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: 2Citation - Scopus: 2Editorial: Population Genomics and Adaptation To Novel Environments: Challenges and Opportunities(Frontiers Media S.A., 2023) Matur, Ferhat; Keskin, Emre; Sezgin, EfeUnderstanding how organisms adapt to novel environments is an active Research Topic in ecological and evolutionary studies. Most ecological and evolutionary studies focus on how organisms find food (utilization of ecological resources), how they avoid being the food (avoidance of predators), or form the next generation (reproductive strategies) in changing environmental conditions. Yet, some novel environments may present with extreme challenges that organisms may need to evolve novel metabolic pathways even just to exist. Population genomics methods can offer reliable estimates of basic population characteristics such as effective population size, inbreeding, demographic history, and population structure, all of which are also important for conservation efforts. Furthermore, population genomics studies can pinpoint specific genetic loci and variants that are under selection for a populations’ ability to evolve and adapt in response to environmental change and manage adaptive variation. The last 10 years have seen a rise in the study of population genetics of non-model organisms, and the findings of this research are increasingly being applied to the conservation and management of wildlife. To understand population genetics and adaptations, it is equally crucial to share and disseminate the research done using these techniques.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.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: 14Citation - Scopus: 16Plaqview 2.0: a Comprehensive Web Portal for Cardiovascular Single-Cell Genomics(Frontiers Media S.A., 2022) Ma, Wei Feng; Turner, Adam W.; Gancayco, Christina; Wong, Doris; Song, Yipei; Mosquera, Jose Verdezoto; Auguste, Gaëlle; Hodonsky, Chani J.; Prabhakar, Ajay; Ekiz, Hüseyin Atakan; van der Laan, Sander W.; Miller, Clint L.Single-cell RNA-seq (scRNA-seq) is a powerful genomics technology to interrogate the cellular composition and behaviors of complex systems. While the number of scRNA-seq datasets and available computational analysis tools have grown exponentially, there are limited systematic data sharing strategies to allow rapid exploration and re-analysis of single-cell datasets, particularly in the cardiovascular field. We previously introduced PlaqView, an open-source web portal for the exploration and analysis of published atherosclerosis single-cell datasets. Now, we introduce PlaqView 2.0 (www.plaqview.com), which provides expanded features and functionalities as well as additional cardiovascular single-cell datasets. We showcase improved PlaqView functionality, backend data processing, user-interface, and capacity. PlaqView brings new or improved tools to explore scRNA-seq data, including gene query, metadata browser, cell identity prediction, ad hoc RNA-trajectory analysis, and drug-gene interaction prediction. PlaqView serves as one of the largest central repositories for cardiovascular single-cell datasets, which now includes data from human aortic aneurysm, gene-specific mouse knockouts, and healthy references. PlaqView 2.0 brings advanced tools and high-performance computing directly to users without the need for any programming knowledge. Lastly, we outline steps to generalize and repurpose PlaqView's framework for single-cell datasets from other fields.Article Citation - WoS: 6Citation - Scopus: 6Analysis of Brain Lipids in the Early-Onset Tay–sachs Disease Mouse Model With the Combined Deficiency of Β-Hexosaminidase a and Neuraminidase 3(Frontiers Media S.A., 2022) Can, Melike; Şengül, Tuğçe; Akyıldız Demir, Seçil; İnci, Orhan K.; Basırlı, Hatice Hande; Seyrantepe, VolkanTay–Sachs disease is an autosomal recessively inherited lysosomal storage disease that results from loss-of-function mutations in the HEXA gene coding βhexosaminidase A. HEXA gene deficiency affects the central nervous system owing to GM2 ganglioside accumulation in lysosomes resulting in progressive neurodegeneration in patients. We recently generated a novel mice model with a combined deficiency of βhexosaminidase A and neuraminidase 3 (Hexa−/−Neu3−/−) that mimics both the neuropathological and clinical abnormalities of early-onset Tay–Sachs disease. Here, we aimed to explore the secondary accumulation of lipids in the brain of Hexa−/ −Neu3−/− mice.Article Citation - WoS: 22Citation - Scopus: 24Conversion of Biomass To Organic Acids by Liquefaction Reactions Under Subcritical Conditions(Frontiers Media S.A., 2020) Yüksel Özşen, AslıRecently, liquefaction of biomass in subcritical water to convert it into value-added substances has been broadly attracting attention. However, there is a gap in literature about the levulinic acid, which is a high worth