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The polymerized protein response (PPR) is a pathway mediated by NFκB p50 homodimers in response to disease-associated variants that aberrantly polymerize and accumulate in the ER. Derlin-2 plays a role as proximal transducer and the downstream gene expression profile, including changes that stabilize p50 homodimers in cytoplasm and nucleus, is distinct from the UPR.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

Researchers designed two-component proteins forming quasisymmetric cages via geometric frustration, enabling tunable virus-like assemblies for cargo delivery, cellular uptake and studying intracellular diffusion and protein localization.

Antibody mediated prevention (AMP) trials with the broadly neutralizing antibody VRC01 showed protection against VRC01-sensitive viruses. Here, by deep sequencing plasma samples from 172 participants of the AMP trials, the authors show a high frequency of multilineage HIV infections (38%), including coinfection with both sensitive and resistant viruses, and demonstrate that VRC01 doesn’t alter the transmission bottleneck.

Allogeneic CAR T cells carry a higher risk of immune rejection, which may limit persistence and therapeutic efficacy. The authors here show that co-expression of an anti-rejection CD70 CAR with a CD19 CAR enhances persistence and activity in preclinical models of cancer and autoimmune disease.

Supported by both experimental and human data, this study reveals that poor sleep weakens immune responses to influenza vaccination and increases infection risk, highlighting sleep as a modifiable determinant for vaccination effectiveness.

Peritoneal metastasis of ovarian cancer is often accompanied by the accumulation of ascitic fluid. Here, the authors find that ascites protects ovarian cancer cells against ferroptosis, thus enabling their spread in the peritoneum.

Genome-wide analyses identify genetic loci and plasma proteins associated with polycystic ovary syndrome (PCOS). This study highlights the hormonal and metabolic foundations of the disease and explores the impact of polygenic risk for PCOS in both sexes.

An absolute photon upconversion efficiency of 8.2% is demonstrated using a liquid triplet fusion medium that behaves as solid on excitonic timescales. The findings may drive higher efficiencies in nanoscale solid-state photochemical upconversion devices.

Global Burden of Disease analysis found that in 2023, suboptimal diet was estimated to be responsible for 4 million deaths and 97 million morbidity burdens from ischemic heart disease.

FOXA1 is a master suppressor of prostate cancer tumorigenesis and lineage plasticity. Here, the authors discover that FOXA1 loss in mice drives basal-squamous de-differentiation and remodels the tumor microenvironment characterized by immunosuppressive myeloid cell accumulation and T-cell dysfunction.

NatD is an acetyltransferase responsible for N-α-terminal acetylation of the histone H4 and H2A and has been linked to cell growth. Here the authors show that NatD-mediated acetylation of histone H4 serine 1 competes with the phosphorylation by CK2α at the same residue thus leading to the upregulation of Slug and tumor progression.

Extracellular vesicles from lung epithelial cells deliver ACE2 and TMPRSS2 to recipient cells, enabling SARS-CoV-2 infection beyond receptor-expressing cells and expanding viral tropism.

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.

The CMS experiment at CERN reports one of the highest-precision measurements of the W boson mass, finding it in line with standard model predictions and at odds with recent anomalous measurements.

The authors resolve 63 structurally diverse haplotype structures for the 22q11.2 deletion syndrome region. Deletion risk differs depending on structure; individuals of African ancestry are enriched for inverted repeats that predispose to inversion.

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.

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.

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 mechanisms driving reversible dedifferentiation events towards a drug-tolerant persister (DTP) state remain to be explored. Here, multi-omics, information-theoretic approaches and dynamic systems modelling highlight the role of the oxidative-stress–mediated NF-κB/RelA axis in driving the transition towards DTP across multiple cancer types.

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

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

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.

Radiocarbon analyses show that dryland soils store organic carbon with a mean age of ~2100 years and release carbon averaging ~520 years old, suggesting that long-stored carbon in drylands is vulnerable to environmental change.

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.

DNA damage burden and inadequate repair in CUX2⁺ cortical layer 2/3 excitatory neurons contributes to selective vulnerability in neuroinflammatory injury.

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.

Androgen activity in the male embryonic hindbrain prolongs hindbrain differentiation in male individuals and drives sex differences in the incidence and prognosis of posterior fossa type A (PFA) ependymoma, an aggressive childhood brain tumour.

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.

After being internalized by cells, nanoparticles can, in rare events, acquire a biomolecular condensate corona. These complexes can reach the extracellular space, where they can deliver their acquired proteins and RNA content to other cells.

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 APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

Robustness checks and reproduction of analyses with existing and updated data based on 110 articles in economics and political science journals with data and code-sharing requirements found high levels of robustness and reproducibility and determined that robustness was not dependent on author characteristics or data availability.

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.

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.

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.

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.

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.

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.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

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.

Global observations show that ecosystems sustain transpiration at temperatures above those that maximize photosynthesis. This thermal gap reveals that carbon uptake declines before water loss under climate warming.

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.