Browsing by Author "Ozdemir, Ozkan"

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Identification of epilepsy related pathways using genome-wide DNA methylation measures: A trio-based approach
(PUBLIC LIBRARY SCIENCE, 2019-01-01) Ozdemir, Ozkan; Egemen, Ece; Iseri, Sibel Aylin Ugur; Sezerman, Osman Ugur; Bebek, Nerses; Baykan, Betul; Ozbek, Ugur
Genetic generalized epilepsies (GGE) are genetically determined, as their name implies and they are clinically characterized by generalized seizures involving both sides of the brain in the absence of detectable brain lesions or other known causes. GGEs are yet complex and are influenced by many different genetic and environmental factors. Methylation specific epigenetic marks are one of the players of the complex epileptogenesis scenario leading to GGE. In this study, we have set out to perform genome-wide methylation profiling to analyze GGE trios each consisting of an affected parent-offspring couple along with an unaffected parent. We have developed a novel scoring scheme within trios to categorize each locus analyzed as hypo or hypermethylated. This stringent approach classified differentially methylated genes in each trio and helped us to produce trio specific and pooled gene lists with inherited and aberrant methylation levels. In order to analyze the methylation differences from a boarder perspective, we performed enrichment analysis with these lists using the PANOGA software. This collective effort has led us to detect pathways associated with the GGE phenotype, including the neurotrophin signaling pathway. We have demonstrated a trio based approach to genome-wide DNA methylation analysis that identified individual and possibly minor changes in methylation marks that could be involved in epileptogenesis leading to GGE.
Immune modulation as a consequence of SARS-CoV-2 infection
(FRONTIERS MEDIA SA, 2022-01-01) Gelmez, Metin Yusuf; Oktelik, Fatma Betul; Tahrali, Ilhan; Yilmaz, Vuslat; Kucuksezer, Umut Can; Akdeniz, Nilgun; Cetin, Esin Aktas; Kose, Murat; Cinar, Cigdem; Oguz, Fatma Savran; Besisik, Sevgi; Koksalan, Kaya; Ozdemir, Ozkan; Senkal, Naci; Gul, Ahmet; Tuzun, Erdem; Deniz, Gunnur
Erroneous immune responses in COVID-19 could have detrimental effects, which makes investigation of immune network underlying COVID-19 pathogenesis a requisite. This study aimed to investigate COVID-19 related alterations within the frame of innate and adaptive immunity. Thirty-four patients clinically diagnosed with mild, moderate and severe COVID-19 disease were enrolled in this study. Decreased ILC1 and increased ILC2 subsets were detected in mild and moderate patients compared to healthy controls. NK cell subsets and cytotoxic capacity of NK cells were decreased in severe patients. Moreover, CD3(+) T cells were reduced in severe patients and a negative correlation was found between CD3(+) T cells and D-dimer levels. Likewise, moderate and severe patients showed diminished CD3(+)CD8(+) T cells. Unlike T and NK cells, plasmablast and plasma cells were elevated in patients and IgG and IgA levels were particularly increased in severe patients. Severe patients also showed elevated serum levels of pro-inflammatory cytokines such as TNF-alpha, IL-6 and IL-8, reduced intracellular IFN-gamma and increased intracellular IL-10 levels. Our findings emphasize that SARS-CoV-2 infection significantly alters immune responses and innate and acquired immunity are differentially modulated in line with the clinical severity of the disease. Elevation of IL-10 levels in NK cells and reduction of CD3(+) and CD8(+) T cells in severe patients might be considered as a protective response against the harmful effect of cytokine storm seen in COVID-19.
