Diseases articles within Nature Communications

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  • Article
    | Open Access

    The role of neutrophils in the development of atherosclerosis has long been an enigma, with few neutrophils detected within the plaque. Here, the authors show that microvesicles released from neutrophils increase vascular inflammation and enhance atherosclerotic plaque formation through delivery of miR-155.

    • Ingrid Gomez
    • , Ben Ward
    •  & Victoria Ridger

  • Article
    | Open Access

    Understanding factors that impact CAR T cell expansion in the clinic is crucial to improving its therapeutic success. Here the authors document heterogeneity in the clonal dynamics of CAR-T cells by tracking individual clones using the endogenous TCR and integration sites and provide further insights into the role of transcriptional states in clonal kinetics.

    • Alyssa Sheih
    • , Valentin Voillet
    •  & Cameron J. Turtle

  • Article
    | Open Access

    Heart failure is a complex syndrome that is associated with many different underlying risk factors. Here, to increase power, the authors jointly analyse cases of heart failure of different aetiologies in a genome-wide association study and identify 11 loci of which ten had not been previously reported.

    • Sonia Shah
    • , Albert Henry
    •  & R. Thomas Lumbers

  • Article
    | Open Access

    Antimicrobial peptide LL37 can bind nucleic acids and potentiate their sensing by endosomal TLRs. Here the authors show that LL37 binds to RNA from neutrophil extracellular traps (NETs), which amplifies inflammation and production of more LL37 and NETs via TLR8/13, suggesting that LL37 contribution to psoriasis may be fueled by NET-associated RNA.

    • Franziska Herster
    • , Zsofia Bittner
    •  & Alexander N. R. Weber

  • Article
    | Open Access

    Detection of Alzheimer’s disease (AD) biomarkers from patients’ blood is challenging because these are present in very low concentrations in the plasma. Here the authors develop a sensor array of densely aligned single-walled carbon nanotubes for clinically accurate detection of femtomolar AD biomarkers in human plasma samples.

    • Kayoung Kim
    • , Min-Ji Kim
    •  & Chan Beum Park

  • Article
    | Open Access

    M. tuberculosis NAD+ synthetase (tbNadE) is of interest as a drug target. Here the authors present the actively trapped Homo sapiens NAD+ synthetase (hsNadE) and tbNadE structures and show key differences in the synthetase active site and in structural elements possibly involved in the allosteric regulation of catalysis to be leveraged for the development of M. tuberculosis selective inhibitors.

    • Watchalee Chuenchor
    • , Tzanko I. Doukov
    •  & Barbara Gerratana

  • Article
    | Open Access

    The role of impaired lung function in lung cancer etiology is complex due to the relation of cigarette smoking to both conditions. Here, supported by Mendelian randomization analysis the authors find a link between pulmonary function impairment and lung cancer risk beyond smoking, implicating immune-related pathways

    • Linda Kachuri
    • , Mattias Johansson
    •  & Rayjean J. Hung

  • Article
    | Open Access

    Here, the authors provide the structure of mature Coxsackie Virus A10 alone and in complex with its receptor KREMEN1, and of A-particles. This shows how the receptor spans the viral canyon and suggests that receptor binding triggers pocket factor release and conformational changes resulting in expanded particles.

    • Yuguang Zhao
    • , Daming Zhou
    •  & David I. Stuart

  • Article
    | Open Access

    DNA damage is associated with metabolic disorders, but the mechanism in unclear. Here, the authors show that persistent DNA damage induced by lack of the endonuclease XPF-ERCC1 triggers extracellular vesicle biogenesis in tissue infiltrating macrophages, and that vesicle uptake stimulates glucose uptake in recipient cells, leading to increased inflammation.

    • Evi Goulielmaki
    • , Anna Ioannidou
    •  & George A. Garinis

  • Article
    | Open Access

    Here, Heaney et al. show that La Niña conditions are associated with higher than average incidence of childhood diarrheal disease in Botswana in the early rainy season. This finding could help to predict childhood diarrhea outbreaks in southern Africa.

