January 2019

Image credit: Tom Deerinck and Mark Ellisman from the UCSD National Center for Imaging and Microscopy Research.

Cover articles

Research articles

    1. Microbiology and Infectious Disease

    Flexible nitrogen utilisation by the metabolic generalist pathogen Mycobacterium tuberculosis

    Aleksandra Agapova et al.
    Metabolomics and stable isotope labelling studies of virulent Mycobacterium tuberculosis reveal a de-centralised metabolic network able to utilise various amino acids as nitrogen sources to a better extent than ammonium.
    1. Neuroscience

    Visualization of currents in neural models with similar behavior and different conductance densities

    Leandro M Alonso, Eve Marder
    Visualization methods display the dynamics of the currents in conductance-based model neurons, and show how their contribution changes in response to perturbation.
    1. Cell Biology
    2. Developmental Biology

    Anillin regulates epithelial cell mechanics by structuring the medial-apical actomyosin network

    Torey R Arnold et al.
    In epithelial cells, anillin organizes the medial-apical actomyosin cortex into a contractile load-bearing structure and increases tissue-level stiffness.
    1. Evolutionary Biology
    2. Neuroscience

    Quantitative uniqueness of human brain evolution revealed through phylogenetic comparative analysis

    Ian F Miller et al.
    The exceptionally large size of the human brain is the result of accelerating evolution towards larger brains in hominins, but is not the product of neocortical expansion.
    1. Computational and Systems Biology

    Generative modeling of multi-mapping reads with mHi-C advances analysis of Hi-C studies

    Ye Zheng et al.
    A statistical model rescues multi-mapping reads with high accuracy and demonstrates their impact in all facets of the analysis of genome-wide high throughput conformation capture datasets.
    1. Human Biology and Medicine

    Comment on 'Palovarotene reduces heterotopic ossification in juvenile FOP mice but exhibits pronounced skeletal toxicity'

    Maurizio Pacifici, Eileen M Shore
    We are writing to communicate our concerns regarding the recently published study by Lees-Shepard et al. (2018).
    1. Human Biology and Medicine
    2. Stem Cells and Regenerative Medicine

    Response to comment on 'Palovarotene reduces heterotopic ossification in juvenile FOP mice but exhibits pronounced skeletal toxicity'

    David J Goldhamer, John B Lees-Shepard
    We respond to concerns expressed by Pacifici and Shore (2019) about our recent paper (Lees-Shepard et al., 2018a).
    1. Chromosomes and Gene Expression
    2. Developmental Biology

    Mi-2/NuRD complex protects stem cell progeny from mitogenic Notch signaling

    Evanthia Zacharioudaki et al.
    Depleting Mi-2 in the progeny of neural stem cells prevents normal enhancer decommissioning so that they become sensitive to Notch activity and re-acquire stem cell properties.
    1. Developmental Biology
    2. Neuroscience

    TIAM-1/GEF can shape somatosensory dendrites independently of its GEF activity by regulating F-actin localization

    Leo TH Tang et al.
    The DMA-1/LRR-TM cell surface receptor signals through partially redundant pathways to cell-autonomously pattern dendrites, including by directly forming a complex with both the TIAM-1/GEF and ACT-4/Actin.
    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    In vivo imaging of β-cell function reveals glucose-mediated heterogeneity of β-cell functional development

    Jia Zhao et al.
    In vivo imaging reveals that gradually increased amount of glucose mediates the heterogeneous functional development of individual β-cells by activating its major downstream calcineurin/NFAT signaling pathway.
    1. Cancer Biology
    2. Cell Biology

    Mitochondrial fusion supports increased oxidative phosphorylation during cell proliferation

    Cong-Hui Yao et al.
    In addition to increasing glycolysis, some proliferating cells exhibiting the Warburg effect also increase oxidative phosphorylation through mitochondrial fusion.
    1. Neuroscience

    Long-term consequences of the absence of leptin signaling in early life

    Angela M Ramos-Lobo et al.
    A mouse model that grew without functional leptin receptors until adulthood reveals that early defects in leptin signaling lead to permanent metabolic and developmental problems.
    1. Developmental Biology
    2. Neuroscience

    Neuroblast-specific open chromatin allows the temporal transcription factor, Hunchback, to bind neuroblast-specific loci

    Sonia Q Sen et al.
    Spatial factors generate neuroblast-specific open chromatin, thereby biasing the subsequent binding of transcription factors to produce neuroblast-specific neurons.
    1. Cell Biology

    A systematic approach to identify recycling endocytic cargo depending on the GARP complex

    Sebastian Eising et al.
    The GARP complex is important for the endocytic recycling of amino phospholipid flippases and cell wall proteins, and thus membrane and lipid organization in yeast.
    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    Potentiation of P2RX7 as a host-directed strategy for control of mycobacterial infection

    Molly A Matty et al.
    An in vivo drug screen of FDA-approved compounds in zebrafish identified host-directed therapies against mycobacterial infection, including the drug clemastine, which targets the P2RX7-inflammasome axis to enhance bacterial control.
    1. Cell Biology
    2. Structural Biology and Molecular Biophysics

