October 2022

Cover articles

    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    Forces inside the intestine

    Jerome Bohere, Buffy L Eldridge-Thomas, Golnar Kolahgar
    1. Genetics and Genomics

    The hunger response in flies

    Kevin P Kelly, Mroj Alassaf ... Akhila Rajan
    1. Developmental Biology

    Regulating neural crest cells

    Erica J Hutchins, Shashank Gandhi ... Marianne E Bronner
    1. Developmental Biology

    Regulating neural crest cells

    Erica J Hutchins, Shashank Gandhi ... Marianne E Bronner

Highlights controls:

Research articles

    1. Neuroscience

    Constitutively active STING causes neuroinflammation and degeneration of dopaminergic neurons in mice

    Eva M Szego, Laura Malz ... Hella Luksch
    Constitutive activation of an innate immunity response in mouse brain causes degeneration of dopaminergic neurons, suggesting novel targets for potentially neuroprotective strategies.
    1. Neuroscience

    Contrast polarity-specific mapping improves efficiency of neuronal computation for collision detection

    Richard Burkett Dewell, Ying Zhu ... Fabrizio Gabbiani
    The processing of light and dark contrast information for detecting impending visual threats within grasshopper neurons reveals new mechanisms of information processing in the brain.
    1. Developmental Biology

    Sex-specific role of myostatin signaling in neonatal muscle growth, denervation atrophy, and neuromuscular contractures

    Marianne E Emmert, Parul Aggarwal ... Roger Cornwall
    Myostatin signaling governs neonatal longitudinal muscle growth and neuromuscular contractures in a sex-dependent manner, identifying a potential avenue for contracture treatment and underscoring the need to consider sex as a biological variable in the pathophysiology of acquired neuromuscular disorders.
    1. Neuroscience

    Precise and stable edge orientation signaling by human first-order tactile neurons

    Vaishnavi Sukumar, Roland S Johansson, J Andrew Pruszynski
    Individual human first-order tactile neurons, those that innervate the mechanoreceptors in the skin, can signal information about edge orientation differences at the limit of what people can feel and across a broad range of speeds relevant for real-world hand use.
    1. Neuroscience

    A DARPin-based molecular toolset to probe gephyrin and inhibitory synapse biology

    Benjamin FN Campbell, Antje Dittmann ... Shiva K Tyagarajan
    Anti-gephyrin synthetic protein binders were screened and developed to specifically and robustly detect gephyrin protein and gephyrin-interacting protein partners in the mouse brain, generating a useful tool set for neuroscience.
    1. Neuroscience

    The role of conjunctive representations in prioritizing and selecting planned actions

    Atsushi Kikumoto, Ulrich Mayr, David Badre
    Time-resolved decoding of EEG reveals the nature of representations of upcoming actions and how the planned action is selected from working memory.
    1. Cancer Biology

    Revised International Staging System (R-ISS) stage-dependent analysis uncovers oncogenes and potential immunotherapeutic targets in multiple myeloma (MM)

    Ling Zhong, Peng Hao ... Bo Gong
    Among multiple myeloma stratified by Revised International Staging System, single-cell transcriptome atlas reveals novel heterogeneities with NKG7+ cytotoxic plasma cells (PCs) enriched in stage II, RRM2+ high proliferative PCs enriched in stage III, and MKI67 up-regulated in EBV-positive patients.
    1. Structural Biology and Molecular Biophysics

    A cryogenic, coincident fluorescence, electron, and ion beam microscope

    Daan B Boltje, Jacob P Hoogenboom ... Sander den Hoedt
    Integrating a cryogenic light microscope with a focused ion beam/scanning electron microscope, allows directly targeting of fluorescent structure when preparing a frozen-hydrated lamella, without the need for repositioning or fiducial markers.
    1. Computational and Systems Biology
    2. Neuroscience

    High-throughput automated methods for classical and operant conditioning of Drosophila larvae

    Elise C Croteau-Chonka, Michael S Clayton ... Kristina T Klein
    A novel high-throughput FPGA-based multi-animal tracking and training system was used to demonstrate trace and operant conditioning in Drosophila larvae.
    1. Structural Biology and Molecular Biophysics

    Computational model of the full-length TSH receptor

    Mihaly Mezei, Rauf Latif, Terry F Davies
    Molecular dynamics simulation of the full-length TSH receptor, a major human autoantigen whose full structure remains uncertain, showed that its linker region is an intrinsically disordered protein, explaining the difficulty of obtaining an experimental structure.
    1. Evolutionary Biology

    Environmental response in gene expression and DNA methylation reveals factors influencing the adaptive potential of Arabidopsis lyrata

    Tuomas Hämälä, Weixuan Ning ... Outi Savolainen
    Environmentally responsive genes evolve under strong selective constraint in Arabidopsis lyrata.
    1. Cell Biology
    2. Developmental Biology

    Osteocytes regulate senescence of bone and bone marrow

    Peng Ding, Chuan Gao ... Junjie Gao
    Partial ablation of osteocytes alters lineage cell specifications in bone and bone marrow, resulting in the acceleration of skeletal aging.
    1. Biochemistry and Chemical Biology

    Z-REX uncovers a bifurcation in function of Keap1 paralogs

    Alexandra Van Hall-Beauvais, Jesse R Poganik ... Yimon Aye
    Two zebrafish Keap1-paralogs are equally adept at electrophile-sensing but manifest divergent and co-regulatory electrophile-signaling behaviors.
    1. Biochemistry and Chemical Biology

    Covalent disruptor of YAP-TEAD association suppresses defective Hippo signaling

    Mengyang Fan, Wenchao Lu ... Nathanael S Gray
    Discovery of potent covalent TEAD palmitoylation inhibitors that represents important tools to investigate the Hippo pathway.
    1. Immunology and Inflammation

    Autoantibody discovery across monogenic, acquired, and COVID-19-associated autoimmunity with scalable PhIP-seq

    Sara E Vazquez, Sabrina A Mann ... Joseph L DeRisi
    A high-throughput extension of PhIP-seq reveals novel antigen specificities leading to new insights across multiple human autoimmune and inflammatory diseases, enables application of machine learning approaches to PhIP-seq datasets, and highlights the importance of controlled PhIP-seq cohorts.
    1. Evolutionary Biology

    Diversification dynamics in the Neotropics through time, clades, and biogeographic regions

    Andrea S Meseguer, Alice Michel ... Fabien L Condamine
    Neotropical outstanding biodiversity emerged from sustained rates of species accumulation over time, although, for some periods, tetrapods were less successful than plants in keeping pace with a changing environment.
    1. Biochemistry and Chemical Biology
    2. Computational and Systems Biology

    Excitatory and inhibitory D-serine binding to the NMDA receptor

    Remy A Yovanno, Tsung Han Chou ... Albert Y Lau
    Molecular dynamics simulations reveal that D-serine competes with glutamate for binding to the NMDA receptor, a finding supported by electrophysiology experiments with consequences for D-serine-focused therapeutic strategies for myriad neurological disorders.
    1. Neuroscience

    Visual and motor signatures of locomotion dynamically shape a population code for feature detection in Drosophila

    Maxwell H Turner, Avery Krieger ... Thomas R Clandinin
    Neurons responsible for detecting local visual features are modulated by visual and motor-related forms of gain control that increase the threshold for detection when self-generated movement signals would dominate visual input.
    1. Neuroscience

    Analyzing the brainstem circuits for respiratory chemosensitivity in freely moving mice

    Amol Bhandare, Joseph van de Wiel ... Nicholas Dale
    Recordings from brainstem nuclei involved in chemosensory regulation of breathing in awake freely behaving mice show different complementary types of neuronal responses to hypercapnia in the retrotrapezoid nucleus and the rostral medullary raphe.
    1. Ecology
    2. Evolutionary Biology

    Wide-ranging consequences of priority effects governed by an overarching factor

    Callie R Chappell, Manpreet K Dhami ... Tadashi Fukami
    Analysis of microbial communities in floral nectar shows that it is possible to identify an overarching factor that governs the eco-evolutionary dynamics of priority effects across multiple levels of biological organization.
    1. Epidemiology and Global Health
    2. Immunology and Inflammation

