npj MicrogravityPub Date : 2024-03-28DOI: 10.1038/s41526-024-00380-w
Marina M Scotti, Brandon K Wilson, Jodi L Bubenik, Fahong Yu, Maurice S Swanson, Josephine B Allen
{"title":"Spaceflight effects on human vascular smooth muscle cell phenotype and function.","authors":"Marina M Scotti, Brandon K Wilson, Jodi L Bubenik, Fahong Yu, Maurice S Swanson, Josephine B Allen","doi":"10.1038/s41526-024-00380-w","DOIUrl":"10.1038/s41526-024-00380-w","url":null,"abstract":"<p><p>The cardiovascular system is strongly impacted by the hazards of spaceflight. Astronauts spending steadily increasing lengths of time in microgravity are subject to cardiovascular deconditioning resulting in loss of vascular tone, reduced total blood volume, and diminished cardiac output. Appreciating the mechanisms by which the cells of the vasculature are altered during spaceflight will be integral to understanding and combating these deleterious effects as the human presence in space advances. In this study, we performed RNA-Seq analysis coupled with review by QIAGEN Ingenuity Pathway Analysis software on human aortic smooth muscle cells (HASMCs) cultured for 3 days in microgravity and aboard the International Space Station to assess the transcriptomic changes that occur during spaceflight. The results of our RNA-Seq analysis show that SMCs undergo a wide range of transcriptional alteration while in space, significantly affecting 4422 genes. SMCs largely down-regulate markers of the contractile, synthetic, and osteogenic phenotypes including smooth muscle alpha actin (αSMA), matrix metalloproteinases (MMPs), and bone morphogenic proteins (BMPs). Additionally, components of several cellular signaling pathways were strongly impacted including the STAT3, NFκB, PI3K/AKT, HIF1α, and Endothelin pathways. This study highlights the significant changes in transcriptional behavior SMCs exhibit during spaceflight and puts these changes in context to better understand vascular function in space.</p>","PeriodicalId":54263,"journal":{"name":"npj Microgravity","volume":"10 1","pages":"41"},"PeriodicalIF":5.1,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10979029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140319921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"物理与天体物理","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
npj MicrogravityPub Date : 2024-03-27DOI: 10.1038/s41526-024-00360-0
Elisa Le Roux, Alexandre Zahariev, Isabelle Chery, Dale A Schoeller, Pierre Bourdier, Alain Maillet, Cecile Thevenot, Maël Garnotel, Guillemette Gauquelin-Koch, Laurie Van Den Berghe, Stéphane Blanc, Chantal Simon, Audrey Bergouignan
{"title":"Substrate metabolism in male astronauts onboard the International Space Station: the ENERGY study.","authors":"Elisa Le Roux, Alexandre Zahariev, Isabelle Chery, Dale A Schoeller, Pierre Bourdier, Alain Maillet, Cecile Thevenot, Maël Garnotel, Guillemette Gauquelin-Koch, Laurie Van Den Berghe, Stéphane Blanc, Chantal Simon, Audrey Bergouignan","doi":"10.1038/s41526-024-00360-0","DOIUrl":"10.1038/s41526-024-00360-0","url":null,"abstract":"<p><p>Bedrest shifts fasting and postprandial fuel selection towards carbohydrate use over lipids, potentially affecting astronauts' performance and health. We investigated whether this change occurs in astronauts after at least 3 months onboard the International Space Station (ISS). We further explored the associations with diet, physical activity (PA), and body composition. Before and during spaceflight, respiratory quotient (RQ), carbohydrate, and fat oxidation were measured by indirect calorimetry before and following a standardized meal in 11 males (age = 45.7 [SD 7.7] years, BMI = 24.3 [2.1] kg m<sup>-</sup>²). Postprandial substrate use was determined by 0-to-260 min postprandial incremental area under the curve (iAUC) of nutrient oxidation and the difference between maximal postprandial and fasting RQ (ΔRQ). Food quotient (FQ) was calculated from diet logs. Fat (FM) and fat-free mass (FFM) were measured by hydrometry and PA by accelerometry and diary logs. Spaceflight increased fasting RQ (P = 0.01) and carbohydrate oxidation (P = 0.04) and decreased fasting lipid oxidation (P < 0.01). An increase