Browsing by Subject "RNA"
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Item Open Access Biological properties of extracellular vesicles and their physiological functions(Taylor & Francis, 2015) Yáñez-Mó, M.; Siljander, P. R. M.; Andreu, Z.; Zavec, A. B.; Borràs, F. E.; Buzas, E. I.; Buzas, K.; Casal, E.; Cappello, F.; Carvalho, J.; Colás, E.; Cordeiro-Da, S. A.; Fais, S.; Falcon-Perez, J. M.; Ghobrial, I. M.; Giebel, B.; Gimona, M.; Graner, M.; Gursel, I.; Gursel, M.; Heegaard, N. H. H.; Hendrix, A.; Kierulf, P.; Kokubun, K.; Kosanovic, M.; Kralj-Iglic, V.; Krämer-Albers, E. M.; Laitinen, S.; Lässer, C.; Lener, T.; Ligeti, E.; Line, A.; Lipps, G.; Llorente, A.; Lötvall, J.; Manček-Keber, M.; Marcilla, A.; Mittelbrunn, M.; Nazarenko, I.; Nolte-'t Hoen, E. N. M.; Nyman, T. A.; O'Driscoll, L.; Olivan, M.; Oliveira, C.; Pállinger, E.; Del Portillo, H. A.; Reventós, J.; Rigau, M.; Rohde, E.; Sammar, M.; Sánchez-Madrid, F.; Santarém, N.; Schallmoser, K.; Ostenfeld, M. S.; Stoorvogel, W.; Stukelj, R.; Grein V. D. S.G.; Helena,ü V. M.; Wauben, M. H. M.; De Wever, O.In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells.While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.Item Open Access A chronic myeloid leukemia-like syndrome case with del (12) (p12) in a Li-Fraumeni syndrome family(Blackwell Publishing Ltd, 2005) Guran, Ş.; Beyan, C.; Nevruz, O.; Yakıcıer, C.; Tunca, Y.Li-Fraumeni syndrome is a familial cancer syndrome characterized by different tumors and hereditary p53 mutations. Here, a chronic myeloid leukemia-like syndrome case in a Li-Fraumeni syndrome family with del (12) (p12) cytogenetic abnormality was presented. A hereditary p53 mutation (pro309ser) supported the Li-Fraumeni syndrome diagnosis in this family. This syndrome was characterized by the clonal myeloproliferative accumulation in bone marrow and peripheral blood with negative bcr/abl gene rearrangement finding. The etiology of this rare syndrome is still unclear. This is the only chronic myeloid leukemia-like syndrome case reported in a Li-Fraumeni syndrome family. Del (12) (p12) was observed in leukemias except chronic myeloid leukemia-like syndrome. The deletion in chromosome 12pl2 with hereditary p53 mutation should have a critical role in chronic myeloid leukemia-like syndrome etiology in our case. © 2005 Blackwell Publishing Ltd.Item Open Access Doxorubicin induces prolonged DNA damage signal in cells overexpressing DEK isoform-2(Public Library of Science, 2022-10-03) Özçelik, Emrah; Kalaycı, Ahmet; Çelik, Büşra; Avcı, Açelya; Akyol, Hasan; Kılıç, İrfan Baki; Güzel, Türkan; Çetin, Metin; Öztürk, Merve Tuzlakoğlu; Çalışkaner, Zihni Onur; Tombaz, Melike; Yoleri, Dilan; Konu, Özlen; Kandilci, AytenDEK has a short isoform (DEK isoform-2; DEK2) that lacks amino acid residues between 49–82. The full-length DEK (DEK isoform-1; DEK1) is ubiquitously expressed and plays a role in different cellular processes but whether DEK2 is involved in these processes remains elusive. We stably overexpressed DEK2 in human bone marrow stromal cell line HS-27A, in which endogenous DEKs were intact or suppressed via short hairpin RNA (sh-RNA). We have found that contrary to ectopic DEK1, DEK2 locates in the nucleus and nucleolus, causes persistent үH2AX signal upon doxorubicin treatment, and couldn’t functionally compensate for the loss of DEK1. In addition, DEK2 overexpressing cells were more sensitive to doxorubicin than DEK1-cells. Expressions of DEK1 and DEK2 in cell lines and primary tumors exhibit tissue specificity. DEK1 is upregulated in cancers of the colon, liver, and lung compared to normal tissues while both DEK1 and DEK2 are downregulated in subsets of kidney, prostate, and thyroid carcinomas. Interestingly, only DEK2 was downregulated in a subset of breast tumors suggesting that DEK2 can be modulated differently than DEK1 in specific cancers. In summary, our findings show distinct expression patterns and subcellular location and suggest non-overlapping functions between the two DEK isoforms. © 2022 Ozçelik et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Item