Research Outputs

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    Publication
    Alteration of cell motility dynamics through collagen fiber density in photopolymerized polyethylene glycol hydrogels
    (Elsevier, 2020) Bayraktar, Halil; N/A; Akalın, Özge Begüm; Master Student; Graduate School of Sciences and Engineering; N/A
    Polyethylene glycol (PEG) hydrogels that have natural fibers mimicking extracellular matrix can be used as a model to understand the role of substrate properties on cell growth and migration. Due to the dependence of cell movement to adhesion, characterization of motility is needed to prepare biocompatible substrates. We demonstrated a method to encapsulate collagen into PEG hydrogel crosslinked via photopolymerization and studied the effect of fiber density on motility dynamics. Porous hydrogel immersed into collagen solution was coated with fibers after neutralizing solution. We provided a detailed study of cell instantaneous/average speed, total displacement, persistence and angular displacement. We found that cells demonstrated a biphasic motility where a maximum speed of 17.4 mu m/h with a total distance of 215 mu m and persistence of 0.43 were obtained at 12 mg/ml collagen. High occurrence of low angular displacement observed at intermediate fiber density suggests that cells tend to move forward along hydrogels. Increased anisotropy at low density was an indication of forward and backward movement. Finally, matrix deformation was determined in the absence of fluorescent beads by tracking fiber displacement at subpixel resolution. Our findings establish a method for preparation of collagen coated hydrogels and provide an insight into cell motility dynamics.
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    PublicationOpen Access
    An efficient framework to identify key miRNA-mRNA regulatory modules in cancer
    (Oxford University Press (OUP), 2020) N/A; Department of Industrial Engineering; Mokhtaridoost, Milad; Gönen, Mehmet; Faculty Member; Department of Industrial Engineering; Graduate School of Sciences and Engineering; College of Engineering; School of Medicine
    Motivation: micro-RNAs (miRNAs) are known as the important components of RNA silencing and post-transcriptional gene regulation, and they interact with messenger RNAs (mRNAs) either by degradation or by translational repression. miRNA alterations have a significant impact on the formation and progression of human cancers. Accordingly, it is important to establish computational methods with high predictive performance to identify cancer-specific miRNA-mRNA regulatory modules. Results: we presented a two-step framework to model miRNA-mRNA relationships and identify cancer-specific modules between miRNAs and mRNAs from their matched expression profiles of more than 9000 primary tumors. We first estimated the regulatory matrix between miRNA and mRNA expression profiles by solving multiple linear programming problems. We then formulated a unified regularized factor regression (RFR) model that simultaneously estimates the effective number of modules (i.e. latent factors) and extracts modules by decomposing regulatory matrix into two low-rank matrices. Our RFR model groups correlated miRNAs together and correlated mRNAs together, and also controls sparsity levels of both matrices. These attributes lead to interpretable results with high predictive performance. We applied our method on a very comprehensive data collection by including 32 TCGA cancer types. To find the biological relevance of our approach, we performed functional gene set enrichment and survival analyses. A large portion of the identified modules are significantly enriched in Hallmark, PID and KEGG pathways/gene sets. To validate the identified modules, we also performed literature validation as well as validation using experimentally supportedmiRTarBase database.
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    PublicationOpen Access
    Bidirectional optical neuromodulation using capacitive charge-transfer
    (The Optical Society (OSA) Publishing, 2020) Department of Electrical and Electronics Engineering; N/A; Department of Chemical and Biological Engineering; Department of Molecular Biology and Genetics; Melikov, Rustamzhon; Srivastava, Shashi Bhushan; Karatüm, Onuralp; Nizamoğlu, Sedat; Doğru-Yüksel, Itır Bakış; Dikbaş, Uğur Meriç; Kavaklı, İbrahim Halil; PhD Student; Researcher; PhD Student; Faculty Member; Master Student; Faculty Member; Department of Electrical and Electronics Engineering; Department of Chemical and Biological Engineering; Department of Molecular Biology and Genetics; Graduate School of Sciences and Engineering; College of Engineering; College of Sciences; N/A; N/A; N/A; 130295; N/A; N/A; 40319
    Artificial control of neural activity allows for understanding complex neural networks and improving therapy of neurological disorders. Here, we demonstrate that utilization of photovoltaic biointerfaces combined with light waveform shaping can generate safe capacitive currents for bidirectional modulation of neurons. The differential photoresponse of the biointerface due to double layer capacitance facilitates the direction control of capacitive currents depending on the slope of light intensity. Moreover, the strength of capacitive currents is controlled by changing the rise and fall time slope of light intensity. This approach allows for high-level control of the hyperpolarization and depolarization of membrane potential at single-cell level. Our results pave the way toward advanced bioelectronic functionalities for wireless and safe control of neural activity.
