A Systems Level, Functional Genomics Analysis of Chronic Epilepsy

Neither the molecular basis of the pathologic tendency of neuronal circuits to generate spontaneous seizures (epileptogenicity) nor anti-epileptogenic mechanisms that maintain a seizure-free state are well understood. Here, we performed transcriptomic analysis in the intrahippocampal kainate model of temporal lobe epilepsy in rats using both Agilent and Codelink microarray platforms to characterize the epileptic processes. The experimental design allowed subtraction of the confounding effects of the lesion, identification of expression changes associated with epileptogenicity, and genes upregulated by seizures with potential homeostatic anti-epileptogenic effects. Using differential expression analysis, we identified several hundred expression changes in chronic epilepsy, including candidate genes associated with epileptogenicity such as Bdnf and Kcnj13. To analyze these data from a systems perspective, we applied weighted gene co-expression network analysis (WGCNA) to identify groups of co-expressed genes (modules) and their central (hub) genes. One such module contained genes upregulated in the epileptogenic region, including multiple epileptogenicity candidate genes, and was found to be involved the protection of glial cells against oxidative stress, implicating glial oxidative stress in epileptogenicity. Another distinct module corresponded to the effects of chronic seizures and represented changes in neuronal synaptic vesicle trafficking. We found that the network structure and connectivity of one hub gene, Sv2a, showed significant changes between normal and epileptogenic tissue, becoming more highly connected in epileptic brain. Since Sv2a is a target of the antiepileptic levetiracetam, this module may be important in controlling seizure activity. Bioinformatic analysis of this module also revealed a potential mechanism for the observed transcriptional changes via generation of longer alternatively polyadenlyated transcripts through the upregulation of the RNA binding protein HuD. In summary, combining conventional statistical methods and network analysis allowed us to interpret the differentially regulated genes from a systems perspective, yielding new insight into several biological pathways underlying homeostatic anti-epileptogenic effects and epileptogenicity

Polymorphism of lipid exchange genes in some populations of South and East Siberia

Lipid metabolism disorders underlie the pathogenesis of a number of diseases. Indigenous peoples of Siberia have a specific genetically determined type of metabolism supporting such lipid blood parameters that favor increased consumption (in comparison with Caucasians) of animal products. At the same time, indigenous Siberian ethnic groups are less susceptible to metabolic diseases. The objective of the presented study was to investigate the allele frequencies of lipid metabolism genes in indigenous populations of Siberia to identify the ethnic features of allele frequency distribution for polymorphic variants in genes CETP (G1264A, rs5882), LPL (C1791G, rs328) and FTO (C83401A, rs8050136) in the samples taken from Buryats, Teleuts and Russians of Eastern Siberia, and to compare them with data on world populations. Samples of the Eastern (N = 132) and Western (N = 278) Buryats, Teleuts (N = 120), Russians (N = 122) and persons of mixed Buryat-Russian origin (N = 56) were genotyped by real-time PCR using competitive TaqMan-probes. The obtained results have for the first time demonstrated that the CETP and FTO allele frequencies in the Buryat samples are intermediate between European and East Asian populations. Significantly lower incidence of the obesity-assossiated 83401A allele of the FTO gene has been shown in Buryats, compared with Russians, which is consistent with lower susceptibility of the indigenous ethnic groups to metabolic disorders. There have been no population differences in the distribution of LPL gene polymorphic variants associated with dyslipidemia, which means they probably do not contribute to the ethnic characteristics of the lipid profile. The intermediate frequencies of the CETP 1264G and FTO 83401A alleles found in the metis group demonstrate that the metabolic disorders associated with these variants can be rather expected in the descendants of mixed marriages than among Buryats. It has also been demonstrated that Teleuts differ by FTO 83401A allele frequency from some of the European groups and have the lowest detected frequency of the allele CETP 1264G associated with the favorable lipid blood parameters

ОЦЕНКИ ВЗАИМОСВЯЗИ ДИНАМИКИ ГЕОФИЗИЧЕСКИХ ПАРАМЕТРОВ С НАПРЯЖЕННО-ДЕФОРМИРОВАННЫМ СОСТОЯНИЕМ ИССЛЕДУЕМЫХ ОБЪЕКТОВ ГЕОСРЕДЫ

