Sarcolab pilot study into skeletal muscle's adaptation to long-term spaceflight.
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ABSTRACT:
SUBMITTER: Rittweger J
PROVIDER: S-EPMC6141586 | biostudies-literature | 2018
REPOSITORIES: biostudies-literature
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Project description:The effect of microgravity on skeletal muscles has so far been examined in rat and mice only after short-term (5-20 day) spaceflights. The mice drawer system (MDS) program, sponsored by Italian Space Agency, for the first time aimed to investigate the consequences of long-term (91 days) exposure to microgravity in mice within the International Space Station. Muscle atrophy was present indistinctly in all fiber types of the slow-twitch soleus muscle, but was only slightly greater than that observed after 20 days of spaceflight. Myosin heavy chain analysis indicated a concomitant slow-to-fast transition of soleus. In addition, spaceflight induced translocation of sarcolemmal nitric oxide synthase-1 (NOS1) into the cytosol in soleus but not in the fast-twitch extensor digitorum longus (EDL) muscle. Most of the sarcolemmal ion channel subunits were up-regulated, more in soleus than EDL, whereas Ca(2+)-activated K(+) channels were down-regulated, consistent with the phenotype transition. Gene expression of the atrophy-related ubiquitin-ligases was up-regulated in both spaceflown soleus and EDL muscles, whereas autophagy genes were in the control range. Muscle-specific IGF-1 and interleukin-6 were down-regulated in soleus but up-regulated in EDL. Also, various stress-related genes were up-regulated in spaceflown EDL, not in soleus. Altogether, these results suggest that EDL muscle may resist to microgravity-induced atrophy by activating compensatory and protective pathways. Our study shows the extended sensitivity of antigravity soleus muscle after prolonged exposition to microgravity, suggests possible mechanisms accounting for the resistance of EDL, and individuates some molecular targets for the development of countermeasures.
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Project description:Human spaceflight has been fascinating man for centuries, representing the intangible need to explore the unknown, challenge new frontiers, advance technology, and push scientific boundaries further. A key area of importance is cardiovascular deconditioning, that is, the collection of hemodynamic changes-from blood volume shift and reduction to altered cardiac function-induced by sustained presence in microgravity. A thorough grasp of the 0G adjustment point per se is important from a physiological viewpoint and fundamental for astronauts' safety and physical capability on long spaceflights. However, hemodynamic details of cardiovascular deconditioning are incomplete, inconsistent, and poorly measured to date; thus a computational approach can be quite valuable. We present a validated 1D-0D multiscale model to study the cardiovascular response to long-term 0G spaceflight in comparison to the 1G supine reference condition. Cardiac work, oxygen consumption, and contractility indexes, as well as central mean and pulse pressures were reduced, augmenting the cardiac deconditioning scenario. Exercise tolerance of a spaceflight traveler was found to be comparable to an untrained person with a sedentary lifestyle. At the capillary-venous level significant waveform alterations were observed which can modify the regular perfusion and average nutrient supply at the cellular level. The present study suggests special attention should be paid to future long spaceflights which demand prompt physical capacity at the time of restoration of partial gravity (e.g., Moon/Mars landing). Since spaceflight deconditioning has features similar to accelerated aging understanding deconditioning mechanisms in microgravity are also relevant to the understanding of aging physiology on the Earth.
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Project description:Astronauts on board the International Space Station (ISS) must adapt to several environmental challenges including microgravity, elevated carbon dioxide (CO2), and isolation while performing highly controlled movements with complex equipment. Head down tilt bed rest (HDBR) is an analog used to study spaceflight factors including body unloading and headward fluid shifts. We recently reported how HDBR with elevated CO2 (HDBR+CO2) affects visuomotor adaptation. Here we expand upon this work and examine the effects of HDBR+CO2 on brain activity during visuomotor adaptation. Eleven participants (34 ± 8 years) completed six functional MRI (fMRI) sessions pre-, during, and post-HDBR+CO2. During fMRI, participants completed a visuomotor adaptation task, divided into baseline, early, late and de-adaptation. Additionally, we compare brain activity between this NASA campaign (30-day HDBR+CO2) and a different campaign with a separate set of participants (60-day HDBR with normal atmospheric CO2 levels, n = 8; 34.25 ± 7.9 years) to characterize the specific effects of CO2. Participants were included by convenience. During early adaptation across the HDBR+CO2 intervention, participants showed decreasing activation in temporal and subcortical brain regions, followed by post- HDBR+CO2 recovery. During late adaptation, participants showed increasing activation in the right fusiform gyrus and right caudate nucleus during HDBR+CO2; this activation normalized to baseline levels after bed rest. There were no correlations between brain changes and adaptation performance changes from pre- to post HDBR+CO2. Also, there were no statistically significant differences between the HDBR+CO2 group and the HDBR controls, suggesting that changes in brain activity were due primarily to bed rest rather than elevated CO2. Five HDBR+CO2 participants presented with optic disc edema, a sign of Spaceflight Associated Neuro-ocular Syndrome (SANS). An exploratory analysis of HDBR+CO2 participants with and without signs of SANS revealed no group differences in brain activity during any phase of the adaptation task. Overall, these findings have implications for spaceflight missions and training, as ISS missions require individuals to adapt to altered sensory inputs over long periods in space. Further, this is the first study to verify the HDBR and elevated CO2 effects on the neural correlates of visuomotor adaptation.
