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Publication Metadata only Beta-blocker timolol has important beneficial action on diabetes-induced kidney tissue damage by enhancing the activities of some antioxidant enzymes(Wiley-Blackwell, 2014) Gökturk, Hilal; Gök, Müslüm; Tuncay, Erkan; Can, Belgin; Turan, Belma; Ulusu, Nuriye Nuray; Faculty Member; School of Medicine; 6807N/APublication Open Access DNA repair by photolyases(Elsevier, 2019) Öztürk, Nuri; Department of Molecular Biology and Genetics; Department of Chemical and Biological Engineering; Kavaklı, İbrahim Halil; Gül, Şeref; Faculty Member; Department of Molecular Biology and Genetics; Department of Chemical and Biological Engineering; College of Sciences; Graduate School of Sciences and Engineering; 40319; N/APhotolyases belong to the cryptochrome/photolyase protein family (CPF) which perform different functions such as DNA repair, circadian photoreceptor, and transcriptional regulation. Photolyase is a flavoprotein that repairs UV-induced DNA damages of cyclobutane pyrimidine dimer (CPD) and pyrimidine-pyrimidone (6-4) photoproducts using blue-light as an energy source. This enzyme has two chromophores: flavin adenine dinucleotide (FAD) as a cofactor and a photoantenna such as methenyltetrahydrofolate (MTHF). The FAD is essential for catalysis of the DNA repair. The second chromophore absorbs photons from the blue light spectrum and transfers energy to FAD to increase the repair efficiency of the enzyme. Phylogenetic analysis in which amino acid sequences of several hundreds of CPF members are used suggests that they form more classes than we have considered so far. In this chapter, we discussed structure-functions and reaction mechanisms of different classes of photolyases.Publication Metadata only Embedding alternative conformations of proteins in protein–protein interaction networks(Humana Press inc, 2020) N/A; N/A; Department of Computer Engineering; Department of Chemical and Biological Engineering; Halakou, Farideh; Gürsoy, Attila; Keskin, Özlem; PhD Student; Faculty Member; Faculty Member; Department of Computer Engineering; Department of Chemical and Biological Engineering; Graduate School of Sciences and Engineering; College of Engineering; College of Engineering; N/A; 8745; 26605While many proteins act alone, the majority of them interact with others and form molecular complexes to undertake biological functions at both cellular and systems levels. Two proteins should have complementary shapes to physically connect to each other. As proteins are dynamic and changing their conformations, it is vital to track in which conformation a specific interaction can happen. Here, we present a step-by-step guide to embedding the protein alternative conformations in each protein–protein interaction in a systems level. All external tools/websites used in each step are explained, and some notes and suggestions are provided to clear any ambiguous point.Publication Open Access Exosomal delivery of therapeutic modulators through the blood-brain barrier; promise and pitfalls(BioMed Central, 2021) Eslami Abriz, Aysan; Zarebkohan, Amir; Rahbarghazi, Reza; Özdemir, Yasemin Gürsoy; Kaya, Mehmet; Sokullu, Emel; Heidarzadeh, Morteza; Faculty Member; Faculty Member; PhD Student; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; Graduate School of Health Sciences; 170592; 10486; 163024; N/ANowadays, a large population around the world, especially the elderly, suffers from neurological inflammatory and degenerative disorders/diseases. Current drug delivery strategies are facing different challenges because of the presence of the BBB, which limits the transport of various substances and cells to brain parenchyma. Additionally, the low rate of successful cell transplantation to the brain injury sites leads to efforts to find alternative therapies. Stem cell byproducts such as exosomes are touted as natural nano-drug carriers with 50-100 nm in diameter. These nano-sized particles could harbor and transfer a plethora of therapeutic agents and biological cargos to the brain. These nanoparticles would offer a solution to maintain paracrine cell-to-cell communications under healthy and inflammatory conditions. The main question is that the existence of the intact BBB could limit exosomal trafficking. Does BBB possess some molecular mechanisms that facilitate the exosomal delivery compared to the circulating cell? Although preliminary studies have shown that exosomes could cross the BBB, the exact molecular mechanism(s) beyond this phenomenon remains unclear. In this review, we tried to compile some facts about exosome delivery through the BBB and propose some mechanisms that regulate exosomal cross in pathological and physiological conditions.Publication Open Access Immature platelet fraction: is a novel early predictive marker for disease severity in patients with Covid-19 pneumonia?