Open Access Examining the annealing schedules for RNA design algorithm(IEEE, 2016-07) Erhan, H. E.; Sav, Sinem; Kalashnikov, S.; Tsang, H. H.RNA structures are important for many biological processes in the cell. One important function of RNA are as catalytic elements. Ribozymes are RNA sequences that fold to form active structures that catalyze important chemical reactions. The folded structure for these RNA are very important; only specific conformations maintain these active structures, so it is very important for RNA to fold in a specific way. The RNA design problem describes the prediction of an RNA sequence that will fold into a given RNA structure. Solving this problem allows researchers to design RNA; they can decide on what folded secondary structure is required to accomplish a task, and the algorithm will give them a primary sequence to assemble. However, there are far too many possible primary sequence combinations to test sequentially to see if they would fold into the structure. Therefore we must employ heuristics algorithms to attempt to solve this problem. This paper introduces SIMARD, an evolutionary algorithm that uses an optimization technique called simulated annealing to solve the RNA design problem. We analyzes three different cooling schedules for the annealing process: 1) An adaptive cooling schedule, 2) a geometric cooling schedule, and 3) a geometric cooling schedule with warm up. Our results show that an adaptive annealing schedule may not be more effective at minimizing the Hamming distance between the target structure and our folded sequence's structure when compared with geometric schedules. The results also show that warming up in a geometric cooling schedule may be useful for optimizing SIMARD. © 2016 IEEE.Item Open Access Extreme clonality in lymphoblastoid cell lines with implications for allele specific expression analyses(2008) Plagnol V.; Uz, E.; Wallace, C.; Stevens H.; Clayton, D.; Ozcelik, T.; Todd J.A.Lymphoblastoid cell lines (LCL) are being actively and extensively used to examine the expression of specific genes and (genome-wide expression profiles, including allele specific expression assays. However, it has recently been shown that approximately 10% of human genes exhibit random patterns of monoallelic expression within single clones of LCLs. Consequently allelic imbalance studies could be significantly compromised if bulk populations of donor cells are clonal, or near clonal. Here, using X chromosome inactivation as a readout, we confirm and quantify widespread near monoclonality in two independent sets of cell lines. Consequently, we recommend where possible the use of bulk, non cell line, ex vivo cells for allele specific expression assays. © 2008 Plagnol et al.Item Open Access Heparin mimetic peptide nanofiber gel promotes regeneration of full thickness burn injury(Elsevier Ltd, 2017) Yergoz, F.; Hastar, N.; Cimenci, C. E.; Ozkan, A. D.; Güler, Mustafa O.; Tekinay, A. B.; Tekinay, T.; Güler, Mustafa O.Burn injuries are one of the most common types of trauma worldwide, and their unique physiology requires the development of specialized therapeutic materials for their treatment. Here, we report the use of synthetic, functional and biodegradable peptide nanofiber gels for the improved healing of burn wounds to alleviate the progressive loss of tissue function at the post-burn wound site. These bioactive nanofiber gels form scaffolds that recapitulate the structure and function of the native extracellular matrix through signaling peptide epitopes, which can trigger angiogenesis through their affinity to basic growth factors. In this study, the angiogenesis-promoting properties of the bioactive scaffolds were utilized for the treatment of a thermal burn model. Following the excision of necrotic tissue, bioactive gels and control solutions were applied topically onto the wound area. The wound healing process was evaluated at 7, 14 and 21 days following injury through histological observations, immunostaining and marker RNA/protein analysis. Bioactive