Physiology articles within Nature Communications

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  • Article
    | Open Access

    The polyol pathway, which converts glucose into sorbitol and fructose, is active in chronic conditions like hepatic steatosis and chronic kidney disease. Here, Andres-Hernandoet al. show that fructose production promotes renal injury and fructokinase inhibition protects against kidney damage during ischaemic acute kidney disease.

    • Ana Andres-Hernando
    • , Nanxing Li
    •  & Miguel A. Lanaspa

  • Article
    | Open Access

    Heavy-load eccentric exercise causes an increase in cytoplasmic Ca2+ that can damage muscles. Here the authors show that the t-tubule system remodels into vacuoles that can sequester calcium from the cytoplasm and are not responsive to store-operated Ca2+ entry, thereby potentially protecting muscles against elevated [Ca2+].

    • Tanya R. Cully
    • , Robyn M. Murphy
    •  & Bradley S. Launikonis

  • Article
    | Open Access

    Frontal eye fields (FEF) and anterior cingulate cortex (ACC) are coactivated during cognitive tasks, but the precise format of their interaction is not known. Here the authors show that phase coupling between ACC -FEF in theta and beta frequency bands better predicts behavioural performance.

    • Sahand Babapoor-Farrokhran
    • , Martin Vinck
    •  & Stefan Everling

  • Article
    | Open Access

    G Protein-Coupled Receptors (GPCRs) can adopt different conformations, each linked to distinct cellular outcomes. Here the authors show that compound 17b, a novel agonist of the GPCR family member FPR, robustly activates cardioprotective but not detrimental FPR signalling, showing beneficial therapeutic effect in a mouse model of cardiac infarction.

    • Cheng Xue Qin
    • , Lauren T. May
    •  & Rebecca H. Ritchie

  • Article
    | Open Access

    The kinase FAK is important for integrin signalling and promotes cell survival. Here, the authors demonstrate FAK regulates adipocyte survival, and is particularly important for maintaining insulin sensitivity during adipose tissue expansion in the context of a calorie-rich diet.

    • Cynthia T. Luk
    • , Sally Yu Shi
    •  & Minna Woo

  • Article
    | Open Access

    Brown adipose tissue (BAT) takes up and burns fatty acids for thermogenesis in mice. Here the authors use PET to show that, in humans, cold stimulation increases BAT dietary fatty acid uptake from plasma and oxidative metabolism, although, unlike mice, human BAT takes up less fatty acids than other metabolic tissues.

    • Denis P. Blondin
    • , Hans C. Tingelstad
    •  & André C. Carpentier

  • Article
    | Open Access

    Breast cancer amplified sequence 2 (BCAS2) is involved in pre-mRNA splicing but its physiological role is unclear. Here, the authors find BCAS2 enriched in mice spermatogonia in the testes, and BCAS2 deletion in germ cells alters alternative splicing of spermatogenesis-related genes, causing male infertility.

    • Wenbo Liu
    • , Fengchao Wang
    •  & Lei Li

  • Article
    | Open Access

    Caloric restriction (CR) delays ageing of model organisms, but whether it works in nonhuman primates has been controversial. Here, the authors pool and reanalyse data from two long-running CR primate studies, concluding that moderate CR indeed improves health and survival of rhesus monkeys.

    • Julie A. Mattison
    • , Ricki J. Colman
    •  & Rozalyn M. Anderson

  • Article
    | Open Access

    T cells contribute to development of high blood pressure but their role in salt-sensitive hypertension is less clear. Liuet al. show that CD8+ T cells upregulate and activate Na-Cl co-transporter NCC in distal convoluted tubules via direct cell-cell contact and ROS-Src activation, leading to Na+retention and salt-sensitive hypertension.

    • Yunmeng Liu
    • , Tonya M. Rafferty
    •  & Shengyu Mu

  • Article
    | Open Access

    Global warming is expected to lead to shifts in species' geographic ranges to track preferred temperatures. Here, the authors show that populations of the common periwinkle vary in their sensitivity to ocean acidification, another major global change driver, which could further restrict range shifts caused by warming.

