Browsing by Author "Öztürk, M."
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Item Open Access Differential expression of full-length and NH2 terminally truncated FAM134B isoforms in normal physiology and cancer(NLM (Medline), 2020-12-14) Keleş, U.; İşcan, E.; Yilmaz, H. E.; Karakülah, G.; Suner, A.; Bal, E.; Çavga, Ayşe Derya; Taşdemir, Nilgün; Ekin, U.; Mutlu, Z.; Kahyaoğlu, S.; Serdar, M. A.; Atabey, N.; Öztürk, M.Selective autophagy of the endoplasmic reticulum (ER), namely ER-phagy, is mediated by ER-localized receptors, which are recognized and sequestered by GABARAP/LC3B-decorated phagophores and transferred to lysosomes for degradation. Being one such receptor, FAM134B plays critical roles in cellular processes such as protein quality control and neuronal survival. FAM134B has also been associated with different cancers, although its exact role remains elusive. We report here that the FAM134B gene encodes not one but at least two different protein isoforms: the full-length and the NH2 terminally truncated forms. Their relative expression shows extreme variation, both within normal tissues and among cancer types. Expression of full-length FAM134B is restricted to the brain, testis, spleen, and prostate. In contrast, NH2 terminally truncated FAM134B is dominant in the heart, skeletal muscle, kidney, pancreas, and liver. We compared wild-type and knockout mice to study the role of the Fam134b gene in starvation. NH2 terminally truncated FAM134B-2 was induced in the liver, skeletal muscle, and heart but not in the pancreas and stomach following starvation. Upon starvation, Fam134b-/- mice differed from wild-type mice by less weight loss and less hyperaminoacidemic and hypocalcemic response but increased levels of serum albumin, total serum proteins, and α-amylase. Interestingly, either NH2 terminally truncated FAM134B or both isoforms were downregulated in liver, lung, and colon cancers. In contrast, upregulation was observed in stomach and chromophobe kidney cancers.NEW & NOTEWORTHY We reported tissues expressing FAM134B-2 such as the kidney, muscle, heart, and pancreas, some of which exhibit stimulated expression upon nutrient starvation. We also demonstrated the effect of Fam134b deletion during ad libitum and starvation conditions. Resistance to weight loss and hypocalcemia, accompanied by an increase in serum albumin and α-amylase levels, indicate critical roles of Fam134b in physiology. Furthermore, the differential expression of FAM134B isoforms was shown to be significantly dysregulated in human cancers.Item Open Access Evaluation of ATAD2 as a potential target in hepatocellular carcinoma(Springer, 2021-11-05) Gürsoy Yüzügüllü, Özge; Ekin, U.; Özen, C.; Korhan, P.; Bağırsakcı, E.; Yılmaz, F.; Uzuner, H.; Alotaibi, H.; Kırmızıbayrak, P. B.; Atabey, N.; Karakülah, G.; Öztürk, M.; Yüzügüllü, HalukPurpose Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide with lack of effec-tive systemic chemotherapy. In this study, we aimed to evaluate the value of ATPase family AAA domain-containing protein 2 (ATAD2) as a biomarker and potential therapeutic target for HCC.Methods The expression of ATAD2 was tested in different HCC patient cohorts by immunohistochemistry and comparative transcriptional analysis. The co-expression of ATAD2 and proliferation markers was compared during liver regeneration and malignancy with different bioinformatics tools. The cellular effects of ATAD2 inactivation in liver malignancy was tested on cell cycle, apoptosis, and colony formation ability as well as tumor formation using RNA interference. The genes affected by ATAD2 inactivation in three different HCC cell lines were identified by global gene expression profiling and bioinformatics tools.Results ATAD2 overexpression is closely correlated with HCC tumor stage. There was gradual increase from dysplasia, well-differentiated and poorly-differentiated HCC, respectively. We also observed transient upregulation of ATAD2 expres-sion during rat liver regeneration in parallel to changes