Physiology articles within Nature Communications

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  • Article
    | Open Access

    Insulin secretion by β-cells is stimulated by glucose and is dependent on the induction of β-cell membrane depolarization, mainly driven by the closure of KATP channels, which in turn promotes voltage-gated Ca2+ channel opening. Here the authors show that LRRC8 volume-regulated anion channels (VRACs) modulate glucose-stimulated calcium increase and insulin secretion.

    • Till Stuhlmann
    • , Rosa Planells-Cases
    •  & Thomas J. Jentsch

  • Article
    | Open Access

    Genome-wide association studies have identified multiple loci for resting heart rate (HR) but the genetic factors associated with HR increase during and HR recovery after exercise are less well studied. Here, the authors examine both traits in a two-stage GWAS design in up to 67,257 individuals from UK Biobank.

    • Julia Ramírez
    • , Stefan van Duijvenboden
    •  & Patricia B. Munroe

  • Article
    | Open Access

    M-current is conveyed by voltage-sensitive KCNQ channels, which are enriched in GABAergic neurons and are activated by anticonvulsants such as retigabine. Here the authors show that GABA directly activates KCNQ3, at the residue required for its anticonvulsant activity.

    • Rían W. Manville
    • , Maria Papanikolaou
    •  & Geoffrey W. Abbott

  • Article
    | Open Access

    Non-invasive techniques to assess the progression of type 1 diabetes prior to clinical onset are needed. Here the authors apply a contrast-enhanced ultrasound measurement of mouse pancreatic blood flow to detect changes in the islet microvasculature that undergoes rearrangements during diabetes and predict disease progression.

    • Joshua R. St Clair
    • , David Ramirez
    •  & Richard K. P. Benninger

  • Article
    | Open Access

    Hutchinson-Gilford Progeria Syndrome is characterized by premature aging with cardiovascular disease being the main cause of death. Here the authors show that inhibition of the NAT10 enzyme enhances cardiac function and fitness, and reduces age-related phenotypes in a mouse model of premature aging.

    • Gabriel Balmus
    • , Delphine Larrieu
    •  & Stephen P. Jackson

  • Article
    | Open Access

    GPR40 is a G-protein coupled receptor that binds to free fatty acids, mediating insulin and incretin secretion. Here, the authors present the crystal structure of human GPR40 with an agonist bound to an allosteric site located near the lipid-rich region that suggests a mechanism for biased agonism.

    • Joseph D. Ho
    • , Betty Chau
    •  & Chafiq Hamdouchi

  • Article
    | Open Access

    As a circadian organ, liver functions are regulated by circadian clock. Here, the authors present a comprehensive proteomics landscape of the mouse liver, including transcription factor binding profiles, phosphorylation and ubiquitylation patterns, nuclear and whole proteome, and the transcriptome.

    • Yunzhi Wang
    • , Lei Song
    •  & Chen Ding

  • Article
    | Open Access

    JMJD1A is essential for thermogenic gene induction in brown adipose tissue. Here the authors show that white adipose tissue beige-ing requires both β-adrenergic-dependent phosphorylation of S265 and demethylation activity of JMJD1A while brown adipose tissue-driven thermogenesis requires β-adrenergic dependent phosphorylation of S265 but is independent of H3K9me2 demethylation.

    • Yohei Abe
    • , Yosuke Fujiwara
    •  & Juro Sakai

  • Article
    | Open Access

    Sexual dimorphism exists in a number of physiological processes, including energy homeostasis. Here, the authors show that pro-opiomelanocortin neurons in female mice fire more rapidly than males, and that deletion of the transcription TAp63 leads to a reduced neuronal firing rate and a male-like susceptibility to diet-induced obesity.

    • Chunmei Wang
    • , Yanlin He
    •  & Yong Xu

  • Article
    | Open Access

    Cathelicidins are antimicrobial peptides that eliminate pathogens and contribute to the innate immune response. Here the authors show that neutrophil-derived LL-37/CRAMP induces platelet activation and promotes arterial thrombosis and thrombo-inflammation.

