December 2017

Research articles

1. 1. Structural Biology and Molecular Biophysics
   2. Neuroscience

   Molecular structure of human KATP in complex with ATP and ADP

   Kenneth Pak Kin Lee, Jue Chen, Roderick MacKinnon

   MgADP binding to the high-affinity 'consensus' ATPase active site of SUR1 and remodeling of the L0-loop (lasso region) overrides tonic ATP inhibition of KATP channels.
2. 1. Neuroscience

   Representation of time interval entrained by periodic stimuli in the visual thalamus of pigeons

   Yan Yang, Qian Wang ... Qian Xiao

   The experience-dependent representation of time interval in the seconds-to-minutes range occurs as early as at the thalamic level in the brain.
3. 1. Neuroscience

   Environmental stimuli shape microglial plasticity in glioma

   Stefano Garofalo, Alessandra Porzia ... Cristina Limatola

   The microenvironment of brain tumors can be modulated by in vivo conditions that change the brain levels of BDNF and IL-15, with effects on innate immune cell activation.
4. 1. Structural Biology and Molecular Biophysics
   2. Developmental Biology

   Cell-accurate optical mapping across the entire developing heart

   Michael Weber, Nico Scherf ... Jan Huisken

   The combination of high-speed light sheet microscopy and suitable data analysis facilitates cell-accurate measurements across entire organs and opens the way to systematic, scale-bridging, in vivo studies of organogenesis.
5. 1. Cell Biology

   Heat stress promotes longevity in budding yeast by relaxing the confinement of age-promoting factors in the mother cell

   Sandro Baldi, Alessio Bolognesi ... Yves Barral

   To promote longevity under heat stress shares yeast aging factors with progeny through a down-regulation of the diffusion barrier in the membranes between the mitotic cells.
6. 1. Developmental Biology

   Regulation of posterior body and epidermal morphogenesis in zebrafish by localized Yap1 and Wwtr1

   David Kimelman, Natalie L Smith ... Didier YR Stainier

   Analysis of a double mutant in the Hippo pathway transcription factors Yap1 and Wwtr1 reveals novel roles for these factors in posterior body formation and epidermal morphogenesis in the vertebrate embryo.
7. 1. Chromosomes and Gene Expression
   2. Genetics and Genomics

   Transcription-factor-dependent enhancer transcription defines a gene regulatory network for cardiac rhythm

   Xinan H Yang, Rangarajan D Nadadur ... Ivan P Moskowitz

   Transcription-factor-dependent noncoding RNA transcription illuminates components of a transcription-factor-dependent gene regulatory network that includes enhancer-associated long noncoding RNAs and is necessary for cardiac rhythm.
8. 1. Computational and Systems Biology
   2. Microbiology and Infectious Disease

   Phenotype inference in an Escherichia coli strain panel

   Marco Galardini, Alexandra Koumoutsi ... Pedro Beltrao

   The mechanistic impact of genetic variants can be combined with previous knowledge on gene function to deliver conditional growth predictions and pave the way for personalized genetic interventions.
9. 1. Neuroscience

   Combining robotic training and inactivation of the healthy hemisphere restores pre-stroke motor patterns in mice

   Cristina Spalletti, Claudia Alia ... Matteo Caleo

   A combined rehabitative protocol after stroke in the mouse normalizes transcallosal inhibition and promotes "true recovery" of forelimb motor function.
10. 1. Computational and Systems Biology

    The kinetics of pre-mRNA splicing in the Drosophila genome and the influence of gene architecture

    Athma A Pai, Telmo Henriques ... Christopher B Burge

    Surprising connections between gene architecture and splicing kinetics are illuminated using short, progressive metabolic labeling/RNA sequencing and novel computational modeling approaches in Drosophila cells.
11. 1. Computational and Systems Biology
    2. Neuroscience

    Stochastic resonance mediates the state-dependent effect of periodic stimulation on cortical alpha oscillations

    Jérémie Lefebvre, Axel Hutt, Flavio Frohlich

    Stochastic resonance, triggered by fluctuations in brain state, is found to determine the outcomes of periodic stimulation and how it interacts with brain oscillations.
12. 1. Structural Biology and Molecular Biophysics
    2. Chromosomes and Gene Expression

    Decoding the centromeric nucleosome through CENP-N

    Satyakrishna Pentakota, Keda Zhou ... Karolin Luger

    A comprehensive structural, biochemical, and cell biological analysis reveals the molecular mechanism and significance of the conserved interaction of centromeric protein N (CENP-N) with the centromeric nucleosome.
13. 1. Neuroscience

    Interactions between stimulus and response types are more strongly represented in the entorhinal cortex than in its upstream regions in rats

    Eun-Hye Park, Jae-Rong Ahn, Inah Lee

    Goal-directed interaction with objects and spatial navigation are subserved by the perirhinal-lateral entorhinal networks and the postrhinal-medial entorhinal networks, respectively, with action-based functional differentiation more strongly represented in the entorhinal cortex than its upstream.
14. 1. Structural Biology and Molecular Biophysics

    Cryo-EM structure of the bifunctional secretin complex of Thermus thermophilus

    Edoardo D'Imprima, Ralf Salzer ... Beate Averhoff

    The pilus extrusion/DNA uptake system of Thermus thermophilus contains a 13-mer of the 757-residue PilQ protein and a tightly bound protein outside the outer membrane with a role in DNA binding.
15. 1. Neuroscience

