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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 811 records · Page 45
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

Aptamer Applications in Neuroscience

Being the predominant cause of disability, neurological diseases have received much attention from the global health community. Over a billion people suffer from one of the following neurological disorders: dementia, epilepsy, stroke, migraine, meningitis, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington’s disease, prion disease, or brain tumors. The diagnosis and treatment options are limited for many of these diseases. Aptamers, being small and non-immunogenic nucleic acid molecules that are easy to chemically modify, offer potential diagnostic and theragnostic applications to meet these needs. This review covers pioneering studies in applying aptamers, which shows promise for future diagnostics and treatments of neurological disorders that pose increasingly dire worldwide health challenges.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Optimization of Molecular Methods for Detecting Duckweed-Associated Bacteria

The bacterial colonization dynamics of plants can differ between phylogenetically similar bacterial strains and in the context of complex bacterial communities. Quantitative methods that can resolve closely related bacteria within complex communities can lead to a better understanding of plant–microbe interactions. However, current methods often lack the specificity to differentiate phylogenetically similar bacterial strains. In this study, we describe molecular strategies to study duckweed–associated bacteria. We first systematically optimized a bead-beating protocol to co-isolate nucleic acids simultaneously from duckweed and bacteria. We then developed a generic fingerprinting assay to detect bacteria present in duckweed samples. To detect specific duckweed–bacterium associations, we developed a genomics-based computational pipeline to generate bacterial strain-specific primers. These strain-specific primers differentiated bacterial strains from the same genus and enabled the detection of specific duckweed–bacterium associations present in a community context. Moreover, we used these strain-specific primers to quantify the bacterial colonization of duckweed by normalization to a plant reference gene and revealed differences in colonization levels between strains from the same genus. Lastly, confocal microscopy of inoculated duckweed further supported our PCR results and showed bacterial colonization of the duckweed root–frond interface and root interior. The molecular methods introduced in this work should enable the tracking and quantification of specific plant-microbe associations within plant-microbial communities.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Polyelectrolyte Complexation of Oligonucleotides by Charged Hydrophobic—Neutral Hydrophilic Block Copolymers

Polyelectrolyte complex micelles (PCMs, core-shell nanoparticles formed by complexation of a polyelectrolyte with a polyelectrolyte-hydrophilic neutral block copolymer) offer a solution to the critical problem of delivering therapeutic nucleic acids, Despite this, few systematic studies have been conducted on how parameters such as polycation charge density, hydrophobicity, and choice of charged group influence PCM properties, despite evidence that these strongly influence the complexation behavior of polyelectrolyte homopolymers. In this article, we report a comparison of oligonucleotide PCMs and polyelectrolyte complexes formed by poly(lysine) and poly((vinylbenzyl) trimethylammonium) (PVBTMA), a styrenic polycation with comparatively higher charge density, increased hydrophobicity, and a permanent positive charge. All of these differences have been individually suggested to provide increased complex stability, but we find that PVBTMA in fact complexes oligonucleotides more weakly than does poly(lysine), as measured by stability versus added salt. Using small angle X-ray scattering and electron microscopy, we find that PCMs formed from both cationic blocks exhibit very similar structure-property relationships, with PCM radius determined by the cationic block size and shape controlled by the hybridization state of the oligonucleotides. These observations narrow the design space for optimizing therapeutic PCMs and provide new insights into the rich polymer physics of polyelectrolyte self-assembly.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2022

Experimental Senecavirus A Infection of Bovine Cell Lines and Colostrum-Deprived Calves

Senecavirus A (SVA) is a causative agent for vesicular disease in swine, which is clinically indistinguishable from other vesicular diseases of swine including foot-and-mouth disease (FMD). Recently, it was reported that buffalo in Guangdong, China were experiencing clinical symptoms similar to FMD including mouth ulcers and lameness tested positive for SVA. The objective of this study was to determine the susceptibility of cattle (Bos taurus) to SVA infection. Initial in vitro work using the PrimeFlow assay demonstrated that bovine cell lines and peripheral blood mononuclear cells from cattle were susceptible to SVA infection. Subsequently, six colostrum-deprived Holstein calves were challenged with SVA intranasally. No vesicular lesions were observed after challenge. Serum, oral, nasal, and rectal swabs tested for SVA nucleic acid did not support significant viral replication and there was no evidence of seroconversion. Therefore, demonstrating cattle from this study were not susceptible to experimental SVA infection.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Molecular insights into RNA and DNA helicase evolution from the determinants of specificity for a DEAD-box RNA helicase

