Exploration of space to achieve scientific breakthroughs.

Living organisms adapt to changing environments using their amazing flexibility to remodel themselves by a process called evolution. Environmental stress causes selective pressure and is associated with genetic and phenotypic shifts for better modifications, maintenance, and functioning of organismal systems. The natural evolution process can be used in complement to rational strain engineering for the development of desired traits or phenotypes as well as for the production of novel biomaterials through the imposition of one or more selective pressures. Space provides a unique environment of stressors (e.g., weightlessness and high radiation) that organisms have never experienced on Earth. Cells in the outer space reorganize and develop or activate a range of molecular responses that lead to changes in cellular properties. Exposure of cells to the outer space will lead to the development of novel variants more efficiently than on Earth. For instance, natural crop varieties can be generated with higher nutrition value, yield, and improved features, such as resistance against high and low temperatures, salt stress, and microbial and pest attacks. The review summarizes the literature on the parameters of outer space that affect the growth and behavior of cells and organisms as well as complex colloidal systems. We illustrate an understanding of gravity-related basic biological mechanisms and enlighten the possibility to explore the outer space environment for application-oriented aspects. This will stimulate biological research in the pursuit of innovative approaches for the future of agriculture and health on Earth.

[1]  M. Bizzarri,et al.  Phenotypic Switch Induced by Simulated Microgravity on MDA-MB-231 Breast Cancer Cells , 2014, BioMed research international.

[2]  D. Ingber Mechanobiology, Tissue Development and Organ Engineering , 2014 .

[3]  Epigenetic Gene Regulation in the Bacterial World , 2006, Microbiology and Molecular Biology Reviews.

[4]  M. Ward,et al.  Time-Scaled Evolutionary Analysis of the Transmission and Antibiotic Resistance Dynamics of Staphylococcus aureus Clonal Complex 398 , 2014, Applied and Environmental Microbiology.

[5]  Masatoshi Nei,et al.  Selectionism and neutralism in molecular evolution. , 2005, Molecular biology and evolution.

[6]  David J. Edwards,et al.  Genome-scale rates of evolutionary change in bacteria , 2016, bioRxiv.

[7]  Sara D. Altenburg,et al.  Increased Filamentous Growth of Candida albicans in Simulated Microgravity , 2008, Genom. Proteom. Bioinform..

[8]  Pietro Goglio,et al.  Livestock and climate change: impact of livestock on climate and mitigation strategies , 2018, Animal frontiers : the review magazine of animal agriculture.

[9]  J. Lake,et al.  Horizontal gene transfer in microbial genome evolution. , 2002, Theoretical population biology.

[10]  J. Davies,et al.  Origins and Evolution of Antibiotic Resistance , 1996, Microbiology and Molecular Biology Reviews.

[11]  L. J. Leandro,et al.  Comparative analysis of Drosophila melanogaster and Caenorhabditis elegans gene expression experiments in the European Soyuz flights to the International Space Station. , 2007, Advances in space research : the official journal of the Committee on Space Research.

[12]  M. Lebert,et al.  Behavioral mutants of Euglena gracilis: functional and spectroscopic characterization. , 1997, Journal of plant physiology.

[13]  F. Medina,et al.  Microsome-associated proteome modifications of Arabidopsis seedlings grown on board the International Space Station reveal the possible effect on plants of space stresses other than microgravity , 2014, Plant signaling & behavior.

[14]  L. Stodieck,et al.  Effects of microgravity on the virulence of Listeria monocytogenes, Enterococcus faecalis, Candida albicans, and methicillin-resistant Staphylococcus aureus. , 2013, Astrobiology.

[15]  J. Gogarten Gene Transfer: Gene Swapping Craze Reaches Eukaryotes , 2003, Current Biology.

[16]  J. Loon,et al.  Simulated microgravity, Mars gravity, and 2g hypergravity affect cell cycle regulation, ribosome biogenesis, and epigenetics in Arabidopsis cell cultures , 2018, Scientific Reports.

[17]  A. Newton Exploitation of Diversity within Crops—the Key to Disease Tolerance? , 2016, Front. Plant Sci..

[18]  P. Parsons Environments and evolution: interactions between stress, resource inadequacy and energetic efficiency , 2005, Biological reviews of the Cambridge Philosophical Society.

[19]  Yunqi Weng,et al.  Plants as Factories for Human Pharmaceuticals: Applications and Challenges , 2015, International journal of molecular sciences.

[20]  Shuangsheng Guo,et al.  Identification of Conserved miRNAs in Solanum Lycopersicum Response to Long-term RPM-treatment , 2013 .

[21]  C. Pál,et al.  Adaptive evolution of bacterial metabolic networks by horizontal gene transfer , 2005, Nature Genetics.

[22]  Vincent Noireaux,et al.  A vesicle bioreactor as a step toward an artificial cell assembly. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[23]  Yit-Heng Chooi,et al.  Metabolic engineering for the production of natural products. , 2011, Annual review of chemical and biomolecular engineering.

[24]  Michael P. Popp,et al.  Arabidopsis gene expression patterns are altered during spaceflight , 2005 .

[25]  Tao Jin,et al.  Evolutionary Methods for Improving the Production of Biorenewable Fuels and Chemicals , 2016 .

[26]  D. Chapman,et al.  Plants and microgravity: Patterns of microgravity effects at the cellular and molecular levels , 2017, Cytology and Genetics.

[27]  H. Ochman,et al.  Lateral gene transfer and the nature of bacterial innovation , 2000, Nature.

[28]  H. Alper,et al.  Remaining Challenges in the Metabolic Engineering of Yeasts for Biofuels , 2015 .

[29]  Yanhua Zheng,et al.  Simulated microgravity affects ciprofloxacin susceptibility and expression of acrAB-tolC genes in E. coli ATCC25922. , 2015, International journal of clinical and experimental pathology.

[30]  S. Carroll,et al.  From DNA to Diversity: Molecular Genetics and the Evolution of Animal Design , 2000 .

[31]  G. Schulze-Tanzil,et al.  Weightlessness induced apoptosis in normal thyroid cells and papillary thyroid carcinoma cells via extrinsic and intrinsic pathways. , 2003, Endocrinology.

[32]  Ruth Hemmersbach,et al.  Comparative studies on gravisensitive protists on ground (2D and 3D clinostats) and in microgravity , 2006 .

[33]  D. Häder,et al.  Gravitational sensory transduction chain in flagellates , 2005 .

[34]  W. Martin,et al.  Networks of Gene Sharing among 329 Proteobacterial Genomes Reveal Differences in Lateral Gene Transfer Frequency at Different Phylogenetic Depths , 2010, Molecular biology and evolution.

[35]  Jonathan S. Dordick,et al.  Spaceflight Promotes Biofilm Formation by Pseudomonas aeruginosa , 2013, PloS one.

[36]  L. Tang,et al.  Establishment of three-dimensional tissue-engineered bone constructs under microgravity-simulated conditions. , 2010, Artificial organs.

[37]  Gordana Vunjak-Novakovic,et al.  Microgravity tissue engineering , 1997, In Vitro Cellular & Developmental Biology - Animal.

[38]  Xuefu You,et al.  Preliminary report on the biological effects of space flight on the producing strain of a new immunosuppressant, Kanglemycin C , 2006, Journal of Industrial Microbiology and Biotechnology.

[39]  Jason B. Wolf,et al.  Evolutionary genetics : concepts and case studies , 2006 .

[40]  Thomas J. Goodwin,et al.  Simulated microgravity conditions enhance differentiation of cultured PC12 cells towards the neuroendocrine phenotype , 1998, In Vitro Cellular & Developmental Biology - Animal.

[41]  P. Gingerich Rates of evolution on the time scale of the evolutionary process , 2004, Genetica.

[42]  Richard E. Edelmann,et al.  Transcriptome analyses of Arabidopsis thaliana seedlings grown in space: implications for gravity-responsive genes , 2013, Planta.

[43]  Honglu Wu,et al.  Interplay of space radiation and microgravity in DNA damage and DNA damage response , 2017, npj Microgravity.

[44]  C. Kurland,et al.  Horizontal gene transfer: A critical view , 2003 .

[45]  Louis Yuge,et al.  Microgravity potentiates stem cell proliferation while sustaining the capability of differentiation. , 2006, Stem cells and development.

[46]  R. MacLean,et al.  Evaluating evolutionary models of stress-induced mutagenesis in bacteria , 2013, Nature Reviews Genetics.

[47]  Weilong Hao,et al.  Uncovering rate variation of lateral gene transfer during bacterial genome evolution , 2008, BMC Genomics.

[48]  N. Kleckner,et al.  IS10 transposition is regulated by DNA adenine methylation , 1985, Cell.

[49]  D. Pierson,et al.  Characterization of Escherichia coli MG1655 grown in a low-shear modeled microgravity environment , 2007, BMC Microbiology.

[50]  A. Clark,et al.  Stress tolerance and metabolic response to stress in Drosophila melanogaster , 1998, Heredity.

[51]  Ronald J. White,et al.  Humans in space , 2001, Nature.

[52]  W. Roos,et al.  The role of the cytoskeleton in sensing changes in gravity by nonspecialized cells , 2014, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[53]  S. Kishore,et al.  Horizontal gene transfer of epigenetic machinery and evolution of parasitism in the malaria parasite Plasmodium falciparum and other apicomplexans , 2013, BMC Evolutionary Biology.

[54]  C. Schiraldi,et al.  Transient increases in intracellular calcium and reactive oxygen species levels in TCam-2 cells exposed to microgravity , 2017, Scientific Reports.

[55]  D. Grimm,et al.  Different responsiveness of endothelial cells to vascular endothelial growth factor and basic fibroblast growth factor added to culture media under gravity and simulated microgravity. , 2010, Tissue engineering. Part A.