in Ki-67 expression. ATAD2 knockdown resulted in apoptosis and decreased cell survival in vitro and decreased tumor formation in some HCC cell lines. However, three other HCC cell lines tested were not affected. Similarly, gene expression response to ATAD2 inactivation in different HCC cell lines was highly heterogeneous.Conclusions ATAD2 is a potential proliferation marker for liver regeneration and HCC. It may also serve as a therapeutic target despite heterogeneous response of malignant cells.Item Open Access Gaussian distribution in current-conduction mechanism of (Ni/Pt) Schottky contacts on wide bandgap AlInGaN quaternary alloy(AVS Science and Technology Society, 2018) Arslan, E.; Altındal, Ş.; Ural, S.; Kayal, Ö. A.; Öztürk, M.; Özbay, EkmelThe current-conduction mechanisms of the as-deposited and annealed at 450 °C (Ni/Pt) Schottky contacts on AlInGaN quaternary alloy have been investigated in the temperature range of 80-320 K. The zero-bias barrier height (BH) (ΦB 0) and ideality factor (n) of them were evaluated using thermionic emission (TE) theory. The ΦB 0 and n values calculated from the I-V characteristics show a strong temperature dependence. Such behavior of ΦB 0 and n is attributed to Schottky barrier inhomogeneities. Therefore, both the ΦB 0 vs n and ΦB 0 vs q/2kT plots were drawn to obtain evidence on the Gaussian distribution (GD) of the barrier height at the metal/semiconductor interface. These plots show two different linear parts at low and intermediate temperatures for as-deposited and annealed Schottky contacts. Thus, the mean value of ΦB 0 and standard deviation (σ0) was calculated from the linear parts of the ΦB 0 vs q/kT plots for both samples. The values of the effective Richardson constant (A) and mean BH were obtained from the modified Richardson plots which included the effect of barrier inhomogeneity. These values of Richardson constant and barrier height for as-deposited contacts were found to be 19.9 A cm-2 K-2 and 0.59 eV, respectively, at low temperature, but 43.3 A cm-2 K-2 and 1.32 eV, respectively, at intermediate temperatures. These values of Richardson constant and barrier height for annealed contacts were found to be 19.6 A cm-2 K-2 and 0.37 eV, respectively, at low temperature, but 42.9 A cm-2 K-2 and 1.54 eV, respectively, at intermediate temperatures. It is clear that the value of the Richardson constant obtained for as-deposited and annealed samples by using double-GD for intermediate temperatures is close to the theoretical value of AlInGaN (=44.7 A cm-2 K-2). Therefore, I-V-T characteristics for the as-deposited and annealed Schottky contacts in the temperature range of 80-320 K can be successfully explained based on TE theory with double-GD of the BHs.Item Open Access Germ line BRCA1 and BRCA2 gene mutations in Turkish breast cancer patients(Elsevier, 2000-10) Özdag, H.; Tez, M.; Sayek, I.; Müslümanoglu, M.; Tarcan, O.; Içli, F.; Öztürk, M.; Özçelik, T.Germ line BRCA1 and/or BRCA2 mutations were screened in 50 Turkish breast and/or ovarian cancer patients composed of hereditary, familial, early onset and male cancer groups. Genomic DNA samples were tested by heteroduplex analysis and DNA sequencing. Two truncating BRCA2 mutations, one novel (6880 insG) and one previously reported (3034 delAAAC), were found in two out of six (33%) hereditary breast and/or ovarian cancer patients. A novel truncating (1200 insA) and a missense (2080A→G) BRCA1 mutation was found in two of 27 (7%) individuals in the early onset group. A total of four (8%) disease-causing mutations in 50 breast cancer patients were identified in BRCA1 and BRCA2 genes. In addition, five BRCA1 sequence variants have been identified in 23 patients. These results indicate that BRCA1 and BRCA2 genes are involved in some, but not all, forms of hereditary predisposition to breast cancer in the Turkish population.Item Open Access A highly sensitive and specific enzyme-linked immunosorbent assay of antibodies to hepatitis C virus(2000) Eroğlu, C.; Yıldız, E.; Öztürk, M.; Pınarbaşı, E.In