How different helicase families with a conserved catalytic ‘helicase core’ evolved to function on varied RNA and DNA substrates by diverse mechanisms remains unclear. In this study, we used Mss116, a yeast DEAD-box protein that utilizes ATP to locally unwind dsRNA, to investigate helicase specificity and mechanism. Our results define the molecular basis for the substrate specificity of a DEAD-box protein. Additionally, they show that Mss116 has ambiguous substrate-binding properties and interacts with all four NTPs and both RNA and DNA. The efficiency of unwinding correlates with the stability of the ‘closed-state’ helicase core, a complex with nucleotide and nucleic acid that forms as duplexes are unwound. Crystal structures reveal that core stability is modulated by family-specific interactions that favor certain substrates. This suggests how present-day helicases diversified from an ancestral core with broad specificity by retaining core closure as a common catalytic mechanism while optimizing substrate-binding interactions for different cellular functions.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2017

Divide and Conquer (DC) BLAST: fast and easy BLAST execution within HPC environments

Bioinformatics is currently faced with very large-scale data sets that lead to computational jobs, especially sequence similarity searches, that can take absurdly long times to run. For example, the National Center for Biotechnology Information (NCBI) Basic Local Alignment Search Tool (BLAST and BLAST+) suite, which is by far the most widely used tool for rapid similarity searching among nucleic acid or amino acid sequences, is highly central processing unit (CPU) intensive. While the BLAST suite of programs perform searches very rapidly, they have the potential to be accelerated. In recent years, distributed computing environments have become more widely accessible and used due to the increasing availability of high-performance computing (HPC) systems. Therefore, simple solutions for data parallelization are needed to expedite BLAST and other sequence analysis tools. However, existing software for parallel sequence similarity searches often requires extensive computational experience and skill on the part of the user. In order to accelerate BLAST and other sequence analysis tools, Divide and Conquer BLAST (DCBLAST) was developed to perform NCBI BLAST searches within a cluster, grid, or HPC environment by using a query sequence distribution approach. Scaling from one (1) to 256 CPU cores resulted in significant improvements in processing speed. Thus, DCBLAST dramatically accelerates the execution of BLAST searches using a simple, accessible, robust, and parallel approach. DCBLAST works across multiple nodes automatically and it overcomes the speed limitation of single-node BLAST programs. DCBLAST can be used on any HPC system, can take advantage of hundreds of nodes, and has no output limitations. Thus, this freely available tool simplifies distributed computation pipelines to facilitate the rapid discovery of sequence similarities between very large data sets.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1970

Cell fine structure and function - Past and present

Electron microscopic studies of nerve membrane fine structure, discussing cell membrane multienzyme and macromolecular energy and information transduction, protein synthesis and nucleic acids interrelations

Fernandez-Moran, H.↗
NASA NTRS1971

Primordial organic chemistry and the origin of life.

Aspects of Darwinian revolution are discussed together with spontaneous generation, the inorganic chemical evolution, the primitive atmosphere, and interstellar matter. The significance of the change of the earth's reducing atmosphere to an atmosphere with oxidizing characteristics is considered. Experiments regarding the abiogenic synthesis of nucleic acids and proteins are reported. It was found that micromolecules can be formed in simulation experiments. The condensation reaction taking place in the presence of water was studied together with the condensation reaction taking place in the relative absence of water or under hypohydrous conditions. Jupiter simulation studies were conducted, and lunar and meteorite material was analyzed.

Ponnamperuma, C.↗
NASA NTRS1972

Mass spectrometry.

Review of the current state of mass spectrometry, indicating its unique importance for advanced scientific research. Mass spectrometry applications in computer techniques, gas chromatography, ion cyclotron resonance, molecular fragmentation and ionization, and isotope labeling are covered. Details are given on mass spectrometry applications in bio-organic chemistry and biomedical research. As the subjects of these applications are indicated alkaloids, carbohydrates, lipids, terpenes, quinones, nucleic acid components, peptides, antibiotics, and human and animal metabolisms. Particular attention is given to the mass spectra of organo-inorganic compounds, inorganic mass spectrometry, surface phenomena such as secondary ion and electron emission, and elemental and isotope analysis. Further topics include mass spectrometry in organic geochemistry, applications in geochronology and cosmochemistry, and organic mass spectrometry.