    Cortical response states for enhanced sensory discrimination

    Diego A Gutnisky, Charles Beaman ... Valentin Dragoi

    Enhanced perceptual discrimination occurs when ongoing population activity in visual cortex is in a 'silent' mode in which neurons optimize information extraction.
16. 1. Developmental Biology
    2. Genetics and Genomics

    CRISPR/Cas9 and active genetics-based trans-species replacement of the endogenous Drosophila kni-L2 CRM reveals unexpected complexity

    Xiang-Ru Shannon Xu, Valentino Matteo Gantz ... Ethan Bier

    Dissection of a cis-regulatory element (CRM) in its native chromosomal context using CRISPR/Cas9 editing and novel 'Active Genetics' reveals new features of CRM function and insights into how such regulatory elements change during evolution.
17. 1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Structural insights into the assembly and polyA signal recognition mechanism of the human CPSF complex

    Marcello Clerici, Marco Faini ... Martin Jinek

    Structural, biochemical, and proteomic analyses of a four-subunit core module of the cleavage and polyadenylation specificity factor complex reveal its molecular architecture and specific determinants of polyadenylation signal recognition in human mRNAs.
18. 1. Neuroscience

    Doc2B acts as a calcium sensor for vesicle priming requiring synaptotagmin-1, Munc13-2 and SNAREs

    Sébastien Houy, Alexander J Groffen ... Jakob Balslev Sørensen

    Doc2B functions in two distinct vesicle priming steps; membrane localization occludes upstream Ca2+-dependent priming, whereas Ca2+-binding and interaction with synaptotagmin-1, SNAREs, and Munc13-2 are involved in downstream priming, which makes vesicles readily releasable.
19. 1. Cell Biology
    2. Neuroscience

    Paxillin facilitates timely neurite initiation on soft-substrate environments by interacting with the endocytic machinery

    Ting-Ya Chang, Chen Chen ... Pei-Lin Cheng

    Hippocampal neurons undergo bi-stable behavior as neurites emerge, and the dominance of either state is determined by environmental mechanical properties and paxillin-associated cellular endocytic activities.
20. 1. Structural Biology and Molecular Biophysics
    2. Cancer Biology

    A bulky glycocalyx fosters metastasis formation by promoting G1 cell cycle progression

    Elliot C Woods, FuiBoon Kai ... Carolyn R Bertozzi

    Mucins, long associated with cancer aggression, remodel the cancer glycocalyx in a way that promotes proliferation in the metastatic site by enhancing integrin-mediated adhesion and thus driving cell cycle progression.
21. 1. Cell Biology

    EGF receptor signaling, phosphorylation, ubiquitylation and endocytosis in tumors in vivo

    Itziar Pinilla-Macua, Alexandre Grassart ... Alexander Sorkin

    A small pool of active epidermal growth factor (EGF) receptors, which are capable of ubiquitylation and efficient endocytosis in vivo, is sufficient to support EGF-receptor-dependent tumor growth by signaling primarily through the Ras-MAPK pathway.
22. 1. Computational and Systems Biology

    Evolutionary dynamics of incubation periods

    Bertrand Ottino-Loffler, Jacob G Scott, Steven H Strogatz

    Evolutionary graph theory solves the longstanding puzzle of why diverse infectious diseases and cancers show similar (approximately lognormal) distributions of their incubation periods.
23. 1. Chromosomes and Gene Expression

    Conserved noncoding transcription and core promoter regulatory code in early Drosophila development

    Philippe J Batut, Thomas R Gingeras

    Gene expression timing during Drosophila development is specified by multiple classes of RNA polymerase II core promoters, and the embryonic transcriptome includes thousands of evolutionarily conserved long noncoding RNAs.
24. 1. Computational and Systems Biology

    Inferring genetic interactions from comparative fitness data

    Kristina Crona, Alex Gavryushkin ... Niko Beerenwinkel

    A new mathematical approach can infer higher order genetic interactions from pairwise fitness comparisons between genotypes.
25. 1. Stem Cells and Regenerative Medicine

    Distinct SoxB1 networks are required for naïve and primed pluripotency

    Andrea Corsinotti, Frederick CK Wong ... Ian Chambers

    Genetic manipulations show that endogenous transcription factors of the SoxB1 class act redundantly to maintain primed pluripotency and reveal differential effects on transitions between pluripotent and differentiation states.
26. 1. Developmental Biology

    The zinc-finger transcription factor Hindsight regulates ovulation competency of Drosophila follicles

    Lylah D Deady, Wei Li, Jianjun Sun

    Hindsight/RREB-1 plays a conserved role in follicle maturation and ovulation by sequential upregulation of matrix metalloproteinase and adrenergic receptor in follicle cells.
27. 1. Neuroscience

    Neural activity in cortico-basal ganglia circuits of juvenile songbirds encodes performance during goal-directed learning

    Jennifer M Achiro, John Shen, Sarah W Bottjer

    Activity in cortico-basal ganglia circuits of juvenile songbirds reflects evaluative signals necessary for comparing self-generated behavior to a goal representation during skill learning.
28. 1. Structural Biology and Molecular Biophysics
    2. Cell Biology

