July 2018

Research articles

    1. Human Biology and Medicine
    2. Neuroscience

    Non-invasive imaging of CSF-mediated brain clearance pathways via assessment of perivascular fluid movement with diffusion tensor MRI

    Ian F Harrison et al.
    The first non-invasive technique to assess the action of brain clearance mechanisms, driven by the perivascular inflow of cerebrospinal fluid, has been developed using magnetic resonance imaging.
    1. Neuroscience

    Rap2 and TNIK control Plexin-dependent tiled synaptic innervation in C. elegans

    Xi Chen et al.
    Plexin controls the spatial distribution of synapses by locally inhibiting Rap2 small GTPase activity along the axon, and a Rap2 effector, TNIK, which also plays a key role in inhibiting synapse number.
    1. Developmental Biology
    2. Evolutionary Biology

    Germ layer-specific regulation of cell polarity and adhesion gives insight into the evolution of mesoderm

    Miguel Salinas-Saavedra et al.
    The expression of 'bilaterian-mesodermal’ genes changes the epithelial properties of the endomesoderm during the embryogenesis of the cnidarian Nematostella vectensis.
    1. Evolutionary Biology

    The origin of the odorant receptor gene family in insects

    Philipp Brand et al.
    The insect odorant receptor gene family evolved at the base of the class Insecta before the evolution of flight and perhaps as an adaptation to terrestriality, and was therefore an important evolutionary novelty for insects.
    1. Structural Biology and Molecular Biophysics

    Structural relationship between the putative hair cell mechanotransduction channel TMC1 and TMEM16 proteins

    Angela Ballesteros et al.
    The structural relationship between TMC and TMEM16 proteins provides insight into the structure and functional mechanisms of the mechanotransduction channel complex in hair cells.
    1. Developmental Biology
    2. Cell Biology

    Wnt/PCP controls spreading of Wnt/β-catenin signals by cytonemes in vertebrates

    Benjamin Mattes et al.
    Wnt signaling regulates its effective signaling range by controlling Wnt ligand transport on signaling filopodia within vertebrate tissues.
    1. Cell Biology
    2. Developmental Biology

    Hair follicle dermal condensation forms via Fgf20 primed cell cycle exit, cell motility, and aggregation

    Leah C Biggs et al.
    The hair follicle dermal condensate is populated via migration, and the cells exhibit early changes in cell shape and cell cycle status; Fgf20 primes these cellular and molecular events.
    1. Developmental Biology

    Branching morphogenesis in the developing kidney is not impacted by nephron formation or integration

    Kieran M Short et al.
    Analysing developing mouse kidneys demonstrates nephron formation does not significantly impact branching morphogenesis of the ureteric bud, suggesting this process is distinct from branching in organs like the mammary gland.
    1. Biochemistry and Chemical Biology

    Control of the polyamine biosynthesis pathway by G2-quadruplexes

    Helen Louise Lightfoot et al.
    An ensemble of conserved G2-quadruplex structures in the untranslated regions of messenger RNAs from genes in the polyamine bioysynthesis pathway sense polyamine levels and regulate polyamine synthesis in cells.
    1. Neuroscience

    Cerebellar implementation of movement sequences through feedback

    Andrei Khilkevich et al.
    The cerebellum can learn a sequence of responses by using a feedback signal from the previous movement to learn the next one.
    1. Neuroscience

    Content-specific activity in frontoparietal and default-mode networks during prior-guided visual perception

    Carlos González-García et al.
    Prior experience alters content-specific neural representations of visual input in frontoparietal and default-mode networks.
    1. Cell Biology
    2. Microbiology and Infectious Disease

    Coalescing beneficial host and deleterious antiparasitic actions as an antischistosomal strategy

    John D Chan et al.
    Engagement of both host and parasite signaling pathways proves a novel approach for developing improved anti-parasitic therapies.
    1. Cancer Biology
    2. Cell Biology

    An alternative splicing switch in FLNB promotes the mesenchymal cell state in human breast cancer

    Ji Li et al.
    Splicing by QKI and RBFOX1 regulates the function of the actin-binding protein FLNB by creating an isoform frequently observed in human cancers that dictates tumor cell plasticity.
    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    Differential expression of Lutheran/BCAM regulates biliary tissue remodeling in ductular reaction during liver regeneration

    Yasushi Miura et al.
    Lutheran is a novel marker for classification of bile duct remodeling in distinct liver injury, and an interesting functional molecule for investigating the nature of liver stem/progenitor cells during regeneration.
    1. Neuroscience

    NPAS4 recruits CCK basket cell synapses and enhances cannabinoid-sensitive inhibition in the mouse hippocampus

    Andrea L Hartzell et al.
    Behaviorally-driven expression of the immediate early gene transcription factor NPAS4 changes local circuit connectivity and short-term plasticity by selectively recruiting CCK basket cell synapses to pyramidal neuron somas.
    1. Chromosomes and Gene Expression
    2. Computational and Systems Biology

    Pooled genome-wide CRISPR screening for basal and context-specific fitness gene essentiality in Drosophila cells

