Results of behavioral tests made postflight after two independent travels of Drosophila melanogaster to International Space Station (ISS) are presented. In Experiment 1, the first instar larvae were launched, and the eclosed imagoes gave the next generation that developed from the egg at ISS. After return to Earth the behavior of adult males of the next generation was examined. In Experiment 2, the newly emerged adult males were launched and after 7.5 days of staying at ISS were tested in the lab. In Experiment 1, we found pronounced influence of development in Space on subsequent locomotor behavior of adult flies. In flies developed in Space, all three independent parameters of locomotor behavior (run frequency, run duration and running speed) were increased, at least at certain time points, during the first hour of registration. At the same time, the climbing ability of experimental flies was reduced. In Experiment 2, no changes in the climbing ability were detected. During the first 30 min after registration beginning the flown flies performed less frequent but more extended runs than the control flies did. However, later the flown flies demonstrated an increased run frequency. Additionally, the interpulse interval in the pulse courtship song was shorter in the flown males. Taken together, the results point to a considerable activation of the central nervous system in flies developed at the ISS and to a minor one in the adult flies travelled to the ISS. This shows that earlier stages of development are more sensitive to spaceflight factors than the adult stage.

This paper presents the results of studying the problem of differential adaptation of genotypes to the extreme conditions of spaceflights. Analysis of the statistical correlations between the integral parameters of the genotype and indicators of endurance against the effects of spaceflight factors (SFFs) was carried out in the cohort of the Russian cosmonauts. The relevance of this study is related to the need to substantiate the possibility, validity, and prospects of using genetic tests to predict individual resistance to SFFs. Various methods of correlation analysis and the method of correspondence analysis were applied. With the help of traditional methods of correlation analysis, weak but statistically significant correlation was revealed between the parameter of individual heterozygosity and indicators of vestibular resistance, as well as with the total indicator of resistance to simulated SFFs. Correspondence analysis confirmed the existence of such associations. The results of the study indicate the need to increase the sample size and to attract a wide range of genetic markers for a statistically significant substantiation of correlation between the indicators of resistance against SFFs and the integral parameters of the genotype.

Blood samples taken from test-subjects in the 7-d immersion experiment were analyzed for blood proteins belonging to alpha1- and alpha2-globulins electrophoretic fractions: alphal-antitripsin (alpha1-AT), a1-acidic glycoprotein (alpha1-AGP), ceruplasmin (Cer), haptoglobin (Hp), alpha2-macroglobulin (alpha2-M), apolipoprotein A (ApoA). Immersion was demonstrated to alter concentrations of the studied proteins; besides, it was shown that return to the normal state could also affect protein concentrations. Immersion effects on blood proteins patterned after acute reaction. Temporal profiles of alpha1-AGP, Cer, alpha2-M, Hp and ApoA were identical in all the test-subjects. Differences were mostly in the speed and amplitude of concentrations shifting. However, alpha1-AT showed a diversity of trends, whereas ApoA was common to all the subjects, three of them had this protein dropped below the bottom reference range. In two of these subject, baseline ApoA concentrations were also significantly lower in comparison to the others. These results infer that monitoring of blood alpha1-AT and ApoA in the period of adaptation to a changed environment may provide information useful for assessment of individual adaptability.

Genetic demographic characteristics and immunogenetic markers (blood groups ABO, Rhesus, MNSs, P, Duffy, Kidd, and Kell) have been studied in a group of 132 Russian cosmonauts and test subjects (CTSG). Analysis of pedigrees has shown a high exogamy in the preceding generations: almost half of the subjects have mixed ethnic background. According to the results of genetic demographic analysis, a sample from the Moscow population was used as control group (CG). Comparison between the CTSG and CG has demonstrated significant differences in genotype frequencies for several blood group systems. The CTSG is characterized by a decreased proportion of rare interlocus genotypic combinations and an increased average heterozygosity. Analysis of the distributions of individual heterozygosity for loci with codominant expression of alleles has shown that the carriers of highly heterozygous genotypes are more frequent in the CTSG. Taking into account that the CTSG has been thoroughly selected from the general population, it is concluded that heterozygosity is related to successful adaptation to a space flight.

