N-Methylmesoporphyrin IX Fluorescence As A Reporter Of Strand Orientation In Guanine Quadruplexes

Guanine quadruplexes (GQ) are four-stranded DNA structures formed by guanine-rich DNA sequences. The formation of GQs inhibits cancer cell growth, although the detection of GQs invivo has proven difficult, in part because of their structural diversity. The development of GQ-selective fluorescent reporters would enhance our ability to quantify the number and location of GQs, ultimately advancing biological studies of quadruplex relevance and function. N-methylmesoporphyrin IX (NMM) interacts selectively with parallel-stranded GQs; in addition, its fluorescence is sensitive to the presence of DNA, making this ligand a possible candidate for a quadruplex probe. In the present study, we investigated the effect of DNA secondary structure on NMM fluorescence. We found that NMM fluorescence increases by about 60-fold in the presence of parallel-stranded GQs and by about 40-fold in the presence of hybrid GQs. Antiparallel GQs lead to lower than 10-fold increases in NMM fluorescence. Single-stranded DNA, duplex, or i-motif, induce no change in NMM fluorescence. We conclude that NMM shows promise as a turn-on\u27 fluorescent probe for detecting quadruplex structures, as well as for differentiating them on the basis of strand orientation

Numerical loop quantum cosmology: an overview

A brief review of various numerical techniques used in loop quantum cosmology and results is presented. These include the way extensive numerical simulations shed insights on the resolution of classical singularities, resulting in the key prediction of the bounce at the Planck scale in different models, and the numerical methods used to analyze the properties of the quantum difference operator and the von Neumann stability issues. Using the quantization of a massless scalar field in an isotropic spacetime as a template, an attempt is made to highlight the complementarity of different methods to gain understanding of the new physics emerging from the quantum theory. Open directions which need to be explored with more refined numerical methods are discussed.Comment: 33 Pages, 4 figures. Invited contribution to appear in Classical and Quantum Gravity special issue on Non-Astrophysical Numerical Relativit

Critical analysis of vendor lock-in and its impact on cloud computing migration: a business perspective

Vendor lock-in is a major barrier to the adoption of cloud computing, due to the lack of standardization. Current solutions and efforts tackling the vendor lock-in problem are predominantly technology-oriented. Limited studies exist to analyse and highlight the complexity of vendor lock-in problem in the cloud environment. Consequently, most customers are unaware of proprietary standards which inhibit interoperability and portability of applications when taking services from vendors. This paper provides a critical analysis of the vendor lock-in problem, from a business perspective. A survey based on qualitative and quantitative approaches conducted in this study has identified the main risk factors that give rise to lock-in situations. The analysis of our survey of 114 participants shows that, as computing resources migrate from on-premise to the cloud, the vendor lock-in problem is exacerbated. Furthermore, the findings exemplify the importance of interoperability, portability and standards in cloud computing. A number of strategies are proposed on how to avoid and mitigate lock-in risks when migrating to cloud computing. The strategies relate to contracts, selection of vendors that support standardised formats and protocols regarding standard data structures and APIs, developing awareness of commonalities and dependencies among cloud-based solutions. We strongly believe that the implementation of these strategies has a great potential to reduce the risks of vendor lock-in

Panel 4 : Report of the Microbiology Panel

Objective. To perform a comprehensive review of the literature from July 2011 until June 2015 on the virology and bacteriology of otitis media in children. Data Sources. PubMed database of the National Library of Medicine. Review Methods. Two subpanels comprising experts in the virology and bacteriology of otitis media were created. Each panel reviewed the relevant literature in the fields of virology and bacteriology and generated draft reviews. These initial reviews were distributed to all panel members prior to meeting together at the Post-symposium Research Conference of the 18th International Symposium on Recent Advances in Otitis Media, National Harbor, Maryland, in June 2015. A final draft was created, circulated, and approved by all panel members. Conclusions. Excellent progress has been made in the past 4 years in advancing our understanding of the microbiology of otitis media. Numerous advances were made in basic laboratory studies, in animal models of otitis media, in better understanding the epidemiology of disease, and in clinical practice. Implications for Practice. (1) Many viruses cause acute otitis media without bacterial coinfection, and such cases do not require antibiotic treatment. (2) When respiratory syncytial virus, metapneumovirus, and influenza virus peak in the community, practitioners can expect to see an increase in clinical otitis media cases. (3) Biomarkers that predict which children with upper respiratory tract infections will develop otitis media may be available in the future. (4) Compounds that target newly identified bacterial virulence determinants may be available as future treatment options for children with otitis media.Peer reviewe

