Temperate grassland conversion to conifer forest destabilises mineral soil carbon stocks.

Tree-planting is increasingly presented as a cost-effective strategy to maximise ecosystem carbon (C) storage and thus mitigate climate change. Its success largely depends on the associated response of soil C stocks, where most terrestrial C is stored. Yet, we lack a precise understanding of how soil C stocks develop following tree planting, and particularly how it affects the form in which soil C is stored and its associated stability and resistance to climate change.

Achieving 3-D Structural Uniformity in Cellulose Gel Beads via Salt Screening.

Cellulose microgel beads fabricated using the dropping technique suffer from structural irregularity and mechanical variability. This limits their translation to biomedical applications that are sensitive to variations in material properties. Ionic salts are often uncontrolled by-products of this technique, despite the known effects of ionic salts on cellulose assembly.

Synthetic augmentation of cancer cell line multi-omic datasets using unsupervised deep learning.

Integrating diverse types of biological data is essential for a holistic understanding of cancer biology, yet it remains challenging due to data heterogeneity, complexity, and sparsity. Addressing this, our study introduces an unsupervised deep learning model, MOSA (Multi-Omic Synthetic Augmentation), specifically designed to integrate and augment the Cancer Dependency Map (DepMap). Harnessing orthogonal multi-omic information, this model successfully generates molecular and phenotypic profiles, resulting in an increase of 32.

Sea-level rise and extreme Indian Ocean Dipole explain mangrove dieback in the Maldives.

Mangrove forests enhance Small Island Developing States' resilience to climate change, yet in 2020, a mangrove dieback impacted ~ 25% of mangrove-containing islands in the Maldives. Using remote sensing, dendrology and sediment geochemistry, we document a significant decrease in mangrove health post-2020 (NDVI: 0.75 ± 0.

Base editing screens define the genetic landscape of cancer drug resistance mechanisms.

Drug resistance is a principal limitation to the long-term efficacy of cancer therapies. Cancer genome sequencing can retrospectively delineate the genetic basis of drug resistance, but this requires large numbers of post-treatment samples to nominate causal variants. Here we prospectively identify genetic mechanisms of resistance to ten oncology drugs from CRISPR base editing mutagenesis screens in four cancer cell lines using a guide RNA library predicted to install 32,476 variants in 11 cancer genes.

High TNF and NF-κB Pathway Dependency Are Associated with AZD5582 Sensitivity in OSCC via CASP8-Dependent Apoptosis.

Mechanistically guided drug repurposing has been made possible by systematically integrating pharmacologic and CRISPR-Cas9 screen data. Our study discovers the biomarker and cell death mechanisms underpinning sensitivity toward AZD5582, an antagonist of the inhibitor of apoptosis family protein. Our findings have important implications for improving future trial design for patients with OSCC using this emerging drug class.

A pan-cancer screen identifies drug combination benefit in cancer cell lines at the individual and population level.

Combining drugs can enhance their clinical efficacy, but the number of possible combinations and inter-tumor heterogeneity make identifying effective combinations challenging, while existing approaches often overlook clinically relevant activity. We screen one of the largest cell line panels (N = 757) with 51 clinically relevant combinations and identify responses at the level of individual cell lines and tissue populations. We establish three response classes to model cellular effects beyond monotherapy: synergy, Bliss additivity, and independent drug action (IDA).

Electrically polarized nanoscale surfaces generate reactive oxygenated and chlorinated species for deactivation of microorganisms.

Because of the decreasing supply of new antibiotics, recent outbreaks of infectious diseases, and the emergence of antibiotic-resistant microorganisms, it is imperative to develop new effective strategies for deactivating a broad spectrum of microorganisms and viruses. We have implemented electrically polarized nanoscale metallic (ENM) coatings that deactivate a wide range of microorganisms including Gram-negative and Gram-positive bacteria with greater than 6-log reduction in less than 10 minutes of treatment. The electrically polarized devices were also effective in deactivating lentivirus and .

Barriers and facilitators to the implementation of rapid HIV testing in Canadian Emergency Departments: a mixed methods study.

Objectives: 1 in 7 Canadians with Human Immunodeficiency Virus (HIV) do not know their status. Patients at increased risk of HIV routinely access the emergency department (ED), yet few are tested, representing a missed opportunity for diagnosis and linkage-to-care. Rapid HIV testing provides reliable results within the same ED encounter but is not routinely implemented.

Leakage of old carbon dioxide from a major river system in the Canadian Arctic.

The Canadian Arctic is warming at an unprecedented rate. Warming-induced permafrost thaw can lead to mobilization of aged carbon from stores in soils and rocks. Tracking the carbon pools supplied to surrounding river networks provides insight on pathways and processes of greenhouse gas release.

Novel WRN Helicase Inhibitors Selectively Target Microsatellite-Unstable Cancer Cells.

Microsatellite-unstable (MSI) cancers require WRN helicase to resolve replication stress due to expanded DNA (TA)n dinucleotide repeats. WRN is a promising synthetic lethal target for MSI tumors, and WRN inhibitors are in development. In this study, we used CRISPR-Cas9 base editing to map WRN residues critical for MSI cells, validating the helicase domain as the primary drug target.

