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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.

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.

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 response to infectious and inflammatory challenges differs among people but the reasons for this are poorly understood. Here the authors explore the impact of variables such as age, sex, and the capacity for controlling inflammation and maintaining immunocompetence, linking this capacity to favourable health outcomes and lifespan.

WDR5 and TBP recruit anaphase-promoting complex to specific transcription start sites in mitosis, initiating a ubiquitin-dependent mechanism that preserves cell identity by linking gene expression and cell division.

A multi-ancestry genome-wide association meta-analysis of kidney cancer identifies 63 regions associated with disease susceptibility including one locus that was associated with increased risk in individuals with African ancestry.

Park, Davis et al. evaluate candidate biomarkers of cancer-associated cachexia in a diverse cohort of pancreatic ductal adenocarcinoma individuals. GDF-15 is better at classifying cachexia than standard biomarkers for non-Hispanic White and Hispanic/Latinx individuals, but not for non-Hispanic Black individuals.

The authors discovered that proinflammatory senescent myeloid cells may recruit peripheral immune cells in the aged mouse brain. Their findings implicate senescent cell clearance as a strategy to counter aged brain inflammation and cognitive decline.

The physical architectures of information storage dictate how data is encoded, organised and accessed. Here the authors use DNA with a single-strand overhang as a physical address to access specific data and do in-storage file operations in a scalable and reusuable manner.

Samples of different body regions from hundreds of human donors are used to study how genetic variation influences gene expression levels in 44 disease-relevant tissues.

Here, the authors report that specific monoclonal antibodies isolated from vaccinated rhesus macaques can neutralize a subset of Tier 2 difficult-to-neutralize HIV-1 that express Env in an open conformation, suggesting that V3 loop-specific targeting can bias the estimation of vaccine-induced bnAbs.

A study finds that a protease called granzyme K can activate the entire complement cascade, explaining how it can drive destructive inflammation in inflammatory diseases such as rheumatoid arthritis.

Orbital angular momentum transfer from optical vortex beams to electronic quantum Hall states is reported in a graphene sheet, showing a robust contribution to the radial photocurrent that depends on the vorticity of light.

Eitan et al. discovered genetic variants in the 3′UTR for the gene encoding IL-18 receptor that protect against ALS. The variant 3′UTR destabilizes the mRNA and dampens microglia NF-κB signaling and neurotoxicity, thus emphasizing the value of noncoding genetic association studies.

Mice possess neurons in the preoptic area of the hypothalamus that are sensitive to violet light; these deep brain neurons sense light via OPN5 and regulate adaptive thermogenesis in brown fat.

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.

Combining a large-scale dataset of 23 ungulate species (in which newborns follow contrasting tactics of predator avoidance) with continuous-time stochastic movement models, the authors reveal that there are multiple dimensions of maternal movement behaviour and space use.

Chromosome-scale assembly for the cultivated octoploid strawberry (Fragaria × ananassa) uncovers the origin and evolutionary processes that shaped this complex allopolyploid, providing a useful resource for genome-wide analyses and molecular breeding.

The epigenetic changes underlying the heterogeneity of RA disease presentation have been the subject of intense scrutiny. In this study, the authors use multiple single-cell sequencing datasets to define ‘chromatin superstates’ in patients with RA, which associate with distinct transcription factors and disease phenotypes.

Optical clock networks have many applications from precision time keeping, sensing to fundamental physics. Here the authors demonstrate robust and free-space femtosecond time synchronization of optical clocks via a moving quadcopter.

Alzheimer’s disease has been associated with increased structural brain aging. Here the authors describe a model that predicts brain aging from resting state functional connectivity data, and demonstrate this is accelerated in individuals with pre-clinical familial Alzheimer’s disease.

Genome-wide association meta-analysis of AAA identifies 121 independent risk loci and highlights potential therapeutic targets such as proprotein convertase, subtilisin/kexin-type 9 (PCSK9).

Spatial multi-omics methodologies are essential for capturing the molecular heterogeneity of complex biological systems. In this study, the authors introduce a multi-omics imaging workflow capable of mapping metabolite-protein interactions with spatial specificity, enabling pathway-level resolution across distinct placental tissue microenvironments.

