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Dependence of cyanobacterium growth and Mars-specific photobioreactor mass on total pressure, pN2 and pCO2. 蓝藻生长和火星特定光生物反应器质量与总压、pN2 和 pCO2 的关系。
IF 4.4 1区 物理与天体物理 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-11-02 DOI: 10.1038/s41526-024-00440-1
Cyprien Verseux, Tiago P Ramalho, Emma Bohuon, Nils Kunst, Viktoria Lang, Christiane Heinicke

In situ resource utilization systems based on cyanobacteria could support the sustainability of crewed missions to Mars. However, their resource-efficiency will depend on the extent to which gases from the Martian atmosphere must be processed to support cyanobacterial growth. The main purpose of the present work is to help assess this extent. We therefore start with investigating the impact of changes in atmospheric conditions on the photoautotrophic, diazotrophic growth of the cyanobacterium Anabaena sp. PCC 7938. We show that lowering atmospheric pressure from 1 bar down to 80 hPa, without changing the partial pressures of metabolizable gases, does not reduce growth rates. We also provide equations, analogous to Monod's, that describe the dependence of growth rates on the partial pressures of CO2 and N2. We then outline the relationships between atmospheric pressure and composition, the minimal mass of a photobioreactor's outer walls (which is dependent on the inner-outer pressure difference), and growth rates. Relying on these relationships, we demonstrate that the structural mass of a photobioreactor can be decreased - without affecting cyanobacterial productivity - by reducing the inner gas pressure. We argue, however, that this reduction would be small next to the equivalent system mass of the cultivation system. A greater impact on resource-efficiency could come from the selection of atmospheric conditions which minimize gas processing requirements while adequately supporting cyanobacterial growth. The data and equations we provide can help identify these conditions.

以蓝藻为基础的原地资源利用系统可以支持载人火星任务的可持续性。然而,其资源效率将取决于必须在多大程度上处理火星大气中的气体以支持蓝藻生长。本研究的主要目的就是帮助评估这一程度。因此,我们首先研究了大气条件变化对蓝藻 Anabaena sp. PCC 7938 的光自养、重氮生长的影响。我们的研究表明,在不改变可代谢气体分压的情况下,将大气压力从 1 bar 降到 80 hPa 不会降低生长率。我们还提供了与莫诺方程类似的方程,描述了生长率与 CO2 和 N2 分压的关系。然后,我们概述了大气压力和成分、光生物反应器外壁的最小质量(取决于内外压差)和生长率之间的关系。根据这些关系,我们证明了光生物反应器的结构质量可以通过降低内部气体压力来减少,而不会影响蓝藻的生产率。不过,我们认为,与培养系统的等效系统质量相比,这种减少是微不足道的。对资源效率影响更大的可能是选择大气条件,在充分支持蓝藻生长的同时最大限度地降低气体处理要求。我们提供的数据和方程有助于确定这些条件。
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引用次数: 0
Formaldehyde initiates memory and motor impairments under weightlessness condition. 甲醛会导致失重状态下的记忆和运动障碍。
IF 4.4 1区 物理与天体物理 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-10-28 DOI: 10.1038/s41526-024-00441-0
Tianhao Mei, Ying Chen, Yajuan Gao, Hang Zhao, Xingzhou Lyu, Jing Lin, Tianye Niu, Hongbin Han, Zhiqian Tong

During space flight, prolonged weightlessness stress exerts a range of detrimental impacts on the physiology and psychology of astronauts. These manifestations encompass depressive symptoms, anxiety, and impairments in both short-term memory and motor functions, albeit the precise underlying mechanisms remain elusive. Recent studies have revealed that hindlimb unloading (HU) animal models, which simulate space weightlessness, exhibited a disorder in memory and motor function associated with endogenous formaldehyde (FA) accumulation in the hippocampus and cerebellum, disruption of brain extracellular space (ECS), and blockage of interstitial fluid (ISF) drainage. Notably, the impairment of the blood-brain barrier (BBB) caused by space weightlessness elicits the infiltration of albumin and hemoglobin from the blood vessels into the brain ECS. However, excessive FA has the potential to form cross-links between these two proteins and amyloid-beta (Aβ), thereby obstructing ECS and inducing neuron death. Moreover, FA can inhibit N-methyl-D-aspartate (NMDA) currents by crosslinking NR1 and NR2B subunits, thus impairing memory. Additionally, FA has the ability to modulate the levels of certain microRNAs (miRNAs) such as miRNA-29b, which can affect the expression of aquaporin-4 (AQP4) so as to regulate ECS structure and ISF drainage. Especially, the accumulation of FA may inactivate the ataxia telangiectasia-mutated (ATM) protein kinase by forming cross-linking, a process that is associated with ataxia. Hence, this review presents that weightlessness stress-derived FA may potentially serve as a crucial catalyst in the deterioration of memory and motor abilities in the context of microgravity.

