December 2021

Research articles

    1. Neuroscience
    2. Physics of Living Systems

    A theory of synaptic transmission

    Bin Wang, Olga K Dudko
    The analytic theory establishes the general principles of synaptic transmission, enables extraction of microscopic parameters of synaptic fusion machinery from experiments, and links molecular constituents to synaptic function.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Generation and diversification of recombinant monoclonal antibodies

    Keith F DeLuca et al.
    Tools and methodologies to create and diversify recombinant antibodies and antibody fragments provide researchers with the ability to generate low-cost, high-yield immunological reagents.
    1. Cell Biology
    2. Immunology and Inflammation

    Robust T cell activation requires an eIF3-driven burst in T cell receptor translation

    Dasmanthie De Silva et al.
    Binding of the translation initiation factor eIF3 to the messenger RNAs encoding the T cell receptor subunits alpha and beta is required to drive a short burst in their translation and promote a strong T cell response.
    1. Neuroscience

    Superior colliculus drives stimulus-evoked directionally biased saccades and attempted head movements in head-fixed mice

    Sebastian H Zahler et al.
    Mouse gaze shifts are unexpectedly flexible.
    1. Structural Biology and Molecular Biophysics

    pH-dependent 11° F1FO ATP synthase sub-steps reveal insight into the FO torque generating mechanism

    Seiga Yanagisawa, Wayne D Frasch
    Single-molecule F1FO studies show mutation-dependent pKa changes of both FO half-channels, and proton translocation-dependent 11° ATP synthase-direction sub-steps, which support a Grotthuss proton transfer-dependent two-step FO torque generating mechanism.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Defining the interactome of the human mitochondrial ribosome identifies SMIM4 and TMEM223 as respiratory chain assembly factors

    Sven Dennerlein et al.
    Definition of the mitoribosome interactome revealed inner membrane proteins and elucidated new assembly factors of the cytochrome c reductase and cytochrome c oxidase.
    1. Medicine

    Bisphosphonate drugs have actions in the lung and inhibit the mevalonate pathway in alveolar macrophages

    Marcia A Munoz et al.
    As well as preventing bone loss, bisphosphonate drugs may boost early immune responses in the lung by acting directly on alveolar macrophages that form one of the first lines of defence against infection.
    1. Neuroscience

    Partial connectomes of labeled dopaminergic circuits reveal non-synaptic communication and axonal remodeling after exposure to cocaine

    Gregg Wildenberg et al.
    3D serial electron microscopy reveals that individual dopamine axons in the nucleus accumbens contain different varicosity types based on their vesicle contents, rarely make synapses, and undergo major structural plasticity in response to cocaine.
    1. Cell Biology
    2. Medicine

    Hepatic MIR20B promotes nonalcoholic fatty liver disease by suppressing PPARA

    Yo Han Lee et al.
    MIR20B has a deteriorating effect in NAFLD by suppressing PPARA, and may serve as a therapeutic target for combination therapy with fenofibrate for NAFLD.
    1. Genetics and Genomics

    aCPSF1 cooperates with terminator U-tract to dictate archaeal transcription termination efficacy

    Jie Li et al.
    Term-seq, genetic and biochemical experiments reveal that the trans-action factor aCPSF1 and the terminator U-tract cis-element work in a noteworthy two-in-one termination mode in archaea, and may represent an archetypal mode of the eukaryotic RNA polymerase II termination machinery.
    1. Neuroscience

    The anterior paired lateral neuron normalizes odour-evoked activity in the Drosophila mushroom body calyx

    Luigi Prisco et al.
    By participating in the microglomerular microcircuit in the Drosophila mushroom body calyx, the anterior paired lateral neuron normalizes odour-evoked representations at the calyx via inhibition proportional to the input strength and localized to the regions where those inputs are positioned.
    1. Neuroscience

    Spatial tuning of face part representations within face-selective areas revealed by high-field fMRI

    Jiedong Zhang et al.
    Consistent spatial clustering and fine-scale neural tuning to different face parts were found within the face-processing regions, which may be the neural implementation of efficient neural computation for face identification.
    1. Developmental Biology

    Delilah, prospero, and D-Pax2 constitute a gene regulatory network essential for the development of functional proprioceptors

    Adel Avetisyan et al.
    Novel binding sites within a chordotonal-specific enhancer of the delilah gene integrates opposing signals of Prospero and D-Pax2 to control the alternative differentiation programs of cap versus scolopale cells.
    1. Neuroscience
    2. Structural Biology and Molecular Biophysics

    Molecular structures and conformations of protocadherin-15 and its complexes on stereocilia elucidated by cryo-electron tomography

    Johannes Elferich et al.
    Direct imaging of individual molecules of the tip-link protein PCDH15 in mouse stereocilia shows that it assembles as a dimer, forms complexes that span stereocilia, and occurs in clusters with multiple copies of the PCDH15 dimer.
    1. Structural Biology and Molecular Biophysics

    A modular platform for automated cryo-FIB workflows

    Sven Klumpe et al.
    SerialFIB is an adaptable open-source software designed for streamlining, advanced development and automation of cryo-focused ion beam-based cellular preparations for in situ cryo-electron tomography.
    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    De novo synthesized polyunsaturated fatty acids operate as both host immunomodulators and nutrients for Mycobacterium tuberculosis

