February 2020

Image by Claudia Prahst

Cover articles

Research articles

    1. Chromosomes and Gene Expression

    Integrated analysis of H2A.Z isoforms function reveals a complex interplay in gene regulation

    Assala Lamaa et al.
    The two H2A.Z isoforms have specific interactors which mediate their differential effects on gene expression.
    1. Structural Biology and Molecular Biophysics

    Structures of the ATP-fueled ClpXP proteolytic machine bound to protein substrate

    Xue Fei et al.
    Cryo-EM structures of the ClpXP protease reveal how protein substrates are bound, show how spiral ClpX hexamers bind symmetry-mismatched heptameric ClpP rings, and suggest mechanisms for processive substrate translocation.
    1. Neuroscience

    Cell-type specific innervation of cortical pyramidal cells at their apical dendrites

    Ali Karimi et al.
    The composition of inhibitory and excitatory synaptic inputs to the apical dendrites of pyramidal cells in mouse cortex is specific to the type of pyramidal cells.
    1. Neuroscience

    Categorical representation from sound and sight in the ventral occipito-temporal cortex of sighted and blind

    Stefania Mattioni et al.
    The categorical organization of the ventral occipito-temporal cortex, typically thought to be a visual region, is actually partially independent of visual input and even visual experience.
    1. Biochemistry and Chemical Biology
    2. Evolutionary Biology

    Homologue replacement in the import motor of the mitochondrial inner membrane of trypanosomes

    Corinne von Känel et al.
    Mitochondrial inner membrane translocation of presequence-containing proteins by the single bifunctional TIM complex of T. brucei requires an non-canonical J domain-containing protein.
    1. Developmental Biology

    Dullard-mediated Smad1/5/8 inhibition controls mouse cardiac neural crest cells condensation and outflow tract septation

    Jean-François Darrigrand et al.
    New views on the relevance of bone morphogenetic protein signalling fine tuning in the cardiac neural crest cells for the heart outflow tract septation and the formation of the great arteries.
    1. Neuroscience

    Experience shapes activity dynamics and stimulus coding of VIP inhibitory cells

    Marina Garrett et al.
    VIP inhibitory neurons are active in response to novel images but are suppressed by familiar stimuli and show ramping activity when expected stimuli are omitted.
    1. Cell Biology

    Ciliary Rab28 and the BBSome negatively regulate extracellular vesicle shedding

    Jyothi S Akella et al.
    The RAB-28 GTPase regulates ciliary extracellular vesicle shedding, which may be important for neuron-glia communication.
    1. Evolutionary Biology

    Resurrection of a global, metagenomically defined gokushovirus

    Paul C Kirchberger, Howard Ochman
    Isolation of a gokushovirus capable of lysogenizing enterobacteria challenges previous notions about the biology of the most prolific phages within the Microviridae and facilitates experimental study in a model organism.
    1. Developmental Biology

    Ordered patterning of the sensory system is susceptible to stochastic features of gene expression

    Ritika Giri et al.
    How gene expression noise is regulated is critical for cell fate and tissue patterning.
    1. Cell Biology
    2. Human Biology and Medicine

    Biallelic TANGO1 mutations cause a novel syndromal disease due to hampered cellular collagen secretion

    Caroline Lekszas et al.
    The first human TANGO1-associated syndromal disease manifests as impaired collagen secretion, highlighting the importance of TANGO1 in human pathophysiology.
    1. Structural Biology and Molecular Biophysics

    Human RPA activates BLM’s bidirectional DNA unwinding from a nick

    Zhenheng Qin et al.
    hRPA permits the BLM helicase to bidirectionally unwind DNA from a nick which could potentially facilitate its function switching in DNA repair and promote end resection in homologous recombination.
    1. Computational and Systems Biology
    2. Neuroscience

    Sodium channels implement a molecular leaky integrator that detects action potentials and regulates neuronal firing

    Marco A Navarro et al.
    Kinetic interactions between sodium channels and auxiliary factors create a molecular computational engine that can sense and regulate cellular excitability.
    1. Genetics and Genomics
    2. Microbiology and Infectious Disease

    Highly regulated, diversifying NTP-dependent biological conflict systems with implications for the emergence of multicellularity

    Gurmeet Kaur et al.
    Multicellular and socially aggregating prokaryotes contain previously undescribed, chaperone-based systems predicted to mediate defensive biological conflicts, several components of which are thematically similar antecedents of eukaryotic apoptosis pathways.
    1. Biochemistry and Chemical Biology

    Dynamics at the serine loop underlie differential affinity of cryptochromes for CLOCK:BMAL1 to control circadian timing

    Jennifer L Fribourgh et al.
    The affinity of circadian repressors CRY1 and CRY2 for their cognate transcription factor CLOCK:BMAL1 is regulated by differential dynamics at the serine loop and interactions with the PER2 corepressor.
    1. Developmental Biology
    2. Neuroscience

    Revisiting the role of Dcc in visual system development with a novel eye clearing method

    Robin J Vigouroux et al.
    A new eye-specific Dcc mutant combined with an improved clearing protocol for the eye and brain (EyeDISCO) reveals the requirement of the receptor Dcc for retinal development and maintenance.
    1. Developmental Biology
    2. Genetics and Genomics

