience

    Loss of Frataxin activates the iron/sphingolipid/PDK1/Mef2 pathway in mammals

    Kuchuan Chen, Tammy Szu-Yu Ho ... Hugo J Bellen
    The iron/sphingolipid/PDK1/Mef2 pathway is activated in mammals upon loss of Frataxin.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Structural basis for the recognition of spliceosomal SmN/B/B’ proteins by the RBM5 OCRE domain in splicing regulation

    André Mourão, Sophie Bonnal ... Michael Sattler
    Interactions with Sm proteins can provide a way in which regulatory factors can modulate alternative splice site choices.
    1. Genetics and Genomics
    2. Evolutionary Biology

    Oral transfer of chemical cues, growth proteins and hormones in social insects

    Adria C LeBoeuf, Patrice Waridel ... Laurent Keller
    The socially exchanged fluid passed mouth-to-mouth during trophallaxis contains molecules that can influence development, potentially mediating communal control of colony phenotypes.
    1. Epidemiology and Global Health

    Structure in the variability of the basic reproductive number (R0) for Zika epidemics in the Pacific islands

    Clara Champagne, David Georges Salthouse ... Bernard Cazelles
    Stochastic models able to reproduce both incidence and seroprevalence data for Zika outbreaks in the Pacific Islands estimate that the basic reproduction number (R0) is between 1.5 and 4.1.
    1. Chromosomes and Gene Expression
    2. Microbiology and Infectious Disease

    A common bacterial metabolite elicits prion-based bypass of glucose repression

    David M Garcia, David Dietrich ... Daniel F Jarosz
    Activity-guided fractionation identifies the first bacterial metabolite that potently induces a prion in nature.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    An essential cell-autonomous role for hepcidin in cardiac iron homeostasis

    Samira Lakhal-Littleton, Magda Wolna ... Peter A Robbins
    The novel role of hepcidin in cell-autonomous iron regulation changes our understanding of tissue-specific iron control, and of its interplay with systemic iron homeostasis.
    1. Biochemistry and Chemical Biology
    2. Evolutionary Biology

    Discovery of methylfarnesoate as the annelid brain hormone reveals an ancient role of sesquiterpenoids in reproduction

    Sven Schenk, Christian Krauditsch ... Florian Raible
    A small brain-derived lipid prevents bristle worms from entering maturation and death, challenging current views of hormone evolution and pesticide specificity.
    1. Structural Biology and Molecular Biophysics
    2. Computational and Systems Biology

    Mechanism of allosteric regulation of β2-adrenergic receptor by cholesterol

    Moutusi Manna, Miia Niemelä ... Ilpo Vattulainen
    Atomistic simulations reveal how lipids can allosterically modulate membrane receptors.
    1. Cell Biology
    2. Developmental Biology

    Epidermal cell turnover across tight junctions based on Kelvin's tetrakaidecahedron cell shape

    Mariko Yokouchi, Toru Atsugi ... Akiharu Kubo
    The three dimensional structure of epidermal cells in the stratum granulosum provides the basis for the homeostasis of the tight junction barrier during cell turnover in the skin.
    1. Chromosomes and Gene Expression
    2. Neuroscience

    Satb2 determines miRNA expression and long-term memory in the adult central nervous system

    Clemens Jaitner, Chethan Reddy ... Galina Apostolova
    The genome-organizer Satb2 has a key role in memory formation by modulating availability of miRNAs that control the function of synapses.
    1. Neuroscience

    Transformation of temporal sequences in the zebra finch auditory system

    Yoonseob Lim, Ryan Lagoy ... Timothy J Gardner
    Songbirds discriminate synthetic sounds composed of temporal patterns of clicks, which they transform into distinct ensemble or spatial patterns in successive stages of neural auditory processing.
    1. Neuroscience

    Lovastatin fails to improve motor performance and survival in methyl-CpG-binding protein2-null mice

    Claudia Villani, Giuseppina Sacchetti ... Roberto William Invernizzi
    Lovastatin ability to rescue motor deficits and survival in a mouse model of Rett syndrome is strongly influenced by the genetic background.
    1. Neuroscience

    A comprehensive excitatory input map of the striatum reveals novel functional organization

    Barbara J Hunnicutt, Bart C Jongbloets ... Tianyi Mao
    The first comprehensive map of all excitatory inputs to the mouse striatum is presented and used to define and demarcate striatal subdivisions, including a previous unappreciated novel subdivision in the posterior striatum.
    1. Neuroscience
    2. Genetics and Genomics

    Regulatory changes in two chemoreceptor genes contribute to a Caenorhabditis elegans QTL for foraging behavior

    Joshua S Greene, May Dobosiewicz ... Cornelia I Bargmann
    A quantitative trait locus that includes two pheromone receptor genes affects foraging behavior; for one of the genes, the two alleles of the QTL have opposite effects because of distinct sites of expression.
    1. Physics of Living Systems
    2. Cell Biology

