Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
Permanent URI for this collectionhttps://hdl.handle.net/11147/9
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Conference Object A Carbohydrate sulfotransferase mutant zebrafish shows importance of keratan sulfate proteoglycan in skeletal structure(Mary Ann Liebert, 2024) Basol, M.; Ersoz, E.; Özaktaş, Helin; Cakan-Akdogan, G.Conference Object Investigation of the role of Wnt/β-catenin signaling in development of Alzheimer's disease in a zebrafish model of mmyloid-β toxicity(Wiley, 2024) Nazlı, Dilek; Ipekgil, D.; Poyraz, Y. K.; Catak, B.; Sahin, E. Turhanlar; Özhan, GüneşThe Wnt/β-catenin signaling pathway, an evolutionarily conserved and pivotal pathway associated with synapse formation in adulthood, plays a crucial role in Alzheimer's disease (AD). AD, marked by various pathologies, is primarily linked to the accumulation of extracellular beta-amyloid plaques. The interplay between this accumulation and disruptions in the Wnt/β-catenin signaling pathway triggers synaptic degeneration, resulting in synaptic dysfunction and AD progression. In this study, we modeled AD induced by the Aβ42 peptide using adult transgenic (6XTCF) zebrafish. To establish the zebrafish AD model, we employed cerebroventricular microinjection (CVMI) with the Aβ42 peptide. Fish, anesthetized prior to CVMI, were positioned on a stable platform, and the Aβ42 peptide was injected into the telencephalon region of the brain by a capillary needle. Brain samples were collected on 1, 3, 4, 7, and 14 days post-CVMI (dpi) to analyze changes in Aβ42 peptide accumulation, the immune system response, synaptic degeneration, apoptosis, and the expression of genes related to proliferation using qPCR and immunofluorescent staining. To examine the role of the Wnt/β-catenin signaling pathway in the molecular mechanism of AD development, fish exhibiting high levels of regeneration on days 7 and 14 were treated with the IWR-1 drug, which inhibits the Wnt/β-catenin signaling by stabilizing the Axin2 protein, thereby suppressing the regenerative response. Our results revealed that the AD model manifested on 3dpi, with the regenerative response reaching its peak on 7dpi and 14dpi. Treatment with IWR-1 resulted in increased Aβ42 accumulation, accelerated synaptic degeneration, and elevated cell deaths in fish where the Wnt signaling pathway was inhibited. In conclusion, our adult zebrafish AD model is poised to elucidate the molecular mechanisms connecting the Wnt signaling pathway and AD, thereby contributing to the development of alternative therapeutic approaches for AD patients.Conference Object Elimination of the B4galnt1 Gene Normalizes Lifespan and Prevents Pathology in Tay-Sachs Disease Mice(Elsevier, 2023) Seyrantepe, VolkanTay-Sachs disease is a neurodegenerative lysosomal storage disorder caused by mutations in the Hexa gene, which encodes the alpha subunit of lysosomal ß-hexaminidase A (HEXA). HEXA is responsible for the conversion of GM2 to GM3, therefore the deficiency leads to the accumulation of GM2 in the lysosomes, neurodegeneration, and eventual death. Currently, there is no efficient therapy for the disease yet.Conference Object Citation - WoS: 1Differential Susceptibility To Senescence in Cart Cells Based on Co-Stimulatory Signaling(American Society of Hematology, 2022) Can, İsmail; Sakemura, Reona Leo; Manriquez-Roman, Claudia; Sirpilla, Olivia; Stewart, Carli M.; Yun, Kun; Cox, Michelle J.; Ekiz, AtakanCD19-directed chimeric antigen receptor (CART19) cells have emerged as a potentially curative immunotherapy in a subset of patients with hematological malignancies. While initial responses are impressive, the majority of responsive patients relapse within a year. Recent studies suggest that CART cells are susceptible to states of dysfunction. We aimed to study the development of T cell senescence in CART cells using similar constructs to the FDA-approved therapies, CART19-BBζ and CART19-28ζ, to determine the impact of co-stimulatory domains on CART cell senescence. We developed an in vitro model for repeated CART cell activation followed by rest to study the development of senescence and its impact on effector T cell functions. We examined CART cell immunophenotype, cell cycle regulators, and transcriptomic profile on days 0 (T cell), D8 (standard CART cell), 15 (after one activation cycle) and 22 (after two activation cycles).Conference Object Detection and Restoration Pipeline for Phase Contrast Microscopy Time Series Images(IEEE, 2022) Iheme, Leonardo O.; Uçar, Mahmut; Önal, Sevgi; Yalçın Özuysal, Özden; Pesen Okvur, Devrim; Töreyin, Behçet U.; Ünay, DevrimWe propose a pre-processing pipeline for the de-tection and restoration of distorted frames in phase-contrast microscopy time-series images. The analysis is based on the average intensity values of the frames within any given time- series image. The extent of the correction of intensity variation in frames is determined by the normalization of the difference between