WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7150
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Article K41-A Enhances the Antiproliferative Efficacy of Cisplatin in Neuroblastoma by Modulating Apoptosis and Autophagy(Oxford University Press, 2026) Sanlav, Gamze; Kum Ozsengezer, Selen; Altun, Zekiye; Bedir, Erdal; Aktas, Safiye; Olgun, NurObjectives Neuroblastoma (NB), the most common extracranial tumor in childhood, has a poor prognosis, especially in cases with MYC gene amplification. Cisplatin (CDDP) is widely used in treatment, but its effectiveness is limited due to chemotherapy resistance. Autophagy plays a dual role in cancer progression, either promoting survival or contributing to cell death.Methods This study explores the anticancer effects of K41-A, a polycyclic polyether molecule, alone and in combination with CDDP in SH-SY5Y and KELLY NB cell lines, the HE-IOC1 noncancerous cochlear cell line, and the NB xenograft model.Key findings For the first time, we demonstrate that K41-A, either alone or combined with CDDP, significantly inhibits cell proliferation selectively in NB cells, sparing noncancerous cells. This study confirmed that K41-A alone and in combination with CDDP induced changes in both apoptotic and autophagic cell death components in NB, resulting in antiproliferative activity in vitro and in vivo. In addition, the combination with CDDP enhanced the therapeutic efficacy of K41-A.Conclusions These results highlight the potential of K41-A as a candidate drug for the treatment of NB.Article Citation - WoS: 1Pupillometric and Perceptual Approaches Provide Independent Estimates of Melanopsin Activity in Humans(Oxford University Press, 2025) Woelders, T.; Didikoglu, A.; Bickerstaff, L.; Brown, T.M.; Lucas, R.J.Study Objectives: Melanopsin-expressing retinal ganglion cells, which provide light information to time sleep and entrain circadian clocks, also influence perceived brightness raising the possibility that psychophysical paradigms could be used to explore the origins and implications of variability in melanopic sensitivity. We aimed to develop accessible psychophysical tests of melanopic vision and relate outcomes with a pupillometric measure of melanopsin function (post-illumination pupil response) and prior light exposure. Methods: Individually calibrated pairs of isoluminant stimuli differing in melanopic radiance from a four primary source were presented sequentially with superimposed random color offsets in a two alternative forced choice brightness preference paradigm to 41 naïve adult participants with personal light exposure data for the prior 7 days and post-illumination pupil response measures defined by comparing maintained pupil constriction for luminance matched “red” vs “blue” pulses. Results: Across participants we observed the expected tendency to report positive melanopsin contrast stimuli as “brighter” (one-tailed t-test p < 0.001), but with substantial inter-individual variability in both sensitivity (melanopsin contrast at criterion preference p = 0.75) and amplitude (preference at maximum melanopic contrast). There was little correlation between these psychophysical outcomes and post-illumination pupil response magnitude, or between either psychophysical or post-illumination pupil response measures and light history metrics (pairwise Pearson correlation coefficients -0.5> < 0.5). Random forest machine learning failed to satisfactorily predict outcome for either psychophysical or post-illumination pupil response measures based upon these inputs. Conclusions: Our findings reveal that estimates of melanopic function provided by perceptual and pupillometric paradigms can be largely independent of one another and of recent history of light exposure. © The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society.Review Citation - Scopus: 5Scientists Without Borders: Lessons From Ukraine(Oxford University Press, 2023) Wolfsberger, W.; Chhugani, K.; Shchubelka, K.; Frolova, A.; Salyha, Y.; Zlenko, O.; Arych, M.Conflicts and natural disasters affect entire populations of the countries involved and, in addition to the thousands of lives destroyed, have a substantial negative impact on the scientific advances these countries provide. The unprovoked invasion of Ukraine by Russia, the devastating earthquake in Turkey and Syria, and the ongoing conflicts in the Middle East are just a few examples. Millions of people have been killed or