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Genome and clonal hematopoiesis stability contrasts with immune,cfDNA,mitochondrial,and telomere length changes during short duration spaceflight

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Precision Clinical Medicine 2024年第1期7卷 1-13页

作者： J.Sebastian Garcia-Medina Karolina Sienkiewicz S.Anand Narayanan Eliah G.Overbey Kirill Grigorev Krista A.Ryon Marissa Burke Jacqueline Proszynski Braden Tierney Caleb M.Schmidt Nuria Mencia-Trinchant Remi Klotz Veronica Ortiz Jonathan Foox Christopher Chin Deena Najjar Irina Matei Irenaeus Chan Carlos Cruchaga Ashley Kleinman JangKeun Kim Alexander Lucaci Conor Loy Omary Mzava Iwijn De Vlaminck Anvita Singaraju Lynn E.Taylor Julian C.Schmidt Michael A.Schmidt Kelly Blease Juan Moreno Andrew Boddicker Junhua Zhao Bryan Lajoie Andrew Altomare Semyon Kruglyak Shawn Levy Min Yu Duane C.Hassane Susan M.Bailey Kelly Bolton Jaime Mateus Christopher E.Mason Department of Physiology and Biophysics Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine Weill Cornell MedicineNew YorkNY 10021USA Department of Immunology Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA Department of Stem Cell Biology and Regenerative Medicine Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033USA Space Exploration Technologies Corporation HawthomeCA 90250USA Sovaris Aerospace BoulderCO 80302USA Advanced Pattern Analysis&Human Performance Group BoulderCO 80302USA Children's Cancer and Blood Foundation Laboratories Departments of Pediatrics and Cell and Developmental BiologyDrukier Institute for Children's HealthMeyer Cancer CenterWeill Cornell MedicineNew YorkNY 10021USA Meyer Cancer Center Weill Cornell MedicineNew YorkNY 10065USA Department of Nutrition and Integrative Physiology Florida State UniversityTallahasseeFL 32306USA Department of Systems Engineering Colorado State UniversityFort CollinsCO 80523USA Element Biosciences San DiegoCA 10055USA Department of Environmental and Radiological Health Sciences Colorado State UniversityFort CollinsCO 80523USA Cell and Molecular Biology Program Colorado State UniversityFort CollinsCO 80523USA BioAstra Inc New YorkNYUSA Washington University St Louis Oncology Division St.LouisMO 63100USA Meinig School of Biomedical Engineering Cornell UniversityIthacaNY 14853USA The Feil Family Brain and Mind Research Institute Weill Cornell MedicineNY 10021USA WorldQuant Initiative for Quantitative Prediction Weill Cornell MedicineNew YorkNY 10021USA

Background The Inspiration4(I4)mission,the first all-civilian orbital flight mission,investigated the physiological effects of short-duration spaceflight through a multi-omic approach.Despite advances,there remains much to learn about human adaptation to spaceflight's unique challenges,including microgravity,immune system perturbations,and radiation exposure.Methods To provide a detailed genetics analysis of the mission,we collected dried blood spots pre-,during,and post-flight for DNA extraction.Telomere length was measured by quantitative PCR,while whole genome and cfDNA sequencing provided insight into genomic stability and immune adaptations.A robust bioinformatic pipeline was used for data analysis,including variant calling to assess mutational burden.Result Telomere elongation occurred during spaceflight and shortened after return to Earth.Cell-free DNA analysis revealed increased immune cell signatures post-flight.No significant clonal hematopoiesis of indeterminate potential(CHIP)or whole-genome instability was observed.The long-term gene expression changes across immune cells suggested cellular adaptations to the space environment persisting months post-flight.Conclusion Our findings provide valuable insights into the physiological consequences of short-duration spaceflight,with telomere dynamics and immune cell gene expression adapting to spaceflight and persisting after return to Earth.CHIP sequencing data will serve as a reference point for studying the early development of CHIP in astronauts,an understudied phenomenon as previous studies have focused on career astronauts.This study will serve as a reference point for future commercial and non-commercial spaceflight,low Earth orbit(LEO)missions,and deep-space exploration.

