Значення акмегерменевтичного підходу в підготовці студентів факультетів мистецтв до виконавської діяльності

The article reveals the significance of the acmehermeneutic approach in the preparation of art faculty students for performance. From the standpoint of the classics of philosophical hermeneutics and the works of modern scientists, the essence of the main concepts of the article, namely: "hermeneutics", "interpretation", "acmeology", was considered. The author's understanding of the acmehermeneutic approach is presented, which is defined as a new direction of performing activities of students of the faculties of arts, which provides a comprehensive coverage of the content of the images of a musical work, which is performed in unity with its form. Proposing the application of an acmehermeneutic approach in the process of performing activities of students of art faculties, we consider it expedient to: deep understanding by students of the figurative essence of a musical work, the formation of students' ability to reveal, understanding of the means of expression that the composer chose to express his feelings, enabling the activation of students' emotional response to a musical work through their involvement in the intellectual understanding of the origins of beauty.   Key words: acmehermeneutic approach, students of art faculties, performing activity, interpretation, works of art, intellectual understanding.Стаття розкриває значення акмегерменевтичного підходу в підготовці студентів факультетів мистецтв до виконавської діяльності. З позиції класиків філософської герменевтики та робіт сучасних науковців розглянуто сутність основних понять статті, а саме: «герменевтика», «інтерпретація», «акмеологія». Подано авторське розуміння акмегерменевтичного підходу, який визначено як новий напрям виконавської діяльності студентів факультетів мистецтв, що забезпечує комплексне охопленню змісту образів музичного твору, який виконується у єдності з його формою. Пропонуючи застосування акмегерменевтичного підходу у процесі виконавської діяльності студентів факультетів мистецтв, вважаємо за доцільне: глибоке осмислення студентами образної сутності музичного твору, формування у студентів здатності до розкриття, розуміння тих засобів виразності, які обрав композитор для вираження своїх почуттів, уможливлення активізації емоційної реакції студентів на музичний твір через залучення їх до інтелектуального осмислення витоків прекрасного.  Ключові слова: акмегерменевтичний підхід, студенти факультетів мистецтв, виконавська діяльність, інтерпретація, мистецькі твори, інтелектуальне осмислення.

Sweet DREAMs for hippo

The Hippo pathway coordinates organ size and cell proliferation. The retinoblastoma family of proteins regulates progression through the G0/G1 phase of the cell cycle. Disruption of either pathway contributes to cancer formation. Three recent studies in Genes & Development reveal how cellular proliferation is coordinated between these pathways. Here we discuss the implications of these studies and the new questions that they raise. © 2011 by Cold Spring Harbor Laboratory Press

Requirements for E1A dependent transcription in the yeast Saccharomyces cerevisiae

<p>Abstract</p> <p>Background</p> <p>The human adenovirus type 5 early region 1A (E1A) gene encodes proteins that are potent regulators of transcription. E1A does not bind DNA directly, but is recruited to target promoters by the interaction with sequence specific DNA binding proteins. In mammalian systems, E1A has been shown to contain two regions that can independently induce transcription when fused to a heterologous DNA binding domain. When expressed in <it>Saccharomyces cerevisiae</it>, each of these regions of E1A also acts as a strong transcriptional activator. This allows yeast to be used as a model system to study mechanisms by which E1A stimulates transcription.</p> <p>Results</p> <p>Using 81 mutant yeast strains, we have evaluated the effect of deleting components of the ADA, COMPASS, CSR, INO80, ISW1, NuA3, NuA4, Mediator, PAF, RSC, SAGA, SAS, SLIK, SWI/SNF and SWR1 transcriptional regulatory complexes on E1A dependent transcription. In addition, we examined the role of histone H2B ubiquitylation by Rad6/Bre1 on transcriptional activation.</p> <p>Conclusion</p> <p>Our analysis indicates that the two activation domains of E1A function via distinct mechanisms, identify new factors regulating E1A dependent transcription and suggest that yeast can serve as a valid model system for at least some aspects of E1A function.</p

Introduction of Coaching Technologies Into Educational Practice

The purpose of the research is to substantiate the theoretical and methodological fundamentals and to identify the problems of implementing coaching technologies in the practice of education. The methodological basis of the research consists of the following methods of economic analysis, namely: observation and system analysis, process approach method, comparative analysis and synthesis, functional-system approach, graphical and tabular methods. Based on the results of the research conducted, it has made it possible to establish that coaching technologies are an effective innovative tool for modernization of the modern education system. They contribute to improving the quality of the educational process due to their ability to develop the education seekers’ skills of self-study, setting goals and achieving them, to increase the level of educational motivation and to ensure successful socialization. The most used methods of coaching have been identified, including as follows: the case study method, the method of emotional stimulation, the discussion method, the mosaic method, the perspective shifting method and the project method

Repurposing Albendazole: new potential as a chemotherapeutic agent with preferential activity against HPV-negative head and neck squamous cell cancer.

Albendazole is an anti-helminthic drug that has been shown to exhibit anti-cancer properties, however its activity in head and neck squamous cell cancer (HNSCC) was unknown. Using a series of in vitro assays, we assessed the ability of albendazole to inhibit proliferation in 20 HNSCC cell lines across a range of albendazole doses (1 nM-10 μM). Cell lines that responded to treatment were further examined for cell death, inhibition of migration and cell cycle arrest. Thirteen of fourteen human papillomavirus-negative HNSCC cell lines responded to albendazole, with an average IC50 of 152 nM. In contrast, only 3 of 6 human papillomavirus-positive HNSCC cell lines responded. Albendazole treatment resulted in apoptosis, inhibition of cell migration, cell cycle arrest in the G2/M phase and altered tubulin distribution. Normal control cells were not measurably affected by any dose tested. This study indicates that albendazole acts to inhibit the proliferation of human papillomavirus-negative HNSCC cell lines and thus warrants further study as a potential chemotherapeutic agent for patients suffering from head and neck cancer

High-throughput testing in head and neck squamous cell carcinoma identifies agents with preferential activity in human papillomavirus-positive or negative cell lines.

