Diseases

  • Article
    | Open Access

    Many domestic animals, among them dogs, have been infected with SARS-CoV-2 during the COVID-19 pandemic. Here, the authors present the crystal structure of the SARS-CoV-2 spike protein receptor binding domain (RBD) bound to its receptor, dog angiotensin-converting enzyme 2 (dACE2), and show that the RBD N501Y mutation increases the infectivity and host range of SARS-CoV-2, which highlights the need to monitor emerging SARS-CoV-2 mutations in domestic animals.

    • Zengyuan Zhang
    • , Yanfang Zhang
    •  & Yeping Sun
  • Article
    | Open Access

    Osteoarthritis is caused by an imbalance between extracellular matrix synthesis and degradation. Here, the authors show that both strands of microRNA-455, -5p and -3p, target HIF2α and regulate cartilage homeostasis, and show that overexpression of these miRNAs is protective against osteoarthritis in mice.

    • Yoshiaki Ito
    • , Tokio Matsuzaki
    •  & Hiroshi Asahara
  • Article
    | Open Access

    Chromosomal translocations involving the AF10 gene, especially with CALM, are associated with aggressive leukemias. Here the authors show that the PZP domain of AF10, a histone reader, is always excluded/impaired in AF10 fusions, whereas incorporation of this domain downregulates Hoxa genes and blocks leukemogenesis.

    • Brianna J. Klein
    • , Anagha Deshpande
    •  & Tatiana G. Kutateladze
  • Article
    | Open Access

    T cells are instrumental to protective immune responses against SARS-CoV-2, the pathogen responsible for the COVID-19 pandemic. Here the authors show that, in convalescent COVID-19 patients, memory T cell responses are detectable up to 317 days post-symptom onset, in which the presence of stem cell-like memory T cells further hints long-lasting immunity.

    • Jae Hyung Jung
    • , Min-Seok Rha
    •  & Eui-Cheol Shin
  • Article
    | Open Access

    Iron is essential during pregnancy for embryo and placental development and maternal health. However, in this study using mouse models, the authors demonstrate that excess maternal iron causes adverse embryo outcomes in pregnancies with underlying systemic inflammation.

    • Allison L. Fisher
    • , Veena Sangkhae
    •  & Elizabeta Nemeth
  • Article
    | Open Access

    Current HIV cure-focused clinical trials rely on analytic treatment interruption (ATI) to evaluate post-treatment control (PTC). Here, combining untargetted metabolomics and glycomics in two HIV clinical cohorts, in vitro assays, and machine learning, the authors identify and validate metabolic and glycomic biomarkers linked to inflammatory pathways and HIV latency reactivation associated with PTC, suggesting non-invasive biomarkers as an alternative to predict HIV remission.

    • Leila B. Giron
    • , Clovis S. Palmer
    •  & Mohamed Abdel-Mohsen
  • Article
    | Open Access

    Abnormal blood lipid levels are important risk factors for cardiovascular and other various diseases. Here the authors conduct a large-scale multi-ethnic epigenome-wide association study combined with epigenetic (cis-QTL and eQTM) data, and identify CpG-lipid traits associations that are specific to or common across racial/ethnic groups.

    • Min-A Jhun
    • , Michael Mendelson
    •  & Themistocles L. Assimes
  • Article
    | Open Access

    Release of freshwater into the oceans as a result of ice sheet melting could impact the distribution of climate-sensitive diseases. Here, the authors show that a rapid ice sheet melting in Greenland could cause an emergence of malaria in Southern Africa whilst transmission risks in West Africa may decline.

    • Alizée Chemison
    • , Gilles Ramstein
    •  & Cyril Caminade
  • Article
    | Open Access

    Human Treg cells are central to immune tolerance, yet their heterogeneity and differentiation remain incompletely understood. Here the authors perform single-cell RNA and T cell receptor sequencing to resolve Treg cells from healthy individuals and patients with or without acute graft-versus-host disease revealing Treg complexity in health and disease.

    • Yuechen Luo
    • , Changlu Xu
    •  & Xiaoming Feng
  • Article
    | Open Access

    Resistance of Neisseria gonorrhoeae to extended spectrum cephalosporins is an increasing concern. Here, the authors conduct whole genome sequencing of isolates from the United States and find that most resistant isolates were associated with a persistent circulating lineage.

    • Jesse C. Thomas IV
    • , Sandeep J. Joseph
    •  & Zach Perry
  • Article
    | Open Access

    Applying complexome profiling, Evers et al. unravel the composition of mitochondrial oxidative phosphorylation complexes in P. falciparum asexual and sexual blood stages. Abundance of these complexes differs between both stages, supporting the hypothesis that a mitochondrial metabolic switch is central to gametocyte development and functioning.

    • Felix Evers
    • , Alfredo Cabrera-Orefice
    •  & Taco W. A. Kooij
  • Article
    | Open Access

    Selection of COVID-19 mitigation measures requires balancing health outcomes with economic impacts. Here, the authors derive a system to set triggers for increasing mitigation measures to preserve healthcare capacity, and describe how it has been used to support public health decision making in Austin, Texas.