The RAS Research Station started geodynamical research at the Bishkek Geodynamic Test Area (BGTA) in 1980s. This test area is located in the Northern Tien Shan, one of most seismically active zones of Central Asia. The distribution patterns of crustal deformation in space and time are investigated by a complex of geophysical, seismological and geodesic methods. Long-offset transient electromagnetic (LOTEM) technique is an important component of the geophysical research carried out at BGTA with the focus on forecasting of seismic activity dynamics. LOTEM is considered to be one of the most informative methods for obtaining data on multilayered conductive anisotropic geologic environment. This article presents the results of integrated interpretation of LOTEM sounding data recorded at permanent electro-magnetic monitoring stations, Ak-Suu and Shavai. The time series of specific electrical resistance are analyzed to reveal a correlation with the stress-strain state of the geologic environment and seismic process in the study region in the period from January 2016 to October 2018. It is established that the deformation process taking place at a depth of more than 8.0 km is reflected in the time series of specific electrical resistance in the form of bay-shaped negative variations. A decrease of apparent resistance is observed when the receiver dipoles of the measurement unit are arranged in the meridian (N-S) direction. The periods of compression in the submeridional direction coincide with the periods with the highest density of seismic events. A comparison of earthquake hypocenter locations against the topographic relief and the data on regional faults shows the maximum density of hypocenters at the axial parts of Northern Tien Shan ridges.Геодинамические исследования пространственно-временного распределения деформаций земной коры на Бишкекском геодинамическом полигоне Научной станции РАН в г. Бишкеке, расположенном на территории Северного Тянь-Шаня, одной из наиболее сейсмоактивных областей Средней Азии, ведутся комплексом геофизических, сейсмологических и геодезических методов начиная с 80-х годов ХХ в. Важной составной частью выполняемых геофизических исследований, связанных с прогнозированием динамики сейсмической активности, и одним из наиболее информативных методов получения данных о многослойной проводящей анизотропной геологической среде является зондирование становлением поля в дальней зоне. Рассмотрены результаты комплексной интерпретации данных, полученных этим методом, для стационарных пунктов электромагнитного мониторинга Ак-Суу и Шавай. Временные ряды кажущегося удельного электрического сопротивления проанализированы на предмет связи с напряженно-деформационным состоянием геологической среды и сейсмическим процессом в исследуемой области в период с января 2016 г. по октябрь 2018 г. Установлено, что деформационный процесс, происходящий на глубинах более 8 км, проявляется во временных рядах удельного электрического сопротивления в виде бухтообразных отрицательных вариаций. Уменьшение кажущегося сопротивления наблюдается при расположении приемных диполей измерительной установки в меридиональном направлении (ориентированных в направлении север – юг). С периодами сжатия в субмеридиональном направлении совпадает наибольшая плотность сейсмических событий. Проведено сравнение расположения гипоцентров землетрясений с рельефом земной поверхности и данными о региональных разломах, которое показало, что максимальная плотность гипоцентров, как правило, приурочена к осевым частям хребтов Северного Тянь-Шаня

Stagnation and renewable growth of enterprises: an empirical analysis by sectors of the Russian economy

An unfavorable external environment requires an emphasis shift in economic researches of enterprise development from factors and mechanisms of growth to the analysis of stagnation processes and the search for mechanisms to enter the path of growth after stagnation. The purpose of this work is to study the intensity of the processes of stagnation and subsequent renewable growth of enterprises in the context of a wide range of sectors of the Russian economy. Signs of stagnation or drop in sales are revealed for 2013–2017, renewable growth – within 4 years after the stagnation period. The research methods are the calculation of economic coefficients and the identification of differences between them using methods of mathematical statistics. It was found that in an unfavorable external environment, significant proportion of Russian enterprises showed signs of stagnation or drop in sales. Certain advantages are shown by high-tech industries, in which the intensity of business stagnation was lower. The most acute period of the crisis was the period 2013–2016. In 2017, there was an adaptation of business to unfavorable environmental conditions, and the share of stagnating enterprises decreased significantly. Calculations showed that the share of enterprises demonstrating long-term renewable growth was at a low level. It reduces their attractiveness to private investors. The “age” factor can be recommended as a significant criterion for investors when choosing firms for financing: young enterprises are less susceptible to stagnation and more likely to enter the path of growth after stagnation