    FGF21 trafficking in intact human cells revealed by cryo-electron tomography with gold nanoparticles

    Maia Azubel et al.
    Specific attachment of molecularly defined gold nanoparticles enables precise localization, critical for structural studies in vivo, of proteins of unknown structure within the cellular milieu by cryo-electron tomography.
    1. Epidemiology and Global Health

    Collider bias and the apparent protective effect of glucose-6-phosphate dehydrogenase deficiency on cerebral malaria

    James A Watson et al.
    Selection bias, also known as collider bias, likely explains the apparent protective effect of G6PD deficiency against cerebral falciparum malaria.
    1. Developmental Biology

    Is it possible to reconstruct an accurate cell lineage using CRISPR recorders?

    Irepan Salvador-Martínez et al.
    Computer simulations reveal the potential and limitations of recently proposed CRISPR-based cell lineage recorders, and suggest how the recorders' design can be optimised to yield more accurate cell lineage trees.
    1. Neuroscience
    2. Structural Biology and Molecular Biophysics

    Molecular basis of synaptic specificity by immunoglobulin superfamily receptors in Drosophila

    Shouqiang Cheng et al.
    Fly protein families Dprs and DIPs can create a multitude of complementary interfaces for homo- and heterophilic adhesion complexes, resulting in instructive roles for connectivity in the motor neuron circuitry.
    1. Developmental Biology
    2. Neuroscience

    Correct setup of the substantia nigra requires Reelin-mediated fast, laterally-directed migration of dopaminergic neurons

    Ankita Ravi Vaswani et al.
    The first comprehensive insight into speed, trajectory and morphology profiles of tangentially migrating dopaminergic neurons and the alterations in their migratory behavior in absence of Reelin signaling.
    1. Computational and Systems Biology
    2. Neuroscience

    Spike-timing-dependent ensemble encoding by non-classically responsive cortical neurons

    Michele N Insanally et al.
    During behavior, many neurons do not have classic trial-averaged responses to behaviorally relevant stimuli, but can still have activity and population dynamics related to stimulus and behavioral choice on single trials.
    1. Structural Biology and Molecular Biophysics

    Hexameric helicase G40P unwinds DNA in single base pair steps

    Michael Schlierf et al.
    Single-molecule FRET experiments reveal that G40P, a DnaB-like helicase, unwinds double-stranded DNA in single base pair steps and its processivity is enhanced by host primase DnaG.
    1. Biochemistry and Chemical Biology
    2. Chromosomes and Gene Expression

    FACT and Ubp10 collaborate to modulate H2B deubiquitination and nucleosome dynamics

    Melesse Nune et al.
    The histone chaperone FACT and the deubiquitinating enzyme Ubp10 act in concert to remove ubiquitin from histone H2B in nucleosomes, and likely coordinate nucleosome assembly during DNA replication and transcription.
    1. Neuroscience

    Motor context dominates output from purkinje cell functional regions during reflexive visuomotor behaviours

    Laura D Knogler et al.
    Purkinje cells of the cerebellum, a conserved vertebrate brain region important for sensorimotor integration, receive sensory and motor information from distinct input streams and are functionally clustered into modules reflecting the larval zebrafish's behavioral repertoire.
    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    scRNA-Seq reveals distinct stem cell populations that drive hair cell regeneration after loss of Fgf and Notch signaling

    Mark E Lush et al.
    Several support cell populations balance progenitor maintenance with differentiation in zebrafish lateral line sensory organs.
    1. Neuroscience

    Oxytocin promotes coordinated out-group attack during intergroup conflict in humans

    Hejing Zhang et al.
    Humans intranasally administered the neuropeptide oxytocin waste less and earn more spoils during intergroup conflict because oxytocin enables group members to better coordinate strategic attacking of out-groups.
    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    Requirements for RNA polymerase II preinitiation complex formation in vivo

    Natalia Petrenko et al.
    The requirements for preinitiation complex formation/stability and transcription by RNA polymerase II in yeast cells are different from those in vitro, thereby altering the current view of basal transcription.
    1. Cancer Biology

    Different genetic mechanisms mediate spontaneous versus UVR-induced malignant melanoma

    Blake Ferguson et al.
    Genetic variation determines whether or not UV exposure accelerates melanoma development.
    1. Chromosomes and Gene Expression

    An ancient germ cell-specific RNA-binding protein protects the germline from cryptic splice site poisoning

    Ingrid Ehrmann et al.
    Cell division by meiosis during sperm production depends on expression of an RNA-binding protein that prevents abnormal RNA-processing pathways.
    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    Nephron progenitor commitment is a stochastic process influenced by cell migration

    Kynan T Lawlor et al.
    Stochastic cell migration modulates exposure to signals that regulate commitment in the nephron progenitor niche.
    1. Chromosomes and Gene Expression

    Exploration of CTCF post-translation modifications uncovers Serine-224 phosphorylation by PLK1 at pericentric regions during the G2/M transition