    An alternatively spliced, non-signaling insulin receptor modulates insulin sensitivity via insulin peptide sequestration in C. elegans

    Bryan A Martinez et al.
    A truncated, non-signaling insulin receptor regulates insulin sensitivity in the nematode C. elegans by sequestering insulin peptides and preventing their interaction with full length receptors.
    1. Neuroscience

    The functional organization of excitation and inhibition in the dendrites of mouse direction-selective ganglion cells

    Varsha Jain et al.
    Accurate direction-selective information is present within small sections of the dendrites, raising the possibility that single dendrites utilize parallel processing schemes to process motion information.
    1. Immunology and Inflammation

    Thioredoxin-1 distinctly promotes NF-κB target DNA binding and NLRP3 inflammasome activation independently of Txnip

    Jonathan Muri et al.
    The thioredoxin-1 (Trx1) system promotes inflammation by positively regulating both NLRP3 inflammasome responses, by detoxifying excessive ROS independently of Txnip and NF-κB binding to target DNA.
    1. Structural Biology and Molecular Biophysics

    Structure and physiological function of the human KCNQ1 channel voltage sensor intermediate state

    Keenan C Taylor et al.
    The intermediate state conformation of the human KCNQ1 potassium channel voltage sensor domain was determined, validated, and shown to be conductive under physiological conditions.
    1. Neuroscience

    Neural mechanisms of economic choices in mice

    Masaru Kuwabara et al.
    Inactivation of the lateral orbital area disrupts economic choice behavior and neurons in this area encode the value of offered and chosen options.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    A native prokaryotic voltage-dependent calcium channel with a novel selectivity filter sequence

    Takushi Shimomura et al.
    The small glycine residue in the Cav selectivity filter is an overlooked feature that determines Ca2+ selectivity and provides new insight into the Ca2+ selectivity mechanism conserved from prokaryotes to eukaryotes.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Agonist-selective recruitment of engineered protein probes and of GRK2 by opioid receptors in living cells

    Miriam Stoeber et al.
    Chemically distinct opioid ligands promote selective protein recruitment by opioid receptors in intact cells.
    1. Epidemiology and Global Health

    Estimated effectiveness of symptom and risk screening to prevent the spread of COVID-19

    Katelyn Gostic et al.
    Even in the best-case scenario, screening for COVID-19 misses well over half of infected travellers.
    1. Developmental Biology
    2. Evolutionary Biology

    Bacterial contribution to genesis of the novel germ line determinant oskar

    Leo Blondel et al.
    Evidence suggests that the oskar gene, a critical germ line determinant in insects, was formed by fusion of bacterial and eukaryotic sequences at least 450 million years ago.
    1. Biochemistry and Chemical Biology

    Mitochondrial ClpX activates an essential biosynthetic enzyme through partial unfolding

    Julia R Kardon et al.
    The mitochondrial protein unfoldase ClpX activates the first enzyme in heme biosynthesis, ALAS, by targeted unfolding that gates access of cofactor to the ALAS active site.
    1. Immunology and Inflammation

    Anti-PD-1 immunotherapy leads to tuberculosis reactivation via dysregulation of TNF-α

    Liku B Tezera et al.
    Immune checkpoint inhibition therapy for cancer paradoxically activates tuberculosis infection, and advanced human cell culture modelling demonstrates excess TNF-α section is the primary driver.
    1. Cell Biology
    2. Neuroscience

    Large-scale cell-type-specific imaging of protein synthesis in a vertebrate brain

    Or David Shahar, Erin Margaret Schuman
    The development of a transgenic zebrafish allows for cell-type-specific labeling of neuronal protein synthesis, enabling brain-wide visualization and quantification of protein synthesis and demonstrating region-specific increases following elevated brain activity.
    1. Computational and Systems Biology
    2. Neuroscience

    Selectivity to approaching motion in retinal inputs to the dorsal visual pathway

    Todd R Appleby, Michael B Manookin
    Cells in the primate retina show unexpected sensitivity to approaching motion and optical flow.
    1. Chromosomes and Gene Expression

    Sphingosine 1-phosphate-regulated transcriptomes in heterogenous arterial and lymphatic endothelium of the aorta

    Eric Engelbrecht et al.
    The sphingosine 1-phosphate receptor-1 (S1PR1) signals in heterogenous populations of mouse adventitial lymphatic (LEC) and arterial endothelial cells (aEC1, aEC2) to regulate chromatin and the transcriptome, thus affecting their phenotypes.
    1. Stem Cells and Regenerative Medicine

    Defining the role of pulmonary endothelial cell heterogeneity in the response to acute lung injury

    Terren K Niethamer et al.
    Single-cell RNA sequencing reveals extensive endothelial cell (EC) heterogeneity throughout the lung vasculature and identifies two distinct populations, Car4-high ECs and proliferative ECs, that preferentially respond to lung injury.
    1. Cell Biology

    Control of cell death/survival balance by the MET dependence receptor

    Leslie Duplaquet et al.
    MET acts as a dependence receptor in vivo by promoting hepatocyte apoptosis, a response induced by a caspase generated fragment able to favor calcium exchange between endoplasmic reticulum and mitochondria.
    1. Developmental Biology
    2. Evolutionary Biology

