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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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At least 559 records · Page 31
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

An accurate and interpretable model for antimicrobial resistance in pathogenic Escherichia coli from livestock and companion animal species

Understanding the microbial genomic contributors to antimicrobial resistance (AMR) is essential for early detection of emerging AMR infections, a pressing global health threat in human and veterinary medicine. Here we used whole genome sequencing and antibiotic susceptibility test data from 980 disease causing Escherichia coli isolated from companion and farm animals to model AMR genotypes and phenotypes for 24 antibiotics. We determined the strength of genotype-to-phenotype relationships for 197 AMR genes with elastic net logistic regression. Model predictors were designed to evaluate different potential modes of AMR genotype translation into resistance phenotypes. Our results show a model that considers the presence of individual AMR genes and total number of AMR genes present from a set of genes known to confer resistance was able to accurately predict isolate resistance on average (mean F 1 score = 98.0%, SD = 2.3%, mean accuracy = 98.2%, SD = 2.7%). However, fitted models sometimes varied for antibiotics in the same class and for the same antibiotic across animal hosts, suggesting heterogeneity in the genetic determinants of AMR resistance. We conclude that an interpretable AMR prediction model can be used to accurately predict resistance phenotypes across multiple host species and reveal testable hypotheses about how the mechanism of resistance may vary across antibiotics within the same class and across animal hosts for the same antibiotic.

Chung, Henri C.↗
DOE OSTI2014

Metabolic Reprogramming During Purine Stress in the Protozoan Pathogen Leishmania donovani

The ability of Leishmania to survive in their insect or mammalian host is dependent upon an ability to sense and adapt to changes in the microenvironment. However, little is known about the molecular mechanisms underlying the parasite response to environmental changes, such as nutrient availability. To elucidate nutrient stress response pathways in Leishmania donovani, we have used purine starvation as the paradigm. The salvage of purines from the host milieu is obligatory for parasite replication; nevertheless, purine-starved parasites can persist in culture without supplementary purine for over 3 months, indicating that the response to purine starvation is robust and engenders parasite survival under conditions of extreme scarcity. To understand metabolic reprogramming during purine starvation we have employed global approaches. Whole proteome comparisons between purine-starved and purine-replete parasites over a 6-48 h span have revealed a temporal and coordinated response to purine starvation. Purine transporters and enzymes involved in acquisition at the cell surface are upregulated within a few hours of purine removal from the media, while other key purine salvage components are upregulated later in the time-course and more modestly. After 48 h, the proteome of purine-starved parasites is extensively remodeled and adaptations to purine stress appear tailored to deal with both purine deprivation and general stress. To probe the molecular mechanisms affecting proteome remodeling in response to purine starvation, comparative RNA-seq analyses, qRT-PCR, and luciferase reporter assays were performed on purine-starved versus purine-replete parasites. While the regulation of a minority of proteins tracked with changes at the mRNA level, for many regulated proteins it appears that proteome remodeling during purine stress occurs primarily via translational and/or post-translational mechanisms.

Environmental Molecular Sciences Laboratory↗
DOE OSTI2011

Avian Diagnostic and Therapeutic Antibodies to Viral Emerging Pathogens

During the current period the following key objectives were achieved: demonstration of high titer antibody production by geese following immunization with inactived H1N1 virus; completion of the epitope mapping of West Nile Virus-specific goose antibodies and initiation of epitope mapping of H1N1 flu-specific goose antibodies; advancement in scalable purification of goose antibodies.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2011

Antibody-Based Diagnostics and Production for High Consequence Animal Pathogens II FINAL REPORT

To produce antigen and antibody reagents for the detection of Rinderpest virus and New Castle Disease virus for specific diagnostic platforms. Expected Results: The identification, production and characterization of appropriate reagents (antigens and antibodies) with the required sensitivity and specificity permitting the configuration, optimization, and certification of diagnostic kits.

