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Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

Precolibactin 886 is a complex microbiome-derived metabolite implicated in colorectal cancer and produced by the clb gene cluster. A chemical synthesis and analysis of precolibactin 886 is reported which shows that its biosynthetic precursor degrades to other known clb metabolites. The data also provide insights into the structures and reactivity of advanced clb products.

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.

Understanding the role of coherent structures in the dynamics of turbulent flows is of high relevance for fluid dynamics, climate systems, and aerodynamics. The authors propose a deep learning approach to evaluate the importance of various types of coherent structure in the flow, to uncover main mechanisms of wall-bounded turbulence and develop techniques for its control.

Chapeau et al. develop a nonallosteric inhibitor of the interaction between YAP and all four TEAD proteins. Treatment with the inhibitor, either as monotherapy or in combination with other treatment modalities, leads to induction of cell death in several in vivo cancer models.

A multi-ancestry meta-regression study analyses diverse genome-wide association studies and genome loci associated with tobacco and alcohol use.

When an extrasolar planet passes in front of its star (transits), its radius can be measured from the decrease in starlight and its orbital period from the time between transits. This study reports Kepler spacecraft observations of a single Sun-like star that reveal six transiting planets, five with orbital periods between 10 and 47 days plus a sixth one with a longer period. The five inner planets are among the smallest for which mass and size have both been measured, and these measurements imply substantial envelopes of light gases.

Using data from wearable activity monitors, this study shows that short bursts of physical activity that are done as part of daily life activities and that are only 1 or 2 minutes in length are associated with lower mortality, similar to the effects of regular exercise.

Globally, new particle formation represents a major source of cloud condensation nuclei. Here, the authors present evidence of frequent occurrence of new particle formation in the upper part of remote marine boundary layer following cold front passages.

The Human Microbiome Project Consortium has established a population-scale framework to study a variety of microbial communities that exist throughout the human body, enabling the generation of a range of quality-controlled data as well as community resources.

Chemotherapy resistance in recurrent gliomas is a large hurdle for successful therapy. Here, the authors show that some recurrent gliomas harbour O-6-methylguanine-DNA methyltransferase (MGMT) genomic rearrangements, and in vitro and in vivo these contribute to temozolomide resistance.

The spike protein of the Omicron variant of SARS-CoV-2 has a higher affinity for ACE2 than Delta, and a marked change in its antigenicity increases Omicron’s evasion of therapeutic and vaccine-elicited neutralizing antibodies.

Soil carbon content is positively related with plant diversity in global grasslands, and this relationship is particularly strong in warm and arid climates. Plant diversity is related to soil carbon via the quality of organic matter.

Anthropogenic eutrophication is a driver of plant community shifts in many grassland ecosystems. Here, the authors use data from a globally distributed experiment to assess how nutrient addition affects multiple facets of grassland ecological stability and their correlations.

The spatial organization of cells in solid tumors is considered to be important for immune response and response to therapy. Here the authors use multiomics including spatial transcriptomics of human lung tumors prior to patients being treated and show among other things an association of stem-immunity hubs rich in stem-like CD8⁺ T cells with positive response to anti-PD-1 therapy.

Lipophilic siRNA conjugates exert therapeutic activity in the mouse CNS.

Assembly of the hexaploid oat genome and its diploid and tetraploid relatives clarifies the evolutionary history of oat and allows mapping of genes for agronomic traits.

Analysis of behaviour, physiology, anatomy and connectomics in Drosophila shows how direction-specific visual information is transformed onto downstream premotor networks and converted into appropriate motor responses.

Analyses of multiregional tumour samples from 421 patients with non-small cell lung cancer prospectively enrolled to the TRACERx study reveal determinants of tumour evolution and relationships between intratumour heterogeneity and clinical outcome.

Beltran and colleagues examine the underlying mechanisms behind the observed heterogeneous expression of the prostate cancer drug target and biomarker, PSMA, in castration-resistant prostate cancer, involving regulatory roles of both HOXB13 and AR.

JWST observations of the planetary nebula NGC 3132 reveal a rich molecular environment containing evidence of multiple stellar interactions on a variety of scales.

Major histocompatibility complex (MHC) loss of heterozygosity, allele-specific mutation and measurement of expression and repression (MHC Hammer) detects disruption to human leukocyte antigens due to mutations, loss of heterogeneity, altered gene expression or alternative splicing. Applied to lung and breast cancer datasets, the tool shows that these aberrations are common across cancer and can have clinical implications.

Results from a phase 1 clinical trial show that a broadly neutralizing, HIV-specific antibody is durably expressed in vivo from a viral vector, highlighting an alternate approach for the delivery of antibodies in humans.

Two exoplanets of Earth’s size have been discovered in orbit around the star Kepler-20.

