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Results for “Genetic prediction”

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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140 records · Page 8
All sourcesNASA NTRSDOE OSTI
NASA NTRS1999

Ionizing radiation-induced mutagenesis: radiation studies in Neurospora predictive for results in mammalian cells

Ionizing radiation was the first mutagen discovered and was used to develop the first mutagenicity assay. In the ensuing 70+ years, ionizing radiation became a fundamental tool in understanding mutagenesis and is still a subject of intensive research. Frederick de Serres et al. developed and used the Neurospora crassa ad-3 system initially to explore the mutagenic effects of ionizing radiation. Using this system, de Serres et al. demonstrated the dependence of the frequency and spectra of mutations induced by ionizing radiation on the dose, dose rate, radiation quality, repair capabilities of the cells, and the target gene employed. This work in Neurospora predicted the subsequent observations of the mutagenic effects of ionizing radiation in mammalian cells. Modeled originally on the mouse specific-locus system developed by William L. Russell, the N. crassa ad-3 system developed by de Serres has itself served as a model for interpreting the results in subsequent systems in mammalian cells. This review describes the primary findings on the nature of ionizing radiation-induced mutagenesis in the N. crassa ad-3 system and the parallel observations made years later in mammalian cells.

NASA Discipline Radiation Health↗
NASA NTRS2001

Dynamic modeling of gene expression data

We describe the time evolution of gene expression levels by using a time translational matrix to predict future expression levels of genes based on their expression levels at some initial time. We deduce the time translational matrix for previously published DNA microarray gene expression data sets by modeling them within a linear framework by using the characteristic modes obtained by singular value decomposition. The resulting time translation matrix provides a measure of the relationships among the modes and governs their time evolution. We show that a truncated matrix linking just a few modes is a good approximation of the full time translation matrix. This finding suggests that the number of essential connections among the genes is small.

NASA Discipline Plant Biology↗
NASA NTRS1997

Evolutionary Design of Controlled Structures

Basic physical concepts of structural delay and transmissibility are provided for simple rod and beam structures. Investigations show the sensitivity of these concepts to differing controlled-structures variables, and to rational system modeling effects. An evolutionary controls/structures design method is developed. The basis of the method is an accurate model formulation for dynamic compensator optimization and Genetic Algorithm based updating of sensor/actuator placement and structural attributes. One and three dimensional examples from the literature are used to validate the method. Frequency domain interpretation of these controlled structure systems provide physical insight as to how the objective is optimized and consequently what is important in the objective. Several disturbance rejection type controls-structures systems are optimized for a stellar interferometer spacecraft application. The interferometric designs include closed loop tracking optics. Designs are generated for differing structural aspect ratios, differing disturbance attributes, and differing sensor selections. Physical limitations in achieving performance are given in terms of average system transfer function gains and system phase loss. A spacecraft-like optical interferometry system is investigated experimentally over several different optimized controlled structures configurations. Configurations represent common and not-so-common approaches to mitigating pathlength errors induced by disturbances of two different spectra. Results show that an optimized controlled structure for low frequency broadband disturbances achieves modest performance gains over a mass equivalent regular structure, while an optimized structure for high frequency narrow band disturbances is four times better in terms of root-mean-square pathlength. These results are predictable given the nature of the physical system and the optimization design variables. Fundamental limits on controlled performance are discussed based on the measured and fit average system transfer function gains and system phase loss.

