PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
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Review Citation - WoS: 1Citation - Scopus: 2Organ-On Platforms for Drug Development, Cellular Toxicity Assessment, and Disease Modeling(Tubitak Scientific & Technological Research Council Turkey, 2024) Khurram, Muhammad Maaz; Cinel, Gokturk; Yesil Celiktas, Ozlem; Bedir, ErdalOrgans-on-chips (OoCs) or microphysiological platforms are biomimetic systems engineered to emulate organ structures on microfluidic devices for biomedical research. These microdevices can mimic biological environments that enable cell-cell interactions on a small scale by mimicking 3D in vivo microenvironments outside the body. Thus far, numerous single and multiple OoCs that mimic organs have been developed, and they have emerged as forerunners for drug efficacy and cytotoxicity testing. This review explores OoC platforms to highlight their versatility in studies of drug safety, efficacy, and toxicity. We also reflect on the potential of OoCs to effectively portray disease models for possible novel therapeutics, which is difficult to achieve with traditional 2D in vitro models, providing an essential basis for biologically relevant research.Article Trna Wobble Base Modifications and Boric Acid Resistance in Yeast: Boron-Resistant Deletion Mutants Induce the General Amino Acid Control Mechanism and Activate Boron Efflux(NLM (Medline), 2020) Uluisik, I.; С Karakaya, H.; Koc, A.Boric acid is essential for plants and has many vital roles in animals and microorganisms. However, its high doses are toxic to all organisms. We previously screened yeast deletion collections to identify boric acid-resistant and susceptible mutants to identify genes that play a role in boron tolerance. Here, we analyzed boron resistant mutants (elplΔ, elp3Δ, elp6Δ, ncs2Δ, ncs6Δ and ktil2Δ) for their abilities to modulate the general amino acid control system (GAAC) and to induce boron efflux pump ATR1. The mutants analyzed in this study lack the genes that play roles in tRNA Wobble base modifications. We found that all of the boron resistant mutants activated Gcn4-dependent reporter gene activity and increased the transcript level of the ATR1 gene. Additionally, boron resistant cells accumulated less boric acid in their cytoplasm compared to the wild type cells upon boron exposure. Thus, our findings suggested that loss of wobble base modifications in tRNA leads to GAAC activation and ATR1 induction, which in turn reduced intracellular boron levels and caused boron resistance.Article Citation - WoS: 5Citation - Scopus: 5Mechanical Behaviour of Photopolymer Cell-Size Graded Triply Periodic Minimal Surface Structures at Different Deformation Rates(Mdpi, 2024) Yilmaz, Yunus Emre; Novak, Nejc; Al-Ketan, Oraib; Erten, Hacer Irem; Yaman, Ulas; Mauko, Anja; Ren, ZoranThis study investigates how varying cell size affects the mechanical behaviour of photopolymer Triply Periodic Minimal Surfaces (TPMS) under different deformation rates. Diamond, Gyroid, and Primitive TPMS structures with spatially graded cell sizes were tested. Quasi-static experiments measured boundary forces, representing material behaviour, inertia, and deformation mechanisms. Separate studies explored the base material's behaviour and its response to strain rate, revealing a strength increase with rising strain rate. Ten compression tests identified a critical strain rate of 0.7 s-1 for "Grey Pro" material, indicating a shift in failure susceptibility. X-ray tomography, camera recording, and image correlation techniques observed cell connectivity and non-uniform deformation in TPMS structures. Regions exceeding the critical rate fractured earlier. In Primitive structures, stiffness differences caused collapse after densification of smaller cells at lower rates. The study found increasing collapse initiation stress, plateau stress, densification strain, and specific energy absorption with higher deformation rates below the critical rate for all TPMS structures. However, cell-size graded Primitive structures showed a significant reduction in plateau and specific energy absorption at a 500 mm/min rate.Article Citation - WoS: 32Citation - Scopus: 31Wien Effect in Interfacial Water Dissociation Through Proton-Permeable Graphene Electrodes(Nature Research, 2022) Cai, Junhao; Griffin, Eoin; Guarochico-Moreira, Victor H.; Barry, D.; Xin, B.; Yağmurcukardeş, Mehmet; Zhang, Sheng; Geim, Andre K.; Peeters, François M.; Lozada-Hidalgo, MarceloStrong electric fields can accelerate molecular dissociation reactions. The phenomenon