Leukemia escapes immunity by imposing a Type-1 regulatory program on neoantigen-specific CD4+ T cells.

The significance of endogenous immune surveillance in acute lymphoblastic leukemia (ALL) remains controversial. Using clinical B-ALL samples and a novel mouse model, we show that neoantigen-specific CD4+ T cells are induced to adopt type-1 regulatory (Tr1) function in the leukemia microenvironment. Tr1s then inhibit cytotoxic CD8+ T cells, preventing effective leukemia clearance.

Supramolecular Peptide Depots for Glucose-Responsive Glucagon Delivery.

Precise blood glucose control continues to be a critical challenge in the treatment and management of type 1 diabetes in order to mitigate both acute and chronic complications. This study investigates the development of a supramolecular peptide amphiphile (PA) material functionalized with phenylboronic acid (PBA) for glucose-responsive glucagon delivery. The PA-PBA system self-assembles into nanofibrillar hydrogels in the presence of physiological glucose levels, resulting in stable hydrogels capable of releasing glucagon under hypoglycemic conditions.

Ablation of FAS confers allogeneic CD3 CAR T cells with resistance to rejection by T cells and natural killer cells.

Allogeneic chimaeric antigen receptor T cells (allo-CAR T cells) derived from healthy donors could provide rapid access to standardized and affordable batches of therapeutic cells if their rejection by the host's immune system is avoided. Here, by means of an in vivo genome-wide CRISPR knockout screen, we show that the deletion of Fas or B2m in allo- T cells increases their survival in immunocompetent mice. Human B2M allo-CAR T cells become highly sensitive to rejection mediated by natural killer (NK) cells, whereas FAS CAR T cells expressing normal levels of human leukocyte antigen I remain resistant to NK cells.

Application of Pan-Viral Metagenomic Sequencing on United States Air Force Academy Wastewater to Uncover Potential Causes of Acute Gastroenteritis.

Introduction: Wastewater surveillance is an important technique to monitor public health and is being studied extensively for pandemic prevention, force health protection and readiness, and as a potential early warning system for chem-bio defense. Wastewater surveillance has traditionally relied on techniques such as quantitative PCR or targeted sequencing, both of which are microbe- or disease-specific tools. Newer pan-viral metagenomics strategies may provide higher specificity for pathogens of interest, resulting in a lower false negative rate and reduced sequencing of undesired background nucleic acids.

Engineering Supramolecular Nanofiber Depots from a Glucagon-Like Peptide-1 Therapeutic.

Diabetes and obesity have emerged as major global health concerns. Glucagon-like peptide-1 (GLP-1), a natural incretin hormone, stimulates insulin production and suppresses glucagon secretion to stabilize and reduce blood glucose levels and control appetite. The therapeutic use of GLP-1 receptor agonists (e.

Efficient multiplex non-viral engineering and expansion of polyclonal γδ CAR-T cells for immunotherapy.

Gamma delta (γδ) T cells are defined by their unique ability to recognize a limited repertoire of non-peptide, non-MHC-associated antigens on transformed and pathogen-infected cells. In addition to their lack of alloreactivity, γδ T cells exhibit properties distinct from other lymphocyte subsets, prompting significant interest in their development as an off-the-shelf cellular immunotherapeutic. However, their low abundance in circulation, heterogeneity, limited methods for expansion, and under-developed methodologies for genetic modification have hindered basic study and clinical application of γδ T cells.

Engineering memory T cells as a platform for long-term enzyme replacement therapy in lysosomal storage disorders.

Enzymopathy disorders are the result of missing or defective enzymes. Among these enzymopathies, mucopolysaccharidosis type I is a rare genetic lysosomal storage disorder caused by mutations in the gene encoding alpha-L-iduronidase (IDUA), which ultimately causes toxic buildup of glycosaminoglycans (GAGs). There is currently no cure and standard treatments provide insufficient relief to the skeletal structure and central nervous system (CNS).

Physical Activity and the Health of a Nation: A National Challenge and Collective Response.

Historic recruitment and retention challenges confront the U.S. military.

Assessing the implementation of evidence-based alcohol policies on Atlantic Canadian post-secondary campuses: A comparative analysis.

Objective: This study assessed the quality of campus alcohol policies against best practice to assist campus decision-makers in strengthening their campus alcohol policies and reducing student alcohol use and harm.

Methods: Drawing on empirical literature and expert opinion, we developed an evidence-based scoring rubric to assess the quality of campus alcohol policies across 10 alcohol policy domains. Campus alcohol policy data were collected from 12 Atlantic Canadian universities.

Body-size-dependent effects of landscape-level resource energetics on pollinator abundance in woodland remnants.

