PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
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Article Notum1a Inhibition Promotes Neurogenesis in the Adult Zebrafish Brain(Nature Portfolio, 2025) Kocagoz, Yigit; Erdogan, Nuray Sogunmez; Ozdinc, Sevval; Ipekgil, Dogac; Katkat, Esra; Ozhan, GunesNotum is a carboxylesterase enzyme that modulates extracellular signaling by hydrolyzing palmitoleoyl residues from proteins, thereby influencing key pathways involved in cell differentiation, survival, and proliferation. While notum1 expression has been identified in the brain, its role in adult neurogenesis remains poorly understood. Using the adult zebrafish brain as a model system, we demonstrate that the notum1a homolog is broadly expressed across various brain cell types but is absent in undifferentiated radial glial cells. Pharmacological inhibition of Notum activity with the small molecule inhibitor ABC99 stimulates activation of radial glial cells, leading to increased neurogenesis. A BrdU pulse-chase assay confirms that ABC99-induced proliferation enhances the production of mature neurons. Despite Notum's established role in Wnt signaling, transcriptional analysis following ABC99 treatment reveals no sustained impact on Wnt pathway targets, suggesting that Notum may regulate neurogenesis through alternative mechanisms. Our findings highlight notum1a as a potential modulator of neural progenitor cell dynamics in the adult brain and suggest that targeting Notum could represent a novel therapeutic strategy for neurodegenerative conditions characterized by impaired neurogenesis.Correction Database Covering the Prayer Movements Which Were Not Available Previously (Vol 10, 276, 2023)(Nature Portfolio, 2025) Mihcin, Senay; Sahin, Ahmet Mert; Yilmaz, Mehmet; Alpkaya, Alican Tuncay; Tuna, Merve; Akdeniz, Sevinc; Sahin, SerapArticle Integrated Spectroscopic and Morphological Analyses Reveal Cellular Shifts in Gene-Silenced Melanoma CSCs(Nature Portfolio, 2025) Ozdil, Berrin; Guler, Gunnur; Ataman, Evren; Aktug, HuseyinIntratumoral heterogeneity remains a major barrier to durable cancer therapies, largely driven by the persistence of cancer stem cells (CSCs). In this study, we employed an integrated, multi-scale approach to investigate how melanoma CSCs respond to siRNA-mediated silencing of three key regulatory genes: KLF4, SHH, and HIF1 alpha. Using a combination of morphological, molecular, spectroscopic, and elemental analyses, we explored structural and biochemical consequences of gene knockdown. Gene silencing resulted in significant changes in cell shape and size, reduced F-actin organization, and decreased PFN1 expression, indicating a loss of stem-like properties. ATR-FTIR spectroscopy revealed shifts in biomolecular composition, notably a reduction in amide III intensity and an increase in lipid ester content. SEM-EDS point-based elemental analysis revealed SEM-EDS point-based elemental analysis revealed relative differences in carbon and nitrogen levels between selected central and peripheral regions of silenced and control cells, at the micron-scale working depth, reflecting broader elemental distribution trends rather than precise subcellular compartmentalization. XPS analysis further confirmed these differences, providing additional insights into the elemental composition of the cellular surface. The integration of FTIR spectroscopy into this study highlights the potential of infrared spectroscopy as a powerful tool in cancer research. These findings demonstrate that targeting critical regulatory pathways induces cytoskeletal and biochemical remodelling in melanoma CSCs, offering a multi-dimensional perspective on cellular plasticity.Article Citation - WoS: 2Citation - Scopus: 2Vibrational Spectroscopy Unveils Distinct Cell Cycle Features of Cancer Stem Cells in Melanoma(Nature Portfolio, 2025) Uslu, Bensu Ruya; Ozdil, Berrin; Tarhan, Enver; Ozcelik, Serdar; Aktug, Huseyin; Guler, GunnurCancer stem cells (CSCs) play a central role in melanoma growth, resistance to treatment, and relapse, however, their dynamic regulatory behavior remains poorly understood. Vibrational spectroscopy offers a unique, label-free approach to investigate cellular heterogeneity at the molecular level. Here, we explored the biochemical and