Characterisation of the ubiquitin E3 ligase COP1

Constitutive photomorphogenic 1 (COP1) is a ubiquitin E3 ligase that has been implicated in development of a variety cancers. The goal was to characterise the ubiquitin E3 ligase activity of COP1 and the relationship between COP1 and its interaction partners—especially the substrate adapters, TRIB1 and TRIB2 in order to better understand their role in tumourigenesis. COP1 consists of a N-terminal RING domain and a C-terminal seven bladed β-propeller fold (WD40 domain), connected by a central coiled-coil. As well as direct substrates, the COP1 WD40 domain binds to the C-terminal tails of TRIB1/2, which recruit further substrates through their pseudo-kinase domains. An expression system for the COP1 WD40 domain in insect cell lines from Spodoptera frugiperda and Trichoplusia ni was developed. The ternary interactions between COP1, TRIB1, and their substrate C/EBPα were characterised using fluorescence polarisation assays. The evidence presented indicates that the interaction of C/EBPα with TRIB1 induces conformational change in TRIB1, which releases the TRIB1 C-terminal tail for interaction with COP1. The relationship between oligomerisation of the COP1 and its ubiquitin E3 ligase activity, was investigated using multiple-angle light scattering and in vitro activity assays. These analyses have revealed that the oligomerisation of COP1 is crucial for its ubiquitin E3 ligase activity. Specifically, dimerisation mediated by the coiled-coil domain significantly enhances the ubiquitin E3 ligase activity of COP1—a common feature of RING-type ubiquitin E3 ligases. Together, these experiments will help elucidate the mechanism through which COP1 functions as a ubiquitin E3 ligase and the interaction with substrates recruited by TRIB1/2, which will guide our understanding of COP1 in the pathogenesis of disease

Kin and Kina: A Study of Emerging Inequalities in a Rural Lowland Society in Papua New Guinea

The thesis describes processes of social and economic change in a lowlands village in Papua New Guinea. The study focuses on the interface between the 'modern' and 'traditional' economies, and is based on an 18 month intensive fieldstudy in 1988/89 of a Wosera village in the East Sepik Province. Data reveal an economic and social division between a poor group of immigrant households (residing in the village for less than 4 generations), and a wealthier group of established households, which have resided in the village for more than 6 generations. Immigrant households hold fewer resources (land, sago and permanent cash crops) than established households. Indigenous exchange networks play a fundamental role in maintaining and accentuating social and economic inequalities. Because immigrant households have few resources, they must enter asymmetrical exchange relationships with resource-rich established lineages for access to the means of production. Through indigenous exchange, immigrants are net givers of wealth and labour, whilst established households are net receivers. Established households are able to supplement their levels of disposable cash incomes by re-directing cash from the indigenous exchange economy to the market economy

Resilience in a Watershed Governance Context: A Primer

Watersheds are complex systems involving social, economic, and ecological dimensions that are constantly interacting and influencing each other, and governance of these systems involve a large and diverse cast of actors that add to the complexity and difficulty in deciding what is best for the watershed and people. Resilience thinking offers a way to understand and navigate the uncertainty, dynamics and complexity of watershed governance. This primer describes key ideas associated with resilience: more inclusive participation; building a shared understanding; inclusion of ecosystem services and functions in long-term planning; strong leadership; institutional and decision making flexibility; and, a decentralized system. This primer is an initial effort to translate the scholarly understanding of these key ideas and initiate a dialogue about their application in the context of watershed governance.Social Sciences and Humanities Research Council of Canada through the Water Economicsw, Policy and Governance Network Social Sciences and Humanities Research Council Insight Development Gran

Aortic haemodynamics: the effects of habitual endurance exercise, age and muscle sympathetic vasomotor outflow in healthy men

PURPOSE: We determined the effect of habitual endurance exercise and age on aortic pulse wave velocity (aPWV), augmentation pressure (AP) and systolic blood pressure (aSBP), with statistical adjustments of aPWV and AP for heart rate and aortic mean arterial pressure, when appropriate. Furthermore, we assessed whether muscle sympathetic nerve activity (MSNA) correlates with AP in young and middle-aged men. METHODS: Aortic PWV, AP, aortic blood pressure (applanation tonometry; SphygmoCor) and MSNA (peroneal microneurography) were recorded in 46 normotensive men who were either young or middle-aged and endurance-trained runners or recreationally active nonrunners (10 nonrunners and 13 runners within each age-group). Between-group differences and relationships between variables were assessed via ANOVA/ANCOVA and Pearson product-moment correlation coefficients, respectively. RESULTS: Adjusted aPWV and adjusted AP were similar between runners and nonrunners in both age groups (all, P > 0.05), but higher with age (all, P < 0.001), with a greater effect size for the age-related difference in AP in runners (Hedges’ g, 3.6 vs 2.6). aSBP was lower in young (P = 0.009; g = 2.6), but not middle-aged (P = 0.341; g = 1.1), runners compared to nonrunners. MSNA burst frequency did not correlate with AP in either age group (young: r = 0.00, P = 0.994; middle-aged: r = − 0.11, P = 0.604). CONCLUSION: There is an age-dependent effect of habitual exercise on aortic haemodynamics, with lower aSBP in young runners compared to nonrunners only. Statistical adjustment of aPWV and AP markedly influenced the outcomes of this study, highlighting the importance of performing these analyses. Further, peripheral sympathetic vasomotor outflow and AP were not correlated in young or middle-aged normotensive men