[56]  T. Rana,et al.  Gene regulation by non-coding RNAs , 2014, Critical reviews in biochemistry and molecular biology.

[57]  Sunil Bajpai,et al.  From Land to Water: the Origin of Whales, Dolphins, and Porpoises , 2009, Evolution: Education and Outreach.

[58]  J. Kiefer,et al.  Repair of cellular radiation damage in space under microgravity conditions , 1999, Radiation and environmental biophysics.

[59]  Robert J. Schmitz,et al.  Epigenetics: Beyond Chromatin Modifications and Complex Genetic Regulation1 , 2014, Plant Physiology.

[60]  Jin Han,et al.  Microgravity may help future organ/tissue manufacture , 2016, Science China Life Sciences.

[61]  A. Cogoli,et al.  Neocartilage formation in 1 g, simulated, and microgravity environments: implications for tissue engineering. , 2010, Tissue engineering. Part A.

[62]  Otto X. Cordero,et al.  The impact of long-distance horizontal gene transfer on prokaryotic genome size , 2009, Proceedings of the National Academy of Sciences.

[63]  G Reitz,et al.  Microorganisms and biomolecules in space environment experiment ES 029 on Spacelab-1. , 1984, Advances in space research : the official journal of the Committee on Space Research.

[64]  A. Higashibata,et al.  Effectiveness of endothelial progenitor cell culture under microgravity for improved angiogenic potential , 2018, Scientific Reports.

[65]  Junzo Tanaka,et al.  Cartilaginous tissue formation from bone marrow cells using rotating wall vessel (RWV) bioreactor. , 2006, Biotechnology and bioengineering.

[66]  C. Vanderburg,et al.  A three-dimensional tissue culture model of bone formation utilizing rotational co-culture of human adult osteoblasts and osteoclasts. , 2013, Acta biomaterialia.

[67]  Bart Devreese,et al.  The influence of microgravity on invasive growth in Saccharomyces cerevisiae. , 2011, Astrobiology.

[68]  P. Ayyaswamy,et al.  Escherichia coli Biofilms Formed under Low-Shear Modeled Microgravity in a Ground-Based System , 2006, Applied and Environmental Microbiology.

[69]  C. Lan,et al.  Enhancement of lipid production using biochemical, genetic and transcription factor engineering approaches. , 2009, Journal of biotechnology.

[70]  Richard D. Hayes,et al.  Draft Genome Sequence of the Sexually Transmitted Pathogen Trichomonas vaginalis , 2007, Science.

[71]  G. Daily,et al.  Biodiversity loss and its impact on humanity , 2012, Nature.

[72]  W. Wohlleben,et al.  Antibiotic drug discovery , 2016, Microbial biotechnology.

[73]  M Dröge,et al.  Horizontal gene transfer as a biosafety issue: a natural phenomenon of public concern. , 1998, Journal of biotechnology.

[74]  R. Shi,et al.  Exposure of Mycobacterium marinum to low-shear modeled microgravity: effect on growth, the transcriptome and survival under stress , 2016, npj Microgravity.

[75]  Robert J. Schmitz,et al.  Rate, spectrum, and evolutionary dynamics of spontaneous epimutations , 2015, Proceedings of the National Academy of Sciences.

[76]  R. Einspanier,et al.  Differential Gene Regulation under Altered Gravity Conditions in Follicular Thyroid Cancer Cells: Relationship between the Extracellular Matrix and the Cytoskeleton , 2011, Cellular Physiology and Biochemistry.

[77]  P. Keightley,et al.  A Comparison of Models to Infer the Distribution of Fitness Effects of New Mutations , 2013, Genetics.

[78]  D. Pierson,et al.  Effect of simulated microgravity and shear stress on microcin B17 production by Escherichia coli and on its excretion into the medium , 1997, Applied and environmental microbiology.

[79]  Natalie Leys,et al.  Effect of microgravity & space radiation on microbes. , 2018, Future microbiology.

[80]  Jens Hauslage,et al.  Pyrocystis noctiluca represents an excellent bioassay for shear forces induced in ground-based microgravity simulators (clinostat and random positioning machine) , 2017, npj Microgravity.

[81]  K. O'Connor,et al.  Tri‐dimensional prostate cell cultures in simulated microgravity and induced changes in lipid second messengers and signal transduction , 2001, Journal of cellular and molecular medicine.

[82]  E. Holmes,et al.  Analyses of evolutionary dynamics in viruses are hindered by a time-dependent bias in rate estimates , 2014, Proceedings of the Royal Society B: Biological Sciences.

[83]  N. Moran,et al.  Phylogenetics and the Cohesion of Bacterial Genomes , 2003, Science.

[84]  D. Grimm,et al.  Decreased E‐Cadherin in MCF7 Human Breast Cancer Cells Forming Multicellular Spheroids Exposed to Simulated Microgravity , 2018, Proteomics.

[85]  Yue Zhang,et al.  Changes in Plastid and Mitochondria Protein Expression in Arabidopsis Thaliana Callus on Board Chinese Spacecraft SZ-8 , 2015 .

[86]  Peng Shang,et al.  Simulated weightlessness alters biological characteristics of human breast cancer cell line MCF-7 , 2008 .

[87]  N. Colegrave,et al.  Estimate of the Spontaneous Mutation Rate in Chlamydomonas reinhardtii , 2012, Genetics.

[88]  M. Pérez‐Losada,et al.  New methods for inferring population dynamics from microbial sequences. , 2007, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[89]  Raul Herranz,et al.  Gravitational and magnetic field variations synergize to cause subtle variations in the global transcriptional state of Arabidopsis in vitro callus cultures , 2012, BMC Genomics.

[90]  D. E. Philpott,et al.  Morphological and biochemical examination of Cosmos 1887 rat heart tissue: Part I — ultrastructure , 1990, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[91]  Otto X. Cordero,et al.  Ecology drives a global network of gene exchange connecting the human microbiome , 2011, Nature.

[92]  E. Nevo Evolution Under Environmental Stress at Macro- and Microscales , 2011, Genome biology and evolution.

[93]  T. Gabaldón,et al.  Acquisition of prokaryotic genes by fungal genomes. , 2010, Trends in genetics : TIG.

[94]  N. Hübner,et al.  Genomic Approach to Identify Factors That Drive the Formation of Three-Dimensional Structures by EA.hy926 Endothelial Cells , 2013, PloS one.

[95]  D. Wion,et al.  N6-methyl-adenine: an epigenetic signal for DNA–protein interactions , 2006, Nature Reviews Microbiology.

[96]  D. Häder,et al.  How Euglena tells up from down , 1996, Nature.

[97]  Daniel J. Gaffney,et al.  Quantifying the slightly deleterious mutation model of molecular evolution. , 2002, Molecular biology and evolution.

[98]  David Bryant,et al.  Endosymbiotic origin and differential loss of eukaryotic genes , 2015, Nature.

[99]  C. Lindenberger,et al.  Stable nuclear transformation of rhodophyte species Porphyridium purpureum: advanced molecular tools and an optimized method , 2018, Photosynthesis Research.

[100]  Christopher S. Brown,et al.  The Fast and Transient Transcriptional Network of Gravity and Mechanical Stimulation in the Arabidopsis Root Apex1[w] , 2004, Plant Physiology.

[101]  G. Vunjak‐Novakovic,et al.  Microgravity cultivation of cells and tissues. , 1999, Gravitational and space biology bulletin : publication of the American Society for Gravitational and Space Biology.

[102]  T. Ohnishi,et al.  Cancer risk in space due to radiation assessed by determining cell lethality and mutation frequencies of prokaryotes and a plasmid during the Second International Microgravity Laboratory (IML-2) Space Shuttle experiment. , 1997, Oncology reports.

[103]  Jason A. Rosenzweig,et al.  The effect of low shear force on the virulence potential of Yersinia pestis: new aspects that space-like growth conditions and the final frontier can teach us about a formidable pathogen , 2012, Front. Cell. Inf. Microbio..

[104]  J. Kiss,et al.  Analyses of tropistic responses using metabolomics. , 2013, American journal of botany.

[105]  D. Grimm,et al.  Real Microgravity Influences the Cytoskeleton and Focal Adhesions in Human Breast Cancer Cells , 2019, International journal of molecular sciences.

[106]  Augusto Cogoli,et al.  Effects of basic fibroblast growth factor on endothelial cells under conditions of simulated microgravity , 2008, Journal of cellular biochemistry.

[107]  Robert Ferl,et al.  Plants in space. , 2002, Current opinion in plant biology.

[108]  M. King,et al.  Evolution at two levels in humans and chimpanzees. , 1975, Science.

[109]  T. Bek,et al.  Reduced Expression of Cytoskeletal and Extracellular Matrix Genes in Human Adult Retinal Pigment Epithelium Cells Exposed to Simulated Microgravity , 2016, Cellular Physiology and Biochemistry.

[110]  Antonios G Mikos,et al.  Formation of three-dimensional cell/polymer constructs for bone tissue engineering in a spinner flask and a rotating wall vessel bioreactor. , 2002, Journal of biomedical materials research.

[111]  James P. Freyer,et al.  The Use of 3-D Cultures for High-Throughput Screening: The Multicellular Spheroid Model , 2004, Journal of biomolecular screening.

[112]  Jianzhi Zhang,et al.  A bacterial antibiotic resistance gene with eukaryotic origins , 1998, Current Biology.

[113]  Thomas G. Doak,et al.  Drift-barrier hypothesis and mutation-rate evolution , 2012, Proceedings of the National Academy of Sciences.

[114]  W. Meyer,et al.  Crystallization of hard-sphere colloids in microgravity , 1997, Nature.

[115]  M. Nei Molecular Evolutionary Genetics , 1987 .

[116]  Jack J. W. A. van Loon,et al.  Some history and use of the random positioning machine, RPM, in gravity related research , 2007 .