    Thomas Laval et al.
    Infection with Mycobacterium tuberculosis triggers de novo synthesis of polyunsaturated fatty acids by host macrophages, which promote their antimicrobial responses but feed the intracellular pathogen.
    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    Human MAIT cells respond to and suppress HIV-1

    Chansavath Phetsouphanh et al.
    In depth phenotyping from tissues and in vitro activation studies reveal antiviral function of MAIT cells- with particular emphasis on HIV infection.
    1. Cell Biology
    2. Developmental Biology

    Nano-scale architecture of blood-brain barrier tight-junctions

    Esther Sasson et al.
    Super-resolution imaging uncovers sparse occludin vs. clustered ZO1/claudin-5 architecture, and claudin-5 arrangement compacting during blood-brain-barrier tight-junction (TJ) maturation in which TJs become first restrictive to large and later to small molecules.
    1. Cancer Biology

    Hyaluronic acid fuels pancreatic cancer cell growth

    Peter K Kim et al.
    Pancreatic cancers can utilize hyaluronic acid, an abundant extracellular matrix component in the tumor microenvironment, to fuel cancer cell metabolism and growth.
    1. Evolutionary Biology

    A dual endosymbiosis supports nutritional adaptation to hematophagy in the invasive tick Hyalomma marginatum

    Marie Buysse et al.
    The invasive tick Hyalomma marginatum relies on a dual partner nutritional system to provide B vitamins and avoid nutritional deficiencies due to its exclusive blood diet.
    1. Cell Biology

    Role of distinct fibroblast lineages and immune cells in dermal repair following UV radiation-induced tissue damage

    Emanuel Rognoni et al.
    UV irradiation, a major cause of skin damage, leads to selective loss of fibroblasts from the upper dermis via a deregulated inflammatory response, and infiltrating T cells can promote fibroblast survival in UV irradiated skin.
    1. Stem Cells and Regenerative Medicine

    External signals regulate continuous transcriptional states in hematopoietic stem cells

    Eva M Fast et al.
    In vivo modulation of the prostaglandin, interferon, or granulocyte colony-stimulating factor pathway induces rapid and specific transcriptional changes in hematopoietic stem cells with significant heterogeneity in the cellular response.
    1. Cell Biology

    Acetyl-CoA production by specific metabolites promotes cardiac repair after myocardial infarction via histone acetylation

    Ienglam Lei et al.
    An acetyl-CoA-mediated metabolic and epigenetic network has been elucidated that stimulates histone acetylation and anti-oxidative stress gene expression for heart repair after myocardial infarction.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Disruption of the TCA cycle reveals an ATF4-dependent integration of redox and amino acid metabolism

    Dylan Gerard Ryan et al.
    Multi-omic analyses reveal a connection between the integrated stress response and the regulation of redox and amino acid metabolism when the TCA cycle is impaired.
    1. Cell Biology
    2. Evolutionary Biology

    Addition of a carboxy-terminal tail to the normally tailless gonadotropin-releasing hormone receptor impairs fertility in female mice

    Chirine Toufaily et al.
    The absence of a carboxy-terminal tail in the GnRH receptor is not required for the preovulatory luteinizing hormone surge and fertility in mammals.
    1. Cancer Biology
    2. Genetics and Genomics

    Crosstalk with keratinocytes causes GNAQ oncogene specificity in melanoma

    Oscar Urtatiz et al.
    G alpha q/11 signaling can either promote or inhibit melanocyte growth through a reversible switch that is controlled by the microenvironment and that shapes the mutational diversity of melanoma subtypes.
    1. Immunology and Inflammation

    Inflammasome activation leads to cDC1-independent cross-priming of CD8 T cells by epithelial cell-derived antigen

    Katherine A Deets et al.
    A mouse model of inducible inflammasome activation in intestinal epithelial cells reveals separate inflammasome-dependent and -independent cross-presentation pathways for epithelial cell-derived antigen.
    1. Neuroscience

    Behavioral evidence for nested central pattern generator control of Drosophila grooming

    Primoz Ravbar et al.
    Complex motor behaviors can be assembled from simpler repeating elements controlled by pattern-generation circuits operating at different time scales.
    1. Biochemistry and Chemical Biology
    2. Plant Biology

    The induction of pyrenoid synthesis by hyperoxia and its implications for the natural diversity of photosynthetic responses in Chlamydomonas

    Peter Neofotis et al.
    The algal pyrenoid is formed at high O2 levels, even when CO2 is high, implying that a product of photosynthesis, most likely H2O2 acts as a signal.
    1. Ecology
    2. Evolutionary Biology

    Mimicry can drive convergence in structural and light transmission features of transparent wings in Lepidoptera

    Charline Sophie Pinna et al.
    Wing transparency in mimetic butterflies and moths is achieved by an unexpected diversity of structural features, and both structures and light transmission properties of wings are under selection for convergence.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Proton transfer pathway in anion channelrhodopsin-1

    Masaki Tsujimura et al.
    Asp234 is deprotonated in the ground state and forms the proton transfer pathway that proceeds from the Schiff base toward Glu68 in the intermediate state of the anion channelrhodopsin GtACR1.
    1. Cancer Biology
    2. Neuroscience