peptide nanofiber-treated burn wounds formed well-organized and collagen-rich granulation tissue layers, produced a greater density of newly formed blood vessels, and exhibited increased re-epithelialization and skin appendage development with minimal crust formation, while non-bioactive peptide nanofibers and the commercial wound dressing 3M™ Tegaderm™ did not exhibit significant efficiency over sucrose controls. Overall, the heparin-mimetic peptide nanofiber gels increased the rate of repair of burn injuries and can be used as an effective means of facilitating wound healing.Item Open Access Heterotrophic ammonium removal by a novel hatchery isolate Acinetobacter calcoaceticus STB1(2012) Sarioglu O.F.; Suluyayla, R.; Tekinay, T.A novel bacterial strain, STB1, was isolated from a commercial sea bass hatchery and found to display high heterotrophic ammonium removal characteristics at different concentrations of ammonium (NH4+-N). The species identity of STB1 was determined via 16S rRNA gene sequence analysis to be Acinetobacter calcoaceticus. We evaluated ammonium removal characteristics of STB1 at varying ammonium concentrations, and observed that STB1 can almost completely remove ammonium at low (50 mg l -1), and medium (100 mg l -1) concentrations within 72 h, while 45% ammonium removal was observed at a higher concentration (210 mg l -1) during the same period. Trace amount of the metabolized ammonium was converted to nitrite or nitrate and 22.16% of total nitrogen was incorporated into cell biomass, while 4.34% of total nitrogen was initially incorporated into cell biomass and subsequently released to the supernatant fraction in the 100 mg l -1 sample. Most of the remaining conversion products are expected to be gaseous denitrification products. Toxicological studies with Artemia salina (brine shrimp) nauplii revealed that STB1 strain is non-toxic to Artemia larvae, which suggests that STB1 can be safely and efficiently utilized in water quality enrichment in aquatic ecosystems. © 2012 Elsevier Ltd.Item Open Access A highly sensitive and specific enzyme-linked immunosorbent assay of antibodies to hepatitis C virus(2000) Eroğlu, C.; Yıldız, E.; Öztürk, M.; Pınarbaşı, E.In this study, a 178 amino acids long portion of the hepatitis C virus (HCV) core gene was cloned, sequenced, expressed in Escherichia coli, and purified. The resulting antigen (C178) was tested with human sera enzyme-linked immunosorbent assay (ELISA) in order to assess its ability to diagnose HCV. It was shown by ELISA that 92% of the patients sera, diagnosed previously by a 3(rd) generation enzyme immunoassay (EIA) as HCV-positive, had antibodies against the C178 antigen. This antigen gave no false positive results when tested with anti-HCV-negative sera.Item Open Access Inositol‐requiring enzyme‐1 regulates phosphoinositide signaling lipids and macrophage growth(Wiley-VCH Verlag, 2020-11) Hamid, S. M.; Çıtır, M.; Terzi, E. M.; Çimen, İ.; Yıldırım, Zehra; Doğan, Aslı Ekin; Kocatürk, B.; Onat, Umut Inci; Arditi, M.; Weber, C.; Traynor‐Kaplan, A.; Schultz, C.; Erbay, E.The ER‐bound kinase/endoribonuclease (RNase), inositol‐requiring enzyme‐1 (IRE1), regulates the phylogenetically most conserved arm of the unfolded protein response (UPR). However, the complex biology and pathology regulated by mammalian IRE1 cannot be fully explained by IRE1’s one known, specific RNA target, X box‐binding protein‐1 (XBP1) or the RNA substrates of IRE1‐dependent RNA degradation (RIDD) activity. Investigating other specific substrates of IRE1 kinase and RNase activities may illuminate how it performs these diverse functions in mammalian cells. We report that macrophage IRE1 plays an unprecedented role in regulating phosphatidylinositide‐derived signaling lipid metabolites and has profound impact on the downstream signaling mediated by the mammalian target of rapamycin (mTOR). This cross‐talk between UPR and mTOR pathways occurs through the unconventional maturation of microRNA (miR) 2137 by IRE1’s RNase activity. Furthermore, phosphatidylinositol (3,4,5) phosphate (PI(3,4,5)P3) 5‐phosphatase‐2 (INPPL1) is a direct target of miR‐2137, which controls PI(3,4,5)P3 levels in macrophages. The modulation of cellular PI(3,4,5)P3/PIP2 ratio and anabolic mTOR signaling by the IRE1‐induced miR‐2137 demonstrates how the ER can provide a critical input into cell growth decisions.Item Open Access Investigation of multi-objective optimization criteria for RNA design(IEEE, 2017-12) Hampson, D. J. D.; Sav, Sinem; Tsang, H. H.RNA design is the inverse of RNA folding and it appears to be NP-hard. In RNA design, a secondary structure is given and the goal is to find a nucleotide sequence that will fold into this structure. To find such sequence(s) involves exploring the exponentially large sequence space. In literature, heuristic algorithms are the standard technique for tackling the RNA design. Heuristic algorithms enable effective and efficient exploration of the high-dimensional sequence-structure space when searching for candidates that fold into a given target structure. The main goal of this paper is to investigate the use of multi-objective criteria in SIMARD and Quality Pre-selection Strategy (QPS). The objectives that we optimize are Hamming distance (between designed structure and target structure) and thermodynamic free energy. We examine the different combinations of optimization criteria, and attempt to draw conclusions about the relationships between them. We find that energy is a poor primary objective but makes an excellent secondary objective. We also find that using multi-objective pre-selection produces viable solutions in far fewer steps than was previously possible with SIMARD. © 2016 IEEE.Item Open Access Oligonucleotide-based label-free detection with optical microresonators: strategies and challenges(Royal Society of Chemistry, 2016) Toren, P.; Ozgur E.; Bayındır, MehmetThis review targets diversified oligonucleotide-based biodetection techniques, focusing on the use of microresonators of whispering gallery mode (WGM) type as optical biosensors mostly integrated with lab-on-a-chip systems. On-chip and microfluidics combined devices along with optical microresonators provide rapid, robust, reproducible and multiplexed biodetection abilities in considerably small volumes. We present a detailed overview of the studies conducted so far, including biodetection of various oligonucleotide biomarkers as well as deoxyribonucleic acids (DNAs), ribonucleic acids (RNAs) and proteins. We particularly advert to chemical surface modifications for specific and selective biosensing.Item Open Access Production and structural characterization of biosurfactant produced by newly isolated staphylococcus xylosus STF1 from petroleum contaminated soil(Elsevier BV, 2015) Keskin, N. O. S.; Han, D.; Ozkan A.D.; Angun, P.; Umu, O. C. O.; Tekinay, T.Petroleum-contaminated soil was used to isolate and characterize biosurfactant producing bacteria. The strain could produce higher amount of biosurfactant in medium supplemented with motor oil as sole source of carbon and energy. A new biosurfactant producing bacterium, designated as Staphylococcus xylosus STF1 based on morphological, physiological, biochemical tests and 16S rRNA gene sequencing. The isolated bacterium was first screened for the ability to produce biosurfactant. Partial sequence of STF1 strain of 16S rDNA gene was highly similar to those of various members of the family Staphylococcaceae. Biochemical characterizations including FT-IR, Raman spectroscopy and Mass spectroscopy studies suggested the biosurfactant to be lipopeptide. Study also confirmed that the cell free supernatant exhibited high emulsifying activity against the different hydrocarbons. Moreover, the partially purified biosurfactant exhibited antimicrobial activity by inhibiting the growth of several bacterial species. The strain could be a potential candidate for the production of polypeptide biosurfactant which could be useful in a variety of biotechnological and industrial processes, particularly in the food and oil industry. © 2015 Elsevier B.V.Item Open Access