A series of fluid physics microgravity experiments with an enough long run time were performed in the ‘‘KIBO,’’ the Japanese Experiment Module aboard the International Space Station, to examine the transition to chaos of the thermocapillary convection in a half zone liquid bridge of silicone oil with a Prandtl number of 112. The temperature difference between the coaxial disks induced the thermocapillary-driven flow, and we experimentally demonstrated that the flow fields underwent a tran- sition from steady flow to oscillatory flow, and finally to chaotic flow with increasing temperature differ- ence. We obtained the surface temperature time series at the middle of the liquid bridge to quantitatively evaluate the transition process of the flow fields. By Fourier analysis, we further confirmed that the flow fields changed from a periodic, to a quasi-periodic, and finally to a chaotic state. The increasing nonlin- earity with the development of the flow fields was confirmed by time-series chaos analysis. The deter- mined Lyapunov exponent and the translation error indicated that the flow fields made transition to the chaotic field with the increasing temperature difference.
Secretory proteins produced by salivary glands are stored in granules and released into saliva. Rodent salivary glands are a reliable experimental model because they are morphologically and functionally similar to those of humans. To determine if the effects of microgravity on secretory proteins are increased on extended flights, their expression in mouse parotid glands, morphological, immuno- cytochemical, and biochemical/molecular methods were employed. Acinar cells of STS-135 (13 day) and Bion-M1 (30 day) flight animals showed an increase of autophagy and apoptosis, while duct cells contained vacuoles with endocytosed proteins. In STS-135, decreases were seen in the regulatory subunit of type II protein kinase A (RII) by Western blotting, and demilune cell and parotid protein (DCPP) and α- amylase (p<0.01) by immunogold labeling, while proline-rich proteins (PRPs, p<0.001) and parotid secretory protein (PSP, p<0.05) were increased. These results suggest microgravity effects on secretion are function-dependent. Microarray analyses showed significant changes in the expression of a number of genes, including components of the cyclic-3',5',-adenosine monophosphate (cyclic AMP) signaling pathway. Compared to habitat ground controls, mice from both flights exhibited altered expression of cyclic AMP-specific phosphodiesterases, adenylate cyclase isoforms, and several A-kinase anchoring proteins. Bion-M1 flight mice showed increases in gene expression for lysozyme and amylase, a decrease in PRPs, and RII expression was unchanged from control values. Secretory protein expression is altered by travel in space, representing a reversible adjustment to microgravity conditions. Ultimately, the goal is to develop a test kit using saliva — an easily obtained body fluid — to assess the physiologic effects of travel in space.
INTRODUCTION: Aerobic deconditioning may occur during International Space Station (ISS) flights. This paper documents findings from exercise testing conducted before, during, and after ISS expeditions. METHODS: There were 30 male and 7 female astronauts on ISS missions (48 to 219 d, mean 163 d) who performed cycle exercise protocols consisting of 5-min stages eliciting 25%, 50%, and 75% peak oxygen uptake (Vo(2peak)). Tests were conducted 30 to 90 d before missions, on flight day 15 and every 30 flight days thereafter, and on recovery (R) days +5 and +30. During pre- and postflight tests, heart rate (HR) and metabolic gas exchange were measured. During flight, extrapolation of the HR and Vo2 relationship to preflight-measured peak HR provided an estimate of Vo(2peak), referred to as the aerobic capacity index (ACI). RESULTS: HR during each exercise stage was elevated (P < 0.05) and oxygen pulse was reduced (P < 0.05) on R+5 compared to preflight; however, no other metabolic gas analysis values significantly changed. Compared to preflight, the ACI declined (P < 0.001) on R+5, but recovered to levels greater than preflight by R+30 (P = 0.008). During flight, ACI decreased below preflight values, but increased with mission duration (P < 0.001). CONCLUSIONS: Aerobic deconditioning likely occurs initially during flight, but ACI recovers toward preflight levels as flight duration increases, presumably due to performance of exercise countermeasures. Elevated HR and lowered oxygen pulse on R+5 likely results from some combination of relative hypovolemia, lowered cardiac stroke volume, reduced cardiac distensibility, and anemia, but recovery occurs by R+30.
