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Effects of Solar Particle Event-Like Proton Radiation and/or Simulated Microgravity on Circulating Mouse Blood Cells. 太阳粒子事件样质子辐射和/或模拟微重力对循环小鼠血细胞的影响。
Ana L Romero-Weaver, Liyong Lin, Alejandro Carabe-Fernandez, Ann R Kennedy

Astronauts traveling in space missions outside of low Earth orbit will be exposed for longer times to a microgravity environment. In addition, the increased travel time involved in exploration class missions will result in an increased risk of exposure to significant doses of solar particle event (SPE) radiation. Both conditions could significantly affect the number of circulating blood cells. Therefore, it is critical to determine the combined effects of exposure to both microgravity and SPE radiation. The purpose of the present study was to assess these risks by evaluating the effects of SPE-like proton radiation and/or microgravity, as simulated with the hindlimb unloading (HU) system, on circulating blood cells using mouse as a model system. The results indicate that exposure to HU alone caused minimal or no significant changes in mouse circulating blood cell numbers. The exposure of mice to SPE-like proton radiation with or without HU treatment caused a significant decrease in the number of circulating lymphocytes, granulocytes and platelets. The reduced numbers of circulating lymphocytes, granulocytes, and platelets, resulting from the SPE-like proton radiation exposure, with or without HU treatment, in mice suggest that astronauts participating in exploration class missions may be at greater risk of developing infections and thrombotic diseases; thus, countermeasures may be necessary for these biological endpoints.

在低地球轨道外执行太空任务的宇航员将长时间暴露在微重力环境中。此外,勘探级任务所涉及的旅行时间的增加将导致暴露于大剂量太阳粒子事件(SPE)辐射的风险增加。这两种情况都会显著影响循环血细胞的数量。因此,确定暴露在微重力和SPE辐射下的综合效应是至关重要的。本研究的目的是通过评估sp样质子辐射和/或微重力对循环血细胞的影响来评估这些风险,用后肢卸载(HU)系统模拟,以小鼠为模型系统。结果表明,单独暴露于HU对小鼠循环血细胞数量的影响很小或没有显著变化。小鼠暴露于sp样质子辐射(伴或不伴HU治疗)导致循环淋巴细胞、粒细胞和血小板数量显著减少。在小鼠中,无论是否接受过HU治疗,sp样质子辐射暴露导致循环淋巴细胞、粒细胞和血小板数量减少,这表明参与探索级任务的宇航员可能面临更大的感染和血栓性疾病风险;因此,可能需要对这些生物终点采取对策。
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引用次数: 0
Effect of Gender on the Radiation Sensitivity of Murine Blood Cells. 性别对小鼠血细胞辐射敏感性的影响。
Paul C Billings, Ana L Romero-Weaver, Ann R Kennedy

Space travel beyond the Earth's protective magnetosphere risks exposing astronauts to ionizing radiation, such as that generated during a solar particle event (SPE). Ionizing radiation has well documented effects on blood cells and it is generally assumed that these effects contribute to the hematopoietic syndrome (HS), observed in animals and humans, following exposure to total body irradiation (TBI). The purpose of the current study was to assess the role of gender on the effects of gamma radiation on blood cells. C3H/HeN mice were irradiated with a 137Cs gamma source. Radiation had similar effects on white blood cells (WBCs), lymphocytes, and granulocytes in male and female C3H/HeN mice, while red blood cell (RBC) counts and hematocrit values remained stable following radiation exposure. Non-irradiated male mice had 13% higher platelet counts, compared with their female counterparts, and showed enhanced recovery of platelets on day 16 following radiation exposure. Hence, gender differences influence the response of platelets to TBI exposure.

