Aggregatibacter actinomycetemcomitans leukotoxin induces cytosol acidification in LFA-1 expressing immune cells

Studies have suggested that Aggregatibacter actinomycetemcomitans leukotoxin (LtxA) kills human lymphocyte function-associated antigen 1 (LFA-1; CD11a/CD18)-bearing immune cells through a lysosomal-mediated mechanism. Lysosomes are membrane-bound cellular organelles that contain an array of acid hydrolases that are capable of breaking down biomolecules. The lysosomal membrane bilayer confines the pH-sensitive enzymes within an optimal acidic (pH 4.8) environment thereby protecting the slightly basic cytosol (pH 6.8-7.5). In the current study, we have probed the effect of LtxA-induced cytolysis on lysosomal integrity in two different K562 erythroleukemia cell lines. K562-puro/LFA-1 cells were stably transfected with CD11a and CD18 cDNA to express LFA-1 on the cell surface while K562-puro, which does not express LFA-1, served as a control. Following treatment with 100 ng ml-1 LtxA cells were analyzed by live cell imaging in conjunction with time-lapse confocal microscopy and by flow cytometry. Using a pH-sensitive indicator (pHrodo®) we demonstrated that the toxin causes a decrease in the intracellular pH in K562-puro/LFA-1 cells that is noticeable within the first 15 min of treatment. This process correlated with the disappearance of lysosomes in the cytosol as determined by both acridine orange and LysoTracker® Red DND-99 staining. These changes were not observed in K562-puro cells or when heat inactivated toxin was added to K562-puro/LFA-1. Our results suggest that LtxA induces lysosomal damage, cytosol acidification, which is followed by cell death in K562-puro/LFA-1 cells. © 2016 John Wiley & Sons A/S

Organizational and methodological approaches to development of accounting policy for formation of integrated accounting of interrelated agricultural companies

The purpose of the article is to determine advantages and drawbacks of existing organizational and methodological approaches to development of accounting policy and develop optimal approach to formation of integrated accounting of interrelated agricultural enterprises. For this purpose, the article uses methods of problem and comparative analysis, method of optimization, and methods of graphical presentation of information. The authors conduct comparative analysis of existing organizational and methodological approaches to development of accounting policy of enterprise and develop optimal approach to formation of integrated accounting of interrelated agricultural enterprises. As a result of the research, the authors come to the conclusion that Russian and international approach to development of accounting policy differ from each other, but neither of these approaches is optimal for formation of integrated accounting of interrelated agricultural enterprises. The developed optimal approach to formation of integrated accounting allows unifying the process of development of accounting policy of enterprise and thus is the best for interrelated agricultural enterprises. This approach is oriented at consumers, due to which it is able not only to simplify the process of formation of corporate accounting of interrelated agricultural enterprises but to turn it into the factor of their competitiveness.peer-reviewe

Inhibition of LtxA Toxicity by Blocking Cholesterol Binding with Peptides

The leukotoxin (LtxA) produced by Aggregatibacter actinomycetemcomitans kills host immune cells, allowing the bacterium to establish an ecological niche in the upper aerodigestive tract of its human host. The interaction of LtxA with human immune cells is both complex and multifaceted, involving membrane lipids as well as cell-surface proteins. In the initial encounter with the host cell, LtxA associates with lymphocyte function-associated antigen-1, a cell surface adhesion glycoprotein. However, we have also demonstrated that the toxin associates strongly with the plasma membrane lipids, specifically cholesterol. This association with cholesterol is regulated by a cholesterol recognition amino acid consensus (CRAC) motif, with a sequence of 334LEEYSKR340, in the N-terminal region of the toxin. Here, we have demonstrated that removal of cholesterol from the plasma membrane or mutation of the LtxA CRAC motif inhibits the activity of the toxin in THP-1 cells. To inhibit LtxA activity, we designed a short peptide corresponding to the CRAC336 motif of LtxA (CRAC336WT). This peptide binds to cholesterol and thereby inhibits the toxicity of LtxA in THP-1 cells. Previously, we showed that this peptide inhibits LtxA toxicity against Jn.9 (Jurkat) cells, indicating that peptides derived from the cholesterol-binding site of LtxA may have a potential clinical applicability in controllinginfections of repeats-in-toxin-producing organisms. © 2016 John Wiley & Sons A/S

