[Dynamics of Reaching Imago Stage by F1 Animals after Terahertz Irradiation of Parental Drosophila].

Terahertz radiation (0.1­10 THz) is increasingly becoming a factor of human habitat. The study of the consequences of radiation allows one to estimate its possible biological danger. Our data indicate that the terahertz irradiation of parental Drosophila shortens the period of embryonic development of their first generation descendants. Significant deviations of data from the control were found, when both females and males were experimental parents. The highest portion of animals with accelerated hatching as compared with the control was found in progenies from irradiated females. The shift of maximal hatching peak to an earlier period was found in descendants of both sexes. Thus, it was for the first time found on the model object (Drosophila) that the terahertz irradiation of parents can have positive or negative consequences in the first generation descendants.

Randomized clinical study: Partially hydrolyzed guar gum (PHGG) versus placebo in the treatment of patients with irritable bowel syndrome.

BACKGROUND: The treatment of Irritable bowel syndrome (IBS) is still challenging. Partially hydrolyzed guar gum (PHGG) is a known prebiotic fiber. To assess the effects of PHGG on clinical symptoms of IBS patients in a prospective randomized double blind placebo-controlled study. METHODS: Suitable IBS patients were recruited into an 18-week-long study (2 weeks of run-in, 12 weeks of treatment and 4 weeks of follow-up). They were blindly randomized to receive 6 gr of PHGG or placebo. Treatment efficacy was evaluated by the Francis Severity IBS score, the IBS quality-of-life scores and scored parameters of weekly journal of symptoms. Deltas of changes between the final and baseline scores were compared between two groups. RESULTS: Of 121 patients who underwent randomization, 108 patients (49 in the PHGG group and 59 in the placebo group) had all the data needed for intention-to-treat analysis. A 12-week administration of PHGG led to a significant improvement of journal bloating score in the PHGG group versus placebo (-4.1±13.4 versus -1.2±11.9, P=0.03), as well as in bloating+gasses score (-4.3±10.4 versus -1.12±10.5, P = 0.035). The effect lasted for at least 4 weeks after the last PHGG administration. PHGG had no effect on other journal reported IBS symptoms or on Severity and Quality of life scores. There were no significant side effects associated with PHGG ingestion. The rate of dropouts was significantly higher among patients in the placebo group compared with the PHGG group (49.15% versus 22.45%, respectively, P = 0.01). CONCLUSIONS: The results of this study support the administration of 6 g/day PHGG for IBS patients with bloating. TRIAL REGISTRATION: NCT01779765.

Enriched environment improves the cognitive effects from traumatic brain injury in mice.

To date, there is yet no established effective treatment (medication or cognitive intervention) for post-traumatic brain injury (TBI) patients with chronic sequelae. Enriched environment (EE) has been recognized of importance in brain regulation, behaviour and physiology. Rodents reared in, or pre-exposed to EE, recovered better from brain insults. Using the concussive head trauma model of minimal TBI in mice, we evaluated the effect of transition to EE following a weight-drop (30g or 50g) induced mTBI on behavioural and cognitive parameters in mice in the Novel Object Recognition task, the Y- and the Elevated Plus mazes. In all assays, both mTBI groups (30g, 50g) housed in normal conditions were equally and significantly impaired 6 weeks post injury in comparison with the no-mTBI (p<0.001 and p<0.03, respectively) and the mTBI+EE groups (p<0.001 for the 30g, and p<0.017 for the 50g). No differences were found between the control and the EE mice. Two separate finding emerge: (1) the significantly positive effects of the placement in EE following mTBI, on the rehabilitative process of the tested behaviours in the affected mice; (2) the lack of difference between the groups of mice affected by 30g or by 50g. Further studies are needed in order to characterize the exact pathways involved in the positive effects of the EE on mice recovery from mTBI. Possible clinical implications indicate the importance of adapting correlates of EE to humans, i.e., prolonged and intensive physical activity - possibly combined with juggling training and intensive cognitive stimulation.

[Terahertz radiation influence on stressed Drosophila life span].

