Klinicheskie, geneticheskiei metabolicheskie osobennostisakharnogo diabetau bol'nykh buryatskoy populyatsii

Цель. Изучение патогенетических механизмов и клинических особенностей СД 1 у больных бурятской популяции. Материалы и методы. Генетические исследования проведены у 76 больных СД 1 бурятской популяции в возрасте от 1 года до 40 лет. Контрольная группа состояла из 61 человека бурятской национальности без аутоиммунных заболеваний и отягощенной наследственности по ним. Для изучения перекисного окисления липидов (ПОЛ) и состояния антиоксидантной системы (АОС) обследовано 65 больных СД 1, которые разделены на две группы: больных русской и бурятской популяций. В первую группу вошли 27 больных СД 1 русской популяции (мужчин ? 12, женщин ? 15), средний возраст ? 32,7?2,3 года, длительность заболевания 12,87?1,97 лет. Вторую группу составили 38 больных СД 1 бурятской популяции (мужчин ? 23, женщин ? 15), средний возраст ? 34,4?1,9 года, длительность заболевания 12,05?1,51 лет. Контрольная группа русской популяции состояла из 23 практически здоровых лиц, средний возраст 27,1?1,9 лет. Контрольная группа бурятской популяции состояла из 34 практически здоровых лиц, средний возраст 30,3?1,3 лет. Типирование полиморфизма гена CTLA4 A49G проводилось с помощью метода PCR-RFLP. Определены восстановленный глутатион (GSH) и окисленный глутатион (GSSG). У больных СД 1 и в контрольной группе бурятской популяции исследовали однонуклеотидный полиморфизм (SNP) гена CTLA4 (49A/G). Результаты. В группе больных СД 1 частота генотипа AG (51,4%) выше, чем в контрольной группе, однако результаты статистически недостоверны. При сравнении свободнорадикальных процессов между группами больных СД 1 русской и бурятской популяций установлена достоверная разница в накоплении продуктов пероксидации. Сравнительный анализ показателей ПОЛ у больных диабетом русской и бурятской популяций с соответствующими контрольными группами русских и бурят показал, что в группах больных диабетом свободнорадикальные процессы усилены, но степень их выраженности разная. Выводы. Распространенность и заболеваемость СД 1 в бурятской популяции ниже российских показателей распространенности и заболеваемости, соответственно составляют 24,18 и 0,73 на 100 тыс. населения. У больных СД 1 бурятской популяции не установлена дислипопротеинемия (повышение холестерина, триглицеридов, ЛПОНП и индекса атерогенности). ПОЛ у больных СД 1 бурятской популяции характеризуется гиполипопероксидацией по сравнению с больными русской популяции, накоплением ДК и Дв.св. относительно контрольной группы бурят. Состояние АОС у больных СД 1 бурятской популяции характеризуется повышением АОА по сравнению с больными русской популяции и разнонаправленными изменениями СОД и АОА по сравнению с контрольной группой бурят. Исследование полиморфизма 49А/в гена CTLA4 не выявило ассоциацию с заболеваемостью СД 1 в бурятской популяции

Silver Itaconate as Single-Source Precursor of Nanocomposites for the Analysis of Chloride Ions

At present, conjugated thermolysis of metal-containing monomers is widely used as single-source precursors to obtain new metal- and metal oxide-containing nanocomposites. In this study, a detailed analysis of the main stages of conjugated thermolysis of silver itaconate was carried out. The obtained nanocomposites containing silver nanoparticles are evenly distributed in a stabilizing carbon matrix. The structural characteristics and properties of the resulting nanomaterials were studied using X-ray diffraction (XRD), atomic force microscopy (AFM), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and energy dispersive X-ray spectroscopy (EDS). We have developed a method of test analysis of chlorides using paper modified with the obtained silver-containing nanocomposites. The analysis technique is based on the in situ conversion of chlorides to molecular chlorine, its dynamic release, and colorimetric detection using NP-modified paper test strips. A simple installation device is described that allows this combination to be realized. The proposed approach seems promising for nanoparticle-based determinations of other analytes that can be converted into volatile derivatives

