Health sciences articles within Nature Communications

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  • Article
    | Open Access

    Rhinovirus (RV) infections can trigger acute exacerbations of respiratory diseases. Here, Niespodziana et al. develop a PreDicta chip that identifies the culprit RV strain from small blood samples and show that RV-A and RV-C strains are associated with most severe symptoms.

    • Katarzyna Niespodziana
    • , Katarina Stenberg-Hammar
    •  & Rudolf Valenta

  • Article
    | Open Access

    Estrogen receptor alpha (ERα) plays critical roles in the etiology and treatment of breast cancer. Here the authors synthesize benzopyrans with variable side chains to identify antiestrogenic compounds and characterize OP-1074, a compound that exhibits pure antiestrogenic activity by inducing the degradation of ERα and possesses greater potency than tamoxifen or fulvestrant in a xenograft model.

    • S. W. Fanning
    • , L. Hodges-Gallagher
    •  & P. J. Kushner

  • Article
    | Open Access

    A limited number of therapeutics is available to treat influenza A virus (IAV) infections. Here, the authors show that defective interfering genes, delivered with a dual-functional peptide that enables intracellular accumulation and prevents endosomal acidification, inhibit IAV replication in vitro and in vivo.

    • Hanjun Zhao
    • , Kelvin K. W. To
    •  & Kwok-Yung Yuen

  • Article
    | Open Access

    Mutations in the cation channel PKD2 cause human autosomal dominant polycystic kidney disease but its channel function and gating mechanism are poorly understood. Here authors study PKD2 using electrophysiology and cryo-EM, which identifies hydrophobic gates and proposes a gating mechanism for PKD2.

    • Wang Zheng
    • , Xiaoyong Yang
    •  & Xing-Zhen Chen

  • Article
    | Open Access

    The ion channel TRPV4 senses many environmental cues, but its role in virus infection is not known. Here, Doñate-Macián et al. show that Zika virus induces TRPV4-mediated Ca2+ influx into cells, resulting in the nuclear accumulation of the DDX3X RNA helicase, which increases virus replication.

    • P. Doñate-Macián
    • , J. Jungfleisch
    •  & M. A. Valverde

  • Article
    | Open Access

    How toxic aggregated forms of α-synuclein lead to neurodegeneration is unclear. Here authors use biophysical and cellular imaging methods to show that specific oligomers of α-synuclein exert effects on mitochondria to induce opening of the permeability transition pore, leading to cell death in Parkinson’s disease.

    • Marthe H. R. Ludtmann
    • , Plamena R. Angelova
    •  & Sonia Gandhi

  • Article
    | Open Access

    Patients with schizophrenia show varied response to antipsychotics. Here, the authors demonstrate in patients under antipsychotics treatment that a haplotype associated with lower dysbindin-1 expression correlated with better executive functions, providing further mechanistic support from mouse models.

    • Diego Scheggia
    • , Rosa Mastrogiacomo
    •  & Francesco Papaleo

  • Article
    | Open Access

    Prostate cancer (PrCa) involves a large heritable genetic component. Here, the authors perform multivariate fine-mapping of known PrCa GWAS loci, identifying variants enriched for biological function, explaining more familial relative risk, and with potential application in clinical risk profiling.

    • Tokhir Dadaev
    • , Edward J. Saunders
    •  & Zsofia Kote-Jarai

  • Article
    | Open Access

    Many diseases, such as rheumatoid arthritis, are characterized by a chronic inflammatory state, but it is not clear whether or how this affects the brain. Here, the authors show that the severity of on-going inflammation predicts altered functional brain connectivity in people with rheumatoid arthritis.

    • Andrew Schrepf
    • , Chelsea M. Kaplan
    •  & Neil Basu

  • Article
    | Open Access

    Increasing excitability in the peri-infarct area enhances motor recovery after stroke. Here the authors show that expressing CREB, a transcription factor known for its role in synaptic plasticity, or increasing activity of CREB-expressing cells near the stroke site improves recovery in an effect that is strong enough that it can be used to turn on and off motor recovery after stroke.

