August 2022

Cover articles

Highlights controls:

Research articles

    1. Cancer Biology
    2. Chromosomes and Gene Expression

    Human WDR5 promotes breast cancer growth and metastasis via KMT2-independent translation regulation

    Wesley L Cai, Jocelyn Fang-Yi Chen ... Qin Yan
    The chromatin regulator WDR5 is a regulator of translation, and small molecule inhibitors or degraders of WDR5 can be used to treat triple-negative breast cancer.
    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    Characterization of sequence determinants of enhancer function using natural genetic variation

    Marty G Yang, Emi Ling ... Thomas Vierbuchen
    Large-scale, allele-resolved mapping of cis-regulatory function in F1-hybrid mice reveals sequence determinants that control transcription factor binding and enhancer activity in native chromatin context.
    1. Cell Biology
    2. Plant Biology

    The Arabidopsis SAC9 enzyme is enriched in a cortical population of early endosomes and restricts PI(4,5)P2 at the plasma membrane

    Alexis Lebecq, Mehdi Doumane ... Marie-Cécile Caillaud
    SAC9 prevents the accumulation of PI(4,5)P2 in intracellular compartments, thereby contributing to clathrin-mediated endocytosis at the plasma membrane and regulating the cortical localization of its protein partner SH3P2.
    1. Computational and Systems Biology

    Decoding mechanism of action and sensitivity to drug candidates from integrated transcriptome and chromatin state

    Caterina Carraro, Lorenzo Bonaguro ... Barbara Gatto
    Combined analyses of transcriptome and chromatin accessibility elucidated the mechanisms underlying cancer cell lines response to antitumor candidates and provided a versatile perturbation-informed basal signature able to predict drug sensitivity.
    1. Computational and Systems Biology

    Quantifying dynamic facial expressions under naturalistic conditions

    Jayson Jeganathan, Megan Campbell ... Michael Breakspear
    A novel computational pipeline uses time-frequency analysis to capture the dynamics of human facial expressions, and demonstrates abnormal facial dynamics in melancholic depression.
    1. Neuroscience

    Diverse states and stimuli tune olfactory receptor expression levels to modulate food-seeking behavior

    Ian G McLachlan, Talya S Kramer ... Steven W Flavell
    Caenorhabditis elegans integrate sensory stimuli and internal state information to alter their expression of olfactory receptors, which impacts the sensorimotor responses of the animal.
    1. Cancer Biology

    Hypoxia-inducible factor underlies von Hippel-Lindau disease stigmata

    Michael Ohh, Cassandra C Taber ... Daniel Tarade
    Previous studies and emerging data on pseudohypoxic diseases suggest that the complex phenotypic spectrum of VHL disease is due to the extent of HIF pathway deregulation in susceptible cell types and not by other purported substrates or functions of pVHL.
    1. Evolutionary Biology

    Transition to siblinghood causes a substantial and long-lasting increase in urinary cortisol levels in wild bonobos

    Verena Behringer, Andreas Berghänel ... Gottfried Hohmann
    In wild bonobos, sibling birth induced a sudden increase in urinary cortisol levels in the older offspring, a physiological response that occurred in all subjects and was independent of their age.
    1. Neuroscience

    Robust cone-mediated signaling persists late into rod photoreceptor degeneration

    Miranda L Scalabrino, Mishek Thapa ... Greg D Field
    The retina compensates for rod death and deteriorating cones to retain high-fidelity visual signaling to the brain.
    1. Neuroscience

    Neuroscout, a unified platform for generalizable and reproducible fMRI research

    Alejandro de la Vega, Roberta Rocca ... Tal Yarkoni
    A web-based analysis platform for public fMRI data using naturalistic stimuli, leveraging state-of-the-art feature extraction models to enable more generalizable and reproducible findings.
    1. Neuroscience

    IL-37 expression reduces acute and chronic neuroinflammation and rescues cognitive impairment in an Alzheimer’s disease mouse model

    Niklas Lonnemann, Shirin Hosseini ... Martin Korte
    Expression of an interleukin that is immune suppressive (IL-37) in mice is able to limit inflammation in the brain after acute inflammatory events and prevent loss of cognitive abilities in a mouse model of AD.
    1. Computational and Systems Biology
    2. Neuroscience

    Contribution of behavioural variability to representational drift

    Sadra Sadeh, Claudia Clopath
    By analysing large-scale datasets from the Allen Brain Observatory, we found that changes in the behavioural state of the animal can significantly contribute to the changes in representational similarity over time.
    1. Medicine

    Activation of targetable inflammatory immune signaling is seen in myelodysplastic syndromes with SF3B1 mutations

    Gaurav S Choudhary, Andrea Pellagatti ... Amit Verma
    SF3B1 mutation in myelodysplastic syndromes and acute myeloid leukemia lead to oncogenic long isoforms of IRAK4 that are therapeutically targetable.
    1. Developmental Biology
    2. Neuroscience

    A Notch-dependent transcriptional mechanism controls expression of temporal patterning factors in Drosophila medulla

    Alokananda Ray, Xin Li
    Cell-cycle-dependent Notch signaling cooperates with temporal transcription factors to promote the progression of the temporal transcription factor cascade in Drosophila medulla neuroblasts.
    1. Cancer Biology
    2. Cell Biology

    Nuclear fascin regulates cancer cell survival

    Campbell D Lawson, Samantha Peel ... Maddy Parsons
    Nuclear fascin accumulation occurs upon inhibition of Histone H3 kinases and results in enhanced and sustained nuclear F-actin bundling leading to reduced cancer cell invasion, viability, and nuclear fascin-specific/driven apoptosis.
    1. Cancer Biology
    2. Cell Biology

    The scaffolding protein flot2 promotes cytoneme-based transport of wnt3 in gastric cancer

    Daniel Routledge, Sally Rogers ... Steffen Scholpp
    Signalling filopodia, also known as cytonemes, are a crucial transport mechanism of Wnt3 in gastric cancer and their emergence is controlled by Flot2.
    1. Neuroscience

    Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling

    Anton Sumser, Maximilian Joesch ... Yoav Ben-Simon
    Mapping neuronal circuits is made substantially faster, simpler and more accurate with this extended toolkit of novel cell lines and vectors.
    1. Epidemiology and Global Health
    2. Genetics and Genomics

    Integrating genomic and epidemiologic data to accelerate progress toward schistosomiasis elimination

    Andrea J Lund, Kristen J Wade ... Elizabeth J Carlton
    Genomic approaches can be integrated with epidemiological and ecological studies to provide high-resolution answers to open questions about schistosomiasis transmission dynamics, offering a level of precision that is actionable, such that schistosomiasis-control programming can be tailored to regional contexts.
    1. Cell Biology

    Non-canonical function of an Hif-1α splice variant contributes to the sustained flight of locusts

    Ding Ding, Jie Zhang ... Le Kang
    The long-distance flight of locusts is greatly facilitated by a muscle-abundantly expressed Hif-1α splice variant, which remains active in normoxia and scavenges flight-induced reactive oxygen species by upregulating the expression of DJ-1 (PARK 7).
    1. Genetics and Genomics

    A moonlighting function of a chitin polysaccharide monooxygenase, CWR-1, in Neurospora crassa allorecognition