Morris, James E↗
DOE OSTI2012

Antibody-Based Diagnostics and Production for High Consequence Animal Pathogens II

New Horizons Diagnostic Corporation (NHD) develops, manufactures, and tests products for the detection of bacteria and toxins in human, environmental, surface, food, and water samples for government, municipal and corporate customers. It offers diverse medical products, such as products for testing cholera, gonorrhea, syphilis, and drug abuse screening products. The major product line for NHD is the development, marketing and sales of rapid antibody based diagnostic kits. Infectious diseases spread through food or water is a common, distressing, and sometimes life-threatening problem for millions of people in the United States and around the world. World Health Organization (WHO) studies have shown that in 1996, infectious and parasitic diseases accounted for 43% of the 40 million deaths in developing countries. The U.S. Centers for Disease Control and Prevention (CDC) estimates 76 million people suffer foodborne illnesses each year in the United States, accounting for 325,000 hospitalizations and more than 5,000 deaths.

Morris, James E↗
DOE OSTI2011

Antibody-Based Diagnostics and Production for High Consequence Animal Pathogens

New Horizons Diagnostic Corporation (NHD) develops and manufactures testing products for the detection of bacteria and toxins in human, environmental, surface, food, and water samples for government, municipal and corporate customers. It offers diverse medical products, such as products for testing cholera, gonorrhea, syphilis, and drug abuse screening products. The major product line for NHD is the development, marketing and sale of rapid antibody based diagnostic kits. World Health Organization (WHO) studies have shown that since 1996, infectious and parasitic diseases accounted for 43% of the 40 million deaths in developing countries. In the US alone, the death rate due to infectious diseases rose 58% from 1980 to 1992. The incidence of food-borne illness continues to rise. Emerging infectious diseases in animals with the potential to afflict human populations, such as BSE and avian influenza, continue to increase in number as well. As many as 81 million illnesses and 9,000 deaths occur each year in the US from food-borne microorganisms. In addition, pesticides in food give rise to an estimated 6,000 cancer cases annually in the US. The Environmental Protection Agency (EPA) estimated, in the early 1990s, that approximately 43% of the water systems serving 120 million people had EPA violations, and nearly one million people became ill due to contaminated water. The company also provides bio threat detection products, including diagnostic kits, collection kits, and environmental kits. The collaborative effort, if successful, will permit the identification and development of new and improved diagnostic kits for the targeted diseases. New Horizon Diagnostics matched DOE’s dollars through a Cooperative Research and Development Agreement (CRADA). That CRADA is the subject of this report. The proposal was ultimately funded and the CRADA between NHD and PNNL was established. PNNL managed the activities at the Russian State Diagnostic and Prevention Center for Human and Animal Diseases (DPC) and its collaborators (Ivanovsky Virology Institute, the All-Russian Institute for Animal Health (ARRIAH), and Gamaleya Institute) to support the efforts between NHD and DPC and it collaborators in developing commercially viable diagnostics and therapeutics.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2010

The Microbial DNA Index System (MiDIS): A tool for microbial pathogen source identification

The microbial DNA Index System (MiDIS) is a concept for a microbial forensic database and investigative decision support system that can be used to help investigators identify the sources of microbial agents that have been used in a criminal or terrorist incident. The heart of the proposed system is a rigorous method for calculating source probabilities by using certain fundamental sampling distributions associated with the propagation and mutation of microbes on disease transmission networks. This formalism has a close relationship to mitochondrial and Y-chromosomal human DNA forensics, and the proposed decision support system is somewhat analogous to the CODIS and SWGDAM mtDNA databases. The MiDIS concept does not involve the use of opportunistic collections of microbial isolates and phylogenetic tree building as a basis for inference. A staged approach can be used to build MiDIS as an enduring capability, beginning with a pilot demonstration program that must meet user expectations for performance and validation before evolving into a continuing effort. Because MiDIS requires input from a a broad array of expertise including outbreak surveillance, field microbial isolate collection, microbial genome sequencing, disease transmission networks, and laboratory mutation rate studies, it will be necessary to assemble a national multi-laboratory team to develop such a system. The MiDIS effort would lend direction and focus to the national microbial genetics research program for microbial forensics, and would provide an appropriate forensic framework for interfacing to future national and international disease surveillance efforts.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Enhanced Filter Material for Pathogen Removal