The factors of space flight provoke some negative shifts in crew health. Improvement of the methods of diagnostics, evaluation of predisposition to diseases and correction of functional deviations is within the scope of the crew medical operations personnel. It is also a new focus of biomedical research referred to as "personalized medicine" the corner stone of which is genetic analysis. Investigations in this area are prediscovery by character; population genetics seems to be the most adequate approach. The authors give examples of candidate genes the genotypes of which could be of significance to medical operations and discuss the genetic safety of space flight. Aside from the applied aspects, the genetic investigations of space crews are of their own concernment in understanding the genetic basis of differences in biological resistance to unhealthy environment.

Protein composition of blood plasma was an object of investigation in 29 Russian cosmonauts flown on the MIR station from 125 to 366 days. Protein fractions were analyzed using acetate cellulose electrophoresis. Concentration of total protein was determined with the help of the biuret reaction on an automated analyzer. On the second day post flight, mean concentration of total protein and percentage of the protein fractions were equal to baseline values. In the interval between days 7 and 14 post flight, total protein was statistically reduced, alphal- N alpha2-globulins increased and y-globulin reduced, whereas albumin and beta-globulins were unchanged in the average. These results may point to development of an acute reaction in the early period of readaptation to the return from long-duration space flight.

Consideration is given to the facts of mutagenesis during orbital space flight and tangibility of development for and application of genetic tests to space crewmembers based on the present-day concepts about the cellular mechanisms of genome maintenance and destabilization.