    HIV skews the SARS-CoV-2 B cell response towards an extrafollicular maturation pathway

    Robert Krause, Jumari Snyman ... Alasdair Leslie
    A skewed B cell response in people living with HIV proceeds via an extrafollicular path and could result in reduced affinity B cell memory and antibody responses.
    1. Cell Biology
    2. Developmental Biology

    Kap-β2/Transportin mediates β-catenin nuclear transport in Wnt signaling

    Woong Y Hwang, Valentyna Kostiuk ... Mustafa K Khokha
    β-catenin, a key effector of the Wnt signaling pathway, is transported into the nucleus via a direct interaction between its PY-NLS and TNPO1 offering new potential targets for cancer therapeutics.
    1. Neuroscience

    Rapid reconstruction of neural circuits using tissue expansion and light sheet microscopy

    Joshua L Lillvis, Hideo Otsuna ... Barry J Dickson
    A new approach for fast, sparse neural circuit mapping allows circuit structure, physiology, and behavior to be quantified in the same animal and across many animals.
    1. Neuroscience

    Evolutionary shaping of human brain dynamics

    James C Pang, James K Rilling ... Luca Cocchi
    Human brains evolved to have neural dynamics that facilitate brain-wide integration supporting complex behavior.
    1. Evolutionary Biology
    2. Genetics and Genomics

    Little skate genome provides insights into genetic programs essential for limb-based locomotion

    DongAhn Yoo, Junhee Park ... Myungin Baek
    The generation of high-quality little skate reference genome enables molecular mechanism studies of gene regulation.
    1. Neuroscience

    Descending neuron population dynamics during odor-evoked and spontaneous limb-dependent behaviors

    Florian Aymanns, Chin-Lin Chen, Pavan Ramdya
    In the fly, Drosophila melanogaster, the population activity of descending neurons (DNs) projecting from the brain to the motor system is predominantly correlated with locomotion with only a few DNs encoding grooming or olfactory signals in the absence of behavior.
    1. Genetics and Genomics
    2. Neuroscience

    Oxytocin signaling in the posterior hypothalamus prevents hyperphagic obesity in mice

    Kengo Inada, Kazoku Tsujimoto ... Kazunari Miyamichi
    Conditional knockout mice revealed that oxytocin secretion from the paraventricular hypothalamic nucleus suppresses hyperphagic obesity partly via the oxytocin receptor expressed in the arcuate hypothalamic nucleus.
    1. Computational and Systems Biology
    2. Neuroscience

    Normative decision rules in changing environments

    Nicholas W Barendregt, Joshua I Gold ... Zachary P Kilpatrick
    In environments that fluctuate over the course of deliberation, optimal decision strategies display novel dynamics that can explain human response behaviors better than commonly used alternatives.
    1. Neuroscience

    Coding of latent variables in sensory, parietal, and frontal cortices during closed-loop virtual navigation

    Jean-Paul Noel, Edoardo Balzani ... Dora E Angelaki
    Primates use their eyes to keep track of spatial goals, and this strategy is reflected by the functional connectivity between a traditionally considered optic flow area (dorsomedial superior temporal area) and prefrontal cortex.
    1. Microbiology and Infectious Disease

    Combining transgenesis with paratransgenesis to fight malaria

    Wei Huang, Joel Vega-Rodriguez ... Marcelo Jacobs-Lorena
    The combination of mosquito transgenesis with paratransgenesis provides maximum parasite-blocking activity and has high potential for fighting malaria.
    1. Immunology and Inflammation
    2. Medicine

    Starting to have sexual intercourse is associated with increases in cervicovaginal immune mediators in young women: a prospective study and meta-analysis

    Sean M Hughes, Claire N Levy ... Alison C Roxby
    The immune system in the vagina becomes more active when young women begin to have sexual intercourse, and this immune activity could influence the risk of acquiring sexually transmitted infections.
    1. Evolutionary Biology
    2. Neuroscience

    Neural defensive circuits underlie helping under threat in humans

    Joana B Vieira, Andreas Olsson
    The activation of defence brain circuits drives decisions to help conspecifics under threat.
    1. Cancer Biology
    2. Immunology and Inflammation

    Continuous sensing of IFNα by hepatic endothelial cells shapes a vascular antimetastatic barrier

    Ngoc Lan Tran, Lorena Maria Ferreira ... Giovanni Sitia
    Continuous perioperative IFNα therapy stimulates hepatic endothelial cells to build up physical vascular barrier that limits tumor cell entry into the liver and promotes long-term antitumor immunity.
    1. Immunology and Inflammation

    Histone H3 clipping is a novel signature of human neutrophil extracellular traps

    Dorothea Ogmore Tilley, Ulrike Abuabed ... Arturo Zychlinsky
    Proteolytic events targeting histones can be harnessed to develop antibodies for neutrophil extracellular traps, improving researchers’ ability to distinguish these chromatin-based structures in human samples.
    1. Cancer Biology
    2. Computational and Systems Biology

    Comprehensive machine-learning survival framework develops a consensus model in large-scale multicenter cohorts for pancreatic cancer

    Libo Wang, Zaoqu Liu ... Yu-ling Sun
    AIDPS derived by 76 machine-learning algorithm combinations in 13 independent multicenter cohorts exhibited superior capability than clinical traits and 86 published prognostic signatures and could serve as an ideal biomarker for stratified management and individualized treatment of pancreatic cancer.
    1. Neuroscience

    Recalibrating vision-for-action requires years after sight restoration from congenital cataracts

    Irene Senna, Sophia Piller ... Marc O Ernst
    Late cataract-treated individuals learn to recalibrate vision for action in the months to years after sight restoration surgery, demonstrating that this ability can develop even in the absence of early pattern vision.
    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    CD169+ macrophages orchestrate plasmacytoid dendritic cell arrest and retention for optimal priming in the bone marrow of malaria-infected mice

    Jamie Moore-Fried, Mahinder Paul ... Gregoire Lauvau
    CD169+ macrophages in the bone marrow of malaria-infected mice uptake infected red blood cells, and establish a functional interaction that is required to activate plasmacytoid dendritic cells to secrete type I interferon and leave the bone marrow.
    1. Neuroscience

    Neural dynamics of causal inference in the macaque frontoparietal circuit

    Guangyao Qi, Wen Fang ... Liping Wang
    In causal inference, the premotor cortex dynamically integrates prior information and current sensory inputs to infer hidden structures, and selectively updates sensory representations in the parietal cortex to support behavior.
    1. Neuroscience

    NaV1.1 is essential for proprioceptive signaling and motor behaviors

    Cyrrus M Espino, Cheyanne M Lewis ... Theanne N Griffith
    The voltage-gated sodium channel Nav1.1 is identified as an essential component of the proprioceptive transmission machinery that is required in vivo for normal motor behavior.
    1. Epidemiology and Global Health
    2. Microbiology and Infectious Disease

    COVID-19 cluster size and transmission rates in schools from crowdsourced case reports

    Paul Tupper, Shraddha Pai ... Caroline Colijn
    Fitting a simple model of COVID-19 transmission to crowdsourced case report data allowed the estimation of mean cluster size and transmission rates in Canadian schools, as well as determining which interventions are most likely to limit transmission.
    1. Chromosomes and Gene Expression

    KAT2-mediated acetylation switches the mode of PALB2 chromatin association to safeguard genome integrity

    Marjorie Fournier, Amélie Rodrigue ... Fumiko Esashi
    The lysine acetyltransferases KAT2A and KAT2B regulate the dynamic chromatin association of the tumour suppressor protein PALB2, protecting active genes and promoting DNA damage repair in a context-dependent manner.
    1. Computational and Systems Biology

    A tug of war between filament treadmilling and myosin induced contractility generates actin rings

    Qin Ni, Kaustubh Wagh ... Garegin A Papoian
    Actin networks form clusters under myosin-induced contractility, while high actin filament treadmilling speed can reshape actin networks into ring-like structures with lower mechanical energy.
    1. Neuroscience

    An inhibitory circuit from central amygdala to zona incerta drives pain-related behaviors in mice