Virgin fruit fly females and males were stressed by placement into a confined space without food for 3 hours. Part of stressed flies were subjected to terahertz irradiation (0.1-2.2 THz) during 30 min. Life span of individual flies was evaluated. Terahertz radiation had some positive influence on male survival during the stage of monotonic decrease in flies number and negative effect during the stage of relatively stable number of flies. The survival of irradiated females on the stage of sharp decline in the number of flies was higher than in stressed and control females. Authors propose that terahertz radiation has an indirect effect on gene expression and signaling pathways which control the survival and life span of Drosophila.

[Unexpected effects of genes--tumor suppressors in fruit fly ontogenesis].

Many of well-known genes-suppressors, beside protecting tissues against unlimited cells division and forming neoplastic tumors, cause various effects on animals development, vital functions, and fitness. Pleiotropic effects of these genes are due to their primary functions related with controlling of key cell processes. By making up complex compounds with other proteins, the products of genes-suppressors form cell contacts and polarity; take part in transmission of molecular signals that govern vitally important processes in a developing organism; control the cell cycle, growth, and proliferation; modulate signal paths of cell survival and preprogrammed death that protect an organism against defective structures in critical situations. Despite of tumor suppressors' vital importance, their lethal mutations are widespread in animal populations, while ensuring higher fitness under natural conditions when being in a heterozygous state.

[Survival and life span of Drosophila melanogaster in response to terahertz radiation].

Life span control is realized by an interaction of many genetic factors with environment. Due to development of new modern technologies based on non-ionized terahertz radiation (0,1-10 THz) the investigation of this radiation influence on living organisms becomes actual. In our study terahertz radiation effects on survival and life span of Oregon R line of Drosophila meanogaster were multidirectional depending on the age of the insects. Terahertz effect on survival was negative or neutral in the early life and positive in the later life. In Drosophila response to terahertz radiation sex differences were manifested. Males were not very sensitive to terahertz radiation. Irradiated female survival was increased significantly in the second half of imago life. Irradiation of Drosophila not influenced significantly on average and maximal values of life span, but the gap between the values of average life span of males and females in this group of insects was increased. Mechanisms of terahertz radiation effects on survival and life span maybe associated with changes in cellular membrane, gene expression and signaling pathways, controlling these properties.

[Parallelism and paradoxes on viability and the life span of two loss-of-function mutations: heat shock protein transcriptional regulator hsf(1) and l(2)gl tumor suppressor in D. melanogaster].

In this study we analyzed how a dosage decrease in mono- and diheterozygotes on both lethal alleles of the lgl-gene and hsfheat shock regulator influences viability and life span at optimal and high temperature 29 degrees C conditions. We found that hsf(1) (1 dosage of active hsf-factor) heterozygote animals had significantly increased viability (up to 30-39%) in case of its development from egg to imago under the stress of 29 degrees C. However, this stress-protective effect of a decreased dosage of HSF1 was suppressed in diheterozygotes, while the dosage of tumor suppressor lgl was simultaneously decreased. Under stress temperature conditions, a decrease in dosage of one of the alleles also increased the average life span and delayed aging, especially in the case of maternal inheritance of each of the loss-of-function mutations. In diheterozygotes the average life span had intermediate meanings. However, in diheterozygote males under stress conditions the positive longevity effect of hsf was suppressed in the presence of the lgl-mutation. Paradoxically, that decrease of expression of each of the studied vital genes provided a positive effect on both viability and life span under stress conditions. However, a simultaneous dosage decrease of two loss-of-function alleles in diheterozygotes resulted in disbalanced effects on the organism level. The received data indicate interaction between HSF1 and LGL gene products during ontogenesis and stress-defending processes.

[Effect of antioxidant responsive element inducing phenol on D. melanogaster life span].

