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At least 307 records · Page 17

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NASA NTRS2017

Informing Rodent Behavior in Space: Gene Expression and Hyper-Emotionality Following Prenatal Stress

As space exploration pushes our boundaries further away from Earth and for longer durations, we will inevitably require the use of multi-generational studies to continue our expansion. Space is a stressful environment not only due to the deleterious effect of spaceflight on physiology, but also due to confinement, limited social interactions, inherently dangerous circumstances, and many other stresses of an unknown environment. Stress can alter the brain chemistry, and these alterations can affect behavior at all stages of development, but it is especially pronounced during the perinatal period and can have longstanding effects, even into adulthood, which manifest through augmented brain function and psychopathology. This study investigated the nexus of brain chemistry and brain function by observing behavior of adult rats whose mothers were exposed to unpredictable variable prenatal stress (UVPS) while they were in the womb. The UVPS consisted of strobe light, tube restraint, and white noise, and was administered at unpredictable times of the day and also varied in length, both of which were measures taken to prevent habituation to the stressor. The offspring rats were then allowed to reach adulthood and at 90 days were subjected to a series of behavioral tests including novel object, startle response, and an unknown intruder to quantify the adult rats stress response and anxiety. Here we report these results of the behavioral analysis and correlate adult behavioral measures with the expression of genes involved in the hypothalamic-pituitary-adrenal axis, which modulates the animals stress response. We hypothesized that hyper-expression of genes involved in the HPA axis would correlate with the observed anxiety-like behaviors associated with early stress.

Moyer, E. L.↗

NASA NTRS2018

Increasing the Statistical Rigor of Cross-Species Differential Expression Analysis

Microgravity inflicts substantial, but undercharacterized, pressure on organisms that induces metabolic responses such as increased microbial virulence and antibiotic resistance, altered organ weights in developing rats, and loss of bone tissue in astronauts. Numerous studies have analyzed the effects of microgravity on specific organisms, tissues, or test conditions, but these projects are necessarily limited by the small sample size of space research. Increasing the sample size of spaceflight studies is non-trivial; however, pooling data from numerous studies can greatly increase the statistical rigor of comparative analyses. The GeneLab houses datasets from 73 spaceflight studies that performed transcription profiling assays. These data encompass a diverse array of organisms ranging from Escherichia coli to Mus musculus to Homo sapiens and comprise studies analyzing ionizing radiation, mammalian pregnancy, etc. Collectively, the GeneLab database contains a large quantity of transcription assays and RNA sequence data analyzing Differential Gene Expression (DGE) between microand normogravity. Xspecies, a cross-species analysis method for DGE developed by Kristiansson, et al. in 2012, identifies homologous genes between species that are universally up- or downregulated in response to test conditions. Previous work by an intern at GeneLab applied Xspecies to 19 datasets containing seven different species and identified 14 homologous groups differentially expressed under spaceflight conditions including several heat shock proteins and cytoskeletal components. Unfortunately, these results may be biased by the disproportionate number of studies on Arabidopsis thaliana (5) and Mus musculus (6) and the results are not normalized by evolutionary distances. Here, we present modifications to the Xspecies algorithm that permits incorporation of multi-omic data and normalizes data for effect size, directionality, and evolutionary distances. We then apply this algorithm to all currently available GeneLab studies