    • Joachim Pircher
    • , Thomas Czermak
    •  & Christian Schulz

  • Article
    | Open Access

    Iron homeostasis dysfunctions have been associated with several metabolic disorders including obesity, steatosis and diabetes. Here the authors demonstrate that the hepcidin repressor matriptase-2 regulates adiposity and its deficiency protects mice against obesity and promotes lipolysis.

    • Alicia R. Folgueras
    • , Sandra Freitas-Rodríguez
    •  & Carlos López-Otín

  • Article
    | Open Access

    A gene regulatory network, including the transcription factor Nkx2-5, regulates cardiac development. Here, the authors show that on deletion of NKX2-5 from human embryonic stem cells, there is impaired cardiomyogenesis and changes in action potentials, and that this is regulated via HEY2.

    • David J. Anderson
    • , David I. Kaplan
    •  & David A. Elliott

  • Article
    | Open Access

    Declining NAD+ levels have been linked to aging-associated pathologies. Here the authors present results of a double-blind, randomized crossover trial on 30 healthy middle-aged individuals to show that nicotinamide riboside effectively elevates NAD+ levels in humans, appears to be well tolerated, and may have potential to improve cardiovascular parameters.

    • Christopher R. Martens
    • , Blair A. Denman
    •  & Douglas R. Seals

  • Article
    | Open Access

    Nucleolar stress can disrupt ribosome biogenesis and in turn energy metabolism and lipid storage, but how this is regulated is unclear. Here, the authors show in C. elegans that the transcription factor PHA-4/FOXA acts as a sensor for nucleolar stress and can regulate expression of lipogenic genes

    • Jieyu Wu
    • , Xue Jiang
    •  & Bin Liang

  • Article
    | Open Access

    Zona incerta (ZI) is an inhibitory subthalamic nucleus with diverse connectivity yet its functional importance has not been extensively studied. Here the authors report that ZI receives mPFC input and can modulate both innate and learned defensive behaviors via its inhibitory projection to the PAG.

    • Xiao-lin Chou
    • , Xiyue Wang
    •  & Huizhong Whit Tao

  • Article
    | Open Access

    High protein diets are known to improve metabolic parameters including adiposity and glucose homeostasis. Here the authors demonstrate that preabsorptive upper small intestinal protein-sensing mechanisms mediated by peptide transporter 1 improve glucose homeostasis by inhibiting hepatic glucose production.

    • Helen J. Dranse
    • , T. M. Zaved Waise
    •  & Tony K. T. Lam

  • Article
    | Open Access

    PIEZO proteins form mechanosensitive ion channels. Here the authors present electrophysiological measurements that show that PIEZO channels are also modulated by voltage and can switch to a purely voltage gated mode, which is an evolutionary conserved property of this channel family.

    • Mirko Moroni
    • , M. Rocio Servin-Vences
    •  & Gary R. Lewin

  • Article
    | Open Access

    Vascular smooth muscle cell (VSMC) dysfunction is a common feature of thoracic aortic aneurysms (TAAs). Here, Lino Cardenas and colleagues show that the formation of a HDAC9-MALAT1-BRG1 complex promotes VSMC dysfunction in TAA by epigenetically altering the expression of key components of the cytoskeleton in VSMCs.

    • Christian L. Lino Cardenas
    • , Chase W. Kessinger
    •  & Mark E. Lindsay

  • Article
    | Open Access

    The nematode C. elegans is known to alter its behavior in response to UV light. Here, the authors show that visible light triggers photo-oxidative stress and a wider stress response in C. elegans, suggesting that light exposure during routine laboratory handling may influence the outcome of lifespan experiments.

    • C. Daniel De Magalhaes Filho
    • , Brian Henriquez
    •  & Andrew Dillin

  • Article
    | Open Access

    Excitatory neurons in the preBötzinger Complex generate bursting activity responsible for breathing, but these alone cannot generate physiological breathing frequencies. Here the authors show how inhibition regulates refractory properties of excitatory neurons to allow dynamic breathing rhythms.

    • Nathan Andrew Baertsch
    • , Hans Christopher Baertsch
    •  & Jan Marino Ramirez

  • Article
    | Open Access

    Polycystic kidney disease (PKD) is characterized by the formation of large fluid-filled cysts. Here Flowers and colleagues show that loss of Lkb1, downregulated in PKD, renders kidney cells dependent on glutamine for growth, and suggest that inhibition of glutamine metabolism may prevent cyst development in PKD.

