January 2022

Cover articles

    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    Testing the pioneer factor hypothesis

    Jeffrey L Hansen, Kaiser J Loell, Barak A Cohen
    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    Activating the p38 immune pathway in C. elegans

    Nicholas D Peterson, Janneke D Icso ... Read Pukkila-Worley
    1. Evolutionary Biology

    Muscle systems in early animals

    Xing Wang, Jean Vannier ... Jian Han

Highlights controls:

Research articles

    1. Evolutionary Biology

    Muscle systems and motility of early animals highlighted by cnidarians from the basal Cambrian

    Xing Wang, Jean Vannier ... Jian Han
    Exceptionally preserved small shelly fossils (SSFs) from the early Cambrian Kuanchuanpu Formation (535 million years ago) reveal the muscular system of ancient cnidarians.
    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    Pathogen infection and cholesterol deficiency activate the C. elegans p38 immune pathway through a TIR-1/SARM1 phase transition

    Nicholas D Peterson, Janneke D Icso ... Read Pukkila-Worley
    A phase transition of TIR-1/SARM1 induced by either pathogen or non-pathogen stress potentiates its intrinsic NADase activity, which activates the p38 PMK-1 signaling cascade to induce protective immune defenses in Caenorhabditis elegans intestinal epithelial cells.
    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    A DCL3 dicing code within Pol IV-RDR2 transcripts diversifies the siRNA pool guiding RNA-directed DNA methylation

    Andrew Loffer, Jasleen Singh ... Craig S Pikaard
    Double-stranded precursors of siRNAs involved in RNA-directed DNA methylation have initiating sequences and overhangs imparted by the RNA polymerases that synthesize them, programming alternative dicing reactions that diversify the siRNA pool.
    1. Physics of Living Systems

    Crowding-induced phase separation of nuclear transport receptors in FG nucleoporin assemblies

    Luke K Davis, Ian J Ford, Bart W Hoogenboom
    Computational modelling predicts spatial segregation of different types of nuclear transport receptors in assemblies of nuclear pore proteins, lending support to the idea of separate transport pathways in the nuclear pore complex as a way to enhance transport efficiency.
    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    m6A modifications regulate intestinal immunity and rotavirus infection

    Anmin Wang, Wanyiin Tao ... Shu Zhu
    RNA m6A level is dually regulated during RV infection and development, METTL3 deficiency in IECs results in increased resistance to rotaviral infection through reduced m6A modificaitons on Irf7.
    1. Neuroscience

    Subcellular proteomics of dopamine neurons in the mouse brain

    Benjamin D Hobson, Se Joon Choi ... Peter A Sims
    APEX2 proximity labeling of genetically targeted neurons enables subcellular and cell type-specific proteomics in the mouse brain, revealing the axonal and somatodendritic proteomes of midbrain dopaminergic neurons.
    1. Genetics and Genomics

    Inter-tissue convergence of gene expression during ageing suggests age-related loss of tissue and cellular identity

    Hamit Izgi, Dingding Han ... Handan Melike Dönertaş
    Cross-sectional transcriptome analysis of mice, covering the whole lifespan, reveals that inter-tissue divergence during development is accompanied by a weaker but widespread convergence during ageing.
    1. Cell Biology
    2. Immunology and Inflammation

    A model of preferential pairing between epithelial and dendritic cells in thymic antigen transfer

    Matouš Vobořil, Jiří Březina ... Dominik Filipp
    Fluorescent protein-based reporter mouse models revealed that thymic cooperative antigen transfer is mediated by preferential pairing between a particular thymic epithelial cell subset and specific subset(s) of thymic dendritic cells.
    1. Genetics and Genomics
    2. Medicine

    Differences in pathways contributing to thyroid hormone effects on postnatal cartilage calcification versus secondary ossification center development

    Gustavo A Gomez, Patrick Aghajanian ... Subburaman Mohan
    Mouse molecular genetics and in vivo functional studies reveal that thyroid hormone is necessary for punctual proximal femur head development by a mechanism that differs temporally and molecularly from the secondary ossification center at the distal femur.
    1. Ecology
    2. Evolutionary Biology

    From Gondwana to the Yellow Sea, evolutionary diversifications of true toads Bufo sp. in the Eastern Palearctic and a revisit of species boundaries for Asian lineages

    Siti N Othman, Spartak N Litvinchuk ... Amael Borzee
    A robust framework of integrative phylogeography and advanced taxonomy to resolve the historical biogeography and species boundaries of true toads across the Eastern Palearctic.
    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    Paraxial mesoderm organoids model development of human somites

    Christoph Budjan, Shichen Liu ... Sahand Hormoz
    Human somites are formed in organoids from human pluripotent stem cells.
    1. Cell Biology
    2. Physics of Living Systems

    Volume growth in animal cells is cell cycle dependent and shows additive fluctuations

    Clotilde Cadart, Larisa Venkova ... Marco Cosentino Lagomarsino
    High-throughput measurement of single-cell volume reveals the short and large timescale fluctuation patterns of animal cell volume growth.
    1. Neuroscience

    Laminar microcircuitry of visual cortex producing attention-associated electric fields

    Jacob A Westerberg, Michelle S Schall ... Jeffrey D Schall
    Simultaneous sampling of electrical voltages outside the brain with neural signals in the cerebral cortex reveals how electrical currents in mosaics of cortical columns produce an electrical signal that can be measured noninvasively to assess the allocation of attention.
    1. Developmental Biology

    Single-cell atlas of early chick development reveals gradual segregation of neural crest lineage from the neural plate border during neurulation

    Ruth M Williams, Martyna Lukoseviciute ... Marianne E Bronner
    A single-cell transcriptomic resource of the early chick epiblast from mid-gastrulation through neurulation highlighting emergence of the neural plate border territory, with emphasis on neural crest specification.
    1. Medicine
    2. Neuroscience

    Virtual mouse brain histology from multi-contrast MRI via deep learning

    Zifei Liang, Choong H Lee ... Jiangyang Zhang
    Deep convolutional neural networks can generate virtual histology from magnetic resonance imaging (MRI) data to map cellular structures in the mouse brain with high specificity, which enables neurobiologists to use MRI to characterize neuropathology effectively.
    1. Neuroscience
    2. Stem Cells and Regenerative Medicine

    Characterization of the neurogenic niche in the aging dentate gyrus using iterative immunofluorescence imaging

    John Darby Cole, Jacobo Sarabia del Castillo ... Sebastian Jessberger
    Iterative immunostaining using 4i enables detailed characterization of complex mouse and human tissues.
    1. Epidemiology and Global Health
    2. Evolutionary Biology

    Primate malarias as a model for cross-species parasite transmission

    Marina Voinson, Charles L Nunn, Amy Goldberg
    Ecological and evolutionary perspectives are critical to understand, predict, prevent, and treat malaria parasites that may spread to humans from our close primate relatives.
    1. Medicine

    Gut microbial trimethylamine is elevated in alcohol-associated hepatitis and contributes to ethanol-induced liver injury in mice

    Robert N Helsley, Tatsunori Miyata ... Jonathan Mark Brown
    The gut microbe-derived metabolite trimethylamine (TMA) is elevated in patients with alcohol-associated hepatitis and inhibition of the gut microbial enzymes that produce TMA may serve as a tractable therapeutic strategy for the treatment of ethanol-induced liver injury.
    1. Cell Biology
    2. Microbiology and Infectious Disease

    Adaptation of the periplasm to maintain spatial constraints essential for cell envelope processes and cell viability

    Eric Mandela, Christopher J Stubenrauch ... Iain D Hay
    The bacterial periplasm must adapt to factors effecting the width of the cell envelope.
    1. Cell Biology
    2. Microbiology and Infectious Disease