Whole genome sequences enable discovery of rare variants which may help to explain the heritability of common diseases. Here the authors find that ultra-rare variants explain ~50% of coronary artery disease (CAD) heritability and highlight several functional processes including cell type-specific regulatory mechanisms as key drivers of CAD genetic risk.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

The severity of ulcerative colitis, and response to treatment, is highly variable. Here, the authors examine rectal gene expression signatures and faecal microbiomes of children and adults with the disease and provide new insights in to pathogenesis.

Analysis of single-nucleus RNA sequencing and single-nucleus assay for transposase-accessible chromatin with sequencing data derived from synovium of patients with rheumatoid arthritis identifies regions with dynamic accessibility that correlate with cell states. Dynamic peaks are more strongly enriched for autoimmune disease heritability.

SCENT is a nonparametric method that models association between chromatin accessibility and gene expression in single-cell multimodal datasets, enabling construction of cell-type-specific enhancer–gene maps to aid mapping of candidate causal variants and genes for common diseases.

Two-step Mendelian randomization, combined with multiple layers of omics evidence, implicates COL6A3-derived endotrophin as a mediator of coronary artery disease risk in the context of obesity.

Room-temperature superconductivity is observed in a photochemically synthesized ternary carbonaceous sulfur hydride system at 15 °C and 267 GPa.

The 3CL protease of SARS-CoV-2 is inhibited by PF-00835231 in vitro. Here, the authors show that the prodrug PF-07304814 has broad spectrum activity, inhibiting SARS-CoV and SARS-CoV-2 in mice and its ADME and safety profile support clinical development.

Phase-resolved mid-infrared observations from JWST of the hot gas giant WASP-43b detect a day–night difference of 659 ± 19 K. Comparison with climate models shows that the observations are compatible with cloudy skies, at least on the nightside, and the lack of methane detection suggests the presence of disequilibrium chemistry.

Whole-genome sequencing of lung cancer in never smokers identifies different copy number subtypes and shows a lack of tobacco smoking signatures, even in cases exposed to secondhand smoke.

The RNA endonuclease CPSF3 was identified as the cellular efficacy target of the small molecule JTE-607, revealing pre-mRNA processing as a vulnerability in cancers such as Ewing’s sarcoma that are characterized by aberrant transcription.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

Integrator is a multi-subunit protein complex with roles in noncoding RNA 3′-end processing and mRNA transcription attenuation. Here, the authors reveal a conserved binding site for IP₆ in the Integrator cleavage module and show that IP₆ binding is required for Integrator function.

Plant-derived phenylpropanoids have diverse industrial applications ranging from flavours and fragrances to polymers and pharmaceuticals. Here the authors present a tripartite microbial coculture with mix-and-match flexibility and had improved stability within an engineered living material platform for de novo production of several plant-derived phenylpropanoids.

Regulating guest access and release in porous materials remains an important goal. Here, May and colleagues elucidate the mechanism by which guest admission can be temperature-regulated in typical microporous materials, and experimentally exploit this process to achieve appreciable and reversible hydrogen storage.

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

Susceptibility to asthma and severity of symptoms are regulated by a number of different genomic regions. Here the authors characterise a 5kb regulatory region and demonstrate genetic and topological regulation of IL33 and association with disease in different human cohorts.

River blindness, a disease affecting millions throughout the tropics, is caused by parasitic worms. Here, Yuet al. report the discovery and structural characterization of potent macrocyclic peptide inhibitors of iPGM, a nematode-specific phosphoglycerate mutase, as potential leads for novel antimicrobial agents.

Adipogenesis associated Mth938 Domain Containing gene (AAMDC) is frequently amplified in the IntClus2 subgroup of ER + breast cancer. Here, the authors show that AAMDC drives tumourigenesis through activating PI3K-AKT-mTOR pathway for metabolic reprogramming.

Emerging SARS-CoV-2 variants raise concerns on immune evasion. Here, the authors evaluate the neutralization efficiency of COVID-19 mRNA vaccinee sera against representative viruses of 13 WHO-designated SARS-CoV-2 variants of concern/interest.

SARS-CoV-2 induces mild infection in ferret model. Here, Ryan et al. characterise optimal infection dosage inducing upper respiratory tract (UTR) viral shedding, progression time of viral shedding, and pathology in ferrets and finally provide evidence for protection after re-challenge.