    Physical basis of large microtubule aster growth

    Keisuke Ishihara, Kirill S Korolev, Timothy J Mitchison
    Autocatalytic growth of a microtubule polymer network allows extremely large egg cells to self-organize and divide rapidly.
    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    Structure of the germline genome of Tetrahymena thermophila and relationship to the massively rearranged somatic genome

    Eileen P Hamilton, Aurélie Kapusta ... Robert S Coyne
    The model organism Tetrahymena thermopile carries two nuclei with distinct genomes: an unrearranged germline genome with five chromosomes, and a somatic genome reduced in size by a third and with 181 chromosomes.
    1. Physics of Living Systems

    Mapping out Min protein patterns in fully confined fluidic chambers

    Yaron Caspi, Cees Dekker
    The geometry selection rules of dynamic Min protein patterns are determined in fully confined fluidic chambers, showing that both oscillations and running waves are derivatives of spiral rotations that are established as the majority pattern.
    1. Computational and Systems Biology
    2. Stem Cells and Regenerative Medicine

    Accelerated cell divisions drive the outgrowth of the regenerating spinal cord in axolotls

    Fabian Rost, Aida Rodrigo Albors ... Osvaldo Chara
    Building on previous work (Rodrigo Albors et al., 2015), we assess the contribution of individual cellular mechanisms in the context of spinal cord regeneration in the axolotl.
    1. Stem Cells and Regenerative Medicine

    Klp10A, a stem cell centrosome-enriched kinesin, balances asymmetries in Drosophila male germline stem cell division

    Cuie Chen, Mayu Inaba ... Yukiko M Yamashita
    Microtubule-depolymerizing kinesin, Klp10A, prevents overgrowth of the mother centrosome to prevent undesirable asymmetries during asymmetric divisions of Drosophila male germline stem cells.
    1. Computational and Systems Biology
    2. Neuroscience

    Connectivity map of bipolar cells and photoreceptors in the mouse retina

    Christian Behrens, Timm Schubert ... Philipp Berens
    A quantitative analysis of the connectivity between photoreceptors and bipolar cells in the mouse retina based on electron microscopy data yields exceptions from established rules of outer retinal connectivity.
    1. Epidemiology and Global Health

    Global mapping of highly pathogenic avian influenza H5N1 and H5Nx clade 2.3.4.4 viruses with spatial cross-validation

    Madhur S Dhingra, Jean Artois ... Marius Gilbert
    The global suitability for avian flu H5N1 in poultry is predicted and spatially cross-validated, highlighting areas where the disease can spread in the absence of prevention and control, and represent a public health threat.
    1. Biochemistry and Chemical Biology
    2. Chromosomes and Gene Expression

    Large-scale remodeling of a repressed exon ribonucleoprotein to an exon definition complex active for splicing

    Somsakul Pop Wongpalee, Ajay Vashisht ... Douglas L Black
    A protein regulator of alternative pre-mRNA splicing arrests spliceosome assembly at a previously unrecognized step that defines new intermediate stages in the formation of exon complexes.
    1. Physics of Living Systems

    Aerotaxis in the closest relatives of animals

    Julius B Kirkegaard, Ambre Bouillant ... Raymond E Goldstein
    The colony-forming choanoflagellate Salpingoeca rosetta is capable of moving towards oxygen using logarithmic sensing of oxygen concentrations and a navigation strategy that involves random movements.
    1. Neuroscience

    Single synapse evaluation of the postsynaptic NMDA receptors targeted by evoked and spontaneous neurotransmission

    Austin L Reese, Ege T Kavalali
    In a population of mammalian central synapses, spontaneous and evoked neurotransmitter release processes are independently distributed; yet, postsynaptic receptors within a single synapse preferentially receive neurotransmitter from only one mode of release.
    1. Neuroscience

    Visual attention is available at a task-relevant location rapidly after a saccade

    Tao Yao, Madhura Ketkar ... B Suresh Krishna
    Spatial attention and saccadic processing co-ordinate to ensure that attention is available at a task-relevant location soon after the beginning of each eye fixation.
    1. Chromosomes and Gene Expression

    Exon junction complex proteins bind nascent transcripts independently of pre-mRNA splicing in Drosophila melanogaster

    Subhendu Roy Choudhury, Anand K Singh ... Saverio Brogna
    Deposition of the exon junction complex is thought to be the missing link between pre-mRNA splicing and translation in multicellular organisms, but no evidence of such deposition has been found in Drosophila.
    1. Developmental Biology
    2. Chromosomes and Gene Expression

    Establishment and maintenance of heritable chromatin structure during early Drosophila embryogenesis

    Shelby A Blythe, Eric F Wieschaus
    The patterns of chromatin architecture that underlie the initial embryonic cell fate decisions are established during a period of intense cell cycle activity, and these patterns are stably maintained even in highly condensed mitotic chromatin.
    1. Cell Biology
    2. Chromosomes and Gene Expression