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Project description:Microbes are responsible for cycling carbon (C) through soils, and predicted changes in soil C stocks under climate change are highly sensitive to shifts in the mechanisms assumed to control the microbial physiological response to warming. Two mecha-nisms have been suggested to explain the long-term warming impact on microbial physiology: microbial thermal acclimation and changes in the quantity and quality of substrates available for microbial metabolism. Yet studies disentangling these two mechanisms are lacking. To resolve the drivers of changes in microbial physiology in response to long-term warming, we sampled soils from 13- and 28-year- old soil warming experiments in different seasons. We performed short-term laboratory incubations across a range of temperatures to measure the relationships between temperature sensitivity of physiology (growth, respiration, carbon use efficiency, and extracellular enzyme activity) and the chemical composition of soil organic matter. We observed apparent thermal acclimation of microbial respiration, but only in sum-mer, when warming had exacerbated the seasonally-induced, already small dissolved organic matter pools. Irrespective of warming, greater quantity and quality of soil carbon increased the extracellular enzymatic pool and its temperature sensitivity. We propose that fresh litter input into the system seasonally cancels apparent thermal acclimation of C-cycling processes to decadal warming. Our findings reveal that long-term warming has indirectly affected microbial physiology via reduced C availability in this system, implying that earth system models including these negative feedbacks may be best suited to describe long-term warming effects on these soils. Citation: Domeignoz-Horta LA, Pold G, Erb H, Sebag D, Verrecchia E, Northen T, Louie K, Eloe-Fadrosh E, Pennacchio C, Knorr MA, Frey SD, Melillo JM, DeAngelis KM. Substrate availability and not thermal acclimation controls microbial temperature sensitivity response to long-term warming. Glob Chang Biol. 2023 Mar;29(6):1574-1590. doi: 10.1111/gcb.16544.
The work (proposal:https://doi.org/10.46936/10.25585/60001340) conducted by the U.S. Department of Energy Joint Genome Institute (https://ror.org/04xm1d337), a DOE Office of Science User Facility, is supported by the Office of Science of the U.S. Department of Energy operated under Contract No. DE-AC02-05CH11231.
2023-08-04 | MSV000092599 | MassIVE
Project description:F344 rats were divided into 4 groups: vehicle control, DEN, DEN+CLO and CLO. After one week of basal diet, rats belonging to the groups DEN and DEN+CLO underwent intraperitoneal injection of DEN (30mg/kg body weight) dissolved in NaCl 9‰. The two other groups were injected with NaCl 9‰ alone. At 30mg/kg, DEN is non-necrogenic thus only exhibiting initiating properties. Twelve days after injection, diet from rats belonging to the groups CLO and DEN+CLO was changed for diet containing 5000ppm CLO for up to 608 days. Series of 5 rats from each group were necropsied at days 18, 46, 102, 264, 377, 447 (reverse phase from day 377: no more CLO in the diet for rats belonging to the DEN+CLO group), and for the CLO and Control group 524, and 608 days after the injection of DEN or saline. From day 524, half of the CLO-treated rats were kept on basal diet (reverse phase) until day 608. Keywords = Clofibric acid Keywords = Diethylnitrosamine Keywords = Rat Keywords: other
2005-03-01 | GSE2216 | GEO
Project description:Geographic atrophy (GA), the late stage of age-related macular degeneration, is a major cause of visual disability whose pathophysiology remains largely unknown. Modern fundus imaging and histology revealed the complexity of the cellular changes that accompanies atrophy. Documenting the activity of the disease in the margins of atrophy, where the transition from health to disease occurs, would contribute to a better understanding of the progression of GA. Time-lapse imaging facilitates the identification of structural continuities in changing environments. In this retrospective pilot study, we documented the long-term changes in atrophy margins by time-lapse imaging of infrared scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT) images in 6 cases of GA covering a mean period of 32.8 months (range, 18-72). The mean interval between imaging sessions was 2.4 months (range, 1.4-3.8). By viewing time-lapse sequences we observed extensive changes in the pattern of marginal hyperreflective spots, which associated fragmentation, increase and/or disappearance. Over the entire span of the follow-up, the most striking changes were those affecting hyperreflective spots closest to margins of atrophy, on the non-atrophic side of the retina; a continuum between the successive positions of some of the hyperreflective spots was detected, both by SLO and OCT. This continuum in their successive positions resulted in a subjective impression of a centrifugal motion of hyperreflective spots ahead of atrophy progression. Such mobilization of hyperreflective spots was detected up to several hundred microns away from atrophic borders. Such process is likely to reflect the inflammatory and degenerative process underlying GA progression and hence deserves further investigations. These results highlight the interest of multimodal time-lapse imaging to document cell-scale dynamics during progression of GA.Clinical trial registrationclinicaltrials.gov, identifier: NCT04128150 and NCT04129021.