known as the Wien effect was previously observed using high-voltage electrolysis cells that produced fields of about 107 V m−1, sufficient to accelerate the dissociation of weakly bound molecules (e.g., organics and weak electrolytes). The observation of the Wien effect for the common case of water dissociation (H2O ⇆ H+ + OH−) has remained elusive. Here we study the dissociation of interfacial water adjacent to proton-permeable graphene electrodes and observe strong acceleration of the reaction in fields reaching above 108 V m−1. The use of graphene electrodes allows measuring the proton currents arising exclusively from the dissociation of interfacial water, while the electric field driving the reaction is monitored through the carrier density induced in graphene by the same field. The observed exponential increase in proton currents is in quantitative agreement with Onsager’s theory. Our results also demonstrate that graphene electrodes can be valuable for the investigation of various interfacial phenomena involving proton transport.Article Citation - WoS: 11Türkiye’de Kutanöz Leyşmanyazis Etkeni Leishmania Tropica’da Antimon Direnç Mekanizmasının Belirlenme(Ankara Mikrobiyoloji Derneği, 2020) Özbilgin, Ahmet; Zeyrek, Fadile Yıldız; Güray, Melda Zeynep; Çulha, Gülnaz; Akyar, Işın; Harman, Mehmet; Gündüz, CumhurDünya Sağlık Örgütü, yaklaşık bir milyar insanın endemik bölgelerde risk altında olduğunu, son beş yıl içinde bir milyon kutanöz leyşmanyazis (KL) olgusunun ve yılda yaklaşık 300.000 viseral leyşmanyazis (VL) olgusunun olduğunu bildirmektedir. Her yıl yaklaşık 20.000 kişinin VL’ye bağlı öldüğü bilinmektedir. Türkiye’de Leishmania tropica’nın ve Leishmania infantum’un neden olduğu KL’de yılda 2500 civarında olgu bildirilmektedir. Başta Akdeniz ve Ege Bölgesi illerinde olmak üzere diğer birçok ilde son yıllarda ortaya çıkan olgu ve odaklarda önemli oranda artış görülmesi önümüzdeki yıllarda enfeksiyon hızının yükseleceğini göstermektedir. Ülkemizdeki KL’nin ana etkeni L.tropica olup tedavide meglumin antimonat kullanılmaktadır. Bu çalışmada, antimona dirençli ve dirençli olmayan L.tropica izolatlarının gen ve protein ekspresyonları karşılaştırılarak L.tropica’ya özgü antimon direnç genlerinin saptanması amaçlanmıştır. Ülkemizin Ege, Akdeniz ve Güneydoğu bölgelerinden antimonat direnci bulunmayan 3 KL hastasından elde edilmiş L.tropica izolatlarında, laboratuvar ortamında meglumin antimonata karşı 3 dirençli izolat geliştirilmiştir. Bu izolatların mikroarray yöntemi ile gen ekspresyon değişimleri, 2 boyutlu jel elektroforezi ile protein profilleri ve MALDI-TOF/TOF MS ile ilgili proteinleri tanımlanarak birbirleriyle karşılaştırma yapılmıştır. Antimon tedavisine yanıt vermemiş 10 KL hastasından elde edilmiş L.tropica izolatlarına antimon bileşiklerine yönelik direnç testleri uygulanmış ve direnç gelişiminden sorumlu genlerin ekspresyonlarını saptamak amacıyla kantitatif gerçek zamanlı polimeraz zincir reaksiyonu uygulanmıştır. Ayrıca, protein profilleri karşılaştırılarak antimon direnci olan ve olmayan izolatlardaki protein ekspresyon düzeylerindeki farklılıklar belirlenmiş ve farklılık saptanan proteinlerin tanımlanması gerçekleştirilmiştir. Bu çalışmalar sonucunda, L.tropica izolatlarının antimon bileşiklerine karşı direnç geliştirilen izolatlarında, direnç geliştirmesinde enolaz, “Elongation factor-2 (EF-2)”, “Heat shock protein 70 (HSP 70)”, tripanotyon redüktaz, protein kinaz C ve metalo-peptidaz proteinlerinin rol oynadığı saptanmış ve hastalardan alınan doğal dirençli izolatlarda da benzer ekspresyon değişimi gösterilmiştir. Sonuç olarak, ülkemizdeki L.tropica izolatlarının deneysel olarak çok kısa sürede meglumin antimonata (Glucantime®) karşı direnç kazandığı saptanmıştır. Ülkemizde yaşayan ve yurt dışından ülkemize giriş yapan KL hastalarının yetersiz ve eksik tedavi görmesi durumunda, dirençli suşların ve olgu sayısının hızla artabileceği ve dirençli leyşmanyazis odaklarının oluşabileceği öngörülmektedir.Article Citation - WoS: 12Citation - Scopus: 12Evaluation of Adjuvant Activity of Astragaloside Vii and Its Combination With Different Immunostimulating Agents in Newcastle Disease Vaccine(Academic Press, 2021) Yakuboğulları, Nilgün; Çöven, Furkan Ozan; Cebi, Nusin; Çöven, Fethiye; Çöven, Nejdet; Genç, Rukan; Bedir, ErdalAstragaloside VII (AST-VII), a major cycloartane saponin isolated from Turkish Astragalus species, turned out to be one of the most active metabolites demonstrating Th1/Th2 balanced immune response. As Quillaja saponins are extensively used in adjuvant systems, this study made an attempt to improve