Association Between Use of Tobacco and Age on Graying of Hair

Aims and Objectives: To determine the association between smoking, chewing tobacco (gutka), and age of individual on graying of hair. Materials and Methods: The present study was conducted on 120 patients attending the Outpatient Department of the DJ College of Dental Sciences and Research, Modinagar, UP. The individuals were classified into four groups (group I, II, III, IV) on the basis of the form of tobacco use (smoking or chewing). The Pearson correlation coefficient was utilized to find the correlation between the mean percentage of individuals with gray hair, risk multiplication factor (RMF), and age of the individual. Results: Mean percentage of individual with gray hair and RMF (r = 0.6487) are found to be positively associated. A significant and positive correlation was observed between the age of the individual and the frequency of individuals with gray hair. Conclusion: This study suggests that there is a significant association between tobacco use and aging on graying of hair.Keywords: Graying of hair, risk multiplication factor, smokin

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

PlantGDB: a resource for comparative plant genomics

PlantGDB (http://www.plantgdb.org/) is a genomics database encompassing sequence data for green plants (Viridiplantae). PlantGDB provides annotated transcript assemblies for >100 plant species, with transcripts mapped to their cognate genomic context where available, integrated with a variety of sequence analysis tools and web services. For 14 plant species with emerging or complete genome sequence, PlantGDB's genome browsers (xGDB) serve as a graphical interface for viewing, evaluating and annotating transcript and protein alignments to chromosome or bacterial artificial chromosome (BAC)-based genome assemblies. Annotation is facilitated by the integrated yrGATE module for community curation of gene models. Novel web services at PlantGDB include Tracembler, an iterative alignment tool that generates contigs from GenBank trace file data and BioExtract Server, a web-based server for executing custom sequence analysis workflows. PlantGDB also hosts a plant genomics research outreach portal (PGROP) that facilitates access to a large number of resources for research and training

Forward genetic screen using a gene-breaking trap approach identifies a novel role of grin2bb-associated RNA transcript (grin2bbART) in zebrafish heart function

LncRNA-based control affects cardiac pathophysiologies like myocardial infarction, coronary artery disease, hypertrophy, and myotonic muscular dystrophy. This study used a gene-break transposon (GBT) to screen zebrafish (Danio rerio) for insertional mutagenesis. We identified three insertional mutants where the GBT captured a cardiac gene. One of the adult viable GBT mutants had bradycardia (heart arrhythmia) and enlarged cardiac chambers or hypertrophy; we named it “bigheart.” Bigheart mutant insertion maps to grin2bb or N-methyl D-aspartate receptor (NMDAR2B) gene intron 2 in reverse orientation. Rapid amplification of adjacent cDNA ends analysis suggested a new insertion site transcript in the intron 2 of grin2bb. Analysis of the RNA sequencing of wild-type zebrafish heart chambers revealed a possible new transcript at the insertion site. As this putative lncRNA transcript satisfies the canonical signatures, we called this transcript grin2bb associated RNA transcript (grin2bbART). Using in situ hybridization, we confirmed localized grin2bbART expression in the heart, central nervous system, and muscles in the developing embryos and wild-type adult zebrafish atrium and bulbus arteriosus. The bigheart mutant had reduced Grin2bbART expression. We showed that bigheart gene trap insertion excision reversed cardiac-specific arrhythmia and atrial hypertrophy and restored grin2bbART expression. Morpholino-mediated antisense downregulation of grin2bbART in wild-type zebrafish embryos mimicked bigheart mutants; this suggests grin2bbART is linked to bigheart. Cardiovascular tissues use Grin2bb as a calcium-permeable ion channel. Calcium imaging experiments performed on bigheart mutants indicated calcium mishandling in the heart. The bigheart cardiac transcriptome showed differential expression of calcium homeostasis, cardiac remodeling, and contraction genes. Western blot analysis highlighted Camk2d1 and Hdac1 overexpression. We propose that altered calcium activity due to disruption of grin2bbART, a putative lncRNA in bigheart, altered the Camk2d-Hdac pathway, causing heart arrhythmia and hypertrophy in zebrafish