    Sculpting ion channel functional expression with engineered ubiquitin ligases

    Scott A Kanner, Travis Morgenstern, Henry M Colecraft

    Engineered E3 ubiquitin ligases are utilized to elucidate mechanisms underlying ubiquitin regulation of membrane proteins, and to achieve robust post-translational functional knockdown of ion channels.
29. 1. Neuroscience

    HCN2 channels in the ventral tegmental area regulate behavioral responses to chronic stress

    Peng Zhong, Casey R Vickstrom ... Qing-song Liu

    HCN2 channels in the ventral tegmental area play an important role in the pathophysiology of chronic mild stress-induced behavioral deficits.
30. 1. Neuroscience

    Paradoxical response reversal of top-down modulation in cortical circuits with three interneuron types

    Luis Carlos Garcia del Molino, Guangyu Robert Yang ... Xiao-Jing Wang

    Computational simulations and mathematical derivations reveal why the response of neural populations to external modulation is sometimes reversed with respect to what intuition would lead to believe in cortical circuits with multiple types of inhibitory neurons.
31. 1. Neuroscience

    Inducible and reversible phenotypes in a novel mouse model of Friedreich’s Ataxia

    Vijayendran Chandran, Kun Gao ... Daniel H Geschwind

    Restoration of endogenous frataxin levels reverses neurologic and cardiac phenotypes associated with Friedreich's ataxia in adult mice even after significant motor dysfunction.
32. 1. Biochemistry and Chemical Biology
    2. Cancer Biology

    Inhibition of intracellular lipolysis promotes human cancer cell adaptation to hypoxia

    Xiaodong Zhang, Alicia M Saarinen ... Jun Liu

    The survival and growth of solid tumor cells in hypoxia is dependent on fatty acid storage in triglyceride lipid droplets promoted by HIG2.
33. 1. Chromosomes and Gene Expression

    The CDK-PLK1 axis targets the DNA damage checkpoint sensor protein RAD9 to promote cell proliferation and tolerance to genotoxic stress

    Takeshi Wakida, Masae Ikura ... Kanji Furuya

    Minimizing anti-proliferation signaling from DNA damage detection machinery is the tactic for the cells to drive proliferation under genotoxic environment, and the function is exerted by Polo-Like-Kinase1 that is frequently over-expressed in cancer cells.
34. 1. Structural Biology and Molecular Biophysics

    Mechanistic insights into the active site and allosteric communication pathways in human nonmuscle myosin-2C

    Krishna Chinthalapudi, Sarah M Heissler ... Dietmar J Manstein

    R788 is part of an allosteric communication pathway that connects the converter at the distal end of the myosin motor domain via the relay helix with switch-2 of the active site.
35. 1. Neuroscience

    Inhibition of PIP4Kγ ameliorates the pathological effects of mutant huntingtin protein

    Ismael Al-Ramahi, Sai Srinivas Panapakkam Giridharan ... Juan Jose Marugan

    This work validates PIP4K gamma as pharmacological target to ameliorate Huntington's disease.
36. 1. Microbiology and Infectious Disease

    Severe infections emerge from commensal bacteria by adaptive evolution

    Bernadette C Young, Chieh-Hsi Wu ... Daniel J Wilson

    Life-threatening S. aureus infections emerge from commensal nose bacteria in association with repeatable adaptive evolution.
37. 1. Ecology
    2. Plant Biology

    The diversity of floral temperature patterns, and their use by pollinators

    Michael JM Harrap, Sean A Rands ... Heather M Whitney

    Flowers of different plant species show distinct and highly diverse patterns of temperature across their surfaces, and bumblebees are able to differentiate between these previously unnoticed but widespread floral cues.
38. 1. Developmental Biology
    2. Chromosomes and Gene Expression

    Natural variation in stochastic photoreceptor specification and color preference in Drosophila

    Caitlin Anderson, India Reiss ... Robert J Johnston

    Binding site affinity and transcription factor levels are finely tuned in nature to regulate stochastic expression, setting the ratio of alternative photoreceptor fates and determining color preference.
39. 1. Neuroscience

    Activation of the dopaminergic pathway from VTA to the medial olfactory tubercle generates odor-preference and reward

    Zhijian Zhang, Qing Liu ... Fuqiang Xu

    The VTA-mOT DAergic pathway mediates a variety of naturalistic reward processes and different types of preferences including odor-preference.
40. 1. Cell Biology

    Ratiometric sensing of BiP-client versus BiP levels by the unfolded protein response determines its signaling amplitude

    Anush Bakunts, Andrea Orsi ... Eelco van Anken

    Restoration of endoplasmic reticulum (ER) homeostatis occurs when levels of the key ER resident chaperone BiP exceed those of accumulating ER clients.
41. 1. Neuroscience

    LRP1 regulates peroxisome biogenesis and cholesterol homeostasis in oligodendrocytes and is required for proper CNS myelin development and repair

    Jing-Ping Lin, Yevgeniya A Mironova ... Roman J Giger

    In oligodendrocyte progenitor cells, lipid metabolism and peroxisome biogenesis are regulated by the low-density lipoprotein related-receptor-1, and if disrupted, impair proper white matter development and adult repair.
42. 1. Neuroscience

    Two-photon imaging in mice shows striosomes and matrix have overlapping but differential reinforcement-related responses