Xspecies↗

NASA NTRS2018

Gene Expression of Pathogens in Simulated Microgravity

Extended exposure to radiation and microgravity in space has been linked to astronauts developing chronic diseases upon returning to Earth. The Gram-negative pathogen Serratia marcescens has been shown to potentially cause significant infections in humans and in insect models on Earth. Our recent findings also showed that S. marcescens shows an increase in virulence after a short period of growth in the spaceflight environment, which raises initiatives to find the correlation between space environment and the increased virulence. Because we know that the health of astronauts is immunocompromised in space, it is possible that the combination of increased bacterial virulence and the weakened immune system will cause astronauts to be more susceptible to chronic diseases in extended spaceflight. With 75% of human disease genes being conserved in the fruit fly Drosophila melanogaster, these insects act as an ideal model organism to study the human immune system. The high accessibility, low cost, high rate of reproductivity, and short lifespans of D. melanogaster facilitate efficient, high-quality research that seeks to understand altered virulence of this opportunistic pathogen. In this ground-based study, we will use a rotating wall vessel apparatus to simulate microgravity and determine how pathogenicity changes by evaluating differences in gene expression for S. marcescens between bacteria grown in simulated microgravity conditions and controls. We will compare the results of our findings to gene expression patterns in actual spaceflight samples of S. marcescens grown on the ISS (International Space Station) during a recent validation mission, to see if there are common mechanisms across our simulated microgravity and actual spaceflight microgravity samples that both show increased virulence in the fruit fly. With extended space travel in the foreseeable future, understanding how human physiology will be affected by these different factors will help mitigate risks and deaths.

spaceflight analogue↗

NASA NTRS2019

Prenatal 2g Exposure Alters Placental Expression of Stress-Related Genes

Extra-terrestrial colonization is of growing interest to space agencies and private entities, emphasizing the importance of research on reproduction and development in the absence of Earth's 1G. Maternal stressors can modify offspring development, exerting significant lifespan and crossgenerational changes through prenatal programming. The space environment is stressful, therefore exposure to altered gravity during pregnancy may impact later life outcomes in offspring. In ground-based studies, we exposed pregnant rats to continuous +G (above Earth gravity), and observed overweight and elevated anxiety in adult male (but not female) offspring, common phenotypes associated with prenatal maternal stress. Here we hypothesize that exposure to increased gravity during pregnancy elicits changes in the expression of stress-related genes in placenta that may mediate emergence of later life outcomes. While the placenta transports maternal factors to the fetus and produces endogenous fetal hormones, stress-induced changes at the placental-uterine interface may also alter communication between mother and fetus, facilitating prenatal transmission of unfavorable later life outcomes and cross-generational epigenetic alterations. Maternal stress elevates maternal glucocorticoids however placental 11b-hydroxysteroid dehydrogenase type 2 (HSD11B2) buffers fetal exposure by converting cortisol/corticosterone into inactive metabolites. Maternal stress during pregnancy down-regulates this enzyme and can induce epigenetic changes in placental and fetal tissues accounting for heightened adult HPA reactivity. Past studies have shown a placenta-specific increase in DNA methyltransferase (DNMT3a) mRNA in stressed mothers, an effect with implications for genome-wide epigenetic changes that may account for diverse phenotypic outcomes following maternal stress. Here we exposed groups of pregnant rats to one of five gravity loads (1, 1.5, 1.75 and 2G) and analyzed placental samples during late gestation. We predicted a systematic dose-response relationship between gravity load and the expression of the HSD11B2 and DNMT3 genes, thereby linking maternal exposure to altered gravity during pregancy with maternal stress.

Kalotia, Simranjit K.↗

NASA NTRS2019

Simulated Microgravity Affects Behavior and Cytokine Expression in the Hippocampus of Adult Mice: Influence of Mitochondrial Reactive Oxygen Species

