The course and effectiveness of combination antiviral therapy of HCV-infection with extrahepatic manifestations

In the coming years is projected to increase the number of patients with chronic HCV-infection. Increases in registration of extrahepatic manifestations of hepatitis С with proven involvement of agent as an etiologic factor. The study shows the clinical manifestations of lesions of the cardiovascular, nervous and urinary systems in HCV-infection. Displaying a more severe course of hepatitis С with extrahepatic manifestations. Marked decrease of sustained virological response in patients with extrahepatic manifestations, which allows us to consider them as an independent predictor of the effectiveness of combination antiviral therapy of HCV-infection.В ближайшие годы прогнозируется увеличение количества больных хронической HCV-инфекцией. Возрастает регистрация внепечёночных проявлений вирусного гепатита С с доказанным участием возбудителя, как этиологического фактора. В исследовании приведены клинические проявления поражения сердечно-сосудистой, нервной, мочевыделительной систем при HCV-инфекции. Показано более тяжёлое течение вирусного гепатита С с внепечёночными проявлениями. Отмечается уменьшение устойчивого вирусологического ответа в группе пациентов с внепечёночными проявлениями, что позволяет рассматривать их как независимый предиктор эффективности комбинированной противовирусной терапии HCV-инфекции

Transcriptome analyses of the Giardia lamblia life cycle

Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Molecular and Biochemical Parasitology 174 (2010): 62-65, doi:10.1016/j.molbiopara.2010.05.010.We quantified mRNA abundance from 10 stages in the Giardia lamblia life cycle in vitro using Serial Analysis of Gene Expression (SAGE). 163 abundant transcripts were expressed constitutively. 71 transcripts were upregulated specifically during excystation and 42 during encystation. Nonetheless, the transcriptomes of cysts and trophozoites showed major differences. SAGE detected co-expressed clusters of 284 transcripts differentially expressed in cysts and excyzoites and 287 transcripts in vegetative trophozoites and encysting cells. All clusters included known genes and pathways as well as proteins unique to Giardia or diplomonads. SAGE analysis of the Giardia life cycle identified a number of kinases, phosphatases, and DNA replication proteins involved in excystation and encystation, which could be important for examining the roles of cell signaling in giardial differentiation. Overall, these data pave the way for directed gene discovery and a better understanding of the biology of Giardia lamblia.BJD, DSR, and FDG were supported by NIH grants AI42488, GM61896, DK35108, and AI051687. DP and SGS were supported by grants from the Swedish Natural Science Research Council, the Swedish Medical Research Council, and the Karolinska Institutet. AGM, SRB, SPP, and MJC were supported by NIH grant AI51089 and by the Marine Biological Laboratory’s Program in Global Infectious Diseases, funded by the Ellison Medical Foundation

The clinical, epidemiological and laboratory characteristics of acute viral hepatitis С whith users of introvenous drugs

Viral hepatitis С remains a global problem of modern health care. It accounts for up to 20% of acute hepatitis, 70% of chronic hepatitis, 40% of liver cirrhosis in the terminal stage, from 15-20 to 60-70% of cases of hepatocellular carcinoma. The virus of hepatitis С has the highest horiogen potential. The aggravating factors have the significantly influence on the pathogenesis and clinical manifestations of HCV - infection, such as: alcoholism, drug addiction, medicinal liver disease, HBV/HCV mixed-infection. The patients with HCV, using drugs, have a shorter incubation period, more pronounced cytolytic and cholestatic syndromes, which affects on the clinical course and prognosis. This dictates the necessity to study the flow characteristics of HCV in drug users.Вирусный гепатит С (ВГС) продолжает оставаться глобальной проблемой современного здравоохранения. На его долю приходится до 20 % острых гепатитов, 70% хронических гепатитов, 40% циррозов печени в терминальной стадии, от 15-20 до 60-70 % случаев гепатоцеллюлярной карциномы. Вирус гепатита С обладает наиболее высоким хрониогенным потенциалом. На патогенез и клинические проявлениях HCV-инфекции существенное влияние оказывают отягощающие факторы: алкоголизм, наркомания, лекарственное поражение печени, HBV/HCV микст-инфекция. У больных ВГС, употребляющих наркотики, отмечается более короткий инкубационный период, более выраженные цитолитический и холестатический синдромы, что оказывает влияние ни клиническое течение и прогноз заболевания. Это диктует необходимость изучения особенностей течения ВГС у наркопотребителей