(De Gruyter, 2021) Taşdemir, Zeynep Atam; Paloğlu, Kerim Erhan; İncir, Said; Komesli, Zeynep; Baygül, Arzu Eden; Çaltı, Hatice Kant; Kapmaz, Mahir; Tekin, Süda; Kılıç, Alparslan; Dağel, Tuncay; Okan, Ayşe; Somay, Kayra; Akpınar, Timur Selçuk; Faculty Member; Doctor; Doctor; Faculty Member; School of Medicine; Koç University Hospital; N/A; N/A; 272290; N/A; N/A; 42146; N/A; N/A; N/A; N/A; N/AObjectives: in many diseases, immature platelet fraction (IPF%) is related to coagulopathy and poor outcome. This study aimed to investigate the predictive value of IPF% for the severity of pneumonia in patients with Coronavirus Disease 2019 (COVID-19). Methods: a total of 154 patients with COVID-19 infections were included. The patients were divided into two groups according to the severity of pneumonia (severe and nonsevere) regarding their oxygen demand. Results: given laboratory parameters, the median IPF% was significantly higher in the severe group (11.9 vs. 3.9%, p<0.001). Mean platelet volume (p<0.001), platelet-large cell ratio (p=0.001), platelet distribution width (p=0.001), D-Dimer (p<0.001), INR (p=0.003), and aPTT (p=0.007) were also found to be significantly higher in the severe group. Moreover, IPF (p=0.014, Odds ratio = 2.000, 95%CI: 1.149-3.482) was an independent predictor for the severity. The curve value from receiver operating characteristics was 0.879 (p<0.001, 95%CI: 0.784-0.943) for determining the severity of pneumonia. IPF% had a sensitivity and specificity value of 69.5 and 92.4% to detect the disease's severity. Conclusions: IPF% is an independent predictor for the severity of COVID-19 pneumonia. Assessment of IPF% may both help to early determine high-risk patients with COVID-19 and to alert the physicians. / Amaç: pek çok hastalıkta, immatür platelet fraksiyonu (%İPF), koagülopati ve kötü sonuçla ilişkilidir. Bu çalışma, Coronavirus Hastalığı 2019 (COVID-19) olan hastalarda pnömoni şiddeti için %İPF’nin prediktif değerini araştırmayı amaçladı. Yöntem: COVID-19 enfeksiyonu olan toplam 154 hasta dahil edildi. Hastalar, oksijen ihtiyaçları göz önüne alınarak pnömoni şiddetine göre (ağır ve ağır olmayan) iki gruba ayrıldı. Bulgular: laboratuvar parametrelerine bakıldığında, medyan İPF yüzdesi ağır grupta anlamlı olarak daha yüksekti (% 11.9?a karşı %3.9, p<0.001). Ortalama trombosit hacmi (p<0.001), trombosit-büyük hücre oranı (p=0.001), trombosit dağılım genişliği (p=0.001), D-Dimer (p<0.001),İNR (p=0.003) ve aPTT (p=0.007) ağır grupta anlamlı olarak daha yüksek bulundu. Ayrıca, İPF (p=0.014, Odds oranı = 2.000, %95 CI: 1.149-3.482) hastalık şiddeti için bağımsız bir öngördürücü olarak bulundu. Algılayıcı işletim eğrisinden gelen eğri değeri, pnömoni şiddetini belirlemek için 0.879 (p<0.001, % 95 CI: 0.784-0.943) idi. İPF, hastalığın şiddetini saptamak için %69.5?lik duyarlılık ve %92.4?lük özgüllük değerine sahipti. Sonuç: İPF, COVID-19 pnömonisinin şiddeti için bağımsız bir öngörücüdür. %İPF’nin değerlendirilmesi, hem COVID-19? lu yüksek riskli hastaları erken belirlemeye hem de hekimleri uyarmaya yardımcı olabilir.Publication Open Access Influence of the butylparaben administration on the oxidative stress metabolism of liver, kidney and spleen(De Gruyter, 2020) Barlas, Nurhayat; Öztaşçı, Burcu; Aydemir, Duygu; Ulusu, Nuriye Nuray; PhD Student; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; School of Medicine; N/A; 6807Objectives: butylparaben is widely used synthetic polymer as preservative in the food, pharmaceutical and cosmetic industries. Although butylparaben is metabolized in the detoxification organs including liver and kidney, some parts of it can retain and accumulate in the body. Parabens can impair developmental and reproductive health, though there is not any published data related with the influence of the butylparaben on the oxidative stress metabolism in the detoxification organs. Therefore, we aimed to evaluate antioxidant enzyme activities in the liver, kidney and spleen of butylparaben-treated rat. Methods: Prepubertal Wistar albino male rats were administered with 0, 100, 200, 400 mg/kg/day butylparaben for 28 days. After treatment, enzyme activities were evaluated as the biomarkers of the oxidative stress. Results: enzyme activities including glucose-phosphate dehydrogenase (G6PD), 6-phosphoglucanate dehydrogenase (6-PGD), glutathione reductase (GR), glutathione s-transferase (GST) and glutathione peroxidase (GPx) were impaired upon butylparaben treatment in the liver, kidney and spleen tissues. Conclusions: exposure to endocrine disruptors may affect enzyme activities of the detoxification organs and change the pentose phosphate glutathione (GSH) metabolisms. According to our data oxidative stress metabolism is impaired in the spleen, kidney and liver tissue upon butylparaben treatment that has been indicated first time in the literature.Publication Metadata only Molecular regulation of concomitant lower urinary tract symptoms and erectile dysfunction in pelvic ischemia(MDPI, 2022) Choi, Han-Pil; Azadzoi, Kazem M.; Tarcan, Tufan; Other; School of Medicine; 173289Aging correlates with greater incidence of lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) in the male population where the pathophysiological link remains elusive. The incidence of LUTS and ED correlates with the prevalence of vascular risk factors, implying potential role of arterial disorders in concomitant development of the two conditions. Human studies have revealed lower bladder and