An Inducible and Reversible Mouse Genetic Rescue System

Inducible and reversible regulation of gene expression is a powerful approach for uncovering gene function. We have established a general method to efficiently produce reversible and inducible gene knockout and rescue in mice. In this system, which we named iKO, the target gene can be turned on and off at will by treating the mice with doxycycline. This method combines two genetically modified mouse lines: a) a KO line with a tetracycline-dependent transactivator replacing the endogenous target gene, and b) a line with a tetracycline-inducible cDNA of the target gene inserted into a tightly regulated (TIGRE) genomic locus, which provides for low basal expression and high inducibility. Such a locus occurs infrequently in the genome and we have developed a method to easily introduce genes into the TIGRE site of mouse embryonic stem (ES) cells by recombinase-mediated insertion. Both KO and TIGRE lines have been engineered for high-throughput, large-scale and cost-effective production of iKO mice. As a proof of concept, we have created iKO mice in the apolipoprotein E (ApoE) gene, which allows for sensitive and quantitative phenotypic analyses. The results demonstrated reversible switching of ApoE transcription, plasma cholesterol levels, and atherosclerosis progression and regression. The iKO system shows stringent regulation and is a versatile genetic system that can easily incorporate other techniques and adapt to a wide range of applications

Human Immunodeficiency Virus Type 1 (HIV-1) Accessory Protein Vpr Induces Transcription of the HIV-1 and Glucocorticoid-Responsive Promoters by Binding Directly to p300/CBP Coactivators

The accessory Vpr protein of human immunodeficiency virus type 1 (HIV-1) is a promiscuous activator of viral and cellular promoters. We report that Vpr enhances expression of the glucocorticoid receptor-induced mouse mammary tumor virus (MMTV) promoter and of the Tat-induced HIV-1 long terminal repeat promoter by directly binding to p300/CBP coactivators. In contrast, Vpr does not bind to p/CAF or to members of the p160 family of nuclear receptor coactivators, such as steroid receptor coactivator 1a and glucocorticoid receptor (GR)-interacting protein 1. Vpr forms a stable complex with p300 and also interacts with the ligand-bound glucocorticoid receptor in vivo. Mutation analysis showed that the C-terminal part of Vpr binds to the C-terminal portion of p300/CBP within amino acids 2045 to 2191. The same p300 region interacts with the p160 coactivators and with the adenovirus E1A protein. Accordingly, E1A competed for binding to p300 in vitro. Coexpression of E1A or of small fragments of p300 containing the Vpr binding site resulted in inhibition of Vpr's transcriptional effects. The C-terminal part of p300 containing the transactivating region is required for Vpr transactivation, whereas the histone acetyltransferase enzymatic region is dispensable. Vpr mutants that bind p300 but not the GR did not activate expression of the MMTV promoter and had dominant-negative effects. These results indicate that Vpr activates transcription by acting as an adapter linking transcription components and coactivators

Efortful Control in Primary Schoolchildren: Links with Personality, Problem Behaviour, Academic Achievement, and Subjective Well-Being

Background: Efortful control is a core aspect of self-regulation and refers to the ability to voluntarily regulate behaviour and attention, measured by temperament questionnaires. Although the Temperament in Middle Childhood Questionnaire is widely used in diferent countries, this measure has not been fully explored. Most research on the links of efortful control with personality and important outcomes has been carried out in Western nations; the possibility of extending these fndings to other cultures requires study. Objective: To examine efortful control and its relations to personality and wellbeing in a community sample of primary schoolchildren in Russia. Design: Parents of 7–10-year-olds (N = 614) completed the abbreviated Efortful Control scale of the TMCQ, the Inventory of Child Individual Diferences–Short version, and the Strengths and Difculties Questionnaire (SDQ); teachers provided SDQ data and school grades; children completed the Students’ Life Satisfaction Scale. Results: Te fndings supported a four-factor structure of Efortful Control, including Attention Focusing, Inhibitory Control, Activation Control, and Low-Intensity Pleasure. Efortful Control was associated with the personality traits of Conscientiousness, Agreeableness, and Openness, and also with Positive Emotions and low Neuroticism. Efortful Control was also associated with academic achievement, subjective well-being, and lower levels of externalising and internalising problems. Structural modelling showed that Attentional Control contributed to problem behaviour and subjective wellbeing; Inhibitory Control contributed to externalising problems; and Activation Control contributed to academic achievement. Conclusion: Efortful Control and its components were strongly related to higherand lower-order personality traits. Te fndings confrmed the important role of efortful control in the academic success and well-being of Russian primary schoolchildren

Unmet needs of child and adolescent psychiatrists among Asian and European countries : does the Human Development Index (HDI) count?

Non peer reviewe

The social determinants of adolescent smoking in Russia in 2004.

OBJECTIVES: To determine the prevalence of adolescent smoking in the Russian Federation and examine what factors are associated with it. METHODS: Data were drawn from Round 13 of the Russia Longitudinal Monitoring Survey (RLMS) carried out in 2004. The sample consists of 815 adolescents (430 boys, 385 girls) aged 14-17 years who answered questions about their health behaviours. RESULTS: Smoking was more prevalent among boys than girls (26.1 vs. 5.7%). Maternal smoking and adolescent alcohol use were associated with smoking among both sexes. The self-assessment of one's socioeconomic position as unfavourable was associated with girls' smoking, while living in a disrupted family, physical inactivity and having a low level of self-esteem were predictive of boys' smoking. CONCLUSIONS: The family environment appears to be an important determinant of adolescent smoking in Russia. In particular, boys and girls may be modelling the negative health behaviour lifestyles of their parents, with unhealthy behaviours clustering. Efforts to reduce adolescent smoking in Russia must address the negative effects emanating from the parental home whilst also addressing associated behaviours such as alcohol use