AST-VII based adjuvant systems by using different immunostimulatory/delivery agents (monophosphoryllipid A (MPL), Astragalus polysaccharide (APS) and squalene) and to induce cellular and humoral immune response against a viral vaccine. For this purpose, Newcastle Disease vaccine (NDV) was chosen as a model vaccine. Swiss albino mice were immunized subcutaneously with LaSota vaccines in the presence/absence of AST-VII or developed adjuvant systems. AST-VII administration both in live/inactivated LaSota vaccines induced neutralizing and NDV specific IgG, IgG1 and IgG2b antibodies response as well as IL-2 and IL-4 production. APS based delivery systems enhanced the production of neutralizing antibody and the minor augmentation of IFN-? and IL-2 levels. Squalene emulsion (SE) alone or combined with AST-VII were effective in NDV restimulated splenocyte proliferation. As a conclusion, AST-VII and AST-VII containing adjuvant systems demonstrated Th1/Th2 balanced antibody and cellular immune responses in NDV vaccines. Thus, these systems could be developed as vaccine adjuvants in viral vaccines as alternative to saponin-based adjuvants.Article Citation - WoS: 3Citation - Scopus: 3Chromatographic Analysis for Targeted Metabolomics of Antioxidant and Flavor-Related Metabolites in Tomato(Bio-Protocol, 2021) Gürbüz Çolak, Nergiz; Tek, Neslihan; Frary, Anne; Doğanlar, SamiTargeted metabolomics is a useful approach to evaluate crop breeding studies. Antioxidant and flavor-related traits are of increasing interest and are considered quality traits in tomato breeding. The present study presents chromatographic methods to study antioxidants (carotenoids, vitamin C, vitamin E, phenolic compounds, and glutathione) and flavor -related characters (sugars and organic acids) in tomato. Two different extraction methods (for polar and apolar entities) were applied to isolate the targeted compounds. The extraction methods developed in this work were time and cost-effective since no further purification was needed. Carotenoids, vitamin C, glutathione, and phenolic acids were analyzed by HPLC-PDA using a RP C18 column at an appropriate wavelength for each compound. Vitamin E and sugars were analyzed by HPLC with RP C18 and NH2 columns and detected by FLD and RI detectors, respectively. In addition, organic acids were analyzed with GC-FID using a Rtx 5DA column after derivatization with MSTFA. As a result, sensitive analytical methods to quantify important plant metabolites were developed and are described herein. These methods are not only applicable in tomato but are also useful to characterize other species for flavor-related and antioxidant compounds. Thus, these protocols can be used to guide selection in crop breeding.Book Part Citation - Scopus: 444 Current Challenges in Mirnomics(Humana Press, 2022) Akgül, Bünyamin; Stadler, Peter F.; Hawkins, Liam J.; Hadj-Moussa, Hanane; Storey, Kenneth B.; Ergin, Kemal; Allmer, JensMature microRNAs (miRNAs) are short RNA sequences about 18–24 nucleotide long, which provide the recognition key within RISC for the posttranscriptional regulation of target RNAs. Considering the canonical pathway, mature miRNAs are produced via a multistep process. Their transcription (pri-miRNAs) and first processing step via the microprocessor complex (pre-miRNAs) occur in the nucleus. Then they are exported into the cytosol, processed again by Dicer (dsRNA) and finally a single strand (mature miRNA) is incorporated into RISC (miRISC). The sequence of the incorporated miRNA provides the function of RNA target recognition via hybridization. Following binding of the target, the mRNA is either degraded or translation is inhibited, which ultimately leads to less protein production. Conversely, it has been shown that binding within the 5? UTR of the mRNA can lead to an increase in protein product. Regulation of homeostasis is very important for a cell; therefore, all steps in the miRNA-based regulation pathway, from transcription to the incorporation of the mature miRNA into RISC, are under tight control. While much research effort has been exerted in this area, the knowledgebase is not sufficient for accurately modelling miRNA regulation computationally. The computational prediction of miRNAs is, however, necessary because it is not feasible to investigate all possible pairs of a miRNA and its target, let alone miRNAs and their targets. We here point out open challenges important for computational modelling or for our general understanding of miRNA-based regulation and show how their investigation is beneficial. It is our hope that this