Diseases

  • Article
    | Open Access

    The percentage of national populations infected during the first stages of the COVID-19 pandemic are unclear owing to limited early testing. Here the authors provide a nation-wide prevalence study of SARS-CoV-2 antibodies in France from the first wave of COVID-19 in 2020, including stratification based on age, sex and region.

    • Stéphane Le Vu
    • , Gabrielle Jones
    •  & Harold Noel
  • Article
    | Open Access

    Lung resident memory T (TRM) cells are important for protection from viral infection in the lungs. Here the authors use paired lung biopsy material and blood to characterize T cell responses in patients with COVID-19 over time and find persistence of antiviral lung TRM cells that might be important to limit reinfection.

    • Judith Grau-Expósito
    • , Nerea Sánchez-Gaona
    •  & Meritxell Genescà
  • Article
    | Open Access

    Influenza forecasting in the United States is challenging and consequential, with the ability to improve the public health response. Here the authors show the performance of the multiscale flu forecasting model, Dante, that won the CDC’s 2018/19 national, regional and state flu forecasting challenges.

    • Dave Osthus
    •  & Kelly R. Moran
  • Article
    | Open Access

    Idiopathic pulmonary fibrosis (IPF) is a fatal adult lung disease. Here the authors investigate the functional significance of PDCD5 in club cells as a mediator of lung fibrosis and potential therapeutic target for IPF.

    • Soo-Yeon Park
    • , Jung Yeon Hong
    •  & Ho-Geun Yoon
  • Article
    | Open Access

    In placental malaria, interactions between parasite protein VAR2CSA and human glycosaminoglycan chondroitin sulfate A (CS) sequesters infected red blood cells in the placenta. Here, the authors provide cryo-EM structures of VAR2CSA and placental CS, identifying molecular interactions that could guide design of placental malaria vaccines.

    • Kaituo Wang
    • , Robert Dagil
    •  & Ali Salanti
  • Article
    | Open Access

    Generics contribute to increased availability of antibiotics, benefiting healthcare systems but potentially leading to increased consumption with implications for antibiotic stewardship and resistance. Here, the authors found no consistent changes in prescribing patterns of the 13 antibiotics that entered the US market as generics from 2000–2012.

    • Cecilia Kållberg
    • , Jemma Hudson
    •  & Ramanan Laxminarayan
  • Article
    | Open Access

    Differences in thalamic structure have been observed in several psychiatric disorders, but the genetic overlap has not been explored. Here, the authors perform a genome-wide association study on thalamic nuclei volume and find genetic loci in common between thalamic volumes and brain disorders.

    • Torbjørn Elvsåshagen
    • , Alexey Shadrin
    •  & Tobias Kaufmann
  • Article
    | Open Access

    Proteolysis targeting chimeras (PROTACs) is an effective alternative to modulate protein homeostasis but can lead to uncontrollable protein degradation and off-target side effects. Here, the authors developed semiconducting polymer nano-PROTACs with phototherapeutic and activatable protein degradation abilities for photo-immunometabolic cancer therapy.

    • Chi Zhang
    • , Ziling Zeng
    •  & Kanyi Pu
  • Article
    | Open Access

    Although enterovirus D68 poses a major global threat to children, neither vaccines nor therapeutics are currently available. Using Cryo-EM, Zhang et al. show that two murine-derived monoclonal antibodies with therapeutic efficacy neutralize virions via binding to the canyon region, creating steric hindrance for sialic acid receptor binding.

    • Chao Zhang
    • , Cong Xu
    •  & Zhong Huang
  • Article
    | Open Access

    CRISPR-Cas9 is a gene editing tool that can be used to modulate gene expression. Here, the authors report the generation of a mouse model that express all components of the CRISPR-Cas9 guide directed Synergistic Activation Mediator (SAM), demonstrate that gene activation can be achieved with various delivery methods and include generation of a disease model of hypercholesterolemia

    • Charleen Hunt
    • , Suzanne A. Hartford
    •  & Guochun Gong
  • Article
    | Open Access

    Estimates of COVID-19-related mortality are limited by incomplete testing. Here, the authors perform counterfactual analyses and estimate that there were 59,000–62,000 deaths from COVID-19 in Italy until 9th September 2020, approximately 1.5 times higher than official statistics.