    Bernard Bloem, Rafiq Huda ... Ann M Graybiel

    Simultaneous 2-photon imaging of striosomes and matrix in mice shows that striosomes preferentially encode reward-predicting cues whereas both striatal compartments demonstrate reward-related activity.
43. 1. Evolutionary Biology

    Free-living human cells reconfigure their chromosomes in the evolution back to uni-cellularity

    Jin Xu, Xinxin Peng ... Chung-I Wu

    Human cell lines regress to become ‘de-sexualized’ by reconfiguring to a 2:3 X/A ratio of high fitness, thus shedding light on the evolution of mammalian sex chromosomes.
44. 1. Neuroscience

    The role of microglia and their CX3CR1 signaling in adult neurogenesis in the olfactory bulb

    Ronen Reshef, Elena Kudryavitskaya ... Raz Yirmiya

    During adult neurogenesis in the olfactory bulb, microglia regulate the elimination (pruning), formation, and maintenance of synapses on newborn neurons, contributing to the functional integrity of the olfactory bulb circuitry.
45. 1. Genetics and Genomics

    Quiescence unveils a novel mutational force in fission yeast

    Serge Gangloff, Guillaume Achaz ... Benoit Arcangioli

    The quiescence-driven mutational landscape reveals replication-independent mutagenesis as a novel evolutionary force.
46. 1. Developmental Biology

    Osteocalcin expressing cells from tendon sheaths in mice contribute to tendon repair by activating Hedgehog signaling

    Yi Wang, Xu Zhang ... Kingston King-Lun Mak

    Cells in tendon sheaths, considered to be extrinsic tissues of tendon, possess stem or progenitor cell properties that are involved in tendon repair by activating the Hh-TGFb/Smad3 axis.
47. 1. Neuroscience

    Human subthalamic nucleus activity during non-motor decision making

    Baltazar A Zavala, Anthony I Jang, Kareem A Zaghloul

    Intraoperative human brain recordings during a memory task reveal that when participants inhibit memory formation, the subthalamic nucleus shows higher beta power and beta coherence with areas of the lateral cortex implicated in memory processing.
48. 1. Biochemistry and Chemical Biology
    2. Cell Biology

    Diverse functions of homologous actin isoforms are defined by their nucleotide, rather than their amino acid sequence

    Pavan Vedula, Satoshi Kurosaka ... Anna Kashina

    CRISPR/Cas9 gene editing in mice reveals that diverse functions of actin isoforms are defined by their nucleotide, rather than their amino acid sequence, suggesting a novel mechanism of nucleotide-dependent protein regulation in eukaryotic genomes.
49. 1. Neuroscience

    Dynamic modulation of activity in cerebellar nuclei neurons during pavlovian eyeblink conditioning in mice

    Michiel M ten Brinke, Shane A Heiney ... Chris I De Zeeuw

    Conditioned olivocerebellar network activity elicits transient spike pauses and timed spike facilitation in the neurons of interposed nuclei that predicts and likely causes conditioned eyelid responses on a trial-by-trial basis.
50. 1. Structural Biology and Molecular Biophysics
    2. Chromosomes and Gene Expression

    The structural basis for dynamic DNA binding and bridging interactions which condense the bacterial centromere

    Gemma LM Fisher, César L Pastrana ... Mark S Dillingham

    A combination of structural, biochemical, single-molecule and in vivo methods are used to show how ParB locally condenses the bacterial chromosome near the origin and earmarks this region for segregation.
51. 1. Cell Biology

    Defective STIM-mediated store operated Ca²⁺ entry in hepatocytes leads to metabolic dysfunction in obesity

    Ana Paula Arruda, Benedicte Mengel Pers ... Gökhan S Hotamisligil

    Store operated calcium entry is defective in hepatocytes of obese mice, and restoring this process is sufficient to improve glucose metabolism.
52. 1. Biochemistry and Chemical Biology
    2. Cell Biology

    SIRT2 and lysine fatty acylation regulate the transforming activity of K-Ras4a

    Hui Jing, Xiaoyu Zhang ... Hening Lin

    A new post-translational regulatory mechanism of K-Ras is identified, which expands the function of reversible protein lysine fatty acylation and offers new possibility to target the K-Ras oncoprotein.
53. 1. Biochemistry and Chemical Biology
    2. Cell Biology

    Live-cell mapping of organelle-associated RNAs via proximity biotinylation combined with protein-RNA crosslinking

    Pornchai Kaewsapsak, David Michael Shechner ... Alice Y Ting

    Live-cell nanometer-resolution RNA labeling method enables transcriptome-wide mapping of endogenous RNAs in nuclear, cytosol, ER, and mitochondrial subcompartments.
54. 1. Cell Biology
    2. Immunology and Inflammation

    Intermittent Ca²⁺ signals mediated by Orai1 regulate basal T cell motility

    Tobias X Dong, Shivashankar Othy ... Michael D Cahalan

    Orai1 channels activate intermittently in motile T cells, generating calcium transients, detected by a novel genetically encoded indicator and inducing pauses that favor antigen scanning.
55. 1. Biochemistry and Chemical Biology
    2. Cell Biology

    Akt regulation of glycolysis mediates bioenergetic stability in epithelial cells

    Yin P Hung, Carolyn Teragawa ... John G Albeck

    Individual cells display heterogeneous fluctuations in metabolic activity, with amplitude and kinetics controlled by interlocking feedbacks between glycolysis and the Insulin/PI3K/Akt signaling pathway.
56. 1. Computational and Systems Biology
    2. Chromosomes and Gene Expression

