Physiology articles within Nature Communications

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  • Article
    | Open Access

    Sudden arrhythmic death is a leading cause of mortality, however approaches to identify at-risk patients are of low sensitivity and specificity. Here, the authors develop a personalized approach to assess arrhythmia risk in post-infarction patients based on cardiac imaging and computational modelling that significantly outperforms existing clinical metrics.

    • Hermenegild J. Arevalo
    • , Fijoy Vadakkumpadan
    •  & Natalia A. Trayanova

  • Article
    | Open Access

    Heart failure is a major public health issue but due to our poor disease understanding the current therapies are symptomatic. Here the authors identify Myoscape as a novel cardiac protein regulating membrane localization of the L-type calcium channel and heart's contractile force, thus promising new therapeutic avenues for heart failure.

    • Matthias Eden
    • , Benjamin Meder
    •  & Norbert Frey

  • Article
    | Open Access

    Exosomes are RNA-containing lipid vesicles with roles in inter-tissue crosstalk. Here the authors show that exosome release from brown adipocytes is increased upon thermogenic activation, both in vitro and in vivo, and demonstrate that serum levels of exosomal miR-92 reflect brown fat activity in humans.

    • Yong Chen
    • , Joschka J. Buyel
    •  & Alexander Pfeifer

  • Article
    | Open Access

    Visceral and subcutaneous fat are associated with different metabolic risk, but mediators of such depot specific effects are not very well known. Here the authors identify the transcriptional regulator, TRIP-Br2, as a regulator of endoplasmic reticulum (ER) stress-induced inflammatory responses specifically in visceral fat.

    • Guifen Qiang
    • , Hyerim Whang Kong
    •  & Chong Wee Liew

  • Article
    | Open Access

    Future dramatic rises in dementia are widely reported, assuming no change in incidence. Matthews and colleagues report that, in contrast to such statements, age-specific incidence has dropped over 20 years, with overall incidence of dementia remaining stable in a large multi-site population study from England.

    • F. E. Matthews
    • , B. C. M. Stephan
    •  & G. Forster

  • Article
    | Open Access

    Human mesenchymal stem cells (hMSC) expressing paracrine factors may enhance therapeutic benefits when transplanted. Here, the authors show that hMSCs stably expressing prostacyclin enhance host regeneration and muscle mass gain in a mouse hindlimb ischaemia model, mediated by the long noncoding RNA H19.

    • Yuxiao Deng
    • , Zhongwei Yang
    •  & Qi Liu

  • Article
    | Open Access

    Changes in global histone trimethylation have been linked to embryonic but not adult stem cell plasticity. Here, Lee et al. find H3 K4/K9/K27me3 levels actively reduced in adult mouse skin and hair follicle stem cells during quiescence (catagen) and link this to active bone morphogen protein signalling.

    • Jayhun Lee
    • , Sangjo Kang
    •  & Tudorita Tumbar

  • Article
    | Open Access

    The protein kinase ASK1 has been linked to cellular stress responses. Here the authors show that ASK1 also regulates gene expression and activity of beige and brown adipocytes, and demonstrate adipocyte ASK1 has a physiological role in regulating thermogenesis in mice.

    • Kazuki Hattori
    • , Isao Naguro
    •  & Hidenori Ichijo

  • Article
    | Open Access

    Aging is associated with impaired pancreatic islet function, increased risk of type 2 diabetes, and changes in DNA methylation. Here the authors find blood-based biomarkers that reflect age-associated DNA methylation changes in human pancreatic islets associated with insulin secretion and diabetes.

    • Karl Bacos
    • , Linn Gillberg
    •  & Charlotte Ling

  • Article
    | Open Access

    Understanding the genetic influences on human aging requires a large number of subjects for a study of sufficient power. Here, Jim Wilson and colleagues use information on parental ages at death to show that common variants near the genes for apolipoprotein E and nicotinic acetylcholine receptor subunit alpha 5 are associated with longer lifespan.

    • Peter K. Joshi
    • , Krista Fischer
    •  & James F. Wilson

  • Article
    | Open Access

    Restricting hypertrophic heart growth in response to pathologic overload is an unmet therapeutic need. Here, the authors show that blocking Ca2+signaling controlled by the transport protein PMCA4 in cardiac fibroblasts enhances secretion of a potent Wnt signaling inhibitor, sFRP2, and prevents the development of pathologic cardiac hypertrophy in mice.

    • Tamer M. A. Mohamed
    • , Riham Abou-Leisa
    •  & Delvac Oceandy

  • Article
    | Open Access

    Although Mg2+is vital for platelet activation and aggregation, its regulation in these cells is still largely unknown. Here, the authors show that TRPM7, a cation channel and a protein kinase, regulates thrombopoiesis and platelet size by affecting the cytoskeleton of these cells in mice and humans.

    • Simon Stritt
    • , Paquita Nurden
    •  & Attila Braun

  • Article
    | Open Access

    Head movements of swimming fishes are thought to exist only because of recoil of the oscillating tail. Here, Akanyeti et al. show that by controlling the timing of head movements, fish can improve their swimming efficiency while simultaneously optimizing sensing and respiration.