Analysis of patients with acute coronary syndrome without ST segment elevation at the prehospital stage

The aim of the study to analyze the clinical, anamnestic, objective parameters of patients with STEMI at the prehospital stage and the tactics of their management.Цель исследования – проанализировать клинические, анамнестические, объективные параметры пациентов с ОКСБПST на догоспитальном этапе и тактику их ведения

The relationship predictors of effectiveness of combined antiviral therapy of the syndrome of endogenous intoxication in the patients with chronic viral hepatitis С

Predictors of the effectiveness of combined antiviral therapy of chronic hepatitis С vims believe: the genotype of the virus, the initial level of viremia, age, sex, race, body weight, the initial level of alanine aminotransferase activity, the severity of fibrosis of the liver, route of transmission, genetic polporphism of IL-28, syndrome of iron overload, duration of infection, adherence to treatment, scheme of therapy. The prevalence of chronic viral hepatitis С infection among young people on the one hand and the increase in frequency stable virologic response to therapy in adolescence on the other, dictate the need for an adequate approach to the treatment of these patients. Assessment of the level of endogenous intoxication in the period of treatment and further observation with chronic viral hepatitis С shows the failure of compensatory mechanisms detoxifying function of the liver, check-in and after the antiviral therapy.Предикторами эффективности комбинированной противовирусной терапии хронического вирусного гепатита С считают: генотип вируса, исходный уровень вирусемии, возраст, пол, расу, массу тела, исходный уровень активности аланинаминотрансферазы, выраженность фиброза печени, путь передачи, генетический полиморфизм гена IL-28B, синдром перегрузки железом, длительность инфицирования, приверженность пациента к лечению, схема терапии. Распространение хронического вирусного гепатита С среди молодёжи с одной стороны и увеличение частоты стойкого вирусологического ответа на терапию в юношеском возрасте с другой, диктуют необходимость адекватного подхода к лечению данной группы пациентов. Оценка уровня эндогенной интоксикации в период лечения и дальнейшего наблюдения при хроническом вирусном гепатите С показывает срыв компенсаторных механизмов дезинтоксикационной функции печени, регистрируемом и после проведённой противовирусной терапии

Molecular Time-Course and the Metabolic Basis of Entry into Dauer in Caenorhabditis elegans

When Caenorhabditis elegans senses dauer pheromone (daumone), signaling inadequate growth conditions, it enters the dauer state, which is capable of long-term survival. However, the molecular pathway of dauer entry in C. elegans has remained elusive. To systematically monitor changes in gene expression in dauer paths, we used a DNA microarray containing 22,625 gene probes corresponding to 22,150 unique genes from C. elegans. We employed two different paths: direct exposure to daumone (Path 1) and normal growth media plus liquid culture (Path 2). Our data reveal that entry into dauer is accomplished through the multi-step process, which appears to be compartmentalized in time and according to metabolic flux. That is, a time-course of dauer entry in Path 1 shows that dauer larvae formation begins at post-embryonic stage S4 (48 h) and is complete at S6 (72 h). Our results also suggest the presence of a unique adaptive metabolic control mechanism that requires both stage-specific expression of specific genes and tight regulation of different modes of fuel metabolite utilization to sustain the energy balance in the context of prolonged survival under adverse growth conditions. It is apparent that worms entering dauer stage may rely heavily on carbohydrate-based energy reserves, whereas dauer larvae utilize fat or glyoxylate cycle-based energy sources. We created a comprehensive web-based dauer metabolic database for C. elegans (www.DauerDB.org) that makes it possible to search any gene and compare its relative expression at a specific stage, or evaluate overall patterns of gene expression in both paths. This database can be accessed by the research community and could be widely applicable to other related nematodes as a molecular atlas

