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The V3 loop on gp120 from human immunodeficiency virus type 1 (HIV-1) is a focus of many research groups involved in anti-AIDS drug development because this region of the protein is a principal target for neutralizing antibodies and a major determinant for cell tropism and syncytium formation. In this study, the nucleotide sequences of the env gene region coding the V3 loop were determined by DNA sequencing methods for four novel HIV-1 strains that circulate in the countries of Eastern Europe, such as Russia, Belarus, Ukraine, etc. Based on the empirical data obtained, the 3D structures of the V3 loops associated with these viral modifications were generated by computer modeling and then compared to discover similarities in the spatial arrangement of this functionally important site of gp120. Despite the HIV-1 genetic variety, several regions of the V3 loop that contain residues critical for cell tropism were shown to be structurally invariant, which may explain its exceptional role in a co-receptor usage. These data together with those on the biological activity of the V3 individual residues clearly show that these conserved structural motifs of gp120 represent potential HIV-1 weak points most suitable for therapeutic intervention.  相似文献   
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Impairments of mitochondrial genome are associated with a wide spectrum of degenerative diseases, development of tumors, aging, and cell death. We studied the content of mitochondrial DNA (mtDNA) with mutations and the total content of mutations in the brain and the spleen of mice subjected to X-ray irradiation at a dose of 1–5 Gy at 8–28 days after treatment. In these mice, we studied the number of mutant copies of extracellular mtDNA (ec-mtDNA) and its total content in blood plasma. We estimated mutations in control and irradiated mice using cleavage of heteroduplexes prepared by hybridization of PCR amplicons of mtDNA (D-loop region) mediated by CEL-I endonuclease, an enzyme that specifically cleaves unpaired bases. Changes in the total number of mtDNA copies relative to nuclear DNA were assessed by real time PCR using the ND-4 and GAPDH genes, respectively. We found that the number of mutant mtDNA copies was significantly increased in the brain and the spleen of irradiated mice and reached the maximum level at the eighth day after treatment; it then decreased by the 28th day after treatment. In nuclear genes similar to mutagenesis, mutagenesis of mtDNA in the brain and spleen tissues linearly depended on irradiation dose. In contrast to mutant nuclear genes, most mutant mtDNA copies were eliminated in the brain and spleen tissues, whereas the total content of mtDNA did not change within 28 days after irradiation. Our data show that, during this period, a high level of ec-mtDNA with mutations was observed in DNA circulating in blood plasma with the maximum level found at the 14th day. We suppose that mutant mtDNA copies are eliminated from cells of animals subjected to irradiation during the posttreatment period. Higher content of ec-mtDNA in blood plasma can be considered as a potential marker of radiation damage to the body.  相似文献   
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Periphyton (epilithon) gross primary production (GPP) was estimated using the DCMU-fluorescence method in the Yenisei River. In the unshaded littoral zone, chlorophyll a concentration (Chl a) and GPP value varied from 0.83 to 973.74 mg m−2and 2–304,425 O2 m−2 day−1 (0.64–95 133 mg C m−2 day−1), respectively. Positive significant correlation (r = 0.8) between daily GPP and periphyton Chl a was found. Average ratio GPP:Chl a for periphyton was 36.36 mg C mg Chl a m−2 day−1. The obtained GPP values for the Yenisei River have a high significant correlation with values predicted by a conventional empirical model for stream periphyton. We concluded that the DCMU-fluorescence method can be successfully used for measuring of gross primary production of stream phytoperiphyton at least as another useful tool for such studies.  相似文献   
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The model of the structural complex of cyclophilin B belonging to the immunophilins family with the HIV-1 subtype A V3 loop presenting the principal neutralizing determinant of the virus gp120 envelope protein as well as determinants of cell tropism and syncytium formation was generated by molecular docking methods. Based on the conformational and energy characteristics of the built complex, computer-aided design of the polypeptide able to block effectively the functionally crucial V3 segments was implemented. Analysis of the results obtained in this study and literature data suggests that the generated molecule represents a promising pharmacological substance, which may be used as the basis structure for realization of the protein engineering projects aimed to develop effective drugs for anti-AIDS therapy.  相似文献   
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Dynamics of changes of and plasma corticosterone was studied in both male and female rats after intraperitoneal injections of adrenaline at a dose of 20 micrograms per 100 g body weight. The control rats were injected with saline. Animals were decapitated 10, 30, 60, 120, 180 and 240 min after the injections. The specific effect of adrenaline was revealed in the first 10 min of adrenaline injection. This effect was significantly increased to 30-60 min after termination of saline--induced activation of the pituitary-adrenal axis. Both saline and adrenaline caused more significant increases in corticosterone levels in female rats than in male ones. There was a significant delay in the return of corticosterone to resting levels in males compared to that in females. It is supposed that the almost two-fold difference in peak plasma corticosterone concentrations observed after stressors may be associated with increased responsiveness of the female hypothalamus with respect to adrenaline secretion.  相似文献   
