Health sciences articles within Nature Communications

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  • Article
    | Open Access

    Declining NAD+ levels have been linked to aging-associated pathologies. Here the authors present results of a double-blind, randomized crossover trial on 30 healthy middle-aged individuals to show that nicotinamide riboside effectively elevates NAD+ levels in humans, appears to be well tolerated, and may have potential to improve cardiovascular parameters.

    • Christopher R. Martens
    • , Blair A. Denman
    •  & Douglas R. Seals

  • Article
    | Open Access

    Histone chaperone ASF1A is often dysregulated in cancers, however the regulation of its abundance is unclear. Here, the authors show that USP52 promotes ASF1A stability through deubiquitination while impairment of this stability reduces breast tumorigenesis and confers sensitivity to DNA damage.

    • Shangda Yang
    • , Ling Liu
    •  & Lei Shi

  • Article
    | Open Access

    The limited size of some neuronal types and their entangled environment renders it difficult to study their transcription regulation. Here the authors present a comparative analysis of histone modifications and transcription in dopaminergic and serotonergic neurons and embryonic neural progenitors.

    • Erik Södersten
    • , Konstantinos Toskas
    •  & Johan Holmberg

  • Article
    | Open Access

    Hyperemesis gravidarum (HG) is a severe form of nausea and vomiting associated with unfavourable outcomes during pregnancy. Here, Fejzo et al. perform genome-wide scans for HG and pregnancy nausea and vomiting and identify genetic associations at two loci implicating the genes GDF15 and IGFBP7.

    • Marlena S. Fejzo
    • , Olga V. Sazonova
    •  & Catherine H. Wilson

  • Article
    | Open Access

    Resistance to chemotherapy is a serious issue that can be influenced by RNA epigenetics and chromatin structure. Here, the authors show in leukaemia cells that RNA 5-methylcytosine (RNA:m5C) and RNA:m5C methyltransferases (RCMTs) mediate chromatin structures that can modulate 5-Azacitidine response and resistance.

    • Jason X. Cheng
    • , Li Chen
    •  & James W. Vardiman

  • Article
    | Open Access

    Understanding of molecular events in cancer requires proteome-level characterisation. Here, proteome profiling of patient samples representing primary and progressed prostate cancer enables the authors to identify pathway alterations that are not reflected at the genomic and transcriptomic levels.

    • Leena Latonen
    • , Ebrahim Afyounian
    •  & Tapio Visakorpi

  • Article
    | Open Access

    The V3 region of HIV Env elicits broadly neutralizing antibodies (bnAbs) in patients and represents a potential vaccine antigen. Here, Fera et al. show that the structure of a synthetic V3-glycopeptide closely resembles the conformation in intact HIV Env and identify amino acids in bnAbs that are important for neutralization breadth.

    • Daniela Fera
    • , Matthew S. Lee
    •  & Stephen C. Harrison

  • Article
    | Open Access

    High protein diets are known to improve metabolic parameters including adiposity and glucose homeostasis. Here the authors demonstrate that preabsorptive upper small intestinal protein-sensing mechanisms mediated by peptide transporter 1 improve glucose homeostasis by inhibiting hepatic glucose production.

    • Helen J. Dranse
    • , T. M. Zaved Waise
    •  & Tony K. T. Lam

  • Article
    | Open Access

    Diabetes is associated with an increased thrombotic response, but the mechanism is unknown. Here the authors demonstrate that compressive force activates integrin αIIbβ3 on discoid diabetic platelets and that platelet aggregates can be eliminated by PI 3-kinase inhibition, but not by anti-thrombotics aspirin or clopidogrel.

    • Lining Ju
    • , James D. McFadyen
    •  & Shaun P. Jackson

  • Article
    | Open Access

    Triple negative breast cancers harbor multiple copy number aberrations driving gene expression changes thought to underpin their malignant phenotypes. Here the authors integrate these features, finding and functionally validating 37 gene addictions among which they identify the mechanism of addiction to KIFC1, a potential selective drug target.