    Hemodynamic molecular imaging of tumor-associated enzyme activity in the living brain

    Mitul Desai et al.
    A vasoactive molecular imaging probe provides capability for sensitive functional imaging of cancer-associated protease activity in vivo.
    1. Evolutionary Biology

    Evolution of brilliant iridescent feather nanostructures

    Klara Katarina Nordén et al.
    Despite having different shapes and structures, the melanosomes (melanin-packed organelles) in bird feathers often produce thin melanin layers, giving rise to brilliant iridescence.
    1. Ecology

    New Caledonian crows keep ‘valuable’ hooked tools safer than basic non-hooked tools

    Barbara C Klump et al.
    Animals’ tool-handling behaviour can be used to make inferences about the value they ascribe to different tool types, unlocking considerable research potential for observational and experimental studies across diverse species.
    1. Immunology and Inflammation

    IL-2/JES6-1 mAb complexes dramatically increase sensitivity to LPS through IFN-γ production by CD25+Foxp3- T cells

    Jakub Tomala et al.
    Strong sustained IL-2 signal selective for CD25+ cells induces emergence of CD25+Foxp3- T cells producing IFN-γ in various organs causing enormous increase in the sensitivity to LPS.
    1. Cell Biology
    2. Structural Biology and Molecular Biophysics

    Determinants shaping the nanoscale architecture of the mouse rod outer segment

    Matthias Pöge et al.
    Cryo-electron tomography of close-to-native rod outer segments resolves connectors between disks and a scaffold at the disk rim enforcing the high membrane curvature of the unique long-range organization in these rhodopsin-rich light-sensitive subcellular organelles.
    1. Epidemiology and Global Health

    3D virtual histopathology of cardiac tissue from Covid-19 patients based on phase-contrast X-ray tomography

    Marius Reichardt et al.
    X-ray phase-contrast tomography reveals pathology of capillaries in heart tissue from patients who succumbed to Covid-19, as well as alterations in the three-dimensional cardiac tissue structure.
    1. Evolutionary Biology

    Evolutionary footprints of a cold relic in a rapidly warming world

    Eva Wolf et al.
    Evolutionary dynamics of polyploid plants of the genus Cochlearia during past periods of rapid climate change indicate increased rates of speciation and diversification in response to pronounced glacial cycles and cold periods in particular.
    1. Cell Biology
    2. Immunology and Inflammation

    In silico-labeled ghost cytometry

    Masashi Ugawa et al.
    Stain-free ‘imaging’ flow cytometry enables high-throughput cell classification and sorting based on machine-predicted labels.
    1. Microbiology and Infectious Disease
    2. Plant Biology

    The decrotonylase FoSir5 facilitates mitochondrial metabolic state switching in conidial germination of Fusarium oxysporum

    Ning Zhang et al.
    The decrotonylase FoSir5 modulates ATP synthesis that supports conidial germination in Fusarium oxysporum through coordinated lysine decrotonylation in different organelles.
    1. Ecology

    Naïve individuals promote collective exploration in homing pigeons

    Gabriele Valentini et al.
    Ephemeral leadership between differently experienced birds regulates the balance between exploration and exploitation over successive homing flights in a manner that facilitates the accumulation of route innovations.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Structure-guided glyco-engineering of ACE2 for improved potency as soluble SARS-CoV-2 decoy receptor

    Tümay Capraz et al.
    Molecular dynamics simulation assisted engineering of recombinant soluble human ACE2 N-glycosylation by site-directed mutagenesis or glycosidase treatment yields a superior SARS-CoV-2 decoy receptor.
    1. Neuroscience

    Light sets the brain’s daily clock by regional quickening and slowing of the molecular clockworks at dawn and dusk

    Suil Kim, Douglas G McMahon
    Light signals adjusting the brain's daily clock induce distinct waveform changes in molecular clock gene rhythms at dawn and dusk, and trigger regionally differential clock changes.
    1. Computational and Systems Biology
    2. Neuroscience

    The energetic basis for smooth human arm movements

    Jeremy D Wong et al.
    An energetic cost related to force rate is quantified in human arm movements, and minimizing this cost predicts smoothness without minimizing variance, unifies motor-planning of smoothness and movement duration, and may help resolve motor redundancies.
    1. Genetics and Genomics
    2. Neuroscience

    5-Hydroxymethylcytosine-mediated active demethylation is required for mammalian neuronal differentiation and function

    Elitsa Stoyanova et al.
    5-Hydroxymethylcytosine-mediated active DNA demethylation occurs in postmitotic neurons, and is required for their terminal differentiation and function.
    1. Cancer Biology
    2. Neuroscience

    NMNAT promotes glioma growth through regulating post-translational modifications of P53 to inhibit apoptosis

    Jiaqi Liu et al.
    NMNAT is genetically required for glioma development and promotes glioma growth by allowing a higher tolerance to DNA damage and inhibiting DNA damage-p53-caspase-3 apoptosis signaling pathway by enhancing NAD+-dependent posttranslational modifications (PTMs) poly(ADP-ribosyl)ation (PARylation) and deacetylation of p53.
    1. Immunology and Inflammation

