cappuccino (capu) is a Drosophila melanogaster gene required for establishing the dorsal-ventral and anterior-posterior axes of the developing egg and embryo. Egg chambers mutant for capu exhibit cytoplasmic streaming during mid-oogenesis that does not normally occur until late oogenesis. All known capu alleles stream at the same speed. Since capu alleles do differ in their effects on the dorsal-ventral axis, it is unlikely that premature streaming is a cause of the dorsal-ventral defects. Premature streaming may, however, cause the posterior defects. Streaming occurs at the same speed if isolated egg chambers are treated with the actin depolymerizing drug cytochalasin D, which suggests that CAPU may act in the actin cytoskeleton. A screen for proteins which physically interact with CAPU identified profilin, a regulator of the actin cytoskeleton as a probable partner of CAPU. This again suggests that CAPU acts in the actin cytoskeleton. CAPU is a member of the formin homology (FH) family of proteins. Sequence analysis of this family makes it possible to multiply align all family members throughout their carboxy-terminal halves. This makes possible better predictions of secondary structure, phylogenetic analysis, and identification of novel regions of conserved sequence. Analysis of the amino-terminal halves suggests that significant alignment is also possible in these more highly divergent regions. Members of the rho family of small GTPases have been implicated in the regulation of the actin cytoskeleton. They physically associate with members of the FH family, including CAPU. All four rho-like proteins tested associate with CAPU in the Interaction Trap system. There are also indications of genetic interactions between capu and the rho-like genes dcdc42 and drac1.

The neuregulins (GGF/ARIA/NDF/Heregulin) are pleiotrophic growth factors that are involved in the development of the nervous system. The neuregulin receptors, erbB2, erbB3, erbB4, are members of the erbB/epidermal growth factor receptor family of receptor tyrosine kinases. Immunoblot analysis with antisera to peptides derived from the carboxy terminus of erbB2, erbB3, erbB4 demonstrate that the three receptors have unique spatial distribution in the brain and have expression patterns which are differentially regulated during development. At a cellular level, erbB2 and erbB4 are expressed by glia and neurons while expression of erbB3 is restricted to glia. We have also found that the distribution of erbB3 is developmentally regulated in avian muscle. Moreover, following denervation in adult rats, erbB3 and erbB4 protein levels are increased sciatic nerve, and in muscle, erbB3 is elevated at 16 and 24 days after denervation.

EM radioautography was used to examine the tissue distribution of cells exhibiting nucleoplasmic labeling after being exposed to $ sp3$H-sugars or $ sp{35}$S-sulphate to indicate the general extent of the occurrence of nucleoplasmic glycoproteins within animal cells. The observation of some degree of such labeling in virtually all cells in tissues of three animal species suggests that nucleoplasmic glycoproteins are a common cellular feature. To better define the distribution and nature of the putative labeled nucleoplasmic glycoproteins, cultured cells were used as a model cell type for both quantitative EM radioautographic and biochemical studies. After exposure to $ sp3$H-sugars, all three lines of cultured cells examined exhibited significant nucleoplasmic reaction in which the euchromatin, heterochromatin and nucleoli were all labeled to some extent. Studies on isolated, envelope-depleted nuclei from myeloma cells confirmed that the molecules in the nucleoplasm itself were the source of the radioautographic reaction observed over nuclei. Biochemical analyses of fractions of isolated nuclei indicated that much of the label resided in nuclear matrix glycoproteins of different molecular weights. Lectin binding studies on nuclear matrix fractions revealed the presence of galactose, fucose, and/or sialic acid residues in proteins. Glycosidase experiments indicated that some but not all of these glycoproteins had N-linked sidechains.

A three-dimensional structural analysis model of the human thoracolumbar spine and rib cage has been developed in order to investigate its stability in relation to adolescent idiopathic scoliosis. Idiopathic scoliosis is one of the most puzzling deformities of the spine, due to the fact that there is no known initiating cause. From the viewpoint that it can be explained in a purely biomechanical manner, one particular hypothesis as to its etiology is investigated in this thesis. The hypothesis is that a lordosis-inducing growth of the thoracic spine [34,100,115] in conjunction with spinal asymmetries in the lateral or horizontal plane [34] is the primary cause of the deformity. / Analyses are performed on the constructed model using the MSC/NASTRAN finite element program. The model consists primarily of interconnected beam elements to represent a realistic geometry of the spine and rib cage. The various stiffness properties needed in the model were obtained from the published literature. Simulations of analyses and experiments performed by other researchers produced comparable results, thereby validating the present model, which is then used to investigate the above hypothesis. / Lordosis-inducing growth, in which the anteriors of the thoracic vertebrae grow faster than the posteriors, is simulated in a geometric nonlinear analysis by differential thermal loading of these parts. Results show that under such loading, the model of the normal spine with its natural asymmetries of the thoracic region, gradually deforms into a shape with displacements and rotations typical of thoracic idiopathic scoliosis. These results therefore constitute a validation of the stated hypothesis, and indicate that a lordosis-inducing growth of the thoracic vertebrae is a likely cause of thoracic idiopathic scoliosis.

