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An evaluation framework isolates perturbation-specific effects in perturbation datasets.

Temporal variability of structural-functional coupling (SFC) remains poorly understood. Here, authors show such variability is underpinned by specific transcriptomic and chemoarchitectural signatures, thereby supporting neurocognitive specialization.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

This study discovers human SERF2 as a key partner in stress granule formation by binding specific RNA G-quadruplexes. SERF2 and these RNAs provide a detailed structural model of protein-RNA interactions driving liquid-liquid phase separation in condensates.

Individuals with schizophrenia show reduced structural similarity in temporal, cingulate, and insular lobes, especially those with worse cognition and symptoms, affecting late maturing association areas with low metabolism and high neurotransmission.

Prime editing is a CRISPR methodology whose efficiency declines with distance from the target sequence. Here the authors demonstrate prime editing with prolonged editing window, proPE, which extends the editing distance, enabling the use of prime editing for therapeutic interventions.

The authors developed a screen to find compounds that modulate intracellular Staphylococcus aureus metabolism and discovered KL1, which sensitizes persisters to antibiotics by reversing host-induced tolerance.

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).

The number of individuals in a given space influences animal interactions and network dynamics. Here the authors identify general rules underlying density dependence in animal networks and reveal some fundamental differences between spatial and social dynamics.

Sex differences are well established in the prevalence and symptoms of depression. Here, the authors identify a novel X chromosome variant, greater genetic risk, and stronger links to metabolic traits in females, highlighting the importance of sex-aware approaches.

CSF total tau (t-tau), often used as a marker of neuronal damage, is more strongly linked to synaptic degeneration. Here, the authors show that t-tau better reflects synaptic dysfunction than axonal or neuronal loss in Alzheimer’s disease.

Basal cells, rather than neuroendocrine cells, have been identified as the probable origin of small cell lung cancer and other neuroendocrine–tuft cancers, explaining neuroendocrine–tuft heterogeneity and offering new perspectives for targeting lineage plasticity.

Transcriptome-scale maps of RNA secondary structure ensembles in living cells detect candidate RNA structural switches.

Despite being a virulence factor, candidalysin toxin is essential for Candida albicans to penetrate the oral epithelium to establish and maintain non-infectious colonization

Enfortumab vedotin (EV) is the current standard treatment for advanced bladder cancer, but resistance typically develops within a year, highlighting the need for new therapies. This study demonstrates that NECTIN4-targeting CAR T cells are effective against bladder cancer, including EV-resistant cells, and their potency can be further enhanced by using rosiglitazone to boost NECTIN4 expression.

The epigenetic mechanisms underlying phenotypic diversity across different metastatic sites in castration-resistant prostate cancer (CRPC) remain to be characterised. Here, multi-omic profiling across metastatic lesions identifies regulatory networks driving tumour lineage programs and potential therapeutic targets.

Advances have been made in thin-film piezoelectrics; however, the linearity of electric-field-induced strain with frequency and temperature still requires improvement. Here, by growing interlocked monoclinic and tetragonal polar nanoregions in (K,Na)NbO₃ thin films, highly linear strains of up to 1.1% are reported at frequencies up to 10⁵ Hz.

The role of the tumour microenvironment in the response to immune checkpoint inhibitors in metastatic melanoma remains poorly understood. Here, single cell profiling of metastatic melanoma samples identifies associations of the mature dendritic enriched in immunoregulatory molecules subtype with immunotherapy response.

This research investigates aperiodic neural activity in depressed individuals versus healthy controls using resting state electroencephalography recordings. Findings reveal significant differences in aperiodic exponent and offset, influenced by lifetime depressive episodes, highlighting the relationship between depression heterogeneity and neural mechanisms.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Online cognitive testing combined with the reach of a digital patient registry revealed a subtype of people with Multiple Sclerosis with significant cognitive impairment but no motor deficits. This hidden disability is often underestimated and left untreated.

pOXA-48 plasmids have emerged as key vectors of carbapenem resistance within Enterobacteriaceae. In this study, the authors use a transposon sequencing (Tn-seq) approach to identify genetic determinants critical for plasmid stability and conjugative transfer.

While alternative splicing is known to drive oncogenesis and be a source of potential therapeutic targets, identifying such drivers on a genome-wide scale has proven difficult. Here, the authors present a computational approach to identify potential cancer-driver exons and evaluate applicability as therapeutic targets.

