Репозиторий Университета

© 2018 Media Sphera Publishing Group.All Rights Reserved. Aim. To analyze the association between the polymorphic markers in CTLA4, TNF, IL10 and IL16 genes and the risk of manifestation of endocrine ophthalmopathy (EO) in patients with Graves' disease (GD). Materials and methods. Case-control study included 248 patients with GD. Using polymerase chain reaction we studied the distribution of alleles and genotypes of polymorphic markers such as A60G (rs3087243) in CTLA4 gene, G(-308)A (rs1800629) in TNF gene, G(-1082)A (rs1800896) in IL10 gene, T3249C (rs4778641) in IL16 gene among 141 patients with Graves' disease and EO and 107 patients with GD without EO. Results and discussion. The frequencies of A alleles and the AA genotypes were significantly increased and the frequencies of G alleles and the GG genotype polymorphic markers rs3087243 of CTLA4 gene and rs1800896 of IL10 gene, as well as the GG genotype polymorphic marker rs1800629 of TNF gene were reduced in patients with GD and EO. The polymorphism in CTLA4 gene was also associated with the activity and the severity of EO. The comparative analysis of the allele and genotype frequency distribution of polymorphic markers of IL16 gene did not show the significant difference. Conclusion. The risk of manifestation and the development of EO in patients with Graves' disease can be caused by not only environmental, but also genetic risk factors.

© Ima-Press Publishing House. All rights reserved. Objective: to investigate the influence of the aesthetic component of dental health on the anxiety level and quality of life of socially active elderly patients. Patients and methods. A total of 32 patients aged 60 to 67 years who had a poor aesthetic appearance of the hard tissues of the front teeth were followed up. All the patients underwent determination of anxiety levels by the Spielberger-Hanin procedure and assessment of quality of life using an abbreviated 26-item version of the World Health Organization Quality of Life (WHOQOL-BREF-26) questionnaire; the updated Oral Health Impact Profile (OHIP-14) was also used. Aesthetic rehabilitation of vital front teeth was carried out using photo composite materials made in Russian and foreign countries. Results. Before treatment, the state anxiety scores were 54±1.4 scores; the trait anxiety ones were 41±1.2 scores; at 1 week after treatment, these were 42±0.5 and 39±0.6, respectively (p ≤ 0.05 for both indicators), and at 6 months, these were 44±0.5 and 43±0.7, respectively. Conclusion. The aesthetic component of dental health in socially active elderly patients is directly proportional to quality of life and inversely proportional to the level of trait or state anxiety. Russian and foreign photo composite restorative materials showed equal sustained performance.

© 2018 The Authors Recent years have witnessed the development of an enormous variety of hydrogel-based systems for neuroregeneration. Formed from hydrophilic polymers and comprised of up to 90% of water, these three-dimensional networks are promising tools for brain tissue regeneration. They can assist structural and functional restoration of damaged tissues by providing mechanical support and navigating cell fate. Hydrogels also show the potential for brain injury therapy due to their broadly tunable physical, chemical, and biological properties. Hydrogel polymers, which have been extensively implemented in recent brain injury repair studies, include hyaluronic acid, collagen type I, alginate, chitosan, methylcellulose, Matrigel, fibrin, gellan gum, self-assembling peptides and proteins, poly(ethylene glycol), methacrylates, and methacrylamides. When viewed as tools for neuroregeneration, hydrogels can be divided into: (1) hydrogels suitable for brain injury therapy, (2) hydrogels that do not meet basic therapeutic requirements and (3) promising hydrogels which meet the criteria for further investigations. Our analysis shows that fibrin, collagen I and self-assembling peptide-based hydrogels display very attractive properties for neuroregeneration.