在地球保护磁层之外的太空旅行可能会使宇航员暴露在电离辐射中,比如太阳粒子事件(SPE)期间产生的电离辐射。电离辐射对血细胞有充分的影响,一般认为这些影响有助于在动物和人类中观察到的全身照射(TBI)后的造血综合征(HS)。当前研究的目的是评估性别对伽马辐射对血细胞影响的作用。用137Cs γ源照射C3H/HeN小鼠。辐射对雄性和雌性C3H/HeN小鼠的白细胞(wbc)、淋巴细胞和粒细胞有相似的影响,而红细胞(RBC)计数和红细胞压积值在辐射暴露后保持稳定。与雌性小鼠相比,未受辐射的雄性小鼠的血小板计数高13%,并且在辐射暴露后的第16天显示出血小板恢复的增强。因此,性别差异影响血小板对创伤性脑损伤的反应。
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引用次数: 0
Interpretation of Backlit Droplet Images from ISS Droplet Combustion Experiments 国际空间站液滴燃烧实验中背光液滴图像的解译
Fei Yu, B. Shaw
ABSTRACT Backlit droplet images are evaluated for droplet combustion experiments that have been performed on the International Space Station. The focus of the present analyses is on non-sooting or lightly-sooting droplets. The influences of diffraction, interference, and partial coherence on droplet images are considered via Fourier optics modeling. It is found that light diffraction at the droplet edge can contribute significantly to errors in droplet size measurements. Other error sources include background light variations and partial coherence effects. An image-processing algorithm is proposed to account for the effects of diffraction, partial coherence, and background light variations on measurements of droplet sizes.
摘要:本文对在国际空间站上进行的液滴燃烧实验中的背光液滴图像进行了评价。本分析的重点是无烟尘或轻度烟尘液滴。通过傅立叶光学模型考虑了衍射、干涉和部分相干对液滴成像的影响。研究发现,液滴边缘处的光衍射对液滴尺寸测量误差有重要影响。其他误差源包括背景光变化和部分相干效应。提出了一种图像处理算法,以考虑衍射、部分相干性和背景光变化对液滴尺寸测量的影响。
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引用次数: 5
Molecular Effects of Spaceflight in the Mouse Eye after Space Shuttle Mission STS-135 航天飞机STS-135任务后小鼠眼中的航天分子效应
C. Theriot, S. Zanello
ABSTRACT Exposure to long-duration microgravity leads to ocular changes in astronauts, manifested by a variety of signs and symptoms during spaceflight that in some cases persist after return to Earth. These morphological and functional changes are only partly understood and are of occupational health relevance. To investigate further into the molecular basis of the changes occurring in ocular tissue upon exposure to spaceflight, eyes were collected from male C57BL/6 mice flown on STS-135 (FLT) on landing day or from their ground control counterparts maintained at similar conditions within the Animal Enclosure Module (AEM). One eye was fixed for histological sectioning while the contralateral eye was dissected to isolate the retina for gene expression profiling. 8-hydroxy-deoxyguanosine (8OHdG) staining showed a statistically significant increase in the inner nuclear layer of FLT samples compared to AEM. Gene expression analysis in isolated retina identified 139 differentially expressed genes in FLT compared to AEM control samples. The genes affected were mainly involved in pathways and processes of endoplasmic reticulum (ER) stress, inflammation, neuronal and glial cell loss, axonal degeneration, and herpes virus activation. These results suggest a concerted change in gene expression in the retina of mice flown in space, possibly leading to retinal damage, degeneration, and remodeling.
