Medical research articles within Nature Communications

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  • Article |

    Platelet-derived growth factor (PDGF) signaling in vascular smooth muscle cells (VSMCs) promotes atherogenesis. Here, the authors show that mutant mice with increased PDGF activity in VSMCs have augmented STAT1-dependent chemokine signals resulting in artery wall inflammation and formation of advanced plaque morphologies clinically relevant in humans.

    • Chaoyong He
    • , Shayna C. Medley
    •  & Lorin E. Olson

  • Article |

    The transcription factor c-Myc is a master regulator of cellular metabolism and has an important role in tumorigenesis. Phanet al. show that 14-3-3σ, an inhibitor of cell cycle progression, also suppresses tumour-promoting metabolic programmes by promoting the degradation of c-Myc.

    • Liem Phan
    • , Ping-Chieh Chou
    •  & Mong-Hong Lee

  • Article
    | Open Access

    The gut epithelium is damaged in inflammatory bowel disease, but capturing such lesions by histology can be difficult. Here, the authors use stereomicroscopy to visualize different 3D inflammatory structures and associated microbes in humans and in 16 genetic mouse models relevant to intestinal inflammation.

    • Alex Rodriguez-Palacios
    • , Tomohiro Kodani
    •  & Fabio Cominelli

  • Article |

    The cause of overactive bladder is largely unknown and there is currently no effective therapy. Gaoet al. show that a membrane protein Pirt controls bladder emptying by inhibiting the neuronal purinergic receptor P2X3 and that treatment with a small Pirt fragment prevents bladder overactivity in mice.

    • Xiao-Fei Gao
    • , Ji-Feng Feng
    •  & Cheng He

  • Article
    | Open Access

    Atherosclerotic plaques with macrocalcification are stable, whereas microcalcification is a key feature of rupture-prone plaques. Here the authors show that18F-NaF PET/CT imaging can distinguish between macro- and microcalcification providing a potential, non-invasive imaging technique to identify patients with high-risk atheroma.

    • Agnese Irkle
    • , Alex T. Vesey
    •  & Anthony P. Davenport

  • Article
    | Open Access

    Aneuploidy may be fatal for the embryo, hence predicting its occurrence is important for successfulin vitrofertilization. Here the authors monitor development of human preimplantation embryos in real-time and correlate the blastomere ploidy with cleavage dynamics and gene expression, identifying 12-transcript signature that determines ploidy.

    • Maria Vera-Rodriguez
    • , Shawn L. Chavez
    •  & Carlos Simon

  • Article
    | Open Access

    The hormone adiponectin is produced by fat cells and has positive metabolic effects. Here, Kim et al.show that DNA methyltransferase 1 (DNMT1) represses adiponectin expression through hypermethylation of its promoter, and that inflammatory cytokines enhance DNMT1 activity in obese mice and humans.

    • A. Young Kim
    • , Yoon Jeong Park
    •  & Jae Bum Kim

  • Article |

    Bile acids exert metabolic effects by modulating FXR receptor activity. Here, Trabelsi et al.show that FXR negatively regulates production of the incretin GLP-1 in enteroendocrine L-cells by reducing glycolysis and that inhibition of FXR improves glucose metabolism by increasing GLP-1 in obese mice.

    • Mohamed-Sami Trabelsi
    • , Mehdi Daoudi
    •  & Sophie Lestavel

  • Article
    | Open Access

    Epstein–Barr virus is associated with nasopharyngeal carcinoma and previous studies have focused on the role of viral proteins in tumour pathology. Here, the authors show that a viral miRNA targets the host protein PTEN and has a critical role in the late stage of nasopharyngeal carcinoma by driving tumour metastasis.

    • Longmei Cai
    • , Yanfen Ye
    •  & Xin Li

  • Article |

    Unlike rodents, humans produce the protein Cidea in white adipose tissue, where it associates with lipid droplets. Here the authors generate mice that express human Cidea in fat tissues to show Cidea exerts beneficial metabolic effects by regulating the expansion of visceral fat in response to a high-fat diet.

    • Gustavo Abreu-Vieira
    • , Alexander W. Fischer
    •  & Natasa Petrovic

  • Article
    | Open Access

    Atherogenesis involves coordinated action of different cell types and factors. Here the authors show that the kinase Pak1 represents a key pro-atherogenic factor affecting the function of macrophages and vascular smooth muscle cells, including their production of proinflammatory cytokine IL-6 and chemokine MCP-1, and retention of cholesterol.