Head and neck squamous cell carcinoma (HNSCC) is a common cancer diagnosis worldwide. Despite advances in treatment, HNSCC has very poor survival outcomes, emphasizing an ongoing need for development of improved therapeutic options. The distinct tumor characteristics of human papillomavirus (HPV)-positive vs. HPV-negative disease necessitate development of treatment strategies tailored to tumor HPV-status. High-throughput robotic screening of 1,433 biologically and pharmacologically relevant compounds at a single dose (4 μM) was carried out against 6 HPV-positive and 20 HPV-negative HNSCC cell lines for preliminary identification of therapeutically relevant compounds. Statistical analysis was further carried out to differentiate compounds with preferential activity against cell lines stratified by the HPV-status. These analyses yielded 57 compounds with higher activity in HPV-negative cell lines, and 34 with higher-activity in HPV-positive ones. Multi-point dose-response curves were generated for six of these compounds (Ryuvidine, MK-1775, SNS-032, Flavopiridol, AZD-7762 and ARP-101), confirming Ryuvidine to have preferential potency against HPV-negative cell lines, and MK-1775 to have preferential potency against HPV-positive cell lines. These data comprise a valuable resource for further investigation of compounds with therapeutic potential in the HNSCC

Conserved region 3 of human papillomavirus 16 E7 contributes to deregulation of the retinoblastoma tumor suppressor

The human papillomavirus (HPV) E7 oncoprotein binds cellular factors, preventing or retargeting their function and thereby making the infected cell conducive for viral replication. A key target of E7 is the product of the retinoblastoma susceptibility locus (pRb). This interaction results in the release of E2F transcription factors and drives the host cell into the S phase of the cell cycle. E7 binds pRb via a high-affinity binding site in conserved region 2 (CR2) and also targets a portion of cellular pRb for degradation via the proteasome. Evidence suggests that a secondary binding site exists in CR3, and that this interaction influences pRb deregulation. Additionally, evidence suggests that CR3 also participates in the degradation of pRb. We have systematically analyzed the molecular mechanisms by which CR3 contributes to deregulation of the pRb pathway by utilizing a comprehensive series of mutations in residues predicted to be exposed on the surface of HPV16 E7 CR3. Despite differences in the ability to interact with cullin 2, all CR3 mutants degrade pRb comparably to wild-type E7. We identified two specific patches of residues on the surface of CR3 that contribute to pRb binding independently of the high-affinity CR2 binding site. Mutants within CR3 that affect pRb binding are less effective than the wild-type E7 in overcoming pRb-induced cell cycle arrest. This demonstrates that the interaction between HPV16 E7 CR3 and pRb is functionally important for alteration of the cell cycle. © 2012, American Society for Microbiology

E1A Activates Transcription of p73 and Noxa to Induce Apoptosis

p73, a member of the p53 family of proteins, transcriptionally activates a number of genes involved in the control of cell cycle and apoptosis. Overexpression of p73 was detected in a large number of primary head and neck cancers, and in the established cell lines examined, these all contained inactivating p53 mutations. The significance of p73 overexpression in the pathogenesis of head and neck cancer is currently unclear. We have shown that the expression of adenovirus 5 E1A in a panel of head and neck cancer cell lines induces apoptosis independently of their p53 status. In this study we examined the role of p73 and its transcriptional targets in E1A-mediated induction of apoptosis. E1A expression resulted in significant activation of the TAp73 promoter but had no effect on the alternative, DeltaNp73 promoter. E1A also increased expression of endogenous TAp73 mRNA and protein. E1A mutants lacking the p300- and/or pRB-binding sites showed reduced ability to activate the TAp73 promoter. Additionally, mutations in the E2F1-binding sites in the TAp73 promoter impaired activation by E1A. Importantly, expression of the 13S isoform of E1A substantially induced the p53 apoptotic target Noxa in several p53-deficient cancer cell lines. Our results indicate that E1A activation of p73 and the p53 apoptotic target Noxa can occur in the absence of a functional p53. This activation is likely to play a key role in the mechanism of p53-independent apoptosis induced by E1A in some cancers and may provide an avenue for future cancer therapies

A Pilot Study Comparing HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinomas by Whole Exome Sequencing.

Background. Next-generation sequencing of cancers has identified important therapeutic targets and biomarkers. The goal of this pilot study was to compare the genetic changes in a human papillomavirus- (HPV-)positive and an HPV-negative head and neck tumor. Methods. DNA was extracted from the blood and primary tumor of a patient with an HPV-positive tonsillar cancer and those of a patient with an HPV-negative oral tongue tumor. Exome enrichment was performed using the Agilent SureSelect All Exon Kit, followed by sequencing on the ABI SOLiD platform. Results. Exome sequencing revealed slightly more mutations in the HPV-negative tumor (73) in contrast to the HPV-positive tumor (58). Multiple mutations were noted in zinc finger genes (ZNF3, 10, 229, 470, 543, 616, 664, 638, 716, and 799) and mucin genes (MUC4, 6, 12, and 16). Mutations were noted in MUC12 in both tumors. Conclusions. HPV-positive HNSCC is distinct from HPV-negative disease in terms of evidence of viral infection, p16 status, and frequency of mutations. Next-generation sequencing has the potential to identify novel therapeutic targets and biomarkers in HNSCC