Vipp1 structure and function in cyanobacteria and chloroplasts

The vesicle inducing protein in plastids 1 (Vipp1) is an essential factor for the development and maintenance of the thylakoid membrane. Depletion of Vipp1 in both Arabidopsis and Synechocystis mutants severely affects their ability to form thylakoids and consequently to perform photosynthesis. This work focuses on structural and functional properties of Vipp1. It was shown that Vipp1 assembles into a homooligomeric complex of ca. 2000 kDa. The presence of the Vipp1 complex was detected in cyanobacteria, green algae and higher plants, thereby identifying oligomerization as an essential feature for the function of Vipp1. A detailed computer analysis of Vipp1 secondary structure in different organisms revealed functionally important characteristics of the protein and allowed to discern specific features of its C-terminal domain. Based on the structural analysis, biochemical characterization of Vipp1 domains was carried out. It appeared that the PspA-like domain of Vipp1 is responsible for both complex formation and localisation of Vipp1 at the inner envelope of chloroplasts while the C-terminal domain is not involved in these processes. In order to closer elucidate the function of Vipp1, an analysis of Arabidopsis plants with moderate deficiency in Vipp1 protein level was performed. From results obtained in this analysis it can be proposed that Vipp1 acts at the initial stages of thylakoid biogenesis. Oligomerization of Vipp1 appeared to be a prerequisite for the process of thylakoid formation to commence. Moreover, the extent of thylakoid membrane formation is directly correlated to the amount of Vipp1 protein available in the chloroplast

Preparation of regulatory documents for sodium heparin

Heparin is a direct-acting anticoagulant that regulates many biochemical and physiological processes. The quality of each drug or substance entering the market to the consumer, its packaging, storage conditions and shelf life, as well as quality control methods are established in accordance with the State Pharmacopoeia of the Russian Federation. However, despite the widespread use of heparin in medical practice, the State Pharmacopoeia of the Russian Federation XIV 2018 does not prescribe articles on the substance and drugs containing it as an active substance. Quality control of medicines is undoubtedly relevant. Thus, a negligent attitude in 2008 in China led to the fact that at the early stages of production, the drug was added to the sulfated chondroitin sulfate, which, like heparin, has anticoagulant properties, but is 100 times cheaper. As a result of the use of this drug, there have been more than 100 deaths in the United States and hundreds of serious adverse reactions in patients in Europe. In this regard, the purpose of this study is to determine the quality of heparin-containing injectable drugs

Genetically engineered biological agents in therapy for systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a prototype for chronic autoimmune disease. Its prevalence is 20 to 70 cases per 100,000 women and varies by race and ethnicity. Despite considerable progress in traditional therapy, many problems associated with the management of these patients need to be immediately solved: thus, 50-80% are found to have activity signs and/or frequent exacerbations and about 30% of the patients have to stop work; Class IV lupus nephritis increases the risk of terminalrenal failure. In the past 20 years great progress has been made in studying the pathogenesis of SLE: biological targets to affect drugs have been sought and fundamentally new therapeutic goals defined. Belimumab is the first genetically biological agent specially designed to treat SLE, which is rightly regarded as one of the most important achievements of rheumatology in the past 50 years

Chloroplast Proteins without Cleavable Transit Peptides

Most chloroplast proteins (cp proteins) are nucleus-encoded, synthesized on cytosolic ribosomes as precursor proteins containing a presequence (cTP), and post-translationally imported via the Tic/Toc complex into the organelle, where the cTP is removed. Only a few unambiguous instances of cp proteins that do not require cTPs (non-canonical cp proteins) have been reported so far. However, the survey of data from large-scale proteomic studies presented here suggests that the fraction of such proteins in the total cp proteome might be as large as approximately 30%. To explore this discrepancy, we chose a representative set of 28 putative non-canonical cp proteins, and used in vitro import and Red Fluorescent Protein (RFP)-fusion assays to determine their sub-cellular destinations. Four proteins, including embryo defective 1211, glycolate oxidase 2, protein disulfide isomerase-like protein (PDII), and a putative glutathione S-transferase, could be unambiguously assigned to the chloroplast. Several others ('potential cp proteins') were found to be imported into chloroplasts in vitro, but failed to localize to the organelle when RFP was fused to their C-terminal ends. Extrapolations suggest that the fraction of cp proteins that enter the inner compartments of the organelle, although they lack a cTP, might be as large as 11.4% of the total cp proteome. Our data also support the idea that cytosolic proteins that associate with the cp outer membrane might account for false positive cp proteins obtained in earlier studies

Перспективы применения внутривенного иммуноглобулина при аутоиммунных ревматических заболеваниях

