Physiology articles within Nature Communications

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  • Article
    | Open Access

    VEGF-C drives lymphangiogenesis through binding to its receptors VEGFR-2 and VEGFR-3. Here, Durré et al. identify uPARAP/Endo180 as a critical regulator of VEGFR-2/VEGFR-3 heterodimerisation and downstream signaling in response to VEGF-C, and show that uPARAP deletion leads to the formation of hyperbranched vasculatures in pathological conditions.

    • Tania Durré
    • , Florent Morfoisse
    •  & Agnès Noel

  • Article
    | Open Access

    Carotid intima-media thickness (cIMT) and plaque are associated with subclinical atherosclerosis and coronary heart disease (CHD). Here, the authors identify and prioritize genetic loci for cIMT and plaque by GWAS and colocalization approaches and further demonstrate genetic correlation with CHD and stroke.

    • Nora Franceschini
    • , Claudia Giambartolomei
    •  & Christopher J. O’Donnell

  • Article
    | Open Access

    Endocannabinoid signaling regulates food intake and is a potential therapeutic target for obesity. Here the authors show that adipocyte O-GlcNAc transferase (OGT) is required for high fat diet-induced hyperphagia via transcriptional activation of de novo lipid desaturation and accumulation of an endogenous appetite-inducing cannabinoid.

    • Min-Dian Li
    • , Nicholas B. Vera
    •  & Xiaoyong Yang

  • Article
    | Open Access

    Assessing biological circuit connections in single cells has been intractable due to lack of appropriate tools. Here, Bleck et al. develop a method to assess mitochondrial network connectivity in muscle cells and observe clear differences consistent with differing energy requirements.

    • Christopher K. E. Bleck
    • , Yuho Kim
    •  & Brian Glancy

  • Review Article
    | Open Access

    Transcranial electrical stimulation techniques, such as tDCS and tACS, are popular tools for neuroscience and clinical therapy, but how low-intensity current might modulate brain activity remains unclear. In this review, the authors review the evidence on mechanisms of transcranial electrical stimulation.

    • Anli Liu
    • , Mihály Vöröslakos
    •  & György Buzsáki

  • Article
    | Open Access

    The mechanisms that regulate the activity of Ca2 +/calmodulin-dependent protein kinase II (CaMKII) in the context of heart failure are incompletely understood. Here the authors show that protein arginine methyltransferase 1 (PRMT1) prevents cardiac hyperactivation of CaMKII and heart failure development by methylating CaMKII at arginine residues 9 and 275.

    • Jung-Hoon Pyun
    • , Hyun-Ji Kim
    •  & Jong-Sun Kang

  • Article
    | Open Access

    Long-range GABAergic hippocampal neurons project to cortical and subcortical areas, while vasoactive intestinal peptide (VIP+) interneurons can inhibit other GABAergic neurons. Here, authors discover a VIP+, long-range projecting GABAergic neuron whose activity is associated with quiet wakefulness.

    • Ruggiero Francavilla
    • , Vincent Villette
    •  & Lisa Topolnik

  • Article
    | Open Access

    Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, the authors perform discovery GWAS for BP in East Asians and meta-analysis in East Asians and Europeans and report ancestry-specific BP SNPs and selection signals.

    • Fumihiko Takeuchi
    • , Masato Akiyama
    •  & Norihiro Kato

  • Article
    | Open Access

    Respiratory failure is one of the leading causes of death following spinal cord injury and it is unclear if normal respiratory motor activity can be recovered after chronic injury-induced paralysis. Here, authors show that treatment with chondroitinase ABC induces robust rescue of breathing up to 1.5 years following complete hemidiaphragm paralysis.

    • Philippa M. Warren
    • , Stephanie C. Steiger
    •  & Jerry Silver

  • Article
    | Open Access

    The molecular mechanisms that underlie associations in GWAS, incl. chronic kidney disease (CKD), are largely unknown. Here, the authors perform an integrative analysis of genetic, transcriptomic and epigenomic data from human kidney to pinpoint plausible molecular pathways of CKD genetic associations.

    • Xiaoguang Xu
    • , James M. Eales
    •  & Maciej Tomaszewski

  • Article
    | Open Access

    While autapses are synapses made by a neuron onto itself, its functional significance in pyramidal cells are not clear. Here, the authors show that in the mammalian neocortex, autapses of pyramidal cells can enhance burst firing and coincidence detection from other inputs.

    • Luping Yin
    • , Rui Zheng
    •  & Yousheng Shu

  • Article
    | Open Access

    While young muscle faithfully regenerates damaged myofibers, aged muscle is impaired. Here the authors show the “anti-aging” protein α-Klotho is upregulated in young muscle after damage via promoter demethylation and this regulation is lost in aging, resulting in mitochondrial damage and an impaired healing response.

    • A. Sahu
    • , H. Mamiya
    •  & F. Ambrosio

  • Article
    | Open Access

    No effective pharmacological treatments exist for nonalcoholic fatty liver disease (NAFLD). Here, the authors show that serotonin concentration in the portal blood is increased in nine human subjects and in mice fed a high-fat diet, and that local serotonin signaling ablation, either genetically or with an antagonist, prevents hepatic steatosis in mice.