    Vaccine-induced COVID-19 mimicry syndrome

    Eric Kowarz, Lea Krutzke ... Rolf Marschalek
    The Spike gene expressed by the vector-based vaccine Vaxzevria bears the risk of cryptic splicing, which in turn may lead to cellular production of soluble, instead of membrane-anchored, Spike protein variants.
    1. Microbiology and Infectious Disease

    Legionella pneumophila modulates host energy metabolism by ADP-ribosylation of ADP/ATP translocases

    Jiaqi Fu, Mowei Zhou ... Zhao-Qing Luo
    Legionella pneumophila modulates host energy metabolism by targeting the ADP/ATP translocase carrier proteins with an effector of ADP-ribosyltransferase activity.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    LRET-derived HADDOCK structural models describe the conformational heterogeneity required for DNA cleavage by the Mre11-Rad50 DNA damage repair complex

    Marella D Canny, Michael P Latham
    Multiple solution-state structures are used for the DNA double-strand break repair functions of the Mre11-Rad50 protein complex.
    1. Microbiology and Infectious Disease

    Multi-omics investigation of Clostridioides difficile-colonized patients reveals pathogen and commensal correlates of C. difficile pathogenesis

    Skye RS Fishbein, John I Robinson ... Gautam Dantas
    Integration of clinical patient data, pathogen information and a multi-omic analysis of the gut microbiome reveals key determinants of disease in C. difficile-colonized patients.
    1. Neuroscience

    Juxtacellular opto-tagging of hippocampal CA1 neurons in freely moving mice

    Lingjun Ding, Giuseppe Balsamo ... Andrea Burgalossi
    The combination of juxtacellular recordings with optogenetics in freely moving mice enables the targeting of genetically defined cell classes for high-resolution, single-cell structure–function analysis.
    1. Computational and Systems Biology
    2. Evolutionary Biology

    Predicting bacterial promoter function and evolution from random sequences

    Mato Lagator, Srdjan Sarikas ... Gašper Tkačik
    An inferred mechanistic model that connects sequence (genotype) to function (constitutive gene expression phenotype) for any random sequence in Escherichia coli reveals the structure of constitutive promoters and how they evolve.
    1. Microbiology and Infectious Disease

    Clp protease and antisense RNA jointly regulate the global regulator CarD to mediate mycobacterial starvation response

    Xinfeng Li, Fang Chen ... Jin He
    Under starvation conditions, anti-carD antisense RNA and Clp protease work together to decrease the CarD level to mediate the adaptation and survival of mycobacterial cells.
    1. Neuroscience

    Simultaneous brain, brainstem, and spinal cord pharmacological-fMRI reveals involvement of an endogenous opioid network in attentional analgesia

    Valeria Oliva, Ron Hartley-Davies ... Jonathan CW Brooks
    Attention-grabbing tasks produce rapid opioid-mediated analgesia via the descending pain modulation network to alter spinal neuronal activity.
    1. Epidemiology and Global Health
    2. Genetics and Genomics

    Disease consequences of higher adiposity uncoupled from its adverse metabolic effects using Mendelian randomisation

    Susan Martin, Jessica Tyrrell ... Hanieh Yaghootkar
    Using genetics, it is possible to uncouple higher adiposity from its adverse metabolic effects and show that some obesity-associated conditions may benefit from treating the metabolic effects alone, whilst others may benefit more from weight loss.
    1. Evolutionary Biology
    2. Microbiology and Infectious Disease

    Evolution of host-microbe cell adherence by receptor domain shuffling

    EmilyClare P Baker, Ryan Sayegh ... Matthew F Barber
    Rapid evolution and gene conversion of a primate cell surface receptor family blocks recognition by pathogenic bacteria.
    1. Stem Cells and Regenerative Medicine

    Kidney organoids recapitulate human basement membrane assembly in health and disease

    Mychel RPT Morais, Pinyuan Tian ... Rachel Lennon
    Kidney organoids are a high-fidelity system for investigating basement membrane regulation in development and disease.
    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    iMyoblasts for ex vivo and in vivo investigations of human myogenesis and disease modeling

    Dongsheng Guo, Katelyn Daman ... Charles P Emerson Jr
    iMyoblasts, a novel iPS-derived PAX3 muscle stem cell for gene editing, muscle engraftment, and stem cell therapeutics to treat muscle injury and muscular dystrophies.
    1. Biochemistry and Chemical Biology
    2. Genetics and Genomics

    Protein visualization and manipulation in Drosophila through the use of epitope tags recognized by nanobodies

    Jun Xu, Ah-Ram Kim ... Norbert Perrimon
    The in vitro and in vivo characterization of two nanobody/NanoTag pairs in the Drosophila system provides a variety of assays for protein detection and manipulation.
    1. Cell Biology

    Female fertility and the zona pellucida

    Paul M Wassarman, Eveline S Litscher
    The ZP is a viscoelastic ECM that provides stability for contacts between projections from the innermost cumulus cells and oocyte microvilli that pass through the ZP and form gap junctions shown to be essential for oocyte growth and follicle development.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Topoisomerase VI is a chirally-selective, preferential DNA decatenase

    Shannon J McKie, Parth Rakesh Desai ... Keir C Neuman
    Topoisomerase VI selectively catalyzes strand passage of DNA molecules juxtaposed at close to a right angle, which explains the observed chiral-dependent activity and preferential DNA decatenation versus supercoil relaxation.
    1. Cell Biology
    2. Neuroscience

    A genetic compensatory mechanism regulated by Jun and Mef2d modulates the expression of distinct class IIa Hdacs to ensure peripheral nerve myelination and repair

    Sergio Velasco-Aviles, Nikiben Patel ... Hugo Cabedo
    Myelin generation during development and nerve regeneration is guaranteed by responsive backup circuits that coordinate class IIa HDACs to repress the expression of negative regulators of myelination and permit Schwann cell differentiation in response to cAMP.
    1. Epidemiology and Global Health

    Urinary metabolic biomarkers of diet quality in European children are associated with metabolic health

    Nikos Stratakis, Alexandros P Siskos ... Leda Chatzi
    Urinary metabolic signatures relate to adherence to the Mediterranean diet and ultra-processed food intake in childhood and reflect associations of these diet quality indicators with metabolic health.
    1. Computational and Systems Biology
    2. Medicine

    Personalized computational heart models with T1-mapped fibrotic remodeling predict sudden death risk in patients with hypertrophic cardiomyopathy

    Ryan P O'Hara, Edem Binka ... Natalia A Trayanova
    Personalized virtual-heart technology for arrhythmia risk assessment could transform the management of hypertrophic cardiomyopathy patients, eliminating many unnecessary primary-prevention defibrillator deployments while ensuring patients at high risk for arrhythmia are adequately protected.
    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    Preexisting memory CD4 T cells in naïve individuals confer robust immunity upon hepatitis B vaccination

    George Elias, Pieter Meysman ... Benson Ogunjimi
    High-throughput sequencing of the memory T cell receptor repertoire and machine learning can predict robust antibody and CD4 T cell response to de novo hepatitis B vaccine.
    1. Neuroscience

    Intrinsic mechanisms in the gating of resurgent Na+ currents

    Joseph L Ransdell, Jonathan D Moreno ... Jeanne M Nerbonne
    Experimental and modeling results reveal that the activation of resurgent sodium currents relies on the recovery of inactivated channels into a conducting state, and that the decay of resurgent currents reflects the accumulation of these channels into a slow-inactivated state.
    1. Developmental Biology
    2. Genetics and Genomics

    A low-tech, cost-effective and efficient method for safeguarding genetic diversity by direct cryopreservation of poultry embryonic reproductive cells

    Tuanjun Hu, Lorna Taylor ... Michael J McGrew
    A simple cryopreservation method using chicken eggs will be a valuable tool to safeguard genetic diversity and conserve the 1600 local breeds of chicken on the planet.
    1. Structural Biology and Molecular Biophysics