The effect of water-soluble synthetic antioxidant TS-13 (sodium 3-(3'-tert-butyl-4'-hydroxyphenyl) propyl thiosulfonate) on life span of different lines of Drosophila melanogaster under normal conditions and survival under oxidative stress induced by hydrogen peroxide and paraquat has been investigated. Introduction to the diet of 1% TS-13 prolonged the life span of males and females of D. melanogaster long-living line Canton S, had no effect on short-living Oregon R life span and reduced the life span of male D. melanogaster line IgI(558)OR/Cy, heterozygous on tumor suppressor recessive lethal mutation. When flies were exposed to hydrogen perexide, TS-13 significantly enhanced Canton Smale and Oregon R female survival. Under the influence of paraquat antioxidant protected Canton S female and Oregon R flies of both sexes. Despite the fact that the anti-aging and protective properties of synthetic phenol antioxidant TS-13 depend essentially on the genotype and gender, in the extreme conditions of oxidative stress its positive effect pronounced.

[Variability of the exogenic antioxidant effect on survival: modeling in Drosophila lines with different lifespan and l(2)gl-tumor suppressor dosage].

Different exogenic antioxidants and geroprotectors are used to decrease age abnormalities and enhance the human life span. However, the antioxidant effect on lifespan is variable and requires detailed analysis. In the present report, we modeled in Drosophila the peculiar character of action of various doses of a new phenol antioxidant TC-13. We studied the TC-13 effect on aging of two Drosophila lines with genetically determined contrast lifespan dynamics. In addition, we tested the TC-13 antioxidant influence on the background of heterozygozity on the loss-of-function mutation of the l(2)gl tumor suppressor. The differing effect of TS-13 on LS, the character of which depends on the antioxidant dosage, genotype of line, and sex of Drosophila, was found. TS-13 in the concentration 0.2% did not affect the lifespan in all studied lines and decreased survival, whereas the antioxidant in a concentration of 1% positively affected the lifespan in both males and females of long-living lines. The antioxidant effect on animal lines with a smaller dose of tumor suppressor l(2)gl resulted in a decrease of the lifespan.

[Population genetic analysis of Drosophila melanogaster longevity: similar effects of endosymbiont Wolbachia and tumor suppressor lgl under conditions of temperature stress].

Before, it has been shown that keeping of Drosophila wild populations under temperature stress leads to prevalence of deletion alleles of tumor suppressor lgl, and higher survival of heterozygous lgl(-)/+ females descendants (haploadaptivity). On the other hand, recent investigations have demonstrated that an additional dose of lgl gene in transgenic males has inadaptive effect--cytoplasmic incompatibility, caused by the gene, is similar to the effect caused by the widespread endosymbiont Wolbachia. Both triple dose of lgl and Wolbachia infection invoke hyperexpression of some cytoskeleton proteins which leads to sperm defects and sterility of hybrid zygotes. Proceeding from this similarity, we studied the Wolbachia effect on Drosophila longevity (LG) depending on the bacteria strain, host genotype and sex, and maintenance temperature. With use of tetracycline, six Wolbachia-free lines were produced, analogical to the infected wild ones. After analyzing LG under optimal temperature conditions (25 degrees C), the lines were subdivided into three genotypic groups, differing by the LG, mortality dynamics, and type of sexual dimorphism. Under conditions of temperature stress (16 degrees C and 29 degrees C) the lines ranks with respect to LG remained as they were, though the distinctions between them were smoothed out. In other words, the effect of the genes regulating LG parameters depends on maintenance conditions. The research also revealed sharp genetic distinctions between LG parameters of two standard laboratory lines Canton and Oregon that were taken as the control. These distinctions do not disappear in crossings. In the infected lines, in seven experiments out of thirty (20% of cases) significant sex-specific influence of Wolbachia on LG was revealed, namely, in two combinations at the optimal temperature 25 degrees C, and in five combinations at stress temperatures. Under the optimal temperature conditions the endosymbiont shortened its host LG in both cases, while at stress temperatures, in four cases out of five, it extended the host LG. Females of the long-living line Bi90 (wMel) from a mountain Kirghiz population appeared to be especially sensitive to the infection carriage--their endosymbiont-caused LG extension was observed both under cold and heat stresses. This result is analogues to the effect of diminishing the oncosupressor lgl dose. In both cases LG extends only under temperature stress, and this positive effect is sex-specific.