    • Nikhlesh K. Singh
    • , Sivareddy Kotla
    •  & Gadiparthi N. Rao

  • Article |

    Aquaporin-3 (AQP3) mediates cellular uptake of water and hydrogen peroxide (H2O2). Here, the authors show that TNF-induced H2O2enters keratinocytes via AQP3, eliciting NF-κB activation and the development of psoriasis, and identify AQP3 as a potential therapeutic target for this inflammatory immune-mediated disease.

    • Mariko Hara-Chikuma
    • , Hiroki Satooka
    •  & A. S. Verkman

  • Article
    | Open Access

    The kinase PI3K is crucial for insulin signalling in the liver but the roles of individual PI3K isoforms are largely unclear. Using mice that lack class II PI3K isoform γ (PI3K-C2γ), the authors here show that PI3K-C2γ selectively activates endosomal Akt2 by regulating the localized production of PIP2.

    • Laura Braccini
    • , Elisa Ciraolo
    •  & Emilio Hirsch

  • Article
    | Open Access

    The growth factor NELL-1 induces bone formation during development, but its role in osteoporosis is unknown. This study shows that NELL-1 binding to integrin ß1 induces Wnt/ß-catenin signalling in the bone and restores bone mineral density in osteoporotic mice and sheep, suggesting the therapeutic potential of NELL-1 for the treatment of bone loss.

    • Aaron W. James
    • , Jia Shen
    •  & Chia Soo

  • Article
    | Open Access

    Familial hypercholesterolemia (FH) is a congenital disease associated with high plasma cholesterol levels. Here, the authors recapitulate FH in chimeric mice, in which livers are repopulated with hepatocytes from an FH patient, and successfully correct the disease using adenovirus-mediated gene therapy.

    • Beatrice Bissig-Choisat
    • , Lili Wang
    •  & Karl-Dimiter Bissig

  • Article
    | Open Access

    Group O/RhD− blood can be safely transfused to any recipient and methods for converting other blood groups into this group hold therapeutic potential. By using programmable nucleases, here the authors edit the gene that determines the RhD blood group and convert the RhD+ into RhD− erythroid progenitor cells.

    • Young-Hoon Kim
    • , Hyun O. Kim
    •  & Hyongbum Kim

  • Article
    | Open Access

    ß-Sheet-rich aggregates of α-synuclein (αS) characterize Parkinson's disease (PD) and recent work suggests that αS exists as α-helix-rich tetramers and related low-nmultimers in normal cells. Here the authors show that αS mutations associated with familial PD decrease the intraneuronal tetramer:monomer ratio and are correlated with neurotoxicity.

    • Ulf Dettmer
    • , Andrew J. Newman
    •  & Dennis Selkoe

  • Article |

    Mutations in the tumour suppressor p53 can produce a protein that has additional functions. Here, the authors describe gain of function mutants of p53 that induce the expression of genes involved in nucleotide metabolism, which increases the activity of GTPases and results in invasion and metastasis.

    • Madhusudhan Kollareddy
    • , Elizabeth Dimitrova
    •  & Luis A. Martinez

  • Article
    | Open Access

    MicroRNAs have a role in the acquisition of stem cell-like properties of cancer cells. Here the authors show that microRNA-27b mediates generation of a side-population of breast cancer stem cells, in part by regulating the protein ENPP1, which has been previously linked to the development of diabetes.

    • Ryou-u Takahashi
    • , Hiroaki Miyazaki
    •  & Takahiro Ochiya

  • Article
    | Open Access

    Cell-based screening assays allow functional testing of chemicals but do not mimic the in vivosituation well. Here, the authors report a method for the discovery of secreted cytoprotective factors in mice and use it to demonstrate that the hormone ghrelin protects cardiac muscle from ischaemic damage.

    • Giulia Ruozi
    • , Francesca Bortolotti
    •  & Mauro Giacca

  • Article
    | Open Access

    The splicing of the penultimate exon of the dystrophin gene is developmentally regulated. Here the authors show that the dysregulation of this exon’s splicing leads to the expression of an embryonic dystrophin form with a C-terminus distinct from the adult isoform, which leads to muscle wasting in zebrafish and mice.