Evaluation of rodent spaceflight in the NASA animal enclosure module for an extended operational period (up to 35 days)
The National Aeronautics and Space Administration Animal Enclosure Module (AEM) was developed as a self-contained rodent habitat for shuttle flight missions that provides inhabitants with living space, food, water, ventilation, and lighting, and this study reports whether, after minimal hardware modification, the AEM could support an extended term up to 35 days for Sprague-Dawley rats and C57BL/6 female mice for use on the International Space Station. Success was evaluated based on comparison of AEM housed animals to that of vivarium housed and to normal biological ranges through various measures of animal health and well-being, including animal health evaluations, animal growth and body masses, organ masses, rodent food bar consumption, water consumption, and analysis of blood contents. The results of this study confirmed that the AEMs could support 12 adult female C57BL/6 mice for up to 35 days with self-contained RFB and water, and the AEMs could also support 5 adult male Sprague-Dawley rats for 35 days with external replenishment of diet and water. This study has demonstrated the capability and flexibility of the AEM to operate for up to 35 days with minor hardware modification. Therefore, with modifications, it is possible to utilize this hardware on the International Space Station or other operational platforms to extend the space life science research use;of mice and rats.
“Newton’s cradle” proton relay with amide–imidic acid tautomerization in inverting cellulase visualized by neutron crystallography
Hydrolysis of carbohydrates is a major bioreaction in nature, catalyzed by glycoside hydrolases (GHs). We used neutron diffraction and high-resolution x-ray diffraction analyses to investigate the hydrogen bond network in inverting cellulase PcCel45A, which is an endoglucanase belonging to subfamily C of GH family 45, isolated from the basidiomycete Phanerochaete chrysosporium. Examination of the enzyme and enzyme-ligand structures indicates a key role of multiple tautomerizations of asparagine residues and peptide bonds, which are finally connected to the other catalytic residue via typical side-chain hydrogen bonds, in forming the “Newton’s cradle”–like proton relay pathway of the catalytic cycle. Amide–imidic acid tautomerization of asparagine has not been taken into account in recent molecular dynamics simulations of not only cellulases but also general enzyme catalysis, and it may be necessary to reconsider our interpretation of many enzymatic reactions.
The actin cytoskeleton is a suppressor of the endogenous skewing behaviour of Arabidopsis primary roots in microgravity
Before plants can be effectively utilised as a component of enclosed life-support systems for space exploration, it is important to understand the molecular mechanisms by which they develop in microgravity. Using the Biological Research in Canisters (BRIC) hardware on board the second to the last flight of the Space Shuttle Discovery (STS-131 mission), we studied how microgravity impacts root growth in Arabidopsis thaliana. Ground-based studies showed that the actin cytoskeleton negatively regulates root gravity responses on Earth, leading us to hypothesise that actin might also be an important modulator of root growth behaviour in space. We investigated how microgravity impacted root growth of wild type (ecotype Columbia) and a mutant (act2-3) disrupted in a root-expressed vegetative actin isoform (ACTIN2). Roots of etiolated wild-type and act2-3 seedlings grown in space skewed vigorously toward the left, which was unexpected given the reduced directional cue provided by gravity. The left-handed directional root growth in space was more pronounced in act2-3 mutants than wild type. To quantify differences in root orientation of these two genotypes in space, we developed an algorithm where single root images were converted into binary images using computational edge detection methods. Binary images were processed with Fast Fourier Transformation (FFT), and histogram and entropy were used to determine spectral distribution, such that high entropy values corresponded to roots that deviated more strongly from linear orientation whereas low entropy values represented straight roots. We found that act2-3 roots had a statistically stronger skewing/coiling response than wild-type roots, but such differences were not apparent on Earth. Ultrastructural studies revealed that newly developed cell walls of space-grown act2-3 roots were more severely disrupted compared to space-grown wild type, and ground control wild-type and act2-3 roots. Collectively, our results provide evidence that, like root gravity responses on Earth, endogenous directional growth patterns of roots in microgravity are suppressed by the actin cytoskeleton. Modulation of root growth in space by actin could be facilitated in part through its impact on cell wall architecture.