    Sudhuman Singh, Torri D Wilson ... Yarimar Carrasquillo
    Inhibition of the zona incerta by central amygdala neurons expressing PKCδ contributes to injury-induced peripheral hypersensitivity in a mouse model of neuropathic pain.
    1. Cancer Biology
    2. Cell Biology

    Augmin prevents merotelic attachments by promoting proper arrangement of bridging and kinetochore fibers

    Valentina Štimac, Isabella Koprivec ... Iva M Tolić
    STED microscopy of human mitotic spindles reveals how augmin-nucleated microtubules protect the cell from erroneous kinetochore-microtubule attachments and ensure a highly organized architecture of the spindle required for mitotic fidelity.
    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    Vinculin recruitment to α-catenin halts the differentiation and maturation of enterocyte progenitors to maintain homeostasis of the Drosophila intestine

    Jerome Bohere, Buffy L Eldridge-Thomas, Golnar Kolahgar
    A subset of intestinal precursor cells is able to sense mechanical forces at cell–cell junctions to control the production of specialised cells.
    1. Epidemiology and Global Health
    2. Medicine

    Cardiovascular disease and subsequent risk of psychiatric disorders: a nationwide sibling-controlled study

    Qing Shen, Huan Song ... Unnur Valdimarsdóttir
    Patients diagnosed with a cardiovascular disease are at higher risk of psychiatric disorders, independent of familial factors shared between full siblings and comorbid conditions.
    1. Computational and Systems Biology
    2. Physics of Living Systems

    Landscape of epithelial–mesenchymal plasticity as an emergent property of coordinated teams in regulatory networks

    Kishore Hari, Varun Ullanat ... Mohit Kumar Jolly
    Investigation of regulatory network topology reveals latent design principles of multistable phenotypic landscape.
    1. Structural Biology and Molecular Biophysics

    Structure and flexibility of the yeast NuA4 histone acetyltransferase complex

    Stefan A Zukin, Matthew R Marunde ... Avinash B Patel
    The core of histone acetyltransferase complex, NuA4, flexibly tethers various histone recognition modules, including the HAT module which is capable of binding nucleosomes marked by H3K4me3 and H3 acetylation.
    1. Neuroscience

    In situ X-ray-assisted electron microscopy staining for large biological samples

    Sebastian Ströh, Eric W Hammerschmith ... Adrian Andreas Wanner
    In situ X-ray imaging of biological tissue samples in staining solution while they are being processed for electron microscopy reveals novel insights into the diffusion-reaction kinetics, tissue mechanics, and staining quality.
    1. Structural Biology and Molecular Biophysics

    Structure of SARS-CoV-2 M protein in lipid nanodiscs

    Kimberly A Dolan, Mandira Dutta ... Stephen G Brohawn
    A cryo-EM structure of the SARS-CoV-2 M protein, the most abundant protein in the viral envelope, provides insight into its essential role in virus assembly.
    1. Immunology and Inflammation

    Enriched dietary saturated fatty acids induce trained immunity via ceramide production that enhances severity of endotoxemia and clearance of infection

    Amy L Seufert, James W Hickman ... Brooke A Napier
    Enriched dietary SFAs, specifically palmitic acid (PA), induce a broad and long-lived innate immune memory response which is harmful during disease exacerbated by inflammation, but beneficial for pathogen clearance.
    1. Neuroscience

    scRNA-sequencing reveals subtype-specific transcriptomic perturbations in DRG neurons of PirtEGFPf mice in neuropathic pain condition

    Chi Zhang, Ming-Wen Hu ... Yun Guan
    Single-cell RNA-sequencing unraveled cell subtype-specific transcriptomic changes in both injured and uninjured primary sensory neurons after nerve injury and demonstrated transcriptomic sexual dimorphism.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Molecular mechanism of Afadin substrate recruitment to the receptor phosphatase PTPRK via its pseudophosphatase domain

    Iain M Hay, Katie E Mulholland ... Janet E Deane
    Substrate recognition by a receptor protein tyrosine phosphatase is mediated by binding to its pseudophosphatase domain via a short helix that is >100 amino acids distant from the target phosphosite, uncovering principles of phosphatase substrate recognition and potential scaffolding functions.
    1. Chromosomes and Gene Expression
    2. Immunology and Inflammation

    Alternative splicing of apoptosis genes promotes human T cell survival

    Davia Blake, Caleb M Radens ... Kristen W Lynch
    Alternative splicing of multiple apoptotic genes is enhanced by CD28 costimulation to promote cell survival.
    1. Immunology and Inflammation

    A novel monocyte differentiation pattern in pristane-induced lupus with diffuse alveolar hemorrhage

    Shuhong Han, Haoyang Zhuang ... Westley H Reeves
    By altering monocyte development, pristane exposure could generate activated Ly6Chi and Ly6Clo/− monocytes, contributing to lung microvascular endothelial injury and DAH susceptibility.
    1. Biochemistry and Chemical Biology

    Didemnin B and ternatin-4 differentially inhibit conformational changes in eEF1A required for aminoacyl-tRNA accommodation into mammalian ribosomes

    Manuel F Juette, Jordan D Carelli ... Scott C Blanchard
    Cyclic peptide natural products didemnin B and ternatin-4 bind the same hydrophobic pocket of eEF1A to inhibit mRNA translation but exhibit kinetic differences that influence rate-limiting conformational changes underpinning aminoacyl-tRNA selection.
    1. Neuroscience

    Neural underpinning of a respiration-associated resting-state fMRI network

    Wenyu Tu, Nanyin Zhang
    Using simultaneous recordings of electrophysiology, respiration, and resting-state fMRI, a respiration-associated neural network is identified.
    1. Cell Biology

    Caveolae couple mechanical stress to integrin recycling and activation

    Fidel-Nicolás Lolo, Dácil María Pavón ... Miguel A del Pozo
    Caveolae regulate integrin mechanosensing by establishing a force threshold for activation and recycling.
    1. Developmental Biology

    A spatiotemporal reconstruction of the C. elegans pharyngeal cuticle reveals a structure rich in phase-separating proteins

    Muntasir Kamal, Levon Tokmakjian ... Peter J Roy
    A meta-analysis yields a spatiotemporal map of gene expression that provides a blueprint for nematode cuticle construction and reveals novel families of cuticular intrinsically disordered proteins.
    1. Cell Biology

    Single-cell analysis of skeletal muscle macrophages reveals age-associated functional subpopulations

    Linda K Krasniewski, Papiya Chakraborty ... Myriam Gorospe
    Single-cell analysis of skeletal mouse reveals highly diverse macrophage subgroups associated with diverse functions and age-related changes.
    1. Neuroscience
    2. Physics of Living Systems

    Nested mechanosensory feedback actively damps visually guided head movements in Drosophila

    Benjamin Cellini, Jean-Michel Mongeau
    Motor context and mechanosensory feedback together influence how flies control head movements during visually guided flight maneuvers.
    1. Cancer Biology

    Therapeutic resistance in acute myeloid leukemia cells is mediated by a novel ATM/mTOR pathway regulating oxidative phosphorylation

    Hae J Park, Mark A Gregory ... James DeGregori
    Cellular and molecular analyses of human AML cells reveal a novel pathway activated by the bone marrow microenvironment that confers resistance to FLT3 inhibition and can be exploited to improve the efficacy of FLT3 inhibitor therapy for AML.
    1. Structural Biology and Molecular Biophysics
    2. Physics of Living Systems

    Architecture of the chikungunya virus replication organelle

    Timothée Laurent, Pravin Kumar ... Lars-Anders Carlson
    The combination of cellular cryo-electron tomography, biochemistry, and mathematical modeling provides the first integrated structural model of the Alphavirus replication organelle.
    1. Structural Biology and Molecular Biophysics

    Structural and thermodynamic analyses of the β-to-α transformation in RfaH reveal principles of fold-switching proteins

    Philipp K Zuber, Tina Daviter ... Stefan H Knauer
    The β-barrel conformation of the KOW domain of the metamorphic protein RfaH is in equilibrium with a low-populated, predominately unstructured state exhibiting helical elements, suggesting that transiently structured elements in unfolded conformations might be a general scheme in fold-switching proteins.
    1. Computational and Systems Biology
    2. Immunology and Inflammation