在太空飞行期间,长时间的失重压力会对宇航员的生理和心理产生一系列不利影响。这些表现包括抑郁症状、焦虑以及短期记忆和运动功能受损,但其确切的内在机制仍然难以捉摸。最近的研究发现,模拟太空失重的后肢卸载(HU)动物模型表现出记忆和运动功能紊乱,这与海马和小脑内源性甲醛(FA)积累、脑细胞外空间(ECS)破坏和间质(ISF)引流受阻有关。值得注意的是,太空失重导致血脑屏障(BBB)受损,引起血管中的白蛋白和血红蛋白渗入脑细胞外空间。然而,过量的 FA 有可能在这两种蛋白质和淀粉样β(Aβ)之间形成交联,从而阻碍 ECS 并导致神经元死亡。此外,FA 还能通过交联 NR1 和 NR2B 亚基抑制 N-甲基-D-天冬氨酸(NMDA)电流,从而损害记忆。此外,FA 还能调节某些微小核糖核酸(miRNA)(如 miRNA-29b)的水平,而 miRNA-29b 可影响水通道蛋白-4(AQP4)的表达,从而调节 ECS 结构和 ISF 排泄。特别是,FA 的积累可能通过形成交联而使共济失调性毛细血管扩张症(ATM)蛋白激酶失活,这一过程与共济失调有关。因此,本综述认为,失重应激产生的 FA 有可能成为微重力环境下记忆和运动能力退化的关键催化剂。
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引用次数: 0
Development and implementation of a simulated microgravity setup for edible cyanobacteria. 开发和实施可食用蓝藻的模拟微重力装置。
IF 4.4 1区 物理与天体物理 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-10-25 DOI: 10.1038/s41526-024-00436-x
Gabriele Ellena, Jana Fahrion, Surya Gupta, Claude-Gilles Dussap, Arianna Mazzoli, Natalie Leys, Felice Mastroleo

Regenerative life support systems for space crews recycle waste into water, food, and oxygen using different organisms. The European Space Agency's MELiSSA program uses the cyanobacterium Limnospira indica PCC8005 for air revitalization and food production. Before space use, components' compatibility with reduced gravity was tested. This study introduced a ground analog for microgravity experiments with oxygenic cyanobacteria under continuous illumination, using a random positioning machine (RPM) setup. L. indica PCC8005 grew slower under low-shear simulated microgravity, with proteome analysis revealing downregulation of ribosomal proteins, glutamine synthase, and nitrate uptake transporters, and upregulation of gas vesicle, photosystem I and II, and carboxysome proteins. Results suggested inhibition due to high oxygen partial pressure, causing carbon limitation when cultivated in low-shear simulated microgravity. A thicker stagnant fluid boundary layer reducing oxygen release in simulated microgravity was observed. These findings validate this RPM setup for testing the effects of non-terrestrial gravity on photosynthetic microorganisms.

