High through-put sequencing of the Parhyale hawaiensis mRNAs and microRNAs to aid comparative developmental studies

Understanding the genetic and evolutionary basis of animal morphological diversity will require comparative developmental studies that use new model organisms. This necessitates development of tools for the study of genetics and also the generation of sequence information of the organism to be studied. The development of next generation sequencing technology has enabled quick and cost effective generation of sequence information. Parhyale hawaiensis has emerged as a model organism of choice due to the development of advanced molecular tools, thus P. hawaiensis genetic information will help drive functional studies in this organism. Here we present a transcriptome and miRNA collection generated using next generation sequencing platforms. We generated approximately 1.7 million reads from a P. hawaiensis cDNA library constructed from embryos up to the germ band stage. These reads were assembled into a dataset comprising 163,501 transcripts. Using the combined annotation of Annot8r and pfam2go, Gene Ontology classifications was assigned to 20,597 transcripts. Annot8r was used to provide KEGG orthology to our transcript dataset. A total of 25,292 KEGG pathway assignments were defined and further confirmed with reciprocal blast against the NCBI nr protein database. This has identified many P. hawaiensis gene orthologs of key conserved signalling pathways involved in development. We also generated small RNA sequences from P. hawaiensis, identifying 55 conserved miRNAs. Sequenced small RNAs that were not annotated by stringent comparison to mirBase were used to search the Daphnia pulex for possible novel miRNAs. Using a conservative approach, we have identified 51 possible miRNA candidates conserved in the Daphnia pulex genome, which could be potential crustacean/arthropod specific miRNAs. Our study presents gene and miRNA discovery in a new model organism that does not have a sequenced genome. The data provided by our work will be valuable for the P. hawaiensis community as well as the wider evolutionary developmental biology community

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

10. Roles, identities, and expectancies: Positive contributions to Normalization and Social Role Valorization

1 INTRODUCTION In 1982, Steve Tullman and Wolf Wolfensberger reformulated the Normalization principle, stating that Normalization hinged upon the attributions of valued social roles to otherwise devalued individuals and classes of people. It was “the insight that the creation of valued social roles for people at risk of social devaluation was the epitome of Normalization” (Wolfensberger, 1983, p. 237). A year later Wolfensberger concluded that this new formulation was such a drastic departure..

Our perverse reliance on prescribed standardized processes as proxies for quality in Ontario Children's Aid Societies: Towards the establishment of direct service and outcomes standards

The Ontario child protection system has, over the past 13 years, gone through two waves of reform but a recent government audit has highlighted ongoing concerns with performance and cost. In response, the Ontario Government set up a "Commission to Promote Sustainable Child Welfare" to address these concerns. The Ontario reform strategy has introduced much standardization and a compliance regime to ensure service quality. In this article, the bona fides and costs of such a strategy are examined and the author proposes that continuous outcomes monitoring and a standard to safeguard direct service time to clients are essential if child protection services are to improve.Accountability Standardization Outcomes Direct service Efficiency Effectiveness Compliance monitoring

1. Normalization and Social Role Valorization at a quarter-century: Evolution, impact, and renewal

There can be little doubt of the central importance of Normalization and Social Role Valorization (SRV) principles in shaping human service policies and practices in several fields over the past quarter-century. This has been very much the case in mental retardation and, to a lesser degree, in mental health and aging, as a few examples will illustrate. Heller, Spooner, Enright, Haney, and Schilit (1991) found that Wolfensberger’s (1972) book The Principle of Normalization in Human Services wa..

The Art of Happiness at Work

In the public sector and in human services particularly, human resources – employees – are the means to the end. The old Defasco steel ad slogan told us “Our product is steel. Our strength is people ” and, in the public sector where the product is the crafting of the public good, the adage about the people is likely more critical. So what about our people? Are they well enough to be the strength of the system that guarantees the public good? Recent surveys (AOL, 2011; Barrows & Wesson, 2001; Burch and Axworthy, 2010) suggest that not all public servants are satisfied with their roles, and these authors recommend systemic change, suggesting that the employer must reform its human resource practices. Organizational, employee and workplace “wellness ” are strategies that put the onus on the employer to create work conditions that promote healthier and happier employees. “If there is injustice, then I think inaction is the wrong response.”- The Dalaï Lama It would seem, however, that the Buddhist tradition, without refuting the possibility of systemic reform, would view such problems from a different and more personal perspective. The Dalaï Lama and Howard Cutler weigh in on the issue of employee happiness in a different and interesting way

454 read length distribution.

<p>A plot showing the distribution of the trimmed <i>P. hawaiensis</i> cDNA sequence reads generated from 454 Titanium sequencing chemistry.</p

The classifications of transcripts according to Gene Ontology (GO) terms.

<p>The classification counts are shown for each of the first tier terms of the three GO database domains; Cellular Component (A), Biological Process (B), and Molecular Function (C).</p

Conserved miRNAs with high expression values identified in <i>P. hawaiensis</i> developing embryos.

<p>The table lists 10 small RNA sequenced from <i>P. hawaiensis</i> embryos with identified homology to known miRNA sequences present in mirBase (release 17). Bases in bold and lower case indicate the allowed mismatch during homology mapping. Tag counts refer to the number of sequence matches found to that particular reference miRNA sequence. Only the sequences greater than 100 tag counts for either of the two stages examined has been listed. All identified miRNAs are presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0033784#pone.0033784.s004" target="_blank">Tables S4</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0033784#pone.0033784.s005" target="_blank">S5</a>.</p

MapMi homology mapping of <i>P. hawaiensis</i> conserved miRNA to the <i>Daphnia pulex</i> genome.

<p>Table shows the result of MapMi homology mapping to the <i>D. pulex</i> genome with <i>P. hawaiensis</i> sequences annotated by known miRNA from mirBase with a tolerance of a 1 bp mismatch. The mapping position on the <i>D. pulex</i> chromosome corresponding to known miRNA sequences are shown with the calculated MapMi score for the mapping and RNA fold analysis.</p