PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
Browse
26 results
Search Results
Now showing 1 - 10 of 26
Article Citation - WoS: 3Citation - Scopus: 5A Novel Thermophilic Hemoprotein Scaffold for Rational Design of Biocatalysts(Springer Verlag, 2018) Efua Aggrey Fynn, Joana; Sürmeli, Nur BaşakHemoproteins are commonly found in nature, and involved in many important cellular processes such as oxygen transport, electron transfer, and catalysis. Rational design of hemoproteins can not only inspire novel biocatalysts but will also lead to a better understanding of structure-function relationships in native hemoproteins. Here, the heme nitric oxide/oxygen-binding protein from Caldanaerobacter subterraneus subsp. tengcongensis (TtH-NOX) is used as a novel scaffold for oxidation biocatalyst design. We show that signaling protein TtH-NOX can be reengineered to catalyze H2O2 decomposition and oxidation of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) by H2O2. In addition, the role of the distal tyrosine (Tyr140) in catalysis is investigated. The mutation of Tyr140 to alanine hinders the catalysis of the oxidation reactions. On the other hand, the mutation of Tyr140 to histidine, which is commonly observed in peroxidases, leads to a significant increase of the catalytic activity. Taken together, these results show that, while the distal histidine plays an important role in hemoprotein reactions with H2O2, it is not always essential for oxidation activity. We show that TtH-NOX protein can be used as an alternative scaffold for the design of novel biocatalysts with desired reactivity or functionality. H-NOX proteins are homologous to the nitric oxide sensor soluble guanylate cyclase. Here, we show that the gas sensor protein TtH-NOX shows limited capacity for catalysis of redox reactions and it can be used as a novel scaffold in biocatalysis design. [GRAPHICS] .Article Citation - WoS: 10Citation - Scopus: 13Analysis of European Hazelnut (corylus Avellana) Reveals Loci for Cultivar Improvement and the Effects of Domestication and Selection on Nut and Kernel Traits(Springer Verlag, 2019) Frary, Amy; Öztürk, Süleyman Can; Balık, Hüseyin İrfan; Kayalak Balık, Selda; Kızılcı, Gökhan; Doğanlar, Sami; Frary, AnneTurkey is a rich source of European hazelnut (Corylus avellana) germplasm with nearly 400 accessions in the national collection. This genetic material encompasses cultivars, landraces and wild genotypes which were characterized for 12 nut and 13 kernel traits over 2years in the 1990s. Analysis of these attributes revealed both the positive and negative impacts that human selection and breeding have had on hazelnut. Thus, while selection has resulted in larger nuts and kernels, cultivars have fewer nuts per cluster and kernels with larger internal cavities. Breeding has also resulted in a propensity for cultivars to have higher proportions of double kernels and empty nuts, two traits which reduce quality and yield. In addition, it is clear that while selection has successfully increased hazelnut fat content it has not impacted overall flavor, a much more complex trait. The nut and kernel phenotypic data were combined with genotypic data from 406 simple sequence repeat marker alleles for association mapping of the quantitative trait loci (QTL) for the traits. A total of 78 loci were detected in the population with the highest proportions for nut (24%) and kernel (26%) appearance parameters followed by quality (19%), shell thickness (16%) and yield-related (15%) traits. It is hoped that some of the identified QTL will be useful for future breeding of hazelnut for improved nut and kernel yield and quality.Article Citation - Scopus: 8The Second Case of Saposin a Deficiency and Altered Autophagy(Springer Verlag, 2018) Köse, Melis; Akyıldız Demir, Seçil; Akıncı, Gülçin; Eraslan, Cenk; Yılmaz, Ünsal; Ceylaner, Serdar; Sözmen Yıldırım, Eser; Seyrantepe, VolkanKrabbe disease is a lysosomal storage disease caused by galactosylceramidase deficiency, resulting in neurodegeneration with a rapid clinical downhill course within the first months of life in the classic infantile form. This process may be triggered by the accumulation of galactosylceramide (GalCer) in nervous tissues. Both the enzyme galactosylceramidase and its in vivo activator molecule, saposin A, are essential during GalCer degradation. A clinical manifestation almost identical to Krabbe disease is observed when, instead of the