太空乘员的再生生命支持系统利用不同的生物将废物回收为水、食物和氧气。欧洲航天局的 MELiSSA 计划利用蓝藻菌 Limnospira indica PCC8005 进行空气活化和食物生产。在太空使用之前,要对组件与重力降低的兼容性进行测试。本研究采用随机定位机(RPM)装置,对连续光照下的含氧蓝藻进行了地面模拟微重力实验。在低剪切力模拟微重力条件下,L. indica PCC8005 的生长速度较慢,蛋白质组分析显示核糖体蛋白、谷氨酰胺合成酶和硝酸盐吸收转运体下调,而气体囊、光系统 I 和 II 以及羧酶体蛋白上调。结果表明,在低剪切模拟微重力条件下培养时,高氧分压导致碳限制,从而造成抑制。在模拟微重力条件下,观察到较厚的停滞流体边界层减少了氧气的释放。这些发现验证了这种 RPM 设置可用于测试非地球重力对光合微生物的影响。
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引用次数: 0
Space Analogs and Behavioral Health Performance Research review and recommendations checklist from ESA Topical Team. 欧空局专题小组的空间模拟和行为健康绩效研究审查和建议清单。
IF 4.4 1区 物理与天体物理 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-10-22 DOI: 10.1038/s41526-024-00437-w
Gabriel G De la Torre, Gernot Groemer, Ana Diaz-Artiles, Nathalie Pattyn, Jeroen Van Cutsem, Michaela Musilova, Wieslaw Kopec, Stefan Schneider, Vera Abeln, Tricia Larose, Fabio Ferlazzo, Pierpaolo Zivi, Alexandra de Carvalho, Gro Mjeldheim Sandal, Leszek Orzechowski, Michel Nicolas, Rebecca Billette de Villemeur, Anne Pavy-Le Traon, Ines Antunes

Space analog research has increased over the last few years with new analogs appearing every year. Research in this field is very important for future real mission planning, selection and training of astronauts. Analog environments offer specific characteristics that resemble to some extent the environment of a real space mission. These analog environments are especially interesting from the psychological point of view since they allow the investigation of mental and social variables in very similar conditions to those occurring during real space missions. Analog missions also represent an opportunity to test operational work and obtain information on which combination of processes and team dynamics are most optimal for completing specific aspects of the mission. A group of experts from a European Space Agency (ESA) funded topical team reviews the current situation of topic, potentialities, gaps, and recommendations for appropriate research. This review covers the different domains in space analog research including classification, main areas of behavioral health performance research in these environments and operational aspects. We also include at the end, a section with a list or tool of recommendations in the form of a checklist for the scientific community interested in doing research in this field. This checklist can be useful to maintain optimal standards of methodological and scientific quality, in addition to identifying topics and areas of special interest.

过去几年来,空间模拟研究不断增加,每年都有新的模拟出现。这一领域的研究对于未来实际飞行任务的规划、宇航员的选拔和培训非常重要。模拟环境具有在一定程度上与实际太空任务环境相似的具体特征。从心理学的角度来看,这些模拟环境特别有趣,因为它们允许在与实际太空任务非常相似的条件下对心理和社会变量进行研究。模拟飞行任务也是测试业务工作的一个机会,可以获得有关完成飞行任务特定方面的最佳流程和团队动力组合的信息。由欧洲航天局(ESA)资助的一个专题小组的专家组成的专家组对专题的现状、潜力、差距和适当的研究建议进行了审查。本综述涵盖空间模拟研究的不同领域,包括分类、这些环境中行为健康表现研究的主要领域和操作方面。最后,我们还以核对表的形式为有兴趣在这一领域开展研究的科学界提供了一份建议清单或工具。除了确定特别感兴趣的主题和领域外,这份清单还有助于保持最佳的方法和科学质量标准。
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引用次数: 0
Surface tension enables induced pluripotent stem cell culture in commercially available hardware during spaceflight. 表面张力使诱导多能干细胞能在太空飞行期间通过市售硬件进行培养。
IF 4.4 1区 物理与天体物理 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-10-15 DOI: 10.1038/s41526-024-00435-y
Maedeh Mozneb, Madelyn Arzt, Pinar Mesci, Dylan M N Martin, Stephany Pohlman, George Lawless, Shankini Doraisingam, Sultan Al Neyadi, Rayyanah Barnawi, Ali Al Qarni, Peggy A Whitson, John Shoffner, Jana Stoudemire, Stefanie Countryman, Clive N Svendsen, Arun Sharma

