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In patients with Crohn’s disease, CD4⁺ T cells with cytotoxic T_H1 cell-like effector functions reactive against dietary and commensal yeasts are increased in blood and inflamed tissue compared with patients with ulcerative colitis and healthy controls.

Peripheral T cell lymphoma (PTCL) not otherwise specified (NOS) is a subgroup of PTCL, which has no distinctive features and is poorly characterized at the genetic level. Here, the authors identify two fusion transcripts that activate T cell receptor complex signalling and confer therapeutic vulnerability in PTCL-NOS.

High frequency semen exposure has been associated with activation of anti-HIV mechanisms in HIV negative sex workers. Here, Abdulhaqq et al. show that repeated vaginal exposure to semen reduces vaginal infection by SIV in non-human primates, and is associated with lower CCR5 expression in CD4 T-cells and a local type-I interferon response.

Single-cell transcriptomics analyses of pretreatment and post-treatment peripheral blood mononuclear cells from patients treated with CD19 chimeric antigen receptor (CAR)-T products reveal a role for CAR-T regulatory cells in treatment relapse.

This very large genome-wide association study identifies hundreds of new genetic variants influencing adult height in at least 180 loci enriched for genes involved in skeletal growth defects. The results show that the likely causal gene is often located near the most strongly associated variant, that many loci have multiple independently associated variants and that associated variants are enriched for likely functional effects on genes.

Vanessa Wong and colleagues report whole-genome sequencing of 1,832 Salmonella enterica serovar Typhi isolates from 63 endemic countries. They identify mutations that define the multidrug resistant (MDR) H58 lineage and report numerous inter- and intracontinental transmissions of this lineage as well as an ongoing MDR typhoid epidemic in Africa.

Steve Brown and colleagues report an analysis of 20 phenotyping tests, including 413 data parameters, across 449 mutant mouse alleles. They identify widespread pleiotropy and assign putative functions to genes that lacked previous phenotypic annotation.

Erik Ingelsson and colleagues report a large-scale genome-wide meta-analysis for associations to the extremes of anthropometric traits, including body mass index, height, waist-to-hip ratio and clinical obesity. They identify four loci newly associated with height and seven loci newly associated with clinical obesity and find overlap in the genetic structure and distribution of variants identified for these extremes of the trait distributions and for the general population.

Expression profiles of several hundred microRNAs in the blood of individuals with disease, including autoimmune disease, cancers, cardiovascular disease and chronic inflammatory disease are reported.

Anna Köttgen and colleagues report genome-wide association studies for serum urate in over 140,000 individuals from the Global Urate Genetics Consortium (GUGC). They identify 18 loci newly associated with serum urate concentrations and confirm 10 known loci, characterize their associations with gout and include a network analysis suggesting a role for inhibins-activins pathways in regulating urate homeostasis.

Stein Aerts, Jan Cools and colleagues report exome sequencing of T-cell acute lymphoblastic leukemia. They identify recurrent somatic mutations in CNOT3 and ribosome genes RPL5 and RPL10.

Porphyromonas gingivalis, an oral anaerobe involved in the pathogenesis of periodontitis, relies on extracellular proteases to degrade proteins into peptides for growth, but how these peptides enter the cell is unknown. Here, the authors identify RagAB as the outer-membrane importer for these peptides and solve its structure, elucidating that it works via a ‘pedal bin’ mechanism of nutrient uptake.

There is currently no disease-modifying treatment for Parkinson’s disease, a common neurodegenerative disorder. Here, the authors use genetic variation associated with gene and protein expression to find putative drug targets for Parkinson’s disease using Mendelian randomization of the druggable genome.

Upscale fabrication of functionalized microparticles is a pending challenge. Here, Kim et al. exploit the rheology of a thixotropic medium to grind sizeable amounts of raw material into well-defined colloidal dispersions, physically stabilized for further production steps.

FR900359 (FR) is a Gq protein inhibitor depsipeptide isolated from an uncultivable plant endosymbiont and synthesized by non-ribosomal peptide synthetases. Here, the authors discover a cultivable bacterial FR producer and show that FrsA thioesterase ___domain catalyses intermolecular transesterification of the FR side chain to the depsipeptide core during biosynthesis, improving Gq inhibition properties.

Hepatocytes grown in a dish are immature and do not metabolize compounds as a real liver would. Here, the authors supply stem cell-derived hepatocytes with amino acids at a higher concentration than nutritionally necessary, changing the metabolism of these cells, making them more mature and useful for drug screening and toxicity studies.

