Physiology articles within Nature Communications

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  • Article
    | Open Access

    Atherosclerosis progression is linked to inflammatory processes in the blood vessel wall. Here, the authors show that, with the progression of atherosclerosis, the resolution of inflammation is impaired as the result of an imbalance between specialized pro-resolving lipid mediators and leukotrienes.

    • Gabrielle Fredman
    • , Jason Hellmann
    •  & Ira Tabas

  • Article
    | Open Access

    Behavioural adaptations in response to stress are thought to be regulated by rapid neurotransmitter action, followed by slower hormonal signalling. Here, using optogenetic approaches, the authors find corticotroph cell populations are capable of rapidly modulating avoidance behaviours immediately after the onset of stress.

    • Rodrigo J. De Marco
    • , Theresa Thiemann
    •  & Soojin Ryu

  • Article
    | Open Access

    Oncogenic mutations of isocitrate dehydrogenases 1 and 2 result in the production of the oncometabolite R-2-hydroxyglutarate. Here the authors show that the oncometabolite promotes mTOR activation in a PTEN/PI3K-independent manner by regulating DEPTOR stability via inhibition of KDM4A activity.

    • Mélissa Carbonneau
    • , Laurence M. Gagné
    •  & Frédérick A. Mallette

  • Article
    | Open Access

    Commensal bacteria, the vast majority of which reside in the gut, are involved in development of many diseases, including atherosclerotic vascular disease. Here the authors show that these bacteria remotely increase expression of vascular microRNA-204, which targets Sirt1 in the endothelium to impair endothelial function.

    • Ajit Vikram
    • , Young-Rae Kim
    •  & Kaikobad Irani

  • Article
    | Open Access

    Bone marrow cells producing the intermediate filament nestin guide monocyte egress to the bloodstream in response to infection. Here, the authors show that nestin-producing stromal cells direct inflammatory cell migration in atherosclerosis, and that stromal Mcp1 is crucial in this process.

    • Raquel del Toro
    • , Raphael Chèvre
    •  & Simón Méndez-Ferrer

  • Article
    | Open Access

    Lymphocytic leukaemia cells are characterized by high respiratory rates. Here, the authors report that the oxysterol-binding protein ORPL4 sustains mitochondrial respiration in T-cell acute lymphoblastic leukaemia cells by regulating Ca2+release from the endoplasmic reticulum.

    • Wenbin Zhong
    • , Qing Yi
    •  & Daoguang Yan

  • Article
    | Open Access

    Insulin receptor levels at the cell surface are reduced in insulin resistance, for reasons that are not fully understood. Here, the authors identify the E3 ubiquitin ligase MARCH1 as a direct regulator of basal insulin receptor surface levels and, therefore, insulin signalling.

    • Arvindhan Nagarajan
    • , Max C. Petersen
    •  & Narendra Wajapeyee

  • Article
    | Open Access

    Epithelia are barriers against environmental insults and express the transcription factor aryl hydrocarbon receptor (AhR). Here the authors show that AhR regulates multiciliogenesis via cyclin O and Multicilin in a Notch-dependent manner and that this is blocked by toxic ligands.

    • Matteo Villa
    • , Stefania Crotta
    •  & Andreas Wack

  • Article
    | Open Access

    MURC protein regulates the function of caveolae, the small invaginations of the plasma membrane in muscle cells. Here the authors show that by interacting with caveolin proteins, MURC affects RhoA/ROCK signalling and regulates proliferation and migration of pulmonary artery smooth muscle cells, suggesting a new target in therapy of pulmonary hypertension.

    • Naohiko Nakanishi
    • , Takehiro Ogata
    •  & Tomomi Ueyama

  • Article
    | Open Access

    Pericytes and vascular smooth muscle cells are crucial for functional blood vessels, but the developmental sources of these cells are incompletely understood. Here, the authors show that endocardial endothelial cells give rise to cardiac mural cells, which are controlled by Wnt signalling.

    • Qi Chen
    • , Hui Zhang
    •  & Ralf H. Adams

  • Article
    | Open Access

    Mitochondrial complex I deficiency is the most common respiratory chain defect in mitochondrial disease in children and currently there is no effective treatment. In this study, the authors show that succinate prodrugs can alleviate metabolic decompensation in Leigh syndrome patient fibroblasts.

