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Atopic dermatitis is a highly heritable skin condition. Here, the authors perform a GWAS meta-analysis of atopic dermatitis and carry out downstream analyses and functional experiments to understand the impact of the variants they identify.

Following first-line therapy, patients with relapsed or refractory acute myeloid leukaemia (AML) have limited therapeutic options. Here, the authors report a phase 1b/2a study investigating bemcentinib (AXL inhibitor) as monotherapy and in combination with low-dose cytarabine (LDAC) in patients with relapsed or refractory AML.

Systematic base-editing and computational screens identify specific cysteine residues on VPS35 in the retromer complex as key sensors that decrease mitochondrial translation in response to reactive oxygen species signals.

The authors present two independent reconstructions and a model simulations of Atlantic hurricane activity over the last millennium and show that it is mainly driven by internal climate variability instead of external forcings.

The Zika virus outbreak is a global health threat and there is an urgent need for drugs against the virus. Here the authors present the structure of the RNA-dependent RNA-polymerase ___domain from Zika non-structural protein 5, which is a template for the design of non-nucleoside polymerase inhibitors.

Research-agency heads from around the world agree to formulate shared principles to aid collaborations.

Genome editing of three SWEET gene promoters endows rice with resistance to all Xanthomonas bacterial blight strains tested.

Analysis of 20 chemical and morphological plant traits at diverse sites across 6 continents shows that the transition from semi-arid to arid zones is associated with an unexpected 88% increase in trait diversity.

Factors underlying the effects of gastric bypass surgery on glucose homeostasis are incompletely understood. Here the authors developed and applied high-throughput mediation analysis to identify proteome/metabolome mediators of improved glucose homeostasis after to gastric bypass surgery, and report that improved glycemia was mediated by the growth hormone receptor.

Rheumatoid arthritis patients respond differently to anti-TNF treatment. Using community-based challenge, the authors show that currently available data does not reveal meaningful genetic predictors of response to anti-TNF therapy, thus confirming clinical observations.

Protection afforded by inorganic minerals is assumed to make mineral-associated organic carbon less susceptible to loss under climate change than particulate organic carbon. However, a global study of soil organic carbon from drylands suggests that this is not the case.

Touch-guided tongue control in mice relies on a collicular mechanosensorimotor map, analogous to collicular visuomotor maps associated with visually guided orienting across many species.

The authors identify a DNA-protein crosslink (DPC) repair pathway orchestrated by poly-ADP-ribosylation. In this process, PARP1 PARylates the DPC, marking it for removal by proteolysis. Consequently, PARP1 facilitates the repair of DPCs located next to DNA breaks, such as topoisomerase 1-DPCs.

Researchers use pulse front curvature and temporal chirp to control the group velocity of a soft X-ray laser pump beam, resulting in improved energy extraction and reduced pulse duration.

High-resolution spacecraft imagery has revealed transient deposits that appear in the early mornings of cold seasons at the high altitudes of the Tharsis volcanoes on Mars, consistent with water frost of atmospheric origin.

Gamma-ray bursts (GRBs) are known to have impact on Earth’s lower ionosphere, but GRB impacts on the upper ionosphere was not observed before. Here, the authors show strong electric field variation at 500 km in the ionosphere caused by GRB221009A.

Power exhaust is one of the biggest challenges stopping fusion energy. This article shows experimental evidence for strategically shaping the power exhaust region as a solution to this challenge, utilising physics understanding to strike a balance between engineering complexity and power exhaust benefits, consistent with reduced models and simulations.

Deubiquitylases (DUBs) remove ubiquitin chains from proteins. Here the authors develop a mass spectrometry-based DUB activity screen using unmodified diubiquitin isomers to characterize substrate specificity for 42 human DUBs, and assess the potency and selectivity of 11 DUB inhibitors.

In the first results from an ongoing global cancer screening data repository, screening program organization was better overall in Europe compared to other continents; however, there were substantial gaps in implementation across both high- and low-resource settings.

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.

Genetic effects on functionally related ‘omic’ traits often co-occur in relevant cellular contexts, such as tissues. Here, the authors introduce X-ING, an integrative analysis method for cross-omics, cross-context associations based on summary-level data. Application to quantitative trait locus analysis yields insights into complex disease/trait mechanisms.

