Browsing by Subject "Skeleton"
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Item Dmp1 Regulates Osteocyte Function Via Wnt/?-Catenin Signaling Pathway(2014-05-06) Lin, ShuxianDMP1, dentin matrix protein 1, was cloned from a rat dentin cDNA library 20 years ago. Initially, this non-collagenous matrix protein was thought to be dentin specific and gained little interest in other scientific communities except the dental research area. Research that identified DMP1 mutations in humans and deletion in mice lead to the discovery of a novel disease: autosomal recessive hypophosphatemic rickets (ARHR). Functional studies reveal that DMP1 is essential for the maturation and functions of osteoblast and osteocyte via two possible mechanisms: 1) as a transcriptional factor that directly regulates osteo-/odonto-specific genes; and 2) as an extracellular matrix (ECM) protein, which controls bone and dentin mineralization. However, both theories appear controversy. Besides, the mechanism by which ARHR patients or Dmp1- null mice develop osteomalacia is largely unknown. In this study, we initially targeted DMP1 either in the nucleus only by replacing the endogenous signal peptide with the NLS signal peptide (named ^(NLS)DMP1), or targeted it in the ECM by using its own signal secretive peptide with the same recombinant DMP1 protein (named ^(SP)DMP1). The ^(NLS)DMP1 transgene, when expressed in the Dmp1-null osteoblast and osteocyte in vivo, failed to rescue the Dmp1-null phenotype, whereas the ^(SP)DMP1 transgene fully rescued the skeletal abnormalities of Dmp1-null mice, indicating that DMP1 functions as an ECM protein in vivo. In a separate research, we revealed an elevated ?-catenin expression level in Dmp1-KO osteocytes, besides, the targeted expression of ?-catenin in the osteocyte recaptured the osteomalacia phenotype, similar to that in Dmp1-KO mice. Furthermore, the targeted expression of DKK1 (a potent inhibitor of Wnt/?-catenin) in Dmp1-KO osteoblasts by crossing Dmp1-KO and 2.3 Col 1-Dkk1 mice, resulting in consequent blockade of Wnt/?-catenin signaling, significantly improved the rachitic/osteomalacic phenotype. The results of this study will expand our understanding of how the osteocytes regulate bone development and mineralization during the early postnatal period. In addition, this study has clinical relevance, as a high Pi diet alone fails to fully restore the osteomalacic status in patients, and normalizing the Wnt/?-catenin signaling may benefit these patients.Item Ontogeny and evolutionary morphology of the skeleton in frogs(2001-08) Yeh, Jennifer Jean; Dudley, Robert, 1961-; Cannatella, David C.Ontogenetic studies, or studies of development, have repeatedly proven insightful in exploring questions of morphological evolution. Here, two projects illuminate the relationship between ontogeny and the evolution of skeletal morphology in frogs. In the first part of this dissertation, I examine the evolution of skull development in pipoid frogs, a group that is exceptional in both morphology and life history. Two methods are used. First, skull bone ossification sequences are examined within a phylogenetic context. Second, studies are made of ontogenetic shape change in the skull using thin-plate spline morphometrics. Important differences between pipoid skull development and that of other frogs are uncovered. These include the convergent evolution of primitive ossification patterns still retained in extant salamanders, and the elaboration of novel trajectories of ontogenetic shape change which create the unusual pipoid morphology. The second part of this dissertation examines the phenomenon of miniaturization in frogs. Because miniaturization has evolved numerous times in frogs and has reached impressive extremes, frogs make an ideal group in which to study the effects of miniaturization on morphological evolution. I use qualitative presence/absence characters in the skull and limbs, as well as shape variables from thin-plate spline morphometrics to identify patterns of morphological change which are statistically associated with the evolution of miniaturization. These statistically significant patterns are discussed in the context of functional constraints and paedomorphosis.Item Segmentation of cervical and lumbar vertebrae in x-ray images using active appearance models and extensions(Texas Tech University, 2003-12) Howe, Benjamin MThis thesis presents a hierarchical segmentation algorithm tailored to the segmentation of cervical and lumbar vertebrae in digitized X-ray images. The algorithm employs the Generalized Hough Transform (GHT) to obtain a suitable initialization for two segmentation stages that utilize Active Appearance Models (AAMs) that were proposed by Cootes et al. The advantage of using AAMs in medical image segmentation applications is that rather than creating models that are purely data driven, AAMs gain a priori knowledge through a thorough observation of the shape and texture variation across a training set. This thesis presents a detailed summary of the theory behind AAM along with proposed extensions and customizations of AAM. The proposed extensions (1) address the shortcomings of using the basic texture alignment procedures when using Neighborhood AAMs, (2) automate the selection of training parameters, and (3) modify the AAM search criterion to encourage the location of the edges of the vertebrae. In addition, AAM is utilized to rank the quality of multiple initializations provided by GHT. The proposed segmentation algorithm was tested on 273 cervical X-ray images and 262 lumbar images. If a successful segmentation is defined as a case in which the point-to-corresponding-point error is less than ten pixels for cervical images and twenty-five pixels for lumbar images, results from the proposed segmentation algorithm indicate a 65% success rate for segmentation of cervical vertebrae and a 68% success rate for lumbar vertebrae.