    Natural changes in light interact with circadian regulation at promoters to control gene expression in cyanobacteria

    Joseph Robert Piechura, Kapil Amarnath, Erin K O'Shea

    Cyanobacteria cope with both predictable day/night changes and natural fluctuations in light during the day by adjusting the expression dynamics of circadian-clock-controlled genes via a network of transcriptional regulators.
57. 1. Cell Biology
    2. Chromosomes and Gene Expression

    cAMP signaling regulates DNA hydroxymethylation by augmenting the intracellular labile ferrous iron pool

    Vladimir Camarena, David W Sant ... Gaofeng Wang

    cAMP is identified to play a novel role in regulating DNA demethylation and gene transcription by augmenting the intracellular reactive Fe(II) pool.
58. 1. Immunology and Inflammation
    2. Cell Biology

    Calcium-mediated shaping of naive CD4 T-cell phenotype and function

    Vincent Guichard, Nelly Bonilla ... Cédric Auffray

    Calcium-calcineurin signaling cascade drives the acquisition of both the phenotype of the most self-reactive naive CD4 T cells and their enhanced cell-intrinsic ability to commit into induced regulatory T cells upon activation.
59. 1. Cell Biology
    2. Immunology and Inflammation

    T-cell calcium dynamics visualized in a ratiometric tdTomato-GCaMP6f transgenic reporter mouse

    Tobias X Dong, Shivashankar Othy ... Michael D Cahalan

    Salsa6f is a novel, ratiometric genetically encoded Ca²⁺ indicator that combines the power of ratiometric chemical Ca²⁺ indicators with the ability, when expressed transgenically, to image cellular Ca²⁺ signals amid complex tissue environments in vivo.
60. 1. Developmental Biology
    2. Physics of Living Systems

    Gene-free methodology for cell fate dynamics during development

    Francis Corson, Eric D Siggia

    Mathematical methods based on geometry that directly embody the developmental concepts of competency, commitment, and determination provide succinct descriptions of morphogenesis and allow quantitative predictions from fits to sparse genetic data in Caenorhabditis elegans.
61. 1. Computational and Systems Biology
    2. Microbiology and Infectious Disease

    Multiple sources of slow activity fluctuations in a bacterial chemosensory network

    Remy Colin, Christelle Rosazza ... Victor Sourjik

    Single-cell FRET measurements reveal large temporal activity fluctuations within this signaling pathway in Escherichia coli, caused by stochasticity of receptor methylation combined with allosteric interactions and slow rearrangements within receptor clusters.
62. 1. Cancer Biology
    2. Immunology and Inflammation

    Endothelial cells express NKG2D ligands and desensitize antitumor NK responses

    Thornton W Thompson, Alexander Byungsuk Kim ... David H Raulet

    Antitumor (natural killer) NK cell responses are negatively regulated by interactions between NK cells and endogenous NKG2D ligands constitutively expressed on lymph node endothelial cells and super-induced on tumor-associated endothelium.
63. 1. Neuroscience

    Oxytocin signaling in the medial amygdala is required for sex discrimination of social cues

    Shenqin Yao, Joseph Bergan ... Catherine Dulac

    Oxytocin signaling plays a critical role in a molecularly defined neuronal population of the Medial Amygdala to modulate the behavioral and physiological responses of male mice to females on a moment-to-moment basis.
64. 1. Epidemiology and Global Health
    2. Plant Biology

    Evolutionary transitions between beneficial and phytopathogenic Rhodococcus challenge disease management

    Elizabeth A Savory, Skylar L Fuller ... Jeff H Chang

    The horizontal acquisition of virulence plasmids is potentiated by production practices in plant nurseries and is sufficient to transition Rhodococcus from being beneficial to being pathogenic.
65. 1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    A picorna-like virus suppresses the N-end rule pathway to inhibit apoptosis

    Zhaowei Wang, Xiaoling Xia ... Xi Zhou

    A picorna-like virus promotes the accumulation of caspase-cleaved drosophila inhibitor of apoptosis 1 by inducing the degradation of NTAN1, a key N-end rule degradation pathway component, leading to apoptosis inhibition and viral replication enhancement.
66. 1. Computational and Systems Biology

    Phenotypic diversity and temporal variability in a bacterial signaling network revealed by single-cell FRET

    Johannes M Keegstra, Keita Kamino ... Thomas S Shimizu

    Noise in a signaling network comprising thousands of molecules shapes diversity across cell populations and generates giant temporal fluctuations at the single-cell level.
67. 1. Neuroscience

    Tracing neuronal circuits in transgenic animals by transneuronal control of transcription (TRACT)

    Ting-hao Huang, Peter Niesman ... Carlos Lois

    A new method that will allow researchers to visualize and genetically manipulate synaptically connected neurons in a brain circuit.
68. 1. Neuroscience

    Molecular basis of fatty acid taste in Drosophila

    Ji-Eun Ahn, Yan Chen, Hubert Amrein

    Molecular-genetic, neural imaging and behavioral analyses reveal how Drosophila melanogaster sense fatty acids, important nutrient compounds, through multimeric Ionoptropic Receptors complexes.
69. 1. Cell Biology
    2. Developmental Biology

