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Background: Schizophrenia is a severe psychiatric disorder with a heterogeneous clinical phenotype. The association of interleukins and other cytokines and their receptors with schizophrenia has been previously reported. Additionally, a number of studies have reported altered mico-RNA (miRNA) expression in schizophrenia and other psychiatric disorders. The aim of our study was to explore the possible association of miR-31, miR-146a, miR-181c and miR-155 with schizophrenia pathogenesis, as well as their link to IL2 gene expression in disease. Methods: For this case-control study, 225 patients with paranoid schizophrenia and 225 sex- and age-matched controls with no family history of schizophrenia were recruited. The expression of studied miRNAs and the IL2 gene was measured using qPCR. DNA samples of all patients and controls were genotyped for IL2 rs2069778 single nucleotide polymorphism (SNP) using PCR with sequence specific primers (PCR-SSP). Statistical analyses include the Mann-Whitney U-test and Fischer’s exact test. Results: All studied miRNAs were over-expressed in schizophrenic patients IL2 gene expression was down-regulated in schizophrenic patients. The IL2 rs2069778 SNP is not associated with schizophrenia but regulates expression of the IL2 gene. Conclusions: Over-expression of studied miRNAs and down-regulation of IL2 gene expression may be considered as genetic risk factors for chronic schizophrenia. Abnormalities in studied miRNA expressions result in the deregulation of the T-cell receptor signaling pathway in schizophrenia.

Background:Alflatoxin B1 (AFB1) is the most hepatotoxic and hepatocarcinogenic of the aflatoxins and occurs as a contaminant in a variety of foods. The toxicity of AFB1 has been shown to be associated with a wide range of pathological events, such as enhanced apoptosis and oxidative events. Currently there is no treatment for mycotoxin exposure. The aim of this study was to evaluate the potential ability of picolinyl-L-phenylalaninate (PLP), picolinyl-L-tryptophanate (PLT), and nicotinyl-L-tryptophanate (NLT) Schiff base amino acid derivatives to act against damaging effects of AFB1 using a rat model of mycotoxicosis. For this purpose, a range of markers of immune and antioxidant systems in liver and blood plasma samples, as well as the apoptotic rate in neutrophils and monocytes was assessed.Methods:Mongrel white pubescent rats (with 180-200g b/w) were used in all experiments. Concentration of the markers of immune and antioxidant systems was measured in plasma by ELISA, using commercially available kits according to manufacturers’ instructions. The rate of apoptosis in neutrophils and monocytes was analyzed by flow cytometry.Results:AFB1 induced mycotoxicosis caused significant elevation of malonic dialdehyde contents (plasma and liver: p = 0.0001 compared with untreated rats), the levels of superoxide dismutase (p=0.005), total non-enzymatic water-soluble antioxidants (p = 0.0001), and terminal complement complex (p = 0.021). Moreover, the increased rates of early and late apoptosis in neutrophils and monocytes were observed as well. Treatment with PLP, PLT and NLT were shown to mitigate these effects, though to a different extent.Conclusions:The results obtained in this study clearly demonstrated that chronic AFB1 exposure induced oxidative cell damage, immunosuppression and apoptosis of circulating immune cells. The oral administration of Schiff base cyclic amino acid derivatives was capable of minimizing the detrimental effects of mycotoxicosis by possessing multi-mechanistic effects that target AFB1-induced pathological events.

Background. Breast cancer is one of the most common cancers in women worldwide. The germline mutations of the BRCA1 and BRCA2 genes are the most significant and well characterized genetic risk factors for hereditary breast cancer. Intensive research in the last decades has demonstrated that the incidence of mutations varies widely among different populations. In this study we attempted to perform a pilot study for identification and characterization of mutations in BRCA1 and BRCA2 genes among Armenian patients with family history of breast cancer and their healthy relatives. Methods. We performed targeted exome sequencing for BRCA1 and BRCA2 genes in 6 patients and their healthy relatives. After alignment of short reads to the reference genome, germline single nucleotide variation and indel discovery was performed using GATK software. Functional implications of identified variants were assessed using ENSEMBL Variant Effect Predictor tool. Results. In total, 39 single nucleotide variations and 4 indels were identified, from which 15 SNPs and 3 indels were novel. No known pathogenic mutations were identified, but 2 SNPs causing missense amino acid mutations had significantly increased frequencies in the study group compared to the 1000 Genome populations. Conclusions. Our results demonstrate the importance of screening of BRCA1 and BRCA2 gene variants in the Armenian population in order to identity specifics of mutation spectrum and frequencies and enable accurate risk assessment of hereditary breast cancers.

Cell signaling pathways are sequences of biochemical reactions that propagate an input signal, such as a hormone binding to a cell-surface receptor, into the cell to trigger a reactive process. Assessment of pathway activities is crucial for determining which pathways play roles in disease versus normal conditions. To date various pathway flow/perturbation assessment tools are available, however they are constrained to specific algorithms and specific data types. There are no accepted standards for evaluation of pathway activities or simulation of flow propagation events in pathways, and the results of different software are difficult to compare. Here we present Pathway Signal Flow Calculator (PSFC), a Cytoscape app for calculation of a pathway signal flow based on the pathway topology and node input data. The app provides a rich framework for customization of different signal flow algorithms to allow users to apply various approaches within a single computational framework.

The KEGG pathway database is a widely accepted source for biomolecular pathway maps. In this paper we present the CyKEGGParser app (http://apps.cytoscape.org/apps/cykeggparser) for Cytoscape 3 that allows manipulation with KEGG pathway maps. Along with basic functionalities for pathway retrieval, visualization and export in KGML and BioPAX formats, the app provides unique features for computer-assisted adjustment of inconsistencies in KEGG pathway KGML files and generation of tissue- and protein-protein interaction specific pathways. We demonstrate that using biological context-specific KEGG pathways created with CyKEGGParser makes systems biology analysis more sensitive and appropriate compared to original pathways.