TERT promoter mutation and H3K27me3 trimethylation loss as focal molecular markers in meningioma aggressiveness

Biomarkers to identify high-grade meningiomas have finally been added to the recent 2021 edition of the World Health Organization (WHO) grading scheme. Among them, are the well-known telomerase reverse transcriptase promoter (TERTp) mutation and the recently emerged epigenetic marker, trimethylation of lysine 27 of histone 3 (H3K27me3). Although the presence of TERTp is now associated with WHO grade 3 meningiomas and the loss of trimethylation of H3K27me3 is implicated with potentially worse prognosis, the question remains as to their ability to predict an event rather than an observed association. Furthermore, the standards for H3K27me3 immunohistochemistry (IHC) in meningiomas have not been set and have led to inconsistencies in reporting. To address these critical clinical concerns, I set out to investigate the prevalence of TERTp mutations in a cohort of suspected high-risk meningiomas through Sanger sequencing. I also conducted a meta-analysis of all H3K27me3 publications to qualify the current assessment of H3K27me3 trimethylation loss as a predictor of tumor aggressiveness. Due to complications with the quality of purified DNA from FFPE tissue, I was unable to obtain satisfactory sequencing results to assess the prevalence of TERTp mutation in my cohort. I did, however, develop an optimized DNA purification protocol for FFPE tissues for future research purposes. The pooled data on H3K27me3 did confirm a significant association between the loss of H3K27me3 trimethylation and more aggressive tumors (p5 years old resulted in significantly higher rates of H3K27me3 loss, implying tissue age and quality had a significant effect on the staining for H3K27me3 loss in meningiomas. Although H3K27me3 is associated substantially with meningiomas of more aggressive nature and thus a higher likelihood of recurrence, several criteria must be met first to standardize the process to ensure accuracy in reporting and ease of implementation into standard clinical workups

ODU Russell Stanger String Quartet and ODU Cello Choir

ODU Russell Stanger String Quartet: Jordan Goodmurphy, Violin Emily Pollard, Violin Joshua Clarke, Viola Michael Russo, Cello ODU Cello Choir: Carter Campbell Trinity Green Joshua Kahn Lexi McGinn Avery Suhay Aleta Tomas Lacey Wilso

Constructing large DNA segments by iterative clone recombination

Methods for constructing large contiguous segments of DNA will be enabling for Synthetic Biology, where the assembly of genes encoding circuits, biosynthetic pathways or even whole microbial organisms is of interest. Currently, in vitro approaches to DNA synthesis are adequate for generating DNAs that are up to 10s of kbp in length, and in vivo recombination strategies are more suitable for building DNA constructs that are 100 kbp or larger. We have developed a vector system for efficient assembly of large DNA molecules by iterative in vivo recombination of fosmid clones. Two custom fosmid vectors have been built, pFOSAMP and pFOSKAN, that support antibiotic switching. Using this technique we rebuilt two non-contiguous regions of the Haemophilus influenzae genome as episomes in recombinogenic Escherichia coli host cells. These regions together comprise190 kbp, or 10.4% of the H. influenze genome

Genome-wide association study of primary tooth eruption identifies pleiotropic loci associated with height and craniofacial distances

Twin and family studies indicate that the timing of primary tooth eruption is highly heritable, with estimates typically exceeding 80%. To identify variants involved in primary tooth eruption we performed a population based genome-wide association study of ‘age at first tooth’ and ‘number of teeth’ using 5998 and 6609 individuals respectively from the Avon Longitudinal Study of Parents and Children (ALSPAC) and 5403 individuals from the 1966 Northern Finland Birth Cohort (NFBC1966). We tested 2,446,724 SNPs imputed in both studies. Analyses were controlled for the effect of gestational age, sex and age of measurement. Results from the two studies were combined using fixed effects inverse variance meta-analysis. We identified a total of fifteen independent loci, with ten loci reaching genome-wide significance (p<5x10−8) for ‘age at first tooth’ and eleven loci for ‘number of teeth’. Together these associations explain 6.06% of the variation in ‘age of first tooth’ and 4.76% of the variation in ‘number of teeth’. The identified loci included eight previously unidentified loci, some containing genes known to play a role in tooth and other developmental pathways, including a SNP in the protein-coding region of BMP4 (rs17563, P= 9.080x10−17). Three of these loci, containing the genes HMGA2, AJUBA and ADK, also showed evidence of association with craniofacial distances, particularly those indexing facial width. Our results suggest that the genome-wide association approach is a powerful strategy for detecting variants involved in tooth eruption, and potentially craniofacial growth and more generally organ development

