September 2019

Research articles

1. 1. Neuroscience

   Light-at-night exposure affects brain development through pineal allopregnanolone-dependent mechanisms

   Shogo Haraguchi, Masaki Kamata ... Kazuyoshi Tsutsui

   Diurnal variation loss of pineal allopregnanolone synthesis by light-at-night induces pituitary adenylate cyclase-activating polypeptide (PACAP) reduction and transcriptional PACAP repression in the cerebellum, with subsequent Purkinje cell death.
2. 1. Cell Biology

   TORC2-Gad8-dependent myosin phosphorylation modulates regulation by calcium

   Karen Baker, Irene A Gyamfi ... Daniel P Mulvihill

   IQ domain phosphorylation regulates calmodulin binding and myosin-1 function.
3. 1. Cell Biology
   2. Developmental Biology

   BMP7 functions predominantly as a heterodimer with BMP2 or BMP4 during mammalian embryogenesis

   Hyung-Seok Kim, Judith Neugebauer ... Jan L Christian

   Endogenous BMP2/7 and BMP4/7 heterodimers form in vivo, and are the predominant functional ligand in many, if not all, tissues of developing mouse embryos.
4. 1. Structural Biology and Molecular Biophysics

   Molecular mechanism of TRPV2 channel modulation by cannabidiol

   Ruth A Pumroy, Amrita Samanta ... Vera Y Moiseenkova-Bell

   Cannabidiol binds to TRPV2 via a previously unidentified, but highly conserved, pocket.
5. 1. Developmental Biology

   NEIL1 and NEIL2 DNA glycosylases protect neural crest development against mitochondrial oxidative stress

   Dandan Han, Lars Schomacher ... Christof Niehrs

   NEIL DNA glycosylases are required to counteract oxidative base damages within the mitochondrial genome to safeguard neural crest cell differentiation.
6. 1. Neuroscience

   Cue-inhibited ventrolateral periaqueductal gray neurons signal fear output and threat probability in male rats

   Kristina M Wright, Thomas C Jhou ... Michael A McDannald

   Ventrolateral periaqueductal gray neurons signal fear output through patterned inhibition of neural activity.
7. 1. Cancer Biology
   2. Developmental Biology

   Coopted temporal patterning governs cellular hierarchy, heterogeneity and metabolism in Drosophila neuroblast tumors

   Sara Genovese, Raphaël Clément ... Cédric Maurange

   About twenty temporal patterning genes are identified that drive an irreversible differentiation trajectory governing the heterogeneity and proliferative properties of cells in neural tumors with an early developmental origin.
8. 1. Cell Biology
   2. Developmental Biology

   Casein kinase 1 family proteins promote Slimb-dependent Expanded degradation

   Alexander D Fulford, Maxine V Holder ... Paulo S Ribeiro

   The tissue growth controlling Hippo signalling pathway is modulated by the activity of the Casein Kinase 1 family, which regulates the protein stability of the upstream Hippo pathway component Expanded.
9. 1. Biochemistry and Chemical Biology

   Allosteric activation of the nitric oxide receptor soluble guanylate cyclase mapped by cryo-electron microscopy

   Benjamin G Horst, Adam L Yokom ... Michael A Marletta

   The full-length structures of the mammalian nitric oxide receptor reveal the molecular activation steps and a binding site for the prototype of FDA-approved stimulators.
10. 1. Neuroscience

    A toolbox of nanobodies developed and validated for use as intrabodies and nanoscale immunolabels in mammalian brain neurons

    Jie-Xian Dong, Yongam Lee ... James S Trimmer

    Nanobodies are developed that target neuronal proteins with restricted subcellular distributions and used as intrabodies to deliver cargo to specific sites within neurons and nanoscale immunolabels for improved imaging resolution.
11. 1. Biochemistry and Chemical Biology

    A new class of disordered elements controls DNA replication through initiator self-assembly

    Matthew W Parker, Maren Bell ... James M Berger

    DNA replication initiation proteins contain a disordered domain that impacts each stage of their function, from chromatin recruitment and initiator co-assembly to the subsequent displacement of the factors from chromatin.
12. 1. Neuroscience
    2. Stem Cells and Regenerative Medicine

    Id4 promotes the elimination of the pro-activation factor Ascl1 to maintain quiescence of adult hippocampal stem cells

    Isabelle Maria Blomfield, Brenda Rocamonde ... Noelia Urbán

    Genetic and protein analyses in vitro and in vivo identifies Id4 as a novel regulator of stem cell quiescence in the adult hippocampus.
13. 1. Biochemistry and Chemical Biology

    Evolution of (p)ppGpp-HPRT regulation through diversification of an allosteric oligomeric interaction

    Brent W Anderson, Kuanqing Liu ... Jue D Wang

    The signaling ligand (p)ppGpp regulates the enzyme HPRT across species by binding to a novel class of conserved motif, yet its specificity is allosterically altered through evolution of enzyme oligomerization.
14. 1. Immunology and Inflammation

    A tissue-like platform for studying engineered quiescent human T-cells’ interactions with dendritic cells

    Enas Abu-Shah, Philippos Demetriou ... Michael L Dustin

    The use of advanced 3D culture systems with engineered quiescent human T-cells, mimicking in vivo cellular dynamics, paves the way to a new era of much needed pre-clinical research tools.
15. 1. Cell Biology

    Cytoplasmic protein misfolding titrates Hsp70 to activate nuclear Hsf1

    Anna E Masser, Wenjing Kang ... Claes Andréasson

    Hsp70 restricts DNA binding activity of Hsf1 to control the width and amplitude of the heat-shock regulon.
16. 1. Structural Biology and Molecular Biophysics