Enhanced polyamine depletion in neuroblastoma models decreases translation of mRNA codons with adenosine in the third position, reprogramming the tumour proteome away from cell cycle progression and towards differentiation.

Cheek swabs are widely used in pediatric epigenetic studies, but changes in their cellular composition with age are unclear. Here the authors show that buccal epithelial cells decline with age until adolescence, then stabilize, while variability increases with age, impacting the precision of tools like the PedBE clock in pediatric epigenetics.

TCR-TRANSLATE, a deep learning framework adapting machine translation to immune design, demonstrates the successful generation of a functional T cell receptor sequence for a cancer epitope from the target sequence alone.

Iridoids are terpenoid metabolites found in thousands of plants. Using single-cell transcriptomics, the authors discovered an unexpected enzyme that has been neofunctionalized to catalyse the cyclization required to form the iridoid scaffold.

Intratumoral hypoxia promotes cancer progression. Here, authors show that hypoxia upregulates RNA Polymerase I activity and ribosome biogenesis in breast cancer cells and targeting RNA Polymerase I with BMH-21 reduces tumor growth and metastasis in murine models.

Weijs, Missura, Potok et al. showed in this study with brain stimulation and electrophysiological methods that self-regulation of pupil size via pupil-based biofeedback modulates cortical excitability, arousal, and task-evoked responses.

Long non-coding RNAs (lncRNA) are known immune regulators, yet a systemic understanding of their regulatory crosstalk is still elusive. Here the authors establish a platform integrating RNA-binding proteome analyses and protein interactomes to map the lncRNA target network in human primary macrophages to build a searchable atlas of lncRNA.

Zaman, Yang and Huang et al. demonstrate MDK’s suppressive effect on amyloid-β and its impact on amyloid burden and microglial activation in Alzheimer disease mice, highlighting its protective role in pathogenesis.

Repetitive head impacts from contact sports are associated with brain inflammation, vascular damage and neuron loss that are independent of hyperphosphorylated tau pathology.

Studies in mice show that acute stress activates hyperglycaemia via activation of a medial amygdala–ventral hypothalamic circuit that controls glucose metabolic responses in the liver, independently of adrenal and pancreatic hormones.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Transancestral GWAS meta-analysis in 160,420 individuals identifies 139 loci associated with refractive error, including myopia. Newly identified genes implicate pathways involved in eye growth and light signaling cascades.

Ipecac alkaloids are plant-derived compounds historically used to induce vomiting. Here the authors elucidate how two evolutionary distant plant species have evolved to produce the same ipecac alkaloid.

ChatGPT provides a way of teaching people about climate change. This research reveals that conversations between climate sceptics and ChatGPT reduced climate scepticism, but these effects are modest, inconsistent across studies and prone to decay over time.

Antarctica is increasingly popular as a site for tourism and scientific research. The growth of marine traffic and the presence of major research stations have increased the anthropogenic deposition of heavy metals into this fragile ecosystem.

Early life is a critical window for immune development, marked by shifts in cell composition and function. Age and sex influence this process and are associated with epigenetic differences in immune-related DNA methylation, based on analysis of whole blood samples collected at ages 1 vs. 5 from a Canadian longitudinal paediatric cohort

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.

Here, the authors provide evidence that marine viruses spread via aerosolization and rain through the natural water cycle. Hosts from the first centimeters of the marine water column show signs of immunity against rain viruses. Those have DNA adaptations facilitating their stay in the air.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

Genome-wide association meta-analyses of attention-deficit/hyperactivity disorder symptom measures and clinical diagnoses identify new risk loci, highlight putative effector genes and yield improved polygenic risk scores.

Familial adenomatous polyposis (FAP) is an inherited gastrointestinal syndrome associated with duodenal adenoma formation. Here the authors show that IL17A-producing NKp44- group 3 innate lymphoid cells accumulate in FAP duodenal tissue and are associated with duodenal adenoma formation in patients with FAP.

Production of proteins at scale and affordable cost has been a major need of the biotech sector for the last several decades. Here the authors present a design algorithm called UNILIB for boosting gene expression in eukaryotic cells developed using an oligo-library and machine learning approach, validated in both yeast and mammalian cells using unseen sequences.

This study assessed COVID-19 social science preprints’ replicability using structured groups. Both beginners and more-experienced participants used a elicitation protocol to make better-than-chance predictions about the reliability of research claims under high uncertainty.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.