WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7150
Browse
13 results
Search Results
Article Citation - WoS: 4Citation - Scopus: 4Autophagic Flux Is Impaired in the Brain Tissue of Tay-Sachs Disease Mouse Model(Public Library of Science, 2023) Şengül, Tuğçe; Can, Melike; Ateş, Nurselin; Seyrantepe, VolkanTay-Sachs disease is a lethal lysosomal storage disorder caused by mutations in the HexA gene encoding the α subunit of the lysosomal β-hexosaminidase enzyme (HEXA). Abnormal GM2 ganglioside accumulation causes progressive deterioration in the central nervous system in Tay-Sachs patients. Hexa-/-mouse model failed to display abnormal phenotype. Recently, our group generated Hexa-/-Neu3-/-mouse showed severe neuropathological indications similar to Tay-Sachs patients. Despite excessive GM2 ganglioside accumulation in the brain and visceral organs, the regulation of autophagy has not been clarified yet in the Tay-Sachs disease mouse model. Therefore, we investigated distinct steps of autophagic flux using markers including LC3 and p62 in four different brain regions from the Hexa-/-Neu3-/-mice model of Tay-Sachs disease. Our data revealed accumulated autophagosomes and autophagolysosomes indicating impairment in autophagic flux in the brain. We suggest that autophagy might be a new therapeutic target for the treatment of devastating Tay-Sachs disease. © 2023 Sengul et al.Article Citation - WoS: 5Citation - Scopus: 9P/Key: Puf Based Second Factor Authentication(Public Library of Science, 2023) Uysal, Ertan; Akgün, MeteOne-time password (OTP) mechanisms are widely used to strengthen authentication processes. In time-based one-time password (TOTP) mechanisms, the client and server store common secrets. However, once the server is compromised, the client’s secrets are easy to obtain. To solve this issue, hash-chain-based second-factor authentication protocols have been proposed. However, these protocols suffer from latency in the generation of OTPs on the client side because of the hash-chain traversal. Secondly, they can generate only a limited number of OTPs as it depends on the length of the hash-chain. In this paper, we propose a second-factor authentication protocol that utilizes Physically Unclonable Functions (PUFs) to overcome these problems. In the proposed protocol, PUFs are used to store the secrets of the clients securely on the server. In case of server compromise, the attacker cannot obtain the seeds of clients’ secrets and can not generate valid OTPs to impersonate the clients. In the case of physical attacks, including side-channel attacks on the server side, our protocol has a mechanism that prevents attackers from learning the secrets of a client interacting with the server. Furthermore, our protocol does not incur any client-side delay in OTP generation.Article Citation - WoS: 5Citation - Scopus: 6Bacterial Heat Shock Protein Groel (hsp64) Exerts Immunoregulatory Effects on T Cells by Utilizing Apoptosis(Public Library of Science, 2016) Nalbant, Ayten; Kant, MelisAggregatibacter actinomycetemcomitans (Aa) expresses a 64-kDa GroEL protein belonging to the heat shock family of proteins. This protein has been shown to influence human host cells, but the apoptotic capacity of the GroEL protein regarding T cells is not yet known. The purpose of this study was to investigate the ability of A. actinomycetemcomitans GroEL (AaGroEL) protein to induce human peripheral blood T-cell apoptosis. Endogenous, purified AaGroEL protein was used as an antigen. In AaGroEL-treated T cells, the data indicated that phosphatidylserine exposure, an early apoptotic event, was dose- and time-dependent. The AaGroEL-treated T cells were also positive for active caspase-3 in a dose-dependent manner. The rate of AaGroEL-induced apoptosis was suppressed by the addition of the general caspase inhibitor Z-VAD-FMK. Furthermore, cleaved caspase-8 bands (40/36 kDa and 23 kDa) were identified in cells responding to AaGroEL. DNA fragmentation was also detected in the AaGroEL-treated T cells. Overall, we demonstrated that the endogenous GroEL from A. actinomycetemcomitans has the capacity to induce T-cell apoptosis. © 2016 Nalbant, Kant. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Article Citation - WoS: 19Citation - Scopus: 29One Step Forward, Two Steps Back; Xeno-Micrornas Reported in Breast Milk Are Artifacts(Public Library of Science, 2016) Bağcı, Caner; Allmer, JensBackground: MicroRNAs (miRNAs) are short RNA sequences that guide post-transcriptional regulation of gene expression via complementarity to their target mRNAs. Discovered only recently, miRNAs have drawn a lot of attention. Multiple protein complexes interact to first cleave a hairpin from nascent RNA, export it into the cytosol, trim its loop, and incorporate it into the RISC complex which is important for binding its target mRNA. This process works within one cell, but circulating miRNAs have been described suggesting a role in cell-cell communication. Motivation: Viruses and intracellular parasites like Toxoplasma gondii use miRNAs to manipulate host gene expression from within the cellular environment. However, recent research has claimed that a rice miRNA may regulate human gene expression. Despite