Differentiation between <I>Yersinia pestis</I> Strains of Altaic-Hissar Group of Non-Main Subspecies by Means of PCR

On the basis of comparison between the genome-wide sequences of Altaic and Hissar strains of non-main subspecies and strains from Talas high-mountain plague focus, identified have been two novel DNA-targets, the usage of which provides for easy rapid subdivision of these closely-related strains of non-main subspecies that fall into separate phylogenetic brunches of plague agent evolution, applying PCR assay. One of the targets is allocated to intergenic region between YPO3333 and YPO3332 genes. In strains of altaica ssp. it contains 122 bps deletion. The other target is YPO2412 gene region which contains 72 bps deletion in Talas strains. Special primers for DNA-targets have been designed. Established have also been test specifications. Efficacy of the method for differentiation between the strains of Altaic-Hissar group of non-main subspecies is validated on 97 Y. pestis strains of various ssp

Identification and Intraspecific Typing of Plague Microbe Strains with Their Potential Virulence Determination Using PCR

Developed is the method of identification and intraspecific typing of plague microbe strains along with their potential virulence determination. Intraspecific differentiation and focal attribution of the examined plague microbe strains can be determined by monolocus VNTR-PCR, and main virulence determinants (chromosomal pigmentation region and calcium-dependence plasmid genes) - by multiplex PCR

Development of a Set of Primers for Drug-Resistance Genes Detection in the Agents of Dangerous Bacterial Infections as Exemplified by <I>Yersinia pestis</I>, <I>Vibrio cholerae</I>, <I>Escherichia coli</I> Strains

A set of primers for detection of genes encoding resistance to streptomycin ( strA, strB ), tetracyclin ( tetA, tetR ), chloramphenicol ( catА ), kanamycin ( npt , aphA ), vankomycin ( sanA ), polymyxin ( pmrD ) has been developed with the aim of rapid and effective detection of drug-resistant strains of dangerous bacterial infections agents. Efficacy of constructed primers has been confirmed against a panel of 40 Yersinia pestis, 49 Vibrio cholerae, and 2 Escherichia coli strains from the State collection of pathogenic bacteria of the RAPI “Microbe”. Drug-resistance genes ntp and catA have been detected in plague agent strains , strA, strB , npt , aphA , tetA and tetR - in cholera agent; strA , tetR , ntp and aphA - in pathogenic strain E. coli О157:H7. Determined is universal character of the designed primers for drug-resistance genes detection in these pathogenic bacteria species

Фармакотерапия подагры – современные подходы и перспективы

The article discusses modern approaches to the gout treatment, presented in foreign and domestic clinical guidelines. While the use of urate-lowering therapy for gout is a necessary and highly effective strategy, in the case of asymptomatic hyperuricemia, the benefits of this approach are not clear. The safety and efficacy of colchicine, as well as its cardioprotective properties, were noted in comorbid patients suffering from gout and cardiovascular diseases. Comparative data on safety and efficacy of the main urate-lowering drugs, allopurinol and febuxostat, are presented. It has been shown that, according to recent studies, febuxostat is more effective than allopurinol in normalizing serum uric acid levels, is not inferior in its cardio safety and is characterized by a lower incidence of other adverse reactions.В статье рассматриваются современные подходы к терапии подагры, представленные в зарубежных и отечественных клинических рекомендациях. Если применение уратснижающей терапии при подагре является необходимой и высокоэффективной стратегией, то в случае бессимптомной гиперурикемии преимущества такого подхода неочевидны. Отмечены безопасность и эффективность колхицина, а также его кардиопротективные свойства у коморбидных пациентов, страдающих подагрой и сердечно-сосудистыми заболеваниями. Приведены сравнительные данные о безопасности и эффективности основных уратснижающих препаратов – аллопуринола и фебуксостата. Показано, что, согласно последним исследованиям, фебуксостат более эффективно, чем аллопуринол, нормализует уровень мочевой кислоты в сыворотке крови, не уступает ему по кардиобезопасности и характеризуется более низкой частотой возникновения других нежелательных реакций

Exploratory Study of the Long-Term Persistence of <i>Yersinia pestis</i> in the Cells of Soil-Inhabiting Ameba - <i>Acanthamoeba Sp.</i>

