Universal design for learning in physical education: Overview and critical reflection

Universal design for learning (UDL) has been advocated for by adapted physical education scholars as a panacea to the challenges associated with teaching disabled and nondisabled students together in physical education. So much so that UDL currently occupies a privileged and largely unquestioned position in adapted physical education scholarship and practice, until now. To move scholarship forward, this article draws on published theoretical and empirical work relating to UDL generally and in physical education in particular to critically discuss the scientific research supporting, or not, the use of UDL as a so-called inclusive approach. We end this article with a call to action for scholars in this field, ourselves included, to conduct theoretically guided and empirically informed research relating to UDL in physical education, which adheres to established hallmarks of research quality that are tied to the ontological and epistemological assumptions of researchers because, at present, it is conspicuous by its absence

Beta-Catenin Phosphorylated at Threonine 120 Antagonizes Generation of Active Beta-Catenin by Spatial Localization in trans-Golgi Network

The stability and subcellular localization of beta-catenin, a protein that plays a major role in cell adhesion and proliferation, is tightly regulated by multiple signaling pathways. While aberrant activation of beta-catenin signaling has been implicated in cancers, the biochemical identity of transcriptionally active beta-catenin (ABC), commonly known as unphosphorylated serine 37 (S37) and threonine 41 (T41) β-catenin, remains elusive. Our current study demonstrates that ABC transcriptional activity is influenced by phosphorylation of T120 by Protein Kinase D1 (PKD1). Whereas the nuclear β-catenin from PKD1-low prostate cancer cell line C4-2 is unphosphorylated S37/T41/T120 with high transcription activity, the nuclear β-catenin from PKD1-overexpressing C4-2 cells is highly phosphorylated at T120, S37 and T41 with low transcription activity, implying that accumulation of nuclear β-catenin alone cannot be simply used as a read-out for Wnt activation. In human normal prostate tissue, the phosphorylated T120 β-catenin is mainly localized to the trans-Golgi network (TGN, 22/30, 73%), and this pattern is significantly altered in prostate cancer (14/197, 7.1%), which is consistent with known down regulation of PKD1 in prostate cancer. These in vitro and in vivo data unveil a previously unrecognized post-translational modification of ABC through T120 phosphorylation by PKD1, which alters subcellular localization and transcriptional activity of β-catenin. Our results support the view that β-catenin signaling activity is regulated by spatial compartmentation and post-translational modifications and protein level of β-catenin alone is insufficient to count signaling activity

SAW: A Method to Identify Splicing Events from RNA-Seq Data Based on Splicing Fingerprints

Splicing event identification is one of the most important issues in the comprehensive analysis of transcription profile. Recent development of next-generation sequencing technology has generated an extensive profile of alternative splicing. However, while many of these splicing events are between exons that are relatively close on genome sequences, reads generated by RNA-Seq are not limited to alternative splicing between close exons but occur in virtually all splicing events. In this work, a novel method, SAW, was proposed for the identification of all splicing events based on short reads from RNA-Seq. It was observed that short reads not in known gene models are actually absent words from known gene sequences. An efficient method to filter and cluster these short reads by fingerprint fragments of splicing events without aligning short reads to genome sequences was developed. Additionally, the possible splicing sites were also determined without alignment against genome sequences. A consensus sequence was then generated for each short read cluster, which was then aligned to the genome sequences. Results demonstrated that this method could identify more than 90% of the known splicing events with a very low false discovery rate, as well as accurately identify, a number of novel splicing events between distant exons

An Evaluation of Prediction Equations for the 6 Minute Walk Test in Healthy European Adults Aged 50-85 Years

This study compared actual 6 minute walk test (6MWT) performance with predicted 6MWT using previously validated equations and then determined whether allometric modelling offers a sounder alternative to estimating 6MWT in adults aged 50-80 years.We compared actual 6MWT performance against predicted 6MWT in 125 adults aged 50-85 years (62 male, 63 female). In a second sample of 246 adults aged 50-85 years (74 male, 172 female), a new prediction equation for 6MWT performance was developed using allometric modelling. This equation was then cross validated using the same sample that the other prediction equations were compared with.Significant relationships were evident between 6MWT actual and 6MWT predicted using all of the commonly available prediction equations (all P<0.05 or better) with the exception of the Alameri et al prediction equation (P>0.05). A series of paired t-tests indicated significant differences between 6MWT actual and 6MWT predicted for all available prediction equations (all P<0.05 or better) with the exception of the Iwama et al equation (P = .540). The Iwama et al equation also had similar bias (79.8m) and a coefficient of variation of over 15%. Using sample 2, a log-linear model significantly predicted 6MWT from the log of body mass and height and age (P = 0.001, adjusted R2 = .526), predicting 52.6% of the variance in actual 6MWT. When this allometric equation was applied to the original sample, the relationship between 6MWT actual and 6MWT predicted was in excess of values reported for the other previously validated prediction equations (r = .706, P = 0.001). There was a significant difference between actual 6MWT and 6MWT predicted using this new equation (P = 0.001) but the bias, standard deviation of differences and coefficient of variation were all less than for the other equations.Where actual assessment of the 6MWT is not possible, the allometrically derived equation presented in the current study, offers a viable alternative which has been cross validated and has the least SD of differences and smallest coefficient of variation compared to any of the previously validated equations for the 6MWT