The effects of microgravity, and social isolation on the CNS are poorly understood. We hypothesize that mitochondrial reactive oxygen species (ROS) play an important role in this process. Since mice are social animals, our lab developed a novel social model of hindlimb unloading (HU), enabling us to determine the effects of both social isolation and simulated microgravity. Responses to 30d of HU were compared in wildtype or transgenic MCAT mice who over-express human catalase in mitochondria. Abundance of 4-Hydroxynonenal, Park7 (a redox-sensitive chaperone and sensor of oxidative stress) and corticosterone were measured by ELISA. Cytokines related to inflammation in the hippocampus and in plasma were analyzed by a protein array. Behavioral data was collected over a 24-hour period.Socially housed HU mice were more active and conducted at least two times more exploratory activities, compared to normally loaded mice. Correlation analysis revealed that specific brain and plasma cytokines correspond with specific behaviors. Simulated microgravity and/or social isolation caused changes in cytokine patterns in the hippocampus and in plasma, with significant interaction effects of HU and genotype in expression levels of five cytokines (out of 35). Interestingly, elevation of these generally pro-inflammatory cytokines by HU in WT mice was mitigated in MCAT mice, suggesting a role for mitochondrial ROS signaling in inflammatory CNS responses to microgravity. Interestingly, socially housed mice had also lower level of 4HNE and higher level of Park7 in the hippocampus compared to singly housed animals. The cytokine responses to social isolation were more extensive in brain vs plasma. Further, there was no overlap in the cytokine repertoire regulated in response to microgravity versus, isolation suggesting divergent mechanisms or downstream signaling. These findings implicate a potentially important role for mitochondrial ROS in CNS responses to the challenges posed both by prolonged missions in space and bedrest on Earth

Guttmann, Linda↗

NASA NTRSDate not supplied

A Gene Expression and Histologic Approach to Study Production and Outflow of Cerebrospinal Fluid in Hindlimb Suspended Rats

INTRODUCTION: The Spaceflight Associated Neuro-ocular Syndrome (SANS) is thought to be associated with weightlessness-induced cephalad fluid shift, possibly associated with a chronic elevation of intracranial pressure (ICP) during long-duration ISS missions. Changes in cerebrospinal fluid (CSF) dynamics and cranial compliance might be involved in the ICP increase. It is not known whether CSF production and/or outflow are altered in microgravity, but changes at the molecular and cellular level in the structures that produce and regulate the transcellular and paracellular secretion and reabsorption of CSF may be relevant. In this study, we used the rat hindlimb suspension (HS) model to examine the relationship between intracranial pressure (ICP) and the cellular responses to the prolonged change in body posture elicited specifically in the choroid plexus (CP). This was evaluated by transcriptomics, histopathology and ultrastructure of the CP and arachnoid villi (AV). METHODS: ICP was measured by telemetry. The morphology, ultrastructure, and gene expression profile of the CP was examined using male 9-month-old Long Evans rats subjected to HS for 14 and 90 days. A subset of animals completing 90-day HS returned to normal posture for 14 and 90 additional days of recovery. All HS rats had age-matched cage controls maintained in normal posture. A group of animals was maintained in conditions of 1% CO2 throughout the entire protocol. The rat brains were carefully removed and preserved for various analyses, including transmission electron microscopy (TEM), immunohistochemical analysis of specific targets involved in CSF regulation, and RNA sequencing analysis of laser capture micro-dissected CP tissue from the lateral ventricles. SUMMARY OF RESULTS: The ICP record was limited, which impacted any conclusions derived from the results. However, the ICP of rats in the CO2-enriched atmosphere appeared increased compared to those in a normal air composition. HS of rats resulted in an altered transcriptomics profile in the choroid plexus compared to animals maintained at normal posture. This was observed during both the HS period and during normal posture recovery period following 90 days of suspension. The greatest number of differentially expressed genes was observed at 90 days HS. Elevated CO2 also led to a different transcriptomics profile in the CP. The histology and ultrastructure results should be considered preliminary due to the limited number of samples. Examination of the CP by TEM showed blood vessel congestion and microvilli swelling in the CP, as well as some subpial and periventricular gliosis, but no associations were observed with treatment. There was no evidence of a reduced clearance of b-amyloid in the periventricular, perivascular and subpial regions of the brain in HS animals versus those in normal posture. Immunohistochemical staining of aquaporin 4, showed the localization to the subpial region and ependyma with increased immunoreactivity in the brains of CO2 exposed rats. This work was supported by awards NNX15AW48G to S.Z. Animal tissue and live data was provided under a tissue/data sharing agreement with Dr. Charles Fuller, UC Davis.