    • Wonsuk Choi
    • , Jun Namkung
    •  & Hail Kim

  • Article
    | Open Access

    Angiogenesis requires dynamic endothelial rearrangements and relative position changes within the vascular tubes. Here the authors show that a PI3K/NUAK1/MYPT1/MLCP pathway regulates actomyosin contractility in endothelial cells and cellular rearrangement during vascular patterning.

    • Ana Angulo-Urarte
    • , Pedro Casado
    •  & Mariona Graupera

  • Article
    | Open Access

    Constitutive deletion of Rcan1 has been previously shown to prevent Angiotensin II-induced aneurysm in mice. Here the authors show that tissue-specific inducible deletion of Rcan1 in vascular cell types predisposes to hypertension-mediated aortic rupture, intramural hematoma, and aneurysm, due to increased GSK-3b-mediated activation of ROCK and induction of a hypercontractile phenotype.

    • Silvia Villahoz
    • , Paula Sofía Yunes-Leites
    •  & Miguel R. Campanero

  • Article
    | Open Access

    Gluten-free diets are increasingly common in the general population. Here, the authors report the results of a randomised cross-over trial involving middle-aged, healthy Danish adults, showing evidence that a low-gluten diet leads to gut microbiome changes, possibly due to variations in dietary fibres.

    • Lea B. S. Hansen
    • , Henrik M. Roager
    •  & Oluf Pedersen

  • Article
    | Open Access

    Uptake and release of glycerol from the small intestine and adipocytes is facilitated by a subclass of aquaporins (AQP), but how glycerol flow is regulated remains poorly understood. Here authors solve the crystal structure of AQP10 and show how lipolysis is coupled to AQP10 regulation in

    • Kamil Gotfryd
    • , Andreia Filipa Mósca
    •  & Pontus Gourdon

  • Article
    | Open Access

    Excess caloric intake leads to increased thermogenesis in brown adipose tissue, to limit weight gain. Here, the authors show that neuropeptide FF receptor-2 signalling promotes thermogenesis via control of NPY expression in the arcuate nucleus, and that it absence in mice leads to a failure of activation of diet-induced thermogenesis and the development of exacerbated obesity.

    • Lei Zhang
    • , Chi Kin Ip
    •  & Herbert Herzog

  • Article
    | Open Access

    Gut microbiota impact host metabolism and gut microbiome composition reflects dietary habits. Here the authors show that, in animals fed obesogenic diets, changes in gut microbiota precede changes in glucose homeostasis. Importantly, long term exposure of the host to the changed microbiota is required to impair glucose homeostasis.

    • Kevin P. Foley
    • , Soumaya Zlitni
    •  & Jonathan D. Schertzer

  • Article
    | Open Access

    Rare genetic variants can contribute to complex traits but this contribution is not well understood. Here, the authors analyse deep whole genome sequencing data across 1457 individuals from an isolated Greek population and find association of rare variant burdens with cardiometabolic traits.

    • Arthur Gilly
    • , Daniel Suveges
    •  & Eleftheria Zeggini

  • Article
    | Open Access

    Organisms could respond to essential resource limitation by increasing metabolic efficiency or resource acquisition ability. Here, the authors experimentally evolve green algae under different resource limitations and show convergent evolution of core metabolism rather than resource specialization.

    • Manu Tamminen
    • , Alexander Betz
    •  & Anita Narwani

  • Article
    | Open Access

    Increased glycolysis and inflammatory responses have been observed in endothelial cells exposed to disturbed flow. However, the role of endothelial glycolysis in atherosclerosis is unclear. Here the authors unveil a protective role for glycolysis by showing that endothelial deletion of Prkaa1 accelerates atherosclerosis in hyperlipidemic mice through a reduction of glycolytic metabolism.

    • Qiuhua Yang
    • , Jiean Xu
    •  & Yuqing Huo

  • Article
    | Open Access

    GABAergic interneurons are known to provide inhibition to allow computational function of neuronal network. Here, Espinoza and colleagues show that connectivity of granule cells and interneurons in the dentate gyrus of mouse hippocampus are consistent with the circuit architecture capable of performing a winners-take-all mechanism.

    • Claudia Espinoza
    • , Segundo Jose Guzman
    •  & Peter Jonas

  • Article
    | Open Access

    Thyroid dysfunction is a common public health problem and associated with cardiovascular co-morbidities. Here, the authors carry out genome-wide meta-analysis for thyroid hormone (TH) levels, hyper- and hypothyroidism and identify SLC17A4 as a TH transporter and AADAT as a TH metabolizing enzyme.

    • Alexander Teumer
    • , Layal Chaker
    •  & Marco Medici

  • Article
    | Open Access

    Direct electrical brain stimulation can induce widespread changes in neural activity, offering a means to modulate network-wide activity and treat disease. Here, the authors show that the low-frequency functional connectivity profile of a stimulation target predicts where induced theta activity occurs.

    • E. A. Solomon
    • , J. E. Kragel
    •  & M. J. Kahana

  • 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

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