Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
Permanent URI for this collectionhttps://hdl.handle.net/11147/9
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Book Part Citation - Scopus: 5Epitranscriptomics Changes the Play: M6a Rna Modifications in Apoptosis(Springer, 2022) Akçaöz, Azime; Akgül, BünyaminApoptosis is a form of programmed cell death that is essential for cellular and organismal homeostasis. Any irregularities that disturb the balance between apoptosis and cell survival have severe implications, such as improper development or life-threatening diseases. Thus, it is highly critical to maintain a proper rate of apoptosis throughout development. In fact, several complex transcriptional and posttranscriptional mechanisms exist in eukaryotes to critically regulate the rate of apoptotic processes. Recent studies suggest that not only RNA sequences but also their modifications, such as m6A methylation, play a fundamental role in these transcriptional and posttranscriptional processes. A specific set of proteins, called writer, eraser, and reader of m6A marks, modulate the rate of apoptosis by determining the m6A repertoire and the fate of certain transcripts associated with apoptosis. In this Review, we will cover the dynamic m6A RNA modifications and their impact on modulation of apoptosis.Article Citation - WoS: 7Citation - Scopus: 7Connexin 32 Overexpression Increases Proliferation, Reduces Gap Junctional Intercellular Communication, Motility and Epithelial-To Transition in Hs578t Breast Cancer Cells(Springer, 2022) Uğur, Deniz; Güngül, Taha Buğra; Yücel, Simge; Özçivici, Engin; Yalçın Özuysal, Özden; Meşe Özçivici, GülistanConnexins (Cx) are primary components of gap junctions that selectively allow molecules to be exchanged between adjacent cells, regulating multiple cellular functions. Along with their channel forming functions, connexins play a variety of roles in different stages of tumorigenesis and their roles in tumor initiation and progression is isoform- and tissue-specific. While Cx26 and Cx43 were downregulated during breast tumorigenesis, Cx32 was accumulated in the cytoplasm of the cells in lymph node metastasis of breast cancers and Cx32 was further upregulated in metastasis. Cx32's effect on cell proliferation, gap junctional communication, hemichannel activity, cellular motility and epithelial-to-mesenchymal transition (EMT) were investigated by overexpressing Cx32 in Hs578T and MCF7 breast cancer cells. Additionally, the expression and localization of Cx26 and Cx43 upon Cx32 overexpression were examined by Western blot and immunostaining experiments, respectively. We observed that MCF7 cells had endogenous Cx32 while Hs578T cells did not and when Cx32 was overexpressed in these cells, it caused a significant increase in the percentages of Hs578T cells at the S phase in addition to increasing their proliferation. Further, while Cx32 overexpression did not induce hemichannel activity in either cell, it decreased gap junctional communication between Hs578T cells. Additionally, Cx32 was mainly observed in the cytoplasm in both cells, where it did not form gap junction plaques but Cx32 overexpression reduced Cx43 levels without affecting Cx26. Moreover, migration and invasion potentials of Hs578T and migration in MCF7 were reduced upon Cx32 overexpression. Finally, the protein level of mesenchymal marker N-cadherin decreased while epithelial marker ZO-1 and E-cadherin increased in Hs578T cells. We observed that Cx32 overexpression altered cell proliferation, communication, migration and EMT in Hs578T, suggesting a tumor suppressor role in these cells while it had minor effects on MCF7 cells.Article Citation - WoS: 8Citation - Scopus: 8Association Analysis of Germination Level Cold Stress Tolerance and Candidate Gene Identification in Upland Cotton (gossypium Hirsutum L.)(Springer, 2022) Akköse Baytar, Asena; Peynircioğlu, Ceng; Sezener, Volkan; Frary, Anne; Doğanlar, SamiCotton originated from ancestors in the Gossypium genus that grew in semi-desert habitats. As a result, it is adversely affected by low temperatures especially during germination and the first weeks of growth. Despite this, there are relatively few molecular studies on cold stress in cotton. This limitation may present a future breeding handicap, as recent years have witnessed increased low temperature damage to cotton production. Cold tolerance is a sustainable approach to obtain good production in case of extreme cold. In the present study, 110 Upland cotton (Gossypium hirsutum) genotypes were evaluated