    Delineating the transcriptional landscape and clonal diversity of virus-specific CD4+ T cells during chronic viral infection

    Ryan Zander, Achia Khatun ... Weiguo Cui
    CD4+ T cells responding to chronic lymphocytic choriomeningitis virus infection display transcriptional heterogeneity that is marked by both lineage-specific gene expression profiles and core gene expression programs that are upregulated and conserved across multiple distinct populations of T helper cells.
    1. Neuroscience

    Arguments for the biological and predictive relevance of the proportional recovery rule

    Jeff Goldsmith, Tomoko Kitago ... John W Krakauer
    The proportional recovery rule, an apparently simple model that nonetheless requires careful statistical treatment, remains an important biological and predictive framework for stroke recovery.
    1. Structural Biology and Molecular Biophysics

    Inhibited KdpFABC transitions into an E1 off-cycle state

    Jakob M Silberberg, Charlott Stock ... Cristina Paulino
    The serine phosphorylated and inhibited KdpFABC complex (KdpFABS162-PC) adopts an off-cycle E1P tight state, due to an impaired E1P/E2P transition.
    1. Biochemistry and Chemical Biology
    2. Neuroscience

    Tissue-specific mitochondrial HIGD1C promotes oxygen sensitivity in carotid body chemoreceptors

    Alba Timón-Gómez, Alexandra L Scharr ... Andy J Chang
    An atypical configuration of mitochondrial electron transport chain proteins may underlie the exquisite sensitivity of the carotid body to small decreases in oxygen availability.
    1. Genetics and Genomics

    A phenotype-based forward genetic screen identifies Dnajb6 as a sick sinus syndrome gene

    Yonghe Ding, Di Lang ... Xiaolei Xu
    Dnajb6 is identified as a novel sick sinus syndrome causative gene that exhibits a unique expression pattern within a subpopulation of sinus node pacemaker cells.
    1. Epidemiology and Global Health
    2. Medicine

    Lack of ownership of mobile phones could hinder the rollout of mHealth interventions in Africa

    Justin T Okano, Joan Ponce ... Sally Blower
    Due to current levels of mobile phone ownership in Africa, it may only be possible to scale up mHealth interventions in a few countries, but not in the vast majority of the 33 countries that encompass ~60% of Africa's population.
    1. Epidemiology and Global Health

    How should COVID-19 vaccines be distributed between the Global North and South: a discrete choice experiment in six European countries

    Janina I Steinert, Henrike Sternberg ... Tim Büthe
    In a large discrete choice experiment, respondents from six European countries reveal preferences for global vaccine solidarity, where female, younger, more educated respondents are most likely to prioritise candidates from the Global South in their allocation choices for COVID-19 vaccines.
    1. Computational and Systems Biology
    2. Medicine

    Spatial modeling reveals nuclear phosphorylation and subcellular shuttling of YAP upon drug-induced liver injury

    Lilija Wehling, Liam Keegan ... Kai Breuhahn
    Nuclear phosphorylation differentially controls the activity of Hippo pathways effectors YAP and TAZ via distinct molecular mechanisms under physiological and tissue damage conditions.
    1. Cell Biology
    2. Immunology and Inflammation

    Non-invasive classification of macrophage polarisation by 2P-FLIM and machine learning

    Nuno GB Neto, Sinead A O'Rourke ... Michael G Monaghan
    Human blood derived macrophage polarisation can be classified by proxy of their metabolism, using advanced microscopy techniques generating single-cell parameters that are clustered and validated using machine learning classification models.
    1. Medicine

    Extrachromosomal circular DNA: Current status and future prospects

    Yiheng Zhao, Linchan Yu ... Xiang Zhou
    Extrachromosomal circular DNA will hold great promise in future biomedical research and clinical translational application.
    1. Epidemiology and Global Health

    Genetically predicted high IGF-1 levels showed protective effects on COVID-19 susceptibility and hospitalization: a Mendelian randomisation study with data from 60 studies across 25 countries

    Xinxuan Li, Yajing Zhou ... Xue Li
    Genetically predicted high insulin-like growth factor levels may decrease the risk of COVID-19 susceptibility and hospitalization.
    1. Neuroscience

    Postsynaptic plasticity of cholinergic synapses underlies the induction and expression of appetitive and familiarity memories in Drosophila

    Carlotta Pribbenow, Yi-chun Chen ... David Owald
    Specific memories can be stored through changes in the postsynaptic cholinergic receptor composition at Drosophila mushroom body synapses.
    1. Neuroscience

    Internally generated time in the rodent hippocampus is logarithmically compressed

    Rui Cao, John H Bladon ... Marc W Howard
    Receptive fields for time in the hippocampus, like receptive fields for retinal space and receptive fields for numerosity, obey the Weber-Fechner law.
    1. Computational and Systems Biology

    Quantifying how post-transcriptional noise and gene copy number variation bias transcriptional parameter inference from mRNA distributions

    Xiaoming Fu, Heta P Patel ... Ramon Grima
    A combined experimental and modeling approach provides insight into potential biases when inferring transcription rates from static mRNA distributions, and shows that correcting for cell-cycle phase and post-transcriptional noise provides rates that agree with live-cell transcription measurements.
    1. Cell Biology

    Discrete GPCR-triggered endocytic modes enable β-arrestins to flexibly regulate cell signaling

    Benjamin Barsi-Rhyne, Aashish Manglik, Mark von Zastrow
    Two modes of GPCR endocytosis by β-arrestin are differentially coupled to downstream signaling.
    1. Medicine

    Trio-based whole exome sequencing in patients with suspected sporadic inborn errors of immunity: A retrospective cohort study

    Anne Hebert, Annet Simons ... Caspar I van der Made
    Systematic assessment of de novo variants in patients with sporadic inborn errors of immunity led to the identification of promising candidate variants in known and novel immune genes, supporting its implementation in the routine diagnostic evaluation of these patients.
    1. Neuroscience

    Disrupted-in-schizophrenia-1 is required for normal pyramidal cell–interneuron communication and assembly dynamics in the prefrontal cortex

    Jonas-Frederic Sauer, Marlene Bartos
    In a mouse model of psychiatric illness, the neuronal network of the medial prefrontal cortex is characterized by reduced activity levels of interneurons, impaired gamma oscillations, and altered activation of cell assemblies.
    1. Immunology and Inflammation
    2. Medicine

    Early immune markers of clinical, virological, and immunological outcomes in patients with COVID-19: a multi-omics study

    Zicheng Hu, Kattria van der Ploeg ... Prasanna Jagannathan
    Immune markers measured at the early stage of COVID-19 infection are associated with various clinical outcomes and can be used to predict disease progression, T cell memory, viral shedding, and the antibody response of the COVID-19 patients.
    1. Neuroscience

    Dynamic proteomic and phosphoproteomic atlas of corticostriatal axons in neurodevelopment

    Vasin Dumrongprechachan, Ryan B Salisbury ... Yevgenia Kozorovitskiy
    A Cre-dependent reporter mouse line is generated, validated, and used to map cell-type-specific proteome and phosphoproteome of corticostriatal projections across postnatal development.
    1. Ecology
    2. Genetics and Genomics

    Anopheles homing suppression drive candidates exhibit unexpected performance differences in simulations with spatial structure

    Samuel E Champer, Isabel K Kim ... Jackson Champer
    Continuous space models indicate that current homing suppression drives may have difficulty eliminating wild mosquito populations, but building a successful drive may still be possible with current tools.
    1. Computational and Systems Biology
    2. Structural Biology and Molecular Biophysics

    Deep mutational scanning and machine learning reveal structural and molecular rules governing allosteric hotspots in homologous proteins

    Megan Leander, Zhuang Liu ... Srivatsan Raman
    Deep mutational scanning of homologous proteins shows conservation in allosteric mechanisms but differences in molecular details within the protein family.
    1. Developmental Biology
    2. Neuroscience