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    Chitosan in cancer therapy: a dual role as a therapeutic agent and drug delivery system
    (Walter de Gruyter Gmbh, 2024) Atmaca, Harika; Ilhan, Suleyman; N/A; Oğuz, Ferdi; Graduate School of Health Sciences
    Although chemotherapy is still the most preferred treatment for cancer, most chemotherapeutic agents target both cancer cells and healthy cells and cause serious side effects due to high toxicity. Improved drug delivery systems (DDSs), which enhance the efficacy of current chemotherapeutic drugs while reducing their toxicity, offer potential solutions to these challenges. Chitosan (CS) and its derivatives are biopolymers with biodegradable, biocompatible, and low-toxicity properties, and their structure allows for convenient chemical and mechanical modifications. In its role as a therapeutic agent, CS can impede the proliferation of tumor cells through the inhibition of angiogenesis and metastasis, as well as by triggering apoptosis. CS and its derivatives are also frequently preferred as DDSs due to their properties such as high drug-carrying capacity, polycationic structure, long-term circulation, and direct targeting of cancer cells. Various therapeutic agents linked to CS and its derivatives demonstrate potent anticancer effects with advantages such as reduced side effects compared to the original drugs, owing to factors like targeted distribution within cancer tissues and sustained release. This review emphasizes the utilization of CS and its derivatives, both as therapeutic agents and as carriers for established chemotherapeutic drugs.
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    Cornerstones of biochemistry in stamps
    (Walter De Gruyter Gmbh, 2016) N/A; Ulusu, Nuriye Nuray; Faculty Member; School of Medicine; 6807
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    COVID-19 may enhance risk of thrombosis and hemolysis in the G6PD deficient patients
    (Taylor & Francis Inc, 2021) Dağlıoğlu, Gülçin; Candevir, Aslıhan; Kurtaran, Behice; Bozdoğan, Sevcan Tan; İnal, Tamer Cevat; N/A; 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; 6807
    COVID-19 has become a major public health problem since December, 2019 and no highly effective drug has been found until now. Numbers of infected people and deaths by COVID-19 are increasing every day worldwide, therefore self-isolation and protection are highly recommended to prevent the spread of the virus and especially to protect major risk groups such as the elderly population and people with comorbidities including diabetes, hypertension, cancer, cardiovascular diseases and metabolic syndrome. on the other hand, young people without any secondary disease have died by COVID-19 as well. In this study we compared two male patients infected by COVID-19 at the same age and one of them was diagnosed with G6PD deficiency. Both COVID-19and G6PD deficiency enhance the risk of hemolysis and thrombosis. Serum biochemistry, hemogram and immunological parameters showed that risk of hemolysis and thrombosis may increase in the G6PD deficient patient infected by COVID-19.
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    PublicationOpen Access
    Curious cases of the enzymes
    (De Gruyter Open, 2015) N/A; Ulusu, Nuriye Nuray; Faculty Member; School of Medicine; 6807
    Life as we know it heavily relies on biological catalysis, in fact, in a very nonromantic version of it, life could be considered as a series of chemical reactions, regulated by the guarding principles of thermodynamics. In ancient times, a beating heart was a good sign of vitality, however, to me, it is actually the presence of active enzymes that counts. Though we do not usually pay attention, the history of enzymology is as old as humanity itself, and dates back to the ancient times. This paper is dedicated to these early moments of this remarkable science that touched our lives in the past and will make life a lot more efficient for humanity in the future. There was almost always a delicate, fundamentally essential relationship between mankind and the enzymes. Challenged by a very alien and hostile Nature full of predators, prehistoric men soon discovered the medicinal properties of the plants, through trial and error. In fact, they accidently discovered the enzyme inhibitors and thus, in crude terms, kindled a sparkling area of research. These plant-derivatives that acted as enzyme inhibitors helped prehistoric men in their pursuit of survival and protection from predators; in hunting and fishing. Later in history, while the underlying purposes of survival and increasing the quality of life stayed intact, the ways and means of enzymology experienced a massive transformation, as the 'trial and error' methodology of the ancients is now replaced with rational scientific theories.
