Physiology articles within Nature Communications

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  • Article
    | Open Access

    Pancreatic islets are composed of alpha-, beta-, as well as delta-cells and appropriate regulation of glucose homeostasis relies on auto- and paracrine cellular communication. Here, the authors study the role of delta-cell filopodia in this context by employing optogenetic and calcium imaging approaches.

    • Rafael Arrojo e Drigo
    • , Stefan Jacob
    •  & Per-Olof Berggren

  • Article
    | Open Access

    Adolescent idiopathic scoliosis (AIS) is a common pediatric disease leading to spinal deformities. Here, the authors report GWAS followed by genome-wide meta-analysis in up to 79,211 Japanese individuals, identifying 20 genetic loci for AIS, 14 of which were previously unreported, and perform in vitro validation for rs1978060.

    • Ikuyo Kou
    • , Nao Otomo
    •  & Shiro Ikegawa

  • Article
    | Open Access

    Genome-wide association studies have only revealed a handful of genetic loci for longevity. Here, in a case–control design based on phenotype definitions of individuals surviving at or beyond the age corresponding to the 90th and 99th survival percentile, the authors report two additional loci located in the APOE locus and near GPR78.

    • Joris Deelen
    • , Daniel S. Evans
    •  & Joanne M. Murabito

  • Article
    | Open Access

    Levels of sodium and potassium in urine are associated with cardiovascular traits. Here, Pazoki et al. perform genome-wide association studies for urinary sodium and potassium secretion and identify 50 and 13 novel loci, respectively, some of which show a potential causal relationship with blood pressure based on MR analysis.

    • Raha Pazoki
    • , Evangelos Evangelou
    •  & Abbas Dehghan

  • Article
    | Open Access

    The glomerular filtration barrier is a complex structure in charge of renal ultrafiltration. Here the authors present a glomerulus-on-a-chip for disease modelling and high-throughput drug screening where human podocytes and human glomerular endothelial cells are separated by an extracellular matrix resembling the in vivo basement membrane.

    • Astgik Petrosyan
    • , Paolo Cravedi
    •  & Stefano Da Sacco

  • Article
    | Open Access

    Insulin replacement is a valuable therapy for insulin deficiency, however, other therapies are being investigated to restore metabolic homeostasis. Here, the authors identify S100A9 as a leptin induced circulating cue that improves glucose and lipid homeostasis and extends survival in insulin deficient mice.

    • Giorgio Ramadori
    • , Sanda Ljubicic
    •  & Roberto Coppari

  • Article
    | Open Access

    Individuals carrying a gain-of-function mutation in PKG1 develop thoracic aortic aneurysms and dissections. Here Schwaerzer et al. show that mice carrying the same mutation recapitulate the human disease, and find that treatment with anti-oxidants including cobinamide, a vitamin B12 analog, prevents disease progression.

    • Gerburg K. Schwaerzer
    • , Hema Kalyanaraman
    •  & Renate B. Pilz

  • Article
    | Open Access

    The circadian clock regulates rhythms of behavior and physiology and the timing of circadian rhythms in liver is influenced by food intake. Here, the authors identify the hepatokine Angptl8 as a mediator of liver clock food entrainment.

    • Siyu Chen
    • , Mengyang Feng
    •  & Chang Liu

  • Article
    | Open Access

    Atherosclerosis results from the accumulation of lipoproteins in the vascular wall. Here, Thierer et al. report the design of a chemiluminescent reporter for atherogenic lipoproteins using fusion of apolipoprotein-B to a luciferase enzyme, and find it bears potential for the identification of regulators of lipoprotein metabolism in vivo.

    • James H. Thierer
    • , Stephen C. Ekker
    •  & Steven A. Farber

  • Article
    | Open Access

    Diabetes is associated with decreased PI3K activation in skeletal muscle. Here, the authors show that p110a is the predominant PI3K subunit in muscle, and show that its ablation in muscle, but not ablation of p110beta, leads to insulin resistance, increased proteosomal and autophagic activity, and altered mitochondria homeostasis in mice.

    • Mengyao Ella Li
    • , Hans P. M. M. Lauritzen
    •  & C. Ronald Kahn

  • Article
    | Open Access

    Rapamycin extends lifespan in model organisms by targeting mTORC1, but exerts off-target side effects via inhibition of mTORC2. Here, the authors report the identification of a selective mTORC1 inhibitor, and show that it inhibits mTORC1 activity both in vitro and in vivo, with reduced side effects on glucose homeostasis, lipid metabolism, and the immune system.

    • Katherine H. Schreiber
    • , Sebastian I. Arriola Apelo
    •  & Dudley W. Lamming

  • Article
    | Open Access

    Glycoprotein ZP1 is a component of the oocyte’s zona pellucida (ZP), and mutations in human ZP1 are linked to female infertility. Here, using structure-function analysis, the authors suggest that filament cross-linking by ZP1 is required to form a stable ZP in human, and infertility mutations interfere with cross-linking.

