Levels of DNA methylation vary at CpG sites across the BRCA1 promoter, and differ according to triple negative and "BRCA-like" status, in both blood and tumour DNA

Triple negative breast cancer is typically an aggressive and difficult to treat subtype. It is often associated with loss of function of the BRCA1 gene, either through mutation, loss of heterozygosity or methylation. This study aimed to measure methylation of the BRCA1 gene promoter at individual CpG sites in blood, tumour and normal breast tissue, to assess whether levels were correlated between different tissues, and with triple negative receptor status, histopathological scoring for BRCA-like features and BRCA1 protein expression. Blood DNA methylation levels were significantly correlated with tumour methylation at 9 of 11 CpG sites examined (p<0.0007). The levels of tumour DNA methylation were significantly higher in triple negative tumours, and in tumours with high BRCA-like histopathological scores (10 of 11 CpG sites; p<0.01 and p<0.007 respectively). Similar results were observed in blood DNA (6 of 11 CpG sites; p<0.03 and 7 of 11 CpG sites; p<0.02 respectively). This study provides insight into the pattern of CpG methylation across the BRCA1 promoter, and supports previous studies suggesting that tumours with BRCA1 promoter methylation have similar features to those with BRCA1 mutations, and therefore may be suitable for the same targeted therapies

Association between Acquired Uniparental Disomy and Homozygous Mutations and HER2/ER/PR Status in Breast Cancer

Background: Genetic alterations in cellular signaling networks are a hallmark of cancer, however, effective methods to discover them are lacking. A novel form of abnormality called acquired uniparental disomy (aUPD) was recently found to pinpoint the region of mutated genes in various cancers, thereby identifying the region for next-generation sequencing. Methods/Principal Findings: We retrieved large genomic data sets from the Gene Expression Omnibus database to perform genome-wide analysis of aUPD in breast tumor samples and cell lines using approaches that can reliably detect aUPD. Aupd was identified in 52.29% of the tumor samples. The most frequent aUPD regions were located at chromosomes 2q, 3p, 5q, 9p, 9q, 10q, 11q, 13q, 14q and 17q. We evaluated the data for any correlation between the most frequent aUPD regions and HER2/neu, ER, and PR status, and found a statistically significant correlation between the recurrent regions of aUPD and triple negative (TN) breast cancers. aUPD at chromosome 17q (VEZF1, WNT3), 3p (SUMF1, GRM7), 9p (MTAP, NFIB) and 11q (CASP1, CASP4, CASP5) are predictors for TN. The frequency of aUPD was found to be significantly higher in TN breast cancer cases compared to HER2/neu-positive and/or ER or PR-positive cases. Furthermore, using previously published mutation data, we found TP53 homozygously mutated in cell lines having aUPD in that locus. Conclusions/Significance: We conclude that aUPD is a common and non-random molecular feature of breast cancer that is most prominent in triple negative cases. As aUPD regions are different among the main pathological subtypes, specific aUPD regions may aid the sub-classification of breast cancer. In addition, we provide statistical support using TP53 as an example that identifying aUPD regions can be an effective approach in finding aberrant genes. We thus conclu

Dcas Supports Cell Polarization and Cell-Cell Adhesion Complexes in Development

Mammalian Cas proteins regulate cell migration, division and survival, and are often deregulated in cancer. However, the presence of four paralogous Cas family members in mammals (BCAR1/p130Cas, EFS/Sin1, NEDD9/HEF1/Cas-L, and CASS4/HEPL) has limited their analysis in development. We deleted the single Drosophila Cas gene, Dcas, to probe the developmental function of Dcas. Loss of Dcas had limited effect on embryonal development. However, we found that Dcas is an important modulator of the severity of the developmental phenotypes of mutations affecting integrins (If and mew) and their downstream effectors Fak56D or Src42A. Strikingly, embryonic lethal Fak56D-Dcas double mutant embryos had extensive cell polarity defects, including mislocalization and reduced expression of E-cadherin. Further genetic analysis established that loss of Dcas modified the embryonal lethal phenotypes of embryos with mutations in E-cadherin (Shg) or its signaling partners p120- and β-catenin (Arm). These results support an important role for Cas proteins in cell-cell adhesion signaling in development

ﻛﺄﻥ بين ﺍﻟﺘﺸﺨﻴﺺ والتشبيه / Ka\u27anna (as if) between Personification and Similitude

