Araştırma Çıktıları

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    Translating Biotechnology to Knowledge-Based Innovation, Peace, and Development? Deploy a Science Peace Corps-An Open Letter to World Leaders
    (MARY ANN LIEBERT, INC, 2014-01-01) Hekim, Nezih; Coskun, Yavuz; Sinav, Ahmet; Abou-Zeid, Alaa H.; Agirbasli, Mehmet; Akintola, Simisola O.; Aynacioglu, Sukru; Bayram, Mustafa; Bragazzi, Nicola Luigi; Dandara, Collet; Dereli, Turkay; Dove, Edward S.; Elbeyli, Levent; Endrenyi, Laszlo; Erciyas, Kamile; Faris, Jack; Ferguson, Lynnette R.; Gogus, Fahrettin; Gungor, Kivanc; Gursoy, Mervi; Gursoy, Ulvi K.; Karaomerlioglu, M. Asim; Kickbusch, Ilona; Kilic, Turker; Kilinc, Metin; Kocagoz, Tanil; Lin, Biaoyang; LLerena, Adrian; Manolopoulos, Vangelis G.; Nair, Bipin; Ozkan, Bulent; Pang, Tikki; Sardas, Semra; Srivastava, Sanjeeva; Toraman, Cengiz; Ustun, Kemal; Warnich, Louise; Wonkam, Ambroise; Yakicier, Mustafa Cengiz; Yasar, Umit; Ozdemir, Vural
    Scholarship knows no geographical boundaries. This science diplomacy and biotechnology journalism article introduces an original concept and policy petition to innovate the global translational science, a Science Peace Corps. Service at the new Corps could entail volunteer work for a minimum of 6 weeks, and up to a maximum of 2 years, for translational research in any region of the world to build capacity manifestly for development and peace, instead of the narrow bench-to-bedside model of life science translation. Topics for translational research are envisioned to include all fields of life sciences and medicine, as long as they are linked to potential or concrete endpoints in development, foreign policy, conflict management, post-crisis capacity building, and/or peace scholarship domains. As a new instrument in the global science and technology governance toolbox, a Science Peace Corps could work effectively, for example, towards elucidating the emerging concept of ``one health{''}-encompassing human, environmental, plant, microbial, ecosystem, and planet health-thus serving as an innovative crosscutting pillar of 21st century integrative biology. An interdisciplinary program of this caliber for development would link 21st century life sciences to foreign policy and peace, in ways that can benefit many nations despite their ideological differences. We note that a Science Peace Corps is timely. The Intergovernmental Panel on Climate Change (IPCC) of the United Nations released the Fifth Assessment Report on March 31, 2014. Worrisomely, the report underscores that no person or nation will remain untouched by the climate change, highlighting the shared pressing life sciences challenges for global society. To this end, we recall that President John F. Kennedy advocated for volunteer work that has enduring, transgenerational, and global impacts. This culminated in establishment of the Peace Corps in 1961. Earlier, President Abraham Lincoln aptly observed, ``nearly all men can stand adversity, but if you want to test a man's character, give him power.{''} We therefore petition President Barack Obama, other world leaders, and international development agencies in positions of power around the globe, to consider deploying a Science Peace Corps to cultivate the essential (and presently missing) ties among life sciences, foreign policy, development, and peace agendas. A Science Peace Corps requires support by a credible and independent intergovernmental organization or development agency for funding, and arbitration in the course of volunteer work when the global versus local (glocal) value-based priorities and human rights intersect in synergy or conflict. In all, Science Peace Corps is an invitation to a new pathway for competence in 21st century science that is locally productive and globally competitive. It can open up scientific institutions to broader considerations and broader inputs, and thus cultivate vital translational science in a world sorely in need of solidarity and sustainable responses to the challenges of 21st century science and society.