    Quantifying β-catenin subcellular dynamics and cyclin D1 mRNA transcription during Wnt signaling in single living cells

    Pinhas Kafri, Sarah E Hasenson ... Yaron Shav-Tal
    Imaging of single cells within a cell population shows the correlation between subcellular accumulation of β-catenin and the transcriptional activation of a target gene.
    1. Cancer Biology
    2. Developmental Biology

    Fetal and neonatal hematopoietic progenitors are functionally and transcriptionally resistant to Flt3-ITD mutations

    Shaina N Porter, Andrew S Cluster ... Jeffrey A Magee
    Age-specific transcriptional responses to Flt3-ITD and cooperating Flt3/Runx1 mutations cause hematopoietic stem cell depletion and myeloid progenitor expansion during adult, but not fetal/neonatal, stages of development.
    1. Neuroscience

    An NMDA receptor-dependent mechanism for subcellular segregation of sensory inputs in the tadpole optic tectum

    Ali S Hamodi, Zhenyu Liu, Kara G Pratt
    An activity-dependent mechanism sculpts subcellular segregation of sensory inputs.
    1. Biochemistry and Chemical Biology

    Mechanism of cargo-directed Atg8 conjugation during selective autophagy

    Dorotea Fracchiolla, Justyna Sawa-Makarska ... Sascha Martens
    Autophagic cargo receptors recruit the E3-like enzyme for Atg8 lipid conjugation to the cargo and thereby promote local formation of Atg8-positive autophagosomal membranes.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Structure of protein O-mannose kinase reveals a unique active site architecture

    Qinyu Zhu, David Venzke ... Junyu Xiao
    Active site migration establishes kinase activity in protein O-mannose kinase.
    1. Neuroscience

    Postprandial sleep mechanics in Drosophila

    Keith R Murphy, Sonali A Deshpande ... William W Ja
    Evidence of food coma has been found in fruit flies, allowing the properties that drive postprandial sleep and their underlying genetic and neuronal mechanisms to be described.
    1. Biochemistry and Chemical Biology
    2. Plant Biology

    Recreating the synthesis of starch granules in yeast

    Barbara Pfister, Antoni Sánchez-Ferrer ... Samuel C Zeeman
    Yeast cells can be engineered to study starch, the semi-crystalline storage carbohydrate from plants that is central to human nutrition.
    1. Neuroscience

    Postictal behavioural impairments are due to a severe prolonged hypoperfusion/hypoxia event that is COX-2 dependent

    Jordan S Farrell, Ismael Gaxiola-Valdez ... G Campbell Teskey
    Local tissue hypoxia follows seizures, is responsible for postictal behavioural dysfunction rather than the seizures per se and can be treated.
    1. Cell Biology

    In vivo vizualisation of mono-ADP-ribosylation by dPARP16 upon amino-acid starvation

    Angelica Aguilera-Gomez, Marinke M van Oorschot ... Catherine Rabouille
    Amino-acid induced Sec body formation is mediated by PARP16 dependent MARylation of Sec16, a component of the endoplasmic reticulum exit site.
    1. Neuroscience

    Chronic social isolation reduces 5-HT neuronal activity via upregulated SK3 calcium-activated potassium channels

    Derya Sargin, David K Oliver, Evelyn K Lambe
    Serotonin neurons in chronically isolated mice become less responsive to excitatory stimulation, but inhibiting a distinctive calcium-activated potassium channel can restore both neuronal activity and behavior.
    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    A Herpesviral induction of RAE-1 NKG2D ligand expression occurs through release of HDAC mediated repression

    Trever T Greene, Maria Tokuyama ... Laurent Coscoy
    Viral infection can induce NKG2D ligand expression through the action of virally encoded histone deacetylase (HDAC) inhibitors, which release HDAC mediated repression of NKG2D ligands.
    1. Immunology and Inflammation

    Actin is an evolutionarily-conserved damage-associated molecular pattern that signals tissue injury in Drosophila melanogaster

    Naren Srinivasan, Oliver Gordon ... Caetano Reis e Sousa
    Extracellular actin is an evolutionarily-conserved signal of tissue injury that is recognised in the fruit fly via similar machinery as reported in vertebrates.
    1. Chromosomes and Gene Expression
    2. Plant Biology

    POWERDRESS interacts with HISTONE DEACETYLASE 9 to promote aging in Arabidopsis

    Xiangsong Chen, Li Lu ... Xuehua Zhong
    Genetic and biochemical studies reveal how a histone deacetylase acts together with other chromatin regulators to promote the onset of plant aging.
    1. Cell Biology
    2. Genetics and Genomics

    Cell culture-based profiling across mammals reveals DNA repair and metabolism as determinants of species longevity

