Dietary cysteine enhances intestinal stemness via CD8 T cell-derived IL-22.

A critical question in physiology is understanding how tissues adapt and alter their cellular composition in response to dietary cues. The mammalian small intestine, a vital digestive organ that absorbs nutrients, is maintained by rapidly renewing Lgr5 intestinal stem cells (ISCs) at the intestinal crypt base. While Lgr5 ISCs drive intestinal adaptation by altering self-renewal and differentiation divisions in response to diverse diets such as high-fat diets and fasting regimens, little is known about how micronutrients, particularly amino acids, instruct Lgr5 ISC fate decisions to control intestinal homeostasis and repair after injury.

Crossing the streams: improving data quality and integration across the One Health genomics continuum with data standards and implementation strategies.

The Canadian Genomics Research and Development Initiative for Antimicrobial Resistance (GRDI-AMR) uses a genomics-based approach to understand how health care, food production and the environment contribute to the development of antimicrobial resistance. Integrating genomics contextual data streams across the One Health continuum is challenging because of the diversity in data scope, content and structure. To better enable data harmonization for analyses, a contextual data standard was developed.

A Phosphatidyl Conjugated Telomerase-Dependent Telomere-Targeting Nucleoside Demonstrates Colorectal Cancer Direct Killing and Immune Signaling.

Telomerase and telomeres are crucial in cancer cell immortalization, making them key targets for anticancer therapies. Currently, 6-thio-dG (THIO) combined with the anti-PD-1 inhibitor Cemiplimab is under phase II clinical investigation (NCT05208944) in NSCLC patients resistant to prior immunotherapies. This study presents the design, synthesis, and evaluation of novel bimodular conjugate molecules combining telomere-targeting nucleoside analogs and phosphatidyl diglyceride groups.

Variation in plasmid conjugation among nontyphoidal serovars.

Conjugation is a complex phenomenon involving multiple plasmid, bacterial, and environmental factors. Here we describe an IncI1 plasmid encoding multidrug antibiotic resistance to aminoglycosides, sulfonamides, and third-generation cephalosporins. This plasmid is widespread geographically among animal, human, and environmental sectors.

Long-telomeropathy is associated with tumor predisposition syndrome.

Telomeres protect chromosomal integrity, and telomere length (TL) is influenced by environmental and genetic factors. While short-telomeres are linked to rare telomeropathies, this study explored the hypothesis that a "long-telomeropathy" is associated with a cancer-predisposing syndrome. Using genomic and health data from 113,861 individuals, a trans-ancestry polygenic risk score for TL (PRS ) was developed.

Bacterial composition and cultural dynamics of microgreens-associated microbiota during selective enrichment for Listeria monocytogenes.

Widely regarded as a so-called "superfood," microgreens have become an increasingly significant food crop from both nutritional and agricultural standpoints. However, similar to other produce commodities that are also cultivated using modernized indoor farming methods, there have been mounting concerns over the potential risks of consuming microgreens contaminated by Listeria monocytogenes. To gain insights into the microbial properties of microgreens, this study characterized the bacterial composition of fresh microgreen retail products using amplicon sequencing of 16S rRNA genes.

The longitudinal behavioral effects of acute exposure to galactic cosmic radiation in female C57BL/6J mice: Implications for deep space missions, female crews, and potential antioxidant countermeasures.

Galactic cosmic radiation (GCR) is an unavoidable risk to astronauts that may affect mission success. Male rodents exposed to 33-beam-GCR (33-GCR) show short-term cognitive deficits but reports on female rodents and long-term assessment are lacking. We asked: What are the longitudinal behavioral effects of 33-GCR on female mice? Also, can an antioxidant/anti-inflammatory compound (CDDO-EA) mitigate the impact of 33-GCR? Mature (6-month-old) C57BL/6J female mice received CDDO-EA (400 μg/g of food) or a control diet (vehicle, Veh) for 5 days and Sham-irradiation (IRR) or whole-body 33-GCR (0.