    • Haoxiang Yang
    • , Özge Sürer
    •  & Lauren Ancel Meyers
  • Article
    | Open Access

    Pernicious anemia shows co-incidence with autoimmune disorders, yet the genetic basis for this condition is understudied. Here, the authors perform a genome-wide association study meta-analysis on pernicious anemia, identifying five susceptibility loci that map to genes with known roles in autoimmune disease.

    • Triin Laisk
    • , Maarja Lepamets
    •  & Reedik Mägi
  • Article
    | Open Access

    Estimating the effectiveness of COVID-19 control measures requires large prospective data including symptoms and personal risk factors. Here, the authors used data from smartphone-based application and found that individual face mask use was associated with a 64% reduced risk of COVID-19 symptoms.

    • Sohee Kwon
    • , Amit D. Joshi
    •  & Andrew T. Chan
  • Article
    | Open Access

    Keratitis is the main cause of corneal blindness worldwide, but most vision loss caused by keratitis can be avoidable via early detection and treatment, which are challenging in resource-limited settings. Here, the authors develop a deep learning system for the automated classification of keratitis and other cornea abnormalities.

    • Zhongwen Li
    • , Jiewei Jiang
    •  & Wei Chen
  • Article
    | Open Access

    Rapid, accurate and specific point-of-care diagnostics can help manage and contain fast-spreading infections. Here, the authors present a nanopore-based system that uses artificial intelligence to discriminate between four coronaviruses in saliva, with little need for sample pre-processing.

    • Masateru Taniguchi
    • , Shohei Minami
    •  & Kazunori Tomono
  • Article
    | Open Access

    Base editing is one approach used to correct mutations causing cause Duchenne muscular dystrophy (DMD), but limitations are in the requirement for a specific PAM motif and the large size beyond the packaging capacity of adeno-associated virus (AAV). Here, the authors modify the NG-targeting adenine base editor to recognize a broader PAM, devise an intein split strategy to package the otherwise oversized adenine base editor into AAV, and show it efficiently restores dystrophin expression in muscle and heart when systemically injected in a mouse model of DMD

    • Li Xu
    • , Chen Zhang
    •  & Renzhi Han
  • Article
    | Open Access

    To provide in depth characterization of HIV reservoir cells, the authors here develop a single-cell approach to simultaneously sequence TCR, integration sites and proviral genomes, called STIP-Seq, and show that the translation-competent reservoir mainly consists of proviruses with short deletions at the 5’-end of the genome.

    • Basiel Cole
    • , Laurens Lambrechts
    •  & Linos Vandekerckhove
  • Article
    | Open Access

    A central problem in the COVID-19 pandemic is that there is not enough testing to prevent infectious spread of SARS-CoV-2, causing surges and lockdowns with human and economic toll. Here, the authors evaluate an alternative strategy based on the monitoring of olfactory dysfunction with a mathematical model.

    • Daniel B. Larremore
    • , Derek Toomre
    •  & Roy Parker
  • Article
    | Open Access

    SARS-CoV-2 3CL protease (3CLpro) is essential for coronavirus replication and of great interest as an antiviral drug target. Here, the authors show that the naturally occurring flavonoid myricetin is a non-peptidomimetic and covalent inhibitor of 3CLpro, and they solve crystal structures of 3CLpro with myricetin and derivatives, which reveal that the pyrogallol group covalently modifies the catalytic cysteine.

    • Haixia Su
    • , Sheng Yao
    •  & Yechun Xu
  • Article
    | Open Access

    Yellow fever virus (YFV) is an arbovirus affecting humans and non-human primates (NHPs) with seasonal transmission. Here Hamlet et al. model the monthly occurrence of YF in humans and NHPs across Brazil and show that seasonality of agriculture is an important predictor of seasonal YF transmission.

    • Arran Hamlet
    • , Daniel Garkauskas Ramos
    •  & Neil M. Ferguson
  • Article
    | Open Access

    Disentangling the impacts of non-pharmaceutical interventions on COVID-19 transmission is challenging as they have been used in different combinations across time and space. This study shows that, early in the epidemic, school/daycare closures and stopping nursing home visits were associated with the biggest reduction in transmission in the United States.

    • Bingyi Yang
    • , Angkana T. Huang
    •  & Derek A. T. Cummings
  • Article
    | Open Access

    Population-based surveys are the gold standard for estimating seroprevalence but are expensive and often only capture a small geographic area or window of time. This study describes a new platform, SCALE-IT, for serosurveillance based on algorithmic sampling of electronic health records, and uses it to estimate the seroprevalence of SARS-CoV-2 in San Francisco.

    • Isobel Routledge
    • , Adrienne Epstein
    •  & Isabel Rodriguez-Barraquer
  • Article
    | Open Access

    New-onset hyperglycemia and complications of preexisting diabetes have been observed in COVID-19 patients, however, the underlying mechanisms are not fully understood. Here, the authors show that SARS-CoV-2 is detectable in both endocrine and exocrine cells of the pancreata of patients with COVID-19.

