Anatomy articles within Nature Communications

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  • Perspective
    | Open Access

    No effective therapies exist for dry age-related macular degeneration. In this perspective, the authors propose that research should emphasize system biology approaches that integrate various ‘omics’ data into mathematical models to establish pathogenic mechanisms on which to design novel treatments, and identify biomarkers that predict disease progression and therapeutic response.

    • James T. Handa
    • , Cathy Bowes Rickman
    •  & Lindsay A. Farrer

  • Article
    | Open Access

    Denervation leads to muscle atrophy and neuromuscular endplate remodeling. Here, the authors show that a balanced activation of mTORC1 contributes to the dynamic regulation of autophagic flux in denervated muscle and that activation of PKB/Akt promotes the nuclear import of HDAC4, which is essential for endplate maintenance upon nerve injury

    • Perrine Castets
    • , Nathalie Rion
    •  & Markus A. Rüegg

  • Article
    | Open Access

    Iatrogenic injury of the ureters is a feared complication of laparoscopic abdominal surgery. Here the authors present the NIR fluorophore ZW800-1 as an intraoperative imaging agent for ureter mapping, showing its safety, pharmacokinetic properties, and efficacy in healthy volunteers and patients undergoing abdominopelvic surgery.

    • Kim S. de Valk
    • , Henricus J. Handgraaf
    •  & Alexander L. Vahrmeijer

  • Article
    | Open Access

    Fibrosis is a hallmark of several cardiac pathologies and its underlying mechanisms are still poorly defined. Here the authors show that macrophage hypoxia signaling following transverse aortic constriction in mice suppresses the activation of cardiac fibroblasts by secreting oncostatin M.

    • Hajime Abe
    • , Norihiko Takeda
    •  & Issei Komuro

  • Article
    | Open Access

    A number of therapeutic agents aimed at reducing pathology in Duchenne muscular dystrophy have been developed, but may have off-target effects when delivered systemically. Here, the authors express the therapeutic LIF transgene in leukocytes, and show this results in targeting to inflamed dystrophic muscle and reduced fibrosis by suppressing type 2 immunity.

    • Steven S. Welc
    • , Ivan Flores
    •  & James G. Tidball

  • Article
    | Open Access

    In vivo decorporation of U(VI) from bones is an unsolved challenge because of the formation of stable uranium phosphate complexes. Here, the authors develop a hydroxypyridonone-based ligand with strong uranium complexation and low cytotoxicity. They find this ligand effectively removes uranium from kidney and bones in mice, and is suitable for oral administration.

    • Xiaomei Wang
    • , Xing Dai
    •  & Shuao Wang

  • 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

    Arthroplasty is the main clinical option for the treatment of osteoarticular lesions, but has limited efficacy. Here, the authors use a wound dressing with autologous mesenchymal stromal cells, functionalised for local BMP2 delivery, and show feasibility and safety in standardised preclinical tests in animal models, suggesting suitability for use in clinical trials.

    • Laetitia Keller
    • , Luc Pijnenburg
    •  & Nadia Benkirane-Jessel

  • Article
    | Open Access

    Berberine has lipid-lowering effects and other metabolic benefits, but it presents with poor bioavailability. Here the authors conjugate berberine to liver-targeting nanoparticles, and show increased accumulation of berberine in the liver, improved metabolic profiles and reduced atherosclerotic plaques in mice.

    • Hui-Hui Guo
    • , Chen-Lin Feng
    •  & Jian-Dong Jiang

  • Article
    | Open Access

    Following muscle damage, an inflammatory response is associated to activation of satellite cells, which drive muscle repair. Here, the authors show that upregulation of Zeb1 in macrophages and muscle fibres regulates inflammation, and also show a role for Zeb1 in maintenance of satellite cell quiescence.

    • Laura Siles
    • , Chiara Ninfali
    •  & Antonio Postigo

  • Article
    | Open Access

    Stimulation of peripheral nerve activity may be used to treat metabolic and inflammatory disorders, but current approaches need implanted devices. Here, the authors present a non-invasive approach, and show that ultrasound-mediated stimulation can be targeted to specific sub-organ locations in preclinical models and alter the response of metabolic and inflammatory neural pathways.

    • Victoria Cotero
    • , Ying Fan
    •  & Christopher Puleo

  • Article
    | Open Access

    Mammalian joints have poor regenerative capacity following amputation. Here, the authors show that in mice, stimulation of the amputation wound with BMP2 and BMP9 stimulates regeneration of a synovial joint that includes bone, cartilage and a synovial cavity.

    • Ling Yu
    • , Lindsay A. Dawson
    •  & Ken Muneoka

  • Article
    | Open Access

    Insulin resistance is associated with development of type 2 diabetes. Here the authors show that TAZ interacts with c-Jun and Tead4, inducing expression of the insulin receptor substrate 1 (IRS1) leading to increased glucose uptake in muscle, and that its activity is counteracted by statin administration.

