Physiology articles within Nature Communications

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  • Article
    | Open Access

    Circadian rhythms usually rely on cyclic variations in gene expression. Red blood cells, however, display circadian rhythms while being devoid of nuclear DNA. Here, Henslee and colleagues show that circadian rhythms in isolated human red blood cells are dependent on rhythmic transport of K+ ions.

    • Erin A. Henslee
    • , Priya Crosby
    •  & Fatima H. Labeed

  • Article
    | Open Access

    Patients with diabetic nephropathy suffer from impaired albumin reabsorption by proximal tubular epithelial cells. Here authors use diabetic and transgenic mouse models and in vitro models to show the cause for this lies in the down regulation and internalization of the ion channels, ORAI1-3.

    • Bo Zeng
    • , Gui-Lan Chen
    •  & Shang-Zhong Xu

  • Article
    | Open Access

    Changes in chromatin structure have been linked to organismal ageing. Here the authors show that altered histone expression and mitochondrial stress during C. elegans development result in chromatin changes and a cytosolic stress response that affects organismal longevity, and depends on HSF-1 and the chromatin remodeller, ISW-1.

    • Olli Matilainen
    • , Maroun S. Bou Sleiman
    •  & Johan Auwerx

  • Article
    | Open Access

    Vps34 is a lipid kinase conserved from yeast to humans and involved in in intracellular vesicular trafficking and autophagy. Here Bilanges et al. show that inhibition of this kinase in mice improves glucose tolerance and diet-induced steatosis by modulating mitochondrial respiration and metabolism.

    • Benoit Bilanges
    • , Samira Alliouachene
    •  & Bart Vanhaesebroeck

  • Article
    | Open Access

    Rod photoreceptors are thought to be saturated under bright light. Here, the authors describe the physiological parameters that mediate response saturation of rod photoreceptors in mouse retina, and show that rods can drive visual responses in photopic conditions.

    • Alexandra Tikidji-Hamburyan
    • , Katja Reinhard
    •  & Thomas A. Münch

  • Article
    | Open Access

    KCNQ1 is a voltage-gated potassium channel that is important in cardiac and epithelial function. Here the authors present a mechanism for KCNQ1 activation and inactivation in which voltage sensor activation promotes pore opening more effectively in the intermediate open state than the fully open state, generating inactivation.

    • Panpan Hou
    • , Jodene Eldstrom
    •  & Jianmin Cui

  • Article
    | Open Access

    The arterial wall is subjected to mechanical forces that modulate endothelial cell responses. Here, Mack and colleagues identify a novel role for Notch1 as a mechanosensor in adult arteries, where it ensures junctional integrity through modulation of calcium signalling and limits atherosclerosis.

    • Julia J. Mack
    • , Thiago S. Mosqueiro
    •  & M. Luisa Iruela-Arispe

  • Article
    | Open Access

    Pericytes are essential for the development, maintenance and function of vascular networks. Here, Eilken and colleagues show that expression of the decoy receptor VEGFR1 by pericytes spatially restricts VEGF signalling, thus regulating VEGF-induced endothelial cell sprouting in developing tissues.

    • Hanna M. Eilken
    • , Rodrigo Diéguez-Hurtado
    •  & Ralf H. Adams

  • Article
    | Open Access

    Cell fusion regulates several physiological events, for example, fusion of myoblasts in skeletal muscle formation, but it is unclear if this process occurs in the heart. Here, the authors use transgenic reporters in zebrafish to show transient cardiomyocyte fusion, modulating cardiac development and function.

    • Suphansa Sawamiphak
    • , Zacharias Kontarakis
    •  & Didier Y. R. Stainier

  • Article
    | Open Access

    Taste sensilla are Drosophila sensory organs containing taste neurons, which have differential tuning for bitter compounds. Here, the authors systematically examine what combinations of gustatory receptor genes confer a specific taste response profile in different bitter taste neurons.

    • Ha Yeon Sung
    • , Yong Taek Jeong
    •  & Seok Jun Moon

  • Article
    | Open Access

    The human heart is composed of distinct regions and cell types, but relatively little is known about their specific protein composition. Here, the authors present a region- and cell type-specific proteomic map of the healthy human heart, revealing functional differences and potential cell type markers.

    • Sophia Doll
    • , Martina Dreßen
    •  & Matthias Mann

  • Article
    | Open Access

    The APOE4 allele is the leading risk factor for late-onset Alzheimer’s disease, but how it might contribute to the disease is not clear. Here the authors show that a mouse expressing the human APOE4 allele displays hyperactivity in the entorhinal cortex due to a decreased inhibitory tone, which may in part explain accelerated Alzheimer’s pathology in APOE4 carriers.