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    PublicationOpen Access
    Effects of the endocrine disrupting chemical, DEHP, on the mitochondrial metabolism of the detoxification organs
    (Wiley, 2019) N/A; N/A; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); Graduate School of Health Sciences; School of Medicine
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    PublicationOpen Access
    Effects of timolol treatment on pancreatic antioxidant enzymes in streptozotocin-induced diabetic rats: an experimental and computational study
    (Sciendo, 2019) Gök, Müslüm; Turan, Belma; N/A; Department of Chemical and Biological Engineering; Ulusu, Nuriye Nuray; Erman, Burak; Faculty Member; Faculty Member; Department of Chemical and Biological Engineering; School of Medicine; College of Engineering; 6807; 179997
    Background: the study aimed to investigate whether timolol-treatment has a beneficial effect on pentose phosphate pathway enzyme activities such as glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGDH) enzyme activities and cAMP level in streptozotocin-induced diabetic rats in pancreatic tissues. Methods: diabetes was induced by streptozotocin (STZ) in 3-month old male Wistar rats. The diabetic rats were treated with timolol (5 mg/kg body weight, for 12 weeks) while the control group received saline. Enzyme activities were determined in pancreas tissue. To support our results, we performed in silico calculations, using Protein Data Bank structures. Results: timolol treatment of STZ-induced diabetic rats had no noteworthy effect on high blood-glucose levels. However, this treatment induced activities of G6PD and 6PGDH in diabetic rats. Timolol treatment significantly increased cAMP level in diabetic pancreatic tissue. We found that timolol cannot bind strongly to either G6PD or 6PGD, but there is a relatively higher binding affinity to adenylyl cyclase, responsible for cAMP production, serving as a regulatory signal via specific cAMP-binding proteins. Conclusions: our data point out that timolol treatment has beneficial effects on the antioxidant defence mechanism enzymes in the pancreas of STZ-induced diabetic rats. / Uvod: cilj istrazivanja je bio da se utvrdi da li tretman timololom ima pozitivan efekat na aktivnosti enzima pentoze fosfata, kao sto su aktivnosti glukoze-6-fosfat dehidrogenaze (G6PD), enzimske aktivnosti 6-fosfoglukonat dehidrogenaze i cAMP nivo u tkivu pankreasa kod pacova kojima je dijabetes izazvan streptozotocionom. Metode: dijabetes je izazvan streptozotocionom (STZ) kod tromesecnih muzjaka vistar pacova. Pacovi sa dijabetesom su tretirani timololom (5 mg/kg telesne tezine tokom 12 nedelja), dok je kontrolna grupa primila fizioloski rastvor. Enzimske aktivnosti su utvrivane u tkivu pankreasa. Da bismo potkrepili nase rezultate, sproveli smo in silico racunanja koristeci strukture Proteinske baze podataka. Rezultati: tretman timololom na pacovima kojima je dijabetes izazvan putem STZ-a nije imao znacajan uticaj na visoke nivoe glukoze u krvi. Medutim, kod takvih pacova ovaj tretman je indukovao aktivnosti G6PD i 6PGDH. Lecenje timololom znacajno je povecalo nivo cAMP-a u dijabeticnom tkivu pankreasa. Utvrdili smo da se timolol ne moze snazno vezati ni za G6PD, ni za 6PGD, ali da postoji relativno veci afinitet vezivanja za adenilil ciklazu, odgovornu za proizvodnju cAMP, koja sluzi kao regulatorni signal putem odredenih cAMP vezivnih proteina. Zakljucak: nasi podaci ukazuju da tretman timololom ima pozitivne efekte na antioksidantne enzime od brambenog sistema u pankreasu pacova sa dijebetesom izazvanim putem STZ-a.
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    PublicationOpen Access
    European recommendations integrating genetic testing into multidisciplinary management of sudden cardiac death
    (Nature Publishing Group (NPG), 2019) Fellmann, Florence; van El, Carla G.; Charron, Philippe; Michaud, Katarzyna; Howard, Heidi C.; Boers, Sarah N.; Clarke, Angus J.; Duguet, Anne-Marie; Forzano, Francesca; Kauferstein, Silke; Lucassen, Anneke; Mendes, Alvaro; Patch, Christine; Radojkovic, Dragica; Rial-Sebbag, Emmanuelle; Sheppard, Mary N.; Tasse, Anne-Marie; Temel, Şehime G.; Sajantila, Antti; Basso, Cristina; Wilde, Arthur A. M.; Cornel, Martina C.; Benjamin, Caroline; Borry, Pascal; Clarke, Angus; Cordier, Christophe; Cornel, Martina; European Society of Human Genetics; European Council of Legal Medicine; European Society of Cardiology working group; European Reference Network for rare, low prevalence and complex diseases of the heart (ERN GUARD-Heart); Association for European Cardiovascular Pathology; N/A; Kayserili, Hülya; Faculty Member; School of Medicine; 7945
    Sudden cardiac death (SCD) accounts for 10-20% of total mortality, i.e., one in five individuals will eventually die suddenly. Given the substantial genetic component of SCD in younger cases, postmortem genetic testing may be particularly useful in elucidating etiological factors in the cause of death in this subset. The identification of genes responsible for inherited cardiac diseases have led to the organization of cardiogenetic consultations in many countries worldwide. Expert recommendations are available, emphasizing the importance of genetic testing and appropriate information provision of affected individuals, as well as their relatives. However, the context of postmortem genetic testing raises some particular ethical, legal, and practical (including economic or financial) challenges. The Public and Professional Policy Committee of the European Society of Human Genetics (ESHG), together with international experts, developed recommendations on management of SCD after a workshop sponsored by the Brocher Foundation and ESHG in November 2016. These recommendations have been endorsed by the ESHG Board, the European Council of Legal Medicine, the European Society of Cardiology working group on myocardial and pericardial diseases, the ERN GUARD-HEART, and the Association for European Cardiovascular Pathology. They emphasize the importance of increasing the proportion of both medical and medicolegal autopsies and educating the professionals. Multidisciplinary collaboration is of utmost importance. Public funding should be allocated to reach these goals and allow public health evaluation.