30 results on '"Kerman, Bilal Ersen"'
Search Results
2. Cholesterol accumulation promotes ABCA1 degradation in astrocytes via Caveolin‐1 mediated endocytosis in ApoE4
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Wang, Shaowei, primary, Li, Boyang, additional, Kerman, Bilal Ersen, additional, Sun, Yi, additional, Bennett, David A. A, additional, Arvanitakis, Zoe, additional, Remaley, Alan T, additional, and Yassine, Hussein N., additional
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- 2023
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3. Manipulation of Dietary DHA does not Alter DHA Brain Uptake Kinetics in Mice Despite Changing Brain and Plasma DHA Levelsvs
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Duro, Marlon Vincent V., primary, Van Valkenburgh, Juno S., additional, Abdullah, Laila, additional, Ingles, Diana E., additional, Cai, Zhiheng, additional, Kerman, Bilal Ersen, additional, Wang, Shaowei, additional, Jacobs, Russell E., additional, Sta. Maria, Naomi, additional, Zanderigo, Francesca, additional, Croteau, Etienne, additional, Cunnane, Stephen, additional, Rapoport, Stanley I., additional, Chen, Kai, additional, and Yassine, Hussein N., additional
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- 2023
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4. A multi-spectral myelin annotation tool for machine learning based myelin quantification
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Çapar, Abdulkerim, primary, Çimen, Sibel, additional, Aladağ, Zeynep, additional, Ekinci, Dursun Ali, additional, Ayten, Umut Engin, additional, Kerman, Bilal Ersen, additional, and Töreyin, Behçet Uğur, additional
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- 2023
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5. Combined segmentation and classification-based approach to automated analysis of biomedical signals obtained from calcium imaging
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Dursun, Gizem, primary, Bijelić, Dunja, additional, Ayşit, Neşe, additional, Kurt Vatandaşlar, Burcu, additional, Radenović, Lidija, additional, Çapar, Abdulkerim, additional, Kerman, Bilal Ersen, additional, Andjus, Pavle R., additional, Korenić, Andrej, additional, and Özkaya, Ufuk, additional
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- 2023
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6. Two phases of macrophages: Inducing maturation and death of oligodendrocytes in vitro co-culture
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Aydınlı, Fatmagül İlayda, primary, Er, Sezgin, additional, and Kerman, Bilal Ersen, additional
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- 2022
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7. Multiple Sclerosis Biomarker Candidates Revealed by Cell-Type-Specific Interactome Analysis
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Yurduseven, Kübra, primary, Babal, Yigit Koray, additional, Celik, Esref, additional, Kerman, Bilal Ersen, additional, and Kurnaz, Işıl Aksan, additional
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- 2022
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8. A multi-spectral myelin annotation tool for machine learning based myelin quantification
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Çapar, Abdulkerim, primary, Çimen, Sibel, additional, Aladağ, Zeynep, additional, Ekinci, Dursun Ali, additional, Ayten, Umut Engin, additional, Kerman, Bilal Ersen, additional, and Töreyin, Behçet Uğur, additional
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- 2022
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9. A multi-spectral myelin annotation tool for machine learning based myelin quantification [version 1; peer review: 1 not approved]
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Çapar, Abdulkerim, Çimen Yetiş, Sibel, Aladağ, Zeynep, Ekinci, Dursun Ali, Ayten, Umut Engin, Kerman, Bilal Ersen, and Töreyin, Behçet Uğur
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Machine Learning ,nervous system ,Fluorescence Images ,Myelin Quantification ,Image Analysis ,Myelin Annotation Tool - Abstract
Myelin is an essential component of the nervous system and myelin damage causes demyelination diseases. Myelin is a sheet of oligodendrocyte membrane wrapped around the neuronal axon. In the fluorescent images, experts manually identify myelin by colocalization of oligodendrocyte and axonal membranes that fit certain shape and size criteria. Because myelin wriggles along x-y-z axes, machine learning is ideal for its segmentation. However, machinelearning methods, especially convolutional neural networks (CNNs), require a high number of annotated images, which necessitates expert labor. To facilitate myelin annotation, we developed a workflow and a software for myelin ground truth extraction from multi-spectral fluorescent images. Additionally, we shared a set of myelin ground truths annotated using this workflow.
