{"title":"Expression of Genes and Their Polymorphism Influences the Risk of Knee Osteoarthritis.","authors":"Abhishek Mishra, Rajeshwar Nath Srivastava, Sachin Awasthi, Devendra Parmar, Priya Mishra","doi":"10.1155/2017/3138254","DOIUrl":"https://doi.org/10.1155/2017/3138254","url":null,"abstract":"<p><strong>Introduction: </strong>Genetic factors including the level of expression of the fingerprint of genes involved in the development of bones and cartilage such as GDF-5 or ESR-<i>α</i> or CALM-1 are known to be strong determinants of the osteoarthritis (OA) in Caucasian and Oriental populations. Because of high prevalence of OA in Indian population and availability of limited genetic data, we determined whether similar genetic factors are involved in Indians as well.</p><p><strong>Methods: </strong>A case control study was carried out involving 500 patients of knee OA and equal number of healthy controls. Genotyping analyses in whole blood, mRNA, and protein expressions in peripheral blood lymphocytes (PBLs) were performed using established protocols.</p><p><strong>Results: </strong>Our results showed a significantly decreased level of mRNA and protein expressions for GDF-5, ESR-<i>α</i>, and CALM-1 genes in PBLs of OA cases when compared to healthy controls. The frequency of variant genotypes of these genes was also increased significantly in cases of OA compared to controls.</p><p><strong>Conclusion: </strong>Our results demonstrated that the decrease in expression of GDF-5, ESR-<i>α</i>, and CALM-1 in PBLs and association of polymorphism in these genes may be important in predicting the severity and thereby the progression of OA in Indian population.</p>","PeriodicalId":16575,"journal":{"name":"Journal of Nucleic Acids","volume":"2017 ","pages":"3138254"},"PeriodicalIF":2.3,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2017/3138254","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35247370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"In What Ways Do Synthetic Nucleotides and Natural Base Lesions Alter the Structural Stability of G-Quadruplex Nucleic Acids?","authors":"Janos Sagi","doi":"10.1155/2017/1641845","DOIUrl":"10.1155/2017/1641845","url":null,"abstract":"<p><p>Synthetic analogs of natural nucleotides have long been utilized for structural studies of canonical and noncanonical nucleic acids, including the extensively investigated polymorphic G-quadruplexes (GQs). Dependence on the sequence and nucleotide modifications of the folding landscape of GQs has been reviewed by several recent studies. Here, an overview is compiled on the thermodynamic stability of the modified GQ folds and on how the stereochemical preferences of more than 70 synthetic and natural derivatives of nucleotides substituting for natural ones determine the stability as well as the conformation. Groups of nucleotide analogs only stabilize or only destabilize the GQ, while the majority of analogs alter the GQ stability in both ways. This depends on the preferred <i>syn</i> or <i>anti</i> N-glycosidic linkage of the modified building blocks, the position of substitution, and the folding architecture of the native GQ. Natural base lesions and epigenetic modifications of GQs explored so far also stabilize or destabilize the GQ assemblies. Learning the effect of synthetic nucleotide analogs on the stability of GQs can assist in engineering a required stable GQ topology, and exploring the <i>in vitro</i> action of the single and clustered natural base damage on GQ architectures may provide indications for the cellular events.</p>","PeriodicalId":16575,"journal":{"name":"Journal of Nucleic Acids","volume":"2017 ","pages":"1641845"},"PeriodicalIF":1.3,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35643795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Delia J Scoville, Tae Kyu Brian Uhm, Jamie A Shallcross, Rebecca J Whelan
