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At least 55 records · Page 3
All sourcesNASA NTRSDOE OSTI
NASA NTRS1999

Long term organ culture of human prostate tissue in a NASA-designed rotating wall bioreactor

PURPOSE: To maintain ex vivo integral prostatic tissue including intact stromal and ductal elements using the NASA-designed Rotating Wall Vessel (RWV) which maintains colocalized cells in an environment that promotes both three-dimensional cellular interactions together with the uniform mass transfer of nutrients and metabolic wastes. MATERIALS AND METHODS: Samples of normal prostate were obtained as a byproduct of transurethral prostatectomy or needle biopsy. Prostatic tissue dissected into small 1 x 1 mm. blocks was cultured in the Rotating Wall Vessel (RWV) Bioreactor for various time periods and analyzed using histological, immunochemical, and total cell RNA assays. RESULTS: We report the long term maintenance of benign explanted human prostate tissue grown in simple culture medium, under the simulated microgravity conditions afforded by the RWV bioreactor. Mesenchymal stromal elements including blood vessels and architecturally preserved tubuloglandular acini were maintained for a minimum of 28 days. Cytokeratins, vimentin and TGF-beta2 receptor and ligand were preserved through the entire culture period as revealed by immunocytochemistry. Prostatic acid phosphatase (PAP) was continuously expressed during the culture period, although somewhat decreased. Prostatic specific antigen (PSA) and its transcript were down regulated over time of culture. Prostatic carcinoma cells from the TSU cell line were able to invade RWV-cultured benign prostate tissue explants. CONCLUSIONS: The RWV bioreactor represents an additional new technology for culturing prostate tissue for further investigations concerning the basic physiology and pathobiology of this clinically important tissue.

Prostate/chemistry/cytology↗
NASA NTRS1992

Glucocorticoids promote development of the osteoblast phenotype by selectively modulating expression of cell growth and differentiation associated genes

To understand the mechanisms by which glucocorticoids promote differentiation of fetal rat calvaria derived osteoblasts to produce bone-like mineralized nodules in vitro, a panel of osteoblast growth and differentiation related genes that characterize development of the osteoblast phenotype has been quantitated in glucocorticoid-treated cultures. We compared the mRNA levels of osteoblast expressed genes in control cultures of subcultivated cells where nodule formation is diminished, to cells continuously (35 days) exposed to 10(-7) M dexamethasone, a synthetic glucocorticoid, which promotes nodule formation to levels usually the extent observed in primary cultures. Tritiated thymidine labelling revealed a selective inhibition of internodule cell proliferation and promotion of proliferation and differentiation of cells forming bone nodules. Fibronectin, osteopontin, and c-fos expression were increased in the nodule forming period. Alkaline phosphatase and type I collagen expression were initially inhibited in proliferating cells, then increased after nodule formation to support further growth and mineralization of the nodule. Expression of osteocalcin was 1,000-fold elevated in glucocorticoid-differentiated cultures in relation to nodule formation. Collagenase gene expression was also greater than controls (fivefold) with the highest levels observed in mature cultures (day 35). At this time, a rise in collagen and TGF beta was also observed suggesting turnover of the matrix. Short term (48 h) effects of glucocorticoid on histone H4 (reflecting cell proliferation), alkaline phosphatase, osteopontin, and osteocalcin mRNA levels reveal both up or down regulation as a function of the developmental stage of the osteoblast phenotype. A comparison of transcriptional levels of these genes by nuclear run-on assays to mRNA levels indicates that glucocorticoids exert both transcriptional and post-transcriptional effects. Further, the presence of glucocorticoids enhances the vitamin D3 effect on gene expression. Those genes which are upregulated by 1,25(OH)2D3 are transcribed at an increased rate by dexamethasone, while those genes which are inhibited by vitamin D3 remain inhibited in the presence of dexamethasone and D3. We propose that the glucocorticoids promote changes in gene expression involved in cell-cell and cell-extracellular matrix signaling mechanisms that support the growth and differentiation of cells capable of osteoblast phenotype development and bone tissue-like organization, while inhibiting the growth of cells that cannot progress to the mature osteoblast phenotype in fetal rat calvarial cultures.

