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Infant colic is a common condition of unknown pathogenesis that brings frustration to families seeking for effective management. Accumulating evidence suggests that some single strains of lactobacilli may play a positive dietary role in attenuation of colic in exclusively breastfed infants. The objective of this study was to evaluate a mixture of two Lactobacillus strains in decreasing infant cry and fuss in this population. Infants aged 4–12 weeks received L. rhamnosus 19070-2 and L. reuteri 12246 in a daily dose of 250 × 106 CFU, 3.33 mg of fructooligosaccharide, and 200 IU of vitamin D3 (84 infants, probiotic group) or just vitamin D3 (84 infants, control group) for 28 days. Cry and fuss time were measured with validated Baby’s Day Diary on days 0 and 28. At baseline, mean (SD) duration of cry and fuss time was comparable in the probiotic and control groups: 305 (81) vs. 315 (90) min., respectively (p = 0.450). On day 28, mean cry and fuss time became statistically different: 142 (89) vs. 199 (72), respectively (p &lt, 0.05). Mean change in cry and fuss time from day 0 through day 28 was −163 (99) minutes in the probiotic and −116 (94) minutes in the control group (p = 0.019). Our findings confirm that lactobacilli decrease cry and fuss time and provide a dietary support in exclusively breastfed infants with colic.

Reductive dehalogenation such as that catalyzed by iodotyrosine deiodinase (IYD) is highly unusual in aerobic organisms but necessary for iodide salvage from iodotyrosine generated during thyroxine biosynthesis. Equally unusual is the dependence of this process on flavin. Rapid kinetics have now been used to define the basic processes involved in IYD catalysis. Time-dependent quenching of flavin fluorescence was used to monitor halotyrosine association to IYD. The substrates chloro-, bromo-, and iodotyrosine bound with similar rate constants (kon) ranging from 1.3 × 10(6) to 1.9 × 10(6) M(-1) s(-1). Only the inert substrate analogue fluorotyrosine exhibited a significantly (5-fold) slower kon (0.3 × 10(6) M(-1) s(-1)). All data fit a standard two-state model and indicated that no intermediate complex accumulated during closure of the active site lid induced by substrate. Subsequent halide elimination does not appear to limit reactions of bromo- and iodotyrosine since both fully oxidized the reduced enzyme with nearly equivalent second-order rate constants (7.3 × 10(3) and 8.6 × 10(3) M(-1) s(-1), respectively) despite the differing strength of their carbon-halogen bonds. In contrast to these substrates, chlorotyrosine reacted with the reduced enzyme approximately 20-fold more slowly and revealed a spectral intermediate that formed at approximately the same rate as the bromo- and iodotyrosine reactions.

The nanocomposite – nanoporous silica (SBA-16) containing ZnO quantum dots – was fabricated by the sublimation method. This novel route of synthesizing ZnO nanoparticles implies physical sorption of zinc acetylacetonate precursor into the matrix pores from the gaseous phase, hydrolysis of the precursor, and thermal decomposition of the product with formation of ZnO nanoclusters directly inside the pores. The nanocomposite was characterized by XRD, nitrogen adsorption-desorption isotherms, and photoluminescence spectroscopy methods. We observed the blue shift of the ultraviolet luminescence of nanocomposite as compared to the luminescence of ZnO nanopowder as well as the decrease of the linewidth of the ultraviolet luminescence line, which points to the encapsulation of ZnO nanoparticles in the silica pores and narrowing of their size distribution.