    • Jun-Ha Hwang
    • , A Rum Kim
    •  & Jeong-Ho Hong

  • Article
    | Open Access

    Osteoarthritis is characterised by degeneration of joint cartilage. Here the authors show that the RNA-binding protein ZFP36L1 is upregulated in chondrocytes of humans and mice with osteoarthritis, and that its knockdown in mouse joints protects chondrocytes against apoptosis by modulating the function of heat shock proteins.

    • Young-Ok Son
    • , Hyo-Eun Kim
    •  & Jang-Soo Chun

  • Article
    | Open Access

    The human stomach is divided into seven anatomically distinct regions but their protein composition is largely unknown. Here, the authors present a region-resolved map of the healthy human stomach mucosa as well as mucosa proteomes of tumor and tumor nearby tissue from gastric cancer patients.

    • Xiaotian Ni
    • , Zhaoli Tan
    •  & Jun Qin

  • Article
    | Open Access

    Optogenetics is a promising alternative approach for restoration of neuromuscular function. Here the authors establish a closed-loop functional optogenetic stimulation for the control of limb joint angle in murine models, which demonstrates improved control and less fatigue than electrical stimulation systems.

    • Shriya S. Srinivasan
    • , Benjamin E. Maimon
    •  & Hugh M. Herr

  • Article
    | Open Access

    SLIT-ROBO alterations arise in pancreatic ductal adenocarcinoma (PDAC), but their role in the pancreas is unclear. Here, the authors use mouse models to show that loss of epithelial Robo2 activates the neighbouring stroma via TGF-β signalling; findings  are relevant to PDAC patients, where ROBO expression correlates with survival outcomes.

    • Andreia V. Pinho
    • , Mathias Van Bulck
    •  & Ilse Rooman

  • Article
    | Open Access

    Myoblast fusion in skeletal muscle is a complex process but how this is regulated is unclear. Here, the authors identify Ash1L, a histone methyltransferase, as modulating myoblast fusion via activation of the myogenesis gene Cdon, and observe decreased Ash1L expression in Duchenne muscular dystrophy.

    • Ilaria Castiglioni
    • , Roberta Caccia
    •  & Davide Gabellini

  • Article
    | Open Access

    Vascular smooth muscle cell (VSMC) accumulation is associated with cardiovascular disease. Here, the authors combine single-cell RNA sequencing with lineage labelling to profile VSMC heterogeneity in healthy mice. They show that upregulation of Sca1 in a rare VSMC subpopulation marks a cell phenotype that is prevalent in disease.

    • Lina Dobnikar
    • , Annabel L. Taylor
    •  & Helle F. Jørgensen

  • Article
    | Open Access

    Inflammatory bowel disease is characterised by epithelial dysfunction. Here the authors show that loss of the nuclear receptor LRH-1 leads to epithelial disruption by altering Notch signaling in mouse intestinal organoids, and that LRH-1 overexpression ameliorates immune-mediated colitis in a mouse model.

    • James R. Bayrer
    • , Hongtao Wang
    •  & Holly A. Ingraham

  • Article
    | Open Access

    The majority of scoliosis is considered idiopathic with onset in adolescence (AIS) and has a genetic contribution. Here, the authors perform an exome wide association study of data from 457 severe AIS cases and 987 controls, and find a missense variant in SLC39A8 is associated with AIS.

    • Gabe Haller
    • , Kevin McCall
    •  & Christina A. Gurnett

  • Article
    | Open Access

    Coordinated proliferation and differentiation of diverse cell populations drive pancreatic epithelial and mesenchymal development. Here, the authors profile cell type dynamics in the developing mouse pancreas using single-cell RNA sequencing, identifying mesenchymal subtypes and undescribed endocrine progenitors.

    • Lauren E. Byrnes
    • , Daniel M. Wong
    •  & Julie B. Sneddon

  • 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

    Fibro-adipogenic progenitors (FAPs) resident in skeletal muscle are involved in both regeneration and maladaptive processes. Here, the authors identify subpopulations of FAPs with biological activities implicated in physiological muscle repair that are altered in pathological conditions such as muscular dystrophies.

    • Barbora Malecova
    • , Sole Gatto
    •  & Pier Lorenzo Puri

  • Article
    | Open Access

    Muscular dystrophies are characterised by extensive myofibre cell death. Here Morgan et al. show that RIPK3-mediated necroptosis contributes to myofibre cell death in Duchenne muscular dystrophy, and that RIPK3 deletion protects dystrophic mice against myofibre degeneration.

    • Jennifer E. Morgan
    • , Alexandre Prola
    •  & Maximilien Bencze

  • Article
    | Open Access

    Endurance and resistance exercise have different effects on skeletal muscle phenotype. Using mouse models and human subjects, the authors show that JNK/Smad2 signaling acts as molecular switch that when activated by resistance exercise leads to hypertrophy, and when inhibited promotes endurance adaptations in muscle.

    • Sarah J. Lessard
    • , Tara L. MacDonald
    •  & Laurie J. Goodyear

  • Article
    | Open Access

    Zika virus (ZIKV) can persist for months in semen and sperm. Here, the authors show that germ cells, compared to other cell types in the reproductive tract, are most susceptible to ZIKV and produce high levels of progeny virus, which coincides with decreased expression of the interferon-stimulated gene Ifi44l.