    Siming Ma, Akhil Upneja ... Vadim N Gladyshev
    Profiling of fibroblasts across mammals captures differences in longevity at the level of global gene expression and metabolite levels and reveals pathways that define these differences.
    1. Neuroscience

    SF-1 expression in the hypothalamus is required for beneficial metabolic effects of exercise

    Teppei Fujikawa, Carlos M Castorena ... Joel K Elmquist
    The transcription factor steroidogenic factor-1 in the hypothalamus is required for adaptive metabolic responses to exercise training.
    1. Chromosomes and Gene Expression
    2. Immunology and Inflammation

    Tet2 and Tet3 cooperate with B-lineage transcription factors to regulate DNA modification and chromatin accessibility

    Chan-Wang Lio, Jiayuan Zhang ... Anjana Rao
    TET methylcytosine oxidases cooperate with B lineage-specific transcription factors to promote immunoglobulin gene rearrangement by depositing 5hmC, facilitating DNA demethylation and increasing chromatin accessibility at enhancers.
    1. Neuroscience

    How prior preferences determine decision-making frames and biases in the human brain

    Alizée Lopez-Persem, Philippe Domenech, Mathias Pessiglione
    Model-based analyses of choice behavior and fMRI activity revealed that prior preferences generate default policies, which frame the decision value signal encoded in the vmPFC, and shift vmPFC pre-choice activity so as to induce a decision bias toward default options.
    1. Developmental Biology

    Neuronal sources of hedgehog modulate neurogenesis in the adult planarian brain

    Ko W Currie, Alyssa M Molinaro, Bret J Pearson
    Planarian brain neurons modulate their turnover by signaling to nearby stem cells.
    1. Evolutionary Biology

    Splicing repression allows the gradual emergence of new Alu-exons in primate evolution

    Jan Attig, Igor Ruiz de los Mozos ... Jernej Ule
    During evolutionary progression of Alu-exons, repressive U-tracts buffer sudden gains in 3' splice site strength and prevent inclusion of cryptic exons.
    1. Cancer Biology
    2. Immunology and Inflammation

    Long-term intravital imaging of the multicolor-coded tumor microenvironment during combination immunotherapy

    Shuhong Qi, Hui Li ... Zhihong Zhang
    Tregs form an "immunosuppressive ring" around solid tumors that is broken down during adoptive cell therapy and cyclophosphamide combination immunotherapy.
    1. Chromosomes and Gene Expression

    Local chromosome context is a major determinant of crossover pathway biochemistry during budding yeast meiosis

    Darpan Medhi, Alastair SH Goldman, Michael Lichten
    Different homologous recombination pathways are dominant in different regions of meiotic chromosomes, indicating that chromosome structure influences recombination biochemistry.
    1. Neuroscience

    Decoding gripping force based on local field potentials recorded from subthalamic nucleus in humans

    Huiling Tan, Alek Pogosyan ... Peter Brown
    Patterns of coordinated activity in the basal ganglia predict how much force we will use to grip objects, suggesting that individuals with paralysis may ultimately be able to use these signals to control graded responses in robotic devices.
    1. Stem Cells and Regenerative Medicine

    Smad4 restricts differentiation to promote expansion of satellite cell derived progenitors during skeletal muscle regeneration

    Nicole D Paris, Andrew Soroka ... Joe V Chakkalakal
    Ablation of canonical TGFβ signaling in muscle stem cells at any age is detrimental, and not beneficial, to effective skeletal muscle regeneration due to the promotion of premature fate commitment at the expense of progenitor amplification.
    1. Neuroscience
    2. Developmental Biology

    Neuroendocrine modulation sustains the C. elegans forward motor state

    Maria A Lim, Jyothsna Chitturi ... Mei Zhen
    RID is a descending peptidergic neuron that sustains the forward motor state.
    1. Chromosomes and Gene Expression

    Successful transmission and transcriptional deployment of a human chromosome via mouse male meiosis

    Christina Ernst, Jeremy Pike ... Duncan T Odom
    Transmission of an entire human chromosome through the mouse male germline reveals an unexpectedly high tolerance of aneuploidy during male meiosis and results in accurate transcriptional deployment despite massive epigenetic remodeling during spermatogenesis.
    1. Structural Biology and Molecular Biophysics

    Structure and dynamics underlying elementary ligand binding events in human pacemaking channels

    Marcel P Goldschen-Ohm, Vadim A Klenchin ... Baron Chanda
    Single-molecule resolution of cAMP binding to the ligand binding domain of pacemaking channels in zero-mode waveguides reveals the dynamics of the distinct steps underlying both binding and isomerization of the binding domain.
    1. Neuroscience

    Inhibition in the auditory brainstem enhances signal representation and regulates gain in complex acoustic environments

    Christian Keine, Rudolf Rübsamen, Bernhard Englitz
    Inhibition in the brainstem has further roles beyond temporal sharpening and improves reproduction for a multitude of sounds.
    1. Cell Biology