Preparation of Reactive Indicator Papers Based on Silver-Containing Nanocomposites for the Analysis of Chloride Ions

In recent decades, metal-containing nanocomposites have attracted considerable attention from researchers. In this work, for the first time, a detailed analysis of the preparation of reactive indicator papers (RIPs) based on silver-containing nanocomposites derived from silver fumarate was carried out. Thermolysis products are silver-containing nanocomposites containing silver nanoparticles uniformly distributed in a stabilizing carbon matrix. The study of the optical properties of silver-containing nanocomposites made it possible to outline the prospects for their application in chemical analysis. RIPs were made by impregnating a cellulose carrier with synthesized silver fumarate-derived nanocomposites, which change their color when interacting with chlorine vapor. This made it possible to propose a method for the determination of chloride ions with preliminary oxidation to molecular chlorine, which is then separated from the solution by gas extraction. The subsequent detection of the active zone of RIPs using colorimetry makes it possible to identify mathematical dependences of color coordinates on the concentration of chloride ions. The red (R) color coordinate in the RGB (red-green-blue) system was chosen as the most sensitive and promising analytical signal. Calibration plots of exponential and linear form and their equations are presented. The limit of detection is 0.036 mg/L, the limits of quantification are 0.15–2.4 mg/L, and the time of a single determination is 25 min. The prospects of the developed technique have been successfully shown in the example of the analysis of the natural waters of the Don River, pharmaceuticals, and food products

Polimorfizm genov HLA klassa II i CTLA4 zdorovykh buryat i bol'nykh sakharnym diabetom 1 tipa v Buryatskoy Respublike

Цель. Идентифицировать аллели 3 генов локуса HLA класса II в двух группах бурят (больных СД 1 и здоровых) с последующим определением диабетогенных гаплотипов. Исспледовать диморфизм гена CTLA4, определить частоты аллелей и генотипов указанных однонуклеотидных полиморфизмов в двух группах бурят (больных СД1 и здоровых) и поиск возможных ассоциаций этих SNP с развитием СД 1 в данной популяции. Материалы и методы. Все больные СД1 и лица контрольной группы относятся к бурятской популяции. Выделение ДНК из лейкоцитов периферической крови проводили по модицифированной методике Gemmell. Идентифицировали аллели локуса HLA. Результаты. Анализ распределения аллелей показал статистически значимые отличия в частотах аллелей DRB1*15, DRB1*11, DQA1*0102, DQA1*0301,DQB1*0302, DQB1*0602-8. Частоты других аллелей генов HLA незначительно отличались у больных и здоровых индивидуумов или эти отличия не были достоверными. Среди вычисленных показателей OR максимальное значение отмечено для аллеля DQB1*0302. Обнаружена позитивная ассоциация гаплотипа DRB1*08 ? DQA1*0301 ? DQB1*0302. Выводы. Гаплотип DRB1*08 ? DQA1*0301 ? DQB1*0302 является гаплотипом, наиболее предрасполагающим к развитию СД 1 типа в бурятской популяции. "Классический" высоко предрасполагающий генотип в европеоидных популяциях DRB1*04 ? DQA1*0301 ? DQB1*0302 / DRB1*17 ? DQA1*0501 ? DQB1*0201 в группе здоровых бурят не наблюдается, а у группе больных частота его составляет 0,068 (примерно 7%), тогда как в европеоидной группе больных СД 1 частота его достигает 35%. Ассоциаций какого-либо из изученных полиморфных маркеров гена CTLA 4 с предрасположенностью к СД1 в бурятской популяции не выявлено

Towards translational modeling of behavioral despair and its treatment in zebrafish