    Brian C Del Rosario et al.
    The chromosome architectural protein, CTCF, is phosphorylated at Ser224 in a cell-cycle-dependent manner and abrogation of phosphorylation leads to a cell growth defect.
    1. Cell Biology

    The Mitotic Exit Network integrates temporal and spatial signals by distributing regulation across multiple components

    Ian Winsten Campbell et al.
    By distributing regulation to both the GTPase and downstream kinases, the Mitotic Exit Network creates a single signal from spatial and temporal inputs.
    1. Chromosomes and Gene Expression

    PLZF targets developmental enhancers for activation during osteogenic differentiation of human mesenchymal stem cells

    Shuchi Agrawal Singh et al.
    A key transcription-factor for osteogenic differentiation, PLZF, acts as a transcriptional activator by binding to active developmental enhancers and facilitates mediator recruitment, but is not involved in enhancer looping.
    1. Cell Biology

    Dynein-mediated transport and membrane trafficking control PAR3 polarised distribution

    Julie Jouette et al.
    In Drosophila oocytes, the exclusion of the scaffold protein PAR3 from the posterior cortex depends on PAR1 and endocytosis, while its anterior localisation requires microtubules and recycling endosomes.
    1. Neuroscience

    S-cone photoreceptors in the primate retina are functionally distinct from L and M cones

    Jacob Baudin et al.
    Heterogeneity in perceptual sensitivity of human cone-mediated vision across wavelength originates in the cone photoreceptors, where S cones exhibit distinct functional properties in comparison to L and M cones.
    1. Neuroscience

    Anillin facilitates septin assembly to prevent pathological outfoldings of central nervous system myelin

    Michelle S Erwig et al.
    Mature myelin sheaths are scaffolded by the anillin-dependent assembly of septin filaments, thereby facilitating rapid nerve conduction in the healthy CNS.
    1. Cell Biology
    2. Microbiology and Infectious Disease

    HIV-1 nuclear import in macrophages is regulated by CPSF6-capsid interactions at the nuclear pore complex

    David Alejandro Bejarano et al.
    Interaction of HIV capsids with the cellular protein cleavage-and-polyadenylation factor 6 at the inner side of nuclear pores promotes nuclear entry of the viral replication complex in primary human macrophages.
    1. Developmental Biology
    2. Plant Biology

    Quantitative analysis of auxin sensing in leaf primordia argues against proposed role in regulating leaf dorsoventrality

    Neha Bhatia et al.
    Top-bottom patterning of leaves is not specified by an asymmetry in the distribution of the plant hormone auxin, in contrast to a previous proposal.
    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    The Crohn’s disease polymorphism, ATG16L1 T300A, alters the gut microbiota and enhances the local Th1/Th17 response

    Sydney Lavoie et al.
    Gnotobiotic and conventional mouse models of the IBD ATG16L1T300A SNP reveal gene-microbiota-immune interactions.
    1. Neuroscience

    Generality and opponency of rostromedial tegmental (RMTg) roles in valence processing

    Hao Li et al.
    Rostromedial tegmental neurons encode motivational valence and opponent responses across a wide range of affective stimulus modalities, while also driving dopamine inhibition and conditioned place aversion to aversive stimuli.
    1. Physics of Living Systems

    High-molecular-weight polymers from dietary fiber drive aggregation of particulates in the murine small intestine

    Asher Preska Steinberg et al.
    Polymers from dietary fiber can control the aggregation of particulates in the murine small intestine in a manner qualitatively consistent with depletion interactions.
    1. Genetics and Genomics

    Molecular safeguarding of CRISPR gene drive experiments

    Jackson Champer et al.
    Genes drives utilizing synthetic target sites and the split-Cas9 system have similar performance to standard drives.
    1. Immunology and Inflammation
    2. Neuroscience

    Absence of TGFβ signaling in retinal microglia induces retinal degeneration and exacerbates choroidal neovascularization

    Wenxin Ma et al.
    TGFβ signaling to retinal microglia is central to the regulation of neuroinflammatory responses relevant to age-related macular degeneration (AMD), a leading cause of blindness in the developed world.
    1. Neuroscience

    A toolbox of IgG subclass-switched recombinant monoclonal antibodies for enhanced multiplex immunolabeling of brain

    Nicolas P Andrews et al.
    This paper describes an effective pipeline for conversion of conventional monoclonal antibodies into recombinant form that results in an IgG subclass switch that greatly expands their utility for multiplex labeling.
    1. Human Biology and Medicine
    2. Microbiology and Infectious Disease

    Gut microbiota density influences host physiology and is shaped by host and microbial factors

    Eduardo J Contijoch et al.
    The density of the gut microbiota influences the host immune system and adiposity, and can be therapeutically manipulated.
    1. Chromosomes and Gene Expression

    Factors affecting template switch recombination associated with restarted DNA replication

    Manisha Jalan et al.
    Genomic deletions and gene conversions, caused by template switching associated with restarted DNA replication, are detected downstream of a collapsed replication fork and are suppressed by several conserved DNA helicases.
    1. Neuroscience

