Physiology articles within Nature Communications

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  • Article
    | Open Access

    Hepatic lipogenesis is a tightly regulated process, which is elevated in obesity. Here the authors report that FGF15/19, bile acid-induced gut hormones, repress lipogenic genes in the late fed-state by activating small heterodimer partner (SHP) and promoting SHP-dependent recruitment of DNA methyltransferase DNMT3A to lipogenic genes.

    • Young-Chae Kim
    • , Sunmi Seok
    •  & Jongsook Kim Kemper

  • Article
    | Open Access

    Skeletal muscle plays a key role in regulating systemic glucose and metabolic homeostasis. Here, the authors show that the catalytic activity of Vav2, an activator of Rho GTPases, modulates those processes by favoring the responsiveness of this tissue to insulin and related factors.

    • Sonia Rodríguez-Fdez
    • , L. Francisco Lorenzo-Martín
    •  & Xosé R. Bustelo

  • Article
    | Open Access

    Breakdown of vascular barriers is a major complication of inflammatory diseases. However, the mechanisms underlying platelet recruitment to inflammatory micro-environments remains unclear. Here, the authors identify haptotaxis as a key effector function of immune-responsive platelets

    • Leo Nicolai
    • , Karin Schiefelbein
    •  & Florian Gaertner

  • Article
    | Open Access

    Neurofibromatosis type I (NF1) is characterized by prominent skeletal abnormalities mediated in part by aberrant ERK pathway activation due to NF1 loss-of-function. Here, the authors report the MEKK2 is a key mediator of this aberrant ERK activation and that MEKK2 inhibitors, including ponatinib, ameliorate skeletal defects in a mouse model of NF1.

    • Seoyeon Bok
    • , Dong Yeon Shin
    •  & Matthew B. Greenblatt

  • Article
    | Open Access

    Circular RNAs contribute to the regulation of β-cell specific functions. Here the authors show that a circular RNA derived from one of the introns of the insulin gene is necessary for optimal insulin secretion from pancreatic islets and that its level is reduced in the islets of diabetic subjects.

    • Lisa Stoll
    • , Adriana Rodríguez-Trejo
    •  & Romano Regazzi

  • Article
    | Open Access

    Current media for neuronal cell and organoid cultures are suboptimal for functional imaging and optogenetics experiments, owing to phototoxicity and unphysiological performance. Here the authors formulate an optimised neuronal medium to support live cell imaging and electrophysiological activity.

    • Michael Zabolocki
    • , Kasandra McCormack
    •  & Cedric Bardy

  • Article
    | Open Access

    The expansion of the white adipose tissue during obesity is accompanied by increased cellular stress, but factors that protect adipocytes from cell death are not well known. Here the authors report that the transcriptional co-activators YAP and TAZ are activated in adipocytes during obesity, which increases adipocyte survival through the proapoptotic factor BIM.

    • Lei Wang
    • , ShengPeng Wang
    •  & Stefan Offermanns

  • Article
    | Open Access

    GABAA receptors mediate most inhibitory synaptic transmission in the brain. Here authors used concatemeric α1β2γ2 GABAA receptors to introduce gain-of-desensitization mutations one subunit at a time, revealing non-concerted rearrangements with a key contribution of the γ2 subunit during desensitization.

    • Marc Gielen
    • , Nathalie Barilone
    •  & Pierre-Jean Corringer

  • Article
    | Open Access

    Molecular mechanisms by which glucose modulates L-type Ca2+ channel activity and vascular reactivity are unclear. Here the authors report a nanocomplex orchestrated by AKAP5 that facilitates local purinergic stimulation of L-type Ca2+ channels and vasoconstriction during diabetic hyperglycemia.

    • Maria Paz Prada
    • , Arsalan U. Syed
    •  & Madeline Nieves-Cintrón

  • Article
    | Open Access

    Social interactions require monitoring others’ actions to optimally organise one’s own actions. Here, the authors show that the pathway from the ventral premotor cortex (PMv) to the medial prefrontal cortex (MPFC) is causally involved in monitoring observed, but not executed, actions.