    Tyler C Detomasi, Adriana M Rico-Ramírez ... N Louise Glass
    Allorecognition in Neurospora crassa requires CWR-1 (cell wall remodeling protein), an essential process that ensures identity of an interconnected fungal syncytial colony and requires the CWR-1 polysaccharide monooxygenase domain, but not its catalytic activity.
    1. Genetics and Genomics

    Dynamic molecular evolution of a supergene with suppressed recombination in white-throated sparrows

    Hyeonsoo Jeong, Nicole M Baran ... Soojin V Yi
    Comprehensive genomic and population genetic analyses of a non-recombining chromosome in white-throated sparrows reveal the actions of purifying selection, positive selection, and balancing selection, expanding our understanding of supergene evolution.
    1. Developmental Biology
    2. Neuroscience

    p75NTR prevents the onset of cerebellar granule cell migration via RhoA activation

    Juan P Zanin, Wilma J Friedman
    The p75 neurotrophin receptor prevents the migration of the granule cell precursors away from its mitogenic niche in the external granule layer of the cerebellum, by maintaining a pool of undifferentiated cells capable of responding to mitogenic signals.
    1. Medicine
    2. Neuroscience

    Sleep EEG in young people with 22q11.2 deletion syndrome: A cross-sectional study of slow-waves, spindles and correlations with memory and neurodevelopmental symptoms

    Nicholas A Donnelly, Ullrich Bartsch ... Matt W Jones
    Measures of sleep features such as spindles and slow waves differentiate between young people with 22q11.2 microdeletion syndrome and healthy controls, and may mediate the relationship between this genotype and psychiatric symptoms.
    1. Biochemistry and Chemical Biology
    2. Immunology and Inflammation

    Mechanism of bisphosphonate-related osteonecrosis of the jaw (BRONJ) revealed by targeted removal of legacy bisphosphonate from jawbone using competing inert hydroxymethylene diphosphonate

    Hiroko Okawa, Takeru Kondo ... Ichiro Nishimura
    The targeted removal of legacy bisphosphonate from the jawbone by competitive equilibrium therapy not only elucidated the pathological mechanism of bisphosphonate-related osteonecrosis of the jaw (BRONJ) but also established a highly translatable therapeutic option for BRONJ.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Structural insight on the mechanism of an electron-bifurcating [FeFe] hydrogenase

    Chris Furlan, Nipa Chongdar ... James A Birrell
    Cryo-EM and particle classification techniques reveal how the electron-bifurcating [FeFe] hydrogenase from Thermotoga maritima multimerizes to connect distant active sites and reveal different conformational states that enable catalysis.
    1. Computational and Systems Biology
    2. Microbiology and Infectious Disease

    Machine learning-assisted discovery of growth decision elements by relating bacterial population dynamics to environmental diversity

    Honoka Aida, Takamasa Hashizume ... Bei-Wen Ying
    A smart combination of machine learning and high-throughput data generation of bacterial population dynamics successfully leads to an intriguing finding of the differentiation in decision-making components for bacterial growth.
    1. Genetics and Genomics

    Characterization of full-length CNBP expanded alleles in myotonic dystrophy type 2 patients by Cas9-mediated enrichment and nanopore sequencing

    Massimiliano Alfano, Luca De Antoni ... Marzia Rossato
    A novel sequencing-based method to characterize CNBP microsatellite expansions in DM2 patients demonstrates benefits for an improved dissection of DM2 genetic architecture, thus potentially ameliorating patient stratification and genetic counseling.
    1. Developmental Biology
    2. Neuroscience

    Photoreceptors generate neuronal diversity in their target field through a Hedgehog morphogen gradient in Drosophila

    Matthew P Bostock, Anadika R Prasad ... Vilaiwan M Fernandes
    Photoreceptors diversify their target field at long range through a graded signal.
    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    A mosaic-type trimeric RBD-based COVID-19 vaccine candidate induces potent neutralization against Omicron and other SARS-CoV-2 variants

    Jing Zhang, Zi Bo Han ... Qi Ming Li
    Animal experiments show that the mosaic-type immunogen integrating key mutations from Omicron and other circulating variants elicits broad neutralization against divergent SARS-CoV-2 strains.
    1. Neuroscience

    Decomposing the role of alpha oscillations during brain maturation

    Marius Tröndle, Tzvetan Popov ... Nicolas Langer
    Applying decomposition of oscillatory and aperiodic signal components to developmental EEG data provides a solution for the problems in the investigation of alpha power during brain maturation.
    1. Cell Biology
    2. Developmental Biology

    GJA1 depletion causes ciliary defects by affecting Rab11 trafficking to the ciliary base

    Dong Gil Jang, Keun Yeong Kwon ... Tae Joo Park
    Ciliogenesis requires a gap junction protein (GJA1) mediated ciliary vesicle deposition and CP110 removal.
    1. Cell Biology

    An improved organ explant culture method reveals stem cell lineage dynamics in the adult Drosophila intestine

    Marco Marchetti, Chenge Zhang, Bruce A Edgar
    An improved culture method for explanted adult Drosophila organs allows the live-imaging of damage response, cell differentiation, and tracing of progenitor cell lineages through multiple rounds of division.
    1. Cell Biology
    2. Structural Biology and Molecular Biophysics

    In situ single particle classification reveals distinct 60S maturation intermediates in cells

    Bronwyn A Lucas, Kexin Zhang ... Nikolaus Grigorieff
    Comparing the relative similarity of cellular molecules to alternate templates allows classification of related complexes in the cell using fewer particles than needed for 3D classification and is more practicable for low abundance complexes.
    1. Cell Biology

    An amphipathic helix in Brl1 is required for nuclear pore complex biogenesis in S. cerevisiae

    Annemarie Kralt, Matthias Wojtynek ... Karsten Weis
    Genetic, proteomic, and structural analyses provide insight into the role of Brl1 during nuclear pore complex biogenesis, suggesting a function in the fusion of outer and inner nuclear membranes.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Single-molecule analysis of the entire perfringolysin O pore formation pathway

    Conall McGuinness, James C Walsh ... Till Böcking
    Arc-shaped PFO oligomers consisting of at least four subunits can insert into the membrane in a kinetically controlled process opening a transmembrane pore, whereby post-insertion growth may ultimately lead to formation of a complete ring.
    1. Neuroscience

    Developmental stage-specific spontaneous activity contributes to callosal axon projections

    Yuta Tezuka, Kenta M Hagihara ... Yoshiaki Tagawa
    The developing neocortex exhibits spontaneous network activity with various synchrony levels, and such activity is selectively required during a critical developmental time window for the formation of long-range axonal projections connecting the two cortical hemispheres.
    1. Neuroscience

    Satellite glia modulate sympathetic neuron survival, activity, and autonomic function

    Aurelia A Mapps, Erica Boehm ... Rejji Kuruvilla
    Satellite glia provide trophic support to adult sympathetic neurons and modulate neuronal activity and autonomic function in mice.
    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    Polycomb-mediated repression of paternal chromosomes maintains haploid dosage in diploid embryos of Marchantia

    Sean Akira Montgomery, Tetsuya Hisanaga ... Frédéric Berger
    Genomic imprinting in the bryophyte Marchantia polymorpha by Polycomb results in maternal dominance of embryonic gene expression.
    1. Cell Biology

    β-cell deletion of the PKm1 and PKm2 isoforms of pyruvate kinase in mice reveals their essential role as nutrient sensors for the KATP channel

