October 2020

Image credit: Vesa Havurinne

Research articles

    1. Structural Biology and Molecular Biophysics

    A sulfur-aromatic gate latch is essential for opening of the Orai1 channel pore

    Priscilla S-W Yeung et al.
    Electrophysiological and molecular modeling studies identify a sulfur-aromatic interaction between the hydrophobic channel gate and a nearby methionine residue, termed the "gate latch", which is essential for Orai1 pore opening.
    1. Neuroscience

    A low affinity cis-regulatory BMP response element restricts target gene activation to subsets of Drosophila neurons

    Anthony JE Berndt et al.
    DNA motifs tuned for low affinity binding of BMP-induced pMad/Medea transcription factors function to restrict gene activation to small subsets of the many Drosophila neurons that exhibit active BMP signaling.
    1. Evolutionary Biology

    The birth of a bacterial tRNA gene by large-scale, tandem duplication events

    Gökçe B Ayan et al.
    A bacterial tRNA gene set rapidly evolves, compensating the loss of one tRNA type by large duplication events that increase the gene copy number of a second, different tRNA type.
    1. Genetics and Genomics
    2. Microbiology and Infectious Disease

    Transcription termination and antitermination of bacterial CRISPR arrays

    Anne M Stringer et al.
    Many bacteria use the Nus factor antitermination complex to prevent premature Rho-dependent transcription termination of their CRISPR arrays.
    1. Neuroscience

    Cellular taxonomy and spatial organization of the murine ventral posterior hypothalamus

    Laura E Mickelsen et al.
    Single cell RNA–sequencing and neuroanatomical methods reveal unexpected molecular diversity and highly segregated spatial organization of neuronal cell types within the mouse ventral posterior hypothalamus, including the mammillary nuclei.
    1. Microbiology and Infectious Disease

    Lipid hijacking: a unifying theme in vector-borne diseases

    Anya J O'Neal et al.
    A conceptual and unifying framework with a critical appraisal of lipid hijacking by microbes cycling between an arthropod vector and a mammalian host is explored.
    1. Developmental Biology

    A universal reading network and its modulation by writing system and reading ability in French and Chinese children

    Xiaoxia Feng et al.
    A cross-cultural study of reading acquisition and reading irmpairment reveals the invariance of the neural correlates of reading across cultures.
    1. Cell Biology

    Functional exploration of heterotrimeric kinesin-II in IFT and ciliary length control in Chlamydomonas

    Shufen Li et al.
    Experimental and modelling analyses suggest a non-linear scaling relationship between IFT velocity and ciliary length that can be accounted for by limitation of the motors.
    1. Cell Biology
    2. Developmental Biology

    Coordinated crosstalk between microtubules and actin by a spectraplakin regulates lumen formation and branching

    Delia Ricolo, Sofia J Araujo
    Lumen formation by single epithelial cells depends on FGF-signalling-dependent expression of a spectraplakin, which can be functionally replaced by Tau.
    1. Cancer Biology
    2. Chromosomes and Gene Expression

    A small protein encoded by a putative lncRNA regulates apoptosis and tumorigenicity in human colorectal cancer cells

    Xiao Ling Li et al.
    Discovery and initial characterization of a conserved small protein translated from a transcript annotated as a human long non-coding RNA.
    1. Genetics and Genomics

    Mutations primarily alter the inclusion of alternatively spliced exons

    Pablo Baeza-Centurion et al.
    Deep mutagenesis reveals that mutations rarely alter the inclusion of highly-included exons.
    1. Evolutionary Biology
    2. Genetics and Genomics

    Recurrent evolution of high virulence in isolated populations of a DNA virus

    Tom Hill, Robert L Unckless
    The same host–virus interactions can evolve multiple times in nature, due to the high effective mutation rate of viruses, and provide interesting systems of study.
    1. Biochemistry and Chemical Biology
    2. Neuroscience

    Probing the ionotropic activity of glutamate GluD2 receptor in HEK cells with genetically-engineered photopharmacology

    Damien Lemoine et al.
    A photoswitchable pore blocker was covalently attached to a cysteine-substituted glutamate delta 2 receptor, to provide optical control of its ion channel function.
    1. Evolutionary Biology
    2. Immunology and Inflammation

    Homology-guided identification of a conserved motif linking the antiviral functions of IFITM3 to its oligomeric state

    Kazi Rahman et al.
    A disease-associated polymorphism in a related protein that regulates neurotransmitter release reveals that antiviral protein IFITM3 forms oligomers to rigidify membranes and inhibit virus fusion with cells.
    1. Computational and Systems Biology
    2. Microbiology and Infectious Disease

    Drivers and sites of diversity in the DNA adenine methylomes of 93 Mycobacterium tuberculosis complex clinical isolates

    Samuel J Modlin et al.
    Fully assembled DNA methylomes from phylogeographically diverse clinical Mycobacterium tuberculosis complex isolates reveals 'intercellular mosaic methylation' as a source of epigenetic diversity.
    1. Epidemiology and Global Health
    2. Microbiology and Infectious Disease

    Sex-based differences in clearance of chronic Plasmodium falciparum infection

    Jessica Briggs et al.
    Lower malaria prevalence in females does not appear to be due to lower rates of infection but rather due to faster clearance of asymptomatic infections.
    1. Cell Biology
    2. Developmental Biology

    Dot1l interacts with Zc3h10 to activate Ucp1 and other thermogenic genes

    Danielle Yi et al.
    Dot1l and its H3K79 methyltransferase activity are required for thermogenesis, and Dot1l is recruited by Zc3h10 to its targets genes to alter chromatin accessibility to activate the thermogenic gene program.
    1. Ecology
    2. Microbiology and Infectious Disease

    Metapopulation ecology links antibiotic resistance, consumption, and patient transfers in a network of hospital wards

    Julie Teresa Shapiro et al.
    Patterns of antibiotic use and the connectivity between wards are independently associated with the incidence of antimicrobial-resistant infections in hospital networks.
    1. Neuroscience