    Raghuvir Viswanatha et al.
    Pooled CRISPR knockout screening in Drosophila cells enables high-resolution, genome-wide functional genomic comparisons in cell-lines across vast evolutionary distance.
    1. Neuroscience

    State-dependent cell-type-specific membrane potential dynamics and unitary synaptic inputs in awake mice

    Aurélie Pala, Carl CH Petersen
    Membrane potential recordings in awake mice from two genetically defined classes of neocortical inhibitory neurons reveal their distinct patterns of activity and unitary excitatory synaptic inputs, which are differentially modulated by behavior and local network activity.
    1. Neuroscience

    Focal optogenetic suppression in macaque area MT biases direction discrimination and decision confidence, but only transiently

    Christopher R Fetsch et al.
    Perceptual decision making in monkeys can be manipulated by using optogenetics to inactivate functional subregions of visual cortex, but the brain has a capacity to compensate for this perturbation.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Distinct and evolutionary conserved structural features of the human nuclear exosome complex

    Piotr Gerlach et al.
    Cryo-EM structure and biochemical characterization of the human nuclear exosome reveals its specific properties with respect to the yeast complex, underscoring the evolutionary conservation of the RNA-channeling mechanisms and hMTR4 helicase recruitment.
    1. Immunology and Inflammation
    2. Structural Biology and Molecular Biophysics

    Unified mechanisms for self-RNA recognition by RIG-I Singleton-Merten syndrome variants

    Charlotte Lässig et al.
    RIG-I Singleton-Merten syndrome mutations either mimic or freeze the protein in an ATP-bound state and lead to autoimmune signalling through a gain-of-function recognition of self-RNA.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Lysosomal cholesterol export reconstituted from fragments of Niemann-Pick C1

    Michael Nguyen Trinh et al.
    The N-terminal domain of one NPC1 molecule can transfer its cholesterol to another NPC1 molecule lacking the N-terminal domain, suggesting that NPC1 forms multimers that transport cholesterol out of lysosomes.
    1. Cell Biology

    Tryparedoxin peroxidase-deficiency commits trypanosomes to ferroptosis-type cell death

    Marta Bogacz, R Luise Krauth-Siegel
    Ferroptosis is an evolutionary ancient process that is counterbalanced by distant peroxidases, GPx4 in mammals and tryparedoxin peroxidases in trypanosomes, and can be induced at distinct subcellular membranes depending on the individual cell type.
    1. Microbiology and Infectious Disease

    Robust manipulation of the behavior of Drosophila melanogaster by a fungal pathogen in the laboratory

    Carolyn Elya et al.
    A newly described isolate of the behavior-manipulating fly pathogen Entomophthora muscae that naturally infects fruit flies can be cultured in the lab, enabling molecular investigation of how microbes induce behavior changes in animal hosts.
    1. Microbiology and Infectious Disease
    2. Structural Biology and Molecular Biophysics

    Structural basis for potent and broad inhibition of HIV-1 RT by thiophene[3,2-d]pyrimidine non-nucleoside inhibitors

    Yang Yang et al.
    High-resolution structures of HIV-1 RT in complex with two newly developed non-nucleoside inhibitors explain how they retain antiviral activities against drug-resistant RT mutants with considerably reduced susceptibility to rilpivirine.
    1. Cell Biology
    2. Developmental Biology

    Developmentally regulated H2Av buffering via dynamic sequestration to lipid droplets in Drosophila embryos

    Matthew Richard Johnson et al.
    In early Drosophila embryos, histone H2Av continuously exchanges between cytoplasmic lipid droplets, a process that modulates H2Av import into nuclei and constitutes a novel post-translational strategy to regulate nuclear H2Av levels.
    1. Neuroscience

    A subcortical circuit linking the cerebellum to the basal ganglia engaged in vocal learning

    Ludivine Pidoux et al.
    The cerebellum sends a functional input to the song-related basal ganglia via the thalamus in songbirds that can modify premotor activity, and it participates to song learning in juvenile birds.
    1. Cell Biology

    Measuring NDC80 binding reveals the molecular basis of tension-dependent kinetochore-microtubule attachments

    Tae Yeon Yoo et al.
    Quantitative experiments and theory show that the tension-dependent regulation of NDC80 binding to kinetochore microtubules arises from a combination of the changing Aurora B concentration at NDC80 and the nonlinearity of Aurora B autoactivation.
    1. Neuroscience
    2. Structural Biology and Molecular Biophysics

    Cryo-EM structure of the benzodiazepine-sensitive α1β1γ2S tri-heteromeric GABAA receptor in complex with GABA

    Swastik Phulera et al.
    Structure of the triheteromeric α1β1γ2S GABAA receptor in complex with GABA illuminates the principles of receptor assembly and agonist binding.
    1. Epidemiology and Global Health

    Quantification of anti-parasite and anti-disease immunity to malaria as a function of age and exposure

    Isabel Rodriguez-Barraquer et al.
    Analyses of detailed clinical and entomological data from cohort studies reveal how anti-parasite and anti-disease immunity against P. falciparum develop as a function of age and transmission intensity.
    1. Evolutionary Biology
    2. Genetics and Genomics