    Cell lineage and cell cycling analyses of the 4d micromere using live imaging in the marine annelid Platynereis dumerilii

    B Duygu Özpolat, Mette Handberg-Thorsager ... Guillaume Balavoine

    Lineage tracing at single-cell resolution reveals the presence of mesoteloblasts, the embryonic origin of mesodermal growth zone cells, and diverse cell cycling patterns of these lineages in the 'Polychaete' annelid Platynereis.
70. 1. Cell Biology
    2. Microbiology and Infectious Disease

    Shigella entry unveils a calcium/calpain-dependent mechanism for inhibiting sumoylation

    Pierre Lapaquette, Sabrina Fritah ... Anne Dejean

    Shigella infection induces a calpain-mediated loss of SUMO conjugates that promotes bacterial entry.
71. 1. Developmental Biology

    Abelson tyrosine-protein kinase 2 regulates myoblast proliferation and controls muscle fiber length

    Jennifer K Lee, Peter T Hallock, Steven J Burden

    Abl2 regulates myoblast proliferation, thereby controlling the size of the pool of myoblasts available for fusion, providing insight into mechanisms that control myofiber length and signaling between muscle and tendon.
72. 1. Chromosomes and Gene Expression

    Genome-wide mapping of sister chromatid exchange events in single yeast cells using Strand-seq

    Clémence Claussin, David Porubský ... Michael Chang

    Genome-wide analysis of sister chromatid exchange using single-cell sequencing reveals that most spontaneous sister chromatid exchange events are not due to the repair of double-strand DNA breaks in wild-type yeast cells.
73. 1. Plant Biology

    An evolutionarily young defense metabolite influences the root growth of plants via the ancient TOR signaling pathway

    Frederikke Gro Malinovsky, Marie-Louise F Thomsen ... Daniel J Kliebenstein

    Young defense metabolites are often believed to be solely outputs but evidence suggests that they can regulate ancient signaling pathways.
74. 1. Developmental Biology

    Glucose inhibits cardiac muscle maturation through nucleotide biosynthesis

    Haruko Nakano, Itsunari Minami ... Atsushi Nakano

    During cardiogenesis, the major role of glucose is not the catabolic extraction of energy but the anabolic biosynthesis of nucleotides.
75. 1. Medicine

    A homozygous FANCM mutation underlies a familial case of non-syndromic primary ovarian insufficiency

    Baptiste Fouquet, Patrycja Pawlikowska ... Micheline Misrahi

    Bilallelic mutations of FANCM, a DNA-damage response gene whose heterozygous mutations predispose to breast cancer, are involved in a familial case of Primary Ovarian Insufficiency establishing a link between infertility and cancer.
76. 1. Structural Biology and Molecular Biophysics

    Structure-based membrane dome mechanism for Piezo mechanosensitivity

    Yusong R Guo, Roderick MacKinnon

    Mechanosensitive Piezo channel induces local membrane curvature to mediate mechanical gating.
77. 1. Neuroscience

    Salt-inducible kinase 3 regulates the mammalian circadian clock by destabilizing PER2 protein

    Naoto Hayasaka, Arisa Hirano ... Yoshitaka Fukada

    Salt-inducible kinase 3 (SIK3) is an essential component of the mammalian circadian clock machinery, which governs robust circadian behavioral and other rhythms by destabilization of a core clock protein PER2 in a phosphorylation-dependent manner.
78. 1. Cell Biology

    Stress-induced Cdk5 activity enhances cytoprotective basal autophagy in Drosophila melanogaster by phosphorylating acinus at serine⁴³⁷

    Nilay Nandi, Lauren K Tyra ... Helmut Krämer

    Cdk5-mediated stabilization of Acinus in postmitotic neurons promotes autophagy and the removal of protein aggregates linked to neurodegeneration in Drosophila melanogaster.
79. 1. Neuroscience

    Eye opening differentially modulates inhibitory synaptic transmission in the developing visual cortex

    Wuqiang Guan, Jun-Wei Cao ... Yong-Chun Yu

    Our work demonstrated that eye opening differentially modulates inhibitory synaptic transmission from Sst-INs and FS-INs to excitatory neurons in the mammalian cortex.
80. 1. Computational and Systems Biology
    2. Ecology

    Tree crickets optimize the acoustics of baffles to exaggerate their mate-attraction signal

    Natasha Mhatre, Robert Malkin ... Daniel Robert

    Tree crickets can optimize the baffles they make to increase call loudness without any progressive optimization, and manufacture an optimal baffle in a single attempt, by using a simple yet highly accurate heuristic.
81. 1. Medicine

    Clearance of senescent decidual cells by uterine natural killer cells in cycling human endometrium

    Paul J Brighton, Yojiro Maruyama ... Jan Joris Brosens

    While acute senescence of decidualizing cells drives the inflammatory response underpinning uterine receptivity, subsequent clearance by activated natural killer cells transiently rejuvenates the cycling endometrium, enabling transition into a gestational tissue upon embryo implantation.
82. 1. Microbiology and Infectious Disease

    A comparative transcriptomic analysis of replicating and dormant liver stages of the relapsing malaria parasite Plasmodium cynomolgi