长期暴露在微重力环境下会导致宇航员的眼部变化,在航天飞行期间表现为各种体征和症状,在某些情况下,这些症状在返回地球后仍然存在。这些形态和功能的变化只是部分理解和职业健康相关。为了进一步研究暴露于太空飞行后眼部组织变化的分子基础,我们收集了着陆当天乘坐STS-135 (FLT)飞行的雄性C57BL/6小鼠的眼睛,以及在动物封闭舱(AEM)中保持类似条件的地面对照小鼠的眼睛。固定一只眼睛进行组织学切片,同时解剖对侧眼睛分离视网膜进行基因表达谱分析。8-羟基脱氧鸟苷(8OHdG)染色显示FLT样品的内核层与AEM相比有统计学意义的增加。基因表达分析在离体视网膜中鉴定出与AEM对照样本相比,FLT中有139个差异表达基因。受影响的基因主要涉及内质网应激、炎症、神经元和胶质细胞损失、轴突变性和疱疹病毒活化的途径和过程。这些结果表明,在太空中飞行的小鼠视网膜中的基因表达发生了一致的变化,可能导致视网膜损伤、变性和重塑。
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引用次数: 8
Oxygen and Silicon Ion Particles Induce Neoplastic Transformation in Human Colonic Epithelial Cells 氧和硅离子颗粒诱导人结肠上皮细胞肿瘤转化
S. B. Kim, Lu Zhang, J. Shay
ABSTRACT High charge (Z) and energy (E) (HZE) particles in deep space have significantly contributed to the biological effects of space radiation, although they only account for less than 1% of the galactic cosmic rays (GCR) particle fluxes. Previously we have shown that combined radiation exposure of 2-Gy proton (1H) followed by 0.5-Gy iron (56Fe) ion particles increase transformation in human colonic epithelial cells (HCEC CT7). The present study was undertaken to characterize if additional HZE ions, such as oxygen (16O) and silicon (28Si) particles, also result in increased cell transformation. HCEC CT7 cells irradiated with 1-Gy 16O (250 MeV/nucleon), followed 24 hours later by 1-Gy 28Si particle (300 MeV/nucleon), showed an increase in proliferation, anchorage-independent growth, migration, and invasion abilities compared to unirradiated controls. In addition, we found that the β-catenin pathway was activated and that subsets of DNA repair genes were under-expressed in these transformed cells. Pretreatment with the radioprotector, CDDO-Me, 18 hours before and during irradiation prevented the HZE-induced transformation. These results can be interpreted to suggest that the mixed radiation exposure of 16O followed by 28Si has carcinogenic potential. Importantly, this transformation can be protected by CDDO-Me pre-treatment.
深空的高电荷粒子(Z)和高能粒子(HZE)虽然只占银河宇宙射线(GCR)粒子通量的不到1%,但它们对空间辐射的生物效应有重要贡献。先前我们已经表明,2 gy质子(1H)和0.5 gy铁(56Fe)离子颗粒的联合辐射暴露增加了人结肠上皮细胞(HCEC CT7)的转化。本研究的目的是表征额外的HZE离子,如氧(16O)和硅(28Si)颗粒是否也会导致细胞转化增加。用1-Gy 16O (250 MeV/nucleon)照射HCEC CT7细胞,24小时后再用1-Gy 28Si颗粒(300 MeV/nucleon)照射,与未照射对照相比,增殖、不依赖锚定生长、迁移和侵袭能力均有所增加。此外,我们发现β-catenin通路被激活,DNA修复基因亚群在这些转化细胞中表达不足。辐照前后18小时用放射性保护剂CDDO-Me预处理可阻止hze诱导的转化。这些结果可以解释为16O和28Si的混合辐射暴露具有致癌潜力。重要的是,这种转化可以通过CDDO-Me预处理来保护。
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引用次数: 2
Delaying Seed Germination and Improving Seedling Fixation: Lessons Learned During Science and Payload Verification Tests for Advanced Plant EXperiments (APEX) 02-1 in Space 延迟种子发芽和改善固苗:先进植物实验(APEX) 02-1空间科学和有效载荷验证试验的经验教训
J. Nakashima, J. A. Sparks, J. Carver, S. D. Stephens, Taegun Kwon, E. Blancaflor
ABSTRACT Here we report on the science verification test (SVT) and the payload verification test (PVT) that we conducted in preparation for experiments evaluating the impact of microgravity on Arabidopsis thaliana root development and cellular structure. Hardware used for these experiments was the Advanced Biological Research System (ABRS) and Kennedy Space Center (KSC) fixation tubes (KFTs). A simple procedure to delay seed germination prior to installation on ABRS involved the construction of a metal box with a single far-red (FR) light-emitting diode (LED). The exposure of Petri dishes containing seeds (ecotype Columbia) to FR light immediately after planting and maintaining Petri dishes in the dark prevented seed germination until exposure to white light on ABRS. Additional tests revealed that germination can be delayed for up to 10 weeks with FR light treatment. Seedlings fixed in KFTs preloaded with glutaraldehyde for subsequent microscopy studies were not adequately preserved. We suspected that poor fixation was due to the extended contact of glutaraldehyde with oxygen while stored on KFTs, which likely contributed to fixative oxidation. During PVT, minor modifications to address fixation problems encountered during SVT included storing KFTs with glutaraldehyde at 4o C in the dark, increasing glutaraldehyde concentration from 3% to 5%, and bubbling nitrogen (N2) gas over the glutaraldehyde solution prior to loading the KFTs. These changes led to improvements in the quality of microscopic images. Lessons learned from SVT and PVT allowed us to optimize some of the preflight protocols needed to successfully implement Advanced Plant EXperiments (APEX) in space.
