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Mechanisms explaining the milder clinical syndrome that is observed in children with SARS-CoV-2 infection.

Known genetic loci account for only a fraction of the genetic contribution to Alzheimer’s disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer’s disease polygenic risk score.

The CNV analysis group of the Psychiatric Genomic Consortium analyzes a large schizophrenia cohort to examine genomic copy number variants (CNVs) and disease risk. They find an enrichment of CNV burden in cases versus controls and identify 8 genome-wide significant loci as well as novel suggestive loci conferring either risk or protection to schizophrenia.

The authors defined a roadmap for investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders. Their proof-of-concept study using the largest available common variant data sets for schizophrenia and volumes of several (mainly subcortical) brain structures did not find evidence of genetic overlap.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

Evidence is growing on the impacts of climate change on human and natural systems. A two-step attribution approach—machine-learning-assisted literature review coupled with grid-cell-level temperature and precipitation—allows comprehensive mapping of the evidence on impacts and tentative attribution to anthropogenic influence.

There is high prevalence of whole genome duplication (WGD) in high grade serous ovarian cancer. Here, the authors compare tumours with and without WGD and find that those that acquired WGD early during tumour evolution are associated with worse survival and have the lowest expression of MHC-II.

Data collected from more than 2,000 taxa provide an unparalleled opportunity to quantify how extreme wildfires affect biodiversity, revealing that the largest effects on plants and animals were in areas with frequent or recent past fires and within extensively burnt areas.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

Inflammatory bowel disease (IBD) has been linked to host-microbiota interactions. Here, the authors investigate mucosa-associated microbiota using endoscopically-targeted biopsies from inflamed and non-inflamed colon in patients with Crohn’s disease and ulcerative colitis, finding associations with inflammation and host epigenomic alterations.

Experiments at the Joint European Torus tokamak show improved thermal ion confinement in the presence of highly energetic ions and Alfvénic instabilities in the plasma.

SIVmac239 infection of macaques is a favored model of human HIV infection, but antibody-mediated protection for SIVmac239 is insufficiently understood. Here, Zhao and Berndsen et al isolated nAbs and confirmed protection against SIVmac239 infection in passive transfer studies in macaques. The nAb was used to provide the first high-resolution structure of a rhesus SIV trimer by CryoEM. Analysis of the glycosylation pattern of this SIV trimer suggests a denser glycan shield on Env for rhesus SIV compared to chimpanzee SIV or HIV-1, which partially explains the poor nAb response of rhesus macaques to SIVmac239 infection.

Phase-resolved mid-infrared observations from JWST of the hot gas giant WASP-43b detect a day–night difference of 659 ± 19 K. Comparison with climate models shows that the observations are compatible with cloudy skies, at least on the nightside, and the lack of methane detection suggests the presence of disequilibrium chemistry.

Azacitidine (AZA) response in myelodysplastic neoplasms is unpredictable. Here, the authors show in a phase 2 trial that while global methylation changes did not differ by response, baseline and initial CpG methylation differences in HSPCs predicted AZA response.

Striatal hyperactivity has been linked to compulsive behavior, but cell-type and pathway specific mechanisms are unclear. Here, the authors show excessive grooming in Sapap3-KO mice is associated with indirect pathway hyperactivity and suppression of hyperactivity normalizes grooming.

Metastatic pancreatic ductal adenocarcinoma (mPDAC) has limited therapeutic options and is associated with a poor prognosis. Here the authors report the results of a randomized phase II trial showing that combining checkpoint inhibitors (durvalumab and tremelimumab) with chemotherapy (gemcitabine and nab-paclitaxel) does not improve survival compared to chemotherapy alone in patients with mPDAC.

Kyle Gaulton, Mark McCarthy, Andrew Morris and colleagues report fine mapping and genomic annotation of 39 established type 2 diabetes susceptibility loci. They find that the set of potential causal variants is enriched for overlap with FOXA2 binding sites in human islet and liver cells, and they show that a likely causal variant near MTNR1B increases FOXA2-bound enhancer activity, providing a molecular mechanism to explain the effect of this locus on disease risk.

The 18-kDa translocator protein (TSPO) has been implicated in steroid biogenesis and neuroinflammation. Here, the authors create viable and fertile global TSPO knockout mice, challenging the assumption that TSPO is essential for mouse development but suggesting that it may have a role under certain disease conditions.

This study uses gene expression predictors for the dorsolateral prefrontal cortex and other brain regions to perform a transcriptomic imputation analysis of schizophrenia, identifying 413 genic associations across 13 brain regions and 36 significantly enriched pathways.

The mechanisms underlying the pathogenesis of vaccine-induced immune thrombotic thrombocytopenia (VITT) remain unclear. Here the authors show that anti-PF4 antibodies are responsible for the activation of platelets and neutrophils, and blockage of FcγRIIa or NETosis in vivo can prevent thrombosis.

Analysing the extent of occurrence and niche hypervolumes of 55 species of frogs in eastern Australia, the authors show that species impacted by the introduction of the pathogenic amphibian chytrid fungus underwent niche contractions, and that these were in a direction that could inhibit chytrid fungus and/or promote host demographic resilience.

Evolutionary change in basal metabolic rate was not coupled with body temperature across endothermic species, although the mechanism by which birds and mammals adapted to colder environments differed.

Pronounced increases in winter temperature result in lower seasonal temperature differences, with implications for vegetation seasonality and productivity. Research now indicates that temperature and vegetation seasonality in northern ecosystems have diminished to an extent equivalent to a southerly shift of 4°– 7° in latitude, and may reach the equivalent of up to 20° over the twenty-first century.