    • Christopher L. Robinson
    • , Angie C. N. Chong
    •  & Shuibing Chen

  • 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

    Insulin secretion by β-cells is stimulated by glucose and is dependent on the induction of β-cell membrane depolarization, mainly driven by the closure of KATP channels, which in turn promotes voltage-gated Ca2+ channel opening. Here the authors show that LRRC8 volume-regulated anion channels (VRACs) modulate glucose-stimulated calcium increase and insulin secretion.

    • Till Stuhlmann
    • , Rosa Planells-Cases
    •  & Thomas J. Jentsch

  • Article
    | Open Access

    CD4+ T cells are critical for the development of lymphedema. Here the authors show how these cells contribute to lymphedema and identify that the sphingosine-1-phosphate receptor modulator FTY720 can prevent lymphedema in a mouse tail injury model by blocking the release of CD4+ T cells from the lymph nodes to the skin.

    • Gabriela D. García Nores
    • , Catherine L. Ly
    •  & Babak J. Mehrara

  • Article
    | Open Access

    Mechanical forces exerted on tendons during locomotion cannot be readily measured without invasive methods. Here, the authors develop a non-invasive wearable device to track tendon loads by measuring shear wave propagation speed, and demonstrate its use during dynamic human movements.

    • Jack A. Martin
    • , Scott C. E. Brandon
    •  & Darryl G. Thelen

  • Article
    | Open Access

    Cathelicidins are antimicrobial peptides that eliminate pathogens and contribute to the innate immune response. Here the authors show that neutrophil-derived LL-37/CRAMP induces platelet activation and promotes arterial thrombosis and thrombo-inflammation.

    • Joachim Pircher
    • , Thomas Czermak
    •  & Christian Schulz

  • Article
    | Open Access

    Type 1 diabetes mellitus (T1DM) is characterized by beta cell loss because of an autoimmune attack. Here the authors show that an agonist for LRH-1/NR5A2, a nuclear receptor known to be protective against beta cell apoptosis, inhibits immune-mediated inflammation and hyperglycemia in T1DM mouse models.

    • Nadia Cobo-Vuilleumier
    • , Petra I. Lorenzo
    •  & Benoit R. Gauthier

  • Article
    | Open Access

    The authors have previously shown that membrane voltage can influence embryonic patterning during development. Here, the authors computationally model how nicotine disrupts Xenopus embryogenesis by perturbing voltage gradients, and rescue nicotine-inducted defects with HCN2 channel expression.

    • Vaibhav P. Pai
    • , Alexis Pietak
    •  & Michael Levin

  • Article
    | Open Access

    Heterotopic ossification (HO) is a painful disease of unknown etiology characterized by extraskeletal bone formation after injury. Here the authors show that TGF-β is increased in HO lesions, where it promotes the early stages of HO pathology, and demonstrate that TGF-β inhibition ameliorates HO in mice.

    • Xiao Wang
    • , Fengfeng Li
    •  & Xu Cao

  • Article
    | Open Access

    Glucagon secretion is promoted during hypoglycemia and inhibited by increased glucose levels. Here, Basco et al. show that glucokinase suppresses glucose-regulated glucagon secretion by modulating the intracellular ATP/ADP ratio and the closure of KATP channels in α-cells.

    • Davide Basco
    • , Quan Zhang
    •  & Bernard Thorens

  • Article
    | Open Access

    Fibrodysplasia ossificans progressiva is a severe disorder characterized by heterotopic ossification, and is caused by mutations in ACVR1. Here, the authors show that expression of mutant ACVR1 in fibro/adipogenic progenitors recapitulates disease progression, and that this can be halted by systemic inhibition of activin A in mice.

    • John B. Lees-Shepard
    • , Masakazu Yamamoto
    •  & David J. Goldhamer

  • Article
    | Open Access

    Adult beta cells, which are highly specialised insulin-secreting cells, rarely replicate. Puri et al. demonstrate that beta cell proliferative capacity is inversely correlated with their functionality and differentiation state, by inducing proliferation of adult cells with ectopic overexpression of the cell cycle regulator c-Myc.

    • Sapna Puri
    • , Nilotpal Roy
    •  & Matthias Hebrok

  • Article
    | Open Access

    Satellite cells can differentiate both into myocytes and brown adipocytes. Here, the authors show that the histone demethylase Lsd1 prevents adipogenic differentiation of satellite cells by repressing expression of Glis1, and that its ablation changes satellite cell fate towards brown adipocytes and delays muscle regeneration in mice.

    • Milica Tosic
    • , Anita Allen
    •  & Roland Schüle

  • Article
    | Open Access

    Communication between osteoblasts and osteoclasts is essential for bone homeostasis, but the mode of interaction is unclear. The authors use intravital two-photon microscopy in mice to show that these cells directly interact, regulating activity of osteoclasts, and that the interaction is modulated by parathyroid hormone administration.

    • Masayuki Furuya
    • , Junichi Kikuta
    •  & Masaru Ishii

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