Can Shrews Avoid Competition When Hutchinson's Ecological Rule Is Disobeyed?

It is established that Hutchinson's ratio of the weights and sizes of the body and foraging organs in similar species is not fully obeyed in shrew species of the genus Sorex. Similarity in the centroid size of the mandible was observed in the large species S. isodon and S. araneus. Differences in the shape of the mandible, which is intensely used in foraging, were detected between the species by geometric morphometrics. Interspecific differences were found in mandibular indices, which reflect trophic specialization and functional features of the mandibles. Shrews can therefore avoid competition even when Hutchinson's rule is violated. The avoidance is due to a transformation and specialization of the mandible and changes in prey capture methods and diet, rather than to changes in size. Hutchinson's ecological rule is thus not mandatory, but is only one of the conditions for reducing competition between closely related species.

Lifespans of Fur Color Morphs in Polymorphic Populations of the Mole Vole and the Hypothesis of Adaptive Polymorphism.

Different lifespans were for the first time demonstrated for three (brown, bicolor, and black) fur color morphs in ten mole vole populations of the Volga, Ural, and Trans-Ural regions. With the longest lifespan of 5 years in the species, morphs that numerically dominate in a population can live 1-4 years longer than accompanying morphs. Spearman's correlation coefficient between the longest lifespan of the morphs and their proportion in the population was Rsp = 0.81 (p < 0.0001). A number of morphological and functional features were identified in the color morphs. The findings are of general biological significance, confirming the hypothesis of adaptive polymorphism. Evolutionary and ecological mechanisms whereby selective advantages develop in morphs (as probable ecomorphs) are possible to evaluate using the morphs as a natural model of the initial step of sympatric form development in different parts of the range.

The contribution of PARP1, PARP2 and poly(ADP-ribosyl)ation to base excision repair in the nucleosomal context.

The regulation of repair processes including base excision repair (BER) in the presence of DNA damage is implemented by a cellular signal: poly(ADP-ribosyl)ation (PARylation), which is catalysed by PARP1 and PARP2. Despite ample studies, it is far from clear how BER is regulated by PARPs and how the roles are distributed between the PARPs. Here, we investigated the effects of PARP1, PARP2 and PARylation on activities of the main BER enzymes (APE1, DNA polymerase ß [Polß] and DNA ligase IIIα [LigIIIα]) in combination with BER scaffold protein XRCC1 in the nucleosomal context. We constructed nucleosome core particles with midward- or outward-oriented damage. It was concluded that in most cases, the presence of PARP1 leads to the suppression of the activities of APE1, Polß and to a lesser extent LigIIIα. PARylation by PARP1 attenuated this effect to various degrees depending on the enzyme. PARP2 had an influence predominantly on the last stage of BER: DNA sealing. Nonetheless, PARylation by PARP2 led to Polß inhibition and to significant stimulation of LigIIIα activities in a NAD+-dependent manner. On the basis of the obtained and literature data, we suggest a hypothetical model of the contribution of PARP1 and PARP2 to BER.

Analysis of Geographical Variability of Morphogenetic Trajectories Using the Mole Vole (Ellobius talpinus Pall.) as an Example.

ABSTTRACT: -Using the methods of geometric morphometrics, we have revealed the phenomenon of geographical variability of morphogenetic trajectories when doing side-by-side comparisons of mandibular shapes in individuals of different ages from three southern Trans-Ural populations of the mole vole (Ellobius talpinus Pall.) in the common morphospace.

Effect of Human XRCC1 Protein Oxidation on the Functional Activity of Its Complexes with the Key Enzymes of DNA Base Excision Repair.

