Physiology articles within Nature Communications

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  • Article
    | Open Access

    The issue whether the cell surface protein c-kit identifies resident cardiac stem cells (CSC) is controversial. By using novel reporter mouse models, Sultana et al. show that c-kit+cells represent a subpopulation of endothelial cells in the developing and adult heart and do not exhibit CSC traits in health or disease.

    • Nishat Sultana
    • , Lu Zhang
    •  & Chen-Leng Cai

  • Article
    | Open Access

    All forms of diabetes eventually lead to a reduction in insulin-secreting pancreatic β-cells. Here, the authors report aminopyrazine derivatives, which induce proliferation of rodent as well as human β-cells and improve glucose metabolism in a mouse model of type 1 diabetes.

    • Weijun Shen
    • , Brandon Taylor
    •  & Bryan Laffitte

  • Article
    | Open Access

    Ageing increases the risk of many diseases. Here the authors compare blood cell transcriptomes of over 14,000 individuals and identify a set of about 1,500 genes that are differently expressed with age, shedding light on transcriptional programs linked to the ageing process and age-associated diseases.

    • Marjolein J. Peters
    • , Roby Joehanes
    •  & Andrew D. Johnson

  • Article
    | Open Access

    Pituitary gonadotropes secrete follicle-stimulating hormone (FSH) in both male and female mice. Roper et al.show that the synaptotagmin isoform syt-9 is specifically required for FSH secretion, but only in females, revealing a mechanism by which specificity can be encoded in complex secretory cells.

    • Lindsey K. Roper
    • , Joseph S. Briguglio
    •  & Edwin R. Chapman

  • Article
    | Open Access

    Haem-free, NO-insensitive soluble guanylate cyclase (apo-sGC) generated during oxidative stress contributes to cardiovascular pathology. By generating and characterizing apo-sGC knock-in mice, Thoonen et al. provide a scientific ground for the therapeutic concept of sGC activators, and dissect the relevance of the NO-sGC axis.

    • Robrecht Thoonen
    • , Anje Cauwels
    •  & Peter Brouckaert

  • Article
    | Open Access

    Functional imaging of proteolytic activity is an emerging strategy to guide patient diagnosis and monitor clinical outcome. Here the authors present a peptide-based probe to detect and localize thrombin activity ex vivoand non-invasively in mouse models of wounding and pulmonary thrombosis.

    • Michael J. Page
    • , André L. Lourenço
    •  & Charles S. Craik

  • Article |

    Mechanical and electrical activity in the heart is propagated through unique cardiomyocyte membrane structures, the intercalated discs (ID). Sharma et al.identify a novel ID protein, Tmem65, that controls Ca2+ signalling and electrical coupling by interacting with and functionally regulating the gap junction protein Cx43.

    • Parveen Sharma
    • , Cynthia Abbasi
    •  & Anthony O. Gramolini

  • Article
    | Open Access

    n-Butanol is a valuable biofuel that can be produced industrially by bacterial fermentation. Here the authors uncover a redox-switch within Clostridium acetobutylicum’s thiolase—a key enzyme involved in n-butanol biosynthesis—that controls the rate of fermentative butanol production.

    • Sangwoo Kim
    • , Yu-Sin Jang
    •  & Kyung-Jin Kim

  • Article
    | Open Access

    PI3K is activated as a result of insulin receptor (IR) signalling. Here the authors show that activation of specific class III PI3Ks in response to insulin promotes IR endocytosis and lysosomal degradation, providing negative feedback on IR signalling by reducing the time IR is activated.

    • Ivan Nemazanyy
    • , Guillaume Montagnac
    •  & Ganna Panasyuk

  • Article
    | Open Access

    Inhibiting the formation of S-adenosyl-methionine (SAM) increases worm but not fly lifespan. Here the authors show that humans and flies possess the SAM-consuming enzyme Gnmt, the activity of which is regulated by lifespan-extending interventions, and that knockdown of Gnmt extends fly lifespan.

    • Fumiaki Obata
    •  & Masayuki Miura

  • Article
    | Open Access

    Transcription factor COUP-TFII is elevated in the hearts of non-ischaemic cardiomyopathy patients, but the nature of this correlation is unknown. Here the authors show that forced cardiac expression of COUP-TFII in mice causes dilated cardiomyopathy because of altered mitochondrial function and impaired metabolic remodelling.

    • San-Pin Wu
    • , Chung-Yang Kao
    •  & Sophia Y. Tsai

  • Article
    | Open Access

    Aerobic glycolysis and diminished oxidative phosphorylation exhibited by tumour cells enables the production of energy necessary to support malignant proliferation. Here the authors show that UCP3 promotes mitochondrial uncoupling and prevents tumorigenesis through a mitochondrially-driven pathway of AKT inhibition.