    Sec24 phosphorylation regulates autophagosome abundance during nutrient deprivation

    Saralin Davis, Juan Wang ... Susan Ferro-Novick
    Phosphorylation of a core trafficking component, the COPII coat subunit Sec24, regulates cross-talk between the secretory and autophagy machinery during starvation.
    1. Cell Biology
    2. Chromosomes and Gene Expression

    A dynamic mode of mitotic bookmarking by transcription factors

    Sheila S Teves, Luye An ... Robert Tjian
    In contrast to published findings showing exclusion, transcription factors in fact bind mitotic chromosomes in a dynamic fashion, allowing for efficient transmission of transcription programs through mitosis.
    1. Ecology

    Dynamic metabolic exchange governs a marine algal-bacterial interaction

    Einat Segev, Thomas P Wyche ... Roberto Kolter
    Physical and chemical interactions with bacteria influence the life and death of Emiliania huxleyi, a bloom-forming micro-alga important in global biogeochemical cycles.
    1. Epidemiology and Global Health
    2. Medicine

    Evaluating mesenchymal stem cell therapy for sepsis with preclinical meta-analyses prior to initiating a first-in-human trial

    Manoj M Lalu, Katrina J Sullivan ... Lauralyn McIntyre
    A rigorous and transparent evaluation of mesenchymal stem cell therapy for sepsis suggests it may be efficacious, although the strength of these findings is tempered by threats to validity in the studies that were included.
    1. Computational and Systems Biology
    2. Microbiology and Infectious Disease

    Cell-wall remodeling drives engulfment during Bacillus subtilis sporulation

    Nikola Ojkic, Javier López-Garrido ... Robert G Endres
    Imaging experiments and simulations reveal that the biophysical mechanism for force generation needed to engulf a forespore is based on coordinated cell wall synthesis and degradation.
    1. Cell Biology

    Elimination of paternal mitochondria in mouse embryos occurs through autophagic degradation dependent on PARKIN and MUL1

    Rebecca Rojansky, Moon-Yong Cha, David C Chan
    The uniparental inheritance of mammalian mitochondria results from elimination of paternal mitochondria by a mitophagic process that requires the E3 ubiquitin ligases PARKIN and MUL1.
    1. Developmental Biology
    2. Neuroscience

    Radial glia regulate vascular patterning around the developing spinal cord

    Ryota L Matsuoka, Michele Marass ... Didier YR Stainier
    Identification of a novel role for central nervous system-resident progenitors in the patterning of the vascular network around the developing spinal cord.
    1. Structural Biology and Molecular Biophysics
    2. Cell Biology

    Crenactin forms actin-like double helical filaments regulated by arcadin-2

    Thierry Izoré, Danguole Kureisaite-Ciziene ... Jan Löwe
    Close evolutionary relationship between eukaryotic F-actin and crenarchaeal crenactin protein is supported by a near-atomic cryoEM structure of double helical filaments, that are inhibited by arcadin-2 through binding to crenactin's hydrophobic groove.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    SPRTN is a mammalian DNA-binding metalloprotease that resolves DNA-protein crosslinks

    Jaime Lopez-Mosqueda, Karthik Maddi ... Ivan Dikic
    SPRTN is a protease essential for the repair of cytotoxic DNA-protein cross links and this function is defective in patients afflicted with Ruijs-Aalfs syndrome -a segmental progeroid syndrome.
    1. Neuroscience

    Activity of the C. elegans egg-laying behavior circuit is controlled by competing activation and feedback inhibition

    Kevin M Collins, Addys Bode ... Michael R Koelle
    The neural circuit that regulates egg-laying behavior in nematode worms is activated by egg production, coupled to the circuit that generates movement, and inhibited by sensory feedback from egg release.
    1. Plant Biology

    Auxin production in the endosperm drives seed coat development in Arabidopsis

    Duarte D Figueiredo, Rita A Batista ... Claudia Köhler
    Auxin is produced in the endosperm after fertilization and drives the development of the seed coat in Arabidopsis.
    1. Neuroscience

    Pan-neuronal screening in Caenorhabditis elegans reveals asymmetric dynamics of AWC neurons is critical for thermal avoidance behavior

    Ippei Kotera, Nhat Anh Tran ... William S Ryu
    Functional screening of the entire neuronal network of C. elegans in response to specific stimuli can discover new neural behavior.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Phospholipase D activity couples plasma membrane endocytosis with retromer dependent recycling

    Rajan Thakur, Aniruddha Panda ... Padinjat Raghu
    Phosphatidic acid regulates recycling of endocytosed plasma membrane vesicles in polarized cells through a retromer and Arf1 dependent process.
    1. Neuroscience