    Evolution of gene dosage on the Z-chromosome of schistosome parasites

    Marion A L Picard et al.
    An analysis of gene dosage at the DNA, RNA and protein level yields new insights into the early stages of Z-chromosome dosage compensation in schistosome parasites.
    1. Chromosomes and Gene Expression
    2. Stem Cells and Regenerative Medicine

    Decoupling the impact of microRNAs on translational repression versus RNA degradation in embryonic stem cells

    Jacob W Freimer et al.
    The deletion of Ddx6 results in the translational upregulation, but not transcript stabilization, of microRNA targets in embryonic stem cells while largely phenocopying the overall impact of global microRNA loss.
    1. Neuroscience

    Functional heterogeneity within the rodent lateral orbitofrontal cortex dissociates outcome devaluation and reversal learning deficits

    Marios C Panayi, Simon Killcross
    The rodent orbitofrontal cortex makes functionally distinct contributions to flexible behavioural control, even within a single putative orbitofrontal subregion, which has important implications for establishing homology between rodent and primate orbitofrontal cortex.
    1. Neuroscience

    A mechanism for exocytotic arrest by the Complexin C-terminus

    Mazen Makke et al.
    The far C-terminal domain of CpxII interferes with SNARE assembly and thereby arrests tonic exocytosis.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Receptor-mediated dimerization of JAK2 FERM domains is required for JAK2 activation

    Ryan D Ferrao et al.
    An intracellular cytokine receptor 'switch' motif is critical for the dimerization of JAK2 and activation of the JAK2 kinase.
    1. Neuroscience

    Pre-post synaptic alignment through neuroligin-1 tunes synaptic transmission efficiency

    Kalina T Haas et al.
    Neuroligin 1 is a critical adhesion molecule which organizes AMPA receptor nanodomains in close vicinity to pre-synaptic release sites, and whose genetic or chemical disruption severely impairs synaptic transmission properties.
    1. Neuroscience

    Neurexin directs partner-specific synaptic connectivity in C. elegans

    Alison Philbrook et al.
    Investigation of synapse development using a single neuron system illuminates how individual neurons specify connectivity with their postsynaptic partners and the central role of the synaptic organizer neurexin in this process.
    1. Neuroscience
    2. Structural Biology and Molecular Biophysics

    The dual role of chloride in synaptic vesicle glutamate transport

    Roger Chang et al.
    Whole endosome recording shows that chloride interacts with vesicular glutamate transporters as both allosteric activator and permeant ion, and although the mode of permeation differs, chloride and glutamate use a related conduction pathway.
    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    Antibiotic-induced acceleration of type 1 diabetes alters maturation of innate intestinal immunity

    Xue-Song Zhang et al.
    Alteration of host gut microbiota by antibiotic exposure in early life remodeled host intestinal immune development and metabolism and enhanced the induction of type 1 diabetes in genetically predisposed animals.
    1. Developmental Biology

    Dkk2 promotes neural crest specification by activating Wnt/β-catenin signaling in a GSK3β independent manner

    Arun Devotta et al.
    Dkk2, a member of the Dikkopf family of Wnt antagonists, acts as a positive regulator of Wnt signaling during neural crest formation.
    1. Structural Biology and Molecular Biophysics

    Gating mechanisms during actin filament elongation by formins

    Fikret Aydin et al.
    Formins slow elongation of actin filament by either sterically blocking the addition of actin subunits or flattening the helical twist of the filament end.
    1. Cell Biology
    2. Developmental Biology

    Cell-intrinsic and -extrinsic mechanisms promote cell-type-specific cytokinetic diversity

    Tim Davies et al.
    Functional molecular analysis of cytokinesis in Caenorhabditis elegans four-cell embryos reveals cell-type-specific variation in the fundamental dependence on a robust f-actin cytoskeleton for successful cell division, mediated by both cell-intrinsic and -extrinsic pathways.
    1. Cell Biology

    A Rho signaling network links microtubules to PKD controlled carrier transport to focal adhesions

    Stephan A Eisler et al.
    The small GTPase Rho connects GPCR signaling with PKD activity at TGN membranes and consequently anterograde trafficking to focal adhesions.
    1. Neuroscience

    Impaired spatial memory codes in a mouse model of Rett syndrome

    Sara E Kee et al.
    Hypersynchrony in a mouse model of Rett syndrome impairs ripple-dependent memory consolidation and leads to a decrease in experience-dependent refinement of place cell activities.
    1. Cell Biology
    2. Developmental Biology

    Novel functions for integrin-associated proteins revealed by analysis of myofibril attachment in Drosophila

    Hannah J Green et al.
    Integrin and actin associated proteins are resolved into four layers within myofibril attachments, an architecture requiring balanced positive and negative regulation of integrin adhesion with integrated mechanotransduction and actin pathways.
    1. Structural Biology and Molecular Biophysics

    Ligand discrimination and gating in cyclic nucleotide-gated ion channels from apo and partial agonist-bound cryo-EM structures

