Activity of Genes with Functions in Human Williams-Beuren Syndrome Is Impacted by Mobile Element Insertions in the Gray Wolf Genome.

In canines, transposon dynamics have been associated with a hyper-social behavioral syndrome, although the functional mechanism has yet to be described. We investigate the epigenetic and transcriptional consequences of these behavior-associated mobile element insertions (MEIs) in dogs and Yellowstone gray wolves. We posit that the transposons themselves may not be the causative feature; rather, their transcriptional regulation may exert the functional impact. We survey four outlier transposons associated with hyper-sociability, with the expectation that they are targeted for epigenetic silencing. We predict hyper-methylation of MEIs, suggestive that the epigenetic silencing of and not the MEIs themselves may be driving dysregulation of nearby genes. We found that transposon-derived sequences are significantly hyper-methylated, regardless of their copy number or species. Further, we have assessed transcriptome sequence data and found evidence that MEIs impact the expression levels of six genes (WBSCR17, LIMK1, GTF2I, WBSCR27, BAZ1B, and BCL7B), all of which have known roles in human Williams-Beuren syndrome due to changes in copy number, typically hemizygosity. Although further evidence is needed, our results suggest that a few insertions alter local expression at multiple genes, likely through a cis-regulatory mechanism that excludes proximal methylation

What spelling errors can tell us about the development of processes involved in children’s spelling

Introduction: Spelling is an essential foundation for reading and writing. However, many children leave school with spelling difficulties. By understanding the processes children use when they spell, we can intervene with appropriate instruction tailored to their needs. Methods: Our study aimed to identify key processes (lexical-semantic and phonological) by using a spelling assessment that distinguishes different printed letter strings/word types (regular and irregular words, and pseudowords). Misspellings in the test from 641 pupils in Reception Year to Year 6 were scored using alternatives to binary correct versus incorrect scoring systems. The measures looked at phonological plausibility, phoneme representations and letter distance. These have been used successfully in the past but not with a spelling test that distinguishes irregularly spelled words from regular words and pseudowords. Results: The findings suggest that children in primary school rely on both lexical-semantic and phonological processes to spell all types of letter string, but this varies depending on the level of spelling experience (younger Foundation/Key stage 1 and older Key stage 2). Although children in younger year groups seemed to rely more on phonics, based on the strongest correlation coefficients for all word types, with further spelling experience, lexical processes seemed to be more evident, depending on the type of word examined. Discussion: The findings have implications for the way we teach and assess spelling and could prove to be valuable for educators

Determining Principal Component Cardinality through the Principle of Minimum Description Length

PCA (Principal Component Analysis) and its variants areubiquitous techniques for matrix dimension reduction and reduced-dimensionlatent-factor extraction. One significant challenge in using PCA, is thechoice of the number of principal components. The information-theoreticMDL (Minimum Description Length) principle gives objective compression-based criteria for model selection, but it is difficult to analytically applyits modern definition - NML (Normalized Maximum Likelihood) - to theproblem of PCA. This work shows a general reduction of NML prob-lems to lower-dimension problems. Applying this reduction, it boundsthe NML of PCA, by terms of the NML of linear regression, which areknown.Comment: LOD 201

On the discovery of K-enhanced and possibly Mg-depleted stars throughout the Milky Way

Stars with unusual elemental abundances offer clues about rare astrophysical events or nucleosynthetic pathways. Stars with significantly depleted magnesium and enhanced potassium ([Mg/Fe] 1) have to date only been found in the massive globular cluster NGC 2419 and, to a lesser extent, NGC 2808. The origin of this abundance signature remains unknown, as does the reason for its apparent exclusivity to these two globular clusters. Here we present 112 field stars, identified from 454,180 LAMOST giants, that show significantly enhanced [K/Fe] and possibly depleted [Mg/Fe] abundance ratios. Our sample spans a wide range of metallicities (-1.5 < [Fe/H] < 0.3), yet none show abundance ratios of [K/Fe] or [Mg/Fe] that are as extreme as those observed in NGC 2419. If confirmed, the identified sample of stars represents evidence that the nucleosynthetic process producing the anomalous abundances ratios of [K/Fe] and [Mg/Fe] probably occurs at a wide range of metallicities. This would suggest that pollution scenarios that are limited to early epochs (such as Population III supernovae) are an unlikely explanation, although they cannot be ruled out entirely. This sample is expected to help guide modelling attempts to explain the origin of the Mg-K abundance signature

