February 2022

Cover articles

    1. Neuroscience

    Gestural communication and brain asymmetries in baboons

    Yannick Becker, Nicolas Claidière ... Adrien Meguerditchian
    1. Developmental Biology

    Epigenetic regulation during organogenesis in mice

    Tingwei Guo, Xia Han ... Yang Chai

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Research articles

    1. Neuroscience

    Perception is associated with the brain’s metabolic response to sensory stimulation

    Mauro DiNuzzo, Silvia Mangia ... Federico Giove
    Perceived and unperceived visual stimuli that are contrast matched to produce similar BOLD responses in V1 elicit clearly distinct changes in the neurochemical profile, implying a perception-related dissociation between neurometabolic and neurovascular response.
    1. Chromosomes and Gene Expression
    2. Microbiology and Infectious Disease

    Ribosome profiling of porcine reproductive and respiratory syndrome virus reveals novel features of viral gene expression

    Georgia M Cook, Katherine Brown ... Ian Brierley
    Combining ribosome profiling and RNA sequencing illuminates novel features of porcine reproductive and respiratory syndrome virus gene expression, including the regulation of polyprotein stoichiometry through temporal modulation of ribosomal frameshifting and the synthesis of non-canonical transcripts.
    1. Neuroscience

    Competition between parallel sensorimotor learning systems

    Scott T Albert, Jihoon Jang ... Reza Shadmehr
    When a common error drives parallel implicit and explicit learning systems, increases in the explicit response will suppress implicit adaptation.
    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    Identification of bipotent progenitors that give rise to myogenic and connective tissues in mouse

    Alexandre Grimaldi, Glenda Comai ... Shahragim Tajbakhsh
    Combined lineage-tracing strategies, single-cell transcriptomic methods and in situ analyses identified mesodermal bipotent progenitors during craniofacial myogenesis that give rise to myogenic and connective tissues, thus redefining the lineage and evolutionary relationships between muscle and associated stroma.
    1. Developmental Biology
    2. Genetics and Genomics

    Augmentation of progestin signaling rescues testis organization and spermatogenesis in zebrafish with the depletion of androgen signaling

    Gang Zhai, Tingting Shu ... Zhan Yin
    Augmentation of progestin signaling promotes testis development and spermatogenesis independent from andorgen signaling in zebrafish.
    1. Cancer Biology
    2. Chromosomes and Gene Expression

    Global and context-specific transcriptional consequences of oncogenic Fbw7 mutations

    H Nayanga Thirimanne, Feinan Wu ... Bruce E Clurman
    Genome-wide analyses reveal how tumor-associated mutations of the Fbw7 ubiquitin ligase impact oncogenic transcription factors and gene expression.
    1. Cell Biology
    2. Developmental Biology

    Apelin signaling dependent endocardial protrusions promote cardiac trabeculation in zebrafish

    Jialing Qi, Annegret Rittershaus ... Christian SM Helker
    Apelin signaling-dependent endocardial protrusions promote cardiac trabeculation through Nrg/ErbB/Erk signaling in zebrafish.
    1. Neuroscience

    Target-specific control of olfactory bulb periglomerular cells by GABAergic and cholinergic basal forebrain inputs

    Didier De Saint Jan
    Muscarinic excitation of a previously ignored subtype of periglomerular interneuron in the olfactory bulb by endogenous synaptic release of acetylcholine.
    1. Developmental Biology

    KDM6B interacts with TFDP1 to activate P53 signaling in regulating mouse palatogenesis

    Tingwei Guo, Xia Han ... Yang Chai
    A comprehensive analysis of mutant animal model shows the important role of KDM6B and how it cooperates with TFDP1 to achieve its functional specificity in regulating Trp53 expression to control the fate of cranial neural crest cells during palatogenesis.
    1. Genetics and Genomics
    2. Neuroscience

    Corticohippocampal circuit dysfunction in a mouse model of Dravet syndrome

    Joanna Mattis, Ala Somarowthu ... Ethan M Goldberg
    Electrophysiology, optogenetics, and imaging in a mouse model of Dravet syndrome reveals dentate gyrus circuit dysfunction driven by hyperexcitability of the perforant path input from entorhinal cortex that can be modulated by recruitment of parvalbumin-expressing inhibitory interneurons.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Structural basis for an unprecedented enzymatic alkylation in cylindrocyclophane biosynthesis

    Nathaniel R Braffman, Terry B Ruskoski ... Emily P Balskus
    The X-ray crystal structure of the unusual carbon–carbon bond-forming biosynthetic enzyme CylK reveals a unique biochemical strategy for selective alkyl halide activation and substitution.
    1. Cancer Biology
    2. Computational and Systems Biology

    Signature-scoring methods developed for bulk samples are not adequate for cancer single-cell RNA sequencing data

    Nighat Noureen, Zhenqing Ye ... Siyuan Zheng
    Dropouts in single cell RNA sequencing data are associated with cell states and can affect gene signature scoring if methods do not account for them.
    1. Neuroscience

    Blocking Kir6.2 channels with SpTx1 potentiates glucose-stimulated insulin secretion from murine pancreatic β cells and lowers blood glucose in diabetic mice

    Yajamana Ramu, Jayden Yamakaze ... Zhe Lu
    The centipede peptide toxin SpTx1 blocks the pore of ATP-sensitive potassium channels in pancreatic β cells to markedly enhance insulin secretion and mitigate hyperglycemia in diabetic mice insensitive to the anti-diabetic sulfonylurea glibenclamide.
    1. Developmental Biology
    2. Evolutionary Biology

    Architecture and evolution of the cis-regulatory system of the echinoderm kirrelL gene

    Jian Ming Khor, Charles A Ettensohn
    The transcriptional control system of a sea urchin gene reveals the deep evolutionary conservation of a gene regulatory network underlying morphogenesis.
    1. Microbiology and Infectious Disease
    2. Structural Biology and Molecular Biophysics

    Colicin E1 opens its hinge to plug TolC

    S Jimmy Budiardjo, Jacqueline J Stevens ... Joanna SG Slusky
    Bacterial warfare protein colicin E1 opens its hinge to plug antibiotic efflux pump TolC and potentiate antibiotics.
    1. Cell Biology
    2. Genetics and Genomics

    Targeting DNA topoisomerases or checkpoint kinases results in an overload of chaperone systems, triggering aggregation of a metastable subproteome

    Wouter Huiting, Suzanne L Dekker ... Steven Bergink
    Various genotoxic stresses trigger widespread aggregation of abundant, liquid-liquid phase separation-prone proteins, suggesting that genotoxic stress is a potential driver of disease-associated protein aggregation.
    1. Neuroscience

    Mechanisms of distributed working memory in a large-scale network of macaque neocortex

    Jorge F Mejías, Xiao-Jing Wang
    An anatomically constrained computational model of the macaque cortical network demonstrates the emergence of large-scale distributed patterns of mnemonic activity sustained by long-range cortico-cortical interactions.
    1. Neuroscience

    Impairing one sensory modality enhances another by reconfiguring peptidergic signalling in Caenorhabditis elegans

    Giulio Valperga, Mario de Bono
    Stimulus-receptivity loss increases coupling of a sensory neuron to a second sensory circuit by upregulating neuropeptide receptors, enhancing output of the second circuit, and providing a mechanism for cross-modal plasticity.
    1. Immunology and Inflammation
    2. Neuroscience

    Atmospheric particulate matter aggravates CNS demyelination through involvement of TLR-4/NF-kB signaling and microglial activation

    Bing Han, Xing Li ... Yuan Zhang
    An atmospheric trigger, the respirable particulate matter boost microglia pathogenic activities in the context of CNS demyelination by activating TLR-4/NF-kB signaling axis in animal models of immune- and toxicity-induced demyelination, as well as myelinogenesis during postnatal development.
    1. Immunology and Inflammation

    Galvanic current activates the NLRP3 inflammasome to promote Type I collagen production in tendon

    Alejandro Peñin-Franch, José Antonio García-Vidal ... Pablo Pelegrín
    Cellular, genetic, and biochemical assays shows that the application of a specific type of currents in mouse tendons induces an inflammatory response that favors the regeneration of the tissue, being a treatment for chronic tendinopathy lesions.
    1. Cell Biology
    2. Immunology and Inflammation