    • Nirmesh Patel
    • , Daniel Weekes
    •  & Andrew N. J. Tutt

  • Article
    | Open Access

    The authors examine the role of monkey populations in the sylvatic cycle of chikungunya virus in the Kédougou region, Senegal. The authors show that monkeys are amplification hosts, as opposed to reservoir hosts for infection. These findings expand our knowledge of the transmission dynamics of chikungunya virus in this region of Senegal.

    • Benjamin M. Althouse
    • , Mathilde Guerbois
    •  & Kathryn A. Hanley

  • Article
    | Open Access

    Eya proteins are characterised by phosphatase activity associated with both the evolutionary conserved region and the less conserved N-terminal domain (NTD). Here the authors show that NTD mediates the interaction with PP2A and regulates c-Myc phosphorylation and stability, potentially switching PP2A from a tumour suppressor to an oncogene.

    • Lingdi Zhang
    • , Hengbo Zhou
    •  & Heide L Ford

  • Article
    | Open Access

    Factor H binding protein (fHbp) and PorA are components of experimental serogroup B N. meningitidis vaccines. Here the authors graft the VR2 loop of PorA onto an fHBp-based scaffold to demonstrate proof-of-principle of a chimeric antigen strategy and vaccination against meningococcal disease.

    • S. Hollingshead
    • , I. Jongerius
    •  &  C. M. Tang

  • Article
    | Open Access

    A Zika virus (ZIKV) vaccine should provide long-lasting immunity, which may be achieved with a live-attenuated vaccine. Here, Kwek et al. select an interferon-restricted, attenuated ZIKV variant and evaluate replication and immunogenicity in mouse and mosquito models.

    • Swee Sen Kwek
    • , Satoru Watanabe
    •  & Eng Eong Ooi

  • Article
    | Open Access

    Senescence has been suggested as causing biliary cholangiopathies but how this is regulated is unclear. Here, the authors generate a mouse model of biliary senescence by deleting Mdm2 in bile ducts and show that inhibiting TGFβ limits senescence-dependent aggravation of cholangiopathies.

    • Sofia Ferreira-Gonzalez
    • , Wei-Yu Lu
    •  & Stuart J. Forbes

  • Article
    | Open Access

    Beige adipocytes can arise from transdifferentiation of mature white adipocytes. Here the authors identify CDK6 as a key molecule involved in the white-to-beige adipocyte transdifferentiation and, therefore, as a regulator of organismal energy homeostasis in mice.

    • Xiaoli Hou
    • , Yongzhao Zhang
    •  & Miaofen G. Hu

  • Article
    | Open Access

    Nontyphoidal Salmonella (NTS) is a major cause of bacteraemia in children and HIV-infected adults in Africa. Here, Gilchrist et al. conduct a genome-wide association study and show that genetic variation in STAT4 is a determinant of NTS in Kenyan and Malawian children.

    • James J. Gilchrist
    • , Anna Rautanen
    •  & Adrian V. S. Hill

  • Article
    | Open Access

    Mutations in the gene encoding iRHOM2 are associated with hyperproliferative epidermal disorders. Here, the authors show that iRHOM2 is a target gene of p63, that together they regulate inflammation, cell survival and response to oxidative stress, and inhibition of p63-iRHOM2 signalling with an antioxidant reduces epidermal inflammation.

    • Paola Arcidiacono
    • , Catherine M. Webb
    •  & Anissa Chikh

  • 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

    Aortic valve stenosis (AS) is the most common valvular heart disease. Here the authors identify two new AS loci that also associate with bicuspid aortic valve, aortic root diameter and/or coronary artery disease implicating both developmental abnormalities and atherosclerosis-like processes in AS.

    • Anna Helgadottir
    • , Gudmar Thorleifsson
    •  & Kari Stefansson

  • Article
    | Open Access

    Progressive remodeling and calcification of the aortic valve leads to calcific aortic valve stenosis (CAVS) and, ultimately, heart failure. In a combined GWAS and TWAS approach, Thériault et al. identify PALMD as a candidate causal gene for CAVS, which is further supported by Mendelian randomization.