    Improving emotional-action control by targeting long-range phase-amplitude neuronal coupling

    Bob Bramson et al.
    Non-invasive manipulation of endogenously coupled neural rhythms enhances human control of social-emotional actions.
    1. Biochemistry and Chemical Biology

    Gradual compaction of the nascent peptide during cotranslational folding on the ribosome

    Marija Liutkute et al.
    HemK NTD cotranslational folding starts within the ribosome exit tunnel upon N-terminal helix synthesis and proceeds sequentially through a series of intermediates becoming less dynamic as the nascent chain grows.
    1. Computational and Systems Biology
    2. Neuroscience

    Bayesian inference for biophysical neuron models enables stimulus optimization for retinal neuroprosthetics

    Jonathan Oesterle et al.
    Bayesian simulator-based inference is used to infer the parameters of complex multicompartment models of retinal neurons from two-photon imaging data.
    1. Chromosomes and Gene Expression

    The S-phase-induced lncRNA SUNO1 promotes cell proliferation by controlling YAP1/Hippo signaling pathway

    Qinyu Hao et al.
    Cell cycle phase-specifically induced long non-coding RNAs regulate cell proliferation by modulating crucial cell signaling pathways.
    1. Neuroscience

    SARM1 depletion rescues NMNAT1-dependent photoreceptor cell death and retinal degeneration

    Yo Sasaki et al.
    A mouse model of retinal degeneration reveals a common mechanism for axonal degeneration and photoreceptor cell death and identifies SARM1 as a therapeutic candidate for retinopathies.
    1. Neuroscience

    Distinct hierarchical alterations of intrinsic neural timescales account for different manifestations of psychosis

    Kenneth Wengler et al.
    fMRI evidence for distinct hierarchical alterations in intrinsic neural timescales for different positive symptoms of schizophrenia support hierarchical perceptual-inference models of psychosis and suggest local increases in excitation-inhibition ratio.
    1. Cell Biology
    2. Evolutionary Biology

    The wtf4 meiotic driver utilizes controlled protein aggregation to generate selective cell death

    Nicole L Nuckolls et al.
    The Wtf4 antidote protein assembles with the Wtf4 poison protein and promotes the transportation of the assembled proteins to the vacuole for sequestration or destruction.
    1. Neuroscience

    VIP interneurons in mouse primary visual cortex selectively enhance responses to weak but specific stimuli

    Daniel J Millman et al.
    Measurements of visual response to motion of different contrasts along with network modeling reveals a microcircuit in superficial layers of cortex that regulates the gain regime.
    1. Microbiology and Infectious Disease

    Specificity in glycosylation of multiple flagellins by the modular and cell cycle regulated glycosyltransferase FlmG

    Silvia Ardissone et al.
    Glycosylation of flagellins with pseudaminic acid in the bacterial cytoplasm governed by an unknown type of modular glycosyltransferase harboring an N-terminal substrate binding domain and a C-terminal glycosyltransferase domain.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Uncovering the basis of protein-protein interaction specificity with a combinatorially complete library

    Thuy-Lan V Lite et al.
    A generalizable approach to understanding the logic of molecular recognition reveals the contributions of individual residues to the specificity of protein-protein interactions.
    1. Chromosomes and Gene Expression
    2. Plant Biology

    A new role for histone demethylases in the maintenance of plant genome integrity

    Javier Antunez-Sanchez et al.
    Plants reset chromatin marks during sexual reproduction to safeguard the stability of the genome.
    1. Neuroscience

    Distinct subpopulations of mechanosensory chordotonal organ neurons elicit grooming of the fruit fly antennae

    Stefanie Hampel et al.
    Anatomically and physiologically distinct subpopulations of mechanosensory neurons on the fruit fly antennae elicit both common and distinct behavioral responses.
    1. Neuroscience

    Variation of connectivity across exemplar sensory and associative thalamocortical loops in the mouse

    Arghya Mukherjee et al.
    Compared to a sensory thalamocortical circuit, the mediodorsal thalamus preferentially innervates prefrontal cortical interneurons, and enhancing excitability of this thalamic structure drives prefrontal activity patterns that are dominated by inhibition.
    1. Cell Biology
    2. Developmental Biology

    Sonic hedgehog signaling directs patterned cell remodeling during cranial neural tube closure

    Eric R Brooks et al.
    Closure of the cranial neural tube, which is essential for mammalian development, is driven by spatially and temporally patterned cell remodeling events that require positionally regulated Sonic hedgehog signaling.
    1. Cell Biology

    A novel checkpoint pathway controls actomyosin ring constriction trigger in fission yeast

    Tomás Edreira et al.
    In fission yeast cell wall stress triggers a cytokinesis blockage specifically in the onset of actomyosin ring constriction.
    1. Neuroscience

    How many neurons are sufficient for perception of cortical activity?

    Henry WP Dalgleish et al.
    Targeted optogenetic activation of small ensembles of neurons is sufficient to trigger a behavioral report while recruiting matched network suppression, suggesting exquisite sensitivity despite network mechanisms that maintain sparseness.
    1. Cancer Biology

    Inhibiting IRE1α-endonuclease activity decreases tumor burden in a mouse model for hepatocellular carcinoma

    Nataša Pavlović et al.
    Inhibiting IRE1α decreases tumor cell proliferation and migration in hepatocellular carcinoma, therefore components of this ER-stress pathway may be therapeutically relevant for liver cancer.
    1. Biochemistry and Chemical Biology
    2. Microbiology and Infectious Disease

    Inhibition of SARS-CoV-2 viral entry upon blocking N- and O-glycan elaboration

    Qi Yang et al.
    A critical role for glycosylation on viral entry and methods to use this knowledge to reduce SARS-CoV-2 infectivity has been demonstrated.
    1. Chromosomes and Gene Expression