© 2018 ABV-Press Publishing House. All rights reserved. Modern anticancer therapy due to its intensity and molecular biology orientation allows achieving higher efficiency and theoretically reducing the incidence of complications. However, the increase in efficacy in the modern oncology really exists, but reducing complication frequency, unfortunately, is far from being solved. In many respects the problems of diagnosis, treatment and complications monitoring are associated with the impact on the complex physiological processes occurring in oncological patient. Timely implementation of modern and adequate programs for the prevention and treatment of these complications defines the concept of "supportive therapy", which provides at least half the effectiveness of antitumor treatment. To date, according to most studies, the most frequent complications of antitumor therapy are hematologic, in particular - anemia. In clinical practice, blood transfusions, recombinant human erythropoietins, hemopoiesis stimulating cofactors are used to correct this type of complications. The need for anemia treatment is determined by its negative impact on quality of life, as well as a negative prognostic impact on the life expectancy of cancer patients, because hypoxia of tumor tissue can be associated with resistance to chemo- and radiation therapy, the stimulation of genetic mutations and neoangiogenesis, which make it difficult to control of tumor growth. In numerous studies using multivariate analysis confirmed the association of low hemoglobin levels and/or tumor tissue hypoxia with worsening prognosis and overall survival in many types of tumors. The modern anemia treatment should not be determined only by increased in hemoglobin level, but should be considered as an active prophylaxis for its reducing. Recombinant forms of human erythropoietin and intravenous forms of iron preparations should be the most popular correction methods in everyday practice. The high cost of complex anemia therapy and the social significance of oncological diseases necessitate a pharmaco-economic analysis of registered in Russia erythropoietin preparations and the optimization of existing anemia treatment regimens in cancer patients in order to reduce the expenditures of the health budget. At present, an active import substitution program is underway in the Russian Federation to support the development of the Russian pharmaceutical industry and provide the population with more affordable medicines while maintaining its quality and efficiency. The need to address these issues, and the effective use of the domestic biological analogue epoetin alfa, served as an excuse for performing a comparative clinical and economic analysis. They were selected drugs that differ in pharmacokinetic properties: Eralfon® - analogue of epoetin alfa and Aranesp® - darbepoetin alfa. The treatment model of adults oncological patients with anemia receiving chemotherapy was created, which takes into account various therapies using erythropoietin preparations. The total therapy cost for an oncological patient with anemia is less when using short-acting erythropoietin - epoetin alfa - 131 609 rubles in comparison with the long-acting erythropoietin - darbepoetin alfa - 245 159.2 rubles, the difference was 113 550.2 rubles (-46 %) in favor of the epoetin alfa. According to pharmaco-economic analysis, the treatment of anemia with a Russian-produced drug epoetin alfa (Eralfon®) is preferred in comparison to darbepoetin alfa (Aranesp) in adult cancer patients with nonmyeloid malignancies in the Russian Federation, as it allows increasing the number of treated patients at a cost reduction.

© 2018 Saint Petersburg Pasteur Institute.All Rights Reserved. Enteroviruses are small RNA viruses, which are ubiquitous and commonly cause outbreaks with various clinical manifestations. In 2006, the Program on enterovirus surveillance was approved in the Russian Federation. Over the last years, molecular-biological and bioinformatics methods for enterovirus epidemiology studies have been developed both in Russia and worldwide. Currently, identification of enteroviruses is carried out by analyzing nucleotide sequence of the full-length VP1 genome region (ca. 900 nt). Routinely, it is sufficient to obtain a partial VP1 genome region sequence (ca. 300 bp) for enteroviruse verification in most cases; however, a more stringent type criterion of 80% sequence identity should be used compared to the 75% sequence identity cut-off for the complete VP1 genome region. Further sequence analysis may be performed by using Bayesian phylogenetic methods, which allow using molecular clock to trace outbreak emergence. Enteroviruses accumulate about 0.5–1% nucleotide substitutions per year. Therefore, a short genome fragment may be used to analyze virus phylodynamics at the level of international transfers and circulating virus variants. On a shorter timescale, a full-length VP1 genome region or a complete genome sequence are preferred for investigating molecular epidemiology, because a short sequence allows to reliably distinguish not more than 1–2 transmission events per year. Thus, determining enterovirus sequences for full-length VP1 genome region or full-genome sequence is preferred for examining viral outbreaks. It is increasingly apparent that analyzing available enterovirus nucleotide sequences reveals limitations related to uneven surveillance efficacy in various countries and short length of genome fragment measured in routine control. As a result, a proper global-scale analysis of enterovirus molecular epidemiology remains problematic. Over the last 20 years, the number of available enterovirus nucleotide sequences increased by hundred times, but understanding emergence of enterovirus infection outbreaks remains limited. Further development of enterovirus surveillance would require new methods for sewage monitoring, affordable high-throughput sequencing and harmonization of global surveillance systems.