displaced, their futures uncertain. These events have resulted in extensive infrastructure collapse, with loss of electricity, transportation, and access to services. Schools, universities, and research centers have been destroyed along with decades' worth of data, samples, and findings. Scholars in disaster areas face short- and long-term problems in terms of what they can accomplish now for obtaining grants and for employment in the long run. In our interconnected world, conflicts and disasters are no longer a local problem but have wide-ranging impacts on the entire world, both now and in the future. Here, we focus on the current and ongoing impact of war on the scientific community within Ukraine and from this draw lessons that can be applied to all affected countries where scientists at risk are facing hardship. We present and classify examples of effective and feasible mechanisms used to support researchers in countries facing hardship and discuss how these can be implemented with help from the international scientific community and what more is desperately needed. Reaching out, providing accessible training opportunities, and developing collaborations should increase inclusion and connectivity, support scientific advancements within affected communities, and expedite postwar and disaster recovery. © 2023 The Author(s). Published by Oxford University Press GigaScience.Article Citation - WoS: 6Citation - Scopus: 10Efficient Privacy-Preserving Whole-Genome Variant Queries(Oxford University Press, 2022) Akgün, Mete; Pfeifer, Nico; Kohlbacher, OliverMotivation: Diagnosis and treatment decisions on genomic data have become widespread as the cost of genome sequencing decreases gradually. In this context, disease-gene association studies are of great importance. However, genomic data are very sensitive when compared to other data types and contains information about individuals and their relatives. Many studies have shown that this information can be obtained from the query-response pairs on genomic databases. In this work, we propose a method that uses secure multi-party computation to query genomic databases in a privacy-protected manner. The proposed solution privately outsources genomic data from arbitrarily many sources to the two non-colluding proxies and allows genomic databases to be safely stored in semi-honest cloud environments. It provides data privacy, query privacy and output privacy by using XOR-based sharing and unlike previous solutions, it allows queries to run efficiently on hundreds of thousands of genomic data. Results: We measure the performance of our solution with parameters similar to real-world applications. It is possible to query a genomic database with 3 000 000 variants with five genomic query predicates under 400 ms. Querying 1 048 576 genomes, each containing 1 000 000 variants, for the presence of five different query variants can be achieved approximately in 6 min with a small amount of dedicated hardware and connectivity. These execution times are in the right range to enable real-world applications in medical research and healthcare. Unlike previous studies, it is possible to query multiple databases with response times fast enough for practical application. To the best of our knowledge, this is the first solution that provides this performance for querying large-scale genomic data.Article Artisans Meet Design: the Reception of the Turkish Handicraft Development Office in Turkey(Oxford University Press, 2020) Emgin, BaharPeter Muller-Munk Associates, an American industrial design firm, established the Turkish Handicraft Development Office in 1957 in Ankara as part of the US technical assistance program to developing nations. The aim of the program was to improve selected local crafts products in order to make them appealing for the American market. To this end, American designers and local craftspeople produced about 150 prototypes formed by creative combinations of meerschaum, copperware, ceramics, woodwork and basket weaving. When the office was closed in the early 1960s because of its failure to mass-produce the samples, it left behind a lively debate regarding the improvement of craft production and its relation to industrialization and economic growth. This article focuses on these debates to determine the place allocated to design within the discussions of crafts as a socio-economic activity. The article will focus on the reception of the design