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    Comparison of a novel antigen detection test with reverse transcription polymerase chain reaction assay for laboratory diagnosis of SARS-CoV-2 infection
    (SPRINGER HEIDELBERG, 2022-01-01) Cirit, Osman Sezer; Mutlu, Esvet; Sancak, Banu; Kocagoz, Tanil; Can, Ozge; Cicek, Candan; Sayiner, Ayca Arzu; Appak, Ozgur; Uyar, Neval Yurttutan; Kulah, Canan; Cicek, Aysegul Copur; Ozgumus, Osman Birol; Altintop, Yasemin Ay; Saatci, Esma; Karsligil, Tekin; Zer, Yasemin; Ozen, Nevgun Sepin; Cekin, Yesim; Karahan, Zeynep Ceren; Evren, Ebru; Karakoc, Ayse Esra; Orhan, Sultan Gulbahce; Mutlu, Derya; Bozdemir, Tugba; Cayci, Yeliz Tanriverdi; Cinar, Canberk; Tasbakan, Meltem; Mert, Merve; Cinar, Ece; Kutsoylu, Oya Ozlem Eren; Kocagoz, Sesin; Erturk, Ayse; Celik, Ilhami; Mete, Ayse Ozlem; Eneyli, Muge Gunalp; Akdemir, Irem; Karakok, Taliha; Inan, Dilara; Atilla, Aynur; Taflan, Sevket Onur; Yoruk, Kagan Etka
    Molecular diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by real-time reverse transcription polymerase chain reaction (RT-PCR) in respiratory specimens is considered the gold standard method. This method is highly sensitive and specific but it has some limitations such as being expensive and requiring special laboratory equipment and skilled personnel. RapidFor (TM) Antigen Rapid Test Kit is a commercially available Ag-RDT which is produced in Turkey and designed to detect the nucleocapsid antigen of SARS-CoV-2 in nasopharyngeal swab samples. The aim of this study was to evaluate the performance of this novel SARS-CoV-2 antigen detection considering the RT-PCR method as the gold standard. Four hundred forty-four nasopharyngeal swab samples which were collected from the patients who met clinical criteria of COVID-19 from ten centers in Turkey between September 2020 and February 2021 were included in the study. All the nasopharyngeal swab samples were tested for SARS-CoV-2 RNA using commercial RT-PCR kits (Bioeksen and A1 Lifesciences, Istanbul, Turkey) according to the manufacturer's instructions. Viral loads were assessed according to the cycle threshold (Ct) values. RapidFor (TM) SARS-CoV-2 antigen test (Vitrosens Biotechnology, Istanbul, Turkey) was used to investigate the presence of SARS-CoV-2 antigen in all samples following the manufacturer's instructions. Out of 444 nasopharyngeal swab samples tested, 346 (77.9\%) were positive and 98 (22.1\%) were negative for SARS-CoV-2 RNA by RTPCR. Overall sensitivity of the RapidFor (TM). Antigen Rapid Test Kit was 80.3\% whereas specificity was found to be 87.8\%. Positivity rate of rapid antigen test in samples with Ct values over 25 and below 30 was 82.7\%, while it increased to 95.7\% in samples 20 <= Ct < 25 and reached 100\% in samples with Ct values below 20. RapidFor (TM) SARS-CoV-2 Ag test might be a good choice in the screening of symptomatic and asymptomatic patients and their contacts for taking isolation measures early, with advantages over RT-PCR as being rapid, easy and being applicable in every laboratory and even at point of care.
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    Diversity of Leishmania Strains Isolated from Cutaneous Leishmaniasis Patients in Turkey and its Reflection to Clinics in Mice Model
    (ANKARA MICROBIOLOGY SOC, 2020-01-01) Ozbilgin, Ahmet; Culha, Gulnaz; Guray, Melda Zeynep; Zeyrek, Fadile Yildiz; Akyar, Isin; Toz, Seray; Ural, Ipek Ostan; Kurt, Ozgur; Kocagoz, Tanil; Cavus, Ibrahim; Gunduz, Cumhur
    Although 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.
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    Design, Synthesis, and Molecular Docking Studies of a Conjugated-Thiadiazole Thiourea Scaffold as Antituberculosis Agents
    (PHARMACEUTICAL SOC JAPAN, 2016-01-01) Tatar, Esra; Karakus, Sevgi; Kucukguzel, Sukriye Guniz; Okullu, Sinem Oktem; Unubol, Nihan; Kocagoz, Tanil; De Clercq, Erik; Andrei, Graciela; Snoeck, Robert; Pannecouque, Christophe; Kalayci, Sadik; Sahin, Fikrettin; Sriram, Dharmarajan; Yogeeswari, Perumal; Kucukguzel, Ilkay
    In view of the emergence and frequency of multidrug-resistant and extensively drug-resistant tuberculosis and consequences of acquired resistance to clinically used drugs, we undertook the design and synthesis of novel prototypes that possess the advantage of the two pharmacophores of thiourea and 1,3,4-thiadiazole in a single molecular backbone. Three compounds from our series were distinguished from the others by their promising activity profiles against Mycobacterium tuberculosis strain H(37)Rv. Compounds 11 and 19 were the most active representatives with minimum inhibitory concentration (MIC) values of 10.96 and 11.48 mu m, respectively. Compound 15 was shown to inhibit M. tuberculosis strain H(37)Rv with an MIC value of 17.81 mu m. Cytotoxicity results in the Vero cell line showed that these three derivatives had selectivity indices between 1.8 and 8.7. In order to rationalize the biological results of our compounds, molecular docking studies with the enoyl acyl carrier protein reductase (InhA) of M. tuberculosis were performed and compounds 11, 15, and 19 were found to have good docking scores in the range of -7.12 to -7.83 kcal/mol.
