The impact of the Hsp67Bc gene product on Drosophila melanogaster longevity, fecundity, and acute heat stress tolerance.

Drosophila melanogaster Hsp67Bc is a heat- and cold-inducible small heat shock protein that participates in the prevention of aggregation of misfolded proteins and in macroautophagy regulation. Overexpression of the Hsp67Bc gene has been shown to enhance macroautophagy in Drosophila S2 cells, and the deletion of this gene leads to the formation of a slightly increased number of autophagic vacuoles in the fruit f ly brain neurons. Recently, we found that Hsp67Bc-null D. melanogaster f lies have poor tolerance to cold stress (0 °C) of various durations. In the present work, we investigated how the Hsp67Bc gene deletion affects the f itness of fruit f lies under normal conditions and their tolerance to elevated temperatures at different developmental stages. Larvae and pupae were not adversely affected by the Hsp67Bc gene deletion, and adult Hsp67Bc-null f lies showed an extended lifespan in comparison with the control at normal (24-25 °C) and elevated temperature (29 °C), and after acute heat stress (37 °C, 2 h). At the same time, the fecundity of the mutant females was lower by 6-13 % in all tested environments, except for permanent maintenance at 29 °C, where the mean numbers of eggs laid by the mutant and control f lies were equal. We explain this phenomenon by a reduced number of ovarioles in Hsp67Bc-null females and enhanced macroautophagy in their germaria, which promotes the death of forming egg chambers. In addition, short heat stress (37 °C, 2 h), which increased the control line's longevity (an effect common for a wide range of organisms), had a negative impact on the lifespan of Hsp67Bc-null f lies. Therefore, Hsp67Bc-null D. melanogaster have an extended lifespan under normal and elevated temperature conditions, and reduced fecundity and thermal stress tolerance.

[Predictors of severe lesions of the central nervous system in the treatment of blood system diseases]. / Prediktory tyazhelykh porazhenii tsentral'noi nervnoi sistemy pri lechenii zabolevanii sistemy krovi.

OBJECTIVE: To determine the types, frequency and key symptoms of severe lesions of the central nervous system (SLCNS) that occurred in patients with hematological malignancies (HM). MATERIALS AND METHODS: The authors conducted a retrospective exploratory study by analyzing the data of 3.620 patients with HM during the period from 01.01.18 to 31.12.19. Thirty-four patients (14 men and 20 women, median age 39 years), who developed SLCNS during treatment, were selected. For comparison with the main group of patients and exclusion of predictors associated with the development of SLCNS, a comparison group was added (by Kernel matching method). A comparison group consisted of 137 patients (59 men and 78 women, median age - 36 years) and was similar to the main group by clinical and laboratory characteristics. A neurological complication was marked as SLCNS if it was an indication for transfer to the intensive care unit (ICU). Statistical analysis included multivariate analysis - multiple binary logistic regression with stepwise inclusion of variables (that were found in the preliminary contingency table analysis) in the model, with control false results (by the false discovery rate method) and estimating the odds ratio, OR (95% CI). RESULTS: SLCNS in patients with HM developed in 0.94% of cases. The main SLCNS in patients with HM were: epileptic seizure (50.0%, n=17), ischemic stroke (20.6%, n=7), hemorrhagic stroke (17.6%, n=6) and meningoencephalitis (11.8%, n=4). The following independent significant (Wald test p≤0.05) predictors associated with the development of SLCNS in patients with HM during inpatient treatment were identified: antibiotic therapy (when more than 5 drugs are prescribed), OR=2.9 (1.2-7, four); polychemotherapy (if more than 4 drugs are prescribed), OR=2.9 (1.1-7.8); thrombocytopenia (with a platelet count less than 50·109 g/l), OR=2.3 (1.0-5.2) and delirium, OR=3.7 (1.3-10.8), and also the presence of neurological disorders in the patient's history, OR=2.6 (1.1-6.3). CONCLUSION: The main types of SLCNS in patients with HM were: epileptic seizure, ischemic and hemorrhagic strokes, and meningoencephalitis. Four predictors associated with the development of SLCNS in the course of HM treatment were identified: massive antibacterial (with more than 5 drugs) and chemotherapeutic (with more than 4 drugs) effects, thrombocytopenia and manifestation of delirium, as well as one risk factor: a history of neurological disorder. These factors need to be considered and monitored during treatment, because each of them increases the risk of developing SLCNS.

MicroRNAs in the Myelodysplastic Syndrome.

