Physiology articles within Nature Communications

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  • Article
    | Open Access

    Modulation of peripheral nervous system signalling has many applications in medicine, neurobiology and machine-man interfaces. Here the authors develop a microscale implantable device for chronic interfacing with a small diameter nerve, and show multi-week in vivo recording and control of activity.

    • Timothy M. Otchy
    • , Christos Michas
    •  & Timothy J. Gardner

  • Article
    | Open Access

    The relationship between DNA damage response (DDR) and regulation of the tolerance to glucose restriction is currently unclear. Here the authors reveal that maintaining a physiological level of histones by Rad53-Spt21 is necessary for glucose tolerance via multiple parallel pathways, including derepression of subtelomeric genes and acetyl-coA regulation by histone acetylation.

    • Christopher Bruhn
    • , Arta Ajazi
    •  & Marco Foiani

  • Article
    | Open Access

    T-cell activation primarily occurs in the lymph nodes, highly organized and specialized secondary lymphoid organs. Here the authors show that the acidic extracellular pH in lymph node paracortical zones limits cytokine production by effector T-cells, but does not alter their activation by antigen-presenting cells.

    • Hao Wu
    • , Veronica Estrella
    •  & Robert J. Gillies

  • Article
    | Open Access

    Hypercholesterolemia is associated with lipid peroxidation induced reactive dicarbonyl adducts. Here the authors show that the dicarbonyl scavenger, 2-hydroxybenzylamine(2-HOBA), decreases reactive dicarbonyl modifications of LDL and HDL, improves HDL function, reduces atherosclerosis and promotes features of stable plaques in a mouse model of hypercholestrolemia.

    • Huan Tao
    • , Jiansheng Huang
    •  & MacRae F. Linton

  • Article
    | Open Access

    Learning skilled movements requires evolution in neural population dynamics both within and across cortical regions. Here, the authors combine simultaneous recordings of motor and premotor cortex with computational methods to show that single-trial cross-area dynamics correlate with single-trial behavior performance and skill acquisition.

    • T. L. Veuthey
    • , K. Derosier
    •  & K. Ganguly

  • Article
    | Open Access

    Although everyday life unfolds continuously, we tend to remember past experiences as discrete events. Here, the authors show that dynamic, pupil-linked arousal states track the encoding of such episodes, as revealed by changes in memory for the temporal order and duration of recent event sequences.

    • David Clewett
    • , Camille Gasser
    •  & Lila Davachi

  • Article
    | Open Access

    To define and distinguish fibroblasts from vascular mural cells have remained challenging. Here, using single-cell RNA sequencing and tissue imaging, the authors provide a molecular basis for cell type classification and reveal inter- and intra-organ diversity of these cell types.

    • Lars Muhl
    • , Guillem Genové
    •  & Christer Betsholtz

  • Article
    | Open Access

    Top-down proteomics can provide unique insights into the biological variations of protein biomarkers but detecting low-abundance proteins in body fluids remains challenging. Here, the authors develop a nanoparticle-based top-down proteomics approach enabling enrichment and detailed analysis of cardiac troponin I in human serum.

    • Timothy N. Tiambeng
    • , David S. Roberts
    •  & Ying Ge

  • Article
    | Open Access

    Defective rhythmic metabolism is associated with high-fat diet feeding and obesity. The authors show that the clock gene BMAL1 drives paraventricular hypothalamic neuron activity via rhythmic GABAergic neurotransmission, and that this mediates diurnal metabolism and diet-induced obesity.

    • Eun Ran Kim
    • , Yuanzhong Xu
    •  & Qingchun Tong

  • Article
    | Open Access

    The origin and diversity of blood vascular endothelial cells (BEC) in lymphoid tissues is unclear. Here, the authors profile murine BECs from peripheral lymph nodes by single cell analysis and identify subsets of cells specialised for immune cell recruitment and vascular homeostasis.

    • Kevin Brulois
    • , Anusha Rajaraman
    •  & Eugene C. Butcher

  • Article
    | Open Access

    Supercentenarians are approaching the current longevity limit by avoiding or surviving major illness, thus identifying biomarkers for exceptional survival might provide insights into the protection against disease of aging. Here, the authors show low NT-proBNP and high albumin in plasma are the biological correlates of survival to the highest ages.

    • Takumi Hirata
    • , Yasumichi Arai
    •  & Nobuyoshi Hirose

  • Perspective
    | Open Access

    Why do human embryos need a yolk sac and how does it form? This Perspective by Thorsten Boroviak and Connor Ross explores the development and function of the yolk sac in primate embryogenesis.

