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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 73 records · Page 4
All sourcesNASA NTRSDOE OSTI
NASA NTRS1974

Experimental-clinical validation of the use of amitetravit, ATP and autologous bone marrow in radiation injuries caused by prolonged radiation

Experimental clinical studies show that early pathogenetic treatment against the effects of prolonged radiation includes amitetravit as a means of increasing natural radio resistance, ATP as protective therapeutic agent, and automyelotransplantation for early pathogenetic treatment. The high effectiveness of the combined use of ATP and amitetravit in tests on dogs indicates an ability to prevent primary damages to genetic structures and accelerated processes of reparation in the first stages of radiopathological processes.

Atamanova, O. M.↗
NASA NTRS1975

Ultrasensitive bioluminescent determinations of adenosine triphosphate (ATP) for investigating the energetics of host-grown microbes

Stability and optimal concentrations of reagents were studied in bioluminescence assay of ATP levels. Luciferase enzyme was prepared and purified using Sephadex G-100. Interdependencies between enzyme and luciferin concentrations in presence of optimal Mg are illustrated. Optimal ionic strength was confirmed to be 0.05 M for the four buffers tested. Adapted features of the R- and H-systems are summarized, as well as the percentages of ATP pools released from representative microbes by heat and chloroform.

Hanks, J. H.↗
NASA NTRS1984

An Investigation of the Adsorption Characteristics of 5'ATP and 5'AMP onto the Surface of Caso4 x 2H2O

A model has been proposed in which solid surfaces can act as a site for cataletic activity of condensation reactions for certain biomolecules. From this model, the adsorption characteristics of 5'ATP and 5'AMP onto the surface of CaSO4.2H2O was chosen for study. It has been proven that 5'ATP and 5'AMP do adsorb onto the surface of CaSO4. Studies were then made to determine the dependence of absorption versus time, concentration, ionic strength and pH. It was found that the adsorption of the nucleotides is highly pH dependent, primarily determined by the phosphate acid groups of the nucleic acid molecule. From this investigation, the data obtained is discussed in relation to the model for the prebiotic earth.

Calderon, J.↗
NASA NTRS1986

An investigation of the adsorption characteristics of 5 prime ATP and 5 prime AMP onto the surface of CaSO sub 4 x 2H sub 2 O

A model has been proposed (Lahev and Chans, 1982) in which solid surfaces can act as a site for catalytic activity of condensation reactions for certain biomolecules. From this model, the adsorption characteristics of 5'ATP and 5'AMP onto the surface of CaSO4 2H2O was chosen for study. It has been proven that 5'ATP and 5'AMP do adsorb onto the surface of CaSO4. Studies were then made to determine the dependence of adsorption versus time, concentration, ionic strength and pH. It was found that the adsorption of the nucleotides is highly pH dependent, primarily determined by the phosphate acid groups of the nucleic acid molecule. From this investigation, the data obtained are discussed in relation to the model for the prebiotic earth.

Calderon, J.↗
NASA NTRS1989

A comparison of an ATPase from the archaebacterium Halobacterium saccharovorum with the F1 moiety from the Escherichia coli ATP Synthase

A purified ATPase associated with membranes from Halobacterium saccharovorum was compared with the F sub 1 moiety from the Escherichia coli ATP Synthase. The halobacterial enzyme was composed of two major (I and II) and two minor subunits (III and IV), whose molecular masses were 87 kDa, 60 kDa, 29 kDa, and 20 kDa, respectively. The isoelectric points of these subunits ranged from 4.1 to 4.8, which in the case of the subunits I and II was consistent with the presence of an excess of acidic amino acids (20 to 22 Mol percent). Peptide mapping of sodium dodecylsulfate-denatured subunits I and II showed no relationship between the primary structures of the individual halobacterial subunits or similarities to the subunits of the F sub 1 ATPase (EC 3.6.1.34) from E. coli. Trypsin inactivation of the halobacterial ATPase was accompanied by the partial degradation of the major subunits. This observation, taken in conjunction with molecular masses of the subunits and the native enzyme, was consistent with the previously proposed stoichiometry of 2:2:1:1. These results suggest that H. saccharovorum, and possibly, Halobacteria in general, possess an ATPase which is unlike the ubiquitous F sub o F sub 1 - ATP Synthase.

