PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
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Article Mitotyping of Random Bred Cats and Pure Breed Cats (turkish Angora and Turkish Van) Using Non-Repetitive Mitochondrial Dna Control Region(Elsevier, 2024) Bilgen, Nuket; Guvendi, Mervenur; Sezgin, Efe; Can, Huseyin; Koseoglu, Ahmet Efe; Alak, Sedef Erkunt; Un, CemalThe Fertile Crescent appears to be the most plausible region where the domestication of cats commenced through a mutually beneficial relationship between wild cats and early agrarian societies. These domesticated cats then journeyed across the globe mirroring the paths of human migration. An examination of mitochondrial DNA (mtDNA) control region-based mitotyping suggested that a significant majority, exceeding 80%, of globally sampled random-bred and pure-bred cats could be categorized into 12 predominant mitotypes. However, the extent of mitotype diversity within random-bred cats from regions proximate to the Fertile Crescent remains inadequately explored. In light of this we aimed to investigate the mitotype diversity in random bred cats sampled from various regions across Turkey. Additionally, we sought to establish a comparison with the mito-type profiles of locally recognized pure breeds, namely the Turkish Angora and Turkish Van. To unravel their evolutionary narratives, we engaged in comprehensive population genetics analyses at both the individual and mitotype-based levels. Our study encompassed a sample size of 240 specimens, forming the basis for both mitotyping and population genetics scrutiny. Our analysis yielded the identification of nine 'universal' mitotypes (A-J), alongside an 'outlier' mitotype group I. Notably mitotypes A and D emerged as particularly prevalent in contrast to the lesser occurrence mitotypes C, G, and H. With the realm of random bred cats the structure of haplotypes exhibited remarkable diversity presenting distinctions from Turkish Angora and Van breeds. Nucleotide diversity was higher compared to previous reports from Turkey and was one of the highest among reported world cat population estimates. Intriguingly, our investigations did not unveil any pronounced instances of strong selection, population expansions or contractions within any specific population or mitotype. To conclude, our study represents a pioneering effort in uncovering the mitotype profiles and haplotype structures inherent to both random-bred and pure breed cats in Turkey. This endeavor not only broadens our understanding of the feline genetic landscape within the region but also lays the foundation for future inquiries into the evolutionary trajectories and genetic legacies of these feline populations.Article Citation - WoS: 6Citation - Scopus: 4Early Detection of Breast Cancer-Related Lymphedema: Accuracy of Indocyanine Green Lymphography Compared With Bioimpedance Spectroscopy and Subclinical Lymphedema Symptoms(Mary Ann Liebert, 2023) Soran, Atilla; Bengur, Fuat Barış; Rodriguez, Wendy; Chroneos, Maria Z.; Sezgin, EfeIntroduction: The reported incidences of breast cancer-related lymphedema (LE) affecting the arms vary greatly. Reason for this variability includes different diagnostic techniques used across studies. In the current study, we compared the accuracy of indocyanine green lymphography (ICG_L) and bioimpedance spectroscopy (BIS) in detecting LE before presentation of clinical signs.Methods and Results: Patients with no initial detectable signs of clinical LE of their arms after axillary lymph node dissection or removal of >5 lymph nodes on sentinel lymph node biopsy were included. Subclinical LE was defined as BIS values outside the normal range [(>= 7 units (or >10 units)] or a 7-unit (or 10 unit) change between two measurements. We tracked ICG_L and BIS measurements for 133 potentially affected arms (n = 123). ICG_L detected signs of lymphatic flow disruption in 63 arms (47%). Based on the BIS value of 7 units, 60 arms (45%) had values outside the normal range. When using ICG_L-identified LE cases as true positives, BIS had a 54% accuracy (area under the curve [AUC] = 0.54) in detecting LE. Accuracy was 61% for subclinical LE symptoms when compared with ICG_L (AUC = 0.62). Both BIS and subclinical LE symptoms had <0.70 AUC-receiver characteristic operator curve, suggesting that BIS and development of subclinical LE symptoms are not adequate for identifying patients with subclinical LE.Conclusion: ICG_L is a reliable diagnostic tool for detecting early signs of lymphatic