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- 2021
10. A multi-spectral myelin annotation tool for machine learning based myelin quantification
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Çapar, Abdulkerim, primary, Çimen Yetiş, Sibel, additional, Aladağ, Zeynep, additional, Ekinci, Dursun Ali, additional, Ayten, Umut Engin, additional, Kerman, Bilal Ersen, additional, and Töreyin, Behçet Uğur, additional
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- 2020
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11. Motoneuron expression profiling identifies an association between an axonal splice variant of HDGF-related protein 3 and peripheral myelination
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Kerman, Bilal Ersen, primary, Genoud, Stéphane, additional, Kurt Vatandaslar, Burcu, additional, Denli, Ahmet Murat, additional, Georges Ghosh, Shereen, additional, Xu, Xiangdong, additional, Yeo, Gene W., additional, Aimone, James Bradley, additional, and Gage, Fred H., additional
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- 2020
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12. DEVELOPMENT OF AUTOMATED ANALYSIS OF BIOMEDICALSIGNALS OBTAINED FROM CALCIUM IMAGING
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Radenovic, Lidija, Pavle R, Andjus, Korenic, Andrej, ÇAPAR, ABDULKERİM, DURSUN, GİZEM, ÖZKAYA, UFUK, KERMAN, BİLAL ERSEN, and Dunja, Bijelic
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- 2019
13. Myelin segmentation in fluorescence microscopy images
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Yetiş, Sibel Çimen, Ekinci, Dursun Ali, Çakır, Ertan, Ekşioglu, Ender Mete, Ayten, Umut Engin, Çapar, Abdülkerim, Töreyin, Behçet Uğur, and Kerman, Bilal Ersen
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Segmentation ,Mikroskobik Floresan Görüntüler ,Segmentasyon ,Fluorescence Microscopy Images ,Myelin ,Miyelin ,Semantic Segmentatio ,Anlamsal Bölütleme - Abstract
Aksonların etrafına sarılmış¸ miyelin kılıf, hızlı bir şekilde sinyal iletimini sağlar ve deformasyonu, Multipl Skleroz (MS) gibi çeşitli nörodejeneratif hastalıklara neden olur. Aday ilaç geliştirilmesi için, miyelinizasyonun miktarının belirlenebiliyor olması gerekmektedir. Miyelin nicelleştirilmesi, genellikle konfokal mikroskoplar tarafından elde edilen mikroskopik floresan görüntülerinde bir uzman tarafından miyelin etiketleme temeline dayanan ve yoğun emek gerektiren bir iştir. Bu çalışmada, floresan mikroskopi görüntülerinde anlamsal bölütlemeye dayalı bir otomatik miyelin belirleme yöntemi geliştirilmiştir. Üç kanallı ve üç boyutlu olarak mikroskoptan alınan, fare kök hücresinden türetilmiş¸ nöron ve oligodendrosit ortak kültürlerinin görüntüleri bir uzman tarafından etiketlenmiştir. Alınan görüntüler e˘gitim için yamalara ayrılmıs¸ ve etiketlerden de her yamanın karşılığı elde edilmiştir. Miyelin içeren ve içermeyen bögeleri tanımlamak üzere eğitim işlemi için 11552 yamadan olus¸an bir veri kümesi kullanılmıştır. Veri kümesinde çeşitli öğrenme algoritmaları kullanılarak anlamsal bölütleme tekniğinin miyelin tespit performansları değerlendirilmiştir. En yüksek doğruluk değeri olan yüzde 97.32, grup boyutu 8 ve devir sayısı 250 iken “RMSprop” öğrenme algoritması ile elde edilmiştir. Sonuçlarımız, önerilen otomatik segmentasyon yaklaşımının miyelin tespiti için uygun olduğunu göstermektedir. Burada açıklanan miyelin segmentasyon yaklaşımı, remiyelinizasyon ilaç taramalarının bir parçası haline gelecek potansiyele sahiptir. Myelin sheath, wrapped around axons, allows rapid neural signal transmission, and degeneration of myelin causes various neurodegenerative diseases, such as, Multiple Sclerosis (MS). For candidate drug discovery, it is essential to quantify myelin. This requires tedious expert labor comprising myelin labelling on microscopic fluorescence images, usually acquired by confocal microscopes. In this study, semantic segmentation based automatic myelin segmentation on fluorescence microscopy images was introduced. Three-channel and three-dimensional fluorescence images of mouse stem cell derived neuron and oligodendrocyte co-cultures were labeled by an expert. The images were divided into patches for training and the labels corresponded to each patch were acquired. A data set of 11552 patches was used for training to identify myelin and non-myelin regions. In the data set, myelin detection performances of semantic segmentation technique were evaluated using 3 different learning algorithms. The highest accuracy value of 97.32 percent was achieved by using 'RMSprop' learning algorithm with a group size of 8 and after 250 epochs. Results suggested that the proposed myelin segmentation method was suitable for detecting myelin. Thus, the outlined myelin segmentation method has the potential to be incorporated into remyelination drug screens.
