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Research Containing: Biological

Spaceflight and ageing: reflecting on Caenorhabditis elegans in space

by cfynanon 9 June 2015in Biology & Biotechnology No comment

The prospect of space travel continues to capture the imagination. Several competing companies are now promising flights for the general population. Previously, it was recognized that many of the physiological changes that occur with spaceflight are similar to those seen with normal ageing. This led to the notion that spaceflight can be used as a model of accelerated ageing and raised concerns about the safety of individuals engaging in space travel. Paradoxically, however, space travel has been recently shown to be beneficial to some aspects of muscle health in the tiny worm Caenorhabditis elegans. C. elegans is a commonly used laboratory animal for studying ageing. C. elegans displays age-related decline of some biological processes observed in ageing humans, and about 35% of C. elegans' genes have human homologs. Space flown worms were found to have decreased expression of a number of genes that increase lifespan when expressed at lower levels. These changes were accompanied by decreased accumulation of toxic protein aggregates in ageing worms' muscles. Thus, in addition to spaceflight producing physiological changes that are similar to accelerated ageing, it also appears to produce some changes similar to delayed ageing. Here, we put forward the hypothesis that in addition to the previously well-appreciated mechanotransduction changes, neural and endocrine signals are altered in response to spaceflight and that these may have both negative (e.g. less muscle protein) and some positive consequences (e.g. healthier muscles), at least for invertebrates, with respect to health in space. Given that changes in circulating hormones are well documented with age and in astronauts, our view is that further research into the relationship between metabolic control, ageing, and adaptation to the environment should be productive in advancing our understanding of the physiology of both spaceflight and ageing.

Related URLs:
http://www.ncbi.nlm.nih.gov/pubmed/24217152

Changes in mouse thymus and spleen after return from the STS-135 mission in space

by cfynanon 9 June 2015in Biology & Biotechnology No comment

Our previous results with flight (FLT) mice showed abnormalities in thymuses and spleens that have potential to compromise immune defense mechanisms. In this study, the organs were further evaluated in C57BL/6 mice after Space Shuttle Atlantis returned from a 13-day mission. Thymuses and spleens were harvested from FLT mice and ground controls housed in similar animal enclosure modules (AEM). Organ and body mass, DNA fragmentation and expression of genes related to T cells and cancer were determined. Although significance was not obtained for thymus mass, DNA fragmentation was greater in the FLT group (P<0.01). Spleen mass alone and relative to body mass was significantly decreased in FLT mice (P<0.05). In FLT thymuses, 6/84 T cell-related genes were affected versus the AEM control group (P<0.05; up: IL10, Il18bp, Il18r1, Spp1; down: Ccl7, IL6); 15/84 cancer-related genes had altered expression (P<0.05; up: Casp8, FGFR2, Figf, Hgf, IGF1, Itga4, Ncam1, Pdgfa, Pik3r1, Serpinb2, Sykb; down: Cdc25a, E2F1, Mmp9, Myc). In the spleen, 8/84 cancer-related genes were affected in FLT mice compared to AEM controls (P<0.05; up: Cdkn2a; down: Birc5, Casp8, Ctnnb1, Map2k1, Mdm2, NFkB1, Pdgfa). Pathway analysis (apoptosis signaling and checkpoint regulation) was used to map relationships among the cancer-related genes. The results showed that a relatively short mission in space had a significant impact on both organs. The findings also indicate that immune system aberrations due to stressors associated with space travel should be included when estimating risk for pathologies such as cancer and infection and in designing appropriate countermeasures. Although this was the historic last flight of NASA's Space Shuttle Program, exploration of space will undoubtedly continue.

Related URLs:
http://www.ncbi.nlm.nih.gov/pubmed/24069384
http://www.plosone.org/article/fetchObject.action?uri=info:doi/10.1371/journal.pone.0075097&representation=PDF

Effects of a simulated microgravity model on cell structure and function in rat testis and epididymis

