Calpain-2 Compensation Promotes Angiotensin II-Induced Ascending and Abdominal Aortic Aneurysms in Calpain-1 Deficient Mice

Background and Objective Recently, we demonstrated that angiotensin II (AngII)-infusion profoundly increased both aortic protein and activity of calpains, calcium-activated cysteine proteases, in mice. In addition, pharmacological inhibition of calpain attenuated AngII-induced abdominal aortic aneurysm (AA) in mice. Recent studies have shown that AngII infusion into mice leads to aneurysmal formation localized to the ascending aorta. However, the precise functional contribution of calpain isoforms (-1 or -2) in AngII-induced abdominal AA formation is not known. Similarly, a functional role of calpain in AngII-induced ascending AA remains to be defined. Using BDA-410, an inhibitor of calpains, and calpain-1 genetic deficient mice, we examined the relative contribution of calpain isoforms in AngII-induced ascending and abdominal AA development. Methodology/Results To investigate the relative contribution of calpain-1 and -2 in development of AngII-induced AAs, male LDLr −/− mice that were either calpain-1 +/+ or −/− were fed a saturated fat-enriched diet and infused with AngII (1,000 ng/kg/min) for 4 weeks. Calpain-1 deficiency had no significant effect on body weight or blood pressure during AngII infusion. Moreover, calpain-1 deficiency showed no discernible effects on AngII-induced ascending and abdominal AAs. Interestingly, AngII infusion induced increased expression of calpain-2 protein, thus compensating for total calpain activity in aortas of calpain-1 deficient mice. Oral administration of BDA-410, a calpain inhibitor, along with AngII-infusion significantly attenuated AngII-induced ascending and abdominal AA formation in both calpain-1 +/+ and −/− mice as compared to vehicle administered mice. Furthermore, BDA-410 administration attenuated AngII-induced aortic medial hypertrophy and macrophage accumulation. Western blot and immunostaining analyses revealed BDA-410 administration attenuated AngII-induced C-terminal fragmentation of filamin A, an actin binding cytoskeletal protein in aorta. Conclusion Calpain-2 compensates for loss of calpain-1, and both calpain isoforms are involved in AngII-induced aortic aneurysm formation in mice

I want it now so you cannot have it later: The role of impulsive choices in competitive environments

Doctor of PhilosophyDepartment of Psychological SciencesMichael YoungPeople commonly prefer smaller-sooner rewards over larger-later rewards, referred to as impulsive choice. Although impulsive choices are strongly associated with negative behaviors, such as poor diet and exercise habits, substance abuse and gambling, larger delayed rewards are more uncertain than smaller immediate rewards regarding if and when they are delivered. The threat of losing out on delayed rewards may then motivate individuals to shift their preferences towards more immediately available goals. One source of uncertainty for delayed rewards is competition, where multiple individuals exclusively pursue limited resources. The impact of competitors may result in individuals selecting more impulsive choices to ensure a relatively greater acquisition of important resources compared to competitors, despite the environment originally incentivizing waiting. Therefore, the purpose of the current dissertation is to study the degree to which competition-based uncertainty increases impulsive choices above and beyond environmental uncertainty. To test this hypothesis, I conducted two experience-based decision-making experiments that manipulated various dimensions of competition that could potentially control participants’ waiting behaviors and performance, such as the visibility of a competitor and the visibility of the competitor’s cumulative rewards. Overall, the results provided weak evidence that competition influenced participants’ impulsive choices above environmental uncertainty, specifically by slightly increasing their likelihood of obtaining rewards rather than their tendency to select impulsive choices. These findings are more consistent with an economic perspective of choice behavior than an evolutionary perspective, and I discuss the theoretical and methodological implications of this novel line of research

Tides of Opportunity: An analysis of the blue economy and its application to U.S. National Marine Sanctuaries

The blue economy is an area of growing investment and evolution across industries, governments, and communities. The rising global population coupled with rapid development in technology and trade has spurred governments across the world to look to the ocean for new sources of economic growth. While the ocean has historically been seen as an endless source of protein and extractive resources, the impacts of climate change are revealing the fallacy of this long-held assumption. Ocean acidification, warmer temperatures, and rising sea levels are resulting in habitat and biodiversity loss, extreme weather patterns, and changes to fish stock compositions and migration patterns. As a result of these changes, it is increasingly important to ensure a sustainable coexistence between humans and marine ecosystems. By developing a blue economy that prioritizes not only economic growth, but also the health of the environment and the livelihoods of local communities, it is possible to build a lasting blue economy for generations to come. The following paper analyzes existing blue economy frameworks utilized around the world to inform a model that assesses the feasibility of implementing blue economy programs in U.S. National Marine Sanctuaries