    Resegmentation is an ancestral feature of the gnathostome vertebral skeleton

    Katharine E Criswell, J Andrew Gillis
    Shared complexities of backbone segmentation between cartilaginous fishes and tetrapods originate much earlier in vertebrate evolution than previously thought.
    1. Evolutionary Biology
    2. Genetics and Genomics

    Rapid sex-specific adaptation to high temperature in Drosophila

    Sheng-Kai Hsu et al.
    Within 100 generations after an environmental shift in an evolution experiment, rapid sex-specific adaptation occurred, which is potentially facilitated by selection on standing variation in sex-specific genetic architecture.
    1. Neuroscience

    Mechanisms that allow cortical preparatory activity without inappropriate movement

    Timothy R Darlington, Stephen G Lisberger
    The use of preparatory activity in the smooth eye movement region of the frontal eye fields as a visual-motor gain signal allows preparation to progress without inappropriate movement.
    1. Stem Cells and Regenerative Medicine

    Multifaceted secretion of htNSC-derived hypothalamic islets induces survival and antidiabetic effect via peripheral implantation in mice

    Yizhe Tang et al.
    A subpopulation of multi-secretory hypothalamic stem cells was developed to form 3D spheres for peripheral application against mortality and symptom of a severe diabetes model.
    1. Computational and Systems Biology
    2. Immunology and Inflammation

    Primary and secondary anti-viral response captured by the dynamics and phenotype of individual T cell clones

    Anastasia A Minervina et al.
    High-throughput clonal tracking quantifies intrinsic differences between primary and secondary T cell response.
    1. Ecology
    2. Microbiology and Infectious Disease

    Targeted induction of a silent fungal gene cluster encoding the bacteria-specific germination inhibitor fumigermin

    Maria Cristina Stroe et al.
    A silent gene cluster of the fungus Aspergillus fumigatus is activated by a bacterium and leads to the production of a novel spore germination inhibitor targeting the inducing bacterium.
    1. Neuroscience

    Synaptic mechanisms underlying modulation of locomotor-related motoneuron output by premotor cholinergic interneurons

    Filipe Nascimento et al.
    The pairing of chemogenetic and electrophysiological approaches reveals mechanisms by which cholinergic synapses modulate the final motor output of the nervous system.
    1. Chromosomes and Gene Expression
    2. Immunology and Inflammation

    Polypyrimidine tract-binding proteins are essential for B cell development

    Elisa Monzón-Casanova et al.
    The RNA-binding protein polypyrimidine tract-binding protein 1 (PTBP1) is essential for B cell development at the pro-B cell stage where it suppresses S-phase entry and promotes progression through mitosis.
    1. Microbiology and Infectious Disease
    2. Physics of Living Systems

    The transpeptidase PBP2 governs initial localization and activity of the major cell-wall synthesis machinery in E. coli

    Gizem Özbaykal et al.
    For initiation of cell-wall insertion, the cross-linking enzyme PBP2 stably binds to a component of the cell envelope that is different from MreB filaments.
    1. Neuroscience

    Rapid regulation of vesicle priming explains synaptic facilitation despite heterogeneous vesicle:Ca2+ channel distances

    Janus RL Kobbersmed et al.
    Heterogeneous distances between vesicles and Ca2+-channels make synapses prone to short-term depression, however, Ca2+-dependent increases in the number of release-ready vesicles supports facilitation even with broadly distributed vesicle:Ca2+-channel distances.
    1. Chromosomes and Gene Expression
    2. Microbiology and Infectious Disease

    ParB spreading on DNA requires cytidine triphosphate in vitro

    Adam SB Jalal et al.
    A biochemical reconstitution shows that the accumulation of Caulobacter crescentus ParB on DNA requires cytidine triphosphate and a closed DNA substrate in vitro.
    1. Neuroscience

    Quantitative properties of a feedback circuit predict frequency-dependent pattern separation

    Oliver Braganza et al.
    The feedback inhibitory microcircuit of the dentate gyrus likely boosts pattern separation during gamma oscillations.
    1. Neuroscience

    The hippocampus encodes delay and value information during delay-discounting decision making

    Akira Masuda et al.
    Two distinct subpopulations of CA1 neurons that increased or decreased their firing rate during delay were identified, suggesting that they have distinct roles in the valuation process in the hippocampus.
    1. Neuroscience

    Stxbp1/Munc18-1 haploinsufficiency impairs inhibition and mediates key neurological features of STXBP1 encephalopathy

    Wu Chen et al.
    Two genetically distinct Stxbp1 haploinsufficiency mouse models exhibit seizures and impairments in cognitive, psychiatric, and motor functions, representing robust preclinical models of STXBP1 encephalopathy with both construct and face validity.
    1. Cell Biology
    2. Developmental Biology

    Mouse retinal cell behaviour in space and time using light sheet fluorescence microscopy

    Claudia Prahst et al.
    Improved 3D and 4D imaging of neurovascular processes across scales reveals new insights into eye disease mouse models and shows retinal vessels are significantly distorted using standard flat-mount confocal imaging.
    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    Tailless/TLX reverts intermediate neural progenitors to stem cells driving tumourigenesis via repression of asense/ASCL1

    Anna E Hakes, Andrea H Brand
    Increased expression of Drosophila Tailless (TLX homologue) reverts intermediate progenitors to neural stem cells, inducing tumourigenesis via Asense repression and reflecting mutually exclusive TLX and ASCL1 expression in human glioblastoma.
    1. Neuroscience