NASA Discipline Musculoskeletal↗
NASA NTRS2005

Transcriptional profile of a myotube starvation model of atrophy

Skeletal muscle wasting is a pervasive phenomenon that can result from a wide range of pathological conditions as well as from habitual muscular inactivity. The present work describes a cell-culture condition that induces significant atrophy in skeletal muscle C2C12 myotubes. The failure to replenish differentiation media in mature myotubes leads to rapid atrophy (53% in diameter), which is referred to here as starvation. Affymetrix microarrays were used to develop a transcriptional profile of control (fed) vs. atrophied (nonfed) myotubes. Myotube starvation was characterized by an upregulation of genes involved in translational inhibition, amino acid biosynthesis and transport, and cell cycle arrest/apoptosis, among others. Downregulated genes included several structural and regulatory elements of the extracellular matrix as well as several elements of Wnt/frizzled and TGF-beta signaling pathways. Interestingly, the characteristic transcriptional upregulation of the ubiquitin-proteasome system, calpains, and cathepsins known to occur in multiple in vivo models of atrophy were not seen during myotube starvation. With the exception of the downregulation of extracellular matrix genes, serine protease inhibitor genes, and the upregulation of the translation initiation factor PHAS-I, this model of atrophy in cell culture has a transcriptional profile quite distinct from any study published to date with atrophy in whole muscle. These data show that, although the gross morphology of atrophied muscle fibers may be similar in whole muscle vs. myotube culture, the processes by which this phenotype is achieved differ markedly.

NASA Discipline Musculoskeletal↗
NASA NTRS2006

The Role of Non-Targeted Effects as Mediators in the Biological Effects of Proton Irradiation

In recent years, the hypothesis that non-DNA targets are primary initiators and mediators of the biological effects of ionizing radiation, such as proton beams and heavy ions, has gained much interest. These phenomena have been denoted as non-targeted or bystander effects to distinguish them from the more traditionally studied model that focuses on direct damage to DNA causing chromosomal rearrangements and mutations as causative of most biological endpoints such as cell killing, tissue damage, and cancer. We review cellular and extra-cellular structures and signal transduction pathways that have been implemented in these recent studies. Non-targeted effects of interest include oxidative damage to the cytoplasm and mitochondria, disruption of the extra-cellular matrix, and modification of cytokine signaling including TGF-beta, and gap junction communication. We present an introduction to these targets and pathways, and contrast there role with DNA damage pathways.

Cucinotta, Francis A.↗
NASA NTRS2009

Development of a GCR Event-based Risk Model

A goal at NASA is to develop event-based systems biology models of space radiation risks that will replace the current dose-based empirical models. Complex and varied biochemical signaling processes transmit the initial DNA and oxidative damage from space radiation into cellular and tissue responses. Mis-repaired damage or aberrant signals can lead to genomic instability, persistent oxidative stress or inflammation, which are causative of cancer and CNS risks. Protective signaling through adaptive responses or cell repopulation is also possible. We are developing a computational simulation approach to galactic cosmic ray (GCR) effects that is based on biological events rather than average quantities such as dose, fluence, or dose equivalent. The goal of the GCR Event-based Risk Model (GERMcode) is to provide a simulation tool to describe and integrate physical and biological events into stochastic models of space radiation risks. We used the quantum multiple scattering model of heavy ion fragmentation (QMSFRG) and well known energy loss processes to develop a stochastic Monte-Carlo based model of GCR transport in spacecraft shielding and tissue. We validated the accuracy of the model by comparing to physical data from the NASA Space Radiation Laboratory (NSRL). Our simulation approach allows us to time-tag each GCR proton or heavy ion interaction in tissue including correlated secondary ions often of high multiplicity. Conventional space radiation risk assessment employs average quantities, and assumes linearity and additivity of responses over the complete range of GCR charge and energies. To investigate possible deviations from these assumptions, we studied several biological response pathway models of varying induction and relaxation times including the ATM, TGF -Smad, and WNT signaling pathways. We then considered small volumes of interacting cells and the time-dependent biophysical events that the GCR would produce within these tissue volumes to estimate how GCR event rates mapped to biological signaling induction and relaxation times. We considered several hypotheses related to signaling and cancer risk, and then performed simulations for conditions where aberrant or adaptive signaling would occur on long-duration space mission. Our results do not support the conventional assumptions of dose, linearity and additivity. A discussion on how event-based systems biology models, which focus on biological signaling as the mechanism to propagate damage or adaptation, can be further developed for cancer and CNS space radiation risk projections is given.