    Cellular and neurochemical basis of sleep stages in the thalamocortical network

    Giri P Krishnan, Sylvain Chauvette ... Maxim Bazhenov
    A computational model of the thalamocortical network explains sleep stages by the coordinated variations in the level of neuromodulators and predicts differences of sleep pattern in human, cat and mouse recordings.
    1. Developmental Biology
    2. Genetics and Genomics

    The genome of the crustacean Parhyale hawaiensis, a model for animal development, regeneration, immunity and lignocellulose digestion

    Damian Kao, Alvina G Lai ... Aziz Aboobaker
    The first malacostracan genome sequence will establish the genetically tractable Parhyale hawaiensis as a model organism in this key animal group.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    An evidence based hypothesis on the existence of two pathways of mitochondrial crista formation

    Max E Harner, Ann-Katrin Unger ... Walter Neupert
    Lamellar and tubular cristae in mitochondria form by two different molecular pathways that form both involve F1FO-ATP synthase dimers and the MICOS complex, but formation of lamellar cristae also relies on Mgm1/Opa1.
    1. Stem Cells and Regenerative Medicine
    2. Chromosomes and Gene Expression

    DNA methylation directs genomic localization of Mbd2 and Mbd3 in embryonic stem cells

    Sarah J Hainer, Kurtis N McCannell ... Thomas G Fazzio
    Two methyl-binding domain proteins have interdependent functions in embryonic stem cells, and this interdependency extends to the DNA methylation/hydroxymethylation machinery.
    1. Neuroscience

    Synaptic transmission parallels neuromodulation in a central food-intake circuit

    Philipp Schlegel, Michael J Texada ... Michael J Pankratz
    Connectomic analysis demonstrates that a brain circuit, that may be conserved between flies and mammals, uses both fast synaptic transmission as well as peptidergic neuromodulation to connect chemosensory and endocrine systems.
    1. Microbiology and Infectious Disease

    Establishment and stability of the latent HIV-1 DNA reservoir

    Johanna Brodin, Fabio Zanini ... Jan Albert
    Building on previous work (Zanini et al, 2015), deep-sequencing is used to show that HIV persistence during suppressive antiretroviral therapy, the main hurdle for HIV cure, is due to homeostatic proliferation and longevity of infected cells rather than ongoing virus replication.
    1. Cell Biology
    2. Neuroscience

    Sam68 promotes self-renewal and glycolytic metabolism in mouse neural progenitor cells by modulating Aldh1a3 pre-mRNA 3'-end processing

    Piergiorgio La Rosa, Pamela Bielli ... Claudio Sette
    The RNA binding protein Sam68 links a key metabolic route to the neural stem cell fate in the developing mouse brain.
    1. Cell Biology
    2. Neuroscience

    Mouse Tmem135 mutation reveals a mechanism involving mitochondrial dynamics that leads to age-dependent retinal pathologies

    Wei-Hua Lee, Hitoshi Higuchi ... Akihiro Ikeda
    The murine protein TMEM135 is a critical link between aging and age-dependent diseases.
    1. Neuroscience

    Rotating waves during human sleep spindles organize global patterns of activity that repeat precisely through the night

    Lyle Muller, Giovanni Piantoni ... Terrence J Sejnowski
    A phase-based analysis reveals wave-like spatiotemporal organization of the human sleep spindle, a brain oscillation critical to sleep-dependent memory consolidation, and elucidates its role in coordinating activity of neural networks distributed across the cortex.
    1. Neuroscience

    Neural circuitry coordinating male copulation

    Hania J Pavlou, Andrew C Lin ... Stephen F Goodwin
    A circuit consisting of motor neurons, inhibitory interneurons and mechanosensory neurons controls copulatory behaviour in male fruit flies.
    1. Structural Biology and Molecular Biophysics

    Accelerated cryo-EM structure determination with parallelisation using GPUs in RELION-2

    Dari Kimanius, Björn O Forsberg ... Erik Lindahl
    Using GPUs for the costly computations in cryo-EM enables structure determination in mere days on a single workstation.
    1. Neuroscience

    Organization and function of Drosophila odorant binding proteins

    Nikki K Larter, Jennifer S Sun, John R Carlson
    A genetic analysis reveals that some olfactory sensilla of Drosophila do not require an abundant odorant binding protein and that one such protein may act in gain control.
    1. Cancer Biology
    2. Developmental Biology

    Targeting mutant RAS in patient-derived colorectal cancer organoids by combinatorial drug screening

    Carla S Verissimo, René M Overmeer ... Hugo J Snippert
    Libraries of patient-derived tumor organoids are a reliable and scalable model system that can help identify and optimize targeted therapies in a pre-clinical setting.
    1. Neuroscience

    Synchronous beta rhythms of frontoparietal networks support only behaviorally relevant representations

    Evan G Antzoulatos, Earl K Miller
    Beta-band oscillations in the frontoparietal network may act as a filter of relevant versus irrelevant neural representations for the ongoing cognitive task.
    1. Cell Biology