    • Ebony M. Flowers
    • , Jessica Sudderth
    •  & Thomas J. Carroll

  • Article
    | Open Access

    The periosteum, a tissue lining the bone surface, and the bone marrow are known to contain bone-forming cells. Here the authors show that skeletal stem cells reside in the mouse periosteum, and that periosteal cells have common embryonic origins with bone marrow stromal/stem cells (BMSCs), but are better at bone repair and long-term integration than BMSCs.

    • Oriane Duchamp de Lageneste
    • , Anaïs Julien
    •  & Céline Colnot

  • Article
    | Open Access

    During cardiac tissue formation it is unclear whether newly generated myocytes originate from cardiac progenitor cells or from pre-existing cardiomyocytes. Here, the authors use a stochastic four-colour reporter system (Rainbow) to identify the source of new cardiomyocytes during mouse development.

    • Konstantina-Ioanna Sereti
    • , Ngoc B. Nguyen
    •  & Reza Ardehali

  • Article
    | Open Access

    IL-17-producing T cells are protective against infection, but the authors of this article previously showed that these cells also contribute to inflammatory bone destruction. Here they show in the context of periodontitis that microbiota-driven Th17-mediated bone destruction may actually be a physiological rather than a pathological process, as associated tooth loss prevents dissemination of oral bacteria.

    • Masayuki Tsukasaki
    • , Noriko Komatsu
    •  & Hiroshi Takayanagi

  • Article
    | Open Access

    Obesity can affect bone marrow cell differentiation and the generation of myeloid and lymphoid cells. Here, the authors show that diet and obesity, as well as low-dose lipopolysaccharide, can alter Toll-like receptor 4 signaling bone marrow cells to skew the myeloid-lymphoid homeostasis in mice.

    • Ailing Liu
    • , Minhui Chen
    •  & Lisa Borghesi

  • Article
    | Open Access

    Embryo implantation initiates the interaction of the blastocyst with the uterus and occurs within a specialised crypt formed by uterine epithelial cells. Here, using 3D imaging techniques of wild type and mutant uteri, the authors show that crypt formation occurs with preexisting glands of the uterus, opening communication between glands and the implanting embryo.

    • Jia Yuan
    • , Wenbo Deng
    •  & Sudhansu. K. Dey

  • Article
    | Open Access

    Glucagon secretion is promoted during hypoglycemia and inhibited by increased glucose levels. Here, Basco et al. show that glucokinase suppresses glucose-regulated glucagon secretion by modulating the intracellular ATP/ADP ratio and the closure of KATP channels in α-cells.

    • Davide Basco
    • , Quan Zhang
    •  & Bernard Thorens

  • Article
    | Open Access

    Methyl metabolites in the one-carbon cycle, such as phosphatidylcholines and S-adenosylmethionine, play a role in hepatic triglyceride regulation. Here Kim et al. show that AhR and SHP are both involved in the expression of several key enzymes of one-carbon metabolism, with the former regulating them early after feeding and the latter inhibiting AhR at later stages.

    • Young-Chae Kim
    • , Sunmi Seok
    •  & Jongsook Kim Kemper

  • Article
    | Open Access

    The T-box transcription factor eomesodermin (EOMES) acts both in endoderm specification as well as heart development, suggesting context-specific function. Here, the authors show that dose-controlled EOMES induction is sufficient for cardiogenic programming of human pluripotent stem cells.

    • Martin J. Pfeiffer
    • , Roberto Quaranta
    •  & Boris Greber

  • Article
    | Open Access

    Resting cortical activity fluctuates, but it is unclear what underlies these variations in activity. Here, the authors show that large-scale fluctuations in fMRI cortical activity are associated with momentary decreases in cortical arousal and opposite activity changes in the basal forebrain and thalamus.