ongoing debates about these findings and general reluctance to accept them, a recent report claimed that foodborne plant miRNAs pass through the digestive tract, travel through blood to be incorporated by alveolar cells excreting milk. The miRNAs are then said to have some immunerelated function in the newborn. Principal Findings: We acquired the data that supports their claim and performed further analyses. In addition to the reported miRNAs, we were able to detect almost complete mRNAs and found that the foreign RNA expression profiles among samples are exceedingly similar. Inspecting the source of the data helped understand how RNAs could contaminate the samples. Conclusion: Viewing these findings in context with the difficulties foreign RNAs face on their route into breast milk and the fact that many identified foodborne miRNAs are not from actual food sources, we can conclude beyond reasonable doubt that the original claims and evidence presented may be due to artifacts. We report that the study claiming their existence is more likely to have detected RNA contamination than miRNAs.Article Citation - WoS: 19Citation - Scopus: 19Irf6 Is Involved in the Regulation of Cell Proliferation and Transformation in Mcf10a Cells Downstream of Notch Signaling(Public Library of Science, 2015) Zengin, Talip; Ekinci, Burcu; Küçükköse, Cansu; Yalçın Özuysal, ÖzdenIRF6, a member of Interferon Regulatory Factors (IRF) family, is involved in orofacial and epidermal development. In breast cancer cell lines ectopic expression of IRF6 reduces cell numbers suggesting a role as negative regulator of cell cycle. IRF6 is a direct target of canonical Notch signaling in keratinocyte differentiation. Notch is involved in luminal cell fate determination and stem cell regulation in the normal breast and is implicated as an oncogene in breast cancer. Notch activation is sufficient to induce proliferation and transformation in non-tumorigenic breast epithelial cell line, MCF10A. ΔNp63, which is downregulated by Notch activation in the breast, regulates IRF6 expression in keratinocytes. In this report, we investigate Notch-IRF6 and ΔNp63-IRF6 interactions in MCF10A and MDA MB 231 cells. We observed that in these cells, IRF6 expression is partially regulated by canonical Notch signaling and ΔNp63 downregulation. Furthermore, we demonstrate that IRF6 abrogation impairs Notch-induced proliferation and transformation in MCF10A cells. Thus, we confirm the previous findings by showing a tissue independent regulation of IRF6 by Notch signaling, and extend them by proposing a context dependent role for IRF6, which acts as a positive regulator of proliferation and transformation in MCF10A cells downstream of Notch signaling.Article Citation - WoS: 10Citation - Scopus: 10High-Copy Overexpression Screening Reveals Pdr5 as the Main Doxorubicin Resistance Gene in Yeast(Public Library of Science, 2015) Demir, Ayşe Banu; Koç, AhmetDoxorubicin is one of the most potent anticancer drugs used in the treatment of various cancer types. The efficacy of doxorubicin is influenced by the drug resistance mechanisms and its cytotoxicity. In this study, we performed a high-copy screening analysis to find genes that play a role in doxorubicin resistance and found several genes (CUE5, AKL1, CAN1, YHR177W and PDR5) that provide resistance. Among these genes, overexpression of PDR5 provided a remarkable resistance, and deletion of it significantly rendered the tolerance level for the drug. Q-PCR analyses suggested that transcriptional regulation of these genes was not dependent on doxorubicin treatment. Additionally, we profiled the global expression pattern of cells in response to doxorubicin treatment and highlighted the genes and pathways that are important in doxorubicin tolerance/toxicity. Our results suggest that many efflux pumps and DNA metabolism genes are upregulated by the drug and required for doxorubicin tolerance.Article Citation - WoS: 6Citation - Scopus: 6Il12, Il10, Ifn Gamma and Tnf Alpha Expression in Human Primary Monocytes Stimulated With Bacterial Heat Shock Groel (hsp64) Protein(Public Library of Science, 2016) Nalbant, Ayten; Saygılı, TahsinActinobacillus (Aggregatibacter) actinomycetemicomitans (Aa) is a bacterium that lives in the oral cavity and plays an important role in periodontal diseases. The effect of A.actinomycetemcomitans's heat shock family protein GroEL on host or immune cells including monocytes is quite limited. In this study, the recombinant A.actinomycetemcomitans's GroEL protein (rAaGroEL) was used as an antigen and its effects on monocytes of peripheral blood mononuclear cells (PBMCs) was investigated. To do that, PBMCs were stimulated with rAaGroEL protein at different time points (16h to 96h) and the cytokines of CD14+ monocytes were detected with intracellular cytokine staining by Flow cytometry. Data showed that AaGroEL protein has an antigenic effect on human primary monocytes. AaGroEL protein responsive CD14 monocytes stimulates the expression of IL12, IL10, IFNγ and TNFα cytokines with different kinetics and expression profile. Therefore, A. actinomycetemcomitans's heat shock GroEL protein can modulate innate and adaptive immune responses and contribute to an