Low Earth Orbit (LEO) has emerged as a unique environment for evaluating altered stem cell properties in microgravity. LEO has become increasingly accessible for research and development due to progress in private spaceflight. Axiom Mission 2 (Ax-2) was launched as the second all-private astronaut mission to the International Space Station (ISS). Frozen human induced pluripotent stem cells (hiPSCs) expressing green fluorescent protein (GFP) under the SOX2 promoter, as well as fibroblasts differentiated from SOX2-GFP hiPSCs, were sent to the ISS. Astronauts then thawed and seeded both cell types into commercially available 96-well plates, which provided surface tension that reduced fluid movement out of individual wells and showed that hiPSCs or hiPSC-derived fibroblasts could survive either in suspension or attached to a Matrigel substrate. Furthermore, both cell types could be transfected with red fluorescent protein (RFP)-expressing plasmid. We demonstrate that hiPSCs and hiPSC-fibroblasts can be thawed in microgravity in off-the-shelf, commercially-available cell culture hardware, can associate into 3D spheroids or grow adherently in Matrigel, and can be transfected with DNA. This lays the groundwork for future biomanufacturing experiments in space.

低地球轨道(LEO)已成为评估微重力下干细胞特性改变的独特环境。由于私人太空飞行的进步,越来越多的人可以利用低地轨道进行研究和开发。Axiom任务2(Ax-2)作为第二次全私人宇航员任务被发射到国际空间站(ISS)。在SOX2启动子下表达绿色荧光蛋白(GFP)的冷冻人类诱导多能干细胞(hiPSC)以及由SOX2-GFP hiPSC分化而成的成纤维细胞被送往国际空间站。宇航员随后解冻了这两种细胞,并将其播种到市售的96孔板中,这些孔板的表面张力可减少液体流出单个孔,结果表明,hiPSC或hiPSC衍生的成纤维细胞既可以悬浮存活,也可以附着在Matrigel基底上存活。此外,这两种细胞类型都能转染表达红色荧光蛋白(RFP)的质粒。我们证明,hiPSC 和 hiPSC-成纤维细胞可以在微重力环境下通过现成的商用细胞培养硬件解冻,可以结合成三维球体或在 Matrigel 中粘附生长,还可以用 DNA 进行转染。这为未来的太空生物制造实验奠定了基础。
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引用次数: 0
Perspectives on the physics of late-type stars from beyond low earth orbit, the moon and mars. 从低地球轨道、月球和火星之外透视晚期类型恒星的物理学。
IF 4.4 1区 物理与天体物理 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-10-05 DOI: 10.1038/s41526-024-00431-2
Savita Mathur, Ângela R G Santos

With the new discoveries enabled thanks to the recent space missions, stellar physics is going through a revolution. However, these discoveries opened the door to many new questions that require more observations. The European Space Agency's Human and Robotic Exploration program provides an excellent opportunity to push forward the limits of our knowledge and better understand stellar structure and dynamics evolution. Long-term observations, Ultra-Violet observations, and a stellar imager are a few highlights of proposed missions for late-type stars that will enhance the already planned space missions.

由于最近的太空任务带来了新的发现,恒星物理学正在经历一场革命。然而,这些发现也为许多新问题打开了大门,需要进行更多的观测。欧洲航天局的人类和机器人探索计划提供了一个绝佳的机会,让我们能够突破知识极限,更好地了解恒星结构和动力学演化。长期观测、紫外线观测和恒星成像仪是拟议中的晚期恒星任务的几个重点,它们将加强已经计划的太空任务。
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引用次数: 0
Profiling muscle transcriptome in mice exposed to microgravity using gene set enrichment analysis. 利用基因组富集分析剖析暴露于微重力环境下的小鼠肌肉转录组。
IF 4.4 1区 物理与天体物理 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-10-04 DOI: 10.1038/s41526-024-00434-z
Anup Mammen Oommen, Phillip Stafford, Lokesh Joshi

Space exploration's advancement toward long-duration missions prompts intensified research on physiological effects. Despite adaptive physiological stability in some variables, persistent changes affect genome integrity, immune response, and cognitive function. Our study, utilizing multi-omics data from GeneLab, provides crucial insights investigating muscle atrophy during space mission. Leveraging NASA GeneLab's data resources, we apply systems biology-based analyses, facilitating comprehensive understanding and enabling meta-analysis. Through transcriptomics, we establish a reference profile of biological processes underlying muscle atrophy, crucial for intervention development. We emphasize the often-overlooked role of glycosylation in muscle atrophy. Our research sheds light on fundamental molecular mechanisms, bridging gaps between space research and terrestrial conditions. This study underscores the importance of interdisciplinary collaboration and data-sharing initiatives like GeneLab in advancing space medicine research.