Depression is a widespread and severely debilitating neuropsychiatric disorder whose key clinical symptoms include low mood, anhedonia and despair (the inability or unwillingness to overcome stressors). Experimental animal models are widely used to improve our mechanistic understanding of depression pathogenesis, and to develop novel antidepressant therapies. In rodents, various experimental models of 'behavioral despair' have already been developed and rigorously validated. Complementing rodent studies, the zebrafish (Danio rerio) is emerging as a powerful model organism to assess pathobiological mechanisms of depression and other related affective disorders. Here, we critically discuss the developing potential and important translational implications of zebrafish models for studying despair and its mechanisms, and the utility of such aquatic models for antidepressant drug screening

Towards Zebrafish Models of CNS Channelopathies

Channelopathies are a large group of systemic disorders whose pathogenesis is associated with dysfunctional ion channels. Aberrant transmembrane transport of K+, Na+, Ca2+ and Cl− by these channels in the brain induces central nervous system (CNS) channelopathies, most commonly including epilepsy, but also migraine, as well as various movement and psychiatric disorders. Animal models are a useful tool for studying pathogenesis of a wide range of brain disorders, including channelopathies. Complementing multiple well-established rodent models, the zebrafish (Danio rerio) has become a popular translational model organism for neurobiology, psychopharmacology and toxicology research, and for probing mechanisms underlying CNS pathogenesis. Here, we discuss current prospects and challenges of developing genetic, pharmacological and other experimental models of major CNS channelopathies based on zebrafish

Generation potential, distribution area and maturity of the Barents-Kara Sea source rocks

Identification of the source rock potential and distribution area is the most important stage of the basin analysis and oil, and gas reserves assessment. Based on analysis of the large geochemical and geological data base of the Petroleum geology department of the Lomonosov Moscow State University and integration of different-scale information (pyrolysis results and regional palaeogeographic maps), generation potential, distribution area and maturity of the main source rock intervals of the Barents-Kara Sea shelf are reconstructed. These source rocks wide distribute on the Barents-Kara Sea shelf and are characterized by lateral variability of generation potential and type of organic matter depending on paleogeography. During regional transgressions in Late Devonian, Early Permian, Middle Triassic and Late Jurassic, deposited source rocks with marine organic matter and excellent generation potential. However in the regression periods, during the short-term transgressions, formed Lower Carboniferous, Upper Permian, Induan, Olenekian and Late Triassic source rocks with mixed and terrestrial organic matter and good potential. Upper Devonian shales contain up to 20.6% (average – 3%) of marine organic matter, have an excellent potential and is predicted on the Eastern-Barents megabasin. Upper Devonian source rocks are in the oil window on the steps, platforms and monoclines, while are overmature in the basins. Lower Permian shale-carbonate source rock is enriched with marine organic matter (up to 4%, average – 1.4%) and has a good end excellent potential. Lower Permian source rocks distribute over the entire Barents shelf and also in the North-Kara basin (Akhmatov Fm). These rocks enter the gas window in the Barents Sea shelf, the oil window on the highs and platforms and are immature in the North-Kara basin. Middle Triassic shales contain up to 11.2% of organic matter, there is a significant lateral variability of the features: an excellent generation potential and marine organic matter on the western Barents Sea and poor potential and terrestrial organic matter in the eastern Barents Sea. Middle Triassic source rocks are in the oil window; in the depocenters it generates gas. Upper Jurassic black shales are enriched with marine and mixed organic matter (up to 27,9%, average – 7.3%) and have an excellent potential. On the most Barents-Kara Sea shelf, Upper Jurassic source rock are immature, but are in the oil window in the South-Kara basin and in the deepest parts of the Barents Sea shelf.publishedVersio

Нефтегазоматеринские толщи Баренцево-Карского шельфа: область распространения и свойства