    Presynaptic GABAB receptors functionally uncouple somatostatin interneurons from the active hippocampal network

    Sam A Booker et al.
    Presynaptic GABAB receptors are highly expressed and strongly suppress synaptic transmission at the input and output of hippocampal somatostatin interneurons.
    1. Neuroscience

    Patterned perturbation of inhibition can reveal the dynamical structure of neural processing

    Sadra Sadeh, Claudia Clopath
    Neuronal networks with strong functional specificity of connections between excitatory and inhibitory neurons show specific dynamics of inhibitory stabilization, accompanied with rapid spontaneous activity transitions between highly selective functional states.
    1. Human Biology and Medicine
    2. Neuroscience

    Opioids depress breathing through two small brainstem sites

    Iris Bachmutsky et al.
    Opioids stop breathing during overdose by silencing two small brain sites, with just 140 neurons in the breathing rhythm generator exerting the key effect.
    1. Neuroscience

    Social structure learning in human anterior insula

    Tatiana Lau et al.
    A domain-general structure learning mechanism, supported by anterior insula, moves beyond explicit category labels and dyadic similarity as the sole inputs to social group representations and predicts ally-choice behavior.
    1. Neuroscience

    A Toll-receptor map underlies structural brain plasticity

    Guiyi Li et al.
    Structural brain plasticity is encoded in the topographic distribution of Toll receptors and their ability to switch between alternative signalling outcomes, thus translating diverse sensory experience into structural change.
    1. Computational and Systems Biology
    2. Evolutionary Biology

    Synteny-based analyses indicate that sequence divergence is not the main source of orphan genes

    Nikolaos Vakirlis et al.
    Homology information implicit in regions of conserved synteny allows quantification of gene origination by complete sequence divergence, revealing a larger-than-expected role for other mechanisms of origin, including de novo origination.
    1. Biochemistry and Chemical Biology
    2. Microbiology and Infectious Disease

    A widely distributed metalloenzyme class enables gut microbial metabolism of host- and diet-derived catechols

    Vayu Maini Rekdal et al.
    A previously unrecognized group of metalloenzymes enables human gut microbes to metabolize dietary molecules and neurotransmitters and likely mediates interactions and metabolism among environmental microorganisms.
    1. Developmental Biology
    2. Plant Biology

    Genetic analysis of the Arabidopsis TIR1/AFB auxin receptors reveals both overlapping and specialized functions

    Michael J Prigge et al.
    Genetic analyses reveal that the TIR1/AFB auxin receptors have broadly overlapping functions throughout plant development, but that the AFB1 receptor has a specialized role in a rapid auxin response.
    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    Plasmodium-infected erythrocytes induce secretion of IGFBP7 to form type II rosettes and escape phagocytosis

    Wenn-Chyau Lee et al.
    Plasmodium parasites use host-derived factors to form more rosettes and hamper phagocytosis, representing a new escape mechanism for the malaria parasites.
    1. Chromosomes and Gene Expression

    Translational initiation in E. coli occurs at the correct sites genome-wide in the absence of mRNA-rRNA base-pairing

    Kazuki Saito et al.
    E. coli ribosomes incapable of base-pairing with the Shine-Dalgarno sequence are still selective for annotated start sites, indicating these sites are hard-wired for initiation by other mRNA features.
    1. Cell Biology
    2. Microbiology and Infectious Disease

    A single-parasite transcriptional atlas of Toxoplasma Gondii reveals novel control of antigen expression

    Yuan Xue et al.
    Single-cell RNA-sequencing resolves the transcriptional landscape of asexual development in Toxoplasma gondii, revealing concerted genetic programs to Plasmodiumfalciparum and a novel transcriptional factor that controls antigen switching.
    1. Cell Biology
    2. Microbiology and Infectious Disease

    Repression of viral gene expression and replication by the unfolded protein response effector XBP1u

    Florian Hinte et al.
    A herpesvirus harnesses the unfolded protein response to regulate its own life cycle, revealing an unexpected role of XBP1u as a potent repressor of the most important viral promoter.
    1. Immunology and Inflammation

    Neonatal-derived IL-17 producing dermal γδ T cells are required to prevent spontaneous atopic dermatitis

    Nicholas A Spidale et al.
    Neonatal-origin dermal Tγδ17 cells are required to maintain normal keratinocytes and prevent spontaneous atopic dermatitis.
    1. Cell Biology

    EDEM2 stably disulfide-bonded to TXNDC11 catalyzes the first mannose trimming step in mammalian glycoprotein ERAD

    Ginto George et al.
    EDEM2 containing mannosidase homology domain functions as an initiator of endoplasmic reticulum-associated degradation of misfolded glycoproteins by conversion of Man9GlcNAc2 to Man8GlcNAc2, only when complexed with TXNDC11 containing thioredoxin-like domains.
    1. Neuroscience

    Medial entorhinal cortex activates in a traveling wave in the rat

    J Jesús Hernández-Pérez et al.
    The existence of traveling waves in the medial entorhinal cortex, like those observed in the hippocampus, supports the hypothesis that traveling waves coordinate the activity of anatomically distributed circuits.
    1. Genetics and Genomics