    • Taihei Ninomiya
    • , Atsushi Noritake
    •  & Masaki Isoda

  • Article
    | Open Access

    Clinical neuroprotective strategies for acute spinal cord injury (SCI) have largely overlooked the heart. Here the authors show cardiac contractility is immediately impaired in a porcine model of T2 SCI, and cardio-centric treatment with dobutamine optimizes cord oxygenation and mitigates haemorrhage.

    • Alexandra M. Williams
    • , Neda Manouchehri
    •  & Christopher R. West

  • Article
    | Open Access

    Leptin treatment is effective to reduce body weight in animal models, but patients with obesity and associated hyperleptinemia do not respond well to leptin therapy. Here the authors report a retrospective analysis of four clinical trials in normo- and mildly hypoleptinemic individuals and show that leptin therapy alters food intake in the short term and reduces weight and fat mass in the long term without effects on energy expenditure.

    • Pavlina Chrysafi
    • , Nikolaos Perakakis
    •  & Christos S. Mantzoros

  • Article
    | Open Access

    There are several pathways for CO2 fixation in photoautotrophic and chemoautotrophic microorganisms. Here, the authors provide experimental demonstration for the operation of the reductive glycine pathway in a natural microorganism, Desulfovibrio desulfuricans.

    • Irene Sánchez-Andrea
    • , Iame Alves Guedes
    •  & Alfons J. M. Stams

  • Article
    | Open Access

    Laboratory performance tests provide the gold standard for running performance but do not reflect real running conditions. Here the authors use a large, real world dataset obtained from wearable exercise trackers to extract parameters that accurately predict race times and correlate with training.

    • Thorsten Emig
    •  & Jussi Peltonen

  • Article
    | Open Access

    Necrotizing enterocolitis (NEC) is one of the most lethal gastrointestinal emergencies in neonates needing precision treatment. Here the authors show that remote ischemic conditioning is a non-invasive therapeutic method that enhances blood flow in the intestine, reduces damage, and improves NEC outcome.

    • Yuhki Koike
    • , Bo Li
    •  & Agostino Pierro

  • Article
    | Open Access

    Early stages of the novel coronavirus disease (COVID-19) have been associated with silent hypoxia and poor oxygenation despite relatively small fractions of afflicted lung. Here, the authors present a mathematical model which reproduces the vascular pulmonary mechanisms observed in patients with early COVID-19.

    • Jacob Herrmann
    • , Vitor Mori
    •  & Béla Suki

  • Article
    | Open Access

    Myeloid cells are involved in hypertension, but their exact role in renin-induced hypertension remains unclear. Here the authors show that impaired vitamin D signaling in myeloid cells causes hypertension via macrophage-specific miR-106b-5p secretion, which activates renin production in the kidney.

    • J. Oh
    • , S. J. Matkovich
    •  & C. Bernal-Mizrachi

  • Article
    | Open Access

    Intercalated discs ensure mechanical and electrochemical coupling during contraction of the heart. Here, the authors show that loss of Xinβ results in cardiomyocyte proliferation defects and cardiomyopathy by influencing the Hippo-YAP signalling pathway, thus affecting cardiac development and function.

    • Haipeng Guo
    • , Yao Wei Lu
    •  & Da-Zhi Wang

  • Article
    | Open Access

    The discovery of interventions that slow aging could be accelerated by employing non-invasive biometrics that predict biological age or life expectancy. Here the authors use longitudinal frailty data from naturally aging mice to develop two such tools, that are responsive to interventions.

    • Michael B. Schultz
    • , Alice E. Kane
    •  & David A. Sinclair

  • Article
    | Open Access

    mTORC1 expression is increased during ageing of muscle, and on the other hand, its activation promotes muscle hypertrophy. Here, the authors assess whether mTORC1 has positive or negative effects on ageing, and show that its long-term inhibition preserves muscle mass and function and neuromuscular junction integrity, whereas muscle-specific activation is associated with sarcopenia.

    • Daniel J. Ham
    • , Anastasiya Börsch
    •  & Markus A. Rüegg

  • Article
    | Open Access

    Little is known about how cardiac metabolism remodels following cardiac injury. Here, the authors show that mitochondrial CaMKII plays an important role in remodeling cardiac metabolism after injury and that replacement of mitochondrial creatine kinase improves energetics and protects against adverse remodeling.