    Telomerase biogenesis requires a novel Mex67 function and a cytoplasmic association with the Sm7 complex

    Yulia Vasianovich et al.
    A new tool that allows specific subpopulations of telomerase RNAs in vivo forces a thorough revision of the telomerase maturation pathway and suggests a new function for Mex67.
    1. Cancer Biology
    2. Immunology and Inflammation

    Cytotoxic T-cells mediate exercise-induced reductions in tumor growth

    Helene Rundqvist et al.
    Exercise can induce metabolic changes that strikingly impact cytotoxic T cell function and in turn affect cancer progression.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    SON and SRRM2 are essential for nuclear speckle formation

    İbrahim Avşar Ilik et al.
    Re-characterization of the targets of a commonly used nuclear speckle marker unexpectedly leads to the discovery of the elusive core of the nuclear speckles.
    1. Genetics and Genomics

    Beyond the RNA-dependent function of LncRNA genes

    Tamer Ali, Phillip Grote
    Recent examples demonstrate that already the transcriptional activity at lncRNA genes does have an important function on gene regulation, while the produced non-coding RNA might be dispensable.
    1. Structural Biology and Molecular Biophysics

    Allosteric mechanism for KCNE1 modulation of KCNQ1 potassium channel activation

    Georg Kuenze et al.
    An integrative structural biology approach provides refined models of the KCNQ1-KCNE1 channel complex, which propose a new mechanism to explain how KCNE1 modulates KCNQ1 channel activation.
    1. Neuroscience

    Structural rearrangement of amyloid-β upon inhibitor binding suppresses formation of Alzheimer’s disease related oligomers

    Tobias Lieblein et al.
    Monitoring the formation of two distinct arrangements in early amyloid-ß aggregation by mass spectrometry and ion mobility allows determination of the effect of potential drug candidates.
    1. Structural Biology and Molecular Biophysics

    Cannabidiol interactions with voltage-gated sodium channels

    Lily Goodyer Sait et al.
    The high resolution crystal structure and electrophysiology of a sodium channel complex with cannabidiol, a drug approved for treatment of severe epilepsies, demonstrate the basis for its structural- functional effects.
    1. Structural Biology and Molecular Biophysics

    Structural basis of ClpXP recognition and unfolding of ssrA-tagged substrates

    Xue Fei et al.
    Cryo-EM structures of the AAA+ ClpXP protease bound to an ssrA degron reveal the mechanism of substrate recognition and show how the machine transitions from recognition to translocation and unfolding.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Structural insight into toxin secretion by contact-dependent growth inhibition transporters

    Jeremy Guerin et al.
    Structures of CdiB outer membrane transporters reveal the channel-gating mechanism for the secretion of large bacterial toxins.
    1. Chromosomes and Gene Expression
    2. Developmental Biology

    ARID1A loss in adult hepatocytes activates β-catenin-mediated erythropoietin transcription

    Rozenn Riou et al.
    A chromatin remodeling factor cooperates with Wnt signaling pathway to transcribe erythropoietin in the adult liver, inducing its secretion and a dramatic erythropoiesis in the spleen.
    1. Microbiology and Infectious Disease

    A single mutation in Crimean-Congo hemorrhagic fever virus discovered in ticks impairs infectivity in human cells

    Brian L Hua et al.
    Tick-derived sequence variation in the fusion glycoprotein of Crimean-Congo hemorrhagic fever virus (CCHFV) drastically impairs infection of mammalian cells, suggesting that certain CCHFV strains undergo purifying selection in mammalian hosts.
    1. Developmental Biology
    2. Neuroscience

    Developmental, cellular, and behavioral phenotypes in a mouse model of congenital hypoplasia of the dentate gyrus

    Amir Rattner et al.
    A mouse mutant in which nearly all dentate gyrus granule cells fail to develop provides a new window on the role of the dentate gyrus in spatial learning and memory.
    1. Cell Biology
    2. Microbiology and Infectious Disease

    Artemisinin exposure at the ring or trophozoite stage impacts Plasmodium falciparum sexual conversion differently

    Harvie P Portugaliza et al.
    Treatment of malaria parasites with the frontline antimalarial drug artemisinin can increase the proportion of parasites that convert into transmission forms.
    1. Cell Biology
    2. Developmental Biology

    Drosophila hedgehog can act as a morphogen in the absence of regulated Ci processing

    Jamie C Little et al.
    Hedgehog acts as a morphogen by regulating proteolytic processing and activation of full-length Ci/Gli transcriptional effectors but can pattern Drosophila wing discs normally in the absence of regulated proteolytic processing.
    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    A broadly neutralizing macaque monoclonal antibody against the HIV-1 V3-Glycan patch

    Zijun Wang et al.
    Rhesus macaques can develop broadly neutralizing antibodies (bNAbs) against the V3-glycan patch of Env that resembles human V3/N332 bNABs.
    1. Evolutionary Biology
    2. Genetics and Genomics

    Gene expression variability in human and chimpanzee populations share common determinants

    Benjamin Jung Fair et al.
    Similar evolutionary pressures on gene expression between human and chimpanzee populations contribute to the observation that inter-individual gene expression variability is similar across genes in these species.
    1. Neuroscience

    An interactive meta-analysis of MRI biomarkers of myelin

    Matteo Mancini et al.
    Most MRI-based myelin biomarkers are not statistically different regarding their relationship with histology.
    1. Neuroscience

    Modulation of sleep-courtship balance by nutritional status in Drosophila

    José M Duhart et al.
    The sleep-courtship balance in Drosophila males is modulated by yeast/protein availability, and dopaminergic neurons projecting to the protocerebral bridge act downstream of courtship-regulating neurons for male sleep regulation.
    1. Developmental Biology

    Neuronal octopamine signaling regulates mating-induced germline stem cell increase in female Drosophila melanogaster