У статті наведені дані літератури та власний досвід застосування оральних провокаційних проб, які є золотим стандартом діагностики харчової алергії і дають можливість не лише підтвердити її, але й визначити толерантність до продукту, провести моніторинг ефективності харчової десенсибілізації. Представлені показання та ризики проведення оральних провокаційних проб. Відзначені труднощі в трактуванні результатів. Зокрема, подано інформацію про те, що найскладніше — оцінювати легковиражені, суб’єктивні або атипові симптоми харчової алергії, оскільки вони можуть не лише свідчити про початок розвитку серйозних реакцій, але й бути результатом впливу емоційних чинників. Описано індивідуальний підхід до вибору дози харчового алергену та інтервалу між його подачею при проведенні оральних провокаційних проб. Власний досвід підтверджує, що симптоми під час оральних провокаційних проб переважно з’являються після введення більших доз алергену. І, відповідно, на більших дозах зазвичай виникають тяжчі симптоми харчової алергії. Короткий часовий інтервал між уведеннями алергену (менше 30 хвилин) може ускладнити інтерпретацію результатів і скомпрометувати проби. У статті наведено клінічний випадок проведення оральної провокаційної проби у 7-місячної дитини, що підтвердив наявність алергії до білків коров’ячого молока. Цей випадок дозволяє прослідкувати особливості діагностичного пошуку та способу проведення проби у дитини раннього віку з використанням дитячих сумішей (стандартної адаптованої молочної та суміші з повним гідролізом білків)., В статье представлены данные литературы и собственный опыт применения оральных провокационных проб, которые являются золотым стандартом диагностики пищевой аллергии и дают возможность не только подтвердить ее, но и определить толерантность к продукту, провести мониторинг эффективности пищевой десенсибилизации. Представлены показания и риски проведения оральных провокационных проб. Отмечены трудности в трактовке результатов. В частности, подана информация о том, что самое сложное — оценивать легковыраженные субъективные или атипичные симптомы пищевой аллергии, поскольку они могут не только свидетельствовать о начале развития серьезных реакций, но и быть результатом влияния эмоциональных факторов. Описан индивидуальный подход к выбору дозы пищевого аллергена и интервала между его подачей при проведении оральных провокационных проб. Собственный опыт подтверждает, что симптомы во время оральных провокационных проб преимущественно появляются после введения больших доз аллергена. И, соответственно, на больших дозах обычно возникают тяжелые симптомы пищевой аллергии. Короткий временной интервал между приемами аллергена (менее 30 минут) может осложнить интерпретацию результатов и скомпрометировать пробы. В статье представлен клинический случай проведения оральной провокационной пробы у 7-месячного ребенка, который подтвердил наличие аллергии к белкам коровьего молока. Данный случай позволяет проследить особенности диагностического поиска и способа проведения пробы у ребенка раннего возраста с использованием детских смесей (стандартной адаптированной молочной и смеси с полным гидролизом белков)., The article presents literature data and therapeutic experience on the use of oral provocation tests. They are considered to be the golden standard for the diagnosis of food allergy and provide an opportunity not only to confirm the pre­sence of the condition, but also to determine the level of to­lerance to the product and to monitor the effectiveness of food desensitization. The risks and indications for oral provocation tests are presented. Difficulties in the results interpretation have also been evaluated. In particular, information about the fact that the mild, subjective, or atypical symptoms of food allergy are most complicated in the evaluation, as they can not only indicate the beginning of the development of serious reactions, but also be the result of the influence of emotional factors. The individual approach to choosing the dose of the food allergen and the interval between its administration during oral provocation tests was described. Our therapeutic experience confirms that symptoms during oral provocation tests predominantly occur after the administration of the allergen in higher doses. And, accordingly, at higher doses, as a rule, there were more severe symptoms of food allergy. A short time interval between the administration of an allergen (less than 30 minutes) can complicate the interpretation of the results and compromise the test. The article presents a clinical case of the oral provocation test in a 7-month-old child, which confirmed the presence of allergy to cow’s milk proteins. This case allows us to trace the peculiarities of the diagnostic investigation and the method of conducting the test at an early age using infant formulas (standard adapted milk and formula with complete protein hydrolysis).