    • Piero Calosi
    • , Sedercor Melatunan
    •  & Simon D. Rundle

  • Article
    | Open Access

    Mammalian eggs release cortical granules to avoid being fertilized by more than a single sperm as polyspermy results in nonviable embryos. Here, the authors describe the mechanism driving translocation of the granules to the cortex in the mouse egg and show this process is essential to prevent polyspermy.

    • Liam P. Cheeseman
    • , Jérôme Boulanger
    •  & Melina Schuh

  • Article
    | Open Access

    Here, the authors combinein vivopatch-clamp recordings and optogenetics to show that balanced dendritic excitation and inhibition provides a sensitive ‘push-pull’ mechanism that generates the bidirectional modulation of Purkinje cell SSp output necessary for normal locomotor behaviour.

    • Marta Jelitai
    • , Paolo Puggioni
    •  & Ian Duguid

  • Article
    | Open Access

    Part of understanding ageing involves knowing how the brain’s connecting pathways change in healthy aging. Here, authors provide a detailed characterisation of data from 3513 UK Biobank participants, and show that the microstructure of these pathways becomes more similar with age.

    • Simon R. Cox
    • , Stuart J. Ritchie
    •  & Ian J. Deary

  • Article
    | Open Access

    Bone development and vascularization are coupled events that share many molecular mechanisms. Here the authors identify osteoblast-secreted Cxcl9 as an inhibitory regulator of angiogenesis and osteogenesis, and show that mTORC1 signaling and STAT1 are critical upstream mediators of the cytokine expression.

    • Bin Huang
    • , Wenhao Wang
    •  & Xiaochun Bai

  • Article
    | Open Access

    Feeding control requires the integration and coordination of motivational, sensory and motor circuits in the brain. Here, the authors discover a set of neurons that regulate feeding inDrosophilaby promoting insulin release, and whose activity reflects physiological hunger and satiety states of flies.

    • Yin Peng Zhan
    • , Li Liu
    •  & Yan Zhu

  • Article
    | Open Access

    Formation of new blood vessels and bone is coupled. Here the authors show that blood flow represents a key regulator of angiogenesis and endothelial Notch signalling in the bone, and that reactivation of Notch signalling in the endothelium of aged mice rejuvenates the bone.

    • Saravana K. Ramasamy
    • , Anjali P. Kusumbe
    •  & Ralf H. Adams

  • Article
    | Open Access

    The water channel AQP2 mediates the concentration of urine in the kidney. Here Ando et al. show that Wnt5 promotes collecting duct permeability by regulating AQP2 expression and localization through activation of the calmodulin/calcineurin signalling pathway.

    • Fumiaki Ando
    • , Eisei Sohara
    •  & Shinichi Uchida

  • Article
    | Open Access

    Diabetes is characterized by prolonged hyperglycaemia and tissue damage in pancreatic islets. Here, Brereton et al. show that chronic high glucose levels lead to glycogen accumulation in β-cells, associated with reduced autophagy, impaired metabolism, insulin granule depletion and apoptosis.

    • Melissa F. Brereton
    • , Maria Rohm
    •  & Frances M. Ashcroft

  • Article
    | Open Access

    Robo4 is a transmembrane protein that regulates vascular permeability. Zhang et al. now reveal the mechanism of Robo4 action and show that Robo4 and UncB are required for VEGF-mediated regulation of vascular barrier by suppressing VEGF-induced phosphorylation of its receptor Vegfr2 on Y949.

    • Feng Zhang
    • , Claudia Prahst
    •  & Anne Eichmann

  • Article
    | Open Access

    Ventricular arrhythmia is a leading cause of death in patients with diabetes. Here the authors show that inflammasome activation and ILK-1β production in cardiac macrophages cause arrhythmia in diabetic mice, which can be successfully treated using agonists to IL-1β receptor or NLRP3 inhibitors.

    • Gustavo Monnerat
    • , Micaela L. Alarcón
    •  & Emiliano Medei

  • Article
    | Open Access

    Glycine sensing in the dorsal vagal complex (DVC) regulates hepatic glucose production in rodents. Here the authors show that pharmacological and molecular inhibition of glycine reuptake in the DVC potentiates NMDA receptors, and improves metabolic homeostasis in animal models of obesity and diabetes.