Comparison of American and European Guideline Recommendations for Diagnostic Workup and Secondary Prevention of Ischemic Stroke and Transient Ischemic Attack.

Guidelines help to facilitate treatment decisions based on available evidence, and also to provide recommendations in areas of uncertainty. In this paper, we compare the recommendations for stroke workup and secondary prevention of ischemic stroke and transient ischemic attack of the American Heart Association (AHA)/American Stroke Association (ASA) with the European Stroke Organization (ESO) guidelines. The primary aim of this paper is to offer clinicians guidance by identifying areas where there is consensus and where consensus is lacking, in the absence or presence of high-level evidence.

MYC-Mediated Inhibition of ARNT2 Uncovers a Key Tumor Suppressor in Glioblastoma.

Tumor initiation and progression rely on intricate cellular pathways that promote proliferation while suppressing differentiation, yet the importance of pathways inhibiting differentiation in cancer remains incompletely understood. Here, we reveal a novel mechanism centered on the repression of the neuronal-specific transcription factor ARNT2 by the MYC oncogene that governs the balance between proliferation and differentiation. We found that MYC coordinates the transcriptional repression of ARNT2 through the activity of polycomb repressive complex 2 (PRC2).

Radioprotective effect of the anti-diabetic drug metformin.

Metformin is a biguanide currently used in the treatment of diabetes mellitus type 2. Besides its anti-glycemic effects, metformin has been reported to induce different cellular pleiotropic effects, depending on concentration and time of treatment. Here we report one administration of metformin (0.

Hydroxyurea to prevent brain injury in children with sickle cell disease (HU Prevent)-A randomized, placebo-controlled phase II feasibility/pilot study.

Central nervous system (CNS) injury is common in sickle cell disease (SCD) and occurs early in life. Hydroxyurea is safe and efficacious for treatment of SCD, but high-quality evidence from randomized trials to estimate its neuroprotective effect is scant. HU Prevent was a randomized (1:1), double-blind, phase II feasibility/pilot trial of dose-escalated hydroxyurea vs.

Tryptophan fuels MYC-dependent liver tumorigenesis through indole 3-pyruvate synthesis.

Cancer cells exhibit distinct metabolic activities and nutritional dependencies compared to normal cells. Thus, characterization of nutrient demands by individual tumor types may identify specific vulnerabilities that can be manipulated to target the destruction of cancer cells. We find that MYC-driven liver tumors rely on augmented tryptophan (Trp) uptake, yet Trp utilization to generate metabolites in the kynurenine (Kyn) pathway is reduced.

Simulated galactic cosmic radiation-induced cancer progression in mice.

Prolonged manned space flight exposure risks to galactic comic radiation, has led to uncertainties in a variety of health risks. Our previous work, utilizing either single ion or multiple ion radiation exposure conducted at the NSRL (NASA Space Radiation Laboratory, Brookhaven, NY) demonstrated that HZE ion components of the GCR result in persistent inflammatory signaling, increased mutations, and higher rates of cancer initiation and progression. With the development of the 33-beam galactic cosmic radiation simulations (GCRsim) at the NSRL, we can more closely test on earth the radiation environment found in space.

The longitudinal behavioral effects of acute exposure to galactic cosmic radiation in female C57BL/6J mice: implications for deep space missions, female crews, and potential antioxidant countermeasures.

Galactic cosmic radiation (GCR) is an unavoidable risk to astronauts that may affect mission success. Male rodents exposed to 33-beam-GCR (33-GCR) show short-term cognitive deficits but reports on female rodents and long-term assessment is lacking. Here we asked: What are the longitudinal behavioral effects of 33-GCR on female mice? Also, can an antioxidant/anti-inflammatory compound mitigate the impact of 33-GCR? Mature (6-month-old) C57BL/6J female mice received the antioxidant CDDO-EA (400 µg/g of food) or a control diet (vehicle, Veh) for 5 days and either Sham-irradiation (IRR) or whole-body 33-GCR (0.

A telomere-targeting drug depletes cancer initiating cells and promotes anti-tumor immunity in small cell lung cancer.