[117]  Michael J. Stanhope,et al.  Phylogenetic analyses do not support horizontal gene transfers from bacteria to vertebrates , 2001, Nature.

[118]  G Hamilton,et al.  Multicellular spheroids as an in vitro tumor model. , 1998, Cancer letters.

[119]  D. Klaus,et al.  Extracellular mass transport considerations for space flight research concerning suspended and adherent in vitro cell cultures. , 2004, Journal of gravitational physiology : a journal of the International Society for Gravitational Physiology.

[120]  Johannes Madlung,et al.  Changes in the effective gravitational field strength affect the state of phosphorylation of stress-related proteins in callus cultures of Arabidopsis thaliana , 2009 .

[121]  I. Nonaka,et al.  Skeletal muscle gene expression in space‐flown rats , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[122]  D. Klaus GRAVITATIONAL INFLUENCE ON BIOMOLECULAR ENGINEERING PROCESSES , 2007 .

[123]  D. Pierson,et al.  Low-Shear Modeled Microgravity Alters the Salmonella enterica Serovar Typhimurium Stress Response in an RpoS-Independent Manner , 2002, Applied and Environmental Microbiology.

[124]  R. Hampp,et al.  Cytosolic calcium, hydrogen peroxide and related gene expression and protein modulation in Arabidopsis thaliana cell cultures respond immediately to altered gravitation: parabolic flight data. , 2014, Plant biology.

[125]  M. West-Eberhard Developmental plasticity and evolution , 2003 .

[126]  M. Hattori,et al.  Complete genome sequence of enterohemorrhagic Escherichia coli O157:H7 and genomic comparison with a laboratory strain K-12. , 2001, DNA research : an international journal for rapid publication of reports on genes and genomes.

[127]  Shinya Takahashi,et al.  Kinetics of colloidal alloy crystallization of binary mixtures of monodispersed polystyrene and/or colloidal silica spheres having different sizes and densities in microgravity using aircraft , 2000 .

[128]  Masaki Kameyama,et al.  Bio-Assessment of RISK in Long- Term Manned Space Exploration - Cell Death Factors in Space Radiation and/or Microgravity: A Review- , 2009 .

[129]  T. Okubo,et al.  Kinetic analyses of colloidal crystallization in microgravity aircraft experiments 1 Paper present , 1999 .

[130]  U. Gophna,et al.  Have archaeal genes contributed to bacterial virulence? , 2004, Trends in microbiology.

[131]  S. Robinson,et al.  Food Security: The Challenge of Feeding 9 Billion People , 2010, Science.

[132]  D M Klaus,et al.  Clinostats and bioreactors. , 2007, Gravitational and space biology bulletin : publication of the American Society for Gravitational and Space Biology.

[133]  H. Kong,et al.  Divergence of duplicate genes in exon–intron structure , 2012, Proceedings of the National Academy of Sciences.

[134]  Benjamin M. Wheeler,et al.  The dynamic genome of Hydra , 2010, Nature.

[135]  John R. Battista,et al.  Deinococcus radiodurans — the consummate survivor , 2005, Nature Reviews Microbiology.

[136]  Xi-qing Sun,et al.  The Impact of Simulated Weightlessness on Endothelium-Dependent Angiogenesis and the Role of Caveolae/Caveolin-1 , 2016, Cellular Physiology and Biochemistry.

[137]  V R Edgerton,et al.  Altered distribution of mitochondria in rat soleus muscle fibers after spaceflight. , 1992, Journal of applied physiology.

[138]  Salinari Francesca,et al.  Downy mildew (Plasmopara viticola) epidemics on grapevine under climate change , 2006 .

[139]  A. Sievers,et al.  Role of the microtubule cytoskeleton in gravisensing Chara rhizoids. , 1994, European journal of cell biology.

[140]  A. Roger,et al.  Lateral Gene Transfer in the Adaptation of the Anaerobic Parasite Blastocystis to the Gut , 2017, Current Biology.

[141]  E. Rocha Evolutionary patterns in prokaryotic genomes. , 2008, Current opinion in microbiology.

[142]  Alamelu Sundaresan,et al.  The Impact of Simulated and Real Microgravity on Bone Cells and Mesenchymal Stem Cells , 2014, BioMed research international.

[143]  James R. Brown,et al.  Gene Descent, Duplication, and Horizontal Transfer in the Evolution of Glutamyl- and Glutaminyl-tRNA Synthetases , 1999, Journal of Molecular Evolution.

[144]  D. Mindell,et al.  SARS associated coronavirus has a recombinant polymerase and coronaviruses have a history of host-shifting , 2003, Infection, Genetics and Evolution.

[145]  H. Schulz,et al.  Microgravity Affects Thyroid Cancer Cells during the TEXUS-53 Mission Stronger than Hypergravity , 2018, International journal of molecular sciences.

[146]  Ole Skovgaard,et al.  Dam methylation: coordinating cellular processes. , 2005, Current opinion in microbiology.

[147]  T. Sharif,et al.  Autophagic homeostasis is required for the pluripotency of cancer stem cells , 2017, Autophagy.

[148]  S. Gelvin Agrobacterium-Mediated Plant Transformation: the Biology behind the “Gene-Jockeying” Tool , 2003, Microbiology and Molecular Biology Reviews.

[149]  H. Hirt,et al.  New insights into an old story: Agrobacterium‐induced tumour formation in plants by plant transformation , 2010, The EMBO journal.

[150]  W. Kegel,et al.  A qualitative confocal microscopy study on a range of colloidal processes by simulating microgravity conditions through slow rotations , 2012 .

[151]  D. Falush,et al.  Helicobacter pylori genome evolution during human infection , 2011, Proceedings of the National Academy of Sciences.

[152]  M. Fromm,et al.  Multiple exposures to drought 'train' transcriptional responses in Arabidopsis , 2012, Nature Communications.

[153]  Agrobacterium tumefaciens-mediated genetic transformation of haptophytes (Isochrysis species) , 2014, Applied Microbiology and Biotechnology.

[154]  Robert J Ferl,et al.  Parabolic flight induces changes in gene expression patterns in Arabidopsis thaliana. , 2011, Astrobiology.

[155]  H. Ochman,et al.  The fate of new bacterial genes. , 2009, FEMS microbiology reviews.

[156]  P. Todd,et al.  Gravity-dependent phenomena at the scale of the single cell. , 1989, ASGSB bulletin : publication of the American Society for Gravitational and Space Biology.

[157]  Michael Lebert,et al.  Photoactivated Adenylyl Cyclase Controls Phototaxis in the Flagellate Euglena gracilis , 2003, Plant Physiology.

[158]  R. Verma,et al.  PTEN/FOXO3/AKT pathway regulates cell death and mediates morphogenetic differentiation of Colorectal Cancer Cells under Simulated Microgravity , 2017, Scientific Reports.

[159]  Yue Zhang,et al.  A proteomic approach to analyzing responses of Arabidopsis thaliana root cells to different gravitational conditions using an agravitropic mutant, pin2 and its wild type , 2011, Proteome Science.

[160]  Peter L Lee,et al.  The SOS response regulates adaptive mutation. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[161]  F. Dietrich,et al.  The Reacquisition of Biotin Prototrophy in Saccharomyces cerevisiae Involved Horizontal Gene Transfer, Gene Duplication and Gene Clustering , 2007, Genetics.

[162]  K. Brayer,et al.  Detection of mutations in transgenic fish carrying a bacteriophage lambda cII transgene target. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[163]  Yue Zhang,et al.  Differential protein expression profiling of Arabidopsis thaliana callus under microgravity on board the Chinese SZ-8 spacecraft , 2014, Planta.

[164]  Hidetaka Ito Plant Models of Transgenerational Epigenetic Inheritance , 2014 .

[165]  Michael W. Gray,et al.  The Frequency of Eubacterium-to-Eukaryote Lateral Gene Transfers Shows Significant Cross-Taxa Variation Within Amoebozoa , 2006, Journal of Molecular Evolution.

[166]  Alamelu Sundaresan,et al.  The impact of microgravity on bone in humans. , 2016, Bone.

[167]  J. Drake Chaos and order in spontaneous mutation. , 2006, Genetics.

[168]  A. Hoffmann,et al.  Environmental Stress as an Evolutionary Force , 2000 .

[169]  D. Pierson,et al.  Gramicidin S Production by Bacillus brevis in Simulated Microgravity , 1997, Current Microbiology.

[170]  M. Lind,et al.  Evolutionary consequences of epigenetic inheritance , 2018, Heredity.

[171]  Wayne L. Nicholson,et al.  Cultivation of Staphylococcus epidermidis in the Human Spaceflight Environment Leads to Alterations in the Frequency and Spectrum of Spontaneous Rifampicin-Resistance Mutations in the rpoB Gene , 2016, Front. Microbiol..

[172]  F. Rhodes,et al.  Gradualism, punctuated equilibrium and the Origin of Species , 1983, Nature.

[173]  M. Shakibaei,et al.  Induction of three-dimensional assembly and increase in apoptosis of human endothelial cells by simulated microgravity: Impact of vascular endothelial growth factor , 2006, Apoptosis.

[174]  A. Buckling,et al.  The Distribution of Fitness Effects of Beneficial Mutations in Pseudomonas aeruginosa , 2009, PLoS genetics.

[175]  D. Klaus,et al.  The effects of space flight on the production of monorden by Humicola fuscoatra WC5157 in solid-state fermentation , 1998, Applied Microbiology and Biotechnology.

[176]  D. Häder,et al.  Gravireceptors in eukaryotes—a comparison of case studies on the cellular level , 2017, npj Microgravity.

[177]  Thomas A. Richards,et al.  Evolutionary Origins of the Eukaryotic Shikimate Pathway: Gene Fusions, Horizontal Gene Transfer, and Endosymbiotic Replacements , 2006, Eukaryotic Cell.

