Physiology articles within Nature Communications

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  • Article
    | Open Access

    The sinus node generates rhythmic heartbeat but the molecular basis of pacemaking is still under debate. Here, the authors combine quantitative proteomics and single-nucleus transcriptomics to characterize the molecular composition of the sinus node and provide insights into the underpinnings of pacemaking.

    • Nora Linscheid
    • , Sunil Jit R. J. Logantha
    •  & Alicia Lundby

  • Article
    | Open Access

    Pericytes are perivascular cells essential for blood-brain barrier maintenance. Here Diéguez-Hurtado et al. show that depletion of the transcription factor RBPJ in pericytes affects their molecular identity and disturbs endothelial cell behaviour, inducing the formation of vascular lesions in the brain.

    • Rodrigo Diéguez-Hurtado
    • , Katsuhiro Kato
    •  & Ralf H. Adams

  • Article
    | Open Access

    In neonatal testes, prospermatogonia generate both spermatogonia for the first wave of spermatogenesis and spermatogonial stem cells (SSCs) for maintenance of spermatogenesis in males. Here the authors characterize the development of mouse SSCs from prospermatogonia using single-cell RNA-seq and transplantation assays.

    • Nathan C. Law
    • , Melissa J. Oatley
    •  & Jon M. Oatley

  • Article
    | Open Access

    Cerebral cavernous malformation is a vascular disease characterized by capillary-venous cavernomas in the central nervous system. Here the authors show that cavernomas display benign tumor characteristics and originate from the clonal expansion of mutated endothelial progenitors which can attract surrounding wild-type cells, inducing their mesenchymal transition and leading to growth of the cavernoma.

    • Matteo Malinverno
    • , Claudio Maderna
    •  & Elisabetta Dejana

  • Article
    | Open Access

    Sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b) is a lipid raft enzyme known to affect membrane lipid composition. Here, Mitrofanova et al. show that increased expression of SMPDL3b in diabetes impairs insulin signaling and ceramide-1-phosphate (C1P) availability in podocytes, and that C1P supplementation protects mice from diabetic kidney disease.

    • A. Mitrofanova
    • , S. K. Mallela
    •  & A. Fornoni

  • Article
    | Open Access

    Men and women differ in their risk of developing coronary artery disease, in part due to differences in their levels of sex hormones. Here, AlSiraj et al. show that the XX sex genotype regulates lipid metabolism and promotes atherosclerosis independently of sex hormones in mice.

    • Yasir AlSiraj
    • , Xuqi Chen
    •  & Lisa A. Cassis

  • Article
    | Open Access

    Muscle loss is associated with altered expression of proteins involved in mitochondrial homeostasis, but whether this is causative remains unclear. Here, the authors show that genetic ablation of the pro-fission protein DRP1 leads to accumulation of abnormal mitochondria that induce muscle atrophy by altering Ca2+ homeostasis and cellular stress responses.

    • Giulia Favaro
    • , Vanina Romanello
    •  & Marco Sandri

  • Article
    | Open Access

    In human adipose tissue (AT), adipocytes are organized into units of lobules. Here the authors identify distinct fibrous septal and stromal compartments within AT lobules that differ in composition and potential between subcutaneous and visceral regions and are disturbed in obesity and metabolic syndrome.

    • D. Estève
    • , N. Boulet
    •  & J. Galitzky

  • Article
    | Open Access

    Hypothalamus is implicated in memory disorders but the neural mechanisms are unknown. Here, the authors report that MCH expressing hypothalamic neurons respond to novel object exposure, are inhibited by local GAD65 expressing neurons and these local circuit interactions are causally involved in object memory formation.

    • Christin Kosse
    •  & Denis Burdakov

  • Article
    | Open Access

    Pancreatic beta-cell glucose metabolism is coupled to insulin secretion. Here the authors set out to characterize changes in beta-cell metabolism in hyperglycemia which may contribute to insufficient insulin secretion in type 2 diabetes and, using a multi-omics approach, find that mitochondrial metabolism is perturbed.

    • Elizabeth Haythorne
    • , Maria Rohm
    •  & Frances M. Ashcroft

  • Article
    | Open Access

    Microbiota impacts all major aspects of physiology, but little is known about its effects on age-related changes in immune responses. Here the authors show that gut microbiota transfer between adult and old mice increases local but not systemic germinal centre responses regardless of age directionality.