by cfynanon 9 June 2015in Biology & Biotechnology No comment

A tail-suspension (TS) rat model used to simulate microgravity was tested for its effects on the anatomy, cell structure, and function of the testis and epididymis in sexually mature male rats. Rats suspended for 7 days without inguinal canal ligation exhibited a significant (P less than or equal to 0.05) reduction in testis weight compared with controls (1.55 +/- 0.04 to 1.1 +/- 0.02 g). Except for the liver, epididymis, and adrenals of TS rats and TS rats allowed to recover for 7 days, no significant (P less than or equal to 0.05) change was observed in the weight of other body and accessory sex organs. A histological examination of the testes and epididymides of model animals revealed disorganized seminiferous tubules and accumulation of large multinucleated cells and spermatids in the lumen of the epididymis. A significant (P less than or equal to 0.05) increase in serum luteinizing hormone (53.1 +/- 6.7 to 66.2 +/- 10.1 ng/ml) and follicle-stimulating hormone (257 +/- 25 to 305 +/- 38 ng/ml) was observed in TS nonligated rats, whereas serum prolactin and testosterone levels were observed to decline from 8.3 +/- 1.3 to 5.1 +/- 0.29 and 7.1 +/- 1.3 to 3.8 +/- 0.25 ng/ml, respectively. Decreases in testis protein content and testosterone levels of the testis, interstitial fluid, and epididymis were also observed in model animals. These data demonstrate that the suspension procedure used in the National Aeronautics and Space Administration TS model results in the testis and epididymis translocating into the abdominal cavity, causing cellular degeneration and organ dysfunction.

Related URLs:
http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med3&AN=1559955
http://sfxhosted.exlibrisgroup.com/mayo?sid=OVID:medline&id=pmid:1559955&id=doi:&issn=8750-7587&isbn=&volume=72&issue=2&spage=748&pages=748-59&date=1992&title=Journal+of+Applied+Physiology&atitle=Effects+of+a+simulated+microgravity+model+on+cell+structure+and+function+in+rat+testis+and+epididymis.&aulast=Hadley&pid=%3Cauthor%3EHadley+JA%3C%2Fauthor%3E&%3CAN%3E1559955%3C%2FAN%3E

Enhanced Daily Load Stimulus to Bone in Spaceflight and on Earth

by cfynanon 9 June 2015in Biology & Biotechnology No comment

INTRODUCTION: It has been hypothesized that bone loss arising from long-duration space travel is caused by a reduction in mechanical stimuli to the skeleton. The daily load stimulus (DLS) theory was first proposed to relate daily time histories of mechanical loading from ground reaction forces to bone homeostasis. In this methods paper, an enhanced daily load stimulus (EDLS) is proposed to account for recently developed theories on saturation and recovery of the osteogenic potential of bone with repeated cyclic loading and the potential benefits of standing. MODEL DEVELOPMENT: To determine periods of continuous activity (sitting, standing, walking, running, and other activity), an activity determination algorithm based on entire days of in-shoe forces was developed. The rainflow peak counting method was used to analyze the in-shoe force data from entire working days in preparation for the calculation of the EDLS. Parameters characterizing saturation and recovery with cyclical loading from running and walking as well as the effects of standing were estimated based on data in the literature. DISCUSSION: The activity algorithm proved to be accurate and robust when applied to in-shoe force data from entire waking days. The EDLS may be useful in prescribing "dose-based" exercise prescriptions to crewmembers during long-duration spaceflights and missions to the Moon and Mars. Validation of the proposed EDLS model will be possible with data from an ongoing human bed rest study examining changes in bone mineral density with controlled skeletal loading.

Related URLs:
http://www.ingentaconnect.com/content/asma/asem/2009/00000080/00000011/art00001
http://dx.doi.org/10.3357/ASEM.2380.2009

On the radiosensitivity of man in space

by cfynanon 9 June 2015in Biology & Biotechnology No comment

Astronauts' radiation exposure limits are based on experimental and epidemiological data obtained on Earth. It is assumed that radiation sensitivity remains the same in the extraterrestrial space. However, human radiosensitivity is dependent upon the response of the hematopoietic tissue to the radiation insult. It is well known that the immune system is affected by microgravity. We have developed a mathematical model of radiation-induced myelopoiesis which includes the effect of microgravity on bone marrow kinetics. It is assumed that cellular radiosensitivity is not modified by the space environment, but repopulation rates of stem and stromal cells are reduced as a function of time in weightlessness. A realistic model of the space radiation environment, including the HZE component, is used to simulate the radiation damage. A dedicated computer code was written and applied to solar particle events and to the mission to Mars. The results suggest that altered myelopoiesis and lymphopoiesis in microgravity might increase human radiosensitivity in space. c2001 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

Related URLs:
http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med4&AN=11642296
http://sfxhosted.exlibrisgroup.com/mayo?sid=OVID:medline&id=pmid:11642296&id=doi:&issn=0273-1177&isbn=&volume=27&issue=2&spage=345&pages=345-54&date=2001&title=Advances+in+Space+Research&atitle=On+the+radiosensitivity+of+man+in+space.&aulast=Esposito&pid=%3Cauthor%3EEsposito+RD%3C%2Fauthor%3E&%3CAN%3E11642296%3C%2FAN%3E