    • Jessica T. Y. Yue
    • , Mona A. Abraham
    •  & Tony K. T. Lam

  • Article
    | Open Access

    Joining the circulatory system of an old with a young animal has been shown to rejuvenate old tissues. Here the authors describe a comparatively simple blood infusion system that allows for the controlled exchange of blood between two animals, and study the effects of a single exchange on various tissues.

    • Justin Rebo
    • , Melod Mehdipour
    •  & Irina M. Conboy

  • Article
    | Open Access

    GPR120 is a G-protein-coupled receptor that binds polyunsaturated fatty acids. Here, the authors show that GPR120 is upregulated in brown fat in cold-exposed mice, and mediates thermogenic activation of brown fat via a mechanism that, at least in part, depends on the release of the adipokine FGF21.

    • Tania Quesada-López
    • , Rubén Cereijo
    •  & Francesc Villarroya

  • Article
    | Open Access

    Interaction between platelets and neutrophils promotes neutrophil activation. Here the authors show that neutrophils initiate the cross-talk with platelets by shuttling arachidonic acid via extracellular vesicles, which platelets convert to thromboxane A2that then elicits neutrophil activation.

    • Jan Rossaint
    • , Katharina Kühne
    •  & Alexander Zarbock

  • Article
    | Open Access

    Mice deficient in the pro-inflammatory cytokine IFNγ have improved glucose tolerance. Here, the authors show that this effect depends on the gut microbeAkkermansia muciniphila, whose abundance increases in the absence IFNγ, and which is known to have beneficial effects on host metabolism.

    • Renee L. Greer
    • , Xiaoxi Dong
    •  & Natalia Shulzhenko

  • Article
    | Open Access

    The stress-reducing effects of social bonds have been hypothesized to accrue either during stressful events or across daily affiliations. Here, Wittiget al. show that the presence of social partners reduces levels of stress hormones in wild chimpanzees beyond stressful contexts, supporting the latter hypothesis.

    • Roman M. Wittig
    • , Catherine Crockford
    •  & Klaus Zuberbühler

  • Article
    | Open Access

    The avian auditory papilla has many similarities to the mammalian cochlea but whether force generation by hair cells amplifies the travelling wave, as it does in mammals, remains unknown. Here the authors show that the chicken basilar papilla does not have a ‘cochlear amplifier’ and that sharp frequency tuning does not derive from mechanical vibrations.

    • Anping Xia
    • , Xiaofang Liu
    •  & John S. Oghalai

  • Article
    | Open Access

    Recent data suggest that muscle contraction is regulated by thick filament mechano-sensing in addition to the well-known thin filament-mediated calcium signalling pathway. Here the authors provide direct evidence that myosin activation in skeletal muscle is controlled by thick filament stress independently of calcium.

    • L. Fusi
    • , E. Brunello
    •  & M. Irving

  • Article
    | Open Access

    The stroke volume of the heart increases in response to an increase in the blood volume filling the heart. Here the authors reveal that this coordinated process is mediated in part by oxidative activation of the protein kinase G Iα, which phosphorylates phospholamban to enhance diastolic relaxation in mice.

    • Jenna Scotcher
    • , Oleksandra Prysyazhna
    •  & Philip Eaton

  • Article
    | Open Access

    Restoring lost excitability of injured tissue is a paramount of regenerative medicine. By using a combined expression of bacterial voltage-gated Na+ channel, Kir2.1, and connexin-43 in non-excitable human fibroblasts, here the authors generate excitable cells that rescue action potential conduction in an in vitromodel of cardiac fibrosis.

    • Hung X. Nguyen
    • , Robert D. Kirkton
    •  & Nenad Bursac

  • Article
    | Open Access

    Raising cellular levels of the metabolic cofactor NAD+ reverses key indicators of aging. Here, Ratajczak et al. show that cellular levels of NAD+ depend on the extracellular catalytic activity of NRK1, which processes two NAD+precursors, nicotinamide mononucleotide and nicotinamide riboside, in mice.

    • Joanna Ratajczak
    • , Magali Joffraud
    •  & Carles Cantó

  • Article
    | Open Access

    Bmal1 is a key transcription factor that controls rhythmicity of diverse biological functions. Here, Pan et al. show that Bmal1 deficiency in mice increases lipoprotein secretion and reduces cholesterol excretion to bile, and decipher the molecular mechanisms underlying hyperlipidaemia and atherosclerosis promoted by the lack of Bmal1.