    Nanoscale binding site localization by molecular distance estimation on native cell surfaces using topological image averaging

    Vibha Kumra Ahnlide, Johannes Kumra Ahnlide ... Pontus Nordenfelt
    A method to carefully measure the molecular distance between a site of interest and a reference surface by the repeated acquisition of the two image channels followed by the statistical calculation of the relative difference.
    1. Cell Biology
    2. Immunology and Inflammation

    In vivo fluorescence lifetime imaging of macrophage intracellular metabolism during wound responses in zebrafish

    Veronika Miskolci, Kelsey E Tweed ... Anna Huttenlocher
    Lifetime imaging of endogenous metabolic coenzymes is sensitive to dynamic changes in macrophage activation in a live animal, providing a label-free imaging approach to study immunometabolism in vivo with single-cell, spatial, and temporal resolution.
    1. Biochemistry and Chemical Biology
    2. Physics of Living Systems

    Complex effects of kinase localization revealed by compartment-specific regulation of protein kinase A activity

    Rebecca LaCroix, Benjamin Lin ... Andre Levchenko
    The regulatory subunit of protein kinase A (PKA) can both activate and suppress the PKA activity at the plasma membrane, with its graded membrane localization capable of inducing a switch in cell migration.
    1. Neuroscience

    Humans perseverate on punishment avoidance goals in multigoal reinforcement learning

    Paul B Sharp, Evan M Russek ... Eran Eldar
    Humans perseverate on previously instructed goals in a novel multigoal reinforcement learning task, and do this to a greater extent for punishment avoidance goals.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Creation of photocyclic vertebrate rhodopsin by single amino acid substitution

    Kazumi Sakai, Yoshinori Shichida ... Takahiro Yamashita
    Through a single mutation at position 188, vertebrate rhodopsin acquires the ability to recover the dark state from the active state by a thermal reaction and by a photoreaction.
    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    Hydrop enables droplet-based single-cell ATAC-seq and single-cell RNA-seq using dissolvable hydrogel beads

    Florian V De Rop, Joy N Ismail ... Stein Aerts
    New open-source method contains all the tools for extracting open chromatin or RNA from thousands of single cells in parallel for <5% of the cost of state-of-the-art commercial alternatives, paving the way for whole-tissue atlasing and new protocol development.
    1. Immunology and Inflammation

    A non-bactericidal cathelicidin provides prophylactic efficacy against bacterial infection by driving phagocyte influx

    Yang Yang, Jing Wu ... Lin Wei
    New insight into non-bactericidal cathelicidin against bacterial infection.
    1. Structural Biology and Molecular Biophysics

    Identification of electroporation sites in the complex lipid organization of the plasma membrane

    Lea Rems, Xinru Tang ... Lucie Delemotte
    Advanced data analysis of molecular dynamics simulations of complex lipid membranes provides a quantitative and predictive model of the molecular features that control electroporation.
    1. Neuroscience

    Environmental enrichment enhances patterning and remodeling of synaptic nanoarchitecture as revealed by STED nanoscopy

    Waja Wegner, Heinz Steffens ... Katrin I Willig
    Two-color time-lapse superresolution imaging of the synaptic nanoorganization in vivo uncovers highly dynamic spine heads and PSD95 assemblies that are less variable in size but more dynamic in their PSD95 nanoorganization after environmental enrichment.
    1. Cell Biology
    2. Genetics and Genomics

    Spatial transcriptomic and single-nucleus analysis reveals heterogeneity in a gigantic single-celled syncytium

    Tobias Gerber, Cristina Loureiro ... J Gray Camp
    Nuclei of the true slime mold Physarum polycephalum are continuously shuttled within the cytoplasmic flow across the gigantic syncytium, yet Physarum can establish and maintain gene expression heterogeneity between different structures of the organism.
    1. Neuroscience

    Unsupervised learning of haptic material properties

    Anna Metzger, Matteo Toscani
    Perceptual haptic representation of materials emerges from unsupervised learning as a consequence of efficient encoding of the physical signals at the input of tactile sensory system.
    1. Developmental Biology
    2. Physics of Living Systems

    Optogenetic inhibition of actomyosin reveals mechanical bistability of the mesoderm epithelium during Drosophila mesoderm invagination

    Hanqing Guo, Michael Swan, Bing He
    Combined optogenetic and computer modeling approaches reveal how mechanical bistability of the mesoderm epithelium works jointly with apical constriction to facilitate mesoderm invagination in Drosophila, a well-characterized model for epithelial folding.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    PEAR, a flexible fluorescent reporter for the identification and enrichment of successfully prime edited cells

    Dorottya Anna Simon, András Tálas ... Ervin Welker
    Prime editor activity reporter (PEAR) is a flexible fluorescent reporter that identifies and enriches prime edited cells.
    1. Plant Biology

    Host casein kinase 1-mediated phosphorylation modulates phase separation of a rhabdovirus phosphoprotein and virus infection

    Xiao-Dong Fang, Qiang Gao ... Xian-Bing Wang
    Liquid-liquid phase separation of a rhabovirus phosphoprotein initiates viral factory formation of barley yellow striate mosaic virus, a plant negative-sense RNA virus, and host casein kinase 1-mediated phosphorylation inhibits phase separation and virus infection.
    1. Biochemistry and Chemical Biology
    2. Chromosomes and Gene Expression

    MicroRNA 3′-compensatory pairing occurs through two binding modes, with affinity shaped by nucleotide identity and position

    Sean E McGeary, Namita Bisaria ... David P Bartel
    Affinity measurements of microRNA sites representing >1000 different pairing architectures reveal that two binding modes can mediate pairing to the microRNA 3′ region, and that microRNA G and oligo(G/C) residues are most impactful.
    1. Evolutionary Biology

    An estimate of the deepest branches of the tree of life from ancient vertically evolving genes

    Edmund RR Moody, Tara A Mahendrarajah ... Tom A Williams
    Relatively few genes have evolved vertically from the last universal common ancestor to modern prokaryotes, and phylogenetic analysis of these genes demonstrates a great genetic distance between Archaea and Bacteria.
    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    SARS-CoV2 variant-specific replicating RNA vaccines protect from disease following challenge with heterologous variants of concern

    David W Hawman, Kimberly Meade-White ... Jesse H Erasmus
    A replicating RNA vaccine platform generated significant immunity against SARS-CoV2 in mice and hamsters, and can be updated to target variants of concern.
    1. Neuroscience

    A dentate gyrus-CA3 inhibitory circuit promotes evolution of hippocampal-cortical ensembles during memory consolidation

    Hannah Twarkowski, Victor Steininger ... Amar Sahay
    Parvalbumin inhibitory neuron-mediated feed-forward inhibition in dentate gyrus-CA3 circuit governs time-dependent re-organization of memory traces in hippocampal-cortical networks to support systems consolidation.
    1. Chromosomes and Gene Expression

    Epigenetic reprogramming by TET enzymes impacts co-transcriptional R-loops

    João C Sabino, Madalena R de Almeida ... Sérgio Fernandes de Almeida
    The deposition of 5-hydroxymethylcytosine epigenetic marks in active genes promotes the annealing of the nascent RNA to the template DNA strand, forming an R-loop.
    1. Neuroscience

    Frequency- and spike-timing-dependent mitochondrial Ca2+ signaling regulates the metabolic rate and synaptic efficacy in cortical neurons

    Ohad Stoler, Alexandra Stavsky ... Ilya Fleidervish
    Optical recordings from L5 cortical pyramidal neurons expressing mitochondria-targeted Ca2+ indicator, mitoGCaMP6m, reveal compartment-specific mitochondrial responses to spike firing and synaptic activity.
    1. Computational and Systems Biology
    2. Genetics and Genomics

    Host ecology regulates interspecies recombination in bacteria of the genus Campylobacter

    Evangelos Mourkas, Koji Yahara ... Samuel K Sheppard
    Horizontal gene transfer can potentially merge genomes from distinct bacterial species, but isolation in different hosts creates a physical barrier to gene flow.
    1. Ecology

    Using aquatic animals as partners to increase yield and maintain soil nitrogen in the paddy ecosystems

    Liang Guo, Lufeng Zhao ... Xin Chen
    Aquatic animals cocultured with rice in paddy ecosystems can increase food production, improve nitrogen (N)-use efficiency, and maintain soil fertility by reducing weeds, and promoting recycle and complementary use of N.
    1. Cancer Biology

