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Still’s disease is an inflammatory syndrome linked to the development of further immune dysregulation and hypercytokinaemia termed macrophage activation syndrome. Here the authors implicate the mechanistic target of rapamycin complex 1 in murine models of Still’s disease and macrophage activation syndrome, and provide associations with clinical cases in patients

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.

CRISPRai simultaneously activates and represses two genes in single cells.

CRISPR base editors are limited by protospacer adjacent motif (PAM) sequences and specific editing windows. Here, authors developed ABE-Ultramax, a suite of adenine base editors with high efficiency, low indel rates, and flexible PAM requirements, enabling precise biallelic editing in zebrafish.

Macrophages are abundant in the microenvironment of diffuse large B-cell lymphoma (DLBCL). Here, the authors use spatial transcriptomics to characterize macrophages in DLBCL and reactive lymphoid tissues, and propose six spatially-derived macrophage signatures that are associated with features like cell of origin and clinical outcomes.

A multi-ancestry genome-wide association study meta-analysis, combined with transcriptome- and methylome-wide association analyses, identifies risk loci associated with colorectal cancer. Credible effector genes and their target tissues are also highlighted, showing that over a third probably act outside the colonic mucosa.

Oncofetal (OnF) reprogramming, driven by YAP and AP-1, induces phenotypic plasticity and therapy resistance in WNT-dependent colorectal cancer (CRC). Targeting the OnF state in combination with chemotherapy substantially attenuates tumor growth in mouse models and patient-derived CRC tumoroids.

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.

STAARpipeline is a comprehensive framework for flexible and scalable rare-variant association analysis using whole-genome sequencing data and annotation information.

Sojka et al. analyse the transcriptomic and epigenomic landscape of human astrocyte maturation and identify an epigenetically regulated intermediate state associated with aberrant development in glioblastoma.

Newly evolved Xanthomonas citri pv. malvacearum isolates triggers recent bacterial blight outbreaks in cotton. Here, the authors show that a recently evolved TALE, Tal7b, activates host susceptibility genes GhSWEET14a and GhSWEET14b rather than GhSWEET10 to confer pathogenicity in these new isolates.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

A polymeric coating with sheltered positive charges establishes strong interactions with coagulation factor XII without inducing surface-induced coagulation activation, being a promising antithrombotic coating for biomedical devices.

Neurons receive their input in three dimensions via their dendrites, but how electrical activity in dendrites is organized is unknown. Here, the authors work out the distinct rules that govern activity across this 3D structure in different brain states.

In vitro modelling of the adipose tissue-liver axis can advance understanding and therapy of metabolic disease, including by distinguishing effects of obesity and inflammation. Here, authors develop such a system based on isogenic human iPSCs and interconnected microphysiological devices.

The physiological function of the mammalian chitinase AMCase is unclear. Wynn and colleagues show that it is dispensable for allergic lung inflammation but is necessary for clearance of intestinal helminths.

Profiling the immune responses of 56 volunteers vaccinated with BNT162b2 reveals how this mRNA vaccine primes the innate immune system to mount a potent response to SARS-CoV-2 after booster immunization.

This Resource describes data, code and tools developed for the Human Reference Atlas and the Human BioMolecular Atlas Program for building and navigating a multiscale human atlas.

Group 2 innate lymphoid cells (ILC2s) are generally considered to have pro-tumor functions. However, Belz and colleagues demonstrate that ILC2s have anti-melanoma effects due to their high production of the inflammatory cytokine granulocyte-macrophage colony-stimulating factor in the tumor microenvironment.

By suppressing the second- and third-order intracavity dispersion using an intracavity spectral pulse shaper, a mode-locked laser that emits pure-quartic soliton pulses that arise from the interaction of the fourth-order dispersion and the Kerr nonlinearity is demonstrated.

The authors summarize the data produced by phase III of the Encyclopedia of DNA Elements (ENCODE) project, a resource for better understanding of the human and mouse genomes.

Samples of different body regions from hundreds of human donors are used to study how genetic variation influences gene expression levels in 44 disease-relevant tissues.

A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.

Large language models show potential in suggesting common functions for a gene set.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

Large genome-wide meta-analysis of clinically diagnosed late-onset Alzheimer’s disease (LOAD) from 94,437 individuals identifies new LOAD risk loci and implicates Aβ formation, tau protein binding, immune response and lipid metabolism.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

Cyprinids fish species contain multiple subgenomes as a result of past duplications. Here, Xu et al. report new genomes of 21 cyprinid fish and conclude that observed subgenome dominance patterns are likely due to both maternal dominance and transposable element densities in each polyploid.

In this work, the authors develop a platform called AGILE or AI Guided Ionizable Lipid Engineering, which streamlines ionizable lipid development. Using AGILE, they rapidly design, synthesize, and evaluate ionizable lipids for mRNA delivery.

Characterizing how genetic variation impacts cell morphology can provide an important links between disease association and cellular function. Here the authors identified the morphological impacts of genomic variants by generating high-throughput morphological profiling and whole genome sequencing data on iPSCs from 297 donors.

Phylogenomic analysis of 7,923 angiosperm species using a standardized set of 353 nuclear genes produced an angiosperm tree of life dated with 200 fossil calibrations, providing key insights into evolutionary relationships and diversification.

The S-layer is a proteinaceous envelope often found in bacterial and archaeal cells. Here, the authors use CRISPR-based technology to silence slaB, encoding the S-layer membrane anchor, to show that an intact S-layer is important for cell division and virus susceptibility in the archaeon Sulfolobus solfataricus.

Brain slices offer an experimental window into human neurophysiology. Using high-density microelectrode array recordings and adeno-associated virus–mediated optogenetics, the authors demonstrate that optogenetic targeting of CAMK2A+ neurons can affect network activity in human hippocampal slices.

The capability of materials to interconvert between phases enables greater control over properties without additional chemical modification but can result in a sacrifice of porosity. Here, the authors synthesize metal-organic polyhedra that interconvert between the liquid-glass-crystal phases and develop a membrane with enhanced porosity and CO₂ selectivity.