    Yuto Yoshinari et al.
    Genetic analyses using the fruit fly illustrate how neuronal system couples germline stem cell increase to an external cue, which is mating, through stem cell niche signaling.
    1. Computational and Systems Biology
    2. Structural Biology and Molecular Biophysics

    Investigating the trade-off between folding and function in a multidomain Y-family DNA polymerase

    Xiakun Chu et al.
    The physical interaction network encoded in the multi-domain protein native structure handles the trade-off between the fast, stable folding and the efficient, reliable function.
    1. Chromosomes and Gene Expression
    2. Neuroscience

    Conditional protein tagging methods reveal highly specific subcellular distribution of ion channels in motion-sensing neurons

    Sandra Fendl et al.
    New protein labeling strategies unravel the subcellular distribution of neurotransmitter receptor subunits and voltage-gated ion channels in motion-sensing T4/T5 neurons of the Drosophila visual system.
    1. Ecology
    2. Evolutionary Biology

    Sex-specific effects of cooperative breeding and colonial nesting on prosociality in corvids

    Lisa Horn et al.
    A systematic experimental comparison of prosocial behavior in eight corvid species reveals sex-specific effects of cooperative breeding and colonial nesting, thereby adding important new insights regarding the evolution of prosociality.
    1. Neuroscience

    Functional links between sensory representations, choice activity, and sensorimotor associations in parietal cortex

    Ting-Yu Chang et al.
    The fidelity of 3D visual object representations, choice-related activity, and experience-dependent sensorimotor associations are functionally linked in the caudal intraparietal area.
    1. Developmental Biology

    Multiscale cardiac imaging spanning the whole heart and its internal cellular architecture in a small animal model

    Graham Rykiel et al.
    Correlative imaging of the heart at multiple spatial scales has the potential to revolutionize the way we understand deficiencies in congenital heart disease.
    1. Cell Biology
    2. Neuroscience

    A feedback loop governs the relationship between lipid metabolism and longevity

    Nicole K Littlejohn et al.
    The dual control of adiposity and longevity emerges from a latent intestinal feedback loop which simultaneously augments fat loss and shields lifespan from the deleterious effects of continuous fat oxidation.
    1. Neuroscience

    Cannabinoids modulate associative cerebellar learning via alterations in behavioral state

    Catarina Albergaria et al.
    Cannabinoid receptors modulate cerebellar learning, not through direct effects on synaptic plasticity, but as a secondary consequence of their modulation of behavioral state.
    1. Cell Biology
    2. Plant Biology

    Photosynthetic sea slugs induce protective changes to the light reactions of the chloroplasts they steal from algae

    Vesa Havurinne, Esa Tyystjärvi
    Slug chloroplasts avoid damage to photosynthesis by maintaining an oxidized electron transfer chain with the help of oxygen-sensitive electron acceptors.
    1. Cell Biology

    Identification of ubiquitin Ser57 kinases regulating the oxidative stress response in yeast

    Nathaniel L Hepowit et al.
    Ser57 phosphorylation of ubiquitin protects the cell during proteotoxic stress.
    1. Neuroscience

    Feeding state functionally reconfigures a sensory circuit to drive thermosensory behavioral plasticity

    Asuka Takeishi et al.
    Starvation modulates thermotaxis behaviors in C. elegans via functional reconfiguration of a sensory network by gut-brain signaling.
    1. Cancer Biology

    Replication Study: Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs

    Hongyan Wang et al.
    Editors' Summary: This Replication Study did not reproduce those experiments in the original paper that it attempted to reproduce.
    1. Genetics and Genomics

    Amino acid synthesis loss in parasitoid wasps and other hymenopterans

    Xinhai Ye et al.
    The synthesis capability of some amino acids is lost during the insect evolution, and hymenopteran parasitoids can make up for these deficiencies by altering free amino acid concentrations in host.
    1. Epidemiology and Global Health
    2. Microbiology and Infectious Disease

    Intestinal microbiology shapes population health impacts of diet and lifestyle risk exposures in Torres Strait Islander communities

    Fredrick M Mobegi et al.
    Host-microbe interactions are an important influence on changing disease burdens in vulnerable remote communities.
    1. Neuroscience

    Neural encoding of task-dependent errors during adaptive learning

    Chang-Hao Kao et al.
    Posterior parietal cortex encodes errors in a task-dependent manner while a large array of frontal regions predict subsequent behavioral changes in response to ambiguous errors.
    1. Cell Biology
    2. Neuroscience

    Burst mitofusin activation reverses neuromuscular dysfunction in murine CMT2A

    Antonietta Franco et al.
    A trial of mitofusin activation shows neuron regeneration and phenotype reversal in vitro and in vivo in experimental Charcot–Marie–Tooth disease type 2A caused by mitofusin 2 mutations.
    1. Medicine
    2. Neuroscience

    APOE2 is associated with longevity independent of Alzheimer’s disease

    Mitsuru Shinohara et al.
    Translational evidence indicates APOE2 benefits longevity independent of its protective effects on Alzheimer’s disease, which preserved activity and the metabolism of apoE protein and associated-lipids would be key to understanding.
    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    NAIP–NLRC4-deficient mice are susceptible to shigellosis

    Patrick S Mitchell et al.
    The NAIP-NLRC4 inflammasome in intestinal epithelial cells protects mice from oral route Shigella infection.
    1. Microbiology and Infectious Disease
    2. Plant Biology

    A virus-encoded protein suppresses methylation of the viral genome through its interaction with AGO4 in the Cajal body

    Liping Wang et al.
    The Cajal body is essential for plants to deploy antiviral DNA methylation.
    1. Medicine

    Postnatal mechanical loading drives adaptation of tissues primarily through modulation of the non-collagenous matrix

    Danae E Zamboulis et al.
    Phase-specific mechanical and proteomic analyses reveal how tendon responds to its mechanical environment during postnatal development to meet functional requirements.
    1. Genetics and Genomics
    2. Medicine

    Effects of lifelong testosterone exposure on health and disease using Mendelian randomization