[Genetic and epigenetic effects of lgl-tumor suppressor mutations on longevity under heat stress].

Human populations are polymorphic for risk factor mutations predisposing to diseases and cancer. The evolutionary conservative gene, tumor suppressor lethal (2) giant larvae (lgl), whose null variants are widespread in natural Drosophila populations, can be used as a model to study this phenomenon. We studied the effect of deletion and insertion mutant alleles of the lgl gene on the survival and longevity of their carriers depending on the genotype, cross direction, and action of permanent or impulse temperature stress. Under constant temperature stress, the viability and longevity of lgl/+ deletion heterozygotes increased compared to the control flies carrying two alleles of this gene. This haploid effect was maternally mediated. Exposure of deletion heterozygotes at successive oogenesis stages to moderate impulse temperature stress affected progeny survival in a similar way. The effect of impulse heating at the preembryonal stage was bidirectional: positive in the case of impulse warming of mature eggs and negative during egg differentiation. However, in both cases, deletion of one allele of the tumor suppressor gene in lgl/+ females increased survival of the next generation and delayed senescence. These data were compared to similar epigenetic transgeneration effects reported earlier for humans.

The effect of a water exercise program on bone density of postmenopausal women.

AIM: The aim of the present study was to examine the effect of a seven months program of water exercise, on bone mineral density (BMD) in postmenopausal women. METHODS: Thirty-five postmenopausal women trained for seven months for three one-hour sessions per week. DEXA test findings for vertebrae L2-L4 showed that although the time factor had a significant effect only on the bone mineral content (BMC), (4.61 P < 0.05), the interaction of time group was found to be significant for each of the variables: BMD (9.25 P < 0.01), BMC (7.99 P < 0.01), z-score (5.35 P < 0.05) and t-score (9.41 P < 0.01). RESULTS: These interactions indicate a general trend towards maintenance or improvement of bone status in the experimental group and a trend towards declining bone status for the control group. DEXA test findings for femoral neck density indicated no significant differences between the groups pre and post treatment. However a significant interaction was found for BMC (8.08 P < 0.01) in the right leg indicating an increase trend in BMC in the experimental group and a trend towards decrease for the control group. CONCLUSION: The findings of the present study support the hypothesis that it is possible to plan and execute a water exercise program that has a positive effect on bone status of post-menopausal women.

Folic acid and its metabolites modulate IGF-I receptor gene expression in colon cancer cells in a p53-dependent manner.

The insulin-like growth factor-I receptor (IGF-IR) has an important role in colorectal cancer development and progression. IGF-IR displays a potent anti-apoptotic activity and is overexpressed in primary tumors and colon cancer-derived cell lines. Folic acid, a member of the vitamin B family, is a chemopreventive agent whose deficiency has been linked to an enhanced colon cancer risk. The present study was aimed at testing the hypothesis that part of the modulatory effect of folic acid on malignant transformation may be attributed to its ability to regulate IGF-IR gene expression. Regulation of IGF-IR gene expression by folic acid was assessed using western blots, RT-PCR, transient transfections and chromatin immunoprecipitation assays. Activation of the IGF-IR signaling pathway was evaluated by measuring phosphorylation of ERK, and apoptosis was assayed using poly (ADP-ribose) polymerase cleavage and annexin V-FITC staining. Results obtained showed that folic acid induced a dose-dependent decrease in IGF-IR protein and mRNA levels in the HCT116 +/+ colon cancer cell line. This effect was associated with a significant reduction in IGF-IR promoter activity. Similar effects were elicited by the folic acid metabolites dihydrofolic acid and tetrahydrofolic acid. In addition, folic acid abrogated the IGF-I-stimulated phosphorylation of the downstream signaling molecule ERK1/2 and exhibited a pro-apoptotic activity. Moreover, folic acid induced a significant decrease in Sp1 binding to the IGF-IR promoter region. Finally, folic acid had no effect in wild-type p53-depleted HCT116 -/- and Caco-2 cells. In conclusion, the mechanism of action of folic acid involves regulation of IGF-IR gene expression. The ability of folic acid to downregulate the IGF-I signal transduction pathway may allow the micronutrient to function as a chemopreventive agent. Folic acid deficiency, on the other hand, may lead to increased IGF-IR gene expression, with ensuing pathological activation by endocrine and/or autocrine/paracrine IGF-I.