    • Alexandra K. Heaney
    • , Jeffrey Shaman
    •  & Kathleen A. Alexander

  • Article
    | Open Access

    The edematous form of severe acute childhood malnutrition (ESAM) presents with more severe multi-organ dysfunction than non-edematous SAM (NESAM). Here the authors assess genome-wide DNA methylation in buccal cells of SAM children and find that ESAM is characterized by hypomethylation at genes associated with disorders of nutrition and metabolism, including fatty liver and diabetes.

    • Katharina V. Schulze
    • , Shanker Swaminathan
    •  & Neil A. Hanchard

  • Article
    | Open Access

    Here, the authors use a molecular epidemiological approach to investigate the frequency and intensity of clustering of HIV with different set-point viral loads and find that frequently transmitted strains in genetic transmission clusters have significantly higher viral loads than nonclustered viruses.

    • Joel O. Wertheim
    • , Alexandra M. Oster
    •  & Walid Heneine

  • Article
    | Open Access

    Uterine adenomyosis often co-occurs with endometriosis or leiomyoma, but little is known about its molecular underpinnings. Here, the authors show that KRAS mutations are frequent in this disease, which might reduce sensitivity to progestin treatment via epigenetic silencing of the progesterone receptor.

    • Satoshi Inoue
    • , Yasushi Hirota
    •  & Hiroyuki Mano

  • Article
    | Open Access

    Psychiatric disorders are often accompanied by alterations in BMI and body composition due to changes in eating behaviour and physical activity. Here, Hübel et al. study the genetic overlap between these traits and find that genetic correlations between psychiatric disorders and body composition are sex-specific and evident only in adulthood.

    • Christopher Hübel
    • , Héléna A. Gaspar
    •  & Gerome Breen

  • Article
    | Open Access

    Skeletal muscle stem cells express the transcription factor Pax7. Here, the authors isolate, from human muscle, cells that are positive for the endothelial marker CLEC14A and show that despite not expressing pax7, these cells regenerate muscle and contribute to the muscle stem cell niche when transplanted into mice.

    • Andreas Marg
    • , Helena Escobar
    •  & Simone Spuler

  • Article
    | Open Access

    Four genome-wide associated loci are currently known for malaria susceptibility. Here, the authors expand on earlier work by combining data from 11 malaria-endemic countries and additional population sequencing informing an African-enriched imputation reference panel, with findings including a previously unreported association on chromosome 6.

    • Gavin Band
    • , Quang Si Le
    •  & Dominic P. Kwiatkowski

  • Article
    | Open Access

    Dengue and Zika virus are related flaviviruses, and introduction of Zika in the Americas may have impacted dengue epidemiology. Here, Borchering et al. show that dengue incidence was unusually low in 2017 in Brazil and Colombia, and simulations incorporating immune-mediated interactions predict reductions in dengue following Zika outbreaks with subsequent rebounds.

    • Rebecca K. Borchering
    • , Angkana T. Huang
    •  & Derek A. T. Cummings

  • Article
    | Open Access

    Progressive familial intrahepatic cholestasis type 3 is a disease caused by mutations in the gene encoding the multidrug resistance protein 3, and has limited treatment options. Here they show that adeno-associated virus mediated gene therapy prevents disease progression in a mouse disease model.

    • Nicholas D. Weber
    • , Leticia Odriozola
    •  & Cristian Smerdou

  • Article
    | Open Access

    Understanding the genomic features of dedifferentiated liposarcoma (DDLPS) is likely to uncover new options for management. Here, the authors reveal three prognostic groups, and highlight molecular markers associated with malignant transformation.

    • Makoto Hirata
    • , Naofumi Asano
    •  & Koichi Matsuda

  • Article
    | Open Access

    Lactobacillus associates with vaginal protection from HIV-1 infection. Here, the authors show that lactobacilli extracellular vesicles contain bacterial proteins and metabolites that inhibit HIV-1 infection in T cells and in human cervico-vaginal and tonsillar tissues ex vivo via altering viral Env proteins.

    • Rogers A. Ñahui Palomino
    • , Christophe Vanpouille
    •  & Leonid Margolis

  • Article
    | Open Access

    Plasmodium growth is adapted to the reproductive cycle of mosquitoes, but underlying mechanisms are unclear. Here, Lampe et al. show that the blood-meal induced miR-276 balances the termination of the mosquito amino acid catabolism and egg development, providing nutrients for Plasmodium sporozoite development.