The myelodysplastic syndrome (MDS) holds a special place among blood cancers, as it represents a whole spectrum of hematological disorders with impaired differentiation of hematopoietic precursors, bone marrow dysplasia, genetic instability and is noted for an increased risk of acute myeloid leukemia. Both genetic and epigenetic factors, including microRNAs (miRNAs), are involved in MDS development. MicroRNAs are short non-coding RNAs that are important regulators of normal hematopoiesis, and abnormal changes in their expression levels can contribute to hematological tumor development. To assess the prognosis of the disease, an international assessment system taking into account a karyotype, the number of blast cells, and the degree of deficiency of different blood cell types is used. However, the overall survival and effectiveness of the therapy offered are not always consistent with predictions. The search for new biomarkers, followed by their integration into the existing prognostic system, will allow for personalized treatment to be performed with more precision. Additionally, this paper explains how miRNA expression levels correlate with the prognosis of overall survival and response to the therapy offered.

[Functions of E3 Ubiquitin Ligase Hyd in Drosophila Tissues].

The ubiquitin-proteasome system (UPS) is an important regulator of the main cellular processes. The components of the UPS are involved in the regulation of the cell cycle, signal transduction, the cell response to DNA damage, metabolism, and transcription control. E3 ubiquitin ligases (the enzymes that covalently attaches ubiquitin to target proteins) play a key role in the functioning of the UPS. The Drosophila tumor suppressor Hyd (hyperplastic discs) is one of the most interesting E3 ligases; it is required for the regulation of proliferation, growth, and cell differentiation. The study of hyd mutations in different tissues of Drosophila demonstrated that depending on the cellular context, Hyd can not only perform proteolytic functions associated with protein degradation, but can also, interacting with other proteins and/or nucleic acids, act as an important regulator of cellular processes.

Migration of primordial germline cells is negatively regulated by surrounding somatic cells during early embryogenesis in Drosophila melanogaster.

Cell migration is an important morphogenetic process necessary at different stages of individual development and body functioning. The initiation and maintenance of the cell movement state requires the activation of many factors involved in the regulation of transcription, signal transduction, adhesive interactions, modulation of membranes and the cytoskeleton. However, cell movement depends on the status of both migrating and surrounding cells, interacting with each other during movement. The surrounding cells or cell matrix not only form a substrate for movement, but can also participate in the spatio-temporal regulation of the migration. At present, there is no exact understanding of the genetic mechanisms of this regulation. To determine the role of the cell environment in the regulation of individual cell migration, we studied the migration of primordial germline cells (PGC) during early embryogenesis in Drosophila melanogaster. Normally, PGC are formed at the 3rd stage of embryogenesis at the posterior pole of the embryo. During gastrulation (stages 6-7), PGC as a consolidated cell group passively transfers into the midgut primordium. Further, PGC are individualized, acquire an amoeboid form, and actively move through the midgut epithelium and migrate to the 5-6 abdominal segment of the embryo, where they form paired embryonic gonads. We screened for genes expressed in the epithelium surrounding PGC during early embryogenesis and affecting their migration. We identified the myc, Hph, stat92E, Tre-1, and hop genes, whose RNA interference leads to premature active PGC migration at stages 4-7 of embryogenesis. These genes can be divided into two groups: 1) modulators of JAK/STAT pathway activity inducing PGC migration (stat92E, Tre-1, hop), and 2) myc and Hph involved in epithelial morphogenesis and polarization, i. e. modifying the permeability of the epithelial barrier. Since a depletion of each of these gene products resulted in premature PGC migration, we can conclude that, normally, the somatic environment negatively regulates PGC migration during early Drosophila embryogenesis.

[Hemostatic Gene Polymorphisms in Acute Coronary Syndrome with Nonobstructive Coronary Atherosclerosis].

