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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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59 records · Page 4

-Omics potential of in vitro skin models for radiation exposure

There is a growing need to uncover biomarkers of ionizing radiation exposure that leads to a better understanding of how exposures take place, including dose type, rate, and time since exposure. As one of the first organs to be exposed to external sources of ionizing radiation, skin is uniquely positioned in terms of model systems for radiation exposure study. The simultaneous evolution of both MS-based -omics studies, as well as in vitro 3D skin models, has created the ability to develop a far more holistic understanding of how ionizing radiation affects the many interconnected biomolecular processes that occur in human skin. However, there are a limited number of studies describing the biomolecular consequences of low-dose ionizing radiation to the skin. As a result, this review will seek to explore the current state-of-the-art technology in terms of in vitro 3D skin models, as well as track the trajectory of MS-based -omics techniques and their application to ionizing radiation research, specifically, the search for biomarkers within the low-dose range.

3D tissue model↗

Pan-cancer proteogenomics characterization of tumor immunity

Despite the successes of immunotherapy in cancer treatment over recent decades, less than <10%–20% cancer cases have demonstrated durable responses from immune checkpoint blockade. To enhance the efficacy of immunotherapies, combination therapies suppressing multiple immune evasion mechanisms are increasingly contemplated. To better understand immune cell surveillance and diverse immune evasion responses in tumor tissues, we comprehensively characterized the immune landscape of more than 1,000 tumors across ten different cancers using CPTAC pan-cancer proteogenomic data. We identified seven distinct immune subtypes based on integrative learning of cell type compositions and pathway activities. We then thoroughly categorized unique genomic, epigenetic, transcriptomic, and proteomic changes associated with each subtype. Further leveraging the deep phosphoproteomic data, we studied kinase activities in different immune subtypes, which revealed potential subtype-specific therapeutic targets. Insights from this work will facilitate the development of future immunotherapy strategies and enhance precision targeting with existing agents.

60 APPLIED LIFE SCIENCES↗

Polyphenol rewiring of the microbiome reduces methane emissions

Methane mitigation is regarded as a critical strategy to combat the scale of global warming. Currently, ~40% of methane emissions originate from microbial sources, which is causing strategies to suppress methanogens—either through direct toxic effects or by diverting their substrates and energy—to gain traction. Problematically, current microbial methane mitigation knowledge lacks detailed microbiome-centered insights, limiting translation across conditions and ecosystems. Here we utilize genome-resolved metatranscriptomes and metabolomes to assess the impact of a proposed methane inhibitor, catechin, on greenhouse gas emissions for high-methane-emitting peatlands. In microcosms, catechin drastically reduced methane emissions by 72%–84% compared to controls. Longitudinal sampling allowed for reconstruction of a catechin degradation pathway involving Actinomycetota and Clostridium, which break down catechin into smaller phenolic compounds within the first 21 days, followed by degradation of phenolic compounds by Pseudomonas_E from Days 21 to 35. These genomes co-expressed hydrogen-uptake genes, suggesting hydrogenases may act as a hydrogen sink during catechin degradation and consequently reduce hydrogen availability to methanogens. In support of this idea, there was decreased gene expression by hydrogenotrophic and hydrogen-dependent methylotrophic methanogens under catechin treatment. There was also reduced gene expression from genomes inferred to be functioning syntrophically with hydrogen-utilizing methanogens. We propose that catechin metabolic redirection effectively starves hydrogen-utilizing methanogens, offering a potent avenue for curbing methane emissions across diverse environments including ruminants, landfills, and constructed or managed wetlands.

54 ENVIRONMENTAL SCIENCES↗

Deep learning methods for drug response prediction in cancer: Predominant and emerging trends

Cancer claims millions of lives yearly worldwide. While many therapies have been made available in recent years, by in large cancer remains unsolved. Exploiting computational predictive models to study and treat cancer holds great promise in improving drug development and personalized design of treatment plans, ultimately suppressing tumors, alleviating suffering, and prolonging lives of patients. A wave of recent papers demonstrates promising results in predicting cancer response to drug treatments while utilizing deep learning methods. These papers investigate diverse data representations, neural network architectures, learning methodologies, and evaluations schemes. However, deciphering promising predominant and emerging trends is difficult due to the variety of explored methods and lack of standardized framework for comparing drug response prediction models. To obtain a comprehensive landscape of deep learning methods, we conducted an extensive search and analysis of deep learning models that predict the response to single drug treatments. A total of 61 deep learning-based models have been curated, and summary plots were generated. Based on the analysis, observable patterns and prevalence of methods have been revealed. This review allows to better understand the current state of the field and identify major challenges and promising solution paths.

60 APPLIED LIFE SCIENCES↗