Land use change alters floral resource availability, thereby contributing to declines in important pollinators. However, the severity of land use impact varies by species, influenced by factors such as dispersal ability and resource specialization, both of which can correlate with body size. Here.

Review of the U.S. Air Force Academy Hepatitis C Virus Screening Program to Ensure High-Value Care.

Introduction: Hepatitis C virus (HCV) is primarily transmitted through blood-to-blood contact. Leading health agencies have called for the elimination of HCV as a public health threat, with universal screening considered a part of the strategy. Hepatitis C virus screening among incoming cadets and cadet candidates at the United States Air Force Academy (USAFA) was implemented in 2023.

Development and testing of a versatile genome editing application reporter (V-GEAR) system.

CRISPR-Cas9 and novel cas fusion proteins leveraging specific DNA targeting ability combined with deaminases or reverse transcriptases have revolutionized genome editing. However, their efficacy heavily relies upon protein variants, targeting single guide RNAs, and surrounding DNA sequence context within the targeted loci. This necessitates the need for efficient and rapid screening methods to evaluate these editing reagents and designs.

Engineering Memory T Cells as a platform for Long-Term Enzyme Replacement Therapy in Lysosomal Storage Disorders.

Enzymopathy disorders are the result of missing or defective enzymes. Amongst these enzymopathies, mucopolysaccharidosis type I, is a rare genetic lysosomal storage disorder caused by mutations in the gene encoding alpha-L-iduronidase (IDUA), ultimately causes toxic build-up of glycosaminoglycans (GAGs). There is currently no cure and standard treatments provide insufficient relief to the skeletal structure and central nervous system (CNS).

Evolution of the clinical-stage hyperactive TcBuster transposase as a platform for robust non-viral production of adoptive cellular therapies.

Cellular therapies for the treatment of human diseases, such as chimeric antigen receptor (CAR) T and natural killer (NK) cells have shown remarkable clinical efficacy in treating hematological malignancies; however, current methods mainly utilize viral vectors that are limited by their cargo size capacities, high cost, and long timelines for production of clinical reagent. Delivery of genetic cargo via DNA transposon engineering is a more timely and cost-effective approach, yet has been held back by less efficient integration rates. Here, we report the development of a novel hyperactive TcBuster (TcB-M) transposase engineered through structure-guided and in vitro evolution approaches that achieves high-efficiency integration of large, multicistronic CAR-expression cassettes in primary human cells.

Environmental DNA methods for biosecurity and invasion biology in terrestrial ecosystems: Progress, pitfalls, and prospects.

Analysis of environmental DNA (eDNA) enables indirect detection of species without the need to directly observe and sample them. For biosecurity and invasion biology, eDNA-based methods are useful to address biological invasions at all phases, from detecting arrivals to confirming eradication of past invasions. We conducted a systematic review of the literature and found that in biosecurity and invasion biology, eDNA has primarily been used to detect new incursions and monitor spread in marine and freshwater ecosystems, with much slower uptake in terrestrial ecosystems, reflecting a broader trend common to the usage of eDNA tools.

Precision Enhancement of CAR-NK Cells through Non-Viral Engineering and Highly Multiplexed Base Editing.

Natural killer (NK) cells' unique ability to kill transformed cells expressing stress ligands or lacking major histocompatibility complexes (MHC) has prompted their development for immunotherapy. However, NK cells have demonstrated only moderate responses against cancer in clinical trials and likely require advanced genome engineering to reach their full potential as a cancer therapeutic. Multiplex genome editing with CRISPR/Cas9 base editors (BE) has been used to enhance T cell function and has already entered clinical trials but has not been reported in human NK cells.

Prevalence of vision zero action plans or strategies: USA, 2021.

Background: Vision Zero is a strategy to eliminate traffic fatalities and to promote equitable mobility options for all road users. Using a nationally representative survey, we aimed to estimate the prevalence of Vision Zero action plans or strategies in the USA.

Methods: Municipal officials were surveyed in 2021.

Meeting the Aerobic and Muscle-Strengthening Physical Activity Guidelines Among Older US Adults, National Health Interview Survey 1998-2018.

The , second edition, recommends older adults participate in ≥150 minutes per week of moderate-intensity equivalent aerobic activity and ≥2 days per week of muscle-strengthening activity. We estimated prevalence and trends of meeting the guidelines among US adults aged ≥65 years from 1998 to 2018. Using the 1998-2018 National Health Interview Survey, we estimated the prevalence of meeting aerobic, muscle-strengthening, and combined physical activity guidelines stratified by age group, sex, race and ethnicity, and education level.