Masters, Brett P.↗
NASA NTRS2016

In-Flight Personalized Medication Management

Current medication selection for treatment of astronauts during spaceflight missions is primarily dictated by the task of efficiently treating the widest possible range of physiological conditions and illnesses with a limited set of medications. Dosage and recommendations on the combination of drugs are based on the assumption of genetically equal drug sensitivity and unchanged metabolism. To our knowledge, there was no pre-flight drug sensitivity testing on a genetic level for any of the previous manned NASA space missions. Although many of the common, binary drug-drug interactions are, most likely, already considered in the ISS Medical kit composition, multi-drug and multi-drug-gene factors are not incorporated in the medication selection or prescription. Furthermore, due to the physiological changes occurring in microgravity environments, astronauts might be susceptible to potential increased drug toxicity as a result of decreased clearance of numerous drugs. In particular, perturbation of CYP450 enzymes which contribute to the hepatic metabolism of the majority of drugs may have significant effects on therapeutic efficacy and increase treatment-related toxicity5. The genes encoding the CYP450 enzymes are highly variable in humans. Inheritable variations of CYP450 hepatic metabolizer enzymes and transport proteins play a crucial role in the inter-individual variability of drug efficiency and risks of adverse drug reactions5. Additionally, there are some reports that document changes in the levels of production of drug-metabolizing enzymes in microgravity. These data can be extrapolated to provide reasonable assumptions of decreased levels of expression for most CYP450 enzymes in human body during prolonged space travel. If the prescribed medication regiment is not fully effective or causes undesirable side effects, the ability of the astronauts to function and maintain peak performance levels during space flight could be seriously compromised. Therefore, technologies capable of predicting and managing medication side effects, interactions, and toxicity of drugs during spaceflight are needed. We propose to develop and customize for NASAs applications available on the market Personalized Prescribing System (PPS) that would provide a comprehensive, non-invasive solution for safer, targeted medication management for every crew member resulting in safer and more effective treatment and, consequently, better performance. PPS will function as both decision support and record-keeping tool for flight surgeons and astronauts in applying the recommended medications for situations arising in flight. The information on individual drug sensitivity will translate into personalized risk assessment for adverse drug reactions and treatment failures for each drug from the medication kit as well as predefined outcome of any combination of them. Dosage recommendations will also be made individually. The mobile app will facilitate ease of use by crew and medical professionals during training and flight missions.

Personalized Medication↗
NASA NTRS2011

Water Impact Prediction Tool for Recoverable Rockets

Reusing components from a rocket launch can be cost saving. NASA's space shuttle system has reusable components that return to the Earth and impact the ocean. A primary example is the Space Shuttle Solid Rocket Booster (SRB) that descends on parachutes to the Earth after separation and impacts the ocean. Water impact generates significant structural loads that can damage the booster, so it is important to study this event in detail in the design of the recovery system. Some recent examples of damage due to water impact include the Ares I-X First Stage deformation as seen in Figure 1 and the loss of the SpaceX Falcon 9 First Stage.To ensure that a component can be recovered or that the design of the recovery system is adequate, an adequate set of structural loads is necessary for use in failure assessments. However, this task is difficult since there are many conditions that affect how a component impacts the water and the resulting structural loading that a component sees. These conditions include the angle of impact with respect to the water, the horizontal and vertical velocities, the rotation rate, the wave height and speed, and many others. There have been attempts to simulate water impact. One approach is to analyze water impact using explicit finite element techniques such as those employed by the LS-Dyna tool [1]. Though very detailed, this approach is time consuming and would not be suitable for running Monte Carlo or optimization analyses. The purpose of this paper is to describe a multi-body simulation tool that runs quickly and that captures the environments a component might see. The simulation incorporates the air and water interaction with the component, the component dynamics (i.e. modes and mode shapes), any applicable parachutes and lines, the interaction of winds and gusts, and the wave height and speed. It is capable of quickly conducting Monte Carlo studies to better capture the environments and genetic algorithm optimizations to reproduce a flight.

Rooker, William↗
NASA NTRS2002

Differential Top10 promoter regulation by six tetracycline analogues in plant cells

The effects of five tetracycline analogues, anhydrotetracycline, doxycycline, minocycline, oxytetracycline, and tetracycline, on Top10 promoter activity in NT1 tobacco tissue culture cells have been analysed. The concentration that repressed Top10 promoter activity, the level of transgene repression and the kinetics of transgene de-repression were determined for each analogue, and could not be predicted from in vitro binding affinity to the tetracycline repressor or from comparison with animal cells. Doxycycline had the most potent effect on the Top10 promoter and completely inhibited transgene expression at 4 nmol l(-1). Tetracycline was the most versatile of the analogues tested; tetracycline inhibited the Top10 promoter at 10 nmol l(-1) and was easily washed out to restore Top10-driven expression in 12-24 h. A study was also made of the suitability for plant research of a novel tetracycline analogue, GR33076X. In animal cells, GR33076X de-repressed Top10 promoter activity in the presence of inhibitory concentrations of anhydrotetracycline. In NT1, it is shown that GR 33076X can antagonize repression of the Top10 promoter in the presence of tetracycline, but not of anhydrotetracycline or of doxycycline. Different tetracycline analogues can therefore be used to regulate the Top10 promoter in plant cells and this property may be exploited in planning an optimum course of transgene regulation.

