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Colonic goblet cell-associated passages allow translocation of live bacteria to other organs in early life, potentially leading to beneficial impacts.

Rice indica varieties have higher nitrogen use efficiency (NUE) than that of japonica varieties. Here, the authors show that natural variation of OsWRKY23 and its interaction with DULL NITROGEN RESPONSE1 (DNR1)-mediated auxin accumulation play a role in NUE divergence between the two rice subspecies.

Regulation of aggregation by light is a useful phenomenon, but the role of the solvent is not often considered. Here, the authors report the development of photoinduced hydrous organic aggregates, emissive in the presence of both water and photoirradiation.

Wu et al. show that glucosamine acts as a P-glycoprotein activator, rapidly enhancing intestinal drug efflux and reducing drug absorption. The authors propose this as a detox strategy to improve survival outcomes following paraquat exposure.

Convergent mutations in hot spots of the spike proteins of currently circulating SARS-CoV-2 Omicron variants increase the binding affinity for the host receptor and promote more efficient fusion with host cell membranes.

Dopaminergic dysfunction is a key of Alzheimer’s disease pathogenesis. Here, the authors developed a multifunctional neural interface that simultaneously monitors dopamine dynamics and neural activity while delivering 40 Hz stimulation to rescue cognitive deficits in APP/PS1 mice.

The authors describe a mechanism for the clearance of macromolecules from cerebrospinal fluid in which macromolecules traverse from periarterial to perivenous spaces, at sites where intersecting leptomeningeal perivascular (arteriovenous) spaces overlap.

The authors use human SEEG recordings during a virtual escape task to identify roles for cognitive and reactive fear circuits in threat evaluation and escape decisions, respectively. They further uncover Theta-band flow from the amygdala to the vmPFC during rapid attacks.

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.

Whether multimorbidity accelerates brain Aβ deposition in humans remains largely unknown. Here, the authors demonstrate that higher self-reported multimorbidity burden predicts increased brain Aβ accumulation rates in the ADNI cohort.

The Somatic Mosaicism across Human Tissues Network aims to create a reference catalogue of somatic mosaicism across different tissues and cells within individuals.

While Bell inequalities have been violated several times—mostly in photonic systems—their violations within particle physics experiments are less explored. Here, the BESIII Collaboration showcases Bell-violating nonlocal correlations between entangled hyperon pairs.

Exposure of mice to high fructose during gestation or early postnatal life causes decreased microglial phagocytosis during brain development and leads to anxiety-like behaviour in adolescence.

The immune response of immunotherapy in colorectal cancer remains low and new adjuvant targets are in demand. By in vivo CRISPR-Cas9 screening that targets membrane and secreted proteins genes, the authors identify that disrupting MBTPS1 in tumor cells upregulates STAT1-transcribed chemokines, promotes CXCR3⁺ CD8 T cells infiltration and potentiates anti-PD-1 therapy.

Wastewater treatment plants are important reservoirs of antibiotic resistance genes (ARGs). Here, the authors analyze ARGs in a global collection of samples from wastewater treatment plants across six continents, providing insights into biotic and abiotic mechanisms that appear to control ARG diversity and distribution.

Genome-wide association study of cerebrospinal fluid and brain metabolites highlights the unique genetic architecture of metabolite levels and metabolite–trait associations with brain-related phenotypes.

Experiments and computations show that the organization and dynamics of molecules within and at interfaces of biomolecular condensates are governed by differential interaction strengths leading to the classification of adsorbents versus scaffolds.

Heo, Xu et al. used comprehensive plasma proteomics to identify 416 plasma proteins (294 new) associated with Alzheimer’s disease and applied machine learning to select 7 proteins that were highly predictive of Alzheimer’s disease across multiple cohorts.

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia is a neurodegenerative disorder caused by pathogenic CSF1R mutations. Here the authors find that microglial loss is linked to reduced myelinating oligodendrocytes, an expansion of neuropilin-2⁺ oligodendrocytes and a maladaptive stress response in astrocytes.

A nanofluidic intracellular delivery (NanoFLUID) patch provides a versatile, biocompatible and efficient method for the targeted delivery of payloads to internal organs for therapeutic purposes and for biomolecular investigations.

Plasma samples from 324 Black and 1,547 white participants underwent analysis with C2N Diagnostics’ Precivity AD test for Aβ42 and Aβ40. Compared to white individuals, Black individuals had higher average plasma Aβ42/40 levels at baseline, consistent with a lower average level of amyloid pathology.

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.

Problems at inferior metal plating/stripping and low voltage hinder the development of Zn batteries. Here, authors propose a nonflammable ternary solid-state eutectic electrolyte via solvation regulation, contributing to deep-reversible Zn plating/stripping and voltage increase of full batteries.

Secondary acute myeloid leukemias (sAMLs) evolving from myeloproliferative neoplasms (MPNs) associate with poor prognosis. Here authors identify RSK1 as a vulnerability for MPN and sAML and show the efficacy of a first-in-class RSK inhibitor, PMD-026, against these types of myeloid malignancies.

The MAPK pathway is an important therapeutic target in pancreatic ductal adenocarcinoma (PDAC), but success is limited by pathway reactivation, which drives resistance. Here, the authors investigate the mechanism underlying HER2-reactivation post KRAS-MAPK inhibition, identifying combination of MAPK and HER2 inhibition as a therapeutic strategy.

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.

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.

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.

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.

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.

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.

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.

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.

This study provides the structural and biochemical characterization of the RSV NS1/MED25 ACID complex, revealing how RSV exploits fuzzy interfaces between coactivators and transcription factors, including ATF3, to modulate host gene transcription.

This study uses genetic crossing to identify the genes underlying the differences in virulence between two Cryptosporidium isolates. Candidate genes are validated using genetic editing, revealing that the small granule protein SKSR1 is a key virulence factor in Cryptosporidium.

The ratio between the levels of two synaptic proteins in cerebrospinal fluid predicts future cognitive resilience versus decline among presymptomatic individuals and individuals with early Alzheimer’s disease harboring amyloid and tau pathology.

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.

Micrometeorite impacts are an important process in forming several Ti oxides, including rutile (TiO₂) and new Ti minerals (trigonal Ti₂O and triclinic Ti₂O). These Ti oxides can alter the photocatalytic properties and reflectance spectra of regolith on the Moon and other airless planetary bodies in the Solar System.

Ding and colleagues use bulk, single-cell and single-nucleus multi-omics together with spatial transcriptomics and multiplex imaging of clinical tumor samples to characterize gene expression and chromatin accessibility of breast cancer lineages.

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.

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.

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.

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.