We solved the problem of development of algorithmic software for processes of content monitoring for solving the problem of recognition of the style of an author of a Ukrainian text based on Web Mining and NLP technology. Decomposition of the method for recognition of the style of an author, based of analysis of the found stop words, was carried out. Specific features of the method include adaptation of morphological and syntactic analysis of lexical units to structural peculiarities of words/ texts in Ukrainian. It is syntactic words (stop words or anchor words) that are significant for an author’s individual style, as they are not related to the theme and content of the publication. Recognition of the author's style is based on analysis of coefficients of lexical author’s language: coherence of speech, lexical diversity, syntactic complexity indices of concentration and exclusivity for the author's fragment. They are used for subsequent comparison and determining of a degree of belonging of the analyzed text to a particular author. We studied internal "dynamics" of a text of randomly selected authors through analysis of coefficients of lexical author’s language for the first k, n and m (without the title) words of the author's fragment and the analyzed one. The obtained results were compared. We obtained results of experimental testing of the proposed method for content-monitoring for determining and analysis of stop words in Ukrainian scientific texts of technical area based on Web Mining technology. It was found that for the selected experimental base that contains 100 works, the method for analysis of an article without compulsory initial information and list of references attains the best results by density criterion. It is achieved through learning of the system and by checking specified blocked words and specified thematic vocabulary. Testing of the proposed method for determining of keywords from other categories of texts – of scientific humanitarian area, belles-lettres, journalistic, etc. – requires subsequent experimental research., Розглянуто особливості застосування технологій лінгвометрії, стилеметрії та глоттохронології для визначення стилю автора публікацій. Лінгвостатистичний аналіз авторського тексту використовує переваги контент-моніторінгу на основі методів NLP для визначення стопових слів. Квантитативний аналіз стопових слів використано для визначення степеня приналежності аналізованого тексту конкретному авторові. Запропоновано метод визначення стилю автора україномовного тексту, Рассмотрены особенности применения технологий лингвометрии, стилеметрии и глоттохронологии для определения стиля автора публикаций. Лингвостатистический анализ авторского текста использует преимущества контент-мониторинга на основе методов NLP для определения стоповых слов. Квантитативный анализ стоповых слов использовано для определения степени принадлежности анализируемого текста конкретному автору. Предложен метод определения стиля автора украиноязычного текста

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by skeletal muscle atrophy and weakness, ultimately leading to respiratory failure. The purpose of this study was to assess changes in skeletal muscle excitation-contraction (E-C) coupling and intracellular Ca2+handling during disease progression in the G93A*SOD1 ALS transgenic (ALS Tg) mouse model. To assess E-C coupling, single muscle fibers were electrically stimulated (10–150 Hz), and intracellular free Ca2+concentration was assessed using fura-2. There were no differences in peak fura-2 ratio at any stimulation frequency at 70 days (early presymptomatic). However, at 90 days (late presymptomatic) and 120–140 days (symptomatic), fura-2 ratio was increased at 10 Hz in ALS Tg compared with wild-type (WT) fibers (0.670 ± 0.02 vs. 0.585 ± 0.02 for 120–140 days; P < 0.05). There was also a significant increase in resting fura-2 ratio at 90 days (0.351 ± 0.008 vs. 0.390 ± 0.009 in WT vs. ALS Tg; P < 0.05) and 120–140 days (0.374 ± 0.001 vs. 0.415 ± 0.003 in WT vs. ALS Tg; P < 0.05). These increases in intracellular Ca2+in ALS Tg muscle were associated with reductions in the sarcoplasmic/endoplasmic reticulum Ca2+ATPase proteins SERCA1 (to 54% and 19% of WT) and SERCA2 (to 56% and 11% of WT) and parvalbumin (to 80 and 62% of WT) in gastrocnemius muscle at 90 and 120–140 days, respectively. There was no change in dihydropyridine receptor/l-type Ca2+channel at any age. Overall, these data demonstrate minimal changes in electrically evoked Ca2+transients but elevations in intracellular Ca2+attributable to decreased Ca2+-clearance proteins. These data suggest that elevations in cellular Ca2+could contribute to muscle weakness during disease progression in ALS mice.

BACKGROUND Since July 1st, 2009 in accord with the statuary order based on the German law for infectious diseases (Infektionsschutzgesetz), MRSA in blood and liquor have to be notified to the public health authorities. The aim of this extension of the notification to report is to improve the surveillance of nosocomial infections and the prevention of nosocomial MRSA infections. In this paper data of the notifications in the year 2011 within the MDRO-Net Rhine-Main, an association of 7 public health authorities in the region, are reported in order to investigate whether the aims of the obligation for notification could be achieved. RESULTS In 2011, 138 MRSA bloodstream infections, including 1 MRSA in liquor culture, were notified to the 7 health protection authorities, resulting in an incidence rate of 5.6/100,000 inhabitants. In urban regions with more hospitals available, the incidence rate was higher than in rural districts with less medical facilities (6.9 vs. 4.4/100,000 inhabitants). Only 46 (35%) of the patients with MRSA cultured in their blood had been detected via anamnesis as patients on risk for MRSA, and 59 (45%) had been screened for MRSA on admission. The incidence rate in the different hospitals was 0.041 ± 0.031/1,000 patient days (range 0-0.145/1,000 patient days). CONCLUSIONS For the first time, data on notification of MRSA cultures in blood specimen are published from a whole MRE Network in Germany encompassing >2.1 million inhabitants. Incidence rates per 100,000 inhabitants alone do not seem adequate to cope with the aims of the obligation for notification. Instead, reference to patient days in the respective clinic enables an external comparison to other medical institutions in the region and is a better base for discussion with these institutions on improvements of surveillance, screening and hygiene.