Conformation of surface exposed N-terminus part of bacteriorhodopsin studied by transferred NOE technique

AbstractInteraction of the monoclonal antibody A5 raised against native bacteriorhodopsin (BR) with the synthetic peptide pGlu1-Ala-Gln-Ile-Thr-Gly-Arg7-NH2, corresponding to the amino acid sequence 1–7 was studied by transferred nuclear Overhauser effect (TRNOE) spectroscopy. The denaturing reagents and the specially designed pulse sequences which eliminate broad signals from the TRNOE spectra were used to favour evaluation of the TRNOE peaks. On the basis of the data obtained, the conformation of peptide bound with A5 was calculated. A model of the mutual arrangement of bacteriorhodopsin N-terminus and the first transmembrane α-helical segment 8–32 was proposed

Smart City as the Basic Construct of the Socio-economic Development of Territories

The relevance of this topic is that any self-respecting city needs a development strategy that develops on the basis of the ideal representations of the future and opportunities. All of the city strive to achieve two fundamental goals. The first is to create a high-quality living environment, which is dictated by growing competition for investment and brains. The second objective - to ensure sustainable development, i.e. the search for the integrated (economic, social, transport, energy, environmental, etc.) model, which would guarantee a dignified existence for at least several generations of citizens. Currently in addressing the challenges of economic modernization and innovative development of Russia a key role to be played by information, knowledge, the widespread use of information and communication technologies, the problems of optimum use of natural resources and ecology, as well as the formation of the social environment, designed to provide optimal conditions for the work of participants the innovation process (Shkurkin, Shestopal, Gurieva, Blaginin and Gurianov 2016). In this context, the problem of creating smart cities is today one of the most pressing. Background of the idea of “smart” city and its development: increase in workload infrastructures. Keywords: Economic development, regional development, smart city, infrastructure, resources JEL Classifications: О13, R1

Metabolic adverse effects of antipsychotics: the state of the problem and management options

Antipsychotic  drugs are widely used for many psychiatric disorders, such as schizophrenia, bipolar affective disorder, delusions and hallucinations  due to neurological  disorders, depression with severe psychotic  symptoms. Metabolic disorders including  weight gain, dyslipidemia and hyperglycemia  are one of the most common side effects of antipsychotic therapy. Psychiatric patients have higher risk of cardiovascular disease, so that the development of metabolic side effects is an important clinical problem that should be solved. Antipsychotic-induced weight gain may cause distress that leads to antipsychotics withdraw and repeated hospitalizations.Lifestyle changes, correction of the antipsychotic treatment, additional medications and their combination are the possible solutions of antipsychotic metabolic side effects. Lifestyle modification is a first-line therapy that should complement other options, when it feasible. At the same time, it can be extremely difficult for patients receiving antipsychotic to adhere dietary and physical activity recommendations. Replacing an antipsychotic with a milder drug is not always possible and may not be enough effective. Metformin seems to be the most well-studied, safe and effective agent that is prescribed to deal with antipsychotic-induced weight gain and associated metabolic disorders. Glucagon-like peptide type 1 receptor agonists and thiazolidinediones  are mentioned as alternative medications, but clinical data on their efficacy and safety in this patient group are extremely limited. Dyslipidemia can develop as an independent antipsychotic side effect even without an increase in body weight. The most effective treatment, as in the general population, is statin therapy. However, the joint appointment of statins and antipsychotic significantly  increases the risk of adverse reactions, such as myalgia, myopathy, increased creatine kinase levels, due to the competition of drugs for the cytochrome system.It is still unknown what scales should be used for cardiovascular risk stratification in patients taking antipsychotic and whether it is possible to use metformin to prevent antipsychotic-induced weight gain, and if so, how to select patients for whom such therapy can be indicated. Finally, more clinical trials are needed to evaluate the efficacy and safety of other classes of hypoglycemic and lipid-lowering drugs in patients on antipsychotics

