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Search Results: 1 - 10 of 462038 matches for " Daria A. Gaykalova "
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Extrinsic and intrinsic nucleosome positioning signals
Alexandre V. Morozov,Karissa Fortney,Daria A. Gaykalova,Vasily M. Studitsky,Jonathan Widom,Eric D. Siggia
Quantitative Biology , 2008,
Abstract: In eukaryotic genomes, nucleosomes function to compact DNA and to regulate access to it both by simple physical occlusion and by providing the substrate for numerous covalent epigenetic tags. While nucleosome positions in vitro are determined by sequence alone, in vivo competition with other DNA-binding factors and action of chromatin remodeling enzymes play a role that needs to be quantified. We developed a biophysical model for the sequence dependence of DNA bending energies, and validated it against a collection of in vitro free energies of nucleosome formation and a nucleosome crystal structure; we also successfully designed both strong and poor histone binding sequences ab initio. For in vivo data from S.cerevisiae, the strongest positioning signal came from the competition with other factors. Based on sequence alone, our model predicts that functional transcription factor binding sites have a tendency to be covered by nucleosomes, but are uncovered in vivo because functional sites cluster within a single nucleosome footprint, making transcription factors bind cooperatively. Similarly a weak enhancement of nucleosome binding in the TATA region for naked DNA becomes a strong depletion when the TATA-binding protein is included, in quantitative agreement with experiment. Predictions at specific loci were also greatly enhanced by including competing factors. Our physically grounded model distinguishes multiple ways in which genomic sequence can influence nucleosome positions and thus provides an alternative explanation for several important experimental findings.
Dose-Dependent Activation of Putative Oncogene SBSN by BORIS
Daria Gaykalova, Rajita Vatapalli, Chad A. Glazer, Sheetal Bhan, Chunbo Shao, David Sidransky, Patrick K. Ha, Joseph A. Califano
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0040389
Abstract: Testis-specific transcription factor BORIS (Brother of the Regulator of Imprinted Sites), a paralog and proposed functional antagonist of the widely expressed CTCF, is abnormally expressed in multiple tumor types and has been implicated in the epigenetic activation of cancer-testis antigens (CTAs). We have reported previously that suprabasin (SBSN), whose expression is restricted to the epidermis, is epigenetically derepressed in lung cancer. In this work, we establish that SBSN is a novel non-CTA target of BORIS epigenetic regulation. With the use of a doxycycline-inducible BORIS expressing vector, we demonstrate that relative BORIS dosage is critical for SBSN activation. At lower concentrations, BORIS induces demethylation of the SBSN CpG island and disruption and activation of chromatin around the SBSN transcription start site (TSS), resulting in a 35-fold increase in SBSN expression in the H358 human lung cancer cell line. Interestingly, increasing BORIS concentrations leads to a subsequent reduction in SBSN expression via chromatin repression. In a similar manner, increase in BORIS concentrations leads to eventual decrease of cell growth and colony formation. This is the first report demonstrating that different amount of BORIS defines its varied effects on the expression of a target gene via chromatin structure reorganization.
Preferential Activation of the Hedgehog Pathway by Epigenetic Modulations in HPV Negative HNSCC Identified with Meta-Pathway Analysis
Elana J. Fertig, Ana Markovic, Ludmila V. Danilova, Daria A. Gaykalova, Leslie Cope, Christine H. Chung, Michael F. Ochs, Joseph A. Califano
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0078127
Abstract: Head and neck squamous cell carcinoma (HNSCC) is largely divided into two groups based on their etiology, human papillomavirus (HPV)-positive and –negative. Global DNA methylation changes are known to drive oncogene and tumor suppressor expression in primary HNSCC of both types. However, significant heterogeneity in DNA methylation within the groups results in different transcriptional profiles and clinical outcomes. We applied a meta-pathway analysis to link gene expression changes to DNA methylation in distinguishing HNSCC subtypes. This approach isolated specific epigenetic changes controlling expression in HPV? HNSCC that distinguish it from HPV+ HNSCC. Analysis of genes identified Hedgehog pathway activation specific to HPV? HNSCC. We confirmed that GLI1, the primary Hedgehog target, showed higher expression in tumors compared to normal samples with HPV? tumors having the highest GLI1 expression, suggesting that increased expression of GLI1 is a potential driver in HPV? HNSCC. Our algorithm for integration of DNA methylation and gene expression can infer biologically significant molecular pathways that may be exploited as therapeutics targets. Our results suggest that therapeutics targeting the Hedgehog pathway may be of benefit in HPV? HNSCC. Similar integrative analysis of high-throughput coupled DNA methylation and expression datasets may yield novel insights into deregulated pathways in other cancers.
