PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
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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: 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: 2Evaluation of Malassezia Species by Fourier Transform Infrared (ft-Ir) Spectroscopy(Ankara Microbiology Society, 2011) Ergin, Çağrı; Vuran, M. Emre; Gök, Yaşar; Özdemir, Durmuş; Karaarslan, Aydın; Kaleli, İlnur; Çon, Ahmet HilmiMalassezia species which are lipophilic exobasidiomycetes fungi, have been accepted as members of normal cutaneous flora as well as causative agent of certain skin diseases. In routine microbiology laboratory, species identification based on phenotypic characters may not yield identical results with taxonomic studies. Lipophilic and lipid-dependent Malassezia yeasts require lipid-enriched complex media. For this reason, Fourier transform infrared (FT-IR) spectroscopy analysis focused on lipid window may be useful for identification of Malassezia species. In this study, 10 different standard Malassezia species (M.dermatis CBS 9145, M.furfur CBS 7019, M.japonica CBS 9432, M.globosa CBS 7966, M.nana CBS 9561, M.obtusa CBS 7876, M.pachydermatis CBS 1879, M.slooffiae CBS 7956, M.sympodialis CBS 7222 and M.yamatoensis CBS 9725) which are human pathogens, have been analyzed by FT-IR spectroscopy following standard cultivation onto modified Dixon agar medium. Results showed that two main groups (M1; M.globosa, Robtusa, M.sympodialis, M.dermatis, M.pachydermatis vs, M2; M.furfur, M.japonica, M.nana, M.slooffiae, M.yamatoensis) were discriminated by whole spectra analysis. M.obtusa in M1 by 1686-1606 cm(-1) wavenumber ranges and M.japonicum in M2 by 2993-2812 cm(-1) wavenumber ranges were identified with low level discrimination power. Discriminatory areas for species differentiation of M1 members as M.sympodialis, M.globosa and M.pachydermatis and M2 members as M.furfur and M.yamatoensis could not be identified. Several spectral windows analysis results revealed that FT-IR spectroscopy was not sufficient for species identification of culture grown Malassezia species.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.Article Citation - WoS: 10Citation - Scopus: 9Bi̇yomalzemelerden İ̇zole Edi̇len Staphylococcus Epidermidis Suşlarinin Yüzey Özelli̇kleri̇ni̇n Beli̇rlenmesi̇(Ankara Mikrobiyoloji Derneği, 2010) Sudağıdan, Mert; Erdem, İlker; Çavuşoğlu, Cengiz; Çiftçioğlu, MuhsinThe surface properties of bacteria play an important role on adhesion to the biomaterial surface. In this study, the surface properties of Staphylococcus epidermidis strains isolated from clinically used polymeric biomaterial surfaces were investigated on the basis of zeta potential, hydrophobicity and surface topography. A total of 10 S.epidermidis strains isolated from intravenous catheters (n= 5), endotracheal tubes (n= 3) and central venous catheters (n= 2) which were used in the patients of pulmonary Intensive Care Unit, Ege University Medical Faculty Hospital, were included to the study. Seven of those isolates were biofilm producers, inhabiting biofilm genes, 2 were non-biofilm producers, however, inhabiting biofilm genes, and 1 was non-biofilm producer, inhabiting no biofilm genes. Zeta potential analysis have been performed in 3 different buffers (phosphate-buffered saline, 1 mM potassium chloride and 1 mM potassium phosphate buffer) and at different pH values (pH 4.1-8.2), in order to simulate in vivo environment of the biomaterials. Hydrophobicities of the strains were examined by bacterial adhesion to hydrocarbon (BATH) test and the surface topography of biofilms and slime layers were visualized by atomic force microscopy (AFM) and scanning electron microscopy (SEM) methods. It was found that all strains have negative zeta potential values (surface charge) in all buffers and pH values. In hydrophobicity analysis, the highest value (86%) was determined for non-biofilm forming S.epidermidis strain YT-169b (endotracheal tube isolate) and the lowest hydrophobicity (2.5%) was determined for biofilm forming S.epidermidis strain YT-212 (central venous catheter isolate). Biofilm and slime layers of the strains were imaginated by AFM and SEM analysis in ?m scale. SEM analysis showed that bacteria highly adhered to rough surfaces on biomaterial surfaces and the produced slime layers covered the surface of bacteria. In conclusion, elucidating the surface properties of opportunistic pathogens in different physiologic buffers will give important clues for the production of non-adhesive materials and antibacterial surfaces for those bacteria. It was also estimated that designing the surface of the biomaterial to have negative surface charge in the body and to be as smooth as possible will hamper biofilm formation.Article Citation - WoS: 19Citation - Scopus: 18Biyomalzeme Yüzeylerinden İzole Edilen Metisiline Dirençli Staphylococcus Aureus Suşlarında Virülans Genlerinin Araştırılması(Ankara Microbiology Society, 2008) Sudağıdan, Mert; Çavuşoğlu, Cengiz; Bacakoğlu, FezaStafilokoklar, biyomalzeme kaynaklı nozokomiyal enfeksiyonların en önemli etkenlerindendir. Bu çalışmada, Göğüs Hastalıkları Yoğun Bakım Ünitesi (YBÜ)'nde yatan 48 hastada kullanılan polimerik biyomalzeme yüzeylerinden