Cadherin gene family members are known to be involved in the differentiation of cytotrophoblasts of the human placenta. In particular, the regulation of cadherin expression is coupled with the development of an invasive phenotype and the formation of the multinucleated syncytiotrophoblast. To investigate further the mechanisms underlying the differential regulation of cadherins during these developmental processes, we have examined the role of the transcription factor known as Twist. Twist is a basic HLH (helix-loop-helix) factor which has been shown to regulate cadherin expression in a variety of human tissues under normal and pathological conditions. Using an siRNA strategy, I have determined that Twist regulates both E-cadherin and N-cadherin in distinct subtypes of human trophoblastic cells in vitro. In particular, suppression of Twist gene expression in poorly invasive BeWo choriocarcinoma cells by using Twist-specific siRNA resulted in a concomitant increase in E-cadherin mRNA and protein levels in these cells. In contrast, transfection of highly invasive extravillous cytotrophoblasts with Twist siRNA decreased N-cadherin mRNA levels in a concentration-dependent manner. Taken together, these observations indicate that Twist differentially regulates E-cadherin and N-cadherin in human trophoblastic cells, two cadherin subtypes that govern the differentiation of these cells along the non-invasive and invasive pathways respectively. Although, the results of my studies do not directly demonstrate this biological function of Twist, they support the speculation that alterations in Twist expression levels will result in cadherin-mediated disorders of pregnancy associated with aberrant trophoblast differentiation.

Cadherin gene family members are known to be involved in the differentiation of cytotrophoblasts of the human placenta. In particular, the regulation of cadherin expression is coupled with the development of an invasive phenotype and the formation of the multinucleated syncytiotrophoblast. To investigate further the mechanisms underlying the differential regulation of cadherins during these developmental processes, we have examined the role of the transcription factor known as Twist. Twist is a basic HLH (helix-loop-helix) factor which has been shown to regulate cadherin expression in a variety of human tissues under normal and pathological conditions. Using an siRNA strategy, I have determined that Twist regulates both E-cadherin and N-cadherin in distinct subtypes of human trophoblastic cells in vitro. In particular, suppression of Twist gene expression in poorly invasive BeWo choriocarcinoma cells by using Twist-specific siRNA resulted in a concomitant increase in E-cadherin mRNA and protein levels in these cells. In contrast, transfection of highly invasive extravillous cytotrophoblasts with Twist siRNA decreased N-cadherin mRNA levels in a concentration-dependent manner. Taken together, these observations indicate that Twist differentially regulates E-cadherin and N-cadherin in human trophoblastic cells, two cadherin subtypes that govern the differentiation of these cells along the non-invasive and invasive pathways respectively. Although, the results of my studies do not directly demonstrate this biological function of Twist, they support the speculation that alterations in Twist expression levels will result in cadherin-mediated disorders of pregnancy associated with aberrant trophoblast differentiation.

Thesis (M.S.)--University of Wisconsin--Madison. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 70-71).

Thesis (M.S.)--University of Wisconsin--Madison, 1981. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 174-177).

Thesis (M.S.)--University of Wisconsin, 1983. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 109-111).

Thesis--University of Wisconsin--Madison. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaf 126).

Cadherin gene family members are known to be involved in the differentiation of cytotrophoblasts of the human placenta. In particular, the regulation of cadherin expression is coupled with the development of an invasive phenotype and the formation of the multinucleated syncytiotrophoblast. To investigate further the mechanisms underlying the differential regulation of cadherins during these developmental processes, we have examined the role of the transcription factor known as Twist. Twist is a basic HLH (helix-loop-helix) factor which has been shown to regulate cadherin expression in a variety of human tissues under normal and pathological conditions. Using an siRNA strategy, I have determined that Twist regulates both E-cadherin and N-cadherin in distinct subtypes of human trophoblastic cells in vitro. In particular, suppression of Twist gene expression in poorly invasive BeWo choriocarcinoma cells by using Twist-specific siRNA resulted in a concomitant increase in E-cadherin mRNA and protein levels in these cells. In contrast, transfection of highly invasive extravillous cytotrophoblasts with Twist siRNA decreased N-cadherin mRNA levels in a concentration-dependent manner. Taken together, these observations indicate that Twist differentially regulates E-cadherin and N-cadherin in human trophoblastic cells, two cadherin subtypes that govern the differentiation of these cells along the non-invasive and invasive pathways respectively. Although, the results of my studies do not directly demonstrate this biological function of Twist, they support the speculation that alterations in Twist expression levels will result in cadherin-mediated disorders of pregnancy associated with aberrant trophoblast differentiation. / Medicine, Faculty of / Obstetrics and Gynaecology, Department of / Graduate

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Twist Capsules are rotating electrical connections that are used when low noise electrical signals are required between a stationary connector and a mechanically oscillating one. Twist capsules are used throughout industry especially in areas that require exceptionally clean signals such as the space satellite industry and military applications. Due to the high cost of replacing parts on satellites launched into space and life-sustaining aspects of military applications, accurate modeling of these devices is essential to predict their behavior. Clock spring twist capsules use a flex tape, copper traces between two layers of Kapton, which rolls onto itself tightening against the shaft at one extreme and rolling out against the frame at the other extreme. This cyclic tightening and loosing can cause stresses on these flex tapes consequently, resulting in their failure due to fatigue. Therefore, it is imperative that some method be used to estimate the stresses in the flex tape in order that the optimal design parameters may be calculated. The natural progression from estimating the stresses is to predict the life of the twist capsule. Current techniques involve iteratively building physical models and heritage (what has worked in the past will work in the future) to build twist capsules. This methodology has been sufficient, but a large factor of safety is used during design to cover the lack of assurance in the method. This thesis proposes a new design method using clock spring equations to estimate the torque in twist capsules and the stresses induced into the flex tapes. This new design method accurately predicts operating range, torque, and stress in the normal operating range of the twist capsule sufficient enough for design purposes in a fraction of the amount of time it would normally take to design a twist capsule. / Master of Science