galactosylceramidase protein, the saposin A molecule is defective. Saposin A results from posttranslational processing of the precursor molecule, prosaposin, encoded by the PSAP gene. Clinical and neuroimaging findings in a 7-month-old child strongly suggested Krabbe disease, but this condition was excluded by enzymatic and genetic testing. However, at whole exome sequencing, the previously undescribed homozygous, obviously pathogenic PSAP gene NM_002778.3: c.209T>G(p.Val70Gly) variant was determined in the saposin A domain of the PSAP gene. Fibroblast studies showed GalCer accumulation and the activation of autophagy for the first time in a case of human saposin A deficiency. Our patient represents the second known case in the literature and provides new information concerning the pathophysiology of saposin A deficiency and its intralysosomal effects.Article Citation - WoS: 4Citation - Scopus: 6Dishevelled Proteins and Cyld Reciprocally Regulate Each Other in Cml Cell Lines(Springer Verlag, 2017) Çalışkan, Ceyda; Pehlivan, Melek; Yüce, Zeynep; Sercan, OgünDishevelled (Dvl) proteins are activated by Wnt pathway stimulation and have crucial roles in the regulation of β-catenin destruction complex. CYLD is a tumor suppressor and a deubiquitination enzyme. CYLD negatively regulates the Wnt/β-catenin signaling pathway by deubiquitinating Dvl proteins. Loss of function and mutations of CYLD were linked to different types of solid tumors. Loss of function in CYLD is associated with Dvl hyper ubiquitination, resulting in the transmission of Wnt signaling to downstream effectors. β-catenin upregulation is observed during disease progression in chronic myeloid leukemia (CML). Deregulated Dvl signaling may be a reason for β-catenin activation in CML; and CYLD may contribute to Dvl deregulation. First, we evaluated mRNA expression in three CML cell lines and mRNA expression of the CYLD gene was found to be present in all (K562, MEG01, KU812). Unlike solid tumors sequencing revealed no mutations in the coding sequences of the CYLD gene. DVL genes were silenced by using a pool of siRNA oligonucleotides and gene expression differences in CYLD was determined by RT-PCR and western blot. CYLD protein expression decreased after Dvl silencing. An opposite approach of overexpressing Dvl proteins resulted in upregulated CYLD expression. While previous reports have described CYLD as a regulator of DVL proteins; our data suggests the presence of a more complicated reciprocal regulatory mechanism in CML cell lines.Article Citation - WoS: 20Citation - Scopus: 24Newly Developed Ssr Markers Reveal Genetic Diversity and Geographical Clustering in Spinach (spinacia Oleracea)(Springer Verlag, 2017) Göl, Şurhan; Göktay, Mehmet; Allmer, Jens; Doğanlar, Sami; Frary, AnneSpinach is a popular leafy green vegetable due to its nutritional composition. It contains high concentrations of vitamins A, E, C, and K, and folic acid. Development of genetic markers for spinach is important for diversity and breeding studies. In this work, Next Generation Sequencing (NGS) technology was used to develop genomic simple sequence repeat (SSR) markers. After cleaning and contig assembly, the sequence encompassed 2.5% of the 980 Mb spinach genome. The contigs were mined for SSRs. A total of 3852 SSRs were detected. Of these, 100 primer pairs were tested and 85% were found to yield clear, reproducible amplicons. These 85 markers were then applied to 48 spinach accessions from worldwide origins, resulting in 389 alleles with 89% polymorphism. The average gene diversity (GD) value of the markers (based on a GD calculation that ranges from 0 to 0.5) was 0.25. Our results demonstrated that the newly developed SSR markers are suitable for assessing genetic diversity and population structure of spinach germplasm. The markers also revealed clustering of the accessions based on geographical origin with clear separation of Far Eastern accessions which had the overall highest genetic diversity when compared with accessions from Persia, Turkey, Europe, and the USA. Thus, the SSR markers have good potential to provide valuable information for spinach breeding and germplasm management. Also they will be helpful for genome mapping and core collection establishment.Article Citation - WoS: 33Citation - Scopus: 44Relationship Between Geographical Origin, Seed Size and Genetic Diversity in Faba Bean (vicia Faba L.) as Revealed by Ssr Markers(Springer Verlag, 