izole edilen metisiline dirençli 11 Staphylococcus aureus suşunda virülans genlerinin varlığının saptanması ve bunların bazılarının fenotipik ifadelerinin araştırılması amaçlanmıştır. Çalışmamızda polimeraz zincir reaksiyonu (PCR) ile özgül primerler kullanılarak, bağlanma ve biyofilm oluşumundan sorumlu genler (icaA, icaC, bap), metisilin direnç geni (mecA), enterotoksin A-E üretiminden sorumlu genler (sea, seb, sec, sed, see), toksik şok sendromu toksini geni [tst), eksfoliatif toksin A ve B genleri (eta ve etb), alfa ve beta-hemolizin genleri (hla ve hlb), stafilokokal ekzotoksin benzeri protein-1 geni (sef1), proteaz genleri (sspA, sspB, aur, serine proteaz geni), lipaz geni (geh) ve regülatör genler (sarA ve agrCA) araştırılmıştır. Ayrıca suşların fenotipik olarak biyofilm oluşturma, antibiyotik duyarlılık, proteaz ve lipaz üretimi gibi özellikleri de değerlendirilmiştir. Biyofilm testlerinde, biyofilm yapan ve "slime" üreten suşlara rastlanmamış, ancak tüm suşların biyofilm yapımında rol oynayan icaA genine sahip olduğu bulunmuştur. Bununla birlikte biyofilm yapımında rol oynayan icaC ve bap genleri tespit edilememiştir. Tüm suşlarda mecA geninin varlığı saptanmış ve suşların hepsinin oksasilin, penisilin G ve gentamisine; 10'unun eritromisine ve dokuzunun da ofloksasine dirençli olduğu bulunmuştur. İzolatların tümü vankomisin, teikoplanin ve ko-trimoksazole duyarlı olarak saptanmıştır. Ekzotoksin ve regülatör genlerinin taranması sonucunda, suşların sea, seti, hla, hlb ve sarA genlerini taşıdığı belirlenmiştir. PCR ile tüm suşların, çalışılan bütün proteaz genlerine (sspA, sspB, aur ve serin proteaz geni) sahip olduğu görülmüş, ancak sütlü (skim milk ve milk agar) ve kazein ağarlarda yapılan proteaz üretimi testlerinde negatif sonuç alınmıştır. Lipaz üretiminin belirlenmesi için Tween 20, Tween 80 ve tributyrin içeren besiyerleri kullanılmış ve tüm suşlarda geç dönemde (inkübasyonun üçüncü günü) pozitif sonuç alınmasına karşın, izolatların hiçbirisinde lipaz üretiminden sorumlu geh geni bulunmamıştır. Sonuç olarak, biyomalzeme yüzeylerinden izole edilen S.aureus suşlarında, araştırılan virülans genlerinden bazılarının varlığı saptanmış, ancak bunların tam olarak fenotipe yansımadığı izlenmiştir. İzolat sayısının azlığına ve tüm genlerin ekspresyonlarının fenotipik olarak çalışılamamış olmasına rağmen, bu genlerin varlığının yoğun bakım hastalan için potansiyel bir risk teşkil edebileceği düşünülmüştür.Editorial Citation - WoS: 3Citation - Scopus: 4La médecine de précision en oncologie: challenges, enjeux et nouveaux paradigmes(John Libbey Eurotext Ltd, 2019) Cox, Stephanie; Rousseau-Tsangaris, Marina; Abou-Zeid, Nancy; Dalle, Stephane; Leurent, Pierre; Cutivet, Arnaud; Baran, YusufL'oncologie médicale a pris, depuis quelques années, un tournant substantiel en intégrant la dimension génomique dans la prise de décision thérapeutique. En raison de l'accès aux technologies de séquençage (exome complet, séquençage ciblé du génome, séquençage de l'ARN, ADN circulant. . .) facilité par la mise en place de plateformes de biologie moléculaire et la diminution des coûts par échantillon, la caractérisation moléculaire est devenue un outil supplémentaire à la disposition du clinicien, s'ajoutant au diagnostic histologique et immunohistochimique et aux données d'imagerie radiologique. Cette approche moléculaire a permis d'identifier de nouvelles formes nosologiques et permet, au-delà de l'aspect cognitif, de renseigner sur les altérations qui sont à prendre en compte dans les décisions thérapeutiques (biomarqueurs prédictifs, activation de voies spécifiques, mutations de résistance). C'est dans ce contexte de profond et rapide changement de pratique médicale et scientifique qu'il a été proposé de réfléchir collectivement aux nouveaux enjeux sous la forme d'un workshop à l'occasion de Biovision qui s'est tenu à Lyon, du 4 au 6 avril 2017.Article Citation - WoS: 24Citation - Scopus: 29Il-17, Il-21, and Il-22 Cytokines of T Helper 17 Cells in Cancer(Mary Ann Liebert, 2019) Nalbant, AytenCD4(+) T helper (Th) cells are important regulators of cellular immune response. Newly discovered interleukin (IL)-17-producing CD4(+) T cells are known as T helper 17 cells (Th17). They are distinct subset from the T helper type 1 (Th1) and 2 (Th2) lineages. The differentiation of Th17 cells has been intensively studied; however, the role of Th17 cells in different diseases including cancer is still under investigation. Besides IL-17 family cytokines, Th17 cells produce IL-22, IL-21, and IL-26. The dysregulated function of Th17 cells and their cytokines could contribute to pathology of diseases, including cancer. The role of cytokines of Th17 cells such as IL-17, IL-21, and IL-22 in cancer will be discussed in this review.Article Citation - WoS: 1Citation - Scopus: 2Trna Wobble Base Modifications and Boric Acid Resistance in Yeast: Boron-Resistant Deletion Mutants Induce the General Amino Acid Control Mechanism and Activate Boron Efflux(Pleiades Publishing, 2020) Uluisik, I.; Karakaya, H.C.; Koc, A.Abstract: 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 (elp1∆, elp3∆, elp6∆, ncs2∆, ncs6∆ and kti12∆) 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. © 2020, Pleiades Publishing, Inc.