There is an ever-increasing requirement for coolant systems and current apparatus typically exhibits low efficiency as well as relying on environmentally detrimental refrigerants. Here, the authors report a design involving a caloric material and the condensation and evaporation of a heat transfer fluid, which achieves a marked increase in performance in comparison to other types of system.

How accurate are social scientists in predicting societal change, and what processes underlie their predictions? Grossmann et al. report the findings of two forecasting tournaments. Social scientists’ forecasts were on average no more accurate than those of simple statistical models.

Tr1 cells are considered an immunosuppressive CD4 T cell population producing IL-10. Here the authors show that IL-10 is insufficient for Tr1 immunosuppression, define surface markers and transcriptional program of the immunosuppressive subset within Tr1, and reveal its deficiency in patients with IBD.

Nicholas Feasey and colleagues report whole-genome sequence analysis of 675 isolates of Salmonella enterica serovar Enteritidis from 45 countries. They find evidence for a global epidemic clade associated with enterocolitis and two novel clades restricted to distinct regions of Africa and associated with invasive disease.

Understanding how parents’ cognitive and non-cognitive skills influence their children’s educational trajectories is important for educational, family and economic policy. Here, the authors investigate parental influence on children’s education using genetic approaches.

Genome-wide association studies have identified regions which confer risk of high-grade serous epithelial ovarian cancer. Here the authors use expression quantitative train locus analysis to identify candidate genes and functionally characterise them, identifying a role for HOXD9 in ovarian cancer.

Most confirmed susceptibility variants for epithelial ovarian cancer lie in non-protein-coding sequences. Here Permuth-Wey and colleagues investigate variants in 3′ untranslated regions (UTRs) and uncover a new susceptibility locus.

HNF1B is overexpressed in the clear cell subtype and epigenetically silenced in the serous subtype of ovarian cancer. Pearce and colleagues now show that genetic variants in HNF1B are differentially associated with risks of developing these two cancer subtypes, possibly through an epigenetic mechanism.

Traumatic brain injury is associated with changes to the metabolome. Here the authors show that acute traumatic brain injury has distinctive serum metabolic patterns which may suggest protective changes of systemic lipid metabolism aiming to maintain lipid homeostasis in the brain.

The BRAIN Initiative Cell Census Network has constructed a multimodal cell census and atlas of the mammalian primary motor cortex in a landmark effort towards understanding brain cell-type diversity, neural circuit organization and brain function.

The recovery of two circularized genomes of the Heimdallarchaeum species from hydrothermal vent enrichment cultures reveals that these Asgard archaea carry diverse mobile genetic elements, such as an integrative viral genome and aloposons. These mobile genetic elements contain several bacteria- and phage-derived genes, modulating the shuffling of information between bacteria and archaea, and potentially influencing eukaryogenesis.

Contrary to the view that urbanization is a major driver of the global rise in obesity, the global increase in body-mass index is shown to be mostly due to increases in the body-mass indexes of rural populations.

Randomized studies and evaluations of large registries have repeatedly shown that epinephrine used as a standard vasopressor for cardiopulmonary resuscitation increases the rate of return of spontaneous circulation. By contrast, epinephrine might decrease long-term survival and impair neurological outcome.

Melanocytic nevus count is associated with melanoma risk. In this study, a meta-analysis of 11 nevus GWAS studies identifies novel SNPs in KITLG and 9q32, and bivariate analysis with melanoma GWAS meta-analysis reveals that most nevus genes affect melanoma risk, while melanoma risk loci do not alter the nevus count.

A meta-analysis of genome-wide association studies of phenotypic variation for height and body mass index in human populations using 170,000 samples shows that one single nucleotide polymorphism at the FTO locus, which is associated with obesity, is also associated with phenotypic variation.

Discovery of causal variants for monogenic disorders has been facilitated by whole exome and genome sequencing, but does not provide a diagnosis for all patients. Here, the authors propose a Full Spectrum of Intolerance to Loss-of-Function (FUSIL) categorization that integrates gene essentiality information to aid disease gene discovery.

Typhoid fever is caused by Salmonella enterica serovar Typhi (S. Typhi). This study examines ∼2,000 clinical isolates of S. Typhi to show highly structured/geographically restricted genomes except rapidly disseminating H58 subclade, and design a genotyping framework for tracking the disease.

Candidate anti-tuberculosis drugs are often identified in whole-cell screens. Here, Petheet al. show that inappropriate carbon-source selection can lead to the identification of compounds devoid of efficacy in vivo, underlining the importance of developing predictive in vitroscreens.

At age 4, children start understanding other peoples' false beliefs, but the related neuroanatomical changes are unknown. Here, authors show that false belief understanding is associated with age-related changes in white matter structure, and that this effect is independent of other cognitive abilities.