    Ret function in muscle stem cells points to tyrosine kinase inhibitor therapy for facioscapulohumeral muscular dystrophy

    Louise A Moyle, Eric Blanc ... Peter S Zammit
    Rescue of DUX4-induced muscle pathology by the RET inhibitor Sunitinib reveals the therapeutic potential for treatment of Facioscapulohumeral muscular dystrophy using tyrosine kinase inhibitors.
    1. Neuroscience

    Divisive suppression explains high-precision firing and contrast adaptation in retinal ganglion cells

    Yuwei Cui, Yanbin V Wang ... Daniel A Butts
    The convergence of two visual pathways at the level of retinal bipolar cells accounts for key features of ganglion cell responses.
    1. Microbiology and Infectious Disease
    2. Plant Biology

    A complete toolset for the study of Ustilago bromivora and Brachypodium sp. as a fungal-temperate grass pathosystem

    Franziska Rabe, Jason Bosch ... Armin Djamei
    The establishment of Ustilago bromivora and Brachypodium as a biotrophic model system provides the foundation for studying new aspects of plant-pathogen interactions and for answering questions about fungal sex and speciation.
    1. Cell Biology
    2. Neuroscience

    FcγRIIb-SHIP2 axis links Aβ to tau pathology by disrupting phosphoinositide metabolism in Alzheimer's disease model

    Tae-In Kam, Hyejin Park ... Yong-Keun Jung
    By binding to Fc gamma receptor IIb, amyloid beta induces a series of phosphorylation events that mediate the damaging effects of hyperphosphorylated tau proteins in Alzheimer's disease.
    1. Biochemistry and Chemical Biology
    2. Chromosomes and Gene Expression

    Heterochromatin assembly by interrupted Sir3 bridges across neighboring nucleosomes

    Reza Behrouzi, Chenning Lu ... Danesh Moazed
    Cooperative association of a histone-binding complex with pairs of appropriately modified nucleosomes, which form fundamental units of binding, mediates selective heterochromatin assembly and spreading.
    1. Cell Biology
    2. Computational and Systems Biology

    Dynamic control of Hsf1 during heat shock by a chaperone switch and phosphorylation

    Xu Zheng, Joanna Krakowiak ... David Pincus
    Quantitative dissection of the roles of chaperone binding and phosphorylation in regulating heat shock factor 1 leads to a predictive model of the dynamics of the yeast heat shock response.
    1. Computational and Systems Biology

    A network of epigenetic modifiers and DNA repair genes controls tissue-specific copy number alteration preference

    Dina Cramer, Luis Serrano, Martin H Schaefer
    The genetic background of a cancer cell and the chromatin organization of the tissue-of-origin impact the amount, length and position of somatic copy number alterations in cancer.
    1. Structural Biology and Molecular Biophysics

    Functional asymmetry and electron flow in the bovine respirasome

    Joana S Sousa, Deryck J Mills ... Werner Kühlbrandt
    Cryo-EM structure of the mammalian respiratory supercomplex containing complexes I, III and IV shows a functional asymmetry of complex III, providing strong evidence for directed electron flow in the respirasome.
    1. Structural Biology and Molecular Biophysics

    A Dynamic molecular basis for malfunction in disease mutants of p97/VCP

    Anne K Schuetz, Lewis E Kay
    Point mutations in a ubiquitous human ATPase called p97/VCP deregulate inter-domain communication, resulting in impaired binding of an adaptor that recruits p97 to endosomal pathways and leading to a degenerative disease of bone, muscle and neurons.
    1. Cancer Biology
    2. Developmental Biology

    Norrin/Frizzled4 signalling in the preneoplastic niche blocks medulloblastoma initiation

    Erin A Bassett, Nicholas Tokarew ... Valerie A Wallace
    The earliest steps of tumor initiation in the cerebellum are regulated by critical interactions between pre-tumor cells and stromal cells, which can be manipulated by targeting the Norrin/Frizzled4 signaling axis.
    1. Neuroscience
    2. Computational and Systems Biology

    A specific role for serotonin in overcoming effort cost

    Florent Meyniel, Guy M Goodwin ... Raphaël Gaillard
    A selective reuptake inhibitor shows a beneficial effect in healthy humans during an effort-benefit tradeoff task, mediated at the computational level by a specific alleviation of effort cost.
    1. Cancer Biology
    2. Immunology and Inflammation

    Domain-swapped T cell receptors improve the safety of TCR gene therapy

    Michael T Bethune, Marvin H Gee ... David Baltimore
    Engineered T cell receptors enable targeted immunotherapy with a reduced risk of harmful autoimmunity.
    1. Ecology
    2. Computational and Systems Biology

    A locally-blazed ant trail achieves efficient collective navigation despite limited information

    Ehud Fonio, Yael Heyman ... Ofer Feinerman
    Ants employ a new kind of trail to resolve group-level navigational difficulties in scenarios where the information available to individuals does not suffice.
    1. Epidemiology and Global Health
    2. Evolutionary Biology