the current frame's average intensity and the median of average intensity of all frames. Our restoration algorithm preserves regional trans-passing pixels, does not cause new distortions, and increases the histogram similarity between the distorted and non-distorted frames. The algorithm was validated on 15,395 time-series image frames from 27 experiments and the results were found to be visually and quantitatively accurate.Conference Object Peptıde Targeted Core Cross-lınked Mıcelles For Dox Delıvery To Her2 Expressıng Cancer Cells(Mary Ann Liebert, 2022) Bayram, Nazende Nur; Ulu, Gizem Tuğçe; Gürdap, Seda; İşoğlu, İsmail Alper; Baran, Yusuf; Dinçer İşoğlu, SevilIn this study, we prepared a novel targeted and extra stable micellar nanocarrier that can facilitate intracellular drug release. First, ((N-3-sulfopropyl-N, N-dimethylammonium)ethyl methacrylate was synthesized by RAFT polymerization, and it was followed by copolymerization of macroCTA with AEM in the presence of an aciddegradable cross-linker. Then, a peptide estimated by phage display for HER-2 recognition was incorporated into these core cross-linked micelles with carbodiimide reaction.Conference Object Citation - WoS: 3Citation - Scopus: 4Deep Learning Based Segmentation Pipeline for Label-Free Phase-Contrast Microscopy Images(IEEE, 2020) Ayanzadeh, Aydın; Yalçın Özuysal, Özden; Okvur, Devrim Pesen; Önal, Sevgi; Töreyin, Behçet Uğur; Ünay, DevrimThe segmentation of cells is necessary for biologists in the morphological statistics for quantitative and qualitative analysis in Phase-contrast Microscopy (PCM) images. In this paper, we address the cell segmentation problem in PCM images. Deep Neural Networks (DNNs) commonly is initialized with weights from a network pre-trained on a large annotated data set like ImageNet have superior performance than those trained from scratch on a small dataset. Here, we demonstrate how encoder-decoder type architectures such as U-Net and Feature Pyramid Network (FPN) can be improved by an alternative encoder which pre-trained on the ImageNet dataset. In particular, our experimental results confirm that the image descriptors from ResNet-18 are highly effective in accurate prediction of the cell boundary and have higher Intersection over Union (IoU) in comparison to the classical U-Net and require fewer training epochs.Conference Object Citation - Scopus: 2Yara İyileşmesi Mikroskopi Görüntü Serilerinin Otomatik Analizi - Bir Ön-çalışma(IEEE, 2020) Mayalı, Berkay; Şaylığ, Orkun; Yalçın Özuysal, Özden; Pesen Okvur, Devrim; Töreyin, Behçet Uğur; Ünay, DevrimCollective cell analysis from microscopy image series is important for wound healing research. Computer-based automation of such analyses may help in rapid acquisition of reliable and reproducible results. In this study phase -contrast optical microscopy image series of an in-vitro wound healing essay is manually delineated by two experts and its analysis is realized, traditional image processing and deep learning based approaches for automated segmentation of wound area are developed and their perlOrmance comparisons are carried out.Conference Object Citation - Scopus: 1A Preliminary Study on Cell Motility Analysis From Phase-Contrast Microscopy Image Series(IEEE, 2020) Kayan, Emre; Kavuşan, Tarık; Önal, Sevgi; Pesen Okvur, Devrim; Yalçın Özuysal, Özden; Töreyin, Behçet Uğur; Ünay, DevrimAnalyses of morphology, polarity, and motility of cells is important for cell biology research such as metastatic and invasive capacity of cells, wound healing, and embryonic development. Automation of such analyses using image series of phase-contrast optical microscopy, which allows label-free imaging of live cells in their living environment, is a need. With this purpose, in this study image series of a cell motility experiment is manually annotated, and an automation algorithm realizing motion and shape analyses of cells using the annotated data is developed. In addition, due to the low number of annotated data at hand, a U-Net based solution is devised for automated segmentation of the cells and its performance is evaluated.Conference Object Citation - Scopus: 1Magnetic Levitation-Based Adipose Tissue Engineering Using Horizontal Magnet Deployment(IEEE, 2020) Sarıgil, Öykü; Tekin, Hüseyin Cumhur; Anıl İnevi, Müge; Anıl İnevi, Müge; Yılmaz, Esra; Sarıgil, Öykü; Özçelik, Özge; Meşe Özçivici, Gülistan; Meşe, Gülistan; Meşe Özçivici, Gülistan; Tekin, H. CumhurMagnetic levitation is a promising technique for tissue engineering with contact- and label-free approach. Levitation-based biofabrication systems emerge as a simple, rapid and versatile alternative to traditional tissue culture systems, since biofabrication specs can easily be tailored via magnet shape and configuration. This study aims at possible magnetic levitation systems for culture of adipose tissue cells. In this study, we performed two different magnet configurations, vertical and horizontal deployment, in an effort to be utilized in adipose tissue engineering.