    • Sara M. Nowinski
    • , Ashley Solmonson
    •  & Edward M. Mills

  • Article
    | Open Access

    The heart forms from combining the first with the second heart field, which in mammals creates left and right ventricle. Here transgenic zebrafish and physiology studies reveal that transcription factors controlling septation in mammals already in teleosts guide muscle coupling by controlling the relative contribution of the two fields to the heart.

    • Christian Mosimann
    • , Daniela Panáková
    •  & Leonard I. Zon

  • Article
    | Open Access

    Intestinal inflammation is often associated with a shift in microbiota composition but the mechanisms are unclear. Here the authors show that an increase in caecal sialidase activity occurring during intestinal inflammation promotes the expansion of Enterobacteriaceae, which can lead to exacerbated inflammatory response.

    • Yen-Lin Huang
    • , Christophe Chassard
    •  & Thierry Hennet

  • Article
    | Open Access

    The transcriptional regulator Tbx15 has a role in organ development. Here Lee et al.show that Tbx15 influences fibre-type determination in murine skeletal muscles, explaining local and systemic metabolic derangements in heterozygous Tbx15 knockout mice.

    • Kevin Y. Lee
    • , Manvendra K. Singh
    •  & C. Ronald Kahn

  • Article
    | Open Access

    Vascular function and repair is impaired in patients with diabetes. Here, Caporali et al.report that activation of the neurotrophin receptor in vascular endothelial cells induces the antiangiogenic miR-503, which impairs the function of neighbouring pericytes upon microparticle-mediated transfer.

    • Andrea Caporali
    • , Marco Meloni
    •  & Costanza Emanueli

  • Article
    | Open Access

    A few bacterial cells within a genetically homogeneous population can become ‘persisters’, or temporarily tolerant to antibiotics. Here Orman and Brynildsen show that development of persisters among growth-arrested E. colicells can be prevented by inhibiting bacterial respiration.

    • Mehmet A. Orman
    •  & Mark P. Brynildsen

  • Article
    | Open Access

    Insulin resistance in adipose tissue is a hallmark of obesity. Here, the authors generate inducible adipocyte-specific PTEN knockout mice to demonstrate that enhanced insulin sensitivity in adipose tissue is directly linked to improved systemic metabolic homeostasis, despite an increase in fat mass.

    • Thomas S. Morley
    • , Jonathan Y. Xia
    •  & Philipp E. Scherer

  • Article
    | Open Access

    CD163 is a glycoprotein receptor expressed on the surface of macrophages. Here, the authors demonstrate that a soluble form of CD163 can act as a decoy receptor for the pro inflammatory cytokine TWEAK, thereby revealing a new mechanism for the regulation of tissue repair after ischaemic injury.

    • Hirokuni Akahori
    • , Vinit Karmali
    •  & Aloke V. Finn

  • Article
    | Open Access

    Previous studies have linked over 100 genomic loci to age-at-menarche but that work was restricted to common autosomal variation. Here, Lunetta et al. identify associations with rare protein-coding and X-linked variants, implicating new mechanisms that regulate puberty timing.

    • Kathryn L. Lunetta
    • , Felix R. Day
    •  & John R. B. Perry

  • Article
    | Open Access

    Little is known about how detritivorous invertebrates cope with high levels of defensive plant polyphenols. Here, Liebekeet al. identify a new class of surface-active metabolites in earthworms exposed to high-polyphenol diets, and show that they play a protective role against precipitation of proteins.

    • Manuel Liebeke
    • , Nicole Strittmatter
    •  & Jacob G. Bundy

  • Article
    | Open Access

    3D microvessels with complex geometries and intact endothelium can be built in vitro. Using these engineered microvessels, here the authors show that the generation of the pathologic meshwork of the blood protein von Willebrand factor is affected by vessel architecture, flow and the proteolytic activity of ADAMTS13.

    • Ying Zheng
    • , Junmei Chen
    •  & José A. López

  • Article |

    Changes in the metabolic state of stem cells can trigger a shift from quiescence into cell cycle entry. Here Maryanovichet al. identify mitochondrial carrier homolog 2 (MCH2) as a negative regulator of mitochondrial oxidative phosphorylation in haematopoietic stem cells, maintaining their homeostasis.

    • Maria Maryanovich
    • , Yehudit Zaltsman
    •  & Atan Gross

  • Article
    | Open Access

    14-3-3 family proteins are adaptor proteins involved in various cellular functions. Here Lim et al. show that 14-3-3ζ regulates adipogenesis in vitro, and the formation of visceral fat in mice, by reducing autophagic degradation of the adipogenic master transcription factor C/EBP-δ.

