Lipids and oxidative stress as mediators of endothelial pathophysiology in obesity

2011 Fall.Includes bibliographical references.Because obesity is a well established independent risk factor for diabetes and coronary artery disease (CAD), it is important to identify factors associated with obesity that are responsible for disease progression and interventions to decrease risk of developing obesity associated co-morbidities. Two of the many mediators of obesity associated risk for diabetes and CAD are oxidative stress and oxidized phospholipids, which have been implicated in vascular disease initiation and progression through endothelial cell activation, macrophage recruitment and advanced plaque rupture. Plasma platelet activating factor acetylhydrolase (Lp-PLA2) is an enzyme that circulates bound to LDL cholesterol and degrades platelet activating factor (PAF), a potent inducer of the platelet coagulation cascade and thrombosis. In addition, Lp-PLA2 degrades oxidized phospholipids to lysophospholipid products and fatty acids that may also induce inflammatory changes in multiple cell types, including vascular endothelial cells. Exogenous antioxidant supplementation has been examined as a means of decreasing vascular oxidative stress. However, data show that exogenous antioxidant supplementation has little or no effect on CVD outcomes, and in some cases it may increase mortality. A novel approach to protecting cells from oxidative stress is to increase cellular endogenous antioxidant defenses. NF-E2-related factor 2 (Nrf2) is a transcription factor that binds to the antioxidant response element (ARE) promoter region of many genes including phase II antioxidant enzymes. Protandim is a combination of phytochemicals that is thought to induce Nrf2 stabilization and translocation to the nucleus, with subsequent increases in phase II antioxidant enzymes and protection against oxidative stress. The overall objectives of the three studies we performed were to 1) globally analyze obesity associated lipid and oxidative stress using lipidomics techniques 2) determine the effects of identified obesity associated oxidative and lipid stress on the vascular endothelium 3) determine whether Protandim treatment could protect vascular endothelial cells from an oxidative challenge, and 4) characterize Lp-PLA2 in human adipose and skeletal muscle. Experiment 1 tested the hypothesis that oxidized phospholipids would be greater in morbidly obese gastric bypass patients compared to lean surgical controls, and that global lipid profiles would differ between groups. To test this hypothesis we performed a combined targeted and global lipidomic analysis of plasma lipids from morbidly obese gastric bypass patients and lean controls. We identified a group of ether-linked lipids that were greater in obese subjects compared to lean, and further examined whether a representative lipid from this group induced pathophysiological phenotypic changes in vascular endothelial cells. Experiment 2 tested the hypothesis that Protandim would protect human coronary artery endothelial cells (HCAEC) against an oxidative challenge by increasing phase II antioxidant enzymes in a Nrf2 dependent manner. To do this we performed a series of in vitro experiments treating HCAEC with Protandim and determined that Protandim induced Nrf2 nuclear localization, increased phase II antioxidant enzyme expression, and protected cells from undergoing apoptosis in response to an oxidative challenge. Silencing Nrf2 prior to the oxidative challenge inhibited the Protandim induced protection. Experiment 3 tested the hypothesis that Lp-PLA2 would be detectable in human adipose tissue and that Lp-PLA2 would be greater in adipose from morbidly obese gastric bypass patients compared to lean. In addition, we examined whether adipose Lp-PLA2 may be related to circulating Lp-PLA2 activity, inflammation, and glucose intolerance. We have identified ether-linked lipids that are elevated in obese subjects compared to lean. We found that Lp-PLA2 is expressed in human adipose for the first time, adipose Lp-PLA2 is co-localized with macrophages, and report relationships between Lp-PLA2 and indices of glucose homeostasis and inflammation. Lastly, we found that Protandim protects endothelial cells from an oxidative challenge in a Nrf2 dependent manner. Collectively, these data provide insight into the oxidative and lipid stress milieu that occurs in obese subjects

Engineering ethanologenic Escherichia coli for levoglucosan utilization

Levoglucosan is a major product of biomass pyrolysis. While this pyrolyzed biomass, also known as bio-oil, contains sugars that are an attractive fermentation substrate, commonly-used biocatalysts, such as Escherichia coli, lack the ability to metabolize this anhydrosugar. It has previously been shown that recombinant expression of the levoglucosan kinase enzyme enables use of levoglucosan as carbon and energy source. Here, ethanologenic E. coli KO11 was engineered for levoglucosan utilization by recombinant expression of levoglucosan kinase from Lipomyces starkeyi. Our engineering strategy uses a codon-optimized gene that has been chromosomally integrated within the pyruvate to ethanol (PET) operon and does not require additional antibiotics or inducers. Not only does this engineered strain use levoglucosan as sole carbon source, but it also ferments levoglucosan to ethanol. This work demonstrates that existing biocatalysts can be easily modified for levoglucosan utilization

Transforming the Library: The Case for Libraries to End Incremental Measures and Solve Problems for Their Campuses Now

In an article published in the Chronicle of Higher Education, University of Texas System Chancellor Mark Yudof wrote, Mark Twain would recognize the situation. Everyone talks about the governance and financing of higher education, although, as in the case of the weather, few feel that they can do anything about it \u27 Much agony has been expressed over higher education\u27s immediate future in the United States and elsewhere, given the movement to regulate academic and financial management from the outside. Many colleges and universities respond to societal pressures by pursuing change in small, incremental steps. Yet those same pressures for accountability, affordability, and access to education require an institutional response that demonstrates agile planning to achieve high performance, including for libraries. What possibilities are there for transformational change in libraries? A case for appropriating transformational models in academic libraries will be explored in the article that follows, focusing in particular on libraries in public colleges and universities