    A survey of optimal strategy for signature-based drug repositioning and an application to liver cancer

    Chen Yang, Hailin Zhang ... Hui Wang
    Computational and experimental analyses show that homoharringtonine may be repurposed as an agent for the treatment and prevention of liver cancer.
    1. Developmental Biology
    2. Neuroscience

    Diversification of multipotential postmitotic mouse retinal ganglion cell precursors into discrete types

    Karthik Shekhar, Irene E Whitney ... Joshua R Sanes
    Single-cell transcriptomic analysis of developing retinal ganglion cells in mice suggests that their diversification into 45 discrete types occurs via the gradual restriction of multipotential precursors.
    1. Immunology and Inflammation
    2. Neuroscience

    TREM2 regulates purinergic receptor-mediated calcium signaling and motility in human iPSC-derived microglia

    Amit Jairaman, Amanda McQuade ... Michael D Cahalan
    Deletion of Alzheimer’s disease risk gene TREM2 augments sensitivity to the purinergic agonist ADP, leading to increased Ca2+ influx and reduced directional migration in human induced pluripotent stem cell-derived microglia.
    1. Evolutionary Biology
    2. Physics of Living Systems

    In vivo intraoral waterflow quantification reveals hidden mechanisms of suction feeding in fish

    Pauline Provini, Alexandre Brunet ... Sam Van Wassenbergh
    The integration of biplanar X-ray videos with 3D X-ray particle tracking revealed that fish use a combination of intraoral 'central jet' waterflow pattern and inertia to guide food toward the digestive tract during suction feeding.
    1. Immunology and Inflammation

    The oxygen sensor prolyl hydroxylase domain 2 regulates the in vivo suppressive capacity of regulatory T cells

    Yousra Ajouaou, Abdulkader Azouz ... Oberdan Leo
    The prolyl hydroxylase domain 2 regulates the Treg development and function in a hypoxia-inducible factor 2α-dependent manner.
    1. Neuroscience

    Low doses of the organic insecticide spinosad trigger lysosomal defects, elevated ROS, lipid dysregulation, and neurodegeneration in flies

    Felipe Martelli, Natalia H Hernandes ... Hugo J Bellen
    The organic insecticide spinosad severely impacts metabolism, the cell biology, and the visual system of the model insect Drosophila, suggesting that it poses a threat to other non-pest insect exposed to it in the field.
    1. Evolutionary Biology
    2. Microbiology and Infectious Disease

    Parallel evolution of Pseudomonas aeruginosa phage resistance and virulence loss in response to phage treatment in vivo and in vitro

    Meaghan Castledine, Daniel Padfield ... Angus Buckling
    Parallel evolutionary dynamics were found in vivo and in vitro, showing that laboratory studies can be predictive of certain phenotypic outcomes of clinical phage therapy (phage-mediated decolonization).
    1. Neuroscience

    Telencephalic outputs from the medial entorhinal cortex are copied directly to the hippocampus

    Sau Yee Tsoi, Merve Öncül ... Gülşen Sürmeli
    A novel pathway from the deep entorhinal cortex to the hippocampus suggests that the hippocampal–neocortical loop is supported by a feedback projection from the entorhinal deep layers that copies entorhinal output to the hippocampus.
    1. Neuroscience

    Paradoxical neuronal hyperexcitability in a mouse model of mitochondrial pyruvate import deficiency

    Andres De La Rossa, Marine H Laporte ... Jean-Claude Martinou
    Glutamatergic neurons lacking the mitochondrial pyruvate carrier show reduced M-type potassium channel activity and hyperexcitability upon intense firing.
    1. Physics of Living Systems

    Epithelial-to-mesenchymal transition proceeds through directional destabilization of multidimensional attractor

    Weikang Wang, Dante Poe ... Jianhua Xing
    Integrated live cell imaging and image analyses in the framework of transition path theories identify epithelial-to-mesenchymal transition proceeds through parallel paths.
    1. Cell Biology

    P2Y1 purinergic receptor identified as a diabetes target in a small-molecule screen to reverse circadian β-cell failure

    Biliana Marcheva, Benjamin J Weidemann ... Joseph Bass
    A genetically sensitized drug screen identifies a circadian diabetes target and establishes a novel discovery pathway to treat β-cell failure.
    1. Computational and Systems Biology
    2. Genetics and Genomics

    STAT3-mediated allelic imbalance of novel genetic variant Rs1047643 and B-cell-specific super-enhancer in association with systemic lupus erythematosus

    Yanfeng Zhang, Kenneth Day, Devin M Absher
    Genetic analyses reveal biological insight of a novel risk locus into systemic lupus erythematosus susceptibility.
    1. Immunology and Inflammation

    Thymocytes trigger self-antigen-controlling pathways in immature medullary thymic epithelial stages

    Noella Lopes, Nicolas Boucherit ... Magali Irla
    Self-reactive CD4+ thymocytes have a broad impact on the composition of medullary thymic epithelial cell (mTEC) subsets by acting upstream of Aire+ mTECs, which conditions the induction of T-cell tolerance.
    1. Physics of Living Systems

    Cellular organization in lab-evolved and extant multicellular species obeys a maximum entropy law

    Thomas C Day, Stephanie S Höhn ... Peter J Yunker
    The distributions of cellular neighborhood volumes in two very different multicellular species - snowflake yeast and Volvox carteri - are found to obey a common functional form arising from maximum entropy consideration, despite great differences in their cell division processes.
    1. Developmental Biology
    2. Neuroscience

    Slow oscillation–spindle coupling strength predicts real-life gross-motor learning in adolescents and adults

    Michael A Hahn, Kathrin Bothe ... Kerstin Hoedlmoser
    Individualized cross-frequency analyses reveal regionally specific slow oscillation–sleep spindle coupling precision as predictor for gross-motor learning dynamics.
    1. Epidemiology and Global Health
    2. Genetics and Genomics

    Environmentally sensitive hotspots in the methylome of the early human embryo

    Matt J Silver, Ayden Saffari ... Andrew M Prentice
    259 CpGs associated with season of conception in rural Gambians constitute a valuable resource for investigating epigenetic mechanisms linking early exposures to lifelong health and disease.
    1. Genetics and Genomics

    Application of ATAC-Seq for genome-wide analysis of the chromatin state at single myofiber resolution

    Korin Sahinyan, Darren M Blackburn ... Vahab D Soleimani
    Single myofiber ATAC-Seq provides assessment of chromatin accessibility of a single myofiber without the confounding effects of other cell types present in skeletal muscle.
    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    Human spinal cord in vitro differentiation pace is initially maintained in heterologous embryonic environments

    Alwyn Dady, Lindsay Davidson ... Kate G Storey
    Comparison of human spinal cord rosette differentiation in vitro and following transplantation into heterologous embryonic environments, reveals cell-intrinsic constraint on human differentiation pace and the importance of timely extrinsic signalling for progression through an intrinsic human neural differentiation programme.
    1. Cell Biology

    Pseudohypoxic HIF pathway activation dysregulates collagen structure-function in human lung fibrosis

    Christopher J Brereton, Liudi Yao ... Mark G Jones
    Oxygen-independent (pseudohypoxic) HIF pathway activation is a core determinant of dysregulated collagen-structure function in human fibrosis.
    1. Evolutionary Biology

    A meta-analysis of the association between male dimorphism and fitness outcomes in humans

    Linda H Lidborg, Catharine Penelope Cross, Lynda G Boothroyd
    While men’s mating success is predicted both by their strength/muscularity, voice pitch, height, and testosterone levels, their reproductive output is only predicted by strength/muscularity.
    1. Cell Biology

    Quantitative mapping of keratin networks in 3D

    Reinhard Windoffer, Nicole Schwarz ... Rudolf E Leube
    Based on 3D visualization of fluorescently labeled cytoskeletal networks, an imaging platform is provided, which allows 3D network reconstruction, immersive visualization and quantification of local network properties serving as blueprints for functional modeling.
    1. Structural Biology and Molecular Biophysics

    Cryo-EM structures reveal high-resolution mechanism of a DNA polymerase sliding clamp loader

    Christl Gaubitz, Xingchen Liu ... Brian A Kelch
    Cryo-EM structures of the eukaryotic clamp loader illustrate the large conformational changes that the clamp loader ATPase undergoes to open the circular sliding clamp and place it onto primer–template DNA.
    1. Cell Biology
    2. Developmental Biology

