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The transcriptional regulation of oligodendrocytes has an essential role in myelin formation and maintenance. Here, the authors identify the transcription factor Tfii-i as a regulator of myelin genes expression in the nervous system and show that its loss enhances myelin thickness and nerve conduction.

The authors spatially and functionally map innate lymphoid cells in the human female genital tract at homeostasis, uncovering tissue-specific and subset-specific distribution and functions, and rapid antiviral responses following HIV exposure.

As Finland’s climate warms, cold-adapted moths are disappearing in the north while warm-loving species move in from the south. This shift in insect communities highlights the threat climate change poses to cold-adapted species.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Symbiosis with nitrogen-fixing bacteria (rhizobia) aids the growth of many legume species, but may also restrict their ability to colonize new regions lacking suitable rhizobia. Here, the authors show that symbiotic legumes are indeed less likely to become established in new regions than their non-symbiotic relatives.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Kathryn Lunetta and colleagues report a meta-analysis of 22 genome-wide association studies for age at menopause. They identify 13 loci newly associated with age at natural menopause, including several candidate genes with roles in DNA repair and immune function.

Inclusion body myositis (IBM) is a progressive inflammatory muscle disease of unknown cause, prevalent in older adults. Through spatial and single nuclear profiling, the authors identify a selective type 2 myofiber pathology in IBM, linked to genomic stress and denervation.

Deep brain stimulation of the basal ganglia restores cognitive flexibility and rebalances exploration disrupted by NMDA receptor antagonism in nonhuman primates, offering insights into the neural basis of psychosis and a potential treatment for schizophrenia.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

Anna Armstrong reviews Encounters at the End of the World by Werner Herzog, Discovery Films: 2007. UK release date: 24 April 2009.

Random segregation of extrachromosomal DNA contributes to intratumoral heterogeneity and facilitates the rapid adaptation of human tumor cells to anticancer drugs.

Lower bounds on the energy-constrained and unconstrained two-way quantum and secret-key capacities of all phase-insensitive bosonic Gaussian channels are provided. It proves that a non-zero capacity exists for all parameters where the phase-insensitive bosonic Gaussian channels are not entanglement breaking.

Ressler et al. perform a phase II clinical trial of neoadjuvant talimogene laherparepvec in cutaneous basal cell carcinoma and report on treatment safety, efficacy and on treatment-induced immune tumor microenvironment changes.

Resident microglia in the central nervous system are identified as the specific macrophage population that regulates myelin growth and integrity.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

The identification of molecular biomarkers in cancer of unknown primary site (CUP) cases may enable the improvement of prognosis in these patients. Here, the authors integrate whole genome/exome, transcriptome and methylome data in 70 CUP patients, recommend therapies based on their analysis and report clinical outcome data.

Lecoutre, Maqdasy and Rizo-Roca show that whole-body pharmacological inhibition or adipocyte-specific deletion of glutaminase in mice activates thermogenesis in inguinal adipocytes and promotes metabolic health. They also link decreased plasma and adipose tissue glutamine-to-glutamate ratios to insulin resistance in humans with obesity.

During female gametogenesis in plants, the Megaspore Mother Cell (MMC) accumulates β−1,3-glucan. Here Pinto et al. show that increased β−1,3-glucanase in the MMC delays β−1,3-glucan deposition, disrupts cell identity, and halts gametogenesis.

Nanobodies are normally made from immunized camelids, Ig transgenic mice or synthetic libraries. In this study, the authors introduce the llama Ig heavy chain locus into mice lacking this locus, thereby generating a line in which nanobodies can be made by direct immunization in the absence of an endogenous antibody repertoire.

Sepsis is associated with a hyperinduction of proinflammatory cytokines. ATF3, a transcription factor, is induced in macrophages under conditions of endotoxic shock and downregulates expression of cytokines, including interleukin-6 (IL-6). Although ATF3 may thereby mitigate the severity of sepsis, Hoetzenecker et al. now show that endotoxin-induced ATF3 increases the susceptibility of mice to secondary pathogenic infections due to suppression of IL-6. Their findings suggest that temporal modulation of ATF3 may be important for the successful resolution of sepsis and the ensuing sepsis-associated immunosuppression.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

A high-throughput chemical screen identifies the salt-inducible kinase inhibitor HG-9-91-01 as a driver of β cell proliferation, acting through an ATF6-dependent unfolded protein response.

Epithelial sheet migration requires polarized and coordinated cell movement. Here, the authors demonstrate serum-activated collective migration followed by polarized asymmetric cell divisions in otherwise quiescent human keratinocyte monolayers in the absence of wound edges.

Beta-adrenergic stimulation of brown adipose tissue leads to thermogenesis via the activating transcription factor 2 (ATF2) mediated expression of the thermogenic genes Ucp1 and Pgc-1α. Here, the authors show that the scaffold protein p62 regulates brown adipose tissue function through modifying ATF2 genomic binding and subsequent Ucp1 and Pgc-1α induction.

Genome-wide data from 400 individuals indicate that the initial spread of the Beaker archaeological complex between Iberia and central Europe was propelled by cultural diffusion, but that its spread into Britain involved a large-scale migration that permanently replaced about ninety per cent of the ancestry in the previously resident population.