Formation of Amyloid-Like Fibrils by Y-Box Binding Protein 1 (YB-1) Is Mediated by Its Cold Shock Domain and Modulated by Disordered Terminal Domains

YB-1, a multifunctional DNA- and RNA-binding nucleocytoplasmic protein, is involved in the majority of DNA- and mRNA-dependent events in the cell. It consists of three structurally different domains: its central cold shock domain has the structure of a β-barrel, while the flanking domains are predicted to be intrinsically disordered. Recently, we showed that YB-1 is capable of forming elongated fibrils under high ionic strength conditions. Here we report that it is the cold shock domain that is responsible for formation of YB-1 fibrils, while the terminal domains differentially modulate this process depending on salt conditions. We demonstrate that YB-1 fibrils have amyloid-like features, including affinity for specific dyes and a typical X-ray diffraction pattern, and that in contrast to most of amyloids, they disassemble under nearly physiological conditions

Integrative Analysis of the Caenorhabditis elegans Genome by the modENCODE Project

We systematically generated large-scale data sets to improve genome annotation for the nematode Caenorhabditis elegans, a key model organism. These data sets include transcriptome profiling across a developmental time course, genome-wide identification of transcription factor-binding sites, and maps of chromatin organization. From this, we created more complete and accurate gene models, including alternative splice forms and candidate noncoding RNAs. We constructed hierarchical networks of transcription factor-binding and microRNA interactions and discovered chromosomal locations bound by an unusually large number of transcription factors. Different patterns of chromatin composition and histone modification were revealed between chromosome arms and centers, with similarly prominent differences between autosomes and the X chromosome. Integrating data types, we built statistical models relating chromatin, transcription factor binding, and gene expression. Overall, our analyses ascribed putative functions to most of the conserved genome

STRUCTURAL ASPECTS OF INFLATIONARY PROCESSES

The article presents the structural analysis of the Russia inflation in 1992 – 2017 according to Rosstat with the focus on the latest phase of development  in terms of the economical sanctions. The inflation is heterogeneous in its  structure, because of the different degree of elements’ coverage in the  economical system and because of the diverse role of each sector in the  reproduction process. Mechanisms and factors of pricing in various sectors of economy have individual features, and the price ratio between them varies according to changing power of inflation. In this content inflation can classified as systemic and local, balanced and unbalanced. The sector of  inflation can be determined as drivers and outsiders of rising prices. In case  of systemic inflation of the price process, structural parts of the system  would be included. Balanced inflation occurs when the growth equality rates of the final products and rate of prices’ growth would be presented. Price  movement through phases of growth and decline forms a sector with minimum and maximum prices

The major mRNA-associated protein YB-1 is a potent 5′ cap-dependent mRNA stabilizer

mRNA silencing and storage play an important role in gene expression under diverse circumstances, such as throughout early metazoan development and in response to many types of environmental stress. Here we demonstrate that the major mRNA-associated protein YB-1, also termed p50, is a potent cap-dependent mRNA stabilizer. YB-1 addition or overexpression dramatically increases mRNA stability in vitro and in vivo, whereas YB-1 depletion results in accelerated mRNA decay. The cold shock domain of YB-1 is responsible for the mRNA stabilizing activity, and a blocked mRNA 5′ end is required for YB-1-mediated stabilization. Significantly, exogenously added YB-1 destabilizes the interaction of the cap binding protein, eIF4E, with the mRNA cap structure. Conversely, sequestration of eIF4E from the cap increases the association of endogenous YB-1 with mRNA at or near the cap, and significantly enhances mRNA stability. These data support a model whereby down-regulation of eIF4E activity or increasing the YB-1 mRNA binding activity or concentration in cells activates a general default pathway for mRNA stabilization