The architecture and implemented a software system parsing schemes of algebraic algebra and their interpretation. The software system allows to generate automated in such schemes create a program and debug the relevant schemes. A clear division of algebraic algebra into separate modules is defined, each of which will be characterized by its functional load. The methods of parsing for the development and presentation of grammar such schemes are used. Automatic transforming it in a list form is implemented. A machine system of algebraic algebra as an abstract interpretation of the mechanism of grammar parser is defined. The vocabulary V consists of finite not empty set of lexical units. The expression on V is a finite-length string of lexical units with V. An empty string does not contain lexical items and is denoted by Λ. The set of all lexical units over V is denoted as V ′. The language over V is a subset V ′. The language displayed through the set of all lexical units of language or through definition criteria, which should satisfy lexical items that belong to the language. Another is one important method to set the language through the use of generative grammar. The grammar consists of a lexical units set of various types and the rules or productions set of expression constructing. Grammar has a vocabulary V, which is the set of lexical units for language expressions building. Some of lexical units of vocabulary (terminal) can not be replaced by other lexical units. The text realizes structural submitted activities through provides subject, object, process, purpose, means and results that appear in content, structural, functional and communicative criteria and parameters. The units of internal organization of the text structure are alphabet, vocabulary (paradigmatics), grammar (syntagmatic) paradigm, paradigmatic relations, syntagmatic relation, identification rules, expressions, unity between phrasal, fragments and blocks. On the compositional level are isolated sentences, paragraphs, sections, chapters, under the chapter, page etc. that (except the sentence) indirectly related to the internal structure because are not considered. With the help of a database (database for terms/morphemes and structural parts of speech) and defined rules of text analysis searching terms. Parsers operate in two stages: lexemes content identifying and a parsing tree creates.

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Under conditions of active development of innovative information technologies (IT) and eliminating the boundaries in providing educational services, human resources (staff, including IT specialists) turn into the main strategic resource of organizations, which ensures their long-term competitiveness and achievement of the set goals. Much emphasis in this problem is given to both the specific features of a recruiting company and to a high level of provision of educational services that meet international standards and requirements for the level of competences of would-be IT specialists. Therefore, the development of new conceptual approaches and promising information technologies of managing human resources acquires special relevance and practical significance. The article highlighted specific features of tasks of managing qualified human resources (MQHR), which allows identifying them as a task of multicriteria analysis and decision making in the fuzzy environment. A generalized conceptual model for decision making in the problems of MQHR was proposed. It was substantiated that in order to enhance effectiveness and transparency of decisions in MQHR, it is appropriate to use multicriteria optimizations based on the TOPSIS method, the advantages of which were shown. A modification of the algorithm for using TOPSIS for making recommendations in recruiting qualified human resources was proposed. The modification implies the integration of additional components of the content management in the decision making algorithm, which provides for the calculation based on the method of analysis of hierarchies (MAH) of coefficients of level or course of attained educational services. Using the TOPSIS and MAH methods and the scale of assessment of competence of qualified human resources, experimental calculations with ranking of alternatives were performed using the example of recruiting, which demonstrated effectiveness of the proposed approach., Выделены специфические особенности задач управления квалифицированными человеческими ресурсами (УКЛР), позволяющие идентифицировать их как задачи многокритериального анализа и принятия решений в нечеткой среде. Предложена модель принятия решений в задачах УКЛР. Обосновано, что для повышения эффективности и прозрачности решений в УКЛР целесообразно применение многокритериальной оптимизации на базе TOPSIS и показаны его преимущества, Виділені специфічні особливості задач управління кваліфікованими людськими ресурсами (УКЛР), що ідентифікують їх як завдання багатокритеріального аналізу і прийняття рішень в нечіткому середовищі. Запропоновано модель прийняття рішень в задачах УКЛР. Обґрунтовано, що для підвищення ефективності та прозорості рішень в УКЛР доцільно застосування багатокритеріальної оптимізації на базі TOPSIS і показані його переваги