    • Chirag Modi
    • , Vanessa Böhm
    •  & Uroš Seljak
  • Article
    | Open Access

    Several prognostic indices are available to predict the long-term fate of emerging infectious diseases and the effect of their containment measures, including a variety of reproduction numbers. Here, the authors introduce the epidemicity index, a complementary index to evaluate the potential for transient increases of SARS-Cov-2 epidemics.

    • Lorenzo Mari
    • , Renato Casagrandi
    •  & Marino Gatto
  • Article
    | Open Access

    Aortic aneurysm and dissection, the major problem linked to Marfan syndrome (MFS), lacks effective pharmacological treatment. Here, the authors show that the NO pathway is overactivated in MFS and that inhibition of guanylate cyclase and cGMP-dependent protein kinase reverts MFS aortopathy in mice.

    • Andrea de la Fuente-Alonso
    • , Marta Toral
    •  & Juan Miguel Redondo
  • Article
    | Open Access

    Placental dysfunction can have catastrophic or barely discernible effects ranging from miscarriage to apparently normal birth. Here the authors present a comprehensive analysis of the human placental transcriptome and identify circular RNAs and piRNAs.

    • Sungsam Gong
    • , Francesca Gaccioli
    •  & D. Stephen Charnock-Jones
  • Article
    | Open Access

    Leptin can rescue hyperglycemia in type 1 diabetes, but the underlying mechanisms for this effect are not clear. Here, the authors report that leptin action is mediated by inhibition of the heightened activity of arcuate GABA neurons in murine models of type 1 diabetes through restoring nutrient sensing.

    • Shengjie Fan
    • , Yuanzhong Xu
    •  & Qingchun Tong
  • Article
    | Open Access

    Indoor residual spraying (IRS) of insecticide is one of the primary malaria vector control initiatives, but implementation is limited. Here, the authors show that discontinuation of IRS in Uganda was associated with increased malaria incidence, and introduction of IRS was associated with decreased incidence.

    • Jane F. Namuganga
    • , Adrienne Epstein
    •  & Isabel Rodriguez-Barraquer
  • Article
    | Open Access

    Polyclonal infections occur when at least two unrelated strains of the same pathogen are detected in an individual. Here, Moreno-Molina et al. analyse sputum and surgical resections from tuberculosis patients, showing that the magnitude of polyclonal infections can be underestimated when only testing sputum samples.

    • Miguel Moreno-Molina
    • , Natalia Shubladze
    •  & Iñaki Comas
  • Article
    | Open Access

    Despite being prevalent yet well studied, ulcerative colitis still has poorly characterized pathophysiology. Here the authors use mouse colitis models to find that type I and III interferon (IFN) both contribute to ameliorating the disease, with IFN signaling in either the epithelial or hematopoietic compartment sufficient for this protective effect.

    • Constance McElrath
    • , Vanessa Espinosa
    •  & Sergei V. Kotenko
  • Review Article
    | Open Access

    At the centre of intestinal health and the fight against obesity and metabolic syndrome is the intestinal microbiota and its interaction with our immune systems. Here the authors Review the current understanding of how these systems interact and how we can capitalize on recent advances to provide better therapeutic options.

    • Saad Khan
    • , Helen Luck
    •  & Daniel A. Winer
  • Article
    | Open Access

    Forecasts of COVID-19 mortality have been critical inputs into a range of policies, and decision-makers need information about their predictive performance. Here, the authors gather a panel of global epidemiological models and assess their predictive performance across time and space.

    • Joseph Friedman
    • , Patrick Liu
    •  & Emmanuela Gakidou
  • Article
    | Open Access

    The role of the CD200–CD200R axis in regulating pulmonary inflammation is not completely understood. Here the authors show CD200R is expressed on type 2 innate lymphoid cells (ILC2s), and its engagement by CD200 ameliorates airway hyperreactivity and allergic asthma via inhibition of NF-κB signaling.

    • Pedram Shafiei-Jahani
    • , Doumet Georges Helou
    •  & Omid Akbari
  • Article
    | Open Access

    The SARS-CoV-2 receptor ACE2 is involved in the Renin-Angiotensin-Aldosterone System (RAAS). Over-activation of RAAS in swine results in a disease state similar to that of COVID-19 in human patients, suggesting that COVID-19 pathophysiology may be driven, at least in part, by an imbalance of this hormonal system.