    Structural mapping of oligomeric intermediates in an amyloid assembly pathway

    Theodoros K Karamanos, Matthew P Jackson ... Sheena E Radford

    Solution NMR provides structural and kinetic information about oligomers on pathway to amyloid fibrils that are precisely structured but not cytotoxic.
17. 1. Developmental Biology

    An RNAi screen unravels the complexities of Rho GTPase networks in skin morphogenesis

    Melanie Laurin, Nicholas C Gomez ... Elaine Fuchs

    An unprecedented large-scale screen in mice for morphogenetic regulators of tissue development provides major new insights into the roles of Rho GTPases in diverse array of skin developmental processes.
18. 1. Developmental Biology
    2. Microbiology and Infectious Disease

    Region-specific regulation of stem cell-driven regeneration in tapeworms

    Tania Rozario, Edward B Quinn ... Phillip A Newmark

    Tapeworms grow and regenerate using stem cells distributed throughout their bodies, but their regeneration competence relies upon the unique micro-environment created by the head and neck.
19. 1. Neuroscience
    2. Physics of Living Systems

    The frequency limit of outer hair cell motility measured in vivo

    Anna Vavakou, Nigel P Cooper, Marcel van der Heijden

    The cells in our inner ear commonly believed to provide fast mechanical feedback are too sluggish to follow the vibrations evoked by high-frequency sounds.
20. 1. Neuroscience

    A mechanism in agrin signaling revealed by a prevalent Rapsyn mutation in congenital myasthenic syndrome

    Guanglin Xing, Hongyang Jing ... Lin Mei

    Asparagine 88 to lysine (N88K), a prevalent congenital myasthenic syndrome mutation of Rapsyn, impairs the neuromuscular junction by disrupting agrin signaling.
21. 1. Cell Biology

    Myogenic vasoconstriction requires G₁₂/G₁₃ and LARG to maintain local and systemic vascular resistance

    Ramesh Chennupati, Angela Wirth ... Stefan Offermanns

    Genetic mouse models identify a critical mechanism of myogenic vasoconstriction and reveal the in vivo function of myogenic autoregulation in protecting from organ overperfusion and in maintaining vascular resistance.
22. 1. Ecology
    2. Evolutionary Biology

    Tooth fracture frequency in gray wolves reflects prey availability

    Blaire Van Valkenburgh, Rolf O Peterson ... John A Vucetich

    Despite risks of infection and reduced fitness, tooth fracture frequency in gray wolves increases rapidly when prey are scarce because they must consume carcasses more completely.
23. 1. Microbiology and Infectious Disease

    Visualizing trypanosomes in a vertebrate host reveals novel swimming behaviours, adaptations and attachment mechanisms

    Éva Dóró, Sem H Jacobs ... Maria Forlenza

    The transparent zebrafish reveals the reality of trypanosomes swimming in a vertebrate host, and their adaptations to an extremely heterogenic environment.
24. 1. Ecology
    2. Evolutionary Biology

    Intergenerational effects of early adversity on survival in wild baboons

    Matthew N Zipple, Elizabeth A Archie ... Susan C Alberts

    In wild baboons, a female's adverse early experiences can influence her offspring's survival years after the original adversity was experienced.
25. 1. Computational and Systems Biology
    2. Neuroscience

    Population adaptation in efficient balanced networks

    Gabrielle J Gutierrez, Sophie Denève

    Neural populations may depend on balanced recurrent connectivity to produce an efficient stimulus representation while also maintaining an accurate stimulus encoding despite the variability introduced by adapting neural responses.
26. 1. Genetics and Genomics

    Large, three-generation human families reveal post-zygotic mosaicism and variability in germline mutation accumulation

    Thomas A Sasani, Brent S Pedersen ... Aaron R Quinlan

    Rates of germline mutation accumulation are highly variable across families of similar genetic ancestry, and post-zygotic mosaicism is a substantial source of de novo mutations.
27. 1. Neuroscience

    Optical dopamine monitoring with dLight1 reveals mesolimbic phenotypes in a mouse model of neurofibromatosis type 1

    J Elliott Robinson, Gerard M Coughlin ... Viviana Gradinaru

    Heterozygous Nf1 knockout mice exhibit distinct dopaminergic phenotypes in vivo, as revealed by the genetically encoded dopamine sensor dLight1, patch clamp electrophysiology, optogenetics, and novel viral tools for morphological analysis.
28. 1. Neuroscience

    An arbitrary-spectrum spatial visual stimulator for vision research

    Katrin Franke, André Maia Chagas ... Thomas Euler

    Towards a community effort, we here present a flexible yet standardised visual stimulator design based on open hardware and software.
29. 1. Developmental Biology
    2. Evolutionary Biology

    Evolutionary emergence of Hairless as a novel component of the Notch signaling pathway

    Steven W Miller, Artem Movsesyan ... James W Posakony

    Hairless emerged as an evolutionarily novel regulatory protein that replaced an ancestral paradigm of direct co-repressor recruitment by Suppressor of Hairless, its partner transcription factor in the Notch signaling pathway.
30. 1. Genetics and Genomics
    2. Neuroscience

    A scalable platform for the development of cell-type-specific viral drivers

    Sinisa Hrvatin, Christopher P Tzeng ... Michael E Greenberg

    Highly paralleled functional evaluation of enhancer activity in single cells generates new cell-type-specific tools with broad medical and scientific applications.
31. 1. Stem Cells and Regenerative Medicine

    Sustained expression of HeyL is critical for the proliferation of muscle stem cells in overloaded muscle

    Sumiaki Fukuda, Akihiro Kaneshige ... So-ichiro Fukada

    Proliferating muscle stem cells in overloaded muscle require special molecular mechanisms that differ from well-known myogenic differentiation model.
32. 1. Biochemistry and Chemical Biology
    2. Physics of Living Systems

    Optical estimation of absolute membrane potential using fluorescence lifetime imaging