{"title":"Selection of DNA Aptamers for Ovarian Cancer Biomarker CA125 Using One-Pot SELEX and High-Throughput Sequencing.","authors":"Delia J Scoville, Tae Kyu Brian Uhm, Jamie A Shallcross, Rebecca J Whelan","doi":"10.1155/2017/9879135","DOIUrl":"https://doi.org/10.1155/2017/9879135","url":null,"abstract":"<p><p>CA125 is a mucin glycoprotein whose concentration in serum correlates with a woman's risk of developing ovarian cancer and also indicates response to therapy in diagnosed patients. Accurate detection of this large, complex protein in patient samples is of great clinical relevance. We suggest that powerful new diagnostic tools may be enabled by the development of nucleic acid aptamers with affinity for CA125. Here, we report on our use of One-Pot SELEX to isolate single-stranded DNA aptamers with affinity for CA125, followed by high-throughput sequencing of the selected oligonucleotides. This data-rich approach, combined with bioinformatics tools, enabled the entire selection process to be characterized. Using fluorescence anisotropy and affinity probe capillary electrophoresis, the binding affinities of four aptamer candidates were evaluated. Two aptamers, CA125_1 and CA125_12, both without primers, were found to bind to clinically relevant concentrations of the protein target. Binding was differently influenced by the presence of Mg<sup>2+</sup> ions, being required for binding of CA125_1 and abrogating binding of CA125_12. In conclusion, One-Pot SELEX was found to be a promising selection method that yielded DNA aptamers to a clinically important protein target.</p>","PeriodicalId":16575,"journal":{"name":"Journal of Nucleic Acids","volume":"2017 ","pages":"9879135"},"PeriodicalIF":2.3,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2017/9879135","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34800867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Corrigendum to \"Plant MicroRNA Prediction by Supervised Machine Learning Using C5.0 Decision Trees\".","authors":"Philip H Williams, Rodney P Eyles, Georg Weiller","doi":"10.1155/2017/7876832","DOIUrl":"https://doi.org/10.1155/2017/7876832","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1155/2012/652979.].</p>","PeriodicalId":16575,"journal":{"name":"Journal of Nucleic Acids","volume":"2017 ","pages":"7876832"},"PeriodicalIF":2.3,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2017/7876832","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35219385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
W-Matthias Leeder, Stephan Voskuhl, H Ulrich Göringer
{"title":"The 2D Structure of the <i>T. brucei</i> Preedited RPS12 mRNA Is Not Affected by Macromolecular Crowding.","authors":"W-Matthias Leeder, Stephan Voskuhl, H Ulrich Göringer","doi":"10.1155/2017/6067345","DOIUrl":"https://doi.org/10.1155/2017/6067345","url":null,"abstract":"<p><p>Mitochondrial transcript maturation in African trypanosomes requires RNA editing to convert sequence-deficient pre-mRNAs into translatable mRNAs. The different pre-mRNAs have been shown to adopt highly stable 2D folds; however, it is not known whether these structures resemble the in vivo folds given the extreme \"crowding\" conditions within the mitochondrion. Here, we analyze the effects of macromolecular crowding on the structure of the mitochondrial RPS12 pre-mRNA. We use high molecular mass polyethylene glycol as a macromolecular cosolute and monitor the structure of the RNA globally and with nucleotide resolution. We demonstrate that crowding has no impact on the 2D fold and we conclude that the MFE structure in dilute solvent conditions represents a good proxy for the folding of the pre-mRNA in its mitochondrial solvent context.</p>","PeriodicalId":16575,"journal":{"name":"Journal of Nucleic Acids","volume":"2017 ","pages":"6067345"},"PeriodicalIF":2.3,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2017/6067345","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35160859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Petra Krafčíková, Erika Demkovičová, Andrea Halaganová, Viktor Víglaský
{"title":"Putative HIV and SIV G-Quadruplex Sequences in Coding and Noncoding Regions Can Form G-Quadruplexes.","authors":"Petra Krafčíková, Erika Demkovičová, Andrea Halaganová, Viktor Víglaský","doi":"10.1155/2017/6513720","DOIUrl":"https://doi.org/10.1155/2017/6513720","url":null,"abstract":"<p><p>The HIV virus is one of the most studied viruses in the world. This is especially true in terms of gene sequencing, and to date more than 9 thousand genomic sequences of HIV isolates have been sequenced and analyzed. In this study, a series of DNA sequences, which have the potential to form G-quadruplex structures, is analyzed. Several such sequences were found in various coding and noncoding virus domains, including the U3 LTR, tat, rev, env, and vpx regions. Interestingly, a homological sequence to the already well-known HIV integrase aptamer was identified in the minus-strand. The sequences derived from original isolates were analyzed using standard spectral and electrophoretic methods. In addition, a recently developed methodology is applied which uses induced circular dichroism spectral profiles of G-quadruplex-ligand (Thiazole Orange) complexes to determine if G-rich sequences can adopt G-quadruplex structure. Targeting the G-quadruplexes or peptide domains corresponding to the G-rich coding sequence in HIV offers researchers attractive therapeutic targets which would be of particular use in the development of novel antiviral therapies. The analysis of G-rich regions can provide researchers with a path to find specific targets which could be of interest for specific types of virus.