Methylation status of the Runx2 p2 promoter in a family with ectopic maxillary canines

Genetic factors contribute to the aetiology of the ectopic canine (EC) (OMIM 189490), the inheritance pattern being autosomal dominant with variable expression and incomplete penetrance. However there is also evidence for an epigenetic component. The Runx2 gene is intimately involved in the mechanism of tooth eruption. It controls differentiation and maturation of osteoblasts and is expressed in the dental follicle and alveolar bone at all stages of development [2,3]. Mutations of this gene result in delayed and ectopic eruption of teeth. There is a large CpG island spanning its proximal promoter, first exon and part of the first intron. Similarities between the inheritance patterns of EC and other methylation disorders raises the hypothesis that differential methylation of the Runx2 promoter may contribute to EC. This study investigates the methylation status of the Runx2 P2 promoter in ectopic canine subjects and unaffected controls. There was no evidence of differential methylation between the groups.peer-reviewe

Maximizing negative thermal expansion via rigid unit modes : a geometry-based approach

Existent rigid unit mode (RUM) models based on rotating squares, which may explain the phenomenon of negative thermal expansion (NTE), are generalized so as to assess the NTE potential for novel systems made from rectangular or rhombic rigid units. Analytical models for the area coefficients of thermal expansion (CTE) of these innovative networks are derived in an attempt to determine the optimal geometrical parameters and connectivity for maximum NTE. It was found that all systems exhibit NTE, the extent of which is determined by the shape and connectivity of the elemental rigid units (side lengths ratio or internal angle). It was also found that some of the networks proposed here should exhibit significantly superior NTE properties when compared with the well-known network of squares, and that for optimal NTE characteristics, pencil-like rigid units should be used rather than square-shaped ones, as these permit larger pore sizes that are more conducive to NTE. All this compliments earlier work on the negative Poisson's ratio (auxetic) potential of such systems and may provide a route for the design of new materials exhibiting superior thermo-mechanical characteristics including specifically tailored CTEs or giant NTE characteristics.peer-reviewe

The State of the Art in Tag Ontologies: A Semantic Model for Tagging and Folksonomies

There is a growing interest on how we represent and share tagging data for the purpose of collaborative tagging systems. Conventional tags, however, are not naturally suited for collaborative processes. Being free-text keywords, they are exposed to linguistic variations like case (upper vs lower), grammatical number (singular vs. plural) as well as human typing errors. Additionally, tags depend on the personal views of the world by individual users, and are not normalized for synonymy, morphology or any other mapping. The bottom line of the problem is that tags have no semantics whatsoever. Moreover, even if a user gives some semantics to a tag while using or viewing it, this meaning is not automatically shared with computers since it’s not defined in a machine-readable way. With tagging systems increasing in popularity each day, the evolution of this technology is hindered by this problem. In this paper we discuss approaches to represent tagging activities at a semantic level. We present criteria for the comparison of existing tag ontologies and discuss their strengths and weaknesses in relation to these criteria

How to feed the squerall with RDF and other data nuts?

Advances in Data Management methods have resulted in a wide array of storage solutions having varying query capabilities and supporting different data formats. Traditionally, heterogeneous data was transformed off-line into a unique format and migrated to a unique data management system, before being uniformly queried. However, with the increasing amount of heterogeneous data sources, many of which are dynamic, modern applications prefer accessing directly the original fresh data. Addressing this requirement, we designed and developed Squerall, a software framework that enables the querying of original large and heterogeneous data on-the-fly without prior data transformation. Squerall is built from the ground up with extensibility in consideration, e.g., supporting more data sources. Here, we explain Squerall’s extensibility aspect and demonstrate step-by-step how to add support for RDF data, a new extension to the previously supported range of data sources

SEMANTEXPLORER : a semantic web browser

The Semantic Web will be the keystone in the creation of machine accessible domains of information scattered around the globe. All information on the World Wide Web will be semantically enhanced with metadata that makes sense to both human and intelligent information retrieval agents. For the Semantic Web to gain ground it is therefore very important that users are able to easily browse through such metadata. In line with such philosophy we are presenting SemantExplorer, a Semantic Web Browser that enables metadata browsing, provides visualization of different levels of metadata detail and allows for the integration of multiple information sources to provide a more complex and complete view of Web resources.peer-reviewe