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    Label-free molecular detection of antibiotic susceptibility forMycobacterium smegmatisusing a low cost electrode format
    (WILEY, 2021-01-01) Guzel, Fatma Dogan; Ghorbanpoor, Hamed; Dizaji, Araz Norouz; Akcakoca, Iremnur; Ozturk, Yasin; Kocagoz, Tanil; Corrigan, Damion K.; Avci, Huseyin
    Today, the emergence of antibiotic resistance in pathogenic bacteria is considered an important problem for society. Excessive consumption of antibiotics, long-term treatments, and inappropriate prescriptions continually increase the severity of the problem. Improving antibiotic stewardship requires improved diagnostic testing, and, therefore,in vitroantibiotic susceptibility testing is becoming increasingly important. This research details the development of an antibiotic susceptibility test forMycobacterium smegmatisusing streptomycin as antibiotics. This strain was selected because it is a member of the slow growingMycobacteriumgenus and serves as a useful surrogate organism forM. tuberculosis. A commercially available and low-cost screen-printed gold electrode in combination with a specifically developed nucleic acid probe sequence for the 16SrRNA region of the mycobacterial genome was employed to monitorM. smegmatisnucleic acid sequences using the techniques of square-wave voltammetry and electrochemical impedance spectroscopy. The results show that it was possible to detectM. smegmatissequences and distinguish antibiotic-treated cells from untreated cells with a label-free molecular detection. As a result, thein vitroantibiotic susceptibility test revealed thatM. smegmatisshowed sensitivity to streptomycin after a 24-H incubation, with the developed protocol representing a potential approach to determining antibiotic susceptibility more quickly and economically than current methods.
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    Polymeric Approach to Adjuvant System in Antibody Production against Leishmaniasis Based on Hybridoma Technology
    (IRANIAN SCIENTIFIC SOCIETY MEDICAL ENTOMOLOGY, 2022-01-01) Yildiz, Asli Pinar Zorba; Koken, Gulnaz Yildirim; Abamor, Emrah Sefik; Bagirova, Melahat; Tosyali, Ozlem Ayse; Kocagoz, Tanil; Allahverdiyev, Adil
    Background: Leishmaniasis is a zoonotic disease, which is one of the serious public health problems in the world. Nowadays, antibody production using hybridoma technology may be a correct approach in terms of sensitivity in the diagnosis of diseases such as leishmaniasis. The aim of this study was investigation of the effectiveness of different adjuvants on polyclonal antibody production against L. tropica based on hybridoma technique.Methods: Accordingly, Freund's adjuvant (1956, M. tuberculosis), as a classic adjuvant in studies, was used comparatively with the non-toxic polymeric based Polyoxidonium adjuvant. All animal immunization procedures were conducted at Bezm-i Alem University Experimental Animal Research Center. The adjuvant response was tested both in the serum sample and in the antibodies produced by the hybridomas. The antibody titers were determined with ELISA.Results: Freund's and Polyoxidonium (PO) group blood titer's increased approximately 5.5 fold compared to control after the 6(th) and 8(th) immunization. Hybridomas produced from mice immunized with PO adjuvant induced only antigen-specific antibody response and did not develop an immune response against the adjuvant.Conclusion: Adjuvant selection is very important in terms of the specificity of antibody responses of cells produced in hybridoma technology. Therefore, PO is recommended as a new adjuvant system in this study.
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    Biologically modified microelectrode sensors provide enhanceds ensitivity for detection of nucleic acid sequences from Mycobacterium tuberculosis
    (ELSEVIER, 2020-01-01) Blair, Ewen O.; Hannah, Stuart; Vezza, Vincent; Avci, Huseyin; Kocagoz, Tanil; Hoskisson, Paul A.; Guzel, Fatma D.; Corrigan, Damion K.
    This paper describes improved sensitivity when using biosensors based on microfabricated microelectrodes to detect DNA, with the goal of progressing towards a low cost and mass manufacturable assay for antibiotic resistance in tuberculosis (TB). The microelectrodes gave an improvement in sensitivity compared to polycrystalline macroelectrodes. In addition, experimental parameters such as redox mediator concentration and experimental technique were investigated and optimised. It was found that lower concentrations of redox mediator gave higher signal changes when measuring hybridisation events and, at these lower concentrations, square wave voltammetry was more sensitive and consistent than differential pulse voltammetry. Together, this paper presents a quantifiable comparison of macroelectrode and microelectrode DNA biosensors. The final assay demonstrates enhanced sensitivity through reduction of sensor size, reduction of redox mediator concentration and judicious choice of detection technique, therefore maintaining manufacturability for incorporation into point of care tests and lab-on-a-chip devices.