inflammatory diseases pathology.Article Citation - WoS: 18Citation - Scopus: 20Serine Carboxypeptidase Scpep1 and Cathepsin a Play Complementary Roles in Regulation of Vasoconstriction Via Inactivation of Endothelin-1(Public Library of Science, 2014) Pan, Xuefang; Grigoryeva, Lubov; Seyrantepe, Volkan; Peng, Junzheng; Kollmann, Katrin; Tremblay, Johanne; Lavoie, Julie L.; Hinek, Aleksander; Lübke, Torben; Pshezhetsky, Alexey V.The potent vasoconstrictor peptides, endothelin 1 (ET-1) and angiotensin II control adaptation of blood vessels to fluctuations of blood pressure. Previously we have shown that the circulating level of ET-1 is regulated through its proteolytic cleavage by secreted serine carboxypeptidase, cathepsin A (CathA). However, genetically-modified mouse expressing catalytically inactive CathA S190A mutant retained about 10-15% of the carboxypeptidase activity against ET-1 in its tissues suggesting a presence of parallel/redundant catabolic pathway(s). In the current work we provide direct evidence that the enzyme, which complements CathA action towards ET-1 is a retinoid-inducible lysosomal serine carboxypeptidase 1 (Scpep1), a CathA homolog with previously unknown biological function. We generated a mouse strain devoid of both CathA and Scpep1 activities (DD mice) and found that in response to high-salt diet and systemic injections of ET-1 these animals showed significantly increased blood pressure as compared to wild type mice or those with single deficiencies of CathA or Scpep1. We also found that the reactivity of mesenteric arteries from DD mice towards ET-1 was significantly higher than that for all other groups of mice. The DD mice had a reduced degradation rate of ET-1 in the blood whereas their cultured arterial vascular smooth muscle cells showed increased ET-1-dependent phosphorylation of myosin light chain 2. Together, our results define the biological role of mammalian serine carboxypeptidase Scpep1 and suggest that Scpep1 and CathA together participate in the control of ET-1 regulation of vascular tone and hemodynamics.Article Citation - WoS: 7Citation - Scopus: 9Automatic Identification of Highly Conserved Family Regions and Relationships in Genome Wide Datasets Including Remote Protein Sequences(Public Library of Science, 2013) Doğan, Tunca; Karaçalı, BilgeIdentifying shared sequence segments along amino acid sequences generally requires a collection of closely related proteins, most often curated manually from the sequence datasets to suit the purpose at hand. Currently developed statistical methods are strained, however, when the collection contains remote sequences with poor alignment to the rest, or sequences containing multiple domains. In this paper, we propose a completely unsupervised and automated method to identify the shared sequence segments observed in a diverse collection of protein sequences including those present in a smaller fraction of the sequences in the collection, using a combination of sequence alignment, residue conservation scoring and graph-theoretical approaches. Since shared sequence fragments often imply conserved functional or structural attributes, the method produces a table of associations between the sequences and the identified conserved regions that can reveal previously unknown protein families as well as new members to existing ones. We evaluated the biological relevance of the method by clustering the proteins in gold standard datasets and assessing the clustering performance in comparison with previous methods from the literature. We have then applied the proposed method to a genome wide dataset of 17793 human proteins and generated a global association map to each of the 4753 identified conserved regions. Investigations on the major conserved regions revealed that they corresponded strongly to annotated structural domains. This suggests that the method can be useful in predicting novel domains on protein sequences.Article Citation - WoS: 17Citation - Scopus: 16Aggregatibacter Actinomycetemcomitans Groel Protein Promotes Conversion of Human Cd4+ T Cells Into Ifn Gamma Il10 Producing Tbet+ Th1 Cells(Public Library of Science, 2012) Saygılı, Tahsin; Akıncılar, Semih Can; Akgül, Bünyamin; Nalbant Aldanmaz, AytenOne of the heat shock family protein (Hsp) expressing bacteria is the gram negative, periodontal pathogen Aggregatibacter actinomycetemcomitans (Aa). A. actinomycetemcomitans' Hsp is a 64-kDa GroEL-protein, which has been shown to influence the host cells. In this study we used recombinant A. actinomycetemcomitans GroEL (rAaGroEL) protein as a model antigen to study GroEL-mediated T cell immune response. Human peripheral mononuclear cells (PBMCs), when stimulated with recombinant rAaGroEL, expressed early activation marker CD69 and IL-2R (CD25). CD25 and CD69 expressions were higher in CD4+ T cells compared to CD8+ T cells. rAaGroEL-responding CD4+ T cells expressed IL-10, IFNγ and TNFα cytokines. Interestingly, there were also IL-10 and IFNγ double cytokine producing CD4+ T cells. Additionally, IFNγ expressing CD4+ T cells were also T-bet positive. Altogether the results suggest that rAaGroEL protein affects CD4+ T cells to differentiate into IFNγ IL10-secreting T-bet+ Th1 cells.