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- 2019
14. Science-inspired sustainable behavior
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Kumar, Brijesh, Jensen, Mark Martin, Strielkowski, Wadim, Johnston, Juliet Tegan, Sharma, Vandana, Dandara, Collet, Shehata, Mahmoud M., Struett. Michelle Micarelli, Nikolaou, Athanasia, Szymanski, David W., Abdul-Ghani, Rashad, Cao, Bo, Varzinczak, Luiz H., Kerman, Bilal Ersen, Arthur, Patrick Kobina, Oda, Fernanda Suemi, Bohon, Wendy, Ellwanger, Joel Henrique, Tyner, Sam, Joseph Jordan, E., and Murphy, Colin
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Behavior ,Science ,Sustainable - Abstract
We asked young scientists this question: How has your awareness of science inspired you to adopt more sustainable and environmentally friendly behavior? Respondents from around the world described scientifi c concepts, images, and research from a range of fi elds that inspire them to make environmentally friendly decisions and model sustainable behavior for others, in both their personal and professional lives.
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- 2019
15. NextGen Voices: Science-inspired sustainable behavior
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Kumar, Brijesh, primary, Jensen, Mark Martin, additional, Strielkowski, Wadim, additional, Johnston, Juliet Tegan, additional, Sharma, Vandana, additional, Dandara, Collet, additional, Shehata, Mahmoud M., additional, Struett, Michelle Micarelli, additional, Nikolaou, Athanasia, additional, Szymanski, David W., additional, Abdul-Ghani, Rashad, additional, Cao, Bo, additional, Varzinczak, Luiz H., additional, Kerman, Bilal Ersen, additional, Arthur, Patrick Kobina, additional, Oda, Fernanda Suemi, additional, Bohon, Wendy, additional, Ellwanger, Joel Henrique, additional, Tyner, Sam, additional, Jordan, E. Joseph, additional, and Murphy, Colin, additional
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- 2019
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16. Refractive index tomography of myelinating glial cells
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Toy, Muhammed Fatih, primary, Vatandaslar, Burcu Kurt, additional, and Kerman, Bilal Ersen, additional
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- 2019
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17. NextGen Voices: Quality mentoring
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Segal, Lauren, primary, Agarwal, Divyansh, additional, Isaacson, Kyle J., additional, Oehmke, Theresa B., additional, Kumar, Brijesh, additional, Chen, Jennifer Shuen, additional, Cusimano, Joseph Michael, additional, Negi, Swati, additional, Tiper, Irina, additional, Bakermans, Adrianus J., additional, Jensen, Mark Martin, additional, Sanganyado, Edmond, additional, Zaidi, Syed Shan-e-Ali, additional, Romero-Molina, Carmen, additional, Martínez, Santiago Esteban, additional, Anderson, Sarah Marie, additional, Santos, Guilherme Martins, additional, De Lella Ezcurra, Ana Laura, additional, Farragher, Janine, additional, Sharma, Vandana, additional, Duncan, Gregg, additional, Dutton-Regester, Ken, additional, Kim, Sun Ae, additional, Yu, Sha, additional, Schwendimann, Beat A., additional, Reichardt, Juergen K. V., additional, Halder, Antarip, additional, Dennis, Allison F., additional, Ellwanger, Joel Henrique, additional, Chiu, Yu-Han, additional, and Kerman, Bilal Ersen, additional
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- 2018
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18. DeepMQ: A Deep Learning Approach Based Myelin Quantification in Microscopic Fluorescence Images
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Çimen, Sibel, primary, Çapar, Abdulkerim, additional, Ekinci, Dursun Ali, additional, Ayten, Umut Engin, additional, Kerman, Bilal Ersen, additional, and Töreyin, Behçet Uğur, additional
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- 2018
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19. Refractive index tomography of myelinating glial cells.
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Toy, Muhammed Fatih, Vatandaşlar, Burcu Kurt, and Kerman, Bilal Ersen
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- 2018
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20. Myelin disorders and stem cells: As therapies and models
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Aydınlı, Fatmagül İlayda, Çelik, Eşref, Kurt Vatandaşlar, Burcu, and Kerman, Bilal Ersen
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Multiple Sclerosis ,Myelin ,Stem Cells ,Induced Pluripotent Stem Cells ,Subacute Sclerosing Panencephalitis ,Pelizaeus–Merzbacher Disease ,Adrenoleukodystrophy - Abstract
Myelin disorders burden millions of people around the world, yet existing therapies are inadequate to cure them. Current remedies commonly treat the symptoms with minimal to no effect on the actual cause of the disorder. The basis and/or the mechanism of demyelination is not known for many of the disorders either. In recent years, stem cells of variable origin have been used in clinical trials as transplant agents to restore the defective biochemical process or the damaged tissue. We summarize the outcomes of these trials for demyelination disorders. The capability of reprograming mature cells into stem cells equips researchers with a new tool to replicate disease phenotypes in cell culture dishes for basic research and therapeutic screens. The applications of in vitro myelination disorder models are also discussed. The combined outcome of the discussed studies offers a promising future as stem cell transplantation generally results in decreased symptoms and improved quality of life. However, the mechanism of action of the interventions is not known and in cases of negative outcomes the reasons are usually obscure. Further basic science studies along with clinical interventions should close the knowledge gap and should help spread the positive results to a larger population.