    • Tal Nuriel
    • , Sergio L. Angulo
    •  & Karen E. Duff

  • Article
    | Open Access

    Modulation of airway surface liquid pH has been proposed as a therapy for cystic fibrosis, but whether pH is indeed altered in cystic fibrosis is controversial. Here, the authors develop a novel fibre-optic based pH measurement technology, and show that pH is not altered in children with cystic fibrosis.

    • André Schultz
    • , Ramaa Puvvadi
    •  & Stephen M. Stick

  • Article
    | Open Access

    The diet consumed during development can have long-lasting effects on adult physiology. Here, the authors show that developmental undernutrition in Drosophila extends lifespan by inhibiting the production of toxic lipids, called autotoxins, on the adult body surface.

    • M. Irina Stefana
    • , Paul C. Driscoll
    •  & Alex P. Gould

  • Article
    | Open Access

    Dysregulation of insulin secretion dynamics plays a role in diabetes development. Here, the authors build a mathematical model of hepatic insulin signaling and propose a sequential model of post-meal control of glucose and lipids, according to which delayed aPKC suppression would contribute to selective hepatic insulin resistance.

    • Gang Zhao
    • , Dagmar Wirth
    •  & Michael Meyer-Hermann

  • Article
    | Open Access

    AMPK regulates cellular energy balance using its γ subunit as an energy sensor of cellular AMP and ADP to ATP ratios. Here, the authors show that γ2 AMPK activation lowers heart rate by reducing the activity of pacemaker cells, whereas loss of γ2 AMPK increases heart rate and prevents the adaptive bradycardia of endurance training in mice.

    • Arash Yavari
    • , Mohamed Bellahcene
    •  & Houman Ashrafian

  • Article
    | Open Access

    Blood clot contraction is a cellular (patho)physiological process essential for wound healing, hemostasis, and thrombosis. Here, the authors describe the physical structural mechanism by which platelet filopodia pull “hand-over-hand” on fibrin fibers to compact them into bundled agglomerates.

    • Oleg V. Kim
    • , Rustem I. Litvinov
    •  & John W. Weisel

  • Article
    | Open Access

    Atherosclerosis is characterized by subendothelial lipid retention believed to be the result of endothelial trancytosis. Here, the authors show that endothelium can take up and process LDL, generating cholesterol crystals that are deposited on the basolateral side of the cells, causing their dysfunction that can be prevented by forskolin/rolipram treatment.

    • Yvonne Baumer
    • , Sara McCurdy
    •  & William A. Boisvert

  • Article
    | Open Access

    Pompe disease is caused by mutations in lysosomal acid α-glucosidase (GAA) and patients are being treated with recombinant human α-glucosidase (rhGAA). Here the authors present the crystal structures of rhGAA and its complexes with inhibitors and a pharmacological chaperone, which is important for drug development.

    • Véronique Roig-Zamboni
    • , Beatrice Cobucci-Ponzano
    •  & Gerlind Sulzenbacher

  • Article
    | Open Access

    KLF family transcription factors (KLFs) regulate many cellular processes, including proliferation, survival and stress responses. Here, the authors position KLFs as important regulators of autophagy and lifespan in C. elegans, a role that may extend to the modulation of age-associated vascular phenotypes in mammals.

    • Paishiun N. Hsieh
    • , Guangjin Zhou
    •  & Mukesh K. Jain

  • Article
    | Open Access

    Brown and beige adipose tissues dissipate heat via uncoupling protein 1 (UCP1). Here the authors show that the stress activated kinase MKK6 acts as a repressor of UCP1 expression, suggesting that its inhibition promotes adipose tissue browning and increases organismal energy expenditure.

    • Nuria Matesanz
    • , Edgar Bernardo
    •  & Guadalupe Sabio

  • Article
    | Open Access

    Astrocytes are involved in chemoreception in brainstem areas that regulate breathing rhythm, and astrocytes are known to release d-serine. Here the authors show that astrocyte release of d-serine contributes to CO2 sensing and breathing in brainstem slices, and in vivo in awake unrestrained mice.

    • S. Beltrán-Castillo
    • , M. J. Olivares
    •  & J. L. Eugenín

  • Article
    | Open Access

    Opioid receptors are important modulators of nociceptive pain. Here the authors show that opioid receptor activation recruits peroxiredoxin 6 (PRDX6) to the receptor-Gαi complex by c-Jun N-terminal kinase, resulting in Gαi depalmitoylation and enhanced receptor-Gαi association.

    • Selena S. Schattauer
    • , Benjamin B. Land
    •  & Charles Chavkin

  • Article
    | Open Access

    Functions of the embryonic brain prior to regulating behavior are unclear. Here, the authors use an amputation assay in Xenopus laevis to demonstrate that removal of the brain early in development alters muscle and peripheral nerve patterning, which can be rescued by modulating bioelectric signals.