Stan-Lotter, Helga↗
NASA NTRS1995

Activation of the ATP-ubiquitin-proteasome pathway in skeletal muscle of cachectic rats bearing a hepatoma

Rats implanted with Yoshida ascites hepatoma (YAH) show a rapid and selective loss of muscle protein due mainly to a marked increase (63-95%) in the rate of protein degradation (compared with rates in muscles of pair-fed controls). To define which proteolytic pathways contribute to this increase, epitrochlearis muscles from YAH-bearing and control rats were incubated under conditions that modify different proteolytic systems. Overall proteolysis in either group of rats was not affected by removal of Ca2+ or by blocking the Ca(2+)-dependent proteolytic system. Inhibition of lysosomal function with methylamine reduced proteolysis (-12%) in muscles from YAH-bearing rats, but not in muscles of pair-fed rats. When ATP production was also inhibited, the remaining accelerated proteolysis in muscles of tumor-bearing rats fell to control levels. Muscles of YAH-bearing rats showed increased levels of ubiquitin-conjugated proteins and a 27-kDa proteasome subunit in Western blot analysis. Levels of mRNA encoding components of proteolytic systems were quantitated using Northern hybridization analysis. Although their total RNA content decreased 20-38%, pale muscles of YAH-bearing rats showed increased levels of ubiquitin mRNA (590-880%) and mRNA for multiple subunits of the proteasome (100-215%). Liver, kidney, heart, and brain showed no weight loss and no change in these mRNA species. Muscles of YAH-bearing rats also showed small increases (30-40%) in mRNA for cathepsins B and D, but not for calpain I or heat shock protein 70. Our findings suggest that accelerated muscle proteolysis and muscle wasting in tumor-bearing rats result primarily from activation of the ATP-dependent pathway involving ubiquitin and the proteasome.

NASA Discipline Musculoskeletal↗
NASA NTRS1992

Dietary protein deficiency reduces lysosomal and nonlysosomal ATP-dependent proteolysis in muscle

When rats are fed a protein deficient (PD) diet for 7 days, rates of proteolysis in skeletal muscle decrease by 40-50% (N. E. Tawa, Jr., and A. L. Goldberg. Am. J. Physiol. 263 (Endocrinol. Metab. 26): E317-325, 1992). To identify the underlying biochemical adaptations, we measured different proteolytic processes in incubated muscles. The capacity for intralysosomal proteolysis, as shown by sensitivity to methylamine or lysosomal protease inhibitors, fell 55-75% in muscles from PD rats. Furthermore, extracts of muscles of PD rats showed 30-70% lower activity of many lysosomal proteases, including cathepsins B, H, and C, and carboxypeptidases A and C, as well as other lysosomal hydrolases. The fall in cathepsin B and proteolysis was evident by 3 days on the PD diet, and both returned to control levels 3 days after refeeding of the normal diet. In muscles maintained under optimal conditions, 80-90% of protein breakdown occurs by nonlysosomal pathways. In muscles of PD rats, this ATP-dependent process was also 40-60% slower. Even though overall proteolysis decreased in muscles of PD rats, their capacity for Ca(2+)-dependent proteolysis increased (by 66%), as did the activity of the calpains (+150-250%). Thus the lysosomal and the ATP-dependent processes decrease coordinately and contribute to the fall in muscle proteolysis in PD animals.

Non-NASA Center↗
NASA NTRS2010

Evaluation of an ATP Assay to Quantify Bacterial Attachment to Surfaces in Reduced Gravity

Aim: To develop an assay to quantify the biomass of attached cells and biofilm formed on wetted surfaces in variable-gravity environments. Methods and Results: Liquid cultures of Pseudomonas aeruginosa were exposed to 30-35 brief cycles of hypergravity (< 2-g) followed by free fall (i.e., reduced gravity) equivalent to either lunar-g (i.e., 0.17 normal Earth gravity) or micro-g (i.e., < 0.001 normal Earth gravity) in an aircraft flying a series of parabolas. Over the course of two days of parabolic flight testing, 504 polymer or metal coupons were exposed to a stationary-phase population of P. aeruginosa strain ERC1 at a concentration of 1.0 x 10(exp 5) cells per milliliter. After the final parabola on each flight test day, half of the material coupon samples were treated with either 400 micro-g/L ionic silver fluoride (microgravity-exposed cultures) or 1% formalin (lunar-gravity-exposed cultures). The remaining sample coupons from each flight test day were not treated with a fixative. All samples were returned to the laboratory for analysis within 2 hours of landing, and all biochemical assays were completed within 8 hours of exposure to variable gravity. The intracellular ATP luminescent assay accurately reflected cell physiology compared to both cultivation-based and direct-count microscopy analyses. Cells exposed to variable gravity had more than twice as much intracellular ATP as control cells exposed only to normal Earth gravity.