NASA Discipline Plant Biology↗
NASA NTRS1998

Co- and/or post-translational modifications are critical for TCH4 XET activity

TCH4 encodes a xyloglucan endotransglycosylase (XET) of Arabidopsis thaliana. XETs endolytically cleave and religate xyloglucan polymers; xyloglucan is one of the primary structural components of the plant cell wall. Therefore, XET function may affect cell shape and plant morphogenesis. To gain insight into the biochemical function of TCH4, we defined structural requirements for optimal XET activity. Recombinant baculoviruses were designed to produce distinct forms of TCH4. TCH4 protein engineered to be synthesized in the cytosol and thus lack normal co- and post-translational modifications is virtually inactive. TCH4 proteins, with and without a polyhistidine tag, that harbor an intact N-terminus are directed to the secretory pathway. Thus, as predicted, the N-terminal region of TCH4 functions as a signal peptide. TCH4 is shown to have at least one disulfide bond as monitored by a mobility shift in SDS-PAGE in the presence of dithiothreitol (DTT). This disulfide bond(s) is essential for full XET activity. TCH4 is glycosylated in vivo; glycosidases that remove N-linked glycosylation eliminated 98% of the XET activity. Thus, co- and/or post-translational modifications are critical for optimal TCH4 XET activity. Furthermore, using site-specific mutagenesis, we demonstrated that the first glutamate residue of the conserved DEIDFEFL motif (E97) is essential for activity. A change to glutamine at this position resulted in an inactive protein; a change to aspartic acid caused protein mislocalization. These data support the hypothesis that, in analogy to Bacillus beta-glucanases, this region may be the active site of XET enzymes.

NASA Discipline Cell Biology↗
NASA NTRS2005

Origin of the Eumetazoa: testing ecological predictions of molecular clocks against the Proterozoic fossil record

Molecular clocks have the potential to shed light on the timing of early metazoan divergences, but differing algorithms and calibration points yield conspicuously discordant results. We argue here that competing molecular clock hypotheses should be testable in the fossil record, on the principle that fundamentally new grades of animal organization will have ecosystem-wide impacts. Using a set of seven nuclear-encoded protein sequences, we demonstrate the paraphyly of Porifera and calculate sponge/eumetazoan and cnidarian/bilaterian divergence times by using both distance [minimum evolution (ME)] and maximum likelihood (ML) molecular clocks; ME brackets the appearance of Eumetazoa between 634 and 604 Ma, whereas ML suggests it was between 867 and 748 Ma. Significantly, the ME, but not the ML, estimate is coincident with a major regime change in the Proterozoic acritarch record, including: (i) disappearance of low-diversity, evolutionarily static, pre-Ediacaran acanthomorphs; (ii) radiation of the high-diversity, short-lived Doushantuo-Pertatataka microbiota; and (iii) an order-of-magnitude increase in evolutionary turnover rate. We interpret this turnover as a consequence of the novel ecological challenges accompanying the evolution of the eumetazoan nervous system and gut. Thus, the more readily preserved microfossil record provides positive evidence for the absence of pre-Ediacaran eumetazoans and strongly supports the veracity, and therefore more general application, of the ME molecular clock.

NASA Discipline Evolutionary Biology↗
NASA NTRS1995

Structural characterization and regulatory element analysis of the heart isoform of cytochrome c oxidase VIa

In order to investigate the mechanism(s) governing the striated muscle-specific expression of cytochrome c oxidase VIaH we have characterized the murine gene and analyzed its transcriptional regulatory elements in skeletal myogenic cell lines. The gene is single copy, spans 689 base pairs (bp), and is comprised of three exons. The 5'-ends of transcripts from the gene are heterogeneous, but the most abundant transcript includes a 5'-untranslated region of 30 nucleotides. When fused to the luciferase reporter gene, the 3.5-kilobase 5'-flanking region of the gene directed the expression of the heterologous protein selectively in differentiated Sol8 cells and transgenic mice, recapitulating the pattern of expression of the endogenous gene. Deletion analysis identified a 300-bp fragment sufficient to direct the myotube-specific expression of luciferase in Sol8 cells. The region lacks an apparent TATA element, and sequence motifs predicted to bind NRF-1, NRF-2, ox-box, or PPAR factors known to regulate other nuclear genes encoding mitochondrial proteins are not evident. Mutational analysis, however, identified two cis-elements necessary for the high level expression of the reporter protein: a MEF2 consensus element at -90 to -81 bp and an E-box element at -147 to -142 bp. Additional E-box motifs at closely located positions were mutated without loss of transcriptional activity. The dependence of transcriptional activation of cytochrome c oxidase VIaH on cis-elements similar to those found in contractile protein genes suggests that the striated muscle-specific expression is coregulated by mechanisms that control the lineage-specific expression of several contractile and cytosolic proteins.