2017) Göl, Şurhan; Doğanlar, Sami; Frary, AnneFaba bean (Vicia faba L.) is an important legume species because of its high protein and starch content. Broad bean can be grown in different climatic conditions and is an ideal rotation crop because of the nitrogen fixing bacteria in its roots. In this work, 255 faba bean germplasm accessions were characterized using 32 SSR primers which yielded 302 polymorphic fragments. According to the results, faba bean individuals were divided into two main groups based on the neighbor-joining algorithm (r = 0.91) with some clustering based on geographical origin as well as seed size. Population structure was also determined and agreed with the dendrogram analysis in splitting the accessions into two subpopulations. Analysis of molecular variance (AMOVA) revealed high levels of within population genetic variation. Genetic similarity and geographical proximity were related with separation of European accessions from African and Asian ones. Interestingly, there was no significant difference between landrace (38%) and cultivar (40%) diversity indicating that genetic variability has not yet been lost due to breeding. A total of 44 genetically well-characterized faba bean individuals were selected for a core collection to be further examined for yield and nutritional traits.Article Citation - WoS: 30Citation - Scopus: 34Gddom: an Online Tool for Calculation of Dominant Marker Gene Diversity(Springer Verlag, 2017) Abuzayed, Mazen; El-Dabba, Nourhan; Frary, Anne; Doğanlar, SamiGene diversity (GD), also called polymorphism information content, is a commonly used measure of molecular marker polymorphism. Calculation of GD for dominant markers such as AFLP, RAPD, and multilocus SSRs is valuable for researchers. To meet this need, we developed a free online computer program, GDdom, which provides easy, quick, and accurate calculation of dominant marker GD with a commonly used formula. Results are presented in tabular form for quick interpretation. © 2016, Springer Science+Business Media New York.Article Citation - WoS: 16Citation - Scopus: 16Therapeutic Effects of Aicar and Dox Conjugated Multifunctional Nanoparticles in Sensitization and Elimination of Cancer Cells Via Survivin Targeting(Springer Verlag, 2017) Dağlıoğlu, Cenk; Okutucu, BurcuPurpose: Resistance to chemotherapy is one of the major problems facing current cancer research. Enhancing tumor cell response to anticancer agents increases chemotherapeutic effectiveness. We have recently addressed this issue and reported on producing multifunctional nanoparticles (Fe3O4@SiO2(FITC)-FA/AICAR/DOX) aiming to overcome chemoresistance with synergetic effect of AICAR and DOX. In the present study, we demonstrated that these nanoparticles not only show enhanced cellular uptake and cytotoxic effect but can also show enhanced pro-apoptotic and anti-proliferative effects in five different tumor-derived cell lines (A549, HCT-116, HeLa, Jurkat and MIA PaCa-2). Methods: The nanoparticles were examined by using flow cytometric analyses of apoptosis and cell cycle. In addition, we performed caspase-3 activity assay, which supported our flow cytometric data. Furthermore, we demonstrated the applicability of this approach in a variety of cancer types confirming the potential widespread utility of this approach. Results: With the concept of co-delivery of AICAR and DOX in the nanoparticle formulation, the use of AICAR against survivin (BIRC5) sensitized cancer cells to DOX chemotherapy which resulted in effective cancer cell elimination. These result showed that combination therapy involving both a molecularly targeted therapy and chemotherapeutic agent has the ability to retain and enhance therapeutic efficacy. Conclusion: Fe3O4@SiO2(FITC)-FA/AICAR/DOX nanoparticles is superior to monotherapy via the synergetic effect of AICAR and DOX and also the nanoparticle formulation could overcome issues of toxicity with targeted therapy while maintaining the potent anticancer effects of AICAR and DOX.Article Citation - WoS: 18Citation - Scopus: 21Intraperitoneal Mesenchymal Stem Cell Administration Ameliorates Allergic Rhinitis in the Murine Model(Springer Verlag, 2017) Işık, Sakine; Karaman, Meral; Adan, Aysun; Kıray, Müge; Bağrıyanık, Hüsnü Alper; Çağlayan Sözmen, Şule; Kozanoğlu, İlknur; Karaman, Özkan; Baran, Yusuf; Uzuner, NevinPrevious studies showed that bone marrow-derived mesenchymal stem cells (BMSCs) could ameliorate a variety of