Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
Permanent URI for this collectionhttps://hdl.handle.net/11147/9
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Article Citation - WoS: 2Citation - Scopus: 2Gas Phase Fragmentation Behavior of Proline in Macrocyclic B7 Ions(American Chemical Society, 2023) Taşoğlu, Çağdaş; Arslanoğlu, Alper; Yalçın, TalatThefragmentation characteristics of b (7) ionsproduced from proline-containing heptapeptides have been studiedin detail. The study has utilized the following C-terminally amidatedmodel peptides: PA(6), APA(5), A(2)PA(4), A(3)PA(3), A(4)PA(2), A(5)PA, A(6)P, PYAGFLV, PAGFLVY, PGFLVYA, PFLVYAG,PLVYAGF, PVYAGFL, YPAGFLV, YAPGFLV, YAGPFLV, YAGFPLV, YAGFLPV, YAGFLVP,PYAFLVG, PVLFYAG, A(2)PXA(3), and A(2)XPA(3) (where X = C, D, F, G, L, V, and Y, respectively). The resultshave shown that b (7) ions undergo head-to-tailcyclization and form a macrocyclic structure. Under the collision-induceddissociation (CID) condition, it generates nondirect sequence ionsregardless of the position of the proline and the neighboring aminoacid residues. This study highlights the unusual and unique fragmentationbehavior of proline-containing heptapeptides. Following the head-to-tailcyclization, the ring opens up and places the proline residue in theN-terminal position while forming a regular oxazolone form of b (2) ions for all peptide series. Then, the fragmentationreaction pathway is followed by the elimination of proline with itsC-terminal neighbor residue as an oxazolone (e.g., PXoxa) for all proline-containing peptide series.Article Citation - WoS: 4Citation - Scopus: 4Mapping of Quantitative Trait Loci for the Nutritional Value of Fresh Market Tomato(Springer, 2023) Gürbüz Çolak, Nergiz; Tek Eken, Neslihan; Ülger, Mehmet; Frary, Anne; Doğanlar, SamiThe incidence of many diseases, such as cancer, cardiovascular diseases, and diabetes, is associated with malnutrition and an unbalanced daily diet. Vegetables are an important source of vitamins and essential compounds for human health. As a result, such metabolites have increasingly become the focus of breeding programs. Tomato is one of the most popular components of our daily diet. Therefore, the improvement of tomato's nutritional quality is an important goal. In the present study, we performed targeted metabolic profiling of an interspecific Solanum pimpinellifolium x S. lycopersicum inbred backcross line (IBL) population and identified quantitative trait loci responsible for the nutritional value of tomato. Transgressive segregation was apparent for many of the nutritional compounds such that some IBLs had extremely high levels of various amino acids and vitamins compared to their parents. A total of 117 QTLs for nutritional traits including 62 QTLs for amino acids, 18 QTLs for fatty acids, 12 QTLs for water-soluble vitamins, and 25 QTLs for fat-soluble vitamins were identified. Moreover, almost 24% of identified QTLs were confirmed in previous studies, and 40 possible gene candidates were found for 18 identified QTLs. These findings can help breeders to improve the nutritional value of tomato.Article Citation - WoS: 3Citation - Scopus: 3Gras-Di Snp-Based Molecular Characterization and Fingerprinting of a Turkish Corylus Avellana Core Set Provide Insights Into the Cultivation and Breeding of Hazelnut in Turkey(Springer, 2023) Yanar, Ertuğrul Gazi; Doğanlar, Sami; Frary, AnneHazelnut (Corylus avellana L.) is an economically and socially important product for Turkey, the country that leads global production of this crop. The preservation of Turkish hazelnut genetic diversity and informed breeding of new cultivars are crucial for maintaining quality and crop yield stability. In this study, genotyping by random amplicon sequencing (GRAS-Di) was used to identify single-nucleotide polymorphisms (SNPs) in a panel of 96 individuals representing the Turkish national hazelnut collection. The resulting 7609 high-quality SNPs were physically mapped to the Tombul cultivar reference genome and used for population structure and diversity analyses. These analyses revealed that cultivars are not less diverse than wild accessions and that 44% of the panel had admixed ancestry. The results also indicated that recently released Turkish cultivars are highly similar to each other, suggesting that diversity analysis is an important tool that should be employed to prevent future genetic bottlenecks in this crop. A minimal marker algorithm was used to select a set of seven SNP markers that were capable of differentiating the panel accessions. These fingerprinting markers should be useful for the propagation of true-to-type elite cultivars that