    • Marisa Stebegg
    • , Alyssa Silva-Cayetano
    •  & Michelle A. Linterman

  • Article
    | Open Access

    Senescent cells increase with ageing and may cause inflammatory conditions, but how this accumulation is mediated is still unclear. Here the authors show that senescent cells express HLA-E to suppress NKG2A-mediated natural killer and CD8 T cell activation to avoid targeted elimination, while blocking NKG2A helps promote immunity against senescent cells.

    • Branca I. Pereira
    • , Oliver P. Devine
    •  & Arne N. Akbar

  • Article
    | Open Access

    Fibroadipogenic precursor cells (FAPs) contribute to fibrosis and adipogenic replacement in muscular dystrophies. Here, the authors show that FAPs contribute to adipogenic loss in mouse models of limb girdle muscular dystrophy 2B via a mechanism dependent on expression of Annexin A2, and that this process can be prevented by its pharmacologic inhibition in mice.

    • Marshall W. Hogarth
    • , Aurelia Defour
    •  & Jyoti K. Jaiswal

  • Article
    | Open Access

    Different sensory experiences can affect longevity in Drosophila. Here the authors find that exposure of Drosophila directly to dead conspecifics affects longevity via a serotonergic mechanism, and that Drosophila exposed to dead conspecifics also become an aversive stimulus to naïve choosers.

    • Tuhin S. Chakraborty
    • , Christi M. Gendron
    •  & Scott D. Pletcher

  • Article
    | Open Access

    Episodic memory retrieval is hypothesized to rely on hippocampal reinstatement of item-context associations which drives reinstatement of item information in cortex. Here, the authors confirm this sequence of events, using iEEG recordings from the human hippocampus and lateral temporal cortex.

    • D. Pacheco Estefan
    • , M. Sánchez-Fibla
    •  & P. F. M. J. Verschure

  • Article
    | Open Access

    Post-translational protein modifications can affect lifespan and aging but age-dependent ubiquitylation changes have not yet been systematically characterized. Here, the authors analyze age-related proteome and ubiquitylome dynamics in Drosophila and identify increasing H2A ubiquitylation as a conserved aging marker.

    • Lu Yang
    • , Zaijun Ma
    •  & Yaoyang Zhang

  • Article
    | Open Access

    The red nucleus (RN) is a midbrain nucleus known to be involved in the fine control of limb movements, but its role in motor learning is unclear. Here, the authors identified a neuronal population within the red nucleus, co-expressing Vglut2, PV and C1Ql2, which undergoes training-dependent plasticity.

    • Giorgio Rizzi
    • , Mustafa Coban
    •  & Kelly R. Tan

  • Article
    | Open Access

    Mitochondrial uncoupling is a treatment strategy for metabolic diseases that reduces the efficiency of mitochondrial oxidative phosphorylation and ATP generation. Here the authors characterize the pharmacokinetic and therapeutic properties of the liver-localized mitochondrial uncoupler OPC-163493, which leads to amelioration of diabetes and hypertension in several rodent disease models.

    • Naohide Kanemoto
    • , Takashi Okamoto
    •  & Seiji Sato

  • Review Article
    | Open Access

    Immune cells adapt distinct metabolic strategies to accommodate specific functions associated with cell types or differentiation stages. Here in this review the authors discuss the nutrients, sensors, and mediators of such a metabolic adaption in nutrient-limiting immune microenvironments such as tumors or infections.

    • Nidhi Kedia-Mehta
    •  & David K. Finlay

  • Article
    | Open Access

    Endothelial cell regeneration is essential for blood vessels to recover from inflammation-induced injury. Here Liu et al. show that the transcription factor Sox17 is required for endothelial regeneration following endotoxemia, and that delivery of a transgene expressing Sox17 to lung endothelial cells enhances recovery after injury.

    • Menglin Liu
    • , Lianghui Zhang
    •  & Asrar B. Malik

  • Article
    | Open Access

    The mechanisms by which organisms adapt their growth according to the availability of oxygen are incompletely understood. Here the authors identify the Drosophila fat body as a tissue regulating growth in response to oxygen sensing via a mechanism involving Hph inhibition, HIF1-a activation and insulin secretion.