There are few effective treatments for small cell lung cancer (SCLC) underscoring the need for innovative therapeutic approaches. This study focuses on exploiting telomerase, a critical SCLC dependency as a therapeutic target. A prominent characteristic of SCLC is their reliance on telomerase activity, a key enzyme essential for their continuous proliferation.

Chronic metabolic stress drives developmental programs and loss of tissue functions in non-transformed liver that mirror tumor states and stratify survival.

Under chronic stress, cells must balance competing demands between cellular survival and tissue function. In metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD/NASH), hepatocytes cooperate with structural and immune cells to perform crucial metabolic, synthetic, and detoxification functions despite nutrient imbalances. While prior work has emphasized stress-induced drivers of cell death, the dynamic adaptations of surviving cells and their functional repercussions remain unclear.

Automated centrifugal microfluidic system for the preparation of adaptor-ligated sequencing libraries.

The intensive workload associated with the preparation of high-quality DNA libraries remains a key obstacle toward widespread deployment of sequencing technologies in remote and resource-limited areas. We describe the development of single-use microfluidic devices driven by an advanced pneumatic centrifugal microfluidic platform, the PowerBlade, to automate the preparation of Illumina-compatible libraries based on adaptor ligation methodology. The developed on-chip workflow includes enzymatic DNA fragmentation coupled to end-repair, adaptor ligation, first DNA cleanup, PCR amplification, and second DNA cleanup.

Alternative lengthening of telomeres (ALT) cells viability is dependent on C-rich telomeric RNAs.

Alternative lengthening of telomeres (ALT) is a telomere maintenance mechanism activated in ~10-15% of cancers, characterized by telomeric damage. Telomeric damage-induced long non-coding RNAs (dilncRNAs) are transcribed at dysfunctional telomeres and contribute to telomeric DNA damage response (DDR) activation and repair. Here we observed that telomeric dilncRNAs are preferentially elevated in ALT cells.

Improving RNA-based crop protection through nanotechnology and insights from cross-kingdom RNA trafficking.

Spray-induced gene silencing (SIGS) is a powerful and eco-friendly method for crop protection. Based off the discovery of RNA uptake ability in many fungal pathogens, the application of exogenous RNAs targeting pathogen/pest genes results in gene silencing and infection inhibition. However, SIGS remains hindered by the rapid degradation of RNA in the environment.

Structural basis for high-order complex of SARNP and DDX39B to facilitate mRNP assembly.

mRNA in eukaryotic cells is packaged into highly compacted ribonucleoprotein particles (mRNPs) in the nucleus and exported to the cytoplasm for translation. mRNP packaging and export require the evolutionarily conserved transcription-export (TREX) complex. TREX facilitates loading of various RNA-binding proteins on mRNA through the action of its DDX39B subunit.

Moderate-high intensity exercise associates with reduced incident alcohol-associated liver disease in high-risk patients.

Background: Therapies to prevent alcohol-associated liver disease (ALD) in high-risk patients are needed.

Aims: In this retrospective association study, we examined whether patients with alcohol use disorder (AUD) who reported greater exercise were less likely to develop liver disease.

Methods: In this retrospective cohort study, we used the Mass General Brigham Biobank to investigate the impact of both moderate-high and light-intensity exercise on the development of ALD in patients with AUD, using clinician-provided diagnostic International Classification of Diseases 10 codes.

Microbiome of Ceca from Broiler Chicken Vaccinated or Not against Coccidiosis and Fed Berry Pomaces.

American cranberry () and lowbush/wild blueberry () pomace are polyphenol-rich products having potentially beneficial effects in broiler chickens. This study investigated the cecal microbiome of broiler-vaccinated or non-vaccinated birds against coccidiosis. Birds in each of the two groups (vaccinated or non-vaccinated) were fed a basal non-supplemented diet (NC), a basal diet supplemented with bacitracin (BAC), American cranberry (CP), and lowbush blueberry (BP) pomace alone or in combination (CP + BP).