    A transmission-virulence evolutionary trade-off explains attenuation of HIV-1 in Uganda

    François Blanquart, Mary Kate Grabowski ... Christophe Fraser
    Analysis of epidemiological data reveals that viral loads in newly HIV-1 infected individuals in Uganda have declined for two decades, and evolutionary modelling shows that attenuation of the virus explains this decline.
    1. Cancer Biology
    2. Cell Biology

    AMP-activated protein kinase fortifies epithelial tight junctions during energetic stress via its effector GIV/Girdin

    Nicolas Aznar, Arjun Patel ... Pradipta Ghosh
    An effector of AMPK is essential for the kinase and its pharmacological activators, including Metformin, to strengthen cell-cell junctions and preserve epithelial cell polarity and barrier functions in the face of energetic stress, as well as to suppress oncogenesis.
    1. Evolutionary Biology
    2. Plant Biology

    Evolution of herbivore-induced early defense signaling was shaped by genome-wide duplications in Nicotiana

    Wenwu Zhou, Thomas Brockmöller ... Shuqing Xu
    Comparative transcriptomic analysis reveals the molecular basis and evolution of herbivore-associated early defense signaling in Nicotiana.
    1. Developmental Biology

    Hand2 inhibits kidney specification while promoting vein formation within the posterior mesoderm

    Elliot A Perens, Zayra V Garavito-Aguilar ... Deborah Yelon
    The Hand2 transcription factor regulates the dimensions of the kidney by controlling cell fate decisions at the interface between organ fields.
    1. Cancer Biology
    2. Computational and Systems Biology

    Computationally designed high specificity inhibitors delineate the roles of BCL2 family proteins in cancer

    Stephanie Berger, Erik Procko ... David Baker
    Six computationally designed and in vitro optimized protein inhibitors serve as molecular probes to reveal BCL2 profiles of different human cancers.
    1. Biochemistry and Chemical Biology
    2. Immunology and Inflammation

    RING finger E3 ligase PPP1R11 regulates TLR2 signaling and innate immunity

    Alison C McKelvey, Travis B Lear ... Bill B Chen
    Novel post-translational modification of pattern recognition receptor TLR2 has consequences in bacterial infection and inflammatory signaling.
    1. Neuroscience

    Profound alteration in cutaneous primary afferent activity produced by inflammatory mediators

    Kristen M Smith-Edwards, Jennifer J DeBerry ... C Jeffery Woodbury
    Inflammatory pain, previously thought to result from increased activity in "pain" neurons, may in fact be due to wholesale changes in afferent output that includes increased and decreased activity that the brain interprets as pain.
    1. Biochemistry and Chemical Biology

    Rational design of aptazyme riboswitches for efficient control of gene expression in mammalian cells

    Guocai Zhong, Haimin Wang ... Michael Farzan
    An empirically derived scoring system for identifying optimal communication modules of aptazymes accelerates the development of ligand-responsive RNA genetic switches functional in mammalian cells.
    1. Computational and Systems Biology
    2. Neuroscience

    Direction-dependent arm kinematics reveal optimal integration of gravity cues

    Jeremie Gaveau, Bastien Berret ... Charalambos Papaxanthis
    Theoretical models and experimental results reveal how the optimal integration of gravity cues fine tunes movement kinematics so that motor effort is minimized in the ubiquitous gravity field.
    1. Neuroscience

    Distinct roles for extracellular and intracellular domains in neuroligin function at inhibitory synapses

    Quynh-Anh Nguyen, Meryl E Horn, Roger A Nicoll
    Electrophysiological recordings reveal domains within the extracellular and intracellular region of neuroligin important for specifying and carrying out its function at inhibitory synapses respectively.
    1. Cell Biology

    CPEB4 is regulated during cell cycle by ERK2/Cdk1-mediated phosphorylation and its assembly into liquid-like droplets

    Jordina Guillén-Boixet, Víctor Buzon ... Raúl Méndez
    CPEB4's switch from translational repressor to activator is regulated during cell cycle by hyperphosphorylation of its intrinsically disordered domain, which controls its phase-separation into RNA-containing liquid-like droplets.
    1. Neuroscience

    Neural pattern change during encoding of a narrative predicts retrospective duration estimates

    Olga Lositsky, Janice Chen ... Kenneth A Norman
    Judgments of how much time elapsed between two events in a story are predicted by changes in fMRI activity patterns.
    1. Structural Biology and Molecular Biophysics
    2. Computational and Systems Biology

    Biomolecular interactions modulate macromolecular structure and dynamics in atomistic model of a bacterial cytoplasm

    Isseki Yu, Takaharu Mori ... Michael Feig
    Crowding and metabolites in a simulated cellular environment alter protein conformations, modulate interactions of functionally related proteins, and lead to significant dynamic heterogeneity.

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