    Jan Rheinberger et al.
    High resolution SthK channel cryo-EM structures in different ligand-bound states combined with single-channel functional data in the same conditions constrain a gating mechanism for CNG channels.
    1. Microbiology and Infectious Disease

    Parvovirus minute virus of mice interacts with sites of cellular DNA damage to establish and amplify its lytic infection

    Kinjal Majumder et al.
    Development of a generally adaptable conformational capture assay for use in-trans identifies the specific direct interaction sites between the parvovirus minute virus of mice and the cellular genome during infection as sites of cellular DNA damage.
    1. Chromosomes and Gene Expression

    Importance of miRNA stability and alternative primary miRNA isoforms in gene regulation during Drosophila development

    Li Zhou et al.
    Selective degradation of mature miRNAs shapes temporal miRNA expression patterns and is important for proper regulation of target genes to support normal development of Drosophila embryos.
    1. Biochemistry and Chemical Biology
    2. Developmental Biology

    The major β-catenin/E-cadherin junctional binding site is a primary molecular mechano-transductor of differentiation in vivo

    Jens-Christian Röper et al.
    The primary molecular mechanosensor involved in a physiological process of mechanically induced cell fate differentiation is revealed here for the first time in vivo, highly sensitive and potentially shared by all metazoan epithelia.
    1. Biochemistry and Chemical Biology
    2. Computational and Systems Biology

    Coevolution-based inference of amino acid interactions underlying protein function

    Victor H Salinas, Rama Ranganathan
    A deep mutational coupling study demonstrates the ability of sequence coevolution methods to reveal the pattern of amino acid interactions underlying protein function.
    1. Cell Biology
    2. Structural Biology and Molecular Biophysics

    Tunable molecular tension sensors reveal extension-based control of vinculin loading

    Andrew S LaCroix et al.
    A quantitative understanding of molecular tension sensor function enables the production of unique sensors with desired mechanical properties as well as the ability to distinguish between protein force and protein deformation in mechanosensitive processes.
    1. Neuroscience

    PDF-1 neuropeptide signaling regulates sexually dimorphic gene expression in shared sensory neurons of C. elegans

    Zoë A Hilbert, Dennis H Kim
    Sex-specific neuropeptide signaling in the shared sensory nervous system regulates sexually dimorphic gene expression and male-specific behavior in C. elegans.
    1. Developmental Biology

    Inhibiting the integrated stress response pathway prevents aberrant chondrocyte differentiation thereby alleviating chondrodysplasia

    Cheng Wang et al.
    Integrated stress response-induced expression of ATF4 and its transactivation of SOX9 causes aberrant chondrocyte differentiation and skeletal defects which can be alleviated by modulating initiation-factor eIF2α phosphorylation translation control.
    1. Human Biology and Medicine
    2. Neuroscience

    Regenerating hair cells in vestibular sensory epithelia from humans

    Ruth Rebecca Taylor et al.
    Immunolabelling and morphological assessment, complemented by complete transcriptomic analysis, demonstrates that supporting cells can be induced to convert towards a hair cell-like phenotype in human vestibular sensory epithelia.
    1. Neuroscience

    UBE3A-mediated p18/LAMTOR1 ubiquitination and degradation regulate mTORC1 activity and synaptic plasticity

    Jiandong Sun et al.
    A new mechanism linking lysosomes to mTOR regulation and synaptic plasticity involves p18 ubiquitination by Ube3a, and underlies some of the pathology observed in Angelman syndrome.
    1. Chromosomes and Gene Expression

    Noncoding RNA-nucleated heterochromatin spreading is intrinsically labile and requires accessory elements for epigenetic stability

    R A Greenstein et al.
    Heterochromatin spreading in fission yeast predominantly produces intergenerationally unstable outcomes, requiring an accessory element that represses histone turnover.
    1. Microbiology and Infectious Disease

    A protein secreted by the Salmonella type III secretion system controls needle filament assembly

    Junya Kato et al.
    A novel component of type III protein secretion systems involved in the assembly of the secretion machine is reported.
    1. Structural Biology and Molecular Biophysics

    KCNE1 tunes the sensitivity of KV7.1 to polyunsaturated fatty acids by moving turret residues close to the binding site

    Johan E Larsson et al.
    An auxiliary subunit alters the effect of a family of small-molecule openers on a voltage-gated potassium channel by inducing structural re-arrangements that promote protonation of the drug molecule.
    1. Microbiology and Infectious Disease
    2. Neuroscience

    Thioredoxin shapes the C. elegans sensory response to Pseudomonas produced nitric oxide

    Yingsong Hao et al.
    C. elegans utilizes bacterially produced nitric oxide as a sensory cue to elicit avoidance of pathogenic bacteria.
    1. Cell Biology
    2. Developmental Biology

    Radially patterned cell behaviours during tube budding from an epithelium

    Yara E Sanchez-Corrales et al.
    Quantitative analysis in quasi-3D reveals apically driven cell behaviours that are closely coordinated across the tissue to allow ordered tube invagination through a focal point.
    1. Cancer Biology