    S-acylation by ZDHHC20 targets ORAI1 channels to lipid rafts for efficient Ca2+ signaling by Jurkat T cell receptors at the immune synapse

    Amado Carreras-Sureda et al.
    ORAI1 ion channel lipid modification is required for a proper immune synapse formation and T cell activation.
    1. Neuroscience

    Parallel processing by distinct classes of principal neurons in the olfactory cortex

    Shivathmihai Nagappan, Kevin M Franks
    In vivo recordings from identified cell classes in the olfactory cortex of a novel transgenic mouse reveal that distinct classes of principal neurons operate largely in parallel and differentially process odor information.
    1. Developmental Biology
    2. Neuroscience

    insomniac links the development and function of a sleep-regulatory circuit

    Qiuling Li et al.
    Spatiotemporal manipulations of insomniac reveal that this gene regulates the birth and development of sleep-regulatory neurons, enabling their proper function in adulthood.
    1. Neuroscience

    Emergence and function of cortical offset responses in sound termination detection

    Magdalena Solyga, Tania Rinaldi Barkat
    Cortical offset responses are not only inherited from the periphery but also amplified and de novo generated, and preventing them decreases the ability to detect sound termination.
    1. Structural Biology and Molecular Biophysics

    Enhanced specificity mutations perturb allosteric signaling in CRISPR-Cas9

    Lukasz Nierzwicki et al.
    Allostery holds critical role in CRISPR-Cas9 specificity enhancement.
    1. Developmental Biology
    2. Physics of Living Systems

    Mechanism of life-long maintenance of neuron identity despite molecular fluctuations

    Joleen JH Traets et al.
    Differential binding kinetics of a master regulator to its target promoters can prevent spontaneous cell fate loss in a Caenorhabditis elegans neuron whose fate is controlled by a reversible switch.
    1. Neuroscience

    Synaptic memory requires CaMKII

    Wucheng Tao et al.
    1. Developmental Biology

    Coronary blood vessels from distinct origins converge to equivalent states during mouse and human development

    Ragini Phansalkar et al.
    Endothelial cells from separate cardiac lineages start off in distinct transcriptional states, but over the course of development converge into transcriptional and functional states which are unrelated to lineage and which are conserved between mouse and human.
    1. Immunology and Inflammation

    Biallelic mutations in calcium release activated channel regulator 2A (CRACR2A) cause a primary immunodeficiency disorder

    Beibei Wu et al.
    Human CRACR2A insufficiency underlies progressive loss of immune competence by uncoupling TCR activation from Ca2+ and MAPK signaling and should be included within the group of combined immunodeficiency disorders in the IEI classification.
    1. Cancer Biology
    2. Cell Biology

    Single-cell transcriptome analysis identifies a unique tumor cell type producing multiple hormones in ectopic ACTH and CRH secreting pheochromocytoma

    Xuebin Zhang et al.
    A novel multi-hormones secreting chromaffin-like cell type was identified using single-cell RNA sequencing, suggesting the molecular mechanism of ectopic ACTH and CRH pheochromocytoma associated with Cushing’s syndrome.
    1. Biochemistry and Chemical Biology

    Allosteric mechanism of signal transduction in the two-component system histidine kinase PhoQ

    Bruk Mensa et al.
    Mutations along the signaling pathway of the E. coli sensor histidine kinase PhoQ alter signal gain and ligand-sensitivity by altering thermodynamic allosteric coupling between domains.
    1. Neuroscience

    Respiration aligns perception with neural excitability

    Daniel S Kluger et al.
    Noninvasive human magnetoencephalography recordings characterize the functional relationship between respiration, neural oscillations, and performance in low-level perception.
    1. Cell Biology

    V-ATPase V0a1 promotes Weibel–Palade body biogenesis through the regulation of membrane fission

    Yasuo Yamazaki et al.
    A V-ATPase component and protein kinase D are required for the segregation of Weibel–Palade bodies from the trans-Golgi network.
    1. Neuroscience

    The landscape of regulatory genes in brain-wide neuronal phenotypes of a vertebrate brain

    Hui Zhang et al.
    Single-cell transcriptomes of larval zebrafish whole brain shed light on the multidimensional landscapes of transcription factors and post-transcriptional regulators in vertebrate whole-brain neuronal classification and revealed principles of how neuronal cell diversity develops and evolves.
    1. Cancer Biology
    2. Cell Biology

    Rpl24Bst mutation suppresses colorectal cancer by promoting eEF2 phosphorylation via eEF2K

    John RP Knight et al.
    Signalling that maintains rapid translation elongation in KRAS-mutant colorectal cancer models can be targeted by mutation of the ribosomal protein RPL24 to suppress tumour proliferation.
    1. Cell Biology

    Rapid genome editing by CRISPR-Cas9-POLD3 fusion

    Ganna Reint et al.
    Novel Cas9 fusion with DNA polymerase delta subunit 3 (POLD3), identified via high-throughput screening of more than 450 DNA repair proteins, enhances editing by speeding up the initiation of DNA repair.
    1. Biochemistry and Chemical Biology

    Assembly status transition offers an avenue for activity modulation of a supramolecular enzyme