    Annemarie Voorberg-van der Wel, Guglielmo Roma ... Thierry Tidiane Diagana

    This comprehensive transcriptomic resource of dormant and replicating malaria liver parasites highlights the dearth of pathways that operate in the hypnozoites and the need to investigate druggability (i.e. selectivity and safety) of core pathways in malaria parasites.
83. 1. Developmental Biology

    Nodal patterning without Lefty inhibitory feedback is functional but fragile

    Katherine W Rogers, Nathan D Lord ... Alexander F Schier

    Lefty-mediated feedback inhibition of Nodal signaling mitigates signaling perturbations, but is dispensable for development.
84. 1. Structural Biology and Molecular Biophysics
    2. Microbiology and Infectious Disease

    Extended low-resolution structure of a Leptospira antigen offers high bactericidal antibody accessibility amenable to vaccine design

    Ching-Lin Hsieh, Christopher P Ptak ... Yung-Fu Chang

    The antibody accessibility of the leptospiral surface protein, LigB, provides a guide for the rational design of improved recombinant chimeric vaccine antigens displayed on a single domain scaffold.
85. 1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Single-molecule studies contrast ordered DNA replication with stochastic translesion synthesis

    Gengjing Zhao, Emma S Gleave, Meindert Hugo Lamers

    Competing DNA polymerases at the DNA sliding clamp are revealed by single-molecule co-localization studies.
86. 1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Structural basis of proton translocation and force generation in mitochondrial ATP synthase

    Niklas Klusch, Bonnie J Murphy ... Werner Kühlbrandt

    Cryo-EM reveals atomic details of two membrane half-channels for translocation of protons that drive rotary catalysis in ATP synthase.
87. 1. Cell Biology

    Deciphering caveolar functions by syndapin III KO-mediated impairment of caveolar invagination

    Eric Seemann, Minxuan Sun ... Britta Qualmann

    Mice lacking the membrane-shaping protein syndapin III show severe reduction of caveolae reminiscent of human caveolinopathies but maintain plasma membrane-associated caveolar coats proteins and thereby unveil physiological impairments associated with lack of invaginated caveolae.
88. 1. Computational and Systems Biology
    2. Neuroscience

    Towards deep learning with segregated dendrites

    Jordan Guerguiev, Timothy P Lillicrap, Blake A Richards

    A multi-compartment spiking neural network model demonstrates that biologically feasible deep learning can be achieved if sensory inputs and higher-order feedback are received by different dendritic compartments.
89. 1. Microbiology and Infectious Disease

    An Aedes aegypti-associated fungus increases susceptibility to dengue virus by modulating gut trypsin activity

    Yesseinia I Angleró-Rodríguez, Octavio AC Talyuli ... George Dimopoulos

    Talaromyces (Tsp_PR) fungus render Aedes aegypti mosquitoes more susceptible to dengue virus infection through secreted molecules that impair midgut digestive enzyme transcription and activity.
90. 1. Neuroscience

    Serotonin enhances excitability and gamma frequency temporal integration in mouse prefrontal fast-spiking interneurons

    Jegath C Athilingam, Roy Ben-Shalom ... Kevin J Bender

    Serotonin changes passive membrane properties in prefrontal fast-spiking interneurons to affect not only neuronal excitability but also the temporal filtering of synaptic inputs with a preference for gamma-frequency summation.
91. 1. Computational and Systems Biology
    2. Structural Biology and Molecular Biophysics

    Conformational dynamics in TRPV1 channels reported by an encoded coumarin amino acid

    Ximena Steinberg, Marina A Kasimova ... Sebastian E Brauchi

    Single-molecule measurement of conformational dynamics using a genetically encoded fluorescent probe suggests that the selectivity filter region of TRPV1 channels undergoes dynamic motion during agonist activation.
92. 1. Genetics and Genomics

    Epigenetic profiling of growth plate chondrocytes sheds insight into regulatory genetic variation influencing height

    Michael Guo, Zun Liu ... Terence D Capellini

    Epigenetic profiling of femoral growth plate chondrocytes helps whittle-down GWAS height variants to fewer putative functional variants.
93. 1. Developmental Biology

    Hedgehog signaling via Gli2 prevents obesity induced by high-fat diet in adult mice

    Yu Shi, Fanxin Long

    Targeted activation of Hedgehog signalling via Gli2 facilitated the reduction of high-fat-diet-induced obesity and improvement of whole-body glucose tolerance and insulin sensitivity in adult mice.
94. 1. Immunology and Inflammation

    A population of innate myelolymphoblastoid effector cell expanded by inactivation of mTOR complex 1 in mice

    Fei Tang, Peng Zhang ... Pan Zheng

    A novel population of hematopoietic cells unmasked by mTORC1 inactivation reveals a new mechanism of innate immune tolerance and a new consequence of defective hematopoiesis.
95. 1. Biochemistry and Chemical Biology

    eIF1A residues implicated in cancer stabilize translation preinitiation complexes and favor suboptimal initiation sites in yeast

    Pilar Martin-Marcos, Fujun Zhou ... Alan G Hinnebusch

    Substitutions in general translation initiation factor eIF1A found as recurring somatic mutations in uveal melanoma destabilize the closed conformation of the preinitiation complex at the start codon and increase discrimination against suboptimal initiation codons genome-wide.
96. 1. Developmental Biology

    Live imaging of heart tube development in mouse reveals alternating phases of cardiac differentiation and morphogenesis