PURPOSE: to study distribution of genes of the coagulation system, unfavorable in relation to the risk of thrombosis, and their influence on serum parameters ofthe hemostasis system in patients with nonobstructive coronary atherosclerosis (NCA) and acute coronary syndrome (ACS). MATERIALS AND METHODS: We included in this nonrandomized open study patients with ACS older than 18 years with intact coronary arteries or confirmed at coronary angiography stenosis <50%. Genotypes of these patients were analyzed by 8 polymorphic variants of the hemostatic system genes which previously were found to be associated with the thrombophilia risk: F2 (20210 G>A) rs1799963, F5 (1691 G>A) rs6025, F7 (10976G>A) rs6046, F13 (163 G>T) rs5985, F1 (-455G>A) rs1800790, GP Ia - Ila (807C>t) rs1126643, GP Ilb-IIIa (1565 T>C) rs5918, PAI-I (-6755G>4G) rs1799889. Activities of protein C, Von Willebrand factor, plasminogen, and antithrombin III were also determined. RESULTS: Of 913 patients with ACS in 30 (3.3%) with mean age 54±11 years we detected NCA. Acute myocardial infarction (AMI) was diagnosed in 24 (80%), unstable angina - in 6 (20%) patients. Only in 1 patient we found no carriage of thrombosis associated genotypes. The frequency of occurrence of the heterozygous genotype of the factor V gene was 1 (3%). Heterozygous genotype of the factor XIII was registered significantly more often in patients with present atherosclerotic lesion compared with those with intact coronary arteries. Mean activity of protein C was 103% [90; 110], antithrombin III - 96% [88; 103], Von Willebrand factor - 137% [114; 162], plasminogen - 109% [102; 112]. At admission lowering of antithrombin III and protein C activities was detected in 4 cases (13%). In dynamics level of these parameters was restored. Elevation of Von Willebrand factor activity at admission was detected in 14 cases (14%) and remained elevated one year after the index event. There was no association between of fibrinogen level, protein C activity, rs1800790 and rs6025 gene polymorphisms, respectively. One-year mortality was 7% (n=2). For one year occurred 1 AIM recurrence (3%), heart failure developed in 15 patients (50%), 11 patients (37%) were repetitively hospitalized due to all causes. No association was revealed between activity of studied blood serum markers and 1 -year outcomes (death, re-AIM, rehospitalization). CONCLUSION: Among ACS patients 3.3% had NCA, what corresponded to the literature data. Carriage of at least 1 polymorphic variant of 8 thrombosis associated genes of the coagulation system was found in 97 % of patients with ACS and NCA. Distribution of these variants was like that in the European population and in patients with AIM at the background of stenosing atherosclerosis. Level of serum markers did not depend on distribution of polymorphic variants of the coagulation system genes, and presence of atherosclerotic coronary artery lesions. There was no association between hospital and long-term outcomes and distribution of polymorphic variants of thrombosis associated coagulation system genes, as well as levels of blood serum markers.

Selective Heterozygous Advantage of Carriers of с.-23+1G>A Mutation in GJB2 Gene Causing Autosomal Recessive Deafness 1A.

We present the results of analysis of skin epidermis thickness in individuals with recessive mutation c.-23+1G>A in the GJB2 gene in comparison with individuals without this mutation living in Eastern Siberia (Yakut population). We examined 152 individuals with different genotypes by GJB2 gene mutation c.-23+1G>A. Homozygotes and heterozygotes by c.-23+1G>A have thicker epidermal layer (0.245 mm and 0.269 mm, respectively) in comparison with individuals without this mutation (0.193 mm) (p<0.05). The obtained data support the hypothesis about selective advantage of carriers of mutant GJB2 gene alleles and partly explain extremely high carrier frequency (10.3%) of c.-23+1G>A mutation in the GJB2 gene in Yakut population in Eastern Siberia.

[Functional Characterization of Septin Complexes].

Septins belong to a family of conserved GTP-binding proteins found in majority of eukaryotic species except for higher plants. Septins form nonpolar complexes that further polymerize into filaments and associate with cell membranes, thus comprising newly acknowledged cytoskeletal system. Septins participate in a variety of cell processes and contribute to various pathophysiological states, including tumorigenesis and neurodegeneration. Here, we review the structural and functional properties of septins and the regulation of their dynamics with special emphasis on the role of septin filaments as a cytoskeletal system and its interaction with actin and microtubule cytoskeletons. We also discuss how septins compartmentalize the cell by forming local protein-anchoring scaffolds and by providing barriers for the lateral diffusion of the membrane proteins.

Molecular features of Ixodes kazakstani: first results.

Ticks of the Ixodes ricinus group are important vectors of human pathogens in both Eurasia and North America; therefore, many studies have focused on their molecular systematics and evolutionary relationships. However, there are species that have not been characterized by molecular genetic methods so far. For the first time, we obtained nucleotide sequences of two nuclear and three mitochondrial genetic markers from four museum specimen of I. kazakstani Olenev et Sorokoumov, 1934, collected in Kyrgyzstan. The phylogenetic analysis showed that I. kazakstani undoubtedly belongs to the I. ricinus group but is not closely related to I. persulcatus, as was expected. Further studies of the genetic features of I. kazakstani, presumably an intermediate between Nearctic and Palearctic species, would elucidate the evolutionary relationships between tick species within the I. ricinus group.

Prevalence and risk factors of sleep breathing disorders in patients with acromegaly from Moscow region.