    • Susanne Rysz
    • , Jonathan Al-Saadi
    •  & Johan Lundberg
  • Article
    | Open Access

    Insulin resistance and lower muscle strength in relation to mass are hallmarks of type 2 diabetes. Here, the authors report alterations in muscle stem cells from individuals with type 2 diabetes that may contribute to these phenotypes through VPS39 mediated effects on autophagy and epigenetics.

    • Cajsa Davegårdh
    • , Johanna Säll
    •  & Charlotte Ling
  • Article
    | Open Access

    The editing of primary human islets could provide insight into diabetes pathogenesis. Here the authors use CRISPR-Cas9 to target regulatory elements associated with T2D susceptibility.

    • Romina J. Bevacqua
    • , Xiaoqing Dai
    •  & Seung K. Kim
  • Article
    | Open Access

    The endothelial glucocorticoid receptor plays a key role in the regulation of many diseases, including diabetes. Loss of this receptor results in accelerated renal fibrosis, a heightened inflammatory milieu, augmented Wnt signaling and suppression of fatty acid oxidation in diabetic kidneys.

    • Swayam Prakash Srivastava
    • , Han Zhou
    •  & Julie Goodwin
  • Article
    | Open Access

    Defective viral genomes (DVGs) can interfere with virus replication and provide a potential approach to control infection. Here, Rezelj et al. use a combined experimental evolution and computational approach to identify DVG sequences that optimally interfere with Zika virus infection and show antiviral activity in mice and mosquitoes.

    • Veronica V. Rezelj
    • , Lucía Carrau
    •  & Marco Vignuzzi
  • Article
    | Open Access

    Massive unemployment during the COVID-19 pandemic could result in an eviction crisis in US cities. Here, the authors model the effect of evictions on SARS-CoV-2 epidemics, simulating viral transmission within and among households in a theoretical and applied urban settings.

    • Anjalika Nande
    • , Justin Sheen
    •  & Alison L. Hill
  • Article
    | Open Access

    Hydroxychloroquine and chloroquine have been investigated as a potential treatment for Covid-19 in several clinical trials. Here the authors report a meta-analysis of published and unpublished trials, and show that treatment with hydroxychloroquine for patients with Covid-19 was associated with increased mortality, and there was no benefit from chloroquine.

    • Cathrine Axfors
    • , Andreas M. Schmitt
    •  & Lars G. Hemkens
  • Article
    | Open Access

    Epithelial tissue mononuclear phagocytes (MNP) can transmit HIV to CD4 T cells, but less is known about sub-epithelial cells. Here, the authors describe MNPs in human anogenital and colorectal tissues and find that CD14+CD1c+ monocyte-derived dendritic cells and langerin-expressing conventional dendritic cells 2 preferentially take up and transmit HIV.

    • Jake W. Rhodes
    • , Rachel A. Botting
    •  & Andrew N. Harman
  • Article
    | Open Access

    Alzheimer’s disease is characterized by progressive dementia and amyloid beta plaque deposition. Here the authors show in three relevant transgenic animal models that accumulation of activated B cells is central to AD pathology and depletion of B cells interferes with both histological and behavioural manifestations of the disease.

    • Ki Kim
    • , Xin Wang
    •  & Arya Biragyn
  • Article
    | Open Access

    High myopia is associated with lens changes, but the underlying mechanisms are unclear. Here, the authors show increased equatorial diameter of the lens in subjects affected by high myopia, and find that these changes are associated with an increase in crystallin expression driven by the transcription factor MAF and TGF-β1 signaling.

    • Xiangjia Zhu
    • , Yu Du
    •  & Yi Lu
  • Article
    | Open Access

    Mitochondrial diseases, including those caused by defects in complex III of the respiratory chain, lack curative treatments. Here the authors report that the small molecule pyocyanin has beneficial effects in cells derived from patients with complex III-deficiency as well as in fly and zebrafish genetic models with reduced complex III activity.

    • Roberta Peruzzo
    • , Samantha Corrà
    •  & Ildikò Szabò
  • Article
    | Open Access

    The human chromosome locus 9p21.3 is a tumour suppressor hub which encodes three CDK inhibitors, p15INK4B, p14ARF and p16INK4A. Here, the authors show that p15INK4B inhibits the cell cycle and glycolysis in a murine model of HRas + ‐mediated urothelial carcinoma and has a more relevant role as a tumour suppressor than its neighbouring p16INK4A.

    • Yong Xia
    • , Yan Liu
    •  & Xue-Ru Wu