    • Frédérique Rau
    • , Jeanne Lainé
    •  & Denis Furling

  • Article |

    Several oncogenic mutations have been identified in melanoma; however, despite exhaustive sequencing, in a subset of melanomas no oncogenic mutation has been identified. Here, the authors identify new genomic rearrangements causing oncogenic fusions between the kinase domain of MET and several N-terminal partners in Spitzoid tumours.

    • Iwei Yeh
    • , Thomas Botton
    •  & Boris C. Bastian

  • Article
    | Open Access

    The enzyme soluble guanylyl cyclase (sGC) regulates differentiation of brown fat. Here, Hoffman et al.show that a small molecule sGC stimulator increases brown fat activity and browning of white fat, thereby inducing energy expenditure, weight loss and partial protection from diet-induced obesity in mice.

    • Linda S. Hoffmann
    • , Jennifer Etzrodt
    •  & Alexander Pfeifer

  • Article |

    The microRNA miR-21 is overexpressed in cancer and is thought to function through anti-apoptotic activity. Here, Ma et al. show that deleting or blocking miR-21 in mice protects against acute pancreatitis and TNF-α-induced tissue damage by inhibiting RIP3-dependent regulated necrosis (necroptosis).

    • Xiaodong Ma
    • , Daniel J. Conklin
    •  & Yong Li

  • Article
    | Open Access

    Brain-iron elevation is implicated in Alzheimer’s disease (AD), but the impact of the metal on disease outcomes has not been analysed in a longitudinal study. Here, the authors examine the association between the levels of ferritin, an iron storage protein, in the cerebrospinal fluid (CSF) of AD patients and show that CSF ferritin levels predict AD outcomes.

    • Scott Ayton
    • , Noel G. Faux
    •  & Ansgar J. Furst

  • Article
    | Open Access

    Adult cardiac progenitor/stem cells (CPSCs) possess valuable potential for heart repair that is limited by the elusiveness of these cells. Here Noseda et al. refine the definition of murine CPSCs producing stem cell antigen 1 (Sca1), mapping the cardiogenic signature and clonogenicity to the subgroup of Sca1+cells expressing PDGFRα.

    • Michela Noseda
    • , Mutsuo Harada
    •  & Michael D. Schneider

  • Article |

    Chronic pancreatitis is an inflammatory disease accompanied by fibrosis. Here the authors show that pancreatic stellate cells produce IL-4 and IL-13 that trigger alternative activation of macrophages, and that genetic or pharmacological inhibition of IL-4/IL-13 signaling ameliorates the disease.

    • Jing Xue
    • , Vishal Sharma
    •  & Aida Habtezion

  • Article |

    Adult expression of fetal haemoglobin is beneficial and thus desirable in patients with haemoglobin disorders. Here the authors introduce a naturally occurring mutation in the γ-globinpromoter and show that it causes binding of an activator TAL1, chromosome looping and revival of fetal haemoglobin expression in erythroid cells.

    • Beeke Wienert
    • , Alister P. W. Funnell
    •  & Merlin Crossley

  • Article |

    Skeletal muscle satellite cells are muscle stem cells believed to contribute only to regenerating myofibres. Here Keefe et al. show that in adult sedentary mice satellite cells continue to fuse with uninjured myofibres, but they are not globally required for the maintenance of aging muscles.

    • Alexandra C. Keefe
    • , Jennifer A. Lawson
    •  & Gabrielle Kardon

  • Article |

    Colitis is a common human disorder but the clinical interventions are limited as the pathological mechanisms are not very clear. Here the authors find an elevated expression of non-muscle-myosin-II heavy chain Myh9 in a colitis mouse model, and show that Myh9 expression reduction or activity inhibition ameliorates epithelial injuries.

    • Bing Zhao
    • , Zhen Qi
    •  & Ye-Guang Chen

  • Article
    | Open Access

    Infectious and chronic diseases display seasonal patterns, yet seasonal changes in physiology are rarely thought to affect human health. Here the authors show seasonal variation in all major blood cells and in gene and protein expression in diverse tissues, suggesting a mechanism for seasonal disease proneness and physiology.

    • Xaquin Castro Dopico
    • , Marina Evangelou
    •  & John A. Todd

  • Article
    | Open Access

    Predicting and monitoring chemotherapy response remains a challenge for glioma treatment. Here the authors show that a microfluidic device can isolate glioma-derived exosomes from patient blood and accurately determine the levels of mRNA of key enzymes important for chemoresponsiveness.