Phenotypic variation and diseases are influenced by factors such as genetic variants and gene expression. Here, Barbeira et al. develop S-PrediXcan to compute PrediXcan results using summary data, and investigate the effects of gene expression variation on human phenotypes in 44 GTEx tissues and >100 phenotypes.

Wherry and colleagues define the kinetics of vaccine-primed recall immune responses during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection, highlighting rapid activation of memory T cells and broadly enhanced immune responses in previously vaccinated individuals.

Extracellular vesicles have been implicated in the transmission of pathogens from the arthropod to the human host. Here the authors show that tick-derived extracellular vesicles play a role in feeding and modulate the outcome of bacterial infection.

To design and construct tissue adhesives tailored for site-specific actions, it is necessary to understand the interaction between the adhesive and the targeted tissue. In this Review, the development of adhesives for soft tissues is outlined, including discussions of in vivo properties and biocompatibility, as well as the key design criteria for accelerating their translation into clinical practice.

Using the GTEx data and others, a comprehensive analysis of adenosine-to-inosine RNA editing in mammals is presented; targets of the various ADAR enzymes are identified, as are several potential regulators of editing, such as AIMP2.

Patients with cancer undergoing anti-PD-1 immune checkpoint blockade can experience immune-related adverse effects. Wherry and colleagues examined the immunity elicited upon immunization of patients with cancer and report that anti-PD-1 immunotherapy dynamically affects influenza vaccine-induced immune responses.

As part of the enhanced GTEx (eGTEx) project, 987 human samples from 9 tissue types and 424 donors are assayed using DNA methylation microarrays. Colocalization of GWAS variants, eQTLs and mQTLs shows diverse links between genetic variation, molecular phenotypes and complex traits.

The authors show that rare genetic variants contribute to large gene expression changes across diverse human tissues and provide an integrative method for interpretation of rare variants in individual genomes.

Multiple transcriptome approaches, including single-cell sequencing, demonstrate that escape from X chromosome inactivation is widespread and occasionally variable between cells, chromosomes, and tissues, resulting in sex-biased expression of at least 60 genes and potentially contributing to sex-specific differences in health and disease.

Despite their key role in the evolution of mammals, the origin and diversification of tooth classes (incisors, canines, premolars and molars) remain relatively obscure. Here the authors use integrative approaches to explain the independent evolution and rapid diversification of two tooth classes, premolar and molars, in noctilionoid bats.

Rolandelli et al. define how immune cells from the tick Ixodes scapularis are affected by infection and show that this cell population have distinct signatures and functions in immunity, metabolism and proliferation.

Arthritis is the most common rheumatic immune-related adverse event (irAE) occurring in cancer patients receiving immune checkpoint inhibitors. Here the authors study the immune landscape of blood and synovial fluid samples from patients with arthritis-irAE, reporting immunological differences and similarities with classic autoimmune arthritis.

It has been reported that the circadian clock regulator Bmal1 can modulate tumorigenesis. Here the authors show that ectopic expression of Bmal1 promotes an immune resistant mesenchymal melanoma cell state associated with increased AP-1 activity.

Little is known about the genetics of sclerosing stromal tumor of the ovary, a rare type of sex cord-stromal tumor. Here, the authors use sequencing strategies to show that in a cohort of 26 tumor samples 65% carry a FHL2-GLI2 fusion gene and demonstrate in vitro that the fusion gene has oncogenic properties.

This article considers the case of a 17-year-old adolescent with a history of Crohn's disease who was receiving infliximab and presented with a new-onset rash. The rash did not resolve with corticosteroid treatment and worsened after further treatment with infliximab and also after subsequent administration of adalimumab. He was diagnosed as having an anti-TNF agent induced psoriasiform rash. The rash resolved after discontinuation of anti-TNF agents and his rash has not recurred during 3 years of follow-up.

Although circulating tumour DNA (ctDNA) can predict immune checkpoint blockade (ICB) responses, its association with tumour biomarkers remains unknown. Here, the authors use ctDNA to inform exome and transcriptome profiling of >100 patients with 30 cancer types on a single clinical ICB trial and identify tumour microenvironment features associated with response.

An improved table-top femtosecond soft X-ray laser with a gain duration of 450 fs is reported.