The permeation of antibiotics through bacterial membranes to their target site is a crucial determinant of drug activity but in many cases remains poorly understood. During screening efforts to discover new broad-spectrum antibiotic compounds from marine sponge samples, we identified a new analog of the peptidyl nucleoside antibiotic blasticidin S that exhibited up to 16-fold-improved potency against a range of laboratory and clinical bacterial strains which we named P10. Whole-genome sequencing of laboratory-evolved strains of Staphylococcus aureus resistant to blasticidin S and P10, combined with genome-wide assessment of the fitness of barcoded Escherichia coli knockout strains in the presence of the antibiotics, revealed that restriction of cellular access was a key feature in the development of resistance to this class of drug. In particular, the gene encoding the well-characterized multidrug efflux pump NorA was found to be mutated in 69% of all S. aureus isolates resistant to blasticidin S or P10. Unexpectedly, resistance was associated with inactivation of norA , suggesting that the NorA transporter facilitates cellular entry of peptidyl nucleosides in addition to its known role in the efflux of diverse compounds, including fluoroquinolone antibiotics.

The approach is proposed to developing an information system of determining the psychological state of personalities based on the five personality dispositions (extraversion/introversion, amiability, integrity, neuroticism, openness to experience), which is based on the content analysis of the Internet resources where users leave their mark (social networks, forums, chats, etc.).In general, to form the status of psychological state of a personality based on the content analysis, it is necessary to solve four problems. First, it is necessary to collect content from various sources from the Internet. Then it is necessary to process it at the initial level (remove the tags, auxilary words, signs, special symbols, hyperlinks, pictures, etc. from the text). Then the content is filtered (to identify spam, detect duplication, format the content, etc.) and sorted out (comments to the comments, likes, posts) according to the statistics over a specific period. The last stage is conducting the content analysis of collected information, which is categorized by the stop-words (markers).To determine the psychological dispositions of a personality we implemented the developed method of the search and analysis of the marked words in the English and Ukrainian languages. We used the Potter stemming, lemmatising and the modified Potter stemming for the Ukrainian texts, designed by the authors. The tables of correlation between the marked words and psychological dispositions were developed. The information system is created for determining the psychological state of personality, based on the developed approach and the methods of the content processing. The system operates by analyzing the messages from the users in a social network based on the traits of the "Big Five". The system is designed in the form of a desktop program, which is the Internet service at the same time, and allows analyzing the psychological state of a particular user of a social network by his/her messages. All collected results are stored in the database. The results are displayed in the form of percent ratio for each trait, the number of tweets, as well as the most frequently used words related to these traits.Potential users of such systems are consulting and marketing companies. The collected and analyzed information on users may be used in hiring or promotion of products/services. Automated compilation of the personality models of users is helpful for social networks and Web services. It improves the quality and efficiency of context advertising, referral systems, recommendations and dating services. The in-depth knowledge of the audience is crucial for business and recruiting.The approbation of functioning of the constructed system was conducted. The results of the work of the system are satisfactory. Such an information system is recommended to use for searching employees for certain positions.Automated analysis of messages of users in a social network to form the status of psychological state of a personality based on the content analysis significantly reduces the time of finding a potentially promising employee among those applied taking into account his/her psychological portrait for a specific position., Предложен подход к разработке системы понимания личности через контент-анализ информационных ресурсов. Использована модель Big-Five на основе пользовательской поведения в социальных сетях. Для определения психологических диспозиций разработан метод анализа англоязычных и украиноязычных постов. Система предназначена для рекрутинга, маркетинга, социальных сетей и Web-сервисов. Анализ аудитории улучшает эффективность контекстной рекламы, систем рекомендаций и служб знакомств, Запропоновано підхід до розроблення системи розуміння особистості через контент-аналіз інформаційних ресурсів. Використано модель Big-Five на основі користувацької поведінки в соціальних мережах. Для визначення психологічних диспозицій розроблено метод аналізу англомовних та україномовних постів. Система призначена для рекрутингу, маркетингу, соціальних мереж і Web-сервісів. Аналіз аудитрії покращує ефективність контекстної реклами, систем рекомендацій і служб знайомств

