Physiology articles within Nature Communications

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  • Article
    | Open Access

    The current hemostasis assays are unable to predict thrombotic or bleeding risk in clinics. Here, Jain et al. present a novel microfluidic device mimicking stenosed arterioles that determines clotting times in vitroand in extracorporeal circuits, offering a simple and reliable monitoring of blood homeostasis and platelet function.

    • Abhishek Jain
    • , Amanda Graveline
    •  & Donald E. Ingber

  • Article
    | Open Access

    Insulin-producing pancreatic beta cells, generatedin vitro, could lead to new anti-diabetic therapies. Here, Zhu et al. convert human fibroblasts into endodermal progenitors that differentiate in vitrointo glucose-responsive beta-like cells that, following transplantation in mice, protect from diabetes.

    • Saiyong Zhu
    • , Holger A. Russ
    •  & Sheng Ding

  • Article
    | Open Access

    Organismal ageing is driven by conserved biological processes. Here the authors build on a comparative RNA-seq analysis in three model organisms to demonstrate that the gene, bcat-1, which catalyses the degradation of branched-chain amino acids, regulates lifespan in worms.

    • Johannes Mansfeld
    • , Nadine Urban
    •  & Michael Ristow

  • Article
    | Open Access

    GLP-1 is a gut hormone with glucose-lowering activity. Here the authors report the peptide, P5, a variant of the GLP-1 receptor agonist exendin-4, with 'biased' signalling activity, and show that P5 improves glucose homeostasis in diabetic mice by increasing adipose tissue hyperplasia.

    • Hongkai Zhang
    • , Emmanuel Sturchler
    •  & Richard A. Lerner

  • Article
    | Open Access

    Globins are best known for their role in respiration, but recent studies suggest they might contribute to redox signalling as well. Here, the authors present biochemical, structural and in vivoevidence that the roundworm globin Glb-12 acts as a superoxide generator necessary for germline development.

    • Sasha De Henau
    • , Lesley Tilleman
    •  & Bart P. Braeckman

  • Article
    | Open Access

    Generalized arterial calcification of infancy (GACI) is a terminal disease caused by the ENPP1 enzyme deficiency. Here, Albrigh et al. show that ENPP1 enzyme replacement therapy prevents the ectopic calcifications and mortality in mice with GACI, suggesting a novel treatment for vascular calcification in humans.

    • Ronald A. Albright
    • , Paul Stabach
    •  & Demetrios T. Braddock

  • Article
    | Open Access

    Unravelling the molecular basis of hypertension remains a major challenge. Here, the authors identify the transcription factor GATA5 as a novel regulator of blood pressure and potential genetic determinant of human hypertension and describe a unique mouse model for research of salt-sensitive hypertension.

    • Smail Messaoudi
    • , Ying He
    •  & Mona Nemer

  • Article
    | Open Access

    Brown adipose tissue (BAT) thermogenesis is an important determinant of organismal energy expenditure in mammals. Here, Whittle et al. report that the protein sLR11 is a negative regulator of BAT activity in mice, repressing thermogenesis by inhibiting BMP/Smad signalling in brown adipocytes.

    • Andrew J. Whittle
    • , Meizi Jiang
    •  & Hideaki Bujo

  • Article
    | Open Access

    Sperm-egg fusion is facilitated by the sperm-specific receptor IZUMO1 and the egg-specific counter-receptor JUNO. Here Inoue et al.show that JUNO first binds to monomeric IZUMO1; IZUMO1 then dimerizes and excludes JUNO from the sperm-egg interface, suggesting the existence of a IZUMO1 dimer receptor.

    • Naokazu Inoue
    • , Yoshihisa Hagihara
    •  & Ikuo Wada

  • Article
    | Open Access

    The aging myopathy is characterized by diastolic dysfunction of unknown aetiology. Rota et al. show that increased late Na+ current (INaL) underlies diastolic dysfunction in the aged heart, and that inhibiting INaLimproves diastolic indices and corrects the kinetics of cardiomyocyte contraction and relaxation in aged mice.

    • Sergio Signore
    • , Andrea Sorrentino
    •  & Marcello Rota

  • Article
    | Open Access

    TheC. elegans nervous system influences organismal lifespan but mechanistic details are poorly understood. Here, Chun et al. show that the neurotransmitter GABA regulates worm lifespan by acting on GABABreceptors in motor neurons, which activate the transcription factor DAF-16 in the intestine.

    • Lei Chun
    • , Jianke Gong
    •  & Jianfeng Liu

  • Article
    | Open Access

    Evidence suggests that the TCA cycle enzyme complex succinate dehydrogenase (SDH) may be dispensable for cell proliferation in some cancer cells. Here the authors show that SDH deficient cells become dependent on the mitochondrial enzyme pyruvate carboxylase for aspartate production and proliferation.

    • Charlotte Lussey-Lepoutre
    • , Kate E. R. Hollinshead
    •  & Daniel A. Tennant

  • 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

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