    Structure of the human ATM kinase and mechanism of Nbs1 binding

    Christopher Warren, Nikola P Pavletich
    Structures of the human ataxia-telangiectasia mutated (ATM) kinase alone and bound to the C-terminus of Nbs1 show the mechanisms underlying ATM autoinhibition and binding by a portion of the Mre11-Rad50-Nbs1 (MRN) activating complex.
    1. Biochemistry and Chemical Biology

    Native proline-rich motifs exploit sequence context to target actin-remodeling Ena/VASP protein ENAH

    Theresa Hwang, Sara S Parker ... Amy E Keating
    Short linear motifs throughout the intrinsically disordered proteome use sequence context in diverse ways to target actin remodeler ENAH.
    1. Microbiology and Infectious Disease

    Lytic transglycosylases mitigate periplasmic crowding by degrading soluble cell wall turnover products

    Anna Isabell Weaver, Laura Alvarez ... Tobias Dörr
    A critical role for bacterial lytic transglycosylases in the clearance of novel, toxic cell wall turnover products that accumulate during vegetative growth is identified through genetic approaches and compositional analysis of solubilized peptidoglycan released from the bacterial cell wall.
    1. Neuroscience

    Impact of long- and short-range fibre depletion on the cognitive deficits of fronto-temporal dementia

    Melissa Savard, Tharick A Pascoal ... Pedro Rosa-Neto
    While semantic symptoms in fronto-temporal dementia patients were mainly dependent on short-range white-matter fibre disruption, long-range white-matter fibres damage was the major contributor to executive dysfunction, highlighting the importance of controlling for risk factors associated with deep white-matter disease.
    1. Ecology

    Environmental selection overturns the decay relationship of soil prokaryotic community over geographic distance across grassland biotas

    Biao Zhang, Kai Xue ... Yanfen Wang
    Environmental selection overwhelmed the geographic 'distance' effect when across biotas, overturning the previously well-accepted geographic pattern for microbes on a large scale.
    1. Neuroscience
    2. Physics of Living Systems

    Sensing complementary temporal features of odor signals enhances navigation of diverse turbulent plumes

    Viraaj Jayaram, Nirag Kadakia, Thierry Emonet
    Effective navigation of odor plumes in the wild requires that animals sense multiple temporal aspects of odor signals, which are encoded naturally by neurons in the fly olfactory circuit.
    1. Medicine

    Gut microbe-targeted choline trimethylamine lyase inhibition improves obesity via rewiring of host circadian rhythms

    Rebecca C Schugar, Christy M Gliniak ... Jonathan Mark Brown
    Small molecule inhibitors of gut microbial choline trimethylamine lyase activity protect against obesity.
    1. Neuroscience

    Multiphoton imaging of neural structure and activity in Drosophila through the intact cuticle

    Max Jameson Aragon, Aaron T Mok ... Nilay Yapici
    Development of imaging methods to capture neural activity and structure through the intact cuticle using 2-photon and 3-photon excitation in the genetic model organism, Drosophila melanogaster.
    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    Distinguishing between recruitment and spread of silent chromatin structures in Saccharomyces cerevisiae

    Molly Brothers, Jasper Rine
    Heterochromatin proteins like the SIR complex in budding yeast use different mechanisms for recruitment to nucleation sites and long-range spread to create a domain of transcriptional silencing.
    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    Comprehensive characterization of the antibody responses to SARS-CoV-2 Spike protein finds additional vaccine-induced epitopes beyond those for mild infection

    Meghan E Garrett, Jared G Galloway ... Julie M Overbaugh
    Sera from vaccinated subjects bound additional linear epitopes compared to sera from individuals with mild infection, in addition the pathways of escape from antibodies from vaccination were more uniform than those from mildly infected individuals.
    1. Cell Biology
    2. Neuroscience

    Dynamics and nanoscale organization of the postsynaptic endocytic zone at excitatory synapses

    Lisa AE Catsburg, Manon Westra ... Harold D MacGillavry
    The postsynaptic endocytic zone is a highly organized structure composed of a diversity of endocytic proteins.
    1. Neuroscience

    Valence biases in reinforcement learning shift across adolescence and modulate subsequent memory

    Gail M Rosenbaum, Hannah L Grassie, Catherine A Hartley
    Relative to children and adults, adolescents placed greater weight on negative prediction errors during learning and these age-varying learning idiosyncrasies biased subsequent memory for information associated with valenced outcomes.
    1. Biochemistry and Chemical Biology

    RNA binding to human METTL3-METTL14 restricts N6-deoxyadenosine methylation of DNA in vitro

    Shan Qi, Javier Mota ... Yogesh K Gupta
    Structured RNA elements bind to the human methyltransferase like-3 (METTL3)-METTL14 enzyme complex with high affinity and restrict the formation of N6-deoxymethyladenosine in DNA.
    1. Neuroscience

    Parallel processing in speech perception with local and global representations of linguistic context

    Christian Brodbeck, Shohini Bhattasali ... Ellen Lau
    Speech processing engages multiple predictive models, using sublexical, word- and sentence contexts in parallel to anticipate upcoming phonemes.
    1. Physics of Living Systems

    Emergence of behaviour in a self-organized living matter network

    Philipp Fleig, Mirna Kramar ... Karen Alim
    Behavioural states emerge from variability in the complexity of underlying active contraction dynamics in a single-cell, network-shaped forager.
    1. Neuroscience

    Synaptic connectivity to L2/3 of primary visual cortex measured by two-photon optogenetic stimulation

    Travis A Hage, Alice Bosma-Moody ... Gabe J Murphy
    A combination of multicellular recording and optogenetic photostimulation was used to deeply characterize the spatial profiles and effective strengths of intralaminar and translaminar synaptic connections from genetically defined neuronal populations in the visual cortex of adult mouse.
    1. Immunology and Inflammation
    2. Medicine

    Effects of IFIH1 rs1990760 variants on systemic inflammation and outcome in critically ill COVID-19 patients in an observational translational study

    Laura Amado-Rodríguez, Estefania Salgado del Riego ... Guillermo M Albaiceta
    Patients with different rs1990760 variants have a differential inflammatory response to severe SARS-CoV-2 infections, so that those with a TT genotype have an attenuated systemic inflammation and may not benefit from steroid therapy.
    1. Cell Biology

    A δ-cell subpopulation with a pro-β-cell identity contributes to efficient age-independent recovery in a zebrafish model of diabetes

    Claudio Andrés Carril Pardo, Laura Massoz ... Isabelle Manfroid
    Most regenerated cells after β-cell damage in zebrafish are Insulin+ Somatostatin+ bihormonal cells that are functional and able to restore glucose control.
    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    Transcriptional correlates of malaria in RTS,S/AS01-vaccinated African children: a matched case–control study

    Gemma Moncunill, Jason Carnes ... Raphael Gottardo
    Prevaccination levels of transcriptional modules related to monocytes, dendritic cells, and other immune categories correlate with clinical malaria risk in RTS,S/AS01E-vaccinated African children, suggesting that certain monocyte subsets may inhibit RTS,S/AS01E-induced protective responses.
    1. Structural Biology and Molecular Biophysics

    Nanofluidic chips for cryo-EM structure determination from picoliter sample volumes

    Stefan T Huber, Edin Sarajlic ... Arjen J Jakobi
    A novel strategy for reproducible cryo-EM sample preparation with minimal sample volumes.
    1. Cell Biology
    2. Microbiology and Infectious Disease

    Absolute quantitation of individual SARS-CoV-2 RNA molecules provides a new paradigm for infection dynamics and variant differences

    Jeffrey Y Lee, Peter AC Wing ... Ilan Davis
    Single-molecule analysis of SARS-CoV-2 RNA identifies significant heterogeneity in cellular viral RNA levels and highlights slower replication kinetics for the Alpha variant compared to the Victoria strain.
    1. Neuroscience

    Judgments of agency are affected by sensory noise without recruiting metacognitive processing