    Suppressing proteasome mediated processing of topoisomerase II DNA-protein complexes preserves genome integrity

    Nicholas Sciascia et al.
    Analysis of genome integrity in primary murine B-cells reveals how depleting 26S proteasome activity enhanced cell survival following treatment with topoisomerase poisons.
    1. Cell Biology

    Competition between kinesin-1 and myosin-V defines Drosophila posterior determination

    Wen Lu et al.
    Posterior determination of Drosophila oocyte is defined by competition between kinesin-1 removing posterior determinants from the cortex and myosin-V anchoring them.
    1. Cancer Biology

    Functional heterogeneity of lymphocytic patterns in primary melanoma dissected through single-cell multiplexing

    Francesca Maria Bosisio et al.
    Multiplexing and digital analysis of melanoma tissue describe functionally the microenvironment associated with brisk/non-brisk infiltrates and expose the functional incongruences of this morphological classification currently in use for tumor-infiltrating lymphocytes.
    1. Ecology
    2. Plant Biology

    Determining the scale at which variation in a single gene changes population yields

    Erica McGale et al.
    Variation in the gene NaMPK4 in plant populations increases reproductive yield, an effect which appears to be independent of soil water availability, neighbor-scale interactions and associations with arbuscular mycorrhizal fungi.
    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    LRRK2 maintains mitochondrial homeostasis and regulates innate immune responses to Mycobacterium tuberculosis

    Chi G Weindel et al.
    Long studied in the context of the central nervous system, LRRK2 also functions in peripheral immunity by maintaining mitochondrial homeostasis in macrophages to regulate the type I interferon response.
    1. Cell Biology
    2. Developmental Biology

    The CHORD protein CHP-1 regulates EGF receptor trafficking and signaling in C. elegans and in human cells

    Andrea Haag et al.
    The co-chaperone CHORDC1 is specifically required for epidermal growth factor receptor trafficking and signaling in Caenorhabditis elegans and in human cells.
    1. Developmental Biology
    2. Genetics and Genomics

    A large-scale resource for tissue-specific CRISPR mutagenesis in Drosophila

    Fillip Port et al.
    A large-scale CRISPR library allows efficient gene disruption with spatial and temporal control in Drosophila.
    1. Biochemistry and Chemical Biology

    Regulation of mRNA translation by a photoriboswitch

    Kelly A Rotstan et al.
    A synthetic riboswitch binding one isoform of a photoreversible ligand provides a photoregulatory tool for bacterial translation initiation.
    1. Neuroscience

    Nodal β spectrins are required to maintain Na+ channel clustering and axon integrity

    Cheng-Hsin Liu et al.
    A combination of sensory-neuron specific conditional knockout mice reveal nodal beta spectrins are required to maintain, but not assemble, nodes of Ranvier.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    The speed of GTP hydrolysis determines GTP cap size and controls microtubule stability

    Johanna Roostalu et al.
    GTPase-deficient microtubules are hyper-stable and have longer EB binding regions, demonstrating that EBs bind the GTP cap.
    1. Neuroscience

    Energy efficient synaptic plasticity

    Ho Ling Li, Mark CW van Rossum
    The metabolic efficiency of learning in networks is improved by using forms of synaptic plasticity with different levels of persistence.
    1. Neuroscience

    Paradoxical network excitation by glutamate release from VGluT3+ GABAergic interneurons

    Kenneth A Pelkey et al.
    Glutamate cotransmission from a subset of cortical GABAergic interneurons can promote network hyperexcitability.
    1. Cell Biology
    2. Computational and Systems Biology

    Mechanisms of chromosome biorientation and bipolar spindle assembly analyzed by computational modeling

    Christopher Edelmaier et al.
    A computational model of fission yeast mitosis can interrogate mechanisms required for successful mitosis, the origin of spindle length fluctuations, and spindle force balance during assembly.
    1. Neuroscience

    Noninvasive quantification of axon radii using diffusion MRI

    Jelle Veraart et al.
    Cell-specific architectural properties such as the axon diameter of the white matter of the human brain can be quantified accurately and non-invasively using diffusion magnetic resonance imaging.
    1. Developmental Biology
    2. Evolutionary Biology

    Developmental variability channels mouse molar evolution

    Luke Hayden et al.
    The nature and extent of developmental variation seen between mouse strains and genetically identical individuals explain why the first upper molar evolves along preferred path in murine rodents.
    1. Neuroscience
    2. Structural Biology and Molecular Biophysics

    The Cryo-EM structure of pannexin 1 reveals unique motifs for ion selection and inhibition

    Kevin Michalski et al.
    The structure of a pannexin 1 uncovers the extracellular loops of pannexin 1 as important structural motifs for ion selectivity and channel inhibition.
    1. Physics of Living Systems

    Overtone focusing in biphonic tuvan throat singing

    Christopher Bergevin et al.
    In light of the mysteries underlying the biphonic nature of Tuvan throat song, information from multiple modalities is combined to explain how this remarkable phenomenon is achieved biomechanically.
    1. Biochemistry and Chemical Biology

    JMJD6 cleaves MePCE to release positive transcription elongation factor b (P-TEFb) in higher eukaryotes

    Schuyler Lee et al.
    JMJD6 helps BRD4 to recruit CDK9 to RNA Polymerase II by disrupting 7SK snRNP complex.
    1. Stem Cells and Regenerative Medicine