AIM: To evaluate the efficacy and safety of collagen biomaterial application during the 4-week follow-up of patients with diabetic foot syndrome.MATERIAL AND METHODS: 75 patients with diabetic foot (Wagner II (69.3%) and III (30.7%)) aged 30-80 years were included in the multicenter study, among them were 50.7% with the wound unhealed for 1.5-6 months and 49.3% over 6-48 months. Patients were randomized into 2 groups: 1) standard therapy (n=37), 2) the additional use of the collagen material Collost (n=38). Observation period was at least 4 weeks for each patient. The size of ulcers, results of general and biochemical blood tests, oximetry, microbiological testing, ultrasound of lower extremities vessels as well as a detailed medical history, social and functional status, level of cardiovascular comorbidity and ongoing therapy were estimated.RESULTS: Additional use of a collagen biomaterial has led to a significant reduction ulcers of all sizes from 13.5 to 2.1 cm2 (in the comparison group - from 12.5 to 7 cm2). The best dynamics have been registered in Wagner II (4.4-fold average wound area regress in Collost group, from 8.8 to 2.0 cm2; average wound area regress by 1.8 times, from 10 to 5.6 cm2 in the comparison group) than in Wagner III group (in the main group from 55 to 21.3 cm2; in the control group from 36 to 32.4 cm2) and in ulcers existing less than 6 months. Treatment with biological material Collost within standard therapy after 4 weeks led to increase of complete epithelialization by 2.6% (21.1% as compared to 14.7%), while decreasing the frequency of ineffective treatment by 4.1 (7.9% in primary and 32.4% in the comparison group).CONCLUSION: We have proved the efficacy and safety of collagen biomaterial topical application in a diabetic foot syndrome treatment.

© 2018 Czech Academy of Sciences. The population structures of different species of Calliphoridae flies are highly diverse at different locations. We investigated populations of the Eastern European L. sericata using chaetotaxy and eight microsatellite loci. Our results strongly indicate that a panmictic population of L. sericata exists in the area studied, possibly with a high rate of intra-population gene flow. Analysis of chaetotaxy also supports the panmictic population hypothesis.

© 2018 ABV-Press Publishing House. All rights reserved. The DNA analysis revealed a transthyretin amyloidosis with a rare Phe53Leu mutation in a woman of 62 y.o. with the late onset progressive generalized axonal sensomotor neuropathy, dry eye syndrome, and an episode of severe unintentionally weight loss. The same mutation was found in her healthy 34 y.o. son, but not in a 42 y.o. daughter. The Congo red staining were negative in nerve and salivar gland biopsies samples. The reassessment of the transthyretin amyloidosis “red flags” showed that the patient fulfilled the criteria of the disease and the absence of amyloid deposition was not the ground to reject the hereditary cause of the condition. The reasons of the misdiagnosis are discussed.

© 2018 Medical Education. All rights reserved. The aim of this study was pharmacoeconomic evaluation of treatment with reslizumab compared to omalizumab in severe eosinophilic asthma. Methods. The study was based on indirect comparison between omalizumab and reslizumab in patients with severe asthma using published data. Costs of treatment with omalizumab, reslizumab, combinations of inhaled corticosteroids and long-acting beta-agonists (ICS/LABA), outpatient treatment, treatment of exacerbations and adverse events were also compared. Сost-effectiveness analysis and budget impact analysis were used. Results. According to results of cost-effectiveness analysis, therapy with reslizumab dominated over therapy with omalizumab in patients with severe asthma in term of exacerbation rate requiring treatment with systemic steroids. According to results of budget impact analysis, switching of 100 patients from omalizumab to reslizumab could save RUB 51.99 million per year that corresponds to 36.6% reduction in general direct costs for treatment of severe asthma. Conclusion. The results of this study demonstrated economic advantage of reslizumab over omalizumab in patients with severe eosinophilic asthma.