A model of radiation-induced myelopoiesis in space

by cfynanon 9 June 2015in Biology & Biotechnology No comment

Astronauts' radiation exposure limits are based on experimental and epidemiological data obtained on Earth. It is assumed that radiation sensitivity remains the same in the extraterrestrial space. However, human radiosensitivity is dependent upon the response of the hematopoietic tissue to the radiation insult. It is well known that the immune system is affected by microgravity. We have developed a mathematical model of radiation-induced myelopoiesis which includes the effect of microgravity on bone marrow kinetics. It is assumed that cellular radiosensitivity is not modified by the space environment, but repopulation rates of stem and stromal cells are reduced as a function of time in weightlessness. A realistic model of the space radiation environment, including the HZE component, is used to simulate the radiation damage. A dedicated computer code was written and applied to solar particle events and to the mission to Mars. The results suggest that altered myelopoiesis and lymphopoiesis in microgravity might increase human radiosensitivity in space.

Related URLs:
http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=emed5&AN=2001313923
http://sfxhosted.exlibrisgroup.com/mayo?sid=OVID:embase&id=pmid:&id=doi:&issn=1120-1797&isbn=&volume=17&issue=SUPPL.+1&spage=181&pages=181-182&date=2001&title=Physica+Medica&atitle=A+model+of+radiation-induced+myelopoiesis+in+space&aulast=Esposito&pid=%3Cauthor%3EEsposito+R.D.%3C%2Fauthor%3E&%3CAN%3E2001313923%3C%2FAN%3E

Physical and biological organ dosimetry analysis for international space station astronauts

by cfynanon 9 June 2015in Biology & Biotechnology No comment

In this study, we analyzed the biological and physical organ dose equivalents for International Space Station (ISS) astronauts. Individual physical dosimetry is difficult in space due to the complexity of the space radiation environment, which consists of protons, heavy ions and secondary neutrons, and the modification of these radiation types in tissue as well as limitations in dosimeter devices that can be worn for several months in outer space. Astronauts returning from missions to the ISS undergo biodosimetry assessment of chromosomal damage in lymphocyte cells using the multicolor fluorescence in situ hybridization (FISH) technique. Individual-based pre-flight dose responses for lymphocyte exposure in vitro to gamma rays were compared to those exposed to space radiation in vivo to determine an equivalent biological dose. We compared the ISS biodosimetry results, NASA's space radiation transport models of organ dose equivalents, and results from ISS and space shuttle phantom torso experiments. Physical and biological doses for 19 ISS astronauts yielded average effective doses and individual or population-based biological doses for the approximately 6-month missions of 72 mSv and 85 or 81 mGy-Eq, respectively. Analyses showed that 80% or more of organ dose equivalents on the ISS are from galactic cosmic rays and only a small contribution is from trapped protons and that GCR doses were decreased by the high level of solar activity in recent years. Comparisons of models to data showed that space radiation effective doses can be predicted to within about a +/-10% accuracy by space radiation transport models. Finally, effective dose estimates for all previous NASA missions are summarized.

Related URLs:
http://www.ncbi.nlm.nih.gov/pubmed/18582161

Computational modeling for the optimization of a cardiogenic 3D bioprocess of encapsulated embryonic stem cells

by cfynanon 9 June 2015in Biology & Biotechnology No comment

We present a computational fluid dynamics (CFD)-based model aimed at the identification of optimized culture conditions promoting efficient cardiogenesis of hydrogel-bead-encapsulated embryonic stem cells (ESCs) within a rotating bioreactor. The numerical approach, integrating diffusion, convection, and multiphase fluid dynamics calculations, allowed to evaluate (i) the microgravity motion of the floating beads, (ii) the O-2 delivery to the cells, also (iii) taking into account the cellularO(2) consumption, as a function of different rotation speeds of the breeding chamber. According to our results, a 25rpm rotation (i) enhances an adequate mixing of the cell carriers, avoiding sedimentation and excessive packing, also maintaining a quite homogeneous distribution of the suspended beads and (ii) imparts a proper cellular O-2 supply, providing cells close to a normoxia condition. The bioreactor working conditions derived from the numerical analysis allowed the attainment of in vitro long-term cell viability maintenance, supporting efficient large-scale generation of ESC-derived cardiomyocytes (ESC-DCs) through a chemical-based conditioning bioprocess. In conclusion, we demonstrated the feasibility of using CFD-based tools, as a reliable and cost-effective strategy to assist the design of a 3D cardiogenic bioprocess.

Related URLs:
<Go to ISI>://WOS:000300230600020

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