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Abstract: Many articulated brachiopods experience marked life habit variations during ontogeny because they experience their fluid environment at successively higher Reynolds numbers, and they can change the configuration of their inhalant and exhalant flows as body size increases. We show that the extant brachiopod Terebratalia transversa undergoes a substantial ontogenetic change in reorientation governed by rotation around the pedicle. T. transversa′s reorientation angle (maximum ability to rotate on the pedicle) decreases during ontogeny, from 180 degrees in juveniles to 10–20 degrees in individuals exceeding 5 mm, to complete cessation of rotation in individuals larger than 10 mm. Rotation ability is substantially reduced after T. transversa achieves the adult lophophore configuration and preferred orientation with respect to ambient water currents at a length of 2.5–5 mm. We hypothesize that the rotation angle of T. transversa is determined mainly by the position of ventral and dorsal points of attachment of dorsal pedicle muscles relative to the pedicle. T. transversa shows a close correlation between the ontogenetic change in reorientation angle and ontogeny of morphological traits that are related to points of attachment of dorsal pedicle muscles, although other morphological features can also limit rotation in the adult stage. The major morphological change in cardinalia shape and the observed reduction of rotation affect individuals 2.5–10 mm in length. The position of ventral insertions of dorsal pedicle muscles remains constant, but contraction of dorsal pedicle muscles is functionally handicapped because dorsal insertions shift away from the valve midline, rise above the dorsal valve floor, and become limited by a wide cardinal process early in ontogeny (<5 mm). The rate of increase of cardinal process width and of distance between dorsal pedicle muscle scars substantially decreases in the subadult stage (5–10 mm), and most of the cardinalia shell traits grow nearly isometrically in the adult stage (>10 mm). T. transversa attains smaller shell length in crevices than on exposed substrates. The proportion of small‐sized individuals and population density is lower on exposed substrates than in crevices, indicating higher juvenile mortality on substrates prone to grazing and physical disturbance. The loss of reorientation ability can be a consequence of morphological changes that strengthen substrate attachment and maximize protection against biotic or physical disturbance (1) by minimizing torques around the pedicle axis and/or (2) by shifting energy investments into attachment strength at the expense of the cost involved in reorientation.  相似文献   
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One of the central paradigms of ecology is that only about 10% of organic carbon production of one trophic level is incorporated into new biomass of organisms of the next trophic level. Many of energy-yielding compounds of carbon are designated as ‘essential’, because they cannot be synthesized de novo by consumers and must be obtained with food, while they play important structural and regulatory functions. The question arises: are the essential compounds transferred through trophic chains with the same efficiency as bulk carbon? To answer this question, we measured gross primary production of phytoplankton and secondary production of zooplankton and content of organic carbon and essential polyunsaturated fatty acids of ω-3 family with 18–22 carbon atoms (PUFA) in the biomass of phytoplankton and zooplankton in a small eutrophic reservoir during two summers. Transfer efficiency between the two trophic levels, phytoplankton (producers) and zooplankton (consumers), was calculated as ratio of the primary production versus the secondary (zooplankton) production for both carbon and PUFA. We found that the essential PUFA were transferred from the producers to the primary consumers with about twice higher efficiency than bulk carbon. In contrast, polyunsaturated fatty acids with 16 carbon atoms, which are synthesized exclusively by phytoplankton, but are not essential for animals, had significantly lower transfer efficiency than both bulk carbon, and essential PUFA. Thus, the trophic pyramid concept, which implicitly implies that all the energy-yielding compounds of carbon are transferred from one trophic level to the next with the same efficiency of about on average 10%, should be specified for different carbon compounds.  相似文献   
10.
The energy metabolism changes in isolated hepatocytes at different levels of proton conductivity of cellular membranes were studied. The low doses of the uncoupler which increased hepatocyte respiration rate but did not markedly affect the mitochondrial potential caused: the reduction in total adenine nucleotide contents (ATP + ADP + AMP), the oxidation of mitochondrial NADH, the increase in the rates of glycogenolysis and net flux via phosphofructokinase without any changes in the rates of glucose, lactate and pyruvate accumulation. High doses of the uncoupler which eliminated completely oxidative phosphorylation decreased Atkinson's energy charge down to 0.5, reduced cytoplasmic NADH, induced a further increase in the glycogenolysis rate, increased the rates of glucose and lactate accumulation, heightened glucose-6-phosphate content and lowered contents of 3-phosphoglycerate and 2-oxoglutarate.  相似文献   
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