Non-NASA Center↗
NASA NTRS2005

Identification of transcribed sequences in Arabidopsis thaliana by using high-resolution genome tiling arrays

Using a maskless photolithography method, we produced DNA oligonucleotide microarrays with probe sequences tiled throughout the genome of the plant Arabidopsis thaliana. RNA expression was determined for the complete nuclear, mitochondrial, and chloroplast genomes by tiling 5 million 36-mer probes. These probes were hybridized to labeled mRNA isolated from liquid grown T87 cells, an undifferentiated Arabidopsis cell culture line. Transcripts were detected from at least 60% of the nearly 26,330 annotated genes, which included 151 predicted genes that were not identified previously by a similar genome-wide hybridization study on four different cell lines. In comparison with previously published results with 25-mer tiling arrays produced by chromium masking-based photolithography technique, 36-mer oligonucleotide probes were found to be more useful in identifying intron-exon boundaries. Using two-dimensional HPLC tandem mass spectrometry, a small-scale proteomic analysis was performed with the same cells. A large amount of strongly hybridizing RNA was found in regions "antisense" to known genes. Similarity of antisense activities between the 25-mer and 36-mer data sets suggests that it is a reproducible and inherent property of the experiments. Transcription activities were also detected for many of the intergenic regions and the small RNAs, including tRNA, small nuclear RNA, small nucleolar RNA, and microRNA. Expression of tRNAs correlates with genome-wide amino acid usage.

Arabidopsis/genetics↗
NASA NTRS2000

Quantitative assessment of Hox complex expression in the indirect development of the polychaete annelid Chaetopterus sp

A prediction from the set-aside theory of bilaterian origins is that pattern formation processes such as those controlled by the Hox cluster genes are required specifically for adult body plan formation. This prediction can be tested in animals that use maximal indirect development, in which the embryonic formation of the larva and the postembryonic formation of the adult body plan are temporally and spatially distinct. To this end, we quantitatively measured the amount of transcripts for five Hox genes in embryos of a lophotrochozoan, the polychaete annelid Chaetopterus sp. The polychaete Hox complex is shown not to be expressed during embryogenesis, but transcripts of all measured Hox complex genes are detected at significant levels during the initial stages of adult body plan formation. Temporal colinearity in the sequence of their activation is observed, so that activation follows the 3'-5' arrangement of the genes. Moreover, Hox gene expression is spatially localized to the region of teloblastic set-aside cells of the later-stage embryos. This study shows that an indirectly developing lophotrochozoan shares with an indirectly developing deuterostome, the sea urchin, a common mode of Hox complex utilization: construction of the larva, whether a trochophore or dipleurula, does not involve Hox cluster expression, but in both forms the complex is expressed in the set-aside cells from which the adult body plan derives.

Non-NASA Center↗
NASA NTRS2002

Size distribution of retrovirally marked lineages matches prediction from population measurements of cell cycle behavior

Mechanisms that regulate neuron production in the developing mouse neocortex were examined by using a retroviral lineage marking method to determine the sizes of the lineages remaining in the proliferating population of the ventricular zone during the period of neuron production. The distribution of clade sizes obtained experimentally in four different injection-survival paradigms (E11-E13, E11-E14, E11-E15, and E12-E15) from a total of over 500 labeled lineages was compared with that obtained from three models in which the average behavior of the proliferating population [i.e., the proportion of cells remaining in the proliferative population (P) vs. that exiting the proliferative population (Q)] was quantitatively related to lineage size distribution. In model 1, different proportions of asymmetric, symmetric terminal, and symmetric nonterminal cell divisions coexisted during the entire developmental period. In model 2, the developmental period was divided into two epochs: During the first, asymmetric and symmetric nonterminal cell divisions occurred, but, during the second, asymmetric and symmetric terminal cell divisions occurred. In model 3, the shifts in P and Q are accounted for by changes in the proportions of the two types of symmetric cell divisions without the inclusion of any asymmetric cell divisions. The results obtained from the retroviral experiments were well accounted for by model 1 but not by model 2 or 3. These findings demonstrate that: 1) asymmetric and both types of symmetric cell divisions coexist during the entire period of neurogenesis in the mouse, 2) neuron production is regulated in the proliferative population by the independent decisions of the two daughter cells to reenter S phase, and 3) neurons are produced by both asymmetric and symmetric terminal cell divisions. In addition, the findings mean that cell death and/or tangential movements of cells in the proliferative population occur at only a low rate and that there are no proliferating lineages "reserved" to make particular laminae or cell types. Copyright 2002 Wiley-Liss, Inc.

