Person: ARĞA, KAZIM YALÇIN
Loading...
Email Address
Birth Date
Research Projects
Organizational Units
Job Title
Last Name
ARĞA
First Name
KAZIM YALÇIN
Name
57 results
Search Results
Now showing 1 - 10 of 57
Publication Metadata only The Stimulatory Effect of Mannitol on Levan Biosynthesis: Lessons from Metabolic Systems Analysis of Halomonas smyrnensis AAD6(T)(WILEY, 2013) TOKSOY ÖNER, EBRU; Ates, Ozlem; Arga, Kazim Y.; Oner, Ebru ToksoyHalomonas smyrnensis AAD(T) is a halophilic, gram-negative bacterium that can efficiently produce levan from sucrose as carbon source via levansucrase activity. However, systems-based approaches are required to further enhance its metabolic performance for industrial application. As an important step toward this goal, the genome-scale metabolic network of Chromohalobacter salexigens DSM3043, which is considered a model organism for halophilic bacteria, has been reconstructed based on its genome annotation, physiological information, and biochemical information. In the present work, the genome-scale metabolic network of C. salexigens was recruited, and refined via integration of the available biochemical, physiological, and phenotypic features of H. smyrnensis AAD6(T). The generic metabolic model, which comprises 1,393 metabolites and 1,108 reactions, was then systematically analyzed in silico using constraints-based simulations. To elucidate the relationship between levan biosynthesis and other metabolic processes, an enzyme-graph representation of the metabolic network and a graph decomposition technique were employed. Using the concept of control effective fluxes, significant links between several metabolic processes and levan biosynthesis were estimated. The major finding was the elucidation of the stimulatory effect of mannitol on levan biosynthesis, which was further verified experimentally via supplementation of mannitol to the fermentation medium. The optimal concentration of 30 g/L mannitol supplemented to the 50 g/L sucrose-based medium resulted in a twofold increase in levan production in parallel with increased sucrose hydrolysis rate, accumulated extracellular glucose, and decreased fructose uptake rate. (c) 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29:1386-1397, 2013Publication Metadata only Genome reprogramming in Saccharomyces cerevisiae upon nonylphenol exposure(AMER PHYSIOLOGICAL SOC, 2017) MERTOĞLU, BÜLENT; Bereketoglu, Ceyhun; Arga, Kazim Yalcin; Eraslan, Serpil; Mertoglu, BulentBioaccumulative environmental estrogen, nonylphenol (NP; 4-nonylphenol), is widely used as a nonionic surfactant and can affect human health. Since genomes of Saccharomyces cerevisiae and higher eukaryotes share many structural and functional similarities, we investigated subcellular effects of NP on S.cerevisiae BY4742 cells by analyzing genome-wide transcriptional profiles. We examined effects of low (1 mg/l; <15% cell number reduction) and high (5 mg/l; > 65% cell number reduction) inhibitory concentration exposures for 120 or 180 min. After 120 and 180 min of 1 mg/l NP exposure, 187 (63 downregulated, 124 upregulated) and 103 genes (56 downregulated, 47 upregulated), respectively, were differentially expressed. Similarly, 678 (168 repressed, 510 induced) and 688 genes (215 repressed, 473 induced) were differentially expressed in cells exposed to 5 mg/l NP for 120 and 180 min, respectively. Only 15 downregulated and 63 upregulated genes were common between low and high NP inhibitory concentration exposure for 120 min, whereas 16 downregulated and 31 upregulated genes were common after the 180-min exposure. Several processes/pathways were prominently affected by either low or high inhibitory concentration exposure, while certain processes were affected by both inhibitory concentrations, including ion transport, response to chemicals, transmembrane transport, cellular amino acids, and carbohydrate metabolism. While minimal expression changes were observed with low inhibitory concentration exposure, 5 mg/l NP treatment induced substantial expression changes in genes involved in oxidative phosphorylation, cell wall biogenesis, ribosomal biogenesis, and RNA processing, and encoding heat shock proteins and ubiquitin-conjugating enzymes. Collectively, these results provide considerable