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Whole-genome sequencing of more than 2,000 colorectal carcinoma samples provides a highly detailed view of the genomic landscape of this cancer and identifies new driver mutations.

This study reveals how the intrinsically disordered region of eIF4B governs its transition from monomers to oligomers and condensed droplets, providing key insights into how its self-association may be regulated to carry out its cellular functions.

How neurons manage protein folding in their projections remain unclear. Here, the authors find that stressed neuron dendrites rely on an on-demand supply of chaperones, driven by the localization and translation of mRNAs encoding these proteins.

The immune suppression required for the resolution of acute inflammation is characterised by molecular and metabolic reprogramming of myeloid cells. Authors here show that the transcription factor ZEB1 is a key mediator of the pathway governing transition from inflammation to immunosuppression via regulating mitochondrial translation in macrophages.

There are conflicting views about the symmetrical/asymmetrical nature of the hydrogen-bond network in water. This theoretical study reveals that water molecules in liquid form highly asymmetric hydrogen bonds and that this asymmetry relaxes rapidly towards an average symmetrical structure.

To study neurodegenerative prion diseases, a method (PMSA) for generating prions spontaneously is presented. Applied to 380+ different prion proteins, their tendency to become pathogenic was ranked, illuminating their formation process.

Inventory data from more than 1 million trees across African, Amazonian and Southeast Asian tropical forests suggests that, despite their high diversity, just 1,053 species, representing a consistent ~2.2% of tropical tree species in each region, constitute half of Earth’s 800 billion tropical trees.

Most genetic studies have been done on European cohorts, which affects the efficacy of polygenic risk scores in non-European populations. Here, the authors demonstrate that a colorectal cancer PRS including Asian and European ancestries has improved performance over the European-centric PRS across racial and ethnic groups.

The second Global Amphibian Assessment finds that the status of amphibians is continuing to deteriorate globally, driven predominantly by climate change, disease and habitat loss.

A rational design of deep eutectic solvents (DESs) is hindered because fundamental DES components, such as choline chloride (ChCl), decompose before melting. Here authors determine the melting properties of ChCl, unveiling ionic plastic crystals as a platform for DESs that meet modern sustainability, health, and safety requirements.

Multiancestry genome-wide association analyses identify new risk loci for stroke and stroke subtypes. Fine mapping and bioinformatics analyses of these risk loci point to mechanisms not previously implicated in stroke pathophysiology.

DNA damage at stalled replication forks activates Chk1 kinase and poly(ADP-ribose) (PAR) polymerase 1. Min et al.find that retention of Chk1 to stalled replication forks depends on its direct interaction with PAR, and show that PAR chain length fine-tunes Chk1 and S-phase checkpoint activation.

Through micropatterning of a soft basement membrane to control Wnt3a protein distribution, the authors demonstrate how the size, shape, and spatial arrangement of intestinal epithelial crypts can be precisely regulated, offering insights into tissue organization mechanisms.

The luminosity of ultraviolet light emitted by the first galaxies in the universe traces the formation and evolution of stars and galaxies which led to the epoch of reionization. Here the authors use data from the Hubble Space Telescope and through a model provide a bound for the total luminosity.

Evidence synthesized from 252 large-herbivore exclusion studies suggests that herbivore-induced change in dominance, independent of site productivity or precipitation, best predicts herbivore effects on biodiversity in grassland and savannah sites.

During the integrated stress response, translation is modulated through the phosphorylation of translation initiation factor eIF2 and the formation of a complex with eIF2B. Here the authors present structures of the eIF2:eIF2B complex with and without phosphorylation, shedding light on how eIF2 phosphorylation regulates translation.

Alternative stable states in forests have implications for the biosphere. Here, the authors combine forest biodiversity observations and simulations revealing that leaf types across temperate regions of the NH follow a bimodal distribution suggesting signatures of alternative forest states.