    Julia R Lazzari-Dean, Anneliese MM Gest, Evan W Miller

    Fluorescence lifetime imaging microscopy, paired with fluorescent, voltage-sensitive dyes, provides a method for measuring and quantifying membrane potentials of living cells.
33. 1. Developmental Biology
    2. Neuroscience

    The NKCC1 antagonist bumetanide mitigates interneuronopathy associated with ethanol exposure in utero

    Alexander GJ Skorput, Stephanie M Lee ... Hermes H Yeh

    Prenatal ethanol exposure results in aberrant tangential migration by altering NKCC1-mediated chloride homeostasis that can be mitigated by bumetanide.
34. 1. Developmental Biology

    An autoregulatory cell cycle timer integrates growth and specification in chick wing digit development

    Joseph Pickering, Kavitha Chinnaiya, Matthew Towers

    A cell cycle timing mechanism similar to one operating in cultured adult oligodendrocyte progenitor cells controls the growth and patterning of the embryonic chick wing bud.
35. 1. Chromosomes and Gene Expression

    TRAIP drives replisome disassembly and mitotic DNA repair synthesis at sites of incomplete DNA replication

    Remi Sonneville, Rahul Bhowmick ... Karim Labib

    The TRAIP ubiquitin ligase is required during mitosis to disassemble the replisome at sites of incomplete DNA replication, and activate the mitotic DNA repair pathway, thus preserving genome integrity.
36. 1. Developmental Biology

    Mamo decodes hierarchical temporal gradients into terminal neuronal fate

    Ling-Yu Liu, Xi Long ... Tzumin Lee

    Neuronal diversity is expanded by a temporal fating paradigm utilizing hierarchical gene regulation.
37. 1. Developmental Biology
    2. Evolutionary Biology

    Fgf-signaling is compartmentalized within the mesenchyme and controls proliferation during salamander limb development

    Sruthi Purushothaman, Ahmed Elewa, Ashley W Seifert

    While movement of Fgf-signaling to the limb mesenchyme accompanied a shift in function, the ultimate outcome remains a convergent tetrapod limb phenotype.
38. 1. Chromosomes and Gene Expression
    2. Microbiology and Infectious Disease

    Viral miRNA adaptor differentially recruits miRNAs to target mRNAs through alternative base-pairing

    Carlos Gorbea, Tim Mosbruger ... Demián Cazalla

    iRICC, a new method to identify RNA-RNA interactions in vivo, provides mechanistic insight into the function of a viral non-coding RNA.
39. 1. Plant Biology

    Proximity labeling of protein complexes and cell-type-specific organellar proteomes in Arabidopsis enabled by TurboID

    Andrea Mair, Shou-Ling Xu ... Dominique C Bergmann

    Proximity-labeling using engineered biotin ligases TurboID and miniTurbo enables detection of cell-type-specific and low abundance protein complexes and subcellular proteomes in Arabidopsis and other plants.
40. 1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    A distinct transition from cell growth to physiological homeostasis in the tendon

    Mor Grinstein, Heather L Dingwall ... Jenna Lauren Galloway

    Mitotic labeling defines a change in cell division kinetics from growth to homeostasis and identifies slowly cycling cells in the adult tendon.
41. 1. Neuroscience

    RIM-BP2 primes synaptic vesicles via recruitment of Munc13-1 at hippocampal mossy fiber synapses

    Marisa M Brockmann, Marta Maglione ... Dietmar Schmitz

    The active zone scaffold protein RIM-BP2 performs distinct functions in vesicle release at two hippocampal synapses, providing insights on how synapses express diversity in release properties.
42. 1. Neuroscience

    ON selectivity in the Drosophila visual system is a multisynaptic process involving both glutamatergic and GABAergic inhibition

    Sebastian Molina-Obando, Juan Felipe Vargas-Fique ... Marion Silies

    A fundamental visual computation, the establishment of ON selectivity, is established across distributed circuits, allowing for more robust and flexible coding than suggested by core circuit motifs.
43. 1. Plant Biology
    2. Structural Biology and Molecular Biophysics

    Protein engineering expands the effector recognition profile of a rice NLR immune receptor

    Juan Carlos De la Concepcion, Marina Franceschetti ... Mark J Banfield

    Structure-led protein engineering can expand the effector recognition profile of plant intracellular NLR immune receptors, providing a proof-of-principle for the development of novel disease resistance mechanisms in plants.
44. 1. Structural Biology and Molecular Biophysics

    Cryo-EM analyses reveal the common mechanism and diversification in the activation of RET by different ligands

    Jie Li, Guijun Shang ... Xiao-chen Bai

    Cryo-EM studies reveal structural basis for the activation, auto-inhibition and regulation of RET receptor tyrosine kinase.
45. 1. Developmental Biology
    2. Evolutionary Biology

    A distinct cardiopharyngeal mesoderm genetic hierarchy establishes antero-posterior patterning of esophagus striated muscle

    Glenda Comai, Eglantine Heude ... Shahragim Tajbakhsh

    Tbx1-Isl1-Met defines a unique genetic hierarchy that regulates esophagus myogenesis and patterning in the mouse.
46. 1. Computational and Systems Biology
    2. Neuroscience

    Rats exhibit similar biases in foraging and intertemporal choice tasks

    Gary A Kane, Aaron M Bornstein ... Jonathan D Cohen

    In both foraging and intertemporal choice tasks, rats prefer immediate rewards to delayed rewards, and this preference can be explained by a form of hyperbolic discounting.
47. 1. Physics of Living Systems

    Phylodynamic theory of persistence, extinction and speciation of rapidly adapting pathogens

    Le Yan, Richard A Neher, Boris I Shraiman

    A model of pathogen co-evolving with host population continuously acquiring immunity is used to identify evolutionary parameters allowing pathogen population to persist without going extinct or splitting into independent lineages.
48. 1. Cell Biology
    2. Genetics and Genomics