assistance program among the local actors to answer how Turkish crafts practitioners and officials perceived design, how the emergent concept of design was linked with handicraft and artisanal production, and how it took place as part of the agenda of economic and industrial development.Article Citation - WoS: 13Multisite Photometric Campaign on the High-Amplitude Delta Scuti Star Kic 6382916(Oxford University Press, 2013) Ulusoy, Ceren; Ulas, B.; Guelmez, T.; Balona, L. A.; Stateva, I.; Iliev, I. Kh.; Carbognani, A.We present results of a multisite photometric campaign on the high-amplitude delta Scuti star KIC 6382916 in the Kepler field. The star was observed over a 85-d interval at five different sites in North America and Europe during 2011. Kepler photometry and ground-based multicolour light curves of KIC 6382916 are used to investigate the pulsational content and to identify the principal modes. High-dispersion spectroscopy was also obtained in order to derive the stellar parameters and projected rotational velocity. From an analysis of the Kepler time series, three independent frequencies and a few hundred combination frequencies are found. The light curve is dominated by two modes with frequencies f(1) = 4.9107 and f(2) = 6.4314 d(-1). The third mode with f(3) = 8.0350 d(-1) has a much lower amplitude. We attempt mode identification by examining the amplitude ratios and phase differences in different wavebands from multicolour photometry and comparing them to calculations for different spherical harmonic degree, l. We find that the theoretical models for f(1) and f(2) are in a best agreement with the observations and lead to value of l = 1 modes, but the mode identification of f(3) is uncertain due to its low amplitude. Non-adiabatic pulsation models show that frequencies below 6 d(-1) are stable, which means that the low frequency of f(1) cannot be reproduced. This is a further confirmation that current models predict a narrower pulsation frequency range than actually observed.Article Citation - WoS: 7Altorfev Facilitates the Prediction of Alternative Open Reading Frames in Eukaryotic Mrnas(Oxford University Press, 2017) Kochetov, Alex V.; Allmer, Jens; Klimenko, Alexandra I.; Zuraev, Bulat S.; Matushkin, Yury G.; Lashin, Sergey A.Motivation: Protein synthesis is not a straight forward process and one gene locus can produce many isoforms, for example, by starting mRNA translation from alternative start sites. altORF evaluator (altORFev) predicts alternative open reading frames within eukaryotic mRNA translated by a linear scanning mechanism and its modifications (leaky scanning and reinitiation). The program reveals the efficiently translated altORFs recognized by the majority of 40S ribosomal subunits landing on the 50-end of an mRNA. This information aids to reveal the functions of eukaryotic genes connected to synthesis of either unknown isoforms of annotated proteins or new unrelated polypeptides.Article Citation - WoS: 12Citation - Scopus: 15Effects of Cell-Mediated Osteoprotegerin Gene Transfer and Mesenchymal Stem Cell Applications on Orthodontically Induced Root Resorption of Rat Teeth(Oxford University Press, 2017) Amuk, Nisa Gül; Kurt, Gökmen; Baran, Yusuf; Seyrantepe, Volkan; Kartal Yandım, Melis; Adan, Aysun; Akyıldız Demir, Seçil; Kiraz, Yağmur; Sönmez, Mehmet FatihAim: The aim of this study is to evaluate and compare therapeutic effects of mesenchymal stem cell (MSCs) and osteoprotegerin (OPG) gene transfer applications on inhibition and/or repair of orthodontically induced inflammatory root resorption (OIIRR). Materials and methods: Thirty Wistar rats were divided into four groups as untreated group (negative control), treated with orthodontic appliance group (positive control), MSCs injection group, and OPG transfected MSCs [gene therapy (GT) group]. About 100 g of orthodontic force was applied to upper first molar teeth of rats for 14 days. MSCs and transfected MSC injections were performed at 1st, 6th, and 11th days to the MSC and GT group rats. At the end of experiment, upper first molar teeth were prepared for genetical, scanning electron microscopy (SEM), fluorescent microscopy, and haematoxylin eosin-tartrate resistant acid phosphatase staining histological analyses. Number of total cells, number of osteoclastic cells, number of resorption lacunae, resorption area ratio, SEM resorption ratio, OPG, RANKL, Cox-2 gene expression levels at the periodontal ligament (PDL) were calculated. Paired t-test, Kruskal-Wallis, and chi-square tests were performed. Results: Transferred MSCs showed marked fluorescence in PDL. The results revealed that number of osteoclastic cells, resorption lacunae, resorption area ratio, RANKL, and Cox-2 were reduced after single MSC injections significantly (P < 0.05). GT group showed the lowest number of osteoclastic cells (P < 0.01), number of resorption lacunae, resorption area ratio, and highest OPG expression (P < 0.001). Conclusions: Taken together all these results, MSCs and GT showed marked inhibition and/or repair effects on OIIRR during orthodontic treatment on rats.Article Citation - WoS: 30Citation - Scopus: 28Bianchi I Model: an Alternative Way To Model the Present-Day Universe(Oxford University Press, 2014) Russell, Esra; Kılınç, Can Battal; Pashaev, OktayAlthough the new era of high-precision cosmology of the cosmic microwave background (CMB) radiation improves our knowledge to understand the infant as well as the presentday Universe, it also leads us to question the main assumption of the exact isotropy of the CMB. There are two pieces of observational evidence that hint towards there being no exact isotropy. These are: first, the existence of small anisotropy deviations from isotropy of theCMB radiation and secondly, the presence of large angle anomalies, although the existence of these anomalies is currently a huge matter of debate. These hints are particularly important since isotropy is one of the two main postulates of the Copernican principle on which the Friedmann Robertson Walker (FRW) models are built. This almost-isotropic CMB radiation implies that the universe is almost an FRW universe, as is proved by previous studies. Assuming that the matter component forms the deviations from isotropy in the CMB density fluctuations when matter and radiation decouples, we here attempt to find possible constraints on the FRW-type scale and Hubble parameter by using the Bianchi type I (BI) anisotropic model which is asymptotically equivalent to the standard FRW. To obtain constraints on such an anisotropic model, we derive average and late-time shear values that come from the anisotropy upper limits of the recent Planck data based on a model independent shear parameter of Maartens, Ellis & Stoeger and from the theoretical consistency relation. These constraints lead us to obtain a BI model which becomes an almost-FRWmodel in time, and which is consistent with the latest observational data of the CMB.Article Citation - WoS: 88Citation - Scopus: 92Sur1-Trpm4 Cation Channel Expression in Human Cerebral Infarcts(Oxford University Press, 2015) Mehta, Rupal I.; Tosun, Çiğdem; Ivanova, Svetlana; Tsymbalyuk, Natalia; Famakin, Bolanle M.; Kwon, Min Seong; Castellani, Rudy J.; Gerzanich, Volodymyr; Simard, J. MarcThe nonselective monovalent cation channel transient receptor potential melastatin 4 (Trpm4) is transcriptionally upregulated in neural and vascular cells in animal models of brain infarction. It associates with sulfonylurea receptor 1 (Sur1) to form Sur1-Trpm4 channels, which have critical roles in cytotoxic edema, cell death, blood-brain barrier breakdown, and vasogenic edema. We examined Trpm4 expression in postmortem brain specimens from 15 patients who died within the first 31 days of the onset of focal cerebral ischemia. We found increased Trpm4 protein expression in all cases using immunohistochemistry; transcriptional upregulation was confirmed using in situ hybridization of Trpm4 messenger RNA. Transient receptor potential melastatin 4 colocalized and coassociated with Sur1 within ischemic endothelial cells and neurons. Coexpression of Sur1 and Trpm4 in necrotic endothelial cells was also associated with vasogenic edema indicated by upregulated perivascular tumor necrosis factor, extravasation of serum immunoglobulin G, and associated inflammation. Upregulated Trpm4 protein was present up to 1 month after the onset of cerebral ischemia. In a rat model of middle cerebral artery occlusion stroke, pharmacologic channel blockade by glibenclamide, a selective inhibitor of sulfonylurea receptor, mitigated perivascular tumor necrosis factor labeling. Thus, upregulated Sur1-Trpm4 channels and associated blood-brain barrier disruption and cerebral edema suggest that pharmacologic targeting of this channel may represent a promising therapeutic strategy for the clinical management of patients with cerebral ischemia.