can be used to renew Turkey's aging hazelnut orchards.Article Citation - WoS: 2Citation - Scopus: 3Investigating the Potential Therapeutic Role of Targeting Stat3 for Overcoming Drug Resistance by Regulating Energy Metabolism in Chronic Myeloid Leukemia Cells(Mashhad University of Medical Sciences, 2022) Tezcanlı Kaymaz, Burçin; Günel, Nur Selvi; Söğütlü, Fatma; Özateş Ay, Neslihan Pınar; Baran, Yusuf; Gündüz, Cumhur; Biray Avcı, ÇığırObjective(s): STATs are one of the initial targets of emerging anti-cancer agents due to their regulatory roles in survival, apoptosis, drug response, and cellular metabolism in CML. Aberrant STAT3 activity promotes malignancy, and acts as a metabolic switcher in cancer cell metabolism, contributing to resistance to TKI nilotinib. To investigate the possible therapeutic effects of targeting STAT3 to overcome nilotinib resistance by evaluating various cellular responses in both sensitive and nilotinib resistant CML cells and to test the hypothesis that energy metabolism modulation could be a mechanism for re-sensitization to nilotinib in resistant cells. Materials and Methods: By using RNAi-mediated STAT3 gene silencing, cell viability and proliferation assays, apoptotic analysis, expressional regulations of STAT mRNA transcripts, STAT3 total, pTyr705, pSer727 protein expression levels, and metabolic activity as energy metabolism was determined in CML model K562 cells, in vitro. Results: Targeting STAT3 sensitized both parental and especially nilotinib resistant cells by decreasing leukemic cell survival; inducing leukemic cell apoptosis, and decreasing STAT3 mRNA and protein expression levels. Besides, cell energy phenotype was modulated by switching energy metabolism from aerobic glycolysis to mitochondrial respiration in resistant cells. RNAi-mediated STAT3 silencing accelerated the sensitization of leukemia cells to nilotinib treatment, and STAT3-dependent energy metabolism regulation could be another underlying mechanism for regaining nilotinib response. Conclusion: Targeting STAT3 is an efficient strategy for improving the development of novel CML therapeutics for regaining nilotinib response, and re-sensitization of resistant cells could be mediated by induced apoptosis and regulation in energy metabolism.Article Citation - WoS: 5Citation - Scopus: 5The Designing of a Gel Formulation With Chitosan Polymer Using Liposomes as Nanocarriers of Amphotericin B for a Non-Invasive Treatment Model of Cutaneous Leishmaniasis(Springer, 2022) Gürbüz, Nergiz; Çetin Uyanıkgil, Emel Öykü; Özbel, Yusuf; Töz, SerayPurpose Leishmaniasis is a disease caused by different Leishmania spp., which are transmitted to humans by a bite of infected female sand flies. Cutaneous leishmaniasis (CL, oriental sore), visceral leishmaniasis (VL), and mucocutaneous leishmaniasis (MCL) are three main clinical forms, however, only CL and VL are seen in Turkey. Cutaneous leishmaniasis is characterized by skin lesion(s) and is one of the most important vector-borne diseases in Turkey with over 2000 cases reported annually in 40 out of 81 provinces. The treatment is usually made invasively and painfully by intralesional injection of pentavalent antimony compounds. Non-invasive and innovative treatment methods are needed as aimed in this study. Methods In the present study, one of the classical antileishmanial drugs, amphotericin B (AmB), encapsulated in liposomes was evaluated using non-invasive design based on chitosan, which is a nontoxic, biocompatible and biodegradable polymer. To avoid the invasive effect of conventional intralesional needle application, the drug was encapsulated in liposomes and incorporated into a chitosan gel for applying topically on the skin lesion. The efficacy of encapsulation of amphotericin B into liposomes and the drug release from liposomes were studied. The chitosan gel was evaluated for viscosity, flowability, appearance and pH. The efficacy of the drug embedded into chitosan gel, liposomal AmB alone and chitosan gel alone in four different concentrations was also tested using Leishmania spp. promastigotes in vitro. Results The findings have shown that AmB was encapsulated into the liposomes with high efficiency (86.6%) and long-term physical and chemical stability. Therefore, designed liposomal formulation was suitable for sustained release. The appearance of the drug-embedded chitosan gel was transparent and appropriate. Chitosan gels showed non- Newtonian behavior and plastic flow. The liposomal AmB also showed higher efficacy with no parasites in all concentrations while drug embedded into chitosan gel and chitosan gel alone were effective in two higher concentrations. The lower