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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 343 records · Page 19

Pilot Readiness Development Program for Autonomous Pathogen Detection System (APDS) (Final Report)

The purpose of this CRADA was to develop, integrate, and test design changes to LLNL’s field prototype autonomous pathogen detection system (APDS). The desired result of this project was an improved design of the APDS, along with test data characterizing performance of the new hardware, software, and processes. This improved design was to be closer to the final production design for operation. The third amendment to the Statement of Work (SOW) significantly redefined the scope of the work from general improvements to creating a NGSS built system that included the improvements from before and prepared the system for head to head testing for the BioWatch Gen-3 program. All deliverables were met on time and on budget.

Henderer, Bruce D.↗

Pilot Readiness Development Program for Autonomous Pathogen Detection System (APDS) Final Report CRADA No. TC02115.0

The purpose of this CRADA was to develop, integrate, and test design changes to LLNL’s field prototype autonomous pathogen detection system (APDS). The desired result of this project was an improved design of the APDS, along with test data characterizing performance of the new hardware, software, and processes. This improved design was to be closer to the final production design for operation. The third amendment to the Statement of Work (SOW) significantly redefined the scope of the work from general improvements to creating a NGSS built system that included the improvements from before and prepared the system for head to head testing for the BioWatch Gen-3 program. All deliverables were met on time and on budget.

59 BASIC BIOLOGICAL SCIENCES↗

Investigation of Polymetric Biofilms Formed by Dangerous Pathogens, and the Prevention of Their Formation by Disinfectants and Bacteriophages Final Report CRADA No. TC02145.0

This was a collaborative effort between Lawrence Livermore National Security, LLC as manager and operator of Lawrence Livermore National Laboratory (LLNL) and Intralytix Inc., to study biofilms formed on the surfaces of polymers by especially dangerous pathogens and nosocomial infections, to explore the possibility of decontamination of surfaces using different classes of disinfectants and specific bacteriophages.

59 BASIC BIOLOGICAL SCIENCES↗

Mechanism of fusion of pathogenic enveloped viruses with the endosomal membrane

Dengue virus is a devastating human pathogen responsible for millions of infections each year. No antiviral therapies for Dengue currently exist, making effective treatment of the virus challenging. Dengue is taken into the cell through endocytosis. Low-pH mediated structural rearrangements of the envelope protein E leads to the formation of fusogenic E trimers that facilitate membrane fusion with late endosomes. The fusion mechanism is not fully understood, but is a key target for inhibiting the viral infection pathway. An important aspect of fusion is the dependence on endosomal membrane composition, and in particular, the requirement of anionic lipids. This study aims to characterize the biophysical reasons for this dependence. The work includes experimental studies and molecular simulations of the interactions of E with lipid membranes. These approaches revealed the structure of E bound to lipid membranes including the depth of its insertion into the membrane and the average angle with respect to the membrane, the fundamental interactions involved, the dependence of adsorption and anchoring energy on membrane composition, the membrane curvature induced upon insertion, and the correlation of the above with fusion efficiency of virus like particles (VLPs) with liposomes. As a part of this work we developed a new biophysical technique to measure the energy for pulling E out of a membrane, and distinguished anchoring (pull-out) and binding energies for this nonequilibrium system. We also developed a modeling approach combining molecular and continuum approaches to provide the first theoretical estimate of the binding energy. Taken together, this work lays the foundation for developing a systematic fundamental understanding of fusion in enveloped viruses that has been elusive to date.