    Neuronal temperature perception induces specific defenses that enable C. elegans to cope with the enhanced reactivity of hydrogen peroxide at high temperature

    Francesco A Servello, Rute Fernandes ... Javier Apfeld
    C. elegans nematodes can assess faithfully the threat that H2O2 poses by coupling the induction of their H2O2 defenses to the perception of high temperature—an inherent enhancer of the reactivity of H2O2.
    1. Neuroscience

    Postsynaptic burst reactivation of hippocampal neurons enables associative plasticity of temporally discontiguous inputs

    Tanja Fuchsberger, Claudia Clopath ... Ole Paulsen
    Neuronal reactivation during dopamine modulation induces input-specific LTP at previously primed hippocampal synapses, suggesting a possible solution to the credit assignment problem and a mechanism for memory linking.
    1. Microbiology and Infectious Disease

    Antibacterial T6SS effectors with a VRR-Nuc domain are structure-specific nucleases

    Julia Takuno Hespanhol, Daniel Enrique Sanchez-Limache ... Ethel Bayer-Santos
    Salmonella antibacterial effectors act on Y-shaped DNA substrates resembling replication forks or transcription bubbles and lead to DNA double-strand breaks.
    1. Neuroscience

    Vocalization categorization behavior explained by a feature-based auditory categorization model

    Manaswini Kar, Marianny Pernia ... Srivatsun Sadagopan
    A theoretical model that uses maximally informative spectrotemporal features to classify vocalizations, trained solely on natural guinea pig vocalizations, predicts guinea pig behavioral performance in classifying natural as well as spectrotemporally manipulated vocalizations.
    1. Immunology and Inflammation
    2. Medicine

    Differences in the immune response elicited by two immunization schedules with an inactivated SARS-CoV-2 vaccine in a randomized phase 3 clinical trial

    Nicolás MS Gálvez, Gaspar A Pacheco ... Alexis M Kalergis
    The humoral and cellular immune responses were evaluated for two immunization schedules for the inactivated SARS-CoV-2 vaccine, CoronaVac, with two doses separated by 2 or 4 weeks, showing that these responses are mostly similar, with differences in neutralization capacities.
    1. Computational and Systems Biology
    2. Neuroscience

    CompoundRay, an open-source tool for high-speed and high-fidelity rendering of compound eyes

    Blayze Millward, Steve Maddock, Michael Mangan
    Rendering compound vision at high speed with high precision, enabling rapid, data-driven exploration of the compound eye design space.
    1. Evolutionary Biology
    2. Genetics and Genomics

    The wtf meiotic driver gene family has unexpectedly persisted for over 100 million years

    Mickaël De Carvalho, Guo-Song Jia ... Sarah E Zanders
    The wtf family of meiotic drivers has maintained the capacity to cause meiotic drive for over 100 million years.
    1. Neuroscience

    Early life stressful experiences escalate aggressive behavior in adulthood via changes in transthyretin expression and function

    Rohit Singh Rawat, Aksheev Bhambri ... Arpita Konar
    Hypothalamic TTR as a novel molecular player of stress-induced long-term impact on behavior.
    1. Neuroscience

    Active tactile discrimination is coupled with and modulated by the cardiac cycle

    Alejandro Galvez-Pol, Pavandeep Virdee ... James Kilner
    Human subjects actively adjust the acquisition of sense data based on how their bodily cycles alter their senses, i.e., sensing tactile stimuli for longer periods when concurrent physiological signals are present vs. sensing for shorter periods when these are quiescent.
    1. Evolutionary Biology
    2. Genetics and Genomics

    High-resolution species assignment of Anopheles mosquitoes using k-mer distances on targeted sequences

    Marilou Boddé, Alex Makunin ... Mara KN Lawniczak
    Large-scale monitoring of Anopheles populations benefits from a robust and accurate species identification and plasmodium detection method that is applicable to the entire genus.
    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    Antiviral function and viral antagonism of the rapidly evolving dynein activating adaptor NINL

    Donté Alexander Stevens, Christopher Beierschmitt ... Matthew D Daugherty
    Evolution-guided functional analyses identify an activating adaptor of the dynein intracellular transportation machinery, NINL, as a novel component of the antiviral immune response and reveal a mechanism by which viruses antagonize NINL function in a species-specific manner.
    1. Cell Biology
    2. Developmental Biology

    The centrosomal protein 83 (CEP83) regulates human pluripotent stem cell differentiation toward the kidney lineage

    Fatma Mansour, Christian Hinze ... Kai M Schmidt-Ott
    CEP83 plays a central role in regulating the development of intermediate mesoderm (IM) nephron progenitors, which may involve direct effects of CEP83 in the nephron progenitor differentiation program and indirect lateral plate mesoderm-mediated effects on the IM.
    1. Cell Biology

    Tumor elimination by clustered microRNAs miR-306 and miR-79 via noncanonical activation of JNK signaling

    Zhaowei Wang, Xiaoling Xia ... Tatsushi Igaki
    miR-306 and miR-79 selectively eliminate JNK-activated tumors, providing a new microRNA-based strategy against cancer.
    1. Physics of Living Systems

    Arnold tongue entrainment reveals dynamical principles of the embryonic segmentation clock

    Paul Gerald Layague Sanchez, Victoria Mochulska ... Alexander Aulehla
    A microfluidic experimental approach combined with dynamical systems theory reveals how to entrain an embryonic oscillator, the segmentation clock, and allows for the quantification of its entrainment properties.
    1. Cell Biology
    2. Neuroscience

    KLC4 shapes axon arbors during development and mediates adult behavior

    Elizabeth M Haynes, Korri H Burnett ... Mary C Halloran
    Newly identified roles for the kinesin-1 light chain subunit KLC4 in patterning developing axon arbors, regulating microtubule dynamics and influencing behavior of larval and adult zebrafish.
    1. Neuroscience

    Transversal functional connectivity and scene-specific processing in the human entorhinal-hippocampal circuitry

    Xenia Grande, Magdalena M Sauvage ... David Berron
    The human entorhinal-hippocampal circuitry is characterized by an information-specific functional organization where two routes, that are preferentially connected to the parahippocampal cortex or the perirhinal and retrosplenial cortices, divide the entorhinal cortex as well as hippocampal subiculum and CA1 subregions.
    1. Cell Biology
    2. Neuroscience

    The Na+/K+ pump dominates control of glycolysis in hippocampal dentate granule cells

    Dylan J Meyer, Carlos Manlio Díaz-García ... Gary Yellen
    Neuronal glycolysis to restore energy consumed by ion movements is activated by engagement of the Na+/K+ pump, either directly by Na+ influx or indirectly, when Ca2+ influx is converted to Na+ accumulation by Na+/Ca2+ exchange.
    1. Immunology and Inflammation

    Interoperability of RTN1A in dendrite dynamics and immune functions in human Langerhans cells

    Małgorzata Anna Cichoń, Karin Pfisterer ... Adelheid Elbe-Bürger
    Reticulon 1A plays a central role not only in cytoskeletal remodeling of resident Langerhans cells but also in their clustering upon Toll-like receptor activation in human skin, suggesting an important role in maintaining tissue homeostasis.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Ligand-induced shifts in conformational ensembles that describe transcriptional activation

    Sabab Hasan Khan, Sean M Braet ... C Denise Okafor
    Transcriptional activity is characterized for five steroid receptors complexed with multiple ligands and it is shown that the extent of transcriptional activation in complexes is accurately described by conformational shifts in computationally-generated ensembles.
    1. Computational and Systems Biology

    A model-based analysis of the health impacts of COVID-19 disruptions to primary cervical screening by time since last screen for current and future disruptions

    Emily A Burger, Inge MCM de Kok ... Megan A Smith
    Despite the overall impact of COVID-19-related cervical cancer screening disruptions on cervical cancer outcomes being small, disruptions disproportionately affect underscreened women, underpinning the importance of reaching such women as a critical area of focus, regardless of temporary disruptions.
    1. Ecology

