Obesity-linked insulin resistance, inflammation, and omega-3 fatty acids : exploring the anti-diabetic potential of novel omega-3 derived pro-resolution mediators

Tableau d'honneur de la Faculté des études supérieures et postdoctorales, 2011-2012L'objectif principal des études présentées dans cette thèse était d'étudier les effets métaboliques et anti-inflammatoires des acides gras oméga-3 et leurs dérivés bioactifs, nommés résolvines et protectines, dans le contexte d'obésité et d'insulino-résistance. Afin d'atteindre ce but, nous avons utilisé une nouvelle lignée de souris transgénique, fat-1, qui nous permet d'augmenter les niveaux d'acides gras oméga-3 sans modifier la diète expérimentale. Dans la première étude, nous avons démontré que le rétablissement des acides gras oméga-3 dans les souris obèses nourries avec une diète riche en gras, pouvait augmenter la synthèse des dérivés bioactifs des acides gras oméga-3, notamment les protectines, dans le tissu adipeux et le muscle squelettique. Ceci était associé à une meilleure capacité à résoudre une réponse inflammatoire aigùe et à une diminution de l'inflammation dans le tissu adipeux. De plus, les souris fat-1 obèses ont démontré une meilleure sensibilité à l'insuline et une plus grande tolérance au glucose. Tout cela avec un gain de poids et accretion de graisse équivalents à leurs homologues sauvages. Dans la seconde étude, nous avons analysé les effets métaboliques et antiinflammatoires de l'administration de la protectine DX dans des macrophages in vitro ainsi que dans les souris in vivo. En plus des activités anti-inflammatoires anticipées, nous avons pu observer que la protectine DX possède une activité antidiabétique unique qui pourrait être expliquée par une sécrétion d'interleukine-6 impliquée dans l'inhibition de l'expression des enzymes de la gluconéogenèse dans le foie. Dans la troisième étude, nous avons effectué une analyse comparative par biopuces du tissu adipeux des souris fat-1 obèses et des souris sauvages. Cette étude nous a permis de révéler cinq voies ciblées par des acides gras oméga-3 dans le tissu adipeux. Nous avons pu valider certaines cibles par PCR quantitatif et par histologie. L'ensemble de nos études démontre le rôle déterminant des acides gras oméga-3 et leurs dérivés, notamment les protectines, dans l'homéostasie métabolique. De plus, nous avons été en mesure d'identifier la protectine DX comme un nouvel agent thérapeutique qui possède un important potentiel pour le traitement du diabète de type 2 et de l'obésité

Behavioral phenotypes of impulsivity related to the ANKK1 gene are independent of an acute stressor

<p>Abstract</p> <p>Background</p> <p>The A1 allele of the <it>ANKK1 Taq</it>IA polymorphism (previously reported as located in the D2 dopamine receptor (DRD2) gene) is associated with reduced DRD2 density in the striatum and with clinical disorders, particularly addiction. It was hypothesized that impulsivity represents an endophenotype underlying these associations with the <it>Taq</it>IA and that environmental stress would moderate the strength of the gene-behavior relationship.</p> <p>Methods</p> <p><it>Taq</it>IA genotyping was conducted on 72 healthy young adults who were randomly allocated to either an acute psychosocial stress or relaxation induction condition. Behavioral phenotypes of impulsivity were measured using a card-sorting index of reinforcement sensitivity and computerized response inhibition and delay discounting tasks.</p> <p>Results</p> <p>Separate analyses of variance revealed associations between the A1 allele and two laboratory measures of impulsivity. The presence of the <it>Taq</it>IA allele (A1+) was associated with slower card-sorting in the presence of small financial reinforcers, but was overcome in a second administration after either a five-minute rest or psychosocial stress induction. A1+ participants also demonstrated significantly poorer response inhibition and faster response times on a computerized stop inhibition task, independent of acute stress exposure.</p> <p>Conclusion</p> <p>These findings indicate the A1 allele is associated with an endophenotype comprising both a "rash impulsive" behavioral style and reinforcement-related learning deficits. These effects are independent of stress.</p

Opportunity to Learn: The Role of Prompting Cognitive Shifts in Understanding and Addressing Educational Inequities