Б. В. АНДРИАНОВ, Н. Л. РЕЗНИК, О. Н. ЛАРИНА ... Институт общей генетики им. Н. И. Вавилова РАН ... Государственный научный центр РФ - Институт медико-биологических проблем РАН ... Рассмотрены особенности мутагенеза в условиях космического полета на орбитальных станциях. На основе современных представлений о клеточных механизмах поддержания и нарушения геномной стабильности обсуждается возможность разработки индивидуальных тестов, позволяющих оценить степень дестабилизации генома космонавтов и их резистентность к условиям космического полета. ... Авиакосмическая и экологическая медицина. 2005. Т. 38. N 3. С. 3 - 9 ... В период пионерских работ в области космической биологии анализировалась норма реакции разных биологических видов на пребывание на борту орбитальных космических станций, а индивидуальные отклонения при этом усреднялись. В результате был сделан вывод о сравнительной безопасности пребывания человека в условиях орбитального космического полета [9]. Космонавты и биологические объекты, находящиеся на орбитальных станциях, подвергаются воздействию комплекса уникальных факторов, которые не встречаются на Земле. Степень опасности этих условий изучена далеко не в полной мере. Поскольку освоение космоса продолжается, в том числе с применением пилотируемых космических станций, в настоящее время акцент переносится на индивидуальные особенности резистентности к факторам космического полета и на возможные отдаленные последствия, в частности на мутационные повреждения зародышевой клеточной линии. ... Открытие в геномах всех эукариот системы ретротранспозонов и эндогенных ретровирусов позволяет с новой точки зрения рассмотреть проблему безопасности космических полетов. Ретротранспозоны существенно влияют на частоту мутагенеза, а их перемещения могут индуцироваться средовыми стрессовыми факторами внешней среды. ... Особенности мутагенеза в условиях космического полета ... Данные о мутагенном эффекте космического полета для растений, животных и микроорганизмов накапливались начиная с первых запусков возвращаемых космических кораблей. Статистически достоверное увеличение частоты нерасхождения Х-хромосом в мейозе у D. melanogaster было обнаружено уже в эксперименте на космическом корабле Восток-1, несмотря на кратковременность полета (108 мин) [10]. ... Позднее эти данные неоднократно подтверждались [6, 13, 48]. Обследования космонавтов также выявили мутагенное действие космического полета на человека. Измерение частоты хромосомных аберраций в группе космонавтов до и после полета на орбитальной станции Мир показало статистически значимое увеличение этого показателя [18]. Существенно, что данный вывод был получен для группы космонавтов, и его нельзя считать доказанным для каждого конкретного космонавта, учитывая индивидуальные различия резистентности. ... Хромосомные аберрации и доминантные летальные мутации отмечаются часто и у различных биологических объектов: в меристеме проростков растений [8, 33], в клеточной культуре млекопитающих [17], в культуре хлореллы [12], в развивающихся эмбрионах [52]. Влияние космического полета на орбитальных станциях на живые организмы своеобразно, причем трудно определить эффекты отдельных факторов. Выявленные частоты мутирования соответствуют величине дозы протонного и гамма-облучения порядка 104 рад. В действительности наблюдаемая доза ионизирующего облучения составляет всего несколько рад. Орбитальные космические станции обращаются на высотах 350 - 460 км. На такой высоте станцию частично защищает магнитосфера Земли. Фон ионизирующего излучения составляет около 0,025 рад/сутки и сильно колеблется при солнечных вспышках. Определенный вклад в наблюдаемую хромосомную нестабильность могут вносить невесомость [48] и галактическое излучение, содержащее тяжелые заряженные частицы с очень высокими энергиями. Эти частицы обладают сильным поражающим действием на клетку даже при невысокой усредненной дозе [1, 7]. Атмосфера защищает земную поверхность от высокоэнергетической составляющей галактического излучения, но на высоте 5000 м оно уже ощутимо, а на орбитальной станции попадание даже единичной частицы в биообъект вызовет гибель нескольких клеток и сильное, но локальное облучение их микроокружения. Изредка наблюдаемые космонавтами световые вспышки, которые не фиксируются приборами, обычно объясняют пролетом тяжелой ... стр. 3 ... заряженной частицы галактического излучения через зрительный анализатор космонавта [20]. ... Действительно, в соответствии с данным предположением хромосомные аберрации обычно выявляются в ткани группами и часто в одной клетке наблюдают множественные аберрации [14]. ... Долгое время различали только виды, чувствительные к условиям орбитального космического полета, такие как дрозофила или арабидопсис, у которых легко можно было наблюдать дестабилизацию генома и нарушения в развитии, и устойчивые виды, такие как мучной хрущак (Tribolium confusum), которые на протяжении нескольких поколений развивались на биоспутниках без каких-либо аномалий [15]. До сравнительно недавнего времени ничего не было известно о влиянии генетической компоненты на дифференциальную устойчивость разных особей одного вида к условиям космического полета, соответственно не имелось и научных оснований для разработки критериев отбора биологических объектов, обладающих максимальной устойчивостью к условиям космических полетов, хотя необходимость выработки таких критериев существует [9].

Prevention and treatment of digestive dysfunction due to hostile environments can be effected by prebiotics i.e. carbohydrates undigestible by the upper GI tract but favorable to selective stimulation of the growth and metabolizing activity of nonpathogenic commensal microflora. There are empiric evidence of the prebiotics positive action on GI cells and tissues, large intestine micro-ecology, mineral and lipid metabolism, and the immune status of humans and animals. Therefore, there is good reason to seek to develop brand new foods that would contain prebiotics, and recommendations on their use in common and extraordinary conditions.

Unlike the monolayer cultures, three-dimensional (multilayer) cultures of living cells make it possible to more closely imitate events occurring in native tissues. Rotating cultivators for three-dimensional cultures create analogous conditions of reduced gravity and, therefore, can be used in ground-based investigations of the biological effects of space flight. We have designed a disposable cultivation cell with diffused gas exchange and a device to rotate the cell at a controlled speed about the horizontal axis. Immortalized CH-fibroblasts were attached to a glass carrier pretreated with polylysine. Cultivation was performed for 2-3 days at 8 rot./min. A rapid growth of three-dimensional cell complexes was observed during the cultivation. The investigation demonstrated that multilayer cultures of immortalized CH-fibroblasts represent a convenient model for studies in cell biology and development of technologies of growing d-dimensional living cell complexes as a source of implants from autologic cells (including stem cells) thus resolving the problem of donator materials.