S B Zanello↗

NASA NTRSDate not supplied

A Gene Expression and Histologic Approach to Study Production and Outflow of Cerebrospinal Fluid in Hindlimb Suspended RATS

S B Zanello↗

NASA NTRSDate not supplied

Gene expression changes in peripheral blood mononuclear cells of ISS crewmembers suggest impacts of spaceflight on cell death

In space, living organisms are exposed to numerous stress factors including microgravity and space radiation. For humans, these harmful environmental factors have been known to cause negative health impacts such as immune dysfunction. Understanding the mechanisms by which spaceflight impacts human health at the molecular level is critical not only for accurately assessing the risks associated with spaceflight, but also for developing effective countermeasures. This study is part of the Functional Immune Project, intended to determine alterations in crewmembers` immunobiology before, during, and after spaceflight. For this project, blood samples were collected from International Space Station (ISS) crewmembers at the following time points: i) at two pre-flight time points of 180 days (L180) and 45 days (L45) before launch. ii) During flight, blood was drawn at approximately the midpoint (mid-flight, MF) of the mission, and shortly before egress from the ISS (late-flight, LF). iii) Post-flight blood samples were collected within 24 hrs (R0), 30 days (R30) and 90 days (R90) after landing. For each crewmember, blood was also drawn from a matching test subject on the ground at the corresponding time point. For both the ISS crewmembers and the ground control subjects, total RNA was isolated from peripheral blood mononuclear cells (PBMC) and mRNA was analysed using next generation RNA-sequencing (NGS). Differentially expressed genes were determined by performing contrast analysis. Using the data from all of the time points from the ground control subjects as a control, a number of dysregulated genes were identified in astronauts at MF, LF and R0, including downregulations of several cell cycle related genes including CDKN1A and VEGFA at MF and LF. Pathway analysis of these differentially expressed genes indicated that, in space, pathways associated with autophagy and senescence were affected. Our analysis also indicated that the genes related to metabolisms were downregulated in the microgravity environment. Taken together, our data suggests that PBMC in the ISS crewmembers may be starved, resulting in autophagy and delayed senescence in space. Such findings are in agreement with delayed cell death in PBMC under simulated microgravity conditions on the ground and offer an explanation for telomere lengthening that has been reported among the ISS astronauts in flight.

Maria Moreno-Villanueva↗

NASA NTRSDate not supplied

Gene Expression Changes in Peripheral Blood Mononuclear Cells of ISS Crewmembers Suggest Impacts of Spaceflight on Cell Death

In space, living organisms are exposed to numerous stress factors including microgravity and space radiation. For humans, these harmful environmental factors have been known to cause negative health impacts such as immune dysfunction. Understanding the mechanisms by which spaceflight impacts human health at the molecular level is critical not only for accurately assessing the risks associated with spaceflight, but also for developing effective countermeasures. This study is part of the Functional Immune Project, intended to determine alterations in crewmembers` immunobiology before, during, and after spaceflight. For this project, blood samples were collected from International Space Station (ISS) crewmembers at the following time points: i) at two pre-flight time points of 180 days (L180) and 45 days (L45) before launch. ii) During flight, blood was drawn at approximately the midpoint (mid-flight, MF) of the mission, and shortly before egress from the ISS (late-flight, LF). iii) Post-flight blood samples were collected within 24 hrs (R0), 30 days (R30) and 90 days (R90) after landing. For each crewmember, blood was also drawn from a matching test subject on the ground at the corresponding time point. For both the ISS crewmembers and the ground control subjects, total RNA was isolated from peripheral blood mononuclear cells (PBMC) and mRNA was analysed using next generation RNA-sequencing (NGS). Differentially expressed genes were determined by performing contrast analysis. Using the data from all of the time points from the ground control subjects as a control, a number of dysregulated genes were identified in astronauts at MF, LF and R0, including downregulations of several cell cycle related genes including CDKN1A and VEGFA at MF and LF. Pathway analysis of these differentially expressed genes indicated that, in space, pathways associated with autophagy and senescence were affected. Our analysis also indicated that the genes related to metabolisms were downregulated in the microgravity environment. Taken together, we hypothesize that PBMC in the ISS crewmembers may be starved, resulting in autophagy and delayed senescence in space. Such findings are in agreement with delayed cell death in PBMC under simulated microgravity conditions on the ground and offer an explanation for telomere lengthening that has been reported among the ISS astronauts in flight