    Pedrum Mohammadi-Shemirani et al.
    Long-term increased testosterone improved body composition and bone density, but lowered HDL and raised risks of hypertension, androgenic alopecia, prostate cancer, and spinal stenosis in males.
    1. Developmental Biology
    2. Evolutionary Biology

    Secondary ossification center induces and protects growth plate structure

    Meng Xie et al.
    The principle underlying the appearance of the growth plate, an organ responsible for longitudinal growth, has implications for various cartilage pathologies including growth abnormalities in children, trauma and osteoarthritis.
    1. Immunology and Inflammation
    2. Stem Cells and Regenerative Medicine

    Macrophages promote endothelial-to-mesenchymal transition via MT1-MMP/TGFβ1 after myocardial infarction

    Laura Alonso-Herranz et al.
    Macrophage production of MT1-MMP upon MI contributes to adverse cardiac remodeling and worsened function by promoting EndMT via TGFB, suggesting MT1-MMP inhibition as a therapeutic option for patients with MI.
    1. Evolutionary Biology
    2. Genetics and Genomics

    A natural variant of the essential host gene MMS21 restricts the parasitic 2-micron plasmid in Saccharomyces cerevisiae

    Michelle Hays et al.
    A novel assay to measure 2-micron stability together with a survey of natural variation among Saccharomyces cerevisiae strains reveals novel means by which yeasts can combat the parasitic 2-micron plasmids.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    High-resolution structures of multiple 5-HT3AR-setron complexes reveal a novel mechanism of competitive inhibition

    Sandip Basak et al.
    Cryo-electron microscopic structures of 5-HT3A receptor in complex with first and second generations of clinically used setron reveal the molecular basis for their binding modes and mechanisms of inhibitory action.
    1. Medicine

    Weight loss, insulin resistance, and study design confound results in a meta-analysis of animal models of fatty liver

    Harriet Hunter et al.
    Animal studies of fatty liver disease over-estimate the benefit of drugs due to publication bias and are confounded by off-target weight loss, illustrating the challenge of successful translational across species.
    1. Biochemistry and Chemical Biology

    Modular metabolite assembly in Caenorhabditis elegans depends on carboxylesterases and formation of lysosome-related organelles

    Henry H Le et al.
    Caenorhabditis elegans homologs of carboxylesterases that localize to intestinal organelles orchestrate the assembly of modular signaling molecules from building blocks that integrate diverse metabolic pathways.
    1. Computational and Systems Biology
    2. Evolutionary Biology

    Evolution of multicellularity by collective integration of spatial information

    Enrico Sandro Colizzi et al.
    Selection for undifferentiated multicellularity emerges in an evolutionary cell-based model because a collective of cells performs chemotaxis better than single cells in a noisy environment.
    1. Neuroscience

    Typical and atypical language brain organization based on intrinsic connectivity and multitask functional asymmetries

    Loïc Labache et al.
    Left-hander's atypical language brain organization, revealed by task-induced rightward asymmetry, is underpinned at rest by homotopic networks wired for language bilaterally and strong intrinsic connectivity through a large corpus callosum.
    1. Neuroscience

    A MAC2-positive progenitor-like microglial population is resistant to CSF1R inhibition in adult mouse brain

    Lihong Zhan et al.
    A hidden population of microglial progenitors with distinct transcriptomic signatures are among homeostatic microglia in adult mouse brain.
    1. Neuroscience

    Divergent projections of the prelimbic cortex bidirectionally regulate active avoidance

    Maria M Diehl et al.
    Projections from the prelimbic prefrontal cortex targeting the ventral striatum or the basolateral amygdala bidirectionally regulate platform-mediated active avoidance in rats.
    1. Cell Biology
    2. Plant Biology

    Parallel global profiling of plant TOR dynamics reveals a conserved role for LARP1 in translation

    M Regina Scarpin et al.
    Plants and humans use a shared mechanism, the eukaryotic metabolic sensor TARGET OF RAPAMYCIN protein kinase and its substrate, an RNA-binding protein called LARP1, to coordinate post-transcriptional gene expression.
    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    GATA6 mutations in hiPSCs inform mechanisms for maldevelopment of the heart, pancreas, and diaphragm

    Arun Sharma et al.
    Analyses of human stem cells with distinct GATA6 mutations revealed a spectrum of molecular responses that drive isolated congenital heart disease or the co-occurrence of pancreas and diaphragm malformations.
    1. Cell Biology

    Single-cell dynamics of pannexin-1-facilitated programmed ATP loss during apoptosis

    Hiromi Imamura et al.
    Cleavage of pannexin-1 channel by caspases facilitates the loss of intracellular ATP level and attenuates glycolytic metabolism of apoptotic cells.
    1. Physics of Living Systems

    Diffusion vs. direct transport in the precision of morphogen readout

    Sean Fancher, Andrew Mugler
    A theory predicts whether diffusion or direct transport establishes a more precise morphogen profile, and this prediction explains data from a wide variety of morphogens in two different organisms.
    1. Developmental Biology

    Cytoplasmic sharing through apical membrane remodeling

    Nora G Peterson et al.
    Apical membrane remodeling in a resorptive Drosophila epithelium generates a shared multinuclear cytoplasm.
    1. Immunology and Inflammation
    2. Physics of Living Systems

    Label-free imaging of immune cell dynamics in the living retina using adaptive optics

    Aby Joseph et al.
    Immune cell motility and vascular response are imaged in vivo and label free in the CNS for the first time, using high-resolution phase-contrast adaptive optics retinal imaging.
    1. Immunology and Inflammation

    Critical role of WNK1 in MYC-dependent early mouse thymocyte development

    Robert Köchl et al.
    Development of mouse thymocytes through the pre-TCR checkpoint requires WNK1 kinase signalling via the OXSR1 and STK39 kinases and the SLC12A2 ion co-transporter leading to MYC-dependent cell proliferation.
    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    3D visualization of macromolecule synthesis