Large-scale Pan-cancer Cell Line Screening Identifies Actionable and Effective Drug Combinations.

Unlabelled: Oncology drug combinations can improve therapeutic responses and increase treatment options for patients. The number of possible combinations is vast and responses can be context-specific. Systematic screens can identify clinically relevant, actionable combinations in defined patient subtypes.

Establishment and Characterization of an Epstein-Barr Virus-positive Cell Line from a Non-keratinizing Differentiated Primary Nasopharyngeal Carcinoma.

Unlabelled: Nasopharyngeal carcinoma (NPC), a cancer that is etiologically associated with the Epstein-Barr virus (EBV), is endemic in Southern China and Southeast Asia. The scarcity of representative NPC cell lines owing to the frequent loss of EBV episomes following prolonged propagation and compromised authenticity of previous models underscores the critical need for new EBV-positive NPC models. Herein, we describe the establishment of a new EBV-positive NPC cell line, designated NPC268 from a primary non-keratinizing, differentiated NPC tissue.

Delayed surgery of elbow Osteochondroma: A case of overcoming barriers in rural Uganda.

Introduction: Osteochondromas are the most common benign bone tumours in children. They typically manifest near the knee, proximal humerus, or distal femur. While often asymptomatic, they can lead to pain, functional impairments, deformities, and pathologic fractures.

Haplotype-specific assembly of shattered chromosomes in esophageal adenocarcinomas.

The epigenetic landscape of cancer is regulated by many factors, but primarily it derives from the underlying genome sequence. Chromothripsis is a catastrophic localized genome shattering event that drives, and often initiates, cancer evolution. We characterized five esophageal adenocarcinoma organoids with chromothripsis using long-read sequencing and transcriptome and epigenome profiling.

Tissue Organoid Cultures Metabolize Dietary Carcinogens Proficiently and Are Effective Models for DNA Adduct Formation.

Human tissue three-dimensional (3D) organoid cultures have the potential to reproduce the physiological properties and cellular architecture of the organs from which they are derived. The ability of organoid cultures derived from human stomach, liver, kidney, and colon to metabolically activate three dietary carcinogens, aflatoxin B (AFB), aristolochic acid I (AAI), and 2-amino-1-methyl-6-phenylimidazo[4,5-]pyridine (PhIP), was investigated. In each case, the response of a target tissue (liver for AFB; kidney for AAI; colon for PhIP) was compared with that of a nontarget tissue (gastric).

scSNV-seq: high-throughput phenotyping of single nucleotide variants by coupled single-cell genotyping and transcriptomics.

CRISPR screens with single-cell transcriptomic readouts are a valuable tool to understand the effect of genetic perturbations including single nucleotide variants (SNVs) associated with diseases. Interpretation of these data is currently limited as genotypes cannot be accurately inferred from guide RNA identity alone. scSNV-seq overcomes this limitation by coupling single-cell genotyping and transcriptomics of the same cells enabling accurate and high-throughput screening of SNVs.

A comprehensive clinically informed map of dependencies in cancer cells and framework for target prioritization.

Genetic screens in cancer cell lines inform gene function and drug discovery. More comprehensive screen datasets with multi-omics data are needed to enhance opportunities to functionally map genetic vulnerabilities. Here, we construct a second-generation map of cancer dependencies by annotating 930 cancer cell lines with multi-omic data and analyze relationships between molecular markers and cancer dependencies derived from CRISPR-Cas9 screens.

Single-cell transcriptomic analysis of human pleura reveals stromal heterogeneity and informs models of mesothelioma.

The pleural lining of the thorax regulates local immunity, inflammation and repair. A variety of conditions, both benign and malignant, including pleural mesothelioma, can affect this tissue. A lack of knowledge concerning the mesothelial and stromal cells comprising the pleura has hampered the development of targeted therapies.

Benchmark Software and Data for Evaluating CRISPR-Cas9 Experimental Pipelines Through the Assessment of a Calibration Screen.

Genome-wide genetic screens using CRISPR-guide RNA libraries are widely performed in mammalian cells to functionally characterize individual genes and for the discovery of new anticancer therapeutic targets. As the effectiveness of such powerful and precise tools for cancer pharmacogenomics is emerging, tools and methods for their quality assessment are becoming increasingly necessary. Here, we provide an R package and a high-quality reference data set for the assessment of novel experimental pipelines through which a single calibration experiment has been executed: a screen of the HT-29 human colorectal cancer cell line with a commercially available genome-wide library of single-guide RNAs.

Peatland pools are tightly coupled to the contemporary carbon cycle.

Peatlands are globally important stores of soil carbon (C) formed over millennial timescales but are at risk of destabilization by human and climate disturbance. Pools are ubiquitous features of many peatlands and can contain very high concentrations of C mobilized in dissolved and particulate organic form and as the greenhouses gases carbon dioxide (CO ) and methane (CH ). The radiocarbon content ( C) of these aquatic C forms tells us whether pool C is generated by contemporary primary production or from destabilized C released from deep peat layers where it was previously stored for millennia.