[178]  Johann Bauer,et al.  Semantic analysis of thyroid cancer cell proteins obtained from rare research opportunities , 2017, J. Biomed. Informatics.

[179]  Diana Risin,et al.  Identification of mechanosensitive genes in osteoblasts by comparative microarray studies using the rotating wall vessel and the random positioning machine , 2007, Journal of cellular biochemistry.

[180]  M. Shakibaei,et al.  Simulated microgravity induces programmed cell death in human thyroid carcinoma cells. , 2002, Journal of gravitational physiology : a journal of the International Society for Gravitational Physiology.

[181]  Rafael Sanjuán,et al.  The distribution of fitness effects caused by single-nucleotide substitutions in an RNA virus. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[182]  Robert J Ferl,et al.  Spaceflight transcriptomes: unique responses to a novel environment. , 2012, Astrobiology.

[183]  M. Braun,et al.  Tip-localized actin polymerization and remodeling, reflected by the localization of ADF, profilin and villin, are fundamental for gravity-sensing and polar growth in characean rhizoids , 2004, Planta.

[184]  K. O'Connor,et al.  Effects of simulated microgravity on DU 145 human prostate carcinoma cells , 2000, Biotechnology and bioengineering.

[185]  K. Arunasri,et al.  Effect of Simulated Microgravity on E. coli K12 MG1655 Growth and Gene Expression , 2013, PloS one.

[186]  O. Monje,et al.  Microgravity effects on leaf morphology, cell structure, carbon metabolism and mRNA expression of dwarf wheat , 2006, Planta.

[187]  P. Foster Adaptive mutation: implications for evolution , 2000, BioEssays : news and reviews in molecular, cellular and developmental biology.

[188]  J. Ma,et al.  Long-term exposure to spaceflight conditions affects bacterial response to antibiotics. , 1999 .

[189]  Jens Hauslage,et al.  ARADISH - Development of a Standardized Plant Growth Chamber for Experiments in Gravitational Biology Using Ground Based Facilities , 2016 .

[190]  Michael Lebert,et al.  Sensory transduction of gravitaxis in Euglena gracilis , 2002 .

[191]  Jeanne M DiFrancesco,et al.  The economics of microgravity research , 2015, npj Microgravity.

[192]  R. Busuttil,et al.  A model system for analyzing somatic mutations in Drosophila melanogaster , 2007, Nature Methods.

[193]  G. Ruyters,et al.  From the Bremen Drop Tower to the international space station ISS – Ways to weightlessness in the German space life sciences program , 2006 .

[194]  Ruifu Yang,et al.  Increased biofilm formation ability in Klebsiella pneumoniae after short‐term exposure to a simulated microgravity environment , 2016, MicrobiologyOpen.

[195]  S. Richards,et al.  Widespread Lateral Gene Transfer from Intracellular Bacteria to Multicellular Eukaryotes , 2007, Science.

[196]  J. L. King,et al.  Non-Darwinian evolution. , 1969, Science.

[197]  Wei Wang,et al.  Proteomic analysis of high yield rice variety mutated from spaceflight , 2007 .

[198]  D. Pierson,et al.  Microbial Responses to Microgravity and Other Low-Shear Environments , 2004, Microbiology and Molecular Biology Reviews.

[199]  Colloidal stability of tannins: astringency, wine tasting and beyond , 2008, 0810.1136.

[200]  Alper Yilmaz,et al.  Components and mechanisms of regulation of gene expression. , 2010, Methods in molecular biology.

[201]  C. Köhler,et al.  Imprinting in plants as a mechanism to generate seed phenotypic diversity , 2015, Front. Plant Sci..

[202]  R. Verma,et al.  Simulated microgravity increases polyploid giant cancer cells and nuclear localization of YAP , 2019, Scientific Reports.

[203]  M. Mergeay,et al.  Conjugation-mediated plasmid exchange between bacteria grown under space flight conditions , 2007 .

[204]  Millie Hughes-Fulford,et al.  Spaceflight and simulated microgravity cause a significant reduction of key gene expression in early T-cell activation. , 2015, American journal of physiology. Regulatory, integrative and comparative physiology.

[205]  M. Braun,et al.  Relocalization of the calcium gradient and a dihydropyridine receptor is involved in upward bending by bulging of Chara protonemata, but not in downward bending by bowing of Chara rhizoids , 1999, Planta.

[206]  D. Pierson,et al.  The adaptation of Escherichia coli cells grown in simulated microgravity for an extended period is both phenotypic and genomic , 2017, npj Microgravity.

[207]  V. Rakyan,et al.  Transgenerational inheritance of epigenetic states at the murine AxinFu allele occurs after maternal and paternal transmission , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[208]  W. Jeffery,et al.  A Potential Benefit of Albinism in Astyanax Cavefish: Downregulation of the oca2 Gene Increases Tyrosine and Catecholamine Levels as an Alternative to Melanin Synthesis , 2013, PloS one.

[209]  Jens Hauslage,et al.  Changes in Gene Expression of Arabidopsis Thaliana Cell Cultures Upon Exposure to Real and Simulated Partial-g Forces , 2016 .

[210]  D. Pierson,et al.  Secondary metabolism in simulated microgravity: β-lactam production by Streptomyces clavuligerus , 1997, Journal of Industrial Microbiology and Biotechnology.

[211]  J. Kiss,et al.  An endogenous growth pattern of roots is revealed in seedlings grown in microgravity. , 2011, Astrobiology.

[212]  Lizhong Xiong,et al.  Genome-wide profiling of histone H3K4-tri-methylation and gene expression in rice under drought stress , 2012, Plant Molecular Biology.

[213]  A. Czirók,et al.  Is bioconvection enhancing bacterial growth in quiescent environments? , 2002, Environmental microbiology.

[214]  M. Braun,et al.  Alterations of the cytoskeleton in human cells in space proved by life-cell imaging , 2016, Scientific Reports.

[215]  E. Raleigh,et al.  On the regulation and diversity of restriction in Escherichia coli. , 1995, Gene.

[216]  M. Model,et al.  Effect of modeled reduced gravity conditions on bacterial morphology and physiology , 2012, BMC Microbiology.

[217]  Ying Huang,et al.  Effects of simulated microgravity and spaceflight on morphological differentiation and secondary metabolism of Streptomyces coelicolor A3(2) , 2015, Applied Microbiology and Biotechnology.

[218]  J. Coyne,et al.  THE LOCUS OF EVOLUTION: EVO DEVO AND THE GENETICS OF ADAPTATION , 2007, Evolution; international journal of organic evolution.

[219]  A. Sievers,et al.  Electron microscopic analysis of gravisensing Chara rhizoids developed under microgravity conditions , 1999, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[220]  C. Mark Ott,et al.  Microgravity as a Novel Environmental Signal Affecting Salmonella enterica Serovar Typhimurium Virulence , 2000, Infection and Immunity.

[221]  Ruth Hemmersbach,et al.  Differential gene expression profile and altered cytokine secretion of thyroid cancer cells in space , 2014, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[222]  J. Washington,et al.  Trends in the antimicrobial susceptibility of bacterial respiratory tract pathogens--findings of the Alexander Project 1992-1996. , 1999, Journal of chemotherapy.

[223]  De Chang,et al.  Simulated microgravity alters the metastatic potential of a human lung adenocarcinoma cell line , 2013, In Vitro Cellular & Developmental Biology - Animal.

[224]  Michael K. Skinner,et al.  Epigenetic Transgenerational Actions of Endocrine Disruptors and Male Fertility , 2005, Science.

[225]  S. Manley,et al.  Limits to gelation in colloidal aggregation. , 2004, Physical review letters.

[226]  V. V. Velkov New Insights into the Molecular Mechanisms of Evolution: Stress Increases Genetic Diversity , 2002, Molecular Biology.

[227]  L. Stodieck,et al.  Investigation of space flight effects on Escherichia coli and a proposed model of underlying physical mechanisms. , 1997, Microbiology.

[228]  Haiying Chen,et al.  Transcriptome Analysis of Oryza sativa Calli Under Microgravity , 2015 .

[229]  J A Eisen,et al.  Microbial Genes in the Human Genome: Lateral Transfer or Gene Loss? , 2001, Science.

[230]  V. Colot,et al.  Arabidopsis epigenetics: when RNA meets chromatin. , 2005, Current opinion in plant biology.

[231]  G Ruyters,et al.  Plant biology in space: recent accomplishments and recommendations for future research. , 2014, Plant biology.

[232]  Ruth Hemmersbach,et al.  Tissue Engineering of Cartilage on Ground-Based Facilities , 2016 .

[233]  Timothy J. Harlow,et al.  Highways of gene sharing in prokaryotes. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[234]  Cato T Laurencin,et al.  Bone tissue engineering: recent advances and challenges. , 2012, Critical reviews in biomedical engineering.

[235]  Matthijn C Hesselman,et al.  Rates of Lateral Gene Transfer in Prokaryotes: High but Why? , 2015, Trends in microbiology.

[236]  D M Porterfield,et al.  Evidence of Root Zone Hypoxia in Brassica rapa L. Grown in Microgravity , 2001, International Journal of Plant Sciences.

[237]  Robert J Ferl,et al.  Plant growth strategies are remodeled by spaceflight , 2012, BMC Plant Biology.

[238]  Monalie C. Saylo,et al.  Punctuated Equilibrium vs. Phyletic Gradualism , 2011 .

[239]  Marian L. Lewis,et al.  Spaceflight alters microtubules and increases apoptosis in human lymphocytes (Jurkat) , 1998, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[240]  Martin Braddock,et al.  From Target identification to Drug Development in Space: Using the Microgravity Assist. , 2020, Current drug discovery technologies.

[241]  G. Reitz,et al.  Life Sciences , 1984, Science.

[242]  J. Sha,et al.  Alterations in the Virulence Potential of Enteric Pathogens and Bacterial–Host Cell Interactions Under Simulated Microgravity Conditions , 2006, Journal of toxicology and environmental health. Part A.

