Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
Permanent URI for this collectionhttps://hdl.handle.net/11147/9
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Article Citation - WoS: 16Cumulative Clinical Experience From a Decade of Use: Imatinib as First-Line Treatment of Chronic Myeloid Leukemia(Dove Medical Press Ltd., 2012) Baran, Yusuf; Saydam, GürayChronic myeloid leukemia (CML) is a malignant disease that originates in the bone marrow and is designated by the presence of the Philadelphia (Ph+) chromosome, a translocation between chromosomes 9 and 22. Targeted therapy against CML commenced with the development of small-molecule tyrosine kinase inhibitors (TKIs) exerting their effect against the oncogenic breakpoint cluster region (BCR)-ABL fusion protein. Imatinib emerged as the first successful example of a TKI used for the treatment of chronic-phase CML patients and resulted in significant improvements in response rate and overall survival compared with previous treatments. However, a significant portion of patients failed to respond to the therapy and developed resistance against imatinib. Second-generation TKIs nilotinib and dasatinib were to have higher efficiency in clinical trials in imatinib- resistant or intolerant CML patients com pared with imatinib. Identification of novel strategies such as dose escalation, drug combination therapy, and use of novel BCR-ABL inhibitors may eventually overcome resistance against BCR-ABL TKIs. This article reviews the history of CML, including the treatment strategies used prediscovery of TKIs and the preclinical and clinical data obtained after the use of imatinib, and the second-generation TKIs developed for the treatment of CML.Article Citation - WoS: 19Citation - Scopus: 21Altered Conductance and Permeability of Cx40 Mutations Associated With Atrial Fibrillation(Rockefeller University Press, 2015) Cruz, Ana Santa; Meşe, Gülistan; Valiuniene, Laima; Brink, Peter R; White, Thomas W.; Valiunas, VirginijusGap junctions ensure the rapid propagation of the action potential throughout the myocardium. Three mutant forms of connexin40 (Cx40; A96S, M163V, and G38D), the primary component of the atrial gap junction channel, are associated with atrial fibrillation and retain the ability to form functional channels. We determined the biophysical properties of these mutant gap junctions in transiently transfected HeLa and N2A cells. All three mutants showed macroscopic junctional conductances over the range of 0.5 to 40 nS, and voltage dependences comparable to those of wild-type (WT) Cx40. However, the unitary conductance of G38D channels was ~1.6-fold higher than that of WT Cx40 channels (~220 vs. ~135 pS), whereas the unitary conductances of the A96S and M163V mutants were similar to that of WT Cx40. Furthermore, the M163V and G38D channels exhibited approximately two- and approximately fivefold higher permeability to the anionic dye Lucifer yellow (LY) relative to K+ (LY/K+) compared with that of WT Cx40, whereas A96S LY transfer was similar to that of WT (G38D > M163V > A96S ? Cx40WT). In contrast, G38D channels were almost impermeable to cationic ethidium bromide (EtBr), suggesting that G38D alters channel selectivity. Conversely, A96S and M163V channels showed enhanced EtBr permeability relative to WT Cx40, with the following permeability order: M163V > A96S > Cx40WT > G38D. Altered conductive and permeability properties of mutant channels suggest an essential role for Cx40-mediated biochemical and electrical coupling in cardiac tissues. The altered properties of the three single-base substitution mutants may play a role in mechanisms of reentry arrhythmias. © 2015 Santa Cruz et al.Conference Object Keratitis-Ichthyosis Syndrome Associated Mutations Impair the Localization and Functions of Connexin 26(Nature Publishing Group, 2015) Aypek, Hande; Meşe, GülistanConnexins (Cx) form gap junctions and non-junctional hemichannels that play roles in several cellular mechanisms, including proliferation and differentiation. The importance of connexins for human physiology was shown by the association of mutations in several isoforms with various human hereditary disorders. Mutations in Cx26 cause both non-syndromic and syndromic deafness associated with skin disorders including keratitis-ichthyosis-deafness (KID) syndrome. In vitro characterization of Cx26 mutations suggested that mutations causing non-syndromic deafness and syndromic deafness show different properties, where the former ones result in loss-of-function and the latter ones cause gain-of-function mutations.Article Citation - WoS: 13Citation - Scopus: 15Cytotoxic Tolerance of Healthy and Cancerous Bone Cells To Anti-Microbial Phenolic Compounds Depend on Culture Conditions(Humana Press, 2019) Karadaş, Özge; Meşe, Gülistan; Özçivici, EnginCarnosol and carnosic acid are polyphenolic compounds found in rosemary and sage with known anti-oxidant, anti-inflammatory, and anti-microbial properties. Here, we addressed the potential use of carnosol and carnosic acid for in vitro bone tissue engineering applications, specifically depending on their cytotoxic effects on bone marrow stromal and stem cells, and osteosarcoma cells in monolayer and 3D cultures. Carnosol and carnosic acid displayed a bacteriostatic effect on Gram-positive bacteria, especially on S. aureus. The viability results indicated that bone marrow stromal cells and bone marrow stem cells were more tolerant to the presence of carnosol compared to osteosarcoma cells. 