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Periventricular heterotopia (PH) is associated with neurodevelopmental delay. Here authors report patient-derived organoids with FAT4 and DCHS1 mutations mimic PH features, showing hyperactivity, synaptic changes and cell morphological alterations.

HIV-transcribing cells in people living with HIV are difficult to study with conventional single-cell RNA-seq. Here the authors develop a technique to increase detection of HIV RNA during scRNA-seq and, comparing the transcriptomes of HIV RNA+ blood cells obtained pre- and post-antiretroviral therapy, provide insights into the persistence of the HIV RNA+ reservoir.

A national prospective study of patients requiring hospitalization for COVID-19 demonstrates global cognitive deficits at 1 year, associated with elevated brain injury markers and reduced gray matter volume.

Single-nucleus epigenomic maps of the adult human brain and spinal cord reveal that adult oligodendroglia retain developmental chromatin patterns, suggesting a molecular memory that may shape repair processes and cancer vulnerability.

Toker et al. present an AI framework that identifies mechanisms of consciousness. The model predicts new drivers of unconsciousness and identifies subthalamic nucleus stimulation as a potential therapy for disorders of consciousness.

Scholl et al. show that PopZ forms filamentous condensates driven by its helical domain and inhibited by its disordered region. Phase-dependent conformations modulate client interactions and disruption of filamentation or condensation impairs cellular function and growth.

How white matter develops along the length of major tracts in humans remains unknown. Here, the authors identify fundamental patterns of human white matter development along distinct axes that reflect brain organization.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

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.

Analyses of biobank data show that human variation such as age, sex and genetics, particularly at the major histocompatibility complex locus, is associated with viral abundance and supports a causal link between abundance of Epstein–Barr virus and Hodgkin’s lymphoma.

Here they combine in vivo imaging with proteomics to characterize a protein complex comprised of Ccdc78 and Ccdc33 that acts at the extreme distal tip of 9 + 2 motile cilia to control tip architecture, cilia length, and cilia beating.

In this work, authors use whole genome tracking in a neonatal intensive care unit to reveal a strong link between Staphylococcus aureus colonization and invasive infection, pinpointing critical new targets for infection prevention in high-risk infants.

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.

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.

A follow-up analysis of a clinical trial that evaluated anti-PD-1 therapy in patients with cancer who are living with HIV provides mechanistic insights into transcriptomic, cellular and cytokine changes related to immune checkpoint inhibitor treatment and identifies a signature associated with clinical response.

Massively parallel reporter assays across five cell types identify thousands of causal, noncoding regulatory variants among 220,000 loci, revealing diverse regulatory mechanisms shaping complex traits and disease.

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.

Tuberculosis is a major global health threat. Here, the authors develop a single-cell drug discovery approach and identify a compound that tunes bacterial phenotypic variation. This enhances the activity of anti-tubercular drugs against the pathogen.

The authors examine magnetoencephalographic recordings during relevant- and irrelevant-feature processing in a visual attention task. As participants attend to stimulus color or motion, a temporal sequence of relevant followed by irrelevant feature activations may bind an attended object's features into a unitary percept.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

Evo 2 is an artificial intelligence-based biological foundation model trained on 9 trillion DNA base pairs spanning all domains of life that predicts functional properties from genomic sequences and provides a rich generative model for researchers in biology.

Magnetic resonance control of spin-correlated radical pairs alters red fluorescent protein emission in transgenic Caenorhabditis elegans, demonstrating in vivo magnetic field modulation of biomolecular processes.

Insights into regulatory T cell biology are accelerating therapeutic innovation in cancer immunotherapy, autoimmune diseases and transplant rejection.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

This study reports a maturation-dependent requirement for transferrin receptor -mediated iron uptake in pancreatic β-cells, whereby iron deficiency disrupts metabolic integrity and survival in developing cells but not in mature β-cells. The results show iron is a cue for β-cell maturation.

The ~200-Myr-old star TOI-2076 hosts a young four-planet system, the orbits and atmospheres of which are still evolving, showing signs of early dynamical reshaping and atmospheric sculpting and offering a rare glimpse of how planetary systems form and transform in their youth.

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.

This paper uses a multi-region model to show that single-region models used by thousands of companies to estimate CO2 emissions related to goods they purchase may drastically underestimate and misidentify the largest sources of upstream emissions.