Suprabasin Is Hypomethylated and Associated with Metastasis in Salivary Adenoid Cystic Carcinoma
Chunbo Shao,Marietta Tan,Justin A. Bishop,Jia Liu,Weiliang Bai,Daria A. Gaykalova,Takenori Ogawa,Ami R. Vikani,Yuri Agrawal,Ryan J. Li,Myoung Sook Kim,William H. Westra,David Sidransky,Joseph A. Califano,Patrick K. Ha
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0048582
Abstract: Salivary gland adenoid cystic carcinoma (ACC) is a rare cancer, accounting for only 1% of all head and neck malignancies. ACC is well known for perineural invasion and distant metastasis, but its underlying molecular mechanisms of carcinogenesis are still unclear.
Expression Microarray Analysis Reveals Alternative Splicing of LAMA3 and DST Genes in Head and Neck Squamous Cell Carcinoma
Ryan Li, Michael F. Ochs, Sun Mi Ahn, Patrick Hennessey, Marietta Tan, Ethan Soudry, Daria A. Gaykalova, Mamoru Uemura, Mariana Brait, Chunbo Shao, William Westra, Justin Bishop, Elana J. Fertig, Joseph A. Califano
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0091263
Abstract: Purpose Prior studies have demonstrated tumor-specific alternative splicing events in various solid tumor types. The role of alternative splicing in the development and progression of head and neck squamous cell carcinoma (HNSCC) is unclear. Our study queried exon-level expression to implicate splice variants in HNSCC tumors. Experimental Design We performed a comparative genome-wide analysis of 44 HNSCC tumors and 25 uvulopalatopharyngoplasty (UPPP) tissue samples at an exon expression level. In our comparison we ranked genes based upon a novel score—the Maximum-Minimum Exon Score (MMES) – designed to predict the likelihood of an alternative splicing event occurring. We validated predicted alternative splicing events using quantitative RT-PCR on an independent cohort. Results After MMES scoring of 17,422 genes, the top 900 genes with the highest scores underwent additional manual inspection of expression patterns in a graphical analysis. The genes LAMA3, DST, VEGFC, SDHA, RASIP1, and TP63 were selected for further validation studies because of a high frequency of alternative splicing suggested in our graphical analysis, and literature review showing their biological relevance and known splicing patterns. We confirmed TP63 as having dominant expression of the short DeltaNp63 isoform in HNSCC tumor samples, consistent with prior reports. Two of the six genes (LAMA3 and DST) validated by quantitative RT-PCR for tumor-specific alternative splicing events (Student's t test, P<0.001). Conclusion Alternative splicing events of oncologically relevant proteins occur in HNSCC. The number of genes expressing tumor-specific splice variants needs further elucidation, as does the functional significance of selective isoform expression.
Novel Insight into Mutational Landscape of Head and Neck Squamous Cell Carcinoma
Daria A. Gaykalova, Elizabeth Mambo, Ashish Choudhary, Jeffery Houghton, Kalyan Buddavarapu, Tiffany Sanford, Will Darden, Alex Adai, Andrew Hadd, Gary Latham, Ludmila V. Danilova, Justin Bishop, Ryan J. Li, William H. Westra, Patrick Hennessey, Wayne M. Koch, Michael F. Ochs, Joseph A. Califano, Wenyue Sun
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0093102
Abstract: Development of head and neck squamous cell carcinoma (HNSCC) is characterized by accumulation of mutations in several oncogenes and tumor suppressor genes. We have formerly described the mutation pattern of HNSCC and described NOTCH signaling pathway alterations. Given the complexity of the HNSCC, here we extend the previous study to understand the overall HNSCC mutation context and to discover additional genetic alterations. We performed high depth targeted exon sequencing of 51 highly actionable cancer-related genes with a high frequency of mutation across many cancer types, including head and neck. DNA from primary tumor tissues and matched normal tissues was analyzed for 37 HNSCC patients. We identified 26 non-synonymous or stop-gained mutations targeting 11 of 51 selected genes. These genes were mutated in 17 out of 37 (46%) studied HNSCC patients. Smokers harbored 3.2-fold more mutations than non-smokers. Importantly, TP53 was mutated in 30%, NOTCH1 in 8% and FGFR3 in 5% of HNSCC. HPV negative patients harbored 4-fold more TP53 mutations than HPV positive patients. These data confirm prior reports of the HNSCC mutational profile. Additionally, we detected mutations in two new genes, CEBPA and FES, which have not been previously reported in HNSCC. These data extend the spectrum of HNSCC mutations and define novel mutation targets in HNSCC carcinogenesis, especially for smokers and HNSCC without HPV infection.
