Ultrasound Transient Shear Wave Elasticity Imaging for Tendon Tissue

Degeneration of tendon tissue is a common cause of tendon dysfunction with the symptoms of repeated episodes of pain and palpable increase of tendon thickness. Tendon mechanical properties are directly related to its physiological composition and the structural organization of the interior collagen fibers which could be altered by tendon degeneration due to overuse or injury. Thus, measuring mechanical properties of tendon tissue may represent a quantitative measurement of pain, reduced function, and tissue health. Ultrasound elasticity imaging has been developed in the last two decades and has proved to be a promising tool for tissue elasticity imaging. To date, however, well established protocols of tendinopathy elasticity imaging for diagnosing tendon degeneration in early stages or late stages do not exist. This thesis describes the re-creation of one dynamic ultrasound elasticity imaging method and the development of an ultrasound transient shear wave elasticity imaging platform for tendon and other musculoskeletal tissue imaging. An experimental mechanical stage with proper supporting systems and accurate translating stages was designed and made. A variety of high-quality tissue-mimicking phantoms were made to simulate homogeneous and heterogeneous soft tissues as well as tendon tissues. A series of data acquisition and data processing programs were developed to collect the displacement data from the phantom and calculate the shear modulus and Young’s modulus of the target. The imaging platform was found to be capable of conducting comparative measurements of the elastic parameters of the phantoms and quantitatively mapping elasticity onto ultrasound B-Mode images. This suggests the system has great potential for not only benefiting individuals with tendinopathy with an earlier detection, intervention and better rehabilitation, but also for providing a medical tool for quantification of musculoskeletal tissue dysfunction in other regions of the body such as the shoulder, elbow and knee.

Selection for Increased Starvation Resistance Using Drosophila melanogaster: Investigating Physiological and Life History Trait Responses to Starvation and Dietary Supplementation in the Context of an Obese Phenotype

Artificial selection for starvation resistance provided insight into the relationships between evolved physiological and life history trait responses following exposure to biologically induced stress. Investigations of alterations to body composition, metabolic rate, movement, and life history traits including development time, female egg production, and longevity in response to brief periods of starvation were conducted on genetically based starvation-resistant and control lines of Drosophila melanogaster. Analysis of the starvation-resistant lines indicated increased energy storage with increased triglyceride deposition and conversion of carbohydrates to lipid, as identified by respiratory quotient values. Correlations between reductions in metabolic rates and movement in the starvation-resistant lines, suggested the presence of an evolved physiological response resulting in energy conservation. Investigations of life history traits in the starvation-resistant lines indicated no significant differences in development time or reproduction between the selected and control lines. Measurements of longevity, however, indicated a significant reduction in starvation-resistant D. melanogaster lifespan. These results suggested that elevated lipid concentrations, similar to that observed with obesity, were correlated with premature mortality. Exposure of the starvation-resistant and control lines to diets supplemented with glucose, palmitic acid, and a 2:1 mixture of casein to albumin were used to investigate alterations in body composition, movement, and life history traits. Results obtained from this study indicated that increased sugar in the diet led to increased carbohydrate, glycogen, total sugar, trehalose, and triglyceride concentrations, while increased fat and protein in the diet resulted in increased soluble protein, carbohydrate, glycogen, total sugar, and trehalose concentrations. Examination of life history trait responses indicated reduced fecundity in females exposed to increased glucose concentrations. Increased supplementations of palmitic acid was consistently correlated with an overall reduction in lifespan in both the starvation-resistant and control Drosophila lines, while measurements of movement indicated increased female activity levels in flies exposed to diets supplemented with fat and protein. Analyses of the physiological and life history trait responses to starvation and dietary supplementation on Drosophila melanogaster used in the present study has implications for investigating the mechanisms underlying the development and persistence of human obesity and associated metabolic disorders.

Physiological Studies on Candida albicans

Candida albicans is a common opportunistic, dimorphic human fungal pathogen. One of its virulence factors is the morphological switch between yeasts and hyphal or pseudohyphal forms, which can invade tissues and cause damage. Our studies focus on factors regulating pseudohyphae and epigenetic modifications of C. albicans. Regulating factors of pseudohyphae are aromatic alcohols and high phosphate. At low concentrations, exogenous aromatic alcohols induced pseudohyphae, as did high phosphate. For addressing the pathways involved in inducing pseudohyphae by aromatic alcohols or high phosphate, we used mutants defective in cAMP dependent PKA pathway (efg1/efg1), MAP kinase pathway (cph1/cph1), or both (cph1/cph1/efg1/efg1). These mutants failed to produce either hyphae or pseudohyphae in the presence of aromatic alcohols; but high phosphate still stimulated pseudohyphae. Gcn4, a transcription activator of more than 500 amino acid related genes, is turned-on in response to amino acid starvation. The accumulation of aromatic alcohols sends nitrogen starvation signals, which inhibit eIF2B, which in turn derepresses Gcn4p. High phosphate also induces pseudohyphae by derepressing Gcn4p, although the pathways involved are still unknown. In sum, aromatic alcohols and high phosphate induce pseudohyphae by derepressing Gcn4. In this study we found a novel posttranslational histone modification in C. albicans, which is biotinylation. Western blot and Mass spectrometry techniques were used to find that Histones H2B and H4 were biotinylated at every condition tested such as yeast vs. hyphae, aerobic growth vs. anaerobic growth, rich medium vs. defined medium. In C. albicans lysines K8, K11 in histone H4 and lysines K17, K18, K31 in histone H2B are biotin attachment sites as found using mass spectrometry. Biotin was also found to enhance the germ tube formation of C. albicans. Germ tube formation assays with biotin-starved cells as inoculum showed low percent of germ tubes (1-5%). Addition of biotin to the media showed 100% germ tubes. Biotinylation of histones were not detected from biotin-starved cells. Appendix-A details work related to Farnesol quantification assays in several strains of C.albicans and Ceratocystis ulmi, and growth studies of class E VPS strains of Saccharomyces Cerevisiae. Adviser: Kenneth W. Nickerson

Academentia: Physiological Stress, Toxic Work Sites and the Neutralization of Blackness by the Whiteness Standards of Professionalization

Using auto-ethnographic methods, supplementing by current race theories, along with interviews from other scholars, I regard academentia as a form of professionalism most readily communicable to academics of color seeking advance. It can also infect those whose embrace of blackness (widely defined across cultures) is the least tolerant of the racial designs of white cultural practices. Where in the interest of students and colleagues, such academics challenge the whiteness criteria defining academic success, most of their peers adhere to the racial standards of professionalism.