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2012-07-01 | E-MTAB-1187 | biostudies-arrayexpress
Project description:Aspergillus fumigatus is an opportunistic, airborne pathogen causing invasive aspergillosis in immunocompromised patients. During the infection process A. fumigatus is challenged by hypoxic microenvironments occurring in inflammatory, necrotic tissue. To gain further insights into the adaptation mechanism, A. fumigatus was cultivated in an oxygen-controlled chemostat under hypoxic and normoxic conditions. Transcriptome analysis revealed significant increases in transcripts associated with cell wall polysaccharide metabolism, amino acid and metal ion transport, nitrogen metabolism and glycolysis. A concomitant reduction in transcript levels was observed with cellular trafficking and G-protein coupled signaling. To learn more about the functional roles of hypoxia-induced transcripts we deleted A. fumigatus genes putatively involved in reactive nitrogen species detoxification (fhpA), NAD+ regeneration (frdA, osmA) nitrogen metabolism (niaD, niiA) and respiration (rcfB). We show that the NO-detoxifying flavohemoprotein fhpA is strongly induced by hypoxia independent of the nitrogen source, but is dispensable for hypoxic survival. By deleting the nitrate reductase gene niaD, the nitrite reductase gene niiA and the two fumarate reductases genes frdA and osmA, we found that alternative electron acceptors such as nitrate and fumarate do not have a significant impact on growth of A. fumigatus during hypoxia, but that functional mitochondrial respiratory chain complexes are essential under these conditions. Inhibition studies indicated that primarily complex III and IV play a crucial role in the hypoxic growth of A. fumigatus.
2014-07-01 | E-MTAB-2699 | biostudies-arrayexpress
Project description:CYBATHLON is an international championship where people with severe physical disabilities compete with the aid of state-of-the-art assistive technology. In one of the disciplines, the BCI Race, tetraplegic pilots compete in a computer game race by controlling an avatar with a brain-computer interface (BCI). This competition offers a perfect opportunity for BCI researchers to study long-term training effects in potential end-users, and to evaluate BCI performance in a realistic environment. In this work, we describe the BCI system designed by the team Mirage91 for participation in the CYBATHLON BCI Series 2019, as well as in the CYBATHLON 2020 Global Edition. Furthermore, we present the BCI's interface with the game and the main methodological strategies, along with a detailed evaluation of its performance over the course of the training period, which lasted 14 months. The developed system was a 4-class BCI relying on task-specific modulations of brain rhythms. We implemented inter-session transfer learning to reduce calibration time, and to reinforce the stability of the brain patterns. Additionally, in order to compensate for potential intra-session shifts in the features' distribution, normalization parameters were continuously adapted in an unsupervised fashion. Across the aforementioned 14 months, we recorded 26 game-based training sessions. Between the first eight sessions, and the final eight sessions leading up to the CYBATHLON 2020 Global Edition, the runtimes significantly improved from 255 ± 23 s (mean ± std) to 225 ± 22 s, respectively. Moreover, we observed a significant increase in the classifier's accuracy from 46 to 53%, driven by more distinguishable brain patterns. Compared to conventional single session, non-adaptive BCIs, the inter-session transfer learning and unsupervised intra-session adaptation techniques significantly improved the performance. This long-term study demonstrates that regular training helped the pilot to significantly increase the distance between task-specific patterns, which resulted in an improvement of performance, both with respect to class separability in the calibration data, and with respect to the game. Furthermore, it shows that our methodological approaches were beneficial in transferring the performance across sessions, and most importantly to the CYBATHLON competitions.
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