flow disruption in subclinical LE. Utilizing ICG_L to diagnose subclinical LE followed by a personalized treatment plan may provide patients the best chance of preventing disease progression.Article Citation - WoS: 11Citation - Scopus: 10Molecular Evolution and Population Genetics of Glutamate Decarboxylase Acid Resistance Pathway in Lactic Acid Bacteria(Frontiers Media S.A., 2023) Sezgin, Efe; Tekin, BurcuGlutamate decarboxylase (GAD) pathway (GDP) is a major acid resistance mechanism enabling microorganisms’ survival in low pH environments. We aimed to study the molecular evolution and population genetics of GDP in Lactic Acid Bacteria (LAB) to understand evolutionary processes shaping adaptation to acidic environments comparing species where the GDP genes are organized in an operon structure (Levilactobacillus brevis) versus lack of an operon structure (Lactiplantibacillus plantarum). Within species molecular population genetic analyses of GDP genes in L. brevis and L. plantarum sampled from diverse fermented food and other environments showed abundant synonymous and non-synonymous nucleotide diversity, mostly driven by low frequency changes, distributed throughout the coding regions for all genes in both species. GAD genes showed higher level of replacement polymorphism compared to transporter genes (gadC and YjeM) for both species, and GAD genes that are outside of an operon structure showed even higher level of replacement polymorphism. Population genetic tests suggest negative selection against replacement changes in all genes. Molecular structure and amino acid characteristics analyses showed that in none of the GDP genes replacement changes alter 3D structure or charge distribution supporting negative selection against non-conservative amino acid changes. Phylogenetic and between species divergence analyses suggested adaptive protein evolution on GDP genes comparing phylogenetically distant species, but conservative evolution comparing closely related species. GDP genes within an operon structure showed slower molecular evolution and higher conservation. All GAD and transporter genes showed high codon usage bias in examined LAB species suggesting high expression and utilization of acid resistance genes. Substantial discordances between species, GAD, and transporter gene tree topologies were observed suggesting molecular evolution of GDP genes do not follow speciation events. Distribution of operon structure on the species tree suggested multiple independent gain or loss of operon structure in LABs. In conclusion, GDP genes in LABs exhibit a dynamic molecular evolutionary history shaped by gene loss, gene transfer, negative and positive selection to maintain its active role in acid resistance mechanism, and enable organisms to thrive in acidic environments.Erratum Correction To: Excessive Replacement Changes Drive Evolution of Global Sheep Prion Protein (prnp) Sequences (heredity, (2022), 128, 5, (377-385), 10.1038/S41437-022-00520-6)(Springer, 2023) Teferedegn, Eden Yitna; Yaman, Yalçın; Sezgin, Efe; Ün, CemalIn this article the affiliation details for Author Cemal Ün were incorrectly given as Armauer Hansen research institute, Biotechnology and Bioinformatic Directorate, Addis Ababa, Ethiopia but should have been Department of Biology, Molecular Biology Division, Ege University, Izmir, Turkey. The original article has been corrected. © 2022, The Author(s), under exclusive licence to The Genetics Society.Article Citation - WoS: 30Citation - Scopus: 33Targeting the Panoptosome With 3,4-Methylenedioxy Reduces Panoptosis and Protects the Kidney Against Renal Ischemia-Reperfusion Injury(Taylor & Francis, 2022) Uysal, Erdal; Dokur, Mehmet; Küçükdurmaz, Faruk; Altınay, Serdar; Polat, Sait; Batçıoğlu, Kadir; Sezgin, EfeObjectıves: The objectives of this study were a) to investigate the effect of targeting the PANoptosome with 3,4-methylenedioxy-β-nitrostyrene (MNS) on PANoptosis in the Renal ischemia-reperfussion (RIR) model b) to investigate the kidney protective effect of MNS toward RIR injury. Methods: Thirty-two rats were divided into four groups randomly. The groups were assigned as Control, Sham, DMSO (dimethyl sulfoxide) and MNS groups. The rats in the MNS group were intraperitoneally given 20 mg/kg of MNS 30 minutes before reperfusion. 