ORegAnno: an open-access community-driven resource for regulatory annotation

ORegAnno is an open-source, open-access database and literature curation system for community-based annotation of experimentally identified DNA regulatory regions, transcription factor binding sites and regulatory variants. The current release comprises 30 145 records curated from 922 publications and describing regulatory sequences for over 3853 genes and 465 transcription factors from 19 species. A new feature called the ‘publication queue’ allows users to input relevant papers from scientific literature as targets for annotation. The queue contains 4438 gene regulation papers entered by experts and another 54 351 identified by text-mining methods. Users can enter or ‘check out’ papers from the queue for manual curation using a series of user-friendly annotation pages. A typical record entry consists of species, sequence type, sequence, target gene, binding factor, experimental outcome and one or more lines of experimental evidence. An evidence ontology was developed to describe and categorize these experiments. Records are cross-referenced to Ensembl or Entrez gene identifiers, PubMed and dbSNP and can be visualized in the Ensembl or UCSC genome browsers. All data are freely available through search pages, XML data dumps or web services at: http://www.oreganno.org

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Parental involvement and student performance : the contributions of economic, cultural, and social capital

The purpose of this study is threefold. First, it is to clarify the construct, parental involvement, by examining its different dimensions both theoretically and empirically. The second purpose is to identify important family factors and institutional factors that affect parental involvement. Finally, this study examines how students' learning outcomes are related to different dimensions of parental involvement. A conceptual framework is proposed that indicates the relationships between school factors, family factors, parental involvement and students' learning outcomes. The construct of "capital" is used as an explanatory tool within this framework. The research was conducted in two phases. Data were collected as part of a larger project which studied the effectiveness of elementary schools in British Columbia (Willms, 1992). Phase I of the study was conducted in 1994. Questionnaires were sent to a population of fifteen hundred B.C. elementary school principals. A total of 831 school administrators returned the questionnaires. Phase II of the study was conducted in 1995. Forty-nine schools were sampled strategically according to the variability of parents' socioeconomic backgrounds. A total of 404 teachers and 1042 fifth-grade students completed questionnaires. Hierarchical Linear Modelling was then used to explore the nature and impact of parental involvement. The extent of parental involvement in grade 5 was generally low in B.C. elementary schools. Levels of parental involvement did not vary substantially among schools; therefore, it was difficult to identify schools which could induce particularly high or low levels of involvement. In exploring the barriers and facilitators of parental involvement, evidence from this study suggests that substantial decentralization of instructional activities, and positive teacher attitudes and practices enhance parental involvement. Another important school factor is the nurturing of social capital within the school. The findings indicate that a positive social climate is a major determinant of parental involvement. An important home factor is cultural capital provided by parents. The results suggest that cultural capital rather than economic capital determines the levels of parental involvement in education. The effects of different types of parental involvement on students' learning outcomes were relatively weak in this study. Home-based involvement was not generally effective for improving children's learning, and school-based involvement had a small positive effect on student's self-esteem but was negatively related to student academic achievement. It appears that parental involvement tended to be reactive rather than proactive. Parents with children at risk academically and socially were more likely to be involved. Yet the study has demonstrated that investment of educational time and monitoring of peer activities were possible intervening variables through which parents could indirectly affect students' learning outcomes. In the conceptual framework of this study, learning outcomes was viewed as a function of the availability of: economic capital, cultural capital and social capital. Among these major forms of resources, social capital nurtured by the school was the most powerful determinant of students' self-esteem. Cultural capital and economic capital had a moderate effect on both students' self-esteem and academic achievement, but their contribution varied from one cognitive characteristic to another. These results provide substantial evidence to support the integration of Coleman's social capital thesis and Bourdieu's cultural capital thesis. An inclusive model, which emphasizes the inclusion of resources from family, school, and community, appears to be the most promising avenue for improving children's learning.Education, Faculty ofGraduat

Educational leadership for parental involvement in an Asian context: Insights from Bourdieu&apos;s theory of practice. The Community Journal

Abstract This article examines how educational leadership defines parental involvement and shapes the nature of home-school collaboration in schools in an Asian context. Results show three major types of principal leadership, or habitus of parental involvement: bureaucratic, utilitarian, and communitarian, which provide a more powerful explanation for the extent and nature of homeschool collaboration than parents&apos; capital in this context. The present article adds to the existing literature by application of Bourdieu&apos;s concepts of field, habitus, and capital to understand the relationship between principals&apos; leadership and different types of home-school relationships

The parent perspective

This chapter discusses the parent perspective in terms of what parents of students attending the SSL think about their child's involvement. Over time, a number of projects have examined parent perceptions but the most recent one is discussed in this chapter. This particular project involved surveying and interviewing parents of students attending the three SSL campuses during Terms 3 and 4 of the 2012 school year. While the sample is not large, it certainly provides support to the large body of anecdotal evidence about the very high level of parent satisfaction with the SSL. The findings from the interviews conducted with 15 parents have already been published in a refereed conference paper, which is referred to later in this chapter. The findings from the pre- and post-surveys completed by 38 parents indicated that parents were aware of both the benefits and challenges faced by their children. Moreover, they had very high expectations in terms of the type of growth in understanding of self, others and the ecosystem in which they were living, as outcomes of the SSL experience. Post-survey results illustrated that these expectations were not only met but exceeded