    Computational modeling of brainstem circuits controlling locomotor frequency and gait

    Jessica Ausborn et al.
    A new computational model of brainstem control of locomotor speed and gait was developed to reproduce and explain recent experimental data and propose predictions for subsequent experimental testing.
    1. Developmental Biology

    Primed Track, high-fidelity lineage tracing in mouse pre-implantation embryos using primed conversion of photoconvertible proteins

    Maaike Welling et al.
    Primed Track is an image analysis tool that allows for computational correction of drifting specimen to enable accurate lineage tracing of mammalian pre-implantation development even for larger imaging time intervals.
    1. Immunology and Inflammation

    HDAC3 restrains CD8-lineage genes to maintain a bi-potential state in CD4+CD8+ thymocytes for CD4-lineage commitment

    Rachael Laura Philips et al.
    CD4 lineage commitment requires HDAC3 to prevent premature upregulation of CD8 lineage genes during T cell development.
    1. Cell Biology
    2. Neuroscience

    Multiple factors maintain assembled trans-SNARE complexes in the presence of NSF and αSNAP

    Eric A Prinslow et al.
    Biophysical analyses indicate that Munc18-1, Munc13-1, synaptotagmin-1 and complexin-1 maintain assembled trans-SNARE complexes in the presence of NSF-alphaSNAP, suggesting that they form part of the primed state of synaptic vesicles.
    1. Chromosomes and Gene Expression
    2. Structural Biology and Molecular Biophysics

    A conserved filamentous assembly underlies the structure of the meiotic chromosome axis

    Alan MV West et al.
    Meiotic chromosome axis 'core' proteins from fungi, plants, and mammals form a conserved filament architecture, and use a common mechanism to recruit HORMAD proteins for meiotic recombination control.
    1. Neuroscience

    Neuronal morphologies built for reliable physiology in a rhythmic motor circuit

    Adriane G Otopalik et al.
    Neurite geometry enables expansive and highly-branched neuronal structures to operate like single electrical compartments and simple linear integrators.
    1. Neuroscience

    Identification of a bilirubin receptor that may mediate a component of cholestatic itch

    James Meixiong et al.
    MRGPRX4 is a bilirubin receptor that may be a therapeutic target for patients suffering from cholestatic itch.
    1. Neuroscience

    Cellular cartography of the organ of Corti based on optical tissue clearing and machine learning

    Shinji Urata et al.
    A method of generating comprehensive maps of cochlear cells was created and enabled researchers to study characteristics of cellular damage in aged and noise-exposed inner ear.
    1. Computational and Systems Biology

    Essential metabolism for a minimal cell

    Marian Breuer et al.
    A near-complete flux balance analysis model of a minimal cell demonstrates the high essentiality of its metabolic genes, agrees well with experimental essentiality data and suggests some further gene removals.
    1. Developmental Biology
    2. Neuroscience

    Synapse maintenance is impacted by ATAT-2 tubulin acetyltransferase activity and the RPM-1 signaling hub

    Melissa A Borgen et al.
    Genetic, developmental and pharmacological analysis in Caenorhabditis elegans demonstrate that ATAT-2 tubulin acetyltransferase activity regulates synapse maintenance by acting within the RPM-1 signaling network, but independent of the DLK-1 MAP3K.
    1. Developmental Biology
    2. Structural Biology and Molecular Biophysics

    Engineering a conserved RNA regulatory protein repurposes its biological function in vivo

    Vandita D Bhat et al.
    Motif length plays a critical role in the specification of biological function within a conserved family of RNA-binding proteins.
    1. Neuroscience

    Nostril-specific and structure-based olfactory learning of chiral discrimination in human adults

    Guo Feng, Wen Zhou
    Training-induced perceptual gain in the discrimination between odor enantiomers is nostril-specific and structure-based, indicating that early olfactory processing of the chemical features of unirhinal input remains plastic in human adults.
    1. Neuroscience

    CaImAn an open source tool for scalable calcium imaging data analysis

    Andrea Giovannucci et al.
    CaImAn is an open-software package that equips the neuroscience community with a set of turnkey, fast and scalable solutions to pre-processing problems arising in single cell calcium imaging data analysis.
    1. Microbiology and Infectious Disease

    TRIM28 promotes HIV-1 latency by SUMOylating CDK9 and inhibiting P-TEFb

    Xiancai Ma et al.
    TRIM28 was found to be a versatile dual-function latency contributor by bridging both suppressive epigenetic modifications and RNAP II transcriptional-pausing, and can be a novel target to develop latency-reversing agents.
    1. Neuroscience

    An afferent white matter pathway from the pulvinar to the amygdala facilitates fear recognition

    Jessica McFadyen et al.
    A subcortical white matter connection from the pulvinar to the amygdala predicts how well we recognise fearful faces and the strength of feed-forward neural connectivity.
    1. Stem Cells and Regenerative Medicine

    Ovaries absent links dLsd1 to HP1a for local H3K4 demethylation required for heterochromatic gene silencing

