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: 15Citation - Scopus: 13Cascade Therapy With Doxorubicin and Survivin-Targeted Tailored Nanoparticles: an Effective Alternative for Sensitization of Cancer Cells To Chemotherapy(Elsevier Ltd., 2019) Dağlıoğlu, Cenk; Kacı, Fatma NecmiyeChemotherapy frequently involves combination treatment protocols to maximize tumor cell killing. Unfortunately these intensive chemotherapeutic regimes, often show disappointing results due to the development of drug resistance and higher nonspecific toxicity on normal tissues. In cancer treatment, it is critically important to minimize toxicity while preserving efficacy. We have previously addressed this issue and proposed a nanoparticle-based combination therapy involving both a molecularly targeted therapy and chemotherapeutic agent for neutralizing antiapoptotic survivin (BIRC5) to potentiate the efficacy of doxorubicin (DOX). Although the particles exhibited strong anticancer effect on the lung carcinoma A549 and the cervical carcinoma HeLa cells, there were lower-level therapeutic outcomes on the colon carcinoma HCT-116, the leukemia Jurkat and the pancreatic carcinoma MIA PaCa-2 cells. Since targeted therapies are one of the key approaches for overcoming drug resistance, tailoring the treatment of cancer cells with distinct characteristics is necessary to improve the therapeutic outcome of cancer therapy and to minimize potential pharmacokinetic interactions of drugs. In the light of this issue, this study examined whether a cascade therapy with low-dose DOX and survivin-targeted tailored nanoparticles is more effective at sensitizing HCT-116, Jurkat and MIA PaCa-2 cancer cells to DOX-chemotherapy than simultaneous combination therapy. The results demonstrated that the sequential therapy with the protocol comprising addition of the nanoparticles after incubation of cells with DOX clearly advanced the therapeutic outcome of related cancer cells, whereas the reverse protocol resulted in a reduction or delay in apoptosis, emphasizing the critical importance of formulating synergistic drug combinations in cancer therapy.Article Citation - WoS: 15Citation - Scopus: 15Identification of Stable Qtls for Fiber Quality and Plant Structure in Upland Cotton (g. Hirsutum L.) Under Drought Stress(Elsevier Ltd., 2018) Akköse Baytar, Asena; Peynircioğlu, Ceng; Sezener, Volkan; Basal, Hüseyin; Frary, Anne; Frary, Amy; Doğanlar, SamiCotton is an economically important commodity for nearly fifty industries including the textile sector which is largely based on cotton fiber. Identification of markers linked to loci for fiber traits under drought stress may be particularly beneficial because such loci could provide the genetic adaptability needed to produce good fiber under water limitation. In the present study, 177 simple sequence repeat (SSR) markers were used to detect significant quantitative trait loci (QTLs) linked to 11 fiber quality and plant structure traits in a panel of 99 Upland cotton (Gossypium hirsutum L.) genotypes using GLM and MLM analysis. The fiber quality traits, including fiber length (FL), fiber fineness (FF), fiber strength (FS), fiber elasticity (FE), fiber uniformity (FU), spinning conversion index (SCI), earliness (EAR), 1st position boll retention (1st PBR), 2nd position boll retention (2nd PBR), total boll number (TBN) and plant height (PH), were tested under both well-watered and water-limited irrigations in two locations. At both locations, GLM identified a total of 74 and 70 QTLs under well-watered and water limited conditions, respectively, at p ≤ 0.005. MLM detected seven and 23 QTLs under well-watered and water-limited conditions, respectively. Of the identified QTLs, some QTLs were detected in both locations: three for well-watered and two for water-stress conditions. Moreover, a total of 19 QTLs were stable under both watering-regimes. The QTLs identified herein could be useful in the development of cotton cultivars that have adaptability to drought conditions worldwide.Article Citation - WoS: 8Citation - Scopus: 7Secreted Wnt Antagonists in Leukemia: a Road Yet To Be Paved(Elsevier Ltd., 2018) Pehlivan, Melek; Çalışkan, Ceyda; Yüce, Zeynep; Sercan, Hakkı OgünWnt signaling has been a topic of research for many years for its diverse and fundamental functions in physiological (such as embryogenesis, organogenesis, proliferation, tissue repair and cellular differentiation) and pathological (carcinogenesis, congenital/genetic diseases, and tissue degeneration) processes. Wnt signaling pathway aberrations are associated with both solid tumors and hematological malignancies. Unregulated Wnt signaling observed in malignancies may be due to a wide spectrum of abnormalities, from mutations in the genes of key players to epigenetic modifications of Wnt antagonists. Of these, Wnt antagonists are gaining significant attention for their potential of being targets for treatment and inhibition of Wnt signaling. In this review, we discuss and summarize the significance of Wnt signaling antagonists in the pathogenesis and treatment of hematological malignancies.Article Citation - WoS: 14Citation - Scopus: 16Transcriptomic Analysis of Boron Hyperaccumulation Mechanisms in Puccinellia Distans(Elsevier Ltd., 