Identification of the source rock potential and distribution area is the most important stage of the basin analysis and oil, and gas reserves assessment. Based on analysis of the large geochemical and geological data base of the Petroleum geology department of the Lomonosov Moscow State University and integration of different-scale information (pyrolysis results and regional palaeogeographic maps), generation potential, distribution area and maturity of the main source rock intervals of the Barents-Kara Sea shelf are reconstructed. These source rocks wide distribute on the Barents-Kara Sea shelf and are characterized by lateral variability of generation potential and type of organic matter depending on paleogeography. During regional transgressions in Late Devonian, Early Permian, Middle Triassic and Late Jurassic, deposited source rocks with marine organic matter and excellent generation potential. However in the regression periods, during the short-term transgressions, formed Lower Carboniferous, Upper Permian, Induan, Olenekian and Late Triassic source rocks with mixed and terrestrial organic matter and good potential. Upper Devonian shales contain up to 20.6% (average – 3%) of marine organic matter, have an excellent potential and is predicted on the Eastern-Barents megabasin. Upper Devonian source rocks are in the oil window on the steps, platforms and monoclines, while are overmature in the basins. Lower Permian shale-carbonate source rock is enriched with marine organic matter (up to 4%, average – 1.4%) and has a good end excellent potential. Lower Permian source rocks distribute over the entire Barents shelf and also in the North-Kara basin (Akhmatov Fm). These rocks enter the gas window in the Barents Sea shelf, the oil window on the highs and platforms and are immature in the North-Kara basin. Middle Triassic shales contain up to 11.2% of organic matter, there is a significant lateral variability of the features: an excellent generation potential and marine organic matter on the western Barents Sea and poor potential and terrestrial organic matter in the eastern Barents Sea. Middle Triassic source rocks are in the oil window; in the depocenters it generates gas. Upper Jurassic black shales are enriched with marine and mixed organic matter (up to 27,9%, average – 7.3%) and have an excellent potential. On the most Barents-Kara Sea shelf, Upper Jurassic source rock are immature, but are in the oil window in the South-Kara basin and in the deepest parts of the Barents Sea shelf

Current State of Modeling Human Psychiatric Disorders Using Zebrafish

Psychiatric disorders are highly prevalent brain pathologies that represent an urgent, unmet biomedical problem. Since reliable clinical diagnoses are essential for the treatment of psychiatric disorders, their animal models with robust, relevant behavioral and physiological endpoints become necessary. Zebrafish (Danio rerio) display well-defined, complex behaviors in major neurobehavioral domains which are evolutionarily conserved and strikingly parallel to those seen in rodents and humans. Although zebrafish are increasingly often used to model psychiatric disorders, there are also multiple challenges with such models as well. The field may therefore benefit from a balanced, disease-oriented discussion that considers the clinical prevalence, the pathological complexity, and societal importance of the disorders in question, and the extent of its detalization in zebrafish central nervous system (CNS) studies. Here, we critically discuss the use of zebrafish for modeling human psychiatric disorders in general, and highlight the topics for further in-depth consideration, in order to foster and (re)focus translational biological neuroscience research utilizing zebrafish. Recent developments in molecular biology research utilizing this model species have also been summarized here, collectively calling for a wider use of zebrafish in translational CNS disease modeling

Genetically Encoded Self-Assembling Protein Nanoparticles for the Targeted Delivery In Vitro and In Vivo

Targeted nanoparticles of different origins are considered as new-generation diagnostic and therapeutic tools. However, there are no targeted drug formulations within the composition of nanoparticles approved by the FDA for use in the clinic, which is associated with the insufficient effectiveness of the developed candidates, the difficulties of their biotechnological production, and inadequate batch-to-batch reproducibility. Targeted protein self-assembling nanoparticles circumvent this problem since proteins are encoded in DNA and the final protein product is produced in only one possible way. We believe that the combination of the endless biomedical potential of protein carriers as nanoparticles and the standardized protein purification protocols will make significant progress in “magic bullet” creation possible, bringing modern biomedicine to a new level. In this review, we are focused on the currently existing platforms for targeted self-assembling protein nanoparticles based on transferrin, lactoferrin, casein, lumazine synthase, albumin, ferritin, and encapsulin proteins, as well as on proteins from magnetosomes and virus-like particles. The applications of these self-assembling proteins for targeted delivery in vitro and in vivo are thoroughly discussed, including bioimaging applications and different therapeutic approaches, such as chemotherapy, gene delivery, and photodynamic and photothermal therapy. A critical assessment of these protein platforms’ efficacy in biomedicine is provided and possible problems associated with their further development are described