    Hannah R Foster, Thuong Ho ... Matthew J Merrins
    Local ATP production by the plasma membrane-associated glycolytic enzyme pyruvate kinase is essential for the nutrient-dependent closure of the ATP-sensitive potassium channels that initiate insulin release from pancreatic β-cells.
    1. Neuroscience

    BehaviorDEPOT is a simple, flexible tool for automated behavioral detection based on markerless pose tracking

    Christopher J Gabriel, Zachary Zeidler ... Laura A DeNardo
    BehaviorDEPOT is a general purpose behavior analysis software that will meet the needs of thousands of behavioral neuroscientists who need accurate, flexible open-source software to analyze naturalistic behaviors and align then with neural data.
    1. Structural Biology and Molecular Biophysics

    Automated systematic evaluation of cryo-EM specimens with SmartScope

    Jonathan Bouvette, Qinwen Huang ... Mario J Borgnia
    SmartScope is the first software package designed to streamline, standardize, and fully automate screening of specimens in cryo-electron microscopy, providing real-time remote control of the microscope and access to data through a standard web interface.
    1. Physics of Living Systems

    Alternation emerges as a multi-modal strategy for turbulent odor navigation

    Nicola Rigolli, Gautam Reddy ... Massimo Vergassola
    A tracking animal's decision to intermittently pause and sniff the air reflects its belief that it is far downwind of the odor source, where benefits of sensing rare airborne cues outweigh the cost of pausing.
    1. Cell Biology
    2. Medicine

    Interleukin-33 regulates the endoplasmic reticulum stress of human myometrium via an influx of calcium during initiation of labor

    Li Chen, Zhenzhen Song ... Guoying Zhang
    IL-33 plays an important role in the initiation of labor by leading to stress of the ER via an influx of calcium ions in human uterine smooth muscle cells.
    1. Evolutionary Biology

    Species-specific chromatin landscape determines how transposable elements shape genome evolution

    Yuheng Huang, Harsh Shukla, Yuh Chwen G Lee
    The ultimate driver for the substantial between-species difference in the success of transposable elements, the widely distributed genetic parasite, may lie in the overall chromatin environment.
    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    Identification of putative enhancer-like elements predicts regulatory networks active in planarian adult stem cells

    Jakke Neiro, Divya Sridhar ... Aziz Aboobaker
    Predicted gene regulatory networks active in planarians adult stem cells provide testable hypotheses about the control of pluripotency and differentiation in animals.
    1. Neuroscience

    Experience-driven rate modulation is reinstated during hippocampal replay

    Margot Tirole, Marta Huelin Gorriz ... Daniel Bendor
    Hippocampal place cells modulate their firing rate during replay events to reflect the increases, or decreases, in firing rate experienced between contexts during behavior.
    1. Cancer Biology
    2. Immunology and Inflammation

    Dendritic cell Piezo1 directs the differentiation of TH1 and Treg cells in cancer

    Yuexin Wang, Hui Yang ... Guangwei Liu
    Detailed in vivo and in vitro experimental data in mice and human cell experimental data provide critical insight for understanding the role of the DC-based mechanical regulation of immunopathology in directing T cell lineage commitment in tumor microenvironments.
    1. Neuroscience

    Epac2 in midbrain dopamine neurons contributes to cocaine reinforcement via enhancement of dopamine release

    Xiaojie Liu, Casey R Vickstrom ... Qing-song Liu
    The cAMP sensor and effector Epac2 facilitates dopamine release and promotes cocaine reward.
    1. Neuroscience

    Rate and oscillatory switching dynamics of a multilayer visual microcircuit model

    Gerald Hahn, Arvind Kumar ... Gustavo Deco
    A computer model of the mouse visual cortex shows that local brain circuits are organized as switches whose states are coded as neuronal oscillations with different frequencies.
    1. Neuroscience

    Botulinum neurotoxin accurately separates tonic vs. phasic transmission and reveals heterosynaptic plasticity rules in Drosophila

    Yifu Han, Chun Chien ... Dion Dickman
    A new tool enables electrophysiological isolation of input-specific neurotransmission in a powerful model glutamatergic circuit.
    1. Stem Cells and Regenerative Medicine

    A regeneration-triggered metabolic adaptation is necessary for cell identity transitions and cell cycle re-entry to support blastema formation and bone regeneration

    Ana S Brandão, Jorge Borbinha ... Antonio Jacinto
    Zebrafish caudal fin amputation induces an increase in the glycolytic influx that leads to dedifferentiation of osteoblasts and their re-entry in the cell cycle, which is essential for blastema formation and bone regeneration.
    1. Cell Biology
    2. Immunology and Inflammation

    HLJ1 amplifies endotoxin-induced sepsis severity by promoting IL-12 heterodimerization in macrophages

    Wei-Jia Luo, Sung-Liang Yu ... Kang-Yi Su
    Single-cell RNA sequencing reveals HLJ1 as a novel immunomodulator for multicellular pathway of macrophages and NK cells, contributing to organ injury and sepsis death through amplified IL-12/IFN-γ axis.
    1. Chromosomes and Gene Expression

    Molecular dissection of condensin II-mediated chromosome assembly using in vitro assays

    Makoto M Yoshida, Kazuhisa Kinoshita ... Tatsuya Hirano
    The pentameric condensin II complex is equipped with a multilayered, self-regulatory mechanism that supports mitotic chromosome assembly.
    1. Computational and Systems Biology
    2. Ecology

    Data-driven causal analysis of observational biological time series

    Alex Eric Yuan, Wenying Shou
    Visualizations, simulations, and examples are used to provide an accessible synthesis of the reasoning and assumptions behind commonly used causal discovery approaches.
    1. Cancer Biology
    2. Cell Biology

    EHMT2 methyltransferase governs cell identity in the lung and is required for KRAS G12D tumor development and propagation

    Ariel Pribluda, Anneleen Daemen ... Melissa R Junttila
    G9a regulates chromatin-bound b-catenin enabling cell-intrinsic control of WNT signaling-mediated cell fate decisions.
    1. Epidemiology and Global Health

    Global variation in force-of-infection trends for human Taenia solium taeniasis/cysticercosis

    Matthew A Dixon, Peter Winskill ... María-Gloria Basáñez
    Marked geographical heterogeneity in global Taenia solium transmission rates indicate the need for setting-specific intervention strategies to achieve the WHO NTD 2021-2030 roadmap milestones for T. solium.
    1. Neuroscience

    Audiovisual task switching rapidly modulates sound encoding in mouse auditory cortex

    Ryan J Morrill, James Bigelow ... Andrea R Hasenstaub
    The brain processes the same multisensory stimulus differently when the way it sounds, as opposed to the way it looks, is useful for making a decision.
    1. Structural Biology and Molecular Biophysics

    Double NPY motifs at the N-terminus of the yeast t-SNARE Sso2 synergistically bind Sec3 to promote membrane fusion

    Maximilian Peer, Hua Yuan ... Gang Dong
    A novel dual-site binding between the yeast t-SNARE Sso2 and Sec3 (a component of the exocyst tethering complex) facilitates the fusion of secretory vesicles with the plasma membrane.
    1. Chromosomes and Gene Expression

    Artificially stimulating retrotransposon activity increases mortality and accelerates a subset of aging phenotypes in Drosophila