    Touch-sensitive stamens enhance pollen dispersal by scaring away visitors

    Deng-Fei Li, Wen-Long Han ... Shuang-Quan Huang
    Botanists have long speculated about the adaptive value of visitor-triggered stamen movements, and here experiments that compare flowers with and without mobile stamens demonstrate large effects of stamen movements on pollen export, receipt, and nectar costs per pollen transport.
    1. Medicine

    Cannabinoid signaling modulation through JZL184 restores key phenotypes of a mouse model for Williams–Beuren syndrome

    Alba Navarro-Romero, Lorena Galera-López ... Andres Ozaita
    A mouse model of Williams–Beuren syndrome allowed us to assess the endocannabinoid system and the impact of targeting the monoacyl glycerol lipase in modulating key phenotypes such as cognitive and hypersocial phenotype as well as the cardiac phenotype.
    1. Developmental Biology
    2. Neuroscience

    EZ Clear for simple, rapid, and robust mouse whole organ clearing

    Chih-Wei Hsu, Juan Cerda III ... Joshua D Wythe
    With three simple steps in 48 hr, EZ Clear effectively renders adult mouse organs optically transparent while simultaneously preserving signal from synthetic and endogenous fluorescent reporters and is compatible with wholemount immunostaining and cryosectioning followed by histological or immunofluorescent staining.
    1. Evolutionary Biology

    Novel multicellular prokaryote discovered next to an underground stream

    Kouhei Mizuno, Mais Maree ... Kazuya Morikawa
    A new bacterium isolated from an underground stream shows a novel multicellularity by self-organizing its filamentous cells like a liquid crystal and accommodating daughter cells in a sequential manner, which would be a new extant model of prokaryotic multicellularity.
    1. Genetics and Genomics

    Variation in ubiquitin system genes creates substrate-specific effects on proteasomal protein degradation

    Mahlon A Collins, Gemechu Mekonnen, Frank Wolfgang Albert
    Genetic mapping reveals widespread, complex genetic effects on protein degradation by the ubiquitin-proteasome system, the primary protein degradation pathway in eukaryotic cells.
    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    Osteoclast-mediated resorption primes the skeleton for successful integration during axolotl limb regeneration

    Camilo Riquelme-Guzmán, Stephanie L Tsai ... Tatiana Sandoval-Guzmán
    In vivo evaluation of mineralized skeleton in the regenerating axolotl limb reveals a significant osteoclast-driven resorption as an early event with long-lasting impact for tissue integration.
    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    A single cell transcriptional roadmap of human pacemaker cell differentiation

    Alexandra Wiesinger, Jiuru Li ... Harsha D Devalla
    Diversification of human pacemaker subpopulations is directed by WNT and TGFβ signaling.
    1. Epidemiology and Global Health
    2. Genetics and Genomics

    Constructing an atlas of associations between polygenic scores from across the human phenome and circulating metabolic biomarkers

    Si Fang, Michael V Holmes ... Tom G Richardson
    A comprehensive resource to systematically evaluate the genetically predicted associations between 125 polygenic risk scores and 249 metabolic traits.
    1. Physics of Living Systems

    Dynamics of cooperative excavation in ant and robot collectives

    S Ganga Prasath, Souvik Mandal ... L Mahadevan
    Observations of ant excavation from a confining corral, along with theoretical models and synthetic robot experiments show the emergence of cooperation induced by pheromones in a malleable environment that is moulded by and moulds collective behavior.
    1. Evolutionary Biology
    2. Genetics and Genomics

    The landscape of transcriptional and translational changes over 22 years of bacterial adaptation

    John S Favate, Shun Liang ... Premal Shah
    Parallel changes in organismal evolution can be observed even with disparate genomic changes due to similarity in functional outcomes, such as changes in molecular phenotypes like gene expression patterns.
    1. Cell Biology
    2. Neuroscience

    Presynaptic Rac1 controls synaptic strength through the regulation of synaptic vesicle priming

    Christian Keine, Mohammed Al-Yaari ... Samuel M Young Jr
    A combination of genetic, electrophysiological, and modeling approaches reveals that presynaptic Rac1 is a key molecule that controls synaptic strength and plasticity by regulating the synaptic vesicle cycle steps controlling the number of fusion competent synaptic vesicles.
    1. Cell Biology
    2. Developmental Biology

    N-myc downstream regulated gene 1 (ndrg1) functions as a molecular switch for cellular adaptation to hypoxia

    Jong S Park, Austin M Gabel ... Rachel Brewster
    Lactate-Ndrg1a signaling protects the kidney from hypoxic injury and functions partly by inducing reversible degradation of the ATP-demanding sodium-potassium ATPase pump.
    1. Cell Biology

    Development of a versatile high-throughput mutagenesis assay with multiplexed short-read NGS using DNA-barcoded supF shuttle vector library amplified in E. coli

    Hidehiko Kawai, Ren Iwata ... Hiroyuki Kamiya
    A sophisticated classical mutagenesis assay with next-generation sequencing technology presents a benefit to future research on mutagenesis, DNA repair, and cancer.
    1. Cell Biology
    2. Developmental Biology

    Decoding the IGF1 signaling gene regulatory network behind alveologenesis from a mouse model of bronchopulmonary dysplasia

    Feng Gao, Changgong Li ... Parviz Minoo
    Publicly available gene expression data and proven methodologies for building model Gene Regulatory Networks are applied to successfully construct the IGF1 signaling GRN behind alveologenesis, serving as a pioneer in transforming how lung development and its associated diseases is approached.
    1. Neuroscience

    Phorbolester-activated Munc13-1 and ubMunc13-2 exert opposing effects on dense-core vesicle secretion

    Sébastien Houy, Joana S Martins ... Jakob Balslev Sørensen
    The priming protein ubMunc13-2 and Synaptotagmin-7 cooperate with phorbolesters/diacylglycerol to stimulate vesicle priming in adrenal chromaffin cells, whereas phorbolesters/diacylglycerol interacting with Munc13-1 inhibit vesicle fusion, which identifies opposing functions of these two Munc13 proteins.
    1. Developmental Biology
    2. Neuroscience

    Transient regulation of focal adhesion via Tensin3 is required for nascent oligodendrocyte differentiation

    Emeric Merour, Hatem Hmidan ... Carlos Parras
    A comprehensive analysis of Tensin3 function in oligodendrogenesis links the fields of transcriptional control in oligodendrocyte lineage cells with morphogenetic changes and integrin signaling mediated cell survival.
    1. Evolutionary Biology
    2. Genetics and Genomics

    Evolutionary rescue of phosphomannomutase deficiency in yeast models of human disease

    Ryan C Vignogna, Mariateresa Allocca ... Gregory I Lang
    Experimental evolution of yeast models of congenital disorders of glycosylation reveals that reduction, but not loss, of phosphoglucomutase activity best compensates for impaired phosphomannomutase activity.
    1. Physics of Living Systems

    Unrestrained growth of correctly oriented microtubules instructs axonal microtubule orientation

    Maximilian AH Jakobs, Assaf Zemel, Kristian Franze
    Biased growth of microtubules in the advancing axon tip contributes to the uniform orientation of microtubules in mature axons, which is essential for proper neuronal functioning.
    1. Plant Biology

    Unbiased proteomic and forward genetic screens reveal that mechanosensitive ion channel MSL10 functions at ER–plasma membrane contact sites in Arabidopsis thaliana

    Jennette M Codjoe, Ryan A Richardson ... Elizabeth S Haswell
    A mechanosensitive ion channel physically and genetically interacts with proteins that function at endoplasmic reticulum–plasma membrane contact sites.
    1. Medicine
    2. Microbiology and Infectious Disease

    Novel fast pathogen diagnosis method for severe pneumonia patients in the intensive care unit: randomized clinical trial

    Yan Wang, Xiaohui Liang ... Wenkui Yu
    A novel species-specific detection method could obtain pathogenic bacteria information in 4 hr with high clinical sensitivity and specificity, which guided the faster antibiotic treatment in ICU and brought some clinical benefit in a real-world scenario.
    1. Structural Biology and Molecular Biophysics

    Determination of oligomeric states of proteins via dual-color colocalization with single molecule localization microscopy

