ЭФФЕКТ ВОЗДЕЙСТВИЯ 1,5-БИС(3,5-ДИМЕТИЛПИРАЗОЛ-1-ИЛ)-3-ОКСАПЕНТАН-ДИАЦЕТАТОМЕДИ НА ОБЩЕЕ СОСТОЯНИЕ ОРГАНИЗМА КРЫС В УСЛОВИЯХ ЭКСПЕРИМЕНТА

Многие производные пиразола проявляют разнообразные фармакологические свойства. Им характерны антиоксидантная, антивирусная активность, противовоспалительные, иммуномодулирующие свойства, а также антидепрессивный и противоопухолевый эффекты. Данная работа основана на результатах морфометрических показателей массы тела и печени и биохимического анализа крови здоровых взрослых самцов белых крыс после однократного и многократного внутрибрюшинного введения 1,5-бис(3,5-диметилпиразол-1-ил)-3-оксапентан-диацетатомеди, растворенного в свежеприготовленном физиологическом растворе (доза 12 мг / кг массы тела). Результаты исследования показали, что при введении препарата в организм крыс проявляются различные эффекты. Установлено, что исследуемое вещество имеет гипогликемический эффект, о чем свидетельствует снижение уровня глюкозы в крови и увеличение количества гликогена в печени. Антилиполитический его эффект подтверждается снижением уровня свободных жирных кислот в крови. Токсическое воздействие препарата проявляется повышением уровня печеночных ферментов аланин аминотрансферазы и аспартат аминотрансферазы, а также снижением уровня альбумина в сыворотке крови и уменьшением массы тела и печени. Эти эффекты проявляются и сохраняются только при многократном ежедневном применении этого препарата в течение 6 недель

Synthesis of nitroxyl radical by direct nucleophilic functionalization of a C-H bond in the azadiene systems

Cyclic dinitrones underwent nucleophilic substitution of the hydrogen atom in the reaction with a paramagnetic carbanion, the lithium derivative of 4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-1-oxyl 3-oxide, to give polyfunctional nitronyl nitroxyls. © 2012 Springer Science+Business Media New York

Электрохимический синтез композиционных материалов на основе никеля, модифицированных наноразмерным оксидом алюминия

Electrochemical synthesis of nickel-based composite coatings and foil reinforced with nanosized aluminum oxide is reported. Ni-Al₂O₃ composites with different content of the modifying phase were prepared by chemical dispersion of aluminum oxide using the “from above down” principle. The influence of the aluminum oxide concentration in the electrolyte on the physicomechanical properties of the reinforced foil was determined. Incorporation of reinforcing phase particles into the metal matrix leads to a decrease in the grain size and enhances by a factor of 2–6 the strength characteristics of the coatings and foil. The topography of the surface and the cross section profile of the composites were examined, and the influence of these characteristics on the properties of the materials was determined.Представлены результаты электрохимического формирования композиционных покрытий и фольг на основе никеля, армированных наноразмерным оксидом алюминия. Для получения композитов Ni-Al₂O₃ с различным содержанием модифицирующей фазы использован метод химического диспергирования оксида алюминия по принципу сверху вниз. Установлено влияние концентрации оксида алюминия в электролите на физико-механические свойства армированных фольг. Включение в основную матрицу металла частиц армирующей фазы приводит к уменьшению размеров зерен и повышает в 2-6 раз прочностные характеристики покрытий и фольг. Изучена топография поверхности и профиль сечения композитов и установлено их влияние на свойства материалов

New approach to synthesis of nitronyl and imino nitroxides based on SNH methodology

It is shown that SN H approach opens new possibilities in the synthesis of polyfunctional nitronyl and imino nitroxides. It is found that the interaction of 4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-3-oxide-1- oxyl lithium salt Li1 with 3,6-diaryl-1,2,4-triazines leads to formation of the corresponding triazines bearing nitronyl nitroxide or imino nitroxide substituent at position 5 of the heterocycle. The reaction of Li1 with pyridazine-N-oxide gives rise to nitroxide with buten-3-ynyl substituent 5. Spin-labeled 5 could be readily transformed by the use of 1,3-dipolar and nucleophilic addition reactions, as well as oxidative coupling, that gives a large group of new paramagnets: 2-(1H-pyrazol-5-yl)vinyl-, 2-ethynylcyclopropyl- , 2-(3-(ethoxycarbonyl) isoxazol-5-yl)vinyl-, 1-(pyrrolidin-1-yl)but-3-ynyl- substituted nitronyl nitroxide and a diradical - 2,2′-((1E,7E)-octa-1,7- dien-3,5-diyne-1,8-diyl)bis(4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-3-oxide- 1-oxyl). The new nitroxides were characterized by X-ray single crystal data, ESR and static magnetic susceptibility measurements. © ARKAT USA, Inc