Maria Moreno-Villanueva↗

NASA NTRSDate not supplied

Expressing Functionality Using Design Patterns, A Real-World Example

Digital Engineering is a transformative strategy that leverages an integrated model-based approach to improve communication, decision making, design understanding, and acquisition efficiency of system development. As modern systems are derived from pre-existing systems, harvesting tacit knowledge from existing systems in a useful, model-based way will reduce the experiential learning and cognition required for new system development, contributing to a Digital Engineering transformation. This study enables such a technique by demonstrating the use of architectural theory in expressing tacit knowledge from existing systems and presenting that knowledge according to the model-based view offered by the Functional Architecture of Systems methodology. By validating the functional information expressed by the design pattern, this work solidifies design patterns as a critical component of a technical architecture and proposes a functional architecture viewpoint for describing mined knowledge in a usable, model-based, way suitable for archival in a modern knowledge management system.

Systems Engineering↗

NASA NTRS2003

Low-shear modeled microgravity: a global environmental regulatory signal affecting bacterial gene expression, physiology, and pathogenesis

Bacteria inhabit an impressive variety of ecological niches and must adapt constantly to changing environmental conditions. While numerous environmental signals have been examined for their effect on bacteria, the effects of mechanical forces such as shear stress and gravity have only been investigated to a limited extent. However, several important studies have demonstrated a key role for the environmental signals of low shear and/or microgravity in the regulation of bacterial gene expression, physiology, and pathogenesis [Chem. Rec. 1 (2001) 333; Appl. Microbiol. Biotechnol. 54 (2000) 33; Appl. Environ. Microbiol. 63 (1997) 4090; J. Ind. Microbiol. 18 (1997) 22; Curr. Microbiol. 34(4) (1997) 199; Appl. Microbiol. Biotechnol. 56(3-4) (2001) 384; Infect Immun. 68(6) (2000) 3147; Cell 109(7) (2002) 913; Appl. Environ. Microbiol. 68(11) (2002) 5408; Proc. Natl. Acad. Sci. U. S. A. 99(21) (2002) 13807]. The response of bacteria to these environmental signals, which are similar to those encountered during prokaryotic life cycles, may provide insight into bacterial adaptations to physiologically relevant conditions. This review focuses on the current and potential future research trends aimed at understanding the effect of the mechanical forces of low shear and microgravity analogues on different bacterial parameters. In addition, this review also discusses the use of microgravity technology to generate physiologically relevant human tissue models for research in bacterial pathogenesis.

NASA Discipline Cell Biology↗

NASA NTRS2002

Gravity-stimulated changes in auxin and invertase gene expression in maize pulvinal cells

Maize (Zea mays) stem gravitropism involves differential elongation of cells within a highly specialized region, the stem internodal pulvinus. In the present study, we investigated factors that control gravitropic responses in this system. In the graviresponding pulvinus, hexose sugars (D-Glc and D-Fru) accumulated asymmetrically across the pulvinus. This correlated well with an asymmetric increase in acid invertase activity across the pulvinus. Northern analyses revealed asymmetric induction of one maize acid invertase gene, Ivr2, consistent with transcriptional regulation by gravistimulation. Several lines of evidence indicated that auxin redistribution, as a result of polar auxin transport, is necessary for gravity-stimulated Ivr2 transcript accumulation and differential cell elongation across the maize pulvinus. First, the auxin transport inhibitor, N-1-naphthylphthalamic acid, inhibited gravistimulated curvature and Ivr2 transcript accumulation. Second, a transient gradient of free indole-3-acetic acid (IAA) across the pulvinus was apparent shortly after initiation of gravistimulation. This temporarily free IAA gradient appears to be important for differential cell elongation and Ivr2 transcript accumulation. This is based on the observation that N-1-naphthylphthalamic acid will not inhibit gravitropic responses when applied to pulvinus tissue after the free IAA gradient peak has occurred. Third, IAA alone can stimulate Ivr2 transcript accumulation in non-gravistimulated pulvini. The gravity- and IAA-stimulated increase in Ivr2 transcripts was sensitive to the protein synthesis inhibitor, cycloheximide. Based on these results, a two-phase model describing possible relationships between gravitropic curvature, IAA redistribution, and Ivr2 expression is presented.