Prostate stem cell antigen is an endogenous lynx1-like prototoxin that antagonizes α7-containing nicotinic receptors and prevents programmed cell death of parasympathetic neurons(2009) Hruska, M.; Keefe J.; Wert, D.; Tekinay, A.B.; Hulce J.J.; Ibañez-Tallon I.; Nishi, R.Vertebrate α-bungarotoxin-like molecules of the Ly-6 superfamily have been implicated as balancers of activity and survival in the adult nervous system. To determine whether a member of this family could be involved in the development of the avian ciliary ganglion, we identified 6 Gallus genes by their homology in structure to mouse lynx1 and lynx2. One of these genes, an ortholog of prostate stem cell antigen (psca), is barely detectable at embryonic day (E) 8, before neuronal cell loss in the ciliary ganglion, but increases > 100-fold as the number of neurons begins to decline between E9 and E14. PSCA is highly expressed in chicken and mouse telencephalon and peripheral ganglia and correlates with expression of α7-containing nicotinic acetylcholine receptors (α7-nAChRs). Misexpressing PSCA before cell death in the ciliary ganglion blocks α7-nAChR activation by nicotine and rescues the choroid subpopulation from dying. Thus, PSCA, a molecule previously identified as a marker of prostate cancer, is a member of the Ly-6 neurotoxin-like family in the nervous system, and is likely to play a role as a modulator of α7 signaling-induced cell death during development. Copyright © 2009 Society for Neuroscience.Item Open Access Reprogramming of replicative senescence in hepatocellular carcinoma-derived cells(National Academy of Sciences, 2006) Ozturk, N.; Erdal, E.; Mumcuoglu, M.; Akcali, K. C.; Yalcin, O.; Senturk, S.; Arslan-Ergul, A.; Gur, B.; Yulug, I.; Cetin Atalay, R.; Yakicier, C.; Yagci, T.; Tez, M.; Ozturk, M.Tumor cells have the capacity to proliferate indefinitely that is qualified as replicative immortality. This ability contrasts with the intrinsic control of the number of cell divisions in human somatic tissues by a mechanism called replicative senescence. Replicative immortality is acquired by inactivation of p53 and p16INK4a genes and reactivation of hTERT gene expression. It is unknown whether the cancer cell replicative immortality is reversible. Here, we show the spontaneous induction of replicative senescence in p53-and p16 INK4a-deficient hepatocellular carcinoma cells. This phenomenon is characterized with hTERT repression, telomere shortening, senescence arrest, and tumor suppression. SIP1 gene (ZFHX1B) is partly responsible for replicative senescence, because short hairpin RNA-mediated SIP1 inactivation released hTERT repression and rescued clonal hepatocellular carcinoma cells from senescence arrest. © 2006 by The National Academy of Sciences of the USA.Item Open Access SIMARD: a simulated annealing based RNA design algorithm with quality pre-selection strategies(IEEE, 2017-12) Sav, Sinem; Hampson, D. J. D.; Tsang, H. H.Most of the biological processes including expression levels of genes and translation of DNA to produce proteins within cells depend on RNA sequences, and the structure of the RNA plays vital role for its function. RNA design problem refers to the design of an RNA sequence that folds into given secondary structure. However, vast number of possible nucleotide combinations make this an NP-Hard problem. To solve the RNA design problem, a number of researchers have tried to implement algorithms using local stochastic search, context-free grammars, global sampling or evolutionary programming approaches. In this paper, we examine SIMARD, an RNA design algorithm that implements simulated annealing techniques. We also propose QPS, a mutation operator for SIMARD that pre-selects high quality sequences. Furthermore, we present experiment results of SIMARD compared to eight other RNA design algorithms using the Rfam datset. The experiment results indicate that SIMARD shows promising results in terms of Hamming distance between designed sequence and the target structure, and outperforms ERD in terms of free energy. © 2016 IEEE.