Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7148
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Editorial Citation - WoS: 1Citation - Scopus: 1Editorial: Biomaterial Applications in Soft Tissue Engineering and Replacement(Frontiers Media S.A., 2023) Hornyak, Istvan; Jedlovszky-Hajdu, Angela; Kehr, SedaThe research related to the application of biomaterials encompasses a large area within the field of tissue engineering and regenerative medicine (TERM), and this Research Topic was dedicated to the versatile possibilities in the use of biomaterials. The sum of 10 manuscripts were submitted to this Research Topic and six were selected for this Research Topic with the contribution of 35 authors, Four of the accepted manuscripts were original research articles and two were review articlesArticle 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.Article Citation - WoS: 2Citation - Scopus: 2Diverse Selection Pressures Shaping the Genetic Architecture of Behçet Disease Susceptibility(Frontiers Media S.A., 2022) Sezgin, Efe; Kaplan, ElifBehçet disease (BD) is a polygenic, multifactorial, multisystem inflammatory condition with unknown etiology. Global distribution of BD is geographically structured, highest prevalence observed among East Asian, Middle Eastern, and Mediterranean populations. Although adaptive selection on a few BD susceptibility loci is speculated, a thorough evolutionary analysis on the genetic architecture of BD is lacking. We aimed to understand whether increased BD risk in the human populations with high prevalence is due to past selection on BD associated genes. We performed population genetics analyses with East Asian (high BD prevalence), European (low/very low BD prevalence), and African (very low/no BD prevalence) populations. Comparison of ancestral and derived alleles’ frequencies versus their reported susceptible or protective effect on BD showed both derived and ancestral alleles are associated with increased BD risk. Variants showing higher risk to and more significant association with BD had smaller allele frequency differences, and showed less population differentiation compared to variants that showed smaller risk and less significant association with BD. Results suggest BD alleles are not unique to East Asians but are also found in other world populations at appreciable frequencies, and argue against selection favoring these variants only in populations with high BD prevalence. BD associated gene analyses showed similar evolutionary histories driven by neutral processes for many genes or balancing selection for HLA (Human Leukocyte Antigen) genes in all three populations studied. However, nucleotide diversity in several HLA region genes was much higher in East Asians suggesting selection for high nucleotide and haplotype diversity in East Asians. Recent selective sweep for genes involved in antigen recognition, peptide processing, immune and cellular differentiation regulation was observed only in East Asians. We conclude that the evolutionary processes shaping the genetic diversity in BD risk genes are diverse, and elucidating the underlying specific selection mechanisms is complex. Several of the genes examined in this study are risk factors (such as ERAP1, IL23R, HLA-G) for other inflammatory diseases. Thus, our conclusions are not only limited to BD but may have broader implications for other inflammatory diseases.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: 79Citation - Scopus: 93Magnetic Force-Based Micro Fluidic Techniques for Cellular and Tissue Bioengineering(Frontiers Media S.A., 2018) Yaman, Sena; Anıl İnevi, Müge; Özçivici, Engin; Tekin, Hüseyin CumhurLive cell manipulation is an important biotechnological tool for cellular and tissue level bioengineering applications due to its capacity for guiding cells for separation, isolation, concentration, and patterning. Magnetic force-based cell manipulation methods offer several advantages, such as low adverse effects on cell viability and low interference with the cellular environment. Furthermore, magnetic-based operations can be readily combined with microfluidic principles by precisely allowing control over the spatiotemporal distribution of physical and chemical factors for cell manipulation. In this review, we present recent applications of magnetic force-based cell manipulation in cellular and tissue bioengineering with an emphasis on applications with microfluidic components. Following an introduction of the theoretical background of magnetic manipulation, components of magnetic force-based cell manipulation systems are described. Thereafter, different applications, including separation of certain cell fractions, enrichment of rare cells, and guidance of cells into specific macro- or micro-arrangements to mimic natural cell organization and function, are explained. Finally, we discuss the current challenges and limitations of magnetic cell manipulation technologies in microfluidic devices with an outlook on future developments in the field.Article Citation - WoS: 39Citation - Scopus: 45Host Genetics of Cytomegalovirus Pathogenesis(Frontiers Media S.A., 2019) Sezgin, Efe; An, Ping; Winkler, Cheryl A.Human cytomegalovirus (HCMV) is a ubiquitous herpes virus (human herpes virus 5) with the highest morbidity and mortality rates compared to other herpes viruses. Risk groups include very young, elderly, transplant recipient, and immunocompromised individuals. HCMV may cause retinitis, encephalitis, hepatitis, esophagitis, colitis, pneumonia, neonatal infection sequelae, inflammatory, and age-related diseases. With an arsenal of genes in its large genome dedicated to host immune evasion, HCMV can block intrinsic cellular defenses and interfere with cellular immune responses. HCMV also encodes chemokines, chemokine receptors, and cytokines. Therefore, genes