regulatory dynamics of CSCs identified by using a time-course design, integrating infrared and Raman spectroscopies with cell cycle analysis and immunocytochemistry targeting the checkpoint proteins p16 and p21. CSCs, non-cancer stem cells (NCSCs), and bulk CHL-1 melanoma cells were monitored at 11, 24, 48, and 72 h. CSCs showed a steady S-phase with an early rise in p16 followed by a subsequent increase in p21 expression, indicating a dynamic state of cell cycle checkpoints. In contrast, NCSCs and CHL-1 cells showed more transient p16/p21 expression and CHL-1 exhibited a marked p16 increase at 24 h. Spectroscopic analysis revealed that CSCs exhibited distinct vibrational profiles, predominantly in the nucleic acid-, protein- and lipid-associated regions. These differences were further supported by principal component and hierarchical clustering analyses, which consistently distinguished CSCs from NCSCs. Our findings underline the potential of vibrational spectroscopy to sensitively detect CSC-specific regulatory patterns and support its use in detecting new therapeutic targets in melanoma.Article Citation - WoS: 7Citation - Scopus: 7Comparative Analysis of Volume Change Behavior of Expansive Road Subgrades Stabilized With Waste Paper Sludge(Nature Portfolio, 2024) Tanyildizi, Muhammed; Goekalp, Islam; Zeybek, Abduelhakim; Uz, Volkan EmreExpansive soils have a high tendency for volume change in case of fluctuations in moisture content, potentially causing significant damage to light structures, particularly road pavements. This paper investigates the influence of waste paper sludge (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\:WPS$$\end{document}) as an alternative sustainable stabilizer on the volume change behavior of expansive road subgrade soils of different origins. For this purpose, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\:WPS$$\end{document} was added to the expansive soils at ratios of 3%, 6%, 9%, 12%, and 15% by dry weight of the soils. A series of Atterberg's limit, swelling, shrinkage, compaction, and consolidation tests were performed on pure soils and soil specimens with \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\:WPS$$\end{document} to attain a comprehensive understanding of the role that \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\:WPS$$\end{document} plays in the volume change behavior of expansive soils. The experimental test results showed that the addition of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\:WPS\:$$\end{document} led to a considerable decrease in the plasticity and swell-shrink potentials of subgrade soils. The consolidation settlement of expansive road subgrades was also reduced to some extent with \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\:WPS$$\end{document}. Moreover, the statistical analysis of the test data indicated a significant relationship among different swelling-shrinkage parameters. The experimental results presented here suggest that the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\:WPS$$\end{document} may be a cost-effective, environmentally friendly, and sustainable stabilizer to reduce the volume change sensitivity of expansive road subgrade soils.Article Citation - WoS: 2Citation - Scopus: 2Image Processing and Artificial Neural Network Based Determination of Surface Mean Texture Depth on Lab-Controlled Chip Seal Pavement Samples(Nature Portfolio, 2024) Gokalp, Islam; Uz, Volkan Emre; Barstugan, Mucahid; Balci, Mehmet CanBecause surface texture is nearly the sole indicator of pavement functional properties and highly correlated with critical operational characteristics of roadways like traffic noise and safety, the change in pavement surface texture because of traffic loadings and environment has to be evaluated routinely. There are numerous direct or indirect evaluation techniques in the market. However, most of these methods have some limitations like requiring lane closure or being expensive. In this study, a 2D image processing method was established to estimate the surface mean texture depth (MTD) of chip sealed pavements. We produced chip sealed pavement samples in the laboratory with different aggregate type, shape, and size ranging between 2 and 19 mm to cover wide range of live conditions. Two well-known