    NHR-14 loss of function couples intestinal iron uptake with innate immunity in C. elegans through PQM-1 signaling

    Malini Rajan, Cole P Anderson ... Elizabeth A Leibold

    Nuclear receptor NHR-14 regulates the subcellular localization of the zinc transcription factor PQM-1 to coordinate innate immunity with iron sequestration during pathogen infection in C. elegans..
49. 1. Immunology and Inflammation

    ENaC-mediated sodium influx exacerbates NLRP3-dependent inflammation in cystic fibrosis

    Thomas Scambler, Heledd H Jarosz-Griffiths ... Michael F McDermott

    Dysfunction and overexpression of ENaC-mediated sodium influx exacerbates activation of NLRP3-inflammasome mediated inflammation in cells with CF-associated mutations and is modulated by inhibition of these amiloride-sensitive sodium (Na⁺) channels.
50. 1. Evolutionary Biology

    Molecular function limits divergent protein evolution on planetary timescales

    Mariam M Konaté, Germán Plata ... Dennis Vitkup

    Orthologous proteins that continuously maintain the same molecular function do not usually diverge beyond a certain level of sequence and structural similarity.
51. 1. Developmental Biology

    Cell-autonomous regulation of epithelial cell quiescence by calcium channel Trpv6

    Yi Xin, Allison Malick ... Cunming Duan

    Genetics, in vivo imaging, and unbiased chemical biology screens reveal that Trpv6 functions as a cellular quiescence regulator and delineates a Trpv6-mediated Ca²⁺ signaling pathway maintaining the quiescent state.
52. 1. Neuroscience

    Self-organization of modular network architecture by activity-dependent neuronal migration and outgrowth

    Samora Okujeni, Ulrich Egert

    Activity-dependent neurite outgrowth and neuronal migration interact to shape modular mesoscale network architecture by homeostatic self-organization.
53. 1. Neuroscience

    Evolution of neuronal anatomy and circuitry in two highly divergent nematode species

    Ray L Hong, Metta Riebesell ... Ralf J Sommer

    The substrate for evolutionary divergence does not lie in changes in neuronal cell number or targeting, but rather in sensory perception and synaptic partner choice within invariant, prepatterned neuronal processes.
54. 1. Microbiology and Infectious Disease
    2. Structural Biology and Molecular Biophysics

    A contractile injection system stimulates tubeworm metamorphosis by translocating a proteinaceous effector

    Charles F Ericson, Fabian Eisenstein ... Nicholas J Shikuma

    Bacteria produce a syringe-like structure, loaded with a single protein within the lumen of its needle-like tube, that is sufficient for stimulating animal metamorphosis.
55. 1. Biochemistry and Chemical Biology

    Mechanisms of iron- and O₂-sensing by the [4Fe-4S] cluster of the global iron regulator RirA

    Ma Teresa Pellicer Martinez, Jason C Crack ... Nick E Le Brun

    Molecular details of how the iron–sulfur cluster cofactor of a bacterial global iron regulatory protein simultaneously senses iron and O₂ are revealed by mass spectrometry and spectroscopy.
56. 1. Cell Biology

    A critical role of VMP1 in lipoprotein secretion

    Hideaki Morishita, Yan G Zhao ... Noboru Mizushima

    The ER transmembrane protein VMP1 is important for release of lipoproteins from the ER membrane into the ER lumen for secretion.
57. 1. Genetics and Genomics
    2. Microbiology and Infectious Disease

    The Photorhabdus asymbiotica virulence cassettes deliver protein effectors directly into target eukaryotic cells

    Isabella Vlisidou, Alexia Hapeshi ... Nicholas R Waterfield

    The insect pathogenic bacterium Photorhabdus has evolved astonishing nano-scale analogues of hypodermic syringes that it uses to inject toxins into host cells.
58. 1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Single molecule mechanics resolves the earliest events in force generation by cardiac myosin

    Michael S Woody, Donald A Winkelmann ... Yale E Goldman

    Cardiac myosin converts energy from ATP into mechanical work by transitioning from a short-lived force-bearing state, to a post working stroke state before the release of inorganic phosphate.
59. 1. Genetics and Genomics
    2. Neuroscience

    Learning is enhanced by tailoring instruction to individual genetic differences

    David G Mets, Michael S Brainard

    Tailoring instructive experience to individual genetic biases improves vocal learning outcomes across genetic backgrounds in the Bengalese finch.
60. 1. Epidemiology and Global Health

    Multivariable two-sample Mendelian randomization estimates of the effects of intelligence and education on health

    Neil Martin Davies, W David Hill ... George Davey Smith

    Many of the effects of intelligence on health and social outcomes later in life are mediated via education.
61. 1. Neuroscience

    Neurexophilin4 is a selectively expressed α-neurexin ligand that modulates specific cerebellar synapses and motor functions

    Xiangling Meng, Christopher M McGraw ... Huda Y Zoghbi

    A combination of mouse genetics and biochemistry approaches reveals neurexophilin4 (Nxph4) as a context-specific α-neurexin ligand, which regulates Golgi-granule cell inhibitory synapses and motor functions.
62. 1. Chromosomes and Gene Expression
    2. Evolutionary Biology

    Dynamic turnover of centromeres drives karyotype evolution in Drosophila

    Ryan Bracewell, Kamalakar Chatla ... Doris Bachtrog

    De novo formation of centromeres creates diverse karyotypes in flies and is accompanied by rapid turnover of centromere-associated satellite repeats.
63. 1. Neuroscience

    Human motor fatigability as evoked by repetitive movements results from a gradual breakdown of surround inhibition

    Marc Bächinger, Rea Lehner ... Nicole Wenderoth

    Motor fatigability is associated with a decrease in inhibition throughout the motor network, suggesting that selective inhibitory control is a key mechanism to maintain motor efficiency during repetitive movements.
64. 1. Developmental Biology