involved in human viral defense mechanisms and those encoding proteins targeted by the CMV proteins are candidates for host control of CMV infection and reactivation. Although still few in number, host genetic studies are producing valuable insights into biological processes involved in HCMV pathogenesis and HCMV-related diseases. For example, genetic variants in the immunoglobulin GM light chain can influence the antibody responsiveness to CMV glycoprotein B and modify risk of HCMV-related diseases. Moreover, CMV infection following organ transplantation has been associated with variants in genes encoding toll-like receptors (TLRs), programmed death-1 (PD-1), and interleukin-12p40 (IL-12B). A KIR haplotype (2DS4+) is proposed to be protective for CMV activation among hematopoietic stem cell transplant patients. Polymorphisms in the interferon lambda 3/4 (IFNL3/4) region are shown to influence susceptibility to CMV replication among solid organ transplant patients. Interestingly, the IFNL3/4 region is also associated with AIDS-related CMV retinitis susceptibility in HIV-infected patients. Likewise, interleukin-10 receptor 1 (IL-10R1) variants are shown to influence CMV retinitis development in patients with AIDS. Results from genome-wide association studies suggest a possible role for microtubule network and retinol metabolism in anti-CMV antibody response. Nevertheless, further genetic epidemiological studies with large cohorts, functional studies on the numerous HCMV genes, and immune response to chronic and latent states of infection that contribute to HCMV persistence are clearly necessary to elucidate the genetic mechanisms of CMV infection, reactivation, and pathogenesis.Article Citation - WoS: 11Citation - Scopus: 13Transcriptomics Analysis of Circular Rnas Differentially Expressed in Apoptotic Hela Cells(Frontiers Media S.A., 2019) Yaylak, Bilge; Erdoğan, İpek; Akgül, BünyaminApoptosis is a form of regulated cell death that plays a critical role in survival and developmental homeostasis. There are numerous reports on regulation of apoptosis by protein-coding genes as well as small non-coding RNAs, such as microRNAs. However, there is no comprehensive investigation of circular RNAs (circRNA) that are differentially expressed under apoptotic conditions. We have performed a transcriptomics study in which we first triggered apoptosis in HeLa cells through treatment with four different agents, namely cisplatin, doxorubicin, TNF-alpha and anti-Fas mAb. Total RNAs isolated from control as well as treated cells were treated with RNAse R to eliminate the linear RNAs. The remaining RNAs were then subjected to deep-sequencing to identify differentially expressed circRNAs. Interestingly, some of the dys-regulated circRNAs were found to originate from protein-coding genes well-documented to regulate apoptosis. A number of candidate circRNAs were validated with qPCR with or without RNAse R treatment as well. We then took advantage of bioinformatics tools to investigate the coding potential of differentially expressed RNAs. Additionally, we examined the candidate circRNAs for the putative miRNA-binding sites and their putative target mRNAs. Our analyses point to a potential for circRNA-mediated sponging of miRNAs known to regulate apoptosis. In conclusion, this is the first transcriptomics study that provides a complete circRNA profile of apoptotic cells that might shed light onto the potential role of circRNAs in apoptosis.Article Citation - Scopus: 45Genes Associated With T Helper 17 Cell Differentiation and Function(Frontiers Media S.A., 2016) Nalbant, Ayten; Eskier, DoğaInterleukin-17 (IL-17)-producing T helper cells (Th17 cells) constitute a lineage of CD4 effector T helper cells that is distinct from the Th1 and Th2 CD4 phenotypes. In humans, Th17 differentiation is induced in the presence of the cytokines IL-1 beta, IL-6 and TGF beta, whereas IL-23 maintains Th17 survival. Effector human Th17 cells express several cytokines and cell surface markers, including IL-17A, IL-17F, IL-22, IL-26, CCR6 and TNFa. Studies on human cells have revealed that the RORC2 transcription factor plays an effective role in Th17 differentiation. Th17 cells contribute to the host immune response by involving various pathologies, including rheumatoid arthritis, multiple sclerosis and Crohn's disease. However, the full extent of their contribution to diseases is being investigated. The differentiation of Th17 cells is controlled by many transcription factors, including ROR gammat, IRF4, RUNX1, BATF, and STAT3. This review covers the general principles of CD4 T helper differentiation and the known transcription factors that play a role in the recently discovered Th17 cells.Article Citation - Scopus: 29Computational Methods for Ab Initio Detection of Micrornas(Frontiers Media S.A., 2012) Allmer, Jens; Yousef, MalikMicroRNAs are small RNA sequences of 18-24 nucleotides in length, which serve as templates to drive post-transcriptional gene silencing. The canonical microRNA pathway starts with transcription from DNA and is followed by processing via the microprocessor complex, yielding a hairpin structure. Which is then exported into the cytosol where it is processed by Dicer and then incorporated into the RNA-induced silencing complex. All of these biogenesis steps add to the overall specificity of miRNA production and effect. Unfortunately, their modes of action are just beginning to be elucidated and therefore computational prediction algorithms cannot model the process but are usually forced to employ machine learning approaches. This work focuses on ab initio prediction methods throughout; and therefore homology-based miRNA detection methods are not discussed. Current ab initio prediction algorithms, their ties to data mining, and their prediction accuracy are detailed.