    Derivation of trophoblast stem cells from naïve human pluripotent stem cells

    Chen Dong et al.
    Naive hPSCs can readily give rise to human trophoblast stem cells, thus demonstrating their extraembryonic lineage potential and providing a new model system to study human trophectoderm specification.
    1. Developmental Biology

    Embryonic geometry underlies phenotypic variation in decanalized conditions

    Anqi Huang et al.
    Gene regulatory networks incorporate information of the embryonic geometrical parameters to give rise to differential individual patterning outputs under decanalized genetics backgrounds.
    1. Evolutionary Biology
    2. Genetics and Genomics

    The evolutionary plasticity of chromosome metabolism allows adaptation to constitutive DNA replication stress

    Marco Fumasoni, Andrew W Murray
    Evolutionary adaptation to a constitutive perturbation of DNA replication reveals that adaptive mutations in three conserved pathways interact to restore faithful chromosome replication and segregation.
    1. Structural Biology and Molecular Biophysics

    Casein kinase 1 dynamics underlie substrate selectivity and the PER2 circadian phosphoswitch

    Jonathan M Philpott et al.
    A conformational switch in the Casein Kinase 1 activation loop controls substrate preference to regulate the abundance of the clock protein PERIOD2 and circadian timekeeping.
    1. Epidemiology and Global Health

    Body height in young adult men and risk of dementia later in adult life

    Terese Sara Høj Jørgensen et al.
    Taller body height in young adulthood, as marker of early-life environment, is associated with lower risk of dementia diagnosis independently of cognitive reserve and family factors shared among brothers.
    1. Biochemistry and Chemical Biology
    2. Neuroscience

    Organic electrochemical transistor arrays for real-time mapping of evoked neurotransmitter release in vivo

    Kai Xie et al.
    An implantable device based on organic electrochemical transistors is developed for quantitative mapping of neurotransmitter release across multiple brain regions, revealing a cross-talk between the mesolimbic and nigrostriatal dopaminergic pathways.
    1. Computational and Systems Biology

    Synthetic and genomic regulatory elements reveal aspects of cis-regulatory grammar in mouse embryonic stem cells

    Dana M King et al.
    The independent effects of transcription factor binding sites are large regardless of sequence context, but the interactions between sites are context dependent.
    1. Microbiology and Infectious Disease
    2. Neuroscience

    A gut bacterial amyloid promotes α-synuclein aggregation and motor impairment in mice

    Timothy R Sampson et al.
    Production of an amyloid protein by bacteria within the gut microbiome can influence the pathophysiology of a mouse model of synucleinopathy.
    1. Neuroscience

    Postural control of arm and fingers through integration of movement commands

    Scott T Albert et al.
    After a movement, the final posture of the arm is stabilized by a subcortical structure that mathematically integrates movement commands over time.
    1. Neuroscience

    Using subthreshold events to characterize the functional architecture of the electrically coupled inferior olive network

    Yaara Lefler et al.
    Non-synaptic electrical events recorded simultaneously from pairs of neurons in the inferior olive nucleus enables accurate estimation of the size and of the clustered organization of the electrically coupled network.
    1. Neuroscience

    Anatomical and single-cell transcriptional profiling of the murine habenular complex

    Michael L Wallace et al.
    Single-cell transcriptional profiling reveals distinct neuronal subtypes of the lateral habenula differentially target downstream neuronal subtypes in the ventral tegmental area and dorsal raphe nucleus.
    1. Immunology and Inflammation

    High-dimensional analysis of intestinal immune cells during helminth infection

    Laura Ferrer-Font et al.
    A systematic optimization of intestinal digestion protocols allows for the isolation and high-dimensional flow cytometric analysis of intestinal immune cells during murine helminth infection.
    1. Cell Biology
    2. Neuroscience

    Small-molecule G-quadruplex stabilizers reveal a novel pathway of autophagy regulation in neurons

    Jose F Moruno-Manchon et al.
    G-quadruplex DNA regulates autophagy in neurons.
    1. Developmental Biology

    Etv transcription factors functionally diverge from their upstream FGF signaling in lens development

    Ankur Garg et al.
    The FGF-induced Etv transcription factors operate outside the confines of upstream signaling in lens development.
    1. Computational and Systems Biology
    2. Genetics and Genomics

    Pan-mammalian analysis of molecular constraints underlying extended lifespan

    Amanda Kowalczyk et al.
    Cancer control, DNA repair, and immunity are key functionalities underlying the evolution of extended lifespan in mammals.
    1. Developmental Biology
    2. Evolutionary Biology

    Origin of the mechanism of phenotypic plasticity in satyrid butterfly eyespots

    Shivam Bhardwaj et al.
    A gradual, step-wise, physiological/molecular response of eyespot size to temperature is a likely adaptation to seasonal variation experienced in the habitat of Bicyclusanynana butterflies.
    1. Epidemiology and Global Health

    Longitudinal trajectories, correlations and mortality associations of nine biological ages across 20-years follow-up

    Xia Li et al.
    Biological ages have the potential to provide aging-related information beyond chronological age and can be predictive of mortality independently of both chronological age and different types of biological ages.
    1. Cell Biology
    2. Plant Biology

    Imaging plant germline differentiation within Arabidopsis flowers by light sheet microscopy

