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Understanding the mechanisms underlying the survival of drug tolerant persister cells following chemotherapy remains elusive. Here, multi-omics analysis and experimental approaches show that the germ-cell-specific H3K4 methyltransferase PRDM9 promotes metabolic rewiring in glioblastoma stem cells.

3-Hydroxypropionic acid (3HP) is a top Department of Energy value-added chemical and precursor to bioplastics, yet cost-effective microbial bioproduction remains elusive. Here the authors establish efficient 3HP production in an acid tolerant yeast and validate its financially viability.

Smc5/6 association with DNA junctions can support genomic functions. Here, the authors show that Smc5/6 junction polarity preferences, targeting, and dwell times are determined by its structural modules as well as the RPA and PCNA genomic factors.

How do low-mass binaries age? Astronomers have constrained a tight, circular orbit of a close-in companion around a dying giant star, raising new questions about how tidal forces shape binary orbits in the final phases of stellar evolution.

While deep learning has enabled the decoding of language from intracranial brain recordings, achieving this with non-invasive recordings remains an open challenge. Here the authors introduce a deep learning pipeline to decode individual words from EEG and MEG signals

Most human genes undergo alternative splicing, but population-level variation is poorly understood. Here, the authors map over 57,000 naturally variable exons across 838 individuals, revealing widespread splicing diversity and its impact on gene expression and genetic interpretation.

Across species, how aging leads to progressive spatial memory decline is not fully understood. This study reports dysfunctional spatial coding by aged entorhinal grid cells and networks related to impaired spatial memory and identifies implicated neuronal gene expression changes.

DNA double strand breaks can be repaired by several pathways leading to different genetic outcomes. Here, the authors define the interplay between the DNA damage response factors 53BP1-RIF1 and core non-homologous end joining factors on diverse repair outcomes.

Warm Atlantic Water was a major driver of both initial NEGIS retreat from 21.6 ka BP and the collapse of its ice shelf ~15.2 ka BP. This study demonstrates the key role of ice-ocean interactions in controlling ice-sheet retreat.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

Establishment and maintenance of appropriate cell size is a prerequisite for cells to function efficiently. Here, Kiriakopulos et al. reveal that the lncRNA CISTR-ACT maintains cell size across cell types in humans and mice by regulating cell morphogenesis genes in trans via guidance of the transcription factor FOSL2.

The role of the immune system in the pathogenesis of psychiatric disorders is unclear. Here, the authors show that genetic risk variants for multiple psychiatric disorders are enriched in regions of the genome active in the brain and in lymphoid cells, especially stimulated T cells, but not in myeloid cells.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

Here, the authors propose a scalable framework for cross-domain identity matching based on bursty dynamics, revealing how coordinated actions propagate across networks.

Langerhans cells (LC) can prime tolerogenic as well as immunogenic responses in the skin. Here the authors show, by transcriptomic, epigenetic and CRISPR editing analyses, that during LC migration and maturation the transcription factor IRF4 regulates expression of antigen presentation and co-stimulatory gene modules while attenuating inflammatory response genes.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Here, the authors perform large trans-ancestry fine-mapping analyses identifying large numbers of association signals and putative target genes for colorectal cancer risk, advancing our understanding of the genetic and biological basis of this cancer.

Melting temperature is the parameter generally used as a measure for stability of enzymes. Here, the authors show that that the melting temperature does not necessarily correlate to the activity observed in the presence of the solvent, and introduce an alternative parameter, the concentration of the co-solvent at the point of 50% protein unfolding at a specific temperature T.

Cellular Z-RNAs generated during active virus infections are bona fide ZBP1 ligands, and position ZBP1-activated cell death as a host response to counter viral disruption of the cellular transcriptional machinery.

Human WNT10A mutations are associated with dental defects and adult onset ectodermal dysplasia. Xuet al. show that WNT10A-activated ß-catenin plays dual roles in adult epithelial progenitor proliferation and differentiation by complexing with KLF4 in differentiating, but not proliferating, cells.

Controlling nanoscale interfaces is key for ensuring stable plasmonic and catalytic function yet remains difficult to achieve under operando conditions. Now it has been shown that transient Au–Cl adlayers function as redox-active Au(I) intermediates, modulating interfacial electrostatics. This modulation stabilizes gold nanogaps and directs ligand rebinding, thereby enabling reproducible regeneration of subnanometre architectures.

Mechanisms that regulate epithelial bending mainly link to cell shape changes, for example, the formation of wedge shaped cells. Here, the authors identify a different cell behaviour in the salivary glands and teeth where initial invagination arises by a coordinated vertical cell movement.