[243]  J. Gogarten,et al.  Concerted gene recruitment in early plant evolution , 2008, Genome Biology.

[244]  P. Mackiewicz,et al.  The case of horizontal gene transfer from bacteria to the peculiar dinoflagellate plastid genome , 2013, Mobile genetic elements.

[245]  Jason A. Rosenzweig,et al.  The effects of modeled microgravity on growth kinetics, antibiotic susceptibility, cold growth, and the virulence potential of a Yersinia pestis ymoA-deficient mutant and its isogenic parental strain. , 2013, Astrobiology.

[246]  W. Doolittle,et al.  Lateral gene transfer and the origins of prokaryotic groups. , 2003, Annual review of genetics.

[247]  E. Koonin,et al.  Genomics of bacteria and archaea: the emerging dynamic view of the prokaryotic world , 2008, Nucleic acids research.

[248]  H. Matsuda,et al.  Biased biological functions of horizontally transferred genes in prokaryotic genomes , 2004, Nature Genetics.

[249]  C. Kenific,et al.  Autophagy in adhesion and migration , 2016, Journal of Cell Science.

[250]  D. Häder,et al.  R3D-B2 – Measurement of ionizing and solar radiation in open space in the BIOPAN 5 facility outside the FOTON M2 satellite , 2009 .

[251]  J. A. Mckenzie,et al.  The genetic, molecular and phenotypic consequences of selection for insecticide resistance. , 1994, Trends in ecology & evolution.

[252]  Xiaomin Hu,et al.  Characterization of Bacilli isolated from the confined environments of the Antarctic Concordia station and the International Space Station. , 2011, Astrobiology.

[253]  A. Badyaev Stress-induced variation in evolution: from behavioural plasticity to genetic assimilation , 2005, Proceedings of the Royal Society B: Biological Sciences.

[254]  Ruth Hershberg,et al.  Mutation--The Engine of Evolution: Studying Mutation and Its Role in the Evolution of Bacteria. , 2015, Cold Spring Harbor perspectives in biology.

[255]  Huan Wang,et al.  Model microgravity enhances endothelium differentiation of mesenchymal stem cells , 2012, Naturwissenschaften.

[256]  Xuedong Zhou,et al.  Effects of simulated microgravity on Streptococcus mutans physiology and biofilm structure. , 2014, FEMS microbiology letters.

[257]  D A Weitz,et al.  Spinodal decomposition in a model colloid-polymer mixture in microgravity. , 2007, Physical review letters.

[258]  W. Martin,et al.  A natural barrier to lateral gene transfer from prokaryotes to eukaryotes revealed from genomes: the 70 % rule , 2016, BMC Biology.

[259]  J. Andersson,et al.  Phylogenetic Analyses of Diplomonad Genes Reveal Frequent Lateral Gene Transfers Affecting Eukaryotes , 2003, Current Biology.

[260]  H. Jenke-Kodama,et al.  Horizontal gene transfer of two cytoskeletal elements from a eukaryote to a cyanobacterium , 2007, Current Biology.

[261]  David I. K. Martin,et al.  Germ-line epigenetic modification of the murine Avy allele by nutritional supplementation , 2006, Proceedings of the National Academy of Sciences.

[262]  Molly T Townsend,et al.  Microgravity control of autophagy modulates osteoclastogenesis. , 2014, Bone.

[263]  J. W. Wilson,et al.  Space flight alters bacterial gene expression and virulence and reveals a role for global regulator Hfq , 2007, Proceedings of the National Academy of Sciences.

[264]  Lixin Zhang,et al.  Secondary metabolism in simulated microgravity and space flight , 2011, Protein & Cell.

[265]  Mark C. Field,et al.  Transcriptome, proteome and draft genome of Euglena gracilis , 2019, BMC Biology.

[266]  S. Mann,et al.  Preparation of Swellable Hydrogel-Containing Colloidosomes from Aqueous Two-Phase Pickering Emulsion Droplets. , 2018, Angewandte Chemie.

[267]  M. Colhone,et al.  Proteoliposomes in nanobiotechnology , 2012, Biophysical Reviews.

[268]  Bernhard Frerich,et al.  Microvascular engineering in perfusion culture: immunohistochemistry and CLSM findings , 2006, Head & face medicine.

[269]  S. Wyatt,et al.  Comparison of Microgravity Analogs to Spaceflight in Studies of Plant Growth and Development , 2019, Front. Plant Sci..

[270]  J. Marshall,et al.  Vision using multiple distinct rod opsins in deep-sea fishes , 2018, Science.

[271]  Diep Ganguly,et al.  Reconsidering plant memory: Intersections between stress recovery, RNA turnover, and epigenetics , 2016, Science Advances.

[272]  Masahiro Chatani,et al.  Microgravity promotes osteoclast activity in medaka fish reared at the international space station , 2015, Scientific Reports.

[273]  M Lebert,et al.  The influence of microgravity on Euglena gracilis as studied on Shenzhou 8. , 2014, Plant biology.

[274]  W. Nicholson,et al.  Comparison of Bacillus subtilis transcriptome profiles from two separate missions to the International Space Station , 2019, npj Microgravity.

[275]  D. Grimm,et al.  Growing blood vessels in space: Preparation studies of the SPHEROIDS project using related ground-based studies , 2019, Acta Astronautica.

[276]  T. Ohta THE NEARLY NEUTRAL THEORY OF MOLECULAR EVOLUTION , 1992 .

[277]  D. Ingber,et al.  How cells (might) sense microgravity , 1999, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[278]  W. J. Dickinson,et al.  Marginal fitness contributions of nonessential genes in yeast. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[279]  M. Braun,et al.  Rhizoids and protonemata of characean algae: model cells for research on polarized growth and plant gravity sensing , 2006, Protoplasma.

[280]  C. Mark Ott,et al.  Media Ion Composition Controls Regulatory and Virulence Response of Salmonella in Spaceflight , 2008, PloS one.

[281]  Masaki Shirakawa,et al.  Four-year bacterial monitoring in the International Space Station—Japanese Experiment Module “Kibo” with culture-independent approach , 2016, npj Microgravity.

[282]  R. Verma,et al.  Genome Wide Expression Profiling of Cancer Cell Lines Cultured in Microgravity Reveals Significant Dysregulation of Cell Cycle and MicroRNA Gene Networks , 2015, PloS one.

[283]  Hoffmann,et al.  Heritable variation and evolution under favourable and unfavourable conditions. , 1999, Trends in ecology & evolution.

[284]  Robert J. Ferl,et al.  Epigenomics in an extraterrestrial environment: organ-specific alteration of DNA methylation and gene expression elicited by spaceflight in Arabidopsis thaliana , 2019, BMC Genomics.

[285]  Miriam Barlow,et al.  What antimicrobial resistance has taught us about horizontal gene transfer. , 2009, Methods in molecular biology.

[286]  A. Eyre-Walker,et al.  The rate of adaptive evolution in enteric bacteria. , 2006, Molecular biology and evolution.

[287]  C. Sams,et al.  T cell activation responses are differentially regulated during clinorotation and in spaceflight , 1999, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[288]  A. Bhagwat,et al.  Cooperation and competition in mismatch repair: very short‐patch repair and methyl‐directed mismatch repair in Escherichia coli , 2002, Molecular microbiology.

[289]  Spatial Analysis of Galactic Cosmic Ray Particles in Low Earth Orbit/Near Equator Orbit Using SPENVIS , 2014 .

[290]  G Richoilley,et al.  Antibiotic activity in space. , 1986, Drugs under experimental and clinical research.

[291]  T G Hammond,et al.  Optimized suspension culture: the rotating-wall vessel. , 2001, American journal of physiology. Renal physiology.

[292]  Adam Eyre-Walker,et al.  The genomic rate of adaptive evolution. , 2006, Trends in ecology & evolution.

[293]  L. Mermel,et al.  Infection prevention and control during prolonged human space travel. , 2013, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[294]  K. Roland,et al.  Physiological fluid shear alters the virulence potential of invasive multidrug-resistant non-typhoidal Salmonella Typhimurium D23580 , 2016, npj Microgravity.

[295]  A Hemprich,et al.  Maturation of capillary-like structures in a tube-like construct in perfusion and rotation culture. , 2008, International journal of oral and maxillofacial surgery.

[296]  R. Kamiya,et al.  Gravitaxis in Chlamydomonas reinhardtii studied with novel mutants. , 2003, Plant & cell physiology.

[298]  Xiaoping Chen,et al.  Transcriptome profiling of peanut (Arachis hypogaea) gynophores in gravitropic response. , 2013, Functional plant biology : FPB.

[299]  Thomas J. Goodwin,et al.  Establishment of a three-dimensional human prostate organoid coculture under microgravity-simulated conditions: Evaluation of androgen-induced growth and psa expression , 1997, In Vitro Cellular & Developmental Biology - Animal.

[300]  L. Kunz-Schughart,et al.  Multicellular tumor spheroids: intermediates between monolayer culture and in vivo tumor , 1999, Cell biology international.

[301]  A. Nedelcu,et al.  Adaptive eukaryote‐to‐eukaryote lateral gene transfer: stress‐related genes of algal origin in the closest unicellular relatives of animals , 2008, Journal of evolutionary biology.

[302]  R. Hampp,et al.  Real-time Recording of Cytosolic Calcium Levels in Arabidopsis thaliana Cell Cultures during Parabolic Flights , 2015 .

[303]  M. Lebert,et al.  Molecular Analysis of the Graviperception Signal Transduction in the Flagellate Euglena , 2009 .

[304]  M. Monk Epigenetic programming of differential gene expression in development and evolution. , 1995, Developmental genetics.

[305]  Sung-Hou Kim,et al.  Global extent of horizontal gene transfer , 2007, Proceedings of the National Academy of Sciences.

