Search

In mouse experiments and in clinical trials in humans, boosting with Omicron-specific mRNA following immunization with Wuhan-1 spike mRNA results in immune responses focused on conserved rather than variant-specific epitopes.

Abnormal amyloid and tau PET in cognitively unimpaired individuals is strongly associated with short-term cognitive decline and subsequent development of dementia.

A NutNet experiment in 57 grasslands across six continents shows that when herbivores are excluded from grasslands with a long coevolutionary history of grazing plant diversity is reduced, while in grasslands without a long grazing history the evolutionary history of the plant species regulates the response of plant diversity.

A study demonstrates that specific interactions between the two committed enzymes for the synthesis of lipopolysaccharide and peptidoglycan enable coordinated assembly of the outer membrane and cell wall in the Gram-negative pathogen Pseudomonas aeruginosa.

In a cohort of 50,556 South Asian individuals, partitioned polygenic scores helped identify genetic susceptibility to insulin deficiency and unfavorable fat distribution as key drivers of young-onset T2D diagnosis and faster progression to diabetes-related complications.

Single-cell intracellular recordings have been used as the primary tool for estimating driving forces across inhibitory receptors within the nervous system. Here, the authors present ORCHID as an all-optical method to measure inhibitory receptor driving forces in targeted brain cell types.

Seven leading geneticists express their views about where the unidentified components of the heritability for complex human diseases might lie and how this could affect the underlying genetic architecture, as well as offering suggestions of how genomic research could be targeted to address this key issue.

CSF MTBR-tau243 is more related to tau tangles and clinical cognitive impairment in Alzheimer’s disease than phospho-tau biomarkers, which are more related to amyloid plaques.

Whole-genome sequence analysis identifies five independent risk loci for Lewy body dementia and demonstrates overlapping genetic architecture with Alzheimer’s and Parkinson’s diseases.

Bivalent vaccines elicit broad immune responses that neutralize ancestral SARS-CoV-2 and variants of concern and offer a customizable approach to protect from COVID-19 as new virus variants emerge.

The immune response to SARS-CoV-2 infection is variable but has been linked to prognosis and the development of severe immunopathology. Here the authors assess a range of immune parameters in both peripheral blood and respiratory samples, providing a comparative assessment of the immune response between these compartments and their potential impact on immune-pathogenesis.

Multi-omic profiling is a powerful approach to dissecting molecular mechanisms in disease. Here the authors generate whole proteome, phosphoproteome and transcriptome profiles from two mouse models of high-grade glioma driven by different oncogenes, and validate identified master regulators with a CRISPR screen.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Rinse Weersma, Carl Anderson and colleagues report the results of a trans-ancestry association study of inflammatory bowel disease. They implicate 38 new susceptibility loci, and show that the variance explained by each IBD risk locus is consistent across diverse ancestries, with a few notable exceptions.

A collaborative study demonstrates that, compared with previous SARS-CoV-2 variants, B.1.1.529 isolates cause less infection and disease in mice and hamsters, in agreement with preliminary data from studies in humans.

Ruth Loos and colleagues report results of a large genome-wide association study for body mass index. They identify 18 new loci associated with this trait, some of which map near key hypothalamic regulators of energy balance.

Neutralizing antibody responses of patients infected with SARS-CoV-2 peak at 3–4 weeks post onset of symptoms, then decline to low levels over the course of 3 months in some individuals.

Sequence analysis identifies gain-of-function somatic mutations in GNA11 or GNAQ in CTNNB1-mutant aldosterone-producing adenomas. Most patients with these mutations presented during puberty, pregnancy or menopause, with elevated LHCGR expression.

Thyroid dysfunction is involved in many diseases. Here, the authors provide insights into the genetics and biological pathways influencing important thyroid function parameters, showing potential causal effects on many clinical outcomes.

An interim report from the GAIN/iCat2 study shows that molecular profiling of pediatric solid malignancies clarifies diagnostic classifications and provides opportunities for matched targeted therapy.

Frequent dispersal and short-lived local transmission clusters fuelled the 2013–2016 Ebola virus epidemic in Guinea, Liberia and Sierra Leone.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

Subunits of the Elongator complex have been implicated in several nervous system pathologies. Here, the authors identify ELP2 variants in six patients with neurodevelopmental anomalies and show in mouse models that these variants impact protein stability and the activity of the complex during brain development.