    Mechanically activated piezo channels modulate outflow tract valve development through the Yap1 and Klf2-Notch signaling axis

    Anne-Laure Duchemin, Hélène Vignes, Julien Vermot

    High resolution in vivo imaging of the zebrafish heart morphogenesis allows quantitative testing of the impact of stretch sensitive channels during outflow tract valve development.
65. 1. Plant Biology

    Anion channel SLAH3 is a regulatory target of chitin receptor-associated kinase PBL27 in microbial stomatal closure

    Yi Liu, Tobias Maierhofer ... Silke Robatzek

    S-type anion channel activity, which promotes stomatal closure and improves anti-fungal immunity in plants, is directly regulated through phosphorylation by a kinase of the chitin receptor complex.
66. 1. Computational and Systems Biology
    2. Stem Cells and Regenerative Medicine

    Self-assembling manifolds in single-cell RNA sequencing data

    Alexander J Tarashansky, Yuan Xue ... Bo Wang

    An iterative self-assembling algorithm identifies the intrinsic structures in single-cell transcriptomic data and helps to discover new cell populations that are undetectable by existing methods.
67. 1. Microbiology and Infectious Disease

    The ER membrane protein complex is required to ensure correct topology and stable expression of flavivirus polyproteins

    Ashley M Ngo, Matthew J Shurtleff ... Andreas S Puschnik

    The ER membrane protein complex (EMC) facilitates the correct topology of the flavivirus non-structural proteins NS4A and NS4B at the ER membrane critical for viral replication.
68. 1. Evolutionary Biology
    2. Microbiology and Infectious Disease

    Evolutionary pathways to antibiotic resistance are dependent upon environmental structure and bacterial lifestyle

    Alfonso Santos-Lopez, Christopher W Marshall ... Vaughn S Cooper

    Bacteria growing in biofilms evolve antimicrobial resistance via different pathways and generate greater genetic diversity than well-mixed populations, selecting fitter but less resistant genotypes.
69. 1. Cell Biology

    Proteostasis collapse, a hallmark of aging, hinders the chaperone-Start network and arrests cells in G1

    David F Moreno, Kirsten Jenkins ... Martí Aldea

    Cells accumulate damaged proteins during aging and, by compromising the function of chaperones in folding newly synthesized G1 cyclins, proteostasis breakdown inhibits cell-cycle entry and drives yeast cells into senescence.
70. 1. Structural Biology and Molecular Biophysics

    Ligand recognition and gating mechanism through three ligand-binding sites of human TRPM2 channel

    Yihe Huang, Becca Roth ... Juan Du

    High-resolution structures of human TRPM2 in different functional states provided the mechanism underlying ligand recognition, channel activation and inhibition.
71. 1. Developmental Biology

    TEADs, Yap, Taz, Vgll4s transcription factors control the establishment of Left-Right asymmetry in zebrafish

    Jonathan Fillatre, Jean-Daniel Fauny ... Bernard Thisse

    Transcription factors downstream of Hippo signaling control formation of the Left-Right Organizer by regulating major signaling pathways, expression of transcription factors and regulators of epigenetic programming involved in this process.
72. 1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    Neural stem cell temporal patterning and brain tumour growth rely on oxidative phosphorylation

    Jelle van den Ameele, Andrea H Brand

    Mitochondrial dysfunction in neural stem cells and brain tumour cells decreases proliferation and affects the generation of neuronal diversity and tumour heterogeneity.
73. 1. Epidemiology and Global Health
    2. Structural Biology and Molecular Biophysics

    Electron cryo-microscopy of bacteriophage PR772 reveals the elusive vertex complex and the capsid architecture

    Hemanth KN Reddy, Marta Carroni ... Martin Svenda

    The structure and composition of the elusive vertex complex in Tectiviridae is finally revealed and the newly reported protein conformations help to maintain the capsid architecture.
74. 1. Cell Biology
    2. Structural Biology and Molecular Biophysics

    Extensive ribosome and RF2 rearrangements during translation termination

    Egor Svidritskiy, Gabriel Demo ... Andrei A Korostelev

    Ensemble cryo-EM visualizes how structural rearrangements poise the newly made protein and release factor RF2 to dissociate in preparation for ribosome recycling.
75. 1. Neuroscience

    Classical conditioning drives learned reward prediction signals in climbing fibers across the lateral cerebellum

    William Heffley, Court Hull

    Cerebellar climbing fibers can generate learned reward-predictive instructional signals, suggesting a role for cerebellar learning in the reinforcement of reward-driven behaviors.
76. 1. Structural Biology and Molecular Biophysics

    Calcium-driven regulation of voltage-sensing domains in BK channels

    Yenisleidy Lorenzo-Ceballos, Willy Carrasquel-Ursulaez ... Ramon Latorre

    Gating currents analysis at different Ca²⁺ concentrations of BK channels reveals a strong allosteric coupling between Ca²⁺- and voltage-sensing modules via equivalent contributions exerted by the RCK1 and RCK2 Ca²⁺-sites.
77. 1. Ecology

    Entomopathogenic nematodes increase predation success by inducing cadaver volatiles that attract healthy herbivores

    Xi Zhang, Ricardo AR Machado ... Christelle AM Robert

    By changing the smell of their host, entomopathogenic nematodes attract future hosts and increase their predation success.
78. 1. Developmental Biology
    2. Neuroscience

    How prolonged expression of Hunchback, a temporal transcription factor, re-wires locomotor circuits

    Julia L Meng, Zarion D Marshall ... Ellie S Heckscher

    In vivo stem cell reprogramming in the well-studied stem cell NB7-1 using the classic temporal transcription factor Hunchback increases motor neuron number and re-specifies dendritic morphology and neuromuscular synaptic partnerships.
79. 1. Developmental Biology