Cucinotta, Francis A.↗
NASA NTRS2009

A Catalog of Terrestrial Gamma-Ray Flashes Observed with the Fermi- Gamma-Ray Burst Monitor: The First Sixteen Months of Operation

The Gamma-ray Burst Monitor (GBM) on the Fermi Gamma-ray Space Telescope Observatory (Fermi) has been detecting on the average about one terrestrial gamma-ray flash every four weeks. This catalog presents the basic characteristics of observed TGFs from the beginning of the Fermi-GBM operation in 2008 July until 2009 October. The thick bismuth germanate (BGO) scintillation detectors of the GBM system have observed photon energies from TGFs at energies above 30 MeV. It is found that the TGF pulses are typically shorter than previously reported, and in several cases less than 0.2ms. Extremely high counting rates are encountered ~200kcps or higher per detector during portions of some TGFs. These high rates require considerable corrections (with inherent assumptions) to the observed data in order to derive the true counting rates.

Fishman, Gerald J.↗
NASA NTRS2010

The Latest Space-Borne Observations of TGFs from Fermi-GBM

The Gamma-ray Burst Monitor (GBM) on the Fermi Gamma-ray Space Telescope Observatory (Fermi) is detecting about two TGFs per week. This rate has increased by a factor of approx.eight since launch when flight software was uploaded to the spacecraft in November 2009 in order to increase the sensitivity of GBM to TGFs. Weaker, un-triggered TGFs are now also being observed about once per day over selected low-latitude regions Americas. The high efficiency and time resolution (2 s) of GBM allows temporal features to be resolved so that some insight may be gained on the origin and transport of the gamma-ray photons through the atmosphere. TGFs are observed to be shorter than previously thought, with an average duration of approx.100 micro-s. The absolute times of TGFs are known to approx.10 micro-s, allowing accurate correlations of TGFs with lightning networks and other lightning-related phenomena. The events are observed in the thick bismuth germanate (BGO) scintillation detectors of GBM with photon energies above 40 MeV. Other new results on the temporal and spectral characteristics of TGFs will be presented, along with properties of several electron-positron TGF events that have been identified.

Fishman, Gerald J.↗
NASA NTRS2010

Terrestrial Gamma-ray Flashes (TGFs) Observed with the Fermi-Gamma-ray Burst Monitor: Temporal and Spectral Properties

The Gamma-ray Burst Monitor (GBM) on the Fermi Gamma-ray Space Telescope Observatory (Fermi) was detecting ~2.1 TGFs per week. This rate has increased by a factor of ~8 since new flight software was uploaded to the spacecraft in November 2009 in order to increase the sensitivity of GBM to TGFs. Further upgrades to Fermi-GBM to allow observations of weaker TGFs are in progress. The high time resolution (2 s) allows temporal features to be resolved so that some insight may be gained on the origin and transport of the gamma-ray photons through the atmosphere. The absolute time of the TGFs, known to several microseconds, also allows accurate correlations of TGFs with lightning networks and other lightning-related phenomena. The thick bismuth germanate (BGO) scintillation detectors of the GBM system have observed photon energies from TGFs at energies above 40 MeV. New results on the some temporal aspects of TGFs will be presented along with spectral characteristics and properties of several electron-positron TGF events that have been identified.

Fishman, G. J.↗
NASA NTRS2010

What Can Geolocated Sferics Tell Us About Terrestrial Gamma-Ray Flashes?

The Fermi Gamma-ray Burst Monitor (GBM) has been detecting TGFs with increasing sensitivity over the past two years, owing to changes in flight software that have lowered its threshold for triggering and, recently, allowed a search for TGFs weaker than those which would cause an onboard trigger. Associations between TGFs detected in the first 18 months of operation and sferics detected using the World Wide Lightning Location Network (WWLLN) show that TGF peaks and lightning discharges are simultaneous to within tens of microseconds, and that GBM triggered on TGFs that occurred up to a distance of 300 km from the sub-spacecraft position. In the work presented here, we look for associations between TGFs detected by the Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI) and WWLLN sferics over the same 18 months, and we compare the match rate and detection horizon of the two instruments. We also look for associations between WWLLN sferics and more recent GBM TGFs, both triggered events and weaker TGFs uncovered in our untriggered search. We discuss whether in this new mode, GBM is detecting TGFs that are more distant from the sub-spacecraft point than 300 km, or whether the weaker TGFs are instead indicative of a luminosity distribution, either because the weaker ones originate deeper in the atmosphere or because they are intrinsically dimmer.

