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This dissertation compares immune responses of resistant and susceptible sheep to infection with Haemonchus contortus during the peri-parturient period and larval stage of infection. Identification of immunological events resulting in parasite resistance in St. Croix hair sheep may provide better targets for differential gene expression analysis and eventual discovery of selectable markers for parasite resistance. Antibody levels of hair ewes and composite Dorset x Finnsheep-Rambouillet wool ewes were measured during breeding and again after parturition. Results demonstrated that hair ewes had higher levels immunoglobulin-A after infection and maintained a higher level of circulating antigen-specific antibody when compared to wool ewes. To characterize immune responses to the larval stage of infection, hair and wool lambs were sacrificed at 0, 3, 5, and 7 d after infection with H. contortus. Neutrophil migration to abomasal mucosa and lymph node development were higher in hair sheep than in wool sheep. Gene expression analysis indicated no difference in the abomasal lymph node as both breeds expressed a general T-helper cell type 2 (TH2) response. However, profound differences in TH2 responses were observed in the abomasal mucosa, where hair sheep expressed more IL-4, -13 and -33 than wool sheep. These data thus document the presence of immunological differences between the breeds. Immune responses to larval parasite infection in wool sheep are generally suppressed and may increase the magnitude and duration of infection whereas immune responses to larval infection in hair sheep was more robust and more strongly polarized towards a TH2 / Ph. D.

Hair cells are transducers found found in the inner ear of vertebrates. They convert a mechanical signal, detected by the deflection of a bundle of cilia extending from their top surface, into an electrochemical signal. This dissertation studies the mechanical influence of the structure and materials on the function of the cells. I introduce two methods to conduct the mechanical analysis. The first uses strength of materials formulae to solve the simplified hair cell bundle models. The second is a finite element analysis, used to better account for the observed complexity of the structure. I then use these two techniques to build a fundamental understanding of the hair cell bundle structure. By first studying simplified models, then adding complexity, the effects of geometric and material variation can be deduced. I then study three actual bundles. These are all taken from vestibular organs of turtles, two from the posterior semicircular canal and one from the utricle. I present estimations of stiffness, tip link tensions, and nonlinear response. Finally, I investigate a single cilium forced by a fluid flow. The problem is solved by finite difference technique. Three different initial conditions are solved. / Ph. D.

The objectives of this study were to determine the effects of handling peri-puberal heifers for 2 h each week on in-chute behavior, isolation behavior, and the time required for each heifer to leave the testing area; and to determine if the location of the facial hair whorl was associated with any of the behavior scores or social dominance order. Crossbred beef heifers (n = 146) were assigned to be walked through, sorted and moved through a chute for 2 hr each wk for 20 wk (HANDLED) or allowed to remain on pasture unless handling was required to treat an injury or disease (CONTROL). In-chute behavior, isolation behavior and exit times were observed and scored at the beginning (0 wk), middle (10 wk) and end of the experiment (20 wk). The facial hair whorl on each heifer was classified as being high (above the eyes), middle (between the eyes), or low (below the eyes). At the end of the experiment pairs of heifers in the HANDLED group competed for a feed source and a social dominance order was estimated. Weekly handling decreased in-chute behavior scores of heifers with facial hair whorl positions classified as medium or low, but not in heifers that exhibited a hair whorl high on their face. Cattle in the HANDLED treatment group which had an initial isolation score of 2 or 3 had the greatest improvement in temperament over the entire experiment when compared to CONTROL animals with the same initial isolation score. The calmest heifers were not negatively affected by the handling, while the most agitated animals in the HANDLED had a similar overall change in isolation score as those animals in the CONTROL group. This indicates that while weekly handling improved the temperament and behavior of heifers with intermediate temperament rating at the outset of the experiment, weekly handling seemed unnecessary for the calmest heifers and did not have a beneficial effect on the heifers rated as the most nervous and agitated at the beginning of the experiment. Social dominance rankings were positively correlated (P < 0.10) with final in-chute behavior scores, but not with the other behavior scores or heifer body weight. Cattle with the hair whorls in the middle of the forehead had higher mean social dominant rank than those with hair whorls higher or lower on the face (P < 0.03). Overall, the results of this experiment indicate that behavior testing can reveal differences in the temperament of heifers and that, other than the most nervous and agitated heifers; repeated handling could serve to improve the temperament of the animals. / Master of Science