太空探索向长期任务迈进,促使人们加强对生理影响的研究。尽管某些变量具有适应性生理稳定性,但持续的变化会影响基因组的完整性、免疫反应和认知功能。我们的研究利用基因实验室的多组学数据,为研究太空任务期间的肌肉萎缩提供了重要的见解。利用美国国家航空航天局基因实验室的数据资源,我们采用了基于系统生物学的分析方法,促进了全面的理解并实现了荟萃分析。通过转录组学,我们建立了肌肉萎缩的生物过程参考图谱,这对干预措施的开发至关重要。我们强调糖基化在肌肉萎缩中经常被忽视的作用。我们的研究揭示了基本的分子机制,弥合了太空研究与地面条件之间的差距。这项研究强调了跨学科合作和数据共享计划(如基因实验室)在推进太空医学研究方面的重要性。
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引用次数: 0
The impact of gravity on perceived object height. 重力对感知物体高度的影响。
IF 4.4 1区 物理与天体物理 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-10-04 DOI: 10.1038/s41526-024-00430-3
Björn Jörges, Nils Bury, Meaghan McManus, Ambika Bansal, Robert S Allison, Michael Jenkin, Laurence R Harris

Altering posture relative to the direction of gravity, or exposure to microgravity has been shown to affect many aspects of perception, including size perception. Our aims in this study were to investigate whether changes in posture and long-term exposure to microgravity bias the visual perception of object height and to test whether any such biases are accompanied by changes in precision. We also explored the possibility of sex/gender differences. Two cohorts of participants (12 astronauts and 20 controls, 50% women) varied the size of a virtual square in a simulated corridor until it was perceived to match a reference stick held in their hands. Astronauts performed the task before, twice during, and twice after an extended stay onboard the International Space Station. On Earth, they performed the task of sitting upright and lying supine. Earth-bound controls also completed the task five times with test sessions spaced similarly to the astronauts; to simulate the microgravity sessions on the ISS they lay supine. In contrast to earlier studies, we found no immediate effect of microgravity exposure on perceived object height. However, astronauts robustly underestimated the height of the square relative to the haptic reference and these estimates were significantly smaller 60 days or more after their return to Earth. No differences were found in the precision of the astronauts' judgments. Controls underestimated the height of the square when supine relative to sitting in their first test session (simulating Pre-Flight) but not in later sessions. While these results are largely inconsistent with previous results in the literature, a posture-dependent effect of simulated eye height might provide a unifying explanation. We were unable to make any firm statements related to sex/gender differences. We conclude that no countermeasures are required to mitigate the acute effects of microgravity exposure on object height perception. However, space travelers should be warned about late-emerging and potentially long-lasting changes in this perceptual skill.

研究表明,改变相对于重力方向的姿势或暴露于微重力环境会影响感知的许多方面,包括尺寸感知。本研究的目的是调查姿势的改变和长期暴露于微重力环境是否会对物体高度的视觉感知产生偏差,并测试这种偏差是否伴随着精确度的变化。我们还探讨了性别差异的可能性。两组参与者(12 名宇航员和 20 名对照组,50% 为女性)在模拟走廊中改变虚拟正方形的大小,直到他们认为该正方形与他们手中的参照棒相匹配。宇航员在国际空间站长期逗留之前、期间和之后各执行了两次任务。在地球上,他们分别完成了直立坐姿和仰卧姿态的任务。在地球上的对照组也完成了五次任务,测试时间间隔与宇航员相似;为了模拟国际空间站上的微重力测试,他们采取了仰卧姿势。与之前的研究不同,我们没有发现微重力对感知物体高度的直接影响。但是,宇航员严重低估了相对于触觉参照物的正方形高度,而且在返回地球 60 天或更长时间后,这些估计值明显变小。在宇航员判断的精确度方面没有发现差异。对照组在第一次测试(模拟飞行前)中低估了仰卧时相对于坐姿的正方形高度,但在后面的测试中没有发现这种情况。虽然这些结果在很大程度上与之前的文献结果不一致,但模拟眼球高度对姿势的影响可能提供了一个统一的解释。我们无法对性/性别差异做出任何肯定的结论。我们的结论是,不需要采取任何对策来减轻微重力暴露对物体高度感知的急性影响。但是,应该提醒太空旅行者注意这种感知能力的后期变化,这种变化可能会持续很长时间。
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引用次数: 0
Using noninvasive imaging to assess manual lymphatic drainage on lymphatic/venous responses in a spaceflight analog. 利用无创成像技术评估人工淋巴引流对太空飞行模拟人淋巴/静脉反应的影响。
IF 4.4 1区 物理与天体物理 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-10-03 DOI: 10.1038/s41526-024-00429-w
Heather Barnhart, Frank Aviles, Johanna Pannunzio, Nathan Sirkis, Chantel Hubbard, Patrick Hardigan, Sabrina Ginsburg, Harvey Mayrovitz, Kristen A Eckert, M Mark Melin