PKC-mediated phosphorylation and activation of the MEK/ERK pathway as a mechanism of acquired trastuzumab resistance in HER2-positive breast cancer

Protein expression, activation and stability are regulated through inter-connected signal transduction pathways resulting in specific cellular states. This study sought to differentiate between the complex mechanisms of intrinsic and acquired trastuzumab resistance, by quantifying changes in expression and activity of proteins (phospho-protein profile) in key signal transduction pathways, in breast cancer cellular models of trastuzumab resistance. To this effect, we utilized a multiplex, bead-based protein assay, DigiWest®, to measure around 100 proteins and protein modifications using specific antibodies. The main advantage of this methodology is the quantification of multiple analytes in one sample, utilising input volumes of a normal western blot. The intrinsically trastuzumab-resistant cell line JIMT-1 showed the largest number of concurrent resistance mechanisms, including PI3K/Akt and RAS/RAF/MEK/ERK activation, b catenin stabilization by inhibitory phosphorylation of GSK3b, cell cycle progression by Rb suppression, and CREB-mediated cell survival. MAPK (ERK) pathway activation was common to both intrinsic and acquired resistance cellular models. The overexpression of upstream RAS/RAF, however, was confined to JIMT 1; meanwhile, in a cellular model of acquired trastuzumab resistance generated in this study (T15), entry into the ERK pathway seemed to be mostly mediated by PKCa activation. This is a novel observation and merits further investigation that can lead to new therapeutic combinations in HER2-positive breast cancer with acquired therapeutic resistance.peer-reviewe

Review and Alignment of Tag Ontologies for Semantically-Linked Data in Collaborative Tagging Spaces

Abstract—As the number of Web 2.0 sites offering tagging facilities for the users ’ voluntary content annotation increases, so do the efforts to analyze social phenomena resulting from generated tagging and folksonomies. Most of these efforts provide different views for the understanding of various web activities. Results from various experimental research should be utilized to improve existing approaches underlying tagging data and contribute further to weaving the Web. However, in practice, there are not enough solutions taking advantage of these results. Even though we can mine social relations via tagging data, it proves no worth for users if this data cannot be reused. In this paper we propose a solution for tag data representation which allows data reuse across different tagging systems. To achieve this goal, we analyze current social tagging practices, existing folksonomy usage as well as Semantic Web approaches to data annotation and tagging. We survey and compare existing tag ontologies in an attempt to investigate mapping possibilities between different conceptual models. Finally, we present our method for federation among existing ontologies in order to generate re-usable, semantically-linked data that will underly tagging data. I

Genome-wide screening for DNA variants associated with reading and language traits

This research was funded by: Max Planck Society, the University of St Andrews - Grant Number: 018696, US National Institutes of Health - Grant Number: P50 HD027802, Wellcome Trust - Grant Number: 090532/Z/09/Z, and Medical Research Council Hub Grant Grant Number: G0900747 91070Reading and language abilities are heritable traits that are likely to share some genetic influences with each other. To identify pleiotropic genetic variants affecting these traits, we first performed a genome‐wide association scan (GWAS) meta‐analysis using three richly characterized datasets comprising individuals with histories of reading or language problems, and their siblings. GWAS was performed in a total of 1862 participants using the first principal component computed from several quantitative measures of reading‐ and language‐related abilities, both before and after adjustment for performance IQ. We identified novel suggestive associations at the SNPs rs59197085 and rs5995177 (uncorrected P ≈ 10–7 for each SNP), located respectively at the CCDC136/FLNC and RBFOX2 genes. Each of these SNPs then showed evidence for effects across multiple reading and language traits in univariate association testing against the individual traits. FLNC encodes a structural protein involved in cytoskeleton remodelling, while RBFOX2 is an important regulator of alternative splicing in neurons. The CCDC136/FLNC locus showed association with a comparable reading/language measure in an independent sample of 6434 participants from the general population, although involving distinct alleles of the associated SNP. Our datasets will form an important part of on‐going international efforts to identify genes contributing to reading and language skills.Publisher PDFPeer reviewe