    Actomyosin regulation by Eph receptor signaling couples boundary cell formation to border sharpness

    Jordi Cayuso, Qiling Xu ... David G Wilkinson

    Boundary cell identity and sharpening of borders are coupled in hindbrain development since both are regulated by mechanical tension.
80. 1. Computational and Systems Biology
    2. Microbiology and Infectious Disease

    Consistent and correctable bias in metagenomic sequencing experiments

    Michael R McLaren, Amy D Willis, Benjamin J Callahan

    A mathematical model of bias in marker-gene and metagenomic sequencing measurements explains systematic errors in defined mixtures of microbial species, and enables quantitative and reproducible investigation of biological communities.
81. 1. Ecology
    2. Evolutionary Biology

    Seminal fluid compromises visual perception in honeybee queens reducing their survival during additional mating flights

    Joanito Liberti, Julia Görner ... Boris Baer

    After insemination, honeybee queens experience a rapid reduction in vision and flight performance, consistent with an ongoing sexual conflict over the number of mating flights that queens embark on.
82. 1. Neuroscience

    Processing of different spatial scales in the human brain

    Michael Peer, Yorai Ron ... Shahar Arzy

    When subjects perform spatial judgments in environments of increasing scale, brain activity shifts along posterior-anterior gradients, advancing from the visual system to the default-mode network.
83. 1. Biochemistry and Chemical Biology

    Lack of activity of recombinant HIF prolyl hydroxylases (PHDs) on reported non-HIF substrates

    Matthew E Cockman, Kerstin Lippl ... Peter J Ratcliffe

    Assays using recombinant HIF prolyl hydroxylases did not support hydroxylation of more than 20 reported non-HIF substrates under conditions where robust HIF hydroxylation was observed.
84. 1. Neuroscience

    MRGPRX4 is a bile acid receptor for human cholestatic itch

    Huasheng Yu, Tianjun Zhao ... Yulong Li

    Bile acid and it's receptor MRGPRX4, but not TGR5, is one of the ligand-receptor pairs for chronic itch in patients with liver diseases.
85. 1. Microbiology and Infectious Disease

    Functional metagenomics-guided discovery of potent Cas9 inhibitors in the human microbiome

    Kevin J Forsberg, Ishan V Bhatt ... Harmit S Malik

    A high-throughput, activity-based selection identifies many phage-derived inhibitors of Cas9 from human fecal and oral metagenomes, with at least one inhibitor acting via a novel mechanism.
86. 1. Neuroscience

    Representational untangling by the firing rate nonlinearity in V1 simple cells

    Merse E Gáspár, Pierre-Olivier Polack ... Gergő Orbán

    Firing rate nonlinearity recovers linear decodability of orientation information from simple cells of the primary visual cortex under uncertainty of nuisance parameters phase and spatial frequency.
87. 1. Neuroscience

    The paraventricular thalamus is a critical mediator of top-down control of cue-motivated behavior in rats

    Paolo Campus, Ignacio R Covelo ... Shelly B Flagel

    A top-down circuit generating from the prelimbic cortex and projecting to the paraventricular nucleus of the thalamus mediates individual differences in cue-elicited responding by affecting subcortical dopamine-dependent incentive learning.
88. 1. Neuroscience

    The nature of the animacy organization in human ventral temporal cortex

    Sushrut Thorat, Daria Proklova, Marius V Peelen

    The animacy organization in human ventral visual cortex is driven by both the presence of animal-diagnostic visual features and the psychological property of agency.
89. 1. Evolutionary Biology

    Evolution of Yin and Yang isoforms of a chromatin remodeling subunit precedes the creation of two genes

    Wen Xu, Lijiang Long ... Patrick T McGrath

    Gene sharing through different isoforms can precede the formation of independent genes.
90. 1. Structural Biology and Molecular Biophysics

    Kinesin and dynein use distinct mechanisms to bypass obstacles

    Luke S Ferro, Sinan Can ... Ahmet Yildiz

    Dynein bypasses obstacles on microtubules more efficiently than single kinesin, and kinesins overcome this limitation when transporting intracellular cargos in teams.
91. 1. Biochemistry and Chemical Biology
    2. Cell Biology

    Mitochondria supply ATP to the ER through a mechanism antagonized by cytosolic Ca²⁺

    Jing Yong, Helmut Bischof ... Randal J Kaufman

    ATP enters the endoplasmic reticulum (ER) lumen through an SLC35B1/AXER-dependentCaATiER mechanism, and ATP usage in the ER renders 'anti-Warburg' effect by increasing ATP regeneration from OxPhos while decreasing glycolysis.
92. 1. Neuroscience

    Long-term adult human brain slice cultures as a model system to study human CNS circuitry and disease

    Niklas Schwarz, Betül Uysal ... Henner Koch

    Viral transduction and gene manipulation of adult human brain slices will be of great value allowing investigations including therapeutic screening, electrophysiological and structural studies of properties of human CNS circuitry.
93. 1. Cell Biology

    Evidence that a positive feedback loop drives centrosome maturation in fly embryos

    Ines Alvarez-Rodrigo, Thomas L Steinacker ... Jordan W Raff

    Polo kinase recruitment by the protein Spd-2 to the pericentriolar scaffold is a key element of the positive feedback loop which drives the expansion of the mitotic centrosomes in flies.
94. 1. Neuroscience

    HCN channel-mediated neuromodulation can control action potential velocity and fidelity in central axons

    Niklas Byczkowicz, Abdelmoneim Eshra ... Stefan Hallermann

    The cAMP-HCN pathway can control action potential conduction velocity providing neuromodulators with the ability to tune energy consumption and temporal delays across axons in the brain.
95. 1. Cell Biology
    2. Developmental Biology