2018) Öztürk, Saniye Elvan; Göktay, Mehmet; Has, Canan; Babaoğlu, Mehmet; Allmer, Jens; Doğanlar, Sami; Frary, AnnePuccinellia distans, common alkali grass, is found throughout the world and can survive in soils with boron concentrations that are lethal for other plant species. Indeed, P. distans accumulates very high levels of this element. Despite these interesting features, very little research has been performed to elucidate the boron tolerance mechanism in this species. In this study, P. distans samples were treated for three weeks with normal (0.5 mg L−1) and elevated (500 mg L−1) boron levels in hydroponic solution. Expressed sequence tags (ESTs) derived from shoot tissue were analyzed by RNA sequencing to identify genes up and down-regulated under boron stress. In this way, 3312 differentially expressed transcripts were detected, 67.7% of which were up-regulated and 32.3% of which were down-regulated in boron-treated plants. To partially confirm the RNA sequencing results, 32 randomly selected transcripts were analyzed for their expression levels in boron-treated plants. The results agreed with the expected direction of change (up or down-regulation). A total of 1652 transcripts had homologs in A. thaliana and/or O. sativa and mapped to 1107 different proteins. Functional annotation of these proteins indicated that the boron tolerance and hyperaccumulation mechanisms of P. distans involve many transcriptomic changes including: alterations in the malate pathway, changes in cell wall components that may allow sequestration of excess boron without toxic effects, and increased expression of at least one putative boron transporter and two putative aquaporins. Elucidation of the boron accumulation mechanism is important in developing approaches for bioremediation of boron contaminated soils.Article Citation - WoS: 4Citation - Scopus: 4Sensitive and Specific Detection of Ligands Using Engineered Riboswitches(Elsevier Ltd., 2018) Morse, Daniel P.; Nevins, Colin E.; Aggrey-Fynn, Joana Efua; Bravo, Rick J.; Pfaeffle, Herman O.I.; Laney, Jess E.Riboswitches are RNA elements found in non-coding regions of messenger RNAs that regulate gene expression through a ligand-triggered conformational change. Riboswitches typically bind tightly and specifically to their ligands, so they have the potential to serve as highly effective sensors in vitro. In B. subtilis and other gram-positive bacteria, purine nucleotide synthesis is regulated by riboswitches that bind to guanine. We modified the xpt-pbuX guanine riboswitch for use in a fluorescence quenching assay that allowed us to specifically detect and quantify guanine in vitro. Using this assay, we reproducibly detected as little as 5 nM guanine. We then produced sensors for 2′-deoxyguanosine and cyclic diguanylate (c-diGMP) by appending the P1 stem of the guanine riboswitch to the ligand-binding domains of a 2′-deoxyguanosine riboswitch and a c-diGMP riboswitch. These hybrid sensors could detect 15 nM 2′-deoxyguanosine and 3 nM c-diGMP, respectively. Each sensor retained the ligand specificity of its corresponding natural riboswitch. In order to extend the utility of our approach, we developed a strategy for the in vitro selection of sensors with novel ligand specificity. Here we report a proof-of-principle experiment that demonstrated the feasibility of our selection strategy.Book Part Citation - WoS: 30Citation - Scopus: 41Nanocarriers for Plant-Derived Natural Compounds(Elsevier Ltd., 2017) Bayraktar, Oğuz; Erdoğan, İpek; Köse, Merve D.; Kalmaz, GülcanNatural products constitute a large fraction in drug discovery processes. The term includes compounds from plants, microorganisms, and animals. Most of the natural products are secondary metabolites derived from plants, which are low in amounts and difficult to isolate. Another issue is the preservation of their bioactivity during process and storage as well as degradation in the gastrointestinal system before reaching circulation. Advances in nanotechnology offer nanoparticles, nanocapsules, and conjugates, which are devoted to site-specific, time-controlled delivery of bioactive agents. Nanoencapsulated systems have the advantage of high drug encapsulation efficiency because of optimized drug solubility in the core, low polymer content compared to other nanoparticulated systems such as nanospheres, drug polymeric shell protection against degradation factors, and the reduction of tissue irritation caused by the polymeric shell. This chapter will discuss nanoencapsulation methods and advances in carrier systems for plant-derived natural compounds.Data Paper Citation - WoS: 3Citation - Scopus: 3Small Rna Data Set That Includes Trna-Derived Fragments From Jurkat Cells Treated With Camptothecin(Elsevier Ltd., 2018) Coşacak, Mehmet İlyas; Erdoğan, İpek; Nalbant, Ayten; Akgül, BünyaminIn this article, we report a small RNA data set obtained from human T cell acute leukemia Jurkat cells, which were treated with the universal apoptotic agent camptothecin. Based on the Annexin-V labeling pattern, we sorted two Jurkat subpopulations in treated cells: one that is sensitive to the drug and the other being relatively more resistant. We report new original data that include the frequency of tRNA-derived fragments (tRF) in drug-sensitive