This retrospective case series (clinicaltrials.gov NCT06405282) used noninvasive imaging devices (NIID) to assess the effect of manual lymphatic drainage (MLD) on dermal/venous fluid distribution, perfusion, and temperature alterations of the head, neck, upper torso, and legs while in the 6-degree head-down tilt validated spaceflight analog. A lymphatic fluid scanner measured tissue dielectric constant levels. Near-infrared spectroscopy assessed perfusion, by measuring tissue oxygenation saturation. Long-wave infrared thermography measured tissue temperature gradients. Fifteen healthy, university students participated. NIID assessments were taken 1 minute after assuming the HDT position and then every 30 minutes, with MLD administered from 180 to 195 minutes. Subjects returned to the sitting position and were assessed at post-225 min NIID demonstrated significant changes from baseline (p < 0.01), although these changes at areas of interest varied. MLD had a reverse effect on all variables. NIID assessment supported the potential use of MLD to mitigate fluid shifts during a spaceflight analog.

这项回顾性病例系列研究(clinicaltrials.gov NCT06405282)使用无创成像设备(NIID)评估了手动淋巴引流术(MLD)对头颈部、躯干上部和腿部真皮/静脉液体分布、灌注和温度变化的影响。淋巴液扫描仪测量了组织介电常数水平。近红外光谱仪通过测量组织氧饱和度来评估灌注情况。长波红外热成像测量组织温度梯度。15 名健康的大学生参加了此次活动。在采取 HDT 体位后 1 分钟进行 NIID 评估,然后每隔 30 分钟进行一次,在 180 至 195 分钟期间进行 MLD 评估。受试者回到坐姿,在 225 分钟后进行 NIID 评估,结果显示与基线相比有显著变化(p
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引用次数: 0
The MyoGravity project to study real microgravity effects on human muscle precursor cells and tissue. MyoGravity 项目,研究微重力对人体肌肉前体细胞和组织的实际影响。
IF 4.4 1区 物理与天体物理 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-10-03 DOI: 10.1038/s41526-024-00432-1
Ester Sara Di Filippo, Sara Chiappalupi, Stefano Falone, Vincenza Dolo, Fernanda Amicarelli, Silvia Marchianò, Adriana Carino, Gabriele Mascetti, Giovanni Valentini, Sara Piccirillo, Michele Balsamo, Marco Vukich, Stefano Fiorucci, Guglielmo Sorci, Stefania Fulle
<p><p>Microgravity (µG) experienced during space flights promotes adaptation in several astronauts' organs and tissues, with skeletal muscles being the most affected. In response to reduced gravitational loading, muscles (especially, lower limb and antigravity muscles) undergo progressive mass loss and alteration in metabolism, myofiber size, and composition. Skeletal muscle precursor cells (MPCs), also known as satellite cells, are responsible for the growth and maintenance of muscle mass in adult life as well as for muscle regeneration following damage and may have a major role in µG-induced muscle wasting. Despite the great relevance for astronaut health, very few data are available about the effects of real µG on human muscles. Based on the MyoGravity project, this study aimed to analyze: (i) the cellular and transcriptional alterations induced by real µG in human MPCs (huMPCs) and (ii) the response of human skeletal muscle to normal gravitational loading after prolonged exposure to µG. We