Social capital and its changes in Armenia: challenges and expectations

Social capital was the Achilles’ heel of the economic competitiveness of Armenia. In the meantime, the country made significant progress in solidifying it since the Velvet Revolution. In this article, we tried to present and analyze those elements of social capital which demonstrated significant progress in post-revolutionary Armenia, as well as the changes thereof. For that purpose, we have formulated the following research questions: What factors led to this growth, and what factors still lag? What hidden challenges can be observed through factual indicators which probably resulted from the slight decrease in the updated scores? What changes can be expected from the turbulent world and in the post-war society? The applied methodology is quantitative. In particular, to answer the research questions we used index analysis, graphic analysis, and comparison, correlation analysis techniques, pared t-test of the mathematical-statistical significance of changes, and Principal Component Analysis. The results of the analysis showed that a significant increase in the level of social capital was recorded in post-revolutionary Armenia, which was mainly due to the progress in institutional trust. Nevertheless, some revealed anomalies and encountered challenges undermined the archived progress in the growth of trust. Therefore, we put forward several recommendations

THE SPREAD OF CHALCEDONISM IN TAYK AND ITS INFLUENCE ON THE FORMATION OF THE HISTORICal AND CULTURAL ENVIRONMENT

In 451, after the Ecumenical Council of Chalcedon, Chalcedonism spread in Armenia, especially in Tayk. With its spread, Georgian penetrated there having an impact on the historic and cultural life and the ethnic image of the region. A part of the Armenians, breaking away from the Armenian Church, became Georgian-speaking. The study aims to analyze the process and the ethno-religious environment resulted from the impact of the new confession. In Tayk, a bishop’s seat was founded as early as the 4th century by Gregory the Illuminator, and it continued to be a diocese of the Armenian Apostolic Church, which is testified by the fact that the names of the bishops of Tayk have been remembered at church meetings etc. until the 9th — 10thcenturies. Chalcedonism and Georgian writing and literature rooted in the region as late as the 9th — 10th centuries, when the Bagratunis, the local ruling elite, accepted the Chalcedonian confession. As a result, the population of Tayk and their rulers were called ‘Georgians’ or ‘Iberians’ in both Armenian and foreign records. In Tayk, even church ceremonies were performed in Georgian, though Armenian was also used

p53-dependent treatment response to DNA-PK inhibition in combination with irradiation in head and neck squamous cell carcinoma models

Aims: M3814 is a small-molecule inhibitor of DNA-PK, a key regulator of nonhomologous end joining (NHEJ). Inhibition of NHEJ along with irradiation (IR)- induced DNA double-strand breaks can potentially increase antitumor treatment efficacy. This study aims to investigate responses of head and neck squamous cell carcinomas with distinct HPV and p53 status to the treatment with IR, DNA-PK inhibition, and their combination. Methods: Three groups of cell lines with various HPV/p53 genotypes (p53-wt/HPV–; p53-mutated/HPV–, and p53-wt/HPV+) were treated by M3814, 4 Gy IR, or a combination of M3814 and IR. In addition to viability and cell cycle assays, caspase 3 activity and senescence-associated β-galactosidase assays were used to evaluate cell fates such as apoptosis and senescence. yH2AX and RAD51 foci immunostainings at different time points were implemented to assess the levels of DNA damage and its repair. NMRI- nu mice with subcutaneous xenografts of p53-wt/HPV+ and p53-wt/HPV- cell lines were treated with either fractionated 10 Gy IR (delivered with the small animal radiation therapy system SmART) alone or in combination with orally distributed M3814. Results: Decreased number of viable cells after IR alone and particularly after combined treatment was observed in most of the cell lines. Inhibition of NHEJ combined with IR induces an abrogation of proliferation with different cell fates. Whereas HPV+ and p53-mutated cells undergo apoptosis due to a common alteration in the p53 pathways, p53-wt cells are preferentially eliminated through senescence. Elevated yH2AX foci formation after 24 and 48 h in the combination treatment group indicates unresolved persistent DNA damage. In vivo, significant effects of IR and of the combination treatment on tumor growth control were observed particularly in p53-wt/HPV+ xenografts. Conclusion: M3814 radiosensitizes HNSCC tumors and leads to better treatment response in dysfunctional p53 cells. Determination of the HPV and p53 status in a particular tumor might be necessary to effectively shape the intervention outcome when combining NHEJ targeting with radiation therapy

A DNA-PK phosphorylation site on MET regulates its signaling interface with the DNA damage response

The DNA damage response (DDR) is intertwined with signaling pathways downstream of oncogenic receptor tyrosine kinases (RTKs). To drive research into the application of targeted therapies as radiosensitizers, a better understanding of this molecular crosstalk is necessary. We present here the characterization of a previously unreported MET RTK phosphosite, Serine 1016 (S1016) that represents a potential DDR-MET interface. MET S1016 phosphorylation increases in response to irradiation and is mainly targeted by DNA-dependent protein kinase (DNA-PK). Phosphoproteomics unveils an impact of the S1016A substitution on the overall long-term cell cycle regulation following DNA damage. Accordingly, the abrogation of this phosphosite strongly perturbs the phosphorylation of proteins involved in the cell cycle and formation of the mitotic spindle, enabling cells to bypass a G2 arrest upon irradiation and leading to the entry into mitosis despite compromised genome integrity. This results in the formation of abnormal mitotic spindles and a lower proliferation rate. Altogether, the current data uncover a novel signaling mechanism through which the DDR uses a growth factor receptor system for regulating and maintaining genome stability.ISSN:0950-9232ISSN:1476-559

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