    • Connor Ross
    •  & Thorsten E. Boroviak

  • Article
    | Open Access

    DPP4 inhibitors are used for the treatment of diabetes, but the impact of DPP4 activity and soluble DPP4 on development of diabetes-associated inflammation remains uncertain. Here the authors study whether DPP4 inhibition controls sDPP4 and inflammatory biomarkers, and demonstrate that DPP4 inhibition is dissociated from changes in inflammation in mice and humans.

    • Laurie L. Baggio
    • , Elodie M. Varin
    •  & Daniel J. Drucker

  • Article
    | Open Access

    Skeletal muscle cells have long been considered to be made primarily of many individual, parallel myofibrils. Here, the authors show that the striated muscle contractile machinery forms a highly branched, mesh-like myofibrillar matrix connected across the entire length and width of the muscle cell.

    • T. Bradley Willingham
    • , Yuho Kim
    •  & Brian Glancy

  • Article
    | Open Access

    Injury repair is characterized by the generation of transient cell states important for tissue recovery. Here, the authors present a single cell RNA-seq map of recovery from bleomycin lung injury in mice and uncover a Krt8+ transitional stem cell state that precedes the regeneration of AT1 cells and persists in human lung fibrosis.

    • Maximilian Strunz
    • , Lukas M. Simon
    •  & Herbert B. Schiller

  • Article
    | Open Access

    Ageing phenotypes are of great interest but are difficult to study genetically, partly due to the sample sizes required. Here, the authors present a multivariate framework to combine GWAS summary statistics and increase statistical power, identifying additional loci enriched for aging.

    • Paul R. H. J. Timmers
    • , James F. Wilson
    •  & Joris Deelen

  • Article
    | Open Access

    Kupffer cells are more resistant to M. tuberculosis when compared with alveolar macrophages. Here the authors show that this distinction is caused by the presence of ornithine and imidazole in Kupffer cells and that these metabolites can drive autophagy and M. tuberculosis killing in alveolar macrophages when given intranasally to infected mice.

    • Ramya Sivangala Thandi
    • , Rajesh Kumar Radhakrishnan
    •  & Ramakrishna Vankayalapati

  • Article
    | Open Access

    Lactate is a by-product of glycolysis that can function via its G protein receptor GPR81. Here the authors show that LPS or Salmonella infection enhances glycolytic metabolism in bone marrow neutrophils, resulting in lactate production, which increases endothelial barrier permeability and mobilization of these neutrophils by targeting endothelial GPR81.

    • Eman Khatib-Massalha
    • , Suditi Bhattacharya
    •  & Tsvee Lapidot

  • Article
    | Open Access

    Chondrocytes have altered cellular metabolism in the context of osteoarthritis, but whether and how these changes are associated with inflammation is a controversial area. Here the authors show that inflammatory NF-κB signalling drives a glycolytic shift in chondrocytes and the production of ROS, which drives cartilage catabolism.

    • Manoj Arra
    • , Gaurav Swarnkar
    •  & Yousef Abu-Amer

  • Article
    | Open Access

    Omecamtiv mecarbil is a small molecule effector under clinical trial for the treatment of systolic heart failure. Here the authors define the molecular mechanisms of its inotropic action and find it can increase the efficiency of contraction in muscle fibres when the orthophosphate concentration rises with the beat frequency.

    • Serena Governali
    • , Marco Caremani
    •  & Marco Linari

  • Article
    | Open Access

    Brown adipose tissue activation of thermogenesis is accompanied by a sequence of events commonly associated with apoptosis, however they evade cell death. Assali et al. show that NCLX prevents mitochondrial calcium overload and apoptosis. Deletion of NCLX, converts a thermogenic signal into a death pathway.

    • Essam A. Assali
    • , Anthony E. Jones
    •  & Orian S. Shirihai

  • Article
    | Open Access

    The sodium-leak channel NALCN controls the resting membrane potentials of neurons. Here, the authors identified two subunits of NALCN, UNC80 and UNC79. Domains in UNC80, which are mutated in individuals with intellectual disability, interact to achieve the dendritic localization of NALCN complex.

    • Jinhong Wie
    • , Apoorva Bharthur
    •  & Dejian Ren

  • Article
    | Open Access

    Non-human primates are useful models for understanding the human brain but application of optogenetics to non-human primates is challenging. The authors used optogenetic intracortical microstimulation in the primary motor cortex of macaques to elicit distinct forelimb movements and muscle activity.

    • Hidenori Watanabe
    • , Hiromi Sano
    •  & Atsushi Nambu

  • Article
    | Open Access

    Extravasated erythrocytes in cerebrospinal fluid (CSF) contribute to the pathogenesis of subarachnoid haemorrhage (SAH). Here, the authors show that meningeal lymphatics drain extravasated erythorcytes and that blockage of this drainage aggravates SAH severity.