    The transcription factor Xrp1 orchestrates both reduced translation and cell competition upon defective ribosome assembly or function

    Marianthi Kiparaki, Chaitali Khan ... Nicholas E Baker
    Ribosomal protein mutations, mutations that affect ribosomal RNA synthesis, or function of the mature ribosome, trigger a transcriptional response mediated by Xrp1 expression which reduces cellular translation via eIF2-alpha phosphorylation and renders cells liable to competition with wild-type neighbors.
    1. Genetics and Genomics

    Mosaic cis-regulatory evolution drives transcriptional partitioning of HERVH endogenous retrovirus in the human embryo

    Thomas A Carter, Manvendra Singh ... Cédric Feschotte
    A 'phyloregulatory' approach reveals how human endogenous retrovirus type-H, a family of human endogenous retroviruses, diversified its regulatory sequences through multiple mutational mechanisms to partition its transcriptional activity spatially and temporally within the human embryo.
    1. Ecology
    2. Immunology and Inflammation

    Hematodinium sp. infection does not drive collateral disease contraction in a crustacean host

    Charlotte E Davies, Jessica E Thomas ... Christopher J Coates
    Neither the presence nor the intensity of Hematodinium sp. parasitisation drives co-infection occurrence, severity, or diversity in the ecologically ubiquitous shore crab, Carcinus maenas.
    1. Neuroscience

    Influence of sensory modality and control dynamics on human path integration

    Akis Stavropoulos, Kaushik J Lakshminarasimhan ... Dora E Angelaki
    Human path integration accuracy is strongly influenced by the underlying control dynamics, but less so when visual, rather than vestibular, feedback is available.
    1. Neuroscience

    The m6A reader YTHDF2 is a negative regulator for dendrite development and maintenance of retinal ganglion cells

    Fugui Niu, Peng Han ... Sheng-Jian Ji
    The m6A reader YTHDF2 negatively regulates retinal ganglion cell dendrite branching through destabilizing its m6A-modified target mRNAs which control dendrite development and maintenance, and Ythdf2 conditional knockout in retina improves visual acuity and alleviates acute ocular hypertension-induced glaucoma in mice.
    1. Developmental Biology

    Hypertrophic chondrocytes serve as a reservoir for marrow-associated skeletal stem and progenitor cells, osteoblasts, and adipocytes during skeletal development

    Jason T Long, Abigail Leinroth ... Matthew J Hilton
    Hypertrophic chondrocytes of the growth plate undergo a process of dedifferentiation to generate marrow associated skeletal stem and progenitor cells (SSPCs), which ultimately re-differentiate into cells of the osteoblast or adipocyte lineages during skeletal development.
    1. Neuroscience

    Cannabidiol activates neuronal Kv7 channels

    Han-Xiong Bear Zhang, Laurel Heckman ... Bruce P Bean
    The phytocannabinoid cannabidiol, an antiepileptic agent whose molecular targets are unclear, was found to potently enhance current carried by cloned human Kv7.2/7.3 channels and native M-current in mouse and rat neurons.
    1. Cell Biology
    2. Neuroscience

    Visualizing cellular and tissue ultrastructure using Ten-fold Robust Expansion Microscopy (TREx)

    Hugo GJ Damstra, Boaz Mohar ... Paul W Tillberg
    Ten-fold Robust Expansion Microscopy (TREx) is a new method for 10-fold physical expansion of specimens in one round of gel embedding, enabling nanoscale imaging of antibody stains and ultrastructural detail.
    1. Developmental Biology
    2. Neuroscience

    Transcriptional heterogeneity of ventricular zone cells in the ganglionic eminences of the mouse forebrain

    Dongjin R Lee, Christopher Rhodes ... Timothy J Petros
    Single-cell sequencing combined with in situ hybridizations reveal dynamic patterns of differentially expressed genes throughout the ventricular and subventricular zone of the embryonic mouse brain, which likely play important roles in cell fate determination.
    1. Physics of Living Systems

    Glycan processing in the Golgi as optimal information coding that constrains cisternal number and enzyme specificity

    Alkesh Yadav, Quentin Vagne ... Madan Rao
    A mathematical model of glycosylation in the Golgi apparatus to investigate how the fidelity of synthesising a complex glycan distribution at the plasma membrane depends on parameters such as the number of Golgi cisternae or enzyme specificity.
    1. Chromosomes and Gene Expression
    2. Developmental Biology

    Allele-specific gene expression can underlie altered transcript abundance in zebrafish mutants

    Richard J White, Eirinn Mackay ... Elisabeth M Busch-Nentwich
    Allele-specific gene expression can affect the results and interpretation of transcriptomic analyses in zebrafish mutants and has broader implications for work in other outbred organisms.
    1. Microbiology and Infectious Disease

    Legionella pneumophila regulates host cell motility by targeting Phldb2 with a 14-3-3ζ-dependent protease effector

    Lei Song, Jingjing Luo ... Zhao-Qing Luo
    A novel bacterial protease activated by a eukaryote-specific factor attacks a host protein involved in cytoskeleton organization to inhibit cell migration during Legionella pneumophila infection.
    1. Ecology

    Mapping the functional connectivity of ecosystem services supply across a regional landscape

    Rachel D Field, Lael Parrott
    Mapping functional relationships between multiple ecosystem services (ES) reveals previously unidentified areas of high ES value, which suggests that the spatial focus of planning for optimal ES provisioning may shift when relationships between several ES are considered.
    1. Neuroscience

    Different computations over the same inputs produce selective behavior in algorithmic brain networks

    Katarzyna Jaworska, Yuening Yan ... Philippe G Schyns
    Four stages of linear and nonlinear computations in hierarchical dynamic brain networks progressively transform the same two visual inputs into the task-specific XOR, AND, and OR behavioral responses.
    1. Microbiology and Infectious Disease

    Discovery of coordinately regulated pathways that provide innate protection against interbacterial antagonism

    See-Yeun Ting, Kaitlyn D LaCourse ... Joseph D Mougous
    Pseudomonas aeruginosa defends against interbacterial antagonism through the coordinated expression of previously uncharacterized pathways that grant threat-specific protection.
    1. Neuroscience

    Constructing the hierarchy of predictive auditory sequences in the marmoset brain

    Yuwei Jiang, Misako Komatsu ... Liping Wang
    fMRI and high-density ECoG recordings reveal a hierarchical gradient along the auditory pathway for auditory sequence processing in the marmoset brain.
    1. Neuroscience

    Endurance exercise ameliorates phenotypes in Drosophila models of spinocerebellar ataxias

    Alyson Sujkowski, Kristin Richardson ... Sokol V Todi
    Genetic, biochemical, and physiologic analyses reveal differential responses of polyQ SCAs to exercise, and identify Sestrin as a mechanistic target that can be leveraged towards therapeutics for patients unable to exercise, or to supplement the benefits of those who can.
    1. Cancer Biology
    2. Microbiology and Infectious Disease

    YAP1 activation by human papillomavirus E7 promotes basal cell identity in squamous epithelia

    Joshua Hatterschide, Paola Castagnino ... Elizabeth A White
    Papillomavirus E7 proteins activate the YAP1 oncogene in basal epithelial cells by degrading PTPN14, in doing so promoting basal cell retention and contributing to carcinogenesis.
    1. Cancer Biology
    2. Epidemiology and Global Health

    Effect of cancer on outcome of COVID-19 patients: a systematic review and meta-analysis of studies of unvaccinated patients

    Giulia Di Felice, Giovanni Visci ... Paolo Boffetta
    A twofold increased risk of adverse outcomes (mortality, ICU admission, and severity of COVID-19) has been demonstrated in unvaccinated COVID-19 patients with cancer compared to COVID-19 patients without cancer.
    1. Cell Biology

    Regulation of canonical Wnt signalling by the ciliopathy protein MKS1 and the E2 ubiquitin-conjugating enzyme UBE2E1

    Katarzyna Szymanska, Karsten Boldt ... Colin A Johnson
    Interacting MKS1 and UBE2E1 regulate canonical Wnt signaling through modulation of beta-catenin levels at the base of primary cilium, providing new insights into ciliopathy disease mechanisms.
    1. Neuroscience

