Physiology articles within Nature Communications

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  • Article
    | Open Access

    The transcription factor DAF-16/FOXO is a downstream effector of insulin/insulin-like growth factor signaling and plays an important role in stress resistance and longevity. Here, the authors show that DAF-16/FOXO can form a complex with HLH-30/TFEB to synergistically regulate transcription of target genes in response to certain stress stimuli.

    • Xin-Xuan Lin
    • , Ilke Sen
    •  & Christian G. Riedel

  • Article
    | Open Access

    Tobacco smoking and cold exposure are environmental modulators of human energy metabolism suppressing appetite and increasing energy expenditure, respectively. Here, the authors develop a novel pharmacological strategy in which they simultaneously mimic the metabolic benefits of both phenomena through small-molecule combination therapy, and show that this treatment improves metabolic health of obese mice.

    • Christoffer Clemmensen
    • , Sigrid Jall
    •  & Matthias H. Tschöp

  • Article
    | Open Access

    The cardiac autonomic nervous system produces various neuropeptides, such as neurokinin substance-P (Sub-P), whose function remains largely unclear. Here, authors show that Sub-P causes a receptor-mediated prolongation of the atrial action potential through a reduced background potassium current, and prevents atrial fibrillation.

    • Marieke W. Veldkamp
    • , Guillaume S. C. Geuzebroek
    •  & Ruben Coronel

  • Article
    | Open Access

    Ischemic reperfusion or nutrient deprivation that produces reactive oxygen species can lead to a loss of muscle contractile function. Here the authors show that glutathionylation of the lysine methyltransferase SMYD2 contributes to degradation or disassembly of sarcomeres.

    • Dhanushka N. P. Munkanatta Godage
    • , Garrett C. VanHecke
    •  & Young-Hoon Ahn

  • Article
    | Open Access

    Common genetic variants in structural proteins contribute to risk of atrial fibrillation (AF). Here, using whole-exome sequencing, the authors identify rare truncating variants in TTN that associate with familial and early-onset AF and show defects in cardiac sarcomere assembly in ttn.2-mutant zebrafish.

    • Gustav Ahlberg
    • , Lena Refsgaard
    •  & Morten S. Olesen

  • Article
    | Open Access

    Reactive oxygen species (ROS) and hypoxia-inducible factors (HIF) mediate regeneration but how is unclear. Here, the authors use an optic-based probe (‘optrode’) to monitor oxygen (O2) during Xenopus tail regeneration, identifying crosstalk between O2 influx, ROS production, and HIF-1α stabilization.

    • Fernando Ferreira
    • , VijayKrishna Raghunathan
    •  & Min Zhao

  • Article
    | Open Access

    Elevated serum urate levels are a risk factor for gout. Here, Tin et al. perform whole-exome sequencing in 19,517 individuals and detect low-frequency genetic variants in urate transporter genes, SLC22A12 and SLC2A9, associated with serum urate levels and confirm their damaging nature in vitro and in silico.

    • Adrienne Tin
    • , Yong Li
    •  & Anna Köttgen

  • Article
    | Open Access

    Transient receptor potential mucolipin 1 (TRPML1) is a lysosomal channel which maintains the low pH and calcium levels for lysosomal function. Here authors use structural biology and electrophysiology to show how lipids bind and allosterically activate TRPML1.

    • Michael Fine
    • , Philip Schmiege
    •  & Xiaochun Li

  • Article
    | Open Access

    The onset of mammalian puberty is sensitive to metabolic changes and nutritional status, but the mechanisms underlying this phenomenon are poorly understood. Here the authors show that the epigenetic regulator of transcription, SIRT1, mediates the effects of under and overnutrition on pubertal timing by controlling the expression of Kiss1 in hypothalamic neurons.

    • M. J. Vazquez
    • , C. A. Toro
    •  & M. Tena-Sempere

  • Article
    | Open Access

    Mitochondrial protein synthesis requires charging a mitochondrial tRNA with its amino acid. Here, the authors describe pathogenic variants in the GatCAB protein complex genes required for the generation of glutaminyl-mt-tRNAGln, that impairs mitochondrial translation and presents with cardiomyopathy.

    • Marisa W. Friederich
    • , Sharita Timal
    •  & Johan L. K. Van Hove

  • Article
    | Open Access

    Inhibitory interneurons play important roles in brain circuits and in several neuropsychiatric disorders. Here, the authors show that excitatory synapses onto interneurons vs. excitatory neurons differ in their ambient synaptic glutamate level, a finding with important implications for selective pharmacological targeting of inhibitory neuron NMDA receptors.

    • Lulu Yao
    • , Teddy Grand
    •  & Qiang Zhou

  • Article
    | Open Access

    Metabolic reprogramming of smooth muscle cells (SMCs) plays an important role in the pathogenesis of pulmonary arterial hypertension (PAH). Here, Dai et al. show that the glycolytic enzyme alpha-enolase contributes to this reprogramming, and that its inhibition limits SMC proliferation and disease progression in animal models of PAH.