    Marika Constant, Roy Salomon, Elisa Filevich
    Explicit judgments of agency incorporate uncertainty by reflecting first-order measures of a noisy signal, but they do not correspond to second-order metacognitive measures of the noise in a signal.
    1. Chromosomes and Gene Expression
    2. Developmental Biology

    The imprinted Zdbf2 gene finely tunes control of feeding and growth in neonates

    Juliane Glaser, Julian Iranzo ... Deborah Bourc'his
    Zdbf2 is a paternally expressed gene that is mainly expressed in the hypothalamus and promotes appetite and body weight gain in neonates.
    1. Neuroscience

    Automated annotation of birdsong with a neural network that segments spectrograms

    Yarden Cohen, David Aaron Nicholson ... Timothy J Gardner
    A machine learning model, TweetyNet, make it possible to scale up annotation of birdsong across individual birds, days of song, and species.
    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    Systematic analysis of naturally occurring insertions and deletions that alter transcription factor spacing identifies tolerant and sensitive transcription factor pairs

    Zeyang Shen, Rick Z Li ... Christopher K Glass
    Collaborative transcription factors (TFs) exhibit a dominant pattern of a relaxed range of spacing and substantial tolerance of spacing alterations resulting from naturally occurring insertions and deletions in comparison to genetic variants directly affecting TF binding sites.
    1. Neuroscience

    An open-source tool for automated analysis of breathing behaviors in common marmosets and rodents

    Mitchell Bishop, Maximilian Weinhold ... Shahriar SheikhBahaei
    The introduced Python tool was used to characterize breathing behaviors of common marmosets in room air and acute hypoxic (10% O2) and hypercapnic (6% CO2) conditions.
    1. Neuroscience

    Global organization of neuronal activity only requires unstructured local connectivity

    David Dahmen, Moritz Layer ... Moritz Helias
    Short-ranged and random connectivity are sufficient to explain complex, long-range activity patterns observed in macaque motor cortex that are, moreover, flexibly adaptable to behavior.
    1. Physics of Living Systems
    2. Structural Biology and Molecular Biophysics

    An empirical energy landscape reveals mechanism of proteasome in polypeptide translocation

    Rui Fang, Jason Hon ... Ying Lu
    Empirical energy landscape allows simulating the structural dynamics of the proteasomal ATPase complex, which yields predictions that are widely consistent with experimental observations and reveals the functional mechanism of the proteasome in substrate degradation.
    1. Computational and Systems Biology
    2. Neuroscience

    Human interictal epileptiform discharges are bidirectional traveling waves echoing ictal discharges

    Elliot H Smith, Jyun-you Liou ... John D Rolston
    Large bursts of brain activity in patients with epilepsy are geometrically related to seizure propagation.
    1. Developmental Biology
    2. Evolutionary Biology

    Xbp1 and Brachyury establish an evolutionarily conserved subcircuit of the notochord gene regulatory network

    Yushi Wu, Arun Devotta ... Anna Di Gregorio
    Research carried out in the simple chordate Ciona has elucidated the regulatory interplay between two evolutionarily conserved transcription factors, Brachyury and Xbp1, and has shed new light on their roles in the formation of the notochord.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Synergistic phase separation of two pathways promotes integrin clustering and nascent adhesion formation

    Lindsay B Case, Milagros De Pasquale ... Michael K Rosen
    Biochemical and cell biological data suggest a model of nascent integrin adhesion complex formation based on synergistic phase separation of pathways surrounding the focal adhesion kinase (FAK) and the adaptor protein p130Cas.
    1. Cell Biology
    2. Immunology and Inflammation

    SNX9-induced membrane tubulation regulates CD28 cluster stability and signalling

    Manuela Ecker, Richard Schregle ... Jeremie Rossy
    Sorting nexin 9, a membrane curvature inducing protein, creates a distinct environment within clusters of the co-receptor CD28 and thereby allows T cell activation to proceed to a successful outcome.
    1. Neuroscience

    Open-source, Python-based, hardware and software for controlling behavioural neuroscience experiments

    Thomas Akam, Andy Lustig ... Mark E Walton
    pyControl is an open-source tool that makes it easy to specify complex behavioural tasks, run them at scale on low-cost hardware, and communicate task logic to other researchers.
    1. Structural Biology and Molecular Biophysics

    Structural organization and dynamics of FCHo2 docking on membranes

    Fatima El Alaoui, Ignacio Casuso ... Laura Picas
    The pioneering endocytic protein FCHo2 promotes clathrin-coated structures assembly via the formation of phosphoinositide-enriched domains at the boundary of cargo receptors.
    1. Developmental Biology

    Differential regulation of cranial and cardiac neural crest by serum response factor and its cofactors

    Colin J Dinsmore, Philippe Soriano
    A novel allele of serum response factor (SRF) reveals distinct co-factor requirements in different developmental contexts, raising issues of redundancy, threshold requirements, or novel co-factor usage.
    1. Neuroscience

    Most primary olfactory neurons have individually neutral effects on behavior

    Tayfun Tumkaya, Safwan Burhanudin ... Adam Claridge-Chang
    Of the 50 primary olfactory channels in vinegar flies, only 10 drive avoidance or approach behavior when activated by themselves, indicating that most olfactory responses are multi-channel responses that follow complex combination rules.
    1. Evolutionary Biology
    2. Neuroscience

    Connexins evolved after early chordates lost innexin diversity

    Georg Welzel, Stefan Schuster
    An in silico analysis of gap junction proteins supports the hypothesis that connexins replaced the primordial innexins in chordate gap junctions due to an evolutionary bottleneck.
    1. Developmental Biology
    2. Neuroscience

    Developmental single-cell transcriptomics of hypothalamic POMC neurons reveal the genetic trajectories of multiple neuropeptidergic phenotypes

    Hui Yu, Marcelo Rubinstein, Malcolm J Low
    Single-cell transcriptomic analyses of hypothalamic POMC neurons performed at seven developmental ages revealed marked cellular heterogeneity and divergent developmental pathways into alternative neuronal phenotypes that lack POMC.
    1. Chromosomes and Gene Expression

    Rif2 protects Rap1-depleted telomeres from MRX-mediated degradation in Saccharomyces cerevisiae

    Fernando Rodrigo Rosas Bringas, Sonia Stinus ... Michael Chang
    Telomere-specific depletion of Rap1, the main sequence-specific telomere-binding protein in Saccharomyces cerevisiae, can be tolerated due to the presence of secondary telomere capping mechanisms, which may help explain the rapid evolution of budding yeast telomeres.
    1. Biochemistry and Chemical Biology
    2. Computational and Systems Biology

    Comprehensive interrogation of the ADAR2 deaminase domain for engineering enhanced RNA editing activity and specificity

    Dhruva Katrekar, Yichen Xiang ... Prashant Mali
    A deep mutational scan of the ADAR2 deaminase domain creates a map for designing tailored ADAR2 variants, and splitting the deaminase between residues 468 and 469 enables highly transcript-specific RNA editing.
    1. Microbiology and Infectious Disease

    Sensitizing Staphylococcus aureus to antibacterial agents by decoding and blocking the lipid flippase MprF

    Christoph J Slavetinsky, Janna N Hauser ... Andreas Peschel
    Blocking the bacterial lipid flippase MprF by monoclonal antibodies enhance staphylococcal clearance by host defense and antibiotics providing a novel proof of concept for antivirulence approaches targeting bacterial resistance mechanisms.
    1. Immunology and Inflammation

    Fine-tuning of β-catenin in mouse thymic epithelial cells is required for postnatal T-cell development

    Sayumi Fujimori, Izumi Ohigashi ... Shinji Takada
    Highly specific gene manipulation in mouse thymic epithelial cells (TECs) shows that fine-tuning of β-catenin expression is required for TECs to generate an optimal thymic microenvironment to support T-cell development.
    1. Ecology
    2. Epidemiology and Global Health