    NMDA receptors in visual cortex are necessary for normal visuomotor integration and skill learning

    Felix C Widmer, Sean M O'Toole, Georg B Keller
    Prediction error responses in layer 2/3 of mouse visual cortex are shaped by experience-dependent modifications of the local cortical circuit.
    1. Cell Biology
    2. Developmental Biology

    A novel mechanism of bulk cytoplasmic transport by cortical dynein in Drosophila ovary

    Wen Lu, Margot Lakonishok ... Vladimir I Gelfand
    Cortical dynein performs bulk cytoplasmic transport by gliding microtubules along the cell cortex and through the ring canals to the oocyte.
    1. Computational and Systems Biology

    Comprehensive and unbiased multiparameter high-throughput screening by compaRe finds effective and subtle drug responses in AML models

    Morteza Chalabi Hajkarim, Ella Karjalainen ... Kyoung-Jae Won
    compaRe can be used to optimize cytometric high-parameter immunophenotypic characterization of heterogeneous cell populations.
    1. Computational and Systems Biology

    Patient-specific Boolean models of signalling networks guide personalised treatments

    Arnau Montagud, Jonas Béal ... Laurence Calzone
    Tailoring Boolean models to 488 prostate cancer patients and 8 cell lines data allows for the experimentally validated personalisation of drug treatments.
    1. Immunology and Inflammation
    2. Stem Cells and Regenerative Medicine

    Erythropoietin directly remodels the clonal composition of murine hematopoietic multipotent progenitor cells

    Almut S Eisele, Jason Cosgrove ... Leïla Perié
    Erythropoietin transiently remodels the hematopoietic stem and progenitor cells pool by directly inducing myeloid-erythroid-megakaryocyte-biased multipotent progenitor clones compensated at the population level by induction of myeloid-B-cell-dendritic-cell-biased clones.
    1. Neuroscience

    PBN-PVT projections modulate negative affective states in mice

    Ya-Bing Zhu, Yan Wang ... Di Mu
    The parabrachial nucleus-thalamic paraventricular nucleus pathway is critical for modulating affective states in mice.
    1. Ecology
    2. Microbiology and Infectious Disease

    Alternate patterns of temperature variation bring about very different disease outcomes at different mean temperatures

    Charlotte Kunze, Pepijn Luijckx ... Ian Donohue
    Temperature variation caused by heatwaves and diurnal fluctuations has distinct effects on host and pathogen traits at different mean temperatures, leading to large and unexpected differences in disease burden making the impact of global warming on diseases hard to predict.
    1. Genetics and Genomics

    Body mass index and adipose distribution have opposing genetic impacts on human blood traits

    Christopher S Thom, Madison B Wilken ... Benjamin F Voight
    Body mass index and adipose distribution have opposing and broad effects on human blood trait variation by Mendelian randomization analysis, helping to clarify the complex interplay between cardiometabolic traits and hematopoiesis at the genetic level.
    1. Cancer Biology
    2. Cell Biology

    Intravital deep-tumor single-beam 3-photon, 4-photon, and harmonic microscopy

    Gert-Jan Bakker, Sarah Weischer ... Peter Friedl
    Infrared high-pulse-energy low-pulse-repetition-rate excitation advances deep intravital microscopy in strongly scattering tissues such as skin tumors and thick bone, thereby bringing previously inaccessible tumor areas in reach with subcellular resolution.
    1. Immunology and Inflammation
    2. Stem Cells and Regenerative Medicine

    Hematopoietic stem and progenitor cells improve survival from sepsis by boosting immunomodulatory cells

    Daniel E Morales-Mantilla, Bailee Kain ... Katherine Y King
    Infusion of hematopoietic stem and progenitor cells rescues mice from lethal Group A streptococcal sepsis.
    1. Neuroscience

    Assessing the effects of stress on feeding behaviors in laboratory mice

    Marie Francois, Isabella Canal Delgado ... Lori Zeltser
    Systematic testing of experimental variables in a common neurobehavioral paradigm revealed that conditions that more closely match human physiology reliably elicit stress eating in mice.
    1. Cell Biology
    2. Medicine

    Repression of hypoxia-inducible factor-1 contributes to increased mitochondrial reactive oxygen species production in diabetes

    Xiaowei Zheng, Sampath Narayanan ... Sergiu-Bogdan Catrina
    The repression of HIF-1 plays a central role in mitochondrial reactive oxygen species (ROS) overproduction and subsequent tissue damage in diabetes, which is mediated by increased mitochondrial respiration, making HIF-1 signaling an attractive therapeutic target for diabetes complications.
    1. Developmental Biology
    2. Evolutionary Biology

    Gene age shapes the transcriptional landscape of sexual morphogenesis in mushroom-forming fungi (Agaricomycetes)

    Zsolt Merényi, Máté Virágh ... László G Nagy
    Allele-specific expression, natural antisense transcripts, and developmental gene expression, but not RNA editing or developmental hourglass, act in concert to shape the transcriptome during the fruiting body formation of complex multicellular fungi.
    1. Cancer Biology
    2. Immunology and Inflammation

    Multiomic characterization of pancreatic cancer-associated macrophage polarization reveals deregulated metabolic programs driven by the GM-CSF–PI3K pathway

    Seth Boyer, Ho-Joon Lee ... Costas A Lyssiotis
    A multiomics, systems biology approach was used to define the metabolic and signaling programs that drive the fate and function of pancreatic tumor-associated macrophages.
    1. Structural Biology and Molecular Biophysics

    Conformational decoupling in acid-sensing ion channels uncovers mechanism and stoichiometry of PcTx1-mediated inhibition

    Stephanie A Heusser, Christian B Borg ... Stephan A Pless
    A peptide toxin with therapeutic potential in stroke and pain induces multiple long-lasting conformational changes in acid-sensing ion channels and affects how the channels respond to endogenous ligands.
    1. Plant Biology

    A guanosine tetraphosphate (ppGpp) mediated brake on photosynthesis is required for acclimation to nitrogen limitation in Arabidopsis

    Shanna Romand, Hela Abdelkefi ... Ben Field
    Guanosine tetraphosphate (ppGpp) is a pivotal regulator of chloroplast activity that is required for acclimation to nitrogen limitation in the model plant Arabidopsis.
    1. Neuroscience

    Three-dimensional multi-site random access photostimulation (3D-MAP)

    Yi Xue, Laura Waller ... Nicolas Pégard
    A one-photon three-dimensional light sculpture technique has been developed and demonstrated for high spatio-temporal resolution photostimulation and imaging of dozens of neurons in the intact mouse brain in vivo.
    1. Neuroscience

    VTA-projecting cerebellar neurons mediate stress-dependent depression-like behaviors

    Soo Ji Baek, Jin Sung Park ... Keiko Tanaka-Yamamoto
    Long-term chemogenetic manipulation of specific cerebellar pathway involving ventral tegmental area revealed a critical role of the pathway as a proactive mediator of the stress-dependent development of depression-like behaviors.
    1. Evolutionary Biology
    2. Genetics and Genomics

    Barcoded bulk QTL mapping reveals highly polygenic and epistatic architecture of complex traits in yeast

    Alex N Nguyen Ba, Katherine R Lawrence ... Michael M Desai
    A bulk barcoded quantitative trait locus approach increases the power and resolution of genotype-phenotype mapping in yeast, revealing that the genetic architecture of 18 complex traits is highly polygenic, and is characterized by widespread epistatic interactions and pleiotropic effects.
    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    Identification of novel HPFH-like mutations by CRISPR base editing that elevate the expression of fetal hemoglobin

    Nithin Sam Ravi, Beeke Wienert ... Kumarasamypet M Mohankumar
    Adenine and cytosine base editing of highly homologous HBG proximal promoter identifies novel target sites that result in adult to fetal globin switching without causing 4.9 kb large deletions.
    1. Cancer Biology

    Serum RNAs can predict lung cancer up to 10 years prior to diagnosis

    Sinan U Umu, Hilde Langseth ... Trine B Rounge
    Prediagnostic RNA levels show early lung cancer progression.
    1. Structural Biology and Molecular Biophysics

    STIM1-dependent peripheral coupling governs the contractility of vascular smooth muscle cells