59 BASIC BIOLOGICAL SCIENCES↗

Detection of Upwind Pathogens Using Aircraft and Ground Stations

The first reported investigations of microorganism occurrence in the air can be traced back to early 19th century. Since then the study of bioaerosols have come a long way, however, it remains a poorly understood area(Després et al. 2012). The actual identity, diversity, and abundance of distinct types of bioaerosol particles as well as their temporal and spatial variability are not well characterized. Bioaerosols play a key role in the dispersal of reproductive units from plants and microbes (pollen, spores, etc.), for which the atmosphere enables transport over geographic barriers and long distances(FröhlichNowoisky et al. 2016). The dispersal of plant, animal, and human pathogens and allergens has major implications for agriculture and public health. We hypothesized that airborne microbes can reach the upper atmosphere (i.e., above the boundary layer ~2 km in altitude) and deliver disease into downwind destinations. We utilized a unique set of bioaerosol samples from atmospheric aircraft observatories (NASA) to study the microbial diversity, abundance, and viability of bioaerosols reaching California during the springtime when the jet stream delivers the largest amount of Asian transpacific aerosols to N. America. We collaborated with a NASA Ames with unique access to upper troposphere and lower stratosphere bioaerosol samples on the Pacific Coast of California. We analyzed the aerosol samples using microbiological techniques, shotgun metagenomic sequencing and advanced bioinformatic tools to identify the viable and total microbial species that were detected. A number of bacterial and fungal species were identified. This study provided a deeper understanding of the microbial species that can survive in the upper atmospheric conditions. This study set the foundation for future studies on better understanding of the potential impact of airborne microbes on disease transmission affecting human, animal, or crop health.

59 BASIC BIOLOGICAL SCIENCES↗

Pathogen Management Kit (Technical Bulletin)

Sandia National Laboratories (SNL) has developed and produced a simple add-on kit (Pathogen Management Kit, or PMK) that can quickly add on to ventilators of all types to disinfect exhaled air to keep healthcare workers safe.

42 ENGINEERING↗

Taking the Air Out of Respiratory Pandemics: An R&D Effort for Developing New, Far Less Disruptive and Frightening Protective Measures to Extinguish Airborne Pathogen Outbreaks

This short concept article discusses four specific ways to eradicate respiratory pandemics once and for all. These include: Protecting the nose, mouth, throat and lungs; New hygiene regimens; Clearing the air; and Biophysical interventions. Technical breakthoughs in all four of these areas would not only protect people from life-threatening pathogens, but also take the dread out of respiratory disease outbreaks.

59 BASIC BIOLOGICAL SCIENCES↗

Genetics and Genomics of Pathogen Resistance in Switchgrass

This project investigates the genetic and genomic bases of resistance/tolerance to disease in switchgrass (Panicum virgatum) populations developed as bioenergy feedstock. The focus is placed populations adapted to the Central Great Plains derived from the hybridization of upland and lowland ecotypes, represented by cultivars Summer and Kanlow, respectively. Resistance was investigated against the rust disease caused by the fungus Puccinia novo-panici (syn. P emaculata) and mosaic disease caused by the virus complex of Panicum mosaic virus and its satellite. Objectives of the project were: 1) to elucidate the genetic and genomic bases of resistance/tolerance in locally adapted upland and lowland switchgrass breeding populations with contrasting disease symptoms under field conditions; 2) determine the molecular underpinnings of why cv Kanlow has broad resistance/tolerance to pathogens; and 3) discover the molecular differences that permit systemic viral infections in some switchgrass plants but not in other genetically-related plants.

09 BIOMASS FUELS↗

In silico analyses of diversity and dissemination of antimicrobial resistance genes and mobile genetics elements, for plasmids of enteric pathogens

The antimicrobial resistance (AMR) mobilome plays a key role in the dissemination of resistance genes encoded by mobile genetics elements (MGEs) including plasmids, transposons (Tns), and insertion sequences (ISs). These MGEs contribute to the dissemination of multidrug resistance (MDR) in enteric bacterial pathogens which have been considered as a global public health risk. To further understand the diversity and distribution of AMR genes and MGEs across different plasmid types, we utilized multiple sequence-based computational approaches to evaluate AMR-associated plasmid genetics. A collection of 1,309 complete plasmid sequences from Gammaproteobacterial species, including 100 plasmids from each of the following 14 incompatibility (Inc) types: A/C, BO, FIA, FIB, FIC, FIIA, HI1, HI2, I1, K, M, N, P except W, where only 9 sequences were available, was extracted from the National Center for Biotechnology Information (NCBI) GenBank database using BLAST tools. The extracted FASTA files were analyzed using the AMRFinderPlus web-based tools to detect antimicrobial, disinfectant, biocide, and heavy metal resistance genes and ISFinder to identify IS/Tn MGEs within the plasmid sequences. In silico prediction based on plasmid replicon types showed that the resistance genes were diverse among plasmids, yet multiple genes were widely distributed across the plasmids from enteric bacterial species. These findings provide insights into the diversity of resistance genes and that MGEs mediate potential transmission of these genes across multiple plasmid replicon types. This notion was supported by the observation that many IS/Tn MGEs and resistance genes known to be associated with them were common across multiple different plasmid types. Our results provide critical insights about how the diverse population of resistance genes that are carried by the different plasmid types can allow for the dissemination of AMR across enteric bacteria. The results also highlight the value of computational-based approaches and in silico analyses for the assessment of AMR and MGEs, which are important elements of molecular epidemiology and public health outcomes.