    • Michael J. Texada
    • , Anne F. Jørgensen
    •  & Kim F. Rewitz

  • Article
    | Open Access

    The use of nonsteroidal anti-inflammatory drugs inhibiting COX-1/2 is associated with an increased risk of heart failure. Here the authors show that mPGES-1, a therapeutic target downstream of COX enzymes, protects from cardiac ischemia/reperfusion injury, limiting leukocyte-endothelial interactions and preserving microvascular perfusion partly via the endothelial EP4 receptor.

    • Liyuan Zhu
    • , Chuansheng Xu
    •  & Miao Wang

  • Article
    | Open Access

    Diabetes is a major cause of kidney disease. Here Kikuchi et al. show that phenol sulfate, a gut microbiota-derived metabolite, is increased in diabetic kidney disease and contributes to the pathology by promoting kidney injury, suggesting phenyl sulfate could be used a marker and therapeutic target for the treatment of diabetic kidney disease.

    • Koichi Kikuchi
    • , Daisuke Saigusa
    •  & Takaaki Abe

  • Article
    | Open Access

    Galvanic vestibular stimulation (GVS) uses transmastoid electrical currents to activate the vestibular system in humans without head movement. Here, the authors apply GVS to monkeys and record the activity of vestibular afferents to both GVS and motion to reveal the neural substrate underlying GVS evoked perceptual, ocular and postural responses.

    • Annie Kwan
    • , Patrick A. Forbes
    •  & Kathleen E. Cullen

  • Article
    | Open Access

    Although Krüppel-associated box zinc finger proteins (KZFPs) were found to mostly repress transposable elements, recent studies found that KFZPs also play other roles in cells. Here, the authors provide evidence that the KZFP ZFP30 promotes adipogenesis by targeting and activating a retrotransposon-derived Pparg2 enhancer in cooperation with co-regulator KRAB-associated protein 1 (KAP1).

    • Wanze Chen
    • , Petra C. Schwalie
    •  & Bart Deplancke

  • Article
    | Open Access

    Cerebral Cavernous Malformations (CCM) are often caused by mutations in CCM1/KRIT1. Here, Chapman et al. elegantly show that the CCM complex promotes apoptosis by regulating zinc homeostasis and storage via a conserved mechanism that likely generates the pathological defects observed in CCM.

    • Eric M. Chapman
    • , Benjamin Lant
    •  & W. Brent Derry

  • Article
    | Open Access

    The miR-17-92 cluster has been shown to regulate cardiomyocyte proliferation in vitro and in genetic mutation and overexpression models. Here the authors show that the cluster member miR-19a/19b regulates cardiomyocyte proliferation in vivo, and that delivery of miR-19a/19b to the heart leads to both short-term and long-term protective responses to myocardial infarction.

    • Feng Gao
    • , Masaharu Kataoka
    •  & Da-Zhi Wang

  • Article
    | Open Access

    Fasting is known for its beneficial effects on obesity and diabetes-related health complications. Here Zhang et al. show that fasting induces expression of arginase-2 (Arg2) in the liver, and that hepatic Arg2, by suppressing the expression of the regulator of G-protein signalling 16, recapitulates the positive effects of fasting in obesity and diabetes.

    • Yiming Zhang
    • , Cassandra B. Higgins
    •  & Brian J. DeBosch

  • Article
    | Open Access

    TMCO1 is a recently described endoplasmic reticular Ca2+ channel. Here, the authors show it is important for osteoblast function and bone formation in mice, and identify a novel pathway linking local increases in Ca2+ at the ER surface with the posttranslational modification of RUNX2.

    • Jianwei Li
    • , Caizhi Liu
    •  & Yingxian Li

  • Article
    | Open Access

    Peroxisome Proliferator Activated Receptor alpha (PPARα) drives fatty acid catabolism. Here, the authors show that in liver of autophagy deficient class 3 phosphoinositide 3-kinase mutant mice PPARα transcriptional repressors fail to degrade in lysosomes and accumulate leading to PPARα inhibition and blunted transcriptional responses during fasting.

    • Anton Iershov
    • , Ivan Nemazanyy
    •  & Ganna Panasyuk

  • Article
    | Open Access

    Proteoglycans are glycosylated proteins that play a number of structural and signalling functions. Here, Corti, Wang et al. show that the N-terminal sequence of proteoglycan Syndecan-2 selectively increases 6-O sulfation of its heparan sulfate chains, and that this promotes formation of a ternary Sdc2/VEGFA/VEGFR2 complex leading to increased angiogenesis.