    Joyce Rigal, Ane Martin Anduaga ... Michael T Marr
    A genetic approach indicates that increased active somatic transposon activity can decrease life span and affect some but not all hallmarks of aging.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Structure of Mycobacterium tuberculosis Cya, an evolutionary ancestor of the mammalian membrane adenylyl cyclases

    Ved Mehta, Basavraj Khanppnavar ... Volodymyr M Korkhov
    Structure of M. tuberculosis Rv1625c/Cya provides clues to the potential functional role of the transmembrane domain in the membrane adenylyl cyclases.
    1. Cell Biology
    2. Computational and Systems Biology

    DetecDiv, a generalist deep-learning platform for automated cell division tracking and survival analysis

    Théo Aspert, Didier Hentsch, Gilles Charvin
    A deep learning-based image classification pipeline unleashes automated division counting and replicative lifespan analyses of single cells growing in microfluidic cellular traps.
    1. Cell Biology
    2. Structural Biology and Molecular Biophysics

    Detecting molecular interactions in live-cell single-molecule imaging with proximity-assisted photoactivation (PAPA)

    Thomas GW Graham, John Joseph Ferrie ... Xavier Darzacq
    Proximity-assisted photoactivation (PAPA) provides a new way to detect protein–protein interactions in single-molecule imaging of live cells.
    1. Evolutionary Biology

    Tradeoff breaking as a model of evolutionary transitions in individuality and limits of the fitness-decoupling metaphor

    Pierrick Bourrat, Guilhem Doulcier ... Katrin Hammerschmidt
    A new model describes evolutionary transitions in individuality in terms of tradeoff and tradeoff-breaking events as opposed to changes in the nature of fitness.
    1. Cell Biology
    2. Microbiology and Infectious Disease

    Temporal and thermal profiling of the Toxoplasma proteome implicates parasite Protein Phosphatase 1 in the regulation of Ca2+-responsive pathways

    Alice L Herneisen, Zhu-Hong Li ... Sebastian Lourido
    Time-resolved phosphoproteomics and thermal proteome profiling reveal the Ca2+-responsive proteome of the model apicomplexan Taxoplasma gondii, identifying PP1 as a Ca2+-responsive enzyme that regulates Ca2+ uptake to promote parasite motility.
    1. Developmental Biology
    2. Genetics and Genomics

    PI3K signaling specifies proximal-distal fate by driving a developmental gene regulatory network in SOX9+ mouse lung progenitors

    Divya Khattar, Sharlene Fernandes ... Daniel T Swarr
    Paired analysis of gene expression and chromatin accessibility in SOX9+ lung progenitor cells identifies a requirement for PI3K in proximal-distal patterning of the mouse lung epithelium.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Membrane-mediated dimerization potentiates PIP5K lipid kinase activity

    Scott D Hansen, Albert A Lee ... Jay T Groves
    Dimerization promotes nonlinear kinetics in PIP5K-dependent lipid phosphorylation reactions.
    1. Medicine

    Biphasic regulation of osteoblast development via the ERK MAPK–mTOR pathway

    Jung-Min Kim, Yeon-Suk Yang ... Jae-hyuck Shim
    Genetic and biochemical analyses uncover a dichotomy of ERK pathway functions in osteoblasts, whereby ERK activation promotes the early differentiation of osteoblast precursors, but inhibits the subsequent differentiation of committed osteoblasts via mTOR-mediated regulation of mitochondrial function and SGK1.
    1. Medicine

    The proportion of randomized controlled trials that inform clinical practice

    Nora Hutchinson, Hannah Moyer ... Jonathan Kimmelman
    The majority of trials possess at least one characteristic that may compromise their ability to guide clinical practice.
    1. Neuroscience

    Value representations in the rodent orbitofrontal cortex drive learning, not choice

    Kevin J Miller, Matthew M Botvinick, Carlos D Brody
    Neurons in the OFC signal expected reward specifically when this information is used for learning rather than for choosing, and silencing these neurons impairs use of this information to learn.
    1. Microbiology and Infectious Disease

    Innate immune signaling in trophoblast and decidua organoids defines differential antiviral defenses at the maternal-fetal interface

    Liheng Yang, Eleanor C Semmes ... Carolyn B Coyne
    Organoids developed from matched human placental tissue define differences in antiviral signaling between cell types comprising the maternal-fetal interface.
    1. Structural Biology and Molecular Biophysics

    Aminomethanesulfonic acid illuminates the boundary between full and partial agonists of the pentameric glycine receptor

    Josip Ivica, Hongtao Zhu ... Lucia G Sivilotti
    The sulfonate analog of glycine is very efficacious in activating glycine channels and causes conformational changes in this pentameric ligand-gated channel that are similar to those produced by glycine itself.
    1. Neuroscience

    An increase of inhibition drives the developmental decorrelation of neural activity

    Mattia Chini, Thomas Pfeffer, Ileana Hanganu-Opatz
    The age-dependent shift of prefrontal excitation-inhibition (E-I) ratio toward inhibition causes sparser and decorrelated activity, while its impairment might relate to neurodevelopmental disorders.
    1. Computational and Systems Biology
    2. Physics of Living Systems

    Defining hierarchical protein interaction networks from spectral analysis of bacterial proteomes

    Mark A Zaydman, Alexander S Little ... Arjun S Raman
    The emergent organization of bacterial proteomes—the integration of proteins into collective networks that encode function—can be defined purely from spectral analysis of ortholog covariation across extant diversity.
    1. Neuroscience

    Seizures, behavioral deficits, and adverse drug responses in two new genetic mouse models of HCN1 epileptic encephalopathy

    Andrea Merseburg, Jacquelin Kasemir ... Bina Santoro
    Two genetic mouse models for HCN1-linked developmental epileptic encephalopathy display distinct biophysical changes in HCN1 ion channel properties but similar worsening of seizures in response to antiepileptic drugs, thereby recapitulating key features of the human disease.
    1. Medicine

    Neuroinflammation in neuronopathic Gaucher disease: Role of microglia and NK cells, biomarkers, and response to substrate reduction therapy

    Chandra Sekhar Boddupalli, Shiny Nair ... Pramod K Mistry
    In neurodegeneration of Gaucher disease, glucosylceramides trigger neuroinflammation via attrition of homeostatic microglia and transition to lipid-laden damage-associated microglia concurrently with infiltration of diverse immune cells including activated NK cells and CCR2+ macrophages, ameliorated by substrate reduction therapy.
    1. Cell Biology
    2. Medicine

    MKK6 deficiency promotes cardiac dysfunction through MKK3-p38γ/δ-mTOR hyperactivation

    Rafael Romero-Becerra, Alfonso Mora ... Guadalupe Sabio
    Lack of cardiac MKK6 results in premature death with the development of heart hypertrophy and cardiac dysfunction in aging.
    1. Neuroscience

    Inhibition of itch by neurokinin 1 receptor (Tacr1) -expressing ON cells in the rostral ventromedial medulla in mice

    Taylor Follansbee, Dan Domocos ... Earl Carstens
    Activation of Tacr1-expressing neurons including ON cells in the rostral ventromedial medulla inhibits acute and chronic itch-related behavior.
    1. Ecology
    2. Evolutionary Biology

    Earliest evidence for fruit consumption and potential seed dispersal by birds

    Han Hu, Yan Wang ... Roger BJ Benson
    Fruit consumption of Jeholornis was evidenced and indicates seed dispersal was present from early in avian radiation.
    1. Microbiology and Infectious Disease