59 BASIC BIOLOGICAL SCIENCES↗

With a Little Help from My Cell Wall: Structural Modifications in Pectin May Play a Role to Overcome Both Dehydration Stress and Fungal Pathogens

Cell wall structural modifications through pectin cross-linkages between calcium ions and/or boric acid may be key to mitigating dehydration stress and fungal pathogens. Water loss was profiled in a pure pectin system and in vivo. While calcium and boron reduced water loss in pure pectin standards, the impact on Allium species was insignificant (p > 0.05). Nevertheless, synchrotron X-ray microscopy showed the localization of exogenously applied calcium to the apoplast in the epidermal cells of Allium fistulosum. Exogenous calcium application increased viscosity and resistance to shear force in Allium fistulosum, suggesting the formation of calcium cross-linkages (“egg-box” structures). Moreover, Allium fistulosum (freezing tolerant) was also more tolerant to dehydration stress compared to Allium cepa (freezing sensitive). Furthermore, the addition of boric acid (H 3 BO 3 ) to pure pectin reduced water loss and increased viscosity, which indicates the formation of RG-II dimers. The Arabidopsis boron transport mutant, bor1, expressed greater water loss and, based on the lesion area of leaf tissue, a greater susceptibility to Colletotrichum higginsianum and Botrytis cinerea. While pectin modifications in the cell wall are likely not the sole solution to dehydration and biotic stress resistance, they appear to play an important role against multiple stresses.

59 BASIC BIOLOGICAL SCIENCES↗

Making a Monkey out of Human Immunodeficiency Virus/Simian Immunodeficiency Virus Pathogenesis: Immune Cell Depletion Experiments as a Tool to Understand the Immune Correlates of Protection and Pathogenicity in HIV Infection

Understanding the underlying mechanisms of HIV pathogenesis is critical for designing successful HIV vaccines and cure strategies. However, achieving this goal is complicated by the virus’s direct interactions with immune cells, the induction of persistent reservoirs in the immune system cells, and multiple strategies developed by the virus for immune evasion. Meanwhile, HIV and SIV infections induce a pandysfunction of the immune cell populations, making it difficult to untangle the various concurrent mechanisms of HIV pathogenesis. Over the years, one of the most successful approaches for dissecting the immune correlates of protection in HIV/SIV infection has been the in vivo depletion of various immune cell populations and assessment of the impact of these depletions on the outcome of infection in non-human primate models. Here, we present a detailed analysis of the strategies and results of manipulating SIV pathogenesis through in vivo depletions of key immune cells populations. Although each of these methods has its limitations, they have all contributed to our understanding of key pathogenic pathways in HIV/SIV infection.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

A novel bivalent chromatin associates with rapid induction of camalexin biosynthesis genes in response to a pathogen signal in Arabidopsis

Temporal dynamics of gene expression underpin responses to internal and environmental stimuli. In eukaryotes, regulation of gene induction includes changing chromatin states at target genes and recruiting the transcriptional machinery that includes transcription factors. As one of the most potent defense compounds in Arabidopsis thaliana , camalexin can be rapidly induced by bacterial and fungal infections. Though several transcription factors controlling camalexin biosynthesis genes have been characterized, how the rapid activation of genes in this pathway upon a pathogen signal is enabled remains unknown. By combining publicly available epigenomic data with in vivo chromatin modification mapping, we found that camalexin biosynthesis genes are marked with two epigenetic modifications with opposite effects on gene expression, trimethylation of lysine 27 of histone 3 (H3K27me3) (repression) and acetylation of lysine 18 of histone 3 (H3K18ac) (activation), to form a previously uncharacterized type of bivalent chromatin. Mutants with reduced H3K27me3 or H3K18ac suggested that both modifications were required to determine the timing of gene expression and metabolite accumulation at an early stage of the stress response. Our study indicates that the H3K27me3-H3K18ac bivalent chromatin, which we name as kairostat, plays an important role in controlling the timely induction of gene expression upon stress stimuli in plants.