The scavenger receptor Scara1, expressed on microglia and macrophages, binds beta amyloid aggregates. In a mouse model of Alzheimer’s disease, the authors show that Scara1deficiency is associated with reduced clearance and increased deposition of aggregates in the brain, which results in early mortality.

Using high-throughput proteomics in a prospective population-based study of older adults, Frick et al. identified over 300 proteins linked to incident late-onset Alzheimer’s disease, including associations dependent on or independent of APOE-ε4 status.

Socioeconomic status is associated with cognitive development, but the extent to which this reflects neuroanatomical differences is unclear. In 1,099 children and adolescents, family income was nonlinearly associated with brain surface area, and this association was greatest among disadvantaged children. Further, surface area mediated links between income and executive functioning.

Genetic and environmental factors impact on lung function, important in the diagnosis of pulmonary diseases. Here the authors use imputation of genotypes to the 1000 Genomes Project reference panel to identify novel, low frequency variants associated with lung function.

A novel multi-omics workflow, combining gut microbiome metagenomics, metatranscriptomics and metabolomics, enabled the identification of the microbial pathways responsible for the degradation of the immunomodulatory drug 5-ASA in the gut of patients with inflammatory bowel disease.

Historic smallpox vaccination and monkeypox virus (MPXV) infection elicit MPXV-neutralizing antibodies, but MPXV-neutralizing antibodies are less frequent and of lower magnitude after vaccination with MVA-BN—the vaccine approved and in use for protection against MPXV and smallpox.

Lineage-restricted transcription factor PAX8 is oncogenic in ovarian cancer cells. Here the authors show that PAX8 interacts and recruits a splice variant of the MECOM locus PRDM3 to control the gene expression module involved in adhesion and extracellular matrix, and consequently promotes ovarian tumorigenesis.

There is currently no disease-modifying treatment for Parkinson’s disease, a common neurodegenerative disorder. Here, the authors use genetic variation associated with gene and protein expression to find putative drug targets for Parkinson’s disease using Mendelian randomization of the druggable genome.

Patients treated with Aurora kinase inhibitors experience dose-limiting neutropenia while other cytopenias are rare. Here, Chou et al. show that this cell-type specific side effect is partly explained by loss of drug efflux pump expression during neutrophil differentiation.

COVID-19 booster immunizations aimed at spike protein from new SARS-CoV-2 variants induce robust germinal centre B cell responses against the original spike protein, as well as de novo B cell responses against the variant spike protein.

While active efforts are advancing medical AI model development and clinical translation, safety issues of medical AI models have emerged. Here, the authors investigate the effects on an AI model and on human experts of potential fake/adversarial images for breast cancer diagnosis.

Children with SARS-CoV-2 infection are more likely to have mild symptoms and may be asymptomatic, but underlying reasons remain unclear. Here, the authors show cellular, cytokine and antibody response to SARS-CoV-2 infection in three children who repeatedly tested negative for the virus by PCR, despite high exposure in the household.

Target 2035 aims to develop a potent and selective pharmacological modulator for every human protein by 2035 with the results made publicly available. This Roadmap article sets out how that will be achieved.

Exome sequencing and copy number analysis are used to define genomic aberrations in early sporadic pancreatic ductal adenocarcinoma; among the findings are mutations in genes involved in chromatin modification and DNA damage repair, and frequent and diverse somatic aberrations in genes known as embryonic regulators of axon guidance.

A translational study demonstrates the role of myeloid inflammatory cells in driving disease progression and treatment resistance in prostate cancer and shows that these cells can be targeted therapeutically.

Studies of the genetic association between vitamin D and cancer risk have typically been underpowered. Here the authors analyse this using Mendelian Randomisation with more than 70 vitamin D variants obtained from the UK Biobank and large-scale data from various consortia, confirming null associations between vitamin D and most cancers.

A randomized trial in patients hospitalized with COVID-19 showed no benefit and potentially increased harm associated with the use of convalescent plasma, with subgroup analyses suggesting that the antibody profile in donor plasma is critical in determining clinical outcomes.

The authors assess the durability and long-term cross-reactivity of neutralizing antibodies raised in response to infections with SARS-CoV-2 or variants of concern in humans.