A quantitative charcterization of control flow context: software measures for programming environments

A review of published measures of control flow complexity in programs reveals three major deficiencies: loss of information, lack of specificity, and lack of analytical support. A new approach is used to characterize the control structure of a program, with the aim of defining properties and measures of control flow that can be of immediate use to programmers, regardless of their utility as complexity measures. Mathematical rigor and analytical evaluation techniques are used to define a set of properties of control structure and a corresponding vector of measures. Instead of defining the properties and measures for an entire flowgraph, they are defined at the node level, reflecting the control flow surrounding each node in a flowgraph. The properties and their measures reflect the following characteristics of control flow: nesting, iteration, structuredness, and predecessors. Algorithms for computing the properties and their measures are presented. An assessment of the computational complexity of the algorithms shows that they are feasible programming environment tools;A finite path set, representing all possible execution sequences, is evaluated as a characterizing property. Desired characteristics of the path set are defined and used to evaluate four published path subset criteria. Those criteria are shown to be deficient, so a fifth criterion is defined. However, the path set satisfying this fifth criterion is shown to be too large to be of practical use to a programmer

A late 19th-Century British perspective on modern foreign language learning, teaching, and reform: the legacy of Prendergast’s “Mastery System”

The late 19th century saw a great rise in private foreign language learning and increasing provision of Modern foreign language teaching in schools. Evidence is presented to document the uptake of innovations in Thomas Prendergast’s (1807–1886) “Mastery System” by both individual language learners and educationalists. Although it has previously been suggested that Prendergast’s method failed to have much impact, this study clearly demonstrates the major influence he had on approaches to language learning and teaching in Britain and around the world both with his contemporaries and long after his death. This detailed case study illuminates the landscape of modern language pedagogy in Victorian Britain

Globalisation and MA TESOL programs in the UK

This article reports the results of a mixed-methods approach to investigating the association between globalisation and MATESOL in UK universities. Qualitative and quantitative data collected from academic staff through eight emails, four interviews and 41 questionnaires indicate that the globalised context of higher education have affected these programmes in a number of ways including an increasing interest in recruiting more international students and a growing awareness about the need for curriculum and content modifications. The analysis of the data suggests that although change has been an inherent characteristic of these MAs over the past decade, it has been implemented gradually and conservatively, often relying on a dialectic relationship between academic staff and universities’ policies. The results imply that factors other than globalisation have also been at work. Many of the participants contend that globalisation has not lowered the quality of these MAs or standards of good practice

Roles of Internal Locus of Control and Self-Efficacy on Managing Job Stressors and Ryff\u27s Six Scales of Psychological Well-Being

The purpose of this study was to investigate the roles internal locus of control and self-efficacy play in moderating how employees manage their perceived work stress and positively engage in the behaviors that facilitate autonomy, environmental mastery, personal growth, self-acceptance, positive relations with others, and purpose in life. Investigators have documented the relationship between perceived workplace stress and strain and showed that how employees cope with perceived stress influences their psychological and physical health. However, there is less information available about the relationship between how employees cope with perceived workplace stress and engage in behaviors that facilitate their psychological well-being. A quasi-experimental methodology was used; male and female tire manufacturing production workers working in a shift work manufacturing environment were surveyed using a secure online server. Data collection tools included the Perceived Stress Scale, the Multidimensional Health Locus of Control Form C 4 subscales, the Perceived Self-Efficacy Scale, and Ryff\u27s 6 Scales of Psychological Well-Being. Hypotheses were analyzed using moderated multiple regression analyses. Employees who operate from an internal locus of control and who demonstrate high levels of self-efficacy reported lower levels of perceived stress and higher levels of self-acceptance. The implications for social change provide organizational leaders with insight into the potential benefits and saving of both financial and human capital by screening and training employees to better understand how to evaluate and develop their abilities to operate from an internal locus of control, as well as how to improve their self-efficacy skills

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