Base excision repair (BER) ensures correction of most abundant DNA lesions in mammals. The efficiency of this multistep DNA repair process that can occur via different pathways depends on the coordinated action of enzymes catalyzing its individual steps. The scaffold XRCC1 (X-ray repair cross-complementing protein 1) protein plays an important coordinating role in the repair of damaged bases and apurinic/apyrimidinic (AP) sites via short-patch (SP) BER pathway, as well as in the repair of single-strand DNA breaks. In this study, we demonstrated for the first time in vitro formation of the ternary XRCC1 complex with the key enzymes of SP BER - DNA polymerase ß (Polß) and DNA ligase IIIα (LigIIIα) - using the fluorescence-based technique. It was found that Polß directly interacts with LigIIIα, but their complex is less stable than the XRCC1-Polß and XRCC1-LigIIIα complexes. The effect of XRCC1 oxidation and composition of the multiprotein complex on the efficiency of DNA synthesis and DNA ligation during DNA repair has been explored. We found that formation of the disulfide bond between Cys12 and Cys20 residues as a result of XRCC1 oxidation (previously shown to modulate the protein affinity for Polß), affects the yield of the final product of SP BER and of non-ligated DNA intermediates (substrates of long-patch BER). The effect of XRCC1 oxidation on the final product yield depended on the presence of AP endonuclease 1. Together with the data from our previous work, the results of this study suggest an important role of XRCC1 oxidation in the fine regulation of formation of BER complexes and their functional activity.

Role of Oxidation of XRCC1 Protein in Regulation of Mammalian DNA Repair Process.

The influence of XRCC1 protein oxidation on the modification of proteins catalyzed by poly(ADP-ribose)polymerases (PARP1 and PARP2) was studied for the first time. XRCC1, PARP1, and PARP2, functioning as scaffold proteins, are responsible for coordination of multistep repair of most abundant DNA lesions. We showed that the XRCC1 oxidation reduces the efficiency of its ADP-ribosylation and the protein affinity for poly(ADP-ribose). The ADP-ribose modification of various XRCC1 forms is enhanced in the presence of DNA polymerase ß (Polß), capable of forming a stable complex with XRCC1. Oxidation suppresses the inhibitory effect of XRCC1 and its complex with Polß on the automodification of PARP1 and PARP2, which may enhance the efficiency of repair. The results of this study indicate that the oxidation of XRCC1 plays a role in fine regulation of poly(ADP-ribosyl)ation levels of proteins and their coordinating functions in DNA repair.

Morphogenetic Effects of Resettlement of Mole Voles (Ellobius talpinus Pall., 1770) from the Southern Population to the Northern Boundary of the Species Range.

Geometric morphometry has been used to reveal transformations of mandible morphogenesis in the offspring of mole voles resettled to the northern part of the species range from a southern population. The transformations were new compared to both the original (southern) and the aboriginal (northern) populations. A significant increase in the intragroup morphological disparity estimated by the mean nearest neighbor distance (MNND) in the resettled animals compared to both aboriginal populations is an indirect indication of an increased developmental instability in the resettled animals exposed to new climatic conditions.

[Inhibitory Properties of Nitrogen-Containing Adamantane Derivatives with Monoterpenoid Fragments Against Tyrosyl-DNA Phosphodiesterase I].

It was found that compounds combining diazaadamantane and monoterpenoid fragments are potent inhibitors of new structural type of human recombinant DNA repair enzyme Tyrosyl-DNA phosphodiesterase I (Tdp1). It was demonstrated that the inhibition efficiency depended on the length and flexibility of the aliphatic chain of the substituent.

[Quality of life and cognitive functions in patients with end-stage renal failure on hemodialysis using a succinate-containing dialyzing solution].