本文报道了在微重力条件下拟南芥根系发育和细胞结构影响的科学验证试验(SVT)和有效载荷验证试验(PVT)。用于这些实验的硬件是先进生物研究系统(ABRS)和肯尼迪航天中心(KSC)固定管(KFTs)。在ABRS上安装之前,一个简单的延迟种子发芽的程序涉及到一个带有单个远红色发光二极管(LED)的金属盒的构造。种植后立即将含有种子的培养皿(生态型哥伦比亚)暴露在FR光下,并在黑暗中保持培养皿,直到暴露在ABRS上的白光下,才能阻止种子发芽。其他试验表明,FR光处理可延迟发芽长达10周。在预载戊二醛的KFTs中固定的幼苗没有得到充分的保存。我们怀疑固定不良是由于在KFTs上储存时戊二醛与氧气长时间接触,这可能导致固定剂氧化。在PVT期间,为了解决SVT期间遇到的固定问题,进行了一些小的修改,包括将kft与戊二醛一起在40℃的黑暗环境中储存,将戊二醛浓度从3%增加到5%,并在加载kft之前在戊二醛溶液上鼓泡氮气(N2)。这些变化导致了显微图像质量的提高。从SVT和PVT中吸取的经验教训使我们能够优化成功实施太空先进植物实验(APEX)所需的一些飞行前协议。
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引用次数: 6
Effect of Gender on the Radiation Sensitivity of Murine Blood Cells 性别对小鼠血细胞辐射敏感性的影响
P. Billings, A. Romero-Weaver, A. Kennedy
ABSTRACT Space travel beyond the Earth’s protective magnetosphere risks exposing astronauts to ionizing radiation, such as that generated during a solar particle event (SPE). Ionizing radiation has well documented effects on blood cells and it is generally assumed that these effects contribute to the hematopoietic syndrome (HS), observed in animals and humans, following exposure to total body irradiation (TBI). The purpose of the current study was to assess the role of gender on the effects of gamma radiation on blood cells. C3H/HeN mice were irradiated with a 137Cs gamma source. Radiation had similar effects on white blood cells (WBCs), lymphocytes, and granulocytes in male and female C3H/HeN mice, while red blood cell (RBC) counts and hematocrit values remained stable following radiation exposure. Non-irradiated male mice had 13% higher platelet counts, compared with their female counterparts, and showed enhanced recovery of platelets on day 16 following radiation exposure. Hence, gender differences influence the response of platelets to TBI exposure.