3D culture conditions increased this tolerance further for healthy cells, while not affecting the cytotoxic potential of carnosol for osteosarcoma cells. Carnosic acid was found to be more cytotoxic for all cell types used in the study. Results suggest that phenolic compounds might have potential use as anti-microbial and anti-carcinogenic agents for bone tissue engineering with further optimization for controlled release.Article Citation - WoS: 9Citation - Scopus: 10Characterization of Long Living Yeast Deletion Mutants That Lack Mitochondrial Metabolism Genes Dss1, Ppa2 and Afg3(Elsevier, 2019) Muid, Khandaker Ashfaqul; Kimyon, Önder; Reza, Shahadat Hasan; Karakaya, Hüseyin Çağlar; Koç, AhmetMolecular mechanisms of aging and longevity are still mostly unknown. Mitochondria play central roles in cellular metabolism and aging. In this study, we identified three deletion mutants of mitochondrial metabolism genes (ppa2 Delta, dss1 Delta, and afg3 Delta) that live longer than wild-type cells. These long-lived cells harbored significantly decreased amount of mitochondria] DNA (mtDNA) and reactive oxygen species (ROS). Compared to the serpentine nature of wild-type mitochondria, a different dynamics and distribution pattern of mitochondria were observed in the mutants. Both young and old long-lived cells produced relatively low but adequate levels of ATP for cellular activities. The status of the retrograde signaling was checked by expression of CIT2 gene and found activated in long-lived mutants. The mutant cells were also profiled for their gene expression patterns, and genes that were differentially regulated were determined. All long-lived cells comprised similar pleiotropic phenotype regarding mitochondrial dynamics and functions. Thus, this study suggests that DSS1, PPA2, and AFG3 genes modulate the lifespan by altering the mitochondrial morphology and functions.Article Citation - WoS: 19Citation - Scopus: 24Intracytoplasmic Re-Localization of Mirisc Complexes(Frontiers Media S.A., 2018) Akgül, Bünyamin; Erdoğan, İpekMicroRNAs (miRNAs) are a conserved class of non-coding RNAs of 22 nucleotides that post-transcriptionally regulate gene expression through translational repression and/or mRNA degradation. A great progress has been made regarding miRNA biogenesis and miRNA-mediated gene regulation. Additionally, an ample amount of information exists with respect to the regulation of miRNAs. However, the cytoplasmic localization of miRNAs and its effect on gene regulatory output is still in progress. We provide a current review of the cytoplasmic miRNA localization in metazoans. We then discuss the dynamic changes in the intracytoplasmic localization of miRNAs as a means to regulate their silencing activity. We then conclude our discussion with the potential molecules that could modulate miRNA localization.Article Citation - WoS: 104Citation - Scopus: 123The Role of Cysteine Cathepsins in Cancer Progression and Drug Resistance(MDPI, 2019) Rudzinska, Magdalena; Parodi, Alessandro; Soond, Surinder M.; Vinarov, Andrey Z.; Korolev, Dmitry O.; Morozov, Andrey O.; Zamyatnin, Andrey A., Jr.; Dağlıoğlu, Cenk; Tutar, YusufCysteine cathepsins are lysosomal enzymes belonging to the papain family. Their expression is misregulated in a wide variety of tumors, and ample data prove their involvement in cancer progression, angiogenesis, metastasis, and in the occurrence of drug resistance. However, while their overexpression is usually associated with highly aggressive tumor phenotypes, their mechanistic role in cancer progression is still to be determined to develop new therapeutic strategies. In this review, we highlight the literature related to the role of the cysteine cathepsins in cancer biology, with particular emphasis on their input into tumor biology.Correction Citation - WoS: 1Citation - Scopus: 2Corrigendum To “the Importance of Boron in Biological Systems” [j. Trace Elem. Med. Biol. 45 (2018) 156–162](Elsevier, 2019) Uluışık, İrem; Karakaya, Hüseyin Çağlar; Koç, Ahmet[No abstract available]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.