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ASLPrep is a software suite for reproducible processing of arterial spin labeled magnetic resonance imaging data.

Many genetic variants identified in genome-wide association studies are associated with gene expression. Here, Porcu et al. propose a transcriptome-wide summary statistics-based Mendelian randomization approach (TWMR) that, applied to 43 human traits, uncovers hundreds of previously unreported gene–trait associations.

The authors develop a methodology to quantify climate physical risks, both chronic and acute, on productive assets. Investor losses are underestimated up to 70% when neglecting asset level information, and up to 82% when neglecting tail acute risks.

In this study, the anti-anginal drug ranolazine is found to sensitize BRAF inhibitor-resistant melanoma to targeted therapy and immunotherapy by rewiring fatty acid oxidation and the methionine salvage pathway.

Recurrent de novo mutations at nucleotide positions 4 and 35 of RNU2-2 cause a neurodevelopmental disorder whose prominent features include intellectual disability, developmental delay and a complex seizure phenotype.

A method named photoacoustic vector tomography now enables the quantification of haemodynamics in veins at depths of more than 5 mm below the skin surface, outperforming current pure optical modalities for deep haemodynamic imaging.

John Perry and colleagues report the results of a large genome-wide association study meta-analysis to identify variants influencing age at natural menopause. They identify 54 independent signals and find enrichment near genes involved in delayed puberty and DNA damage response.

NKp46⁺ innate lymphoid cells are identified as pivotal signal amplifiers of autoinflammatory responses in lupus nephritis.

It remains unclear how to best model local field potential gamma oscillations. Here, the authors show that gamma dynamics are well-captured by a damped harmonic oscillator model.

Although single-cell RNA sequencing analysis now allows simultaneous examination of transcriptome and T cell receptor repertoire sequences, integrating these two modalities remains a challenge. Here, the authors develop mvTCR, a generative deep learning model that integrates transcriptome and T cell receptor data into a joint representation capturing cell functions and phenotypes.

The nucleus is a mechanically stiff organelle of the cell and the DNA damage response protein ATR can localize to the nuclear envelope upon mechanical stress. Here, the authors show that ATR may contribute to the integrity of the nuclear envelope and may play a role in cell migration.

A study of 580 tomato lines resulting from a cross between a wild desert-adapted species and a domesticated cultivar elucidates the genetic basis of gene expression and metabolite variation associated with fruit traits and defense against pathogens.

The JAK2^V617F mutation leads to epigenetic rewiring in a cell-intrinsic and cell-type-specific manner, influencing inflammation states and differentiation trajectories in patients with myeloproliferative neoplasms.

Multiomic factor analysis of blood multiomic data, including single-cell transcriptomics, for individuals with either acute or chronic coronary syndrome identifies immune cell signatures that correlate with treatment outcomes.

Here the authors structurally characterize respiratory supercomplexes, revealing that, in addition to the known ‘canonical’ respirasome, mammalian mitochondria contain two novel respirasome types, one of which incorporates supercomplex assembly factor SCAF1.

Rhythmic trafficking of dendritic cells to the tumour draining lymph node governs a circadian response of tumour-antigen-specific CD8⁺ T cells that is dependent on the circadian expression of the co-stimulatory molecule CD80.

Sumoylation is important for the assembly and function of the SMN complex, which plays a central role in RNA processing. Here the authors show that loss of this posttranslational modification impairs the ability of SMN to correct selective deficits in the sensory-motor circuit of animal models of spinal muscular atrophy.

Ruth Loos and colleagues report results of a large genome-wide association study for body mass index. They identify 18 new loci associated with this trait, some of which map near key hypothalamic regulators of energy balance.

A very uncommon detached binary system with a 20.5-min orbital period has been discovered to harbour a carbon–oxygen white dwarf star and a low-mass subdwarf B star with a seven-Earth radius that traces the theoretical limit of binary evolution predicted 20 years ago.

Friction forces at the interface between tissues play a key role in tissue morphogenesis. Now friction at the cellular scale is shown to influence cell shape and cell rearrangements.

The immune system is tolerized against the neuromyelitis optica autoantigen AQP4 by thymic B cells, which present their endogenous AQP4 to AQP4-reactive thymocytes.

