Search

Global analysis of obesity trends from 1980 to 2024 in 200 countries and territories using data from 4,050 population-based studies reveals that framing obesity as a single global epidemic masks the highly varied dynamics across countries and age groups.

Extracellular vesicles from lung epithelial cells deliver ACE2 and TMPRSS2 to recipient cells, enabling SARS-CoV-2 infection beyond receptor-expressing cells and expanding viral tropism.

Myopathy caused by BAG3 mutation disrupts muscle protein homeostasis and leads to severe muscle weakness. In mouse models, the authors demonstrate that impaired autophagy drives the pathology, while gene therapy targeting the mutated BAG3 improves muscle function.

This study found higher RSV antibody levels were associated with lower RSV risk in children outside the hospital. An earlier rise in incidence and higher incidence rates were observed among children <5 years compared to older children and adults.

Pocillopora species, sampled on the TARA Pacific Expedition, have greater phenotypic plasticity in response to environmental variables than Porites species, whose phenotypes were dictated by coral host genetics and past climate, according to extensive multi-biomarker analysis.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Analysis of a placebo-controlled trial of a BCMA-targeting CAR-T cell therapy in patients with myasthenia gravis shows that CAR-T cell infusion selectively remodels the systemic immune environment, with elimination of BCMA-high plasma cells and activated plasmacytoid dendritic cells and changes in the autoreactive B cell repertoire.

The authors found that the Alzheimer’s disease-associated protein tau, widely considered pathogenic when hyperphosphorylated, has a natural function as part of the innate immune system in the brain and can protect against herpes simplex virus 1.

The authors analyze white matter alterations in bipolar II depression, revealing significant correlations with inflammation and psychiatric symptoms. These findings suggest that childhood emotional maltreatment may exacerbate these effects and offer insights into potential therapeutic targets.

The Cancer Genome Atlas Research Network report integrated genomic and molecular analyses of 164 squamous cell carcinomas and adenocarcinomas of the oesophagus; they find genomic and molecular features that differentiate squamous and adenocarcinomas of the oesophagus, and strong similarities between oesophageal adenocarcinomas and the chromosomally unstable variant of gastric adenocarcinoma, suggesting that gastroesophageal adenocarcinoma is a single disease entity.

The authors find that TDP-43 loss of function—the pathology defining the neurodegenerative conditions ALS and FTD—induces novel mRNA polyadenylation events, which have different effects, including an increase in RNA stability, leading to higher protein levels.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Maternal and perinatal morbidity and mortality remain high in Malawi, partially due to gaps in the coverage and quality of health services. Here the authors develop an individual-based simulation model of maternal and perinatal health and healthcare in Malawi, situated in the Thanzi La Onse ‘whole health system, all-disease’ framework, and apply it to estimate the impact of current and improved coverage and quality of maternity services on health in Malawi between 2023 and 2030.

Analyses of samples from patients with acute myeloid leukaemia reveal that drug response is associated with mutational status and gene expression; the generated dataset provides a basis for future clinical and functional studies of this disease.

Children receiving chest radiotherapy for childhood cancer have a higher risk of developing breast cancer later in life. Here, using the data from the Childhood Cancer Survivor Study, the authors investigate the treatment and survival outcomes of breast cancer patients who previously survived childhood cancer finding them to receive altered treatment and having increased mortality.

Amyotrophic Lateral Sclerosis is characterized by TDP-43 proteinopathy in the brain. Here, the authors find TDP-43 aggregation might be mediated by the loss of Asparaginase-like 1, an enzyme that degrades detrimental isoaspartates and is downregulated by the endogenous retrovirus HML-2.

Patients with partial recombination-activating gene (RAG) deficiency (pRD) present variable late-onset autoimmune clinical phenotypes. Walter and colleagues identified a restricted primary B cell antigen receptor repertoire enriched for autoreactivity and clonal persistence in pRD. They described dysregulated B cell maturation with expansion of T-bet⁺ B cells revealing how RAG impacts stringency of tolerance and B cell fate in the periphery.

An integrated analysis of de novo and inherited coding variants in 42,607 individuals with autism spectrum disorder identifies 60 risk genes of which five have not previously been associated with neurodevelopmental disorders.

The Cancer Genome Atlas reports on molecular evaluation of 295 primary gastric adenocarcinomas and proposes a new classification of gastric cancers into 4 subtypes, which should help with clinical assessment and trials of targeted therapies.

Paul Pharoah and colleagues report the results of a large genome-wide association study of ovarian cancer. They identify new susceptibility loci for different epithelial ovarian cancer histotypes and use integrated analyses of genes and regulatory features at each locus to predict candidate susceptibility genes, including OBFC1.