关键词： genomes clonal hematopoiesis stability immune mitochondria ribosomes spaceflight

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Variation of photosynthesis,secondary metabolites and antioxidant activities in third generation of spaceflight-induced Salvia miltiorrhiza

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Chinese Herbal Medicines 2022年第4期14卷 592-601页

作者： Liang Peng Mei Ru Zongsuo Liang College of Pharmacy Shaanxi University of Chinese MedicineXi’an 710000China College of Life Sciences and Medicine Zhejiang Sci-Tech UniversityHangzhou 310000China College of Life Sciences Northwest A&F UniversityYangling 712100China College of Pharmacy Guangxi University of Chinese MedicineNanning 530200China

Objective: spaceflight has long been perceived as an effective way to improve the quantity and quality of plants with wide applications. In order to obtain stable and inheritable descendants of spaceflightinduced Salvia miltiorrhiza lines, we investigated and analyzed four lines m16, m50, m51, m57(three individuals of each line) and the ground control(three individuals) of the third generation of spaceflight-induced S. miltiorrhiza from primary/secondary metabolism and antioxidative abilities.Methods: A portable photosynthesis system(Li-6400) with red/blue LED light source was used to perform the photosynthetic characteristics to evaluate their primary productivity. The secondary metabolites(phenolic acids, tanshinones, total phenolics and flavonoids) and antioxidant activity of roots were analyzed to assess their quality.Results: Compared with control, line m16 presented weak photosynthetic ability, but high apparent quantum yield(AQY), higher contents of secondary metabolites, and stronger antioxidative abilities.Line m57 had a strong gas exchange ability, relatively higher secondary metabolites contents, and ascending antioxidative abilities. Lines m50 and m51 were in the middle level of lines m16 and m57.The principal component analysis for all the original data revealed three components including a rootrelated index, a leaf-related index, and a CO_(2) response parameter could be used to distinguish spaceflight-induced S. miltiorrhiza lines.Conclusion: Line m57 could be an appropriate material for the investigation of targeted breeding towards high production, and line m16 could be used to identify essential genes and unravel sophisticated pathways underlying the secondary metabolisms.

关键词： antioxidative ability Salvia miltiorrhiza Bge. secondary metabolism spaceflight third generation primary metabolism

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spaceflight decelerates the epigenetic clock orchestrated with a global alteration in DNA methylome and transcriptome in the mouse retina

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Precision Clinical Medicine 2021年第2期4卷 93-108页

作者： Zhong Chen Seta Stanbouly Nina CNishiyama Xin Chen Michael D.Delp Hongyu Qiu Xiao WMao Charles Wang Center for Genomics School of MedicineLoma Linda UniversityLoma LindaCA 92350USA Division of Radiation Research Department of Basic SciencesSchool of MedicineLoma Linda UniversityLoma LindaCA 92354USA Department of Nutrition and Integrative Physiology Florida State UniversityTallahasseeFL 32306USA Center for Molecular and Translational Medicine Institute of Biomedical ScienceGeorgia State UniversityAtlantaGA 30303USA Division of Microbiology and Molecular Genetics Department of Basic SciencesSchool of MedicineLoma Linda UniversityLoma LindaCA 92350USA

Astronauts exhibit an assortment of clinical abnormalities in their eyes during long-duration spaceflight.The purpose of this studywas to determinewhether spaceflight induces epigenomic and transcriptomic reprogramming in the retina or alters the epigenetic clock.The mice were flown for 37 days in animal enclosure modules on the International Space Station;ground-based control animals weremaintained under similar housing conditions.Mouse retinas were isolated and both DNA methylome and transcriptome were determined by deep sequencing.We found that a large number of genes were differentially methylated with spaceflight,whereas there were fewer differentially expressed genes at the transcriptome level.Several biological pathways involved in retinal diseases such as macular degeneration were significantly altered.Our results indicated that spaceflight decelerated the retinal epigenetic clock.This study demonstrates that spaceflight impacts the retina at the epigenomic and transcriptomic levels,and such changes could be involved in the etiology of eye-related disorders among astronauts.

关键词： spaceflight DNA methylome transcriptome epigenetic clock

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Effects of spaceflight and simulated microgravity on microbial growth and secondary metabolism

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Military Medical Research 2018年第4期5卷 335-349页

作者： Bing Huang Dian-Geng Li Ying Huang Chang-Ting Liu Nanlou Respiratory Diseases Department Chinese PLA General Hospital/Chinese PLA Postgraduate Medical School State Key Laboratory of Microbial Resources Institute of Microbiology Chinese Academy of Sciences

spaceflight and ground-based microgravity analog experiments have suggested that microgravity can affect microbial growth and metabolism. Although the effects of microgravity and its analogs on microorganisms have been studied for more than 50 years, plausible conflicting and diverse results have frequently been reported in different experiments, especially regarding microbial growth and secondary metabolism. Until now, only the responses of a few typical microbes to microgravity have been investigated; systematic studies of the genetic and phenotypic responses of these microorganisms to microgravity in space are still insufficient due to technological and logistical hurdles. The use of different test strains and secondary metabolites in these studies appears to have caused diverse and conflicting results. Moreover, subtle changes in the extracellular microenvironments around microbial cells play a key role in the diverse responses of microbial growth and secondary metabolisms. Therefore, "indirect" effects represent a reasonable pathway to explain the occurrence of these phenomena in microorganisms. This review summarizes current knowledge on the changes in microbial growth and secondary metabolism in response to spaceflight and its analogs and discusses the diverse and conflicting results. In addition, recommendations are given for future studies on the effects of microgravity in space on microbial growth and secondary metabolism.