    Fu Yang et al.
    A Drosophila fertility gene is identified that acts as a linker between HP1a and local H3K4 demethylation during HP1a-mediated gene silencing that is required for ovary development and transposon silencing..
    1. Structural Biology and Molecular Biophysics

    Structural basis of Ca2+-dependent activation and lipid transport by a TMEM16 scramblase

    Maria E Falzone et al.
    Structures of a TMEM16 phospholipid scramblase reveal that its Ca2+-dependent activation entails global conformational changes and how these rearrangements affect the membrane to enable transbilayer lipid transfer.
    1. Cell Biology
    2. Developmental Biology

    Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm cell migration

    Daniel Čapek et al.
    Uniform activation of Frizzled7 signaling is required and sufficient for directional mesendoderm cell migration during zebrafish gastrulation.
    1. Evolutionary Biology
    2. Microbiology and Infectious Disease

    The presence and absence of periplasmic rings in bacterial flagellar motors correlates with stator type

    Mohammed Kaplan et al.
    A correlation between the periplasmic embellishment of the flagellar motor and its stator system type is described, motors with dual H+-dependent stator systems have one periplasmic ring formed by MotY.
    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    Fine-mapping cis-regulatory variants in diverse human populations

    Ashley Tehranchi et al.
    A map of the genetic variants affecting chromatin accessibility in 1000 individuals from 10 diverse populations reveals how cis-regulatory variants impact transcription and disease.
    1. Neuroscience

    Schwann cells, but not Oligodendrocytes, Depend Strictly on Dynamin 2 Function

    Daniel Gerber et al.
    In the peripheral nervous system, the large GTPase dynamin 2 is required for Schwann cell survival, developmental radial sorting of axons, myelination, and myelin maintenance.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Pat1 promotes processing body assembly by enhancing the phase separation of the DEAD-box ATPase Dhh1 and RNA

    Ruchika Sachdev et al.
    The protein Pat1 functions in the assembly of processing bodies, cellular membraneless organelles, by promoting the liquid–liquid phase separation of the DEAD-box ATPase Dhh1 and RNA.
    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    Reprogramming the antigen specificity of B cells using genome-editing technologies

    James E Voss et al.
    Antibody paratopes can be added to the human repertoire by CRISPR-Cas9 editing of B lymphocytes using a strategy that allows for hypermutation and class switching of resulting B cell receptors.
    1. Computational and Systems Biology
    2. Neuroscience

    Discovering and deciphering relationships across disparate data modalities

    Joshua T Vogelstein et al.
    Multiscale Graph Correlation, an interpretable hypothesis test with strong theoretical guarantees for discerning relationships in complex data, requires about half the sample size as other methods, whilst maintaining computational tractability.
    1. Microbiology and Infectious Disease

    Programmed genome editing of the omega-1 ribonuclease of the blood fluke, Schistosoma mansoni

    Wannaporn Ittiprasert et al.
    Gene knock-out of the omega-1 ribonuclease of Schistosoma mansoni eggs resulted in immunologically impaired phenotype, showcasing the novel application of CRISPR/Cas9 genome editing and utility for functional genomics in schistosomes.
    1. Microbiology and Infectious Disease

    Programmed knockout mutation of liver fluke granulin attenuates virulence of infection-induced hepatobiliary morbidity

    Patpicha Arunsan et al.
    Gene knockout of liver fluke granulin by CRISPR/Cas9 attenuates the virulence of infection with a carcinogenic liver fluke.
    1. Genetics and Genomics
    2. Stem Cells and Regenerative Medicine

    Global DNA methylation remodeling during direct reprogramming of fibroblasts to neurons

    Chongyuan Luo et al.
    Induced neuronal cells acquire epigenomic signatures specific to matured neurons.
    1. Neuroscience
    2. Structural Biology and Molecular Biophysics

    Conserved allosteric pathways for activation of TRPV3 revealed through engineering vanilloid-sensitivity

    Feng Zhang et al.
    TRPV channels share general mechanisms of activation while exhibiting subtype-specific features along the activation pathway that can determine their apparent sensitivity to stimuli.
    1. Ecology
    2. Evolutionary Biology

    Molecular basis of wax-based color change and UV reflection in dragonflies

    Ryo Futahashi et al.
    UV-reflective dragonfly wax is shown to consist of very long-chain methyl ketones and aldehydes, and a synthetic dragonfly wax spontaneously forms light-scattering fine structures with strong UV reflection.
    1. Plant Biology

    Convergent recruitment of TALE homeodomain life cycle regulators to direct sporophyte development in land plants and brown algae

    Alok Arun et al.
    TALE homeodomain transcription factors have been independently recruited to regulate gametophyte to sporophyte transitions in two complex multicellular eukaryotic supergroups, land plants in Archaeplastida and brown algae in Chromalveolata.
    1. Genetics and Genomics
    2. Human Biology and Medicine

    Quantitative proteomics reveals key roles for post-transcriptional gene regulation in the molecular pathology of facioscapulohumeral muscular dystrophy