    Both consumptive and non-consumptive effects of predators impact mosquito populations and have implications for disease transmission

    Marie C Russell, Catherine M Herzog ... Andrew C McCall
    While predators can clearly reduce mosquito populations by consumption, they can also have non-consumptive effects on mosquito body size and oviposition behavior, and these effects on vector traits can influence infectious disease dynamics.
    1. Cell Biology

    Lipid kinases VPS34 and PIKfyve coordinate a phosphoinositide cascade to regulate retriever-mediated recycling on endosomes

    Sai Srinivas Panapakkam Giridharan, Guangming Luo ... Lois S Weisman
    The synthesis of multiple phosphoinositides function in an ordered pathway to promote recycling of some receptors to the plasma membrane.
    1. Evolutionary Biology
    2. Genetics and Genomics

    Genetic basis and dual adaptive role of floral pigmentation in sunflowers

    Marco Todesco, Natalia Bercovich ... Loren H Rieseberg
    Variation in patterns of floral UV pigmentation is controlled by a single transcription factor in sunflower and affects both pollinator attraction and responses to environmental stresses.
    1. Computational and Systems Biology
    2. Neuroscience

    Hippocampal sharp wave-ripples and the associated sequence replay emerge from structured synaptic interactions in a network model of area CA3

    András Ecker, Bence Bagi ... Szabolcs Káli
    Simulations of a detailed network model show that the pattern of synaptic interactions resulting from learning is critical for the emergence of population bursts, sequential neuronal activity, and fast oscillations in the hippocampus.
    1. Medicine
    2. Stem Cells and Regenerative Medicine

    Therapeutic downregulation of neuronal PAS domain 2 (Npas2) promotes surgical skin wound healing

    Yoichiro Shibuya, Akishige Hokugo ... Reza Jarrahy
    A small molecule compound Dwn1, identified through high-throughput screening using Npas2 as the molecular target, enhances wound healing in a murine incisional wound model.
    1. Cancer Biology
    2. Ecology

    Mitochondrial genome sequencing of marine leukaemias reveals cancer contagion between clam species in the Seas of Southern Europe

    Daniel Garcia-Souto, Alicia L Bruzos ... Jose MC Tubio
    Genome sequencing analysis dissects the origins and evolution of cancer transmission between clam species in the Seas of Southern Europe.
    1. Developmental Biology
    2. Physics of Living Systems

    Emergence of a geometric pattern of cell fates from tissue-scale mechanics in the Drosophila eye

    Kevin D Gallagher, Madhav Mani, Richard W Carthew
    Formation of a triangular lattice of photoreceptor clusters in the compound eye is driven by highly regulated cell flows in the eye epithelium, through a mechanochemical mechanism.
    1. Computational and Systems Biology
    2. Neuroscience

    An image reconstruction framework for characterizing initial visual encoding

    Ling-Qi Zhang, Nicolas P Cottaris, David H Brainard
    A computational model of the initial visual encoding together with Bayesian image reconstruction quantifies how that encoding, combined with the statistical regularities of natural images, shapes key aspects of visual perception.
    1. Cell Biology
    2. Developmental Biology

    The NDNF-like factor Nord is a Hedgehog-induced extracellular BMP modulator that regulates Drosophila wing patterning and growth

    Shu Yang, Xuefeng Wu ... Xiaoyan Zheng
    The NDNF-like factor Nord is a Hedgehog-induced and extracellular-localized dosage-dependent BMP modulator that regulates Drosophila wing patterning and growth.
    1. Microbiology and Infectious Disease

    A qnr-plasmid allows aminoglycosides to induce SOS in Escherichia coli

    Anamaria Babosan, David Skurnik ... Thomas Guillard
    A mechanism whereby aminoglycosides-mediated SOS induction in Escherichia coli also promote high-level fluoroquinolone resistance.
    1. Computational and Systems Biology
    2. Medicine

    A human-based multi-gene signature enables quantitative drug repurposing for metabolic disease

    James A Timmons, Andrew Anighoro ... Stuart M Phillips
    Optimising the use of transcriptomics enables screening of thousands of compounds and illustrates an approach that yields quantitative pharmacology at the single-gene and pathway level.
    1. Cell Biology

    A phosphoswitch at acinus-serine437 controls autophagic responses to cadmium exposure and neurodegenerative stress

    Nilay Nandi, Zuhair Zaidi ... Helmut Krämer
    The metal-dependent protein phosphatase Nilkantha, a Drosophila PPM1A/B homolog, dephosphorylates Acinus thereby restraining starvation-independent autophagy.
    1. Evolutionary Biology
    2. Genetics and Genomics

    Repeated origins, widespread gene flow, and allelic interactions of target-site herbicide resistance mutations

    Julia M Kreiner, George Sandler ... Stephen I Wright
    The spread of herbicide resistance in one of the most problematic weeds in North America occurs through both recent, repeated mutational origins and gene flow across an international network of agricultural fields.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    The mitotic spindle protein CKAP2 potently increases formation and stability of microtubules

    Thomas S McAlear, Susanne Bechstedt
    Demonstration of the biochemical capacity of the spindle protein CKAP2 as the most potent assembly factor of microtubules.
    1. Developmental Biology

    Regeneration of the larval sea star nervous system by wounding induced respecification to the Sox2 lineage

    Minyan Zheng, Olga Zueva, Veronica F Hinman
    Seastar larvae can regenerate their nervous system by specifying cells to express the gene sox2 to enter neural progenitor states that then follow embryonic gene regulatory modes to form new neurons.
    1. Epidemiology and Global Health
    2. Genetics and Genomics

    DunedinPACE, a DNA methylation biomarker of the pace of aging

    Daniel W Belsky, Avshalom Caspi ... Terrie E Moffitt
    DunedinPACE is a novel DNA methylation biomarker of the pace of biological aging for intervention trials and natural experiment studies investigating how the rate of aging may be changed by behavioral or drug therapy, or by environmental modification.
    1. Plant Biology

    CASP microdomain formation requires cross cell wall stabilization of domains and non-cell autonomous action of LOTR1

    Andreas Kolbeck, Peter Marhavý ... Niko Geldner
    Localized lignin impregnations, forming a pan-endodermal net-like diffusion barrier strongly relies on stabilizing signals from neighbors.
    1. Microbiology and Infectious Disease

    Breaking antimicrobial resistance by disrupting extracytoplasmic protein folding

    R Christopher D Furniss, Nikol Kaderabkova ... Despoina AI Mavridou
    Disruption of disulfide bond formation sensitizes resistant Gram-negative bacteria expressing β-lactamases and mobile colistin resistance enzymes to currently available antibiotics.
    1. Immunology and Inflammation

    ACE2 is the critical in vivo receptor for SARS-CoV-2 in a novel COVID-19 mouse model with TNF- and IFNγ-driven immunopathology

    Riem Gawish, Philipp Starkl ... Sylvia Knapp
    Only three Spike mutations enable murine SARS-CoV-2 infection, which is still strictly ACE2 dependent and causes a COVID-19-like disease in mice with immunopathology-driven lung damage.
    1. Epidemiology and Global Health
    2. Genetics and Genomics

    Epigenetic scores for the circulating proteome as tools for disease prediction

    Danni A Gadd, Robert F Hillary ... Riccardo E Marioni
    Epigenetic scores for blood protein levels identify those at risk of multiple age-related morbidities, up to 14 years prior to onset.
    1. Structural Biology and Molecular Biophysics

    Structural basis of Plasmodium vivax inhibition by antibodies binding to the circumsporozoite protein repeats

    Iga Kucharska, Lamia Hossain ... Jean-Philippe Julien
    Biophysical and structural studies reveal how two inhibitory antibodies targeting CSP on malaria-causing Plasmodium vivax parasites lock its intrinsically flexible repeat into predominant coiled conformations, contributing molecular details of Pv inhibition by antibodies to enable structure-based engineering of PvCSP-based vaccines.
    1. Genetics and Genomics