Assessment of subclinical magnesium deficiency in pregnant women

Introduction. The question of the ratio of calcium and magnesium in the body in the scientific community is not discussed as often as the role of each of these elements. Experts pay even less attention to the ratio of minerals in the body of pregnant women.Aim. To analyze the content of magnesium and calcium in the blood of pregnant women at different gestation periods and evaluate the ratio of magnesium / calcium in order to establish the calculated coefficient.Materials and methods. 272 pregnant women (age 31.85 ± 5.0 years) at different gestation periods were included in the study. The subjects did not complain, typical for the clinic of magnesium and calcium deficiency. All surveyed gave written consent to the study. A biochemical blood test (determination of the concentration of total calcium, magnesium) was carried out in the laboratory of LLC DNKOM in Moscow. Blood sampling from the cubital vein was carried out according to the standard method in the morning on an empty stomach after 10–12 hours of fasting.Results and discussion. Concentration of  total calcium in  the serum was (M  ±  SD) 2.28  ±  0.11  mmol/l, total magnesium  – 0.78 ± 0.07 mmol/l, magnesium/calcium ratio – 0.34 ± 0.03. Mean concentrations of calcium and magnesium were significantly lower in women in the II and III trimesters compared with the I trimester (p < 0.001). A decrease in magnesium concentration below the optimal for pregnant women of 0.8 mmol / l was observed in 37.5% of women in the first trimester, in 77.3% and 84.1% in the II and III trimesters, respectively. Serum magnesium concentration less than 0.7 mmol / l, reflecting a profound magnesium deficiency, was detected in the first trimester in 3.6% of women, in the second trimester – in 11.3% of women, in the third trimester – in 15.9% of pregnancies. Hypocalcemia (total calcium concentration less than 2.15 mmol/l) was recorded in 0.9%, 11.3% and 22.3% of pregnant women in the I, II and III trimesters. When calculating the magnesium/calcium ratio, subclinical magnesium deficiency was detected in 96.7% of pregnant women throughout pregnancy. Conclusion. The data obtained indicate the need for pregravid examination and early correction of metabolic disorders.>< 0.001). A decrease in magnesium concentration below the optimal for pregnant women of 0.8 mmol / l was observed in 37.5% of women in the first trimester, in 77.3% and 84.1% in the II and III trimesters, respectively. Serum magnesium concentration less than 0.7 mmol / l, reflecting a profound magnesium deficiency, was detected in the first trimester in 3.6% of women, in the second trimester – in 11.3% of women, in the third trimester – in 15.9% of pregnancies. Hypocalcemia (total calcium concentration less than 2.15 mmol/l) was recorded in 0.9%, 11.3% and 22.3% of pregnant women in the I, II and III trimesters. When calculating the magnesium/calcium ratio, subclinical magnesium deficiency was detected in 96.7% of pregnant women throughout pregnancy.Conclusion. The data obtained indicate the need for pregravid examination and early correction of metabolic disorder

Experience with the use of oral probiotic Streptococcus salivarius K12 for the prevention of recurrence of pharyngotonsillar

Relevance. Pharyngotonsillitis (PhT) is one of the most common recurrent upper respiratory tract diseases. Viruses are the most common cause of disease (Respiratory viruses, Enterov iruses, Herpesviruses), 30% are of bacterial origin. The most serious types of PhT are associated with group of β-hemolytic streptococcus (GAS) - Streptococcus pyogenes, in which antibiotic therapy is the first choice of therapy. In order to reduce the use of antibiotics, to prevent relapses of pharyngotonsillar episodes, a specific probiotic therapy was carried out using Streptococcuss alivarius K12 (SsK12). K12 (SsK12) is a probiotic strain that inhibits the growth of Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis in vitro. Materials and methods. A study was conducted in 90 patients with recurrent pharyngotonsillitis (PhT) of bacterial origin, in whom Streptococcus pyogenes was isolated during bacteriolog ical examination. The course of treatment for patients of all groups was 30 days. Patients of group 1 (30 people) were treated with standard methods. In 30 patients of group 2 (30 people), in addition to standard therapy, the respiratory probiotic "Bactoblis" was used for a course of 30 days. In 30 patients of group 3, standard therapy was carried out with the use of the respiratory probiotic drug "Bactoblis" and additional sanitation of the lacunae of the palatine tonsils by vacuum extraction. As a result, in patients of groups 2 and 3, the frequency of PhT episodes significantly decreased, and the use of antibiotics decreased too. The most persistent effect of treatment was in patients of group 3 - the quality of treatment and prevention increased, the number of exacerbations decreased, the severity of clinical manifestations, and the drug load decreased. Individual intolerance to the components of the drug has not been identified. However, 6 months after the observation was started, the clinical and laboratory parameters of the main groups began to deteriorate, approaching those of the control group, and more stable therapeutic effect was observed in patients of group 3. Conclusions. The authors consider it expedient to perform tonsil sanitation twice a year, with further use of the drug "Bactoblis" in patients suffering from PhT. All human studies were conducted in compliance with the rules of the Helsinki Declaration of the World Medical Association "Ethical principles of medical research with human participation as an object of study". Informed consent was obtained from all participants