[306]  Robert J Ferl,et al.  High magnetic field induced changes of gene expression in arabidopsis , 2006, Biomagnetic research and technology.

[307]  Jason A. Rosenzweig,et al.  Low-shear force associated with modeled microgravity and spaceflight does not similarly impact the virulence of notable bacterial pathogens , 2014, Applied Microbiology and Biotechnology.

[308]  W. Doolittle,et al.  Systematic overestimation of gene gain through false diagnosis of gene absence , 2007, Genome Biology.

[309]  Y. Li,et al.  Effect of Change in Spindle Structure on Proliferation Inhibition of Osteosarcoma Cells and Osteoblast under Simulated Microgravity during Incubation in Rotating Bioreactor , 2013, PloS one.

[310]  M. Lynch The origins of eukaryotic gene structure. , 2006, Molecular biology and evolution.

[311]  Neil McRoberts,et al.  The global burden of pathogens and pests on major food crops , 2019, Nature Ecology & Evolution.

[312]  A. Nordheim,et al.  Alterations in Protein Expression of Arabidopsis thaliana Cell Cultures During Hyper- and Simulated Micro-Gravity , 2009 .

[313]  Vladimir Pletser,et al.  Short duration microgravity experiments in physical and life sciences during parabolic flights: the first 30 ESA campaigns. , 2004, Acta astronautica.

[314]  M. Moline,et al.  Bioluminescence in the sea. , 2010, Annual review of marine science.

[315]  D. Häder,et al.  Molecular characterization of a calmodulin involved in the signal transduction chain of gravitaxis in Euglena gracilis , 2010, Planta.

[316]  S. Rosenberg Evolving responsively: adaptive mutation , 2001, Nature Reviews Genetics.

[317]  Gary L. Sanford,et al.  Three-dimensional growth of endothelial cells in the microgravity-based rotating wall vessel bioreactor , 2002, In Vitro Cellular & Developmental Biology - Animal.

[318]  Diane O. Inglis,et al.  Spaceflight Enhances Cell Aggregation and Random Budding in Candida albicans , 2013, PloS one.

[319]  Alexander F. Palazzo,et al.  Non-coding RNA: what is functional and what is junk? , 2015, Front. Genet..

[320]  D. Häder,et al.  CAMP IS INVOLVED IN GRAVITAXIS SIGNAL TRANSDUCTION OF EUGLENA GRACILIS , 1998 .

[321]  Wei Sha,et al.  A proteomic approach to analysing responses of Arabidopsis thaliana callus cells to clinostat rotation. , 2006, Journal of experimental botany.

[322]  Leszek Rychlewski,et al.  The Phaeodactylum genome reveals the evolutionary history of diatom genomes , 2008, Nature.

[323]  C. Burch,et al.  Experimental Estimate of the Abundance and Effects of Nearly Neutral Mutations in the RNA Virus ϕ6 , 2007, Genetics.

[324]  D. W. Kim,et al.  Shigella sonnei genome sequencing and phylogenetic analysis indicate recent global dissemination from Europe , 2012, Nature Genetics.

[325]  Jasmine Shong,et al.  Effect of spaceflight on Pseudomonas aeruginosa final cell density is modulated by nutrient and oxygen availability , 2013, BMC Microbiology.

[326]  Michael Lebert,et al.  The involvement of a protein kinase in phototaxis and gravitaxis of Euglena gracilis , 2011, Planta.

[327]  M. Huynen,et al.  Horizontal gene transfer from Bacteria to rumen Ciliates indicates adaptation to their anaerobic, carbohydrates-rich environment , 2006, BMC Genomics.

[328]  G. Stephanopoulos,et al.  Accessing Nature’s diversity through metabolic engineering and synthetic biology , 2016, F1000Research.

[329]  D M Klaus,et al.  Buoyant plumes from solute gradients generated by non-motile Escherichia coli , 2008, Physical biology.

[330]  M. Lynch Rate, molecular spectrum, and consequences of human mutation , 2010, Proceedings of the National Academy of Sciences.

[331]  Karsten B. Sieber,et al.  Lateral gene transfer between prokaryotes and eukaryotes. , 2017, Experimental cell research.

[332]  J. Palmer,et al.  Horizontal gene transfer in eukaryotic evolution , 2008, Nature Reviews Genetics.

[333]  Millie Hughes-Fulford,et al.  Spaceflight alters expression of microRNA during T‐cell activation , 2011, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[334]  D. Kalpana,et al.  Comparative growth, cross stress resistance, transcriptomics of Streptococcus pyogenes cultured under low shear modeled microgravity and normal gravity , 2015, Saudi journal of biological sciences.

[335]  H. Heng,et al.  Stress, genomic adaptation, and the evolutionary trade-off , 2014, Front. Genet..

[336]  R. Singh,et al.  Metabolic Engineering of Enzyme-Regulated Bioprocesses , 2019, Advances in Enzyme Technology.

[337]  Wolfgang Hanke,et al.  Conductance and Capacity of Plain Lipid Membranes under Conditions of Variable Gravity , 2016 .

[338]  Ruth Hemmersbach,et al.  Mechanisms of three-dimensional growth of thyroid cells during long-term simulated microgravity , 2015, Scientific Reports.

[339]  J. Doyle,et al.  Adaptive horizontal transfer of a bacterial gene to an invasive insect pest of coffee , 2012, Proceedings of the National Academy of Sciences.

[340]  M. Miyamoto,et al.  Mutation rate variation in multicellular eukaryotes: causes and consequences , 2007, Nature Reviews Genetics.

[341]  M. Bizzarri,et al.  How Microgravity Affects the Biology of Living Systems , 2015, BioMed research international.

[342]  Myungjoon Kim,et al.  Time-averaged simulated microgravity (taSMG) inhibits proliferation of lymphoma cells, L-540 and HDLM-2, using a 3D clinostat , 2017, Biomedical engineering online.

[343]  Peipei Xu,et al.  Single-base resolution methylome analysis shows epigenetic changes in Arabidopsis seedlings exposed to microgravity spaceflight conditions on board the SJ-10 recoverable satellite , 2018, npj Microgravity.

[344]  A. Newton,et al.  Intraspecific genetic diversity and composition modify species-level diversity-productivity relationships. , 2015, The New phytologist.

[345]  Robin Holliday,et al.  Epigenetics: A Historical Overview , 2006, Epigenetics.

[346]  J. Akabutu,et al.  Induction of vascular endothelial phenotype and cellular proliferation from human cord blood stem cells cultured in simulated microgravity. , 2005, Acta astronautica.

[347]  N. Moran,et al.  Evolutionary Origins of Genomic Repertoires in Bacteria , 2005, PLoS biology.

[348]  Robert J Ferl,et al.  Organ-specific remodeling of the Arabidopsis transcriptome in response to spaceflight , 2013, BMC Plant Biology.

[349]  Identification of a flagellar protein implicated in the gravitaxis in the flagellate Euglena gracilis , 2018, Scientific Reports.

[350]  S. Rutherford,et al.  From genotype to phenotype: buffering mechanisms and the storage of genetic information , 2000, BioEssays : news and reviews in molecular, cellular and developmental biology.

[351]  L. Hyman,et al.  Modeled microgravity increases filamentation, biofilm formation, phenotypic switching, and antimicrobial resistance in Candida albicans. , 2011, Astrobiology.

[352]  P. Sniegowski,et al.  Mutation Rates: How Low Can You Go? , 2013, Current Biology.

[353]  J. Hauslage,et al.  Membrane Fluidity Changes, A Basic Mechanism of Interaction of Gravity with Cells? , 2017 .

[354]  D. Grimm,et al.  Three-dimensional growth of human endothelial cells in an automated cell culture experiment container during the SpaceX CRS-8 ISS space mission - The SPHEROIDS project. , 2017, Biomaterials.

[355]  Y. Harada,et al.  Intracellular temperature mapping with a fluorescent polymeric thermometer and fluorescence lifetime imaging microscopy , 2012, Nature Communications.

[356]  Tal Dagan,et al.  Modular networks and cumulative impact of lateral transfer in prokaryote genome evolution , 2008, Proceedings of the National Academy of Sciences.

[357]  Richard E. Lenski,et al.  Distribution of fitness effects caused by random insertion mutations in Escherichia coli , 2004, Genetica.

[358]  L. Boto Horizontal gene transfer in evolution: facts and challenges , 2010, Proceedings of the Royal Society B: Biological Sciences.

[359]  P. Maurer,et al.  Nanometre-scale thermometry in a living cell , 2013, Nature.

[360]  D. Grimm,et al.  Fighting Thyroid Cancer with Microgravity Research , 2019, International journal of molecular sciences.

[361]  Alison M. Smith,et al.  The importance of starch biosynthesis in the wrinkled seed shape character of peas studied by Mendel , 1993, Plant Molecular Biology.

[362]  Tomoo Ishii,et al.  Rotating three‐dimensional dynamic culture of adult human bone marrow‐derived cells for tissue engineering of hyaline cartilage , 2009, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[363]  E. Koonin,et al.  Horizontal gene transfer in prokaryotes: quantification and classification. , 2001, Annual review of microbiology.

[364]  J. Andersson,et al.  Lateral gene transfer in eukaryotes , 2005, Cellular and Molecular Life Sciences CMLS.

[365]  S. Salzberg,et al.  Evidence for lateral gene transfer between Archaea and Bacteria from genome sequence of Thermotoga maritima , 1999, Nature.

[366]  Jian‐Kang Zhu,et al.  Developing naturally stress-resistant crops for a sustainable agriculture , 2018, Nature Plants.

[367]  G. Schulze-Tanzil,et al.  Simulated microgravity alters differentiation and increases apoptosis in human follicular thyroid carcinoma cells , 2002, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[368]  Janice K. Wiedenbeck,et al.  Origins of bacterial diversity through horizontal genetic transfer and adaptation to new ecological niches. , 2011, FEMS microbiology reviews.