    Disruption of PIKFYVE causes congenital cataract in human and zebrafish

    Shaoyi Mei, Yi Wu ... Jun Zhao
    Deleterious genetic variants in the PIP kinase domain of PIKFYVE are directly associated with the occurrence of congenital cataract in human and zebrafish.
    1. Neuroscience

    Shallow neural networks trained to detect collisions recover features of visual loom-selective neurons

    Baohua Zhou, Zifan Li ... Damon A Clark
    When artificial networks modeled on a Drosophila neuron are tasked with discriminating objects on collision course from other visual scenes, their optimized solutions reproduce many functional features of the original loom-selective neuron.
    1. Biochemistry and Chemical Biology
    2. Developmental Biology

    Maternal diet-induced obesity during pregnancy alters lipid supply to mouse E18.5 fetuses and changes the cardiac tissue lipidome in a sex-dependent manner

    Lucas C Pantaleão, Isabella Inzani ... Susan E Ozanne
    Maternal obesity alters the fetal cardiac and serum lipidome, promoting early fetal cardiac metabolic maturation, with evidence that the female heart lipidome is more responsive to an in utero obesogenic environment.
    1. Neuroscience

    A novel and accurate full-length HTT mouse model for Huntington’s disease

    Sushila A Shenoy, Sushuang Zheng ... Chenjian Li
    A novel BAC226Q mouse recapitulating robust, age-dependent, progressive Huntington’s disease (HD)-like phenotypes will be a valuable tool for studying disease mechanisms, identifying biomarkers, and testing gene-targeting therapeutic approaches for HD.
    1. Genetics and Genomics
    2. Medicine

    GWAS and ExWAS of blood mitochondrial DNA copy number identifies 71 loci and highlights a potential causal role in dementia

    Michael Chong, Pedrum Mohammadi-Shemirani ... Guillaume Paré
    An ethnically robust pipeline for inferring mitochondrial DNA copy number from genotyping arrays was developed and applied to the UKBiobank, elucidating several common and rare loci in genes involved in the synthesis, maintenance, and organization of mitochondrial DNA.
    1. Developmental Biology
    2. Genetics and Genomics

    Drosophila p53 isoforms have overlapping and distinct functions in germline genome integrity and oocyte quality control

    Ananya Chakravarti, Heshani N Thirimanne ... Brian R Calvi
    Drosophila p53 protein isoforms function during oogenesis to ensure the integrity of the transmitted genome, a function that is conserved to humans.
    1. Cancer Biology
    2. Cell Biology

    Chromatin topology defines estradiol-primed progesterone receptor and PAX2 binding in endometrial cancer cells

    Alejandro La Greca, Nicolás Bellora ... Patricia Saragüeta
    Binding of progesterone receptor and transcription factor PAX2 to pre-assembled permissive chromatin compartments regulates endometrial cancer gene expression under estrogenic conditions.
    1. Evolutionary Biology
    2. Genetics and Genomics

    The Mutationathon highlights the importance of reaching standardization in estimates of pedigree-based germline mutation rates

    Lucie A Bergeron, Søren Besenbacher ... Mikkel H Schierup
    This first comparison of different methodologies to estimate germline mutation rate from pedigrees resulted in almost a 2-fold variation in the estimated rates, discrepancies mainly caused by different filtering methods.
    1. Neuroscience

    Motor planning brings human primary somatosensory cortex into action-specific preparatory states

    Giacomo Ariani, J Andrew Pruszynski, Jörn Diedrichsen
    Movement planning elicits finger-specific activity in primary somatosensory cortex that is strongly correlated to the finger-specific activity elicited during movement execution.
    1. Biochemistry and Chemical Biology

    Systematic investigation of the link between enzyme catalysis and cold adaptation

    Catherine Stark, Teanna Bautista-Leung ... Daniel Herschlag
    Increased catalysis has been suggested to be an adaptive trait of enzymes to growth at lower temperature, but systematic analysis suggests that temperature exerts a weak selection pressure on enzyme rate enhancement, with observed variation arising from other evolutionary forces.
    1. Developmental Biology
    2. Neuroscience

    Myelinating Schwann cells and Netrin-1 control intra-nervous vascularization of the developing mouse sciatic nerve

    Sonia Taïb, Noël Lamandé ... Isabelle Brunet
    Angiogenesis and vascular development within peripheral nerve is regulated by Netrin-1, Schwann cells, and myelination.
    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    Recapitulating human cardio-pulmonary co-development using simultaneous multilineage differentiation of pluripotent stem cells

    Wai Hoe Ng, Elizabeth K Johnston ... Xi Ren
    An induced pluripotent stem-cell-based, human heart and lung co-differentiation model reveals their shared signaling requirement and enables investigation of their developmental mutual interaction and tissue boundary formation.
    1. Medicine
    2. Neuroscience

    Metabolic sensing in AgRP neurons integrates homeostatic state with dopamine signalling in the striatum

    Alex Reichenbach, Rachel E Clarke ... Zane B Andrews
    Hunger-sensitive AgRP neurons must sense changes in calorie availability to transmit metabolic information into dopamine release in the NAc and dorsal striatum, albeit over different time frames, to increase motivated food reward seeking.
    1. Cell Biology
    2. Genetics and Genomics

    Allele-specific endogenous tagging and quantitative analysis of β-catenin in colorectal cancer cells

    Giulia Ambrosi, Oksana Voloshanenko ... Michael Boutros
    Bi-allelic tagging enables the biophysical analysis of oncogenic β-catenin genetic variants in Wnt signaling.
    1. Medicine

    ACE2 pathway regulates thermogenesis and energy metabolism

    Xi Cao, Ting-Ting Shi ... Jin-Kui Yang
    A series of functional assays in mouse models and primary brown adipocytes confirm that the ACE2 pathway regulates glucose and lipid homeostasis, and maintains thermogenesis and systemic energy metabolism by both the Akt and PKA signaling.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Directed evolution of the rRNA methylating enzyme Cfr reveals molecular basis of antibiotic resistance

    Kaitlyn Tsai, Vanja Stojković ... Danica Galonić Fujimori
    Directed evolution of the resistance enzyme Cfr under antibiotic selection identifies increased Cfr expression and stability as strategies to boost resistance and reveals that Cfr modification of the ribosome confers resistance by sterically occluding binding of antibiotics.
    1. Physics of Living Systems

    Humans optimally anticipate and compensate for an uneven step during walking

    Osman Darici, Arthur D Kuo
    Humans can predict and optimally plan goal-directed dynamic walking tasks that have transient events such as negotiating a sidewalk curb.
    1. Neuroscience

    Assessment of neurovascular coupling and cortical spreading depression in mixed mouse models of atherosclerosis and Alzheimer’s disease

    Osman Shabir, Ben Pendry ... Jason Berwick
    Mice modelling atherosclerosis show neurovascular breakdown in the cortex compared to healthy controls, and inducing atherosclerosis in mice modelling Alzheimer's disease increases the number of amyloid plaques in the hippocampus.
    1. Cell Biology
    2. Immunology and Inflammation

    Stable flow-induced expression of KLK10 inhibits endothelial inflammation and atherosclerosis

    Darian Williams, Marwa Mahmoud ... Hanjoong Jo
    KLK10 is a flow-sensitive endothelial protein that serves as an anti-inflammatory, barrier-protective, and anti-atherogenic factor with therapeutic potential.
    1. Microbiology and Infectious Disease

    Golden Syrian hamster as a model to study cardiovascular complications associated with SARS-CoV-2 infection

    Zaigham Abbas Rizvi, Rajdeep Dalal ... Amit Awasthi
    SARS-CoV-2 infection in hamsters causes cardiovascular pathologies.
    1. Computational and Systems Biology

    Response to comment on ‘SARS-CoV-2 suppresses anticoagulant and fibrinolytic gene expression in the lung’