Saccharopine dehydrogenase (SDH) catalyzes the final reaction in the α-aminoadipate pathway, the conversion of l-saccharopine to l-lysine (Lys) and α-ketoglutarate (α-kg) using NAD⁺ as an oxidant. The enzyme utilizes a general acid-base mechanism to conduct its reaction with a base proposed to accept a proton from the secondary amine of saccharopine in the oxidation step and a group proposed to activate water to hydrolyze the resulting imine. Crystal structures of an open apo form and a closed form of the enzyme with saccharopine and NADH bound have been determined at 2.0 and 2.2 A resolution, respectively. In the ternary complex, a significant movement of domain I relative to domain II that closes the active site cleft between the two domains and brings H96 and K77 into the proximity of the substrate binding site is observed. The hydride transfer distance is 3.6 A, and the side chains of H96 and K77 are properly positioned to act as acid-base catalysts. Preparation of the K77M and H96Q single-mutant and K77M/H96Q double-mutant enzymes provides data consistent with their role as the general acid-base catalysts in the SDH reaction. The side chain of K77 initially accepts a proton from the e-amine of the substrate Lys and eventually donates it to the imino nitrogen as it is reduced to a secondary amine in the hydride transfer step, and H96 protonates the carbonyl oxygen as the carbinolamine is formed. The K77M, H976Q, and K77M/H96Q mutant enzymes give 145-, 28-, and 700-fold decreases in V/E(t) and >10³-fold increases in V₂/K(Lys)E(t) and V₂/K(α-kg)E(t) (the double mutation gives >10⁵-fold decreases in the second-order rate constants). In addition, the K77M mutant enzyme exhibits a primary deuterium kinetic isotope effect of 2.0 and an inverse solvent deuterium isotope effect of 0.77 on V₂/K(Lys). A value of 2.0 was also observed for (D)(V₂/K(Lys))(D₂O) when the primary deuterium kinetic isotope effect was repeated in D₂O, consistent with a rate-limiting hydride transfer step. A viscosity effect of 0.8 was observed on V₂/K(Lys), indicating the solvent deuterium isotope effect resulted from stabilization of an enzyme form prior to hydride transfer. A small normal solvent isotope effect is observed on V, which decreases slightly when repeated with NADD, consistent with a contribution from product release to rate limitation. In addition, V₂/K(Lys)E(t) is pH-independent, which is consistent with the loss of an acid-base catalyst and perturbation of the pK(a) of the second catalytic group to a higher pH, likely a result of a change in the overall charge of the active site. The primary deuterium kinetic isotope effect for H96Q, measured in H₂O or D₂O, is within error equal to 1. A solvent deuterium isotope effect of 2.4 is observed with NADH or NADD as the dinucleotide substrate. Data suggest rate-limiting imine formation, consistent with the proposed role of H96 in protonating the leaving hydroxyl as the imine is formed. The pH-rate profile for V₂/K(Lys)E(t) exhibits the pK(a) for K77, perturbed to a value of ∼9, which must be unprotonated to accept a proton from the e-amine of the substrate Lys so that it can act as a nucleophile. Overall, data are consistent with a role for K77 acting as the base that accepts a proton from the e-amine of the substrate lysine prior to nucleophilic attack on the α-oxo group of α-ketoglutarate, and finally donating a proton to the imine nitrogen as it is reduced to give saccharopine. In addition, data indicate a role for H96 acting as a general acid-base catalyst in the formation of the imine between the e-amine of lysine and the α-oxo group of α-ketoglutarate.

Aim. To investigate the levels of specific autoantibodies against tyrosyl-tRNA synthetase and its individual modules in the blood serum of people with heart failure caused by dilated cardiomyopathy, myocarditis and ischemic heart disease compared with healthy donors. Methods. Recombinant proteins were obtained using bacterial strains transformed with appropriate plasmid vectors and were purified by chromatography on Ni-NTA-agarose. The levels of specific autoantibodies were investigated by ELISA. Results. The increased levels of autoantibodies specific to tyrosyl-tRNA synthetase, its N-terminal catalytic module and non-catalytic C-module, were found in the blood serum of patients, compared with healthy donors. Conclusions. The results obtained demonstrate the possible role of tyrosyl-tRNA synthetase in adaptive changes of the myocardium in response to stress factors.