Connaughton, V.↗
NASA NTRS2011

New Modeling Approaches to Investigate Cell Signaling in Radiation Response

Ionizing radiation damages individual cells and tissues leading to harmful biological effects. Among many radiation-induced lesions, DNA double-strand breaks (DSB) are considered the key precursors of most early and late effects [1] leading to direct mutation or aberrant signal transduction processes. In response to damage, a flow of information is communicated to cells not directly hit by the radiation through signal transduction pathways [2]. Non-targeted effects (NTE), which includes bystander effects and genomic instability in the progeny of irradiated cells and tissues, may be particularly important for space radiation risk assessment [1], because astronauts are exposed to a low fluence of heavy ions and only a small fraction of cells are traversed by an ion. NTE may also have important consequences clinical radiotherapy [3]. In the recent years, new simulation tools and modeling approaches have become available to study the tissue response to radiation. The simulation of signal transduction pathways require many elements such as detailed track structure calculations, a tissue or cell culture model, knowledge of biochemical pathways and Brownian Dynamics (BD) propagators of the signaling molecules in their micro-environment. Recently, the Monte-Carlo simulation code of radiation track structure RITRACKS was used for micro and nano-dosimetry calculations [4]. RITRACKS will be used to calculate the fraction of cells traversed by an ion and delta-rays and the energy deposited in cells in a tissue model. RITRACKS also simulates the formation of chemical species by the radiolysis of water [5], notably the .OH radical. This molecule is implicated in DNA damage and in the activation of the transforming growth factor beta (TGF), a signaling molecule involved in NTE. BD algorithms for a particle near a membrane comprising receptors were also developed and will be used to simulate trajectories of signaling molecules in the micro-environment and characterize autocrine and paracrine cell communication and signal transduction.

Plante, Ianik↗
NASA NTRS2011

Space-Borne Observations of Intense Gamma-Ray Flashes (TGFs) Above Thunderstorms

Intense millisecond flashes of MeV photons have been observed with space-borne detectors. These terrestrial gamma-ray flashes (TGFs) were discovered with the Burst and Transient Source Experiment (BATSE) aboard the Compton Gamma- Ray Observatory (CGRO) in the early 1990s. They are now being observed with several other instruments, including the Gamma-ray Burst Monitor (GBM) detectors on the Fermi Gamma-ray Space Telescope. Although Fermi-GBM was designed and optimized for the observation of cosmic gamma-ray bursts (GRBs), it has unprecedented capabilities for these TGF observations. On several occasions, intense beams of high-energy electrons and positrons have been observed at the geomagnetic conjugate points of TGFs.

Fishman, Gerald J.↗
NASA NTRS2012

Terrestrial Gamma-Ray Flashes (TGFs) Above Thunderstorms

Intense of gamma rays have been observed by five different space-borne detectors. The TGFs have hard spectra, with photons extending to over 50 MeV. Most of these flashes last less than a millisecond. Relativistic electrons and positrons associated with TGFs are also seen by orbiting instruments In a special mode of operation, the Fermi-GBM detectors are now detecting an average of about one TGF every two hours. The Fermi spacecraft has been performing special orientations this year which has allowed the Fermi-LAT instrument also detect TGFs. The most likely origin of these high energy photons is bremsstrahlung radiation from electrons, produced by relativistic runaway electrons in intense electric fields within or above thunderstorm regions; the altitude of origin is uncertain. These TGFs may produce an appreciable radiation dose to passengers and crew in nearby aircraft. The observational aspects of TGFs will be the main focus of this talk; theoretical aspects remain speculative.

Fishman, Gerald J.↗
NASA NTRS2012

A Multiscale Computational Model of the Response of Swine Epidermis After Acute Irradiation

Radiation exposure from Solar Particle Events can lead to very high skin dose for astronauts on exploration missions outside the protection of the Earth s magnetic field [1]. Assessing the detrimental effects to human skin under such adverse conditions could be predicted by conducting territorial experiments on animal models. In this study we apply a computational approach to simulate the experimental data of the radiation response of swine epidermis, which is closely similar to human epidermis [2]. Incorporating experimentally measured histological and cell kinetic parameters into a multiscale tissue modeling framework, we obtain results of population kinetics and proliferation index comparable to unirradiated and acutely irradiated swine experiments [3]. It is noted the basal cell doubling time is 10 to 16 days in the intact population, but drops to 13.6 hr in the regenerating populations surviving irradiation. This complex 30-fold variation is proposed to be attributed to the shortening of the G1 phase duration. We investigate this radiation induced effect by considering at the sub-cellular level the expression and signaling of TGF-beta, as it is recognized as a key regulatory factor of tissue formation and wound healing [4]. This integrated model will allow us to test the validity of various basic biological rules at the cellular level and sub-cellular mechanisms by qualitatively comparing simulation results with published research, and should lead to a fuller understanding of the pathophysiological effects of ionizing radiation on the skin.