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- 2016
21. Particular phosphorylation of PI3K/Akt on Thr308 via PDK-1 and PTEN mediates melatonin's neuroprotective activity after focal cerebral ischemia in mice
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Kilic, Ulkan, primary, Caglayan, Ahmet Burak, additional, Beker, Mustafa Caglar, additional, Gunal, Mehmet Yalcin, additional, Caglayan, Berrak, additional, Yalcin, Esra, additional, Kelestemur, Taha, additional, Gundogdu, Reyhan Zeynep, additional, Yulug, Burak, additional, Yılmaz, Bayram, additional, Kerman, Bilal Ersen, additional, and Kilic, Ertugrul, additional
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- 2017
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22. Science-inspired sustainable behavior.
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Sills, Jennifer, Kumar, Brijesh, Jensen, Mark Martin, Strielkowski, Wadim, Johnston, Juliet Tegan, Sharma, Vandana, Dandara, Collet, Shehata, Mahmoud M., Struett, Michelle Micarelli, Nikolaou, Athanasia, Szymanski, David W., Abdul-Ghani, Rashad, Cao, Bo, Varzinczak, Luiz H., Kerman, Bilal Ersen, Arthur, Patrick Kobina, Oda, Fernanda Suemi, Bohon, Wendy, Ellwanger, Joel Henrique, and Tyner, Sam
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- 2019
23. Oligodendrocyte interactome in healthy and diseased nervous system.
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Kerman, Bilal Ersen, Aydınlı, Fatmagül İlayda, Vatandaşlar, Burcu Kurt, Yurduseven, Kübra, Vatandaşlar, Emre, Çelik, Eşref, Yetiş, Sibel Çimen, Çapar, Abdulkerim, Aladağ, Zeynep, Ekinci, Dursun Ali, Ayten, Umut Engin, Töreyin, Behçet Uğur, and Kurnaz, Işıl Aksan
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NEUROLOGICAL disorders , *OLIGODENDROGLIA , *MYELIN proteins , *NERVOUS system , *DEMYELINATION , *MYELIN , *MULTIPLE sclerosis - Abstract
Objective: Myelin is essential for a healthy nervous system. Myelin formed by oligodendrocytes, accelerates impulse propagation and supports neuronal survival. Demyelination leads to neurodegeneration. In multiple sclerosis (MS) immune attack results in demyelination. Our goal is to dissect interactions among oligodendrocytes, neurons, and immune cells to improve our understanding of myelination and the demyelinating diseases. We aim to discover new targets for remyelination therapies. Methods: We are building tools for analyzing protein-protein and cell-to-cell interactions. To identify genes involved in myelination and MS, we developed a bioinformatics-based strategy, interactome analysis, which combines proteome and gene expression methodologies. Identified genes are evaluated in peripheral blood of MS patients and in mouse models. To accelerate drug discovery, 23 machine learning-based methodologies were assessed for myelin identification in fluorescent microscopy images. Results: Interactome analysis identified hundreds of proteinprotein interactions between pairs of oligodendrocytes, neurons, macrophages, microglia, and T cells. Most significant interactions are further analyzed in vivo and in vitro. Our customizedconvolutional neural network and Boosted Tree methods segmented myelin at over 98% accuracy. Identified myelin can be quantified and visualized in 3D. Conclusion: The interactome analysis yielded novel genes that are likely to be linked to MS. Machine learning-based methodologies are very effective in accelerating myelin quantification and thus, drug screens against demyelinating diseases such as MS. Overall, our innovative analysis strategies employing computer assistance produced novel avenues of exploration for myelination and demyelinating diseases. This study was supported TUBITAK (218S495,316S026), Istanbul Medipol University (BAP2018/06), and Turkish Academy of Sciences (GEBIP). [ABSTRACT FROM AUTHOR]