in FQ (P < 0.001) indicated dietary modifications onboard the ISS. Spaceflight-induced RQ changes adjusted for ground RQ correlated with inflight FQ (P < 0.01). In postprandial conditions, nutrient oxidation and ΔRQ were unaffected on average. Lipid oxidation changes negatively correlated with FFM changes and inflight aerobic exercise and positively with FM changes. The opposite was observed for carbohydrate oxidation. ΔRQ changes were negatively and positively related to FM and FFM changes, respectively. In conclusion, fasting substrate oxidation shift observed during spaceflight may primarily result from dietary modifications. Between-astronaut variability in postprandial substrate oxidation depends on body composition changes and inflight PA.</p>","PeriodicalId":54263,"journal":{"name":"npj Microgravity","volume":"10 1","pages":"39"},"PeriodicalIF":5.1,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10973451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140307814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"物理与天体物理","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
npj MicrogravityPub Date : 2024-03-23DOI: 10.1038/s41526-024-00382-8
Zheng Zhang, Yu Jing, Ang Zhang, JiShan Liu, Heming Yang, Xiaotong Lou, Liyan Xu, Min Liu, Yikun Zhang, Jianwen Gu
{"title":"Long non-coding RNA-NONMMMUT004552.2 regulates the unloading-induced bone loss through the miRNA-15b-5p/Syne1 in mice.","authors":"Zheng Zhang, Yu Jing, Ang Zhang, JiShan Liu, Heming Yang, Xiaotong Lou, Liyan Xu, Min Liu, Yikun Zhang, Jianwen Gu","doi":"10.1038/s41526-024-00382-8","DOIUrl":"10.1038/s41526-024-00382-8","url":null,"abstract":"<p><p>Exercise-induced mechanical loading can increase bone strength whilst mechanical unloading enhances bone-loss. Here, we investigated the role of lncRNA NONMMUT004552.2 in unloading-induced bone-loss. Knockout of lncRNA NONMMUT004552.2 in hindlimb-unloaded mice caused an increase in the bone formation and osteoblast activity. The silencing of lncRNA NONMMUT004552.2 also decreased the osteoblast apoptosis and expression of Bax and cleaved caspase-3, increased Bcl-2 protein expression in MC3T3-E1 cells. Mechanistic investigations demonstrated that NONMMUT004552.2 functions as a competing endogenous RNA (ceRNA) to facilitate the protein expression of spectrin repeat containing, nuclear envelope 1 (Syne1) by competitively binding miR-15b-5p and subsequently inhibits the osteoblast differentiation and bone formation in the microgravity unloading environment. These data highlight the importance of the lncRNA NONMMUT004552.2/miR-15b-5p/Syne1 axis for the treatment of osteoporosis.</p>","PeriodicalId":54263,"journal":{"name":"npj Microgravity","volume":"10 1","pages":"37"},"PeriodicalIF":5.1,"publicationDate":"2024-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10960867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140195090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"物理与天体物理","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cooling of a granular gas mixture in microgravity.","authors":"Dmitry Puzyrev, Torsten Trittel, Kirsten Harth, Ralf Stannarius","doi":"10.1038/s41526-024-00369-5","DOIUrl":"10.1038/s41526-024-00369-5","url":null,"abstract":"<p><p>Granular gases are fascinating non-equilibrium systems with interesting features such as spontaneous clustering and non-Gaussian velocity distributions. Mixtures of different components represent a much more natural composition than monodisperse ensembles but attracted comparably little attention so far. We present the observation and characterization of a mixture of rod-like particles with different sizes and masses in a drop tower experiment. Kinetic energy decay rates during granular cooling and collision rates were determined and Haff's law for homogeneous granular cooling was confirmed. Thereby, energy equipartition between the mixture components and between individual degrees of freedom is violated. Heavier particles keep a slightly higher average kinetic energy than lighter ones. Experimental results are supported by numerical simulations.</p>","PeriodicalId":54263,"journal":{"name":"npj Microgravity","volume":"10 1","pages":"36"},"PeriodicalIF":5.1,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10959983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140195089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"物理与天体物理","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