Direct Regulation of CLOCK Expression by REV-ERB

Circadian rhythms are regulated at the cellular level by transcriptional feedback loops leading to oscillations in expression of key proteins including CLOCK, BMAL1, PERIOD (PER), and CRYPTOCHROME (CRY). The CLOCK and BMAL1 proteins are members of the bHLH class of transcription factors and form a heterodimer that regulates the expression of the PER and CRY genes. The nuclear receptor REV-ERBα plays a key role in regulation of oscillations in BMAL1 expression by directly binding to the BMAL1 promoter and suppressing its expression at certain times of day when REV-ERBα expression levels are elevated. We recently demonstrated that REV-ERBα also regulates the expression of NPAS2, a heterodimer partner of BMAL1. Here, we show that REV-ERBα also regulates the expression another heterodimer partner of BMAL1, CLOCK. We identified a REV-ERBα binding site within the 1st intron of the CLOCK gene using a chromatin immunoprecipitation – microarray screen. Suppression of REV-ERBα expression resulted in elevated CLOCK mRNA expression consistent with REV-ERBα's role as a transcriptional repressor. A REV-ERB response element (RevRE) was identified within this region of the CLOCK gene and was conserved between humans and mice. Additionally, the CLOCK RevRE conferred REV-ERB responsiveness to a heterologous reporter gene. Our data suggests that REV-ERBα plays a dual role in regulation of the activity of the BMAL1/CLOCK heterodimer by regulation of expression of both the BMAL1 and CLOCK genes

Investigating charge-up and fragmentation dynamics of oxygen molecules after interaction with strong X-ray free-electron laser pulses

During the last decade, X-ray free-electron lasers (XFELs) have enabled the study of light–matter interaction under extreme conditions. Atoms which are subject to XFEL radiation are charged by a complex interplay of (several subsequent) photoionization events and electronic decay processes within a few femtoseconds. The interaction with molecules is even more intriguing, since intricate nuclear dynamics occur as the molecules start to dissociate during the charge-up process. Here, we demonstrate that by analyzing photoelectron angular emission distributions and kinetic energy release of charge states of ionic molecular fragments, we can obtain a detailed understanding of the charge-up and fragmentation dynamics. Our novel approach allows for gathering such information without the need of complex ab initio modeling. As an example, we provide a detailed view on the processes happening on a femtosecond time scale in oxygen molecules exposed to intense XFEL pulses

Effects of HMGN variants on the cellular transcription profile

High mobility group N (HMGN) is a family of intrinsically disordered nuclear proteins that bind to nucleosomes, alters the structure of chromatin and affects transcription. A major unresolved question is the extent of functional specificity, or redundancy, between the various members of the HMGN protein family. Here, we analyze the transcriptional profile of cells in which the expression of various HMGN proteins has been either deleted or doubled. We find that both up- and downregulation of HMGN expression altered the cellular transcription profile. Most, but not all of the changes were variant specific, suggesting limited redundancy in transcriptional regulation. Analysis of point and swap HMGN mutants revealed that the transcriptional specificity is determined by a unique combination of a functional nucleosome-binding domain and C-terminal domain. Doubling the amount of HMGN had a significantly larger effect on the transcription profile than total deletion, suggesting that the intrinsically disordered structure of HMGN proteins plays an important role in their function. The results reveal an HMGN-variant-specific effect on the fidelity of the cellular transcription profile, indicating that functionally the various HMGN subtypes are not fully redundant

Ultrafast resonant interatomic coulombic decay induced by quantum fluid dynamics

Interatomic processes play a crucial role in weakly bound complexes exposed to ionizing radiation; therefore, gaining a thorough understanding of their efficiency is of fundamental importance. Here, we directly measure the timescale of interatomic Coulombic decay (ICD) in resonantly excited helium nanodroplets using a high-resolution, tunable, extreme ultraviolet free-electron laser. Over an extensive range of droplet sizes and laser intensities, we discover the decay to be surprisingly fast, with decay times as short as 400 fs, nearly independent of the density of the excited states. Using a combination of time- dependent density functional theory and ab initio quantum chemistry calculations, we elucidate the mechanisms of this ultrafast decay process, where pairs of excited helium atoms in one droplet strongly attract each other and form merging void bubbles, which drastically accelerates ICD