information on effects of NP at the molecular level.Publication Metadata only Metabolic Biomarkers and Neurodegeneration: A Pathway Enrichment Analysis of Alzheimer's Disease, Parkinson's Disease, and Amyotrophic Lateral Sclerosis(MARY ANN LIEBERT, INC, 2016) KAZAN, DİLEK; Kori, Medi; Aydin, Busra; Unal, Semra; Arga, Kazim Yalcin; Kazan, DilekNeurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) lack robust diagnostics and prognostic biomarkers. Metabolomics is a postgenomics field that offers fresh insights for biomarkers of common complex as well as rare diseases. Using data on metabolite-disease associations published in the previous decade (2006-2016) in PubMed, ScienceDirect, Scopus, and Web of Science, we identified 101 metabolites as putative biomarkers for these three neurodegenerative diseases. Notably, uric acid, choline, creatine, L-glutamine, alanine, creatinine, and N-acetyl-L-aspartate were the shared metabolite signatures among the three diseases. The disease-metabolite-pathway associations pointed out the importance of membrane transport (through ATP binding cassette transporters), particularly of arginine and proline amino acids in all three neurodegenerative diseases. When disease-specific and common metabolic pathways were queried by using the pathway enrichment analyses, we found that alanine, aspartate, glutamate, and purine metabolism might act as alternative pathways to overcome inadequate glucose supply and energy crisis in neurodegeneration. These observations underscore the importance of metabolite-based biomarker research in deciphering the elusive pathophysiology of neurodegenerative diseases. Future research investments in metabolomics of complex diseases might provide new insights on AD, PD, and ALS that continue to place a significant burden on global health.Publication Metadata only Omics of Selenium Biology: A Prospective Study of Plasma Proteome Network Before and After Selenized-Yeast Supplementation in Healthy Men(MARY ANN LIEBERT, INC, 2016) ARĞA, KAZIM YALÇIN; Sinha, Indu; Karagoz, Kubra; Fogle, Rachel L.; Hollenbeak, Christopher S.; Zea, Arnold H.; Arga, Kazim Y.; Stanley, Anne E.; Hawkes, Wayne C.; Sinha, RaghuLow selenium levels have been linked to a higher incidence of cancer and other diseases, including Keshan, Chagas, and Kashin-Beck, and insulin resistance. Additionally, muscle and cardiovascular disorders, immune dysfunction, cancer, neurological disorders, and endocrine function have been associated with mutations in genes encoding for selenoproteins. Selenium biology is complex, and a systems biology approach to study global metabolomics, genomics, and/or proteomics may provide important clues to examining selenium-responsive markers in circulation. In the current investigation, we applied a global proteomics approach on plasma samples collected from a previously conducted, double-blinded placebo controlled clinical study, where men were supplemented with selenized-yeast (Se-Yeast; 300g/day, 3.8mol/day) or placebo-yeast for 48 weeks. Proteomic analysis was performed by iTRAQ on 8 plasma samples from each arm at baseline and 48 weeks. A total of 161 plasma proteins were identified in both arms. Twenty-two proteins were significantly altered following Se-Yeast supplementation and thirteen proteins were significantly changed after placebo-yeast supplementation in healthy men. The differentially expressed proteins were involved in complement and coagulation pathways, immune functions, lipid metabolism, and insulin resistance. Reconstruction and analysis of protein-protein interaction network around selected proteins revealed several hub proteins. One of the interactions suggested by our analysis, PHLD-APOA4, which is involved in insulin resistance, was subsequently validated by Western blot analysis. Our systems approach illustrates a viable platform for investigating responsive proteomic profile in before and after' condition following Se-Yeast supplementation. The nature of proteins identified suggests that selenium may play an important role in complement and coagulation pathways, and insulin resistance.Publication Open Access Drug Repositioning for Effective Prostate Cancer Treatment(FRONTIERS MEDIA SA, 2018-05-15) TURANLI, BESTE; Turanli, Beste; Grotli, Morten; Boren, Jan; Nielsen, Jens; Uhlen, Mathias; Arga, Kazim