    Sona Valuchova et al.
    Light sheet microscopy was used to establish a method for live imaging of cellular events within Arabidopsis flower and for constructing a 3D model of flower at subcellular resolution.
    1. Immunology and Inflammation

    c-Maf restrains T-bet-driven programming of CCR6-negative group 3 innate lymphoid cells

    Caroline Tizian et al.
    c-Maf is a novel key regulator of the type 3-to-1 conversion of CCR6 ILC3s that controls the functional plasticity of ILC3s by acting as a cell-intrinsic gatekeeper of T-bet expression.
    1. Cell Biology
    2. Ecology

    Ubiquitous macropinocytosis in anthozoans

    Philippe Ganot et al.
    Macropinocytosis, the process of non-specific endocytosis, is a major gateway for large volumes of surrounding medium and nanoparticles to coral cells.
    1. Neuroscience

    Inter- and intra-animal variation in the integrative properties of stellate cells in the medial entorhinal cortex

    Hugh Pastoll et al.
    Setpoints that determine the integrative properties of neurons in the medial entorhinal cortex are established at a population level and differ between animals.
    1. Structural Biology and Molecular Biophysics

    Structural basis of transcription inhibition by the DNA mimic protein Ocr of bacteriophage T7

    Fuzhou Ye et al.
    DNA mimicry Ocr protein, a well-studied T7 phage protein that inhibits host restriction enzymes, can also inhibit host transcription through competing with sigma factors in binding to RNA polymerase.
    1. Neuroscience

    Inhibition of protein synthesis in M1 of monkeys disrupts performance of sequential movements guided by memory

    Machiko Ohbayashi
    Inhibition of protein synthesis in primary motor cortex (M1) of monkeys disrupted the performance of skilled sequential movements suggesting that M1 is involved in maintenance of skilled sequential movements.
    1. Computational and Systems Biology
    2. Developmental Biology

    Analysis of zebrafish periderm enhancers facilitates identification of a regulatory variant near human KRT8/18

    Huan Liu et al.
    Analysis of zebrafish periderm enhancers illuminates the conserved DNA of epithelial enhancers across species and prioritizes orofacial-cleft-associated regulatory variants near KRT18/KRT8.
    1. Neuroscience

    β11-12 linker isomerization governs acid-sensing ion channel desensitization and recovery

    Matthew L Rook et al.
    The rotation of the β11-12 linker is a crucial control point for acid-sensing ion channel gating and motion of this linker is required for the channel to desensitize.
    1. Neuroscience

    The contribution of temporal coding to odor coding and odor perception in humans

    Ofer Perl et al.
    Human participants fail to discriminate between odor sequences that activate the same neurons at different orders, pointing against a substantial role for neuron activation time in the odor code.
    1. Neuroscience

    Clusters of cooperative ion channels enable a membrane-potential-based mechanism for short-term memory

    Paul Pfeiffer et al.
    Independently gating ion channels typically act fast within milliseconds, but cooperative interactions within a cluster of channels allow for a memory of previous electrical activity for several seconds.
    1. Neuroscience

    Spatiotemporal dynamics of multi-vesicular release is determined by heterogeneity of release sites within central synapses

    Dario Maschi, Vitaly A Klyachko
    Release site heterogeneity represents a previously unknown level of structural and functional organization within individual active zones in central synapses, which determines the spatiotemporal dynamics of multi-vesicular release.
    1. Developmental Biology
    2. Plant Biology

    Selective egg cell polyspermy bypasses the triploid block

    Yanbo Mao et al.
    A ménàge à trois introduces extra DNA only to plant embryos, thus skipping endosperm-induced seed hybridization barriers.
    1. Physics of Living Systems

    Stochastic yield catastrophes and robustness in self-assembly

    Florian M Gartner et al.
    Fluctuations in the availability of particles for binding can completely jeopardize yield in heterogeneous self-assembly.
    1. Immunology and Inflammation

    Quantitative analysis of how Myc controls T cell proteomes and metabolic pathways during T cell activation

    Julia M Marchingo et al.
    Myc-dependent induction of amino acid transporter expression in response to T cell receptor activation is essential to enable T cell proteome remodelling upon immune activation.
    1. Cell Biology
    2. Neuroscience

    Ser/Thr kinase Trc controls neurite outgrowth in Drosophila by modulating microtubule-microtubule sliding

    Rosalind Norkett et al.
    Microtubule-microtubule sliding and neurite outgrowth in Drosophila is controlled by a Ser/Thr kinase Tricornered via phosphorylation of a 'mitotic' motor protein Pavarotti.
    1. Microbiology and Infectious Disease

    Defective lytic transglycosylase disrupts cell morphogenesis by hindering cell wall de-O-acetylation in Neisseria meningitidis

    Allison Hillary Williams et al.
    Lytic transglycosylase enhances the activity of its protein partner, and its catalytic domain can be targeted to disrupt cell-wall integrity, protein partner function, and bacterial survival (Neisseria meningitidis) in hosts.
    1. Stem Cells and Regenerative Medicine

    Cohesin controls intestinal stem cell identity by maintaining association of Escargot with target promoters

    Aliaksandr Khaminets et al.
    Cohesin-regulated 3D genome conformation controls activity of transcription factor Escargot in intestinal stem cells, prevents premature differentiation into enterocytes and maintains intestinal homeostasis.
    1. Neuroscience