Communicating in Complex Situations: A Normative Approach to HIV-Related Talk Among Parents Who Are HIV+

Parents with HIV/AIDS are confronted with unique challenges when discussing HIV-related information with their children. Strategies for navigating these challenges effectively have not been systematically examined. In this study, we conducted in-depth interviews with 76 parents with HIV/AIDS who had children ages 10–18 years. Guided by O\u27Keefe and Delia\u27s definition of a complex communication situation and Goldsmith\u27s normative approach to interpersonal communication, we examined parents’ goals for discussing HIV-related information, factors that made conversations challenging, and instances where these conversational purposes conflicted with one another. Our data reveal the following parent–adolescent communication predicaments: relaying safety information about HIV while minimizing child anxiety, modeling open family communication without damaging one\u27s parental identity, and balancing parent–child relational needs amid living with an unpredictable health condition. Parents also described a variety of strategies for mitigating challenges when discussing HIV-related topics. Strategies parents perceived as effective included reframing HIV as a chronic, manageable illness; keeping talk educational; and embedding HIV-related topics within more general conversations. The theoretical and practical applications of these findings are discussed with regard to their relevance to health communication scholars and HIV care professionals

Lifting the lid on period poverty in higher education: a student engagement perspective

In 2018/19, Liverpool John Moores University became the first university in England to offer free menstrual products on campus.  This paper shares insights from the project – called The Free Period – which was established to tackle period poverty, or menstrual hygiene management (MHM).  The authors reflect on student engagement as a significant proportion of menstruators had missed classes owing to period poverty.  The paper highlights the need for better dialogue and communication to: improve data; tackle stigma and taboos; and cultivate healthier relationships on campus

Cinq façons de maîtriser la logistique organisationnelle, les backends et les flux de travail

Organizational backends and logistics are often complex and many institutions set-up their workflows based on manual and tedious processes that negatively shape their interactions with stakeholders. Incorporating new technologies can be intimidating, however there exists a plethora of financially and technically accessible resources, that don’t require any coding knowledge, that institutions can utilize to enhance their organizational workflow and stakeholder experience. Guided by our own learning experiences in optimal logistical set-up and user design, we wish to highlight five effective and easily implementable tricks to aid higher institutions and student groups in healthcare accomplish their administrative duties.Les backends et la logistique des organisations sont souvent complexes et de nombreuses institutions établissent leurs flux de travail sur la base de processus manuels et fastidieux qui influencent négativement leurs interactions avec les parties prenantes. L'intégration de nouvelles technologies peut être intimidante, mais il existe une pléthore de ressources financièrement et techniquement accessibles, qui ne nécessitent aucune connaissance en codage, que les institutions peuvent utiliser pour améliorer leur flux de travail organisationnel et l'expérience des parties prenantes. Guidés par nos propres expériences d'apprentissage en matière de mise en place d'une logistique optimale et de conception pour l'utilisateur, nous souhaitons mettre en avant cinq astuces efficaces et faciles à mettre en œuvre pour aider les établissements supérieurs et les groupes d'étudiants en soins de santé à accomplir leurs tâches administratives

Human-assisted Movements of Raccoons, Procyon lotor, and Opossums, Didelphis virginiana, between the United States and Canada

Movements of Raccoons (Procyon lotor) (mean = 479 km) and Opossums (Didelphis virginiana) (mean = 688 km) by means of transport trailers and a train from the USA and Quebec into Ontario were significantly greater than Raccoon movements (mean = 15 km) from Ontario to New York State determined by mark-recapture. Human-assisted movements of wildlife could have significant impacts with respect to cross-border movements of diseases such as rabies. Proactive communication programs, especially at International border crossing areas, should be encouraged to decrease the occurrence of the unintentional movement of wildlife and associated diseases

A simulation approach to assessing environmental risk of sound exposure to marine mammals

Intense underwater sounds caused by military sonar, seismic surveys, and pile driving can harm acoustically sensitive marine mammals. Many jurisdictions require such activities to undergo marine mammal impact assessments to guide mitigation. However, the ability to assess impacts in a rigorous, quantitative way is hindered by large knowledge gaps concerning hearing ability, sensitivity, and behavioral responses to noise exposure. We describe a simulation-based framework, called SAFESIMM (Statistical Algorithms For Estimating the Sonar Influence on Marine Megafauna), that can be used to calculate the numbers of agents (animals) likely to be affected by intense underwater sounds. We illustrate the simulation framework using two species that are likely to be affected by marine renewable energy developments in UK waters: gray seal (Halichoerus grypus) and harbor porpoise (Phocoena phocoena). We investigate three sources of uncertainty: How sound energy is perceived by agents with differing hearing abilities; how agents move in response to noise (i.e., the strength and directionality of their evasive movements); and the way in which these responses may interact with longer term constraints on agent movement. The estimate of received sound exposure level (SEL) is influenced most strongly by the weighting function used to account for the specie's presumed hearing ability. Strongly directional movement away from the sound source can cause modest reductions (~5 dB) in SEL over the short term (periods of less than 10 days). Beyond 10 days, the way in which agents respond to noise exposure has little or no effect on SEL, unless their movements are constrained by natural boundaries. Most experimental studies of noise impacts have been short-term. However, data are needed on long-term effects because uncertainty about predicted SELs accumulates over time. Synthesis and applications. Simulation frameworks offer a powerful way to explore, understand, and estimate effects of cumulative sound exposure on marine mammals and to quantify associated levels of uncertainty. However, they can often require subjective decisions that have important consequences for management recommendations, and the basis for these decisions must be clearly described.Publisher PDFPeer reviewe