conventional test methods, Sand Patch (SP) and Hydrotimer (HT), were used to determine MTDs of chip seal samples. Subsequently numerous photos were taken on surface of the samples with a camera for 2-D image processing that was done based on surface void ratio (SVR) approach. With the image processing, SVR of all samples were determined. At the point of whether there is a relationship or not, correlation analysis was made between the MTDs obtained with SP and HT and the data obtained by SVR approach with the artificial neural network method. The results show that the proposed SVR approach construed on 2D image processing method can be a reliable alternative to evaluate the surface texture of pavements.Article Citation - WoS: 19Citation - Scopus: 20Experimental Investigation of Zinc Ferrite/Insulation Oil Nanofluid Natural Convection Heat Transfer, Ac Dielectric Breakdown Voltage, and Thermophysical Properties(Nature Portfolio, 2024) Pourpasha, Hadi; Heris, Saeed Zeinali; Javadpour, Reza; Mohammadpourfard, Mousa; Li, YaqingImproving the thermal and dielectric properties of insulation oil (INO) with nanoadditives is an important challenge, and achieving dispersion stability in these nanofluids is quite challenging, necessitating further investigation. The main goal of this study is the synthesis and use of the hydrophobicity of zinc ferrite (ZnFe2O4) nanoparticles, which can improve both the thermal and dielectric properties of the INO. This oil is made from distillate (petroleum), including severely hydrotreated light naphthenic oil (75-85%) and severely hydrotreated light paraffinic oil (15-25%). A comprehensive investigation was carried out, involving the creation of nanofluids with ZnFe2O4 nanoparticles at various concentrations, and employing various characterization methods such as X-ray diffraction (XRD), Fourier-transform infrared (FTIR), scanning electron microscopy, energy dispersive X-ray (EDX), zeta potential analysis, and dynamic light scattering (DLS). The KD2 Pro thermal analyzer was used to investigate the thermal characteristics, including the thermal conductivity coefficient (TCC) and volumetric heat capacity (VHC). Under free convection conditions, the free convection heat transfer coefficient (FCHTC) and Nusselt numbers (Nu) were evaluated, revealing enhancements ranging from 14.15 to 11.7%. Furthermore, the most significant improvement observed in the AC Breakdown voltage (BDV) for nanofluids containing 0.1 wt% of ZnFe2O4 amounted to 17.3%. The most significant finding of this study is the improvement in the heat transfer performance, AC BDV, and stability of the nanofluids.Article Citation - WoS: 9Citation - Scopus: 6Fluorescence Lifetime Multiplexing With Fluorogen Activating Protein Fast Variants(Nature Portfolio, 2024) Bogdanova, Yulia A.; Solovyev, Ilya D.; Baleeva, Nadezhda S.; Myasnyanko, Ivan N.; Gorshkova, Anastasia A.; Gorbachev, Dmitriy A.; Baranov, Mikhail S.In this paper, we propose a fluorescence-lifetime imaging microscopy (FLIM) multiplexing system based on the fluorogen-activating protein FAST. This genetically encoded fluorescent labeling platform employs FAST mutants that activate the same fluorogen but provide different fluorescence lifetimes for each specific protein-dye pair. All the proposed probes with varying lifetimes possess nearly identical and the smallest-in-class size, along with quite similar steady-state optical properties. In live mammalian cells, we target these chemogenetic tags to two intracellular structures simultaneously, where their fluorescence signals are clearly distinguished by FLIM. Due to the unique structure of certain fluorogens under study, their complexes with FAST mutants display a monophasic fluorescence decay, which may facilitate enhanced multiplexing efficiency by reducing signal cross-talks and providing optimal prerequisites for signal separation upon co-localized and/or spatially overlapped labeling. A genetically encoded labeling system uses smallest-in-class fluorogen-activating protein tags for time-resolved fluorescence multiplexed cellular imaging, offering monoexponential decay and potential for sophisticated fluorescence lifetime analysis.Article Citation - WoS: 6Citation - Scopus: 6Tumour-Intrinsic Endomembrane Trafficking by Arf6 Shapes an Immunosuppressive