    Arid1a restrains Kras-dependent changes in acinar cell identity

    Geulah Livshits et al.
    Arid1a loss in the pancreas enables an irreversible reprogramming of cell fate that is dependent on both cellular and genetic context.
    1. Ecology
    2. Plant Biology

    Cytokinin transfer by a free-living mirid to Nicotiana attenuata recapitulates a strategy of endophytic insects

    Christoph Brütting et al.
    Cytokinin-dependent manipulation of plant metabolism is a strategy employed not only by gallers and leaf-miners but also by a free-living insect, Tupiocoris notatus, which directly transfers cytokinins at feeding sites to manipulate its host plant.
    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    Introgression of regulatory alleles and a missense coding mutation drive plumage pattern diversity in the rock pigeon

    Anna I Vickrey et al.
    Different kinds of molecular changes at one genetic locus control different feather pigmentation patterns, and the darkest patterns resulted from hybridization with another species.
    1. Cell Biology
    2. Neuroscience

    Adaptation to constant light requires Fic-mediated AMPylation of BiP to protect against reversible photoreceptor degeneration

    Andrew T Moehlman et al.
    Tuning of BiP activity by Fic-mediated AMPylation is required for Drosophila photoreceptor plasticity and attenuation of the unfolded protein response.
    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    Genetics of trans-regulatory variation in gene expression

    Frank Wolfgang Albert et al.
    A genetic mapping study in more than 1000 yeast individuals reveals the complexity of trans-acting genetic influences on transcriptome variation in unprecedented depth and detail.
    1. Structural Biology and Molecular Biophysics

    Insights into the ubiquitin transfer cascade catalyzed by the Legionella effector SidC

    David Jon Wasilko et al.
    Structural and biochemical studies reveal the molecular mechanisms for ubiquitin transfer by two unique bacterial ubiquitin E3 ligases.
    1. Cell Biology
    2. Neuroscience

    Matrin 3-dependent neurotoxicity is modified by nucleic acid binding and nucleocytoplasmic localization

    Ahmed M Malik et al.
    The deposition of Matrin 3, a DNA/RNA binding protein implicated in ALS and FTD, results in neurodegeneration dependent upon its localization, self-association, and ability to bind nucleic acids.
    1. Cell Biology
    2. Developmental Biology

    Dual roles for ATP in the regulation of phase separated protein aggregates in Xenopus oocyte nucleoli

    Michael H Hayes et al.
    The equilibrium between solubility and aggregation of proteins in the nucleus is controlled by co-aggregates like RNA and the action of ATP as both an energy source and a destabilizing chemical agent.
    1. Biochemistry and Chemical Biology
    2. Microbiology and Infectious Disease

    A selective gut bacterial bile salt hydrolase alters host metabolism

    Lina Yao et al.
    The deletion of a single gene encoding a selective bile salt hydrolase from the abundant human gut bacterium Bacteroides thetaiotaomicron significantly alters host metabolism.
    1. Developmental Biology
    2. Evolutionary Biology

    Wnt/β-catenin regulates an ancient signaling network during zebrafish scale development

    Andrew J Aman et al.
    Zebrafish scales depend on interactions among Wnt, Ectodysplasin and Hedgehog signaling pathways similar to those underlying feathers, teeth and hair follicles, suggesting a deep homology of ectodermal appendages in vertebrates.
    1. Microbiology and Infectious Disease
    2. Structural Biology and Molecular Biophysics

    Membrane insertion of α-xenorhabdolysin in near-atomic detail

    Evelyn Schubert et al.
    Cryo-EM and X-ray structures of α-xenorhabdolysin in soluble and pore form of Xenorhabdus nematophila give novel insights into the mechanism of action of bi-component α-pore-forming toxins.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Synergy between the small intrinsically disordered protein Hsp12 and trehalose sustain viability after severe desiccation

    Skylar Xantus Kim et al.
    Two small, energy independent stress effectors are able to counteract all of the major insults imposed by severe water loss.
    1. Cell Biology
    2. Neuroscience

    Hypoxia-inducible factor cell non-autonomously regulates C. elegans stress responses and behavior via a nuclear receptor

    Corinne L Pender, H Robert Horvitz
    The hypoxia-inducible factor HIF drives transcription of the gene cyp-36A1, which encodes a cytochrome P450 enzyme that acts via a putative intercellular signal to regulate the nuclear receptor NHR-46 and consequently stress resistance and behavior.
    1. Human Biology and Medicine

    SLC6A14, an amino acid transporter, modifies the primary CF defect in fluid secretion

    Saumel Ahmadi et al.
    Loss of an amino acid transporter and tissue depletion of nitric oxide worsens the intestinal function of CF mice, a finding that potentially explains variation in disease severity amongst CF individuals.
    1. Biochemistry and Chemical Biology
    2. Human Biology and Medicine

    Unexpected similarities between C9ORF72 and sporadic forms of ALS/FTD suggest a common disease mechanism