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- 2020
24. The investigation of effect of macrophages on neural cells of the central nervous system.
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Aydınlı, Fatmagül İlayda, Çelik, Eşref, and Kerman, Bilal Ersen
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MACROPHAGES ,MULTIPLE sclerosis ,MYELINATION - Abstract
Objective: Macrophages have a dual effect on multiple sclerosis (MS) they promote remyelination via secreted factors and they phagocytose myelin causing demyelination. Thus, signaling pathways regulating macrophage physiology are investigated as therapeutic targets. Among those pathways, dopamine and adenosine signaling pathways, drew attention due to positive results in animal models. Additionally, the two pathways were shown to act synergistically in in vitro experiments. Therefore, synergistic modulation of dopamine and adenosine pathways in macrophages may be a key target for MS therapy. Goal of this study is to investigate the effect of modulation of dopamine and adenosine pathways on myelin damage and remyelination using macrophage oligodendrocyte co-cultures. Methods: First, co-cultures were established with inactivated and lipopolysaccharide (LPS)-activated macrophages isolated from adult mice peritoneum and oligodendrocytes differentiated from the cortex of newborn mice. 48-hour old co-cultures were treated with single, double and triple combinations of dopamine signaling pathway agonist (Quinpirole), adenosine signaling pathway agonist (Istradefylline) and antagonist (CGS21680). Then, co-cultures were fixed and analyzed using immunocytochemistry. Macrophages were labeled with CD11b, oligodendrocytes with SOX10 and mature oligodendrocytes with Myelin Basic Protein (MBP) and quantified by cell counting. Results: In co-cultures with inactivated and LPS-activated macrophages, an increase in the number of mature oligodendrocytes was observed while the total number of oligodendrocytes did not change. However, a triple combination of agonists and antagonist treatment reduced number of mature oligodendrocytes in the LPS-activated macrophage-oligodendrocyte co-cultures. Conclusion: Inactive and LPS-activated macrophages increased the number of mature oligodendrocytes under co-culture conditions. Therefore, macrophages have a positive effect on oligodendrocytes when not activated by MS cues or to a similar extend and LPS treatment alone is not enough to simulate MS like conditions. Observed positive effect can be inhibited by modulating dopamine and adenosine signaling pathways. We thank TUBITAK for their support. [ABSTRACT FROM AUTHOR]
- Published
- 2018
25. Investigation of myelin membrane expansion dynamics of the central nervous system.
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Oğuz, Tuba and Kerman, Bilal Ersen
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CENTRAL nervous system , *OLIGODENDROGLIA , *MEMBRANE transport proteins , *FLUORESCENT proteins , *MEMBRANE lipids , *LIPID rafts - Abstract
Objective: Function of the myelin membrane is to accelerate impulse propagation and support metabolism and health of an axon that may extend a long distance off the neuronal body. In the central nervous system specialized glia cells -oligodendrocyteswrap the axons. An oligodendrocyte has to generate a striking amount of membrane as it can wrap up to 30-40 internodes, which are myelinated regions between nodes of Ranvier. During the expansion of the oligodendrocyte membrane towards the nodes of Ranvier large amounts of lipid and protein are trafficked to the cell membrane. Thus, defects in the cellular vesicular transport may result in myelin disorders such as "Pelizaeus-Merzbacher" disease (PMD). Cellular transport and the resulting membrane expansion processes were studied in detail at the ultrastructural level mainly by immunocytochemistry and electron microscopy, yet their dynamics are poorly understood during myelination. In order to fill the gap in our understanding, we aim to monitor lipid and protein transport to the cellular membrane in real-time. Methods: Using oligodendrocytes derived from stem cells, the cargo vesicles, lipids and lipid rafts in oligodendrocytes were monitored in real-time during myelin formation using fluorescent dyes and fluorescent proteins. Monitored oligodendrocytes were categorized according to their maturation status. Results: Our early results revealed that membrane lipids and cargo vesicles carrying different proteins followed different transportation patterns and integrated to the membrane at different locations. Conclusion: Higher temporal and spatial resolution observations are needed to reach a more detailed description of molecular physiology of myelination. Increased knowledge on myelination will not only result in a better understanding of the basic biology of the oligodendrocytes but will also improve our understanding of the myelination disorders such as PMD. [ABSTRACT FROM AUTHOR]