Computational fluid dynamics and finite element analysis were employed to study vestibular hair cell bundle mechanics under physiologic stimulus conditions. CFD was performed using ANSYS CFX and FEA utilized a custom MATLAB model. Nine varieties of hair cell bundles were modeled using tip-forcing only (commonly used experimentally), fluid-flow only (physiologic for free-standing bundles), and combined loading (physiologic for bundles with tip attachments) conditions to determine how the bundles behaved in each case. The bundles differed in the heights of their components, their length and width, and their number of steriocilia. Tip links were modeled to determine ion-channel opening behavior. Results show that positive pressures, negative pressures, and shear stresses on the exterior of the bundles are of comparable magnitude. Under combined loading, some bundles experienced very high suction pressures on their interior. The bundles with tall steriocilia are hindered by the endolymph while those with short steriocilia and much taller kinocilia are assisted by the fluid flow. Each bundle type has a different range over which it is most sensitive so that the bundles cumulatively cover a very large range of stimuli; the order in which bundles respond from smallest stimulus magnitude to largest is free-standing extrastriolar bundles, attached striolar bundles, attached extrastriolar bundles, and free-standing extrastriolar bundles. A short examination of off-axis loading shows that the prevailing theory suggesting that bundle response is proportional to the cosine of the angle between the stimulus direction and the bundle's direction of maximum excitation is incorrect. / Ph. D.

This research details the creation and characterization of a new biomimetic artificial inner hair cell sensor in an artificial cochlear environment. Designed to mimic the fluid flows around the inner hair cells of the human cochlea, the artificial cochlear environment produces controlled, linear sinusoidal fluid flows with frequencies between 25 and 400 Hz. The lipid bilayer-based artificial inner hair cell generates current through changes in the bilayer's capacitance. This capacitance change occurs as the sensor's artificial stereocilium transfers the force in the fluid flow to the bilayer. Frequency tuning tests are performed to characterize the artificial inner hair cell's response to a linear chirp signal from 1 to 400 Hz. The artificial inner hair cell's response peaks at a resonant frequency of approximately 83 Hz throughout most of the tests. Modelling the artificial stereocilium as a pinned free beam with a rotational spring at the pinned end yields a rotational spring stiffness of 177*10^-6 Nm/rad. Results with 0 mV potential applied across the bilayer indicate that current generation at 0 mV likely comes from other sources besides the bilayer. Increasing the voltage potential increases the broadband power output of the system, with an approximately linear relationship. A final test keeps the fluid flow frequency constant and varies the fluid velocity and applied voltage potential. Manipulation of the applied voltage potential results in a fluid velocity to RMS current relationship reminiscent of the variable sensitivity of the human cochlea. / Master of Science

Yes / Skin development is governed by complex programs of gene activation and silencing, including microRNA-dependent modulation of gene expression. Here, we show that miR-214 regulates skin morphogenesis and hair follicle (HF) cycling by targeting β-catenin, a key component of the Wnt signaling pathway. miR-214 exhibits differential expression patterns in the skin epithelium, and its inducible overexpression in keratinocytes inhibited proliferation, which resulted in formation of fewer HFs with decreased hair bulb size and thinner hair production. The inhibitory effects of miR-214 on HF development and cycling were associated with altered activities of multiple signaling pathways, including decreased expression of key Wnt signaling mediators β-catenin and Lef-1, and were rescued by treatment with pharmacological Wnt activators. Finally, we identify β-catenin as one of the conserved miR-214 targets in keratinocytes. These data provide an important foundation for further analyses of miR-214 as a key regulator of Wnt pathway activity and stem cell functions during normal tissue homeostasis, regeneration, and aging.