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.”

Aggressiveness is a hereditary behavioral pattern that forms a social hierarchy and affects the individual social rank and accordingly quality and duration of life. Thus, genome-wide studies of human aggressiveness are important. Nonetheless, the aggressiveness-related genome-wide studies have been conducted on animals rather than humans. Recently, in our genome-wide study, we uncovered natural selection against underexpression of human aggressiveness-related genes and proved it using F1 hybrid mice. Simultaneously, this natural selection equally supports two opposing traits in humans (dominance and subordination) as if self-domestication could have happened with its disruptive natural selection. Because there is still not enough scientific evidence that this could happen, here, we verified this natural selection pattern using quantitative PCR and two outbred rat lines (70 generations of artificial selection for aggressiveness or tameness, hereinafter: domestication). We chose seven genes-Cacna2d3, Gad2, Gria2, Mapk1, Nos1, Pomc, and Syn1-over-or underexpression of which corresponds to aggressive or domesticated behavior (in humans or mice) that has the same direction as natural selection. Comparing aggressive male rats with domesticated ones, we found that these genes are overexpressed statistically significantly in the hypothalamus (as a universal behavior regulator), not in the periaqueductal gray, where there was no aggressiveness-related expression of the genes in males. Database STRING showed statistically significant associations of the human genes homologous to these rat genes with long-term depression, circadian entrainment, Alzheimer's disease, and the central nervous system disorders during chronic IL-6 overexpression. This finding more likely supports positive perspectives of further studies on self-domestication syndromes.

Abstract:Here we present the analysis of alternative splicing events on an example of glioblastoma cell culture samples using a set of computer tools in combination with database integration. The gene expression profiles of glioblastoma were obtained from cell culture samples of primary glioblastoma which were isolated and processed for RNA extraction. Transcriptome profiling of normal brain samples and glioblastoma were done by Illumina sequencing. The significant differentially expressed exon-level probes and their corresponding genes were identified using a combination of the splicing index method. Previous studies indicated that tumor-specific alternative splicing is important in the regulation of gene expression and corresponding protein functions during cancer development. Multiple alternative splicing transcripts have been identified as progression markers, including generalized splicing abnormalities and tumor-and stage-specific events. We used a set of computer tools which were recently applied to analysis of gene expression in laboratory animals to study differential splicing events. We found 69 transcripts that are differentially alternatively spliced. Three cancer-associated genes were considered in detail, in particular: APP (amyloid beta precursor protein), CASC4 (cancer susceptibility candidate 4) and TP53. Such alternative splicing opens new perspectives for cancer research.

SummaryDetailed investigation of socially important diseases with modern experimental methods has resulted in the generation of large volume of valuable data. However, analysis and interpretation of this data needs application of efficient computational techniques and systems biology approaches. In particular, the techniques allowing the reconstruction of associative networks of various biological objects and events can be useful. In this publication, the combination of different techniques to create such a network associated with an abstract cell environment is discussed in order to gain insights into the functional as well as spatial interrelationships. It is shown that experimentally gained knowledge enriched with data warehouse content and text mining data can be used for the reconstruction and localization of a cardiovascular disease developing network beginning with MUPP1/MPDZ (multi-PDZ domain protein).