    Gradients in the mammalian cerebellar cortex enable Fourier-like transformation and improve storing capacity

    Isabelle Straub et al.
    Electrophysiological and computational approaches show that superficial and deep cerebellar granule cells preferentially fire during low- and high-frequency inputs, respectively, enabling a Fourier-like transformation in the granule cell layer.
    1. Epidemiology and Global Health
    2. Microbiology and Infectious Disease

    Potential impact of outpatient stewardship interventions on antibiotic exposures of common bacterial pathogens

    Christine Tedijanto et al.
    Antibiotic stewardship in the outpatient setting can substantially reduce exposures of potential pathogens to common antibiotics, and complementary efforts are needed to reduce remaining exposures that occur in 'necessary' contexts.
    1. Cell Biology

    Loss of flavin adenine dinucleotide (FAD) impairs sperm function and male reproductive advantage in C. elegans

    Chia-An Yen et al.
    Loss of FAD stemming from cell autonomous defects in mitochondrial proline catabolism impairs sperm quality male reproductive advantage in C. elegans.
    1. Neuroscience

    Opposite changes in APP processing and human Aβ levels in rats carrying either a protective or a pathogenic APP mutation

    Marc D Tambini et al.
    APP mutations that either cause or prevent dementia alter APP metabolism in a complex and opposite fashion, suggesting a link between multiple APP processing events, dementia and ageing-dependent cognitive decline.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    A Fyn biosensor reveals pulsatile, spatially localized kinase activity and signaling crosstalk in live mammalian cells

    Ananya Mukherjee et al.
    Unique biosensor design and protein-engineering enables direct visualization of the active form of Fyn kinase with high specificity, minimal perturbation and shows cellular signaling to be compartmentalized and pulsatile.
    1. Evolutionary Biology
    2. Microbiology and Infectious Disease

    Discovery of several thousand highly diverse circular DNA viruses

    Michael J Tisza et al.
    A bioinformatics pipeline has annotated over 2,500 complete genomes of circular DNA viruses belonging to dozens of established and emerging viral families.
    1. Cancer Biology

    Understanding the glioblastoma immune microenvironment as basis for the development of new immunotherapeutic strategies

    Ana Rita Pombo Antunes et al.
    The heterogeneity of immune cell types in glioblastoma tumors depends on the tumor's genetic make-up and treatment status and is an incompletely mined source of novel therapeutic targets.
    1. Immunology and Inflammation

    Inhibition of IRF4 in dendritic cells by PRR-independent and -dependent signals inhibit Th2 and promote Th17 responses

    Jihyung Lee et al.
    Reprogramming of transcription factors by PRR-independent (cAMP) and PRR-dependent (curdlan) signaling induces new dendritic cell subset.
    1. Epidemiology and Global Health

    Previously undetected super-spreading of Mycobacterium tuberculosis revealed by deep sequencing

    Robyn S Lee et al.
    Incorporating within-host diversity in transmission, as identified by deep sequencing, can significantly change previously-held inferences, with major implications for genomic studies of transmission in tuberculosis and other pathogens as well.
    1. Cell Biology

    Single cell analysis reveals multiple requirements for zinc in the mammalian cell cycle

    Maria N Lo et al.
    Zinc affects the proliferation-quiescence cell fate decision of mammalian cells, demonstrating that micronutrients can regulate the cell cycle.
    1. Ecology
    2. Epidemiology and Global Health

    Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence

    Cara E Brook et al.
    Bats' uniquely robust innate antiviral immune defenses select for faster transmitting viruses likely to generate extreme virulence upon spillover to secondary hosts with immune systems divergent from those of bat.
    1. Cell Biology

    Distinct regulatory ribosomal ubiquitylation events are reversible and hierarchically organized

    Danielle M Garshott et al.
    A hierarchical relationship among highly conserved regulatory ribosomal ubiquitylation events and the presence of antagonistic deubiquitylating enzymes suggests a dynamic ubiquitin code impacts ribosome-associated activities.
    1. Microbiology and Infectious Disease

    RNA polymerase mutations cause cephalosporin resistance in clinical Neisseria gonorrhoeae isolates

    Samantha G Palace et al.
    Ceftriaxone resistance has arisen multiple times in clinical gonococcal populations via previously undescribed RNA polymerase mutations, underscoring the importance of continued surveillance for novel resistance determinants.
    1. Cell Biology
    2. Plant Biology

    Reticulon proteins modulate autophagy of the endoplasmic reticulum in maize endosperm

    Xiaoguo Zhang et al.
    Plant reticulons bind Atg8 under ER stress to promote reticulophagy and ameliorate ER stress in the maize endosperm.
    1. Stem Cells and Regenerative Medicine

    Transcriptional landscape of myogenesis from human pluripotent stem cells reveals a key role of TWIST1 in maintenance of skeletal muscle progenitors

    In Young Choi et al.
    Using multiple genetic reporter system in human pluripotent stem cells, a transcriptional database for human early myogenesis has been established.

Magazine

  1. Research Culture: Setting the right tone

    Tanita Casci, Elizabeth Adams
    1. Neuroscience

    Physical Inference: How the brain represents mass

    Grant Fairchild, Jacqueline C Snow