    • Sébastien Thériault
    • , Nathalie Gaudreault
    •  & Yohan Bossé

  • Article
    | Open Access

    A critical determinant of tumor eradication by adoptive immunotherapy is the tumor associated antigen recognized by cytotoxic T lymphocytes. Here the authors generate ex vivo autologous cytotoxic T lymphocytes by exposure to antigens induced by DNA demethylation and report the results of a phase 1 trial of 25 patients with recurrent glioblastoma multiforme with tumor regression in three patients.

    • Alexei F. Kirkin
    • , Karine N. Dzhandzhugazyan
    •  & Walter Fischer

  • Article
    | Open Access

    Individuals with different genotypes may respond differently to environmental variation. Here, Favé et al. find substantial impacts of different environment exposures on the transcriptome and clinical endophenotypes when controlling for genetic ancestry by analyzing data from ∼1000 individuals from a founder population in Quebec.

    • Marie-Julie Favé
    • , Fabien C. Lamaze
    •  & Philip Awadalla

  • Article
    | Open Access

    Matrix metalloproteinases (MMP) are involved in vascular remodeling associated with plaque progression. Little is known about their immune regulatory role in vascular disorders. Here, the authors report that MT4-MMP-deficiency increases the recruitment of patrolling monocytes to early atherosclerotic lesions, which accelerates atherosclerosis.

    • Cristina Clemente
    • , Cristina Rius
    •  & Alicia G. Arroyo

  • Article
    | Open Access

    The population of Madagascar arose from admixture of Austronesian and Bantu genetic backgrounds. Analyzing local ancestry in genomes of 700 Malagasy, Pierron et al. identify signals of recent positive selection for African ancestry in a region on chromosome 1 with implications for physiology and disease risk.

    • Denis Pierron
    • , Margit Heiske
    •  & Thierry Letellier

  • Article
    | Open Access

    Adipocyte hyperplasia is thought to have beneficial metabolic effects in obesity, but definitive evidence is lacking. Here, Shao et al. promote de novo formation of adipocytes in visceral white adipose tissue (WAT) of adult mice through inducible overexpression of Pparg in Pdgfrβ+ preadipocytes and show that this protects from pathological WAT remodeling.

    • Mengle Shao
    • , Lavanya Vishvanath
    •  &  Rana K. Gupta

  • Article
    | Open Access

    Circulating tumor DNA (ctDNA) may provide a prediction of treatment response, but could be impacted by tumor heterogeneity. Here, the authors investigate ctDNA in CDK4/6 inhibitor treatment in advanced breast cancer, finding ctDNA levels predict progression-free survival and anticipate clonal selection.

    • Ben O’Leary
    • , Sarah Hrebien
    •  & Nicholas C. Turner

  • Article
    | Open Access

    Hepatocellular-cholangiocarcinoma (H-ChC) is a rare subtype of liver cancer with features of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Here, the authors utilize whole exome sequencing to highlight the monoclonal origin and stemness of H-ChC, as well as substantial intratumoral heterogeneity.

    • Anqiang Wang
    • , Liangcai Wu
    •  & Haitao Zhao

  • Article
    | Open Access

    Response of the heart rate (HR) to exercise is associated with cardiac fitness and risk of cardiac death. Here, in a genome-wide association study, Verweij et al. identify 23 loci for HR increase during exercise or HR recovery, and highlight pleiotropy with blood pressure by polygenic risk score analysis.

    • Niek Verweij
    • , Yordi J. van de Vegte
    •  & Pim van der Harst

  • Article
    | Open Access

    DNA methylation is associated with breast cancer risk. Here the authors measure DNA methylation in the blood of individuals from 25 Australian families with multiple cases of breast cancer but not known mutations associated with breast cancer risk to identify possible heritable methylation markers.

    • Jihoon E. Joo
    • , James G. Dowty
    •  & Yoland Antill

  • Article
    | Open Access

    Aggregation is sequence-specific and nucleated by short aggregating protein segments (APR). Here authors use a multidisciplinary approach to show that in E.coli some frequently occurring APRs lead to protein aggregation and ultimately bacterial cell death, which could serve as antibacterial strategy.

    • Ladan Khodaparast
    • , Laleh Khodaparast
    •  & Joost Schymkowitz

  • Article
    | Open Access

    Broadly neutralizing antibodies targeting HIV Env could potentially be utilized as therapeutics. Here, Steinhardt et al. engineer a trispecific antibody with specificity for the receptor-binding site, a conserved Env glycan patch and the Env membrane proximal region with nearly pan-isolate neutralization breadth and high potency.