A Global Potential Analysis of the 16^{16}O+28^{28}Si Reaction Using a New Type of Coupling Potential

A new approach has been used to explain the experimental data for the $^{16}$O+$^{28}$Si system over a wide energy range in the laboratory system from 29.0 to 142.5 MeV. A number of serious problems has continued to plague the study of this system for a couple of decades. The explanation of anomalous large angle scattering data; the reproduction of the oscillatory structure near the Coulomb barrier; the out-of-phase problem between theoretical predictions and experimental data; the consistent description of angular distributions together with excitation functions data are just some of these problems. These are long standing problems that have persisted over the years and do represent a challenge calling for a consistent framework to resolve these difficulties within a unified approach. Traditional frameworks have failed to describe these phenomena within a single model and have so far only offered different approaches where these difficulties are investigated separately from one another. The present work offers a plausible framework where all these difficulties are investigated and answered. Not only it improves the simultaneous fits to the data of these diverse observables, achieving this within a unified approach over a wide energy range, but it departs for its coupling potential from the standard formulation. This new feature is shown to improve consistently the agreement with the experimental data and has made major improvement on all the previous coupled-channels calculations for this system.Comment: 21 pages with 12 figure

Dysfunction in Ribosomal Gene Expression in the Hypothalamus and Hippocampus following Chronic Social Defeat Stress in Male Mice as Revealed by RNA-Seq

Chronic social defeat stress leads to the development of anxiety-and depression-like states in male mice and is accompanied by numerous molecular changes in brain. The influence of 21-day period of social stress on ribosomal gene expression in five brain regions was studied using the RNA-Seq database. Most Rps, Rpl, Mprs, and Mprl genes were upregulated in the hypothalamus and downregulated in the hippocampus, which may indicate ribosomal dysfunction following chronic social defeat stress. There were no differentially expressed ribosomal genes in the ventral tegmental area, midbrain raphe nuclei, or striatum. This approach may be used to identify a pharmacological treatment of ribosome biogenesis abnormalities in the brain of patients with "ribosomopathies.&quot

Study of the process e+e−→ppˉe^+e^-\to p\bar{p} in the c.m. energy range from threshold to 2 GeV with the CMD-3 detector

Using a data sample of 6.8 pb$^{-1}$ collected with the CMD-3 detector at the VEPP-2000 $e^+e^-$ collider we select about 2700 events of the $e^+e^- \to p\bar{p}$ process and measure its cross section at 12 energy ponts with about 6\% systematic uncertainty. From the angular distribution of produced nucleons we obtain the ratio $|G_{E}/G_{M}| = 1.49 \pm 0.23 \pm 0.30$

Measurement of the e+e−→K+K−π+π−e^+e^- \to K^+K^-\pi^+\pi^- cross section with the CMD-3 detector at the VEPP-2000 collider

The process $e^+e^- \to K^+K^-\pi^+\pi^-$ has been studied in the center-of-mass energy range from 1500 to 2000\,MeV using a data sample of 23 pb$^{-1}$ collected with the CMD-3 detector at the VEPP-2000 $e^+e^-$ collider. Using about 24000 selected events, the $e^+e^- \to K^+K^-\pi^+\pi^-$ cross section has been measured with a systematic uncertainty decreasing from 11.7\% at 1500-1600\,MeV to 6.1\% above 1800\,MeV. A preliminary study of $K^+K^-\pi^+\pi^-$ production dynamics has been performed

Chaotic Scattering in Heavy--Ion Reactions

We discuss the relevance of chaotic scattering in heavy--ion reactions at energies around the Coulomb barrier. A model in two and three dimensions which takes into account rotational degrees of freedom is discussed both classically and quantum-mechanically. The typical chaotic features found in this description of heavy-ion collisions are connected with the anomalous behaviour of several experimental data.Comment: 35 pages in RevTex (version 3.0) plus 27 PostScript figures obtainable by anonymous ftp from VAXFCT.CT.INFN.IT in directory kaos. Fig. 1 upon request to the authors. To be published in the October Focus issue on chaotic scattering of CHAO