    Yao Chen et al.
    Mechanistic studies of glutamine synthetase reveals how the complex quaternary structure organizations of a supramolecular enzyme provides a platform necessary for intricate activity regulation machinery to take place.
    1. Immunology and Inflammation

    Regulation of positive and negative selection and TCR signaling during thymic T cell development by capicua

    Soeun Kim et al.
    Deficiency of capicua, a transcription factor that suppresses autoimmunity, impairs positive and negative selection processes by attenuating TCR signaling in CD4+CD8+ double-positive thymocytes.
    1. Cell Biology

    Combined effect of cell geometry and polarity domains determines the orientation of unequal division

    Benoit G Godard et al.
    Cell geometry and polarity domains act in concert to determine spindle positioning, with cell geometry modulating the effect of cortical polarity domains by influencing the position of the spindle relative to those polarity domains.
    1. Cancer Biology

    Concomitant activation of GLI1 and Notch1 contributes to racial disparity of human triple negative breast cancer progression

    Sumit Siddharth et al.
    Elucidation of GLI1-Notch1 axis as key determinant of racial disparity in TNBC growth in African American and White American women.
    1. Evolutionary Biology

    The population genetics of collateral resistance and sensitivity

    Sarah M Ardell, Sergey Kryazhimskiy
    A theoretical model that considers the diversity of collateral effects among drug resistance mutations provides insights into the development of robust sequential antibiotic treatments.
    1. Neuroscience

    Bidirectional synaptic plasticity rapidly modifies hippocampal representations

    Aaron D Milstein et al.
    Dendritic calcium spikes translocate hippocampal place fields by inducing a non-Hebbian form of bidirectional synaptic plasticity that operates over a seconds-long timescale called behavioral timescale synaptic plasticity.
    1. Cell Biology

    Cytoplasmic dynein-1 cargo diversity is mediated by the combinatorial assembly of FTS–Hook–FHIP complexes

    Jenna R Christensen et al.
    The combinatorial assembly of different adaptor complexes is a mechanism that dynein uses to interact with multiple cargos.
    1. Neuroscience

    Dopamine enhances model-free credit assignment through boosting of retrospective model-based inference

    Lorenz Deserno et al.
    Cooperation between model-free and model-based control systems is boosted by enhancing dopamine levels.
    1. Computational and Systems Biology

    How the insect central complex could coordinate multimodal navigation

    Xuelong Sun et al.
    The copy-and-shift mechanism modelled in the insect central complex facilitates multimodal navigation, providing a general computation model explaining flexible navigation behaviours.
    1. Microbiology and Infectious Disease

    Reverting the mode of action of the mitochondrial FOF1-ATPase by Legionella pneumophila preserves its replication niche

    Pedro Escoll et al.
    During infection, L. pneumophila reverses the ATP-synthase activity of the mitochondrial FOF1-ATPase to ATP-hydrolase activity in a type 4 secretion-dependent manner to prevent early cell death, thereby preserving its replication niche.
    1. Developmental Biology

    ZAF, the first open source fully automated feeder for aquatic facilities

    Merlin Lange et al.
    ZAF (Zebrafish Automated Feeder) is the first fully automated, easy to build, and open source fish feeder designed for small and medium sized labs of which there are an estimated 3250 in 100 countries working with Zebrafish alone today.
    1. Neuroscience

    Identification of a stereotypic molecular arrangement of endogenous glycine receptors at spinal cord synapses

    Stephanie A Maynard et al.
    Quantitative super-resolution correlative light and electron microscopy reveals a constant glycine receptor density at native spinal cord synapses that is maintained in the oscillator mouse model of human hyperekplexia.
    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    Blood-brain barrier-restricted translocation of Toxoplasma gondii from cortical capillaries

    Gabriela C Olivera et al.
    The invasion of Toxoplasma to the CNS across cortical capillaries is restricted by the integrity of the blood-brain barrier (BBB) and exacerbated by the inflammatory response.
    1. Biochemistry and Chemical Biology

    Assessing target engagement using proteome-wide solvent shift assays

    Jonathan G Van Vranken et al.
    Solvent shift assays such as solvent proteome profiling and solvent-PISA are valuable tools for identifying protein-ligand interactions on a proteome-wide scale and can be used to determine drug target engagement, which should benefit future drug discovery efforts.
    1. Developmental Biology
    2. Neuroscience

    Nuclear NAD+-biosynthetic enzyme NMNAT1 facilitates development and early survival of retinal neurons

    David Sokolov et al.
    NMNAT1, a ubiquitously expressed metabolic enzyme linked to inherited blinding disease, is crucial for the proper differentiation of photoreceptor cells and subsequent survival of multiple cell types in the retina.
    1. Neuroscience

    Tightly coupled inhibitory and excitatory functional networks in the developing primary visual cortex

    Haleigh N Mulholland et al.
    In vivo calcium imaging reveals that prior to visual experience, inhibitory spontaneous activity in the developing visual cortex is highly modular and participates in large-scale correlated networks that are co-aligned to excitatory activity.
    1. Evolutionary Biology
    2. Microbiology and Infectious Disease

    Antigenic evolution of human influenza H3N2 neuraminidase is constrained by charge balancing