    Vivek Krishnan, Sher Ali ... Scott Earley
    STIM1 regulates the contractility of blood vessels and blood pressure by organizing membrane contact sites and ion channel activity in vascular smooth muscle cells in a manner that is independent of its canonical function in store-operated Ca2+entry.
    1. Biochemistry and Chemical Biology
    2. Microbiology and Infectious Disease

    Extracellular electron transfer increases fermentation in lactic acid bacteria via a hybrid metabolism

    Sara Tejedor-Sanz, Eric T Stevens ... Maria L Marco
    Lactic acid bacteria engage a hybrid metabolism which blends features of fermentation and respiration when they perform extracellular electron transfer.
    1. Neuroscience

    Coding of chromatic spatial contrast by macaque V1 neurons

    Abhishek De, Gregory D Horwitz
    Many V1 double-opponent cells integrate light information across their receptive fields as linearly as simple cells do.
    1. Evolutionary Biology

    Evolution of sexual conflict in scorpionflies

    Agnieszka Soszyńska-Maj, Ewa Krzemińska ... Wiesław Krzemiński
    The fossil record of abdominal modifications in male scorpionflies documents a relatively late evolution of oppressive behaviour toward a female during mating and suggest degree of sexual coercion greater in Eocene than in any other known scorpionfly, extinct or extant.
    1. Evolutionary Biology
    2. Genetics and Genomics

    Genetic integration of behavioural and endocrine components of the stress response

    Thomas M Houslay, Ryan L Earley ... Alastair Wilson
    Behavioural and physiological stress response components are integrated on the major axis of genetic covariation, with implications for health and the understanding of the evolutionary response to stressors.
    1. Cell Biology
    2. Genetics and Genomics

    Multiple motors cooperate to establish and maintain acentrosomal spindle bipolarity in C. elegans oocyte meiosis

    Gabriel Cavin-Meza, Michelle M Kwan, Sarah M Wignall
    Rapid depletion of dynein from oocytes yielded new insights into acentrosomal pole organization and also led to the first evidence that the kinesin-5 motor BMK-1 plays a role in microtubule organization during C. elegans meiosis.
    1. Structural Biology and Molecular Biophysics

    The MIDAS domain of AAA mechanoenzyme Mdn1 forms catch bonds with two different substrates

    Keith J Mickolajczyk, Paul Dominic B Olinares ... Tarun M Kapoor
    The MIDAS domain of Mdn1, an ATP-driven mechanoenzyme involved in ribosome biogenesis, forms catch bonds with two different ubiquitin-like domain-containing ribosomal assembly factors.
    1. Neuroscience

    A vibrissa pathway that activates the limbic system

    Michaël Elbaz, Amalia Callado Perez ... Martin Deschenes
    A predominant but less studied sensory pathway for both vibrissa self-motion and touch inputs is shown to broadcast broadly to brainstem regions involved in regulation of autonomic functions as well as forebrain regions involved in expression of emotional reactions.
    1. Neuroscience

    A unifying mechanism governing inter-brain neural relationship during social interactions

    Wujie Zhang, Maimon C Rose, Michael M Yartsev
    Experiments and modeling suggest that a mechanism involving positive and negative feedback can explain the relationship between the neural activity of socially interacting bats.
    1. Genetics and Genomics

    Human embryoid bodies as a novel system for genomic studies of functionally diverse cell types

    Katherine Rhodes, Kenneth A Barr ... Yoav Gilad
    Embryoid bodies produce diverse cell types and can enable the study of gene regulatory dynamics at unprecedented spatial and temporal resolution.
    1. Genetics and Genomics

    A novel gene ZNF862 causes hereditary gingival fibromatosis

    Juan Wu, Dongna Chen ... Wei Li
    The third causative gene ZNF862 was novelly identified for hereditary gingival fibromatosis in a large Chinese family.
    1. Neuroscience

    A neural network model of when to retrieve and encode episodic memories

    Qihong Lu, Uri Hasson, Kenneth A Norman
    A neural network showed better prediction of upcoming states when it was selective in when it encoded and retrieved episodic memories, thereby explaining why humans show this selectivity in studies of naturalistic memory.
    1. Cell Biology

    Cdc6 is sequentially regulated by PP2A-Cdc55, Cdc14, and Sic1 for origin licensing in S. cerevisiae

    Jasmin Philip, Mihkel Örd ... Amy E Ikui
    Pre-RC component Cdc6 is primed for origin licensing by phosphatases and Cdk1 inhibitor.
    1. Developmental Biology

    The E3 ubiquitin ligase mindbomb1 controls planar cell polarity-dependent convergent extension movements during zebrafish gastrulation

    Vishnu Muraleedharan Saraswathy, Akshai Janardhana Kurup ... Maximilian Fürthauer
    Mindbomb1 acts independently of it well-known role in Notch signalling to control the endocytic internalization of the Wnt co-receptor Ryk and thereby modulate the activity of the Planar Cell Polarity pathway that governs morphogenetic movements during embryonic development.
    1. Epidemiology and Global Health
    2. Medicine

    External validation of a mobile clinical decision support system for diarrhea etiology prediction in children: A multicenter study in Bangladesh and Mali

    Stephanie Chow Garbern, Eric J Nelson ... Daniel T Leung
    A smartphone app incorporating clinical prediction models using patient-specific and location-specific data sources in a modular approach could predict viral-only etiology of diarrhea in children under five in Bangladesh and Mali.
    1. Microbiology and Infectious Disease

    Ribonucleotide reductase, a novel drug target for gonorrhea

    Jana Narasimhan, Suzanne Letinski ... Arthur Branstrom
    Novel small molecule inhibitors act against Neisseria including multi-drug resistant isolates by uniquely targeting RNR thereby enabling single pathogen therapy whilst sparing the microbiome.
    1. Epidemiology and Global Health

    Inference of the SARS-CoV-2 generation time using UK household data

    William S Hart, Sam Abbott ... Robin N Thompson
    Updated estimates of the generation time of SARS-CoV-2 infections indicate that the generation time has become shorter.
    1. Neuroscience

    KIF2C regulates synaptic plasticity and cognition in mice through dynamic microtubule depolymerization

    Rui Zheng, Yonglan Du ... Junyu Xu
    KIF2C plays an important role in synaptic plasticity and cognition behaviors in mice by regulating activity-dependent microtubule dynamic.
    1. Cell Biology
    2. Immunology and Inflammation

    Heparan sulfate-dependent RAGE oligomerization is indispensable for pathophysiological functions of RAGE

    Miaomiao Li, Chih Yean Ong ... Ding Xu
    Heparan sulfate-RAGE interaction is essential for normal function of RAGE in osteoclastogenesis and drug-induced liver damage, which can be targeted to curb RAGE activation as a new opportunity.
    1. Computational and Systems Biology

    Fibroblast mechanotransduction network predicts targets for mechano-adaptive infarct therapies

    Jesse D Rogers, William J Richardson
    Mechanotransduction signaling analysis suggests that mechanical tension can sensitize, desensitize, and reverse cell responses to biochemical agonists, as well as provide mechano-adaptive targets for regionally specific drug responses.
    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    Homeostatic interferon-lambda response to bacterial microbiota stimulates preemptive antiviral defense within discrete pockets of intestinal epithelium

    Jacob A Van Winkle, Stefan T Peterson ... Timothy J Nice
    The enteric bacterial microbiota stimulates a highly localized interferon-lambda signal within the intestinal epithelium that protects against murine rotavirus infection.
    1. Medicine

    Differences in local immune cell landscape between Q fever and atherosclerotic abdominal aortic aneurysms identified by multiplex immunohistochemistry

    Kimberley RG Cortenbach, Alexander HJ Staal ... Roland RJ Van Kimmenade
    Persistent Coxiella burnetii infected abdominal aorta aneurysms are associated with an immune-suppressed microenvironment.
    1. Biochemistry and Chemical Biology
    2. Evolutionary Biology

    Pyruvate:ferredoxin oxidoreductase and low abundant ferredoxins support aerobic photomixotrophic growth in cyanobacteria

    Yingying Wang, Xi Chen ... Kirstin Gutekunst
    Synechocystis switches its redox pools under reducing photomixotrophic conditions from utilizing NAD(H)- to ferredoxin-dependent enzymes and thereby balances its metabolism in a trade-off between energy conservation and chemical driving forces.
    1. Cell Biology
    2. Developmental Biology