The published data on efficiency of intravenous immunoglobulin (IVIG) in patients with autoimmune rheumatic diseases (RD) are analyzed. IVIG is the drug of choice in patients with Kawasaki disease, idiopathic thrombocytopenic purpura, dermatomyositis, etc. It is reasonable to use IVIG in RD patients with immune deficiency, infectious complications, ineffectiveness of glucocorticoid and cytostatic treatment in patients with developing autoimmune cytopenia, central nervous system dysfunction, and vasculitis. In patients with antiphospholipid syndrome, IVIG can be effective in case of the risk of miscarriage and ineffective anticoagulant therapy.Проанализированы данные литературы об эффективности внутривенного иммуноглобулина (ВВИГ) при аутоиммунных ревматических заболеваниях (РЗ). ВВИГ является препаратом выбора при болезни Кавасаки, идиопатической тромбоцитопенической пурпуре, дерматомиозите и др. Применение ВВИГ у больных с РЗ целесообразно при иммунодефиците, инфекционных осложнениях, неэффективности глюкокортикоидов и цитостатиков в случае развития аутоиммунной цитопении, поражении ЦНС и васкулите. При антифосфолипидном синдроме ВВИГ может быть эффективным при угрозе потери плода и отсутствии эффекта антикоагулянтов

ASSESSMENT OF OVERBANK SEDIMENTATION RATES AND ASSOCIATED POLLUTANT TRANSPORT WITHIN THE SEVERNYA DVINA RIVER BASIN

It is now widely recognized that significant proportion of pollutants in rivers is transported with suspended sediments. This paper presents a combination of reconstruction of recent floodplain sedimentation rates based on detailed description of sediment sections and 137Cs stratigraphy with geochemical analysis of overbank deposits at selected sites on rivers of the Severnaya Dvina River basin. Overbank sedimentation rates for sections sampled on floodplains of the Severnaya Dvina and Vychegda Rivers are characterized by noticeable decrease from ≈1.5–4.0 cm/year between 1954 and 1963 to <1.0 cm/year at present. It can be explained by the natural evolution of the floodplain segments sampled. In contrast, highest modern floodplain aggradation rates (≈1.8 cm/year) observed for the relatively small Toshnya River are definitely associated with human impact—locally intensive agriculture. Evaluation of geochemical properties of overbank sediments has shown that general levels of the sediment contamination by heavy metals are low

Генно-инженерные биологические препараты в терапии системной красной волчанки

Systemic lupus erythematosus (SLE) is a prototype for chronic autoimmune disease. Its prevalence is 20 to 70 cases per 100,000 women and varies by race and ethnicity. Despite considerable progress in traditional therapy, many problems associated with the management of these patients need to be immediately solved: thus, 50-80% are found to have activity signs and/or frequent exacerbations and about 30% of the patients have to stop work; Class IV lupus nephritis increases the risk of terminalrenal failure. In the past 20 years great progress has been made in studying the pathogenesis of SLE: biological targets to affect drugs have been sought and fundamentally new therapeutic goals defined. Belimumab is the first genetically biological agent specially designed to treat SLE, which is rightly regarded as one of the most important achievements of rheumatology in the past 50 years.Системная красная волчанка (СКВ) является прототипом хронического аутоиммунного заболевания. Распространенность СКВ составляет от 20 до 70 случаев на 100 тыс. женщин и варьирует в зависимости от расовой и этнической принадлежности. Несмотря на значительные успехи традиционной терапии, многие проблемы, связанные с ведением этих больных, требуют незамедлительного решения: так у 50-80% больных СКВ выявляются признаки активности и/или частые обострения, около 30% вынуждены прекратить работу, наличие IV класса волчаночного нефрита увеличивает риск развития терминальной почечной недостаточности. За последние 20 лет достигнут огромный прогресс в изучении патогенеза СКВ: найдены биологические мишени для воздействия лекарственных средств и определены принципиально новые терапевтические задачи. Белимумаб – первый генно-инженерный биологический препарат, созданный специально для лечения СКВ, что по праву рассматривается как одно из наиболее крупных достижений ревматологии за последние 50 лет

Intravenous immunoglobulin: prospects in patients with autoimmune rheumatic diseases

The published data on efficiency of intravenous immunoglobulin (IVIG) in patients with autoimmune rheumatic diseases (RD) are analyzed. IVIG is the drug of choice in patients with Kawasaki disease, idiopathic thrombocytopenic purpura, dermatomyositis, etc. It is reasonable to use IVIG in RD patients with immune deficiency, infectious complications, ineffectiveness of glucocorticoid and cytostatic treatment in patients with developing autoimmune cytopenia, central nervous system dysfunction, and vasculitis. In patients with antiphospholipid syndrome, IVIG can be effective in case of the risk of miscarriage and ineffective anticoagulant therapy