    Alan E Mast, Alisa S Wolberg ... Daniel Jacobson
    We are writing to respond to the comment by FitzGerald and Jamieson, 2022 on our article about the drivers of coagulopathy in the lungs of COVID-19 patients (Mast et al., 2021).
    1. Medicine

    Aging is associated with increased brain iron through cortex-derived hepcidin expression

    Tatsuya Sato, Jason Solomon Shapiro ... Hossein Ardehali
    Aging is associated with mitochondrial and cytosolic iron accumulation in the brain, which is through increased local expression of hepcidin, and subsequent iron accumulation due to decreased iron export through ferroportin-1.
    1. Neuroscience

    Clathrin-independent endocytic retrieval of SV proteins mediated by the clathrin adaptor AP-2 at mammalian central synapses

    Tania López-Hernández, Koh-ichiro Takenaka ... Shigeo Takamori
    At mammalian synapses the clathrin adaptor AP-2 plays a crucial role in the endocytic retrieval of a subset of synaptic vesicle proteins from the presynaptic cell surface, while clathrin is dispensable.
    1. Microbiology and Infectious Disease

    Comment on ‘SARS-CoV-2 suppresses anticoagulant and fibrinolytic gene expression in the lung’

    Ethan S FitzGerald, Amanda M Jamieson
    We are writing to comment on an article by Mast et al., 2021, about the drivers of coagulopathy in the lungs of COVID-19 patients.
    1. Neuroscience

    Myelination synchronizes cortical oscillations by consolidating parvalbumin-mediated phasic inhibition

    Mohit Dubey, Maria Pascual-Garcia ... Maarten HP Kole
    Demyelination disrupts fast inhibition of pyramidal neurons, thereby changing neocortical rhythms and causing the emergence of brief epileptic-like discharges.
    1. Cell Biology
    2. Physics of Living Systems

    Correlative all-optical quantification of mass density and mechanics of subcellular compartments with fluorescence specificity

    Raimund Schlüßler, Kyoohyun Kim ... Jochen Guck
    The combination of optical diffraction tomography and Brillouin microscopy in a single setup enables to quantitatively map the viscoelastic properties of cellular compartments such as aggregates and stress granules in vivo.
    1. Structural Biology and Molecular Biophysics

    Structural and functional properties of a magnesium transporter of the SLC11/NRAMP family

    Karthik Ramanadane, Monique S Straub ... Cristina Manatschal
    The structural and functional characterization of EleNRMT defines the basis for the distinct ion selectivity of a clade of the SLC11/NRAMP family which, instead of transporting transition metal ions, have evolved as uncoupled transporters of Mg2+.
    1. Genetics and Genomics

    Comparative transcriptomic analysis reveals translationally relevant processes in mouse models of malaria

    Athina Georgiadou, Claire Dunican ... Aubrey J Cunnington
    Comparative transcriptomics of whole blood can be used to evaluate the systemic host response and its concordance between human and mouse malaria and aid the selection of appropriate models for translational malaria research.
    1. Cell Biology
    2. Immunology and Inflammation

    RNA N6-methyladenosine modulates endothelial atherogenic responses to disturbed flow in mice

    Bochuan Li, Ting Zhang ... Degang Liang
    METTL3 and m6A modifications could alleviate endothelial activation and atherogenesis through accelerated degradation of oscillatory flow-induced EGFR mRNA expression.
    1. Cancer Biology
    2. Genetics and Genomics

    Functional CDKN2A assay identifies frequent deleterious alleles misclassified as variants of uncertain significance

    Hirokazu Kimura, Raymond M Paranal ... Nicholas J Roberts
    Over 40% of CDKN2A variants of uncertain significance identified in patients with pancreatic cancer are functionally deleterious and can be reclassified as likely pathogenic with implications for care of patients and their relatives.
    1. Neuroscience

    Archerfish number discrimination

    Davide Potrich, Mirko Zanon, Giorgio Vallortigara
    Archerfish (Toxotes jaculatrix) can encode an abstract concept of number in relative numerousness judgements, without the influence of any continuous physical variables, including spatial frequency.
    1. Cell Biology
    2. Structural Biology and Molecular Biophysics

    Structural basis for cytoplasmic dynein-1 regulation by Lis1

    John P Gillies, Janice M Reimer ... Samara L Reck-Peterson
    A 3.1 Å structure of cytoplasmic dynein-1 in complex with its regulator Lis1 reveals the interfaces between dynein and Lis1, all of which are important for dynein function in vitro and in vivo.
    1. Microbiology and Infectious Disease

    An intestinally secreted host factor promotes microsporidia invasion of C. elegans

    Hala Tamim El Jarkass, Calvin Mok ... Aaron W Reinke
    A forward genetic screen in Caenorhabditis elegans identifies a secreted host protein that ensures proper microsporidia spore orientation, resulting in efficient invasion of intestinal cells.
    1. Developmental Biology
    2. Neuroscience

    PRC1 sustains the integrity of neural fate in the absence of PRC2 function

    Ayana Sawai, Sarah Pfennig ... Jeremy S Dasen
    Regulation of neuronal diversity and fate through protein complexes involved in gene repression and chromatin condensation.
    1. Neuroscience

    Context-dependent relationships between locus coeruleus firing patterns and coordinated neural activity in the anterior cingulate cortex

    Siddhartha Joshi, Joshua I Gold
    Simultaneous recordings in brainstem and cortex, combined with pupillometry, show that changes in coordinated activity in anterior cingulate cortex are related to distinct patterns of pupil-linked activation of the locus coeruleus-norepinephrine system.
    1. Genetics and Genomics
    2. Microbiology and Infectious Disease

    Stress conditions promote Leishmania hybridization in vitro marked by expression of the ancestral gamete fusogen HAP2 as revealed by single-cell RNA-seq

    Isabelle Louradour, Tiago Rodrigues Ferreira ... David Sacks
    Following exposure of Leishmania culture promastigotes to DNA stress, single-cell RNA sequencing reveals discrete clusters of cells associated with efficient generation of hybrids between different species and strains in vitro marked by expression of the ancestral gamete fusogen HAP2.
    1. Plant Biology

    Plant Trans-Golgi Network/Early Endosome pH regulation requires Cation Chloride Cotransporter (CCC1)

    Daniel W McKay, Heather E McFarlane ... Stefanie Wege
    Cation chloride cotransporter CCC1 has a central function in plant cells and is the missing ion efflux component of the transport circuit necessary to regulate pH in the lumen of the trans-Golgi-network/early endosome, the major cargo hub in plant cells.
    1. Developmental Biology

    Tracking cell lineages in 3D by incremental deep learning

    Ko Sugawara, Çağrı Çevrim, Michalis Averof
    Incremental deep learning enables accurate tracking of cell lineages in 3D with a modest investment in time and effort.
    1. Evolutionary Biology
    2. Genetics and Genomics

    Unique structure and positive selection promote the rapid divergence of Drosophila Y chromosomes

    Ching-Ho Chang, Lauren E Gregory ... Amanda M Larracuente
    Differences in the usage of DNA repair pathways may give rise to the unique patterns of Y-linked mutations that, together with natural selection, shape rapid Y chromosome evolution.
    1. Microbiology and Infectious Disease

    Human monoclonal antibodies against Staphylococcus aureus surface antigens recognize in vitro and in vivo biofilm

    Lisanne de Vor, Bruce van Dijk ... Suzan HM Rooijakkers
    Antibody-based biologicals could provide an alternative approach to improve the diagnosis of Staphylococcus aureus biofilm-related infections.
    1. Neuroscience

    Increasing stimulus similarity drives nonmonotonic representational change in hippocampus

    Jeffrey Wammes, Kenneth A Norman, Nicholas Turk-Browne
    Hippocampal learning in dentate gyrus follows a U-shaped function, with moderate, but not high or low, overlap between representations leading to differentiation of neural patterns.
    1. Cell Biology
    2. Plant Biology