3-D structures were obtained at rotatory cultivation of CH immortalyzed human fibroblasts attached to glass microcarrier beads. The morphology of cells from these cultures was studied by scanning electron microscopy. A number of structural alterations in fibrillar filopodia of CH cells were revealed as compared with cells grown in stationary monolayer cultures, namely, smaller length, uneven caliber, the presence of curvatures, and disturbed branching pattern. Filopodia displayed unusual formations: protuberance-like and "mammoth's tusk"-like off-shoots, foamy spreadings in distal segments, and spiral windings of filopodia. The susceptibility of CH cells morphology to mechanical environment makes them a promising model for gravitational biology studies.

The review is dedicated to the biotechnological studies in space. The main directions of studies in the space biotechnology are the developments of life support systems, crystallogenesis of biological macromolecules, separation of proteins and cells with the help of electrophoresis as well as the studies of cellular, subcellular and molecular processes induced by the spaceflight factors effect. The experience gained in the cultivation of unicellular organisms, the selection of perspective species and strains of microorganisms, the use of them in the ecological life-support system under development is considered in detail. The development of tooling designed for performing the overall technological chain ranged from growing the cell cultures to isolating the individual macromolecules and their storage has been followed. Findings gained in the studies of the transmittance of genetic material in the microorganisms allow one to hope that in perspective the microgravity conditions will be capable of cultivating the highly effective strains of the producers.

The investigation was performed with three test-subjects who were locked in a chamber with simulated spaceflight environment for 135 days. Samples of venous plasma were collected to determine concentrations of total protein, total cholesterol (TCh), cholesterol of high density lipoproteins (HDLP), alpha 1-inhibitor of proteolysis (alpha 1-Pl), alpha 2-microglobulin (alpha 2 M), and haptoglobin (Hp). Concentrations of cholesterol of low density lipoproteins (Ch LDLP) and HDLP-LDLP ratio were calculated. Relative content of electrophoretic fractions of alpha 1- and alpha 2-globulins and a qualitative pattern of electrophoretic separation of lipoproteins were also determined. Data from the investigation showed significant decreases in alpha 1-Pl, alpha 2-M, Hp, and the alpha 2-globulin fraction that could be consequent to suppression of protein synthesis in the liver. Considering that at some points in the investigation concentrations of proteolysis-inhibiting and regulating alpha 1-Pl and alpha 2-M dropped to or went beyond the bottom margin of the norm, these effects have physiological implications. On days 2 and 7 after exit from the chamber, a weak acute-phase reaction was apparently linked with the emotional stress. Two test-subjects had chronologically differing periods of elevated TCh and Ch HDLP. Yet, the HDLP-LDLP ratios have never left boundaries of the physiological norm.

Twelve cosmonauts flown aboard the Mir orbital station for 6-12 months and twelve candidates for cosmonauts were examined in an effort to determine a degree of urolithiasis risk. Prior to flight, on flight day 310 (in one cosmonaut) and after flight, the daily urinary excretion of the components influencing lithiasis formation was determined as well as a computer-aided calculation of urine saturation by lithogenic salts was performed (Ch. Pak, USA). In the in- and postflight periods, the greater number of indices under study were negatively changed in cosmonauts. Excretion dynamics of the lithogenesis inhibitors, i.e., citrates and magnesium, is of polar directionality. Frequency of deviations from the normal indices of urolithic risk in cosmonauts is primarily conditioned by low diuresis, urine supersaturation with calcium oxalate, undissociated uric acid, brushit, hypercalciuria, and changed pH.