AIM: To assess changes in quality of life (QL) and cognitive functions in patients with end-stage renal failure (ESRF) treated with hemodialysis using a succinate-containing dialyzing solution (SCDS). SUBJECTS AND METHODS: Sixty-seven patients with ESRF on hemodialysis using SCDS were examined. The investigators determined QL indicators using a Russianized variant of the Kidney Disease Quality of Life Short Form (KDQOL-SF) and the indicators of cognitive functions by the Benton visual retention test intended to evaluate visual short-term memory. The 6-minute walk test was used to evaluate exercise tolerance. The patients were examined before and 6 months after initiation of SCDS use. RESULTS: Following 6 months of SCDS treatment, the patients showed positive changes in a number of QL indicators. Their exercise capacity (p = 0.03) and the quality of sleep (p = 0.03), and social interaction (p = 0.02) were improved. The magnitude of the complaints related to disease and treatment decreased (p = 0.001). The level of patient frustration was reduced (p < 0.001). Different limitations associated with chronic kidney disease and dialysis therapy came to disturb the patients to a lesser degree (p = 0.02). The Bentoin visual retention test exhibited fewer errors (p = 0.04). CONCLUSION: Hemodialysis treatment with SCDS improved a number of QL indicators and cognitive functions in the patients.

[Clinical and laboratory evaluation of the efficiency of chronic hemodialysis treatment using acidosuccinate in patients with terminal renal failure].

AIM: To evaluate the efficiency of using a succinate-containing dialysis solution (SCDS) in terminal renal failure patients treated with chronic hemodialysis (CHD). SUBJECTS AND METHODS: Ninety patients from two hemodialysis units took part in the crossover study and were allocated to 2 groups. For 6 months, study group patients received CHD using SCDS and control group patients had CHD with a standard bicarbonate dialysis solution after 3-month washout period followed by decussation. The time course of changes in blood biochemical parameters, 24-hour ECG monitoring data, and quality of life indicators were estimated in the patients. RESULTS: After using acidosuccinate during hemodialysis, there was a significant reduction in the predialysis serum level of inorganic phosphate, a calcium phosphate product, gamma-glutamyl transpeptidase, urea, and aldosterone as compared to the control group. The blood concentration of total protein was also increased. After 6-month administration of acidosuccinate, the patients showed reductions in systolic blood pressure, heart rate, and the frequency and duration of ST-segment depression episodes. There were positive changes in the quality of life of patients according to the KDQOL-SF questionnaire. CONCLUSION: The use of SCDS in patients with CHD causes positive changes in a number of laboratory parameters and improves the physical and general status, and quality of life of patients.

[Chemotherapy of tuberculosis: problems and perspectives].

Challenges of tuberculosis chemotherapy under conditions of high drug resistant (DR) tuberculosis burden are discussed. Ultimate results of treatment by standard regimens of 1658 patients with new tuberculosis cases and relapses were analyzed. Favorable ultimate results were observed among both patients with new tuberculosis cases and relapses having drugs sensitivity. Efficacy of tuberculosis treatment by standard regimens of chemotherapy is decreasing as a result of DR amplification. Risk factors of unfavorable ultimate result among pulmonary tuberculosis patients are primary resistance to isoniazid (OR = 2.1) and multiple drug resistance of M. tuberculosis (OR = 8.0). Earlier onset of treatment and correct individual therapy with second line drugs as a result of rapid methods of DR tuberculosis diagnostics are those approaches which provide the best therapeutic effect among multiple drug resistant tuberculosis patients both in culture conversion (97.7%) and cavity closure rate (82.7%).

[Evaluating regional system of occupational medical service organization].

The article covers analysis of regional occupational pathology service designed for primary medical and sanitary care for workers and specialized care in occupational pathology center. The authors proved cooperation between occupational pathology center and Occupational Pathology department of the Medical University to be optimal.

[Diagnosis of tuberculous pericarditis in patients with HIV-infection].