Interaction of Molecules of Phosphorus-Containing Inorganic Additives with Iron Surface: Quantum-Chemical Analysis and Tribotechnical Testing  [PDF]
Yuri F. Migal, Vladimir I. Kolesnikov, Maria A. Savenkova, Daria N. Solodovnikova
Advances in Materials Physics and Chemistry (AMPC) , 2013, DOI: 10.4236/ampc.2013.36038
Abstract: Сondensed phosphates of metaphosphatic structure with the equal relation of metal oxide and phosphorus pentoxide are promising inorganic oleophilic antifrictional, antiwear and anti-seize, heat-resistant and eco-friendly additives to greases. We study in detail one group of these compounds, phosphorowolframates of alkaline metals MIPWO6 (MI = Li, Na, K, Rb, Cs), by using the ADF software package based on the DFT approach. Three stages of interaction of molecules of these substances with an iron surface are investigated: change of the shape of molecules near a surface, formation of the adsorptive complex and its disintegration. It is shown that a strong covalent binding between molecules of phosphorowolframates and a surface appears in the course of adsorption. High strength of this binding and also low inner strength of the chain and its flexibility provide effective protection of iron surface against wear. It is also found that at adsorption of phosphorowolframates on an iron surface, there is a change of local structure of the surface.
Cascaded third harmonic generation in hybrid graphene-semiconductor waveguides
Daria A. Smirnova,Alexander S. Solntsev
Physics , 2015, DOI: 10.1103/PhysRevB.92.155410
Abstract: We study cascaded harmonic generation of hybrid surface plasmons in integrated planar waveguides composed of a graphene layer and a doped-semiconductor slab. We derive a comprehensive model of cascaded third harmonic generation through phase-matched nonlinear interaction of fundamental, second harmonic and third harmonic plasmonic modes supported by the structure. We show that hybrid graphene-semiconductor waveguides can simultaneously phase-match these three interacting harmonics, increasing the total third-harmonic output by a factor of 5 compared to the non-cascaded regime.
Simulation of Thermal Explosion of Catalytic Granule in Fluctuating Temperature Field  [PDF]
Igor Derevich, Daria Galdina
Journal of Applied Mathematics and Physics (JAMP) , 2013, DOI: 10.4236/jamp.2013.15001
Abstract:

Method for numerical simulation of the temperature of granule with internal heat release in a medium with random temperature fluctuations is proposed. The method utilized the solution of a system of ordinary stochastic differential equations describing temperature fluctuations of the surrounding and granule. Autocorrelation function of temperature fluctuations has a finite decay time. The suggested method is verified by the comparison with exact analytical results. Random temperature behavior of granule with internal heat release qualitatively differs from the results obtained in the deterministic approach. Mean first passage time of granules temperature intersecting critical temperature is estimated at different regime parameters.

Service Quality Experience and Customers’ Behavioural Intentions in Active Sport Tourism  [PDF]
Anna Romiti, Daria Sarti
Modern Economy (ME) , 2016, DOI: 10.4236/me.2016.712127
Abstract: This paper analyzes the role played by experience in the loyalty and intent to return of sports tourists to a running race. The data for this study were collected through an online questionnaire filled in by 984 participants of one of the most important international running races in Italy. A regression analysis was conducted to evaluate the data. The results showed that aesthetic dimensions (the valence and the venue) were the principal determinant of loyalty for active sports tourists. The principal determinants of the intent to return were the venue and the technical quality (the value and the challenge). This study provides suggestions for future research and gives useful insights into managerial implications for sports tourism management.
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