    Yiquan Wang et al.
    The local fitness landscape of an antigenic region in influenza neuraminidase was determined by combinatorial mutagenesis and next-generation sequencing.
    1. Neuroscience

    Double-μPeriscope, a tool for multilayer optical recordings, optogenetic stimulations or both

    Mototaka Suzuki et al.
    Interactions between near but distinct (<1 mm) structures such as cortical layers in the rodent brain can be studied by a new micro-optical tool that is low-cost and capable of multilayer optical recordings, optogenetic stimulations, or both.
    1. Neuroscience

    Specialized neurons in the right habenula mediate response to aversive olfactory cues

    Jung-Hwa Choi et al.
    An asymmetric olfactory projection innervates a small subset of identified neurons in the right habenula, which are activated by a repulsive odorant and mediate prolonged aversive behavior, providing further evidence for lateralization of the zebrafish brain.
    1. Cancer Biology
    2. Computational and Systems Biology

    Investigating the replicability of preclinical cancer biology

    Timothy M Errington et al.
    A project to repeat experiments from high-impact papers in cancer biology found that the effects observed in replications were frequently weaker than, or inconsistent with, the effects reported in the original papers.
    1. Neuroscience

    Cortico-subcortical β burst dynamics underlying movement cancellation in humans

    Darcy A Diesburg et al.
    Burst-like neural activity in the β-frequency band conveys inhibitory commands within long-proposed cortico-subcortical networks for motor inhibition, with inhibitory activity in STN preceding thalamic activity, which has strong implications for movement disorders marked by abnormalities in β-bursting.
    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    Analysis of long and short enhancers in melanoma cell states

    David Mauduit et al.
    Multi-level massively parallel reporter assays (H3K27ac, ATAC and short tiles) in a panel of melanoma cell lines, together with a deep learning model, reveal location, multiplicity and grammar of subtype specific enhancers.
    1. Biochemistry and Chemical Biology
    2. Chromosomes and Gene Expression

    Serine ADP-ribosylation marks nucleosomes for ALC1-dependent chromatin remodeling

    Jugal Mohapatra et al.
    A technology to produce homogenously poly-ADP-ribosylated proteins reveals key molecular mechanisms that govern ATP-dependent chromatin remodeling activity at DNA damage sites.
    1. Evolutionary Biology
    2. Microbiology and Infectious Disease

    Pathogen invasion-dependent tissue reservoirs and plasmid-encoded antibiotic degradation boost plasmid spread in the gut

    Erik Bakkeren et al.
    Bacterial gut pathogens that invade into host tissues during infection can boost the spread and accumulation of plasmids over time by forming reservoirs containing these plasmids within host tissues.
    1. Microbiology and Infectious Disease

    Characterization of the endogenous DAF-12 ligand and its use as an anthelmintic agent in Strongyloides stercoralis

    Zhu Wang et al.
    Regulation of a nuclear receptor signaling pathway may cure the often-lethal disease caused by the endemic parasitic roundworm, Strongyloides stercoralis.
    1. Neuroscience

    Rat sensitivity to multipoint statistics is predicted by efficient coding of natural scenes

    Riccardo Caramellino et al.
    Visual sensitivity to correlation patterns in rats matches that previously measured in humans, as well as predictions from efficient coding theory based on the statistics of natural images.
    1. Developmental Biology
    2. Neuroscience

    Mechanisms underlying microglial colonization of developing neural retina in zebrafish

    Nishtha Ranawat, Ichiro Masai
    Genetic and imaging analysis reveal that microglial precursors use ocular blood vessels as a pathway to enter the optic cup and subsequently infiltrate the retina preferentially through the neurogenic region.
    1. Microbiology and Infectious Disease

    Highly synergistic combinations of nanobodies that target SARS-CoV-2 and are resistant to escape

    Fred D Mast et al.
    A large repertoire of nanobodies that target discrete regions of SARS-CoV-2 spike shows effective neutralization against variants of concern with many pairwise combinations resistant to escape and demonstrating synergistic neutralization activities.
    1. Cancer Biology

    Experiments from unfinished Registered Reports in the Reproducibility Project: Cancer Biology

    Timothy M Errington et al.
    A project to repeat experiments from high-impact papers in cancer biology did not complete all replications, with challenges ranging from mundane reasons to unexpected methodological issues.
    1. Evolutionary Biology
    2. Stem Cells and Regenerative Medicine

    A conserved strategy for inducing appendage regeneration in moon jellyfish, Drosophila, and mice

    Michael J Abrams et al.
    Amino acid and sugar supplement induce appendage/limb regeneration in cnidarians, insects, and mammals.
    1. Biochemistry and Chemical Biology

    Allosteric ligands control the activation of a class C GPCR heterodimer by acting at the transmembrane interface

    Lei Liu et al.
    Functional analysis reveals a distinct mode of action of the allosteric modulators in the GABAB receptor in a pocket that is formed only in the active state and identifies a region in the GABAB2 subunit important for allosteric agonism.
    1. Epidemiology and Global Health
    2. Medicine

    Association of lipid-lowering drugs with COVID-19 outcomes from a Mendelian randomization study