It was determined that spherical silver (Ag) nanoparticles either bound to 316 stainless-steel filter material or as unbound nanomaterials in deionized water had anti-microbial activity on Escherichia coli K-12 (E. coli) cultures when aerosolized or waterborne. This effect however was attenuated when in the presence of the high-salt growth media. Nanoparticles are known to agglomerate in high salt solutions and this may have limited their ability to cross the cell membrane of the microorganisms and cause fatal damage.

36 MATERIALS SCIENCE↗
DOE OSTI2021

Development of Membrane Platforms to Interrogate Host-Pathogen Interactions

Membrane fusion is a critical step in enveloped virus entry and infection; however, molecular understanding of enveloped virus entry and treatment options remain limited. In recent decades, advances in imaging have facilitated the development of methods to study single virus events and membrane organization providing insight towards entry mechanisms. Through these advances, membrane composition and organization have been shown to play a critical role in the entry process. This LDRD uses model membrane platforms and basic biophysics to investigate entry mechanisms of enveloped viruses and understand membrane-based delivery technologies. This team has established foundations for using membrane-based platforms and biophysical techniques at Sandia to characterize membrane fusion.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Genetics and Genomics of Pathogen Resistance in Switchgrass (Final Report)

This project was funded by DOE under Grant no. DE-SC0016108. Originally approved for the 2016-2019 period, two no-cost extensions were solicited and approved, which prolonged the lifespan through July 2021. This final report informs on the results obtained so far from the research implemented. The research hinged on integrating genomics (genomic selection, RNAseq, virus-plant interactions) with classical genetics (conventional breeding) to incorporate durable resistance to fungal (rust) and viral (mosaic) diseases in switchgrass (Panicum virgatum) populations being bred for bioenergy. Higher biomass yield, higher quality (low lignin content), and durable disease resistance are key features to make lignocellulosic switchgrass feedstocks economically competitive and sustainable. Genomic selection is being applied on three generations of a switchgrass population derived from crossing two ecotypes (Kanlow as lowland female and Summer as upland male) with differential performance in terms of biomass yield and quality, disease resistance, and winter survivability. Target populations were screened for rust and mosaic in field and/or lab and phenotyped for biomass yield and quality traits. Genetic analyses were applied across generations to capture the joint inheritance of the targeted traits and predict breeding values for parents and progeny with greater accuracy. Parental and a panel of different switchgrass populations were genotyped with the DArTseq technology to develop SNP (0, 1, 2) and in-silico (presence/absence) DArT markers. Rust inoculations techniques were developed and applied successfully on switchgrass. The original populations (Kanlow and Summer) were sequenced with RNAseq to capture the gene expression profiles across sequential time-points and appraise the basis of greater resistance in the Kanlow vs the Summer ecotype. Constructs of PMV and sPMV mosaic virus were assembled and tested first on proso millet to find the best protocol to use later on switchgrass. Results from the preliminary analyses indicate that 1) ample additive genetic variation is available for selection and improving this inter-ecotypic population for yield, quality, and disease traits, 2) significant gains are to be expected with the genetic correlations being favorable between yield and lignin content and between yield and disease ratings, 3) substantial differences exist in the genetic regions controlling rust resistance in the two ecotypes, 4) co-infection with PMV isolates from Nebraska and its satellite from Kansas elicit severe mosaic symptoms, and 5) two different genetic systems are responsible for imparting resistance to rust and virus in switchgrass.

59 BASIC BIOLOGICAL SCIENCES↗