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Using a sample of more than 1 million individuals, Hatoum et al. identify genomic loci associated with general and substance-specific addiction risk.

The Cancer Genome Atlas Research Network reports an integrative analysis of more than 400 samples of clear cell renal cell carcinoma based on genomic, DNA methylation, RNA and proteomic characterisation; frequent mutations were identified in the PI(3)K/AKT pathway, suggesting this pathway might be a potential therapeutic target, among the findings is also a demonstration of metabolic remodelling which correlates with tumour stage and severity.

Bradford, Zhang and colleagues generate a mouse model harboring a mutation that impacts PKP2 splicing and show that one-time administration of AAV-PKP2 in neonatal mice could restore PKP2 and prevent the onset of key pathological features of arrhythmogenic right ventricular cardiomyopathy, and one-time administration in adult mice could rescue the phenotype and prevent sudden death up to 4 months post treatment.

In this study, Kagan et al. highlight the relevance of adequate cardiolipin homeostasis by offering mechanistic insight into the pathogenesis of Barth syndrome. The study shows how altered accumulation of mono-lyso-cardiolipin, one of the derivatives of the mitochondrial lipid cardiolipin, forms an anomalous peroxidase complex with cytochrome c, thus leading to increased oxidation of polyunsaturated phospholipids.

The authors report on a temperate Earth-sized planet orbiting the cool M6 dwarf LP 791-18 with a radius of 1.03 ± 0.04 R_⊕ and an equilibrium temperature of 300–400 K, with the permanent night side plausibly allowing for water condensation.

The aboveground carbon stock of a montane African forest network is comparable to that of a lowland African forest network and two-thirds higher than default values for these montane forests.

Radiomitigating compounds could be used to protect against ionizing radiation. In this study, mitochondria-targeted oleic and stearic acid derivatives are shown to inhibit pro-apoptotic oxidative events, prevent cell death, and protect mice against lethal doses of radiation.

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.

The influence of X chromosome genetic variation on blood lipids and coronary heart disease (CHD) is not well understood. Here, the authors analyse X chromosome sequencing data across 65,322 multi-ancestry individuals, identifying associations of the Xq23 locus with lipid changes and reduced risk of CHD and diabetes mellitus.

The Atlantic meridional overturning circulation has weakened over the past decade. Examination of a global reanalysis that matches independent observations shows that the decline is consistent with recovery from an earlier invigoration.

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.

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.

A consortium reports the tripling of the number of genetic markers in Phase II of the International HapMap Project. This map of human genetic variation will continue to revolutionize discovery of susceptibility loci in common genetic diseases, and study of genes under selection in humans.

Mycobacterium tuberculosis has the ability to survive within the host for months to decades in an asymptomatic state, and adaptations to hypoxia are thought to have an important role in pathogenesis; here a systems-wide reconstruction of the regulatory network provides a framework for understanding mycobacterial persistence in the host.

Hata and colleagues identify lorlatinib analogs that overcome acquired therapy resistance to current ALK inhibitors and show their efficacy in preclinical models of non-small cell lung cancer bearing compound therapy-resistant ALK alterations.

The Cancer Genome Atlas consortium reports on their genome-wide characterization of somatic alterations in colorectal cancer; in addition to revealing a remarkably consistent pattern of genomic alteration, with 24 genes being significantly mutated, the study identifies new targets for therapeutic intervention and suggests an important role for MYC-directed transcriptional activation and repression.

This report from the 1000 Genomes Project describes the genomes of 1,092 individuals from 14 human populations, providing a resource for common and low-frequency variant analysis in individuals from diverse populations; hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites, can be found in each individual.

Hakon Hakonarson and colleagues report the identification of two new susceptibility loci for inflammatory bowel disease (IBD). One variant is near a gene encoding tumor necrosis factor receptor subfamily member 6B and is associated with increased levels of this protein in serum from individuals with IBD.

The vertebrate body plan shows marked bilateral symmetry, although this can be disrupted in conditions such as scoliosis. Here, a mutation in Rere is found that leads to the formation of asymmetrical somites in mouse embryos; furthermore, Rere is shown to control retinoic acid signalling, which is required to maintain somite symmetry by interacting with Fgf8. The results provide insight into how bilateral symmetry is maintained.

UBE2W catalyzes the ubiquitination of protein N-termini but its substrate spectrum is largely unknown. Here, the authors discover mAbs selective for peptides derived from N-terminally ubiquitinated proteins, solve the structure of a peptide-bound mAb and apply the mAbs to map endogenous UBE2W substrates by proteomics.