[Regulation of development of wing venation in Drosophila melanogaster by a network of signalling pathways].

The paradigm of contemporary phenogenetics consists in that ontogenetic development of animals is regulated by a set of cell signalling pathways. The main signalling pathways controlling the wing development are Hedgehog, Notch, Wingless, Epidermal growth factor receptor, and Decapentaplegic. Expression of many genes in the imaginal disc is specific for both cells competent for transformation into veins and adjacent cells forming wing cells. Individual genetic programs control differentiation of each longitudinal vein and determination of its position on the wing. The gene net plays an important role in wing venation of D. melanogaster. Mutations causing some ectopic expressions of transcriptional factors and the activities of signalling cascades are, possibly, involved in phylogenetic transformation of the insect wing.

[Animal ontogenetic cell signaling pathways by the example of Notch cascade of Drosophila melanogaster]. / Signal'nye puti kletok v ontogeneze zhivotnykh na primere Notch kaskada u Drosophila melanogaster.

Intercellular communications are coordinated in developing vertebrates and invertebrates embryos by a few signaling pathways. Structural and functional components of the pathways are encoded by cascade of genes. The signal transduction from cell surface to the nucleus is the common feature of these pathways. It is initiated by interaction of secreted ligand (signal) with the outer segment of transmembrane receptor. Then, activation of the intracellular segment of receptor provides modification of signal transducers in cytoplasm including transcription factors that regulates expression of target genes. Cell signal transduction development is conserved between species. In individual organism signal pathways provide various responses due to a time or spatial disjunction of gene expression. Morphogenetic features, genetic structure and signal transduction sequence of events are considered by the example of Notch cascade of Drosophila melanogaster.

Correction of anemia in patients with congestive heart failure increases resting energy expenditure.

BACKGROUND & AIM: Congestive heart failure (CHF) and anemia were reported to affect resting energy expenditure (REE). The aim of this study was to evaluate the effect of the correction of anemia on REE in subjects with CHF. PATIENTS AND METHODS: Nine anemic patients with compensated CHF and CRF were studied before and after correction of anemia. REE was studied by an open circuit indirect calorimeter, body composition by dual-energy-X-ray absorption and total body and extracellular water by multi-frequency bioelectrical impedence. Four anemic and 5 non-anemic CHF patients who did not receive any new treatment served as controls. RESULTS: After the correction of their anemia patients tended to increase weight (P<0.06), but no significant changes were observed in body composition. Daily caloric intake increased significantly (P<0.02). Ejection fraction increased (P<0.05) and pulse rate decreased significantly (P<0.001). REE and REEPP were in the normal range before correction but increased significantly afterwards (1402+/-256 vs. 1496+/-206 kcal/d, and 101+/-9 vs. 109+/-8, P<0.023 and P<0.006, respectively). CONCLUSION: Correction of anemia in patients with CHF increases their REE. This can be related either to improved tissue oxygenation and/or to increased caloric intake.

Nasojejunal feeding in hyperemesis gravidarum--a preliminary study.

