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Study shows PTSD predisposition shares distinct genes and genomic regions with several cardiovascular conditions. Here the findings reveal neuronal, immune, and metabolic pathways, and repurposed drug targets that further the understanding of the comorbidity.

Paul Pharoah and colleagues report the results of a large genome-wide association study of ovarian cancer. They identify new susceptibility loci for different epithelial ovarian cancer histotypes and use integrated analyses of genes and regulatory features at each locus to predict candidate susceptibility genes, including OBFC1.

The authors mapped the dendritic morphology of thousands of striatal D1-type and D2-type medium spiny neurons in healthy and Huntington’s disease mouse brains, revealing dendritic modules with distinct neuronal shapes, spatial distributions and cortical inputs.

Technologies for profiling biological environments with high spatiotemporal resolution are in demand to enable the discovery of new targets for addressing unmet clinical needs. Now, a deep red light-mediated photocatalytic strategy for the targeted activation of aryl azides has been developed. This platform enables mapping of protein microenvironments in physiologically relevant systems.

In lung adenocarcinoma, antibodies against endogenous retroviruses promote anti-tumour activity, and expression of endogenous retroviruses can predict outcomes of immunotherapy.

The authors generate ~1-km² growth curves for aboveground live carbon in regrowing forests, globally. They show that maximum carbon removal rates can vary by 200-fold spatially and with age, with the greatest rates estimated at about 30 ± 12 years, highlighting the role of secondary forests in carbon cycling.

Armfield X-linked disability (XLID) disorder has previously been linked to a locus in Xq28. Here, the authors report rare missense variants in FAM50A at Xq28, show that FAM50A interacts with the spliceosome, and that mis-splicing is enriched in knockout zebrafish suggesting it is a spliceosomopathy.

Severe sepsis has a high mortality rate. Here, the authors provide genomic, transcriptomic, proteomic and metabolomic data across four sepsis-causing pathogens and identify a signature of global increase in fatty acid and lipid biosynthesis as well as cholesterol acquisition.

A genome-wide CRISPR screen for suppressors and enhancers of C9ORF72 dipeptide-repeat protein toxicity identifies candidate genes involved in nucleocytoplasmic transport and other pathways including RNA processing and chromatin modification.

Participants at Nature's conference on "The brain in well-being and disease" (12–13 November) were excited that hitherto intractable problems are now beginning to crack under the impact of powerful new techniques.

The authors present 7 cryo-EM structures of hallucinogenic and non-hallucinogenic compounds across multiple chemotypes bound to the 5-HT2A receptor, shedding light onto ligand specificity and signaling bias.

DNA from ancient wolves spanning 100,000 years sheds light on wolves’ evolutionary history and the genomic origin of dogs.

A new phylogenomic tree for butterflies is constructed using 391 genes from 2,300 species, representing 92% of genera. It suggests that butterflies originated around 100 million years ago in what is now the Americas and originally fed on Fabaceae.

Using an integrated metabologenomics approach, the biosynthetic pathway for the pestalamides is revealed and over 200 high-confidence targets are identified for future studies.

Sexual dimorphism in genetic vulnerability to schizophrenia, systemic lupus erythematosus and Sjögren’s syndrome is linked to differential protein abundance from alleles of complement component 4.

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.

Joel Hirschhorn and colleagues report results of a large-scale genome-wide association and replication study for obesity-related traits. The newly discovered loci are enriched for genes expressed in the central nervous system, and may thus contribute to weight gain by modulating food intake. Similar results are reported in a related study by Gudmar Thorleifsson and colleagues.

Wastewater treatment plants are important reservoirs of antibiotic resistance genes (ARGs). Here, the authors analyze ARGs in a global collection of samples from wastewater treatment plants across six continents, providing insights into biotic and abiotic mechanisms that appear to control ARG diversity and distribution.

Trees come in all shapes and size, but what drives this incredible variation in tree form remains poorly understood. Using a global dataset, the authors show that a combination of climate, competition, disturbance and evolutionary history shape the crown architecture of the world’s trees and thereby constrain the 3D structure of woody ecosystems.

Results for the final phase of the 1000 Genomes Project are presented including whole-genome sequencing, targeted exome sequencing, and genotyping on high-density SNP arrays for 2,504 individuals across 26 populations, providing a global reference data set to support biomedical genetics.

Open science practices are becoming more common in the social sciences, but there is limited data on their popularity and prevalence. Here, using survey data, the authors provide evidence that levels of adoption are relatively high and underestimated by many in the field.

Muscle weakness has been associated with morbidity and mortality in older people. Here, the authors have investigated this trait further by performing a genome-wide meta-analysis of grip strength and Mendelian randomization to discover causal relationships between muscle weakness and other diseases.

Mesenchymal stromal cells (MSCs) demonstrate therapeutic benefits in multiple diseases, but the mechanisms remain unclear as infused MSCs do not persist in the body. Here, the authors show that MSC apoptosis is an important mechanistic element, as MSCs rendered genetically incapable of apoptosis lose their ability to ameliorate disease.

Surveys from 2,584 sites across the Indo-Pacific identify key climate, socioeconomic and environmental drivers associated with hard coral assemblages. This informs a strategic approach to protect, recover or transform coral reef management.