Optical matter consisting of nanoparticle constituents in solution is of key interest due to the exhibited self-assembling mechanisms. The authors propose a principal components analysis based data-driven approach to determine the collective modes of colloidal clusters mimicking optical binding used in colloidal self-assembly.

The Cancer Genome Atlas presents an integrative genome-wide analysis of genetic alterations in 279 head and neck squamous cell carcinomas (HNSCCs), which are classified by human papillomavirus (HPV) status; alterations in EGFR, FGFR, PIK3CA and cyclin-dependent kinases are shown to represent candidate targets for therapeutic intervention in most HNSCCs.

Phosphorus fertilizer use has roughly quadrupled in the past century. Budgets constructed from historical data show that phosphorus rapidly accumulates in river basins during periods of high inputs and continues to mobilize after inputs decline.

A comprehensive study of the Kepler-138 system reveals the twin nature of Kepler-138 c and d and the presence of a fourth planet. Remarkably, the warm-temperate planet Kepler-138 d is probably composed of 50% volatiles by volume, indicative of a water world, rather than a rocky world, despite its small ~1.5 R_⊕ size.

Allogeneic hematopoietic cell transplantation (allo-HCT) has led to the cure of HIV in one individual, but the underlying mechanisms are unclear. Here, the authors present a model of allo-HCT in SHIV-infected nonhuman primates and show that the SHIV reservoir persists in multiple tissues early after transplantation.

The detrimental effects of aged blood on cognition and nervous system function in mice can be combatted by targeting brain endothelial cell dysfunction via inhibition of aberrant VCAM1 signaling at the blood–brain barrier.

A genome-wide association study identifies 17 genetic loci that are associated with the risk of myeloproliferative neoplasms (MPNs), and shows that the modulation of haematopoietic stem cell function drives MPN risk.

The bed bug, Cimex lectularius, is a ubiquitous human ectoparasite with global distribution. Here, the authors sequence the genome of the bed bug and identify reductions in chemosensory genes, expansion of genes associated with blood digestion and genes linked to pesticide resistance.

Conventional B cells express clonally specific antigen receptors, but a small subset of B cells from patients and mice with systematic lupus erythematosus simultaneously expresses two distinct antigen receptors. Here the authors show that these dual-specificity B cells have higher levels of MHC-II, depend on IL-21 for expansion, and mount stronger memory response.

Watson et al. demonstrate that astrocyte mitochondria can be horizontally transferred to glioblastoma cells in a GAP43-dependent manner, leading to changes in mitochondrial respiration and metabolism that promote proliferation and tumor growth.

NMR structure of an HIV-1 Rev peotide complexed with either the Rev binding elements or an RNA aptamer show that the helical peotide inserts into a widened major groove. However, significant local differences are observed.

Environmental influences during prenatal development may have implications for health and disease later in life. Here, Czamara et al. assess DNA methylation in cord blood from new-born under various models including environmental and genetic effects individually and their additive or interaction effects.

A screening approach involving ten larval zebrafish behavior assays and the similarity search tool, phenoBlast, for compounds that phenocopy the antipsychotic haloperidol identifies finazines that may work partially through the sigma-1 (σ₁) receptor.

A new DNA analysis method termed long fragment read technology is described, and the approach is used to determine parental haplotypes and to sequence human genomes cost-effectively and accurately from only 10 to 20 cells.

Sorghum is an African grass that is grown for food, animal feed and fuel. The current paper presents an initial analysis of the ∼730 megabase genome of Sorghum bicolor. Genome analysis and its comparison with maize and rice shed light on grass genome evolution and also provide insights into the evolution of C₄ photosynthesis, as well as protein coding genes and miRNAs that might contribute to sorghum's drought tolerance.

Laryngeal carcinoma is a heterogeneous disease and multiple genes have been implicated in its pathogenesis. Here, Fanjul-Fernández et al. identify mutations in the cell–cell adhesion genes catenin α2 and catenin α3 in 15% of a cohort of homogeneous laryngeal carcinomas.

Comprehensive analyses of 178 lung squamous cell carcinomas by The Cancer Genome Atlas project show that the tumour type is characterized by complex genomic alterations, with statistically recurrent mutations in 11 genes, including TP53 in nearly all samples; a potential therapeutic target is identified in most of the samples studied.

Human settlements are often associated with degraded landscapes. Trant and colleagues now show that near-shore settlements in British Columbia have locally enhanced forest productivity over millennia by enriching soils with calcium and phosphorous derived from shellfish remnants.

A statistical framework for breast-cancer recurrence uses long-term follow-up data and a knowledge of molecular subcategories to model distinct disease stages and to predict the risk of relapse.