Post-translational modifications (PTM) of histones are important for epigenetic regulation in mammals. Here, Cheeseman et al. report dynamic changes in H3K18 PTM during the differentiation stages of Theileria parasites and they identify a SET-domain methyltransferase (TaSETup1) as the relevant enzyme promoting this modification.

Using quantitative imaging and monitoring transcription in living embryos, Bellec et al., provide evidence that the pioneer factor GAF acts as a stable mitotic bookmarker during early Drosophila development.

The authors collate a meta-collection of ex situ living plant diversity held in 50 botanical collections worldwide, spanning a century of data and currently containing ~500,000 accessions. Their analyses examine the capacities and constraints within living plant collections, reveal the impact of the Convention on Biological Diversity and its consequences for material exchange and conservation, and call for the re-evaluation of strategic priorities.

Genome-wide analyses identify 30 independent loci associated with obsessive–compulsive disorder, highlighting genetic overlap with other psychiatric disorders and implicating putative effector genes and cell types contributing to its etiology.

This study finds that glaciers have existed in the Transantarctic Mountains for the past 60 million years, and that warm-based mountain glaciers were present in Antarctica long before ice sheets came to dominate the continent.

Current tools for single-cell spatial omics still face barriers with regard to incomplete molecular profiling, tissue loss, and probe failure. Here, the authors use machine learning for the imputation of protein abundance in tissue-based cyclic immunofluorescence, showing that the spatial context can improve the accuracy of the imputation outputs.

Transposons can be co-transcribed with genes in plant genomes. Here, the authors show the global production of chimeric transposon-gene transcripts and their epigenetic regulation in Arabidopsis thaliana.

The phase-out of coal will require targeted strategies. New research assesses the retirement vulnerability of coal plants in the USA based on similarity to plants with announced retirements. The findings highlight strategies to guide and accelerate phase-out.

The authors show that activation of GluK2-containing kainate receptors on hippocampal neurons, by either agonist application or high-frequency synaptic stimulation, leads to a new form of NMDA-receptor-independent LTP. Induction of this form of plasticity requires the metabotropic action of postsynaptic kainate receptors, which triggers spine growth and potentiation of AMPA-receptor-mediated transmission.

While population transfer between electronic states occurs instantly in two-state model systems, here the authors show that real-world systems with coupling to additional states can exhibit measurable delays for transfer on a single femtosecond timescale.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

DNA 5-hydroxymethylcytosine (5hmC) modification is associated with gene transcription and used as a mark of mammalian development. Here the authors report a comprehensive 5hmC tissue map and analysis of 5hmC genomic distributions in 19 human tissues derived from 10 organ systems, thus providing insights into the role of 5hmC in tissue-specific development.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

Histone post-translational modifications are known key regulators of gene expression. Here, the authors characterize histone crotonylation at histone H3 lysine 18 in intestinal epithelia and find that it is a highly dynamic cell cycle regulated mark under the regulation of the HDAC deacetylases.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

2D semiconductors are attracting attention as a potential alternative for post-silicon electronics, but the fabrication of high-performance 2D p-type transistors remains a challenge. Here, the authors report the realization of bilayer WSe₂ p-type transistor arrays with on-state currents up to 421 μA/μm, on/off ratios exceeding 10⁷ and subthreshold swings as low as 75 mV/decade.

In colorectal cancer (CRC), finding loci associated with risk may give insight into disease aetiology. Here, the authors report a genome-wide association analysis in Europeans of 34,627 CRC cases and 71,379 controls, and find 31 new risk loci and 17 new risk SNPs at previously reported loci.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

By matching antigenicity prediction with a forecast of circulating strains in the next season, a model is shown to outperform standard recommendations for vaccine design in terms of vaccine effectiveness and disease burden in multiple evaluations throughout different influenza seasons.

Combined patch clamp recording, biocytin staining and single-cell RNA-sequencing of human neurocortical neurons shows an expansion of glutamatergic neuron types relative to mouse that characterizes the greater complexity of the human neocortex.

Autism genes converge in midfetal cortical co-expression networks, and chromatin regulators such as CHD8 are increasingly associated with autism spectrum disorder (ASD). Here the authors map CHD8 targets in developing brain, and find that CHD8 directly regulates other ASD risk genes during human neurodevelopment.

Multivariate genome-wide association analyses of the latent genetic architecture of frailty identify one general factor of genetic overlap across all frailty deficits and six factors indexing a shared genetic signal across specific groups of deficits.