substance, production from biomass using subcritical water. As a green chemistry approach, decomposition of biomass could be obtained using subcritical water effectively. In this case, water uses as a solvent so that it gives a possibility to take place a reaction for the decomposition of biomass. Subcritical water, which liquid water and its temperature is higher than the normal boiling point of water, has higher ion product as well as higher concentrations of H+ and OH- ions. Additionally, it has high diffusivity, low viscosity and much lower dielectric constant. For instance, whereas dielectric constant of subcritical water is 80 at 298 K, it is 2 at 673 K. The point of this research paper is to assess the impacts of different reaction parameters on cellulose conversion as the principle segment of lignocellulosic biomasses for the production of value-added chemicals, particularly levulinic acid. Hazelnut shell waste was chosen as model biomass since hazelnut is a standout amongst the most cultivated agricultural crops in Turkey. Besides, Turkey provide 70% of the world's total hazelnut production. It was found that as reaction temperature increases, a considerable improvement on the amount of formed levulinic acid and conversion of hazelnut shell was observed. For instance, when the reaction temperature, time and acid concentration were 280 degrees C, 120 min and 50 mM, respectively, levulinic acid yield and conversion of hazelnut shell were found as 13.05 and 65.40%, respectively. Addition of H2SO4 enhanced the production of levulinic acid from waste hazelnut shell. Another method which is hybrid process could be used to produce value-added chemicals from lignocellulosic biomass. Hybrid process basically combines hydrolysis and electrolysis in subcritical water. Subcritical water has much lower dielectric constant than liquid water at ambient temperature. So, it was claimed that if constant current was applied to the reaction medium through specially designed electrodes in subcritical water environment, electrolysis could alter the hydrolysis reaction of cellulose in a way of protonation of intra-and inter-molecular hydrogen bonding around anode and as a result electrolysis in subcritical water could decrease necessary thermal energy to hydrolyze the beta(1-4) glycosidic linkage. Therefore, we developed a green hybrid process by combining hydrolysis and electrolysis in subcritical water without using any toxic, organic solvents and catalyst. Effects of especially applied current and temperature on the product distribution and conversions of cellulose were revealed and hydrothermal electrolysis reaction pathway of cellulose was proposed. The significance of the interaction indicated that, applied voltage had major impact on cellulose hydrolysis. Maximum cellulose conversion (82%) was achieved at 230 degrees C and 180 min of reaction time in 25 mM of H2SO4. Application of 8.0 V of applied voltage to the reaction medium at reaction temperature of 230 degrees C increased the TOC conversion (50.3%) with acid concentration of 25 mM in comparison with current-free experiments. Thus, the idea of electrochemically generated acid layer due to the dissociation of water around anode is supported. As future perspective, the output of the study gave an idea about converting cellulose and various biomass wastes, which may have high cellulose, content and led the way in obtaining valuable chemicals from no utilized real biomass sources such as hazelnut shell waste. The studies with other biomasses are undergoing.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: 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: 28Citation - Scopus: 31Lysosomal Cathepsin a Plays a Significant Role in the Processing of Endogenous Bioactive Peptides(Frontiers Media S.A., 2016) Timur, Zehra Kevser; Akyıldız Demir, Seçil; Seyrantepe, VolkanLysosomal serine carboxypeptidase Cathepsin A (CTSA) is a multifunctional enzyme with distinct protective and catalytic function. CTSA present in the lysosomal multienzyme complex to facilitate the correct lysosomal routing, stability and activation of with beta-galactosidase and alpha-neuraminidase. Beside CTSA has role in inactivation of bioactive peptides including bradykinin, substances P, oxytocin, angiotensin I and endothelin-I by cleavage of 1 or 2 amino acid(s) from C-terminal ends. In this study, we aimed to elucidate the regulatory role of CTSA on bioactive peptides in knock-in mice model of CTSA(S190A). We investigated the level of bradykinin, substances P, oxytocin, angiotensin I and endothelin-I in the kidney, liver, lung, brain and serum from CTSA(S190A) mouse model at 3- and 6-months of age. Our results suggest CTSA selectively contributes to processing of bioactive peptides in different tissues from CTSA(S190A) mice compared to age matched WT mice.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.