2% DMSO solvent that dissolves MNS were given to the rats in DMSO group. Left nephrectomy was performed on the rats under anesthesia at the 6th hour after reperfusion. Glutathione peroxidase (GPx), malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD) and 8-Okso-2′-deoksiguanozin (8-OHdG) levels were measured. Immunohistochemical analysis, electron microscopic and histological examinations were carried out in the tissues. Results: Total tubular injury score was lower in the MNS group (p < 0.001). Caspase-3, Gasdermin D and MLK (Mixed Lineage Kinase Domain Like Pseudokinase) expressions were considerably decreased in the MNS group (p < 0.001). Apoptotic index (AI) was found to be low in the MNS group (p < 0.001). CAT and SOD levels were higher in the MNS Group (p = 0.006, p = 0.0004, respectively). GPx, MDA, and 8-OH-dG levels were similar (p > 0.05) in all groups. MNS considerably improved the tissue structure, based on the electron microscopic analysis. Conclusıons: Our results suggested that MNS administrated before the reperfusion reduces pyroptosis, apoptosis and necroptosis. These findings suggest that MNS significantly protects the kidney against RIR injury by reducing PANoptosis as a result of specific inhibition of Nod-like receptor pyrin domain-containing 3 (NLRP 3), one of the PANoptosome proteins.Article Citation - WoS: 1Aso Visual Abstract: Intervention for Hepatic and Pulmonary Metastases in Breast Cancer Patients-Prospective, Multi-Institutional Registry Study: Imet; Protocol Mf 14-02(Springer, 2022) Soran, Atilla; Özbaş, Serdar; Özçınar, Beyza; Işık, Arda; Doğan, L.; Şenol, Kazım; Dağ, Ahmet; Karanlık, Hasan; Aytaç, Özgür; Karadeniz Çakmak, Güldeniz; Dalcı, Kubilay; Doğan, Mutlu; Sezer, Atakan Y.; Gökgöz, Şehsuvar; Özyar, Enis; Sezgin, EfeThe aim of our prospective, multicenter registry study was to investigate the importance of interventions for operable lung and/or liver metastasis for breast cancer (BC) survival (https://doi.org/10.1245/s10434-022-12239-z). The results reveal that surgical resection or ablative interventions may contribute to survival in patients with BC with limited number and operable metachronous hepatic/pulmonary metastases. Ultimately, randomized studies will determine whether intervention on lung and liver metastatic sites should be performed. In the meantime, such interventions can be considered on select patients.Article Citation - WoS: 6Citation - Scopus: 8Intervention for Hepatic and Pulmonary Metastases in Breast Cancer Patients: Prospective, Multi-Institutional Registry Study-Imet, Protocol Mf 14-02(Springer, 2022) Soran, Atilla; Özbaş, Serdar; Özçınar, Beyza; Işık, Arda; Doğan, Lütfi; Şenol, Kazım; Dağ, Ahmet; Karanlık, Hasan; Aytaç, Özgür; Karadeniz Çakmak, Güldeniz; Dalcı, Kubilay; Doğan, Mutlu; Sezer, Atakan Y.; Gökgöz, Şehsuvar; Özyar, Enis; Sezgin, EfeBackground: One fourth of early-stage breast cancer cases become metastatic during the follow-up period. Limited metastasis is a metastatic disease condition in which the number of metastatic sites and the extent of the disease both are limited, and the disease is amenable to metastatic intervention. This prospective study aimed to evaluate intervention for limited metastases in the lung, liver, or both. Methods: The study enrolled luminal A/B and/or human epidermal growth factor receptor 2 (HER2)-neu+ patients with operable lung and/or liver metastases in the follow-up assessment after completion of primary breast cancer treatment and patients with a diagnosis of metastasis after 2014. Demographic, clinical, tumor-specific, and metastasis detection-free interval (MDFI) data were collected. Bone metastasis in addition to lung and liver metastases also was included in the analysis. The patients were divided into two groups according to the method of treatment for metastases: systemic therapy alone (ST) group or intervention (IT) group.Article Citation - WoS: 8Citation - Scopus: 10Factors Associated With the Occurrence and Healing of Umbilical Pilonidal Sinus: a Rare Clinical Entity(Lippincott Williams and Wilkins Ltd., 2022) Işık, Arda; Wysocki, Arkadiusz Peter; Memiş, Ufuk; Sezgin, Efe; Yezhikova, Assel; Islambekov, YersultanObjective: Pilonidal sinus disease (PSD) is a chronic inflammatory condition of skin that is thought to be related to implanted loose hair. Although PSD is most frequently seen in the sacrococcygeal region, it can also occur at the axilla, perineum, suprapubic regions, hands, and umbilicus. The aim of this project was to find factors influencing the development and treatment of umbilical PSD. Methods: In this retrospective study, the authors evaluated 82 patients (19 women, 63 men) with a history of umbilical PSD between 2012 and 2020 to determine predisposing