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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).

Analyzing data of the Mexican Biobank project, a new study finds regional differences in clinically relevant genetic frequencies and presents MexVar, a publicly accessible resource designed to support ancestry-informed genetic testing.

In forests, trait expression is influenced by tree-tree interactions. Castro Sánchez-Bermejo et al. show how phenotypic variability of tree species decreases with tree diversity and contributes importantly to functional diversity in forests.

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.

Here the authors apply machine learning approaches to Alzheimer’s genetics, confirm known associations and suggest novel risk loci. These methods demonstrate predictive power comparable to traditional approaches, while also offering potential new insights beyond standard genetic analyses.

CRISPR-Cas13 RNA-targeting systems comprise an invaluable set of tools in the fields of basic and applied sciences. Here, Moreno-Sánchez, Hernández-Huertas, and Nahón-Cano et al. enhanced the use of the CRISPR-RfxCas13d system in zebrafish for targeted depletion of endogenous mRNAs.

PAM requirement is a constraint for genome editing but this has been circumvented by engineered Cas9 nucleases as SpG and SpRY recognizing minimal PAM sequences. Here, the authors validate and optimize SpG and SpRY in vivo expanding the targeting landscape in animals.

Polygenic risk scores for Alzheimer’s disease derived from individuals of European ancestry can show improved performance in multiancestry settings after incorporating genome-wide association summary statistics from diverse populations.

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.

Genotype and exome sequencing of 150,000 participants and whole-genome sequencing of 9,950 selected individuals recruited into the Mexico City Prospective Study constitute a valuable, publicly available resource of non-European sequencing data.

Genetic and Structural analysis of COVID patients cohort reveals a correlation between mitochondrial haplogroup and SARS-CoV-2 severity.

A comparison of alpha diversity (number of plant species) and dark diversity (species that are currently absent from a site despite being ecologically suitable) demonstrates the negative effects of regional-scale anthropogenic activity on plant diversity.

Sul-2 is a steroid sulfatase in c.elegans. Here the authors show that, in the absence of sul-2 enzymatic activity, worm lifespan is increased, and that chemical inhibition ameliorates symptoms of neurodegenerative disorders in worms and mice.

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.

This Review highlights fundamental optical phenomena that have been redefined at the nanoscale by anisotropic polaritons, including anomalous cases of refraction, reflection and focusing.

Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality.

Here, the authors find that BMAL1, best known for controlling the body clock, partners with TRIM28 in naïve pluripotent stem cells to repress retrotransposons.

Drug resistance remains a major challenge in cancer treatment. Here, the authors identify Connexin43 as target that enhances BRAF/MEKi efficacy by interfering with DNA repair pathways, overcoming drug resistance. They develop an mRNA therapy that improves efficacy and sensitizes resistant cells.

Crop wild relatives’ genetic diversity is usually not considered in conservation planning. Here, the authors introduce an approach to identify conservation areas based on evolutionary and threat processes, by developing proxies of genetic differentiation, and including taxa’s habitat preferences.

Autoimmune thyroid diseases (AITD) are complex conditions involving multiple cellular components of the thyroid tissue. In this study, the authors use spatial transcriptomics data to examine thyroid tissue, identifying distinct subsets of damaged thyroid follicular cells, myofibroblasts and capillaries in AITD.

Predictions suggest that a high proportion of plant species will be threatened with extinction in the near future. A global assessment of the threat status of cacti suggests that these iconic plants are amongst the most threatened taxonomic groups, with 31% of the 1,478 evaluated species at risk of extinction.

Ecosystem services provided by dung beetles are an underappreciated component of terrestrial ecosystems. Here, the authors report a standardized distributed experiment which shows that dung removal rate, a key ecosystem process in pastures, is greater under high beetle functional diversity regardless of grazing intensity.

T cells communicate with antigen-presenting cells (APC) via the signaling crosstalk at the immunological synapse (IS). Here the authors use bead-supported lipid bilayers as synthetic APCs to find that trans-synaptic vesicles produced by T cells in the IS carry specialized cargos distinct from constitutive extracellular vesicles to serve as intercellular messengers.

Imidazole propionate produced by gut microbiota is associated with atherosclerosis in mouse models and in humans, and causes the development of atherosclerosis through activation of the imidazoline-1 receptor in myeloid cells.

CD4⁺ T cells have been shown to be important in CD8⁺ T cell responses through a process of DC:T cell interaction. Here the authors further characterise this DC:T cell interaction and show that after CD4⁺ T cell help these post-synaptic DCs have increased lipid peroxidation and increased MHC class I proteins associated with increased cross-presentation function.

A DNA double strand break can be repaired through either the non-homologous end-joining or the homologous recombination pathways. Here the authors conduct a genome-wide screen and identify a role for CCAR2 in pathway choice by regulating DNA end resection by CtIP.

Immunological stressors are linked to the transformation of preleukemic B cells to B-cell acute lymphoblastic leukemia. Here the authors show a dysregulation of innate immune signaling in preleukemic precursor B cells and link to the development of B-cell acute lymphoblastic leukemia in a murine model.

This work identified immune signatures of COVID-19 including broad Interferon signatures that are unique to infants. Compared with infected adults, infants display similar Interferon signatures in monocytes but enhanced signatures in T and B cells.

Two genome-wide association studies have independently identified genetic risk factors for Parkinson disease (PD). One study, conducted in individuals of European ancestry, provides further evidence for an association between PD risk and the genes SNCA and MAPT. The other study, conducted in a Japanese series, identified two novel loci that are associated with PD risk.

Patritumab deruxtecan (HER3-DXd) is a promising therapy for breast cancer, targeting HER3. Here, the authors analyse the genomic factors that affect the response to HER3-DXd in patients with early-stage HER2-negative breast cancer as part of the SOLTI-1805 TOT-HER3 clinical trial and report outcomes for Part B of the trial using lower HER3-DXd dose in patients with HER2-negative breast cancer.