NASA Discipline Developmental Biology↗
NASA NTRS2003

Common 5S rRNA variants are likely to be accepted in many sequence contexts

Over evolutionary time RNA sequences which are successfully fixed in a population are selected from among those that satisfy the structural and chemical requirements imposed by the function of the RNA. These sequences together comprise the structure space of the RNA. In principle, a comprehensive understanding of RNA structure and function would make it possible to enumerate which specific RNA sequences belong to a particular structure space and which do not. We are using bacterial 5S rRNA as a model system to attempt to identify principles that can be used to predict which sequences do or do not belong to the 5S rRNA structure space. One promising idea is the very intuitive notion that frequently seen sequence changes in an aligned data set of naturally occurring 5S rRNAs would be widely accepted in many other 5S rRNA sequence contexts. To test this hypothesis, we first developed well-defined operational definitions for a Vibrio region of the 5S rRNA structure space and what is meant by a highly variable position. Fourteen sequence variants (10 point changes and 4 base-pair changes) were identified in this way, which, by the hypothesis, would be expected to incorporate successfully in any of the known sequences in the Vibrio region. All 14 of these changes were constructed and separately introduced into the Vibrio proteolyticus 5S rRNA sequence where they are not normally found. Each variant was evaluated for its ability to function as a valid 5S rRNA in an E. coli cellular context. It was found that 93% (13/14) of the variants tested are likely valid 5S rRNAs in this context. In addition, seven variants were constructed that, although present in the Vibrio region, did not meet the stringent criteria for a highly variable position. In this case, 86% (6/7) are likely valid. As a control we also examined seven variants that are seldom or never seen in the Vibrio region of 5S rRNA sequence space. In this case only two of seven were found to be potentially valid. The results demonstrate that changes that occur multiple times in a local region of RNA sequence space in fact usually will be accepted in any sequence context in that same local region.

NASA Discipline Exobiology↗
NASA NTRS2002

Genes encoding calmodulin-binding proteins in the Arabidopsis genome

Analysis of the recently completed Arabidopsis genome sequence indicates that approximately 31% of the predicted genes could not be assigned to functional categories, as they do not show any sequence similarity with proteins of known function from other organisms. Calmodulin (CaM), a ubiquitous and multifunctional Ca(2+) sensor, interacts with a wide variety of cellular proteins and modulates their activity/function in regulating diverse cellular processes. However, the primary amino acid sequence of the CaM-binding domain in different CaM-binding proteins (CBPs) is not conserved. One way to identify most of the CBPs in the Arabidopsis genome is by protein-protein interaction-based screening of expression libraries with CaM. Here, using a mixture of radiolabeled CaM isoforms from Arabidopsis, we screened several expression libraries prepared from flower meristem, seedlings, or tissues treated with hormones, an elicitor, or a pathogen. Sequence analysis of 77 positive clones that interact with CaM in a Ca(2+)-dependent manner revealed 20 CBPs, including 14 previously unknown CBPs. In addition, by searching the Arabidopsis genome sequence with the newly identified and known plant or animal CBPs, we identified a total of 27 CBPs. Among these, 16 CBPs are represented by families with 2-20 members in each family. Gene expression analysis revealed that CBPs and CBP paralogs are expressed differentially. Our data suggest that Arabidopsis has a large number of CBPs including several plant-specific ones. Although CaM is highly conserved between plants and animals, only a few CBPs are common to both plants and animals. Analysis of Arabidopsis CBPs revealed the presence of a variety of interesting domains. Our analyses identified several hypothetical proteins in the Arabidopsis genome as CaM targets, suggesting their involvement in Ca(2+)-mediated signaling networks.

NASA Discipline Plant Biology↗