    • Xiaoyue Pan
    • , Christopher A. Bradfield
    •  & M. Mahmood Hussain

  • Article
    | Open Access

    NAD+ is an important coenzyme that mediates cellular metabolism and defends against stresses due to age and overnutrition. Here the authors demonstrate unique bioavailability of the NAD+ precursor vitamin nicotinamide riboside (NR) in mice and humans, and show that NR safely elevates human NAD+.

    • Samuel A. J. Trammell
    • , Mark S. Schmidt
    •  & Charles Brenner

  • Article
    | Open Access

    How both BMP and Wnt signalling pathways regulate lineage specification early in development is unclear. Here, the authors show that endoglin via Jdp2, an AP-1 family member, modulates BMP and Wnt signalling to commit mesodermal progenitors to a haematopoietic fate at the expense of the cardiac lineage.

    • June Baik
    • , Alessandro Magli
    •  & Rita C. R. Perlingeiro

  • Article
    | Open Access

    Obesity is associated with higher breast cancer risk and poor prognosis. Here, the authors show that obesity promotes breast cancer through the recruitment of macrophages with activated NLRC4 inflammasome, which activate IL-1β production, resulting in VEGFA expression in adipocytes and angiogenesis.

    • Ryan Kolb
    • , Liem Phan
    •  & Weizhou Zhang

  • Article
    | Open Access

    Type 2 diabetes and obesity are associated with increased hepatic gluconeogenesis and lipogenesis, known as selective insulin resistance. Here Kubota et al. explain selective insulin resistance in the liver with the zonal distribution and selective insulin-mediated regulation of Irs1 and Irs2.

    • Naoto Kubota
    • , Tetsuya Kubota
    •  & Takashi Kadowaki

  • Article
    | Open Access

    Identification of non-coding variants has outstripped our ability to annotate and interpret them. Dickel et al. present a compendium of over 80,000 putative human heart enhancers and demonstrate that two conserved enhancers are required for proper cardiac function in mice.

    • Diane E. Dickel
    • , Iros Barozzi
    •  & Len A. Pennacchio

  • Article
    | Open Access

    Hypothalamic melanocortin-4-receptors (MC4R) regulate food preference in rodents, but their role in humans is unclear. Here, the authors perform food preference and liking tests in humans with MC4R mutations and find that they prefer fatty food more, but sweet food less, than people without MC4R mutations.

    • Agatha A. van der Klaauw
    • , Julia M. Keogh
    •  & I. Sadaf Farooqi

  • Article
    | Open Access

    Fever is a defence mechanism against infection, but it may also cause abnormal heart rhythm viaunknown mechanism. Here the authors identify FHF2 protein as a key regulator of myocardial excitability that protects the heart against conduction failure in response to an increase in body temperature.

    • David S. Park
    • , Akshay Shekhar
    •  & Glenn I. Fishman

  • Article
    | Open Access

    Immune system participates in the development of high blood pressure. Here the authors show that cholinergic-sympathetic pathway mediated by the α7nAChR receptor and the activation of splenic T cells prime immunity during hypertension and that selective splenic denervation protects against the onset of hypertension in mice.

    • Daniela Carnevale
    • , Marialuisa Perrotta
    •  & Giuseppe Lembo

  • Article
    | Open Access

    The platelets detect and respond to shear stress generated by blood flow. Here the authors show that the binding of the soluble von Willebrand factor to its receptor GPIba under physiological shear stress induces receptor's domain unfolding on the platelet and signalling into the platelet, leading to platelets clearance.

    • Wei Deng
    • , Yan Xu
    •  & Renhao Li

  • Article
    | Open Access

    FHFs are known to regulate voltage-gated sodium channels (NaVs). Here, the authors compare the role of FHFs in cerebellar granule cell propagation, and find NaVs in the distal axon function independently of FHFs, allowing for faster inactivation rates and reducing energy demands during repetitive spiking.

    • Katarzyna Dover
    • , Christopher Marra
    •  & Mitchell Goldfarb

  • 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

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