    • Elizabeth D. Luczak
    • , Yuejin Wu
    •  & Mark E. Anderson

  • Article
    | Open Access

    Blood–brain barrier dysfunction occurs in ageing and in neurodegenerative diseases. Here, the authors use scRNA-seq to identify transcriptomic changes in endothelial cell subtypes in the aged mouse brain, some of which may generalize to human and can be reversed by treatment with a GLP-1R agonist.

    • Lei Zhao
    • , Zhongqi Li
    •  & Ho Ko

  • Article
    | Open Access

    How the developmental capacity of long-lived animals copes with fluctuations in the food supply is unclear. Here, the authors show using the sea anemone Nematostella vectensis that the crosstalk between Target of Rapamycin and fibroblast growth factor signalling in ring muscles links postembryonic tentacle patterning with food availability.

    • Aissam Ikmi
    • , Petrus J. Steenbergen
    •  & Matthew C. Gibson

  • Article
    | Open Access

    Salt levels in culture affect the polarisation of Th17 cells, which normally protect the host from fungal and bacterial infections. Here, the authors study patients with salt-losing tubulopathies (SLT) to find that, while Th17 immunity is dampened in SLT patients, their Th17-inducing signaling pathways are intact and can be reinvigorated by exogenous salt.

    • Rhys D. R. Evans
    • , Marilina Antonelou
    •  & Alan D. Salama

  • Article
    | Open Access

    The failing heart is characterised by both alterations in mitochondrial metabolism and an elevation of cytosolic sodium. Here, the authors use 23Na NMR and metabolic profiling to show these are related, and that elevation in intracellular Na reprograms cardiac substrate utilisation via effects on mitochondrial Na/Ca exchange.

    • Dunja Aksentijević
    • , Anja Karlstaedt
    •  & Michael J. Shattock

  • Article
    | Open Access

    Ketamine is a general anesthetic that is used also as an anti-depressant, but its use is associated with cystitis. Here, the authors show that ketamine is an antagonist of the Cav1.2 channel in bladder smooth muscle cells, that ablation of this channel in mice mimics the cystitis induced by ketamine, and show that this effect can be abrogated by an agonist of this ion channel.

    • Huan Chen
    • , David H. Vandorpe
    •  & Weiqun Yu

  • Article
    | Open Access

    “Life in a seasonal environment requires appropriate timing of physiological changes to survive, but how the circadian clockwork times these changes remains unclear. Here the authors show that the circadian clock genes BMAL2 and DEC1, in concert with epigenetic pathways in the pituitary, have a central role in seasonal timekeeping in mammals.”

    • S. H. Wood
    • , M. M. Hindle
    •  & A. S. I. Loudon

  • Article
    | Open Access

    Organ transplantation involving aged donors is often confounded by reduced post-transplantation organ survival. By studying both human organs and mouse transplantation models, here the authors show that pretreating the donors with senolytics to reduce mitochondria DNA and pro-inflammatory dendritic cells may help promote survival of aged organs.

    • Jasper Iske
    • , Midas Seyda
    •  & Stefan G. Tullius

  • Article
    | Open Access

    Epigenetic regulators contribute to the modulation of adipose thermogenesis by sensing environmental cues and regulating gene expression in response. Here the authors report that a DNA demethylase TET1 mediates epigenetic changes to repress thermogenic genes in mouse adipose tissue.

    • Sneha Damal Villivalam
    • , Dongjoo You
    •  & Sona Kang

  • Article
    | Open Access

    The structural organization of excitatory inputs supporting spike-timing-dependent plasticity (STDP) in dendritic spines remains unknown. Using a spine STDP protocol, the authors uncover the STDP rules for single, clustered and distributed dendritic spines in the basal dendrites of layer 5 pyramidal neurons in juvenile mice.

    • Sabrina Tazerart
    • , Diana E. Mitchell
    •  & Roberto Araya

  • Article
    | Open Access

    Na+ has been suggested to accumulate in tissues, particularly skin, in a hypertonic manner and to exert local pathogenic effects. Here, we reappraise this phenomenon which is systemic in nature and reflects isotonic changes in the relative extracellular volume in tissues, e.g. subclinical oedema; as such, it occurs in human hypertension and aging.