AIM: To study specific features of the incidence, course and diagnosis of tuberculosis pericarditis (TP) in patients with HIV-infection. MATERIAL AND METHODS: We analysed results of diagnosis of 304 primary patients with organ tuberculosis in combination with HIV infection treated in Moscow tuberculosis hospital N 7 in 2006-2010. CD4 lymphocyte count median in tuberculosis onset was 140 in 1 mcl, 63.2% patients had a baseline level of CD4 lymphocytes under 200 in 1 mcl. RESULTS: TP incidence in primary patients with tuberculosis and HIV-infection was 6.3% while in patients with tuberculosis of multiple locations--13.7%. Cardiac tamponade symptoms were registered only in one case. Pericardial effusion was classified as moderate and large in 68.4% patients. Patients with large effusion (more than 20 mm in isolation of pericardial leaves) have undergone diagnostic pericardiocentesis and, in some cases, microdrainage. Sensitivity of exudate test for M. tuberculosis DNA with use of polymerase chain reaction was 100%. CONCLUSION: Active surgical policy in massive effusion tuberculosis pericarditis in line with adequate antituberculosis and antiretrovirus therapy in HIV-infected patients results in rapid resorption of the effusion.

[Analysis of lethal outcomes in patients with newly-diagnosed tuberculosis of the respiratory organs in combination with HIV-infection].

AIM: To analyse lethal outcomes in patients with newly-diagnosed respiratory tuberculosis comorbid with HIV-infection depending on initial count of CD4+ lymphocytes. MATERIAL AND METHODS: Of 304 HIV patients with newly-diagnosed tuberculosis treated in Moscow Tubercusis Hospital N 7 in 2006-2010, 40 (13.2%) patients died. Tuberculosis diagnosis was made after detection of M. tuberculosis (MT) by different tests, MT DNA in different biological material, histological verification or by effectiveness of specific antituberculous therapy. Postmortem examinations were made according to the protocol. RESULTS: Significant differences were detected in patients with initial count of CD4+ lymphocytes less than 50 in 1 mcl. Specific CNS affection was found in patients with initial lymphocyte count CD4+ less than 100 in 1 mcl. Most of autopsy examinations registered generalized acutely progressive tuberculosis with multiple lesions of internal organs and lymph nodes (LN). Microscopy revealed obscure morphological picture of specific inflammation with prevalence of alternative-exudative tissue reactions in the absence of a productive inflammation component. Cases with submiliary dissemination which was invisible in macroscopic examination due to a bright picture of exudative tissue reaction (rare plethora of the lungs, alveolar and interstitial edema, perifocal inflammatory reaction of nonspecific reactive nature) and small size of the lesions. The comparison of clinical and autopsy diagnoses revealed that involvement of intrathoracic LN and miliary dissemination, according to autopsy, occurred much more frequently than shown by antemortem standard x-ray examination of the chest. CONCLUSION: It is strongly recommended to perform computed tomography of the chest in all HIV-infected patients with long-term fever but without visible alterations on chest x-ray.

Postvaccinal changes in the nitric oxide system after immunization with live dry tularemia vaccine.

Immunization of outbred male albino mice with live dry tularemia vaccine in a dose of 50 CFU/mouse was associated with stimulation of the NO system and accumulation of NO metabolites (nitrites and nitrates) in splenic and hepatic tissues. High levels of these metabolites persisted by day 14 after the initial and repeated immunization. These results suggest that the immunotropic effect of live dry tularemia vaccine manifested by not only modulation of the functions of immunocompetent T and B cells, NK and K cells, micro- and macrophages, but also by stimulation of intracellular anti-infection defense at the tissue level via intensification of NO synthesis.

Interferon status in children during acute respiratory infections. Therapy with interferon.

We studied interferon status in children during acute respiratory infections and found that it depends on etiology, course of the disease, and individual features of the organism. The efficiency of IFN inductor anaferon (pediatric formulation) and the possibility of its application in the therapy of children with acute respiratory infections were demonstrated.

[Evaluation of hepatic function in new cases of pulmonary tuberculosis due to the use of standard chemotherapy regimens I and IIB].