Objective of the study is to explore the feasibility of the long-term persistence of Yersinia pestis strains in association with ameba - Acanthamoeba sp. Materials and methods. Investigated has been interaction of ameba - Acanthamoeba sp., isolated from rodent burrows in the Pre-Caspian sandy, Volga-Ural steppe, and Pre-Caspian North-Western steppe natural foci, with 4 strains of Y. pestis of the main subspecies, 1 strain of caucasica and 1 strain of altai subspecies. Results and discussion. It is established that the strains of the main subspecies survive in the cells of ameba at 26 °C and 20 % humidity (modeling of the drought conditions in the natural plague foci) within 2-4 months of experiment, and 10-20 times longer that in pure culture. Two strains of the non-main ssp. have not demonstrated an increase in persistency in association with Acanthamoeba sp., which may occur due to degraded resistance to phagocytosis in the ameba of this specie. Using fluorescent and transmission electronic microscopy, it is determined that the cells of plague agent persist in ameba cells in individual vacuoles, enclosed in endoplasmic reticulum. The data obtained may testify to the possible involvement of ameba Acanthamoeba sp. . into sustainment of Y. pestis in soil biocoenoses of natural plague foci

Hematopoietic stem cell transplantation with alpha/beta T-lymphocyte depletion and short course of eculizumab in adolescents and young adults with paroxysmal nocturnal hemoglobinuria

The main goal is to optimize hematopoietic stem cell transplantation (HSCT) approach among adolescents and young adults with paroxysmal nocturnal hemoglobinuria (PNH) by means of Graft-versus-host disease (GVHD) and post-transplant complications risk lowering. Materials and methods. We report our experience of HSCT from HLA-matched unrelated donors using TCR alfa/beta and CD19 depletion in 5 pts (1M/4F) with PNH, developed after successful immunosuppressive therapy (IST) of acquired aplastic anemia (AA). Median age of pts at the moment of transplantation was 17,8 years (range 14,5-22,7), median interval from IST to PNH was 4 years (5mo - 6,5 y). In all patients non-severe pancytopenia was present: granulocytes 0,8х109/l (0,8-1,8 х109/l) platelets 106 х109/l (27-143 х109/l) and Hb -78 g/l, median PNH clone size in granulocytes was 94 (range 75-99)%. One pts previously developed sinus thrombosis. Conditioning consisted of thoraco-abdominal irradiation 4-6 Gy, cyclophosphamide 100 mg/kg, fludarabine 150 mg/m2 and anti-thymocyte globulin (ATG) or alemtuzumab. Eculizumab was given from day (-7) till day (+14) (every 7 days, only 4 times). GVHD prophylaxis was tacrolimus ± methotrexate. Results. Infusedgraft characteristics were: CD34+ - 8,1х106/kg, CD3TCRab·150х103/kg, CD3gd+ - 7,3х106/kg, СD19+ - 221х103/kg, NK -6,4х108/kg. Engraftment was achieved in all 5 pts with a median of 15(12-18) и 13(10-18) days for granulocytes and platelets, respectively. Skin acute GVHD grade I developed in only 1 pt, and subsided with short course of glucocorticoids. CMV reactivation occurred in 1 pt; there were no episodes of Epstein-Barr Virus (EBV) o rAdenovirus (AdV) reactivation. Full donor myeloid chimerism was established in all pts by day +30. Immune reconstitution was delayed until 6 months after transplant but no severe infections occurred. All pts are alive 1,7-5,5 years (med 4 years) after HSCT with normal hematopoiesis and immune function, full donor chimerism and no late sequelae. Conclusions. Transplantation of TCRalfa/beta and CD19 depleted hematopoietic cells from matched unrelated donor after immunoablative conditioning and supported with short course of eculizumab is perfectly safe and efficient technology leading to cure in young patients with PNH

First circumpolar assessment of Arctic freshwater phytoplankton and zooplankton diversity : Spatial patterns and environmental factors

Arctic freshwaters are facing multiple environmental pressures, including rapid climate change and increasing land-use activities. Freshwater plankton assemblages are expected to reflect the effects of these stressors through shifts in species distributions and changes to biodiversity. These changes may occur rapidly due to the short generation times and high dispersal capabilities of both phyto- and zooplankton. Spatial patterns and contemporary trends in plankton diversity throughout the circumpolar region were assessed using data from more than 300 lakes in the U.S.A. (Alaska), Canada, Greenland, Iceland, the Faroe Islands, Norway, Sweden, Finland, and Russia. The main objectives of this study were: (1) to assess spatial patterns of plankton diversity focusing on pelagic communities; (2) to assess dominant component of beta diversity (turnover or nestedness); (3) to identify which environmental factors best explain diversity; and (4) to provide recommendations for future monitoring and assessment of freshwater plankton communities across the Arctic region. Phytoplankton and crustacean zooplankton diversity varied substantially across the Arctic and was positively related to summer air temperature. However, for zooplankton, the positive correlation between summer temperature and species numbers decreased with increasing latitude. Taxonomic richness was lower in the high Arctic compared to the sub- and low Arctic for zooplankton but this pattern was less clear for phytoplankton. Fennoscandia and inland regions of Russia represented hotspots for, respectively, phytoplankton and zooplankton diversity, whereas isolated regions had lower taxonomic richness. Ecoregions with high alpha diversity generally also had high beta diversity, and turnover was the most important component of beta diversity in all ecoregions. For both phytoplankton and zooplankton, climatic variables were the most important environmental factors influencing diversity patterns, consistent with previous studies that examined shorter temperature gradients. However, barriers to dispersal may have also played a role in limiting diversity on islands. A better understanding of how diversity patterns are determined by colonisation history, environmental variables, and biotic interactions requires more monitoring data with locations dispersed evenly across the circumpolar Arctic. Furthermore, the importance of turnover in regional diversity patterns indicates that more extensive sampling is required to fully characterise the species pool of Arctic lakes.Peer reviewe