for cold tolerance at the germination stage. We identified vigorous genotypes with cold-related parameters that outperformed the panel’s average performance (x¯ = 76.9% CG, 83.9% CSI, 167.5 CWVI). Molecular genetic diversity analysis with 101 simple sequence repeat (SSR) markers yielding 416 loci was used to select tolerant genotypes that could be important materials for breeding this trait. A total of 16 marker-cold tolerance trait associations (p < 0.005) were identified with 10 of them having major effects (PVE > 10%). Based on the positions of these markers, candidate genes for cold tolerance in the G. hirsutum genome were identified. Three of these markers (BNL0569, CIR081 and CIR202) are important candidates for use in marker-assisted breeding for cold tolerance because they mapped to genes previously associated with cold tolerance in other plant species such as Arabidopsis thaliana, rice and tomato.Article Citation - WoS: 5Citation - Scopus: 5Sialidase Neu4 Deficiency Is Associated With Neuroinflammation in Mice(Springer, 2021) Timur, Zehra Kevser; İnci, Orhan Kerim; Akyıldız Demir, Seçil; Seyrantepe, VolkanSialidases catalyze the removal of sialic acid residues from glycoproteins, oligosaccharides, and sialylated glycolipids. Sialidase Neu4 is in the lysosome and has broad substrate specificity. Previously generated Neu4-/- mice were viable, fertile and lacked gross morphological abnormalities, but displayed a marked vacuolization and lysosomal storage in lung and spleen cells. In addition, we showed that there is an increased level of GD1a ganglioside and a markedly decreased level of GM1 ganglioside in the brain of Neu4-/- mice. In this study, we further explored whether sialidase Neu4 deficiency causes neuroinflammation. We demostrated that elevated level of GD1a and GT1b is associated with an increased level of LAMP1-positive lysosomal vesicles and Tunel-positive neurons correlated with alterations in the expression of cytokines and chemokines in adult Neu4-/- mice. Astrogliosis and microgliosis were also significantly enhanced in the hippocampus, and cerebellum. These changes in brain immunity were accompanied by motor impairment in these mice. Our results indicate that sialidase Neu4 is a novel mediator of an inflammatory response in the mouse brain due to the altered catabolism of gangliosides.Article Citation - WoS: 5Citation - Scopus: 5Low Magnitude High Frequency Vibrations Expedite the Osteogenesis of Bone Marrow Stem Cells on Paper Based 3d Scaffolds(Springer, 2020) Karadaş, Özge; Meşe, Gülistan; Özçivici, EnginAnabolic effects of low magnitude high frequency (LMHF) vibrations on bone tissue were consistently shown in the literature in vivo, however in vitro efforts to elucidate underlying mechanisms are generally limited to 2D cell culture studies. Three dimensional cell culture platforms better mimic the natural microenvironment and biological processes usually differ in 3D compared to 2D culture. In this study, we used laboratory grade filter paper as a scaffold material for studying the effects of LHMF vibrations on osteogenesis of bone marrow mesenchymal stem cells in a 3D system. LMHF vibrations were applied 15 min/day at 0.1 g acceleration and 90 Hz frequency for 21 days to residing cells under quiescent and osteogenic conditions. mRNA expression analysis was performed for alkaline phosphatase (ALP) and osteocalcin (OCN) genes, Alizarin red S staining was performed for mineral nodule formation and infrared spectroscopy was performed for determination of extracellular matrix composition. The highest osteocalcin expression, mineral nodule formation and the phosphate bands arising from the inorganic phase was observed for the cells incubated in osteogenic induction medium with vibration. Our results showed that filter paper can be used as a model scaffold system for studying the effects of mechanical loads on cells, and LMHF vibrations induced the osteogenic differentiation of stem cells.Book Part Citation - Scopus: 15Stem Cell Culture Under Simulated Microgravity(Springer, 2020) Anıl İnevi, Müge; Sarıgil, Öykü; Kızılkaya, Melike; Meşe, Gülistan; Tekin, Hüseyin Cumhur; Özçivici, EnginChallenging environment of space causes several pivotal alterations in living systems, especially due to microgravity. The possibility of simulating microgravity by ground-based systems provides research opportunities that may lead to the understanding of in vitro biological effects of microgravity by eliminating the challenges inherent to spaceflight experiments. Stem cells are one of the most prominent