The US National Institute of Allergy and Infectious Diseases (NIAID) and the Foundation for the National Institutes of Health (FNIH) held a three-day workshop to assess the landscape of long COVID clinical studies and develop plans for the RECOVER-TLC clinical trials program.

The exfoliation of 2D nanosheets from nonlayered 3D crystals has the potential to generate new 2D materials, but the exfoliation mechanisms remain unclear. Here, the authors identify the important role of intrinsic stacking faults in 3D boron crystals in the liquid-phase exfoliation of 2D boron nanosheets.

De Blank and colleagues examine data from childhood cancer survivors diagnosed between 1970 and 1999 and find that exposure to radiation decreased over time, and radiation was associated with a higher risk of late mortality and subsequent neoplasms.

In a pooled analysis of six international studies involving about 17,900 female survivors of childhood cancer, the use of doxorubicin was associated with a dose-dependent risk of subsequent breast cancer, irrespective of prior chest radiotherapy exposure.

Timothy Frayling, Joel Hirschhorn, Peter Visscher and colleagues report a meta-analysis of genome-wide association studies for adult height in 253,288 individuals. They identify 697 variants in 423 loci significantly associated with adult height and find that these variants cluster in pathways involved in growth and together explain one-fifth of the heritability for this trait.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

A longitudinal analysis of humoral immune responses in patients with COVID-19 with varying disease severities reveals that mortality does not correlate with antiviral antibody levels but, instead, with slower seroconversion.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

A new study from the WHO African Region identifies features of countries that predict timing of the first case and the per capita mortality rate for the first and second waves of the COVID-19 epidemics.

Mouse models of NF1-associated optic pathway glioma show that tumour initiation and growth are driven by aberrantly high levels of NLGN3 shedding in the optic nerve in response to retinal neuron activity.

Hakon Hakonarson and colleagues report the identification of two new susceptibility loci for inflammatory bowel disease (IBD). One variant is near a gene encoding tumor necrosis factor receptor subfamily member 6B and is associated with increased levels of this protein in serum from individuals with IBD.

The authors show pro-inflammatory responses are needed for Marburg virus control in its natural bat reservoir, and that if reduced, humanlike disease and shedding results, suggesting that natural immunomodulatory stressors may increase spillover risk.

In the early stages of atherosclerosis, macrophages in the vessel wall convert into foam cells, which promote the rise of atherosclerotic plaques. Here Hamada et al. show that the macrophage transcription factor MafB inhibits foam-cell apoptosis, and that its absence promotes atherosclerosis development in mice.

Bitter taste receptors (TAS2Rs) are a subfamily of G-protein coupled receptors (GPCRs). Here, the authors report a cryo-EM structure of the human TAS2R14 in complex with its signaling partner gustducin, and bound to an anti-inflammatory drug flufenamic acid (FFA).

Genome-wide association meta-analyses of waist-to-hip ratio adjusted for body mass index in more than 224,000 individuals identify 49 loci, 33 of which are new and many showing significant sexual dimorphism with a stronger effect in women; pathway analyses implicate adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution.

Mislocalisation of tau occurs in several neurodegenerative diseases and is thought to contribute to synaptic function. The authors show that presynaptically, tau binds to synaptic vesicles via the N-terminus which contributes to synaptic dysfunction.

This paper describes molecular subtypes of cervical cancers, including squamous cell carcinoma and adenocarcinoma clusters defined by HPV status and molecular features, and distinct molecular pathways that are activated in cervical carcinomas caused by different somatic alterations and HPV types.

SARS-CoV-2 infection is milder in children, but direct comparison with adults is rare. Here the authors show that immune responses are higher in children, retained for 12 months or longer and can neutralize Alpha, Beta and Delta variants.

A high-resolution kidney cellular atlas of 51 main cell types, including rare and previously undescribed cell populations, represents a comprehensive benchmark of cellular states, neighbourhoods, outcome-associated signatures and publicly available interactive visualizations.

Edelson and colleagues show that the transcription factor Bhlhe40 is required in a cell-intrinsic manner for the self-renewal and maintenance of large peritoneal macrophages, but not that of other tissue-resident macrophages.

Analyses of the relationships between temperature, moisture and seven key plant functional traits across the tundra and over time show that community height increased with warming across all sites, whereas other traits lagged behind predicted rates of change.

Egyptian rousette bats (ERBs) are natural reservoirs for Marburg virus (MARV), but these bats have not been linked to the MARV Angola strain that caused the largest and deadliest outbreak on record. Here, Amman et al., in a multi-institutional surveillance effort, identify and isolate Angola-like MARV in ERBs in West Africa.