    Somite morphogenesis is required for axial blood vessel formation during zebrafish embryogenesis

    Eric Paulissen, Nicholas J Palmisano ... Benjamin L Martin
    Retinoic acid-dependent somite morphogenesis induces notochord-endoderm separation required for midline angioblast migration and axial blood vessel development.
    1. Biochemistry and Chemical Biology
    2. Medicine

    Covalent inhibition of endoplasmic reticulum chaperone GRP78 disconnects the transduction of ER stress signals to inflammation and lipid accumulation in diet-induced obese mice

    Dan Luo, Ni Fan ... Jianhui Rong
    Celastrol covalently inhibited the chaperone activity of GRP78 and could disconnect the transduction of ER stress signal to downstream inflammatory response and lipid metabolism.
    1. Cell Biology
    2. Developmental Biology

    Pathway-specific effects of ADSL deficiency on neurodevelopment

    Ilaria Dutto, Julian Gerhards ... Travis H Stracker
    Analysis of adenylosuccinate lyase (ADSL) deficiency in multiple experimental systems reveals cell and organismal phenotypes and impaired neurodevelopment due to the attenuation of ADSL's roles in distinct pathways.
    1. Neuroscience

    Coupling of pupil- and neuronal population dynamics reveals diverse influences of arousal on cortical processing

    Thomas Pfeffer, Christian Keitel ... Joachim Gross
    Spontaneous fluctuations in pupil-indexed arousal shape human cortical dynamics in a frequency-dependent and spatially diverse manner.
    1. Epidemiology and Global Health
    2. Medicine

    Investigating phenotypes of pulmonary COVID-19 recovery: A longitudinal observational prospective multicenter trial

    Thomas Sonnweber, Piotr Tymoszuk ... Judith Löffler-Ragg
    Protracted systemic and microvascular inflammation, as well as high anti-SARS-CoV-2 antibody levels, is associated with a high risk of persistent structural and functional lung deficits 6 months after COVID-19.
    1. Medicine

    Connexin hemichannels with prostaglandin release in anabolic function of bone to mechanical loading

    Dezhi Zhao, Manuel A Riquelme ... Jean X Jiang
    Connexin 43 hemichannel activation associated with prostaglandin release in osteocytes plays an important role in anabolic function of mechanical loading on bone tissue and hemichannels could be a potential new therapeutic target for treating bone loss and osteoporosis.
    1. Cell Biology

    Reversing chemorefraction in colorectal cancer cells by controlling mucin secretion

    Gerard Cantero-Recasens, Josune Alonso-Marañón ... Vivek Malhotra
    Genetic analysis and biochemical approaches reveal that chemorefractory properties are reversed by inhibiting mucin secretion, thus providing a means to curb the growth and spread of colorectal cancer.
    1. Cell Biology
    2. Microbiology and Infectious Disease

    Protein-lipid interaction at low pH induces oligomerization of the MakA cytotoxin from Vibrio cholerae

    Aftab Nadeem, Alexandra Berg ... Sun Nyunt Wai
    MakA, a pore-forming cytotoxin produced by Vibrio cholerae, forms oligomers and remodels membranes into high-curvature tubes, resulting in membrane integrity loss inside acidified organelle lumens or when cultured with cells in an acidic medium.
    1. Biochemistry and Chemical Biology
    2. Developmental Biology

    Phosphoproteomics of ATR signaling in mouse testes

    Jennie R Sims, Vitor M Faça ... Marcus B Smolka
    An in-depth map of ATR signaling during mouse meiosis is revealed using a combination of genetic and pharmacological approaches coupled to quantitative mass spectrometry.
    1. Cell Biology
    2. Genetics and Genomics

    Multiple 9-1-1 complexes promote homolog synapsis, DSB repair, and ATR signaling during mammalian meiosis

    Catalina Pereira, Gerardo A Arroyo-Martinez ... Robert S Weiss
    Alternative 9-1-1 complexes have evolved to play essential roles in mammalian meiosis and function to activate the protein kinase ATR and promote key meiotic events necessary for fertility.
    1. Chromosomes and Gene Expression

    Telomere length regulation by Rif1 protein from Hansenula polymorpha

    Alexander N Malyavko, Olga A Petrova ... Olga A Dontsova
    Novel mechanistic aspects of function of the important DNA metabolism regulator Rif1 are uncovered in an alternative model organism.
    1. Structural Biology and Molecular Biophysics

    Mg2+-dependent conformational equilibria in CorA and an integrated view on transport regulation

    Nicolai Tidemand Johansen, Marta Bonaccorsi ... Lise Arleth
    The Mg2+-channel CorA explores a wide conformational landscape of non-conducting states irrespective of bound Mg2+, but only in abscence of Mg2+, conducting states become accessible due to increased backbone dynamics.
    1. Genetics and Genomics
    2. Immunology and Inflammation

    Extensive age-dependent loss of antibody diversity in naturally short-lived turquoise killifish

    William John Bradshaw, Michael Poeschla ... Dario Riccardo Valenzano
    Naturally short-lived turquoise killifish undergo systemic and mucosal spontaneous decline in antibody-repertoire diversity during aging, recapitulating in a few months the aging-dependent decline of adaptive immunity.
    1. Biochemistry and Chemical Biology
    2. Chromosomes and Gene Expression

    SWI/SNF senses carbon starvation with a pH-sensitive low-complexity sequence

    J Ignacio Gutierrez, Gregory P Brittingham ... Liam J Holt
    A combination of single-cell analysis, genomics, and simulations shows that a glutamine-rich low-complexity sequence in the SWI/SNF chromatin remodeling complex senses transient intracellular acidification as a signal for cells to switch their global transcriptional program.
    1. Developmental Biology

    The Cl--channel TMEM16A is involved in the generation of cochlear Ca2+ waves and promotes the refinement of auditory brainstem networks in mice

    Alena Maul, Antje Kathrin Huebner ... Christian A Hübner
    Ano1 deletion disrupts Ca2+ waves within Kölliker’s organ, reduces burst-firing activity and frequency selectivity of auditory brainstem neurons in the medial nucleus of the trapezoid body, and impairs the functional refinement of its projections to the lateral superior olive.
    1. Neuroscience

    Rapid odor processing by layer 2 subcircuits in lateral entorhinal cortex

    Sebastian H Bitzenhofer, Elena A Westeinde ... Jeffry S Isaacson
    Electrophysiological recordings reveal how cells encode odor identity and intensity in the lateral entorhinal cortex of awake mice.
    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    Novel insights from a multiomics dissection of the Hayflick limit

    Michelle Chan, Han Yuan ... David G Hendrickson
    A comprehensive molecular description of the cellular transition into replicative senescence provides evidence of metabolic, epigenetic, and regulatory rewiring that links senescence with wound healing and fibrosis.
    1. Stem Cells and Regenerative Medicine

    Induction of osteogenesis by bone-targeted Notch activation

    Cong Xu, Van Vuong Dinh ... Ralf H Adams
    Bone formation in adult mice can be induced by a bone-binding, recombinant version of the Notch ligand Delta-like 4 without triggering adverse effects in other organs.
    1. Ecology
    2. Evolutionary Biology

    Interactions between strains govern the eco-evolutionary dynamics of microbial communities

    Akshit Goyal, Leonora S Bittleston ... Otto X Cordero
    Rapidly diversifying biotic interactions decouple the dynamics of nearly identical strains.
    1. Plant Biology

    Plant SYP12 syntaxins mediate an evolutionarily conserved general immunity to filamentous pathogens

    Hector M Rubiato, Mengqi Liu ... Mads E Nielsen
    To effectively ward off some of the most damaging groups of filamentous pathogens, plants rely on an evolutionarily conserved syntaxin function to block the pathogen from entering the host cell and proliferate.
    1. Developmental Biology
    2. Genetics and Genomics

    The transcriptional corepressor CTBP-1 acts with the SOX family transcription factor EGL-13 to maintain AIA interneuron cell identity in Caenorhabditis elegans

    Josh Saul, Takashi Hirose, H Robert Horvitz
    The maintenance of diverse cell identities might be coordinated through the interaction between widely acting transcriptional corepressors and cell-specific transcription factors to repress undesired gene expression in a cell-type-specific manner.
    1. Cell Biology
    2. Genetics and Genomics