    Timothy J Duerr et al.
    Whole mount 3D visualization of macromolecule synthesis with light sheet fluorescence microscopy enables quantitative, multiscale analysis at the organ, cellular, and molecular levels of organization.
    1. Cell Biology
    2. Genetics and Genomics

    Cytoprotection by a naturally occurring variant of ATP5G1 in Arctic ground squirrel neural progenitor cells

    Neel S Singhal et al.
    A genetic basis underlying cell resilience against metabolic stress in cells of a hibernator, Arctic ground squirrels, has been discovered.
    1. Neuroscience

    Dopaminergic and opioidergic regulation during anticipation and consumption of social and nonsocial rewards

    Sebastian Korb et al.
    Administration of dopamine and opioid receptor antagonists resulted in reduced reward anticipation (effort and increased negative facial reactions), but only administration of opioid antagonists resulted in reduced liking (facial reactions).
    1. Cancer Biology
    2. Computational and Systems Biology

    Dynamics of nevus development implicate cell cooperation in the growth arrest of transformed melanocytes

    Rolando Ruiz-Vega et al.
    Spontaneous growth arrest of transformed melanocytes (resulting in benign “moles”) does not result from cell-autonomous oncogene-induced senescence, but can be explained by collective mechanisms used in normal tissue size control.
    1. Developmental Biology
    2. Neuroscience

    Adrenergic activation modulates the signal from the Reissner fiber to cerebrospinal fluid-contacting neurons during development

    Yasmine Cantaut-Belarif et al.
    The Reissner fiber in the cerebrospinal fluid is required for a signal integrated by developing sensory neurons and modulated by catecholamines to control the embryo posterior axis morphogenesis.
    1. Microbiology and Infectious Disease
    2. Structural Biology and Molecular Biophysics

    Full-length Plasmodium falciparum myosin A and essential light chain PfELC structures provide new anti-malarial targets

    Dihia Moussaoui et al.
    The structure of full-length myosin A provides some hints about its atypical mechanism, and reveals that the light chain PfELC is a target to block malaria pathogenesis.
    1. Computational and Systems Biology
    2. Immunology and Inflammation

    Cytotoxic T cells swarm by homotypic chemokine signalling

    Jorge Luis Galeano Niño et al.
    Killer T cells swarm around tumour targets by accelerating the recruitment of distant T cells, which upon arrival and target engagement augment the chemotactic signal in a positive feedback loop.
    1. Cell Biology
    2. Chromosomes and Gene Expression

    Predicting the effect of statins on cancer risk using genetic variants from a Mendelian randomization study in the UK Biobank

    Paul Carter et al.
    Genetic evidence in humans suggests that statins reduce cancer risk via a cholesterol-independent pathway.
    1. Chromosomes and Gene Expression

    Exploring chromosomal structural heterogeneity across multiple cell lines

    Ryan R Cheng et al.
    Chromosomal structural ensembles are fluid yet are cell-type-specific, despite apparent disorder, appropriate collective variables uncover evidence of structural transitions associated with gene activity and cell differentiation.
    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    PRDM9 activity depends on HELLS and promotes local 5-hydroxymethylcytosine enrichment

    Yukiko Imai et al.
    Biochemical and genetic approaches uncover a chromatin remodeler for PRDM9 binding and the parallel local epigenetic modification of cytosines in mouse spermatocytes.
    1. Neuroscience

    Extended field-of-view ultrathin microendoscopes for high-resolution two-photon imaging with minimal invasiveness

    Andrea Antonini et al.
    Aberration correction using 3D microprinting in ultrathin microendoscopes allows two-photon imaging of large neuronal networks with homogeneously high spatial resolution and minimal invasiveness in the deep mouse brain.
    1. Neuroscience

    Retinotectal circuitry of larval zebrafish is adapted to detection and pursuit of prey

    Dominique Förster et al.
    The retinotectal map in zebrafish exhibits location-specific, functional specializations to match prey object movement in the visual field during the hunting sequence.
    1. Medicine
    2. Microbiology and Infectious Disease

    Early prediction of level-of-care requirements in patients with COVID-19

    Boran Hao et al.
    Using data for 2566 COVID-19 patients from five hospitals, models are developed to predict for each patient hospitalization and critical care needs, based on demographics, comorbidities, medications, and laboratory findings.
    1. Neuroscience

    DMT alters cortical travelling waves

    Andrea Alamia et al.
    Psychedelics induce a pattern of cortical activity very similar to the one observed during visual perception, despite participants had shut eyes.
    1. Neuroscience

    Natural ITD statistics predict human auditory spatial perception

    Rodrigo Pavão et al.
    Human brain has incorporated natural statistics of spatial cues to the neural code supporting perception of sound location.
    1. Medicine
    2. Stem Cells and Regenerative Medicine

    Lysosomal protein surface expression discriminates fat- from bone-forming human mesenchymal precursor cells

    Jiajia Xu et al.
    CD107a expression divides osteogenic from adipogenic perivascular precursor cells within human white adipose tissue.
    1. Neuroscience

    Rapid purification and metabolomic profiling of synaptic vesicles from mammalian brain

    Lynne Chantranupong et al.
    Extensive mass spectrometry-based profiling of polar metabolites within synaptic vesicles that are rapidly isolated either from cultured mouse neurons or directly from mouse brains reveals their neurotransmitter composition.
    1. Neuroscience

    Social dominance mediates behavioral adaptation to chronic stress in a sex-specific manner

    Stoyo Karamihalev et al.
    Social dominance has opposing effects on behavior following stress in male vs. female mice indicating an important role in sex differences in the stress response.
    1. Neuroscience

    Hippocampal inputs engage CCK+ interneurons to mediate endocannabinoid-modulated feed-forward inhibition in the prefrontal cortex