© ISUCT Publishing. The macrolide antibiotic oligomycin A (1), produced by actinomycetes Streptomyces,[1] is a well-known inhibitor of FO F1 ATP-synthase, which is regarded as a molecular target for new drugs in the treatment of tumors and infections. Oligomycin A (1) exhibits antifungal and cytotoxic activities, but Gram-negative and Gram-positive bacteria are resistant to 1 except actinobacteria.[2] In micromolar concentrations, oligomycin binds to FO c-subunit, blocks proton translocation and disrupts bioenergetic metabolism.[3] However, a clinical application of oligomycin A is limited by high cytotoxicity for mammalian cells. The searches of new derivatives of oligomycin A with more selective pharmacological activity and low toxicity for normal cells are of great interest. New semi-synthetic oligomycins also would be valuable for SAR studies and depicting the mechanism of FO F1 ATP-synthase inhibition. The complicity of oligomycin structure and its lability in basic conditions[4] significantly impede modifications and an applicability of this antibiotic. However, previously we have managed this challenge and developed some modifications of the side chain and chemical transformations of the lactone moiety of 1.[4-9] In this paper, throughout our research we describe synthesis and biological investigation of novel oligomycin A derivatives, namely 16,33-O,O-diformyl-16,17-dihydro-16(S),17(R)-dihydroxyoligomycin A (3) and 33-O-formyloligomycin A (4). First, we have studied Prilezhaev epoxidation of double bonds in core structure of oligomycin A. It was found that treatment 1 with m-CPBA at -17oC in dichloromethane led to 16,17-epoxyoligomycin (2). Unfortunately, all attempts for isolation of product 2 were failed due to its instability on silica gel, and, consequently, we were unable to determine the structure of 2 by direct physicochemical and spectral methods. The presence of epoxide at C16-C19 positions was confirmed by tandem mass spectrometry, but its exact localization was still elusive. We assumed that it might be at C16-C17 positions, because C18-C19 double bond is hindered by ethyl side chain at C20. In order to obtain a stable oligomycin A derivative we performed an epoxide ring-opening reaction by the treatment of the crude epoxyoligomycin 2 with formic acid. This acid-catalyzed opening of the epoxide accompanied with acylation of 33-OH group and led to16,33-O,O-diformyl-16,17-dihydro-16(S),17(R)-dihydroxyoligomycin A (3). The structure of 3 was confirmed by NMR spectroscopy and high resolution mass spectrometry. Configurations at C16 and C17 positions were determined by detecting correlations in1H-1H ROESY spectrum. Obtained results allowed to confirm an assumption about localization of the epoxide ring and establish the structure of 2 as (R,R)-16,17-epoxyoligomycin A, since inversion of configuration has taken place at the attacked carbon atom.[23] It is known that O-acyl derivatives of pharmacologically active agents are widely used as prodrugs.[24] Acylation of 2-hydroxypropyl side chain in 2 prompts us to examine the reaction of oligomycin A (1) with formic acid. Thus, stirring the solution of 1 in HCOOH (98 %) for 2 h at room temperature afforded 33-O-formyloligomycin A (4) in a good yield. The structure of 4 was confirmed by NMR-spectroscopy and high resolution mass spectrometry. Also, biological data of new derivatives were evaluated. The modification of C16-C17 positions of the macrocycle as well as acylation of C33 hydroxyl group led to the decreasing of activity against S. fradiae, Candida spp. and filamentous fungi. Obtained results were in agreement with docking studies. A simulation of an interaction of 1, 3 and 4 with the FO subunit of the ATP-synthase (PDB: 4f4s) revealed that these modifications led to a significant change in the solvation energy and an increase in the conformational capacity of the ligands during the binding with the target. This resulted in decrease of the binding affinity for derivatives 2, 3. However, 33-O-formyloligomycin A (4) showed similar antiproliferative activity against tumor cell lines (HCT-116 colon carcinoma, К562 myeloid leukemia cell lines and MDR K562/4 subline) as for 1, but less cytotoxic for non-malignant human cells.