this study, a 178 amino acids long portion of the hepatitis C virus (HCV) core gene was cloned, sequenced, expressed in Escherichia coli, and purified. The resulting antigen (C178) was tested with human sera enzyme-linked immunosorbent assay (ELISA) in order to assess its ability to diagnose HCV. It was shown by ELISA that 92% of the patients sera, diagnosed previously by a 3(rd) generation enzyme immunoassay (EIA) as HCV-positive, had antibodies against the C178 antigen. This antigen gave no false positive results when tested with anti-HCV-negative sera.Item Open Access Human MLH1 deficiency predisposes to hematological malignancy and neurofibromatosis type 1(American Association for Cancer Research, 1999) Ricciardone, M. D.; Özçelik, T.; Cevher, B.; Özdaǧ, H.; Tuncer, M.; Gürgey, A.; Uzunalimoǧlu, O.; Çetinkaya, H.; Tanyeli, A.; Erken, E.; Öztürk, M.Heterozygous germ-line mutations in the DNA mismatch repair genes lead to hereditary nonpolyposis colorectal cancer. The disease susceptibility of individuals who constitutionally lack both wild-type alleles is unknown. We have identified three offspring in a hereditary nonpolyposis colorectal cancer family who developed hematological malignancy at a very early age, and at least two of them displayed signs of neurofibromatosis type 1 (NF1). DNA sequence analysis and allele-specific amplification in two siblings revealed a homozygous MLH1 mutation (C676T → Arg226Stop). Thus, a homozygous germ- line MLH1 mutation and consequent mismatch repair deficiency results in a mutator phenotype characterized by leukemia and/or lymphoma associated with neurofibromatosis type 1.Item Open Access Indium rich InGaN solar cells grown by MOCVD(Springer New York LLC, 2014) Çakmak, H.; Arslan, E.; Rudziński, M.; Demirel, P.; Unalan, H. E.; Strupiński, W.; Turan, R.; Öztürk, M.; Özbay, EkmelThis study focuses on both epitaxial growths of InxGa 1-xN epilayers with graded In content, and the performance of solar cells structures grown on sapphire substrate by using metal organic chemical vapor deposition. The high resolution X-ray and Hall Effect characterization were carried out after epitaxial InGaN solar cell structures growth. The In content of the graded InGaN layer was calculated from the X-ray reciprocal space mapping measurements. Indium contents of the graded InGaN epilayers change from 8.8 to 7.1 % in Sample A, 15.7-7.1 % in Sample B, and 26.6-15.1 % in Sample C. The current voltage measurements of the solar cell devices were carried out after a standard micro fabrication procedure. Sample B exhibits better performance with a short-circuit current density of 6 mA/cm2, open-circuit voltage of 0.25 V, fill factor of 39.13 %, and the best efficiency measured under a standard solar simulator with one-sun air mass 1.5 global light sources (100 mW/cm2) at room temperature for finished devices was 0.66 %.Item Open Access Mind problem: From biology to philosophy'-A symposium organized by the Neuropsychiatric Research Center at the Gazi University, September 22-23, 2006(2006) Yamaç, K.; Aytekin, A.M.; Aysever L.; Bolay H.; Bolay, S.H.; Candansayar, S.; Firth P.; Güzel, C.; Öksüz I.; Öztürk, M.; Türkdoǧan, T.Recent advances in neuroscience not only lead to a better understanding of neurologic and psychiatric diseases and developments of novel treatment strategies, but also provide valuable tools to reveal neurobiological mechanisms underlying higher cortical functions of healthy brain. Currently, understanding and explanation of complex mental functions that distinguishes human beings from other living organisms such as, thinking, planning, desicion making and predicting future seem possible. Those developments shed light in to the mind- body problem and generate new issues that need to be discussed collectively by many diciplines studying the brain and mind such as neurology, psychiatry, genetics, biochemistry, physiology, neuroimaging, anthropology, sociology, philosophy and theology. This paper includes abstracts of lectures