    Zika virus causes placental pyroptosis and associated adverse fetal outcomes by activating GSDME

    Zikai Zhao, Qi Li ... Jing Ye
    Zika virus infection induces the gasdermin E-mediated pyroptosis in placental cells through TNF-α-caspase-8-caspase-3 signaling pathway, which contributes to adverse fetal outcomes in pregnant mouse model.
    1. Epidemiology and Global Health

    Effects of side-effect risk framing strategies on COVID-19 vaccine intentions: a randomized controlled trial

    Nikkil Sudharsanan, Caterina Favaretti ... Alain Vandormael
    Small changes to the way COVID-19 vaccine side-effect rates are framed and communicated have meaningful impacts on individuals' vaccination intentions.
    1. Neuroscience

    Mutual interaction between visual homeostatic plasticity and sleep in adult humans

    Danilo Menicucci, Claudia Lunghi ... Angelo Gemignani
    The study of sleep following monocular deprivation has shown that sleep slow oscillations and spindles occurring during non-REM sleep have a role in homeostatic ocular dominance plasticity even in the adulthood, beyond synaptic homeostatic hypothesis that applies to Hebbian phenomena.
    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    Transcriptional heterogeneity and cell cycle regulation as central determinants of Primitive Endoderm priming

    Marta Perera, Silas Boye Nissen ... Joshua M Brickman
    The simultaneous expansion of G1 and acceleration of the cell cycle, while ensuring synchronous inheritance of these properties, progressively induces cell identity in differentiation.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    PH domain-mediated autoinhibition and oncogenic activation of Akt

    Hwan Bae, Thibault Viennet ... Philip A Cole
    Structural and biochemical analysis of semisynthetic Akt forms and mutants has revealed the importance of a key interaction network involving Arg86, Glu17, and Tyr18 that controls Akt conformation and activity.
    1. Neuroscience

    TRPV1 drugs alter core body temperature via central projections of primary afferent sensory neurons

    Wendy Wing Sze Yue, Lin Yuan ... David Julius
    Capsaicin and other vanilloid receptor ligands alter core body temperature by perturbing central thermoregulatory pathways through activation/inhibition of TRPV1 receptors on peripheral sensory nerve fibers.
    1. Neuroscience

    Understanding implicit sensorimotor adaptation as a process of proprioceptive re-alignment

    Jonathan S Tsay, Hyosub Kim ... Richard B Ivry
    A new computational model reveals how implicit sensorimotor adaptation is elicited to re-align one's felt and desired hand position.
    1. Developmental Biology
    2. Genetics and Genomics

    Feedback between a retinoid-related nuclear receptor and the let-7 microRNAs controls the pace and number of molting cycles in C. elegans

    Ruhi Patel, Himani Galagali ... Alison R Frand
    A genetic oscillator composed of NHR-23 and let-7 family of microRNAs links the molting cycle timer and the heterochronic pathway to regulate the pace of molting in C. elegans and ensure that worms molt only four times.
    1. Cell Biology

    PLK4 drives centriole amplification and apical surface area expansion in multiciliated cells

    Gina M LoMastro, Chelsea G Drown ... Andrew Jon Holland
    Genetically engineered mouse models show that PLK4 protein and kinase activity are essential for multiciliogenesis, demonstrating that the early steps of centriole assembly are conserved between cycling and multiciliated cells.
    1. Immunology and Inflammation

    Tissue-specific modifier alleles determine Mertk loss-of-function traits

    Yemsratch T Akalu, Maria E Mercau ... Sourav Ghosh
    Current understanding of Mertk biology, such as in retinal degeneration and tumor immunity, is redefined by gene knockout in C57BL/6 mice.
    1. Neuroscience

    Local field potentials reflect cortical population dynamics in a region-specific and frequency-dependent manner

    Cecilia Gallego-Carracedo, Matthew G Perich ... Juan Álvaro Gallego
    There is a frequency-dependent association between the local field potential and the coordinated activity of populations of single neurons, which remains constant during different aspects of behaviour but changes across regions of primate sensorimotor cortex.
    1. Structural Biology and Molecular Biophysics

    Structures of topoisomerase V in complex with DNA reveal unusual DNA-binding mode and novel relaxation mechanism

    Amy Osterman, Alfonso Mondragón
    Structural and biochemical studies explain the topoisomerase V DNA relaxation mechanism by showing that it adopts an unusual conformation when bound to DNA that exposes the active site.
    1. Cell Biology
    2. Chromosomes and Gene Expression

    STAG2 promotes the myelination transcriptional program in oligodendrocytes

    Ningyan Cheng, Guanchen Li ... Hongtao Yu
    Brain-specific inactivation of cohesin-STAG2 in the mouse causes myelination defects, thus implicating hypomyelination as a contributing factor to cohesinopathy and establishing oligodendrocytes as a cell system to probe the physiological function of cohesin-mediated genome folding.
    1. Genetics and Genomics

    Closely related type II-C Cas9 orthologs recognize diverse PAMs

    Jingjing Wei, Linghui Hou ... Yongming Wang
    Closely related type II-C Cas9 orthologs recognize diverse PAMs, which facilitates us to expand the targeting scope.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Multi-step recognition of potential 5' splice sites by the Saccharomyces cerevisiae U1 snRNP

    Sarah R Hansen, David S White ... Aaron A Hoskins
    The yeast U1 snRNP recognizes multiple features of target RNAs to reversibly identify splicing-competent 5' splice sites.
    1. Stem Cells and Regenerative Medicine

    Generation of functional hepatocytes by forward programming with nuclear receptors

    Rute A Tomaz, Ekaterini D Zacharis ... Ludovic Vallier
    Forward programming of human pluripotent stem cells with a combination of four transcription factors allows the production of functional hepatocytes.
    1. Immunology and Inflammation

    Inflammatory stress signaling via NF-kB alters accessible cholesterol to upregulate SREBP2 transcriptional activity in endothelial cells

    Joseph Wayne M Fowler, Rong Zhang ... William C Sessa
    Detailed biochemical and metabolic analysis of the inflammatory response in human endothelial cells reveals that inflammation directly regulates cholesterol homeostasis.
    1. Computational and Systems Biology
    2. Neuroscience

    Information flows from hippocampus to auditory cortex during replay of verbal working memory items

    Vasileios Dimakopoulos, Pierre Mégevand ... Johannes Sarnthein
    Precisely tracking the anatomical sources of neural computations infers functional directed connectivity between hippocampal memory neurons and cortical sensory neurons, it reveals information flowing from cortex to hippocampus during encoding but the reverse direction during maintenance.
    1. Physics of Living Systems

    Learning to predict target location with turbulent odor plumes

    Nicola Rigolli, Nicodemo Magnoli ... Agnese Seminara
    Intensity of an odor and timing of its detection are complementary attributes of turbulent plumes and enable robust prediction of the location of a distant target.
    1. Computational and Systems Biology
    2. Ecology

    A systematic, complexity-reduction approach to dissect the kombucha tea microbiome

    Xiaoning Huang, Yongping Xin, Ting Lu
    Kombucha tea microbiome analysis demonstrates the identification, characterization and extrapolation of minimal cores as a promising framework for mechanistic investigation of microbiome behaviors.
    1. Immunology and Inflammation

    Th2 single-cell heterogeneity and clonal distribution at distant sites in helminth-infected mice