    Sujatha Jagannathan et al.
    The myopathic transcription factor DUX4 induces discordant dysregulation of transcript and protein levels, demonstrating a key role for post-transcriptional gene regulation in facioscapulohumeral muscular dystrophy.
    1. Genetics and Genomics

    Genomics of 1 million parent lifespans implicates novel pathways and common diseases and distinguishes survival chances

    Paul RHJ Timmers et al.
    Genomic associations with lifespan principally reflect heart disease/smoking/dementia but not other cancers, and distinguish lifespan differences of five years between top/bottom deciles of a score derived from DNA alone.
    1. Developmental Biology
    2. Physics of Living Systems

    Rapid changes in tissue mechanics regulate cell behaviour in the developing embryonic brain

    Amelia J Thompson et al.
    During embryonic development, tissue stiffness, which provides an important signal to motile cells, changes locally within tens of minutes in a well-controlled manner.
    1. Cancer Biology

    GREB1 amplifies androgen receptor output in human prostate cancer and contributes to antiandrogen resistance

    Eugine Lee et al.
    Prostate cancer cells maintain heterogeneous androgen receptor transcriptional activity through upregulation of AR-regulated coactivator GREB1, and cells with high activity rapidly develop resistance to antiandrogen therapy in a GREB1-dependent manner.
    1. Cell Biology

    SUMO peptidase ULP-4 regulates mitochondrial UPR-mediated innate immunity and lifespan extension

    Kaiyu Gao et al.
    SUMOylation regulates mitochondrial UPR signaling through modulation of transcription factors DVE-1 and ATFS-1.
    1. Structural Biology and Molecular Biophysics

    High resolution cryo-EM structure of the helical RNA-bound Hantaan virus nucleocapsid reveals its assembly mechanisms

    Benoît Arragain et al.
    Hantaan virus nucleocapsid cryo-EM structure determined at 3.3 Å resolution reveals how nucleoproteins assemble into a metastable helix containing a continuous RNA-binding groove compatible with genome encapsidation and compaction.
    1. Neuroscience

    PARIS, an optogenetic method for functionally mapping gap junctions

    Ling Wu et al.
    As the first fully genetically encoded method, PARIS allows cell-specific, long-term, repeated measurements of gap junctional coupling with high spatiotemporal resolution, facilitating its study in both health and disease.
    1. Developmental Biology

    Hedgehog signaling patterns the oral-aboral axis of the mandibular arch

    Jingyue Xu et al.
    SHH signaling acts through FOXF1/2 transcription factors and antagonizes BMP signaling to specify oral fate and pattern the oral-aboral axis of the mandibular arch to ensure proper formation of jaws.
    1. Biochemistry and Chemical Biology

    Insights into AMS/PCAT transporters from biochemical and structural characterization of a double Glycine motif protease

    Silvia C Bobeica et al.
    Structural and biochemical characterization of the protease domain of an ABC transporter demonstrates the basis for recognition of substrate leader peptides.
    1. Microbiology and Infectious Disease

    The Acinetobacter baumannii Mla system and glycerophospholipid transport to the outer membrane

    Cassandra Kamischke et al.
    An Acinetobacter baumannii ABC transporter likely facilitates transport of glycerophospholipids from the inner to the outer membrane.
    1. Genetics and Genomics

    Single cell functional genomics reveals the importance of mitochondria in cell-to-cell phenotypic variation

    Riddhiman Dhar et al.
    A genome-wide quantitative microscopy screen implicates mitochondria in single cell variation in proliferation and drug resistance in yeast.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    The conserved aspartate ring of MCU mediates MICU1 binding and regulation in the mitochondrial calcium uniporter complex

    Charles B Phillips et al.
    Biochemical analysis reveals molecular mechanisms underlying the activation of the mitochondrial Ca2+ uniporter by intracellular Ca2+ signals.
    1. Microbiology and Infectious Disease

    Determination of host proteins composing the microenvironment of coronavirus replicase complexes by proximity-labeling

    Philip V'kovski et al.
    The molecular microenvironment of coronaviral replicase complexes provides functional and spatial links between conserved cellular processes and viral RNA synthesis, and highlights potential targets for the development of novel antivirals.
    1. Stem Cells and Regenerative Medicine

    Integrin alpha11 is an Osteolectin receptor and is required for the maintenance of adult skeletal bone mass

    Bo Shen et al.
    Integrin a11 is identified as an Osteolectin receptor, revealing a new mechanism for adult skeletal bone maintenance in which Osteolectin/a11b1 signaling promotes bone formation by activating the Wnt pathway.
    1. Genetics and Genomics
    2. Stem Cells and Regenerative Medicine

    The novel lncRNA lnc-NR2F1 is pro-neurogenic and mutated in human neurodevelopmental disorders

    Cheen Euong Ang et al.
    lnc-Nr2f1, a long non-coding RNA focally deleted in autism patients, directly occupies and regulates neuronal genes.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Molecular mechanisms of gating in the calcium-activated chloride channel bestrophin