collection of challenges will lead to their resolution in the near future. © 2022, Springer Science+Business Media, LLC, part of Springer Nature.Article Citation - WoS: 8Citation - Scopus: 12Adjuvant Potency of Astragaloside Vii Embedded Cholesterol Nanoparticles for H3n2 Influenza Vaccine(TÜBİTAK, 2020) Genç, Rukan; Yakuboğulları, Nilgün; Nalbantsoy, Ayşe; Coven, Fethiye; Bedir, ErdalAdjuvants are substances that increase the immune response to a given antigen. In the development of novel vaccine adjuvants/systems, saponins are one of the most attractive molecules due to their altered immunomodulatory activities. In this study, we tried to develop PEG (polyethylene glycol)/cholesterol-based lipid nanoparticles (LNPs) to deliver the Astragaloside VII (AST-VII) and potentiate adjuvant properties of AST-VII for the influenza vaccine. In the formation of PEG/cholesterol/AST-VII-based LNPs (PEG300: Chol-AST-VII LNPs), 3 different primary solvents (acetone, ethanol, and chloroform) were evaluated, employing their effects on hydrodynamic particle size, distribution, surface chemistry, and colloidal stability. Prepared nanoparticles were simply admixtured with inactivated influenza antigen (H3N2) and applied to PMA (phorbol 12-myristate 13-acetate)-ionomycin treated human whole blood to evaluate their cytokine release profile. PEG300: Chol-AST-VII LNPs (80.2 +/- 7.7 nm) were obtained using chloroform as a desolvation agent. Co-treatment of PMA-ionomycin with AST-VII and PEG300: Chol-AST-VII LNPs significantly increased the levels of IL-2 and IFN-gamma, compared to PMA-ionomycin alone. In the presence of H3N2, AST-VII was able to augment IL-17A, while PEG300: Chol-AST-VII LNPs stimulated the production of IFN-gamma. Hemolysis was only observed in PEG300: Chol-AST-VII LNPs (250 mu g/mL) treatment. AST-VII and AST-VII-integrated LNPs could be used as efficacious adjuvants for an inactivated H3N2 vaccine in vitro, and cytokine response through Th1/Th17 route was reported.Article Citation - WoS: 2Türkiye’de Kutanöz Leyşmanyazis Hastalarından Elde Edilen Leishmania İzolatlarındaki Farklılıklar ve Bunların Fare Modeline Klinik Yansıması(Ankara Microbiology Society, 2020) Özbilgin, Ahmet; Çulha, Gülnaz; Güray, Melda Zeynep; Zeyrek, Fadile Yıldız; Akyar, Işın; Toz, Seray; Gündüz, CumhurAlthough asexual reproduction has been attributed to Leishmania species, genetic exchange has recently been demonstrated, which helped emerging of hybrid isolates. Situated on the crossroads between three continents, Leishmania hybrids may be present in Turkey. In Turkey, visceral leishmaniasis caused by Leishmania infantum is less common, while cutaneous leishmaniasis (CL) caused by Leishmania tropica and L.infantum could reach 2500 reported cases a year. Our aim was to investigate genetic variability of local Leishmania species and presence of hybrid Leishmania strains in Turkey. Twenty CL patients from Sanliurfa and Hatay, where only L.tropica and both L.tropica and L.infantum cause CL, respectively, were registered equally. All isolates were assessed with real-time polymerase chain reaction (Rt-PCR), isoenzyme analysis, gene sequencing, two-dimensional gel electrophoresis (2D-PAGE) and MALDI-TOF/TOF-MS followed by in vivo analyses on mouse model. Identification of differentially expressed proteins was performed. These proteins were confirmed by sequence analysis. All isolates from Sanliurfa were found to be L.tropica which caused cutaneous infection in mice. However, one of 10 isolates from Hatay was found as Leishmania major which caused cutaneous infection. Five isolates were found as L.tropica with Rt-PCR and gene sequencing, one of which had one different protein from the reference L.tropica strain and caused cutaneous infection. Four of the five isolates had five different proteins compared to reference strain and caused both cutaneous and visceral infections. Remaining four isolates showed double melting curves in Rt-PCR, which were concordant with L.tropica and L.infantum. Their sequencing and isoenzyme analyses indicated them as L.infantum. They had six different proteins compared to reference L.infantum strain and caused cutaneous and visceral infections. It is concluded that the isolates with different proteins were hybrid Leishmania species. In the present study, outcomes of the proteomics, genomics, clinical manifestations and tissue tropism on animal models were evaluated together for the first time. In addition to L. tropica and L.infantum, L.major was identified as a causative agent for CL and hybrids of Linfantum/tropica were also shown to be present.