prostate blood flow in patients with LUTS suggesting that the severity of LUTS and ED correlates with the severity of vascular disorders. A close link between increased prostatic vascular resistance and greater incidence of LUTS and ED has been documented. Experimental models of atherosclerosis-induced chronic pelvic ischemia (CPI) showed increased contractile reactivity of prostatic and bladder tissues, impairment of penile erectile tissue relaxation, and simultaneous development of detrusor overactivity and ED. In the bladder, short-term ischemia caused overactive contractions while prolonged ischemia provoked degenerative responses and led to underactivity. CPI compromised structural integrity of the bladder, prostatic, and penile erectile tissues. Downstream molecular mechanisms appear to involve cellular stress and survival signaling, receptor modifications, upregulation of cytokines, and impairment of the nitric oxide pathway in cavernosal tissue. These observations may suggest pelvic ischemia as an important contributing factor in LUTS-associated ED. The aim of this narrative review is to discuss the current evidence on CPI as a possible etiologic mechanism underlying LUTS-associated ED.Publication Metadata only Purification and characterization of a type III photolyase from caulobacter crescentus(Amer Chemical Soc, 2008) Öztürk, Nuri; Kao, Ya-Ting; Selby, Christopher P.; Kavakli, I. Halil; Partch, Carrie L.; Zhong, Dongping; Sancar, Aziz; Department of Chemical and Biological Engineering; Kavaklı, İbrahim Halil; Faculty Member; Department of Chemical and Biological Engineering; College of Engineering; 40319The photolyase/cryptochrome family is a large family of flavoproteins that encompasses DNA repair proteins, photolyases, and cryptochromes that regulate blue-light-dependent growth and development in plants, and light-dependent and light-independent circadian clock setting in animals. Phylogenetic analysis has revealed a new class of the family, named type III photolyase, which cosegregates with plant cryptochromes. Here we describe the isolation and characterization of a type III photolyase from Caulobacter crescentus. Spectroscopic analysis shows that the enzyme contains both the methenyl tetrahydrofolate photoantenna and the FAD catalytic cofactor. Biochemical analysis shows that it is a bona fide photolyase that repairs cyclobutane pyrimidine dimers. Mutation of an active site Trp to Arg disrupts FAD binding with no measurable effect on MTHF binding. Using enzyme preparations that contain either both chromophores or only folate, we were able to determine the efficiency and rate of transfer of energy from MTHF to FAD.Publication Metadata only SYBR green dye-based probe-free SNP genotyping: Introduction of T-Plex real-time PCR assay(Elsevier, 2013) Etlik, Ozdal; Koksal, Vedat; Ocak, Zeynep; Baris, Saniye Tugba; Department of Molecular Biology and Genetics; Barış, İbrahim; Teaching Faculty; Department of Molecular Biology and Genetics; College of Sciences; 111629Single-nucleotide polymorphism (SNP) genotyping is widely used in genetic association studies to characterize genetic factors underlying inherited traits. Despite many recent advances in high-throughput SNP genotyping, inexpensive and flexible methods with reasonable throughput levels are still needed. Real-time PCR methods for discovering and genotyping SNPs are becoming increasingly important in various fields of biology. In this study, we introduce a new, single-tube strategy that combines the tetra-primer ARMS PCR assay, SYBR Green I-based real-time PCR, and melting-point analysis with primer design strategies to detect the SNP of interest. This assay, T-Plex real-time PCR, is based on the T. discrimination of the amplified allele-specific amplicons in a single tube. The specificity, sensitivity, and robustness of the assay were evaluated for common mutations in the FV, PII, MTHFR, and FGFR3 genes. We believe that T-Plex real-time PCR would be a useful alternative for either individual genotyping requests or large epidemiological studies.Publication Open Access The role of biotin metabolism in the COVID-19 infection(De Gruyter, 2020) Aydemir, Duygu; Ulusu, Nuriye Nuray; PhD Student; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; School of Medicine; N/A; 6807COVID-19 pandemic has become the major health problem in 2020 worldwide and no treatment or cure has been developed until now, however medical doctors use approved anti-viral drugs alone or in combination to treat patients infected by COVID-19. Thus, the outcome and the information of the applied treatments are changing daily basis. One of the changes in the COVID-19 patients has been depilation of the eyebrow and eyelashes. Biotin is a vital cofactor for biotin-dependent enzymes for fatty acids, amino acids, and glucose metabolism. It is known that, biotin deficiency may cause loss of hair, eyebrows and eyelashes. However, either COVID-19 infection or treatment against to cure this infection cause impairment in the biotin metabolism that should be further investigated to better understand possible mechanisms behind the COVID-19 infection and outcomes of the treatment approach to treat it.