FROM↗
NASA NTRS2012

Using an A-10 Aircraft for Airborne measurements of TGFs

Plans are underway to convert an A-10 combat attack aircraft into a research aircraft for thunderstorm research. This aircraft would be configured and instrumented for flights into large, convective thunderstorms. It would have the capabilities of higher altitude performance and protection for thunderstorm conditions that exceed those of aircraft now in use for this research. One area of investigation for this aircraft would be terrestrial gamma ]ray flashes (TGFs), building on the pioneering observations made by the Airborne Detector for Energetic Lightning Emissions (ADELE) project several years ago. A new and important component of the planned investigations are the continuous, detailed correlations of TGFs with the electric fields near the aircraft, as well as detailed measurements of nearby lightning discharges. Together, the x-and gamma-radiation environments, the electric field measurements, and the lightning observations (all measured on microsecond timescales) should provide new insights into this TGF production mechanism. The A -10 aircraft is currently being modified for thunderstorm research. It is anticipated that the initial test flights for this role will begin next year.

Fishman, Gerald J.↗
NASA NTRS2012

New Therapeutic Window of Regenerative Opportunity in Diabetic Retinopathy by VESGEN Analysis

Vascular pattern may serve as a useful new biomarker principle of complex, multi-scale signaling in pathological, physiological angiogenesis and microvascular remodeling. Each angiogenesis stimulator or inhibitor we have analyzed, including VEGF, bFGF, TGF-beta1, angiostatin and triamcinolone acetonide, has induced a novel "fingerprint" or "signature" biomarker vascular pattern that is spatio-temporally unique. Remodeling vasculature thereby provides an informative read-out of dominant molecular signaling, when analyzed by innovative, fractal-based VESsel GENeration (VESGEN) Analysis software. Using VESGEN to analyze ophthalmic clinical vascular images, we recently introduced a potential paradigm shift to the understanding of early-stage progression that suggests new regenerative opportunities for human diabetic retinopathy (DR), the major blinding disease for working-aged adults. In a pilot study, we discovered that angiogenesis oscillates as a surprising, homeostatic-like regeneration of retinal vessels during early progression of DR (IOVS 51(1):498). Results suggest that the term non-proliferative DR may be a misnomer. In new studies, normalization of the vasculature will be determined from the response of vascular pattern to therapeutic monitoring and treatment. We have mapped and quantified in vivo experimental models of angiogenesis, lymphangiogenesis and intravital blood flow from cellular/molecular to higher systems levels that include a murine model of infant retinopathy of prematurity (ROP); developing and pathological coronary and placental-like vessel models; progressive intestinal inflammation, growing murine tumors, and other pathological, physiological and therapeutically treated tissues of transgenic mice and avian embryos. Vascular Alterations, Visual Impairments (VIIP) & Increased Intracranial Pressure (ICP), Immunosuppression & Bone Loss: NASA-defined risk categories for human space exploration and ISS Utilization

Parsons-Wingert, Patricia A.↗
NASA NTRS2014

Chronic Lunar Dust Exposure on Rat Cornea: Evaluation by Gene Expression Profiling