    • Kaoru Nishimura
    • , Elisa Dioguardi
    •  & Luca Jovine

  • Article
    | Open Access

    Epigenetic differences in nasal epithelium have been proposed as a biomarker for lower airway disease and asthma. Here, in epigenome-wide association studies for asthma and other airway traits using nasal swabs, the authors identify differentially methylated CpGs that highlight genes involved in TH2 response.

    • Andres Cardenas
    • , Joanne E. Sordillo
    •  & Diane R. Gold

  • Article
    | Open Access

    Spinal CPGs transmit movement commands through rhythmic synaptic drive onto the spinal premotor network. Here, the authors use paired recordings to demonstrate that spinal neurons have decorrelated synaptic activity suggesting a CPG network with sparse convergent connectivity.

    • Marija Radosevic
    • , Alex Willumsen
    •  & Rune W. Berg

  • Article
    | Open Access

    The sinus node generates rhythmic heartbeat but the molecular basis of pacemaking is still under debate. Here, the authors combine quantitative proteomics and single-nucleus transcriptomics to characterize the molecular composition of the sinus node and provide insights into the underpinnings of pacemaking.

    • Nora Linscheid
    • , Sunil Jit R. J. Logantha
    •  & Alicia Lundby

  • Article
    | Open Access

    Pericytes are perivascular cells essential for blood-brain barrier maintenance. Here Diéguez-Hurtado et al. show that depletion of the transcription factor RBPJ in pericytes affects their molecular identity and disturbs endothelial cell behaviour, inducing the formation of vascular lesions in the brain.

    • Rodrigo Diéguez-Hurtado
    • , Katsuhiro Kato
    •  & Ralf H. Adams

  • Article
    | Open Access

    In neonatal testes, prospermatogonia generate both spermatogonia for the first wave of spermatogenesis and spermatogonial stem cells (SSCs) for maintenance of spermatogenesis in males. Here the authors characterize the development of mouse SSCs from prospermatogonia using single-cell RNA-seq and transplantation assays.

    • Nathan C. Law
    • , Melissa J. Oatley
    •  & Jon M. Oatley

  • Article
    | Open Access

    Cerebral cavernous malformation is a vascular disease characterized by capillary-venous cavernomas in the central nervous system. Here the authors show that cavernomas display benign tumor characteristics and originate from the clonal expansion of mutated endothelial progenitors which can attract surrounding wild-type cells, inducing their mesenchymal transition and leading to growth of the cavernoma.

    • Matteo Malinverno
    • , Claudio Maderna
    •  & Elisabetta Dejana

  • Article
    | Open Access

    Sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b) is a lipid raft enzyme known to affect membrane lipid composition. Here, Mitrofanova et al. show that increased expression of SMPDL3b in diabetes impairs insulin signaling and ceramide-1-phosphate (C1P) availability in podocytes, and that C1P supplementation protects mice from diabetic kidney disease.

    • A. Mitrofanova
    • , S. K. Mallela
    •  & A. Fornoni

  • Article
    | Open Access

    Men and women differ in their risk of developing coronary artery disease, in part due to differences in their levels of sex hormones. Here, AlSiraj et al. show that the XX sex genotype regulates lipid metabolism and promotes atherosclerosis independently of sex hormones in mice.

    • Yasir AlSiraj
    • , Xuqi Chen
    •  & Lisa A. Cassis

  • Article
    | Open Access

    Muscle loss is associated with altered expression of proteins involved in mitochondrial homeostasis, but whether this is causative remains unclear. Here, the authors show that genetic ablation of the pro-fission protein DRP1 leads to accumulation of abnormal mitochondria that induce muscle atrophy by altering Ca2+ homeostasis and cellular stress responses.

    • Giulia Favaro
    • , Vanina Romanello
    •  & Marco Sandri

  • Article
    | Open Access

    In human adipose tissue (AT), adipocytes are organized into units of lobules. Here the authors identify distinct fibrous septal and stromal compartments within AT lobules that differ in composition and potential between subcutaneous and visceral regions and are disturbed in obesity and metabolic syndrome.

    • D. Estève
    • , N. Boulet
    •  & J. Galitzky

  • Article
    | Open Access

    Hypothalamus is implicated in memory disorders but the neural mechanisms are unknown. Here, the authors report that MCH expressing hypothalamic neurons respond to novel object exposure, are inhibited by local GAD65 expressing neurons and these local circuit interactions are causally involved in object memory formation.

    • Christin Kosse
    •  & Denis Burdakov

  • Article
    | Open Access

    Pancreatic beta-cell glucose metabolism is coupled to insulin secretion. Here the authors set out to characterize changes in beta-cell metabolism in hyperglycemia which may contribute to insufficient insulin secretion in type 2 diabetes and, using a multi-omics approach, find that mitochondrial metabolism is perturbed.