    • Jinman Chen
    • , Linmei Wang
    •  & Yongjun Wang

  • Article
    | Open Access

    PIEZO2 is a critical component of the mechanism by which innocuous touch causes pain (tactile allodynia). Here, authors find that the dietary fatty acid margaric acid decreases PIEZO2 function in a dose-dependent manner and counteracts neuronal mechanical sensitization by a proalgesic agent.

    • Luis O. Romero
    • , Rebeca Caires
    •  & Valeria Vásquez

  • Article
    | Open Access

    Changes in EEG delta-activity are widely used as proxy of sleep propensity. Here the authors demonstrate in mice and humans the presence of two types of delta-waves, only one of which reports on prior sleep-wake history with dynamics denoting a wake-inertia process accompanying deepest non-rapid-eye-movement sleep (NREM) sleep.

    • Jeffrey Hubbard
    • , Thomas C. Gent
    •  & Paul Franken

  • Article
    | Open Access

    Bone marrow adipose tissue (BMAT) comprises over 10% of total fat mass but its systemic metabolic role is unclear. Here, the authors show that BMAT glucose uptake is not insulin or cold responsive; however, BMAT basal glucose uptake is higher than in white adipose tissue or skeletal muscle, underscoring BMAT’s potential to influence systemic glucose homeostasis.

    • Karla J. Suchacki
    • , Adriana A. S. Tavares
    •  & William P. Cawthorn

  • Article
    | Open Access

    Fat uptake and storage in subcutaneous adipose tissue (SAT) prevents ectopic fat accumulation and associated metabolic complications, however, the underlying mechanisms are incompletely understood. Here, the authors show that adipose angiopoietin-2 (Angpt2) enhances SAT size via increased endothelial fatty acid transport.

    • Hosung Bae
    • , Ki Yong Hong
    •  & Gou Young Koh

  • Article
    | Open Access

    Calorimetry is widely used for metabolic studies, but measurements of single cells and small organisms are limited by the sensitivity of current techniques. Here the authors develop a sensitive platform for performing time-resolved metabolic measurements of single C. elegans worms from larval to adult stages.

    • Sunghoon Hur
    • , Rohith Mittapally
    •  & Edgar Meyhofer

  • Article
    | Open Access

    Aging is the major risk factor for cardiovascular diseases due to chronic, low-grade inflammation stemmed from pro-inflammatory factors circulating in the body. Here, the authors identify a role of hepatocyte specific peroxisomal import in mediating non-autonomous regulation of cardiac aging, through upregulation of IL6-like inflammatory cytokine.

    • Kerui Huang
    • , Ting Miao
    •  & Hua Bai

  • Article
    | Open Access

    Joint analysis of multiple traits can increase power and provide insights into shared genetic architecture. Here, Nguyen et al. develop multi-trait TADA (mTADA), an extension of TADA (transmission and de novo association test) that jointly analyses de novo mutations of traits for improved risk-gene identification power.

    • Tan-Hoang Nguyen
    • , Amanda Dobbyn
    •  & Eli A. Stahl

  • Article
    | Open Access

    Immune cells are important regulators of adipose tissue function, including adaptive thermogenesis. Here the authors show that mice with Krüppel-like factor 3 (KLF3) deficiency in bone marrow-derived cells have increased adipose tissue beiging which may at least in part be due to altered eosinophil paracrine signaling.

    • Alexander J. Knights
    • , Emily J. Vohralik
    •  & Kate G. R. Quinlan

  • Article
    | Open Access

    White adipose inflammation can occur in obesity and is at least in part mediated by inflammatory immune cells. Here the authors show that the Type I Interferon/Interferon alpha-beta receptor axis promotes an inflammatory, glycolysis associated adipocyte phenotype.

    • Calvin C. Chan
    • , Michelle S. M. A. Damen
    •  & Senad Divanovic

  • Article
    | Open Access

    Adrenal aldosterone production is regulated by plasma angiotensin and potassium levels. Here the authors report that the neuropeptide substance P stimulates aldosterone production via neurokinin type 1 receptors (NK1R), and report a proof-of-concept placebo controlled clinical trial showing that a NK1R antagonist decreases aldosterone levels.

    • Julien Wils
    • , Céline Duparc
    •  & Hervé Lefebvre

  • Article
    | Open Access

    On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.

    • Ioanna Ntalla
    • , Lu-Chen Weng
    •  & Patricia B. Munroe

  • Article
    | Open Access

    Calcium imaging has been used to visualize the activity of individual synapses, but cannot be scaled up to monitor thousands of synapses in tissue. Here, the authors present genetic tools that can be photoconverted from green to red to create a map of active synapses.

    • Alberto Perez-Alvarez
    • , Brenna C. Fearey
    •  & Thomas G. Oertner

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