    • Huilin Shao
    • , Jaehoon Chung
    •  & Ralph Weissleder

  • Article |

    Autoantibodies targeting citrunillated proteins are common in rheumatoid arthritis patients. Here the authors show that vinculin (a human protein) and some microbial proteins are recognized by these antibodies and by CD4+T cells, and this response is absent in patients carrying a protective HLA allele.

    • Jurgen van Heemst
    • , Diahann T. S. L. Jansen
    •  & René E. Toes

  • Article
    | Open Access

    Phospholamban (PLN) is a regulator of heart contractility. Here the authors show that cardiomyocytes derived from induced pluripotent stem cells of a cardiomyopathy patient with mutant PLN exhibit functional defects consistent with the disease, and that this mutation can be functionally corrected by genome editing and gene therapy.

    • Ioannis Karakikes
    • , Francesca Stillitano
    •  & Roger J. Hajjar

  • Article
    | Open Access

    The protein p16INK4a promotes senescence in tissue stem cells and thereby contributes to organismal ageing. Here the authors reveal that p16INK4a also downregulates expression of a-klotho, thereby revealing an additional ageing-promoting function of 16INK4athat is independent from its role in senescence.

    • Seidai Sato
    • , Yuka Kawamata
    •  & Eiji Hara

  • Article
    | Open Access

    Fibroblast growth factor (FGF) family proteins have anti-diabetic effects, but how they work is currently unclear. Here the authors show that injections of FGF1 or FGF19 into the brain of diabetic rats alter glucose and lipid homeostasis by suppressing activity of the hypothalamic-pituitary-adrenal signalling axis.

    • Rachel J. Perry
    • , Sangwon Lee
    •  & Gerald I. Shulman

  • Article |

    African Americans have much higher colon cancer rates than rural South Africans, which is associated with dietary and metabolic differences. Here, O’Keefe et al.show that switching quantities of fat and fibre leads to reciprocal changes in gut microbiota, metabolites and cancer biomarkers.

    • Stephen J. D. O’Keefe
    • , Jia V. Li
    •  & Erwin G. Zoetendal

  • Article
    | Open Access

    Mutations in the FTO gene have been linked to obesity. Here, Merkestein et al. provide in vitro and in vivo evidence that FTOdirectly regulates adipogenesis in mice at the stage of mitotic clonal expansion, likely by modulating the expression of the transcription factor RUNX1T1.

    • Myrte Merkestein
    • , Samantha Laber
    •  & Roger D. Cox

  • Article |

    In response to injury, satellite cells (SCs) asymmetrically divide to self-renew and repair muscle. Here the authors show that a cytokine G-CSF is crucial for long-term expansion of activated SCs and muscle regeneration in mice, suggesting that G-CSF treatment may have beneficial effect in Duchenne muscular dystrophy.

    • Nozomi Hayashiji
    • , Shinsuke Yuasa
    •  & Keiichi Fukuda

  • Article
    | Open Access

    The neurotransmitter serotonin has both central and peripheral effects. Here, the authors show that adipocyte-derived serotonin regulates organismal energy homeostasis in mice by acting on adipocyte serotonin receptors on fat cells, which regulates lipolysis and thermogenesis in white and brown fat tissue.

    • Chang-Myung Oh
    • , Jun Namkung
    •  & Hail Kim

  • Article
    | Open Access

    Benzodiazepines (BDZs) target GABAA receptors to alleviate pain but these also cause side effects. Here the authors use mice in which only one GABAA receptor is BDZ-sensitive at a time to identify α2GABAAas the receptor that provides maximal analgesic activity but minimal side-effects in response to BDZs.

    • William T. Ralvenius
    • , Dietmar Benke
    •  & Hanns Ulrich Zeilhofer

  • Article |

    Metabolomic profiling provides clues at alterations in cellular biochemistry. Here, the authors perform metabolomics analyses on samples from the Framingham Heart Study, and a Danish validation cohort, to identify small-molecule biomarkers prospectively associated with longevity or ageing.

    • Susan Cheng
    • , Martin G. Larson
    •  & Thomas J. Wang

  • Article
    | Open Access

    Collagen 3 is increased during tendon repair, but is then replaced by Collagen 1 that has superior biomechanical properties. Here the authors show that IL-33 is induced by tendon damage and regulates miR-29a, which controls Collagen 3 production and feeds back on IL-33, orchestrating tendon repair.

    • Neal L. Millar
    • , Derek S. Gilchrist
    •  & Iain B. McInnes

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