Pulmonary arterial hypertension (PAH) is a rare, but devastating, disease characterized by progressive obliteration of the pulmonary microvasculature. Over the past decade, an increasing number of therapies targeting the prostacyclin, endothelin, and nitric oxide pathways have been shown to improve the symptoms of PAH and even slow disease progression. O'Callaghan and colleagues review the pharmacological agents currently available for the treatment of PAH and discuss potential novel therapeutic targets in this disease.

Mutations in PTEN have been associated with various human disease, including autism spectrum disorder (ASD) and cancer. Here, the authors assess the function of 106 PTEN variants in yeast, invertebrate models and cell culture and report that PTEN variants generally decrease protein stability.

FKRP mutations cause muscular dystrophies with varied clinical presentations. The target of FKRP is α-dystroglycan, but here the authors show that FKRP also directs sialylation of fibronectin, a process that is essential for recruitment o collagen to the muscle basement membrane.

Genome-wide association studies have identified regions which confer risk of high-grade serous epithelial ovarian cancer. Here the authors use expression quantitative train locus analysis to identify candidate genes and functionally characterise them, identifying a role for HOXD9 in ovarian cancer.

Single-cell RNA-seq and ATAC-seq, combined with spatial transcriptomics, identify age- and location-related cellular dynamics of diffuse midline gliomas, such as variable oligodendrocyte precursor-like tumor stem cell populations and increased mesenchymal states with age.

Maternal genome-wide analyses identify variants associated with gestational duration and preterm delivery. Maternal alleles positively associated with gestational duration exhibit negative fetal effects on birth weight, likely reflecting antagonistic pleiotropy.

Human leucocyte antigen E (HLA-E) directly engages NK cells but also presents antigen to CD8⁺ T cells. Here the authors show crystal structures of HLA-E in complex with peptides derived from HIV and Mycobacterium tuberculosis, and describe binding conformations, the positional impact of residues involved and discuss implications for functional presentation to CD8⁺ T cells.

Pulmonary function is influenced by environmental factors, lifestyle, and genetics. Here, in a multiethnic GWAS meta-analysis for pulmonary function traits, the authors identify over 50 additional genetic loci, a subset of which are specific for European, African, Asian, or Hispanic/Latino ancestry.

Evaluation of mitigation actions often focuses on cost and overlooks the direct effects on well-being. This work shows demand-side measures have large mitigation potential and beneficial effects on well-being outcomes.

Relatives of patients with amyotrophic lateral sclerosis have an unexpectedly high incidence of schizophrenia. Here, the authors show a genetic link between the two conditions, suggesting shared neurobiological mechanisms.

Mark Caulfield, Paul Elliott and colleagues use data from the UK Biobank to perform genome-wide association analysis for blood pressure traits. They identify and validate 107 novel loci and highlight new biological pathways for potential therapeutic intervention for hypertension.

The sensing mechanism of the gut and the effector systems with which they communicate interact intimately on an anatomical and functional level. Here, John Furness and colleagues discuss how recent discoveries are enabling us to develop a comprehensive understanding of the integrated responses of the gut to the sensory information it receives.

Schizophrenia is a highly heritable genetic disorder, however, identification of specific genetic risk variants has proven difficult because of its complex polygenic nature—a large multi-stage genome-wide association study identifies 128 independent associations in over 100 loci (83 of which are new); key findings include identification of genes involved in glutamergic neurotransmission and support for a link between the immune system and schizophrenia.

The tumour microenvironment provides signals to support leukaemic stem cells (LSC) maintenance and chemoresistance. Here, the authors show that disrupting niche-associated signalling by inhibiting receptor-mediated endocytosis with a dynamin GTPase inhibitor overcomes chemoresistance of LSC.

MEG shows that the aging brain reshapes its functional organisation during musical sequence recognition, with increased sensory regions activity and reduced memory regions functionality, indicating novel neural compensatory mechanisms in aging.

Genetic variants in ionotropic glutamate receptors have been implicated in neurodevelopmental disorders. Here, the authors report heterozygous de novo mutations in the GRIA2 gene in 28 individuals with intellectual disability and neurodevelopmental abnormalities associated with reduced Ca²⁺ transport and AMPAR currents.”

Emerging limitations on climate and low-carbon technology would require adjusting our 15.C climate change mitigation pathways. However, this could increase average annual emissions reductions to around 3GtCO₂/year using a broad portfolio of mitigation measures.

Determining progress in adaptation to climate change is challenging, yet critical as climate change impacts increase. A stocktake of the scientific literature on implemented adaptation now shows that adaptation is mostly fragmented and incremental, with evidence lacking for its impact on reducing risk.

Biochar promotes plant growth via a slow release of nutrients; however, a mechanistic understanding of nutrient storage in biochar is lacking. Here, using high-resolution spectromicroscopy and mass spectrometry, the authors identify an organic coating on co-composted particles that enhances nutrient retention.

Amory B. Lovins, a consultant physicist, and British Representative of Friends of the Earth Inc., the US sister-group of the independent UK group FOE Ltd., argues that US pressurised water reactors are an economic disaster

Diabetic neuropathy is a complication of diabetes mellitus that results in loss of sensory function beginning in the extremities. This Primer summarizes the epidemiology, mechanisms, diagnosis and treatment of diabetic nephropathy and discusses the quality-of-life issues faced by patients.