    • Jingbo Dai
    • , Qiyuan Zhou
    •  & Guofei Zhou

  • Article
    | Open Access

    Omecamtiv mecarbil (OM) is a positive cardiac inotrope in clinical trials for the treatment of heart failure whose mechanism of action is incompletely understood. Here the authors show that OM inhibits myosin's working stroke and prolongs actomyosin attachment and propose a model that reconciles the OM-induced increase in cardiac performance in vivo with the inhibitory actions observed in vitro.

    • Michael S. Woody
    • , Michael J. Greenberg
    •  & E. Michael Ostap

  • Article
    | Open Access

    The role of the gut microbiota in hepatic lipid metabolism is controversial and incompletely understood. Here the authors perform multi-omics analyses of altered lipid metabolic processes in germ-free and specific pathogen-free mice, revealing how the gut microbiota affects hepatic fatty acid desaturation and elongation.

    • Alida Kindt
    • , Gerhard Liebisch
    •  & Josef Ecker

  • Article
    | Open Access

    Activation of integrin αIIbβ3 at the surface of platelets is required for their aggregation and for thrombus formation. Here Xu et al. identify apolipoprotein A-IV as a novel ligand for platelet αIIbβ3 integrin, and find it inhibits platelet aggregation and thrombosis.

    • Xiaohong Ruby Xu
    • , Yiming Wang
    •  & Heyu Ni

  • Article
    | Open Access

    Brown adipose tissue (BAT) thermogenesis counteracts obesity and promotes metabolic health. The role of long non-coding RNAs (lncRNAs) in the regulation of this process is not well understood. Here the authors identify a maternally expressed lncRNA, H19, that increases BAT oxidative metabolism and energy expenditure.

    • Elena Schmidt
    • , Ines Dhaouadi
    •  & Jan-Wilhelm Kornfeld

  • Article
    | Open Access

    Somatostatin+ (SOM+ ) GABAergic interneurons are known to fine-tune synaptic plasticity as they inhibit dendritic spikes and burst firing. Here, the authors show that both SOM+ and NOS+ interneurons preferentially recruit nonlinear outward-rectifying GABA(A)R with alpha5 subunit, and that this inhibition with slow gating kinetics matches voltage and time-dependent activation of synaptic NMDARs, thereby controlling the generation of dendritic NMDA spikes.

    • Jan M. Schulz
    • , Frederic Knoflach
    •  & Josef Bischofberger

  • Article
    | Open Access

    There is interest in mimicking striated muscle for a range of applications including nanomachines. Here, the authors report on synthetic 1D nanomachines which are used to study an ensemble of myosin motors interacting with an actin filament with potential to create assays of muscle related diseases

    • Irene Pertici
    • , Lorenzo Bongini
    •  & Pasquale Bianco

  • Article
    | Open Access

    The molecular mechanisms leading to heart failure in patients with Duchenne muscular dystrophy are unclear. Here the authors show that NF-κB is activated in the heart of dystrophin-deficient mice and that its ablation rescues cardiac function through chromatin remodeling and activation of gene expression.

    • Jennifer M. Peterson
    • , David J. Wang
    •  & Denis C. Guttridge

  • Article
    | Open Access

    Common genetic variants associated with plasma lipids have been extensively studied for a better understanding of common diseases. Here, the authors use whole-genome sequencing of 16,324 individuals to analyze rare variant associations and to determine their monogenic and polygenic contribution to lipid traits.

    • Pradeep Natarajan
    • , Gina M. Peloso
    •  & Sebastian Zoellner

  • Article
    | Open Access

    Ceramides are signalling molecules that regulate several physiological functions including insulin sensitivity. Here the authors report a selective ceramide synthase 1 inhibitor that counteracts lipid accumulation within the muscle and adiposity by increasing fatty acid oxidation but without affecting insulin sensitivity in mice fed with an obesogenic diet.

    • Nigel Turner
    • , Xin Ying Lim
    •  & Anthony S. Don

  • Review Article
    | Open Access

    Gut microbial metabolites are known to impact many physiological processes of the host and play a critical role in immune-homeostasis. Here the authors review our current understanding and appreciation of the importance of microbially derived tryptophan catabolites during both health and disease.

    • Henrik M. Roager
    •  & Tine R. Licht

  • Article
    | Open Access

    Dietary fatty acids have different effects on human health. Here, the authors show that ingestion of the fatty acid C18:0, but not of C16:0, rapidly leads to fusion of mitochondria and fatty acid oxidation in humans, possibly explaining the health benefits of C18:0.

    • Deniz Senyilmaz-Tiebe
    • , Daniel H. Pfaff
    •  & Aurelio A. Teleman

  • Article
    | Open Access

    Pulmonary alveolar proteinosis (PAP) is associated with defective macrophage clearance of surfactant. Here, the authors show that patients with PAP have altered cholesterol-to-phospholipid ratio in their surfactant, and that more importantly, statin therapy and reduction of cholesterol accumulation in macrophages can ameliorate PAP in both humans and mice.

    • Cormac McCarthy
    • , Elinor Lee
    •  & Bruce C. Trapnell

  • Article
    | Open Access

    Cholesterol homeostasis can modulate immunity via multiple pathways. Here the authors show that apolipoprotein E, an important regulator of cholesterol, produced by myeloid cells can regulate T cell activation by controlling the antigen presentation activity of dendritic cells in both humans and mice.