    • Johannes K. Ehinger
    • , Sarah Piel
    •  & Eskil Elmér

  • Article
    | Open Access

    Branching morphogenesis is essential for the formation of most epithelial organs. Here, the authors show that Neurofibromatosis 2 (NF2), the Hippo pathway kinases LATS1 and LATS2, and the transcriptional co-activators YAP and TAZ control tip identity, RET signalling and branching morphogenesis in the mouse kidney.

    • Antoine Reginensi
    • , Leonie Enderle
    •  & Helen McNeill

  • Article
    | Open Access

    GRIP1 cooperates with the glucocorticoid receptor to repress inflammatory genes. Here the authors show that GRIP1 also controls macrophage polarization, by promoting KLF4-driven activation in response to IL-4, and that mice lacking GRIP1 in macrophages develop severe metabolic dysfunction on a high-fat diet.

    • Maddalena Coppo
    • , Yurii Chinenov
    •  & Inez Rogatsky

  • Article
    | Open Access

    Angiopoietin-like 4 protein (ANGPTL4) is a regulator of lipoprotein metabolism whose role in atherosclerosis has been controversial. Here the authors show that ANGPTL4 deficiency in haematopoietic cells increases atherogenesis by promoting myeloid progenitor cell expansion and differentiation, foam cell formation and vascular inflammation.

    • Binod Aryal
    • , Noemi Rotllan
    •  & Carlos Fernández-Hernando

  • Article
    | Open Access

    Since the birth of the first cloned animal, Dolly the sheep, concerns have been raised about potential long-term health consequences of cloning. Here the authors report on a cohort of 13 aged cloned sheep, including four created from the same cells as Dolly, and find they are healthy and seem to age normally.

    • K. D. Sinclair
    • , S. A. Corr
    •  & D. S. Gardner

  • Article
    | Open Access

    The origin and fate of myofibroblasts, the cells responsible for cardiac remodelling and fibrosis, is controversial. Here the authors show that cardiac myofibroblasts express periostin, derive exclusively from tissue-resident fibroblasts, are necessary for scar formation after injury, and can revert back to a less-activated state upon injury resolution.

    • Onur Kanisicak
    • , Hadi Khalil
    •  & Jeffery D. Molkentin

  • Article
    | Open Access

    Glycolytic regulator PFKFB3 is a key player in vessel sprouting. Here the authors develop a computational model predicting that PFKFB3 drives endothelial cell rearrangement during vessel sprouting by promoting filopodia formation and reducing intercellular adhesion, and empirically validate this prediction.

    • Bert Cruys
    • , Brian W. Wong
    •  & Peter Carmeliet

  • Article
    | Open Access

    Lysine hydroxylation of procollagen precursors by LH3 is required for collagen fibril crosslinking and stabilization. Here the authors show that the trafficking protein VIPAR is required for correct sorting of LH3 into post-Golgi collagen carriers and for correct collagen modification and structure.

    • Blerida Banushi
    • , Federico Forneris
    •  & Paul Gissen

  • Article
    | Open Access

    The accumulation of lipid droplets is often observed in hepatitis C virus infection, but the mechanism of their formation is not known. Here the authors show that septin 9 expression is increased in infected livers, and a septin 9/phosphatidylinositol 5-phosphate signalling pathway regulates the growth of lipid droplets.

    • Abdellah Akil
    • , Juan Peng
    •  & Ama Gassama-Diagne

  • Article
    | Open Access

    The identity of mechanosensors within aortic baroreceptors that sense fluctuations in blood pressure is unclear. Here, Lau et al.show that a cation channel TRPC5 acts as a transducer of mechanical stimuli in aortic baroreceptor neurons in rodents.

    • On-Chai Lau
    • , Bing Shen
    •  & Xiaoqiang Yao

  • Article
    | Open Access

    Heart function after injury improves upon formation of new blood vessels. Here, the authors show that ablating a transcription factor RBPJ in the murine heart increases vascularization and maintains cardiac function after injury by increasing responsiveness to hypoxia, suggesting a new approach to treat heart injury.

    • Ramón Díaz-Trelles
    • , Maria Cecilia Scimia
    •  & Mark Mercola

  • Article
    | Open Access

    Semaphorin ligands and cognate receptors are important in patterning the vasculature. Here, Aghajanian et al.report an unexpected role for ErbB2 in endothelial cells where it partners with Nrp1 to form a novel semaphoring holoreceptor required for embryonic vascular patterning.