[369]  D. Grimm,et al.  Tissue Engineering Under Microgravity Conditions-Use of Stem Cells and Specialized Cells. , 2018, Stem cells and development.

[370]  James W. Wilson,et al.  Conservation of the Low-shear Modeled Microgravity Response in Enterobacteriaceae and Analysis of the trp Genes in this Response , 2014, The open microbiology journal.

[371]  Michael Y. Galperin,et al.  Comparison of archaeal and bacterial genomes: computer analysis of protein sequences predicts novel functions and suggests a chimeric origin for the archaea , 1997, Molecular microbiology.

[372]  Jing Ma,et al.  The influence of simulated microgravity on proliferation and apoptosis in U251 glioma cells , 2017, In Vitro Cellular & Developmental Biology - Animal.

[373]  J. Gogarten,et al.  Evolution of Acetoclastic Methanogenesis in Methanosarcina via Horizontal Gene Transfer from Cellulolytic Clostridia , 2007, Journal of bacteriology.

[374]  Antonio Di Pietro,et al.  The Top 10 fungal pathogens in molecular plant pathology. , 2012, Molecular plant pathology.

[375]  S. Donadio,et al.  Discovering new bioactive molecules from microbial sources , 2014, Microbial biotechnology.

[376]  Paul Anthony,et al.  Expression of transcription factors after short-term exposure of Arabidopsis thaliana cell cultures to hypergravity and simulated microgravity (2-D/3-D clinorotation, magnetic levitation) , 2007 .

[377]  G. Rotilio,et al.  Low-Shear Modeled Microgravity Enhances Salmonella Enterica Resistance to Hydrogen Peroxide Through a Mechanism Involving KatG and KatN , 2012, The open microbiology journal.

[378]  Louis S. Stodieck,et al.  Spaceflight Environment Induces Mitochondrial Oxidative Damage in Ocular Tissue , 2013, Radiation research.

[379]  H. Soares,et al.  Non-Coding RNAs: Multi-Tasking Molecules in the Cell , 2013, International journal of molecular sciences.

[380]  Julie A Law,et al.  Dynamic DNA Methylation , 2009, Science.

[381]  Eric J Alm,et al.  Horizontal gene transfer and the evolution of bacterial and archaeal population structure. , 2013, Trends in genetics : TIG.

[382]  J. Conrad,et al.  Differential dynamic microscopy of bidisperse colloidal suspensions , 2017, npj Microgravity.

[383]  Stanley J. Roux,et al.  Gene expression changes induced by space flight in single-cells of the fern Ceratopteris richardii , 2008, Planta.

[384]  J. B. Reid,et al.  Mendel’s Genes: Toward a Full Molecular Characterization , 2011, Genetics.

[385]  W. Doolittle,et al.  Phylogenetic analyses of cyanobacterial genomes: quantification of horizontal gene transfer events. , 2006, Genome research.

[386]  H Philippe,et al.  Reverse gyrase from hyperthermophiles: probable transfer of a thermoadaptation trait from archaea to bacteria. , 2000, Trends in genetics : TIG.

[387]  Barbara E. Wright,et al.  Stress‐directed adaptive mutations and evolution , 2004, Molecular microbiology.

[388]  Francisco Javier Medina,et al.  Microgravity Induces Changes in Microsome-Associated Proteins of Arabidopsis Seedlings Grown on Board the International Space Station , 2014, PloS one.

[389]  D. Häder,et al.  Aquacells — Flagellates under long-term microgravity and potential usage for life support systems , 2006 .

[390]  Donald E Ingber,et al.  Co-culture of Living Microbiome with Microengineered Human Intestinal Villi in a Gut-on-a-Chip Microfluidic Device. , 2016, Journal of visualized experiments : JoVE.

[391]  James R. Brown Ancient horizontal gene transfer , 2003, Nature Reviews Genetics.

[392]  Jens Hauslage,et al.  Ground-based facilities for simulation of microgravity: organism-specific recommendations for their use, and recommended terminology. , 2013, Astrobiology.

[393]  D. Häder,et al.  Signal transduction in gravisensing of flagellates , 2006 .

[394]  Crystallization of Charged Colloids under Microgravity during Aircraft Parabolic Flights , 2018 .

[395]  G. Vunjak‐Novakovic,et al.  Tissue engineering of cartilage in space. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[396]  Sophia Sonnewald,et al.  Changes of Gene Expression in Euglena gracilis Obtained During the 29th DLR Parabolic Flight Campaign , 2019, Scientific Reports.

[397]  G. Müller,et al.  Embryonic motility: environmental influences and evolutionary innovation , 2003, Evolution & development.

[398]  D. Klaus,et al.  Microgravity, bacteria, and the influence of motility , 2007 .

[399]  M. Rhee,et al.  Influence of Low-Shear Modeled Microgravity on Heat Resistance, Membrane Fatty Acid Composition, and Heat Stress-Related Gene Expression in Escherichia coli O157:H7 ATCC 35150, ATCC 43889, ATCC 43890, and ATCC 43895 , 2016, Applied and Environmental Microbiology.

[400]  Jianhua Zhu,et al.  Role of miRNAs and siRNAs in biotic and abiotic stress responses of plants. , 2012, Biochimica et biophysica acta.

[401]  E. Rocha,et al.  Horizontal Transfer, Not Duplication, Drives the Expansion of Protein Families in Prokaryotes , 2011, PLoS genetics.

[402]  M. Braun,et al.  How to Activate a Plant Gravireceptor. Early Mechanisms of Gravity Sensing Studied in Characean Rhizoids during Parabolic Flights1 , 2005, Plant Physiology.

[403]  C. Dijkstra,et al.  Bacillus thuringiensis conjugation in simulated microgravity. , 2009, Astrobiology.

[404]  Masatoshi Nei,et al.  Mutation-Driven Evolution , 2013 .

[405]  Mari L. Salmi,et al.  Changes in gravity rapidly alter the magnitude and direction of a cellular calcium current , 2011, Planta.

[406]  L. Leff,et al.  Escherichia coli growth under modeled reduced gravity , 2004, Microgravity science and technology.

[407]  M. Babbick,et al.  Microgravity-related changes in gene expression after short-term exposure of Arabidopsis thaliana cell cultures , 2006, Protoplasma.

[408]  William L. Poehlman,et al.  RNA-seq analyses of Arabidopsis thaliana seedlings after exposure to blue-light phototropic stimuli in microgravity. , 2019, American journal of botany.

[409]  Clive R. Taylor,et al.  Human Breast Cancer Histoid , 2011, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[410]  D. Grimm,et al.  Key Proteins Involved in Spheroid Formation and Angiogenesis in Endothelial Cells After Long-Term Exposure to Simulated Microgravity , 2018, Cellular Physiology and Biochemistry.

[411]  D. Grimm,et al.  Semantic Analysis of Posttranslational Modification of Proteins Accumulated in Thyroid Cancer Cells Exposed to Simulated Microgravity , 2018, International journal of molecular sciences.

[412]  H. Seifert,et al.  Opportunity and Means: Horizontal Gene Transfer from the Human Host to a Bacterial Pathogen , 2011, mBio.

[413]  Marc A Suchard,et al.  Using Time-Structured Data to Estimate Evolutionary Rates of Double-Stranded DNA Viruses , 2010, Molecular biology and evolution.

[414]  K. Rice,et al.  Investigation of simulated microgravity effects on Streptococcus mutans physiology and global gene expression , 2017, npj Microgravity.

[415]  M. Lynch Evolution of the mutation rate. , 2010, Trends in genetics : TIG.

[416]  Jinling Huang,et al.  Horizontal gene transfer: building the web of life , 2015, Nature Reviews Genetics.

[417]  C. Mark Ott,et al.  Transcriptional and Proteomic Responses of Pseudomonas aeruginosa PAO1 to Spaceflight Conditions Involve Hfq Regulation and Reveal a Role for Oxygen , 2010, Applied and Environmental Microbiology.

[418]  M. Kacena,et al.  Effects of space flight and mixing on bacterial growth in low volume cultures. , 1999, Microgravity science and technology.

[419]  M. Melkonian,et al.  The ancestor of the Paulinella chromatophore obtained a carboxysomal operon by horizontal gene transfer from a Nitrococcus-like γ-proteobacterium , 2007, BMC Evolutionary Biology.

[420]  S. Roux,et al.  RNA-seq analysis identifies potential modulators of gravity response in spores of Ceratopteris (Parkeriaceae): evidence for modulation by calcium pumps and apyrase activity. , 2013, American journal of botany.

[421]  G. Vannacci,et al.  Emerging infectious diseases of crop plants in developing countries: impact on agriculture and socio-economic consequences , 2010, Food Security.

[422]  D. Pierson,et al.  Evaluation of Acquired Antibiotic Resistance in Escherichia coli Exposed to Long-Term Low-Shear Modeled Microgravity and Background Antibiotic Exposure , 2019, mBio.

[423]  Andrew D. S. Cameron,et al.  Horizontal transfer of antibiotic resistance genes in clinical environments. , 2019, Canadian journal of microbiology.

[424]  S. Garcia-Vallvé,et al.  Horizontal gene transfer of glycosyl hydrolases of the rumen fungi. , 2000, Molecular biology and evolution.

[425]  Xiaoguang Liu,et al.  Metabolic Engineering – Applications, Methods, and Challenges , 2007 .

[426]  A. Popova Comparative characteristic of mitochondria ultrastructural organization in Chlorella cells under altered gravity conditions. , 2003, Advances in space research : the official journal of the Committee on Space Research.

[427]  T. Fahima,et al.  Evolution and Adaptation of Wild Emmer Wheat Populations to Biotic and Abiotic Stresses. , 2016, Annual review of phytopathology.