59 BASIC BIOLOGICAL SCIENCES↗

Effects of mutation and some environmental factors on the physiology and pathogenicity of selected bacteria

Studies with mutants of Staphylococcus aureus lacking some virulence factors suggest that the presence of deoxyribonuclease correlates with mouse pathogenicity of S. aureus, while the ability to ferment mannitol or the possession of coagulases are not required for virulence. Autotrophy investigations on mycobacteria demonstrate a complete correlation between the ability to grow with hydrogen and the species of scotochromogenic mycobacterium tested. All tested strains of M. gordonae, a saprophyte, could grow autotrophically while none of the tested strains of M. scrofulaceum, a clinically important species, possessed this ability. A series of heat tolerant mutants of Pseudomonas fluorescences were obtained which can grow at temperatures up to 54 C, in contrast to a maximum growth temperature of 37 C for the wild type.

Decicco, B. T.↗

Survival of Potentially Pathogenic Human-Associated Bacteria in the Rhizosphere of Hydroponically Grown Wheat

Plants may serve as reservoirs for human-associated bacteria (H-AB) in long-term space missions containing bioregenerative life support systems. The current study examined the abilities of five human-associated potential pathogens, Pseudomonas aeruginosa, Pseudomonas cepacia, Staphylococcus aureus, Streptococcus pyogenes, and Escherichia coli, to colonize and grow in the rhizosphere of hydroponically grown wheat, a candidate crop for life support. All of these bacteria have been recovered from past NASA missions and present potential problems for future missions. The abilities of these organisms to adhere to the roots of axenic five-day-old wheat (Triticum aestivum L. cv. Yecora rojo) were evaluated by enumeration of the attached organisms after a one hour incubation of roots in a suspension (approximately 10(exp 8 cu/ml)) of the H-AB. Results showed that a greater percentage of P. aeruginosa cells adhered to the wheat roots than the other four H-AB. Similarly incubated seedlings were also grown under attempted axenic conditions for seven days to examine the potential of each organism to proliferate in the rhizosphere (root colonization capacity). P. cepacia and P. aeruginosa showed considerable growth. E. coli and S. aureus showed no significant growth, and S. pyogenes died off in the wheat rhizosphere. Studies examining the effects of competition on the survival of these microorganisms indicated that P. aeruginosa was the only organism that survived in the rhizosphere of hydroponically grown wheat in the presence of different levels of microbial competition.

Morales, Anabelle↗

Differential effects of catecholamines on in vitro growth of pathogenic bacteria

Supplementation of minimal medium inoculated with bacterial cultures with norepinephrine, epinephrine, dopamine, or isoproterenol resulted in marked increases in growth compared to controls. Norepinephrine and dopamine had the greatest enhancing effects on growth of cultures of Pseudomonas aeruginosa and Klebsiella pneumoniae, while epinephrine and isoproterenol also enhanced growth to a lesser extent. The growth of Escherichia coli in the presence of norepinephrine was greater than growth in the presence of the three other neurochemicals used in the study. Growth of Staphylococcus aureus was also enhanced in the presence of norepinephrine, but not to the same degree as was the growth of gram negative bacteria. Addition of culture supernatants from E. coli cultures that had been grown in the presence of norepinephrine was able to enhance the growth of K. pneumoniae. Addition of the culture supernatant fluid culture from E. coli cultures that had been grown in the presence of norepinephrine did not enhance growth of P. aeruginosa or S. aureus. Culture supernatant fluids from bacteria other than E. coli grown in the presence of norepinephrine were not able to enhance the growth of any bacteria tested. The results suggest that catecholamines can enhance growth of pathogenic bacteria, which may contribute to development of pathogenesis; however, there is no uniform effect of catecholamines on bacterial growth.

Non-NASA Center↗