    • Celia Herrera-Rincon
    • , Vaibhav P. Pai
    •  & Michael Levin

  • Article
    | Open Access

    Current approaches to visualise brown adipose tissue (BAT) rely primarily on markers that reflect its metabolic activity. Here, the authors show that PD-L1 is expressed on brown adipocytes, does not change upon BAT activation, and that BAT volume in mice can be measured by PET-CT with a radiolabeled anti-PD-L1 antibody.

    • Jessica R. Ingram
    • , Michael Dougan
    •  & Hidde L. Ploegh

  • Article
    | Open Access

    Clarifying the source of proteins in mixed biological environments, such as after transplantation or parabiosis, remains a challenge. Here, the authors address this need with a mouse strain that incorporates a methionine derivate into proteins, allowing for their detection using click chemistry and antibody arrays.

    • Yan Liu
    • , Michael J. Conboy
    •  & Irina M. Conboy

  • Article
    | Open Access

    Pathological angiogenesis in the retina is a major cause of blindness. Here the authors show that adenosine receptor A2A drives pathological angiogenesis in the oxygen-induced retinopathy mouse model by promoting glycolysis in endothelial cells via the ERK/Akt/HIF-1α pathway, thereby suggesting new therapeutic targets for disease treatment.

    • Zhiping Liu
    • , Siyuan Yan
    •  & Yuqing Huo

  • Article
    | Open Access

    HDAC3 is a critical mediator of hepatic lipid metabolism and its loss leads to fatty liver. Here, the authors characterize the liver HDAC3 interactome in vivo, provide evidence that HDAC3 interacts with PROX1, and show that HDAC3 and PROX1 control expression of genes regulating lipid homeostasis.

    • Sean M. Armour
    • , Jarrett R. Remsberg
    •  & Mitchell A. Lazar

  • Article
    | Open Access

    Axon-glial communication is important for myelination. Here the authors show that during postnatal development in rats, a subpopulation of pre-myelinating oligodendrocytes in the auditory brainstem receive excitatory inputs and can generate Nav 1.2-driven action potentials, and that such process promotes myelination.

    • Emmanuelle Berret
    • , Tara Barron
    •  & Jun Hee Kim

  • Article
    | Open Access

    Caloric restriction has been shown to increase lifespan in mammals. Here, the authors provide evidence that age-related methylation drift correlates with lifespan and that caloric restriction in mice and rhesus monkeys results in attenuation of age-related methylation drift.

    • Shinji Maegawa
    • , Yue Lu
    •  & Jean-Pierre J. Issa

  • Article
    | Open Access

    A major drawback in the clinical use of the oral anticoagulants that directly inhibit factor Xa in order to prevent blood clot formation is the potential for life threatening bleeding events. Here the authors describe factor Xa variants that are refractory to inhibition by these anticoagulants and could serve as rescue agents in treated patients.

    • Daniël Verhoef
    • , Koen M. Visscher
    •  & Mettine H. A. Bos

  • Article
    | Open Access

    The misalignment between internal circadian rhythm and the day-night cycle can be caused by genetic, behavioural and environmental factors, and may have a profound impact on human physiology. Here West et al. show that desynchrony between the internal clock and the external environment alter metabolic parameters and cardiac function in mice.

    • Alexander C. West
    • , Laura Smith
    •  & David A. Bechtold

  • Article
    | Open Access

    The mechanistic link between metabolic stress and associated cardiomyopathy is unknown. Here the authors show that high fat diet causes calpain-1-dependent degradation of ERK5 leading to mitochondrial dysfunction, suggesting the maintenance of cardiac ERK5 as a therapeutic approach for cardiomyopathy prevention and/or treatment.

    • Wei Liu
    • , Andrea Ruiz-Velasco
    •  & Xin Wang

  • Article
    | Open Access

    Islet transplantation is considered one of the potential treatments for T1DM but limited islet survival and their impaired function pose limitations to this approach. Here Loh et al. show that the Y1 receptor is expressed in β- cells and inhibition of its signalling, both genetic and pharmacological, improves mouse and human islet function.

    • Kim Loh
    • , Yan-Chuan Shi
    •  & Herbert Herzog

  • Article
    | Open Access

    The hypothalamic-pituitary-thyroid (HPT) axis regulates a wide range of physiological processes. Here the authors show that hypothalamic tanycytes play a role in the homeostatic regulation of the HPT axis; activation of TRH signaling in tanycytes elevates their intracellular Ca2+ via Gαq/11 pathway, ultimately resulting in reduced TRH release into the pituitary vessels.

    • Helge Müller-Fielitz
    • , Marcus Stahr
    •  & Markus Schwaninger

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