AIM: Assessment of prevalence and risk factors of sleep breathing disorders in patients with acromegaly from Moscow region. MATERIALS AND METHODS: Cardiorespiratory monitoring was executed to 55 patients with acromegaly (18 men and 37 women): 27 patients with de novo disease, 28 patients on treatment of acromegaly (including 18 patietns with uncontrolled and 10 - with controlled acromegaly). All subgroups did not differ on sex, BMI and age. Also 24-hour monitoring of arterial blood pressure was carried out in 39 patients (12 men and 27 women, 14 patients with de novo acromegaly, 15 and 10 patients with uncontrolled and controlled acromegaly, respectively). RESULTS: The high prevalence of sleep breathing disorders (SBD) was revealed in patients with acromegaly from Moscow Region. SBD was found in 92.6%, 83.5% and 70.0% patients with newly diagnosed, uncontrolled and controlled acromegaly, respectively. The majority of patients had severe/moderate SBD in all subgroups (78.8%, 72.2% and 60.0%, respectively). In patients with newly diagnosed and uncontrolled acromegaly index of apnea-hypopnea (31 and 38.5 respectively), number of apnoe episodes (76 and 72) and saturation level (93% and 93.5%) did not differ significantly while these parameters were better in patients with a controlled acromegaly (apnea-hypopnea index 20, apnea episodes 45.5 and saturation level 95%). The peak of desaturation was subphysiological in 91.7%, 86.7% and 77.8% of patients with newly diagnosed, uncontrolled and controlled acromegaly, respectively. Severity of SBD did not depend on GH and IGF-1 levels as well as acromegaly duration. Such all-population risk factors of SBD as BMI and age were valuable for patients with acromegaly, however gender did not matter. SBD were associated with lack of physiological decrease of systolic and diastolic night BP. CONCLUSION: Acromegaly per se is a strong risk factor of sleep breathing disorders. The high prevalence of sleep breathing disorders in patients with acromegaly even after achievement of control over a disease emphasized need of specialized treatment of these violations.

The Role of Pnut and its Functional Domains in Drosophila Spermatogenesis.

The Drosophila Pnut protein belongs to the family of septins, which are conserved GTPases participating in cytokinesis and many more other fundamental cellular processes. Because of their filamentous appearance, membrane association, and functions, septins are considered as the fourth component of the cytoskeleton, along with actin, microtubules, and intermediate filaments. However, septins are much less studied than the other cytoskeleton elements. We had previously demonstrated that the deletion of the pnut gene leads to mitotic abnormalities in somatic cells. The goal of this work was to study the role of the pnut in Drosophila spermatogenesis. We designed a construct for pnut RNA interference allowing pnut expression to be suppressed ectopically. We analyzed the effect of pnut RNA interference on Drosophila spermatogenesis. Germline cells at the earliest stages of spermatogenesis were the most sensitive to Pnut depletion: the suppression of the pnut expression at these stages leads to male sterility as a result of immotile sperm. The testes of these sterile males did not show any significant meiotic defects; the axonemes and mitochondria were normal. We also analyzed the effect of mutations in the Pnut's conservative domains on Drosophila spermatogenesis. Mutations in the GTPase domain resulted in cyst elongation defects. Deletions of the C-terminal domain led to abnormal testis morphology. Both the GTPase domain and C-terminal domain mutant males were sterile and produced immotile sperm. To summarize, we showed that Pnut participates in spermiogenesis, that is, the late stages of spermatogenesis, when major morphological changes in spermatocytes occur.

[Determination of polioksin B in the air environment and in washouts from skin of operators by HPLC].

Polyoxin B being an effective inhibitor of synthesis of chitin of the cell wall of many phytopathogenic fungi, is recommended as a fungicide for control of phytopathogenic organisms that cause damage to crop. For the determination of the exposure of employees working with pesticides there was developed the method of the measurement of concentrations of polyoxin B in air of working area, atmospheric air of populated areas and washouts from the operators ' integuments, based on high performance liquid chromatography with ultraviolet detector (detection wavelength of270 nm), including sampling air environment in the sorption tube ORBO-44, filled with sorbent XAD-2, extraction of the sorbent with polyoxin by a mixture of carbinol-water (in a ratio of 95:5,on volume), washout from the surface of the skin with ethyl alcohol by way of washing, concentrating, quantitative chromatographic analysis. Lower limits of the quantification ofpolyoxin B in the air ofworking area - 0.2 mg/m at the aspiration of 2 dm of air, atmospheric air - 0.016 mg/m at the aspiration of 25 dm of air, in washouts from the operators' integuments - 0.4 pg/wash, the linear range of the defined concentrations accounted for of 0.2 - 2.4 pg/cm, the total error of measurement of the concentrations of polyoxin B in air is 17%; in washouts from the operators' integuments - 16%. The developed method was approbated for the determination of polyoxin in samples of air of working zone, atmospheric air within the sanitary gap, washouts from the operators ' integuments and air drift samples taken under processing of roses in the hothouse and in the monitoring of the phytosanitary condition of the plants every other day after treatment.

