A mitochondria-targeted mass spectrometry probe to detect glyoxals: implications for diabetes

The glycation of protein and nucleic acids that occurs as a consequence of hyperglycaemia disrupts cell function and contributes to many pathologies, including those associated with diabetes and aging. Intracellular glycation occurs following the generation of the reactive 1,2-dicarbonyls methylglyoxal and glyoxal and disruption to mitochondrial function is associated with hyperglycemia. However, the contribution of these reactive dicarbonyls to mitochondrial damage in pathology is unclear due to uncertainties about their levels within mitochondria in cells and in vivo. To address this we have developed a mitochondria-targeted reagent (MitoG) designed to assess the levels of mitochondrial dicarbonyls within cells. MitoG comprises a lipophilic triphenylphosphonium cationic function, which directs the molecules to mitochondria within cells and an o-phenylenediamine moiety that reacts with dicarbonyls to give distinctive and stable products. The extent of accumulation of these diagnostic heterocyclic products can be readily and sensitively quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS), enabling changes to be determined. Using the MitoG-based analysis we assessed the formation of methylglyoxal and glyoxal in response to hyperglycaemia in cells in culture and in the Akita mouse model of diabetes in vivo. These findings indicated that the levels of methylglyoxal and glyoxal within mitochondria increase during hyperglycaemia in both cells and in vivo, suggesting that they can contribute to the pathological mitochondrial dysfunction that occurs in diabetes and aging

Building our health: optimizing human health in architectural design

Given that we spend most of our time indoors- within homes, schools, and offices- it is critical to explore the physical and mental health consequences of how we design and operate buildings. The built environment can both positively and negatively affect our health, both physical and mental. Controllable conditions, such as air quality, daylighting, and potential for movement have an impact on the physical health of occupants. Building features such as the presence of nature and allowance of personal control and space influence the mental health of those who interact with an indoor environment. While designers aim to provide the most functional buildings, it is imperative to utilize strategies that provide the healthiest environments possible. This paper will examine the aspects of building design that make a difference in human health and outline strategies for improvement in both new construction projects and renovations.Thesis (B.?)Honors Colleg