    Xingchen Liu et al.
    Endocannabinoids modulate ventral hippocampal inputs to the infralimbic prefrontal cortex by dampening feed-forward inhibition mediated by cholecystokinin-expressing (CCK+) interneurons onto layer 5 intratelencephalic (IT) cells.
    1. Biochemistry and Chemical Biology

    Genome-wide effects of the antimicrobial peptide apidaecin on translation termination in bacteria

    Kyle Mangano et al.
    Inhibition of bacterial protein synthesis by an antimicrobial peptide apidaecin triggers translation arrest at the stop codons, ribosome queuing and pervasive stop codon readthrough.
    1. Neuroscience

    Cadherin preserves cohesion across involuting tissues during C. elegans neurulation

    Kristopher M Barnes et al.
    A coordinated tissue movement during C. elegans central nervous system internalization reveals a novel role for HMR-1/cadherin in maintaining cohesion, and extends the concept of neurulation beyond vertebrates.
    1. Cell Biology

    PLK-1 promotes the merger of the parental genome into a single nucleus by triggering lamina disassembly

    Griselda Velez-Aguilera et al.
    The polo-like kinase (Plk1) phophorylates the C. elegans lamin LMN-1 to promote timely lamina disassembly, which is essential for the merging of the parental chromosomes at the beginning of life.
    1. Medicine

    Lack of airway submucosal glands impairs respiratory host defenses

    Lynda S Ostedgaard et al.
    Submucosal glands are critical for two key respiratory host defenses, bactericidal activity and mucociliary transport, in an animal model that has lungs like humans.
    1. Developmental Biology
    2. Immunology and Inflammation

    Eater cooperates with Multiplexin to drive the formation of hematopoietic compartments

    Gábor Csordás et al.
    The mutual interaction between the basement membrane protein Multiplexin and the phagocytosis receptor Eater expressed by the immune cells drives the formation and maintenance of the hematopoietic tissues in Drosophila.
    1. Cell Biology
    2. Biochemistry and Chemical Biology

    Feedback control of Wnt signaling based on ultrastable histidine cluster co-aggregation between Naked/NKD and Axin

    Melissa V Gammons et al.
    An unusual molecular mechanism has been revealed based on ultrastable histidine cluster co-aggregation underlying feedback control of an ancient cell communication pathway.
    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    RUNX1 marks a luminal castration-resistant lineage established at the onset of prostate development

    Renaud Mevel et al.
    The transcription factor RUNX1 marks a distinct lineage of luminal castration-resistant prostate cells established early during development and enriched in the periurethral region of adult mouse prostate.
    1. Cancer Biology
    2. Cell Biology

    Collagen-rich omentum is a premetastatic niche for integrin α2-mediated peritoneal metastasis

    Yen-Lin Huang et al.
    Inhibition of ITGA2-mediated cancer cell-collagen interaction or targeting focal adhesion kinase activity may present an opportunity for therapeutic intervention of metastatic spread in ovarian cancer.
    1. Microbiology and Infectious Disease

    Biofilms deform soft surfaces and disrupt epithelia

    Alice Cont et al.
    The growth of multicellular bacterial structures called biofilms generates forces that deform soft material substrates and disrupt epithelial cell layers, potentially mechanically damaging host tissue.
    1. Neuroscience

    Cerebellar patients have intact feedback control that can be leveraged to improve reaching

    Amanda M Zimmet et al.
    A control system model of cerebellar patients' movements provides insight into the cerebellum's role in reaching and informs a virtual reality intervention to improve patient reaches.
    1. Cancer Biology
    2. Cell Biology

    A versatile system to record cell-cell interactions

    Rui Tang et al.
    A novel reporter system that employs cell surface antigen-nanobody pairing enables physical interaction-dependent labeling and functional modification between diverse cell types.
    1. Developmental Biology
    2. Physics of Living Systems

    Nuclear crowding and nonlinear diffusion during interkinetic nuclear migration in the zebrafish retina

    Afnan Azizi et al.
    The evolving spatial distribution of nuclei between apical and basal surfaces of the developing retinal neuroepithelium is quantitatively described by a nonlinear diffusion equation accounting for crowding within the tissue.
    1. Neuroscience

    Optical control of ERK and AKT signaling promotes axon regeneration and functional recovery of PNS and CNS in Drosophila

    Qin Wang et al.
    Precise spatiotemporal optogenetic activation of ERK and AKT signaling pathways reveals neural repair mechanisms of the peripheral and central nervous systems in live Drosophila larvae.
    1. Microbiology and Infectious Disease

    Metabolic profiling during malaria reveals the role of the aryl hydrocarbon receptor in regulating kidney injury

    Michelle M Lissner et al.
    Illustrating the impact of host metabolism on infection outcome, loss of the aryl hydrocarbon receptor in radioresistant cells leads to heme-mediated kidney toxicity during malaria.
    1. Neuroscience

    Ubiquitin-dependent regulation of a conserved DMRT protein controls sexually dimorphic synaptic connectivity and behavior

    Emily A Bayer et al.
    The sex-specificity of a transcription factor required for sexual differentiation of a neural circuit is regulated by a novel post-transcriptional mechanism.
    1. Immunology and Inflammation

    The HIV-1 latent reservoir is largely sensitive to circulating T cells

    Joanna A Warren et al.
    HIV-specific T cells remain detectable for years in HIV-infected individuals on antiretroviral therapy and importantly, mostly (68%) recognize HIV viruses that have the capacity to rebound following treatment interruption.
    1. Neuroscience

    M2 cortex-dorsolateral striatum stimulation reverses motor symptoms and synaptic deficits in Huntington’s disease

    Sara Fernández-García et al.
    M2 cortex-dorsolateral striatum circuit is functionally altered in Huntington's disease and, by boosting its activity, we reverse symptoms at behavioral, physiological, and morphological level in symptomatic mice.
    1. Microbiology and Infectious Disease
    2. Structural Biology and Molecular Biophysics