    • Gareth E. Lim
    • , Tobias Albrecht
    •  & James D. Johnson

  • Article |

    Platelet-derived growth factor (PDGF) signaling in vascular smooth muscle cells (VSMCs) promotes atherogenesis. Here, the authors show that mutant mice with increased PDGF activity in VSMCs have augmented STAT1-dependent chemokine signals resulting in artery wall inflammation and formation of advanced plaque morphologies clinically relevant in humans.

    • Chaoyong He
    • , Shayna C. Medley
    •  & Lorin E. Olson

  • Article
    | Open Access

    Growing evidence from neuroimaging studies suggests that the brain is dynamically organized into functionally connected networks. Here, the authors develop a new technique for decomposing spontaneous activity into temporally overlapping building blocks that assemble standard functional networks.

    • Fikret Işik Karahanoğlu
    •  & Dimitri Van De Ville

  • Article
    | Open Access

    The capacity for thermoregulation deteriorates with age, particularly in cold environments. Here the authors demonstrate inDrosophilathat age-related changes in cold avoidance result from a shift in the relative contribution of two parallel mushroom body circuits that are modulated by dopamine.

    • Hsiang-Wen Shih
    • , Chia-Lin Wu
    •  & Ann-Shyn Chiang

  • Article
    | Open Access

    The hormone adiponectin is produced by fat cells and has positive metabolic effects. Here, Kim et al.show that DNA methyltransferase 1 (DNMT1) represses adiponectin expression through hypermethylation of its promoter, and that inflammatory cytokines enhance DNMT1 activity in obese mice and humans.

    • A. Young Kim
    • , Yoon Jeong Park
    •  & Jae Bum Kim

  • Article |

    Bile acids exert metabolic effects by modulating FXR receptor activity. Here, Trabelsi et al.show that FXR negatively regulates production of the incretin GLP-1 in enteroendocrine L-cells by reducing glycolysis and that inhibition of FXR improves glucose metabolism by increasing GLP-1 in obese mice.

    • Mohamed-Sami Trabelsi
    • , Mehdi Daoudi
    •  & Sophie Lestavel

  • Article
    | Open Access

    We currently lack a detailed understanding of the neurobiological basis for the decline of male sexual desire with age. Here the authors demonstrate that restoring impaired dopaminergic signalling in a specific cluster of neurons in the Drosophilabrain increases sexual behaviour in ageing male flies.

    • Shu-Yun Kuo
    • , Chia-Lin Wu
    •  & Tsai-Feng Fu

  • Article |

    Unlike rodents, humans produce the protein Cidea in white adipose tissue, where it associates with lipid droplets. Here the authors generate mice that express human Cidea in fat tissues to show Cidea exerts beneficial metabolic effects by regulating the expansion of visceral fat in response to a high-fat diet.

    • Gustavo Abreu-Vieira
    • , Alexander W. Fischer
    •  & Natasa Petrovic

  • Article
    | Open Access

    KDEL receptors are known to be involved in retrotransporting chaperones to the endoplasmic reticulum from the Golgi complex. Here the authors unravel a role of KDEL receptor 1 in regulating integrated stress responses in naïve T cells through its association with protein phosphatase 1.

    • Daisuke Kamimura
    • , Kokichi Katsunuma
    •  & Masaaki Murakami

  • Article
    | Open Access

    Bile acids are important for the absorption of nutrients. Here the authors provide a molecular explanation for the oscillatory release of bile acids, showing that diurnal expression of the transcription factor KLF15 regulates FGF15 secretion from enterocytes, which then inhibits bile acid synthesis in the liver.

    • Shuxin Han
    • , Rongli Zhang
    •  & Mukesh K. Jain

  • Article
    | Open Access

    Lipid droplets (LDs) supply fatty acids to cellular processes and move bidirectionally on microtubules. Here the authors show that nutrient starvation causes dispersal of mitochondria and LD to the periphery of the cell along detyrosinated microtubules and increases LD–mitochondria interactions in an AMPK-dependent manner.

    • Albert Herms
    • , Marta Bosch
    •  & Albert Pol

  • Article
    | Open Access

    The enzyme soluble guanylyl cyclase (sGC) regulates differentiation of brown fat. Here, Hoffman et al.show that a small molecule sGC stimulator increases brown fat activity and browning of white fat, thereby inducing energy expenditure, weight loss and partial protection from diet-induced obesity in mice.

    • Linda S. Hoffmann
    • , Jennifer Etzrodt
    •  & Alexander Pfeifer

  • Article
    | Open Access

    Diabetes is associated with aberrations in glucose metabolism. Here the authors perform a genomic screen in fruit flies to identify new regulators of fly glucose metabolism, and show that mice lacking the murine homologue of one of their hits, the protein kinase CK1alpha, in the adipose lineage develop diabetes.

    • Rupali Ugrankar
    • , Eric Berglund
    •  & Jonathan M. Graff

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