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- 2019
26. Refractive index tomography of myelinating glial cells
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Popescu, Gabriel, Park, YongKeun, Toy, Muhammed Fatih, Vatandaslar, Burcu Kurt, and Kerman, Bilal Ersen
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- 2019
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27. Development of fluorescence imaging tools for investigation of myelin mechanics
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Aladağ, Zeynep and Kerman, Bilal Ersen
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Multiple Sclerosis ,Myelin ,Miyelin ,Live Imaging ,Oligodendrocyte ,Oligodendrosit ,Canlı Görüntüleme ,Multıpl Skleroz - Abstract
Merkezi sinir sisteminde bulunan oligodendrositler, nöronlara trofik destek sağlayan ve elektrik sinyallerini daha hızlı ve daha verimli iletmelerini kolaylaştıran miyelin kılıfının oluşumundan sorumludur. Bu nedenle, miyelin kılıfı sağlıklı bir sinir sisteminin gelişiminde önemli bir rol oynar. Fare embriyonik kök hücre bazlı bir in vitro miyelinasyon sistemi geliştirilmiştir ve bu sistem SARAPE adı verilen miyelizasyon modelini oluşturmak için kullanılmıştır. Bu modelde, miyelinazyonun çapa atma evresi nöron ve oligodendrosit membran arasındaki ilk temastır. Caspr proteinin nöronların yüzeyindeki Contactin'e bağlandığı ve daha sonra, miyelinasyon sürecinin başından sonuna kadar kırılmayan bir etkileşim oluşturmak için oligodendrosit membranı üzerindeki NF155 proteinine bağlandığı bilinmektedir. Ana amacımız, bu proteinleri kullanarak uzun süreli canlı görüntülemeye uygun moleküler araçlar ve protokoller geliştirerek, miyelin zarının oluşumunun arkasındaki ayrıntılı mekanizmayı anlamaya yardımcı olmaktır. Bu amaçla NF155, Caspr ve Contactin proteinlerinin floresan etiketli versiyonu, lentiviral plazmitler içerisindeki oligodendrosit ve nörona spesifik promotörler altına klonlanmış ve lentivirüsler elde edilmiştir. Daha sonra, zenginleştirme işlemi yapılarak NPH'ler de kalıcı Caspr ifadesi sağlanmış ve hücreler canlı görüntülemeye uygun hale getirilmiştir. Myelin, produced by oligodendrocytes in the central nervous system and schwann cells in the peripheral nervous system, is one of the main components required for the efficient functioning of the nervous system. By virtue of the myelin membrane, the speed and efficiency of signal transmission increases, trophic support is provided to neurons and it is easier for them to survive. Therefore, myelin sheath plays essential role in the development of a healthy nervous system. A mouse embryonic stem cell-based in vitro myelination system is developed and used to create a myelization model called SARAPE. In this model, anchoring phase of the myelination is the first contact between neuron and oligodendrocyte membrane. It has been studied that Caspr bind to Contactin on the surface of neurons. Then, they interact with their binding target on the oligodendrocyte membrane, NF155, to form an interaction which is never broken from the beginning to the end of the myelination process. Our main aim is to help understanding the detailed mechanism behind the formation of the myelin membrane by generating molecular tools and protocols using these proteins, compatible with long-term live imaging. For this purpose, fluorescent tagged version of NF155, Caspr and Contactin proteins were cloned under the oligodendrocyte and neuron specific promoters in lentiviral constructs and by using cloned constructs, lentivirus particles were obtained. Next, by performing enrichment process, NPCs with permanent Caspr expression were generated. Finally, these cells were shown to compatible for live imaging.
- Published
- 2021
28. İndüklenmiş pluripotent kök hücre tabanlı multiple skleroz modelinde oligodendrositlere özgü fenotiplerin araştırılması
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Kurt Vatandaşlar, Burcu, Kerman, Bilal Ersen, and Sinir Bilimi Anabilim Dalı
- Subjects
Fizyoloji ,Multiple Sclerosis ,İndüklenebilir Pluripotent Kök Hücre ,Physiology ,Sox10 ,Induced Pluripotent Stem Cells ,Stem cells ,Multiple sclerosis ,Phenotype ,Multiple Skleroz ,Cell differentiation ,Oligodendrocytes Differentation ,Cell culture techniques ,Oligodendrosit Farklılaşması - Abstract