efficacy of the drug-embedded chitosan gel in 24 h in in-vitro study was probably due to slow release of the drug. Conclusion The gel design created in this study will provide ease of use for the lesions of CL patients that do not have a specific number, size, and shape. Follow-up studies by the ex-vivo macrophage infection model with Leishmania intracellular amastigote forms and Leishmania-infected animal models are needed to understand the present design's efficacy better.Editorial Citation - Scopus: 1Lessons From a Ten-Year Journey: Building a Student-Driven Computational Biology Society Across Turkey(F1000 Research, 2022) Kaya, Yasin; Karakulak, Tülay; Saylan, Cemil Can; Gür, E. Ravza; Tatlıdil, Engin; Güleşen, Sevilay; Betül Dinçaslan, Fatma; Dönertaş, Handan MelikeThe Regional Student Group Turkey (RSG-Turkey) is officially associated with the International Society for Computational Biology (ISCB) Student Council (SC). At the RSG-Turkey, we aim to contribute to the early-career researchers in computational biology and bioinformatics fields by providing opportunities for improving their academic and technical skills in the field. Over the last ten years, we have built a well-known student-driven academic society in Turkey that organizes numerous events every year and continues to grow with over 650 current members. Celebrating the 10th anniversary of RSG-Turkey, in this communication, we share our experiences, five main lessons we learned, and the steps to establish a long-standing academic community: having a clear mission, building a robust structure, effective communication, turning challenges into opportunities, and building collaborations. We believe that our experiences can help students and academics establish long-standing communities in fast-developing areas like bioinformatics.Article Gas-Phase Fragmentation Reactions of A7 Ions Containing a Glutamine Residue(Wiley-Blackwell, 2021) Atik, Ahmet; Arslanoğlu, Alper; Yalçın, Talat; Atik, Ahmet; Arslanoğlu, Alper; Yalçın, TalatThe gas-phase fragmentation reactions of the a7 ions derived from glutamine (Q) containing model heptapeptides have been studied in detail with low-energy collision-induced dissociation (CID) tandem mass spectrometry (MS/MS). Specifically, the positional effect of the Q residue has been investigated on the fragmentation reactions of a7 ions. The study involves two sets of permuted isomers of the Q containing model heptapeptides. The first set contains the QAAAAAA sequence, and the second set involves of QYAGFLV sequence, where the position of the Q residue is changed from N- to C-terminal gradually for both peptide series. An intense loss of ammonia from the a7 ions followed by internal amino acid eliminations strongly supports forming the imine-amides structure via cyclization/rearrangement reaction for all studied a7 ions. This is in agreement with the pioneering study reported by Bythell et al. (2010, 10.1021/ja101556g). A novel rearrangement reaction is detected upon fragmentation of imine-amide structure, which yields a protonated C-terminal amidated hexapeptide excluding the Q residue. A possible fragmentation mechanism was proposed to form the protonated C-terminal amidated hexapeptide, assisted via nucleophilic attack of the side chain amide nitrogen of the Q residue on its N-protonated imine carbon atom of the rearranged imine-amide structure. Highlights: The gas-phase fragmentation reactions of a7 ions obtained from protonated model peptides containing glutamine residue were studied by ESI-MS/MS. A rearranged imine-amide structure is the predominant even for a7 ions. Novel rearrangement reaction is observed which forms a protonated C-terminal amidated hexapeptide excluding Q residue upon fragmentation of the imine-amide structure.Article Citation - WoS: 6Citation - Scopus: 6Therapeutic Potentials of Inhibition of Jumonji C Domain-Containing Demethylases in Acute Myeloid Leukemia(Aves, 2020) Koca, Duygu; Hastar, Nurcan; Engür, Selin; Kiraz, Yağmur; Ulu, Gizem Tuğçe; Çekdemir, Demet; Baran, YusufAcute myeloid leukemia (AML) is a complex disease affected by both genetic and epigenetic factors. Histone methylation and demethylation are types of epigenetic modification in chromatin remodeling and gene expression. Abnormal expression of histone demethylases is indicated in many types of cancer including AML. Although many commercial drugs are available to treat AML, an absolute cure has not been discovered yet. However, inhibition of demethylases could be a potential cure for AML. Methylstat is a chemical agent that inhibits the Jumonji C domain-containing demethylases.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.