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Depletion of a transcriptional factor ZBTB11 using molecular glue degraders can overcome oxidative-phosphorylation-mediated KRAS inhibitor resistance in pancreatic ductal adenocarcinoma with low acute neurotoxicity.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

Antibiotic resistance poses a critical global health threat. Here, the authors identify a carbapenem resistant clone of uropathogenic Escherichia coli with atypical virulence features as an increasing cause of urinary tract infection

In this 4-year unblinded follow-up study, the authors evaluate 63% of the participants of a double-blind randomised control trial that assessed the effects of faecal microbiota transplantation (FMT) on adolescents with obesity.

Using cryo-electron microscopy, the interactions of Sestrin2 and CASTOR1 with GATOR2 were resolved, revealing how mTORC1 activation is regulated and how nutrient availability triggers signalling for cellular growth.

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.

Whether and how prefrontal astrocyte Ca²⁺ signaling modulates different neuronal populations in aiding or inhibiting anxiety-like behavior remains not fully understood. Here authors show that prefrontal astrocytes encode anxiogenic cues and modulate excitatory and inhibitory neurons differently. Silencing prefrontal astrocytes heightens anxiety-like behavior and induces proteomic changes in astrocytes and neurons.

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.

Hutchinson-Gilford Progeria Syndrome is characterized by premature aging with cardiovascular disease being the main cause of death. Here the authors show that inhibition of the NAT10 enzyme enhances cardiac function and fitness, and reduces age-related phenotypes in a mouse model of premature aging.

Exon Junction Complexes influence many aspects of mRNA fate. Here, the authors show that the disassembly factor PYM1 primarily acts in translation-independent EJC removal, with resistant EJCs accumulating at non-canonical sites and impacting mRNA stability in a gene architecture dependent manner.

Transcriptome-scale maps of RNA secondary structure ensembles in living cells detect candidate RNA structural switches.

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.

Superconductivity is a complex and fascinating phenomenon, made more so by its coexistence with other collective electronic states. A study of the layered compound 1T-TaS₂ under pressure enables the various states of the material to be investigated and compared with other commonly studied layered superconductors.

An analysis of data from the Sherlock-Lung study provides insight into the mutational processes that contribute to lung cancer in never smokers, and looks at the possible role of factors such as air pollution and passive smoking.

Chronic alcohol use in humans and mice downregulates small intestinal mAChR4 and reduces goblet-cell-associated antigen passage formation, disrupting antimicrobial immunity.

Here the authors spatially map human pediatric low-grade gliomas using imaging mass cytometry, focusing on immunosuppressive myeloid cell populations and their functionality in tumor–immune interactions and tumor progression.

Wastewater surveillance for disease outbreaks currently requires lab testing which causes delays. Here, authors develop ultra-sensitive quantum sensors enabling 2-hour near-source pathogen detection from raw wastewater with high sensitivity and specificity, creating a portable “lab-in-a-suitcase” system.

Hydrogel materials have emerged as versatile platforms for biomedical applications. Here this group reports an mRNA lipid nanoparticle-incorporated microgel matrix for immune cell recruitment/antigen expression and presentation/cellular interaction thereby eliciting antitumor efficacy with a single dose.

John et al. show that upon classical activation, macrophages undergo nitric oxide-driven reprogramming of nucleotide metabolism, which affects immune functions and responses.

Pulmonary large cell neuroendocrine carcinoma is an aggressive subtype of lung cancer. Here, the authors identify distinct subtypes based on genomic alterations and transcriptomic alterations.

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.

Identifying genes involved in MYC-driven lymphoma reveals therapeutic vulnerabilities. Here, the authors show by using CRISPR knockout screens in primary cells in vivo that the GATOR1 complex suppresses MYC-driven lymphomagenesis, and that GATOR1-deficient lymphomas are sensitive to mTOR inhibitors.

Here the authors show in a case-control study with more than 800 children that HIV indirectly affects early post-discharge growth in children recovering from severe malnutrition by impacting baseline anthropometry and altering proteins key to bone mineralisation, growth signalling, and humoral immune response.

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.

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.

The authors highlight inconsistencies and divergencies in the literature reporting data on indirect calorimetry for studies on whole-body energy homeostasis, and propose harmonization of standards to facilitate data comparison and interpretation across different datasets.

Hominin fossils from the Ledi-Geraru Research Project area, Ethiopia, suggest that early Homo and Australopithecus species co-existed in the region more than 2.5 million years ago.

Species’ traits and environmental conditions determine the abundance of tree species across the globe. Here, the authors find that dominant tree species are taller and have softer wood compared to rare species and that these trait differences are more strongly associated with temperature than water availability.

Alfajaro et al identify that a bat MERS-like coronavirus HKU5 uses ACE2 as a receptor from its natural bat reservoir Pipistrellus abramus and American mink. Structural analyses demonstrate a unique interaction between the HKU5 receptor binding domain and bat ACE2. This highlights the receptor flexibility of merbecoviruses and identifies mink as potential intermediate hosts, informing viral surveillance and countermeasure development.

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 mechanism of the charge density wave in kagome metals is under intense debate. Here, by using a combination of diffuse scattering and inelastic x-ray scattering, the authors show that the charge density wave transition in (Cs,Rb)V₃Sb₅ is of the order-disorder type.

Flores et al. show that brain-penetrant eIF2B agonists suppress ISR activation in cellular and mouse models of ALS and reduce ISR biomarkers in humans, enabling further clinical studies of ISR inhibition in individuals with neurological diseases

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.

In this study, the authors assess the global response to the toxic aldehyde glyoxal (GO) in Pseudomonas aeruginosa, suggesting that GO controls quorum sensing during infection through a mechanism involving a novel protein, ArqI.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

In strongly correlated systems, how magnetic excitations are renormalized by charge carriers remains an open question. An experiment now reports the observation of magnon-polarons—magnons dressed by doped holes—in a Fermi–Hubbard quantum simulator.

Cells can regulate their mass density. Here, the authors demonstrate how eukaryotes establish and maintain a lower density in the nucleus than in the cytoplasm via pressure balance, and how deviations emerge during pathophysiological states like senescence.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

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 protein p53 responds to DNA damage and intracellular infection by activating pathways that arrest the cell cycle, repair DNA, and elicit apoptosis. Here, Allen et al. show that the obligate intracellular bacterium Orientia tsutsugamushi inhibits p53 expression and protects host cells from DNA damage, thus delaying apoptosis and favouring bacterial replication.

In a randomized trial of patients with a previous myocardial infarction and with residual inflammation, a monoclonal antibody targeting the LOX-1 receptor, thought to contribute to atherosclerotic plaque progression and inflammation, reduced soluble LOX-1 and interleukin-6 levels but did not lead to a substantial reduction in coronary plaque volume.

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.

Haematopoietic stem cell numbers are restricted at both systemic and local levels.

Magic state distillation is achieved with logical qubits on a neutral-atom quantum computer using a dynamically reconfigurable architecture for parallel quantum operations.

Malnutrition during pregnancy has lasting effects on maternal and offspring health. Its adverse impacts are modified by the maternal microbiome and attenuated by gestational treatment with select microbial metabolites.

Using viral barcode tracing to detect interactions between glioblastoma cells and non-malignant astrocytes in patient samples, investigators discovered a pathway that reduces tumour-specific immunity and identified potential therapeutic targets.

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.

Genome-wide analyses identify 30 independent loci associated with obsessive–compulsive disorder, highlighting genetic overlap with other psychiatric disorders and implicating putative effector genes and cell types contributing to its etiology.