Hyperemesis gravidarum is a severe form of nausea and vomiting during the first trimester of pregnancy. Our objective was to assess the feasibility of nasojejunal feeding in our patients. Eleven pregnant women aged 23-46 years with hyperemesis gravidarum, persisting in spite of an in-hospital treatment of 2-15 days by intravenous fluids and antiemetic drugs and accompanied by weight loss, consented to have a nasojejunal feeding tube inserted endoscopically. Mean in-hospital weight loss prior to tube insertion was 2.2+/-1.1 kg (range 0.9-5.1 kg). A clear reduction in the extent of vomiting was already apparent within the first 48 h after tube insertion, but vomiting ceased completely after a mean of 5+/-4 days (range 1-13 days). Weight gain was recorded in six patients who stayed on tube feeding for more than 4 days. Patients were encouraged to start drinking and eating along tube feeding after 3-4 days. Ceasing vomiting and a concomitant sufficient oral intake of at least 1000 kcal/day resulted in the decision to remove the tube after 4-21 days. In three cases, however, the tube was expelled by recurrent vomiting after 1-4 days, or was blocked as in one case. The tube was not reintroduced and patients did not resume vomiting. There were no complications associated with this feeding approach in this population. Only one patient was readmitted. None of the rest resumed vomiting after tube withdrawal.The above suggests that nasojejunal enteral feeding can be an effective option in hyperemesis gravidarum persisting despite intravenous fluids and antiemetic drugs.

Increased resting energy expenditure in subjects with Emery-Dreifuss muscular dystrophy.

We have studied changes in energy expenditure and body composition in adult males with Emery-Dreifuss muscular dystrophy, age-matched males with hyperCKemia and age-matched healthy controls. All participants were studied twice, 2-3 years apart. Resting energy expenditure was studied by indirect calorimetry, lean body mass and body fat by dual X-ray absorptiometry, and muscle mass was estimated based on 24-h urinary creatinine excretion. At baseline and 2-3 years later, body fat was significantly higher (P < 0.011 and P < 0.003, respectively) and lean body mass significantly lower (P < 0.024 and P < 0.012, respectively) in patients with Emery-Dreifuss muscular dystrophy as compared to subjects with hyperCKemia and healthy controls. Resting energy expenditure, over the study period, increased significantly in patients with Emery-Dreifuss muscular dystrophy (P < 0.031), but not in patients with hyperCKemia nor in healthy controls. Our study suggests that patients with Emery-Dreifuss muscular dystrophy may have increased energy expenditure relative to healthy subjects. If not met by increased caloric intake, this greater energy expenditure may partially contribute to a further deterioration in their muscle performance.

[Multiple allelism of the net gene in Drosophila melanogaster and Drosophila simulans]. / Mnozhestvennyi allelizm po genu net u Drosophila melanogaster i Drosophila simulans.

The net gene mutations are known to cause abnormal pattern of veining in all wing regions except for the first posterior cells. In natural populations of Drosophila melanogaster, the net alleles were identified, which differ in phenotypic expression from standard mutations. The mutants net-extra-analis from a population Belokurikha-2000 have only a single additional vein in the third posterior cell. A line from Chernobyl-1986 population have another nontypical allele netCh86 and shows a lower degree of abnormalities than that usually observed. About 10% of these flies have an additional vein fragment in the first posterior cell. In both males and females of D. simulans population Tashkent-2001, which exhibit netST91 mutation, a net of additional veins is formed as a specific additional fragment in the first posterior cell. The pattern of veining conferred by alleles net-extra-analis and netCh86 is altered to a lesser extent; these alleles are dominant with respect to alleles net2-45 and netST91, which cause more abnormalities. The heterozygotes for alleles netST9 and netCh86 and for Df(2) net62 deletion have an additional fragment in the first posterior cell and show similarly strong deviations from normal wing vein pattern. The natural net alleles correspond, presumably, to different molecular gene defects involved into uncertain local interactions with numerous modifying factors and other genes that specify the wing vein pattern.

[Interzonal microtubules and meiotic restitution in the dycots]. / Interzonal'nye mikrotrubochki i meioticheskaia restitytsiia dvudol'nykh.

Dynamics of the microtubule cytoskeleton at mobile stages of female meiosis in the dycots was studied. A new stage of MT rearrangement was revealed referred to as centrifugal movement of interzone MTs at telophase 1. A disruption of this process leads to the displacement of daughter nuclei to the equatorial region and a common (fused) spindle formation. This is the cause of dyad (instead of tetrads) formation in mutant ps of Beta vulgaris.