</p>","PeriodicalId":16575,"journal":{"name":"Journal of Nucleic Acids","volume":"2017 ","pages":"6513720"},"PeriodicalIF":2.3,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2017/6513720","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35847953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Erika Demkovičová, Ľuboš Bauer, Petra Krafčíková, Katarína Tlučková, Petra Tóthova, Andrea Halaganová, Eva Valušová, Viktor Víglaský
{"title":"Telomeric G-Quadruplexes: From Human to <i>Tetrahymena</i> Repeats.","authors":"Erika Demkovičová, Ľuboš Bauer, Petra Krafčíková, Katarína Tlučková, Petra Tóthova, Andrea Halaganová, Eva Valušová, Viktor Víglaský","doi":"10.1155/2017/9170371","DOIUrl":"https://doi.org/10.1155/2017/9170371","url":null,"abstract":"<p><p>The human telomeric and protozoal telomeric sequences differ only in one purine base in their repeats; TTAGGG in telomeric sequences; and TTGGGG in protozoal sequences. In this study, the relationship between G-quadruplexes formed from these repeats and their derivatives is analyzed and compared. The human telomeric DNA sequence G<sub>3</sub>(T<sub>2</sub>AG<sub>3</sub>)<sub>3</sub> and related sequences in which each adenine base has been systematically replaced by a guanine were investigated; the result is <i>Tetrahymena</i> repeats. The substitution does not affect the formation of G-quadruplexes but may cause differences in topology. The results also show that the stability of the substituted derivatives increased in sequences with greater number of substitutions. In addition, most of the sequences containing imperfections in repeats which were analyzed in this study also occur in human and <i>Tetrahymena</i> genomes. Generally, the presence of G-quadruplex structures in any organism is a source of limitations during the life cycle. Therefore, a fuller understanding of the influence of base substitution on the structural variability of G-quadruplexes would be of considerable scientific value.</p>","PeriodicalId":16575,"journal":{"name":"Journal of Nucleic Acids","volume":"2017 ","pages":"9170371"},"PeriodicalIF":2.3,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2017/9170371","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35831976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Devender Kumar Sharma, Kamiko R. Bressler, H. Patel, Nirujah Balasingam, N. Thakor
{"title":"Role of Eukaryotic Initiation Factors during Cellular Stress and Cancer Progression","authors":"Devender Kumar Sharma, Kamiko R. Bressler, H. Patel, Nirujah Balasingam, N. Thakor","doi":"10.1155/2016/8235121","DOIUrl":"https://doi.org/10.1155/2016/8235121","url":null,"abstract":"Protein synthesis can be segmented into distinct phases comprising mRNA translation initiation, elongation, and termination. Translation initiation is a highly regulated and rate-limiting step of protein synthesis that requires more than 12 eukaryotic initiation factors (eIFs). Extensive evidence shows that the transcriptome and corresponding proteome do not invariably correlate with each other in a variety of contexts. In particular, translation of mRNAs specific to angiogenesis, tumor development, and apoptosis is altered during physiological and pathophysiological stress conditions. In cancer cells, the expression and functions of eIFs are hampered, resulting in the inhibition of global translation and enhancement of translation of subsets of mRNAs by alternative mechanisms. A precise understanding of mechanisms involving eukaryotic initiation factors leading to differential protein expression can help us to design better strategies to diagnose and treat cancer. The high spatial and temporal resolution of translation control can have an immediate effect on the microenvironment of the cell in comparison with changes in transcription. The dysregulation of mRNA translation mechanisms is increasingly being exploited as a target to treat cancer. In this review, we will focus on this context by describing both canonical and noncanonical roles of eIFs, which alter mRNA translation.","PeriodicalId":16575,"journal":{"name":"Journal of Nucleic Acids","volume":"2016 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2016-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2016/8235121","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64555931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jennifer A. Martin, Y. Chushak, J. Chávez, J. Hagen, N. Kelley-Loughnane