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    Investigation of the Effect of Channel Structure and Flow Rate on On-Chip Bacterial Lysis
    (IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC, 2021-01-01) Dizaji, Araz Norouz; Ozturk, Yasin; Ghorbanpoor, Hamed; Cetak, Ahmet; Akcakoca, Iremnur; Kocagoz, Tanil; Avci, Huseyin; Corrigan, Damion; Guzel, Fatma Dogan
    Successful lysis of cells/microorganisms is a key step in the sample preparation in fields like molecular biology, bioengineering, and biomedical engineering. This study therefore aims to investigate the lysis of bacteria on-chip and its dependence on both microfluidic channel structure and flow rate. Effects of temperature on lysis on-chip were also investigated. To perform these investigations, three different microfluidic chips were designed and produced (straight, zigzag and circular configurations), while the length of the channels were kept constant. As an exemplary case, Mycobacterium smegmatis was chosen to represent the acid-fast bacteria. Bacterial suspensions of 1.5 McFarland were injected into the chips at various flow rates (0.6-8 mu l/min) either at room temperature or 50 degrees C. In order to understand the on-chip lysis performance fully, off-chip experiments were carried out at durations which are equal to those bacteria spent in the channel from inlet to the outlet at different flow rates. We also performed COMSOL multiphysics program simulations to evaluate further the effect of the applied parameters. As a result, we found that the structure and the flow rate do not affect lysis over all in all investigated channel types, however on-chip experiments at room temperature produced more effective lysis compared to the on-chip and the off-chip samples performed at higher temperatures. Interestingly on-chip experiments at higher tempratures do not result in effective lysis.
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    Multiplex-PCR-Based Screening and Computational Modeling of Virulence Factors and T-Cell Mediated Immunity in Helicobacter pylori Infections for Accurate Clinical Diagnosis
    (PUBLIC LIBRARY SCIENCE, 2015-01-01) Oktem-Okullu, Sinem; Tiftikci, Arzu; Saruc, Murat; Cicek, Bahattin; Vardareli, Eser; Tozun, Nurdan; Kocagoz, Tanil; Sezerman, Ugur; Yavuz, Ahmet Sinan; Sayi-Yazgan, Ayca
    The outcome of H. pylori infection is closely related with bacteria's virulence factors and host immune response. The association between T cells and H. pylori infection has been identified, but the effects of the nine major H. pylori specific virulence factors
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    A rapid, ultrasensitive voltammetric biosensor for determining SARS-CoV-2 spike protein in real samples
    (ELSEVIER ADVANCED TECHNOLOGY, 2021-01-01) Liv, Lokman; Coban, Gizem; Nakiboglu, Nuri; Kocagoz, Tanil
    The ongoing coronavirus disease 2019 (COVID-19) pandemic continues to threaten public health systems all around the world. In controlling the viral outbreak, early diagnosis of COVID-19 is pivotal. This article describes a novel method of voltammetrically determining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein with a newly designed sensor involving bovine serum albumin, SARS-CoV-2 spike antibody and a functionalised graphene oxide modified glassy carbon electrode (BSA/AB/f-GO/GCE) or screen-printed electrode (BSA/AB/f-GO/SPE). The oxidation reaction based on the antibody-antigen protein interaction was evaluated as a response to SARS-CoV-2 spike protein at -200 mV and 1430 mV with the BSA/AB/f-GO/SPE and BSA/AB/fGO/GCE, respectively. The developed sensors, BSA/AB/f-GO/SPE and BSA/AB/f-GO/GCE, could detect 1 ag/mL of virus spike protein in synthetic, saliva and oropharyngeal swab samples in 5 min and 35 min, and both sensors demonstrated a dynamic response to the SARS-CoV-2 spike protein between 1 ag/mL and 10 fg/mL. Real-time polymerase chain reaction (RT-PCR), rapid antigen test and the proposed method were applied to saliva samples. When compared to RT-PCR, it was observed that the developed method had a 92.5\% specificity and 93.3\% sensitivity. Moreover, BSA/AB/f-GO/SPE sensor achieved 91.7\% accuracy compared to 66.7\% accuracy of rapid antigen test kit in positive samples. In view of these findings, the developed sensor provides great potential for the diagnosing of COVID-19 in real samples.