    Kenzo Ivanovitch, Susana Temiño, Miguel Torres

    Tissue-level coordination of cardiac progenitor cells in the early mouse embryo produces a temporal compartmentalization of differentiation and morphogenesis essential for heart tube formation.
97. 1. Neuroscience

    Brainstem network dynamics underlying the encoding of bladder information

    Anitha Manohar, Andre L Curtis ... Rita J Valentino

    Neural and network activity within a pontine-cortical micturition circuit are finely coordinated with urodynamics to assure appropriate voiding behaviors.
98. 1. Neuroscience

    Neurophysiological evidence of efference copies to inner speech

    Thomas J Whitford, Bradley N Jack ... Mike E Le Pelley

    The silent production of words in one's mind generates an efference copy that is similar in nature to the efference copy associated with overt vocalization.
99. 1. Structural Biology and Molecular Biophysics
    2. Immunology and Inflammation

    Computationally-driven identification of antibody epitopes

    Casey K Hua, Albert T Gacerez ... Chris Bailey-Kellogg

    The combination of computational modeling and protein design can reveal key determinants of antibody–antigen binding and optimize small sets of antigen variants for efficient experimental localization of epitopes.
100. 1. Cell Biology
     2. Developmental Biology

     Single-cell transcriptome analysis of avian neural crest migration reveals signatures of invasion and molecular transitions

     Jason A Morrison, Rebecca McLennan ... Paul M Kulesa

     Single cell transcriptome analysis of an embryonic collective migratory cell population provides new insights into the heterogeneity of transcriptional signatures within a neural crest cell migratory stream.
101. 1. Neuroscience

     The AMPA receptor-associated protein Shisa7 regulates hippocampal synaptic function and contextual memory

     Leanne J M Schmitz, Remco V Klaassen ... Sabine Spijker

     Shisa7 is a bona-fide AMPAR modulatory protein affecting channel kinetics of hippocampal AMPARs, and is necessary for synaptic plasticity and memory recall.
102. 1. Structural Biology and Molecular Biophysics

     Cryo-EM structures reveal specialization at the myosin VI-actin interface and a mechanism of force sensitivity

     Pinar S Gurel, Laura Y Kim ... Gregory M Alushin

     Cryo-EM structures of actomyosin VI in multiple nucleotide states reveal a unique actin-myosin interface and a mechanism of force-sensitivity; furthermore, myosin VI remodels F-actin, suggesting a role for actin structural plasticity during force generation.
103. 1. Developmental Biology

     Dephosphorylation of the NPR2 guanylyl cyclase contributes to inhibition of bone growth by fibroblast growth factor

     Leia C Shuhaibar, Jerid W Robinson ... Laurinda A Jaffe

     Fibroblast growth factor induces dephosphorylation and inactivation of the NPR2 guanylyl cyclase, thus decreasing cyclic GMP production in growth plate chondrocytes and contributing to FGF-dependent decreases in bone growth.
104. 1. Neuroscience

     A selective role for ventromedial subthalamic nucleus in inhibitory control

     Benjamin Pasquereau, Robert S Turner

     Single-unit activity consistent with a selective causal role in reactive stopping or switching behaviors is found only in the most ventromedial subregion of the subthalamic nucleus.
105. 1. Neuroscience

     Synaptic and peptidergic connectome of a neurosecretory center in the annelid brain

     Elizabeth A Williams, Csaba Verasztó ... Gáspár Jékely

     A combination of electron microscopic reconstruction and the analysis of single cell transcriptome data is used to reconstruct synaptic and peptidergic signaling networks in a neurosecretory centre.
106. 1. Cell Biology

     Ragulator and GATOR1 complexes promote fission yeast growth by attenuating TOR complex 1 through Rag GTPases

     Kim Hou Chia, Tomoyuki Fukuda ... Kazuhiro Shiozaki

     The Rag-family GTPases, known activators of TOR complex 1 (TORC1), also function as attenuator that prevents deregulated hyperactivation of TORC1 signaling.
107. 1. Cell Biology
     2. Developmental Biology

     Stimulation of hair follicle stem cell proliferation through an IL-1 dependent activation of γδT-cells

     Pedro Lee, Rupali Gund ... Colin Jamora

     Wounded epidermal keratinocytes emit a signal that activates a specialized T-cell in the skin, leading to an increase in hair follicle stem cell numbers that contributes to tissue repair.
108. 1. Cancer Biology
     2. Cell Biology

     LAST, a c-Myc-inducible long noncoding RNA, cooperates with CNBP to promote CCND1 mRNA stability in human cells

     Limian Cao, Pengfei Zhang ... Mian Wu

     A c-Myc-transcribed long noncoding RNA namely LAST (LncRNA-assisted stabilization of transcripts) collaborates with a cellular factor CNBP to promote the stability of CCND1/cyclin D1 mRNA post-transcriptionally, ensuring the proper G1/Sphase transition of the cell cycle.
109. 1. Developmental Biology

     Shaping of inner ear sensory organs through antagonistic interactions between Notch signalling and Lmx1a

     Zoe F Mann, Héctor Gálvez ... Nicolas Daudet

     A dynamic confrontation between Notch signalling and the transcription factor Lmx1a at the borders of the developing inner ear sensory patches regulates their segregation and the positioning of their boundaries.