npj MicrogravityPub Date : 2024-03-21DOI: 10.1038/s41526-024-00386-4
Nadab H Wubshet, Grace Cai, Samuel J Chen, Molly Sullivan, Mark Reeves, David Mays, Morgan Harrison, Paul Varnado, Benjamin Yang, Esmeralda Arreguin-Martinez, Yunjia Qu, Shan-Shan Lin, Pamela Duran, Carlos Aguilar, Shelby Giza, Twyman Clements, Allen P Liu
{"title":"Cellular mechanotransduction of human osteoblasts in microgravity.","authors":"Nadab H Wubshet, Grace Cai, Samuel J Chen, Molly Sullivan, Mark Reeves, David Mays, Morgan Harrison, Paul Varnado, Benjamin Yang, Esmeralda Arreguin-Martinez, Yunjia Qu, Shan-Shan Lin, Pamela Duran, Carlos Aguilar, Shelby Giza, Twyman Clements, Allen P Liu","doi":"10.1038/s41526-024-00386-4","DOIUrl":"10.1038/s41526-024-00386-4","url":null,"abstract":"<p><p>Astronauts experience significant and rapid bone loss as a result of an extended stay in space, making the International Space Station (ISS) the perfect laboratory for studying osteoporosis due to the accelerated nature of bone loss on the ISS. This prompts the question, how does the lack of load due to zero-gravity propagate to bone-forming cells, human fetal osteoblasts (hFOBs), altering their maturation to mineralization? Here, we aim to study the mechanotransduction mechanisms by which bone loss occurs in microgravity. Two automated experiments, microfluidic chips capable of measuring single-cell mechanics via aspiration and cell spheroids incubated in pressure-controlled chambers, were each integrated into a CubeLab deployed to the ISS National Laboratory. For the first experiment, we report protrusion measurements of aspirated cells after exposure to microgravity at the ISS and compare these results to ground control conducted inside the CubeLab. We found slightly elongated protrusions for space samples compared to ground samples indicating softening of hFOB cells in microgravity. In the second experiment, we encapsulated osteoblast spheroids in collagen gel and incubated the samples in pressure-controlled chambers. We found that microgravity significantly reduced filamentous actin levels in the hFOB spheroids. When subjected to pressure, the spheroids exhibited increased pSMAD1/5/9 expression, regardless of the microgravity condition. Moreover, microgravity reduced YAP expression, while pressure increased YAP levels, thus restoring YAP expression for spheroids in microgravity. Our study provides insights into the influence of microgravity on the mechanical properties of bone cells and the impact of compressive pressure on cell signaling in space.</p>","PeriodicalId":54263,"journal":{"name":"npj Microgravity","volume":"10 1","pages":"35"},"PeriodicalIF":4.4,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10957960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140186276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"物理与天体物理","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
npj MicrogravityPub Date : 2024-03-20DOI: 10.1038/s41526-024-00377-5
Alessia Simonini, Michael Dreyer, Annafederica Urbano, Francesco Sanfedino, Takehiro Himeno, Philipp Behruzi, Marc Avila, Jorge Pinho, Laura Peveroni, Jean-Baptiste Gouriet
{"title":"Cryogenic propellant management in space: open challenges and perspectives.","authors":"Alessia Simonini, Michael Dreyer, Annafederica Urbano, Francesco Sanfedino, Takehiro Himeno, Philipp Behruzi, Marc Avila, Jorge Pinho, Laura Peveroni, Jean-Baptiste Gouriet","doi":"10.1038/s41526-024-00377-5","DOIUrl":"10.1038/s41526-024-00377-5","url":null,"abstract":"<p><p>This paper presents open challenges and perspectives of propellant management for crewed deep space exploration. The most promising propellants are liquid hydrogen and liquid methane, together with liquid oxygen as an oxidizer. These fluids remain liquid only at cryogenic conditions, that is, at temperatures lower than 120 K. To extend the duration of space exploration missions, or even to enable them, the storage and refueling from a cryogenic on-orbit depot is necessary. We review reference missions, architectures, and technology demonstrators and explain the main operations that are considered as enablers for cryogenic storage and transfer. We summarize the state of the art for each of them, showing that many gaps in physical knowledge still need to be filled. This paper is based on recommendations originally proposed in a White Paper for ESA's SciSpacE strategy.