How flat slabs at subduction zones are created remains unclear. Here, the authors show that the Nazca slab has retreated at ∼2 cm per year since 50 Ma but no rollback has occurred in the last ∼12 Myr in the flat slab, implying that an overpressured sub-slab mantle can impede rollback and maintain a flat slab.

mmBCFAs are endogenous fatty acids synthesized from BCAAs by brown and white adipose tissue via CrAT and FASN promiscuity. BCAA catabolism and mmBCFA lipogenesis are decreased by obesity-induced adipose hypoxia and influenced by the microbiome.

Genomic analyses of large population-based cohorts uncover the genetic determinants of perivascular space burden, an MRI marker of cerebral small vessel disease, across the lifespan, and reveal potential pathways implicated in the etiology of stroke and dementia.

The molecular mechanisms underlying metastasis in pheochromocytoma/paraganglioma (mPPGL) remain to be explored. Here, the authors perform genomic and immunogenomic profiling of mPPGL tumors and suggest potential biomarkers for risk of metastasis and immunotherapy response.

Genome-wide association analyses of prostate cancer in men from sub-Saharan Africa identify population-specific risk variants and regional differences in effect sizes. Founder effects contribute to continental differences in the genetic architecture of prostate cancer.

This work presents SUM-seq, an ultra-high-throughput method for co-profiling chromatin accessibility and gene expression in single nuclei across multiplexed samples, advancing the study of gene regulation in diverse biological systems.

Mutations in the metalloproteinase Zmpste24 preclude prelamin A processing and cause premature ageing. Here, de la Rosaet al.create mosaic Zmpste24 mice, revealing that cell-extrinsic effects are essential for accelerated ageing caused by prelamin A accumulation and that prelamin A reduces invasiveness of cancer cells.

It has been unclear whether human FEF and early visual cortex play a role in the perceptual modulations preceding saccades. Here, the authors show that V1/2 TMS reduces sensitivity at the contralateral target just before saccade onset, and rFEF+TMS enhances sensitivity where presaccadic perception is poor.

Castells-Nobau et al. provide insight into how bacteriophages in the gut microbiome contribute to regulating food addiction by modulating tryptophan and tyrosine metabolism in the host.

Somatically determined preferential allelic expression of select genes that when mutated cause inborn errors of immunity corresponds with disease phenotypes, suggesting that the penetrance and expressivity of monogenic disorders is also dependent on the ‘transcriptotype’.

Genomic, transcriptomic and epigenetic analyses of malignant pleural mesothelioma identify molecular axes and specialized tumor profiles underlying intertumoral heterogeneity.

While coffee and tea consumption has been associated with risk of diseases, their mechanisms of action remain elusive. Here the authors present a large EWAS on coffee and tea consumption in cohorts of European and African-American ancestries, finding that coffee consumption is associated with differential DNA methylation levels at multiple CpGs.

Impaired myocardial metabolic flexibility is associated with cardiac dysfunction in diabetes and heart failure. McCommis et al. reveal a critical role for mitochondrial pyruvate use in cardiac function, and use dietary interventions to enhance cardiac fat metabolism in dilated cardiomyopathy.

Bone tools shaped by knapping found within Olduvai Gorge in Tanzania precede any other evidence of systematic bone tool production by more than 1 million years.

Tropical carbon stocks are essential for proper accounting of global carbon budgets, but difficult to monitor on a large scale. L-band microwave observations used here enable direct and spatially explicit accounting of annual carbon fluxes from different types of land surface.

Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits.

A proteomics approach using MS2 as an RNA tag is used to provide snapshots of nascent preribosomal particles from budding yeast, thus allowing the determination of the stage-specific order in which 70 ribosome-assembly factors associate with pre-rRNA domains.

In an analysis of long-term safety events in 783 patients treated with T cell therapy in 38 trials, 2.3% of patients developed second primary malignancies, and vector integration analyses revealed no pathological insertions.

Strontium isotope analysis can be applied to animal and plant tissues to help determine their provenance. Here, the authors generate a strontium isoscape of sub-Saharan Africa using data from 2266 environmental samples and demonstrate its efficacy by tracing the African roots of individuals from historic slavery contexts.

How adhesive forces are transduced and integrated into biochemical signals at focal adhesions (FAs) is poorly understood. Here authors show that force- FAK signaling coupling coordinates cell migration and tissue-scale forces to promote microtissue repair.