Thesis advisor: Diana C. PullinThis dissertation examines how district- and school-level leaders' understanding of achievement gaps influences the work of leadership in addressing educational inequities and broadening students' opportunity to learn. While the reporting of disaggregated data by student subgroup confirms that achievement gaps exist, reports from high-stakes testing fail to provide district- and school-level leaders with the diagnostic data needed to identify key factors inhibiting student performance. Yet, identifying and understanding factors hindering student performance is critical knowledge for leaders to cultivate as they work to address elements within their school or district that may need to change if student learning is to improve. Results from this single case study in a diverse urban district illuminate how district- and school-level leaders can challenge and support their community as they work collectively to confront and address issues related to disparities in student performance. Drawing on previous research, which introduced the cognitive shift as a unit of analysis for studying the work of leadership, this study identifies shifts in thinking that district- and school-level leaders attempted to prompt in others, as well as the framing strategies district- and school-level leaders used in their attempts to prompt identified shifts in thinking. The study found that district- and school-level leaders attempted to prompt a common set of cognitive shifts using a range of framing strategies. Furthermore, the study found a correlation between leaders' use of a particular of framing strategy and their level of leadership (i.e., district or school), with common patterns of strategy use unique to each level of leadership. Additionally, distinct patterns of strategy use also emerged for the leaders of the district's top performing schools which differed from the patterns of strategy use that emerged for the leaders of the district's lower performing schools. These findings suggest that certain framing strategies may be more effective than others.Thesis (EdD) — Boston College, 2014.Submitted to: Boston College. Lynch School of Education.Discipline: Educational Leadership and Higher Education

Opportunity to Learn: the Role of Interactions in Understanding and Addressing Educational Inequities

Thesis advisor: Diana PullinA number of scholars are examining factors hindering student performance. Scholars suggest that understanding these factors is critical knowledge for leaders to cultivate as they work to address elements within their school or district that need to change if student learning is to improve. What is often overlooked in the literature is how educators understand the achievement gap and the impact this understanding has on the learning environment. Exploring how district- and school-level leaders understand disparities in student performance and how these understandings then influence the work of leadership may offer insight into factors hindering student performance. The study was conducted in a small, diverse urban district designated by the state as low performing based on state indicators. Many scholars have explored interactions among leaders as a factor hindering student performance. These researchers indicate the significance of the role that interactions between district- and school-level leaders play in school improvement efforts. Although this is a central focus area in the literature, there is limited scholarship on how those interactions specifically impact leaders' understanding of barriers to students' opportunity to learn. Therefore, analyzing these relations may result in an increased awareness of their impact on the learning environment. This single case study uses document reviews and interview data to analyze leader relations and practice. Findings reveal interactions among leaders resulted in an understanding of barriers in the learning environment; lack of trust hindered some relations but despite this, all leaders engaged in tasks intended to enhance student learning.Thesis (EdD) — Boston College, 2014.Submitted to: Boston College. Lynch School of Education.Discipline: Educational Leadership and Higher Education

Opportunity to Learn: The Role of Professional Learning in Understanding and Addressing Educational Inequities

Thesis advisor: Diana PullinAs district- and school-level leaders face increasing pressure from federal, state, and local accountability mandates, there has been increased dependence on using and analyzing student data to help improve student performance. While the reporting of disaggregated data by student subgroup confirms that achievement gaps exist, it does not provide district- and school-level leaders with the descriptive data needed to identify key factors inhibiting student performance. Identifying and understanding factors hindering student performance is critical knowledge for leaders to cultivate as they work to address elements within their school or district that may need to change if student learning is to improve. This research study examined specific ways district- and school-level leaders go about challenging and helping their community to face the problem of student performance disparities, as well as specific aspects of the situation that may be contributing to the community's collective capacity, to address student performance disparities. Without proper district-level leadership, effectively addressing operational conditions that may lead to disparities in student learning is unlikely. Currently, few studies exist about district-level leaders' use of professional learning to support the development of school-level leaders. However, a review of the literature revealed that some district-level leaders have turned to professional learning to transform school-level leaders' practice in their effort to understand and address disparities, as well as their knowledge about and skills related to working with diverse students. This qualitative single case study in a diverse urban district utilized interview and document data to further understanding on the use of professional learning by district leaders with school leaders. Findings revealed that district-level leaders sought to leverage and foster professional learning for school-level leaders as an action to further learn about, understand, and address the barriers that may be inhibiting students' opportunity to learn.Thesis (EdD) — Boston College, 2014.Submitted to: Boston College. Lynch School of Education.Discipline: Educational Leadership and Higher Education