    Erin G Conlon et al.
    Idiopathic patients along a complex motor neuron disease-dementia spectrum exhibit mRNA splicing changes that are due to multi-protein insolubility.
    1. Biochemistry and Chemical Biology
    2. Microbiology and Infectious Disease

    Lipoate-binding proteins and specific lipoate-protein ligases in microbial sulfur oxidation reveal an atpyical role for an old cofactor

    Xinyun Cao et al.
    An unexpected new biological function was discovered for the universally conserved cofactor lipoate, as lipoate-binding proteins proved essential for a novel wide-spread prokaryotic sulfur oxidation pathway.
    1. Structural Biology and Molecular Biophysics

    Cryo-EM structure of the polycystin 2-l1 ion channel

    Raymond E Hulse et al.
    The selectivity characteristics of PC-2L1, which make it a principal source of calcium in primary cilia function, is presented and advances understanding of the similarity and differences of TRPP ion channels.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Multisite dependency of an E3 ligase controls monoubiquitylation-dependent cell fate decisions

    Achim Werner et al.
    Simultaneous phosphorylation of multiple substrate motifs drives switch-like target recognition and monoubiquitylation by an E3 ligase during metazoan development.
    1. Structural Biology and Molecular Biophysics

    How small-molecule inhibitors of dengue-virus infection interfere with viral membrane fusion

    Luke H Chao et al.
    Single-particle studies of dengue-virus membrane fusion and the effect of small-molecule inhibitors of infection clarify the viral fusion mechanism.
    1. Structural Biology and Molecular Biophysics

    Valid molecular dynamics simulations of human hemoglobin require a surprisingly large box size

    Krystel El Hage et al.
    Simulations of the unliganded human hemoglobin tetramer, which for the first time yield a thermodynamically stable system, cast doubts on the use of standard solvent box sizes for molecular dynamics studies of biological macromolecules.
    1. Cell Biology

    E-cadherin binds to desmoglein to facilitate desmosome assembly

    Omer Shafraz et al.
    Two critical events initiate and promote efficient desmosome assembly: stable binding of opposing E-cadherin cell-cell adhesion proteins; and direct interaction of E-cadherin and Desmoglein.
    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    Embryonic hematopoiesis modulates the inflammatory response and larval hematopoiesis in Drosophila

    Wael Bazzi et al.
    Distinct hematopoietic waves interact via transcriptional cascades specific to embryonic hemocytes to ensure the proper immune response in Drosophila.​.
    1. Cancer Biology
    2. Computational and Systems Biology

    Highly multiplexed immunofluorescence imaging of human tissues and tumors using t-CyCIF and conventional optical microscopes

    Jia-Ren Lin et al.
    t-CyCIF can be used to collect spatially-encoded, multiparametric data from fixed and embedded research or clinical specimens making it possible to probe the organization of tumors and tissues at a single-cell level.
    1. Chromosomes and Gene Expression
    2. Human Biology and Medicine

    A promoter interaction map for cardiovascular disease genetics

    Lindsey E Montefiori et al.
    Promoter capture Hi-C in human iPSCs and iPSC-derived cardiomyocytes provides a platform to interrogate gene-regulatory dynamics of cardiomyocyte differentiation and directly links thousands of cardiovascular disease risk loci to hundreds of distal target genes.
    1. Cell Biology
    2. Neuroscience

    Presenilin mutations deregulate mitochondrial Ca2+ homeostasis and metabolic activity causing neurodegeneration in Caenorhabditis elegans

    Shaarika Sarasija et al.
    In C. elegans, presenilin functions, independent of its gamma-secretase proteolytic activity, to regulate mitochondrial metabolism by controlling ER-mitochondrial calcium transfer and, even in the absence of Abeta signaling, loss of this activity leads to neurodegeneration.
    1. Human Biology and Medicine
    2. Neuroscience

    Down regulation of vestibular balance stabilizing mechanisms to enable transition between motor states

    Romain Tisserand et al.
    Down regulation of the gain from the vestibular sensory sources prior to the initiation of movement is a motor control solution to overcome the reflex-stabilizing mechanisms to enable motion from a postural orientation.
    1. Neuroscience

    Characterization of developmental and molecular factors underlying release heterogeneity at Drosophila synapses

    Yulia Akbergenova et al.
    Active zone release probability is correlated with calcium channel density and calcium influx at single release sites, with release strength increasing in an activity-dependent manner during synapse maturation.
    1. Computational and Systems Biology
    2. Physics of Living Systems

    Biophysical clocks face a trade-off between internal and external noise resistance

    Weerapat Pittayakanchit et al.
    Molecular clocks that are robust to external fluctuations are vulnerable to internal fluctuations and vice versa.
    1. Cancer Biology

    BRET-based RAS biosensors that show a novel small molecule is an inhibitor of RAS-effector protein-protein interactions

    Nicolas Bery et al.
    A biosensor resource has been developed to monitor the intracellular interactions of RAS family proteins with effector molecules and the effects of inhibitors as an aid to drug development.
    1. Cell Biology

    CYK-4 functions independently of its centralspindlin partner ZEN-4 to cellularize oocytes in germline syncytia