    • Haig Aghajanian
    • , Young Kuk Cho
    •  & Jonathan A. Epstein

  • Article
    | Open Access

    More than 90% of genetic variants associated with type 2 diabetes occur in non-coding regions. Scott et al. report genomes, epigenomes and transcriptomes of skeletal muscle from 271 participants with a range of glucose tolerances, revealing a genetic regulatory architecture enriched in muscle stretch/super enhancers.

    • Laura J. Scott
    • , Michael R. Erdos
    •  & Stephen C. J. Parker

  • Article
    | Open Access

    Altered function of the muscle LIM protein (MLP) causes dilated cardiomyopathy in mice and humans. Lange et al. explain the molecular role of MLP in the heart by showing that it affects the signalling complex at the intercalated discs of failing hearts that consists of PKCα, PLCβ1 and CARP by inhibiting PKCα auto-phosphorylation and function.

    • Stephan Lange
    • , Katja Gehmlich
    •  & Elisabeth Ehler

  • Article
    | Open Access

    Ceruloplasmin has an important role in the stabilization and nuclear transport of HIF-1α, thus regulating VEGF expression. Here the authors show that the transcription factor SARI reduces colorectal cancer growth and angiogenesis in vivoby inducing the degradation of ceruloplasmin, thereby inhibiting the HIFα/VEGF axis.

    • Lei Dai
    • , Xueliang Cui
    •  & Hongxin Deng

  • Article
    | Open Access

    Cardiac voltage-gated sodium channels (Nav1.5) are crucial regulators of heart electric activity. Here the authors show that palmitoylation, a process of lipid modification of cysteine residues, modulates Nav1.5 function and affects cardiomyocyte excitability, representing a potential target in treating cardiac diseases.

    • Zifan Pei
    • , Yucheng Xiao
    •  & Theodore R. Cummins

  • Article
    | Open Access

    Cancer cells rely on glutamine to replenish the TCA cycle. Here, the authors show that oncogenic PIK3CAmutations drive this metabolic rewiring in colorectal cancer cells by up-regulating glutamate pyruvate transaminase expression, thus increasing sensitivity to glutamine starvation.

    • Yujun Hao
    • , Yardena Samuels
    •  & Zhenghe Wang

  • Article
    | Open Access

    Males help care for offspring in about 10% of mammal species. Here, West and Capellini perform phylogenetic comparative analyses on a sample of 529 mammal species and find that male care is associated with shorter lactation periods by females, larger litters of offspring, and more frequent breeding events.

    • Hannah E. R. West
    •  & Isabella Capellini

  • Article
    | Open Access

    Mice lacking the tumour suppressor p53 are partially protected from developing diabetes. Here the authors show that p53 is upregulated in the pancreas of diabetic mice where it impairs β cell function by repressing expression of mitochondrial pyruvate carboxylase, thereby inhibiting insulin secretion.

    • Xiaomu Li
    • , Kenneth K. Y. Cheng
    •  & Aimin Xu

  • Article
    | Open Access

    Deficit in transcription factor Tbx1 causes heart defects in humans and mice. Here the authors show that Tbx1 regulates gene expression by recruiting histone methyltransferases that affect chromatin marks, and that a drug inhibiting histone demethylation ameliorates the cardiovascular phenotype in Tbx1 haploinsufficient or hypomorphic mice.

    • Filomena Gabriella Fulcoli
    • , Monica Franzese
    •  & Antonio Baldini

  • Article
    | Open Access

    A fundamental question in evolutionary biology is how complex innovations requiring multiple genetic changes arise. Here the authors provide lines of evidence that changing environments facilitate the adaptive evolution of complex metabolic innovations via stepwise acquisition of single reactions.

    • Balázs Szappanos
    • , Jonathan Fritzemeier
    •  & Balázs Papp

  • Article
    | Open Access

    The posterior signalling centre (PSC) in Drosophilalarva regulates blood cell differentiation but it is unclear how this is controlled. Here, the authors show that Slit/Robo signalling from the vascular system regulates PSC morphology and function, in turn, regulating blood cell differentiation.

    • Ismaël Morin-Poulard
    • , Anurag Sharma
    •  & Michèle Crozatier

  • Article
    | Open Access

    Within species, there tends to be a tight relationship between genital size and body size, suggesting strong stabilizing selection. Here, Booksmythe et al.artificially select relative genital size in mosquitofish and find that novel genital size-body size combinations do not lead to expected fitness reductions.

    • Isobel Booksmythe
    • , Megan L. Head
    •  & Michael D. Jennions

  • 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

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