    • Fabrizia Bonacina
    • , David Coe
    •  & Giuseppe D. Norata

  • Article
    | Open Access

    Locations along the cochlea are tuned to different sound frequencies, and the individual vibration components are dynamically compressed before being converted to neural activity for further auditory processing. Here, the authors use optical coherence tomography to map sound-evoked vibrations and find a “hotspot” region with larger vibrations.

    • Nigel P. Cooper
    • , Anna Vavakou
    •  & Marcel van der Heijden

  • Article
    | Open Access

    Hypertrophic cardiomyocytes switch their metabolism from fatty acid oxidation to glucose use, but the functional role of this change is unclear. Here the authors show that high intracellular glucose inhibits the degradation of branched-chain amino acids, which is required for the activation of pro-growth mTOR signaling.

    • Dan Shao
    • , Outi Villet
    •  & Rong Tian

  • Article
    | Open Access

    Antibiotic-induced microbiome depletion is one of the most common approaches to modulate the gut microbiome. Here the authors demonstrate that it affects gut homeostasis and glucose metabolism by decreasing luminal short chain fatty acids and leading to a shift of energy utilization by colonocytes.

    • Amir Zarrinpar
    • , Amandine Chaix
    •  & Satchidananda Panda

  • Article
    | Open Access

    Circulating lipoprotein(a) is an important risk factor for cardiovascular disease and shows variability between different ethnic groups. Here, Zekavat et al. perform whole-genome sequencing in individuals of European and African ancestries and find ancestry-specific genetic determinants for lipoprotein(a) levels.

    • Seyedeh M. Zekavat
    • , Sanni Ruotsalainen
    •  & Sebastian Zoellner

  • Article
    | Open Access

    FXR plays an important role in bile acid homeostasis by transcriptionally modulating several enterohepatic genes, including intestinal FGF19, that repress hepatic bile acid synthesis. Here the authors show that postprandial FGF19 regulates FXR transcriptional activity via its action on the tyrosine kinase Src, which phosphorylates FXR.

    • Sangwon Byun
    • , Dong-Hyun Kim
    •  & Jongsook Kim Kemper

  • Article
    | Open Access

    Human embryonic stem cell-derived cardiomyocytes (hESC-CM) are a widely used model to study cardiac genomics. Here, Choy et al. perform promoter capture Hi-C to map long-range chromosomal interactions of hESC-CMs and to study overlap of such regions with genetic loci associated with cardiac phenotypes.

    • Mun-Kit Choy
    • , Biola M. Javierre
    •  & Bernard D. Keavney

  • Article
    | Open Access

    The transcription factor FOXA2 is specifically expressed in uterine glands. Here, using two conditional FOXA2 knockout mouse models, the authors show that glandular epithelia of the endometrium are required for timely embryo implantation and subsequent endometrial decidualization during successful pregnancy establishment.

    • Andrew M. Kelleher
    • , Jessica Milano-Foster
    •  & Thomas E. Spencer

  • Article
    | Open Access

    During atherosclerosis, endothelial cells release purines in response to oxidized phospholipids. Here, Hitzel et al. show that oxidized phospholipids activate an MTHFD2-regulated gene network in endothelial cells which reprograms amino acid metabolism towards production of purines and thus compensates for their loss.

    • Juliane Hitzel
    • , Eunjee Lee
    •  & Ralf P. Brandes

  • Article
    | Open Access

    Osmotic forces do not suffice to explain the rate of cerebrospinal fluid (CSF) production. Here, the authors show that the Na+/K+/2Cl− cotransporter in the choroid plexus contributes substantially to CSF production via its inherent ability to cotransport water.

    • Annette B. Steffensen
    • , Eva K. Oernbo
    •  & Nanna MacAulay

  • Article
    | Open Access

    Hepatic fibrosis represents the liver response to chronic injury and can lead to cirrhosis. Here the authors show that mucosal-associated invariant T cells mediate chronic inflammation and fibrogenesis in the liver by inducing a proinflammatory phenotype in macrophages and myofibroblasts and proliferation of the latter.

    • Pushpa Hegde
    • , Emmanuel Weiss
    •  & Sophie Lotersztajn

  • Article
    | Open Access

    Hyperinsulinemia can precede the development of insulin resistance. Here the authors identify a PKD2 mutation that leads to hyperinsulinemia and insulin resistance in Rhesus monkey and show that PKD2 deficiency promotes beta cell insulin secretion by activating L-type Ca2+ channels.

    • Yao Xiao
    • , Can Wang
    •  & Xiuqin Zhang

  • Article
    | Open Access

    Late-differentiating second heart field progenitors contribute to atrium, ventricle, and outflow tract in the zebrafish heart but how remains unclear. Here, the authors image heart formation in transgenics based on the cardiopharyngeal gene tbx1 and show that progenitors are continuously added.

    • Anastasia Felker
    • , Karin D. Prummel
    •  & Christian Mosimann

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