</p>","PeriodicalId":54263,"journal":{"name":"npj Microgravity","volume":"10 1","pages":"34"},"PeriodicalIF":5.1,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10954726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140177726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"物理与天体物理","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
npj MicrogravityPub Date : 2024-03-20DOI: 10.1038/s41526-024-00372-w
Jessica Ward, Robert J Reynolds, Erin Connell, Wilma Anton, Avalon Kabeel, Jacqueline M Charvat, Nicholas Nartey, Kristina Marotta, Ahmed Abukmail, Dan M Buckland, Mary Van Baalen, Erik Antonsen
{"title":"Levels of evidence for human system risk evaluation.","authors":"Jessica Ward, Robert J Reynolds, Erin Connell, Wilma Anton, Avalon Kabeel, Jacqueline M Charvat, Nicholas Nartey, Kristina Marotta, Ahmed Abukmail, Dan M Buckland, Mary Van Baalen, Erik Antonsen","doi":"10.1038/s41526-024-00372-w","DOIUrl":"10.1038/s41526-024-00372-w","url":null,"abstract":"<p><p>NASA uses a continuous risk management process to seek out new knowledge of spaceflight-induced risk to human health and performance. The evidence base that informs the risk assessments in this domain is constantly changing as more information is gleaned from a continuous human presence in space and from ongoing research. However, the limitations of this evidence are difficult to characterize because fewer than 700 humans have ever flown in space, and information comes from a variety of sources that span disciplines, including engineering, medicine, food and nutrition, and many other life sciences. The Human System Risk Board (HSRB) at NASA is responsible for assessing risk to astronauts and communicating this risk to agency decision-makers. A critical part of that communication is conveying the uncertainty regarding the understanding of the changes that spaceflight induces in human processes and the complex interactions between humans and the spacecraft. Although the strength of evidence grades is common in the academic literature, these scores are often not useful for the problems of human spaceflight. The HSRB continues to update the processes used to report the levels of evidence. This paper describes recent updates to the methods used to assign the level of evidence scores to the official risk postures and to the causal diagrams used by the HSRB.</p>","PeriodicalId":54263,"journal":{"name":"npj Microgravity","volume":"10 1","pages":"33"},"PeriodicalIF":5.1,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10954631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140177727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"物理与天体物理","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
npj MicrogravityPub Date : 2024-03-19DOI: 10.1038/s41526-024-00375-7
Erik Antonsen, Robert J Reynolds, Jacqueline Charvat, Erin Connell, Avalon Monti, Devan Petersen, Nicholas Nartey, Wilma Anton, Ahmed Abukmail, Kristina Marotta, Mary Van Baalen, Daniel M Buckland
{"title":"Causal diagramming for assessing human system risk in spaceflight.","authors":"Erik Antonsen, Robert J Reynolds, Jacqueline Charvat, Erin Connell, Avalon Monti, Devan Petersen, Nicholas Nartey, Wilma Anton, Ahmed Abukmail, Kristina Marotta, Mary Van Baalen, Daniel M Buckland","doi":"10.1038/s41526-024-00375-7","DOIUrl":"10.1038/s41526-024-00375-7","url":null,"abstract":"<p><p>For over a decade, the National Aeronautics and Space Administration (NASA) has tracked and configuration-managed approximately 30 risks that affect astronaut health and performance before, during and after spaceflight. The Human System Risk Board (HSRB) at NASA Johnson Space Center is responsible for setting the official risk posture for each of the human system risks and determining-based