    Regulation of immune receptor kinase plasma membrane nanoscale organization by a plant peptide hormone and its receptors

    Julien Gronnier, Christina M Franck ... Cyril Zipfel
    The perception of endogenous RALF signaling peptides modulates the plasma membrane nanoscale organization of receptor kinases to regulate plant immune signaling.
    1. Neuroscience

    Synaptic mechanisms of top-down control in the non-lemniscal inferior colliculus

    Hannah M Oberle, Alexander N Ford ... Pierre F Apostolides
    Optogenetic and electrophysiological experiments show how a behaviorally relevant 'feedback' pathway from auditory cortex controls neural activity in the inferior colliculus, an auditory midbrain region important for processing complex time-varying sounds such as speech.
    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    A test of the pioneer factor hypothesis using ectopic liver gene activation

    Jeffrey L Hansen, Kaiser J Loell, Barak A Cohen
    Pioneering activity may be a property of all transcription factors with sufficient affinity for their targets rather than a property of specific classes of transcription factors.
    1. Epidemiology and Global Health

    Risk factors relate to the variability of health outcomes as well as the mean: A GAMLSS tutorial

    David Bann, Liam Wright, Tim J Cole
    We provide a tutorial to use GAMLSS, applied using cohort data to study how risk factors may influence both the mean and variability of body mass index and mental health.
    1. Genetics and Genomics

    Functional profiling of long intergenic non-coding RNAs in fission yeast

    Maria Rodriguez-Lopez, Shajahan Anver ... Jürg Bähler
    Phenomics assays reveal hundreds of mutant phenotypes for long non-coding RNAs grown in specific environmental or physiological contexts, indicating that most of these RNAs exert cellular functions under certain conditions.
    1. Evolutionary Biology

    Activation by cleavage of the epithelial Na+ channel α and γ subunits independently coevolved with the vertebrate terrestrial migration

    Xue-Ping Wang, Deidra M Balchak ... Ossama B Kashlan
    Proteolytic activation of a sodium-permeable channel that aids in gas exchange and fluid homeostasis likely evolved at the water to land transition in vertebrates.
    1. Epidemiology and Global Health
    2. Medicine

    Development, validation, and application of a machine learning model to estimate salt consumption in 54 countries

    Wilmer Cristobal Guzman-Vilca, Manuel Castillo-Cara, Rodrigo M Carrillo-Larco
    A machine learning model could accurately estimate daily salt consumption in the general population and can be applied to countries lacking urine sample to compute the mean salt consumption at the population level.
    1. Medicine
    2. Neuroscience

    The role of action potential changes in depolarization-induced failure of excitation contraction coupling in mouse skeletal muscle

    Xueyong Wang, Murad Nawaz ... Mark M Rich
    Detailed studies of excitation contraction coupling allowed determination of quantitative relationships between resting potential, generation of action potentials, conduction of action potentials, and generation of Ca2+ transients in individual mouse skeletal muscle fibers.
    1. Structural Biology and Molecular Biophysics

    Allosteric modulation of the adenosine A2A receptor by cholesterol

    Shuya Kate Huang, Omar Almurad ... R Scott Prosser
    Cholesterol exhibits transient interaction with A2AR and regulates receptor conformational equilibria through indirect membrane effects.
    1. Developmental Biology
    2. Evolutionary Biology

    Cavefish cope with environmental hypoxia by developing more erythrocytes and overexpression of hypoxia-inducible genes

    Corine M van der Weele, William R Jeffery
    Astyanax mexicanus cavefish cope with hypoxic environments by expanding embryonic hematopoietic domains, increasing the capacity for erythrocyte development, and constitutive overexpression of hypoxia-inducible genes.
    1. Cancer Biology
    2. Cell Biology

    Type I and II PRMTs inversely regulate post-transcriptional intron detention through Sm and CHTOP methylation

    Maxim I Maron, Alyssa D Casill ... David Shechter
    Biochemical, transcriptomic, and proteomic analyses reveal that protein arginine methyltransferases post-transcriptionally regulate intron detention—introns that persist in nuclear polyadenylated RNA—through methylation of RNA splicing and processing factors.
    1. Neuroscience

    The anterior cingulate cortex and its role in controlling contextual fear memory to predatory threats

    Miguel Antonio Xavier de Lima, Marcus Vinicius C Baldo ... Newton Sabino Canteras
    The anterior cingulate cortex provides predictive relationships between the context and the predator threat and influences the acquisition and expression of fear memory to predatory threat.
    1. Neuroscience

    Respiratory alkalosis provokes spike-wave discharges in seizure-prone rats

    Kathryn A Salvati, George MPR Souza ... Mark P Beenhakker
    Respiratory alkalosis recruits the midline thalamus to provoke absence seizures.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Polyunsaturated fatty acids inhibit a pentameric ligand-gated ion channel through one of two binding sites

    Noah M Dietzen, Mark J Arcario ... Wayland WL Cheng
    Docosahexaenoic acid (DHA) inhibits ELIC through state-dependent binding to a single site.
    1. Chromosomes and Gene Expression
    2. Developmental Biology

    Establishment of developmental gene silencing by ordered polycomb complex recruitment in early zebrafish embryos

    Graham JM Hickey, Candice L Wike ... Bradley R Cairns
    Zebrafish early embryos initially package their developmental genes and enhancers in 'active' chromatin that subsequently receives polycomb repressive complex 1 (PRC1)-mediated histone H2A ubiquitylation, which confers silencing/poising – prior to Aebp2-PRC2-guided H3K27me3 addition.
    1. Neuroscience

    Similar neural and perceptual masking effects of low-power optogenetic stimulation in primate V1

    Spencer Chin-Yu Chen, Giacomo Benvenuti ... Eyal Seidemann
    Simultaneous optogenetic stimulation and calcium imaging in V1 of behaving macaques reveals that low-power optostimulation can substitute a visual mask and significantly reduce perceptual and neural detection sensitivities.
    1. Neuroscience
    2. Stem Cells and Regenerative Medicine

    Transcriptional regulation of neural stem cell expansion in the adult hippocampus

    Nannan Guo, Kelsey D McDermott ... Amar Sahay
    Kruppel-like factor 9 (Klf9) is a transcriptional regulator of neural stem cell expansion in the adult hippocampus.
    1. Cell Biology
    2. Developmental Biology

    Autophagosomes fuse to phagosomes and facilitate the degradation of apoptotic cells in Caenorhabditis elegans

    Omar Peña-Ramos, Lucia Chiao ... Zheng Zhou
    The crosstalk between autophagy and the phagocytosis of apoptotic cells, two cellular clearance pathways, promotes the fusion of the double-membrane autophagosomes to the phagosomes and plays an important role in the degradation of engulfed apoptotic cells.
    1. Cell Biology
    2. Developmental Biology

    Chlamydomonas ARMC2/PF27 is an obligate cargo adapter for intraflagellar transport of radial spokes

    Karl F Lechtreck, Yi Liu ... Pinfen Yang
    The cargo adapter ARMC2 mediates the association of radial spoke complexes to IFT trains ensuring radial spoke import and assembly in Chlamydomonas flagella.
    1. Neuroscience

    Fluorescence activation mechanism and imaging of drug permeation with new sensors for smoking-cessation ligands

    Aaron L Nichols, Zack Blumenfeld ... Henry A Lester
    Pharmacokinetics, the venerable science that measures the dynamics and concentrations an administered drug attains in organs, has been extended to the subcellular level – organelles – by a generalizable new paradigm.
    1. Neuroscience

    Dissociation of impulsive traits by subthalamic metabotropic glutamate receptor 4

    Lukasz Piszczek, Andreea Constantinescu ... Wulf Haubensak
    Metabotropic glutamate receptors modulate impulse control by the subthalamic nucleus, dissociating trait impulsivity from basal ganglia motor function.