    Ebola and Marburg virus matrix layers are locally ordered assemblies of VP40 dimers

    William Wan et al.
    Cryo-electron tomography reveals the structure and arrangement of the VP40 matrix protein lattice that mediates the formation of Ebola and Marburg virus particles.
    1. Neuroscience

    nNOS-expressing interneurons control basal and behaviorally evoked arterial dilation in somatosensory cortex of mice

    Christina T Echagarruga et al.
    The diameter of cortical arteries is not controlled by the overall neural activity, but rather by a subset of specialized neurons.
    1. Chromosomes and Gene Expression

    Reassessment of the involvement of Snord115 in the serotonin 2c receptor pathway in a genetically relevant mouse model

    Jade Hebras et al.
    Knockout of Snord115 has mild impact on expression and function of the serotonin 2C receptor.
    1. Chromosomes and Gene Expression
    2. Computational and Systems Biology

    Caenorhabditis elegans methionine/S-adenosylmethionine cycle activity is sensed and adjusted by a nuclear hormone receptor

    Gabrielle E Giese et al.
    Metabolic activity of the methionine/S-adenosylmethionine cycle is sensed and transcriptionally regulated by a nuclear hormone receptor in Caenorhabditis elegans in order to maintain metabolic homeostasis in a tightly controlled regime.
    1. Neuroscience

    Optogenetic inhibition-mediated activity-dependent modification of CA1 pyramidal-interneuron connections during behavior

    Igor Gridchyn et al.
    The optogenetic manipulation of hippocampal neuronal circuit activity revealed plastic changes of pyramidal-interneuron connections in behaving animals, which were primarily governed by the firing rate change of postsynaptic interneurons.
    1. Cancer Biology

    A powerful drug combination strategy targeting glutamine addiction for the treatment of human liver cancer

    Haojie Jin et al.
    Combination of glutaminase inhibitor CB-839 and ASCT2 inhibitor V-9302 showed efficient antitumor effect against glutamine addicted liver cancer cells via glutathione depletion and reactive oxygen species (ROS) induction.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Structural insights into mRNA reading frame regulation by tRNA modification and slippery codon–anticodon pairing

    Eric D Hoffer et al.
    Chemical modifications near the tRNA anticodon and specific mRNA–tRNA pairs combine to control the ribosomal three-nucleotide mRNA reading frame, essential for the sequential addition of amino acids into polypeptide chains.
    1. Cell Biology

    GAS5 protects against osteoporosis by targeting UPF1/SMAD7 axis in osteoblast differentiation

    Ming Li et al.
    GAS5 is related to osteoporosis by regulating the differentiation of bone marrow stromal cells that acts as a promising treatment target for osteoporosis.
    1. Genetics and Genomics
    2. Medicine

    Patient-specific genomics and cross-species functional analysis implicate LRP2 in hypoplastic left heart syndrome

    Jeanne L Theis et al.
    Hypoplastic left heart syndrome is reflected by reduced proliferative capacity of patient iPSC-derived cardiomyocytes and requires the activity of LRP2/APOB proteins, likely in conjunction with SHH and WNT signaling pathways.
    1. Neuroscience

    Pathway-specific dysregulation of striatal excitatory synapses by LRRK2 mutations

    Chuyu Chen et al.
    Although human Parkinson's disease is linked to dopamine loss, two distinct mutations in a kinase associated with familial Parkinson's operate downstream, altering excitatory synapses on dopamine-sensing neurons.
    1. Developmental Biology

    Gli3 utilizes Hand2 to synergistically regulate tissue-specific transcriptional networks

    Kelsey H Elliott et al.
    Context-dependent optimization of Gli-binding site occupancy, in the presence of Hand2, is critical for modulating tissue-specific transcriptional output within tissues that lack an obvious Hedgehog morphogen gradient.
    1. Neuroscience

    Vicarious reward unblocks associative learning about novel cues in male rats

    Sander van Gurp et al.
    Rats learn to interpret cues predicting rewards delivered to social partners as valuable, but only if social information exchange is possible.
    1. Evolutionary Biology
    2. Microbiology and Infectious Disease

    Dynamically evolving novel overlapping gene as a factor in the SARS-CoV-2 pandemic

    Chase W Nelson et al.
    A novel, overlapping, putatively functional gene in SARS-CoV-2, ORF3d, is absent from close relatives of SARS-CoV-2 and may have contributed to the biology, emergence, or spread of the virus.
    1. Developmental Biology
    2. Neuroscience

    Cadherins regulate nuclear topography and function of developing ocular motor circuitry

    Athene Knüfer et al.
    Cadherin-dependent cell adhesion controls the contralateral migration and clustering of ocular motor subpopulations and is required for the development of functional eye movements driven by those neurons.
    1. Developmental Biology
    2. Neuroscience

    Establishment and maintenance of motor neuron identity via temporal modularity in terminal selector function

    Yinan Li et al.
    The terminal selector-type transcription factor UNC-3/Ebf partially modifies the suite of its target genes at different life stages to establish and maintain the identity of C. elegans motor neurons.
    1. Cancer Biology

    Functional interrogation of HOXA9 regulome in MLLr leukemia via reporter-based CRISPR/Cas9 screen

    Hao Zhang et al.
    The HOXA9 reporter and genetic screens facilitated the functional interrogation of the HOXA9 regulome and advanced our understanding of the molecular regulation network in HOXA9-driven leukemia.
    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    Myogenin is an essential regulator of adult myofibre growth and muscle stem cell homeostasis

    Massimo Ganassi et al.
    Cellular and molecular analyses reveal how Myogenin controls muscle stem cell quiescence and growth of adult muscle fibres.
    1. Neuroscience

    Dopamine promotes instrumental motivation, but reduces reward-related vigour

    John P Grogan et al.
    Dopaminergic medication dissociates contingent motivation from reward expectation effects on invigoration of movements in PD patients, confirming they are separate processes with different dopaminergic functions.