Multiple skleroz (MS), birçok vücut fonksiyonunu etkileyerek dünya çapında çok sayıda kişinin hayatını zorlaştırmakta ve ölümlerine neden olmaktadır. Mevcut tedavi yöntemlerinde büyük ilerlemeler kaydedilmiş olsa da hayvan modelleri, postmortem örnekler ve hayvanlardan izole edilen hücrelerle yapılan çalışmalarda hastalığın patogenezinin tam olarak anlaşılamaması, uygulanan tedavilerin yetersiz kalmasına neden olmuştur. Çalışmamızda bir in vitro insan miyelinizasyon modeli geliştirerek, hasta ve sağlıklı birey hücrelerinden üretilen oligodendrositlerin fenotiplerinin karşılaştırılması ve hastalığın orjini ve seyri hakkında detaylı bilgiye ulaşılması amaçlanmıştır. Bu amacın ilk adımı olarak, MS hastalarına ve sağlıklı bireylere ait indüklenebilir pluripotent kök hücrelerden türetilen oligogenik nöral öncül hücrelerin morfolojik incelemelerinde MS hücreleri, fenotipik farklılıklar olabileceğini destekler biçimde kontrollere göre daha basık bulunmuştur. Oligogenik nöral öncül hücrelerin erken oligodendrosit oluşuncaya kadar geçirdikleri farklılaşma evreleri Sox10 ile işaretlenerek incelendiğinde MS ve kontrol hücrelerinin aynı farklılaşma potansiyeline sahip olduğu görülmüştür. Hücrelerin çoğalma hızları incelendiğinde, MS grubundaki hücrelerin çoğalma potansiyellerinin kontrol grubuna göre biraz daha yüksek olduğu görülmüştür. Apoptotik hücre oranının erken oligodendrosit evresine doğru bir miktar azaldığı ve bu oranın MS grubunda kontrole göre biraz daha düşük olduğu gözlenmiştir. Tüm bu bulgular, kullandığımız protokol ile yüksek verimlilikte erken oligodendrosit elde edebildiğimizi ve her iki hücre grubu arasında düşük oranlarda fenotipik farklılıklar olduğunu ortaya koymuştur. Multiple sclerosis (MS) burdens lives of many people worldwide and results in their early deaths by impairing several bodily functions. Although great progress has been made with the current therapeutic methods, they remain ineffective to cure the disease and the pathogenesis of MS is still not fully understood. This is in part due to insufficiency of the animal models, postmortem samples and cells isolated from animals to reflect the exact mechanisms underlying the disease. We aimed to develop an in vitro human myelination model to analyze the origin and the course of the disease by investigating oligodendrocyte phenotypes. The morphological analysis of oligogenic neural precursor cells that were differentiated from induced pluripotent stem cells of the MS patients and healthy individuals revealed that MS cells were less round than the controls. This can be an indicator of the proposed phenotypic differences. MS patients and healthy control cells were found to have the same differentiation potency as measured by Sox10 protein expression. During the differentiation process, proliferation of MS cells was slightly higher than the control cells. It was observed that the proportion of apoptotic cells in total population showed a slight decrease in the early oligodendrocyte stage compared to the oligodendrocyte precursor cells. This ratio was slightly lower in the MS group than in the control group. All these findings reveal that we can obtain early oligodendrocytes with high efficiency via our protocol and there are slight phenotypic differences between the control and MS cells. 60
- Published
- 2018
29. Miyelin interaktomu: İkili graf tabanlı protein-protein etkileşimli ağlarla multipl skleroz'da hücre-hücre etkileşimlerinin tanımlanması
- Author
-
Çelik, Eşref, Kerman, Bilal Ersen, and Histoloji ve Embriyoloji Anabilim Dalı
- Subjects
Proteomics ,Oligodentrosit ,Multiple Sclerosis ,Bağışıklık Hücreleri ,Macrophages ,Immune Cells ,Immunity-cellular ,Signal transduction ,Proteom ,Oligodendrocyte ,Multiple sclerosis ,Multipl Skleroz ,Biology ,Biyoloji - Abstract
Miyelin kılıfı, bilginin nöronlar üzerinde verimli transferini sağlar ve nöronların işlevi ve sağ kalımı için elzemdir. Miyelin gelişiminde gözlenen bozuklukların veya miyelin hasarının (demiyelinizasyon), elektriksel sinyal iletimini sekteye uğratarak, nöronları atrofiye iterek ve kalıcı fonksiyonel bozukluğa neden olarak multipl skleroz (MS) gibi birçok nörolojik hastalığın kökeninde yattığı bilinmektedir. Bu çalışmada merkezi sinir sisteminde demiyelinizasyonu anlamak için oligodendrosit ve makrofaj hücreleri arasındaki protein-protein etkileşimlerinin belirleyerek MS'de etkili olan ve ilaçlar tarafından hedeflenebilecek yeni sinyal yolaklarının tanımlanmasını amaçladık. Bu amaçlara ulaşmak için, büyük veri yöntemlerini kullanarak oligodendrositler ile makrofaj hücreleri arasındaki protein-protein etkileşimlerinin bir atlası oluşturuldu. Benzersiz bir şekilde, metodolojimiz, tek bir hücre tipi içindeki proteinlerden ziyade hücre-hücre interakt eden proteinleri analiz etti. Ayrıca, MS hastalarının ve kontrollerinin gen ifade profilleri, protein etkileşim verileri ile birlikte değerlendirildi. Sonuç olarak, MS ile ilişkili membran ve hücre dışı proteinler tanımlanmıştır. Bu proteinlerden nörogenezde etkili ve reseptör-ligand gibi özel ilişkisi olan tirozin kinaz ailesinden efrin A7 reseptörü (EphA7) seçilerek hücre kültürü ve fare beyin kesitlerinde boyanıp mikroskopta incelendi. İncelemeler sonucunda EphA7'nin makrofaj