在地球保护磁层之外的太空旅行有使宇航员暴露于电离辐射的风险,例如在太阳粒子事件(SPE)期间产生的电离辐射。电离辐射对血细胞有充分的影响,一般认为这些影响有助于在动物和人类中观察到的全身照射(TBI)后的造血综合征(HS)。当前研究的目的是评估性别对伽马辐射对血细胞影响的作用。用137Cs γ源照射C3H/HeN小鼠。辐射对雄性和雌性C3H/HeN小鼠的白细胞(wbc)、淋巴细胞和粒细胞有相似的影响,而红细胞(RBC)计数和红细胞压积值在辐射暴露后保持稳定。与雌性小鼠相比,未受辐射的雄性小鼠的血小板计数高13%,并且在辐射暴露后的第16天显示出血小板恢复的增强。因此,性别差异影响血小板对创伤性脑损伤的反应。
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引用次数: 30
The Effects of Gamma and Proton Radiation Exposure on Hematopoietic Cell Counts in the Ferret Model. γ和质子辐射暴露对雪貂模型中造血细胞计数的影响。
Jenine K Sanzari, X Steven Wan, Gabriel S Krigsfeld, Andrew J Wroe, Daila S Gridley, Ann R Kennedy

Exposure to total-body radiation induces hematological changes, which can detriment one's immune response to wounds and infection. Here, the decreases in blood cell counts after acute radiation doses of γ-ray or proton radiation exposure, at the doses and dose-rates expected during a solar particle event (SPE), are reported in the ferret model system. Following the exposure to γ-ray or proton radiation, the ferret peripheral total white blood cell (WBC) and lymphocyte counts decreased whereas neutrophil count increased within 3 hours. At 48 hours after irradiation, the WBC, neutrophil, and lymphocyte counts decreased in a dose-dependent manner but were not significantly affected by the radiation type (γ-rays verses protons) or dose rate (0.5 Gy/minute verses 0.5 Gy/hour). The loss of these blood cells could accompany and contribute to the physiological symptoms of the acute radiation syndrome (ARS).

暴露在全身辐射下会引起血液学变化,从而损害人体对伤口和感染的免疫反应。这里,在雪貂模型系统中报道了在太阳粒子事件(SPE)期间预期的剂量和剂量率下,急性辐射剂量γ射线或质子辐射暴露后血细胞计数的减少。暴露于γ射线或质子辐射后,雪貂外周血总白细胞(WBC)和淋巴细胞计数在3小时内减少,而中性粒细胞计数增加。照射后48小时,白细胞、中性粒细胞和淋巴细胞计数呈剂量依赖性下降,但不受辐射类型(γ射线vs质子)或剂量率(0.5 Gy/分钟vs 0.5 Gy/小时)的显著影响。这些血细胞的丧失可能伴随并促成急性放射综合征(ARS)的生理症状。
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引用次数: 0
The Effects of Spaceflight on Mucin Production in the Mouse Uterus 太空飞行对小鼠子宫黏液蛋白产生的影响
A. Forsman, H. Nier
ABSTRACT The effects of microgravity on biological tissues are relatively unexplored, especially in regard to the mammalian female reproductive system. To begin to address this issue, the uterine tissue of female mice flown on NASA shuttle mission STS-118 was studied. Three sets of female mice, each consisting of 12 animals, were utilized in this study: flight animals, ground control animals, and baseline animals. The flight animals were housed in the Animal Enclosure Module (AEM) of the Commercial Biomedical Testing Module-2 (CBMT-2), which was a part of the payload of the shuttle’s mid-deck locker. Ground control animals were housed in ground-based AEMs, which were kept in a room specifically designed to mimic the environmental conditions of the flight units with regard to temperature, humidity, and light/dark cycles on a 48 hour delay. Baseline animals were housed in standard rodent cages at ambient temperature and humidity and a 12/12 light/dark cycle. The uterine tissue was stained using an Alcian Blue Periodic Acid Schiff staining procedure and the apical mucin layer thickness was subsequently analyzed. Analysis of the mucin layer in the uterus revealed that the thickness of the mucin layer in the flight tissue was significantly thicker that the mucin layers of the ground control and baseline tissue.