The precancer risk of betel quid chewing, tobacco use and alcohol consumption in oral leukoplakia and oral submucous fibrosis in southern Taiwan

In areas where the practise of betel quid chewing is widespread and the chewers also often smoke and drink alcohol, the relation between oral precancerous lesion and condition to the three habits is probably complex. To explore such association and their attributable effect on oral leukoplakia (OL) and oral submucous fibrosis (OSF), a gender–age-matched case–control study was conducted at Kaohsiung, southern Taiwan. This study included 219 patients with newly diagnosed and histologically confirmed OL or OSF, and 876 randomly selected community controls. All information was collected by a structured questionnaire through in-person interviews. A preponderance of younger patients had OSF, while a predominance of older patients had OL. Betel quid chewing was strongly associated with both these oral diseases, the attributable fraction of OL being 73.2% and of OSF 85.4%. While the heterogeneity in risk for areca nut chewing across the two diseases was not apparent, betel quid chewing patients with OSF experienced a higher risk at each exposure level of chewing duration, quantity and cumulative measure than those who had OL. Alcohol intake did not appear to be a risk factor. However, cigarette smoking had a significant contribution to the risk of OL, and modified the effect of chewing based on an additive interaction model. For the two oral premalignant diseases combined, 86.5% was attributable to chewing and smoking. Our results suggested that, although betel quid chewing was a major cause for both OL and OSF, its effect might be difference between the two diseases. Cigarette smoking has a modifying effect in the development of oral leukoplakia

FusionSeq: a modular framework for finding gene fusions by analyzing paired-end RNA-sequencing data

We have developed FusionSeq to identify fusion transcripts from paired-end RNA-sequencing. FusionSeq includes filters to remove spurious candidate fusions with artifacts, such as misalignment or random pairing of transcript fragments, and it ranks candidates according to several statistics. It also has a module to identify exact sequences at breakpoint junctions. FusionSeq detected known and novel fusions in a specially sequenced calibration data set, including eight cancers with and without known rearrangements

Disease-associated alleles in genome-wide association studies are enriched for derived low frequency alleles relative to HapMap and neutral expectations

<p>Abstract</p> <p>Background</p> <p>Genome-wide association studies give insight into the genetic basis of common diseases. An open question is whether the allele frequency distributions and ancestral vs. derived states of disease-associated alleles differ from the rest of the genome. Characteristics of disease-associated alleles can be used to increase the yield of future studies.</p> <p>Methods</p> <p>The set of all common disease-associated alleles found in genome-wide association studies prior to January 2010 was analyzed and compared with HapMap and theoretical null expectations. In addition, allele frequency distributions of different disease classes were assessed. Ages of HapMap and disease-associated alleles were also estimated.</p> <p>Results</p> <p>The allele frequency distribution of HapMap alleles was qualitatively similar to neutral expectations. However, disease-associated alleles were more likely to be low frequency derived alleles relative to null expectations. 43.7% of disease-associated alleles were ancestral alleles. The mean frequency of disease-associated alleles was less than randomly chosen CEU HapMap alleles (0.394 vs. 0.610, after accounting for probability of detection). Similar patterns were observed for the subset of disease-associated alleles that have been verified in multiple studies. SNPs implicated in genome-wide association studies were enriched for young SNPs compared to randomly selected HapMap loci. Odds ratios of disease-associated alleles tended to be less than 1.5 and varied by frequency, confirming previous studies.</p> <p>Conclusions</p> <p>Alleles associated with genetic disease differ from randomly selected HapMap alleles and neutral expectations. The evolutionary history of alleles (frequency and ancestral vs. derived state) influences whether they are implicated in genome-wide assocation studies.</p

Plasma cytokines in women with chronic fatigue syndrome

© 2009 Fletcher et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Poly (A)+ Transcriptome Assessment of ERBB2-Induced Alterations in Breast Cell Lines

We report the first quantitative and qualitative analysis of the poly (A)+ transcriptome of two human mammary cell lines, differentially expressing (human epidermal growth factor receptor) an oncogene over-expressed in approximately 25% of human breast tumors. Full-length cDNA populations from the two cell lines were digested enzymatically, individually tagged according to a customized method for library construction, and simultaneously sequenced by the use of the Titanium 454-Roche-platform. Comprehensive bioinformatics analysis followed by experimental validation confirmed novel genes, splicing variants, single nucleotide polymorphisms, and gene fusions indicated by RNA-seq data from both samples. Moreover, comparative analysis showed enrichment in alternative events, especially in the exon usage category, in ERBB2 over-expressing cells, data indicating regulation of alternative splicing mediated by the oncogene. Alterations in expression levels of genes, such as LOX, ATP5L, GALNT3, and MME revealed by large-scale sequencing were confirmed between cell lines as well as in tumor specimens with different ERBB2 backgrounds. This approach was shown to be suitable for structural, quantitative, and qualitative assessment of complex transcriptomes and revealed new events mediated by ERBB2 overexpression, in addition to potential molecular targets for breast cancer that are driven by this oncogene