Mutational landscape of SARS-CoV-2 genome in Turkey and impact of mutations on spike protein structure
(PUBLIC LIBRARY SCIENCE, 2021-01-01) Hatirnaz Ng, Ozden; Akyoney, Sezer; Sahin, Ilayda; Soykam, Huseyin Okan; Bayram Akcapinar, Gunseli; Ozdemir, Ozkan; Kancagi, Derya Dilek; Sir Karakus, Gozde; Yurtsever, Bulut; Kocagoz, Ayse Sesin; Ovali, Ercument; Ozbek, Ugur
The Coronavirus Disease 2019 (COVID-19) was declared a pandemic in March 2020 by the World Health Organization (WHO). As of May 25th, 2021 there were 2.059.941 SARS-COV2 genome sequences that have been submitted to the GISAID database, with numerous variations. Here, we aim to analyze the SARS-CoV-2 genome data submitted to the GISAID database from Turkey and to determine the variant and clade distributions by the end of May 2021, in accordance with their appearance timeline. We compared these findings to USA, Europe, and Asia data as well. We have also evaluated the effects of spike protein variations, detected in a group of genome sequences of 13 patients who applied to our clinic, by using 3D modeling algorithms. For this purpose, we analyzed 4607 SARS-CoV-2 genome sequences submitted by different lab centers from Turkey to the GISAID database between March 2020 and May 2021. Described mutations were also introduced in silico to the spike protein structure to analyze their isolated impacts on the protein structure. The most abundant clade was GR followed by G, GH, and GRY and we did not detect any V clade. The most common variant was B.1, followed by B.1.1, and the UK variant, B.1.1.7. Our results clearly show a concordance between the variant distributions, the number of cases, and the timelines of different variant accumulations in Turkey. The 3D simulations indicate an increase in the surface hydrophilicity of the reference spike protein and the detected mutations. There was less surface hydrophilicity increase in the Asp614Gly mutation, which exhibits a more compact conformation around the ACE-2 receptor binding domain region, rendering the structure in a ``down{''} conformation. Our genomic findings can help to model vaccination programs and protein modeling may lead to different approaches for COVID-19 treatment strategies.
SCREENING SLC2A1 GENE FOR SEQUENCE AND COPY NUMBER VARIATIONS ASSOCIATED WITH GLUT-1 DEFICIENCY SYNDROME
(ISTANBUL UNIV, FAC MEDICINE, PUBL OFF, 2020-01-01) Ornek Erguzeloglu, Cemre; Kara, Bulent; Karacan, Ilker; Ozdemir, Ozkan; Kesim, Yesim; Bebek, Nerses; Ozbek, Ugur; Ugur Iseri, Sibel Aylin
Objective: Glucose transporter-1 deficiency syndrome (GLUT1- DS) is defined as a metabolic encephalopathy that is associated with heterozygous and usually de novo pathogenic variations in the SLC2A1 (solute carrier family2 member1) gene. Materials and Methods: In this study, all coding exons and neighboring intronic regions of SLC2A1 were Sanger sequenced in 12 patients with clinically suspected GLUT1-DS. For de novo variations revealed after sequencing and segregation analysis, we also performed genome wide Single Nucleotide Polymor- phism (SNP) genotyping to confirm parental relatedness with the proband. In patients without any sequence variations, real-time quantitative real-time polymerase chain reaction (qPCR) was applied to determine the presence of any copy number variations (CNV). Results: Sanger sequencing followed by bioinformatics analysis, segregation in the family and SNP array genotyping revealed two novel and de novo pathogenic variations associated with the GLUT1-DS phenotype in 2 patients. qPCR results were compatible with one copy loss of SLC2A1 gene in another patient. All variations identified herein are likely to have caused null al-leles and resulted in GLUT1-DS through haplo insufficiency. Disscussion : In this study we used a series of molecular genetic approaches in order to identify all possible variations in SLC2A1 that may be associated with GLUT1-DS. This collective effort fa- cilitated diagnosis in 3 patients.
The modulatory action of C-Vx substance on the immune system in COVID-19
(TAYLOR \& FRANCIS LTD, 2022-01-01) Tahrali, Ilhan; Akdeniz, Nilgun; Yilmaz, Vuslat; Kucuksezer, Umut C.; Oktelik, Fatma B.; Ozdemir, Ozkan; Cetin-Aktas, Esin; Ogutmen, Yelda; Ergen, Arzu; Abaci, Neslihan; Tuzun, Erdem; Oncul, Oral; Deniz, Gunnur
The modulatory effect of C-Vx, a novel therapeutic agent, on the immune system of COVID-19 patients was investigated. The functions of T and NK cells of COVID-19 patients with different disease severity were evaluated by flow cytometry in response to C-Vx stimulation. The levels of pro- and anti-inflammatory cytokines were detected by multiplex assay in supernatants after cell culture with C-Vx. Bradykinin, IRF3, and IFN-alpha levels were also measured by ELISA in the presence or absence of C-Vx stimulation. As a result, increased CD107a expression was observed on NK cells in response to C-Vx addition. The proliferation of T cell subsets was increased by C-Vx, decreasing by disease severity. IL-4 and IL-10 levels were elevated while IFN-gamma and IL-17 levels were reduced in T cells following C-Vx stimulation. However, the levels of pro-inflammatory IL-1 beta, IL-6, IL-8, IFN-gamma and GM-CSF were significantly increased upon C-Vx stimulation. IFN-alpha levels tended to increase after incubation with C-Vx. These findings support an immunomodulatory action of C-Vx on the immune system of patients with a mild and moderate phase of COVID-19.