presented in the 'Mind Problem: From Biology to Philosophy' symposium organized by Gazi University Neuropsyciatry Research Center between September 22nd - 23rd 2006 at Gazi University. The aim of the neurophilosophy symposium is to provide a platform for biological and social scientists to share their perspectives on mind concept. We hope that this interactive meeting would lead to a new synthesis in participants mind and raise new queries to search. Consistent with the aim of the symposium, each presentation is given with different subtitles in the paper.Item Open Access Scattering analysis of ultrathin barrier (<7 nm) GaN‑based heterostructures(Springer, 2019) Narin, P.; Arslan, Engin; Öztürk, M.; Öztürk, Mustafa; Lisesivdin, S. B.; Özbay, EkmelIn this study, two-dimensional electron gas (2DEG) mobility analysis of AlN/GaN and InAlN/GaN structures with ultrathin barrier layers by metal organic chemical vapor deposition (MOCVD) has been performed with Hall efect measurements which is carried out under temperature from 15 to 350 K and a single magnetic feld of 0.5 T. As a result of the scattering analysis made with Matthiessen’s rule, it is shown that while the interface roughness scattering mechanism is dominated on the 2DEG mobility at low temperatures, the 2DEG mobility has been dominated by the polar optical phonon-scattering mechanism at high temperatures. Also, the acoustic phonon-scattering mechanism is efective on the 2DEG mobility at middle temperature. Furthermore, the interface and the quantum well parameters such as deformation potential, quantum well width, and correlation length of the interface are determined for each. As well as experimental measurements, the conduction band energy diagrams of the studied samples have been calculated using one-dimensional (1D) self-consistent Schrödinger–Poisson equations. A 2D quasitriangular quantum well formation has been shown for each studied samples. 2DEG probability density of samples has been investigated.Item Open Access Systems medicine and integrated care to combat chronic noncommunicable diseases(BioMed Central Ltd., 2011) Bousquet, J.; Anto, J. M.; Sterk, P. J.; Adcock, I. M.; Chung, K. F.; Roca, J.; Agusti, A.; Brightling, C.; Cambon-Thomsen, A.; Cesario, A.; Abdelhak, S.; Antonarakis, S. E.; Avignon, A.; Ballabio, A.; Baraldi, E.; Baranov, A.; Bieber, T.; Bockaert, J.; Brahmachari, S.; Brambilla, C.; Bringer, J.; Dauzat, M.; Ernberg, I.; Fabbri, L.; Frogue, P.; Galas, D.; Gojobori2, T.; Hunter, P.; Jorgensen, C.; Kauffmann, F.; Kourilsky, P.; Kowalski, M. L.; Lancet, D.; Le Pen, C.; Mallet, J.; Mayosi, B.; Mercier, J.; Metspalu, A.; Nadeau, J. H.; Ninot, G.; Noble, D.; Öztürk, M.; Palkonen, S.; Préfaut, C.; Rabe, K.; Renard, E.; Roberts, R. G.; Samolinski, B.; Schünemann, H. J.; Simon, H. U.; Soares, M. B.; Superti-Furga, G.; Tegner, J.; Verjovski-Almeida, S.; Wellstead, P.; Wolkenhauer, O.; Wouters, E.; Balling, R.; Brookes, A. J.; Charron, D.; Pison, C.; Chen, Z.; Hood, L.; Auffray, C.We propose an innovative, integrated, cost-e ective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensive patient-centered integrated care and multi-scale, multi-modal and multilevel systems approaches to tackle NCDs as a common group of diseases. Rather than studying each disease individually, it will take into account their intertwined gene-environment, socio-economic interactions and co-morbidities that lead to individual-speci c complex phenotypes. It will implement a road map for predictive, preventive, personalized and participatory (P4) medicine based on a robust and extensive knowledge management infrastructure that contains individual patient information. It will be supported by strategic partnerships involving all stakeholders, including general practitioners associated with patient-centered care. This systems medicine strategy, which will take a holistic approach to disease, is designed to allow the results to be used globally, taking into account the needs and speci cities of local economies and health systems.