    Daniel Radtke, Natalie Thuma ... David Voehringer
    Th2 cell heterogeneity was revealed by combined transcriptome and T-cell receptor sequencing of single Th2 cells from lung and lymph node of helminth-infected mice and led to identification of a helminth-specific T-cell receptor.
    1. Cell Biology
    2. Genetics and Genomics

    Circadian oscillations in Trichoderma atroviride and the role of core clock components in secondary metabolism, development, and mycoparasitism against the phytopathogen Botrytis cinerea

    Marlene Henríquez-Urrutia, Rebecca Spanner ... Luis F Larrondo
    The biocontrol fungus Trichoderma atroviride possess a functional circadian clock, whose components impact the production of secondary metabolites and also play a role in the interaction with fungi such as the phytopathogen Botrytis cinerea.
    1. Computational and Systems Biology
    2. Neuroscience

    Parallel processing, hierarchical transformations, and sensorimotor associations along the ‘where’ pathway

    Raymond Doudlah, Ting-Yu Chang ... Ari Rosenberg
    Hierarchical transformations of visual representations, saccade-related activity, and sensorimotor associations occur in parallel at the juncture of visual and parietal cortex.
    1. Immunology and Inflammation

    Soluble MAC is primarily released from MAC-resistant bacteria that potently convert complement component C5

    Dennis J Doorduijn, Marie V Lukassen ... Suzan HM Rooijakkers
    Bacteria that resist direct complement-mediated killing by pores can still potently activate the complement system and trigger release of incomplete pores into human serum.
    1. Developmental Biology

    Positive feedback regulation of frizzled-7 expression robustly shapes a steep Wnt gradient in Xenopus heart development, together with sFRP1 and heparan sulfate

    Takayoshi Yamamoto, Yuta Kambayashi ... Stefan Hoppler
    Biomolecular experiments and computer simulations revealed that morphogen receptors expressed via a positive feedback loop impart robustness against variations in morphogen secretion rate and speed of development.
    1. Immunology and Inflammation

    SMAD4 and TGFβ are architects of inverse genetic programs during fate determination of antiviral CTLs

    Karthik Chandiran, Jenny E Suarez-Ramirez ... Linda S Cauley
    Pathogen-specific CTLs are programmed to provide customized responses against infection, by inflammatory molecules that promote localization in peripheral and lymphoid tissues using alternative signaling mechanisms.
    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    Defining the ultrastructure of the hematopoietic stem cell niche by correlative light and electron microscopy

    Sobhika Agarwala, Keun-Young Kim ... Owen J Tamplin
    Multiple imaging modalities resolved the ultrastructure of single hematopoietic stem cells in their endogenous niche, allowing identification of dopamine beta-hydroxylase positive cells as a functional niche cell type.
    1. Epidemiology and Global Health

    COVID-19 pandemic dynamics in South Africa and epidemiological characteristics of three variants of concern (Beta, Delta, and Omicron)

    Wan Yang, Jeffrey L Shaman
    Model-inference reconstructed SARS-CoV-2 transmission dynamics in South Africa during March 2020 to February 2022, and quantified the immune erosion potential and transmissibility of three major variants (Beta, Delta, and Omicron), highlighting their common characteristics and the need for more proactive preparedness.
    1. Computational and Systems Biology
    2. Medicine

    Modeling osteoporosis to design and optimize pharmacological therapies comprising multiple drug types

    David J Jörg, Doris H Fuertinger ... Peter Kotanko
    A mathematical model of osteoporosis explains why the sequence of osteoporosis medications matters for short-term and long-term treatment success.
    1. Cell Biology

    Isoform-specific mutation in Dystonin-b gene causes late-onset protein aggregate myopathy and cardiomyopathy

    Nozomu Yoshioka, Masayuki Kurose ... Hirohide Takebayashi
    Dystonin-b-specific mutant mice exhibit late-onset myopathy and cardiomyopathy.
    1. Computational and Systems Biology

    Integrative small and long RNA omics analysis of human healing and nonhealing wounds discovers cooperating microRNAs as therapeutic targets

    Zhuang Liu, Letian Zhang ... Ning Xu Landén
    A comprehensive microRNA expression and function landscape of human wounds unraveled miRNAs highly relevant to venous ulcer pathology.
    1. Cell Biology
    2. Neuroscience

    Lactate receptor HCAR1 regulates neurogenesis and microglia activation after neonatal hypoxia-ischemia

    Lauritz Kennedy, Emilie R Glesaaen ... Johanne E Rinholm
    HCAR1 knockout mice are unable to initiate brain tissue repair after a hypoxic-ischemic injury.
    1. Developmental Biology
    2. Neuroscience

    Temporal analysis of enhancers during mouse cerebellar development reveals dynamic and novel regulatory functions

    Miguel Ramirez, Yuliya Badayeva ... Daniel Goldowitz
    An analysis of enhancer activity during mouse cerebellar development provides an invaluable resource for studying gene expression regulation by enhancers in the developing cerebellum and delivers a rich dataset of novel gene-enhancer associations providing a basis for future in-depth studies.
    1. Cell Biology
    2. Developmental Biology

    Banp regulates DNA damage response and chromosome segregation during the cell cycle in zebrafish retina

    Swathy Babu, Yuki Takeuchi, Ichiro Masai
    Banp is a transcription activator of cell cycle genes like cenpt, ncapg, and wrnip1 to prevent genotoxic stress during rapid cell division and its repercussions on development and disease.
    1. Evolutionary Biology
    2. Microbiology and Infectious Disease

    Pre-existing chromosomal polymorphisms in pathogenic E. coli potentiate the evolution of resistance to a last-resort antibiotic

    Pramod K Jangir, Qiue Yang ... R Craig MacLean
    Interactions between a mobile resistance gene and chromosomal mutations drive the evolution of high-level antibiotic resistance.
    1. Cell Biology
    2. Genetics and Genomics

    The VINE complex is an endosomal VPS9-domain GEF and SNX-BAR coat

    Shawn P Shortill, Mia S Frier ... Elizabeth Conibear
    The yeast VARP homolog forms a new sorting nexin complex that promotes its own membrane recruitment through GEF activity and regulates the distribution of endosomal proteins.
    1. Epidemiology and Global Health

    Adiposity may confound the association between vitamin D and disease risk – a lifecourse Mendelian randomization study

    Tom G Richardson, Grace M Power, George Davey Smith
    Genetic analyses provide evidence that adiposity influences vitamin D levels at different timepoints over the lifecourse, suggesting that associations previously reported between vitamin D deficiency and disease by conventional epidemiological studies may have been prone to confounding.
    1. Cell Biology

    A pulse-chasable reporter processing assay for mammalian autophagic flux with HaloTag

    Willa Wen-You Yim, Hayashi Yamamoto, Noboru Mizushima
    HaloTag becomes resistant to lysosomal proteolysis upon ligand binding, enabling us to measure various types of autophagic flux easily and precisely by using HaloTag-containing reporters for processing assays.
    1. Epidemiology and Global Health
    2. Microbiology and Infectious Disease

    Estimation and worldwide monitoring of the effective reproductive number of SARS-CoV-2

    Jana S Huisman, Jérémie Scire ... Tanja Stadler
    A new and throughly validated method for timely estimation of the effective reproductive number of SARS-CoV-2 aided in the public health response to the COVID-19 pandemic.
    1. Structural Biology and Molecular Biophysics