The expression of HSP60 in the mRNA level in human hearts at the end-stage of dilated cardiomyopathy (DCM) as well as in the hearts of mice with disease model similar to human DCM was investigated. We observed a significant increase in the Hsp60 mRNA level at the beginning of the disease and decrease to a normal level at the end stage. As the Hsp60 level was increased during the disease up to the end stage we can presume some changes in the regulation of Hsp60 synthesis or its degradation at DCM progression

International audience; AbstractTitanium dioxide nanoparticles (TiO2-NPs) are one of the most produced NPs in the world. Their toxicity has been studied for a decade using acute exposure scenarios, i.e. high exposure concentrations and short exposure times. In the present study, we evaluated their genotoxic impact using long-term and low concentration exposure conditions. A549 alveolar epithelial cells were continuously exposed to 1?50??g/mL TiO2-NPs, 86% anatase/14% rutile, 24?±?6?nm average primary diameter, for up to two months. Their cytotoxicity, oxidative potential and intracellular accumulation were evaluated using MTT assay and reactive oxygen species measurement, transmission electron microscopy observation, micro-particle-induced X-ray emission and inductively-coupled plasma mass spectroscopy. Genotoxic impact was assessed using alkaline and Fpg-modified comet assay, immunostaining of 53BP1 foci and the cytokinesis-blocked micronucleus assay. Finally, we evaluated the impact of a subsequent exposure of these cells to the alkylating agent methyl methanesulfonate. We demonstrate that long-term exposure to TiO2-NPs does not affect cell viability but causes DNA damage, particularly oxidative damage to DNA and increased 53BP1 foci counts, correlated with increased intracellular accumulation of NPs. In addition, exposure over 2 months causes cellular responses suggestive of adaptation, characterized by decreased proliferation rate and stabilization of TiO2-NP intracellular accumulation, as well as sensitization to MMS. Taken together, these data underline the genotoxic impact and sensitization effect of long-term exposure of lung alveolar epithelial cells to low levels of TiO2-NPs.

Although the biological effects of titanium dioxide nanoparticles (TiO2-NPs) have been studied for more than two decades, the mechanisms governing their toxicity are still unclear. We applied 2D-gel proteomics analysis on A549 epithelial alveolar cells chronically exposed for 2months to 2.5 or 50μg/mL of deeply characterized TiO2-NPs, in order to obtain comprehensive molecular responses that may reflect functional outcomes. We show that exposure to TiO2-NPs impacts the abundance of 30 protein species, corresponding to 22 gene products. These proteins are involved in glucose metabolism, trafficking, gene expression, mitochondrial function, proteasome activity and DNA damage response. Besides, our results suggest that p53 pathway is activated, slowing down cell cycle progression and reducing cell proliferation rate. Moreover, we report increased content of chaperones-related proteins, which suggests homeostasis re-establishment. Finally, our results highlight that chronic exposure to TiO2-NPs affects the same cellular functions as acute exposure to TiO2-NPs, although lower exposure concentrations and longer exposure times induce more intense cellular response.Our results make possible the identification of new mechanisms that explain TiO2-NP toxicity upon long-term, in vitro exposure of A549 cells. It is the first article describing -omics results obtained with this experimental strategy. We show that this long-term exposure modifies the cellular content of proteins involved in functions including mitochondrial activity, intra- and extracellular trafficking, proteasome activity, glucose metabolism, and gene expression. Moreover we observe modification of content of proteins that activate the p53 pathway, which suggest the induction of a DNA damage response. Technically, our results show that exposure of A549 cells to a high concentration of TiO2-NPs leads to the identification of modulations of the same functional categories than exposure to low, more realistic concentrations. Still the intensity differs between these two exposure scenarios. We also show that chronic exposure to TiO2-NPs induces the modulation of cellular functions that have already been reported in the literature as being impacted in acute exposure scenarios. This proves that the exposure protocol in in vitro experiments related to nanoparticle toxicology might be cautiously chosen since inappropriate scenario may lead to inappropriate and/or incomplete conclusions.

In review provides information about the function oft the body of chaperones and their role in the development of pathological processes, including--atherosclerosis and coronary heart disease. Marked comminications systems chaperones to the immune and endocrine systems, and inflammation.