    Physiological TLR4 regulation in human fetal membranes as an explicative mechanism of a pathological preterm case

    Corinne Belville, Flora Ponelle-Chachuat ... Loïc Blanchon
    Methylomic and trancriptomic analyses demonstrate the regulation of the toll-like receptor 4 inflammatory gene expression, an essential actor of the fetal membrane weakening at the end of pregnancy.
    1. Immunology and Inflammation

    Widespread discrepancy in Nnt genotypes and genetic backgrounds complicates granzyme A and other knockout mouse studies

    Daniel J Rawle, Thuy T Le ... Andreas Suhrbier
    Granzyme A-/- mice, which have contributed to a body of research into this enzyme, emerge to have a mixed C57BL/6J-C57BL/6N genetic background, compromising our understanding of granzyme A and highlighting a widespread problem for knockout mouse studies generally.
    1. Cell Biology

    α-/γ-Taxilin are required for centriolar subdistal appendage assembly and microtubule organization

    Dandan Ma, Fulin Wang ... Jianguo Chen
    Super-resolution microscopy, biochemical and functional analyses reveal how α-taxilin and γ-taxilin are assembled at the subdistal appendages and their roles in microtubule organization.
    1. Neuroscience

    Cell-type-specific responses to associative learning in the primary motor cortex

    Candice Lee, Emerson F Harkin ... Simon Chen
    Major neuronal subtypes in M1 show differential responses to reward and reward-associated stimuli and undergo cell-type-specific plasticity following associative learning.
    1. Cell Biology
    2. Immunology and Inflammation

    Zinc finger protein Zfp335 controls early T-cell development and survival through β-selection-dependent and -independent mechanisms

    Xin Wang, Anjun Jiao ... Baojun Zhang
    Genetically modified mouse model and comprehensive analysis reveal the molecular mechanisms regulating early T-cell development through intracellular TCRβ expression-mediated β-selection and independent cell survival signaling.
    1. Immunology and Inflammation

    Overriding impaired FPR chemotaxis signaling in diabetic neutrophil stimulates infection control in murine diabetic wound

    Ruchi Roy, Janet Zayas ... Sasha H Shafikhani
    Therapeutic potential of CCL3 for the treatment of diabetic foot ulcers if it is applied topically after the surgical debridement.
    1. Cell Biology
    2. Immunology and Inflammation

    Functional visualization of NK cell-mediated killing of metastatic single tumor cells

    Hiroshi Ichise, Shoko Tsukamoto ... Michiyuki Matsuda
    Live imaging of the duel of an NK cell versus a metastatic cancer cell on pulmonary epithelial cells reveals a novel survival tactics adopted by cancer cells.
    1. Genetics and Genomics
    2. Microbiology and Infectious Disease

    Host-pathogen genetic interactions underlie tuberculosis susceptibility in genetically diverse mice

    Clare M Smith, Richard E Baker ... Christopher M Sassetti
    A novel dual genome approach that combines genetically diverse mice and a library of bacterial mutants to define the genome-wide host pathogen interactions that drive distinct outcomes to tuberculosis.
    1. Neuroscience

    Mapping dopaminergic projections in the human brain with resting-state fMRI

    Marianne Oldehinkel, Alberto Llera ... Christian F Beckmann
    A functional connectivity gradient in striatum is obtained that maps onto DaT SPECT-derived dopaminergic projections and thereby likely provides a new biomarker for investigating dopaminergic (dys)function in the human brain.
    1. Biochemistry and Chemical Biology

    Rolling circle RNA synthesis catalyzed by RNA

    Emil Laust Kristoffersen, Matthew Burman ... Philipp Holliger
    All steps of a viroid-like replication cycle can be catalyzed by RNA alone.
    1. Neuroscience

    Broca's cerebral asymmetry reflects gestural communication's lateralisation in monkeys (Papio anubis)

    Yannick Becker, Nicolas Claidière ... Adrien Meguerditchian
    A brain MRI imaging study on brain and manual lateralisation in 50 baboons shows that communicative manual gesturing is related to a Broca's area marker.
    1. Biochemistry and Chemical Biology

    Cooperation among c-subunits of FoF1-ATP synthase in rotation-coupled proton translocation

    Noriyo Mitome, Shintaroh Kubo ... Shoji Takada
    Biochemical analysis on hetero-mutated c10 subunits ring and molecular dynamics simulations demonstrate the cooperation among c-subunits of FoF1-ATP synthase in rotation-coupled proton translocation.
    1. Genetics and Genomics

    Genetically engineered insects with sex-selection and genetic incompatibility enable population suppression

    Ambuj Upadhyay, Nathan R Feltman ... Michael Smanski
    Two distinct genetic biocontrol methods work synergistically to yield a novel approach in the fight against pest organisms.
    1. Neuroscience

    Pupil diameter is not an accurate real-time readout of locus coeruleus activity

    Marine Megemont, Jim McBurney-Lin, Hongdian Yang
    Pupil diameter cannot accurately predict spiking activity in the locus coeruleus on a moment-by-moment basis, and exhibited large fluctuations to identical stimulation in the LC.
    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    A single full-length VAR2CSA ectodomain variant purifies broadly neutralizing antibodies against placental malaria isolates

    Justin YA Doritchamou, Jonathan P Renn ... Patrick E Duffy
    VAR2CSA, the leading candidate antigen for a placental malaria vaccine, displays epitopes targeted by naturally acquired broadly neutralizing antibodies of African multigravidae.
    1. Cell Biology
    2. Microbiology and Infectious Disease

    Response to comment on 'Unexpected plasticity in the life cycle of Trypanosoma Brucei'

    Jaime Lisack, Brooke Morriswood, Markus Engstler
    We are writing to respond to the comment by Matthews and Larcombe, 2022 on our article about the life cycle of Trypanosoma brucei (Schuster et al., 2021).
    1. Cell Biology
    2. Chromosomes and Gene Expression

    Eco1-dependent cohesin acetylation anchors chromatin loops and cohesion to define functional meiotic chromosome domains

    Rachael E Barton, Lucia F Massari ... Adèle L Marston
    Meiotic recombination and chromosome segregation require the establishment of chromatin boundaries by the acetyltransferase Eco1, which anchors both chromatin loops and cohesion.
    1. Neuroscience

    Reciprocally inhibitory circuits operating with distinct mechanisms are differently robust to perturbation and modulation

    Ekaterina Morozova, Peter Newstein, Eve Marder
    Nuanced changes in the mechanism of oscillation in reciprocally inhibitory circuits can profoundly alter the circuit stability in response to perturbations and inputs.
    1. Cell Biology
    2. Chromosomes and Gene Expression

    Time-resolved single-cell sequencing identifies multiple waves of mRNA decay during the mitosis-to-G1 phase transition

    Lenno Krenning, Stijn Sonneveld, Marvin Tanenbaum
    mRNA decay contributes to reshape the transcriptome as a parent cell divides into daughter cells.
    1. Microbiology and Infectious Disease

    Comment on ‘Unexpected plasticity in the life cycle of Trypanosoma brucei

    Keith R Matthews, Stephen Larcombe
    We are writing to comment on the article by Schuster et al., 2021 about the life cycle of Trypanosoma brucei.
    1. Epidemiology and Global Health

    Adverse childhood experiences and resilience among adult women: A population-based study

    Hilda Björk Daníelsdóttir, Thor Aspelund ... Unnur Anna Valdimarsdóttir
    Cumulative exposure to adverse childhood experiences is associated with lower adult resilience among women in a dose-dependent manner, independent of adult socioeconomic factors and social support, indicating that adult female resilience is consolidated in early life.
    1. Neuroscience

    Charting brain growth and aging at high spatial precision

    Saige Rutherford, Charlotte Fraza ... Andre F Marquand
    During an individual's lifetime, their brain undergoes a unique transformation that we have precisely mapped across thousands of people to create and share reference growth charts of the human brain's lifespan which allow for single subject exploration and inference.
    1. Neuroscience

    ExSTED microscopy reveals contrasting functions of dopamine and somatostatin CSF-c neurons along the lamprey central canal

    Elham Jalalvand, Jonatan Alvelid ... Ilaria Testa
    Expansion microscopy combined with light-sheet and STED microscopy elucidated the spatial organization and subcellular composition of two distinct GABAergic CSF-c neuronal subtypes in the lamprey spinal cord.