    • L. Caracciolo
    • , M. Marosi
    •  & S. T. Carmichael

  • Article
    | Open Access

    It is not clear whether and how incoming HIV-1 Tat accumulates in uninfected cells. Here, Chopard et al. show that, in uninfected cells, incoming Tat is palmitoylated on Cys31 by DHHC-20, which increases its affinity for PI(4,5)P2 and results in its accumulation at the plasma membrane.

    • Christophe Chopard
    • , Phuoc Bao Viet Tong
    •  & Bruno Beaumelle

  • Article
    | Open Access

    Atherosclerosis and osteoporosis are epidemiologically associated, and oxidation specific epitopes (OSEs), which can be neutralized by innate antibodies, are pathogenic for both. Here, the authors show that mice expressing antibody fragments targeted to OSEs are protected from the bone loss induced by high-fat diet and have increased bone mass when fed a normal diet, and that levels of innate antibodies to OSEs decrease with ageing.

    • Elena Ambrogini
    • , Xuchu Que
    •  & Robert L. Jilka

  • Article
    | Open Access

    Activation of an immune response is critical for the efficacy of cancer therapies. Here, the authors show that combination of ROCK inhibitor with chemotherapeutics that induce immunogenic cell death of cancer cells leads to increased dendritic cells’ maturation and synergistic CD8+ cytotoxic T cell priming and infiltration into the tumours, leading to suppressed tumour growth and improved overall survival in syngeneic and genetically engineered tumour models.

    • Gi-Hoon Nam
    • , Eun Jung Lee
    •  & In-San Kim

  • Article
    | Open Access

    Laminins are important regulators of epidermal wound healing. Here, the authors show that laminins bind to multiple growth factors via their heparin-binding domains, and that incorporation of these domains into fibrin matrices increases growth factor retention, promoting wound healing in type 2 diabetic mouse models.

    • Jun Ishihara
    • , Ako Ishihara
    •  & Jeffrey A. Hubbell

  • Article
    | Open Access

    Synthetic prions have previously been generated from recombinant rodent PrP. Here the authors generate synthetic human prions, by seeding human PrP with CJD prions, and characterize its infectivity in mice.

    • Chae Kim
    • , Xiangzhu Xiao
    •  & Jiri G. Safar

  • Article
    | Open Access

    FOS has been linked to bone tumour pathogenesis, and viral homologue v-fos causes osteosarcoma in mice. Here, the authors report rearrangement of FOS and its paralogue FOSB in osteoblastoma and osteoid osteoma, revealing human bone tumours that are defined by mutations of FOS and FOSB.

    • Matthew W. Fittall
    • , William Mifsud
    •  & Sam Behjati

  • Article
    | Open Access

    High frequency oscillations (HFO) are a promising biomarker for identifying epileptogenic zones without the need to monitor spontaneous seizure episodes. Here the authors report that there is much variability in the location of HFOs offering a note of caution toward using HFO locations from short recordings as a guide for surgery.

    • Stephen V. Gliske
    • , Zachary T. Irwin
    •  & William C. Stacey

  • Article
    | Open Access

    Steatosis is characterized by initial accumulation of lipids, followed by inflammation and ultimately fibrosis. Here the authors show that the histone demethylase Plant Homeodomain Finger 2 protects liver form steatosis progression by acting as a co-activator of ChREBP, thus, favouring lipid accumulation without inflammation.

    • Julien Bricambert
    • , Marie-Clotilde Alves-Guerra
    •  & Renaud Dentin

  • 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

    A bottleneck in developing new anti-fibrosis therapies is the absence of suitable in vitro models that recapitulate key features of fibrogenesis. Here the authors develop a tissue-on-a-chip model of lung fibrosis and test the therapeutic efficacy of two recent FDA-approved drugs.

    • Mohammadnabi Asmani
    • , Sanjana Velumani
    •  & Ruogang Zhao

  • Article
    | Open Access

    Testosterone deficiency is associated with autoimmunity and increased B cell numbers, but the underlying mechanism is unclear. Here the authors show that testosterone may modulate the production of B cell survival factor BAFF by fibroblastic reticular cells via regulation of splenic neurotransmitter levels.

    • Anna S. Wilhelmson
    • , Marta Lantero Rodriguez
    •  & Åsa Tivesten

  • Article
    | Open Access

    Diffuse intrinsic pontine gliomas exhibit a characteristic mutation of lysine 27 to methionine (K27M) in genes encoding histone H3.3. Here the authors show that the H3.3K27M mutation imposes a specific pattern of H3.3K27 methylation by altering the target search dynamics of PcG proteins.