微重力对生物组织的影响尚未得到充分研究,尤其是对哺乳动物雌性生殖系统的影响。为了解决这个问题,研究人员研究了NASA航天飞机STS-118任务中雌性小鼠的子宫组织。本研究采用三组雌性小鼠,每组12只,分别为飞行鼠、地面对照鼠和基线鼠。这些飞行动物被安置在商业生物医学测试模块-2 (CBMT-2)的动物封闭模块(AEM)中,该模块是航天飞机中层储物柜有效载荷的一部分。地面控制动物被安置在地面AEMs中,这些AEMs被放置在一个专门设计的房间里,模拟飞行单元的环境条件,包括48小时延迟的温度、湿度和光/暗循环。基线动物被安置在标准啮齿动物笼中,环境温度和湿度,12/12光/暗循环。采用阿利新蓝周期酸希夫染色法对子宫组织进行染色,并分析子宫顶端黏液层厚度。子宫黏液层分析显示,飞行组织黏液层的厚度明显比地面对照和基线组织的黏液层厚。
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引用次数: 4
Housing in the Animal Enclosure Module Spaceflight Hardware Increases Trabecular Bone Mass in Ground-Control Mice 太空飞行硬件增加地面对照小鼠的骨小梁质量
Shane A. J. Lloyd, Virginia Ferguson, S. Simske, A. W. Dunlap, E. Livingston, T. Bateman
ABSTRACT During spaceflight, mice are housed in specially designed cages called the Animal Enclosure Module (AEM). Utilization of this flight hardware may affect the skeletal properties of housed animals, independent of microgravity considerations. To address this issue, we studied the effect of 13 days of AEM housing versus standard vivarium enclosure on female C57BL/6J mice (n=12/group). The effects of AEM housing were most pronounced in the trabecular compartment. AEM mice had 44% and 144% greater trabecular bone volume fraction and connectivity density, respectively, versus vivarium. A similar response was seen at the proximal humerus. We noted a decrease in proximal tibia osteoclast surface (-65%) and eroded surface (-73%) for AEM versus vivarium, while tibia trabecular mineralizing surface (MS/BS) was nearly three-fold greater. Surprisingly, there was also decreased osteoblast surface, as well as lower osteoid volume, surface, and thickness at this site. The effects of AEM housing on femur cortical bone were modest: there was greater periosteal MS/BS, with no effect at the endocortical surface, and lower femur stiffness. Taken together, we have demonstrated significant effects of AEM housing on ground control mice, particularly in the trabecular bone compartment. These findings suggest that an early increase in bone formation, perhaps due to altered behavior and loading in this unique housing environment, was followed by decreased bone formation and resorption as the animals adapted to their new environment. Characterization of spaceflight animal housing is critical to elucidating the true effects of microgravity on skeletal parameters and for the proper selection of ground-based controls.
在太空飞行中,老鼠被安置在被称为动物围护舱(AEM)的特殊设计的笼子里。这种飞行硬件的使用可能会影响动物的骨骼特性,独立于微重力的考虑。为了解决这一问题,我们研究了AEM饲养13天与标准饲养对雌性C57BL/6J小鼠(n=12/组)的影响。AEM的作用在小梁间室最为明显。AEM小鼠的骨小梁体积分数和连通性密度分别比体内小鼠高44%和144%。肱骨近端也有类似的反应。我们注意到AEM与体内相比,胫骨近端破骨细胞表面(-65%)和侵蚀表面(-73%)减少,而胫骨小梁矿化表面(MS/BS)几乎增加了三倍。令人惊讶的是,该部位的成骨细胞表面也减少,类骨体积、表面和厚度也减少。AEM外壳对股骨皮质骨的影响不大:骨膜MS/BS较高,皮质内表面无影响,股骨刚度较低。综上所述,我们已经证明了AEM住房对地面对照小鼠的显著影响,特别是在小梁骨室。这些发现表明,早期骨形成增加,可能是由于在这种独特的居住环境中改变了行为和负荷,随后随着动物适应新环境,骨形成和吸收减少。航天动物外壳的表征对于阐明微重力对骨骼参数的真实影响以及正确选择地面控制至关重要。
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引用次数: 4
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Gravitational and space research : publication of the American Society for Gravitational and Space Research
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