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Biochemist who revealed biology behind obesity.

Patients with primary mitochondrial disease manifesting cardiomyopathy are twice as likely to die compared to those without cardiomyopathy. Here, the authors show that a modest increase in cardiac mitochondrial energetics via gene therapy can significantly improve cardiac function and is effective in treating mitochondrial cardiomyopathy.

Chan and colleagues report that tumor ecosystem and microbiome features are associated with response to anti-PD-L1 avelumab plus chemoradiotherapy in patients with locally advanced head and neck cancer.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

The Foundation for the National Institutes of Health Biomarkers Consortium is celebrating two decades of advancing biomarker science to enable earlier interventions, personalized medicine and improved outcomes in disease prevention, detection, diagnosis and treatment.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

Fire emissions can be an important source of nutrients such as iron, particularly for the oceans. Here the authors estimate that climate-change-driven changes in fire emissions could increase iron deposition in ocean ecosystems, enhancing productivity particularly in the North Atlantic.

It is not fully understood why some patients respond or do not respond to antidepressant treatment. Here the authors show that in the blood of individuals with depression, GPR56 expression increases in responders to antidepressant treatment, but not in non-responders.

Simulated heatwaves shifted carbon fluxes in estuarine flats, with stronger effects after longer heatwave durations. Findings reveal that degradation state will influence heatwave effects on carbon dynamics including changes in source/sink status.

Yang–Mills theory is the basis of the standard model of particle physics. The Yang–Mills Millennium Prize problem, to show that the theory is mathematically well defined and that it has the mass gap property, is one of the great challenges of mathematical physics. This Review explores the problem from both physical and mathematical points of view and surveys promising approaches from recent years.

In males, amphetamine in adolescence misroutes mesolimbic dopamine axons to the PFC, increasing DAT levels and methylphenidate-induced dopamine release in the adult PFC; CRISPRa-driven DCC receptor upregulation in adolescence prevents these effects.

The mechanisms of neurovascular adaptations underlying stress resilience remain unclear. Here the authors show that the astrocytic endocannabinoid system modulates the blood–brain barrier changes during stress in adult mice.

Gustavo Turecki and colleagues report that miR-1202, a miRNA specific to primates, is decreased in individuals with depression and seems to be differentially regulated in individuals who will end up showing beneficial responses to antidepressant treatment compared to those who will not respond.

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.

BioID detection of Ebola virus–host interactions when computationally integrated with existing host protein-protein networks, revealed functional cell protein complexes supporting infection, including the RNA decapping complex.

Cold-sensitive engrams contribute to learned thermoregulation in mice that are returned to an environment in which they previously experienced a cold challenge, through a network formed between the hippocampus and hypothalamus that enables the recall of cold-related memories.

While depression and chronic pain are frequently comorbid, underlying neuronal circuits and their psychopathological relevance remain poorly defined. Here, authors show the critical role of the BLA-ACC pathway in pain and emotional processing, and their comorbidity.

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.

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.

The transcription factor ELK-1 is upregulated in patients with major depressive disorder, and selective inhibition of hippocampal ELK-1 produces rapid antidepressive effects in rodent models of depression.

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.

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.

Antidepressant drugs are the most common treatment for depressive episodes but only a fraction of patients experience adequate response. Here the authors find dysregulation of miRNAs in peripheral blood samples from depressed patients after antidepressant treatment, and show that the miRNAs are regulators of psychiatrically relevant signalling pathways.

Typical quantum error correcting codes assign fixed roles to the underlying physical qubits. Now the performance benefits of alternative, dynamic error correction schemes have been demonstrated on a superconducting quantum processor.

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.

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.

Schneeberger et al. show that glutamatergic neurons within the dorsal raphe nucleus of the brainstem are enriched with the orexin 1 receptor Hcrtr1, which can be pharmacologically targeted to treat obesity in mice.

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.

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

de Souza et al. examine whether visceral adipose tissue (VAT) and hepatic fat (HF) are related to carotid atherosclerosis beyond traditional cardiovascular risk factors. Findings reveal that higher VAT and HF are linked to cardiovascular risks such as hypertension, diabetes, and high cholesterol, as well as increased carotid atherosclerosis.

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.

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.

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.

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.

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.

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.

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.

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.

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.