    • Xiao Liu
    • , Jacco A. de Zwart
    •  & Jeff H. Duyn

  • Article
    | Open Access

    About a quarter of pre-menopausal women will suffer from heavy menstrual bleeding in their lives. Here, Maybin and colleagues show hypoxia and subsequent activation of HIF-1α during menses are required for normal endometrial repair, and identify pharmacological stabilisation of HIF-1α as a potential therapeutic strategy for this debilitating condition.

    • Jacqueline A. Maybin
    • , Alison A. Murray
    •  & Hilary O. D. Critchley

  • Article
    | Open Access

    White adipose tissue can undergo a process of beiging and acquire functional characteristics similar to brown adipose tissue, including the ability to dissipate energy via uncoupled respiration. Here, Velazquez-Villegas et al. show that activation of the bile acid membrane receptor, TGR5, leads to white adipocyte beiging by promoting mitochondrial fission.

    • Laura A. Velazquez-Villegas
    • , Alessia Perino
    •  & Kristina Schoonjans

  • Article
    | Open Access

    Capsaicin prevents atherosclerotic plaque formation by activating TRPV1 cation channels, but its toxicity precludes its use in clinical settings. Here, Tang and colleagues use copper sulfide nanoparticles as a photothermal switch to locally and temporally activate TRPV1 in vascular smooth muscle cells and reduce plaque formation without apparent toxicity.

    • Wen Gao
    • , Yuhui Sun
    •  & Bo Tang

  • Article
    | Open Access

    FFAR1 receptor is highly expressed in beta cells and its activation has been suggested as therapy against type-2 diabetes. Here, Tunaru et al. show that 20-hydroxyeicosatetraenoic acid, produced within the islets upon glucose stimulation, acts in an autocrine manner to stimulate insulin secretion via FFAR1 activation.

    • Sorin Tunaru
    • , Remy Bonnavion
    •  & Stefan Offermanns

  • Article
    | Open Access

    Mitochondrial Ca2+ homoeostasis is tightly regulated and export of Ca2+ is mediated by an Na+Ca2+ exchanger. Here authors show that in depolarised mitochondria the exchanger initially operates in reverse mode, transporting cytosolic Ca2+ into the matrix before it reverts to its forward mode state.

    • Krishna Samanta
    • , Gary R. Mirams
    •  & Anant B. Parekh

  • Article
    | Open Access

    Histone post-translational modifications are known key regulators of gene expression. Here, the authors characterize histone crotonylation at histone H3 lysine 18 in intestinal epithelia and find that it is a highly dynamic cell cycle regulated mark under the regulation of the HDAC deacetylases.

    • Rachel Fellows
    • , Jérémy Denizot
    •  & Patrick Varga-Weisz

  • Article
    | Open Access

    Non-circulating, tissue-resident T cells have been reported for non-lymphoid organs, but their characterization and regulation in secondary lymphoid organs (SLO) are still lacking. Here the authors show that age and microbiota both exert SLO-specific effects for the various tissue-resident T cell subsets.

    • Aurélie Durand
    • , Alexandra Audemard-Verger
    •  & Bruno Lucas

  • Article
    | Open Access

    The ‘pace of life’ depends on both metabolic rate and life history traits; however, whether these evolve similarly in response to the environment is not clear. Here, Auer et al. show parallel evolution of metabolic rate and a suite of life history traits in response to predator environment in Trinidadian guppies.

    • Sonya K. Auer
    • , Cynthia A. Dick
    •  & David N. Reznick

  • Article
    | Open Access

    High homocysteine plasma levels are associated with cardiovascular diseases. Here, Li and colleagues find that homocysteine aggravates vascular injury by direct binding to the angiotensin II type 1 receptor (AT1R), identifying AT1R inhibition as a potential strategy to counteract the deleterious vascular effects of hyperhomocysteinemia.

    • Tuoyi Li
    • , Bing Yu
    •  & Wei Kong

  • Article
    | Open Access

    Type 2 diabetes is associated with impaired wound healing, which can lead to limb loss. Here, the authors show that in Type 2 diabetic mouse models, Dnmt1 is upregulated in hematopoietic stem cells, leading to impaired differentiation towards macrophages, reduced macrophage infiltration in the wound and skewed M1/M2 polarization.

    • Jinglian Yan
    • , Guodong Tie
    •  & Louis M. Messina

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