Lunar dust is capable of entering habitats and vehicle compartments by sticking to spacesuits or other objects that are transferred into the spacecraft from the lunar surface and has been reported to cause irritation upon exposure. During the Apollo missions, crewmembers reported irritation specifically to the skin and eyes after contamination of the lunar and service modules. It has since been hypothesized that ocular irritation and abrasion might occur as a result of such exposure, impairing crew vision. Recent work has shown that both ultrafine and unground lunar dust exhibited minimal irritancy of the ocular surface (i.e., cornea); however, the assessment of the severity of ocular damage resulting from contact of lunar dust particles to the cornea has focused only on macroscopic signs of mechanical irritancy and cytotoxicity. Given the chemical reactive properties of lunar dust, exposure of the cornea may contribute to detrimental effects at the molecular level including but not limited to oxidative damage. Additionally, low level chronic exposures may confound any results obtained in previous acute studies. We report here preliminary results from a tissue sharing effort using 10‐week‐old Fischer 344 male rats chronically exposed to filtered air or jet milled lunar dust collected during Apollo 14 using a Jaeger‐NYU nose‐only chamber for a total of 120 hours (6 hours daily, 5 days a week) over a 4‐week period. RNA was isolated from corneas collected from rats at 1 day and 7 days after being exposed to concentrations of 0, 20, and 60 mg/m3 of lunar dust. Microarray analysis was performed using the Affymetrix GeneChip Rat Genome 230 2.0 Array with Affymetrix Expression Console and Transcriptome Analysis Console used for normalization and secondary analysis. An Ingenuity iReport"TM" was then generated for canonical pathway identification. The number of differentially expressed genes identified increases with dose compared to controls suggesting a more severe response to the lunar dust insult at higher levels. Pathways of interests that have been identified in all exposed samples include oxidative stress response, mitochondrial dysfunction, fibrosis, epithelial healing, TGF-Beta signaling, and extracellular matrix remodeling. Several biological processes related to cell migration, cellular proliferation, and eye development were also identified to be altered by exposure to lunar dust. Our preliminary results suggest that even a chronic insult of lunar dust as low as 20 mg/m(exp 3) elicits a molecular response in cornea tissue. Lunar dust on the surface of the moon would have the added properties of ionization and activation potentially leading to further damage to the cornea and greater sensitivity to any other environmental insult such as exposure to radiation. Additional studies are required to fully assess the risk of vision impairment and the mechanistic responses initiated in cornea exposed to lunar dust as well as the potential for long‐term effects to astronaut health

Theriot, C. A.↗
NASA NTRS2020

Circulating miRNA Signature Predicts Health Risks Associated with Cancer and Spaceflight

Biological risks associated with space radiation and microgravity are major concerns for long-term space travel. Through a Systems Biology approach, our previous NASA work has shown both TGF signaling pathways and miRNAs have a critical impact on defining health risks with and without space irradiation. We hypothesize that circulating microRNA (miRNA) signatures are driving microvascular disease and muscle degeneration associated with accelerating aging and will be enhanced by exposure to the space environment (radiation and microgravity). We are investigating this hypothesis with both in vivo and in vitro models to test novel antagonist therapies to these miRNA signatures as countermeasures to reduce space radiation-induced health risks. A comprehensive Systems Biology approach is utilized to examine the influence by high atomic number by high (H) atomic number (Z) and energy (E) (HZE) irradiation. To simulate low-dose exposure due to galactic cosmic rays (GCR), we used ions, energy, and doses determined by a NASA consensus formula of 7 different ions to represent GCR (referred to as GCR sim model). To similate high-dose radiation exposure due to solar particle events (SPE), we used a solar particle event (SPE) sim model which gave a total dose of 1Gy protons with energy ranges from 50MeV to 150MeV. C57BL/6 wild-type female mice were utilized for the irradiations with our established simulated microgravity model (hindlimb suspension model) and an in vitro 3D microvasculature tissue model under simulated microgravity (clinostat) conditions was also irradiated. To expand on the circulating miRNA signature determined from our preliminary data, we determined a group of conserved miRNAs which are commonly being regulated in the majority of the organs and tissues throughout the host using our established techniques. MiRNA-sequencing was done on serum (at time of sacrifice), liver, heart, and muscle (soleus muscle) tissue for all radiation groups. Additional validation of the key miRNAs was performed by droplet digital PCR (ddPCR). This revealed a key circulating miRNA signature (consisting of multiple miRNAs) impacting cardiovascular and muscular disease risk. Further in vitro experiments with CRISPR/Cas9 system to knockout the key miRNA signatures, novel self-delivering antagomirs, overexpression of the miRNAs test the functional impact of the miRNA signatures on both microvascular disease and muscle degeneration due to space irradiation. The current work has started to allow the possible development of a novel minimally invasive miRNA based radioprotector to be used as a countermeasure for space radiation. Collectively, understanding of how whole body space radiation impacts microvascular and tissue degeneration through circulating miRNAs will greatly enhance health risk prognostication and provide possible new mechanisms for protection against space radiation. This work is supported by the Translational Research Institute through NASA Cooperative Agreement NNX16AO69A (T-0404) awarded to AB.

Beheshti, Afshin↗