{"title":"Microarrays as Model Biosensor Platforms to Investigate the Structure and Affinity of Aptamers","authors":"Jennifer A. Martin, Y. Chushak, J. Chávez, J. Hagen, N. Kelley-Loughnane","doi":"10.1155/2016/9718612","DOIUrl":"https://doi.org/10.1155/2016/9718612","url":null,"abstract":"Immobilization of nucleic acid aptamer recognition elements selected free in solution onto the surface of biosensor platforms has proven challenging. This study investigated the binding of multiple aptamer/target pairs immobilized on a commercially available microarray as a model system mimicking biosensor applications. The results indicate a minimum distance (linker length) from the surface and thymine nucleobase linker provides reproducible binding across varying conditions. An indirect labeling method, where the target was labeled with a biotin followed by a brief Cy3-streptavidin incubation, provided a higher signal-to-noise ratio and over two orders of magnitude improvement in limit of detection, compared to direct Cy3-protein labeling. We also showed that the affinities of the aptamer/target interaction can change between direct and indirect labeling and conditions to optimize for the highest fluorescence intensity will increase the sensitivity of the assay but will not change the overall affinity. Additionally, some sequences which did not initially bind demonstrated binding when conditions were optimized. These results, in combination with studies demonstrating enhanced binding in nonselection buffers, provided insights into the structure and affinity of aptamers critical for biosensor applications and allowed for generalizations in starting conditions for researchers wishing to investigate aptamers on a microarray surface.","PeriodicalId":16575,"journal":{"name":"Journal of Nucleic Acids","volume":"2016 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2016-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2016/9718612","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64634716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Avinash M Veerappa, Prakash Padakannaya, Nallur B Ramachandra
{"title":"Copy Number Variation of UGT 2B Genes in Indian Families Using Whole Genome Scans.","authors":"Avinash M Veerappa, Prakash Padakannaya, Nallur B Ramachandra","doi":"10.1155/2016/1648527","DOIUrl":"https://doi.org/10.1155/2016/1648527","url":null,"abstract":"<p><p>Background and Objectives. Uridine diphospho-glucuronosyltransferase 2B (UGT2B) is a family of genes involved in metabolizing steroid hormones and several other xenobiotics. These UGT2B genes are highly polymorphic in nature and have distinct polymorphisms associated with specific regions around the globe. Copy number variations (CNVs) status of UGT2B17 in Indian population is not known and their disease associations have been inconclusive. It was therefore of interest to investigate the CNV profile of UGT2B genes. Methods. We investigated the presence of CNVs in UGT2B genes in 31 members from eight Indian families using Affymetrix Genome-Wide Human SNP Array 6.0 chip. Results. Our data revealed >50% of the study members carried CNVs in UGT2B genes, of which 76% showed deletion polymorphism. CNVs were observed more in UGT2B17 (76.4%) than in UGT2B15 (17.6%). Molecular network and pathway analysis found enrichment related to steroid metabolic process, carboxylesterase activity, and sequence specific DNA binding. Interpretation and Conclusion. We report the presence of UGT2B gene deletion and duplication polymorphisms in Indian families. Network analysis indicates the substitutive role of other possible genes in the UGT activity. The CNVs of UGT2B genes are very common in individuals indicating that the effect is neutral in causing any suspected diseases. </p>","PeriodicalId":16575,"journal":{"name":"Journal of Nucleic Acids","volume":"2016 ","pages":"1648527"},"PeriodicalIF":2.3,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2016/1648527","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34473343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}