    Kian-Yong Lee et al.
    The CYK-4 subunit of the broadly conserved intercellular bridge component centralspindlin, but not its ZEN-4 subunit, is essential for the cytokinesis-like closure of intercellular bridges that cellularizes oocytes to separate them from germline syncytia.
    1. Microbiology and Infectious Disease
    2. Stem Cells and Regenerative Medicine

    Stem cell heterogeneity drives the parasitic life cycle of Schistosoma mansoni

    Bo Wang et al.
    Distinct stem cell populations drive larval, somatic, and germline development of the human parasitic flatworm, Schistosoma mansoni.
    1. Immunology and Inflammation

    Variations in HLA-B cell surface expression, half-life and extracellular antigen receptivity

    Brogan Yarzabek et al.
    Lymphocytes and monocytes maintain their cell surface HLA-B via different mechanisms, which in turn differently influence cell-surface expression, half-life and peptide receptivity of HLA-B allotypes.
    1. Neuroscience

    Adaptive coding for dynamic sensory inference

    Wiktor F Młynarski, Ann M Hermundstad
    To make reliable but metabolically efficient perceptual inferences in a changing world, neural systems should dynamically adapt based on surprise and uncertainty about the sensory environment.
    1. Biochemistry and Chemical Biology
    2. Neuroscience

    Inert and seed-competent tau monomers suggest structural origins of aggregation

    Hilda Mirbaha et al.
    Tau protein exists as two conformational ensembles, one inert, and another that has intrinsic properties of self-association, triggers seeding in cells and in vitro, and is associated with Alzheimer's disease.
    1. Microbiology and Infectious Disease

    NSF-mediated disassembly of on- and off-pathway SNARE complexes and inhibition by complexin

    Ucheor B Choi et al.
    NSF is part of a membrane trafficking quality control system that disassembles both properly formed and off-pathway SNARE complexes, and the disassembly activity may be regulated by complexin.
    1. Biochemistry and Chemical Biology
    2. Chromosomes and Gene Expression

    Rad52-Rad51 association is essential to protect Rad51 filaments against Srs2, but facultative for filament formation

    Emilie Ma et al.
    The association of Rad52 with Rad51, while not critical for Rad51 filament formation, is crucial to protect Rad51 filaments from Srs2 translocase activity through the association of Rad52 with complete Rad51 filaments.
    1. Cell Biology
    2. Computational and Systems Biology

    Removing physiological motion from intravital and clinical functional imaging data

    Sean C Warren et al.
    Image-based motion correction enables the use of fluorescence lifetime and other functional imaging modalities in an intravital and clinical context in the presence of physiological motion.
    1. Computational and Systems Biology
    2. Developmental Biology

    Vertex sliding drives intercalation by radial coupling of adhesion and actomyosin networks during Drosophila germband extension

    Timothy E Vanderleest et al.
    Tricellular vertices possess sliding behaviors that harness radial forces and drive cell shape changes and intercalation in an epithelial tissue.
    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    JNK signaling triggers spermatogonial dedifferentiation during chronic stress to maintain the germline stem cell pool in the Drosophila testis

    Salvador C Herrera, Erika A Bach
    JNK pathway activity induces spermatogonial dedifferentiation under challenging conditions to maintain the germline stem cell pool and to endow it with potentially fitter cells that have increased proliferation.
    1. Neuroscience

    Inferring circuit mechanisms from sparse neural recording and global perturbation in grid cells

    John Widloski et al.
    A novel experimental method and analysis is conceived, based on perturbation and sparse recording, to elucidate the circuit structure and mechanisms underlying the responses of grid cells.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Engineering ER-stress dependent non-conventional mRNA splicing

    Weihan Li et al.
    Ire1's RNase specificity and its cleavage sites coordination shape the evolutionary specialization of the unfolded protein response.
    1. Chromosomes and Gene Expression

    PARP1-dependent recruitment of the FBXL10-RNF68-RNF2 ubiquitin ligase to sites of DNA damage controls H2A.Z loading

    Gergely Rona et al.
    Upon genotoxic stress, the FBXL10-RNF68-RNF2 ubiquitin ligase complex mono-ubiquitylates histone H2A and mediates H2A/H2A.Z exchange to repress transcription and ensures proper high fidelity homologous recombination repair.
    1. Neuroscience

    An automated high-resolution in vivo screen in zebrafish to identify chemical regulators of myelination

    Jason J Early et al.
    A fully automated high-resolution in vivo screening platform for zebrafish was implemented and used to identify novel compounds that regulate oligodendrocyte lineage progression.
    1. Cell Biology
    2. Computational and Systems Biology

    Multiple inputs ensure yeast cell size homeostasis during cell cycle progression

    Cecilia Garmendia-Torres et al.
    Yeast cell size homeostasis is not controlled by a G1-specific mechanism alone but is likely to be an emergent property resulting from the integration of several mechanisms that coordinate cell and bud growth with division.
    1. Developmental Biology
    2. Neuroscience

    Loss of Atoh1 from neurons regulating hypoxic and hypercapnic chemoresponses causes neonatal respiratory failure in mice