The frequency and magnitude of hepatotoxic reactions were compared in 147 new cases of pulmonary tuberculosis within the first three months of chemotherapy (CT) by standard regimen 1 [H, R, Z, S (E)] (Group 1) and regimen 2B [the same drugs + kanamycin (amikacin) and fluoroquinolones] (Group 2). Their efficiency was evaluated from 6 serum indices--the level of bilirubin, the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP), and gamma-glutamyl transpeptidase (GGTP), and thymol test results. Tests were monthly carried out. The results were separately analyzed in patients with and without baseline abnormalities in the indices being tested. Within the first two months of CT, the patients without baseline abnormalities showed the slightly higher frequency and magnitude of hepatotoxic reactions on receiving regimen 2B. Following 3 months of CT combined with hepatoprotectors, the patients treated by standard regimen 1 had solitary laboratory signs of hepatic damage, but there was a regular elevation of GGTP in the regimen 2B group. After a month of regimen 1 CT in combination with hepatoprotectors, the patients with baseline abnormalities has positive changes in all the studied indices. In the patients treated by regimen 2B in combination with hepatoprotectors, the changes were the same, except for GGTP that remained to be at the increased baseline levels. Following 2 months of CT, in Group 1 positive changes continued in the studied markers and, with regimen 2B treatment, abnormal changes began increasing again. After 3 months abnormal changes were single in the markers of hepatic damage with regimen 1 treatment and there was a repeated significant rise in the values of AP and GGTP with regimen 2B. It is concluded that in addition to ALT and AST, GGTP is of great informative value in controlling the hepatotoxic effects of CT.

Interaction of human phenylalanyl-tRNA synthetase with specific tRNA according to thiophosphate footprinting.

The interaction of human cytoplasmic phenylalanyl-tRNA synthetase (an enzyme with yet unknown 3D-structure) with homologous tRNA(Phe) under functional conditions was studied by footprinting based on iodine cleavage of thiophosphate-substituted tRNA transcripts. Most tRNA(Phe) nucleotides recognized by the enzyme in the anticodon (G34), anticodon stem (G30-C40, A31-U39), and D-loop (G20) have effectively or moderately protected phosphates. Other important specificity elements (A35 and A36) were found to form weak nonspecific contacts. The D-stem, T-arm, and acceptor stem are also among continuous contacts of the tRNA(Phe) backbone with the enzyme, thus suggesting the presence of additional recognition elements in these regions. The data indicate that mechanisms of interaction between phenylalanyl-tRNA synthetases and specific tRNAs are different in prokaryotes and eukaryotes.

[Systemic transplantation of autologous mesenchymal stem cells of the bone marrow in the treatment of patients with multidrug-resistant pulmonary tuberculosis].

The study undertaken 3 years ago examined the effect of systemic transplantation of autologous mesenchymal stem cells (MSC) in the complex therapy of 27 patients with pulmonary tuberculosis, including 15 patients with multidrug-resistant pulmonary tuberculosis and 12 with extensive drug resistance of Mycobacterium tuberculosis. All the patients were bacteria-discharging persons with disseminated destructive processes in lung tissue, most (n=17) of them had chronic fibrocavernous tuberculosis. In all the patients, previous long specific antituberculous treatment was ineffective or inadequately effective. After systemic MSC transplantation, 16 patients were followed up for 1.5-2 years or more and the remaining 11 patients for at least 6 months. After MSC administration, a positive clinical effect was observed in all 27 cases; bacterial discharge stopped in 20 patients after 3-4 months; resolution of sustained lung tissue cavities further occurred in 11 patients. At present, a persistent remission of a tuberculous process may be stated in 9 of the 16 patients in whom MSCs were transplanted 1.5-2 years, significant positive bacteriological and morphological changes are observed in 6 patients. Thus, inclusion of transplantation of the autologous MSCs propagated in the culture into a course of antituberculous therapy may be a promising procedure for enhancing the efficiency of therapy in patients with resistant forms of pulmonary tuberculosis.