© 2018, Nizhny Novgorod State Medical Academy. All rights reserved. The aim of the study was to demonstrate a good diagnostic potential of atomic force microscopy (AFM) in tracking morphological changes in the extracellular matrix (ECM) of connective tissue due to pathological processes. Here we summarize our experience in AFM application in a number of biomedical studies on the connective tissue disease, both for the research and clinical purposes. Materials and Methods. Depending on the project application (experimental or clinical), the tissue specimens were harvested either from animals, or from patients in the course of their surgical treatment, or post mortem. AFM images of fixed tissue slices on glass slides were acquired with a Solver P47 AFM instrument (NT-MDT, Russia), in the semi-contact mode. For mechanical properties mapping, the images were acquired on air in the PeakForce Quantitative Nanomechanical Mapping mode (PeakForce QNM®), using a MultiMode 8 atomic force microscope (Bruker, USA). The regions of interest for scanning were selected in accordance with the histological assignments for the same sample, based on the view of a sample in the built-in optical microscope of the AFM instrument setup. To quantify the changes in the ECM morphology visualized by AFM imaging, we applied flicker-noise spectroscopy parameterization. Results. AFM has been shown to reveal visible deviations from the normal morphology of the ECM in diseased tissues. We found that AFM and related techniques are capable of tracking disease-related changes at different levels of collagen organization in the ECM. At the microscale, AFM may detect loosening and disorganization of collagen fibers (e.g., in a dysplastic process), or the opposite process of their packing into tight parallel bundles in a fibrotic process. AFM may also monitor the ratio between collagen and non-fibrous material of the ECM, for example, in inflammatory and neoplastic processes. At the level of collagen fibrils, AFM may reveal early signs of the matrix destruction and remodeling not visible at the microscopic level. The flicker-noise spectroscopy parameters provide quantification of the morphological changes visualized by AFM. The PeakForce QNM® and nanoindentation studies give a further insight into the state of ECM via tracking changes in the local mechanical and adhesive properties. All our AFM studies appeared in a good agreement with the histological findings and generally had a superior sensitivity to pathology-related ECM rearrangements. Conclusion. AFM may serve as a valuable complementary diagnostic tool for tracking pathological changes in the connective tissue.

© 2018 Ima-Press Publishing House. All Rights Reserved. The paper presents the proceedings of the Round Table with the participation of leading neurologists, which is devoted to chronic cerebrovascular diseases. It is noted that chronic cerebral ischemia (CCI), or dyscirculatory encephalopathy (DEP), is one of the most common neurological diagnoses in our country. The pathogenesis, clinical presentations, diagnosis and treatment of CCI (DEP) and its matching with vascular cognitive impairment (CI), which is regarded in foreign literature as the main manifestation of chronic cerebrovascular disease (CVD) were considered. The authors analyze clinical trials evaluating the efficacy of vinpocetine (Cavinton) in chronic CVD, dizziness, Cl, as well as the use of new vinpocetine formulations, such as Cavinton Comforte, in various neurological diseases, dysphagia in particular, in poststroke patients.

© 2018 Russian Electronic Journal of Radiology.All Rights Reserved. agnetic iron oxide nanoparticles (MNP) show great potential as the contrast agent for magnetic resonance imaging (MRI). Purpose. To evaluate the efficiency and safety of the contrast agent based on HSA-coated MNP on the model of the C6 glioma. Materials and methods. Extensive preclinical research of specific activity has been performed. Studies were conducted on the model of the orthotopic C6 glioma. Results. In the preclinical studies, it was demonstrated that HSA-coated magnetic iron oxide nanoparticles (MNP-HSA) accumulate in the tumor and its large vessels. Conclusion. Magnetic resonance imaging with contrast agent allows visualization of the tumor tissue and its vascularization.

© 2018 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reserved. Vaccination against pneumococcal infections by 13-va-lent conjugate vaccine (PCV13) can significantly reduce morbidity and mortality. The study has been aimed to evaluate the social and pharmacoeconomic aspects of PCV13 vaccination of 65-year-old patients with various risks of pneumococcal infection. Material and methods. Markov model with 5 and 15 years time horizon was used for the analysis from the position of the health care system. The analysis was carried out for 65-year-old citizens with low (absence of immunocompromized conditions and chronic diseases), moderate (patients with chronic diseases without immunodeficiency) and high (immunocompromized conditions) risk of pneumococcal infection as well as for the entire population of 65-year-old citizens, regardless of the risk level. In base-case assumption has been made that 1 dose of PCV13 should be administered for the patients from low and moderate risk groups and in the high-risk group 1 dose of PCV13 and in 8 weeks a dose of polysaccharide pneumococcal vaccine (PPV23) should be given. The treatment and physician visit costs have been calculated using CHI rates for St. Petersburg in 2018. Vaccination cost was calculated using the auction price to purchase PCV13 and PPV23 in 2018. Results. Vaccination of 1 cohort of 65-year-old citizens in Russian Federation within 5 years will result in prevention of 2200 deaths, 3900 cases of invasive pneumococcal diseases (IPD) and 48700 cases of community-acquired pneumonia. In 15 years prevention of about 4,3 thousand deaths, 6,6 thousand IPD and 101,1 thousand cases of CAP will be provided. Within 15-year horizon the cost-effectiveness ratio will be RUR 30,3, 82,4 and 410,0 thousand per QALY in high, moderate and low risk groups, respectively. Even if the time horizon is reduced to 5 years the PCV13 vaccination can be considered as an economically high-efficient intervention in moderate and high risk groups (cost-effectiveness ratio - RUR 279,2 and 221,7 thousand / QALY, respectively). In the 15-year-horizon noting the distribution of 65-year-olds by risk levels the cost-effectiveness ratio of PCV13 in population as a whole will be RUR 216,4 thousand / QALY. If moderate and high risk groups only are vaccinated, the average cost-effectiveness ratio will drop to RUR 67,6 thousand /QALY. At universal PCV13 vaccination of 65 years old in 5 year time horizon return of investment to the health care system budget will be 33.2% and at vaccination of persons with moderate and high risk return of investment will be 44.0%. With the assumption of vaccination during the planned physician visit (without additional visit) the return to the budget will be 46.8% and 60.9% for vaccination of all 65-year-olds and patients from the moderate and high risk groups, respectively. Conclusions. Vaccination of the 65-year-old persons against PCV13 pneumococcal infection in Russian Federation can be considered as a highly socially and economically effective intervention resulting in significant reduction of pneumococcal infection incidence and related mortality. The cost-effectiveness of vaccination is increasing along with the level of the risk. PCV13 vaccination of patients with moderate and high risk only provides a significant reduction in the burden for the health care budget in comparison with the vaccination of the entire population of 65-year-olds.

