Ophthalmic changes have occurred in a subset of astronauts on International Space Station missions. Visual deterioration is considered the greatest human health risk of spaceflight. Affected astronauts exhibit higher concentrations of 1-carbon metabolites (e.g., homocysteine) before flight. We hypothesized that genetic variations in 1-carbon metabolism genes contribute to susceptibility to ophthalmic changes in astronauts. We investigated 5 polymorphisms in the methionine synthase reductase (MTRR), methylenetetrahydrofolate reductase (MTHFR), serine hydroxymethyltransferase (SHMT), and cystathionine beta-synthase (CBS) genes and their association with ophthalmic changes after flight in 49 astronauts. The number of G alleles of MTRR 66 and C alleles of SHMT1 1420 both contributed to the odds of visual disturbances. Preflight dehydroepiandrosterone was positively associated with cotton wool spots, and serum testosterone response during flight was associated with refractive change. Block regression showed that B-vitamin status and genetics were significant predictors of many of the ophthalmic outcomes that we observed. In one example, genetics trended toward improving (P = 0.10) and B-vitamin status significantly improved (P < 0.001) the predictive model for refractive change after flight. We document an association between MTRR 66 and SHMT1 1420 polymorphisms and spaceflight-induced vision changes. This line of research could lead to therapeutic options for both space travelers and terrestrial patients.
Related URLs:
http://www.ncbi.nlm.nih.gov/pubmed/26316272
ELITE S2 – AN INSTRUMENT FOR MOTION ANALYSIS ON BOARD THE INTERNATIONAL SPACE STATION
This paper describes the activities for utilization and control of ELITE S2 on board the International Space Station (ISS). ELITE S2 is a payload of the Italian Space Agency (ASI) for quantitative human movement analysis in weightlessness. Within the frame of a bilateral agreement with NASA, ASI has funded a number of facilities, enabling different scientific experiments on board the ISS. ELITE S2 has been developed by the ASI contractor Kayser Italia, delivered to the Kennedy Space Center in 2006 for pre-flight processing, launched in 2007 by the Space Shuttle Endeavour (STS-118), integrated in the U.S. lab and used during the Increments 16 and 17 through 2008. The ELITE S2 flight segment comprises equipment mounted into an Express Rack and a number of stowed items to be deployed for experiment performance (video cameras and accessories). The ground segment consists in a User Support Operations Center (based at Kayser Italia) enabling real-time payload control and a number of User Home Bases (located at the ASI and PIs premises), for the scientific assessment of the experiment performance. Two scientific protocols on reaching and cognitive processing have been successfully performed in five sessions involving two ISS crewmembers: IMAGINE 2 and MOVE.
Space, the final frontier: A critical review of recent experiments performed in microgravity
Space biology provides an opportunity to study plant physiology and development in a unique microgravity environment. Recent space studies with plants have provided interesting insights into plant biology, including discovering that plants can grow seed-to-seed in microgravity, as well as identifying novel responses to light. However, spaceflight experiments are not without their challenges, including limited space, limited access, and stressors such as lack of convection and cosmic radiation. Therefore, it is important to design experiments in a way to maximize the scientific return from research conducted on orbiting platforms such as the International Space Station. Here, we provide a critical review of recent spaceflight experiments and suggest ways in which future experiments can be designed to improve the value and applicability of the results generated. These potential improvements include: utilizing in-flight controls to delineate microgravity versus other spaceflight effects, increasing scientific return via next-generation sequencing technologies, and utilizing multiple genotypes to ensure results are not unique to one genetic background. Space experiments have given us new insights into plant biology. However, to move forward, special care should be given to maximize science return in understanding both microgravity itself as well as the combinatorial effects of living in space.
Related URLs:
http://www.ncbi.nlm.nih.gov/pubmed/26795156
The SCD – Stem Cell Differentiation ESA Project: Preparatory Work for the Spaceflight Mission
Due to spaceflight, astronauts experience serious, weightlessness-induced bone loss because of an unbalanced process of bone remodeling that involves bone marrow mes- enchymal stem cells (BMSCs), as well as osteoblasts, osteo- cytes, and osteoclasts. The effects of microgravity on osteo- cells have been extensively studied, but it is only recently that consideration has been given to the role of BMSCs. Pre- vious researches indicated that human BMSCs cultured in simulated microgravity (sim-μg) alter their proliferation and differentiation. The spaceflight opportunities for biomedical experiments are rare and suffer from a number of opera- tive constraints that could bias the validity of the experiment itself, but remain a unique opportunity to confirm and explain the effects due to microgravity, that are only par- tially activated/detectable in simulated conditions. For this reason, we carefully prepared the SCD – STEM CELLS DIFFERENTIATION experiment, selected by the European Space Agency (ESA) and now on the International Space Station (ISS). Here we present the preparatory studies per- formed on ground to adapt the project to the spaceflight constraints in terms of culture conditions, fixation and stor- age of human BMSCs in space aiming at satisfying the biological requirements mandatory to retrieve suitable sam- ples for post-flight analyses. We expect to understand better the molecular mechanisms governing human BMSC growth and differentiation hoping to outline new countermeasures against astronaut bone loss.