Microenvironment That Drives Melanomagenesis and Response To Checkpoint Blockade Therapy(Nature Portfolio, 2024) Wee, Yinshen; Wang, Junhua; Wilson, Emily C.; Rich, Coulson P.; Rogers, Aaron; Tong, Zongzhong; Grossmann, Allie H.Tumour-host immune interactions lead to complex changes in the tumour microenvironment (TME), impacting progression, metastasis and response to therapy. While it is clear that cancer cells can have the capacity to alter immune landscapes, our understanding of this process is incomplete. Herein we show that endocytic trafficking at the plasma membrane, mediated by the small GTPase ARF6, enables melanoma cells to impose an immunosuppressive TME that accelerates tumour development. This ARF6-dependent TME is vulnerable to immune checkpoint blockade therapy (ICB) but in murine melanoma, loss of Arf6 causes resistance to ICB. Likewise, downregulation of ARF6 in patient tumours correlates with inferior overall survival after ICB. Mechanistically, these phenotypes are at least partially explained by ARF6-dependent recycling, which controls plasma membrane density of the interferon-gamma receptor. Collectively, our findings reveal the importance of endomembrane trafficking in outfitting tumour cells with the ability to shape their immune microenvironment and respond to immunotherapy. The small GTPase ARF6 is known to regulate endocytosis and recycling of plasma membrane proteins. Here the authors show that tumourintrinsic ARF6 promotes an immunosuppressive microenvironment that accelerates melanoma progression but that is vulnerable to immune checkpoint blockade, mechanistically linked to ARF6-dependent recycling of interferon-gamma receptors in tumour cells.Article Citation - WoS: 9Citation - Scopus: 11Mesenchymal Stem Cells From Adipose Tissue Prone To Lose Their Stemness Associated Markers in Obesity Related Stress Conditions(Nature Portfolio, 2024) Al-Sammarraie, Sura Hilal Ahmed; Ayaz-Guner, Serife; Acar, Mustafa Burak; Simsek, Ahmet; Siniksaran, Betuel Seyhan; Bozalan, Habibe Damla; Ozcan, ServetObesity is a health problem characterized by large expansion of adipose tissue. During this expansion, genotoxic stressors can be accumulated and negatively affect the mesenchymal stem cells (MSCs) of adipose tissue. Due to the oxidative stress generated by these genotoxic stressors, senescence phenotype might be observed in adipose tissue MSCs. Senescent MSCs lose their proliferations and differentiation properties and secrete senescence-associated molecules to their niche thus triggering senescence for the rest of the tissue. Accumulation of senescent cells in adipose tissue results in decreased tissue regeneration and functional impairment not only in the close vicinity but also in the other tissues. Here we hypothesized that declined tissue regeneration might be associated with loss of stemness markers in MSCs population. We analyzed the expression of several stemness-associated genes of in vitro cultured MSCs originated from adipose tissue of high-fat diet and normal diet mice models. Since the heterogenous MSCs population covers a small percentage of the pluripotent stem cells, which have roles in proliferation and tissue regeneration, we measured the percentage of these cells via TRA-1-60 pluripotent state antigen. Additionally, by conducting a shotgun proteomic approach using LC-MS/MS, whole cell proteome of the adipose tissue MSCs of high-fat diet and normal diet mice were analyzed and identified proteins were evaluated via gene ontology and PPI network analysis. MSCs of obese mice showed senescent phenotype and altered cell cycle distribution due to a hostile environment with oxidative stress in adipose tissue where they reside. Additionally, the number of pluripotent markers expressing cells declined in the MSC population of the high-fat diet mice. Gene expression analysis evidenced the loss of stemness with a decrease in the expression of stemness-associated genes. Of the proteomic comparison of the normal and the high-fat diet group, MSCs revealed that stemness-associated molecules were decreased while inflammation and senescence-associated phenotypes emerged in obese mice MSCs. Our results showed us that the MSCs of adipose tissue may lose their stemness properties due to obesity-associated stress conditions.