Exercise training can be therapeutic but how mitochondria respond remains unclear. Here, the authors use multiple omics techniques to reveal a complex network of non-stoichiometric mitochondrial adaptations that are prioritized or deprioritised during different phases of exercise training.

The prognosis of castration-resistant prostate cancers remains dismal, but accurate preclinical models can lead to effective therapies. Here the Melbourne Urological Research Alliance establish prostate cancer patient-derived xenografts, use the tumors for organoids and single-cell RNA-seq, and show the efficacy of PARP inhibitor combination treatments.

Parhizkar et al. show that lemborexant, an orexin receptor antagonist, protects against neurodegeneration in male tau transgenic mice by preventing tau protein build-up and inflammation, highlighting its potential for preventing neurodegeneration.

Targeting a non-natural micropeptide ‘killswitch’ to several biomolecular condensates altered condensate compositions and revealed condensate functions in human cells

Patients with metastatic cancers of unknown primary (CUP) are currently unable to gain access to drugs through standard of care or clinical trials. Here, the authors perform whole-genome and transcriptome sequencing (WGTS) on 72 patients with CUP and demonstrate the feasibility of using WGTS to determine the specific cancer types of CUP, thereby clinically benefiting patients with CUP.

Although progress in the coverage of routine measles vaccination in children in low- and middle-income countries was made during 2000–2019, many countries remain far from the goal of 80% coverage in all districts by 2019.

Here the authors conduct a multi-ancestry meta-analysis of telomere length, used diverse approaches to identify genes underlying association signals, and experimentally validated POP5 and KBTBD6 as regulators of telomere length in human cells.

In this study using an adult-onset mouse model of Alzheimer’s pathology, we uncovered a neuron-type-specific mechanism responsible for region-specific circuit dysfunction. Short-term expression of human amyloid precursor protein (hAPP) led to hyperexcitability in the entorhinal cortex, but not in isocortex, due to a distinct vulnerability of PV interneurons in the entorhinal region.

Jamel Chelly, Nicholas Cowan and colleagues report mutations in TUBG1, DYNC1H1, KIF2A and KIF5C in individuals with malformations of cortical development and microcephaly. Their findings emphasize the importance of centrosomal and microtubule-related proteins for normal brain development.

In a GWAS study of 32,438 adults, the authors discovered five novel loci for intracranial volume and confirmed two known signals. Variants for intracranial volume were also related to childhood and adult cognitive function and to Parkinson's disease, and enriched near genes involved in growth pathways, including PI3K-AKT signaling.

Patients with mild COVID-19 show a pattern of interferon-stimulated gene (ISG) expression across all major cell types, but in patients with severe disease, antibodies block the production of these ISG-expressing cells.

This genome-wide study of age at first sexual intercourse and first birth identifies 371 signals driven by reproductive biology, externalising behaviour and environmental effects, with later onset associated with lower incidence of some diseases.

Exome sequencing of 47 ALS trios (patients and their unaffected parents) identified de novo mutations, including a mutation in the neuronal chromatin remodeling complex component, SS18L1. SS18L1 interacted with the ALS protein FUS, and mutation of SS18L1 in primary neurons resulted in impaired neurite outgrowth.

Tumours consist of heterogeneous cell types that respond differently to treatment. Here, on the basis of the expression of three different proteins, the authors describe a subset of prostate cancer cells that have stem cell-like properties that are able to initiate tumour formationin vivo.

A large international panel of experts reach consensus on a new standard for reporting settings in psychedelic trials, identifying 30 key non-pharmacological factors to strengthen the rigor of psychedelic research.

An exciting genome-wide association study in the British population for seven common diseases. This analysis confirms previously identified loci and provides strong evidence for many novel disease susceptibility loci.

Myeloid cells are able to utilize a variety of monosaccharides from our diet, including fructose. Here the authors show that when monocytes are reliant on fructose as a carbon energy source they are reprogrammed towards oxidative metabolism, glutamine anaplerosis and a pro-inflammatory phenotype owing to excess pro-inflammatory cytokine production.

Chromosomal instability enables the continuous selection of somatic copy number alterations, which are established as ordered events that often occur in parallel, throughout tumour evolution and metastasis.

5-hydroxymethylcytosine, the sixth DNA base, plays a key role in brain aging and Alzheimer’s disease. Here, the authors study over 1000 deceased brains to identify genes with 5-hydroxymethylcytosine alterations linked to Alzheimer’s pathology.

Oral ulcerations are sores of the mucous membrane of the mouth and highly prevalent in the population. Here, in a genome-wide association study, the authors identify 97 loci associated with mouth ulcers highlighting genes involved in T cell-mediated immunity and T_H1 responses.

Isolating and studying haematopoietic stem cells in young and aged mice demonstrates evolutionary processes related to blood production and provides a framework for interpreting future work using laboratory mice to study stem cell ageing.

A risk score based on a 34-gene signature for outcome prediction in meningioma was developed and validated in large multi-institutional cohorts and showed better performance in discriminating postoperative menignioma outcomes compared with existing meningioma classification systems.

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