Microgravity exposure as well as chronic muscle disuse are two of the main causes of physiological adaptive skeletal muscle atrophy in humans and murine animals in physiological condition. The aim of this study was to investigate at both morphological and global gene expression level skeletal muscle adaptation to microgravity in mouse soleus and extensor digitorum longus (EDL). Adult male mice C57BL/N6 were flown aboard the BION-M1 biosatellite for 30 days on orbit (BF) or housed in a replicate flight habitat on Earth (BG) as reference flight control. In this study we investigated for the first time gene expression adaptation to 30 days of microgravity exposure in mouse soleus and EDL highlighting potential new targets for improvement of countermeasures able to ameliorate or even prevent microgravity-induced atrophy in future spaceflights. Overall Design: C57BL/N6 mice were randomly divided in 3 groups: Bion Flown (BF) mice flown aboard the Bion M1 biosatellite in microgravity environment for 30 days; Bion Ground (BG) mice housed in the same habitat of flown animals but exposed to earth gravity; and Flight Control (FC) mice housed in a standard animal facility.

Genome-wide transcriptional profiling showed that reducing gravity levels in the International Space Station (ISS) causes important alterations in Drosophila gene expression intimately linked to imposed spaceflight-related environmental constrains during Drosophila metamorphosis. However simulation experiments on ground testing space-related environmental constraints show differential responses. Curiously although particular genes are not common in the different experiments the same GO groups including a large multigene family related with behavior stress response and organogenesis are over represented in them. A global and integrative analysis using the gene expression dynamics inspector (GEDI) self-organizing maps reveals different degrees in the responses of the transcriptome when using different environmental conditions or microgravity/hypergravity simulation devices. These results suggest that the transcriptome is finely tuned to normal gravity. In regular environmental conditions the alteration of this constant parameter on Earth can have mild effects on gene expression but when environmental conditions are far from optimal the gene expression is much more intense and consistent effects.

The total RNA was extracted from 2T3 pre-osteoblast cells exposed to static or simulated microgravity (Rotating Wall Vessel) conditions. The RNA was then sent to Affymetrix microarray core facility at Baylor College of Medicine (Houston TX) for microarray analysis.

Proton irradiation is touted for its improved tumor targeting due to the physical advantages of ion beams for radiotherapy. Recent studies from our laboratory have shown that in addition to targeting advantages proton irradiation can inhibit angiogenic and immune factors and thereby modulate tumor progression. High-energy protons also constitute a principal component of the galactic cosmic rays to which astronauts are exposed. Increased understanding of the biological effects of proton exposure would thus contribute to both improved cancer therapy and carcinogenesis risk assessment for space travel. In addition age plays a major role in tumor incidence and is a critical consideration for estimating cancer risk. We investigated the effects of host age and proton exposure on tumor progression. Tumor lag time and growth dynamics were tracked following injection of murine Lewis lung carcinoma (LLC) cells into young (68 day) versus old (736 day) mice with or without coincident irradiation. Tumor progression was suppressed in old compared to young mice. Differences in progression were further modulated by proton irradiation (1GeV) with increased inhibition evident in old mice. Through global transcriptome analysis TGFB1 and TGFB2 were determined to be key players that contributed to the tumor dynamics observed. These findings point to older hosts providing decreased systemic tumor support which can be further inhibited by proton irradiation. Overall design: For genome-wide expression profiling of tumor tissue Mouse WG-6 BeadArray chips (Illumina San Diego CA) were used. Total RNA was amplified with the Ambion Illumina TotalPrep Amplification Kit (Ambion Austin TX) and labeled from all replicate biological samples for each condition. For tumor replicates thirty tumor samples from adolescent and thirty tumor samples from old mice for a total of 60 tumor samples were used. All replicate samples were run individually. For each age group ten tumor samples had received proton irradiation while twenty tumor samples were from unirradiated mice (as described above). Total RNA was isolated and purified using TRIzol (Invitrogen) and quantified using an Agilent Bioanalyzer. Samples were deemed suitable for amplification and hybridization if they had 28s/18s = 2:1 RIN >7. Total RNA of 500ng per sample was amplified using AmbionTotalPrep and 1.5ug of the product was loaded onto the chips. Following hybridization at 55C the chips were washed and then scanned using the Illumina iScan System. The data was checked with GenomeStudio (Illumina) for quality control. In GenomeStudio data was background subtracted and rank invariant normalization was applied. Data was imported into MultiExperiment Viewer MeV for statistical analysis. The statistically significant genes were determined using MeV by applying a one-way ANOVA analysis with standard Bonferroni correction with a FDR <0.05 that resulted in a list of significant genes. Average gene expression signals <10 were filtered out due to signal being

In recent times long-term stay has become a common occurrence in the International Space Station (ISS). However adaptation to the space environment can sometimes pose physiological problems to the astronauts after their return. Therefore it is important to develop healthcare technologies for astronauts. In this study hair an easy-to-obtain sample was identified as the candidate. In order to investigate the genetic changes in human hair during space flight the hair follicles of 10 astronauts were analyzed by DNA microarray and real time q-PCR analyses. Space environment induced gene expression of hair follicles of astronaut was measured 6 differnent times included 2 in flight on orbit. Ten independent experiments were performed on differing astronauts. and the sampling day was differed for each astronaut because of their schedules.