Y.; Mardinoglu, AdilDrug repositioning has gained attention from both academia and pharmaceutical companies as an auxiliary process to conventional drug discovery. Chemotherapeutic agents have notorious adverse effects that drastically reduce the life quality of cancer patients so drug repositioning is a promising strategy to identify non-cancer drugs which have anti-cancer activity as well as tolerable adverse effects for human health. There are various strategies for discovery and validation of repurposed drugs. In this review, 25 repurposed drug candidates are presented as result of different strategies, 15 of which are already under clinical investigation for treatment of prostate cancer (PCa). To date, zoledronic acid is the only repurposed, clinically used, and approved non-cancer drug for PCa. Anti-cancer activities of existing drugs presented in this review cover diverse and also known mechanisms such as inhibition of mTOR and VEGFR2 signaling, inhibition of PI3K/Akt signaling, COX and selective COX-2 inhibition, NF-kappa B inhibition, Wnt/beta - Catenin pathway inhibition, DNMT1 inhibition, and GSK-3 beta inhibition. In addition to monotherapy option, combination therapy with current anti-cancer drugs may also increase drug efficacy and reduce adverse effects. Thus, drug repositioning may become a key approach for drug discovery in terms of time- and cost-efficiency comparing to conventional drug discovery and development process.Publication Metadata only Combining various heterogeneous biological features to obtain a highly reliable almost complete protein interaction network of yeast(ELSEVIER SCIENCE BV, 2012) ARĞA, KAZIM YALÇIN; Karagoz, Kubra; Arga, Kazim YalcinPublication Metadata only Triple Negative Breast Cancer: A Multi-Omics Network Discovery Strategy for Candidate Targets and Driving Pathways(MARY ANN LIEBERT, INC, 2015) ARĞA, KAZIM YALÇIN; Karagoz, Kubra; Sinha, Raghu; Arga, Kazim YalcinTriple negative breast cancer (TNBC) represents approximately 15% of breast cancers and is characterized by lack of expression of both estrogen receptor (ER) and progesterone receptor (PR), together with absence of human epidermal growth factor 2 (HER2). TNBC has attracted considerable attention due to its aggressiveness such as large tumor size, high proliferation rate, and metastasis. The absence of clinically efficient molecular targets is of great concern in treatment of patients with TNBC. In light of the complexity of TNBC, we applied a systematic and integrative transcriptomics and interactomics approach utilizing transcriptional regulatory and protein-protein interaction networks to discover putative transcriptional control mechanisms of TNBC. To this end, we identified TNBC-driven molecular pathways such as the Janus kinase-signal transducers, and activators of transcription (JAK-STAT) and tumor necrosis factor (TNF) signaling pathways. The multi-omics molecular target and biomarker discovery approach presented here can offer ways forward on novel diagnostics and potentially help to design personalized therapeutics for TNBC in the future.Publication Metadata only Genomic analysis of Brevibacillus thermoruber 423 reveals its biotechnological and industrial potential(SPRINGER, 2015) TOKSOY ÖNER, EBRU; Yildiz, Songul Yasar; Radchenkova, Nadja; Arga, Kazim Yalcin; Kambourova, Margarita; Oner, Ebru ToksoyBrevibacillus thermoruber 423 is a Gram-positive, motile, red-pigmented, spore-forming, aerobic, and thermophilic bacterium that is known to produce high levels of exopolysaccharide (EPS) with many potential uses in food, feed, cosmetics, and pharmaceutical and chemical industries. This bacterium not only is among the limited number of reported thermophilic EPS producers but also exceeds other thermophilic producers in light of the high level of polymer synthesis. By a systems-based approach, whole-genome analysis of this bacterium was performed to gain more insight about the biological mechanisms and whole-genome organization of thermophilic EPS producers and hence to develop rational strategies for the genetic and metabolic optimization of EPS production. Also with this study, the first genome analysis was performed on a thermophilic Brevibacillus species. Essential