    Alexandria N Miller et al.
    Cryo-EM structures of the gating cycle of bestrophin reveal the molecular underpinnings of activation and inactivation gating in this calcium-activated chloride channel and reveal a surprisingly wide pore.
    1. Neuroscience

    Balance between BDNF and Semaphorins gates the innervation of the mammary gland

    Hadas Sar Shalom et al.
    The innervation of the mammary gland is controlled by opposing effects of neurotrophic and repulsive factors and, once trophic signaling is inhibited the repulsive factors, may promote axonal pruning.
    1. Structural Biology and Molecular Biophysics

    A hydrophobic gate in the inner pore helix is the major determinant of inactivation in mechanosensitive Piezo channels

    Wang Zheng et al.
    A functionally conserved inactivation gate in the inner helix of Piezo channels controls the majority of the inactivation process via a hydrophobic mechanism.
    1. Computational and Systems Biology
    2. Developmental Biology

    Cis-activation in the Notch signaling pathway

    Nagarajan Nandagopal et al.
    Activation of Notch receptors by ligands in the same cell (cis-activation) is a prevalent and functional mode of signaling in the Notch pathway, and co-exists with trans-activation and cis-inhibition.
    1. Neuroscience

    Comparisons between the ON- and OFF-edge motion pathways in the Drosophila brain

    Kazunori Shinomiya et al.
    A complete connectome of the ON and OFF motion pathways of the Drosophila optic lobe is acquired using three-dimensional EM methods, and the similarities and differences of the two pathways are uncovered.
    1. Neuroscience

    Complex spike synchrony dependent modulation of rat deep cerebellar nuclear activity

    Tianyu Tang et al.
    The importance of synchronous Purkinje cell complex spikes for controlling cerebellar output was investigated by simultaneously recording from cerebellar nuclear cells and arrays of Purkinje cells that synapse onto them.
    1. Biochemistry and Chemical Biology
    2. Neuroscience

    eIF2B activator prevents neurological defects caused by a chronic integrated stress response

    Yao Liang Wong et al.
    Boosting the function of translation factor eIF2B by chronic small molecule administration prevents pathology in a neurodegenerative model of Vanishing White Matter disease characterized by a maladaptive stress response.
    1. Plant Biology

    A florigen paralog is required for short-day vernalization in a pooid grass

    Daniel Woods et al.
    In Brachypodiumdistachyon, a single locus accounts for natural variation in whether perception of short day-lengths confers competence to flower.
    1. Evolutionary Biology
    2. Genetics and Genomics

    Immune genes are hotspots of shared positive selection across birds and mammals

    Allison J Shultz, Timothy B Sackton
    Pathogens, particularly viruses, target the same genes over deep evolutionary time, resulting in shared signatures of positive selection and transcriptional responses at the same genes.
    1. Neuroscience

    Statistical structure of locomotion and its modulation by odors

    Liangyu Tao et al.
    A fly's locomotion can be decomposed into a small number of locomotor features which can be modulated by odors and other sensory information.
    1. Computational and Systems Biology
    2. Genetics and Genomics

    Genetic effects on promoter usage are highly context-specific and contribute to complex traits

    Kaur Alasoo et al.
    Re-analysis of large gene expression datasets with state-of-the-art quantification methods reveals additional candidate genes mediating complex trait associations.
    1. Evolutionary Biology
    2. Genetics and Genomics

    Predicting mutational routes to new adaptive phenotypes

    Peter A Lind et al.
    A combination of genetics, experimental evolution and mathematical modelling defines information necessary to predict the outcome of short-term adaptive evolution.
    1. Chromosomes and Gene Expression
    2. Developmental Biology

    Individual long non-coding RNAs have no overt functions in zebrafish embryogenesis, viability and fertility

    Mehdi Goudarzi et al.
    Defining the biological functions of long non-coding RNAs, individually or as a class, and teasing apart the role of underlying genomic sequences remains the biggest challenge for this field.
    1. Biochemistry and Chemical Biology
    2. Chromosomes and Gene Expression

    The elemental mechanism of transcriptional pausing

    Jason Saba et al.
    Biochemical analyses of transcription complexes, including kinetic studies and probes of translocational and conformational states, establish the elemental mechanism of pausing, which underlies regulation of gene expression in all organisms.
    1. Neuroscience

    Decreased brain connectivity in smoking contrasts with increased connectivity in drinking

    Wei Cheng et al.
    The findings have a major impact in understanding the different reward systems involved in two types of addictive behavior, and these advances have implications for prevention and treatment.
    1. Evolutionary Biology

    A β-carotene-binding protein carrying a red pigment regulates body-color transition between green and black in locusts

    Meiling Yang et al.
    Body color change of locusts reveals a new 'palette effect' mechanism by which the red βCBP–β-carotene pigment complex acts as a switch to coordinate between black and green coloration.
    1. Developmental Biology

    Arid3a regulates nephric tubule regeneration via evolutionarily conserved regeneration signal-response enhancers