A comprehensive analysis of models of brain metastasis and multiple cohorts of patient samples identifies a targetable molecular mechanism underlying the resistance to whole-brain radiotherapy that can inform patient selection for personalized radiotherapy.

The authors propose Detect, a browser-based anomaly detection framework for diffusion magnetic resonance imaging tractometry data. The tool leverages normative microstructural brain features derived from healthy participants using deep autoencoders to detect anomalies at the individual level.

The heterogeneity of androgen receptor (AR) gene alterations across metastases in prostate cancer remains unresolved. Here, the authors characterise AR genomic complexity across spatially separated lethal metastases from 10 prostate cancer patients and investigate how AR alterations evolve.

SARS-CoV-2 induces mild infection in ferret model. Here, Ryan et al. characterise optimal infection dosage inducing upper respiratory tract (UTR) viral shedding, progression time of viral shedding, and pathology in ferrets and finally provide evidence for protection after re-challenge.

Evolutionarily conserved gene modules mediate neurodegenerative dementia in a variety of mouse models and in postmortem brain tissue from patients.

Llorente, Blasco, Espuny and colleagues show that MAF regulates the genomic distribution of ERα and modulates the expression of metastasis genes via KDM1A, thereby driving metastatic spread in breast cancer.

Variant-to-gene-to-program is a new approach to building maps of genome function to link risk variants to disease genes and to convergent signalling pathways in an unbiased manner; its strength is demonstrated in coronary artery disease.

Pathway optimization and chassis engineering are usually carried out in a step-wise and trial-and-error manner. Here the authors present ’SCRaMbLE-in’ that combines in-vitro pathway rapid prototyping with in-vivo genome integration and optimization.

A genome-wide association meta-analysis study here shows novel genetic loci to be associated to body fat percentage, and describes cross-phenotype association that further demonstrate a close relationship between adiposity and cardiovascular disease risk.

Luis Pérez-Jurado, Stephen Chanock and colleagues detect clonal chromosomal abnormalities in peripheral blood or buccal samples from individuals in the general population. They show that the frequency of such events increases with age and is associated with elevated risk of developing subsequent hematological cancers.

Reorganization of the sensorimotor cortex due to loss of sensory input is implicated in phantom pain. Makin and colleagues use functional MRI to show that phantom pain experience is instead associated with maintained local functional and structural cortical representations but disrupted inter-regional connectivity.

The brain extracellular matrix (ECM) is altered in brain tumors, but its role in cancer progression and drug sensitivity are difficult to study. Here the authors develop a 3D bioengineered brain tissue model using patient-derived samples and tunable brain-derived ECM to examine the interplay between cells and the ECM.

Polygenic Priority Score (PoPS) prioritizes candidate effector genes at complex trait loci by integrating genome-wide association summary statistics with other data types. Combining PoPS with methods that leverage local genetic signals further improves the performance.

The DANIO-CODE consortium leverages a large-scale multiomic dataset to improve zebrafish genome annotation. They identify ~140,000 cis-regulatory elements throughout development and perform a comparison with the mouse regulatory landscape.

Structural disorder in materials is challenging to characterise. Here, the authors use multivariate analysis of atomic pair distribution functions to study structural collapse and melting of metal–organic frameworks, revealing powerful mechanistic and kinetic insight.

Here, in a randomized trial of 147 infants receiving distinct antibiotic regimens for early-onset neonatal sepsis, Reyman et al. characterize the gut microbiome and resistance profiles, finding differential effects of antibiotic combinations on microbial community composition and antimicrobial resistance genes.

Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, the authors perform discovery GWAS for BP in East Asians and meta-analysis in East Asians and Europeans and report ancestry-specific BP SNPs and selection signals.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

Obesity is a major risk factor for cancer related death. Here, the authors show that visceral adipose-derived factors promote vasculogenesis and metastatic dissemination by activation of STAT3, which inhibits miR-200a and enhances ZEB2 expression, effectively reprogramming colorectal cancer cells into a highly metastatic phenotype.

Plasma pTau181 concentrations are elevated specifically in patients diagnosed with Alzheimer’s disease compared to those diagnosed with frontotemporal lobar degeneration or elderly controls, supporting its further development as a blood-based biomarker for AD.