Meta-Analysis of Differentiating Mouse Embryonic Stem Cell Gene Expression Kinetics Reveals Early Change of a Small Gene Set

Stem cell differentiation involves critical changes in gene expression. Identification of these should provide endpoints useful for optimizing stem cell propagation as well as potential clues about mechanisms governing stem cell maintenance. Here we describe the results of a new meta-analysis methodology applied to multiple gene expression datasets from three mouse embryonic stem cell (ESC) lines obtained at specific time points during the course of their differentiation into various lineages. We developed methods to identify genes with expression changes that correlated with the altered frequency of functionally defined, undifferentiated ESC in culture. In each dataset, we computed a novel statistical confidence measure for every gene which captured the certainty that a particular gene exhibited an expression pattern of interest within that dataset. This permitted a joint analysis of the datasets, despite the different experimental designs. Using a ranking scheme that favored genes exhibiting patterns of interest, we focused on the top 88 genes whose expression was consistently changed when ESC were induced to differentiate. Seven of these (103728_at, 8430410A17Rik, Klf2, Nr0b1, Sox2, Tcl1, and Zfp42) showed a rapid decrease in expression concurrent with a decrease in frequency of undifferentiated cells and remained predictive when evaluated in additional maintenance and differentiating protocols. Through a novel meta-analysis, this study identifies a small set of genes whose expression is useful for identifying changes in stem cell frequencies in cultures of mouse ESC. The methods and findings have broader applicability to understanding the regulation of self-renewal of other stem cell types

Likelihood of mechanistic roles for dopaminergic, serotonergic and glutamatergic receptors in tardive dyskinesia:A comparison of genetic variants in two independent patient populations

Objectives: An established theory for the pathogenesis of tardive dyskinesia is disturbed dopaminergic receptor sensitivity and/or dopaminergic intracellular signaling. We examined associations between genetic variants of neurotransmitter receptors and tardive dyskinesia. Methods: We assessed tardive dyskinesia in Caucasian psychiatric inpatients from Siberia (N = 431) and a long-stay population from the Netherlands (N = 168). These patients were genotyped for 43 tag single nucleotide polymorphisms in five neurotransmitter receptor genes, and the results for the two populations were compared. Results: Several significant associations with tardive dyskinesia were identified, but only GRIN2A (rs1345423) was found in both patient populations. This lack of agreement was probably due to the small effect size of the associations, the multiple testing and the small sample size of the Dutch patient population. After reviewing the literature, we propose that the constitutive stimulatory activity of serotonergic type 2 receptors may be relevant. Conclusions: Inactivity of the serotonergic, type 2C receptor or blockade of these receptors by atypical antipsychotic drugs may decrease the vulnerability to develop tardive dyskinesia

Ethno-cultural Component in Modern Design

Abstract The article considers ethnic elements in design, in particular, by the example of a package as an element of a visual identity of modern graphic design. The authors carried out a search for the balance between the universal and the national graphic design, studied the phenomenon of an ethnic component in the search for new forms of expression and images in design. The authors took the products of Russian and foreign large corporations as an example. The authors analyzed the problem of the relations between the national component and a unique heritage by the example of traditional ornamental motifs in the creation of a conceptual image of the package. The socio-cultural approach to the study allows to reveal objective laws of changes in design due to social and cultural changes in society. The art approach and the analysis of design projects conducted within its framework contributed to the objective and thorough review of this component of modern culture. The semiotic approach contributed to the analysis of the symbolic design elements that accumulate and transmit the information using symbols and signs as reflected in the artistic solution. The ethno-cultural component is of particular importance in developing and searching for new solutions in the design which is based on the borrowing of traditional art forms and adaptation of these forms at the present time. The article can be viewed as one of the possible methodological approaches to further research in modern design

The Problems of Detection and Registration of Infections Specific to the Perinatal Period in Neonates

Objective. The frequency of diagnosing intrauterine infections is increasing every year. assessment of the frequency of intra-amniotic infection of the fetus using the standard case definition.Subject and methods: a study, conducted in one of the maternity hospitals of St. Petersburg, included 110 newborn children with an established diagnosis of intra-amniotic infection. To clarify the diagnosis, we have applied the probable and confirmed standard definitions of the case.Results: a study showed that the diagnosis of intraamniotic infection was consistent with the standard case definition in 30.9% of cases.Conclusion:  the introduction of standard case definitions will make it possible to unify the registration and notification of the intrauterine infections by different specialists in all types of healthcare settings and will allow a unified approach to identification of the intrauterine infections, both in maternity hospitals and in the neonatal units of children's hospitals