immune-mediated and inflammatory diseases due to their immunomodulatory and anti-inflammatory effects. In this study, we developed a mouse model of ovalbumin (OVA) induced allergic inflammation in the upper airways and evaluated the effects of the intraperitoneal administration of BMSCs on allergic inflammation. Twenty-five BALB/c mice were divided into five groups; group I (control group), group II (sensitized and challenged with OVA and treated with saline-placebo group), group III (sensitized and challenged with OVA and treated with 1 × 106 BMSCs), group IV (sensitized and challenged with OVA and treated with 2 × 106 BMSCs), and group V (sensitized and challenged with phosphate buffered saline (PBS) and treated with 1 × 106 BMSCs). Histopathological features (number of goblet cells, eosinophils and mast cells, basement membrane, epithelium thickness, and subepithelial smooth muscle thickness) of the upper and lower airways and BMSCs migration to nasal and lung tissue were evaluated using light and confocal microscopes. Levels of cytokines in the nasal lavage fluid and lung tissue supernatants were measured using enzyme-linked immunosorbent assay (ELISA). Confocal microscopic analysis showed that there was no significant amount of BMSCs in the nasal and lung tissues of group V. However, significant amount of BMSCs were observed in group III and IV. In OVA-induced AR groups (group II, III, and IV), histopathological findings of chronic asthma, such as elevated subepithelial smooth muscle thickness, epithelium thickness, and number of goblet and mast cells, were determined. Furthermore, the number of nasal goblet and eosinophil cells, histopathological findings of chronic asthma, and IL-4, IL-5, IL-13, and NO levels was significantly lower in both BMSCs-treated groups compared to the placebo group. Our findings indicated that histopathological findings of chronic asthma were also observed in mice upon AR induction. BMSCs migrated to the nasal and lung tissues following intraperitoneal delivery and ameliorated to the airway remodeling and airway inflammation both in the upper and lower airways via the inhibition of T helper (Th) 2 immune response in the murine model of AR.Article Citation - WoS: 62Citation - Scopus: 80Anti-Proliferative, Apoptotic and Signal Transduction Effects of Hesperidin in Non-Small Cell Lung Cancer Cells(Springer Verlag, 2015) Çinçin, Zeynep Birsu; Ünlü, Miray; Kıran, Bayram; Bireller, Elif Sinem; Baran, Yusuf; Çakmakoğlu, BediaPurpose: Hesperidin, a glycoside flavonoid, is thought to act as an anti-cancer agent, since it has been found to exhibit both pro-apoptotic and anti-proliferative effects in several cancer cell types. The mechanisms underlying hesperidin-induced growth arrest and apoptosis are, however, not well understood. Here, we aimed to investigate the anti-proliferative and apoptotic effects of hesperidin on non-small cell lung cancer (NSCLC) cells and to investigate the mechanisms involved. Methods: The anti-proliferative and apoptotic effects of hesperidin on two NSCLC-derived cell lines, A549 and NCI-H358, were determined using a WST-1 colorimetric assay, a LDH cytotoxicity assay, a Cell Death Detection assay, an AnnexinV-FITC assay, a caspase-3 assay and a JC-1 assay, respectively, all in a time- and dose-dependent manner. As a control, non-cancerous MRC-5 lung fibroblasts were included. Changes in whole genome gene expression profiles were assessed using an Illumina Human HT-12v4 beadchip microarray platform, and subsequent data analyses were performed using an Illumina Genome Studio and Ingenuity Pathway Analyser (IPA). Results: We found that after hesperidin treatment, A549 and NCI-H358 cells exhibited decreasing cell proliferation and increasing caspase-3 and other apoptosis-related activities, in conjunction with decreasing mitochondrial membrane potential activities, in a dose- and time-dependent manner. Through a GO analysis, by which changes in gene expression profiles were compared, we found that the FGF and NF-κB signal transduction pathways were most significantly affected in the hesperidin treated NCI-H358 and A549 NSCLC cells. Conclusions: Our results indicate that hesperidin elicits an in vitro growth inhibitory effect on NSCLC cells by modulating immune response-related pathways that affect apoptosis. When confirmed in vivo, hesperidin may serve as a novel anti-proliferative agent for non-small cell lung cancer.
- «
- 1 (current)
- 2
- 3
- »