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Risk associated with genetically defined forms of autism spectrum disorder (ASD) can propagate by means of transcriptional regulation to affect convergently dysregulated pathways, providing insight into the convergent impact of ASD genetic risk on human neurodevelopment.

The high-plasticity cell state (HPCS) is a critical hub that enables reciprocal transitions between cancer cell states, and targeting the HPCS may suppress cancer progression and eradicate treatment resistance.

The authors of this study map the human E3 ubiquitin ligome using a metric learning approach, revealing a unified classification framework that explains preserved patterns and functional segregation of E3 families, linking enzymes to substrates and drug interactions, and guiding strategies for targeted therapies.

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).

Birth season has been associated with differences in epigenetic, developmental and health outcomes, but associations to developing metabolome are unclear. Here the authors report a secondary exploratory analysis of The Early Life Interventions for Childhood growth and development in Tanzania (ELICIT) trial showing that in rural Tanzania, an infant’s birth season shapes their metabolism up to 18 months of life, linked to rainfall, food insecurity and breastmilk composition.

Here, by integrating faecal metabolomics, metagenomics, and habitual dietary data of two large human cohorts, the authors show that faecal metabolites reflect diet and gut microbiome interactions, predict dietary patterns, and indicate cardiovascular risk, offering insights for diet-based health interventions.

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.

Whether higher-order visual areas exhibit a fine-grained functional organization remains poorly understood. Here, the authors use high-resolution fMRI to reveal that category-selective regions in macaques are organized into mesoscale functional units which form distinct long-range mesoscale functional networks.

TDP-43 dysfunction in ALS/FTD causes faulty splicing of the KCNQ2 ion channel, leading to toxic protein buildup, neuron hyperactivity and a potential new biomarker and treatment target using RNA-based therapies.

The authors show that the CD4 mimetic CJF-III-288 stabilizes HIV-1 Env in an asymmetric “open” State-3 conformation, guiding anti-CoRBS antibodies to boost ADCC against infected cells and delay viral rebound in vivo, underscoring therapeutic promise.

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.

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.

In an integrated analysis of transcriptomic data from the SUBSPACE consortium and public datasets of patients with sepsis, acute respiratory distress syndrome, trauma and burns, dysregulation within four consensus molecular clusters related to myeloid and lymphoid cells is associated with mortality and illness severity.

There is still a need for effective HIV vaccines. In this phase I clinical trial, the authors show that an HIV-1 vaccine candidate, ConM SOSIP.v7, is well-tolerated in HIV-negative adults and that it elicits a strain-specific neutralising antibody response that differed between female and male participants.

This study investigates the role of SMAD2 genetic variants associated with congenital heart disease on renal development using a CRISPR-engineered human induced pluripotent stem cell model on a microphysiological system.

A report from the first 2,000 newborns enrolled in the Early Check program, which offered genome screening covering 198 genes associated with early-onset diseases, shows the feasibility and potential clinical utility of the approach, leading to 28 true positive results.

Analysis of snRNA genes in individuals with rare disorders identifies de novo and recurrent variants in RNU5B-1 and RNU5A-1, in addition to previously unreported cases with pathogenic or likely pathogenic variants in RNU4-2.

The Altiplano-Puna magma body is located in the world's second highest plateau, the Altiplano-Puna, but the influence of melt production in the surface uplift of the Central Andes is unclear. Perkinset al. link surface topography and isotactic modelling to constrain the melt production in the magma body.

A free-living trial in people with overweight or obesity found that minimally processed diets led to greater weight loss and cardiometabolic improvements than ultraprocessed diets following UK healthy eating guidelines at 8 weeks.

Cellular nuisance compounds are a burden in chemical biology and drug screening. Here the authors profile prototypical cytotoxic and nuisance compounds using the cell painting assay to systematically characterise cellular morphologies associated with compound-dependent cellular injury and nuisance activity.

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.

Vaccination efficiency in HIV infection is hampered by the low immunogenicity of HIV-1 Env glycoprotein (Env). Here authors optimise the neutralising antibody response to Env by stabilizing the Env trimers in the context of expressing them in a Newcastle Disease Virus-like particle and providing conditions that mimics replicating virus infection.

Lipid particles loaded with RNA coding for tumour-unspecific antigens can enhance early responses of type-I interferons, mediating the success of immune checkpoint inhibitors as well as epitope spreading.

Solid organ transplant recipients are at increased risk of infectious disease and have unique molecular pathophysiology. Here the authors use host-microbe profiling to assess SARS-CoV-2 infection and immunity in solid organ transplant recipients, showing enhanced viral abundance, impaired clearance, and increased expression of innate immunity genes.

CRISPR-Cas9-based screens have allowed the study of gene-drug interactions. Here, the authors develop CRISPR-Cas9 knock-out, activation and repression screens in human gastric 3D organoids, also integrating single-cell CRISPR screens, to identify genes involved in the response to cisplatin in gastric cancer.

Complement proteome engagement is strongly linked to kidney outcomes in diabetes. This translational study leveraged five cohorts of over 4,500 person-years and high-throughput proteomics to enable potential biomarker-guided drug development.

Whilst superlattices containing thin films of 5d transition metal oxides are expected to yield strong interfacial coupling, only weak effects have been observed. Here, the authors report strong coupling between 3d SrMnO₃ and 5d SrIrO₃due to the interplay of strong Coulomb and spin orbit interactions.

Industrial chemicals can pose serious health risks in the workplace, and monitoring them is of vital importance. Researchers now show that an optoelectronic nose based on a colorimetric sensor array of nanoporous pigments can rapidly identify a wide range of toxic gases at their IDLH (immediately dangerous to life or health) concentrations.

Severe febrile illnesses in children may be various in presentation and aetiology but involve immune dysfunction amenable to immunomodulation. Here, the authors identify shared neutrophil and T cell dysfunction and a distinct interferon signature in critically ill children with severe febrile illness.

Microbiome analyses of living trees show that a single tree can host approximately one trillion bacteria, with microbial communities distinctly partitioned between heartwood and sapwood and with minimal similarity to other tissues or ecosystem components.

Post-acute sequelae of SARS-CoV-2 (PASC) is still not well understood. Here the authors provide patient reported outcomes from 590 hospitalized COVID-19 patients and show association of PASC with higher respiratory SARS-CoV-2 load and circulating antibody titers, and in some an elevation in circulating fibroblast growth factor 21.

Stochastic or genetic effects can drive variability in X-chromosome inactivation (XCI) ratios among mammals, though their relative contributions are poorly understood. This study measures distributions of XCI ratios for 10 species and finds the embryonic stochasticity of XCI is a general explanatory model for mammalian XCI ratio variability.

Targeting proinflammatory/oxidative enzymes is a promising approach to treat inflammatory diseases. Here the authors present a dual-specificity inhibitor for the simultaneous targeting of Vascular Adhesion Protein-1 and Myeloperoxidase, two cooperative but functionally independent enzymes, and report potent anti-inflammatory effects of the dual inhibitor in multiple animal models of inflammatory disease.

Available wheat genomes are annotated by projecting Chinese Spring gene models across the new assemblies. Here, the authors generate de novo gene annotations for the 9 wheat genomes, identify core and dispensable transcriptome, and reveal conservation and divergence of gene expression balance across homoeologous subgenomes.