NASA Discipline Plant Biology↗

NASA NTRS2003

CCAAT-binding factor regulates expression of the beta1 subunit of soluble guanylyl cyclase gene in the BE2 human neuroblastoma cell line

Soluble guanylyl cyclase (sGC) is a cytosolic enzyme producing the intracellular messenger cyclic guanosine monophosphate (cGMP) on activation with nitric oxide (NO). sGC is an obligatory heterodimer composed of alpha and beta subunits. We investigated human beta1 sGC transcriptional regulation in BE2 human neuroblastoma cells. The 5' upstream region of the beta1 sGC gene was isolated and analyzed for promoter activity by using luciferase reporter constructs. The transcriptional start site of the beta1 sGC gene in BE2 cells was identified. The functional significance of consensus transcriptional factor binding sites proximal to the transcriptional start site was investigated by site deletions in the 800-bp promoter fragment. The elimination of CCAAT-binding factor (CBF) and growth factor independence 1 (GFI1) binding cores significantly diminished whereas deletion of the NF1 core elevated the transcription. Electrophoretic mobility-shift assay (EMSA) and Western analysis of proteins bound to biotinated EMSA probes confirmed the interaction of GFI1, CBF, and NF1 factors with the beta1 sGC promoter. Treatment of BE2 cells with genistein, known to inhibit the CBF binding to DNA, significantly reduced protein levels of beta1 sGC by inhibiting transcription. In summary, our study represents an analysis of the human beta1 sGC promoter regulation in human neuroblastoma BE2 cells and identifies CBF as a critically important factor in beta1 sGC expression.

Non-NASA Center↗

NASA NTRS2002

Radiation-induced gene expression in the nematode Caenorhabditis elegans

We used the nematode C. elegans to characterize the genotoxic and cytotoxic effects of ionizing radiation in a simple animal model emphasizing the unique effects of charged particle radiation. Here we demonstrate by RT-PCR differential display and whole genome microarray hybridization experiments that gamma rays, accelerated protons and iron ions at the same physical dose lead to unique transcription profiles. 599 of 17871 genes analyzed (3.4%) showed differential expression 3 hrs after exposure to 3 Gy of radiation. 193 were up-regulated, 406 were down-regulated and 90% were affected only by a single species of radiation. A novel statistical clustering technique identified the regulatory relationships between the radiation-modulated genes and showed that genes affected by each radiation species were associated with unique regulatory clusters. This suggests that independent homeostatic mechanisms are activated in response to radiation exposure as a function of track structure or ionization density.

Non-NASA Center↗

NASA NTRS2002

Up-regulation of phosphoinositide metabolism in tobacco cells constitutively expressing the human type I inositol polyphosphate 5-phosphatase