Related URLs:
http://link.springer.com/article/10.1007/s12217-015-9466-5
Attachment of LcrV from Yersinia pestis at dual binding sites to human TLR-2 and human IFN-gamma receptor.
The virulence antigen (V-antigen, LcrV) of Yersinia pestis, the causative agent of bubonic plague, is an established protective antigen known to regulate, target, and mediate type III translocation of cytotoxic yersiniae outer proteins termed Yops; LcrV also prompts TLR2-dependent upregulation of anti-inflammatory IL-10. In this study, we determined the parameters of specific interaction of LcrV with TLR2 expressed on human transfected HEK293 cells (TLR2+/CD14-), VTEC2.HS cells (TLR2+/CD14-), primary monocytes (TLR2+/CD14+), and THP-1 cells (TLR2+/CD14+). The IRRL314-317 motif of the extracellular domain of human and mouse TLR2 accounted for high-affinity binding of LcrV. The CD14 co-receptor did not influence this interaction. LcrV did not bind to human U937 (TLR2-/CD14-) and alveolar macrophages (TLR2-/CD14+) in the absence of receptor-bound human IFN-gamma or a synthetic C-terminal fragment (hIFN-gamma132-143). The latter, but not mouse IFN-gamma (or synthetic control peptides), shared a GRRA138-141 site necessary for high-affinity specific binding. LcrV of Y. pestis shares the N-terminal LEEL32-35 binding site of Yersinia enterocolitica and also has an exposed internal DEEI203-206 binding site. Comparison of binding constants and consideration of steric restrictions indicate that binding is not cooperative and only the internal site binds LcrV to target cells. Both the LEEL32-35 and DEEI203-206 binding sites are removed by five amino acids from DKN residues associated with biological activity of bound LcrV. LcrV of Y. pestis promoted both TLR2/CD14-dependent and TLR2/CD14-independent amplification of IL-10 and concomitant downregulation of TNF-alpha in human target cells. The ability of LcrV to utilize human IFN-gamma (a major inflammatory effector of innate immunity) to minimize inflammation is insidious and may account in part for the severe symptoms of plague in man.
Related URLs:
http://www.ncbi.nlm.nih.gov/pubmed/17441749
Interaction of Yersinia pestis Virulence Factors with IL-1R/TLR Recognition System
The virulence antigen (V-antigen, LcrV) of Yersinia pestis, the causative agent of bubonic plague, is an established protective antigen known to regulate, target, and mediate type III translocation of cytotoxic yersiniae outer proteins termed Yops; LcrV also prompts TLR2-dependent upregulation of anti-inflammatory IL-10. In this study, we determined the parameters of specific interaction of LcrV with TLR2 expressed on human transfected HEK293 cells (TLR2+/CD14-), VTEC2.HS cells (TLR2+/CD14-), primary monocytes (TLR2+/CD14+), and THP-1 cells (TLR2+/CD14+). The IRRL314-317 motif of the extracellular domain of human and mouse TLR2 accounted for high-affinity binding of LcrV. The CD14 co-receptor did not influence this interaction. LcrV did not bind to human U937 (TLR2-/CD14-) and alveolar macrophages (TLR2-/CD14+) in the absence of receptor-bound human IFN-γ or a synthetic C-terminal fragment (hIFN-γ132-143). The latter, but not mouse IFN-γ (or synthetic control peptides), shared a GRRA138-141 site necessary for high-affinity specific binding. LcrV of Y. pestis shares the N-terminal LEEL32-35 binding site of Yersinia enterocolitica and also has an exposed internal DEEI203-206 binding site. Comparison of binding constants and consideration of steric restrictions indicate that binding is not cooperative and only the internal site binds LcrV to target cells. Both the LEEL32-35 and DEEI203-206 binding sites are removed by five amino acids from DKN residues associated with biological activity of bound LcrV. LcrV of Y. pestis promoted both TLR2/CD14-dependent and TLR2/CD14-independent amplification of IL-10 and concomitant downregulation of TNF-α in human target cells. The ability of LcrV to utilize human IFN-γ (a major inflammatory effector of innate immunity) to minimize inflammation is insidious and may account in part for the severe symptoms of plague in man.
Related URLs:
http://link.springer.com/chapter/10.1007%2F978-1-59745-569-5_23
PROTEIN CRYSTALLIZATION FOR DRUG DEVELOPMENT: A Prospective Empirical Appraisal of Economic Effects of ISS Microgravity
The paper proceeds as follows. Section two below discusses the topic of protein crystallization in biomedical research as well as our current understanding regarding the contribution of microgravity in developing better quality crystals. Section three addresses possible policy intervention, also including the introduction of a government funded consortium to diffuse risk. Section four outlines a specific model that has recently been developed by RTI International, which provides an interesting quantitative framework for measuring private sector costs. The outcome of this section is essentially a list of needed data and data sources. Finally, Section five concludes.