factors and treatment modalities. Results: There was a 20% concordance with intergluteal PSD. Smoking was the only modifying factor for recurrence. The three different treatment methods studied (conservative treatment, surgical treatment, silver nitrate) did not differ in recurrence rate (P =.57). Conclusions: Because of its rare nature, umbilical PSD can be misdiagnosed or underdiagnosed. Key aspects of treatment include smoking cessation and a conservative approach.Article Citation - WoS: 2Citation - Scopus: 2Importance of Multigene Panel Test in Patients With Consanguineous Marriage and Family History of Breast Cancer(Spandidos Publications, 2022) Özmen, Vahit; Çağlayan, Ahmet Okay; Yararbaş, Kanay; Ordu, Çetin; Aktepe, Fatma; Özmen, Tolga; Sezgin, EfeNext-generation sequencing (NGS) technology is used to evaluate hereditary cancer risks of patients worldwide; however, information concerning the germline multigene mutational spectrum among patients with breast cancer (BC) with consanguineous marriage (CM) is limited. Therefore, this prospective study aimed to determine the molecular characteristics of patients with BC who were tested with multigene hereditary cancer predisposition NGS panel and to show the effect of CM on cancer-related genes. Patients with BC with or without CM and family history (FH) of BC treated in our breast center were selected according to The National Comprehensive Cancer Network (NCCN) criteria for hereditary BC. In these patients, the analysis of a panel of 33 genes involved in hereditary cancer predisposition was performed after genetic counseling by using NGS. The pathogenic variant (PV) and the variant of uncertain significance (VUS) were found to be 15.8 and 47.4%, respectively. PVs were identified in 10/33 genes in 34 patients; 38.2% in BRCA1/2 genes; 6, 24, and 14% in other high, moderate and low-risk genes, respectively. The CM rate was 17.7% among the 215 patients with BC. The PV rate was 13.2% in patients with CM and 16.4% in patients without CM (P=0.80). When PV and VUS were evaluated together, the PV+VUS ratio was significantly higher in patients with CM and FH of BC than patients without CM and FH of BC (88.2 vs. 63.3%, P=0.045). Analysis of multigene panel provided 9.76% additional PVs in moderate/low-risk genes. The PV rate was similar in patients with BC with or without CM. A high PV+VUS ratio in patients with CM and FH of BC suggests that genes whose importance are unknown are likely to be pathogenic genes later.Article Citation - WoS: 6Citation - Scopus: 5Excessive Replacement Changes Drive Evolution of Global Sheep Prion Protein (prnp) Sequences(Springer, 2022) Sezgin, Efe; Teferedegn, Eden Yitna; Ün, Cemal; Yaman, YalçınSheep prion protein (PRNP) is the major host genetic factor responsible for susceptibility to scrapie. We aimed to understand the evolutionary history of sheep PRNP, and primarily focused on breeds from Turkey and Ethiopia, representing genome-wise ancient sheep populations. Population molecular genetic analyses are extended to European, South Asian, and East Asian populations, and for the first time to scrapie associated haplotypes. 1178 PRNP coding region nucleotide sequences were analyzed. High levels of nucleotide diversity driven by extensive low-frequency replacement changes are observed in all populations. Interspecific analyses were conducted using mouflon and domestic goat as outgroup species. Despite an abundance of silent and replacement changes, lack of silent or replacement fixations was observed. All scrapie-associated haplotype analyses from all populations also showed extensive low-frequency replacement changes. Neutrality tests did not indicate positive (directional), balancing or strong negative selection or population contraction for any of the haplotypes in any population. A simple negative selection history driven by prion disease susceptibility is not supported by the population and haplotype based analyses. Molecular function, biological process enrichment, and protein-protein interaction analyses suggested functioning of PRNP protein in multiple pathways, and possible other functional constraint selections. In conclusion, a complex selection history favoring excessive replacement changes together with weak purifying selection possibly driven by frequency-dependent selection is driving PRNP sequence evolution. Our results is not unique only to the Turkish and Ethiopian samples, but can be generalized to global sheep populations.
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