genes associated with EPS biosynthesis were detected by genome annotation, and together with experimental evidences, a hypothetical mechanism for EPS biosynthesis was generated. B. thermoruber 423 was found to have many potential applications in biotechnology and industry because of its capacity to utilize xylose and to produce EPS, isoprenoids, ethanol/butanol, lipases, proteases, cellulase, and glucoamylase enzymes as well as its resistance to arsenic.Publication Metadata only Novel Genomic Biomarker Candidates for Cervical Cancer As Identified by Differential Co-Expression Network Analysis(MARY ANN LIEBERT, INC, 2019) ARĞA, KAZIM YALÇIN; Kori, Medi; Gov, Esra; Arga, Kazim YalcinCervical cancer is the second most common malignancy and the third reason for mortality among women in developing countries. Although infection by the oncogenic human papilloma viruses is a major cause, genomic contributors are still largely unknown. Network analyses, compared with candidate gene studies, offer greater promise to map the interactions among genomic loci contributing to cervical cancer risk. We report here a differential co-expression network analysis in five gene expression datasets (GSE7803, GSE9750, GSE39001, GSE52903, and GSE63514, from the Gene Expression Omnibus) in patients with cervical cancer and healthy controls. Kaplan-Meier Survival and principle component analyses were employed to evaluate prognostic and diagnostic performances of biomarker candidates, respectively. As a result, seven distinct co-expressed gene modules were identified. Among these, five modules (with sizes of 9-45 genes) presented high prognostic and diagnostic capabilities with hazard ratios of 2.28-11.3, and diagnostic odds ratios of 85.2-548.8. Moreover, these modules were associated with several key biological processes such as cell cycle regulation, keratinization, neutrophil degranulation, and the phospholipase D signaling pathway. In addition, transcription factors ETS1 and GATA2 were noted as common regulatory elements. These genomic biomarker candidates identified by differential co-expression network analysis offer new prospects for translational cancer research, not to mention personalized medicine to forecast cervical cancer susceptibility and prognosis. Looking into the future, we also suggest that the search for a molecular basis of common complex diseases should be complemented by differential co-expression analyses to obtain a systems-level understanding of disease phenotype variability.Publication Metadata only Cardiomyogenic differentiation potential of human lipoaspirate-derived stem cells on hyaluronic acid/gelatin plasma gels(TUBITAK SCIENTIFIC & TECHNICAL RESEARCH COUNCIL TURKEY, 2016) ARĞA, KAZIM YALÇIN; Gov, Esra; Kenar, Halime; Halbutogullari, Zehra Seda; Arga, Kazim Yalcin; Karaoz, ErdalCardiomyogenic differentiation from mesenchymal stem cells has emerged as a novel approach for repair of damaged myocardium. Cell transplantation through direct cell injection is not an optimal method due to the lack of cell-extracellular matrix interactions. In the present study, differentiation potential of human adipose-derived stem cells (ASCs) to cardiomyocytes has been investigated by growing them on hyaluronic acid/gelatin (HA/G) plasma gels and coverslips and supplementing the growth medium with chemical modifiers (activin-a, BMP-4, insulin, valproic acid, and 5-azacytidine) in various combinations. The HA/G plasma gels were produced from human blood plasma-derived fibrinogen, gelatin, and human umbilical cord-derived hyaluronic acid. A network-based approach was employed to select marker genes for cardiomyogenic differentiation, and the expression levels of three markers (GATA4, TBX5, and cTnI) were followed by RT-qPCR to investigate the cardiomyogenic differentiation potential of ASCs. Results indicated that each combination of chemical modifiers led to different expression levels in the aforementioned cardiac markers, and this was material-dependent, too. The cardiac gene expression on HA/G plasma gels in the presence of activin-a + BMP-4 or insulin + valproic acid was more pronounced than in the presence of 5-azacytidine only, and scaffold and chemical modifier combinations were crucial for cardiomyogenic differentiation.