Birmele, Michele N.↗
DOE OSTI2021

Enhancement of anticancer drug sensitivity in multidrug resistance cells overexpressing ATP-binding cassette (ABC) transporter ABCC10 by CP55, a synthetic derivative of 5-cyano-6-phenylpyrimidin

Highlights: • Multidrug resistance (MDR) in cancer is one of the major obstacles in chemotherapy. • ABCC10 mediates resistance to wide spectrum of chemotherapeutic agents, but only limited number of studies are available. • Overexpression of ABCC10 has been linked to various types of cancers including colorectal, gastric and lung cancer. • CP55 is a potent ABCC10 inhibitor which enhances the anticancer drug sensitivity in ABCC10-overexpression MDR cells. ATP-binding cassette (ABC) transporter C10 (ABCC10), also named multidrug resistance protein 7 (MRP7), is a member of ABC transporter superfamily and has been revealed to transport a wide range of chemotherapeutic agents including taxanes, epothilone B, Vinca alkaloids, and anthracyclines. In our previous study, a 5-cyano-6-phenylpyrimidin derivative CP55 was synthesized and found significantly reversal effect of multidrug resistance (MDR) mediated by ABCB1. In this study, we found CP55 also efficiently reversed MDR mediated by ABCC10. Our in vitro study showed that co-treatment with CP55 significantly increased the efficacy of ABCC10-substrate anticancer drugs in MDR cells overexpressing ABCC10. Furthermore, we showed that treatment with CP55 increased the intracellular accumulation of [{sup 3}H]-labeled anticancer drugs and in-turn decreasing drug efflux by inhibiting the transport activity, without altering ABCC10 protein ex-pression level or cellular localization. Potential CP55-ABCC10 interactions were predicted via docking analysis using human ABCC10 homology model and obtained high docking score. Therefore, CP55 represents a promising therapeutic agent in the combinational treatment of chemo-resistant cancer related to ABCC10.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2006

Star Tracker Based ATP System Conceptual Design and Pointing Accuracy Estimation

A star tracker based beaconless (a.k.a. non-cooperative beacon) acquisition, tracking and pointing concept for precisely pointing an optical communication beam is presented as an innovative approach to extend the range of high bandwidth (> 100 Mbps) deep space optical communication links throughout the solar system and to remove the need for a ground based high power laser as a beacon source. The basic approach for executing the ATP functions involves the use of stars as the reference sources from which the attitude knowledge is obtained and combined with high bandwidth gyroscopes for propagating the pointing knowledge to the beam pointing mechanism. Details of the conceptual design are presented including selection of an orthogonal telescope configuration and the introduction of an optical metering scheme to reduce misalignment error. Also, estimates are presented that demonstrate that aiming of the communications beam to the Earth based receive terminal can be achieved with a total system pointing accuracy of better than 850 nanoradians (3 sigma) from anywhere in the solar system.

star tracker↗
DOE OSTI2021

Relaxed tarantula skeletal muscle has two ATP energy-saving mechanisms

Myosin molecules in the relaxed thick filaments of striated muscle have a helical arrangement in which the heads of each molecule interact with each other, forming the interacting-heads motif (IHM). In relaxed mammalian skeletal muscle, this helical ordering occurs only at temperatures >20°C and is disrupted when temperature is decreased. Recent x-ray diffraction studies of live tarantula skeletal muscle have suggested that the two myosin heads of the IHM (blocked heads [BHs] and free heads [FHs]) have very different roles and dynamics during contraction. Here, we explore temperature-induced changes in the BHs and FHs in relaxed tarantula skeletal muscle. We find a change with decreasing temperature that is similar to that in mammals, while increasing temperature induces a different behavior in the heads. At 22.5°C, the BHs and FHs containing ADP.Pi are fully helically organized, but they become progressively disordered as temperature is lowered or raised. Our interpretation suggests that at low temperature, while the BHs remain ordered the FHs become disordered due to transition of the heads to a straight conformation containing Mg.ATP. Above 27.5°C, the nucleotide remains as ADP.Pi, but while BHs remain ordered, half of the FHs become progressively disordered, released semipermanently at a midway distance to the thin filaments while the remaining FHs are docked as swaying heads. We propose a thermosensing mechanism for tarantula skeletal muscle to explain these changes. Our results suggest that tarantula skeletal muscle thick filaments, in addition to having a superrelaxation–based ATP energy-saving mechanism in the range of 8.5–40°C, also exhibit energy saving at lower temperatures (<22.5°C), similar to the proposed refractory state in mammals.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Jasmonate primes plant responses to extracellular ATP

SUMMARYExtracellular ATP (eATP) signaling in Arabidopsis thaliana is mediated by the purinoceptor P2K1. Previous studies have clarified that the downstream transcriptional responses to eATP involve jasmonate (JA)‐based signaling components such as the JA receptor (COI1) and JA‐responsive bHLH transcription factors (MYCs). However, the specific contributions of JA itself on eATP signaling are unexplored. Here, we report that JA primes plant responses to eATP through P2K1. Our findings show that JA treatment significantly upregulates P2K1 transcription, corroborating our observation that JA facilitates eATP‐induced cytosolic calcium elevation and transcriptional reprogramming in a JA signaling‐dependent manner. Additionally, we find that salicylic acid pre‐treatment represses eATP‐induced plant response. These results suggest that JA accumulation during biotic or abiotic stresses potentiates eATP signaling, enabling plants to better cope with subsequent stress events.