关键词： Microbial growth Secondary metabolism spaceflight Microgravity Simulated microgravity Microgravity analogs

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Physiological effects of weightlessness: countermeasure system development for a long-term Chinese manned spaceflight

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Frontiers of Medicine 2019年第2期13卷 202-212页

作者： Linjie Wang Zhili Li Cheng Tan Shujuan Liu Jianfeng Zhang Siyang He Peng Zou Weibo Liu Yinghui Li State Key Laboratory of Space Medicine Fundamentals and Application China Astronaut Research and Training CenterBeijing 100094China

The Chinese space station will be built around 2020. As a national space laboratory, it will offer unique opportunities for studying the physiological effects of weightlessness and the efficacy of the countermeasures against such effects. In this paper, we described the development of countermeasure systems in the Chinese space program. To emphasize the need of the Chinese space program to implement its own program for developing countermeasures, we reviewed the literature on the negative physiological effects of weightlessness, the challenges of completing missions, the development of countermeasure devices, the establishment of countermeasure programs, and the efficacy of the countermeasure techniques in American and Russian manned spaceflights. In addition, a brief overview was provided on the Chinese research and development on countermeasures to discuss the current status and goals of the development of countermeasures against physiological problems associated with weightlessness.

关键词： countermeasure physiological effects of weightlessness effect evaluation long-term manned spaceflight

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An online error calibration method for spaceflight TT&C systems based on LEO-ground DDGPS

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Frontiers of Information Technology & Electronic Engineering 2019年第6期20卷 829-841页

作者： Qiao WANG Xiao-jun JIN Wei ZHANG Shi-ming MO Zhao-bin XU Zhong-he JIN Micro-Satellite Research Center Zhejiang University Hangzhou 310027 China

To overcome the shortcomings of the traditional measurement error calibration methods for spaceflight telemetry, tracking and command(TT&C) systems, an online error calibration method based on low Earth orbit satellite-to-ground doubledifferential GPS(LEO-ground DDGPS) is proposed in this study. A fixed-interval smoother combined with a pair of forward and backward adaptive robust Kalman filters(ARKFs) is adopted to solve the LEO-ground baseline, and the ant colony optimization(ACO) algorithm is used to deal with the ambiguity resolution problem. The precise baseline solution of DDGPS is then used as a comparative reference to calibrate the systematic errors in the TT&C measurements, in which the parameters of the range error model are solved by a batch least squares algorithm. To validate the performance of the new online error calibration method, a hardware-in-the-loop simulation platform is constructed with independently developed spaceborne dual-frequency GPS receivers and a Spirent GPS signal generator. The simulation results show that with the fixed-interval smoother, a baseline estimation accuracy(RMS, single axis) of better than 10 cm is achieved. Using this DDGPS solution as the reference, the systematic error of the TT&C ranging system is effectively calibrated, and the residual systematic error is less than 5 cm.

关键词： spaceflight low Earth orbit (LEO) Filter Optimization Calibration

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Long-term spaceflight and the cardiovascular system

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Precision Clinical Medicine 2020年第4期3卷 284-291页

作者： Nicholas A.Vernice Cem Meydan Ebrahim Afshinnekoo Christopher E.Mason The Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine Weill Cornell Medicine1305 York AvenueNew YorkNY 10021USA Department of Physiology and Biophysics Weill Cornell Medicine1300 York AvenueNew YorkNY 10021USA The WordQuant Initiative for Quantitative Prediction Weill Cornell Medicine1300 York AvenueNew YorkNY 10021USA The Feil Family Brain and Mind Research Institute Weill Cornell Medicine1300 York Avenue New YorkNY 10021USA