International audience; After decades of intensive research, high-grade gliomas are still resistant to therapies, including surgery, chemotherapy, and radiotherapy or a combination thereof. The most important advance in the treatment of these tumors has been the introduction of a new chemotherapy drug called temozolomide, in combination with external beam photon irradiation [1]. One of the goals of the association of the CHU/UJF/ INSERM and ESRF teams has been to develop research on synchrotron radiotherapy up to clinics.

Les gliomes de haut grade sont des tumeurs cérébrales de très mauvais pronostic. Le traitement standard proposé combine la chirurgie, la radiothérapie et parfois l'utilisation de témozolomide (agent de chimiothérapie). Une limitation majeure de la radiothérapie provient de la radiosensibilité des tissus sains. La radiothérapie stéréotaxique par rayonnement synchrotron est une technique innovatrice dont le principe est de combiner un rayonnement basse énergie (inférieur à 100 keV) à la présence d'atomes lourds dans la zone tumorale afin d'augmenter la dose déposée et ainsi accroître le différentiel de dépôt de dose entre la tumeur et les tissus sains environnants. Dans cette étude, plusieurs composés contenant des atomes lourds tels que les agents de chimiothérapie : cisplatine/carboplatine, un analogue d'une base de l'ADN : la 5-iodo-2'-désoxyuridine (IUdR) ou bien des nanoparticules d'or ont été considérés. Des études cellulaires ont permis de quantifier les facteurs d'augmentation de dose induits par la présence de ces composés dans l'environnement extracellulaire pour certains et intracellulaire pour d'autres. Lors d'études in vivo effectuées sur des rats porteurs de gliomes, la toxicité, cinétique de distribution et la localisation de ces composés a été déterminée, ainsi que l'efficacité potentielle du traitement associant injection cérébrale et irradiation basse énergie.

We have conducted a complex clinical and paraclinical study of 108 women, 78 of which had diabetes and 30 healthy women that made a control group. In 60.3% of the pregnant patients type 1 diabetes was diagnosed, in 11.5%--type 2. Gestational diabetes was found in 28.2% of pregnant women. The vast number of the surveyed pregnant women (52.6%) was diagnosed with moderate and severe (38.5%) degree of the disease. In 12.5% of them the disease was compensated, in 82.1% subcompensated, while in 5.1%--decompensated. In pregnant women with diabetes a high incidence of extragenital diseases was revealed, the most common of which was iron deficiency anemia, which complicated the pregnancy of more than half of the pregnant of the basic group (57.7%), while in the control--in 13.3% of women (p0.05). Thyroid diseases in the study group were more than three times more common compared to the control group (47.4% and 13.3%, p0.05), while in pregnant women with type 1 diabetes in 55.3% of the patients. Herewith in 29.4% of cases were diagnosed with hypothyroidism, in 52.9--subclinical hypothyroidism, in 25.5% of pregnant women were found autoimmune thyroiditis. These data indicate the need of screening of the pregnant women with diabetes to identify the pathology of the thyroid gland even if the clinical symptom are absent, particularly in the areas of iodine deficiency.

International audience; The possibility to induce the formation of covalent cross-links between polyamines and guanine following one electron oxidation of double stranded DNA has been evaluated. For such a purpose, a strategy has been developed to chemically synthesize the polyamine-C8-guanine adducts, and efforts have been made to characterize them. Then, an analytical method, based on HPLC separation coupled through electrospray ionization to tandem mass spectrometry, has been setup for their detection and quantification. Using such a sensitive approach, we have demonstrated that polyamine-C8-guanine adducts could be produced with significant yields in double stranded DNA following a one-electron oxidation reaction induced by photosensitization. These adducts, involving either putrescine, spermine, or spermidine, are generated by the nucleophilic addition of primary amino groups of polyamines onto the C8 position of the guanine radical cation. Our data demonstrate that such a nucleophilic addition of polyamines is much more efficient than the addition of a water molecule that leads to 8-oxo-7,8-dihydroguanine formation.

We have used a newly presented self-consistent version of the BCS+RQRPA method for a nucleus-by-nucleus study of the double beta decay in the medium-heavy region. The results have been compared to the previously used approaches, namely the QRPA and the RQRPA approximations. We have shown that inclusion of the quasiparticle correlations at the BCS level reduces ground state correlations in the particle–particle channel of the proton–neutron interaction, resulting in the systematic reduction of the double beta decay matrix elements.