ICRPfinder: a fast pattern design algorithm for coding sequences and its application in finding potential restriction enzyme recognition sites

<p>Abstract</p> <p>Background</p> <p>Restriction enzymes can produce easily definable segments from DNA sequences by using a variety of cut patterns. There are, however, no software tools that can aid in gene building -- that is, modifying wild-type DNA sequences to express the same wild-type amino acid sequences but with enhanced codons, specific cut sites, unique post-translational modifications, and other engineered-in components for recombinant applications. A fast DNA pattern design algorithm, ICRPfinder, is provided in this paper and applied to find or create potential recognition sites in target coding sequences.</p> <p>Results</p> <p>ICRPfinder is applied to find or create restriction enzyme recognition sites by introducing silent mutations. The algorithm is shown capable of mapping existing cut-sites but importantly it also can generate specified new unique cut-sites within a specified region that are guaranteed not to be present elsewhere in the DNA sequence.</p> <p>Conclusion</p> <p>ICRPfinder is a powerful tool for finding or creating specific DNA patterns in a given target coding sequence. ICRPfinder finds or creates patterns, which can include restriction enzyme recognition sites, without changing the translated protein sequence. ICRPfinder is a browser-based JavaScript application and it can run on any platform, in on-line or off-line mode.</p

Measurement of e⁺e⁻-->e⁺e⁻ and e⁺e⁻-->gammagamma at energies up to 36.7 GeV

e+e- +- +- ... + e e und e e + yy wurden bel Energlen zwischen 33.0 und 36.7 GeV gemessen. Die Ergebnisse stimmen mit den Vorhersagen der Quantenelektrodynamik überein. Ein Vergleich mit dem Standardmodell der elektroschwachen Wechselwirkung liefert sin 20w= 0.25 ± 0.13

Event shapes in e+e- annihilation and deep inelastic scattering

This article reviews the status of event-shape studies in e+e- annihilation and DIS. It includes discussions of perturbative calculations, of various approaches to modelling hadronisation and of comparisons to data.Comment: Invited topical review for J.Phys.G; 40 pages; revised version corrects some nomenclatur

Design and Synthesis of a Quintessential Self-Transmissible IncX1 Plasmid, pX1.0

DNA exchange in bacteria via conjugative plasmids is believed to be among the most important contributing factors to the rapid evolution- and diversification rates observed in bacterial species. The IncX1 plasmids are particularly interesting in relation to enteric bacteria, and typically carry genetic loads like antibiotic resistance genes and virulence factors. So far, however, a “pure” version of these molecular parasites, without genetic loads, has yet to be isolated from the environment. Here we report the construction of pX1.0, a fully synthesized IncX1 plasmid capable of horizontal transfer between different enteric bacteria. The designed pX1.0 sequence was derived from the consensus gene content of five IncX1 plasmids and three other, more divergent, members of the same phylogenetic group. The pX1.0 plasmid was shown to replicate stably in E. coli with a plasmid DNA per total DNA ratio corresponding to approximately 3–9 plasmids per chromosome depending on the growth phase of the host. Through conjugation, pX1.0 was able to self-transfer horizontally into an isogenic strain of E. coli as well as into two additional species belonging to the family Enterobacteriaceae. Our results demonstrate the immediate applicability of recent advances made within the field of synthetic biology for designing and constructing DNA systems, previously existing only in silica