Jewell, Jeremy B. [Institute of Biological Chemist↗
DOE OSTI2022

A non-traditional crystal-based compound screening method targeting the ATP binding site of Plasmodium falciparum GRP78 for identification of novel nucleoside analogues

Drug resistance to front-line malarial treatments represents an ongoing threat to control malaria, a vector borne infectious disease. The malarial parasite, Plasmodium falciparum has developed genetic variants, conferring resistance to the current standard therapeutic artemisinin and its derivatives commonly referred to as artemisinin-combination therapies (ACTs). Emergence of multi-drug resistance parasite genotypes is a warning of potential treatment failure, reaffirming the urgent and critical need to find and validate alternate drug targets to prevent the spread of disease. An attractive and novel drug target includes glucose-regulated protein 78 kDa (GRP78, or BiP), an essential molecular chaperone protein involved in the unfolded protein response that is upregulated in ACT treated P. falciparum parasites. We have shown that both sequence and structure are closely related to human GRP78 (hGRP78), a chaperone belonging to the HSP70 class of ATPase proteins, which is often upregulated in cellular stress responses and cancer. By screening a library of nucleoside analogues, we identified eight ‘hit’ compounds binding at the active site of the ATP binding domain of P. falciparum GRP78 using a high-throughput ligand soaking screen using x-ray crystallography. These compounds were further evaluated using protein thermal shift assays to assess target binding activity. The nucleoside analogues identified from our screen provide a starting point for the development of more potent and selective antimalarial inhibitors. In addition, we have established a well-defined, high-throughput crystal-based screening approach that can be applied to many crystallizable P. falciparum proteins for generating anti-Plasmodium specific compounds.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Deletion of an African Swine Fever Virus ATP-Dependent RNA Helicase QP509L from the Highly Virulent Georgia 2010 Strain Does Not Affect Replication or Virulence

African swine fever virus (ASFV) produces a lethal disease (ASF) in domestic pigs, which is currently causing a pandemic deteriorating pig production across Eurasia. ASFV is a large and structurally complex virus with a large genome harboring more than 150 genes. ASFV gene QP509L has been shown to encode for an ATP-dependent RNA helicase, which appears to be important for efficient virus replication. Here, we report the development of a recombinant virus, ASFV-G-ΔQP509L, having deleted the QP509L gene in the highly virulent field isolate ASFV Georgia 2010 (ASFV-G). It is shown that ASFV-G-ΔQP509L replicates in primary swine macrophage cultures as efficiently as the parental virus ASFV-G. In addition, the experimental inoculation of pigs with 10 2 HAD 50 by the intramuscular route produced a slightly protracted but lethal clinical disease when compared to that of animals inoculated with virulent parental ASFV-G. Viremia titers in animals infected with ASFV-G-ΔQP509L also had slightly protracted kinetics of presentation. Therefore, ASFV gene QP509L is not critical for the processes of virus replication in swine macrophages, nor is it clearly involved in virus replication and virulence in domestic pigs.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Structural and biophysical analysis of a Haemophilus influenzae tripartite ATP-independent periplasmic (TRAP) transporter

Tripartite ATP-independent periplasmic (TRAP) transporters are secondary-active transporters that receive their substrates via a soluble-binding protein to move bioorganic acids across bacterial or archaeal cell membranes. Recent cryo-electron microscopy (cryo-EM) structures of TRAP transporters provide a broad framework to understand how they work, but the mechanistic details of transport are not yet defined. Here we report the cryo-EM structure of the Haemophilus influenzae N-acetylneuraminate TRAP transporter (HiSiaQM) at 2.99 Å resolution (extending to 2.2 Å at the core), revealing new features. The improved resolution (the previous HiSiaQM structure is 4.7 Å resolution) permits accurate assignment of two Na + sites and the architecture of the substrate-binding site, consistent with mutagenic and functional data. Moreover, rather than a monomer, the HiSiaQM structure is a homodimer. We observe lipids at the dimer interface, as well as a lipid trapped within the fusion that links the SiaQ and SiaM subunits. We show that the affinity (K D ) for the complex between the soluble HiSiaP protein and HiSiaQM is in the micromolar range and that a related SiaP can bind HiSiaQM. This work provides key data that enhances our understanding of the ‘elevator-with-an-operator’ mechanism of TRAP transporters.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1972

A reusable prepositioned ATP reaction chamber

Luminescence biometer detects presence of life by means of light-emitting chemical reaction of luciferin and luciferase with adenosine triphosphate (ATP) that occurs in all living cells. Amount of light in reaction chamber is measured to determine presence and extent of life.

Hoffman, D. G.↗