    • Federico Corti
    • , Yingdi Wang
    •  & Michael Simons

  • Article
    | Open Access

    Insulin/IGF-1 signalling plays an important role in the regulation of metabolism and ageing. Here the authors show that inactivation of the pathway component PI3K p110α in the adipose tissue of mice produces a beneficial metabolic effect by enhancing β-adrenergic signalling thus energy expenditure.

    • Caroline Araiz
    • , Anqi Yan
    •  & Lazaros C. Foukas

  • Article
    | Open Access

    SREBP transcription factors activate lipid synthesis and generate raw materials to lipidate various proteins. Here, the authors show that a stiff cellular environment causes RhoA lipidation and acto-myosin contraction, which inhibits SREBP1 and connects the extracellular matrix to lipid metabolism.

    • Rebecca Bertolio
    • , Francesco Napoletano
    •  & Giannino Del Sal

  • Article
    | Open Access

    Sociality explains substantial variation in ageing across species, but less is known about this relationship within species. Here, the authors show that female dominant Seychelles warblers with helpers at the nest have higher late-life survival and lower telomere attrition and the probability of having helpers increases with age.

    • Martijn Hammers
    • , Sjouke A. Kingma
    •  & David S. Richardson

  • Article
    | Open Access

    Studying adrenergic signalling in the heart requires perfusion with receptor agonists, which lacks cell specificity and spatiotemporal control. Here the authors use the light sensitive G-coupled receptor JellyOp to optogenetically control Gs-signaling in cardiomyocytes and intact hearts with high spatiotemporal precision.

    • Philipp Makowka
    • , Tobias Bruegmann
    •  & Philipp Sasse

  • Article
    | Open Access

    Platelet aggregates generate contractile forces that contribute to their cohesion and adhesion. Here, Ting et al. develop a microfluidic device to measure contractile forces generated by platelet aggregates, and find it can detect the response of platelets to pharmacological agents and predict bleeding risk in trauma patients.

    • Lucas H. Ting
    • , Shirin Feghhi
    •  & Nathan J. Sniadecki

  • Article
    | Open Access

    Sleep is essential for homeostasis and insufficient or excessive sleep are associated with adverse outcomes. Here, the authors perform GWAS for self-reported habitual sleep duration in adults, supported by accelerometer-derived measures, and identify genetic correlation with psychiatric and metabolic traits

    • Hassan S. Dashti
    • , Samuel E. Jones
    •  & Richa Saxena

  • Article
    | Open Access

    Epidemiological studies have associated circulating levels of the amino acid glycine with cardiometabolic outcomes. Here, in a genome-wide meta-analysis of 80,003 individuals, Wittemans et al. identify 22 novel genetic loci for glycine and find a causal relationship with coronary heart disease using MR.

    • Laura B. L. Wittemans
    • , Luca A. Lotta
    •  & Claudia Langenberg

  • Article
    | Open Access

    Magnetoencephalography (MEG) is a non-invasive method of measuring neural activity but the hippocampus and amygdala are difficult to measure with MEG because of their deep localization. Here, the authors show with simultaneous MEG and invasive recordings that hippocampus and amygdala activity can be retrieved from the surface.

    • Francesca Pizzo
    • , N. Roehri
    •  & C. G. Bénar

  • Article
    | Open Access

    Aging impacts lung functionality and makes it more susceptible to chronic diseases. Combining proteomics and single cell transcriptomics, the authors chart molecular and cellular changes in the aging mouse lung, discover aging hallmarks, and predict the cellular sources of regulated proteins.

    • Ilias Angelidis
    • , Lukas M. Simon
    •  & Herbert B. Schiller

  • Article
    | Open Access

    Chemically modified mRNA is a new approach for therapeutic protein expression that could be applied to angiogenesis. Here the authors show in a phase 1 clinical trial that a modified mRNA encoding VEGF-A is well tolerated in patients with type 2 diabetes.

    • Li-Ming Gan
    • , Maria Lagerström-Fermér
    •  & Regina Fritsche-Danielson

  • Article
    | Open Access

    Although ageing is the most important risk factor for chronic ailments, effective interventions remain rare. Here, the authors identify the flavonoid 4,4’-dimethoxychalcone and demonstrate that it extends lifespan and promotes health in multiple organisms by inducing autophagy.

    • Didac Carmona-Gutierrez
    • , Andreas Zimmermann
    •  & Frank Madeo

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