and resistant cells. We also present partially analyzed data to show the origin of reads on tRNAs as well as the borders of the fragments. We believe that this data can benefit the science community working in the field of tRF and/or apoptosis.Article Citation - WoS: 1Cellular Distribution of Invadopodia Is Regulated by Nanometer Scale Surface Protein Patterns(Elsevier Ltd., 2017) Batı Ayaz, Gizem; Can, Ali; Pesen Okvur, DevrimInvadopodia are proteolytic structures formed by cancer cells. It is not known whether their cellular distribution can be regulated by the organization of the extracellular matrix or the organization of the golgi complex or whether they have an adhesion requirement. Here, we used electron beam lithography to fabricate fibronectin (FN) nanodots with isotropic and gradient micrometer scale spacings on K-casein and laminin backgrounds. Investigating cancer cells cultured on protein nanopatterns, we showed that (i) presence of FN nanodots on a K-casein background decreased percent of cells with neutral invadopodia polarization compared to FN control surfaces; (ii) presence of a gradient of FN nanodots on a K-casein background increased percent of cells with negative invadopodia polarization compared to FN control surfaces; (iii) polarization of the golgi complex was similar to that of invadopodia in agreement with a spatial link; (iv) local adhesion did not necessarily appear to be a prerequisite for invadopodia formation.Book Part Citation - WoS: 10Citation - Scopus: 16Plant-Microbe Interactions in Phytoremediation(Elsevier Ltd., 2014) Özyiğit, İbrahim İlker; Doğan, İlhanOur atmosphere, water resources and soil are becoming increasingly contaminated with inorganic and organic compounds as a result of anthropogenic-driven inputs, mainly from industry, mining, motorized traffic, agriculture, logging and military actions. Alleviation and prevention of environmental pollution can be achieved by utilization of plants and their associated microbes. Recent advances in plant-microbe interaction research revealed that plants are able to shape their rhizosphere microbiome through active secretion of substrates that are known to vary between plant species. Soil-borne microorganisms such as actinobacteria, algae, protozoa and different types of bacteria having different capabilities of functional activities can vary extensively in soils and occur in associations in the rhizosphere of plants. Microbial associations are known to affect mobility and availability of substances to the plant through the release of chelating agents, acidification, phosphate solubilization and redox changes and exudates derived from the plant can help to stimulate the survival and action of these microorganisms. A broad knowledge about the mechanisms in plants for the uptake, translocation, storage, and detoxification of contaminants, and interactions between plants and microorganisms are critical in developing technologies and best management practices for environmental clean-up. A comprehensive understanding of interactions between plants and rhizospheric microorganisms in the rhizosphere and plant-based processes will provide new opportunities to develop more efficient plants and better management practices for removal of contaminants. This chapter reviews plant-microbe interactions in phytoremediation with particular reference to the microbial dynamics in the rhizosphere of plants growing on contaminated soils.Article Citation - WoS: 7Citation - Scopus: 8Protein Based Flushing Related Blood Urea Nitrogen Effects on Ovarian Response, Embryo Recovery and Embryo Quality in Superovulated Ewes(Elsevier Ltd., 2017) Tur, İrfan; Dinç, Dursun Ali; Semacan, AhmetThe present study is the first report that evaluates effects of nutritional effects of flushing with differing diet crude protein ratios on blood urea nitrogen (BUN) levels, related some reproductive parameters and embryo quality in ewe. During mating season, before synchronization protocol ewes were fed on alfalfa hay and additive concentrate feeding as flushing. Intra vaginal FGA containing sponges applied for 12 days for the purpose of synchronization and pFSH was administered by 8 declining doses for the purpose of superovulation. Uterus was flushed in the morning of the seventh day of mating and embryos were collected surgically. Collected embryos were qualified according to IETS criterion. There is no dependency found between BUN values measured at different days and at different diet crude protein concentrations. An increase in uterine pH levels due to increasing protein amounts was observed but this increase was not significant among groups. Ovarian function was evaluated by ovarian responses (CL + large follicle) showed difference between groups (p < 0.05) and the lowest protein intake group gave highest ovarian response. In addition, embryo recovery rates revealed difference between groups (p < 0.05) and it was observed that the lowest ovarian response group showed the highest rates of embryo recovery. It is concluded that, in some Anatolian native sheep breeds, the application of diet flushing with different crude protein concentrates influence ovarian responses and embryo recovery rates but has no effect on BUN levels; uterus physiology or embryonic quality.