The role of nelarabine in the treatment of T-cell acute lymphoblastic leukemia: literature review and own experience

Aim. The analysis of experience of nelarabine use in refractory/relapsed T-cell acute lymphoblastic leukemia (T-ALL) depending on the immunophenotype and the line of therapy. Materials and methods. All the patients with relapsed or refractory T-ALL aged from 0 to 18 years who received treatment with nelarabine as a part of the therapeutic element R6 were included in the study. For all patients a detailed immunological analysis of leukemia cells with discrimination of immunological variants TI, TII, TIII or TIV was performed. Patients administered with nelarabine as a first therapeutic element were referred to the first-line therapy group, other patients were referred to the second-line therapy group. Nelarabine was administered as intravenous infusion at a dose of 650 mg/m2, on days 1-5. Allogeneic hematopoietic stem cells transplantation (allo-HSCT) was considered for all patients. Results. From 2009 to 2017, 54 patients with refractory/relapsed T-ALL were treated with nelarabine. Five-year event-free survival (EFS) and overall survival (OS) was 28% for all patients, cumulative risk of relapse (CIR) was 27%. EFS was significantly higher in nelarabine first-line therapy group in comparison with second-line therapy group (34±8% vs 8±8%, p=0,05). In patients after allo-HSCT EFS, OS and CIR were 51±10%, 50±10% and 39,1±9,5% accordingly. The best results were achieved in patients with TI immunophenotype. No toxicity-related mortality as well as severe neurologic complications or discontinuation of therapy associated with use of nelarabine were reported. Conclusion. The use of nelarabine is an effective strategy for the treatment of relapsed and refractory T-ALL. The best treatment outcomes were obtained in patients with TI immunophenotype and in the first-line therapy group. Optimal dosage regimens can be established during controlled clinical trials

Studies of Biofilm Formation in Non-Pigmented and Plasmid-Deprived Mutants of <I>Yersinia pestis</I> on Biotic Surfaces, <I>in vivo</I> and <I>in vitro</I> Conditions

In non-pigmented and plasmid-deprived mutants – isogenic variants of highly virulent Yersinia pestis 231 strain – studied is the mechanism of biofilm formation on biotic surfaces, both in vitro (on the laboratory model of nematode Caenorhabdiitis elegans) and in vivo (inside the alimentary tract of Nosopsyllus laeviceps flea). It is determined that spontaneous loss of ability to form biofilms and generate pigmented colonies in the mutants is probably caused not only by the deletion of the whole chromosome pigmentation fragment, but also by a point(single base) mutation in structural hms operon. It is demonstrated that the absence of pCad, pFra or pPst plasmids does not have an impact on the ability of plasmid-deprived mutants to form biofilm on the cuticle of nematode C. elegans

Corpus annotation for mining biomedical events from literature

<p>Abstract</p> <p>Background</p> <p>Advanced Text Mining (TM) such as semantic enrichment of papers, event or relation extraction, and intelligent Question Answering have increasingly attracted attention in the bio-medical domain. For such attempts to succeed, text annotation from the biological point of view is indispensable. However, due to the complexity of the task, semantic annotation has never been tried on a large scale, apart from relatively simple term annotation.</p> <p>Results</p> <p>We have completed a new type of semantic annotation, event annotation, which is an addition to the existing annotations in the GENIA corpus. The corpus has already been annotated with POS (Parts of Speech), syntactic trees, terms, etc. The new annotation was made on half of the GENIA corpus, consisting of 1,000 Medline abstracts. It contains 9,372 sentences in which 36,114 events are identified. The major challenges during event annotation were (1) to design a scheme of annotation which meets specific requirements of text annotation, (2) to achieve biology-oriented annotation which reflect biologists' interpretation of text, and (3) to ensure the homogeneity of annotation quality across annotators. To meet these challenges, we introduced new concepts such as Single-facet Annotation and Semantic Typing, which have collectively contributed to successful completion of a large scale annotation.</p> <p>Conclusion</p> <p>The resulting event-annotated corpus is the largest and one of the best in quality among similar annotation efforts. We expect it to become a valuable resource for NLP (Natural Language Processing)-based TM in the bio-medical domain.</p