Over 50 million people worldwide suffer from epilepsy, and many patients remain resistant to medication. Here, the authors hypothesized that targeting thalamic nuclei with precise anatomical and functional connections to SOZ (hodological matching) can enhance neuromodulatory effects in focal epilepsy.

The functions of the vast majority of brain-expressed spliced isoforms are unknown. Here the authors describe an isoform-resolution perturbation system coupled to a single cell transcriptomics read-out, and through this approach identify neuronal microexons that control autism-linked signatures underlying neuronal maturation and function

Five-year survival data and biomarker analysis of the PRADO extension cohort of the phase 2 OpACIN-neo trial, in which patients with high-risk stage III melanoma received neoadjuvant ipilimumab and nivolumab and underwent pathologic response-directed surgery and adjuvant therapy, show 71% event-free survival and 88% overall survival, with tumor mutational burden, IFNγ signature and PD-L1 expression associated with favorable outcomes.

Early life RSV infection contributes to risk of childhood asthma. Here, the authors develop a statistical model to predict age at first RSV infection in the United States based on birthdate, demographics, and RSV surveillance data which could be used to identify groups at risk of chronic respiratory sequalae like asthma.

Rising electricity and freshwater needs limit conventional hydrogen production. Here, the authors report a self-sufficient, electricity-free system that harvests atmospheric moisture to produce green hydrogen, offering a scalable and sustainable path to alleviate global green-hydrogen scarcity.

A multimodal analysis of patients with 22 different immune-mediated monogenic diseases versus matched healthy controls leads to the development of the immune health metric, which could be implemented broadly to predict responses to aging, vaccination and other immune perturbations.

Post-transcriptional regulation of mRNA translation was explored using Ribo-STAMP and single-cell RNA sequencing to reveal cell-type-specific and isoform-specific translation patterns across hippocampal neuronal and non-neuronal cell types, highlighting functional differences between CA1 and CA3.

Ahmad et al. show that soluble histone H4 binds at histone genes and acts as a repressor of their expression. These findings suggest that histone H4 is a sensor of ongoing DNA replication. Ongoing chromatin assembly uses up soluble H4 and relieves histone gene repression; however, once DNA replication ceases, soluble H4 accumulates and represses the histone genes.

BamA carries out the essential process of folding outer membrane β-barrels in Gram-negative bacteria and is a potential antibiotic target. Here, the authors discover macrocyclic peptide inhibitors that trap BamA in distinct structural conformations.

A combination of biochemical, cell biological and electron microscopy analyses reveal a ‘nucleotide code’ that coordinates Lis1–dynein binding stoichiometry, which in turn governs Lis1’s ability to relieve dynein autoinhibition.

The authors detail human antibodies that neutralize all three serotypes of poliovirus and mimic poliovirus receptor binding, accelerating antiviral development to further efforts to eradicate poliovirus.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

Mutation of conserved prolines enhances correct pairing of light and heavy chains for bispecific IgG-like antibody production.

Allele-preferential transcription factor binding can influence pancreatic ductal adenocarcinoma risk loci function. Here, the authors show allele-specific JunB and JunD binding at chr1p36.33 and propose a role for KLHL17 in protein homeostasis by mitigating inflammation.

The interactions of CAR-T cells and solid tumors are modeled on a chip.

Subcellular compartmentalization of the glycolytic enzyme PFKM regulates cell fate and metabolic switch during skeletal muscle differentiation.

Hiʻiaka is the largest moon of the distant dwarf planet Haumea. Here, the authors report the first multi-chord stellar occultations of Hiʻiaka, revealing its size, shape, and density, suggesting an origin from Haumea’s icy mantle.

Leveraging pythons as an extreme model of feeding and fasting behaviour, this study uncovers para-tyramine-O-sulphate as a conserved postprandial metabolite that links nutrient intake to energy balance by activating hypothalamic neurons and suppressing food intake in pythons and mice.

Acute ischemic stroke impacts men and women differently. Here, the authors show how different lesion patterns in men and women are linked to the extent of stroke severity.

Comparison between structures of human, mouse and rat P2X7 receptors define ortholog-specific pharmacology and facilitated structure-based drug design of UB-MBX-46, an antagonist that selectively inhibits the human P2X7 receptor with sub-nanomolar potency.

The authors study a disordered β-Ta film, finding that quasiparticle recombination is governed by the phonon scattering time, which is faster than conventional recombination in ordered superconductors. The authors interpret the results in terms of quasiparticle localization, which helps to understand the quasiparticle relaxation in disordered superconducting circuits.