cell types, due to their self-renewal and differentiation capabilities. Research on stem cells under simulated microgravity has generated many important findings, enlightening the impact of microgravity on molecular and cellular processes of stem cells with varying potencies. Simulation techniques including clinostat, random positioning machine, rotating wall vessel and magnetic levitation-based systems have improved our knowledge on the effects of microgravity on morphology, migration, proliferation and differentiation of stem cells. Clarification of the mechanisms underlying such changes offers exciting potential for various applications such as identification of putative therapeutic targets to modulate stem cell function and stem cell based regenerative medicine. © Springer Nature Switzerland AG 2020.Conference Object Preparing Sequence Databases for Application in Proteogenomics(Springer, 2016) Has, Canan; Mungan, Mehmet Direnç; Çiftçi, Cansu; Allmer, JensProteomics involves the identification of proteins from complex mixtures which is performed using mass spectrometry (MS) followed by computational data analysis. MS/MS spectra can either be sequenced de novo if no sequence is available for the proteins in the mixture, or by using database search algorithms such as OMSSA, X!Tandem, and MSGF+.Conference Object Database Normalization Is Crucial for Reliable Protein Identification in Mass Spectrometry-Based Proteomics(Springer, 2016) Has, Canan; Mungan, Mehmet Direnç; Çiftçi, Cansu; Allmer, JensResearch in proteomics is driven by mass spectrometry, especially the identification of proteins from complex samples. Computational analysis of the resulting data determines the peptide sequences of the recorded spectra and integrates identifications into proteins. For this, database search algorithms can be employed, but they need a list of amino acid sequences that are expected to exist in the sample. Many algorithms have been proposed and consensus scoring has been performed. While the comparison/integration among results from different algorithms is important, there has been no attempt to integrate the results from searching multiple databases. This is, however, important since it poses technical problems when all databases, needed for a study, are simply concatenated. Unfortunately, it has been shown that databases of different size influence scoring and prohibit the direct comparison of results.Book Part Citation - WoS: 59Citation - Scopus: 68Stem Cell Therapy for Multiple Sclerosis(Springer, 2019) Genç, Bilgesu; Bozan, Hemdem Rodi; Genç, Şermin; Genç, KürşadMultiple sclerosis (MS) is a chronic inflammatory, autoimmune, and neurodegenerative disease of the central nervous system (CNS). It is characterized by demyelination and neuronal loss that is induced by attack of autoreactive T cells to the myelin sheath and endogenous remyelination failure, eventually leading to functional neurological disability. Although recent evidence suggests that MS relapses are induced by environmental and exogenous triggers such as viral infections in a genetic background, its very complex pathogenesis is not completely understood. Therefore, the efficiency of current immunosuppression-based therapies of MS is too low, and emerging disease-modifying immunomodulatory agents such as fingolimod and dimethyl fumarate cannot stop progressive neurodegenerative process. Thus, the cell replacement therapy approach that aims to overcome neuronal cell loss and remyelination failure and to increase endogenous myelin repair capacity is considered as an alternative treatment option. A wide variety of preclinical studies, using experimental autoimmune encephalomyelitis model of MS, have recently shown that grafted cells with different origins including mesenchymal stem cells (MSCs), neural precursor and stem cells, and induced-pluripotent stem cells have the ability to repair CNS lesions and to recover functional neurological deficits. The results of ongoing autologous hematopoietic stem cell therapy studies, with the advantage of peripheral administration to the patients, have suggested that cell replacement therapy is also a feasible option for immunomodulatory treatment of MS. In this chapter, we overview cell sources and applications of the stem cell therapy for treatment of MS. We also discuss challenges including those associated with administration route, immune responses to grafted cells, integration of these cells to existing neural circuits, and risk of tumor growth. Finally, future prospects of stem cell therapy for MS are addressed.