    • O. Akanyeti
    • , P. J. M. Thornycroft
    •  & J. C. Liao

  • Article
    | Open Access

    The precise rotational manipulation of single cells is technically challenging and relies on the optical, magnetic and electrical properties of the biospecimen. Here the authors develop an acoustic-based, on-chip manipulation method that can rotate single microparticles, cells and organisms.

    • Daniel Ahmed
    • , Adem Ozcelik
    •  & Tony Jun Huang

  • Article
    | Open Access

    Using forward genetic screen in fetal mice, Gregory Pazour and colleagues describe mutants affecting kidney/urinary tract development. The authors also show that mutants that cause kidney defects overlaps with those leading to congenital heart defects, thus linking renal anomalies and congenital heart disease.

    • Jovenal T. San Agustin
    • , Nikolai Klena
    •  & Gregory J. Pazour

  • Article
    | Open Access

    The enzyme G6PD generates the reductive metabolite NADPH, which has antioxidant effects, but has also been linked to tumour growth. Here the authors generate mice that modestly overexpress G6PD and report increased lifespan in females, and no negative effects on tumour formation in various genetic models.

    • Sandrina Nóbrega-Pereira
    • , Pablo J. Fernandez-Marcos
    •  & Manuel Serrano

  • Article
    | Open Access

    Low density lipoprotein receptor (LDLR) is crucial for cholesterol homeostasis. Here, the authors show that components of the CCC-protein complex, CCDC22 and COMMD1, facilitate the endosomal sorting of LDLR and that mutations in these genes cause hypercholesterolemia in dogs and mice, providing new insights into regulation of cholesterol homeostasis.

    • Paulina Bartuzi
    • , Daniel D. Billadeau
    •  & Bart van de Sluis

  • Article
    | Open Access

    Brown and beige adipose tissues contribute to organismal energy expenditure by generating heat. Here, Klepac et al. survey G protein-coupled receptors in brown fat and show that Gq-coupled receptors inhibit expression of thermogenic proteins in mice and in human adipocytes.

    • Katarina Klepac
    • , Ana Kilić
    •  & Alexander Pfeifer

  • Article
    | Open Access

    AMPK regulates the metabolism and so drugs that activate AMPK might have potential for the treatment of metabolic disease. Here, the authors report the structure of AMPK bound to an activating compound, revealing two binding sites and indicating that dual therapy might be a good drug strategy.

    • Christopher G. Langendorf
    • , Kevin R. W. Ngoei
    •  & Bruce E. Kemp

  • Article
    | Open Access

    Histone deacetylases (HDACs) regulate energy metabolism in peripheral tissues, but whether HDACs expressed in the brain influence systemic metabolism is unknown. Here the authors show that hypothalamic HDAC5 expression is affected by the diet and HDAC5 regulates leptin sensitivity by deacetylating STAT3.

    • Dhiraj G. Kabra
    • , Katrin Pfuhlmann
    •  & Paul T. Pfluger

  • Article
    | Open Access

    Heart contraction, which is decreased in disease, is determined by Ca2+binding to troponin C. Here, the authors combine a protein engineering approach with gene therapy to modulate heart contractility in mice with the use of rationally designed Troponin C variants, suggesting a new therapy for diseased hearts.

    • Vikram Shettigar
    • , Bo Zhang
    •  & Jonathan P. Davis

  • Article
    | Open Access

    Reliable assessments of oocyte developmental potential are lacking, making it difficult to select the best quality embryos for transfer after in vitrofertilization. Here, the authors show that a non-invasive measurement of viscoelastic properties predicts developmental potential in both humans and mice.

    • Livia Z. Yanez
    • , Jinnuo Han
    •  & David B. Camarillo

  • Article
    | Open Access

    Misfolding of transthyretin can cause amyloid aggregation disorders that can be treated by stabilizing the tetrameric form with tafamidis. Here the authors show that tolcapone, a drug already FDA-approved for Parkinson disease, has strong transthyretin stabilizing function and might be a superior therapeutic option for CNS amyloidosis as it can cross the blood brain barrier.

    • Ricardo Sant'Anna
    • , Pablo Gallego
    •  & Salvador Ventura

  • Article
    | Open Access

    Expansion of visceral adipose tissue is usually associated with insulin resistance and metabolic disease. Here, the authors show that the membrane protein TNMD is upregulated in visceral fat of insulin resistant obese individuals and promotes healthy adipose tissue expansion through increasing adipogenesis.

    • Ozlem Senol-Cosar
    • , Rachel J. Roth Flach
    •  & Michael P. Czech

  • Article
    | Open Access

    The RNAse III endonuclease Dicer is crucial for processing of pre-miRNAs in health and disease. Here the authors show that endothelial Dicer promotes atherosclerosis by increasing miR-103 levels leading to suppression of the anti-inflammatory transcription factor KLF4, thus suggesting a novel approach to treat this disease.