The ecological impact of ocean acidification as a result of climate change is difficult to predict. A natural CO₂ venting site is used here to demonstrate the shifts occurring in a rocky shore marine community as a result of a pH gradient.

HIV binding is mediated via CD4 and chemokine co-receptors, but this does not explain the preferential infection of central memory CD4+ T cells. Here the authors show HIV targets L-selectin, induces shedding from the infected cell, and inhibition of L-selectin reduces HIV infection and release.

On 1–2 November 2024, the annual Biomarkers of Aging conference welcomed academic and industry scientists, and partners from governmental and nongovernmental organizations, to Harvard Medical School in Boston, USA, to discuss new insights into measuring and monitoring human aging, with the aim of clinical translation. In this Meeting Report, we summarize the conference and offer potential future directions for the Biomarkers of Aging Consortium and the longevity science community at large.

In a new study including 200 families who experienced perinatal death, adding genomic analyses to standard autopsies improved the identification of underlying pathogenic causes and informed genetic counseling.

Computational analyses integrating whole-genome sequencing, cardiac epigenomic data and RNA-binding-protein data identify a role for noncoding de novo mutations in congenital heart disease.

In the TRACERx cohort of 171 patients with lung cancer, the ultrasensitive detection of ctDNA improves preoperative patient stratification, also in early-stage disease.

Sun et al. report human lifespan changes in the brain’s functional connectome in 33,250 individuals, which highlights critical growth milestones and distinct maturation patterns and offers a normative reference for development, aging and diseases.

Photosynthetic bacteria growing in low light environments have evolved to use small amounts of light with high efficiency. Here, Coles et al. demonstrate strong exciton–photon coupling of about 1,000 chlorosomes to a confined cavity mode thus modifying the energy levels of the light-harvesting process.

A systematic analysis of viral protein phosphorylation elucidates the signalling network of the vaccinia virus F10 kinase and H1 phosphatase, identifying new functions for the reversible phosphorylation of the I7 protease and A7 transcription factor.

Fine-mapping of blood cell traits in the UK Biobank identifies putative causal variants and enrichment of fine-mapped variants in accessible chromatin of hematopoietic progenitor cells. The study provides an analytical framework for single-variant and single-cell analyses of genetic associations.

Dopamine regulates multiple brain functions through coexisting tonic and phasic release modalities. Here, the authors describe an approach for monitoring tonic and phasic dopamine release simultaneously via on-demand chemogenetic tuning of a dopamine sensor.

M. Valentini et al. study superconducting quantum interference devices (SQUIDs) where the weak link of the Josephson junctions is a germanium 2D hole gas. They report signatures of the tunneling of pairs of Cooper pairs. For a particular microwave drive power, they observe a 100% efficient superconducting diode effect.

The role of alternative splicing in pancreatic cancer (PDAC) development remains to be explored. Here, RBFOX2 is shown to regulate exon splicing events in transcripts encoding proteins involved in cytoskeletal remodelling programs and its downregulation promotes PDAC progression and liver metastasis.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

The KL-VS haplotype of the Klotho gene has been associated with reduced risk of Alzheimer’s disease and dementia. Here the authors show an association between the KL-VS haplotype and amyloid-dependent tau accumulation using PET data.

For many neurodevelopmental disorder (NDD) risk genes, the significance for mutational burden is unestablished. Here, the authors sequence 125 candidate NDD genes in over 16,000 NDD cases; case-control mutational burden analysis identifies 48 genes with a significant burden of severe ultra-rare mutations.

Natural killer (NK) cells are important innate immune cells with diverse functions. Here the authors use single-cell RNA-sequencing of purified human bone marrow and peripheral blood NK cells to define five populations of NK cells with distinct transcriptomic profile to further our understanding of NK development and heterogeneity.

Multi-modal profiling reveals major alterations in colonic B cells in patients with ulcerative colitis, including reduced clonal diversity of plasma cells, and suggests that circulating gut-homing plasmablasts could serve as a biomarker for disease activity.

Disease-specific gut microbiome signatures have been previously defined for patients with liver cirrhosis or hepatocellular carcinoma (HCC). Here the authors examine the composition of the gut microbiota in cirrhotic patients with non-alcoholic fatty liver disease with or without HCC and evaluate how dysbiosis influences peripheral immune responses.

It is hypothesized that there are a number of tumor specific driver genes for metastatic prostate cancer. Here, the authors perform genome-wide CRISPRi screens and integrate these data with metastatic prostate cancer functional and clinical genomics data to show that KIF4A and WDR62 drive aggressive prostate cancer phenotypes.

In a prespecified interim analysis of a pivotal phase 2 trial, tisagenlecleucel, an autologous CD19-targeting CAR-T cell therapy, produced a high rate of complete responses with a manageable safety profile in adults with relapsed or refractory follicular lymphoma