Search

COMPLEXES of manganese(ii) with bipyridine (bpy) have the potential to act as catalysts for oxidation of alkanes and alkenes when the complex is oxidized in acidic conditions^1–6. But their catalytic activity in solution is limited by their catalase activity⁷—their tendency to decompose H₂O₂. Because of their polynuclear nature such complexes cannot induce epoxidation of alkenes, and other epoxidation catalysts suffer from self-oxidation and side reactions^8–11. Moreover, all of these homogeneous catalytic processes require phase-transfer conditions. Here we report that, when encapsulated in the supercages of zeolites X and Y, cis-[Mn(bpy)₂]²⁺ complexes can catalyse selective epoxidation of alkenes without complications from competing processes such as self-oxidation or catalase activity. Epoxidation of cycloalkenes is followed by acid-catalysed ring-opening, carbon–carbon bond cleavage and formation of alkenedioic acids (Fig. 1). All of the various intermediates in the process can be obtained selectively by controlling the reaction conditions and zeolite acidity. Thus this supramolecular system provides a clean, one-step heterogeneous catalytic route to useful industrial products.

Van Ouwerkerk and colleagues examine the benefits of renewable energy investments for German households during the recent energy crisis. They find a typical household with a heat pump saved 1850 € and reduced emissions by 250 g/kWh annually, leading to greater gains in resilience when compared to temporary price breaks on energy.

Hallmarks of post-acute consequences of SARS-CoV-2 infection are still insufficiently understood. Here, the authors identify alveolar bronchiolization, interstitial fibrosis, and exercise-induced lung function impairment as features of respiratory long COVID in aged hamsters.

A combination of mutant phenotype analysis, genome comparisons and proteomics has elucidated the metabolic network of Salmonella during typhoid fever and enteritis infections. Owing to many redundant pathways, Salmonella metabolism is surprisingly robust, thus severely limiting the number of new drug targets.

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 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.

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.

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.

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.

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.

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.

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.

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.

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 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.

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

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.

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.

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.

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.

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 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.

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.

How ischaemic stroke affects the brain borders is not fully understood. Here the authors show that a stroke-associated myeloid cell population occurs exclusively in brain parenchyma that shares features with neurodegenerative microglia and blockade of proteins on these cells can ameliorate stroke symptoms.

From 1980 to 2018, the levels of total and non-high-density lipoprotein cholesterol increased in low- and middle-income countries, especially in east and southeast Asia, and decreased in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe.

Asian soybean rust caused by Phakopsora pachyrhizi is an important plant pathogen, but an accurate genome assembly for this fungus has been lacking. This study sequenced three independent P. pachyrhizi isolates and generated reference quality assemblies and genome annotations, representing a critical step for further in-depth studies of this pathogen and the development of new methods of control.

Functional magnetic resonance imaging (fMRI) is a powerful method to understand neural mechanisms of cognition but imaging of small animals can be challenging. The authors present an event-related fMRI platform to visualize the neural fundaments of perceptual and cognitive functions in awake birds.

Linterman and colleagues examine germinal center formation in older individuals. They find that aged T_FH cells have dysregulated CXCR4 expression, which causes spatial mislocalization of these cells in germinal centers, impairing their ability to provide help to B cells and to promote antibody production.

A high-throughput chemical–genetic screening approach for the discovery of targets and chemicals to treat Mycobacterium tuberculosis yields tenfold more hit compounds than conventional whole-cell screening methods.

Genome-wide analysis identifies variants associated with the volume of seven different subcortical brain regions defined by magnetic resonance imaging. Implicated genes are involved in neurodevelopmental and synaptic signaling pathways.

Thousands of recombinant antibodies enriched for specificity against defined targets are assembled in multivalent mixtures with enhanced therapeutic activity.

NOD2 has been shown to be crucial for immune recognition of Aspergillus infection. Here the authors show that a common NOD2 genetic variant associated with Crohn’s disease is associated with reduced risk of disease due to enhanced antifungal activates of monocytes and macrophages.

Izar and colleagues demonstrate that loss of Pip4k2c in melanoma cells promotes liver metastatic tropism driven by PI3K-AKT pathway activation in the insulin-rich liver milieu, which can be abrogated by inhibition of SGLT2 or a ketogenic diet.

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.

While micro-RNAs are known regulators of haematopoiesis and leukemogenesis, the role of long non-coding RNAs is less clear. Here the authors provide a non-coding RNA expression landscape of the human hematopoietic system, highlighting their role in the formation and maintenance of the human blood hierarchy.

The hippocampus in mammalian brain varies in size across individuals. Here, Hibar and colleagues perform a genome-wide association meta-analysis to find six genetic loci with significant association to hippocampus volume.

Retrograde signalling ensures message communication between organelles and the nucleus. A pivotal regulator of plant retrograde signalling, GENOMES UNCOUPLED1, is now found to regulate protein import into chloroplast during chloroplast biogenesis or under stress conditions.