    • Elizabeth Haythorne
    • , Maria Rohm
    •  & Frances M. Ashcroft

  • Article
    | Open Access

    Microbiota impacts all major aspects of physiology, but little is known about its effects on age-related changes in immune responses. Here the authors show that gut microbiota transfer between adult and old mice increases local but not systemic germinal centre responses regardless of age directionality.

    • Marisa Stebegg
    • , Alyssa Silva-Cayetano
    •  & Michelle A. Linterman

  • Article
    | Open Access

    Senescent cells increase with ageing and may cause inflammatory conditions, but how this accumulation is mediated is still unclear. Here the authors show that senescent cells express HLA-E to suppress NKG2A-mediated natural killer and CD8 T cell activation to avoid targeted elimination, while blocking NKG2A helps promote immunity against senescent cells.

    • Branca I. Pereira
    • , Oliver P. Devine
    •  & Arne N. Akbar

  • Article
    | Open Access

    Fibroadipogenic precursor cells (FAPs) contribute to fibrosis and adipogenic replacement in muscular dystrophies. Here, the authors show that FAPs contribute to adipogenic loss in mouse models of limb girdle muscular dystrophy 2B via a mechanism dependent on expression of Annexin A2, and that this process can be prevented by its pharmacologic inhibition in mice.

    • Marshall W. Hogarth
    • , Aurelia Defour
    •  & Jyoti K. Jaiswal

  • Article
    | Open Access

    Different sensory experiences can affect longevity in Drosophila. Here the authors find that exposure of Drosophila directly to dead conspecifics affects longevity via a serotonergic mechanism, and that Drosophila exposed to dead conspecifics also become an aversive stimulus to naïve choosers.

    • Tuhin S. Chakraborty
    • , Christi M. Gendron
    •  & Scott D. Pletcher

  • Article
    | Open Access

    Episodic memory retrieval is hypothesized to rely on hippocampal reinstatement of item-context associations which drives reinstatement of item information in cortex. Here, the authors confirm this sequence of events, using iEEG recordings from the human hippocampus and lateral temporal cortex.

    • D. Pacheco Estefan
    • , M. Sánchez-Fibla
    •  & P. F. M. J. Verschure

  • Article
    | Open Access

    Post-translational protein modifications can affect lifespan and aging but age-dependent ubiquitylation changes have not yet been systematically characterized. Here, the authors analyze age-related proteome and ubiquitylome dynamics in Drosophila and identify increasing H2A ubiquitylation as a conserved aging marker.

    • Lu Yang
    • , Zaijun Ma
    •  & Yaoyang Zhang

  • Article
    | Open Access

    The red nucleus (RN) is a midbrain nucleus known to be involved in the fine control of limb movements, but its role in motor learning is unclear. Here, the authors identified a neuronal population within the red nucleus, co-expressing Vglut2, PV and C1Ql2, which undergoes training-dependent plasticity.

    • Giorgio Rizzi
    • , Mustafa Coban
    •  & Kelly R. Tan

  • Article
    | Open Access

    Mitochondrial uncoupling is a treatment strategy for metabolic diseases that reduces the efficiency of mitochondrial oxidative phosphorylation and ATP generation. Here the authors characterize the pharmacokinetic and therapeutic properties of the liver-localized mitochondrial uncoupler OPC-163493, which leads to amelioration of diabetes and hypertension in several rodent disease models.

    • Naohide Kanemoto
    • , Takashi Okamoto
    •  & Seiji Sato

  • Review Article
    | Open Access

    Immune cells adapt distinct metabolic strategies to accommodate specific functions associated with cell types or differentiation stages. Here in this review the authors discuss the nutrients, sensors, and mediators of such a metabolic adaption in nutrient-limiting immune microenvironments such as tumors or infections.

    • Nidhi Kedia-Mehta
    •  & David K. Finlay

  • Article
    | Open Access

    Endothelial cell regeneration is essential for blood vessels to recover from inflammation-induced injury. Here Liu et al. show that the transcription factor Sox17 is required for endothelial regeneration following endotoxemia, and that delivery of a transgene expressing Sox17 to lung endothelial cells enhances recovery after injury.

    • Menglin Liu
    • , Lianghui Zhang
    •  & Asrar B. Malik

  • Article
    | Open Access

    The mechanisms by which organisms adapt their growth according to the availability of oxygen are incompletely understood. Here the authors identify the Drosophila fat body as a tissue regulating growth in response to oxygen sensing via a mechanism involving Hph inhibition, HIF1-a activation and insulin secretion.

    • Michael J. Texada
    • , Anne F. Jørgensen
    •  & Kim F. Rewitz

  • Article
    | Open Access

    The use of nonsteroidal anti-inflammatory drugs inhibiting COX-1/2 is associated with an increased risk of heart failure. Here the authors show that mPGES-1, a therapeutic target downstream of COX enzymes, protects from cardiac ischemia/reperfusion injury, limiting leukocyte-endothelial interactions and preserving microvascular perfusion partly via the endothelial EP4 receptor.

    • Liyuan Zhu
    • , Chuansheng Xu
    •  & Miao Wang

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