    • Giacomo Rossitto
    • , Sheon Mary
    •  & Christian Delles

  • Article
    | Open Access

    Modulation of peripheral nervous system signalling has many applications in medicine, neurobiology and machine-man interfaces. Here the authors develop a microscale implantable device for chronic interfacing with a small diameter nerve, and show multi-week in vivo recording and control of activity.

    • Timothy M. Otchy
    • , Christos Michas
    •  & Timothy J. Gardner

  • Article
    | Open Access

    The relationship between DNA damage response (DDR) and regulation of the tolerance to glucose restriction is currently unclear. Here the authors reveal that maintaining a physiological level of histones by Rad53-Spt21 is necessary for glucose tolerance via multiple parallel pathways, including derepression of subtelomeric genes and acetyl-coA regulation by histone acetylation.

    • Christopher Bruhn
    • , Arta Ajazi
    •  & Marco Foiani

  • Article
    | Open Access

    T-cell activation primarily occurs in the lymph nodes, highly organized and specialized secondary lymphoid organs. Here the authors show that the acidic extracellular pH in lymph node paracortical zones limits cytokine production by effector T-cells, but does not alter their activation by antigen-presenting cells.

    • Hao Wu
    • , Veronica Estrella
    •  & Robert J. Gillies

  • Article
    | Open Access

    Hypercholesterolemia is associated with lipid peroxidation induced reactive dicarbonyl adducts. Here the authors show that the dicarbonyl scavenger, 2-hydroxybenzylamine(2-HOBA), decreases reactive dicarbonyl modifications of LDL and HDL, improves HDL function, reduces atherosclerosis and promotes features of stable plaques in a mouse model of hypercholestrolemia.

    • Huan Tao
    • , Jiansheng Huang
    •  & MacRae F. Linton

  • Article
    | Open Access

    Learning skilled movements requires evolution in neural population dynamics both within and across cortical regions. Here, the authors combine simultaneous recordings of motor and premotor cortex with computational methods to show that single-trial cross-area dynamics correlate with single-trial behavior performance and skill acquisition.

    • T. L. Veuthey
    • , K. Derosier
    •  & K. Ganguly

  • Article
    | Open Access

    Although everyday life unfolds continuously, we tend to remember past experiences as discrete events. Here, the authors show that dynamic, pupil-linked arousal states track the encoding of such episodes, as revealed by changes in memory for the temporal order and duration of recent event sequences.

    • David Clewett
    • , Camille Gasser
    •  & Lila Davachi

  • Article
    | Open Access

    To define and distinguish fibroblasts from vascular mural cells have remained challenging. Here, using single-cell RNA sequencing and tissue imaging, the authors provide a molecular basis for cell type classification and reveal inter- and intra-organ diversity of these cell types.

    • Lars Muhl
    • , Guillem Genové
    •  & Christer Betsholtz

  • Article
    | Open Access

    Top-down proteomics can provide unique insights into the biological variations of protein biomarkers but detecting low-abundance proteins in body fluids remains challenging. Here, the authors develop a nanoparticle-based top-down proteomics approach enabling enrichment and detailed analysis of cardiac troponin I in human serum.

    • Timothy N. Tiambeng
    • , David S. Roberts
    •  & Ying Ge

  • Article
    | Open Access

    Defective rhythmic metabolism is associated with high-fat diet feeding and obesity. The authors show that the clock gene BMAL1 drives paraventricular hypothalamic neuron activity via rhythmic GABAergic neurotransmission, and that this mediates diurnal metabolism and diet-induced obesity.

    • Eun Ran Kim
    • , Yuanzhong Xu
    •  & Qingchun Tong

  • Article
    | Open Access

    The origin and diversity of blood vascular endothelial cells (BEC) in lymphoid tissues is unclear. Here, the authors profile murine BECs from peripheral lymph nodes by single cell analysis and identify subsets of cells specialised for immune cell recruitment and vascular homeostasis.

    • Kevin Brulois
    • , Anusha Rajaraman
    •  & Eugene C. Butcher

  • Article
    | Open Access

    Supercentenarians are approaching the current longevity limit by avoiding or surviving major illness, thus identifying biomarkers for exceptional survival might provide insights into the protection against disease of aging. Here, the authors show low NT-proBNP and high albumin in plasma are the biological correlates of survival to the highest ages.

    • Takumi Hirata
    • , Yasumichi Arai
    •  & Nobuyoshi Hirose

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