    Wuqing Huang et al.
    A two-sample Mendelian randomization study suggested a potential causal relationship between HMGCR inhibition and the reduced risk of COVID-19 hospitalization.
    1. Ecology
    2. Evolutionary Biology

    Reversal of the adipostat control of torpor during migration in hummingbirds

    Erich R Eberts et al.
    Ruby-throated hummingbirds switch from using torpor to survive nighttime energy emergencies in the breeding season to using it to spare fat stores and gain premigratory mass in the late summer.
    1. Cell Biology

    Src activates retrograde membrane traffic through phosphorylation of GBF1

    Joanne Chia et al.
    Src phosphorylates GBF1, promoting binding of the Sec7 domain to Arf1 and the formation of GALNTs containing tubules emanating from the Golgi.
    1. Biochemistry and Chemical Biology
    2. Neuroscience

    Neurotoxin-mediated potent activation of the axon degeneration regulator SARM1

    Andrea Loreto et al.
    The identification of the mechanism of action of vacor, an environmental neurotoxin which causes neurodegeneration by activating the pro-degenerative enzyme SARM1, raises important questions on SARM1 as a mediator of environmental neurotoxicity and has implications for drug discovery.
    1. Physics of Living Systems

    Antagonism between killer yeast strains as an experimental model for biological nucleation dynamics

    Andrea Giometto et al.
    Like physical systems that exhibit nucleation phenomena, an invading population of a strong microbial antagonist requires a critical inoculum size to successfully invade a population of a weaker microbial antagonist.
    1. Developmental Biology

    Endogenous protein tagging in medaka using a simplified CRISPR/Cas9 knock-in approach

    Ali Seleit et al.
    Highly efficient, precise, and scalable CRISPR/Cas9-mediated generation of endogenously tagged alleles in a vertebrate model.
    1. Microbiology and Infectious Disease

    The enteric pathogen Cryptosporidium parvum exports proteins into the cytosol of the infected host cell

    Jennifer E Dumaine et al.
    Following initial invasion events, intracellular life stages of C. parvum rely upon an N-terminal host-targeting motif and proteolytic processing at a specific leucine residue to deliver proteins into the infected enterocyte.
    1. Structural Biology and Molecular Biophysics

    Molecular pathology of the R117H cystic fibrosis mutation is explained by loss of a hydrogen bond

    Márton A Simon, László Csanády
    The striking reduction in open probability of CFTR channels harboring the R117H cystic fibrosis mutation is caused by loss of a strong hydrogen bond between positions 117 and 1124, which is formed in wild-type channels selectively in the open state.
    1. Immunology and Inflammation

    SARS-CoV-2 spike protein induces inflammation via TLR2-dependent activation of the NF-κB pathway

    Shahanshah Khan et al.
    Recognition of SARS-CoV-2 spike protein by innate immune sensor TLR2 leads to the induction of inflammatory mediators and constitutes a mechanism for cytokine storm during COVID-19.
    1. Developmental Biology
    2. Neuroscience

    Constitutive deficiency of the neurogenic hippocampal modulator AP2γ promotes anxiety-like behavior and cumulative memory deficits in mice from juvenile to adult periods

    Eduardo Loureiro-Campos et al.
    Constitutive deficiency of AP2γ transcription factor impairs hippocampal glutamatergic neurogenesis and induces alterations on limbic-cortical connectivity that contribute to anxiety-like behavior and cumulative memory deficits in mice from juvenile to adult periods.
    1. Cell Biology

    Simultaneous recording of multiple cellular signaling events by frequency- and spectrally-tuned multiplexing of fluorescent probes

    Michelina Kierzek et al.
    FASTM is a novel technique that leverages phase-sensitive signal detection for time-resolved multiplexing of probes with millisecond time resolution, opening new opportunities for interrogating rapid cellular signaling and (bio)chemical reactions.
    1. Neuroscience

    Taste sensing and sugar detection mechanisms in Drosophila larval primary taste center

    G Larisa Maier et al.
    Drosophila larvae show taste multimodality and combinatorial sensing at gustatory organ level but also systemically as they employ complementary external and internal taste in sugar detection.
    1. Neuroscience

    Working memory capacity of crows and monkeys arises from similar neuronal computations

    Lukas Alexander Hahn et al.
    Despite differences in cellular architecture the brains of monkeys and crows produce comparable limits of working memory with comparable mechanisms.
    1. Developmental Biology
    2. Neuroscience

    CRMP4-mediated fornix development involves Semaphorin-3E signaling pathway

    Benoît Boulan et al.
    CRMP4 is a new actor in the guidance cue Semaphorin-3E pathway, crucially involved in the establishment of the fornix, a key axonal tract for memory and emotional control.
    1. Cell Biology
    2. Microbiology and Infectious Disease

    Toxoplasma bradyzoites exhibit physiological plasticity of calcium and energy stores controlling motility and egress

    Yong Fu et al.
    Live-cell imaging and biochemical studies reveal that bradyzoites exhibit reduced Ca2+ stores, dampened calcium responses, and reduced energy levels consistent with their quiescent sate, but that they rapidly respond to environmental conditions to emerge from dormancy.
    1. Microbiology and Infectious Disease
    2. Physics of Living Systems