[428]  P. Schall,et al.  Colloidal aggregation in microgravity by critical Casimir forces. , 2011, Physical review letters.

[429]  Jens Hauslage,et al.  Impact of a high magnetic field on the orientation of gravitactic unicellular organisms--a critical consideration about the application of magnetic fields to mimic functional weightlessness. , 2014, Astrobiology.

[430]  W. Doolittle,et al.  Prokaryotic evolution in light of gene transfer. , 2002, Molecular biology and evolution.

[431]  R. Hemmersbach,et al.  A Bird’s-Eye View of Molecular Changes in Plant Gravitropism Using Omics Techniques , 2015, Front. Plant Sci..

[432]  Kriss Westphal,et al.  A delayed type of three-dimensional growth of human endothelial cells under simulated weightlessness. , 2009, Tissue engineering. Part A.

[433]  M. Egli,et al.  Effect of simulated microgravity on growth and production of exopolymeric substances of Micrococcus luteus space and earth isolates. , 2010, FEMS immunology and medical microbiology.

[434]  J. Reseland,et al.  Changes in Human Foetal Osteoblasts Exposed to the Random Positioning Machine and Bone Construct Tissue Engineering , 2019, International journal of molecular sciences.

[435]  W. J. Dickinson,et al.  A genome-wide view of the spectrum of spontaneous mutations in yeast , 2008, Proceedings of the National Academy of Sciences.

[436]  A. Takahashi,et al.  Analysis of deletion mutations of the rpsL gene in the yeast Saccharomyces cerevisiae detected after long-term flight on the Russian space station Mir. , 2000, Mutation research.

[437]  B. Boyan,et al.  Differentiation of human mesenchymal stem cell spheroids under microgravity conditions , 2012, Cell Regeneration.

[438]  P. Insel,et al.  A Single Amino Acid Mutation Contributes to Adaptive Beach Mouse Color Pattern , 2006, Science.

[439]  R. Knuechel,et al.  A heterologous 3-D coculture model of breast tumor cells and fibroblasts to study tumor-associated fibroblast differentiation. , 2001, Experimental cell research.

[440]  R. Hampp,et al.  Hyper-gravity effects on the Arabidopsis transcriptome. , 2003, Physiologia plantarum.

[441]  M. Meselson,et al.  Massive Horizontal Gene Transfer in Bdelloid Rotifers , 2008, Science.

[442]  Dinesh Yadav,et al.  Overview and Principles of Bioengineering: The Drivers of Omics Technologies , 2018 .

[443]  W. Reik,et al.  Epigenetic Reprogramming in Plant and Animal Development , 2010, Science.

[444]  M. Shimada,et al.  Genome fragment of Wolbachia endosymbiont transferred to X chromosome of host insect , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[445]  Liz H. Coelho,et al.  Effects of the Extraterrestrial Environment on Plants: Recommendations for Future Space Experiments for the MELiSSA Higher Plant Compartment , 2014, Life.

[446]  Cecilia Alsmark,et al.  Patterns of prokaryotic lateral gene transfers affecting parasitic microbial eukaryotes , 2013, Genome Biology.

[447]  V. Colot,et al.  Hyperosmotic priming of Arabidopsis seedlings establishes a long-term somatic memory accompanied by specific changes of the epigenome , 2013, Genome Biology.

[448]  Cyrus Chothia,et al.  Protein Family Expansions and Biological Complexity , 2006, PLoS Comput. Biol..

[449]  W. Burggren Epigenetic Inheritance and Its Role in Evolutionary Biology: Re-Evaluation and New Perspectives , 2016, Biology.

[450]  Michal Shapira,et al.  Transgene Expression in Microalgae—From Tools to Applications , 2016, Front. Plant Sci..

[451]  Meng-Pin Weng,et al.  Contrasting genetic paths to morphological and physiological evolution , 2010, Proceedings of the National Academy of Sciences.

[452]  A. Brack,et al.  Survival of microorganisms in space protected by meteorite material: results of the experiment 'EXOBIOLOGIE' of the PERSEUS mission. , 2002, Advances in space research : the official journal of the Committee on Space Research.

[453]  V K Ilyin,et al.  Microbiological status of cosmonauts during orbital spaceflights on Salyut and Mir orbital stations. , 2005, Acta astronautica.

[454]  Yan Cui,et al.  Effect of Weightlessness on the 3D Structure Formation and Physiologic Function of Human Cancer Cells , 2019, BioMed research international.

[455]  Bernard B. Suh,et al.  The genome of the protist parasite Entamoeba histolytica , 2005, Nature.

[456]  Stacia Marie Nordin,et al.  Food, the source of Nutrition , 2017 .

[457]  S. Rétaux,et al.  Evolution of eye development in the darkness of caves: adaptation, drift, or both? , 2013, EvoDevo.

[458]  W. Nicholson,et al.  Alterations in the Spectrum of Spontaneous Rifampicin-Resistance Mutations in the Bacillus subtilis rpoB Gene after Cultivation in the Human Spaceflight Environment , 2018, Front. Microbiol..

[459]  K. S. Narayan,et al.  Three-dimensional growth patterns of various human tumor cell lines in simulated microgravity of a NASA bioreactor , 1997, In Vitro Cellular & Developmental Biology - Animal.

[460]  Gemma L. Kay,et al.  Eighteenth-century genomes show that mixed infections were common at time of peak tuberculosis in Europe , 2015, Nature Communications.

[461]  T. Richards,et al.  Horizontal gene transfer in eukaryotic plant pathogens. , 2014, Annual review of phytopathology.

[462]  Jinling Huang,et al.  Horizontal gene transfer in eukaryotes: The weak-link model , 2013, BioEssays : news and reviews in molecular, cellular and developmental biology.

[463]  S. Rutherford,et al.  Between genotype and phenotype: protein chaperones and evolvability , 2003, Nature Reviews Genetics.

[464]  F. J. Bruijn Stress and environmental regulation of gene expression and adaptation in bacteria , 2016 .

[465]  E. Kordyum,et al.  Plant cell gravisensitivity and adaptation to microgravity. , 2014, Plant biology.

[466]  E. Kordyum,et al.  A role for the cytoskeleton in plant cell gravisensitivity and Ca2+‐signaling in microgravity , 2003, Cell biology international.

[467]  Jin Han,et al.  Restoration of mandibular bone defects with demineralized bone matrix combined with three-dimensional cultured bone marrow-derived mesenchymal stem cells in minipig models , 2018, Journal of Materials Science: Materials in Medicine.

[468]  Bao Liu,et al.  Spaceflight-induced genetic and epigenetic changes in the rice (Oryza sativa L.) genome are independent of each other. , 2010, Genome.

[469]  D. Pizzol,et al.  Spaceflight osteoporosis: current state and future perspective. , 2015, Endocrine regulations.

[470]  Kay Nieselt,et al.  A Whole-Genome Microarray Study of Arabidopsis thaliana Semisolid Callus Cultures Exposed to Microgravity and Nonmicrogravity Related Spaceflight Conditions for 5 Days on Board of Shenzhou 8 , 2015, BioMed research international.

[471]  L. Stodieck,et al.  The effect of space flight on the production of actinomycin D by Streptomyces plicatus , 2002, Journal of Industrial Microbiology and Biotechnology.

[472]  A. Kuzminov Recombinational Repair of DNA Damage inEscherichia coli and Bacteriophage λ , 1999, Microbiology and Molecular Biology Reviews.

[473]  H. Bohnert,et al.  Involvement of Arabidopsis HOS15 in histone deacetylation and cold tolerance , 2008, Proceedings of the National Academy of Sciences.

[474]  P. Richter,et al.  Calcium is involved in the gravitactic orientation in colorless flagellates. , 2001, Journal of plant physiology.

[475]  D. Pierson,et al.  Growth of Streptomyces hygroscopicus in rotating-wall bioreactor under simulated microgravity inhibits rapamycin production , 2000, Applied Microbiology and Biotechnology.

[476]  S. Rosenberg,et al.  Double-strand-break repair recombination in Escherichia coli: physical evidence for a DNA replication mechanism in vivo. , 1999, Genes & development.

[477]  Hartmut Löwen,et al.  Gravitaxis of asymmetric self-propelled colloidal particles , 2014, Nature Communications.

[478]  Anna Tesei,et al.  Anticancer drug discovery using multicellular tumor spheroid models , 2019, Expert opinion on drug discovery.

[479]  Peter Daszak,et al.  Emerging infectious diseases of plants: pathogen pollution, climate change and agrotechnology drivers. , 2004, Trends in ecology & evolution.

[480]  John Z. Kiss,et al.  Mechanisms of the early phases of plant gravitropism. , 2000 .

[481]  R. Martienssen,et al.  Reprogramming of DNA Methylation in Pollen Guides Epigenetic Inheritance via Small RNA , 2012, Cell.

[482]  Y. Ilnytskyy,et al.  Transgenerational Adaptation of Arabidopsis to Stress Requires DNA Methylation and the Function of Dicer-Like Proteins , 2010, PloS one.

[483]  M. Nei,et al.  Concerted and birth-and-death evolution of multigene families. , 2005, Annual review of genetics.

[484]  J. Chung,et al.  Microgravity induces autophagy via mitochondrial dysfunction in human Hodgkin’s lymphoma cells , 2018, Scientific Reports.

[485]  Laurence Vico,et al.  Effects of long-term microgravity exposure on cancellous and cortical weight-bearing bones of cosmonauts , 2000, The Lancet.

[486]  Stephen Mann,et al.  Designs for life: protocell models in the laboratory. , 2012, Chemical Society reviews.

[487]  C. Lindenberger,et al.  An optimized method and a dominant selectable marker for genetic engineering of an industrially promising microalga—Pavlova lutheri , 2018, Journal of Applied Phycology.

[488]  Andrew J. Bannister,et al.  Regulation of chromatin by histone modifications , 2011, Cell Research.