    Multistep loading of a DNA sliding clamp onto DNA by replication factor C

    Marina Schrecker, Juan C Castaneda ... Richard K Hite
    Single-particle cryo-EM structures reveal a multistep process of how DNA is loaded into the DNA sliding clamp proliferating cell nuclear antigen by the canonical clamp loader replication factor C.
    1. Genetics and Genomics

    Nomograms of human hippocampal volume shifted by polygenic scores

    Mohammed Janahi, Leon Aksman ... Andre Altmann
    Accounting for genetic information improved normative models of hippocampal volume in humans by accounting for change equivalent to around 3 years of normal loss for a person aged 65.
    1. Cancer Biology
    2. Chromosomes and Gene Expression

    Polysome-CAGE of TCL1-driven chronic lymphocytic leukemia revealed multiple N-terminally altered epigenetic regulators and a translation stress signature

    Ariel Ogran, Tal Havkin-Solomon ... Rivka Dikstein
    Examination of the changes in the transcription start site selection in TCL1-driven chronic lymphocytic leukemia and their impact on mRNA translation revealed a marked elevation of intra-genic cryptic promoters, which are predicted to generate multiple N-terminally truncated or modified proteins.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    An auto-inhibited state of protein kinase G and implications for selective activation

    Rajesh Sharma, Jeong Joo Kim ... Choel Kim
    The crystal structure of a mammalian protein kinase G reveals contacts between the regulatory and catalytic domains, indicates how cGMP binding alters domain conformations and thus domain:domain interactions, and informs a model for enzyme auto-inhibition and cooperative activation.
    1. Cell Biology

    trim-21 promotes proteasomal degradation of CED-1 for apoptotic cell clearance in C. elegans

    Lei Yuan, Peiyao Li ... Hui Xiao
    The phagocytic receptor CED-1 is kept at the appropriate level by E3 ligase trim-21-mediated ubiquitination-proteasomal degradation for apoptotic cell clearance, which is independent of retromer-dependent recycling and lysosomal degradation.
    1. Computational and Systems Biology
    2. Neuroscience

    Allosteric stabilization of calcium and phosphoinositide dual binding engages several synaptotagmins in fast exocytosis

    Janus RL Kobbersmed, Manon MM Berns ... Alexander M Walter
    A mathematical model of neurotransmitter release predicts that a mutual stabilization of calcium and membrane phospholipids binding to synaptotagmin proteins allows several synaptotagmins to work together for fast synaptic transmission.
    1. Neuroscience

    Stereotyped behavioral maturation and rhythmic quiescence in C. elegans embryos

    Evan L Ardiel, Andrew Lauziere ... Hari Shroff
    Systematic analysis of behavioral maturation in the Caenorhabditis elegans embryo reveals a stereotyped developmental progression, including rhythmic behavioral quiescence elicited by a sleep-promoting neuron (RIS) releasing somnogenic peptides (FLP-11).
    1. Cell Biology

    Septin7 is indispensable for proper skeletal muscle architecture and function

    Mónika Gönczi, Zsolt Ráduly ... László Csernoch
    Septin7 is described as a novel component of skeletal muscle cytoskeleton with essential roles in muscle development and the proper organization of the myofilaments and the mitochondrial network while its absence leeds to reduced force and skeletal deformities.
    1. Computational and Systems Biology
    2. Neuroscience

    A computational account of why more valuable goals seem to require more effortful actions

    Emmanuelle Bioud, Corentin Tasu, Mathias Pessiglione
    Behavioural evidence and computational analyses suggest that people tend to decline the pursuit of more rewarded goals because they, wrongly, expect them to require more effortful actions.
    1. Cell Biology

    Modular, cascade-like transcriptional program of regeneration in Stentor

    Pranidhi Sood, Athena Lin ... Wallace F Marshall
    Regeneration of single Stentor coeruleus cells is accompanied by a program of gene expression that can be decomposed into distinct modules, showing a cascade-like organization, and involving genes with conserved function in development and cell cycle control.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Coupling to short linear motifs creates versatile PME-1 activities in PP2A holoenzyme demethylation and inhibition

    Yitong Li, Vijaya Kumar Balakrishnan ... Yongna Xing
    The coupling of the enzyme/structure core to different short linear motifs represents a novel mechanism to diversify and expand the function of signaling proteins.
    1. Evolutionary Biology
    2. Microbiology and Infectious Disease

    The evolution of a counter-defense mechanism in a virus constrains its host range

    Sriram Srikant, Chantal K Guegler, Michael T Laub
    Bacteriophage can rapidly evolve resistance to anti-phage defense elements in bacteria by amplifying latent counter-defense genes, though this amplification comes at a cost of compensatory deletions that eliminate other counter-defense genes.
    1. Neuroscience

    Expansion and contraction of resource allocation in sensory bottlenecks

    Laura R Edmondson, Alejandro Jiménez Rodríguez, Hannes P Saal
    A simple efficient coding model predicts complex trade-offs in resource allocation for sensory inputs with heterogeneous receptor densities and activation levels.
    1. Cell Biology
    2. Chromosomes and Gene Expression

    Hematopoietic plasticity mapped in Drosophila and other insects

    Dan Hultmark, István Andó
    A critical analysis of recent single-cell transcriptomic studies of Drosophila blood cells confirms the extreme plasticity of the major phagocyte class, identifies a new class of blood cell, and suggests relationships to blood cells in other insects.
    1. Cancer Biology

    Robust and Efficient Assessment of Potency (REAP) as a quantitative tool for dose-response curve estimation

    Shouhao Zhou, Xinyi Liu ... J Jack Lee
    A novel approach together with a user-friendly web-based analytic tool, coined 'REAP', was proposed to improve the quantitative assessment of dose-response relationship and drug potency.
    1. Developmental Biology

    Maternal H3K36 and H3K27 HMTs protect germline development via regulation of the transcription factor LIN-15B

    Chad Steven Cockrum, Susan Strome
    The H3K36 and H3K27 histone methyltransferases MES-4 and PRC2 protect survival of the nascent germline in Caenorhabditis elegans by repressing expression of X-linked genes, including the key transcription factor LIN-15B.
    1. Epidemiology and Global Health
    2. Evolutionary Biology

    Estimating the potential to prevent locally acquired HIV infections in a UNAIDS Fast-Track City, Amsterdam

    Alexandra Blenkinsop, Mélodie Monod ... Oliver Ratmann
    Phylogenetic evidence suggests that the majority of HIV infections occurring in the UNAIDS Fast-track city Amsterdam continue to have an Amsterdam resident as source, indicating that the majority of HIV infections in Amsterdam could be prevented through city-level interventions.
    1. Immunology and Inflammation

    Distinct impact of IgG subclass on autoantibody pathogenicity in different IgG4-mediated diseases

    Yanxia Bi, Jian Su ... Fubin Li
    The IgG4 subclass, previously considered anti-inflammatory due to its weak effector function, could either reduce or exacerbate autoantibody pathogenicity in the context of different IgG4-mediated autoimmune diseases.
    1. Ecology
    2. Genetics and Genomics

    Genomic evidence for global ocean plankton biogeography shaped by large-scale current systems

    Daniel J Richter, Romain Watteaux ... Olivier Jaillon
    Analysis of genomic DNA composition of surface plankton communities reveals a stable, ocean basin-scale plankton biogeography that emerges from the intertwined effects of environmental variations and currents.
    1. Neuroscience
    2. Structural Biology and Molecular Biophysics