    Hua Leonhard Tan, Stefanie Bungert-Plümke ... Gabriel Stölting
    The DCC-SMLM algorithm allows to determine protein oligomeric states in situ, using the information obtained from the colocalization of fluorescent markers, overcoming the need for extraction of proteins from cells or complicated experimental setups when using microscopy.
    1. Developmental Biology

    A single-cell atlas of the cycling murine ovary

    Mary E Morris, Marie-Charlotte Meinsohn ... David Pépin
    A survey of the transcriptomic landscape of the mouse ovary at the single-cell level reveals both the cellular complexity of this organs and the dynamic nature of the cellular states that accompany estrous cycling.
    1. Developmental Biology

    Zbtb14 regulates monocyte and macrophage development through inhibiting pu.1 expression in zebrafish

    Yun Deng, Haihong Wang ... Jun Zhu
    Transcription factor Zbtb14 plays an important role in monocyte and macrophage development through the modulation of pu.1 expression.
    1. Cell Biology
    2. Medicine

    Association of lithocholic acid with skeletal muscle hypertrophy through TGR5-IGF-1 and skeletal muscle mass in cultured mouse myotubes, chronic liver disease rats and humans

    Yasuyuki Tamai, Akiko Eguchi ... Hayato Nakagawa
    Lithocholic acid associates with skeletal muscle mass and plays an important role in skeletal muscle hypertrophy through activation of the bile acid receptor.
    1. Ecology

    Stability and asynchrony of local communities but less so diversity increase regional stability of Inner Mongolian grassland

    Yonghui Wang, Shaopeng Wang ... Bernhard Schmid
    The regional stability across distant local communities is related to the stability of and asynchronous dynamics among local communities, which are strongly impacted by population dynamics of a few abundant species and relative weakly by species diversity.
    1. Neuroscience

    A novel rhesus macaque model of Huntington’s disease recapitulates key neuropathological changes along with motor and cognitive decline

    Alison R Weiss, William A Liguore ... Jodi L McBride
    mHTT delivery in key cortical and subcortical brain regions leads to hallmark mHTT aggregate formation, gray and white matter degenerative changes, along with motor and cognitive decline in a new macaque model of Huntington's disease.
    1. Cell Biology
    2. Neuroscience

    Distinct neurexin-cerebellin complexes control AMPA- and NMDA-receptor responses in a circuit-dependent manner

    Jinye Dai, Kif Liakath-Ali ... Thomas C Südhof
    A genetic manipulation of the Nrxn1/3SS4+-Cbln1/2 complex reveals this signaling pathway has no role in synapse formation but functions to shape the NMDAR- and AMPAR-content at multiple types of synapses with distinct facets in diverse circuits.
    1. Neuroscience

    Drosophila mechanical nociceptors preferentially sense localized poking

    Zhen Liu, Meng-Hua Wu ... Xin Liang
    A fly larval mechanical nociceptor develops dedicated neuronal mechanisms to support its sensory preference in detecting localized poking forces, and this sensory feature well supports the physiological function of the nociceptor in sensing the physical attack of its natural enemy.
    1. Genetics and Genomics

    Fat body phospholipid state dictates hunger-driven feeding behavior

    Kevin P Kelly, Mroj Alassaf ... Akhila Rajan
    Behavioral, lipidomic, and genetic analyses of adult Drosophila on a chronic high-sugar regime identified that fat body activity of a phospholipid biosynthesis enzyme, Pect, regulates insulin sensitivity and hunger response.
    1. Microbiology and Infectious Disease

    Ferric reductase-related proteins mediate fungal heme acquisition

    Udita Roy, Shir Yaish ... Daniel Kornitzer
    A new class of plasma membrane proteins involved in heme-iron utilization provides a molecular link between the extracellular and intracellular parts of the fungal heme acquisition pathway, and reveals the evolutionary origin of this pathway.
    1. Structural Biology and Molecular Biophysics

    Dynamic allostery in substrate binding by human thymidylate synthase

    Jeffrey P Bonin, Paul J Sapienza, Andrew L Lee
    The mechanism of substrate binding cooperativity in human thymidylate synthase does not derive from millisecond dynamic interconversion between active and inactive conformations in solution, but instead results primarily from differential changes in faster side-chain motions (conformational entropy), facilitated by a disordered N-terminus.
    1. Physics of Living Systems

    Label-free imaging of M1 and M2 macrophage phenotypes in the human dermis in vivo using two-photon excited FLIM

    Marius Kröger, Jörg Scheffel ... Maxim E Darvin
    The noninvasive visualization of dermal M1 and M2 macrophage phenotypes is shown for the first time in vivo.
    1. Immunology and Inflammation

    Single-cell RNA sequencing analysis of shrimp immune cells identifies macrophage-like phagocytes

    Peng Yang, Yaohui Chen ... Fan Wang
    A novel innate immune cell subset in shrimp shows similarities with human macrophage.
    1. Cell Biology
    2. Developmental Biology

    Independent regulation of mitochondrial DNA quantity and quality in Caenorhabditis elegans primordial germ cells

    Aaron ZA Schwartz, Nikita Tsyba ... Jeremy Nance
    Caenorhabditis elegans utilize multiple strategies to optimize germline mitochondrial genome integrity at the foundational stage of gonad development.
    1. Evolutionary Biology
    2. Genetics and Genomics

    Broad-scale variation in human genetic diversity levels is predicted by purifying selection on coding and non-coding elements

    David A Murphy, Eyal Elyashiv ... Guy Sella
    Background selection is shown to be the dominant mode of linked selection in humans, with marked effects on diversity levels throughout autosomes.
    1. Biochemistry and Chemical Biology
    2. Neuroscience

    Chronic Ca2+ imaging of cortical neurons with long-term expression of GCaMP-X

    Jinli Geng, Yingjun Tang ... Xiaodong Liu
    Focusing on calcium oscillations in relation to neuronal morphology both in vitro and in vivo, rationally designed GCaMP-X provides a simple solution to neuronal toxicity of conventional GCaMP in imaging applications involving prolonged and/or strong expression of calcium probes.
    1. Neuroscience

    Contextual effects in sensorimotor adaptation adhere to associative learning rules

    Guy Avraham, Jordan A Taylor ... Samuel D McDougle
    Core associative learning phenomena that are observed in studies of eyeblink conditioning are also observed in sensorimotor adaptation, pointing to a common framework for these distinct cerebellar-dependent motor learning processes.
    1. Neuroscience
    2. Computational and Systems Biology

    The individuality of shape asymmetries of the human cerebral cortex

    Yu-Chi Chen, Aurina Arnatkevičiūtė ... Kevin M Aquino
    Asymmetries between the shape of the left and right human cortex are highly unique to individuals, akin to a neuroanatomical fingerprint, related to cognitive function, and primarily driven by person-specific environmental influences.
    1. Developmental Biology
    2. Immunology and Inflammation

    Single-cell transcriptomics reveals functionally specialized vascular endothelium in brain

    Hyun-Woo Jeong, Rodrigo Diéguez-Hurtado ... Ralf H Adams
    Reactive endothelial venules are a new vessel subtype characterized by consistent expression of cell adhesion molecules, preferential leukocyte transmigration, association with perivascular macrophages, and the initiation of CNS immune responses.
    1. Cell Biology
    2. Developmental Biology

    Murine endothelial serine palmitoyltransferase 1 (SPTLC1) is required for vascular development and systemic sphingolipid homeostasis

    Andrew Kuo, Antonio Checa ... Timothy Hla
    Endothelial sphingolipid biosynthesis is essential for maintaining vascular development, neovascular proliferation, non-CNS tissue sphingolipid levels, and hepatocyte response to stress.
    1. Epidemiology and Global Health
    2. Microbiology and Infectious Disease

    An international observational study to assess the impact of the Omicron variant emergence on the clinical epidemiology of COVID-19 in hospitalised patients

    Bronner P Gonçalves, Matthew Hall ... ISARIC Clinical Characterisation Group
    Combined analyses of publicly available population-level variant data and detailed individual-level clinical data can be used to quantify the clinical impact of new SARS-CoV-2 variants in different settings.
    1. Chromosomes and Gene Expression