Suppression of Hydroxycinnamate Network Formation in Cell Walls of Rice Shoots Grown under Microgravity Conditions in Space
Network structures created by hydroxycinnamate cross-links within the cell wall architecture of gramineous plants make the cell wall resistant to the gravitational force of the earth. In this study, the effects of microgravity on the formation of cell wall-bound hydroxycinnamates were examined using etiolated rice shoots simultaneously grown under artificial 1 g and microgravity conditions in the Cell Biology Experiment Facility on the International Space Station. Measurement of the mechanical properties of cell walls showed that shoot cell walls became stiff during the growth period and that microgravity suppressed this stiffening. Amounts of cell wall polysaccharides, cell wall-bound phenolic acids, and lignin in rice shoots increased as the shoot grew. Microgravity did not influence changes in the amounts of cell wall polysaccharides or phenolic acid monomers such as ferulic acid (FA) and p-coumaric acid, but it suppressed increases in diferulic acid (DFA) isomers and lignin. Activities of the enzymes phenylalanine ammonia-lyase (PAL) and cell wall-bound peroxidase (CW-PRX) in shoots also increased as the shoot grew. PAL activity in microgravity-grown shoots was almost comparable to that in artificial 1 g-grown shoots, while CW-PRX activity increased less in microgravity-grown shoots than in artificial 1 g-grown shoots. Furthermore, the increases in expression levels of some class III peroxidase genes were reduced under microgravity conditions. These results suggest that a microgravity environment modifies the expression levels of certain class III peroxidase genes in rice shoots, that the resultant reduction of CW-PRX activity may be involved in suppressing DFA formation and lignin polymerization, and that this suppression may cause a decrease in cross-linkages within the cell wall architecture. The reduction in intra-network structures may contribute to keeping the cell wall loose under microgravity conditions.
Related URLs:
http://www.ncbi.nlm.nih.gov/pubmed/26378793
Extracellular Lipase and Protease Production from a Model Drinking Water Bacterial Community Is Functionally Robust to Absence of Individual Members
Bacteria secrete enzymes into the extracellular space to hydrolyze macromolecules into constituents that can be imported for microbial nutrition. In bacterial communities, these enzymes and their resultant products can be modeled as community property. Our goal was to investigate the impact of individual community member absence on the resulting community production of exoenzymes (extracellular enzymes) involved in lipid and protein hydrolysis. Our model community contained nine bacteria isolated from the potable water system of the International Space Station. Bacteria were grown in static conditions individually, all together, or in all combinations of eight species and exoproduct production was measured by colorimetric or fluorometric reagents to assess short chain and long chain lipases, choline-specific phospholipases C, and proteases. The exoenzyme production of each species grown alone varied widely, however, the enzyme activity levels of the mixed communities were functionally robust to absence of any single species, with the exception of phospholipase C production in one community. For phospholipase C, absence of Chryseobacterium gleum led to increased choline-specific phospholipase C production, correlated with increased growth of Burkholderia cepacia and Sphingomonas sanguinis. Because each individual species produced different enzyme activity levels in isolation, we calculated an expected activity value for each bacterial mixture using input levels or known final composition. This analysis suggested that robustness of each exoenzyme activity is not solely mediated by community composition, but possibly influenced by bacterial communication, which is known to regulate such pathways in many bacteria. We conclude that in this simplified model of a drinking water bacterial community, community structure imposes constraints on production and/or secretion of exoenzymes to generate a level appropriate to exploit a given nutrient environment.
Related URLs:
http://www.ncbi.nlm.nih.gov/pubmed/26599415
Assessing Sensorimotor Function Following ISS with Computerized Dynamic Posturography
INTRODUCTION: Postflight postural ataxia reflects both the control strategies adopted for movement in microgravity and the direct effects of deconditioning. Computerized dynamic posturography (CDP) has been used during the first decade of the International Space Station (ISS) expeditions to quantify the initial postflight decrements and recovery of postural stability. METHODS: The CDP data were obtained on 37 crewmembers as part of their pre- and postflight medical examinations. Sensory organization tests evaluated the ability to make effective use of (or suppress inappropriate) visual, vestibular, and somatosensory information for balance control. This report focuses on eyes closed conditions with either a fixed or sway-referenced base of support, with the head erect or during pitch-head tilts (+/- 20 degrees at 0.33 Hz). Equilibrium scores were derived from peak-to-peak anterior-posterior sway. Motor-control tests were also used to evaluate a crewmember’s ability to automatically recover from unexpected support-surface perturbations. RESULTS: The standard Romberg condition was the least sensitive. Dynamic head tilts led to increased incidence of falls and revealed significantly longer recovery than head-erect conditions. Improvements in postflight postural performance during the later expeditions may be attributable to higher preflight baselines and/or advanced exercise capabilities aboard the ISS. CONCLUSIONS: The diagnostic assessment of postural instability is more pronounced during unstable-support conditions requiring active head movements. In addition to supporting return-to-duty decisions by flight surgeons, the CDP provides a standardized sensorimotor measure that can be used to evaluate the effectiveness of countermeasures designed to either minimize deconditioning on orbit or promote reconditioning upon return to Earth.
Related URLs:
http://www.ncbi.nlm.nih.gov/pubmed/26630195