    Notch signaling restricts FGF pathway activation in parapineal cells to promote their collective migration

    Lu Wei, Amir Al Oustah ... Myriam Roussigné

    Notch signaling controls the collective migration of parapineal cells through its capacity to restrict FGF pathway activation to a few leading cells.
96. 1. Cell Biology
    2. Computational and Systems Biology

    Remote control of microtubule plus-end dynamics and function from the minus-end

    Xiuzhen Chen, Lukas A Widmer ... Yves Barral

    A mechanism for yeast centrosomes to differentiate the microtubule cytoskeleton.
97. 1. Neuroscience

    Entrained neuronal activity to periodic visual stimuli in the primate striatum compared with the cerebellum

    Masashi Kameda, Shogo Ohmae, Masaki Tanaka

    Neurons in the striatum exhibited periodic firing in monkeys attempting to detect omission of repetitive visual stimulus, while the phase of neuronal activity differed from that observed in the cerebellum.
98. 1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Regulation of Eag1 gating by its intracellular domains

    Jonathan R Whicher, Roderick MacKinnon

    Interactions between the voltage sensor and intracellular domains modulate voltage-dependent gating and calmodulin inhibition in the voltage-gated potassium channel Eag1.
99. 1. Cell Biology

    Regulator of G protein signaling 12 enhances osteoclastogenesis by suppressing Nrf2-dependent antioxidant proteins to promote the generation of reactive oxygen species

    Andrew Ying Hui Ng, Ziqing Li ... Shuying Yang

    Rgs12 protein is a novel regulator of the Nrf2 protein by facilitating the proteasomal degradation of the transcription factor during osteoclast differentiation.
100. 1. Neuroscience

     An open cortico-basal ganglia loop allows limbic control over motor output via the nigrothalamic pathway

     Sho Aoki, Jared B Smith ... Xin Jin

     A novel connection from ventral striatum to motor cortex enables emotion and motivation to influence action and motor control.
101. 1. Neuroscience

     RIM is essential for stimulated but not spontaneous somatodendritic dopamine release in the midbrain

     Brooks G Robinson, Xintong Cai ... Pascal S Kaeser

     Midbrain dopamine neurons use sophisticated secretory machinery to establish specialized sites for action potential-evoked release of dopamine from their cell bodies and dendrites.
102. 1. Neuroscience

     TRPC3 is a major contributor to functional heterogeneity of cerebellar Purkinje cells

     Bin Wu, François GC Blot ... Martijn Schonewille

     Purkinje cells feature molecular heterogeneity that introduces differentiation in physiological properties between zebrin-identified cerebellar modules and thereby underlies the differential control on sensorimotor integration.
103. 1. Neuroscience

     Altered gating of K_v1.4 in the nucleus accumbens suppresses motivation for reward

     Bernadette O'Donovan, Adewale Adeluyi ... Pavel I Ortinski

     Low effort-based motivation to pursue naturally rewarding stimuli can be increased pharmacologically, by targeting inactivation of a single voltage-gated potassium channel within the mesolimbic dopamine reward system.
104. 1. Structural Biology and Molecular Biophysics

     Decoding WW domain tandem-mediated target recognitions in tissue growth and cell polarity

     Zhijie Lin, Zhou Yang ... Mingjie Zhang

     A systematic and quantitative investigation showing how highly specific WW domain-mediated protein-protein interaction network is organized in cell growth and polarity.
105. 1. Evolutionary Biology

     Asexual reproduction reduces transposable element load in experimental yeast populations

     Jens Bast, Kamil S Jaron ... Tanja Schwander

     Sexual reproduction is responsible for the evolutionary success of selfish transposable elements.
106. 1. Cell Biology
     2. Physics of Living Systems

     Myosin II isoforms play distinct roles in adherens junction biogenesis

     Mélina L Heuzé, Gautham Hari Narayana Sankara Narayana ... Benoit Ladoux

     Myosin isoforms exhibit different functions in the formation of adherens junctions and the transmission of mechanical forces.
107. 1. Biochemistry and Chemical Biology
     2. Cell Biology

     Release of cholesterol-rich particles from the macrophage plasma membrane during movement of filopodia and lamellipodia

     Xuchen Hu, Thomas A Weston ... Loren G Fong

     Macrophages release 30-nm vesicular particles enriched in accessible cholesterol during cellular locomotion, a discovery that is likely relevant to cholesterol disposal by these cells.
108. 1. Computational and Systems Biology
     2. Immunology and Inflammation

     Deep generative models for T cell receptor protein sequences

     Kristian Davidsen, Branden J Olson ... Frederick A Matsen IV

     Deep learning improves estimation of T cell receptor cohort frequencies and learns the rules of VDJ recombination, potentially making it helpful for vaccine design.
109. 1. Neuroscience

     TMEM16B regulates anxiety-related behavior and GABAergic neuronal signaling in the central lateral amygdala

     Ke-Xin Li, Mu He ... Lily Yeh Jan

     SOM⁺ GABAergic neuronal signaling and inhibitory transmission in the central lateral amygdala is regulated by TMEM16B, which is also involved in fear and anxiety-like behaviors.
110. 1. Cancer Biology
     2. Cell Biology

     Activation of hedgehog signaling in mesenchymal stem cells induces cartilage and bone tumor formation via Wnt/β-Catenin

     Qi Deng, Ping Li ... Baojie Li

     Cartilage and bone tumors arise from chondrocyte or osteoblast progenitors but not differentiated cells or multipotent mesenchymal stem cells (MSCs) via the IHH-Wnt/β-Catenin pathway.
111. 1. Cell Biology
     2. Stem Cells and Regenerative Medicine