on evaluation of the available evidence-when that risk posture changes. The ultimate purpose of tracking and researching these risks is to find ways to reduce spaceflight-induced risk to astronauts. The adverse effects of spaceflight begin at launch and continue throughout the duration of the mission, and in some cases, across the lifetime of the astronaut. Historically, research has been conducted in individual risk \"silos\" to characterize risk, however, astronauts are exposed to all risks simultaneously. In January of 2020, the HSRB at NASA began assessing the potential value of causal diagramming as a tool to facilitate understanding of the complex causes and effects that contribute to spaceflight-induced human system risk. Causal diagrams in the form of directed acyclic graphs (DAGs) are used to provide HSRB stakeholders with a shared mental model of the causal flow of risk. While primarily improving communication among those stakeholders, DAGs also allow a composite risk network to be created that can be tracked and configuration managed. This paper outlines the HSRB's pilot process for this effort, the lessons learned, and future goals for data-driven risk management approaches.</p>","PeriodicalId":54263,"journal":{"name":"npj Microgravity","volume":"10 1","pages":"32"},"PeriodicalIF":4.4,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10951288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140177725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"物理与天体物理","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
npj MicrogravityPub Date : 2024-03-18DOI: 10.1038/s41526-024-00381-9
Alla Yemets, Ruslana Shadrina, Rostyslav Blume, Svitlana Plokhovska, Yaroslav Blume
{"title":"Autophagy formation, microtubule disorientation, and alteration of ATG8 and tubulin gene expression under simulated microgravity in Arabidopsis thaliana.","authors":"Alla Yemets, Ruslana Shadrina, Rostyslav Blume, Svitlana Plokhovska, Yaroslav Blume","doi":"10.1038/s41526-024-00381-9","DOIUrl":"10.1038/s41526-024-00381-9","url":null,"abstract":"<p><p>Autophagy plays an important role in plant growth and development, pathogen invasion and modulates plant response and adaptation to various abiotic stress stimuli. The biogenesis and trafficking of autophagosomes involve microtubules (MTs) as important actors in the autophagic process. However, initiation of autophagy in plants under microgravity has not been previously studied. Here we demonstrate how simulated microgravity induces autophagy development involving microtubular reorganization during period of autophagosome formation. It was shown that induction of autophagy with maximal autophagosome formation in root cells of Arabidopsis thaliana is observed after 6 days of clinostating, along with MT disorganization, which leads to visible changes in root morphology. Gradual decrease of autophagosome number was indicated on 9<sup>th</sup> and 12<sup>th</sup> days of the experiment as well as no significant re-orientation of MTs were identified. Respectively, analysis of α- and β-tubulins and ATG8 gene expression was carried out. In particular, the most pronounced increase of expression on both 6<sup>th</sup> and 9<sup>th</sup> days in response to simulated microgravity was detected for non-paralogous AtATG8b, AtATG8f, AtATG8i, and AtTUA2, AtTUA3 genes, as well as for the pair of β-tubulin duplicates, namely AtTUB2 and AtTUB3. Overall, the main autophagic response was observed after 6 and 9 days of exposure to simulated microgravity, followed by adaptive response after 12 days. These findings provide a key basis for further studies of cellular mechanisms of autophagy and involvement of cytoskeletal structures in autophagy biogenesis under microgravity, which would enable development of new approaches, aimed on enhancing plant adaptation to microgravity.</p>","PeriodicalId":54263,"journal":{"name":"npj Microgravity","volume":"10 1","pages":"31"},"PeriodicalIF":5.1,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10948825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140159477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"物理与天体物理","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}