Search

The success of targeting KRAS for cancer therapy is limited by resistance due to compensatory mechanism, making combinatorial approaches attractive. Here, the authors use a KRAS signature drug repurposing screen and identify the multityrosine kinase PKC inhibitor Midostaurin as synergistic with MEK and KRAS inhibitors in KRAS-mutated lung adenocarcinoma.

This study examines long-term changes in species richness across tropical forests in the Andes and Amazon. Hotter, drier and more seasonal forests in the eastern and southern Amazon are losing species, while Northern Andean forests are accumulating species, acting as a refuge for climate-displaced species.

Deciphering body-brain communication pathways is key to a deeper understanding of brain physiology and pathology. Here, the authors define the astrocyte endfoot proteome and show dynamic vascular-to-astrocyte signaling relevant to human neuropathology.

The authority created to safeguard the ocean floor now leans towards licensing its exploitation. Here’s how to reset the balance.

Proteomics must target specific synapse types to reveal how molecules shape their unique functions. Here, authors show that hippocampal synapses differ in proteome and that neuron-specific glutamate receptor regulation shapes synaptic diversity.

Non-nutritive sensory components of high-fat diet, such as bacon flavour, are sufficient to impair metabolic health in offspring in mice.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

Early- and late-onset preeclampsia pose serious maternal-fetal risks, yet non-invasive early prediction remains challenging. Here, the authors show that cfRNA signatures reveal distinct decidual and multiorgan signals, enabling accurate, externally validated prediction of both subtypes.

T cells undergo age-related changes that impair their organismal functions. Here Soto-Heredero et al. show that regulatory T cells characterized by the expression of KLRG1 accumulate with age in both mice and humans and exhibit features including mitochondrial decline and an inflammatory phenotype.

Wood density is a key control on tree biomass, and understanding its spatial variation improves estimates of forest carbon stock. Sullivan et al. measure >900 forest plots to quantify wood density and produce high resolution maps of its variation across South American tropical forests.

Bailón, Alarcón-Soto et al. perform a pooled analysis of individual data from two randomized clinical trials evaluating HTI-based therapeutic HIV vaccines with or without a TLR7 agonist in early-treated people with HIV. They identify an vaccine-immune response threshold that predicts virological outcomes after treatment interruption.

Creative experiences such as dance, music, drawing, and strategy video games might preserve brain health. The authors show that regular practice or short training in these activities is linked to brains that look younger and work more efficiently.

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.

The authors analyse tree responses to an extreme heat and drought event across South America to understand long-term climate resistance. While no more sensitive to this than previous lesser events, forests in drier climates showed the greatest impacts and thus vulnerability to climate extremes.

In this work, authors show that β-lactamase enzymes not only confer antibiotic resistance but also increase susceptibility to other antibiotics.

Brain age gaps (BAGs) highlight deviations from healthy brain aging, yet their biophysical underpinnings in aging and dementia are not well understood. Here, the authors use EEG connectivity and generative modeling across diverse populations to reveal that BAGs are influenced by geography, income, sex and education, with implications for understanding accelerated aging and dementia.

Vega-Gutiérrez et al. present cryo-electron microscopy structures of GluA4-containing AMPA receptors, which are key for brain signaling. They show GluA4-specific conformations and explain how subunit composition shapes receptor architecture, dynamics and function.

Checkpoint inhibitor (CPI) therapy is modestly effective in Glioblastoma patients, with some patients not benefitting at all. Authors here present the outcomes of single arm prospective clinical trial employing combination CPI therapy in newly diagnosed GBM and identify the pre-treatment genetic, microbiome and immunological factors that might contribute to sensitivity.

A combination of analysis of plasmid diversity in the gut of hospitalized patients with experimental evolution shows that the evolution of plasmid-mediated antibiotic resistance involves a trade-off between antibiotic resistance levels and bacterial fitness.

Randomised controlled experiments are the gold standard for scientific inference, but environmental and social scientists often rely on different study designs. Here the authors analyse the use of six common study designs in the fields of biodiversity conservation and social intervention, and quantify the biases in their estimates.

Here the authors report results from a randomized clinical trial testing a combination of ChAOx1/MVA.HTI vaccines and the TLR7 agonist vesatolimod in men living with HIV-1. While the treatment showed a good safety profile and induction of HTI-focused T-cell responses, viral rebound was similar in treatment arm and placebo arm.

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.

The Amazon rainforest is dominated by relatively few tree species, yet the degree to which this hyperdominance influences carbon cycling remains unknown. Here, the authors analyse 530 forest plots and show that ∼1% of species are responsible for 50% of the aboveground carbon storage and productivity.

An increased incidence of malformations of the genital tract, and neoplasms of the testis, uterus, and breast has been observed during the past half century following the introduction of endocrine disrupting chemicals into the environment. This Review discusses the theoretical underpinnings and corresponding evidence connecting development and carcinogenesis. The data gathered thus far linking exposure to these chemicals to cancer warrant action to protect public health.

Kelp forests could face up to 16 times more marine heatwave exposure by 2100. With less than 3% of kelp forests in highly restrictive marine protected areas, urgent conservation and climate adaptation actions are needed

Most instances of Alzheimer’s disease (AD) are sporadic or not associated with a particular mutation. Here, the authors develop knock-in mice that express wildtype human Aβ under control of the mouse App locus, which may have potential for modelling some aspects of sporadic late onset AD.

Analyses of neuroimaging datasets from 5,306 participants across 15 countries found generally larger brain-age gaps in Latin American compared with non-Latin American populations, which were influenced by disparities in socioeconomic and health-related factors.

An analysis of habitat fragmentation using a dataset of more than 4,000 species worldwide shows that fragmentation reduces biodiversity at all scales, and that increases in β diversity do not compensate for the loss of α diversity.

The UK Government aims to reduce premature deaths from non-communicable diseases by one-third by 2030 (SDG 3). Using life table methodology and data from the UK Biobank, this study indicates that sustained dietary changes—from median or unhealthy to a longevity-associated dietary pattern or to the Eatwell Guide recommendations—could lead to substantial life expectancy gains.

Investigations in wild bats and non-human primates in Brazil and Costa Rica inform about diverse Morbillivirus ecology in neotropical bats and host jumps, and about zoonotic potential of morbilliviruses in Latin America.

A catalogue of predicted loss-of-function variants in 125,748 whole-exome and 15,708 whole-genome sequencing datasets from the Genome Aggregation Database (gnomAD) reveals the spectrum of mutational constraints that affect these human protein-coding genes.

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.

A genomic constraint map for the human genome constructed using data from 76,156 human genomes from the Genome Aggregation Database shows that non-coding constrained regions are enriched for regulatory elements and variants associated with complex diseases and traits.

A strategy for inferring phase for rare variant pairs is applied to exome sequencing data for 125,748 individuals from the Genome Aggregation Database (gnomAD). This resource will aid interpretation of rare co-occurring variants in the context of recessive disease.