     Human perivascular stem cell-derived extracellular vesicles mediate bone repair

     Jiajia Xu, Yiyun Wang ... Aaron Watkins James

     Perivascular extracellular vesicles induce bone repair, and do so via tetraspanin binding to recipient skeletal progenitor cells.
112. 1. Microbiology and Infectious Disease

     Neighbor predation linked to natural competence fosters the transfer of large genomic regions in Vibrio cholerae

     Noémie Matthey, Sandrine Stutzmann ... Melanie Blokesch

     Whole-genome sequencing reveals the remarkable extent of horizontally moving genetic material in naturally competent Vibrio cholerae after a prey-killing DNA acquisition process.
113. 1. Computational and Systems Biology
     2. Evolutionary Biology

     Correlated evolution between repertoire size and song plasticity predicts that sexual selection on song promotes open-ended learning

     Cristina M Robinson, Kate T Snyder, Nicole Creanza

     A longer birdsong-learning window evolves in response to sexual selection for song complexity and is associated with faster evolution of song performance characteristics.
114. 1. Epidemiology and Global Health

     Parental vaccination to reduce measles immunity gaps in Italy

     Valentina Marziano, Piero Poletti ... Stefano Merler

     Offering measles vaccination to parents who bring their children to receive any dose of measles vaccine can accelerate measles elimination in Italy.
115. 1. Developmental Biology

     MicroRNA-mediated control of developmental lymphangiogenesis

     Hyun Min Jung, Ciara T Hu ... Brant M Weinstein

     Lymphatic-enriched microRNA miR-204 is required for lymphatic development through its effects on the key lymphatic transcription factor NFATC1.
116. 1. Genetics and Genomics
     2. Microbiology and Infectious Disease

     Adaptation of hepatitis C virus to interferon lambda polymorphism across multiple viral genotypes

     Nimisha Chaturvedi, Evguenia S Svarovskaia ... Jacques Fellay

     Integrated analysis of IFN-λ and HCV amino acid variation indicates the key role of host innate immunity in viral control.
117. 1. Cancer Biology

     FAK activity sustains intrinsic and acquired ovarian cancer resistance to platinum chemotherapy

     Carlos J Diaz Osterman, Duygu Ozmadenci ... David D Schlaepfer

     Genomic gains in ovarian cancer can promote cisplatin resistance via a FAK, Wnt/beta-catenin and Myc signaling pathway supporting pluripotency genes and tumorspheres that can acquire FAK dependence for survival.
118. 1. Ecology
     2. Evolutionary Biology

     Reduced metabolism supports hypoxic flight in the high-flying bar-headed goose (Anser indicus)

     Jessica U Meir, Julia M York ... William K Milsom

     Measurements of bar-headed geese flying in a wind tunnel in hypoxia reveal that these birds sustain aerobic flight at high altitude via a reduction in metabolism.
119. 1. Developmental Biology
     2. Evolutionary Biology

     Hemimetabolous insects elucidate the origin of sexual development via alternative splicing

     Judith Wexler, Emily Kay Delaney ... Artyom Kopp

     Sexual differentiation controlled by sex-specific mRNA splicing evolved in a step-wise manner in insects.
120. 1. Chromosomes and Gene Expression

     Androgen-regulated transcription of ESRP2 drives alternative splicing patterns in prostate cancer

     Jennifer Munkley, Ling Li ... David J Elliott

     The male steroid hormone testosterone regulates splicing patterns by controlling the expression of a key splicing regulator protein.
121. 1. Cell Biology
     2. Structural Biology and Molecular Biophysics

     Structural state recognition facilitates tip tracking of EB1 at growing microtubule ends

     Taylor A Reid, Courtney Coombes ... Melissa K Gardner

     EB1 targeting to growing microtubule plus-ends is facilitated by tapered microtubule tip structures.
122. 1. Genetics and Genomics

     Single-amino acid variants reveal evolutionary processes that shape the biogeography of a global SAR11 subclade

     Tom O Delmont, Evan Kiefl ... A Murat Eren

     An in-depth metagenomic analysis of possibly the most abundant and widespread microbial lineage in the surface ocean teases apart evolutionary processes that maintain its genomic heterogeneity and biogeography.
123. 1. Ecology
     2. Microbiology and Infectious Disease

     Endangered wild salmon infected by newly discovered viruses

     Gideon J Mordecai, Kristina M Miller ... Curtis A Suttle

     Newly discovered viruses in dead and dying farmed Chinook salmon are widely distributed in threatened wild Chinook and sockeye salmon populations.
124. 1. Genetics and Genomics
     2. Microbiology and Infectious Disease

     Interferon lambda 4 impacts the genetic diversity of hepatitis C virus

     M Azim Ansari, Elihu Aranday-Cortes ... Vincent Pedergnana

     Interferon lambda 4, a protein part of the innate immune response, drives major amino acids selection in patients chronically infected with hepatitis C virus.
125. 1. Cancer Biology
     2. Chromosomes and Gene Expression

     A single H/ACA small nucleolar RNA mediates tumor suppression downstream of oncogenic RAS

     Mary McMahon, Adrian Contreras ... Davide Ruggero

     Cancer-associated changes in small nucleolar RNAs and site-specific pseudouridine modifications impact ribosome activity.
126. 1. Neuroscience

     Cortical tau deposition follows patterns of entorhinal functional connectivity in aging

     Jenna N Adams, Anne Maass ... William J Jagust

     Tau deposition in the aging brain follows patterns of functional connectivity that correspond to specific neural memory networks, and this relationship is strengthened in the presence of amyloid-β.
127. 1. Developmental Biology
     2. Neuroscience

     Retrograde Ret signaling controls sensory pioneer axon outgrowth

     Adam Tuttle, Catherine M Drerup ... Alex V Nechiporuk

     Long-range Ret receptor signaling promotes axon outgrowth and regulates growth cone dynamics in pioneer neurons by inducing transcriptional changes in Myosin-X expression.