Controlled hypobaria presents biology with an environment that is never encountered in terrestrial ecology yet the apparent components of hypobaria are stresses typical of terrestrial ecosystems. High altitude for example presents terrestrial hypobaria always with hypoxia as a component stress since the relative partial pressure of O2 is constant in the atmosphere. Laboratory-controlled hypobaria however allows the dissection of pressure effects away from the effects typically associated with altitude in particular hypoxia as the partial pressure of O2 can be varied. In this study whole transcriptomes of plants grown in ambient (97 kPa/pO2 = 21 kPa) atmospheric conditions were compared to those of plants transferred to five different atmospheres of varying pressure and oxygen composition for 24 h: 50 kPa/pO2 = 10 kPa 25 kPa/pO2 = 5 kPa 50 kPa/pO2 = 21 kPa 25 kPa/pO2 = 21 kPa or 97 kPa/pO2 = 5 kPa. The plants exposed to these environments were 10 day old Arabidopsis seedlings grown vertically on hydrated nutrient plates. In addition 5 day old plants were also exposed for 24 h to the 50 kPa and ambient environments to evaluate age-dependent responses. The gene expression profiles from roots and shoots showed that the hypobaric response contained more complex gene regulation than simple hypoxia and that adding back oxygen to normoxic conditions did not completely alleviate gene expression changes in hypobaric responses.

Age plays a crucial role in the interplay between tumor and host; with further perturbations induced by irradiation. Proton irradiation on tumors induces biological modulations including inhibition of angiogenic and immune factors critical to hallmark processes impacting tumor development in addition to physical targeting advantages. These advantages have provided promising results for proton therapy in cancer. Additionally protons have implications for carcinogenesis risk of space travel (due to the high proportion of high energy protons in space radiation). Through a systems biology approach we investigated how host tissue (i.e. splenic tissue) of tumor-bearing mice is altered with age with or without whole-body proton exposure. Transcriptome analysis was performed on splenic tissue from adolescent (68 day) versus old (736 day) C57BL/6 male mice injected with Lewis lung carcinoma cells with or without three fractionations of 0.5Gy (1GeV) proton irradiation. Global transcriptome analysis indicated that proton irradiation of adolescent hosts caused significant signaling changes within splenic tissues that support carcinogenesis within the mice as compared to old subjects. Increases in cell cycling and immunosuppression in irradiated adolescent hosts with CDK2 MCM7 CD74 and RUVBL2 as the key players were involved in the regulatory changes in host environment response (i.e. spleen). These results suggest a significant biological component to proton irradiation operative through host age that would indicate a modulation of host s ability to support carcinogenesis in adolescence and the bestowal of resistance to immunosuppression carcinogenesis and genetic perturbation by old age.

Entire microRNA expression were analyzed using the Filgen Array miRNA Caenorhabditis elegans 232 probes (Filgen). In the microRNA expression analysis we compared the expression data between two groups: micro-gravity samples (4 d and 8 d) and controls (4 d and 8 d ground control and 1 G centrifuge onboard ISS).

The present study concerns the effects of 21 days of sustained recumbence (bedrest) on skeletal muscle gene expression. 14 male subjects participated in normoxic bedrest (NBR) with muscle unloading for 21 days this is a substudy of tha PlanHab-study which apart from normoxic bedrest also involved hypoxic bedrest and hypoxic ambulation. Throughout both bedrest interventions each subject remained in a horizontal position at all times. He was allowed one pillow for the head and to occasionally lean on an elbow while eating or being transferred to a gurney. Muscular exercise was prohibited. During the HAMB confinement each subject was allowed to move freely within the hypoxic area. To mimic a normal level of physical activity subjects performed 30 minutes of low-to-moderate-intensity exercise twice daily. Muscle samples from Vastus lateralis.

Spaceflight results in a number of adaptations to skeletal muscle including atrophy and shifts towards faster muscle fiber types. To identify changes in gene expression that may underlie these adaptations microarray expression analysis was performed on gastrocnemius from mice flown on the STS-108 shuttle flight (11 days 19 hours) versus mice maintained on earth for the same period. Additionally to identify changes that were due to unloading and reloading microarray analyses were conducted on calf muscle from ground-based mice subjected to hindlimb suspension (12 days) and mice subjected to hindlimb suspension plus a brief period of reloading (3.5 hours) to simulate the time between landing and sacrifice of the spaceflight mice.