hücrelerinde in vivo ve in vitro ifade olduğu gözlemlendi. EphA7'nin bilinen ligandlarından olan EfrinA1, A3, A4 ve A5'in oligodendrosit hücrelerinde farelerde in vivo ve in vitro ifade olduğu gözlemlendi. EphA7'nin oligodendrositlerde eskpresyonu gözlemlenmezken, makrofajlarda efrinA1, efrinA3, A4 ve A5'in ifade edildiği gözlemlendi. Ayrıca efrin ligandlarının astrositlerde de ifade edildiği gözlemlendi. Sonuç olarak EphA7'nin makrofajlarda/mikroglialarda ifade edildiği gözlemlendi. EfrinA1, A3, A4 ve A5 ligandlarının oligodendrosit ve astrosit hücrelerinde ifade edildiği gözlemlendi.Anahtar Kelimeler: Bağışıklık Hücreleri, Multipl Skleroz, Oligodentrosit, Proteom Myelin sheath facilitates efficient transfer of information over neurons and is essential for the function and survival of neurons. Thus, incorrect development of myelin or myelin damage is at the root of many neurological diseases such as multiple sclerosis (MS). Dysmyelination or demyelination disrupts electrical signal transmission, causing neuronal atrophy and permanent functional damage. In order to investigate demyelination in the central nervous system, we aimed to identify the novel MS-associated signaling pathways by identifying protein-protein interactions between oligodendrocyte and immune cells. To achieve this goal, a map of protein-protein interactions between oligodendrocytes and immune system cells was generated using large data methodologies. Uniquely, our methodology analyzed cell-to-cell interacting proteins rather than proteins within a single cell type. In addition, gene expression profiles of MS patients and controls were evaluated along with the protein interaction data. Consequently, MS-associated membrane and extracellular proteins were identified. Ephrin A7 receptor (EphA7) is a member of the tyrosine kinase family and functions in neurogenesis emerged as the top candidate protein. I examined EphA7's expression in cell culture and mouse brain sections using microscopy. EphA7 was expressed macrophages in vitro and in vivo in mouse. Moreover, Ephrins A1, A3, A4, and A5, which are known ligands of EphA7, were expressed in oligodendrocytes in vitro and in vivo in mouse. EphA7 was not present in oligodendrocytes. Ephrins A1, A3, A4, and A5 were expressed in macrophages and Ephrins A1, A3, A4, and A5 was also expressed in astrocytes. As a result, it was observed that EphA7 was expressed in macrophages/microglia. EfrinA1, A3, A4 and A5 ligands were observed to be expressed in oligodendrocyte and astrocyte cells.Key words: Immune Cells, Multiple Sclerosis, Oligodendrocyte, Proteom 82
- Published
- 2018
30. Multiple Sclerosis Biomarker Candidates Revealed by Cell-Type-Specific Interactome Analysis.
- Author
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Yurduseven K, Babal YK, Celik E, Kerman BE, and Kurnaz IA
- Subjects
- Biomarkers metabolism, Brain metabolism, Gray Matter metabolism, Humans, Magnetic Resonance Imaging, Membrane Proteins metabolism, RNA-Binding Proteins metabolism, Multiple Sclerosis genetics, Multiple Sclerosis metabolism, White Matter metabolism
- Abstract
Multiple sclerosis (MS) is a demyelinating disorder that affects multiple regions of the central nervous system such as the brain, spinal cord, and optic nerves. Susceptibility to MS, as well as disease progression rates, displays marked patient-to-patient variability. To date, biomarkers that forecast differences in clinical phenotypes and outcomes have been limited. In this context, cell-type-specific interactome analyses offer important prospects and hope for novel diagnostics and therapeutics. We report here an original study using bioinformatic analysis of MS data sets that revealed interaction profiles as well as specific hub proteins in white matter (WM) and gray matter (GM) that appear critical for disease mechanisms. First, cell-type-specific interactome analyses suggested that while interactions within the WM were focused on oligodendrocytes, interactions within the GM were mostly neuron centric. Second, hub proteins such as APP, EGLN3, PTEN, and LRRK2 were identified to be differentially regulated in MS data sets. Lastly, a comparison of the brain and peripheral blood samples identified biomarker candidates such as NRGN, CRTC1, CDC42, and IFITM3 to be differentially expressed in different types of MS. These findings offer a unique cell-type-specific cell-to-cell interaction network in MS and identify potential biomarkers by comparative analysis of the brain and the blood transcriptomics. From a study design and methodology perspective, we suggest that the cell-type-specific interactome analysis is an important systems science frontier that might offer new insights on other neurodegenerative and brain disorders as well.
- Published
- 2022
- Full Text
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