    Distinguishing different modes of growth using single-cell data

    Prathitha Kar et al.
    Single-cell data analysis must be guided by an underlying model.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Low-affinity integrin states have faster ligand-binding kinetics than the high-affinity state

    Jing Li et al.
    Faster ligand-binding kinetics of integrin low-affinity states suggests that integrin binding to ligand and intracellular adapters and the actin cytoskeleton precedes their stabilization, together with tensile force, of the high-affinity, extended-open integrin conformation.
    1. Neuroscience

    REST/NRSF drives homeostatic plasticity of inhibitory synapses in a target-dependent fashion

    Cosimo Prestigio et al.
    A combination of electrophysiological, immunocytochemical, and biochemical approaches elucidate the mechanisms by which the transcriptional regulator REST/NRSF rescues neuronal homeostasis by upregulating GABAergic transmission selectively onto excitatory neurons in response to hyperactivity.
    1. Neuroscience

    Silencing long ascending propriospinal neurons after spinal cord injury improves hindlimb stepping in the adult rat

    Courtney T Shepard et al.
    Silencing L2 neurons that project to C6 after a T9 contusion, effectively removing spared axons, results in improved paw placement timing and order, and normalizes speed-dependent changes in swing and stance representing a significant neuroanatomical-functional paradox for spinal cord injury.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Molecular architecture of the human tRNA ligase complex

    Alena Kroupova et al.
    Biochemical and structural investigations of the human tRNA ligase complex reveal the details of its molecular assembly and provide insights into the reaction mechanism of its catalytic subunit.
    1. Immunology and Inflammation

    Histone deacetylase 3 represses cholesterol efflux during CD4+ T-cell activation

    Drew Wilfahrt et al.
    Histone deacetylase 3 is required for CD4+ T cells to downregulate two cholesterol efflux transport proteins, ABCA1 and ABCG1, for successful proliferation after antigenic stimulation.
    1. Immunology and Inflammation

    Single-cell-level protein analysis revealing the roles of autoantigen-reactive B lymphocytes in autoimmune disease and the murine model

    Takemichi Fukasawa et al.
    Single-cell analysis revealed that autoantigen-reactive B cells changed the type of cytokines they produced from anti-inflammatory IL-10 and IL-35 to pro-inflammatory IL-6 and IL-23 as affinity to autoantigen increased.
    1. Neuroscience

    Gated recurrence enables simple and accurate sequence prediction in stochastic, changing, and structured environments

    Cédric Foucault, Florent Meyniel
    Small gated recurrent neural networks can dynamically adapt to inferred changes in the environment, represent and use the precision of their estimate to weight their updates, and leverage the environment's latent hierarchical structure, like the Bayesian agent and the brain.
    1. Biochemistry and Chemical Biology

    A distributed residue network permits conformational binding specificity in a conserved family of actin remodelers

    Theresa Hwang et al.
    A peptide from PCARE achieves >100-fold binding specificity for the EVH1 domain of ENAH, a protein important for metastasis, using a conformational shift mechanism unavailable to ENAH's closely related paralogs VASP and EVL.
    1. Neuroscience

    Structure and function of axo-axonic inhibition

    Casey M Schneider-Mizell et al.
    Electron microcopy-based connectomics, in vivo functional imaging, and biophysical modeling reveal that mouse visual cortex chandelier cells, a type of GABAergic interneuron, are driven by arousal and distribute their synapses according to the individual properties of target cells.
    1. Cancer Biology
    2. Cell Biology

    Cyclin F drives proliferation through SCF-dependent degradation of the retinoblastoma-like tumor suppressor p130/RBL2

    Taylor P Enrico et al.
    The SCF-family of ubiquitin ligases regulates the key cancer proliferation node by controlling the degradation of RB-like tumor suppressor RBL2/p130.
    1. Developmental Biology
    2. Neuroscience

    Transcriptional profiling of sequentially generated septal neuron fates

    Miguel Turrero García et al.
    A combination of single-cell RNA sequencing of the developing septum and genetic fate mapping is used to analyze the origin of septal neurons.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    MCPH1 inhibits Condensin II during interphase by regulating its SMC2-Kleisin interface

    Martin Houlard et al.
    Chromosome condensation by condensin II is inhibited during interphase by direct interaction with MCPH1, which regulates opening of the condensin II interface between SMC2 and NCAPH2, in a similar fashion to how WAPL regulates Cohesin.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Disentangling bias between Gq, GRK2, and arrestin3 recruitment to the M3 muscarinic acetylcholine receptor

    Anja Flöser et al.
    Ligand-specific-induced conformations of M3 muscarinic receptors reveal similar requirements for G protein-coupled receptor kinase 2 and Gq protein binding, whereas arrestin3 binding is mediated by distinct receptor conformations.
    1. Ecology
    2. Plant Biology

    Wild cereal grain consumption among Early Holocene foragers of the Balkans predates the arrival of agriculture

    Emanuela Cristiani et al.
    A consistent pattern of consumption of Triticeae tribe grasses documented in the Danube Gorges of the Balkans since the Early Mesolithic might have facilitated a quick uptake of domesticated cereals due to a developed cultural taste and specific stone tool processing technology.

Magazine

    1. Neuroscience

    Pain: Why sex matters

    Josette J Wlaschin et al.