    • Roubina Tatavosian
    • , Huy Nguyen Duc
    •  & Xiaojun Ren

  • Article
    | Open Access

    The distinct genomic and epidemiological features of Chinese lung cancer patients suggest the presence of alternative causal mechanisms. Here, the authors present the genomic landscape of 149 Chinese NSCLC patients and reveal distinct mutational signatures associated with inflammatory microenvironments.

    • Cheng Wang
    • , Rong Yin
    •  & Hongbing Shen

  • Article
    | Open Access

    T- and NK-cell lymphomas (TCL) are a group of lymphoid malignancies characterized by poor prognosis, but the absence of appropriate pre-clinical models has hampered the development of effective therapies. Here the authors establish several pre-clinical models and identify vulnerabilities that could be further exploited to treat patients afflicted by these diseases.

    • Samuel Y. Ng
    • , Noriaki Yoshida
    •  & Raphael Koch

  • Article
    | Open Access

    Systemic chronic hypoxia is a feature of many diseases and may influence the communication between bone marrow and gut microbiota. Here, the authors show that chronic hypoxia predisposes bone marrow stem cells to premature senescence, which may be due to gut dysbiosis and gut microbiota-derived d-galactose accumulation.

    • Junyue Xing
    • , Yongquan Ying
    •  & Hao Zhang

  • Article
    | Open Access

    Intron retention (IR) can increase protein diversity and function, and yet unregulated IR may be detrimental to cellular health. This study shows that aberrant IR occurs in ALS and finds nuclear loss of an RNA-binding protein called SFPQ as a new molecular hallmark in this devastating condition.

    • Raphaelle Luisier
    • , Giulia E. Tyzack
    •  & Rickie Patani

  • 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

    Myotonic dystrophy (DM) type 2 is a neuromuscular pathology caused by large expansions of CCTG repeats. Here the authors find that rbFOX1 RNA binding protein binds to CCUG RNA repeats and competes with MBNL1 for the binding to CCUG repeats, releasing MBNL1 from sequestration in DM2 muscle cells.

    • Chantal Sellier
    • , Estefanía Cerro-Herreros
    •  & Nicolas Charlet-Berguerand

  • Article
    | Open Access

    Lung squamous carcinomas (LUSC) are poorly molecularly characterized, but sub-populations show promising response to immune checkpoint inhibitors. Here, the authors identify a subset of LUSC characterized by infiltration of inflammatory monocytes, where metastasis is linked to Factor XIIIA promoting fibrin cross-linking.

    • Alessandro Porrello
    • , Patrick L. Leslie
    •  & Chad V. Pecot

  • Article
    | Open Access

    The blood-brain barrier often limits effective delivery  of treatments for glioblastoma . In this study, the authors develop transferrin-functionalized nanoparticles able to traverse the intact blood-brain barrier and deliver combination temozolomide and bromodomain inhibitor therapy to  glioma-bearing mice.

    • Fred C. Lam
    • , Stephen W. Morton
    •  & Paula T Hammond

  • Article
    | Open Access

    In leukemia, diverse fusion proteins involving the MLL gene can drive oncogenic activity. Here, the authors describe a dependency of MLL-leukemia cells on the methyltransferase SETD2 to maintain genomic integrity during leukemia initiation and maintenance.

    • Anna Skucha
    • , Jessica Ebner
    •  & Florian Grebien

  • 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

    The timing of female reproductive capacity is influenced by genetic and environmental factors. Here, in genome-wide association studies, the authors identify genetic loci for age at menarche and onset of menopause in Japanese women, and highlight differences with European populations.

    • Momoko Horikoshi
    • , Felix R. Day
    •  & John. R. B. Perry

  • 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

    Neuromyelitis optica (NMO) is a rare autoimmune condition characterized by inflammation and demyelination of the optic nerve and the spinal cord. Here, Estrada et al. identify NMO susceptibility variants in the MHC region and find that autoantibody-positive NMO genetically overlaps with lupus.

    • Karol Estrada
    • , Christopher W. Whelan
    •  & Daniel G. MacArthur

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