Analysis of satellite-derived Arctic tropospheric BrO columns in conjunction with aircraft measurements during ARCTAS and ARCPAC

We derive tropospheric column BrO during the ARCTAS and ARCPAC field campaigns in spring 2008 using retrievals of total column BrO from the satellite UV nadir sensors OMI and GOME-2 using a radiative transfer model and stratospheric column BrO from a photochemical simulation. We conduct a comprehensive comparison of satellite-derived tropospheric BrO column to aircraft in-situ observations of BrO and related species. The aircraft profiles reveal that tropospheric BrO, when present during April 2008, was distributed over a broad range of altitudes rather than being confined to the planetary boundary layer (PBL). Perturbations to the total column resulting from tropospheric BrO are the same magnitude as perturbations due to longitudinal variations in the stratospheric component, so proper accounting of the stratospheric signal is essential for accurate determination of satellite-derived tropospheric BrO. We find reasonably good agreement between satellite-derived tropospheric BrO and columns found using aircraft in-situ BrO profiles, particularly when satellite radiances were obtained over bright surfaces (albedo \u3e0.7), for solar zenith angl

Athletics & Recreation Master Plan Sub‐Committee Final Report

In 2000 the Athletics & Recreation Department at UMass Boston Implemented a five year strategic plan that would more realistically align sports sponsorship with available financial and facility resources. We reduced the number of sports sponsored from 20 to 14 maintaining 7 sports for women and 7 sports for men. The only sports maintained without a facility were Men’s baseball and Cross Country Track. We eliminated football, swimming and indoor & outdoor track and field for men and women. Since 2005 The Athletics & Recreation Department has been focused on University wide transition and planning efforts. In that period we have experienced three changes in the Chancellors office, two changes in Athletics Director Position and our operation has moved from a university department to a university division. We have engaged in university‐wide strategic planning and master planning while redefining the role of athletics within the campus community. This four year process of transition & planning has been at the same time taxing and invigorating while allowing the Division of Athletics & Recreation, Special Programs & Projects to emerge as a university service entity supportive of the primary mission of the university. The division has engaged in areas of the university heretofore out of its purview. It has established internal and external partnerships that are transformative and beneficial to the entire community. This report focuses on facilities that will allow for the established partnerships to flourish, that will uphold the new standards for high quality facilities that have been implemented over the last four years on our campus and most importantly this report addresses in a comprehensive way a vision for athletics & recreation at UMass Boston that will put us in the fore front of those institutions that offer athletics & recreation for the purpose of the health and both physical and mental wellness of students, faculty and staff. It does begin with a pride of place

The influence of habitual endurance exercise on carotid artery strain and strain-rate in young and middle-aged men

Central arterial stiffness is an independent predictor of cardiovascular risk that can be modified by exercise training. However, conventional local measures of carotid artery stiffness display conflicting responses to habitual endurance exercise in young and older adults. 2D-Strain imaging of the common carotid artery (CCA) quantifies circumferential deformation (strain) of the arterial wall across the cardiac cycle, which is more sensitive at detecting age-related alterations in CCA stiffness than conventional methods. Therefore, the study was designed to examine the relationship between habitual endurance exercise (running) and CCA 2D-Strain parameters in young and middle-aged men. Short-axis ultrasound images of the CCA were obtained from 13 young nonrunners (23 years [95% CI: 21-26]), 19 young runners (24 [22-26]), 13 middle-aged nonrunners (54 [52-56]) and 19 middle-aged runners (56 [54-58]). Images were analysed for peak circumferential strain (PCS; magnitude of deformation) as well as systolic and diastolic strain-rate (S-SR and D-SR; deformation velocity) and group differences were examined via two-way ANOVA. PCS, S-SR and D-SR were attenuated in middle-aged males when compared to young men (all P ≤ 0.001). PCS and S-SR were elevated in young and middle-aged runners when compared to nonrunners (P = 0.002 and P =0.009 respectively), but no age*training status interaction was observed. In contrast, there was no influence of habitual running on D-SR. Habitual exercise is associated with comparable improvements in CCA 2D-Strain parameters in young and middle-aged men, but the age-related decline in PCS and S-SR may be more amenable to habitual endurance exercise than D-SR

Building integrated health systems: lessons from HIV, sexual and reproductive health integration.

A synthetic strategy to access 2,6-disubstituted pyridines from triazolopyridines through a regioselective nickel-catalyzed alkenylation reaction of the C7–H bond is described. The N₂ fragment embedded in the resulting C–H functionalized triazolopyridine can be readily excised using acidic or oxidative conditions to unmask the pyridine