    • Lena Lampe
    • , Marius Jentzsch
    •  & Elena A. Levashina

  • Article
    | Open Access

    Here, Bhattacharya et al. chemically mutagenize Leishmania and identify genes associated with resistance to miltefosine and paromomycin by next generation sequencing. The study shows that a protein kinase (CDPK1) can mediate resistance to paromomycin by affecting translation.

    • Arijit Bhattacharya
    • , Philippe Leprohon
    •  & Marc Ouellette

  • Article
    | Open Access

    Relapse, reinfection and recrudescence can all cause recurrent infection after treatment of Plasmodium vivax malaria in endemic areas, but are difficult to distinguish. Here the authors show that they can be differentiated probabilistically and thereby demonstrate the high efficacy of primaquine treatment in preventing relapse.

    • Aimee R. Taylor
    • , James A. Watson
    •  & Nicholas J. White

  • Article
    | Open Access

    Climate affects dynamics of infectious diseases, but the impact on respiratory syncytial virus (RSV) epidemiology isn’t well understood. Here, Baker et al. model the influence of temperature, humidity and rainfall on RSV epidemiology in the USA and Mexico and predict impact of climate change on RSV dynamics.

    • Rachel E. Baker
    • , Ayesha S. Mahmud
    •  & Bryan T. Grenfell

  • Article
    | Open Access

    Urinary tract infections (UTIs) are associated with changes in the gut microbiome. Here, the authors evaluate the relationship between the gut microbiome and development of UTI in kidney transplant patients and show that uropathogenic gut abundance might represent a risk factor for development of bacteriuria and UTI.

    • Matthew Magruder
    • , Adam N. Sholi
    •  & John Richard Lee

  • Article
    | Open Access

    Here, the authors investigate the outcome of prevention services scale-up on HIV incidence in a South African large population-based HIV surveillance cohort with over a decade of follow-up and associate a 43% reduction in incidence to earlier male medical circumcision and increased levels of antiretroviral therapy coverage.

    • Alain Vandormael
    • , Adam Akullian
    •  & Frank Tanser

  • Article
    | Open Access

    Histology data exists for many cancer samples and the ability to automatically image this data may provide prognostic information. Here, the authors generated an algorithm to measure tumour infiltrating lymphocytes in melanoma histology specimens and show that the ratio of these immune cells to tumour cells has prognostic value.

    • Balazs Acs
    • , Fahad Shabbir Ahmed
    •  & David L. Rimm

  • Article
    | Open Access

    Identification of clinically relevant gene expression signatures for cancer stratification remains challenging. Here, the authors introduce a flexible nonlinear signal superposition model that enables dissection of large gene expression data sets into signatures and extraction of gene interactions.

    • Michael Grau
    • , Georg Lenz
    •  & Peter Lenz

  • Article
    | Open Access

    Memories linking environmental cues to alcohol reward are involved in the development and maintenance of heavy drinking. Here, the authors show that a single dose of ketamine, given after retrieval of alcohol-reward memories, disrupts the reconsolidation of these memories and reduces drinking in humans.

    • Ravi K. Das
    • , Grace Gale
    •  & Sunjeev K. Kamboj

  • Article
    | Open Access

    ‘Missing self’ is a mode of natural killer (NK) cell activation aimed to detect the lack of HLA-I molecules on infected or neoplastic cells. Here, the authors show that mismatch between donor HLA-I and cognate receptors on recipient NK cells mediates microvascular inflammation-associated graft rejection, a pathology that is preventable by mTOR inhibition.

    • Alice Koenig
    • , Chien-Chia Chen
    •  & Olivier Thaunat

  • Article
    | Open Access

    Histone deacetylase 3 (HDAC3) is a regulator of lipid homeostasis in several tissues, however, its role in intestinal lipid metabolism was not yet known. Here the authors study intestine specific HDAC3 knock out mice and report that these animals have increased fatty acid oxidation and undergo remodeling of the intestinal epithelial cell lipidome.

    • Mercedes Dávalos-Salas
    • , Magdalene K. Montgomery
    •  & John M. Mariadason

  • Article
    | Open Access

    Genome sequencing is being widely adopted for diagnosis of genetic diseases, but identifying the causal variants remains challenging. Here, the authors introduce a tool that incorporates tissue-specific gene expression data into predicting variant pathogenicity, improving accuracy.