Opportunity to Learn: The Role of Structures and Routines in Understanding and Addressing Educational Inequities

Thesis advisor: Diana C. PullinAs district- and school-level leaders face increasing pressure from federal, state, and local accountability mandates there has been increased dependence on using and analyzing student data to help improve student performance. While the reporting of disaggregated data by student subgroup confirms that achievement gaps exist, it does not provide district- and school-level leaders with the diagnostic data needed to identify key factors inhibiting student performance. Identifying and understanding factors hindering student performance is critical knowledge for leaders to cultivate as they work to address elements within their school or district that may need to change if student learning is to improve. This research study examined specific ways district- and school-level leaders go about challenging and helping their community to face the problem of student performance disparities, as well as specific aspects of the situation that may be contributing to the community's collective capacity, to address student performance disparities. Without proper district-level leadership, effectively addressing operational conditions that may lead to disparities in student learning is unlikely. Yet, little is known about which structures and routines district- and school-level leaders perceive to be important when analyzing student data. This single case study presents the results of an examination of student data analysis structures and routines within a small diverse urban Massachusetts district designated by the state as low-performing based on state indicators. In order to further understand structures and routines, interview and document data were reviewed. Four primary findings identified the district leadership's response to educational inequities: (1) a mandate for using data war-rooms and student data walls; (2) a traveling cabinet to ensure uniform review of student data across the schools in the district; (3) a mandate for individual school improvement plans; and (4) the use of school-based instructional coaches.Thesis (EdD) — Boston College, 2014.Submitted to: Boston College. Lynch School of Education.Discipline: Educational Leadership and Higher Education

The Primacy of Public Health Considerations in Defining Poor Quality Medicines

Paul Newton and colleagues argue that public health, and not intellectual property or trade issues, should be the prime consideration in defining and combating counterfeit medicines, and that the World Health Organization (WHO) should take a more prominent role

High Resolution Melt (HRM) analysis is an efficient tool to genotype EMS mutants in complex crop genomes

Background: Targeted Induced Loci Lesions IN Genomes (TILLING) is increasingly being used to generate and identify mutations in target genes of crop genomes. TILLING populations of several thousand lines have been generated in a number of crop species including Brassica rapa. Genetic analysis of mutants identified by TILLING requires an efficient, high-throughput and cost effective genotyping method to track the mutations through numerous generations. High resolution melt (HRM) analysis has been used in a number of systems to identify single nucleotide polymorphisms (SNPs) and insertion/deletions (IN/DELs) enabling the genotyping of different types of samples. HRM is ideally suited to high-throughput genotyping of multiple TILLING mutants in complex crop genomes. To date it has been used to identify mutants and genotype single mutations. The aim of this study was to determine if HRM can facilitate downstream analysis of multiple mutant lines identified by TILLING in order to characterise allelic series of EMS induced mutations in target genes across a number of generations in complex crop genomes. Results: We demonstrate that HRM can be used to genotype allelic series of mutations in two genes, BraA.CAX1a and BraA.MET1.a in Brassica rapa. We analysed 12 mutations in BraA.CAX1.a and five in BraA.MET1.a over two generations including a back-cross to the wild-type. Using a commercially available HRM kit and the Lightscanner™ system we were able to detect mutations in heterozygous and homozygous states for both genes. Conclusions: Using HRM genotyping on TILLING derived mutants, it is possible to generate an allelic series of mutations within multiple target genes rapidly. Lines suitable for phenotypic analysis can be isolated approximately 8-9 months (3 generations) from receiving M3 seed of Brassica rapa from the RevGenUK TILLING service

Lofar Low-Band Antenna Observations of the 3C 295 and Bootes Fields: Source Counts and Ultra-Steep Spectrum Sources

We present Low Frequency Array (LOFAR) Low Band observations of the Boötes and 3C 295 fields. Our images made at 34, 46, and 62 MHz reach noise levels of 12, 8, and 5 mJy beam-1, making them the deepest images ever obtained in this frequency range. In t

Characterizing Lightning-Initiated Wildfire to Develop New Nowcasting Techniques for Wildfire Identification

No abstract availabl