Burlingame, A. L.↗
NASA NTRS1973

Possibilities for the evolution of the genetic code from a preceding form

Analysis of the interaction between mRNA codons and tRNA anticodons suggests a model for the evolution of the genetic code. Modification of the nucleic acid following the anticodon is at present essential in both eukaryotes and prokaryotes to ensure fidelity of translation of codons starting with A, and the amino acids which could be coded for before the evolution of the modifying enzymes can be deduced.

Jukes, T. H.↗
NASA NTRS1974

On a fundamental problem in radiation biology

Experimental evidence indicates that the radiation dose required to reduce a surviving population to a certain fraction of its original population is lower for vertebrate cells than for viruses. On the other hand, the number of ionizations per cell required to inactivate that cell is greater for vertebrate cells than for viruses. The apparent conflict between these two findings is investigated. It is found that the apparent contradiction is probably a result of the fractional power dependence of the radiation-dose value on the nucleic acid weight.

Dugan, V.↗
NASA NTRS1974

A study of immunological reactions in dogs exposed to prolonged chronic radiation

Immunomorphological studies on dog tissues exposed to long term gamma irradiation show that the number of cells containing antibodies increased and that the blast transformation reaction was activated. Prolonged radiation did not cause a reliable change in the synthesis of nucleic acids in spleen cells.

Konstantinova, I. V.↗
NASA NTRS1976

Solution to a gene divergence problem under arbitrary stable nucleotide transition probabilities

A nucleic acid chain, L nucleotides in length, with the specific base sequence B(1)B(2) ... B(L) is defined by the L-dimensional vector B = (B(1), B(2), ..., B(L)). For twelve given constant non-negative transition probabilities that, in a specified position, the base B is replaced by the base B' in a single step, an exact analytical expression is derived for the probability that the position goes from base B to B' in X steps. Assuming that each base mutates independently of the others, an exact expression is derived for the probability that the initial gene sequence B goes to a sequence B' = (B'(1), B'(2), ..., B'(L)) after X = (X(1), X(2), ..., X(L)) base replacements. The resulting equations allow a more precise accounting for the effects of Darwinian natural selection in molecular evolution than does the idealized (biologically less accurate) assumption that each of the four nucleotides is equally likely to mutate to and be fixed as one of the other three. Illustrative applications of the theory to some problems of biological evolution are given.

Holmquist, R.↗
NASA NTRS1978

Computer display and manipulation of biological molecules

This paper describes a computer model that was designed to investigate the conformation of molecules, macromolecules and subsequent complexes. Utilizing an advanced 3-D dynamic computer display system, the model is sufficiently versatile to accommodate a large variety of molecular input and to generate data for multiple purposes such as visual representation of conformational changes, and calculation of conformation and interaction energy. Molecules can be built on the basis of several levels of information. These include the specification of atomic coordinates and connectivities and the grouping of building blocks and duplicated substructures using symmetry rules found in crystals and polymers such as proteins and nucleic acids. Called AIMS (Ames Interactive Molecular modeling System), the model is now being used to study pre-biotic molecular evolution toward life.

Coeckelenbergh, Y.↗
NASA NTRS1979

Coprecipitation of thermal lysine-rich proteinoids with polyribonucleotides

An experimental study was conducted to determine whether the precipitation of thermal proteinoids with homopolynucleotides can serve as a tool for studying the specificities between proteins and polynucleotides. Attention is given to exploring the best means of quantitation of the precipitate and the effect of varying the lysine content and the amount of Mg(2+) on the results. The formation of microparticles was monitored both by turbidity and by the mass of precipitate formed. Only under certain conditions was the turbidity a reliable indication of the amount of precipitate. Increasing concentration of Mg(2+) tended to displace proteinoid from the complex with polynucleotide. The results indicate that the interaction of thermal proteinoids with polynucleotides appears to be a suitable tool for studying specificities of interactions between proteins and nucleic acids.

Lacey, J. C., Jr.↗