[The main question which this article poses and proceeds to investigate is: how did the classical Arab critics and rhetoricians deal with ka\u27anna (as if)? This particle was normally categorized in their critical writings as the tool by which comparison based on resemblance (tashbīh) is constructed. However, there are many instances where its usage revealed it to be closely linked to personification (tashkhīs) and metaphor (\u27isti\u27āra). In such examples, it becomes especially difficult to identify the two poles of the comparison which are otherwise evident in similes. This article argues that the investigation of such a particular problem sheds light on more general theoretical issues, namely the signification and usage of literary critical terminology in early Arab critical writings, particularly with regard to simile, personification and metaphor. A reading of some late Arabic texts on rhetoric and grammar, especially those produced by the Kūfī critics, reveals that there indeed had been a debate over the signification and usage of ka\u27anna beyond that of establishing comparison based on resemblance (similitude). Among such instances were the use of ka\u27anna to establish approximation (al-taqrīb), assumption (al-ẓann), reckoning (al-ḥusbān) and uncertainty (al-shakk). However, most of these texts, even as they cited instances of such varied usages, continued to ascertain, in accordance with the rule of the majority, that ka\u27anna was used to construct a simile. When the article comes to the later critics, such as Amidī and Jurjānī, who represent the period of maturation of classical Arabic literary criticism, it shows that the former cited examples of ka\u27anna in conceits and strained metaphors (\u27istiʿāra baʿīda) and the latter cited examples of it in personification. Nevertheless, neither one stops to consider the signification of such usages and modify the role of ka\u27anna. Finally, the article seeks to understand why classical Arab critics and rhetoricians paid no attention to such usages of ka\u27anna, despite their citations of instances of its use in metaphor and personification, by providing two possible explanations. First, it argues that the early texts, which dealt with poetics and Quranic interpretation, were devoid of such examples. Hence the absence of the debate. Second, the article argues that the signification of the term simile had a much broader sense for the classical critics so that it encompassed the term metaphor.

Time-Frequency Analysis by Evolutionary Periodogram with Application in Mechanical Fault Diagnosis

The evolutionary periodogram has been introduced to mechanical fault diagnosis and relationship between the evolutionary periodogram and time-frequency spectrogram has been investigated. The evolutionary periodogram is unveiled as an especially windowed spectrogram, and is applied to gearbox fault diagnosis. It has been shown that the window used in the evolutionary periodogram is not a single function but a combination of a set of functions. Two cases of gearbox diagnosis are presented as examples of application. Vibration signals and a synchronous signal are collected for the analysis. The time synchronous averaging is used to reduce background noise or random transients to enhance the periodicity of a specific gear rotation. The performance of the evolutionary periodogram has been compared with the spectrogram for gear diagnosis, showing that the evolutionary periodogram is an alternative technique in time-frequency analysis for fault detection and better resolution can be obtained as more choices are offered by the way of constructing the window

Self-Perception of Dental Esthetics among Dental Students at King Saud University and Their Desired Treatment

Objective. Dental esthetic procedures are popular worldwide, and dentists are responsible for recommending several treatment options to their patients. To do this competently, dentists must have an educated opinion of their features. Therefore, we aimed to evaluate the self-perception of dental esthetics among male and female dental students and assess its effect on their desired treatment. Methodology. We conducted a questionnaire-based cross-sectional study involving 450 male and female dental students from five academic years with different grade point averages (GPAs) and monthly household incomes. The questionnaire comprised four sections. The subjects selected their teeth-color preferences using a commercial shade guide. The outcomes were presented using descriptive statistics and were compared with Pearson’s chi-square test. The level of statistical significance was set at a p-value of 0.05. Results. Female students (52%) showed a significantly higher preference for changing their tooth color (shade B1 was desired most often), whereas male students reported a higher need for orthodontic treatment and ceramic veneers (p<0.0001 and p=0.002). Fifth-year students were more satisfied with their teeth color as compared with 1st-year students (p=0.047). High-GPA students showed significantly lower confidence regarding their smiles (p=0.030). A high percentage of students (39.1%) with household incomes of less than 10,000 SR preferred tooth-colored restorations. Conclusion. We concluded that the majority of dental students were confident about their smiles. Senior students were more satisfied with their teeth color, while younger students desired whiter teeth. Bleaching and orthodontics were the most desired treatment options

A modified S-transform for EEG signals analysis

Due to the advantages offered by the S-transform (ST) distribution, it has been recently successfully implemented for various applications such as seismic and image processing. The desirable properties of the ST include a globally referenced phase as the case with the short time Fourier transform (STFT) while offering a higher spectral resolution as the wavelet transform (WT). However, this estimator suffers from some inherent disadvantages seen as poor energy concentration with higher frequencies. In order to improve the performance of the distribution, a modification to the existing technique is proposed. Additional parameters are proposed to control the window's width which can greatly enhance the signal representation in the time–frequency plane. The new estimator's performance is evaluated using synthetic signals as well as biomedical data. The required features of the ST which include invertability and phase information are still preserved