Результаты изучения зеленных культур семейства Apiaceae как генетических ресурсов для вертикального овощеводства с использованием природных иммуномодуляторов

Relevance. New technologies Plenty-type in greenhouse vegetable production is wide spread in some countries of Europe, America, South-East Asia and support with main investors of these countries. Project “Vertical farming” was started in FSBSI “Federal Scientific Vegetable Center” at 2010. The goal of our study is the results of the testing plants Apiaceae family at multy circle hydroponic installation using the natural regulators from glycosides class.Materials and methods. Objects of study: plants Apiaceae family – Coriandrum sativum L. (variety Jubilar), Anethum graveolens L. (variety Rusich), Apium graveolens L. (variety Aeliksir); flavonoid glycoside linarozid from plants Linaria vulgaris Mill. L., steroid glycoside moldstim from seeds Capsicum annuum L.. Methods of study: seed treatment with 0,001% water solutions of glycosides, cultivation of plants Apiaceae family at the multi circle hydroponic construction.Results. First experiment by cultivation of plants Apiaceae family at multi circle hydroponic construction was successful and show, that plants Apiaceae family can cultivate at vertical installations Plenty-type. Reaction on the seed treatment with water solutions of glycosides is depended on the species of plants. Seed treatment with glycosides increased height of plants and weight of leaves of Coriandrum sativum L. Anethum graveolens L. increased germination of seeds after seed treatment with water solution of linarozide. Apium graveolens L. increased germination of seeds, height of plants and weight of leaves after seed treatment with water solutions of glycosides. But water solution of moldstim was more effective in 2020, and water solution of linarozide was more effective in 2021.Актуальность. Новые технологии в тепличном овощеводстве Plenty (вертикальное овощеводство) получили широкое распространение и материальную поддержку ведущих инвесторов в странах Европы, Америки и Юго-Восточной Азии. В Российской Федерации программа по вертикальному овощеводству стартовала в ФГБНУ «Федеральный научный центр овощеводства» в 2010 году.Цель исследований: испытание зеленных культур семейства Apiaceae на многоярусной гидропонной установке с использованием природных иммуномодуляторов.Материалы и методы. Объекты исследований: растения семейства Apiaceae – Coriandrum sativum L. (сорт Юбиляр), Anethum graveolens L. (сорт Русич), Apium graveolens L. (сорт Эликсир); флавоноидный гликозид линарозид из растений Linaria vulgaris Mill. L., стероидный гликозид молдстим из семян Capsicum annuum L..Методы исследований: обработка семян водными растворами гликозидов, культивирование растений семейства Apiaceae на пятиярусной гидропонной конструкции, биометрия и статистический анализ результатов исследований по Б.А. Доспехову (1985).Результаты исследований. Растения семейства Apiaceae могут культивироваться на многоярусных вертикальных гидропонных конструкциях типа Plenty. Реакция на обработку семян природными иммуномодуляторами зависит от вида растения. Кориандр посевной реагировал существенным повышением высоты растений и зелёной массы, укроп пахучий – существенным повышением всхожести семян, сельдерей листовой – существенным повышением всхожести, высоты растений и массы надземной части. Но водный раствор молдстима был более эффективным в 2020 году, а водный раствор линарозида был более эффективным в 2021 году