To evaluate the impact of suppressing inositol 1,4,5-trisphosphate (InsP(3)) in plants, tobacco (Nicotiana tabacum) cells were transformed with the human type I inositol polyphosphate 5-phosphatase (InsP 5-ptase), an enzyme which specifically hydrolyzes InsP(3). The transgenic cell lines showed a 12- to 25-fold increase in InsP 5-ptase activity in vitro and a 60% to 80% reduction in basal InsP(3) compared with wild-type cells. Stimulation with Mas-7, a synthetic analog of the wasp venom peptide mastoparan, resulted in an approximately 2-fold increase in InsP(3) in both wild-type and transgenic cells. However, even with stimulation, InsP(3) levels in the transgenic cells did not reach wild-type basal values, suggesting that InsP(3) signaling is compromised. Analysis of whole-cell lipids indicated that phosphatidylinositol 4,5-bisphosphate (PtdInsP(2)), the lipid precursor of InsP(3), was greatly reduced in the transgenic cells. In vitro assays of enzymes involved in PtdInsP(2) metabolism showed that the activity of the PtdInsP(2)-hydrolyzing enzyme phospholipase C was not significantly altered in the transgenic cells. In contrast, the activity of the plasma membrane PtdInsP 5 kinase was increased by approximately 3-fold in the transgenic cells. In vivo labeling studies revealed a greater incorporation of (32)P into PtdInsP(2) in the transgenic cells compared with the wild type, indicating that the rate of PtdInsP(2) synthesis was increased. These studies show that the constitutive expression of the human type I InsP 5-ptase in tobacco cells leads to an up-regulation of the phosphoinositide pathway and highlight the importance of PtdInsP(2) synthesis as a regulatory step in this system.

NASA Discipline Cell Biology↗

NASA NTRS2002

The western red cedar (Thuja plicata) 8-8' DIRIGENT family displays diverse expression patterns and conserved monolignol coupling specificity

The isolation and characterization of a multigene family of the first class of dirigent proteins (namely that mainly involved in 8-8' coupling leading to (+)-pinoresinol in this case) is reported, this comprising of nine western red cedar (Thuja plicata) DIRIGENT genes (DIR1-9) of 72-99.5% identity to each other. Their corresponding cDNA clones had coding regions for 180-183 amino acids with each having a predicted molecular mass of ca. 20 kDa including the signal peptide. Real time-PCR established that the DIRIGENT isovariants were differentially expressed during growth and development of T. plicata (P < 0.05). The phylogenetic relationships and the rates and patterns of nucleotide substitution suggest that the DIRIGENT gene may have evolved via paralogous expansion at an early stage of vascular plant diversification. Thereafter, western red cedar paralogues have maintained an high homogeneity presumably via a concerted evolutionary mode. This, in turn, is assumed to be the driving force for the differential formation of 8-8'-linked pinoresinol derived (poly)lignans in the needles, stems, bark and branches, as well as for massive accumulation of 8-8'-linked plicatic acid-derived (poly)lignans in heartwood.

Non-NASA Center↗

NASA NTRS2001

Antisense expression of an Arabidopsis ran binding protein renders transgenic roots hypersensitive to auxin and alters auxin-induced root growth and development by arresting mitotic progress

We cloned a cDNA encoding an Arabidopsis Ran binding protein, AtRanBP1c, and generated transgenic Arabidopsis expressing the antisense strand of the AtRanBP1c gene to understand the in vivo functions of the Ran/RanBP signal pathway. The transgenic plants showed enhanced primary root growth but suppressed growth of lateral roots. Auxin significantly increased lateral root initiation and inhibited primary root growth in the transformants at 10 pM, several orders of magnitude lower than required to induce these responses in wild-type roots. This induction was followed by a blockage of mitosis in both newly emerged lateral roots and in the primary root, ultimately resulting in the selective death of cells in the tips of both lateral and primary roots. Given the established role of Ran binding proteins in the transport of proteins into the nucleus, these findings are consistent with a model in which AtRanBP1c plays a key role in the nuclear delivery of proteins that suppress auxin action and that regulate mitotic progress in root tips.

Non-NASA Center↗

NASA NTRS1989

Influence of performance on gene expression in skeletal muscle: effects of forced inactivity

Joint immobilization and hindlimb suspension are used to examine muscle protein expression and mRNA quantities in rats. A decrease in protein synthesis was not associated with alteration in alpha-actin mRNA, cytochrome c mRNA, or beta-myosin heavy chain mRNA early in treatment. Percentage declines after seven days are compared with early treatment quantities to determine acute and chronic response to muscular atrophy.

Non-NASA Center↗