INTRODUCTION: Cardiovascular deconditioning apparently progresses with flight duration, resulting in a greater incidence of orthostatic intolerance following long-duration missions. Therefore, we anticipated that the proportion of astronauts who could not complete an orthostatic tilt test (OTT) would be higher on landing day and the number of days to recover greater after International Space Station (ISS) than after Space Shuttle missions. METHODS: There were 20 ISS and 65 Shuttle astronauts who participated in 10-min 80 degrees head-up tilt tests 10 d before launch, on landing day (R+0), and 3 d after landing (R+3). Fisher’s Exact Test was used to compare the ability of ISS and Shuttle astronauts to complete the OTT. Cox regression was used to identify cardiovascular parameters associated with OTT completion and mixed model analysis was used to compare the change and recovery rates between groups. RESULTS: The proportion of astronauts who completed the OTT on R+0 (2 of 6) was less in ISS than in Shuttle astronauts (52 of 65). On R+3, 13 of 15 and 19 of 19 of the ISS and Shuttle astronauts, respectively, completed the OTT. An index comprised of stroke volume and diastolic blood pressure provided a good prediction of OTT completion and was altered by spaceflight similarly for both astronaut groups, but recovery was slower in ISS than in Shuttle astronauts. CONCLUSIONS: The proportion of ISS astronauts who could not complete the OTT on R+0 was greater and the recovery rate slower after ISS compared to Shuttle missions. Thus, mission planners and crew surgeons should anticipate the need to tailor scheduled activities and level of medical support to accommodate protracted recovery after long-duration microgravity exposures.
The scoring quality of astronauts’ sleeps using Fuzzy C-Means (FCM) during microgravity effect in the International Space Station (ISS)
For successful health programme of Japanese astronauts during space activity in the International Space Station (ISS), we looked into the sleep quality of astronauts by using Fuzzy C-Means (FCM). At the first step, we collected observation data by following sleep schedule of astronaut Noguchi for fifteen days (26 July 2005 to 9 August 2005) during STS-114 spaceflight. The Fuzzy C-Mean (FCM) was used to design the score quality of astronauts’ sleeps. We defined three condition of sleep quality (e.g. sleepy, sleep, deep sleep) with the minimum score (zero) and maximum score (nine). Based on the preliminary result, we found that the minimum sleep score of astronaut Noguchi was from 7 to 9 August 2005 which was due to landing process and the maximum sleep score we found was later than 27 July 2005 during docking on ISS.
Pluripotent stem cells (PSCs) have the ability to spontaneously generate structured tissues in vitro reminiscent of embryonic tissue development. Recently, complex organoids such as cortical tissues, cerebral brain organoids, optical cups, intestinal tissues, and liver buds have been generated from PSCs derived from healthy individuals and patients with genetic diseases, providing powerful tools to understand morphogenesis and disease pathology. This article highlights recent advances in the state-of-art generation of organoids from PSCs, possible signaling pathways and mechanisms involved in organogenesis, and the understanding of extracellular microenvironment. Challenges involved in the organoid generation such as increasing organoid size, enhancing the tissue complexity, and improving functional maturation are also discussed.
Long-duration spaceflight results in a loss of muscle strength that poses both operational and medical risks, particularly during emergency egress, upon return to Earth, and during future extraterrestrial exploration. Isokinetic testing of the knee, ankle, and trunk quantifies movement-specific strength changes following spaceflight and offers insight into the effectiveness of in-flight exercise countermeasures. We retrospectively evaluated changes in isokinetic strength for 37 ISS crewmembers (Expeditions 1–25) following 163 +/- 38 d (mean +/- SD) of spaceflight. Gender, in-flight resistance exercise hardware, and preflight strength were examined as potential modifiers of spaceflight-induced strength changes. Mean isokinetic strength declined 8–17% following space ight. One month after return to Earth, strength had improved, but small defcits of 1–9% persisted. Space flight-induced strength losses were not different between men and women. Mean strength losses were as much as 7% less in crewmembers who flew after the Advanced Resistive Exercise Device (ARED) replaced the interim Resistive Exercise Device (iRED) as the primary in-flight resistance exercise hardware, although these differences were not statistically significant. Absolute and relative preflight strength were moderately correlated (r= -0.47 and -0.54, respectively) with post flight strength changes. In-flight resistance exercise did not prevent decreased isokinetic strength after long-duration spaceflight. However, continued utilization of ARED, a more robust resistance exercise device providing higher loads than iRED, may result in greater benefits as exercise prescriptions are optimized. With reconditioning upon return to Earth, strength is largely recovered within 30 d.