While early investigations into the physiological effects of spaceflight suggest the body’s ability to reversibly adapt,the corresponding effects of long-term spaceflight(>6months)aremuch less conclusive.Prolonged exposure to microgravity and radiation yields profound effects on the cardiovascular system,including a massive cephalad fluid translocation and altered arterial pressure,which attenuate blood pressure regulatory mechanisms and increase cardiac output.Also,central venous pressure decreases as a result of the loss of venous compression.The stimulation of baroreceptors by the cephalad shift results in an approximately 10%–15%reduction in plasma volume,with fluid translocating from the vascular lumen to the interstitium.Despite possible increases in cardiac workload,myocyte atrophy and notable,yet unexplained,alterations in hematocrit have been observed.Atrophy is postulated to result from shunting of protein synthesis from the endoplasmic reticulum to the mitochondria via mortalin-mediated action.While data are scarce regarding their causative agents,arrhythmias have been frequently reported,albeit sublethal,during both Russian and American expeditions,with QT interval prolongation observed in long,but not short duration,spaceflight.Exposure of the heart to the proton and heavy ion radiation of deep space has also been shown to result in coronary artery degeneration,aortic stiffness,carotid intima thickening via collagen-mediated action,accelerated atherosclerosis,and induction of a pro-inflammatory state.Upon return,long-term spaceflight frequently results in orthostatic intolerance and altered sympathetic responses,which can prove hazardous should any rapidmobilization or evacuation be required,and indicates that these cardiac risks should be especially monitored for future missions.

关键词： microgravity cardiovascular system spaceflight aerospace medicine

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Speed kills: Highly relativistic spaceflight would be fatal for passengers and instruments

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Natural Science 2012年第10期4卷 749-754页

作者： William A. Edelstein Arthur D. Edelstein Johns Hopkins School of Medicine Baltimore USA University of California San Francisco San Francisco USA

Highly relativistic speeds are desirable for interstellar travel. Relativistic time dilation would reduce the subjective duration of the trip for the travelers, so that they can cover galaxy-scale distances in a reasonable amount of personal time. Unfortunately, as spaceship velocities approach the speed of light, interstellar hydrogen H, although only present at a density of approximately 1.8 atoms/cm3, turns into intense radiation that would quickly kill passengers and destroy electronic instrumentation. In addition, the energy loss of ionizing radiation passing through the ship’s hull represents an increasing heat load that necessitates large expenditures of energy to cool the ship. Stopping or diverting this flux, either with material or electromagnetic shields, is a daunting problem. Going slow to avoid severe H irradiation sets an upper speed limit of v ~ 0.5 c. This velocity only gives a time dilation factor of about 15%, which would not substantially assist galaxy-scale voyages. Diffuse interstellar H atoms are the ultimate cosmic space mines and represent a formidable obstacle to interstellar travel.

关键词： Interstellar Travel spaceflight Relativistic spaceflight Space Travel Radiation

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Estimation Method of Schedule-cost Correlation Coefficient of spaceflight Project

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工程科学（英文版） 2007年第3期5卷 69-75页

作者： Liu Yanqiong(Humanity and Social Science School,National University of Defence Technology,Changsha,410073,China)

To evaluate the cost risk and the schedule risk of the spaceflight project,the schedule-cost(S-C) correlation coefficient is directly appointed according to the experts' experience usually.This paper deduces SDMCU(the schedule distribution model considering the effect of the cost uncertainty),and then proposes the approximate formula to estimate the ln(S)-C correlation coefficient based on the models of SDMCU and CDMSU(the cost distribution model considering the effect of the schedule uncertainty).Furthermore,an approximate relationship expression of the S-C and the ln(S)-C correlation coefficients is put forward according to general facts and the Taylor expansion,and advanced by means of mass numerical validation is the general rule of obtaining the estimation value of the schedule-cost correlation coefficient based on the historical data.

关键词： spaceflight project risk cost schedule correlation coefficient

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Mutagenic Effects of spaceflight Treatment on the Second-Generation Seeds of Alfalfa

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Animal Husbandry and Feed Science 2010年第8期2卷 47-48页

作者： WANG Mi REN Wei-bo GUO Hui-qin XU Zhu CHEN Li-bo College of Life Sciences Inner Mongolia Agricultural University Hohhot 010018 China Grassland Research Institute Chinese Academy of Agricultural Sciences Hohhot 010010 China

[ Objective] To explore the effects of spaceflight on the second-generation seeds of alfalfa and provide a theoretical basis for mutation breeding. [Method] The seeds of Medicago stavia L. lines no. 1, no. 2 and no. 4 were carried into space by the Shijian-8 seed breeding satellite for a 15-d spaceflight treatment. After returning to the ground, seedlings were transplanted to field. Traits of the second-generation seeds of alfalfa were evaluated. [Result] The 1 000-grain weight of the second-generation seeds were 5% -9% significantly higher than that the control （P 〈 0.05）. The germination rate, seedling weight, shoot length and root length were significantly increased （P 〈 0.05）. The hard seed rate and the rate of moldy seeds were significantly decreased （ P 〈 0.05）. However, the rate of dead seeds was increased. [ Conclusion] spaceflight treatment has positive mutagenic effects on the second-generation seeds of alfalfa.

关键词： spaceflight Medicago sativa Second-generation seeds

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