    • Petra Hartmann
    • , Zhe Zhou
    •  & Andreas Schober

  • Article
    | Open Access

    Protein kinase R (PKR) has been suggested to act as a mediator of ER stress and inflammation in obesity. Here, Lancaster et al. find that genetic loss of PKR does not alter the development of obesity, and suggest that the use of littermate controls may explain differences in mouse knockout phenotypes.

    • G. I. Lancaster
    • , H. L. Kammoun
    •  & M. A. Febbraio

  • Article
    | Open Access

    Vascular calcification (VC) increases morbidity and mortality in cardiovascular and metabolic diseases. Here, Kwon et al.show that calcification stimuli induce MDM2- mediated ubiquitination and proteasomal degradation of HDAC1, suggesting a possible therapeutic strategy for treatment of VC patients.

    • Duk-Hwa Kwon
    • , Gwang Hyeon Eom
    •  & Hyun Kook

  • Article
    | Open Access

    This meta-analysis of genome-wide association studies identifies four genetic loci associated with circulating leptin levels independent of adiposity. Examination in mouse adipose tissue explants provides functional support for the leptin-associated loci.

    • Tuomas O. Kilpeläinen
    • , Jayne F. Martin Carli
    •  & Ruth J. F. Loos

  • Article
    | Open Access

    Dietary choline metabolites, such as trimethylamine N-oxide and betaine, have been associated with coronary artery disease (CAD). Here, Hartiala et al. identify two genetic loci for betaine levels on chromosomes 2q34 and 5q14.1 and find that the 2q34 locus was also associated with other pathway intermediates, and decreased risk of CAD in women.

    • Jaana A. Hartiala
    • , W. H. Wilson Tang
    •  & Hooman Allayee

  • Article
    | Open Access

    Timothy Syndrome (TS) is a multisystem disorder caused by two mutations leading to dysfunction of the CaV1.2 channel. Here, Dick et al. uncover a major and mechanistically divergent effect of both mutations on Ca2+/calmodulin-dependent inactivation of CaV1.2 channels, suggesting genetic variant-tailored therapy for TS treatment.

    • Ivy E. Dick
    • , Rosy Joshi-Mukherjee
    •  & David T. Yue

  • Article
    | Open Access

    The melanocortin receptor, MC3R, regulates organismal energy homeostasis. Here, Lee et al. create knock-in mice with the a mutated version of the human MC3R receptor found in obese children, and show these mice have more fat and smaller bone, yet are by and large metabolically healthy.

    • Bonggi Lee
    • , Jashin Koo
    •  & Jack A. Yanovski

  • Article
    | Open Access

    mTOR signalling pathway is a critical regulator of cardiac hypertrophy. Here the authors show that two kinases, p38γ and p38δ, control heart growth by promoting mTOR activity via phosphorylation and consequent proteasome degradation of mTOR inhibitor DEPTOR, extending our knowledge of cardiac hypertrophy regulation.

    • Bárbara González-Terán
    • , Juan Antonio López
    •  & Guadalupe Sabio

  • Article
    | Open Access

    Decrease in Apolipoprotein C-III (ApoC-III) yields a cardioprotective lipoprotein profile. Here, Valleix et al.reveal a novel ApoC-III variant conferring low plasma ApoC-III concentration and cardioprotection despite renal insufficiency, and, unexpectedly, causing dominant hereditary systemic amyloidosis due to its fibrillogenic nature.

    • Sophie Valleix
    • , Guglielmo Verona
    •  & Vittorio Bellotti

  • Article
    | Open Access

    The study of germline mutations has been greatly enhanced by massive parallel sequencing technologies. Here the authors use deep sequencing data from nearly 700 parent-child trios to show maternal age has a small but significant correlation with the number of de novomutations in the offspring.

    • Wendy S. W. Wong
    • , Benjamin D. Solomon
    •  & John E. Niederhuber

  • Article
    | Open Access

    The use of stem cell-derived cardiomyocytes for heart repair is hampered by their immature structural and contractile properties that may cause arrhythmia. Here, Eng et al.show that electrical conditioning of human cardiomyocytes in 3D culture can enhance connectivity and provide resistance to arrhythmia.

    • George Eng
    • , Benjamin W. Lee
    •  & Gordana Vunjak-Novakovic

  • Article
    | Open Access

    Obesity is associated with an elevated risk of prostate cancer. Here, the authors show that periprostatic adipose tissue promotes the migration and local invasion of prostate cancer cells by secreting the chemokine, CCL7, and that this process is enhanced in the context of obesity.

    • Victor Laurent
    • , Adrien Guérard
    •  & Catherine Muller

  • Article
    | Open Access

    Spontaneous phenotypic heterogeneity confers a population-level advantage to cells that are exposed to fluctuating environments. Here the authors show that the endothelium of some organs displays a dynamic mosaicism in expression of Von Willebrand factor, suggesting bet hedging as a strategy for adaptive homeostasis.

    • Lei Yuan
    • , Gary C. Chan
    •  & William C. Aird

  • 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

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