    • James J. Steinhardt
    • , Javier Guenaga
    •  & Yuxing Li

  • Article
    | Open Access

    More than 100 risk loci for schizophrenia have been identified by genome-wide association studies. Here, the authors apply an integrative genomic approach to prioritize risk genes and validate GLT8D1 and CSNK2B as candidate causal genes by in vitro studies in neural stem cells.

    • Cui-Ping Yang
    • , Xiaoyan Li
    •  & Xiong-Jian Luo

  • Article
    | Open Access

    Endothelial cells release extracellular matrix components that regulate inflammation. Here the authors demonstrate that the extracellular matrix component epidermal growth factor-like protein 7 regulates inflammation in experimental autoimmune encephalomyelitis in the mouse.

    • Catherine Larochelle
    • , Timo Uphaus
    •  & Frauke Zipp

  • Article
    | Open Access

    Polycystic kidney disease (PKD) is characterized by the formation of large fluid-filled cysts. Here Flowers and colleagues show that loss of Lkb1, downregulated in PKD, renders kidney cells dependent on glutamine for growth, and suggest that inhibition of glutamine metabolism may prevent cyst development in PKD.

    • Ebony M. Flowers
    • , Jessica Sudderth
    •  & Thomas J. Carroll

  • Article
    | Open Access

    Stormorken syndrome is associated with the R304W mutation in STIM1, which is a Calcium sensor in the endoplasmic reticulum. Here authors use FRET and electrophysiology to show that R304W induces STIM1 conformational extension by a dual mechanism resulting in constitutive activation of Ca2+ channels.

    • Marc Fahrner
    • , Michael Stadlbauer
    •  & Christoph Romanin

  • Article
    | Open Access

    Chordoid glioma is a rare low-grade brain tumor that originates from the anterior wall of the third ventricle where surgical resection is challenging; the clinical outcome of patients after subtotal resection or disease recurrence is poor. Here the authors identify a recurrent missense mutation in PRKCA that may serve as a potential therapeutic target in this uncommon brain cancer.

    • Benjamin Goode
    • , Gourish Mondal
    •  & David A. Solomon

  • Article
    | Open Access

    Synovial fibroblasts are thought to be central mediators of joint destruction in rheumatoid arthritis (RA). Here the authors use single-cell transcriptomics and flow cytometry to identify synovial fibroblast subsets that are expanded and display distinct tissue distribution and function in patients with RA.

    • Fumitaka Mizoguchi
    • , Kamil Slowikowski
    •  & Michael B. Brenner

  • Article
    | Open Access

    Aging skeletal muscle shows declining numbers and activity of satellite cells. Here, Franco et al. show that in satellite cells of the human leg muscle vastus lateralis, somatic mutations accumulate with age and that these mutations become enriched in exons and promoters of genes involved in muscle function.

    • Irene Franco
    • , Anna Johansson
    •  & Maria Eriksson

  • Review Article
    | Open Access

    This review summarizes how predictive modeling, a method that uses brain features to predict individual differences in behavior, is used to understand developmental periods. Rosenberg et al focus specifically on adolescence and examples of characteristic adolescent behaviors such as risk-taking.

    • Monica D. Rosenberg
    • , B. J. Casey
    •  & Avram J. Holmes

  • Article
    | Open Access

    In a lupus environment, basophils accumulate in secondary lymphoid organs where they affect pathogenesis by stimulating autoantibody production. Here the authors show this accumulation is driven by PGD2-induced CXCR4 surface expression and trafficking of basophils.

    • Christophe Pellefigues
    • , Barbara Dema
    •  & Nicolas Charles

  • Review Article
    | Open Access

    Recall-by-Genotype (RbG) is an approach to recall participants from genetic studies based on their specific genotype for further, more extensive phenotyping. Here, the authors discuss examples of RbG as well as practical and ethical considerations and provide an online tool to aid in designing RbG studies.

    • Laura J. Corbin
    • , Vanessa Y. Tan
    •  & Nicholas J. Timpson

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