Репликативный полипротеин 1а вируса желтухи свеклы (ВЖС) содержит консервативные домены лидерной папаин-подобной протеиназы (РСР), метилтрансферазы (MTR) и РНК хеликазы (HEL). Центральный район (central region, CR) между MTR и HEL ранее считали «вариабельным». Нами проведен компьютерный анализ CR, который позволил выявить новый консервативный домен между позициями 1287-1390 (здесь и далее приводится нумерация аминокислотных остатков белка 1а вируса желтухи свеклы, BYV), сохраняющийся у всех представителей рода Closterovirus. Этот домен содержит 4 предсказанных альфа-спиральных участка (альфа А – D) и три строго консервативные позиции – глютамат-1291, пролин-1380 и аргинин-1384. Кроме того, биоинформатический анализ позволил предсказать амфипатическую спираль в позициях 1368-1380 (входящую в состав участка альфа D). Гидрофобный домен CR-2 (позиции 1305-1494 белка 1а), вызывающий при экспрессии в растениях реструктуризацию эндоплазматического ретикулюма и образование подвижных глобул диаметром ~1 мкм, включает участки альфа В, С и D. Установлено, что экспрессия в растениях слитных белков CR-2:GFP и GFP:CR-2 вызывает сходный «глобулообразующий» фенотип, т.е. N-концевое или C-концевое положение маркера GFP в слитном белке не влияет на переформатирование мембран эндоплазматического ретикулюма. Проведен делеционный анализ CR-2 BYV. Показано, что делеционные варианты 1355-1494 и 1325-1484 сохраняют фенотип дикого типа (образование глобул и реструктуризация ЭР вокруг ядра клетки). Варианты 1375-1484, 1368-1484 и 1368-1432 индуцировали образование глобул, но утрачивали способность к реструктуризации ЭР. Внесение замен гидрофобных аминокислотных остатков на остатки серина и глицина в «минимальном» делеционном мутанте 1368-1432 блокировало образование глобул. Предложена рабочая гипотеза о влиянии консервативной амфипатической спирали 1368-1385 в белке 1а BYV на ремоделирование мембран ЭР растительной клетки и создание репликативных платформ при клостеровирусной инфекции.