    Meike E van der Heijden, Huda Y Zoghbi
    Atoh1 promotes the development of two different neural circuits involved in hypoxic and hypercapnic respiratory responses that together are essential for neonatal respiratory drive and survival.
    1. Cell Biology
    2. Microbiology and Infectious Disease

    Timing of ESCRT-III protein recruitment and membrane scission during HIV-1 assembly

    Daniel S Johnson et al.
    During viral assembly, ESCRTIII and VPS4 are recruited after most of the HIV-1 membrane is bent but disappear prior to scission of the virion from the cell.
    1. Microbiology and Infectious Disease
    2. Structural Biology and Molecular Biophysics

    Structural basis of malodour precursor transport in the human axilla

    Gurdeep S Minhas et al.
    Discovery of the structural basis for recognition and uptake of a human precursor for body odour production reveals an important role for bacterial peptide transport and novel routes to prevent its production in humans.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Single-color, ratiometric biosensors for detecting signaling activities in live cells

    Brian L Ross et al.
    A novel panel of homoFRET biosensors that detect kinase and second messenger activity, called FLAREs, enables multiparameter imaging of signaling activities within a single live cell with a quantitative and ratiometric readout.
    1. Evolutionary Biology

    A multispecies coalescent model for quantitative traits

    Fábio K Mendes et al.
    A model for evolutionary inferences at both micro- and macroevolutionary scales is proposed and evaluated theoretically and through simulations.
    1. Neuroscience

    Recurrent network model for learning goal-directed sequences through reverse replay

    Tatsuya Haga, Tomoki Fukai
    The combination of short-term and long-term plasticity enables hippocampus to learn goal-directed paths through replay in a reversed order.
    1. Human Biology and Medicine

    Nanoscale dysregulation of collagen structure-function disrupts mechano-homeostasis and mediates pulmonary fibrosis

    Mark G Jones et al.
    Nanoscale changes to individual collagen fibrils drive lung fibrosis.
    1. Neuroscience

    Dual leucine zipper kinase is required for mechanical allodynia and microgliosis after nerve injury

    Josette J Wlaschin et al.
    The DLK response pathway in neurons initiates the cascade of events leading to neuropathic pain after injury.
    1. Neuroscience
    2. Structural Biology and Molecular Biophysics

    Cryo-EM structure of alpha-synuclein fibrils

    Ricardo Guerrero-Ferreira et al.
    The alpha-synuclein fibril structure reported here buries residues 50-57 at the interface between its two protofilaments, suggesting that familial Parkinson's disease associated mutations in these residues lead to a structure not compatible with the one presented here.
    1. Developmental Biology

    Neurogenic decisions require a cell cycle independent function of the CDC25B phosphatase

    Frédéric Bonnet et al.
    The cell cycle phosphatase CDC25B controls cell cycle progression and neurogenesis through independent pathways.
    1. Cell Biology

    TRPV4 is the temperature-sensitive ion channel of human sperm

    Nadine Mundt et al.
    The molecular identity of the temperature-sensitive ion channel of human sperm that ensures depolarization is TRPV4.
    1. Neuroscience

    Bidirectional encoding of motion contrast in the mouse superior colliculus

    Jad Barchini et al.
    Two photon calcium imaging experiments show that excitatory and inhibitory neurons in the mouse superior colliculus are differentially modulated by the motion contrast between stimulus center and surround.
    1. Cell Biology
    2. Computational and Systems Biology

    A positive-feedback-based mechanism for constriction rate acceleration during cytokinesis in Caenorhabditis elegans

    Renat N Khaliullin et al.
    Positive feedback between contractile ring myosin and compression-driven cortical flow can explain the exponential accumulation of contractile ring components and constriction rate acceleration that ensures timely cell separation during cytokinesis.
    1. Biochemistry and Chemical Biology

    Control of cyclic oligoadenylate synthesis in a type III CRISPR system

    Christophe Rouillon et al.
    Generation of the anti-viral second messenger cyclic oligoadenylate by type III CRISPR systems is tightly controlled in response to viral RNA load and sequence.
    1. Neuroscience

    Different contributions of preparatory activity in the basal ganglia and cerebellum for self-timing

    Jun Kunimatsu et al.
    Neuronal activity in the striatum keeps track of elapsed time during the time production task while that in the cerebellum correlates with stochastic variation of self-timing in the range of several hundreds of milliseconds.
    1. Structural Biology and Molecular Biophysics

    BK channel inhibition by strong extracellular acidification

    Yu Zhou et al.
    Analysis of iconic and gating currents of wild type and mutated BK channels reveals a strong inhibition of this channel by extracellular acidification and elucidates the underlying mechanism that is potentially applicable to other voltage-dependent cation channels.
    1. Neuroscience

    Assessing reliability in neuroimaging research through intra-class effect decomposition (ICED)

    Andreas M Brandmaier et al.
    In human neuroimaging, the intra-class effect decomposition (ICED) framework indexes overall reliability, and enables researchers to identify and quantify multi-source contributions to measurement error with the goal of developing more reliable measures.