    Depletion or cleavage of cohesin during anaphase differentially affects chromatin structure and segregation

    Jonay Garcia-Luis, Hélène Bordelet ... Luis Aragon
    Cohesin role in chromosome organisation during anaphase is necessary for the segregation of chromosomes.
    1. Developmental Biology

    The cardiopharyngeal mesoderm contributes to lymphatic vessel development in mouse

    Kazuaki Maruyama, Sachiko Miyagawa-Tomita ... Hiroki Kurihara
    Genetic lineage tracing reveals the cardiopharyngeal mesoderm as a cellular origin of craniofacial and cardiac lymphatic vessels, which most often affected in lymphatic malformation patients.
    1. Neuroscience

    The Neurodata Without Borders ecosystem for neurophysiological data science

    Oliver Rübel, Andrew Tritt ... Kristofer E Bouchard
    The NWB data language enables reproduction, interchange, and reuse of diverse neurophysiology data, and the design principles of NWB are generally applicable to enhance discovery across biology through data FAIRness.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Targeting A-kinase anchoring protein 12 phosphorylation in hepatic stellate cells regulates liver injury and fibrosis in mouse models

    Komal Ramani, Nirmala Mavila ... Eki Seki
    Site-specific phosphorylation of the A-kinase anchoring protein 12 (AKAP12) in hepatic stellate cells modulates its scaffolding function and promotes liver fibrosis.
    1. Evolutionary Biology

    The evolution of manipulative cheating

    Ming Liu, Stuart Andrew West, Geoff Wild
    By considering a new form of social cheat strategy, arms-races-like dynamics between coevolving selfish traits could emerge from the tragedy of the commons and help explain the variations in cheating levels observed in many microbes and eusocial insects.
    1. Cell Biology

    Hepatic inactivation of murine Surf4 results in marked reduction in plasma cholesterol

    Vi T Tang, Joseph McCormick ... David Ginsburg
    Inactivation of SURF4 leads to impaired secretion of PCSK9 and apolipoproteins resulting in low plasma cholesterol without detrimental consequences to the liver.
    1. Cell Biology

    Telocytes regulate macrophages in periodontal disease

    Jing Zhao, Anahid A Birjandi ... Paul Sharpe
    A poorly understood cell type, the telocyte, is shown to regulate macrophages.
    1. Computational and Systems Biology
    2. Medicine

    Early stage NSCLS patients’ prognostic prediction with multi-information using transformer and graph neural network model

    Jie Lian, Jiajun Deng ... Varut Vardhanabhuti
    It provides evidence for the feasibility of using combined graph convolutional neural network and transformers’ based systems with patient demographics, and CT-derived imaging features as inputs into the transformer model for survival prediction in early stage lung cancer patients.
    1. Cancer Biology
    2. Computational and Systems Biology

    Machine learning-assisted elucidation of CD81–CD44 interactions in promoting cancer stemness and extracellular vesicle integrity

    Erika K Ramos, Chia-Feng Tsai ... Huiping Liu
    Machine learning-assisted experiments reveal CD81 as a novel binding partner of CD44 in driving cancer stemness, tumor cell clustering, and extracellular vesicle integrity in human and mouse breast cancer.
    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    The Drosophila ZAD zinc finger protein Kipferl guides Rhino to piRNA clusters

    Lisa Baumgartner, Dominik Handler ... Julius Brennecke
    Kipferl, a ZAD zinc finger protein from Drosophila, determines the chromatin binding specificity of the heterochromatin protein variant Rhino, defining piRNA clusters and preventing Rhino sequestration by selfish Satellite repeats.
    1. Ecology
    2. Evolutionary Biology

    Experimental evidence that group size generates divergent benefits of cooperative breeding for male and female ostriches

    Julian Melgar, Mads F Schou ... Charlie K Cornwallis
    Experimental manipulations of social groups of ostriches show that the benefits of cooperative parental care for females, and the costs of sexual competition for males, lead to sex differences in optimal group sizes.
    1. Cell Biology
    2. Computational and Systems Biology

    Age-dependent aggregation of ribosomal RNA-binding proteins links deterioration in chromatin stability with challenges to proteostasis

    Julie Paxman, Zhen Zhou ... Nan Hao
    The interaction between rDNA instability and proteostasis stress, two major aging hallmarks, underlies single-cell aging trajectories in yeast.
    1. Chromosomes and Gene Expression

    The structure-selective endonucleases GEN1 and MUS81 mediate complementary functions in safeguarding the genome of proliferating B lymphocytes

    Keith Conrad Fernandez, Laura Feeney ... Jayanta Chaudhuri
    A novel conditional mouse model to interrogate the requirements of structure-selective endonucleases in the development, functionality, and genome stability of B lymphocytes.
    1. Cell Biology
    2. Genetics and Genomics

    Real time, in vivo measurement of neuronal and peripheral clocks in Drosophila melanogaster

    Peter S Johnstone, Maite Ogueta ... Deniz Top
    Locally activatable bioluminescence (LABL) is a genetically encoded reporter that allows real time, in vivo measurement of distinct clocks in different cells and tissues in Drosophila.
    1. Neuroscience

    A visual sense of number emerges from divisive normalization in a simple center-surround convolutional network

    Joonkoo Park, David E Huber
    A set of canonical computational principles implemented in a simple feedforward neural network naturally gives rise to the network's sensitivity to numerosity and its illusory effects, providing an explanation for the ubiquity of the number sense in the animal kingdom.
    1. Developmental Biology

    RNA-binding protein Elavl1/HuR is required for maintenance of cranial neural crest specification

    Erica J Hutchins, Shashank Gandhi ... Marianne E Bronner
    The RNA-binding protein Elavl1 directly binds to and stabilizes a single gene product—Draxin mRNA—to prevent premature delamination and maintain specification in cranial neural crest.
    1. Cell Biology
    2. Medicine

    Notch signaling functions in noncanonical juxtacrine manner in platelets to amplify thrombogenicity

    Susheel N Chaurasia, Mohammad Ekhlak ... Debabrata Dash
    Notch signaling in human platelets functions in noncanonical juxtacrine manner to amplify platelet reactivity and thrombogenicity.
    1. Immunology and Inflammation

    The transcription factor Bach2 negatively regulates murine natural killer cell maturation and function

    Shasha Li, Michael D Bern ... Wayne M Yokoyama
    Deficiency of the transcriptional repressor, Bach2, results in more mature mouse natural killer cells.
    1. Biochemistry and Chemical Biology
    2. Cancer Biology

    S6K1 phosphorylates Cdk1 and MSH6 to regulate DNA repair

    Adi Amar-Schwartz, Vered Ben Hur ... Rotem Karni
    Unbiased proteomics and molecular analysis revealed a new role for S6K1 in regulating DNA repair through the orchestrated phosphorylation of CDK1 and MSH6. The findings may explain why RPS6KB1 gene amplification contributed to breast cancer drug resistance.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Molecular mechanism of active Cas7-11 in processing CRISPR RNA and interfering target RNA

    Hemant N Goswami, Jay Rai ... Hong Li
    Three-dimensional structure of CRISPR Cas7-11 shed light on protein evolution and guide development of biotechnology for RNA manipulations in cells.
    1. Evolutionary Biology
    2. Genetics and Genomics

    A novel lineage of the Capra genus discovered in the Taurus Mountains of Turkey using ancient genomics

    Kevin G Daly, Benjamin S Arbuckle ... Daniel G Bradley
    A relative of the tur, wild goat species now endemic to the Caucasus, lived at least 14,000 years ago in southern Turkey.

Magazine

    1. Genetics and Genomics

    Allorecognition: Knowing friend from foe

    Magnus Hallas-Møller, Katja S Johansen
  1. Illustration portraying conversations about many different aspects of science

    Talking Points: A Series of Interviews

    Edited by Helga Groll et al.
  2. Scientific Publishing: Peer review without gatekeeping

    Michael B Eisen, Anna Akhmanova ... Mone Zaidi
    1. Ecology
    2. Evolutionary Biology

    Group Size: The balance of the sexes

    Ralf HJM Kurvers, Lysanne Snijders