    Nanoka Suzuki et al.
    Arid3a, a component of H3K9 me3 demethylases, regulates regeneration of the proximal nephric tubule through the evolutionarily conserved regeneration signal-response enhancer.
    1. Computational and Systems Biology
    2. Neuroscience

    Contrast sensitivity reveals an oculomotor strategy for temporally encoding space

    Antonino Casile et al.
    Fixational eye movements transform the spatial scene into temporal modulations on the retina, which, together with the known sensitivities of retinal neurons, provide a comprehensive account of human spatial sensitivity.
    1. Ecology

    The return to water in ancestral Xenopus was accompanied by a novel mechanism for producing and shaping vocal signals

    Ursula Kwong-Brown et al.
    When ancestral Xenopus returned to water ~170mya, they evolved a new method for producing courtship calls underwater without airflow, using vibrations that also preserve essential acoustic information on species identity.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Crystal structure of a natural light-gated anion channelrhodopsin

    Hai Li et al.
    The atomic structure of GtACR1 provides new insight into the chemical mechanism of natural light-gated anion membrane conductance, and enables its optimization for optogenetic photoinhibition of neuron firing.
    1. Physics of Living Systems

    Body size-dependent energy storage causes Kleiber’s law scaling of the metabolic rate in planarians

    Albert Thommen et al.
    A combination of experimental and theoretical analysis identifies body size-dependent energy storage as the physiological cause of 3/4-power law scaling of the metabolic rate in planarians.
    1. Plant Biology

    Identification and characterisation of hypomethylated DNA loci controlling quantitative resistance in Arabidopsis

    Leonardo Furci et al.
    Analysis of epigenetic recombinant inbred lines of Arabidopsis identified four hypomethylated DNA loci controlling quantitative disease resistance, which is associated with genome-wide priming of defence genes without affecting plant growth.
    1. Neuroscience

    High-throughput synapse-resolving two-photon fluorescence microendoscopy for deep-brain volumetric imaging in vivo

    Guanghan Meng et al.
    Improved two-photon fluorescence microendoscopy enables volumetric imaging of synapses and neurons in deep brain structures in vivo.
    1. Microbiology and Infectious Disease

    Mycobacterium tuberculosis SatS is a chaperone for the SecA2 protein export pathway

    Brittany K Miller et al.
    SatS of Mycobacterium tuberculosis is a new protein export chaperone with a role in exporting proteins by the specialized SecA2 pathway and a role in intracellular growth in macrophages.
    1. Biochemistry and Chemical Biology

    Mechanisms of PDZ domain scaffold assembly illuminated by use of supported cell membrane sheets

    Simon Erlendsson et al.
    Investigations of binding of the scaffold protein PICK1 to transmembrane proteins in their native membrane environment demonstrate potent but slow dynamics and reveal distinct binding modes supporting different biological functions.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Synergy between RecBCD subunits is essential for efficient DNA unwinding

    Rani Zananiri et al.
    A new optical tweezers assay sheds light on the mechanism of cooperation and force generation by the subunits of RecBCD, critical for the repair of double strand breaks in bacteria.
    1. Neuroscience

    Functionally defined white matter of the macaque monkey brain reveals a dorso-ventral attention network

    Ilaria Sani et al.
    Primate attention is not limited to a dorsal fronto-parietal network, but includes a ventral temporal node and its dorso-ventral interactions with other attentional areas.
    1. Biochemistry and Chemical Biology
    2. Computational and Systems Biology

    ATP-induced asymmetric pre-protein folding as a driver of protein translocation through the Sec machinery

    Robin A Corey et al.
    How the process of protein folding may be controlled by the Sec machinery to assist protein transport across membranes.
    1. Chromosomes and Gene Expression
    2. Structural Biology and Molecular Biophysics

    CtIP forms a tetrameric dumbbell-shaped particle which bridges complex DNA end structures for double-strand break repair

    Oliver J Wilkinson et al.
    Structural and biochemical analysis of human CtIP provides new insights into DNA break recognition, binding and bridging during homologous recombination.
    1. Biochemistry and Chemical Biology

    RNA-binding proteins distinguish between similar sequence motifs to promote targeted deadenylation by Ccr4-Not

    Michael W Webster et al.
    Biochemical reconstitution of deadenylation and analysis of binding kinetics reveals how RNA-binding proteins select their mRNA targets.
    1. Cell Biology
    2. Computational and Systems Biology

    Chronology of motor-mediated microtubule streaming

    Arvind Ravichandran et al.
    Microtubule streaming driven by molecular motors covers characteristic times that span several orders of magnitude from fast, single-microtubule sliding on molecular scales to slow, collective motion on cellular scales.
    1. Neuroscience

    Timing mechanism of sexually dimorphic nervous system differentiation

    Laura Pereira et al.
    The timing of sexual differentiation in the brain of the nematode Caenorhabditis elegans is controlled by a phylogenetically conserved pathway of gene regulatory factors.

Magazine

    1. Neuroscience

    Sexual Differentiation: A matter of timing

    Michael W Perry, Claude Desplan