    • Denise Anderson
    • , Gareth Baynam
    •  & Timo Lassmann

  • Article
    | Open Access

    Cellular overgrowth and fibrosis in the foreign body response can compromise the function of transplanted cells. Here, the authors report on the zwitterionically modified alginates for the encapsulation of cells to reduce cellular overgrowth and demonstrate application in mice, dogs and pigs.

    • Qingsheng Liu
    • , Alan Chiu
    •  & Minglin Ma

  • Article
    | Open Access

    T cells from narcolepsy patients were recently reported to recognize hypocretin, a wakefulness-promoting neurohormone, suggesting autoimmune origin of the disease. Here the authors show that hypocretin-specific T cells expand both in healthy controls and in narcolepsy patients, and identify preliminary features that may distinguish them.

    • Wei Jiang
    • , James R. Birtley
    •  & Elizabeth D. Mellins

  • Article
    | Open Access

    Pulmonary arterial hypertension (PAH) is characterised by progressive pulmonary vascular remodelling. Here, Arnold et al. develop a therapeutic antibody targeting osteoprotegerin and find it attenuates pulmonary vascular remodelling in multiple rodent models of PAH, alone or in combination with standard of care vasodilator therapy.

    • Nadine D. Arnold
    • , Josephine A. Pickworth
    •  & Allan Lawrie

  • Article
    | Open Access

    The brain’s capacity to produce new neurons in response to injury is limited. Here, the authors transplant GABAergic progenitor cells and show that they synaptically incorporate into the damaged hippocampus and rescue memory problems and post-traumatic seizures caused by traumatic brain injury.

    • Bingyao Zhu
    • , Jisu Eom
    •  & Robert F. Hunt

  • Article
    | Open Access

    The build-up of iron in the body can have serious consequences; current treatment therapies suffer from adverse side effects and toxicity. Here, the authors developed renal clearable nanochelators with improved pharmacodynamics and demonstrated their efficacy and safety in iron overload animal models.

    • Homan Kang
    • , Murui Han
    •  & Jonghan Kim

  • Article
    | Open Access

    The oncogenic fusion protein AML1-ETO has the ability of AML1 to interact with DNA but blocks AML1-dependent transcription. Here the authors report that histone lysine methyltransferase EZH1 interacts with AML1-ETO and methylates AML1-ETO at lysine 43, promoting AML1-ETO transcriptional repression in leukemia.

    • Liping Dou
    • , Fei Yan
    •  & Li Yu

  • Article
    | Open Access

    Immune cells contribute to the aortic wall destruction during abdominal aortic aneurysm (AAA) development. Here, Peshkova et al. show that cytokine signaling through interleukin-27 receptor is required for Angiotensin II-induced myelopoiesis and mature myeloid cells production, thus contributing to their aortic accumulation and aneurysm progression

    • Iuliia O. Peshkova
    • , Turan Aghayev
    •  & Ekaterina K. Koltsova

  • Article
    | Open Access

    The role of the transmembrane glycoprotein CD47 in healing injured intestinal mucosa is unclear. Here, the authors show that selective loss of CD47 in the murine intestinal epithelium results in defective mucosal repair after colonic wounding, with suggested impaired cell migration in vitro.

    • Michelle Reed
    • , Anny-Claude Luissint
    •  & Charles A. Parkos

  • Article
    | Open Access

    Here, in a cohort of infants unexposed to maternal antibiotics, the authors analyse the gut microbiome development of children born naturally and by caesarean section, finding a higher abundance of known pathogens in the latter group, and an association between these bacteria and a higher incidence of respiratory infections in the first year of life.

    • Marta Reyman
    • , Marlies A. van Houten
    •  & Debby Bogaert

  • Article
    | Open Access

    Here, Thorsen et al. examine the microbiota during the first three months of life in a cohort of 700 children and find that microbial diversity and the relative abundances of Veillonella and Prevotella in the airways at one month of age are associated with topical immune mediators and asthma by age 6 years.

    • Jonathan Thorsen
    • , Morten A. Rasmussen
    •  & Hans Bisgaard

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