evaluated the transcriptomic changes induced by µG on board the International Space Station (ISS) in differentiating huMPCs isolated from Vastus lateralis muscle biopsies of a pre-flight astronaut and an age- and sex-matched volunteer, in comparison with the same cells cultured on the ground in standard gravity (1×g) conditions. We found that huMPCs differentiated under real µG conditions showed: (i) upregulation of genes related to cell adhesion, plasma membrane components, and ion transport; (ii) strong downregulation of genes related to the muscle contraction machinery and sarcomere organization; and (iii) downregulation of muscle-specific microRNAs (myomiRs). Moreover, we had the unique opportunity to analyze huMPCs and skeletal muscle tissue of the same astronaut before and 30 h after a long-duration space flight on board the ISS. Prolonged exposure to real µG strongly affected the biology and functionality of the astronaut's satellite cells, which showed a dramatic reduction of responsiveness to activating stimuli and proliferation rate, morphological changes, and almost inability to fuse into myotubes. RNA-Seq analysis of post- vs. pre-flight muscle tissue showed that genes involved in muscle structure and remodeling are promptly activated after landing following a long-duration space mission. Conversely, genes involved in the myelination process or synapse and neuromuscular junction organization appeared downregulated. Although we have investigated only one astronaut, these results point to a prompt readaptation of the skeletal muscle mechanical components to the normal gravitational loading, but the inability to rapidly recover the physiological muscle myelination/innervation pattern after landing from a long-duration space flight. Together with the persistent functional deficit observed in the astronaut's satellite cells after prolonged exposure to real µG, these results lead us to hypothesize that a condition of inefficient regeneration is likely
太空飞行期间经历的微重力(µG)促进了宇航员多个器官和组织的适应,其中骨骼肌受到的影响最大。为了应对重力负荷的降低,肌肉(尤其是下肢肌肉和反重力肌肉)的质量会逐渐下降,新陈代谢、肌纤维大小和成分也会发生变化。骨骼肌前体细胞(MPCs)又称卫星细胞,负责成年后肌肉质量的生长和维持,以及肌肉受损后的再生,可能在 µG 诱导的肌肉萎缩中扮演重要角色。尽管µG 与宇航员的健康息息相关,但有关实际 µG 对人体肌肉影响的数据却寥寥无几。基于 MyoGravity 项目,本研究旨在分析:(i) 真实 µG 在人类 MPCs(huMPCs)中诱导的细胞和转录变化;(ii) 人类骨骼肌在长期暴露于 µG 后对正常重力负荷的反应。我们评估了µG 在国际空间站(ISS)上对从一名飞行前宇航员和一名年龄与性别匹配的志愿者的腹外肌活检组织中分离出来的分化 huMPCs 所诱导的转录组变化,并与在地面标准重力(1×g)条件下培养的相同细胞进行了比较。我们发现,在真实 µG 条件下分化的 huMPCs 表现出以下特征(i) 与细胞粘附、质膜成分和离子转运有关的基因上调;(ii) 与肌肉收缩机制和肌节组织有关的基因强烈下调;(iii) 肌肉特异性 microRNAs(myomiRs)下调。此外,我们还获得了一个独特的机会,在国际空间站上进行长时间太空飞行之前和之后 30 小时,对同一宇航员的 huMPCs 和骨骼肌组织进行了分析。长期暴露在真实微戈(real µG)环境中对宇航员卫星细胞的生物学和功能产生了强烈影响,卫星细胞对活化刺激的反应性和增殖率急剧下降,形态发生变化,几乎无法融合成肌管。对飞行后与飞行前的肌肉组织进行的RNA-Seq分析表明,参与肌肉结构和重塑的基因在长时间太空任务后着陆后迅速被激活。相反,参与髓鞘化过程或突触和神经肌肉接头组织的基因则出现了下调。虽然我们只对一名宇航员进行了研究,但这些结果表明,骨骼肌的机械成分能迅速重新适应正常的重力负荷,但从长期太空飞行中着陆后,无法迅速恢复生理性的肌肉髓鞘化/神经支配模式。再加上在宇航员的卫星细胞中观察到的长期暴露于真实微戈后的持续功能缺陷,这些结果使我们推测,飞行后宇航员的肌肉在受损后很可能会出现低效再生的情况。
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