[Analysis of Phenotypic Manifestation of peanut Gene Expression Suppression by RNAi in Drosophila Oogenesis].

The peanut gene functions in Drosophila melanogaster oogenesis were studied. It was demonstrated that the suppression of peanut expression by RNA interference in the ovary follicular cells results in the violation of oocyte polarization, anomalous cytokinesis in the chorion cells, and violation of the chromatin condensation in follicular cells. No oogenesis violations were observed in females with decreased peanut gene expression or an absence of the Pnut protein in the ovary generative cells. However, embryos produced by such females had a decreased survival rate caused by two death peaks.

[Characteristics of substance use disorders among women]. / Osobennosti addiktivnykh rasstroistv u zhenshchin.

Significant gender differences have been noted in the course of substance abuse and dependence. Prevalence rates of substance abuse and dependence among women have been substantially increasing. This research examines gender differences in biological responses, predictors, comorbidity of addiction psychiatric disorders, and barriers to treatment entry, management of substance dependence during pregnancy and possible outcomes.

[Pharmacotherapy and psychotherapy of comorbid anxiety disorders and alcoholism].

Anxiety disorders commonly co-occur with substance use disorders. It is known that alcohol-dependent patients are at greater risk of a relapse if they have a comorbid anxiety disorder. There is a lot of literature reporting on the efficacy of treatments that target anxiety or alcohol addiction separately but less research has examined treatments that address these disorders when they co-occur. Anxiety treatment for alcohol-dependent patients with a co-occuring anxiety disorder can alleviate anxiety symptoms but has no significant effect on the outcomes of alcohol treatment. Efficient combinations of psychotherapy and pharmacotherapy can improve outcomes of comorbid disorders.

[The experience of using fingolimod (gilenya) in patients with relapsing-remitting multiple sclerosis].

We present the results of a one-year follow-up study of 11 patients treated with gilenya. The results of cardiomonitoring (ECG and daily arterial pressure monitoring) during the treatment with the first dose of the drug are presented. No clinically significant disturbances of functions in patients without cardiovascular diseases were noted. In these cases, no progression of disease was identified. Relapses were not observed in 82% of patients.

Drosophila male-sterile mutation emmenthal specifically affects the mitochondrial morphogenesis.

Proper mitochondrial morphogenesis is crucial for successful development of motile sperm. It was known that recessive Drosophila melanogaster mutation emm caused anomalies in the formation of a mitochondrial derivative--nebenkern and led to male sterility. Here we identified primary mutation effect and showed that emm is required for the formation and maintenance of inner mitochondrial structure starting from early spermatocytes. Abnormal mitochondria structure affects subsequent cellular processes in spermatogenesis such as meiotic cytokinesis and spermatid elongation.

[A new gamasid mite species, Haemogamasus limneticus sp. n. (Parasitoformes: Gamasoidea), from Kyrgyzstan].

A new mite species of the genus Haemogamasus Berlese is described from the muskrat in Kyrgyzstan. Differential diagnoses of species of this genus from Kyrgyzstan are given.

[Allelic polymorphism of six microsatellite DNA loci in populations of Sakha (Yakutia)].

The distribution of allele frequencies of six STR-loci (D3S1358, D16S539, THOI, D8S1179, LPL, HUMvWFII), used in forensic practice, was analyzed in populations of Sakha (Yakutia) (three ethnogeographical groups of Sakha (Yakuts), Evenks, Yukagirs, Dolgans, Russians). Significant differences were revealed between the Russians and all other populations by five markers. Values of total discriminative potential (PD) of studied system for each population were estimated. The level of interpopulation genetic differences (F(ST)) was 0.005. On the basis of allelic polymorphism of STR-loci we estimated phylogenetic relationships between populations under study and populations of different regions--East Europe, South Siberia, Chukotka and Kamchatka.

[A newly diagnosed intraventricular septal defect in a pregnant woman presenting with pulmonary hypertension].

This clinical description of pregnancy follow-up and labour management in women with severe pulmonary hypertension caused by an interventricular septum defect is intended to familiarize practicing physicians with the methods for maintaining pregnancy and ensuring spontaneous delivery despite the said pathology. Indispensable conditions for the attainment of these goals include thorough clinical and laboratory control, comprehensive analysis of possible complications, efficacious epidural anesthesia, and correct choice of medicines.