Human B-cell receptor-associated protein BAP31 (HsBAP31) is the endoplasmic reticulum-resident protein involved in protein sorting and transport as well as pro-apoptotic signaling. Plant orthologs of HsBAP31 termed 'plant BAP-like proteins' (PBL proteins) have thus far remained unstudied. Recently, the PBL protein from Nicotiana tabacum (NtPBL) was identified as an interactor of Nt-4/1, a plant protein known to interact with plant virus movement proteins and affect the long-distance transport of potato spindle tuber viroid (PSTVd) via the phloem. Here, we have compared the sequences of PBL proteins and studied the biochemical properties of NtPBL. Analysis of a number of fully sequenced plant genomes revealed that PBL-encoding genes represent a small multigene family with up to six members per genome. Two conserved motifs were identified in the C-terminal region of PBL proteins. The NtPBL C-terminal hydrophilic region (NtPBL-C) was expressed in bacterial cells, purified, and used for analysis of its RNA binding properties in vitro. In gel shift experiments, NtPBL-C was found to bind several tested RNAs, showing the most efficient binding to microRNA precursors (pre-miRNA) and less efficient interaction with PSTVd. Mutational analysis suggested that NtPBL-C has a composite RNA-binding site, with two conserved lysine residues in the most C-terminal protein region being involved in binding of pre-miRNA but not PSTVd RNA. Virus-mediated transient expression of NtPBL-C in plants resulted in stunting and leaf malformation, developmental abnormalities similar to those described previously for blockage of miRNA biogenesis/function. We hypothesize that the NtPBL protein represents a previously undiscovered component of the miRNA pathway.

В области изучения нейробиологии униполярных депрессивных расстройств (УДР) перспективными считаются нейровизуализационные методы, особенно позитронно-эмиссионная томография (ПЭТ) и функциональная магнитно-резонансная томография (фМРТ). В статье приводится обзор современных нейровизуализационных данных, касающихся структурно-функциональных особенностей головного мозга у лиц, страдающих УДР. Результаты отдельных исследований представлены в зависимости от особенностей методов их проведения (состояние покоя, выполнение когнитивных и эмоциональных тестов) и соотнесены с основными нейробиологическими концепциями развития депрессивных расстройств. Отдельно рассмотрены возможности нейровизуализационных исследований для оценки и прогнозирования результатов антидепрессивной терапии.

Проведен анализ научной литературы за период с 1991 по 2016 г., посвященной хирургической подготовке костной ткани челюстей к дентальной имплантации путем применения синтетических остеопластических материалов. Подбор научной литературы проводился в Центральной научной медицинской библиотеке, электронной медицинской библиотеке eLIBRARY.RU, а также по базе данных медицинских публикаций PubMed. В обзоре проанализированы результаты экспериментальных и клинических исследований особенностей и эффективности применения таких материалов, сроки их замещения на новообразованную костную ткань, а также эффективность применения синтетических заменителей и других видов остеопластических материалов.

According to current guidelines, non-sedative H1-antihistamines (nsAH) are the first-line therapy of chronic spontaneous urticaria (CSU). But even up-dosed antihistamines (to four times the standard dose) produce symptom resolution in less than 50% of patients. Biomarkers that can predict the response to nsAH are still unknown. We carried out a prospective study and used discriminant analysis to evaluate the combination of D-dimer, fibrinogen, C-reac- tive protein and ESR values for predicting the outcome of treatment with levocetirizine in 84 CSU patients. We found that elevation of these parameters is associated with more active disease, low quality of life and lack of response to standard doses of levocetirizine. Thus, eval-uation of these markers may be considered useful before starting treatment with nsAH. The mechanisms behind the increase in these parameters in CSU patients need to be elucidated in further studies.

Plant defense is achieved mainly through the induction of microbe-associated molecular patterns (MAMP)-triggered immunity (MTI), effector-triggered immunity (ETI), systemic acquired resistance (SAR), induced systemic resistance (ISR), and RNA silencing. Plant immunity is a highly complex phenomenon with its own unique features that have emerged as a result of the arms race between plants and pathogens. However, the regulation of these processes is the same for all living organisms, including plants, and is controlled by proteases. Different families of plant proteases are involved in every type of immunity: some of the proteases that are covered in this review participate in MTI, affecting stomatal closure and callose deposition. A large number of proteases act in the apoplast, contributing to ETI by managing extracellular defense. A vast majority of the endogenous proteases discussed in this review are associated with the programmed cell death (PCD) of the infected cells and exhibit caspase-like activities. The synthesis of signal molecules, such as salicylic acid, jasmonic acid, and ethylene, and their signaling pathways, are regulated by endogenous proteases that affect the induction of pathogenesis-related genes and SAR or ISR establishment. A number of proteases are associated with herbivore defense. In this review, we summarize the data concerning identified plant endogenous proteases, their effect on plant-pathogen interactions, their subcellular localization, and their functional properties, if available, and we attribute a role in the different types and stages of innate immunity for each of the proteases covered. View Full-Text