Optimal search strategies for identifying sound clinical prediction studies in EMBASE

BACKGROUND: Clinical prediction guides assist clinicians by pointing to specific elements of the patient's clinical presentation that should be considered when forming a diagnosis, prognosis or judgment regarding treatment outcome. The numbers of validated clinical prediction guides are growing in the medical literature, but their retrieval from large biomedical databases remains problematic and this presents a barrier to their uptake in medical practice. We undertook the systematic development of search strategies ("hedges") for retrieval of empirically tested clinical prediction guides from EMBASE. METHODS: An analytic survey was conducted, testing the retrieval performance of search strategies run in EMBASE against the gold standard of hand searching, using a sample of all 27,769 articles identified in 55 journals for the 2000 publishing year. All articles were categorized as original studies, review articles, general papers, or case reports. The original and review articles were then tagged as 'pass' or 'fail' for methodologic rigor in the areas of clinical prediction guides and other clinical topics. Search terms that depicted clinical prediction guides were selected from a pool of index terms and text words gathered in house and through request to clinicians, librarians and professional searchers. A total of 36,232 search strategies composed of single and multiple term phrases were trialed for retrieval of clinical prediction studies. The sensitivity, specificity, precision, and accuracy of search strategies were calculated to identify which were the best. RESULTS: 163 clinical prediction studies were identified, of which 69 (42.3%) passed criteria for scientific merit. A 3-term strategy optimized sensitivity at 91.3% and specificity at 90.2%. Higher sensitivity (97.1%) was reached with a different 3-term strategy, but with a 16% drop in specificity. The best measure of specificity (98.8%) was found in a 2-term strategy, but with a considerable fall in sensitivity to 60.9%. All single term strategies performed less well than 2- and 3-term strategies. CONCLUSION: The retrieval of sound clinical prediction studies from EMBASE is supported by several search strategies

Forkhead box K2 modulates epirubicin and paclitaxel sensitivity through FOXO3a in breast cancer

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Impact on genitourinary function and quality of life following focal irreversible electroporation of different prostate segments

© Turkish Society of Radiology 2018. PURPOSE We aimed to evaluate the genitourinary function and quality of life (QoL) following the ablation of different prostate segments with irreversible electroporation (IRE) for localized prostate cancer (PCa). METHODS Sixty patients who received primary focal IRE for organ-confined PCa were recruited for this study. Patients were evaluated for genitourinary function and QoL per prostate segment treated (anterior vs. posterior, apex vs. base vs. apex-to-base, unilateral vs. bilateral). IRE system settings and patient characteristics were compared between patients with preserved vs. those with impaired erectile function and urinary continence. Data were prospectively collected at baseline, 3, 6, and 12 months using the expanded prostate cancer index composite, American Urological Association symptom score, SF-12 physical and mental component summary surveys. Difference over time within segments per questionnaire was evaluated using the Wilcoxon’s signed rank test. Outcome differences between segments were assessed using covariance models. Baseline measurements included questionnaire scores, age, and prostate volume. RESULTS There were no statistically significant changes over time for overall urinary (P = 0.07-0.89), bowel (P = 0.06-0.79), physical (P = 0.18-0.71) and mental (P = 0.45-0.94) QoL scores within each segment. Deterioration of sexual function scores was observed at 6 months within each segment (P = 0.001-0.16). There were no statistically significant differences in QoL scores between prostate segments (P = 0.08-0.97). Older patients or those with poor baseline sexual function at time of treatment were associated with a greater risk of developing erectile dysfunction. CONCLUSION IRE is a feasible modality for all prostate segments without any significantly different effect on the QoL outcomes. Older patients and those with poor sexual function need to be counseled regarding the risk of erectile dysfunction