Down-regulation of serotonergic genes expression in the raphe nuclei of midbrain under chronic social defeat stress in male mice

Background: 
There is ample experimental evidence supporting the hypothesis that the brain serotonergic system is involved in the control of chronic social defeat stress (CSDS), depression and anxiety. The study aimed to analyze mRNA levels of the serotonergic genes in the raphe nuclei of the midbrain that may be associated with chronic social defeats consistently shown by male mice in special experimental settings. 

Methodology/Principal Findings: 
The serotonergic genes were the Tph2, Sert, Maoa and Htr1a. The Bdnf, Creb, Cphn, Gapdh, Hprt, B2M, 18S and Actb genes were also studied. The experimental groups were composed of male mice with experience of defeats in 21 daily encounters and male mice with the same track record of defeats followed by a no-defeat period without agonistic interactions (relative rest for 14 days). It has been shown that mRNA levels of the Tph2, Maoa, Sert, Htr1a, Bdnf and Creb genes in the raphe nuclei of defeated mice are decreased as compared with the controls. Under CSDS the Cphn, Gapdh, Hprt, B2M, 18S, Actb genes are also down-regulated. The expression of the serotonergic genes as well as the Cphn and Creb genes is not restored to the control level after the 2 weeks of relative rest. mRNA levels of other genes are not recovered to the control levels, although some up-regulation was observed in rested losers. Significant positive correlations were found between the total time of avoidance behavior demonstrated by the 21-day defeaters in agonistic interactions and Sert, Maoa, Bdnf, Gapdh and 18S mRNA levels. 

Conclusions: 
CSDS experience inducing the development of mixed anxious/depression-like state in male mice down-regulates the serotonergic genes expression associated with the synthesis, inactivation and reception of serotonin. The Bdnf and Creb genes as well as the cell and metabolic Cphn, Gapdh, Hprt, B2M, Actb and 18S genes in the midbrain raphe nuclei are also down-regulated under CSDS. Period of relative rest is not enough for most genes to recover expression to the control levels

36 Months Survivability And Its Predictors In Patients With Chronic Heart Failure And Decreased Fraction Of Left Ventricular Ejection Depending On Sex

Aim of the work: to compare survivability parameters during 36 months and their predictors among men and women with chronic heart failure and decreased fraction of left ventricular ejection.Materials and methods: the research included 356 patients with CHF (NYHA ІІ –ІV) with decreased LVEF<40 %, 18–75 years old. Using Kaplan-Meier method, there was analyzed the survivability in men and women during 36 months, then there were analyzed independent factors that influenced survivability terms depending on sex using the multiple logistic regression.Results. Our analysis of the survivability of patients with CHF with decreased LVEF demonstrated that the cumulative survival after 3 years of observation was 49 and 51 % for men and women, respectively. The curves of 36 months survivability didn\u27t reliably differ. At the analysis of factors, associated with the bad prognosis, there were observed differences between groups of men and women with CHF. Thus, in men the predictors of 36 month survival were: the thickness of the right ventricle wall, size of the right atrium, end-diastolic volume and end-systolic volume of LV, indices of EDV and ESV of LV, urinary acid level, value of LVEF. In women the predictors of survivability during 3 years were the following parameters: BMI, DM type 2 in an anamnesis, end-diastolic size of LV, end-systolic size of LV, blood glucose level, LVEF.Conclusion. The survivability of men and women with CHF with decreased LVEF during 36 months didn\u27t reliably differ and was 49 and 51 % respectively. But predictors of the lethal outcome in men and women essentially differed during 36 months, and their number is essentially higher in men

Complete list of Darboux Integrable Chains of the form t1x=tx+d(t,t1)t_{1x}=t_x+d(t,t_1)

We study differential-difference equation of the form $$\frac{d}{dx}t(n+1,x)=f(t(n,x),t(n+1,x),\frac{d}{dx}t(n,x))$$ with unknown $t(n,x)$ depending on continuous and discrete variables $x$ and $n$. Equation of such kind is called Darboux integrable, if there exist two functions $F$ and $I$ of a finite number of arguments $x$, $\{t(n\pm k,x)\}_{k=-\infty}^\infty$, ${\frac{d^k}{dx^k}t(n,x)}_{k=1}^\infty$, such that $D_xF=0$ and $DI=I$, where $D_x$ is the operator of total differentiation with respect to $x$, and $D$ is the shift operator: $Dp(n)=p(n+1)$. Reformulation of Darboux integrability in terms of finiteness of two characteristic Lie algebras gives an effective tool for classification of integrable equations. The complete list of Darboux integrable equations is given in the case when the function $f$ is of the special form $f(u,v,w)=w+g(u,v)$

Prediction of the Antiinflammatory Activity of New S-alkyl Derivatives of 1,2,4-triazol-3-thiones Using the PASS Computer Program and Molecular Docking

The strategy of rational approaches to the search for selective COX-2 inhibitors as potential antiinflammatory agents has been proposed and elaborated. It is based on the use of PASS-prediction and molecular docking. The choice of the basic structure of 4-amino-3-thio-1,2,4-triazole as a promising object of chemical modification has been substantiated. Using a modification of the primary molecule, a virtual library of S-derivatives of 5-substituted 4-amino(pyrrol)3-thio-4H-1,2,4-triazoles in the amount of 100 compounds (ten groups) has been obtained by introducing various pharmacophore fragments. Based on the analysis of the results of the PASS-prediction and molecular docking, six of the ten planned groups of compounds have been selected for the synthesis as promising selective COX-2 inhibitors. The reliability of the prediction results has already been confirmed for one of the promising group 4-amino-5-(pyridine-4-yl)-1,2,4-triazole (4Н)-3-yl-thioacetamides

Russia as Seen by Heine’s “La Mouche” (I. S. Turgenev and Camille Selden)

The article offers for the first time an analysis of a series of critiques written by the French author Camille Selden (pseudonym of Elise Krinitz) and devoted to I. S. Turgenev’s works. Published in 1879 by the Paris newspaper “Le XIXe siècle,” these articles were read and appreciated by the writer in a letter addressed to Selden that is being now introduced into scientific circulation. “La Mouche” is known in literary circles as Heinrich Heine’s last love: he dedicated six poems to her and addressed her at least two dozens of letters. It was from Heine that Eliza received the nickname “La Mouche.” Later, she turned out to be an insightful critic who highly appreciated the work of the Russian writer. Despite numerous flaws, and sometimes not a very careful reading of Turgenev’s texts, Selden showed wide familiarity with the writer’s works, although often her assessments look more exotic than deep. In general, Selden’s view of Russia caused Turgenev’s rejection

Problems of Educational Processes Development and Labor Market Needs Analysis in Russia

This article is dedicated to the analysis of the problems of the educational process development and its relation to the labor market. Main problems caused by inconsistency of the education system and labor market needs were revealed. The study of the educational expectations and needs of graduates and students (using questionnaires) was made herein. Labor market analysis wad done to show the main negative and positive aspects of its development. Market industry forecast trends and the education market tendency for the next few years were built to reveal disproportion of the industry needs and educational system outcomes