    • Charlotte Steenblock
    • , Stefanie Richter
    •  & Stefan R. Bornstein
  • Article
    | Open Access

    Restricted and repetitive behaviors (RRBs) are a core clinical feature of autism, yet the brain basis of RRBs is unknown. Here, the authors demonstrate that aberrant cognitive control and motor circuit dynamics differentially predict three distinct symptom clusters that define RRBs.

    • Kaustubh Supekar
    • , Srikanth Ryali
    •  & Vinod Menon
  • Article
    | Open Access

    Technical advancements have significantly improved early diagnosis of cervical cancer, but accurate diagnosis is still difficult due to various practical factors. Here, the authors develop an artificial intelligence assistive diagnostic solution to improve cervical liquid-based thin-layer cell smear diagnosis according to clinical TBS criteria in a large multicenter study.

    • Xiaohui Zhu
    • , Xiaoming Li
    •  & Yanqing Ding
  • Article
    | Open Access

    Some patients with COVID-19 fail to clear the viral infection quickly, yet our understanding for the underlying immune characteristics is still lacking. Here the authors use single-cell RNA sequencing and other data form such patients to show that persistent infection is associated with immune suppression and reduced expression of ribosomal protein genes.

    • Bin Yang
    • , Junpeng Fan
    •  & Chaoyang Sun
  • Article
    | Open Access

    Penetrance of variants in monogenic disease and clinical utility of common polygenic variation has not been well explored on a large-scale. Here, the authors use exome sequencing data from 77,184 individuals to generate penetrance estimates and assess the utility of polygenic variation in risk prediction of monogenic variants.

    • Julia K. Goodrich
    • , Moriel Singer-Berk
    •  & Miriam S. Udler
  • Article
    | Open Access

    Many job sectors classified as ‘essential’ have continued operating with limited restrictions during the COVID-19 pandemic, potentially placing workers at higher risk of infection. Here, the authors show that seropositivity rates in workers vary widely across and between job sectors in Geneva, Switzerland.

    • Silvia Stringhini
    • , María-Eugenia Zaballa
    •  & Idris Guessous
  • Article
    | Open Access

    Matthew M. Hernandez and Ana S. Gonzalez-Reiche and colleagues report evidence of SARSCoV-2 infections in respiratory pathogen-negative nasopharyngeal specimens collected in New York, which date back to over one month before the first officially documented case in the state. The findings provide insights in to the origins of the virus in New York.

    • Matthew M. Hernandez
    • , Ana S. Gonzalez-Reiche
    •  & Emilia Mia Sordillo
  • Article
    | Open Access

    Genetic variants in CD36 have been associated with metabolic syndrome. Here, the authors found that lymphatic vessel integrity and lipid transport are influenced by CD36 expression, and lymphatic endothelial cell CD36 deficiency causes visceral obesity and insulin resistance, which are risk factors for metabolic syndrome and diabetes.

    • Vincenza Cifarelli
    • , Sila Appak-Baskoy
    •  & Nada A. Abumrad
  • Article
    | Open Access

    Impaired wound healing is a serious complication in diabetic patients, and is associated with reduced HIF1α stability. Here, the authors design a small molecule that stabilizes HIF1α by blocking its interaction with VHL and show that it promotes wound healing in mouse models of diabetes.

    • Guodong Li
    • , Chung-Nga Ko
    •  & Chung-Hang Leung
  • Article
    | Open Access

    During insulin-resistance, the compensatory expansion of beta-cell mass is able to delay or the onset of overt type 2 diabetes. Here, the authors report that beta-arrestin-1, an intracellular protein known to regulate signalling through G protein-coupled receptors, is essential for beta-cell replication and function in insulin-resistant mice.

    • Luiz F. Barella
    • , Mario Rossi
    •  & Jürgen Wess
  • Article
    | Open Access

    Mechanisms underlying the cardiotoxicity associated with thoracic irradiation and doxorubicin treatment during anticancer therapy remain poorly understood. Here the authors show that treatment with an antibody against the L1 cell adhesion molecule inhibits nuclear L1CAM translocation, thereby controlling vascular DNA damage and preventing cardiotoxicity.

    • Jae-Kyung Nam
    • , A-Ram Kim
    •  & Yoon-Jin Lee
  • Article
    | Open Access

    Here, using diagnostic tools in a longitudinal cohort of ZIKV-infected pregnant women of the French Guiana Western Hospital Center (CHOG) and their infants, the authors investigate the long term neuropathological effects of congenital infection, finding that a laboratory confirmed congenital ZIKV infection at birth is associated with higher risks of adverse neurological outcomes up to three years of life.

    • Najeh Hcini
    • , Yaovi Kugbe
    •  & Léo Pomar
  • Article
    | Open Access

    As the leading cause of vision loss in working-age adults, diabetic retinopathy requires routinely retinal screening. Here the authors develop a deep learning system that can facilitate the screening by providing real-time image quality assessment, lesions detection, and grades across the disease spectrum.

    • Ling Dai
    • , Liang Wu
    •  & Weiping Jia