    Structural motifs for subtype-specific pH-sensitive gating of vertebrate otopetrin proton channels

    Bochuan Teng, Joshua P Kaplan ... Emily R Liman
    The sour receptor, OTOP1, and related proton channel OTOP3 are steeply activated by extracellular protons while OTOP2 is active over a broad pH range and differences in gating are partly attributed to extracellular domains.
    1. Developmental Biology

    Tension-driven multi-scale self-organisation in human iPSC-derived muscle fibers

    Qiyan Mao, Achyuth Acharya ... Frank Schnorrer
    In vitro grown human muscle fibers display remarkable self-organisation capacities at the tissue, cellular, and molecular levels that are coordinated by mechanical tension.
    1. Biochemistry and Chemical Biology
    2. Chromosomes and Gene Expression

    Multiple UBX proteins reduce the ubiquitin threshold of the mammalian p97-UFD1-NPL4 unfoldase

    Ryo Fujisawa, Cristian Polo Rivera, Karim PM Labib
    UBX proteins reduce the ubiquitin threshold of mammalian p97-UFD1-NPL4.
    1. Cell Biology
    2. Stem Cells and Regenerative Medicine

    Full spectrum flow cytometry reveals mesenchymal heterogeneity in first trimester placentae and phenotypic convergence in culture, providing insight into the origins of placental mesenchymal stromal cells

    Anna Leabourn Boss, Tanvi Damani ... Anna ES Brooks
    Full spectrum flow cytometry reveals a high degree of placental mesenchymal cell heterogeneity, which is lost with culture, highlighting the importance of detailed ex vivo phenotyping to optimise the use of these cells in downstream applications.
    1. Epidemiology and Global Health
    2. Evolutionary Biology

    Genomic epidemiology of the first two waves of SARS-CoV-2 in Canada

    Angela McLaughlin, Vincent Montoya ... Jeffrey B Joy
    Canadian COVID-19 travel restrictions imposed in March 2020 greatly reduced SARS-CoV-2 importations, but were insufficient to prevent new sublineages of similar transmissibility from being introduced and replacing early sublineages.
    1. Epidemiology and Global Health
    2. Genetics and Genomics

    Integrated analyses of growth differentiation factor-15 concentration and cardiometabolic diseases in humans

    Susanna Lemmelä, Eleanor M Wigmore ... Athena Matakidou
    Elevated growth differentiation factor-15 (GDF15) levels do not appear to be a causal factor in body mass index (BMI) in humans but higher BMI does cause increases in GDF15.
    1. Evolutionary Biology
    2. Genetics and Genomics

    A paternal bias in germline mutation is widespread in amniotes and can arise independently of cell division numbers

    Marc de Manuel, Felix L Wu, Molly Przeworski
    A paternal bias in germline mutation is seen throughout amniotes and may be explained by sex differences in DNA damage and repair after primordial germ cell specification.
    1. Immunology and Inflammation

    Glutamine metabolism modulates chondrocyte inflammatory response

    Manoj Arra, Gaurav Swarnkar ... Yousef Abu-Amer
    Glutamine deprivation reprograms chondrocytes, attenuates inflammation, and such intervention may be protective against joint inflammation.
    1. Computational and Systems Biology
    2. Evolutionary Biology

    Artificial selection methods from evolutionary computing show promise for directed evolution of microbes

    Alexander Lalejini, Emily Dolson ... Luis Zaman
    Multiobjective artificial selection methods from evolutionary computing show promise for improving directed evolution outcomes when selecting for multiple traits of interest.
    1. Computational and Systems Biology

    Disruption in structural–functional network repertoire and time-resolved subcortical fronto-temporoparietal connectivity in disorders of consciousness

    Rajanikant Panda, Aurore Thibaut ... Prejaas Tewarie
    Loss of nonstationary connectivity in a subcortical fronto-temporoparietal network distinguishes patients with minimal conscious state and unresponsive wakefulness state, strongly supporting the mesocircuit hypothesis.
    1. Computational and Systems Biology

    Focal seizures are organized by feedback between neural activity and ion concentration changes

    Damiano Gentiletti, Marco de Curtis ... Piotr Suffczynski
    Biophysically realistic computational model reveals how inhibitory interneurons initiate paroxysmal discharges and how changes in the ionic concentrations shape electrographic features of human seizures.
    1. Biochemistry and Chemical Biology
    2. Medicine

    Structure-activity relationships of mitochondria-targeted tetrapeptide pharmacological compounds

    Wayne Mitchell, Jeffrey D Tamucci ... Nathan N Alder
    Sequence-variant analogs of mitochondria-targeted tetrapeptides have distinct patterns of membrane-bound conformations, effects on membrane properties, and abilities to protect mitochondria subject to stress, illuminating how side chain variation can be leveraged in the development of more effective therapeutic compounds.
    1. Structural Biology and Molecular Biophysics

    Mechanism of the cadherin–catenin F-actin catch bond interaction

    Amy Wang, Alexander R Dunn, William I Weis
    Deleting the first helix of the α-catenin actin-binding domain results in a slip bond interaction between the cadherin–catenin complex and F-actin, such that the binding interaction is stable at low force.
    1. Medicine

    Evolution of multiple omics approaches to define pathophysiology of pediatric acute respiratory distress syndrome

    Jane E Whitney, In-Hee Lee ... Sek Won Kong
    Multiple -omics approaches have provided valuable insight into the pathobiology of pediatric acute respiratory distress syndrome, and novel unbiased techniques hold promise for future discoveries.
    1. Neuroscience

    Enteroendocrine cell types that drive food reward and aversion

    Ling Bai, Nilla Sivakumar ... Zachary A Knight
    A method for the genetic manipulation of enteroendocrine cells reveals how different intestinal cell types control food intake and drive post-ingestive learning.
    1. Cell Biology

    Prolonged β-adrenergic stimulation disperses ryanodine receptor clusters in cardiomyocytes and has implications for heart failure

    Xin Shen, Jonas van den Brink ... William E Louch
    Prolonged β-adrenergic stimulation causes ryanodine receptor clusters to disperse, drastically altering the frequency and kinetics of Ca2+ release events called ‘Ca2+ sparks’ in a process that is dependent on CaMKII and PKA.
    1. Medicine

    Microscopic colitis: Etiopathology, diagnosis, and rational management

    Ole Haagen Nielsen, Fernando Fernandez-Banares ... Darrell S Pardi
    State-of-the-art knowledge of microscopic colitis, a disease often more prevalent than ulcerative colitis and Crohn’s disease among elderly people, is provided from a global perspective with the overall aim to create better awareness and improve rational management.
    1. Computational and Systems Biology
    2. Epidemiology and Global Health

    The unmitigated profile of COVID-19 infectiousness

    Ron Sender, Yinon Bar-On ... Ron Milo
    In the absence of COVID-19 mitigation measures, SARS-CoV-2 remains infectious for longer than previously estimated.
    1. Cancer Biology
    2. Cell Biology

    Hypoxia-induced proteasomal degradation of DBC1 by SIAH2 in breast cancer progression

    Qiangqiang Liu, Qian Luo ... Yushan Zhu
    SIAH2 and OTUD5 orchestrate DBC1 ubiquitination and degradation under hypoxic conditions.