The need for the development of rigorous analytical models of the knee joint to clarify the role of mechanical factors in joint disorders such as that caused by meniscal tears, long been recognized. In response to this need, a general three dimensional nonlinear finite element model has been developed as part of this work and has been applied to the investigation of the meniscal responses when the joint itself is subjected to 3D complex loading. / The geometry of the model has been obtained from the results of in vitro measurements performed on three adult human knee specimens. The method of measurements combination of computed tomography, a travelling dial gauge system, and a cutting procedure. / The model's analysis accounts for both geometric and material nonlinearities, and is based on a representation of each meniscus as a composite of collagen fibers reinforcing matrix or ground substance. The sticking, sliding, and separation conditions at the meniscus-bone and at the ligament-bone interfaces have been treated as a general moving contact problem. The stress-strain relations, describing the materials of the meniscal matrix and fibers, have been derived from the results of elongation tests of more than 500 samples prepared from different zones and regions of human menisci. Similarly, the stress-strain relations, describing the materials of the major ligaments of the knee joint including transverse ligament, have been derived from elongation tests of bone-ligament-bone prepared from 10 human cadaveric knees. / The model predictions have been validated by direct comparison with measurements, performed on human cadaveric knee as part of the present work and with the measurements reported in the literature. The responses of the menisci have then been determined and analyzed for a joint under a compressive load alone, or combined with a tibial axial rotation, and a tibial anterior translation. The stress strain results have been correlated with the meniscal injuries reported clinically. Furthermore, an injury mechanism for the meniscal tears has been proposed and the supporting clinical evidence has been presented.

No description available.

The fetal liver plays an important role in hemopoiesis during mammalian development. Morphological and immunocytochemical studies were carried out to identify and characterize cellular components that may be responsible for producing the liver hemopoietic environment. Cytospot preparations, from fetal livers of 11-18 days gestation, reacted with specific antibodies enabled us to characterize and quantitate the different cell populations. / Light microscope observations also showed areas of close cell associations involving two classes of central cells and peripheral erythroid cells. Such associations were distinguished based on their immunocytochemical characteristics (AFP vs. Mac-1 central cells) and quantitative appearance throughout cytospots. / The presence of these significant cell associations was also observed in ultrastructural studies that produced further characteristics of these central cells. Characteristic lipid inclusions, glycogenic particles and positive AFP reactions were localized to central hepatocytes. Macrophages in cell associations contained numerous phagocytic particles and distinct peroxidase activity within the nuclear envelope and endoplasmic reticulum. Extra-cellular matrix components of electron dense nature were noted to emanate from delicate cytoplasmic processes that appeared to keep these associations intact. Fibronectin positive reactions were also specifically localized to central hepatocytes in cell associations. Further morphological and immunocytochemical features of these cell associations in the liver hemopoietic microenvironment are discussed.

It has long been postulated that the facet joint geometry (FJG) has an important influence on lumbar segmental motion. Although their sagittal orientation has been described in detail, there are very few studies describing the three-dimensional (3D) FJG. None correlates the latter to segmental kinematics. In view, we developed a method to quantify 3D FJG and compared the results to segmental kinematics. / In the ex-vivo set-up, facets of individual cadaveric vertebrae taken from a previous biomechanical. study were digitized using a 3D morphometer and the geometry of the facet joints in respect to the vertebra's local coordinate system was quantified. In the in-vivo set-up, re-recruited subjects from a previous kinematic study had a MRI of their lumbar spine. The images were digitized and the facet joint's 3D geometry was evaluated. The two methods used for FJG measurements were validated. Kinematic data derived from both previous studies was correlated with their respective FJG. / We did not find a significant influence of the FJG or tropism on lumbar segmental kinematics. Different coupling patterns were measured in the ex-vivo and in in-vivo experiments. This is likely due to the absence of muscle activity in the cadaveric specimen. Future in-vivo studies should be done with simultaneous muscle activity recording to better understand the coupling patterns. Studying FJG in defined spinal pathologies may render valuable information on the etiology of spinal diseases.

The replacement of the hyaline cartilage model by bone tissue during osseous development involves an extensive resorption of cartilage. The current study examines the role played by matrix metalloproteinases (MMPs) in cartilage resorption in the tibial epiphysis of 8 and 10 day old rats. The entry of cellular, highly vascularized channels requires the degradation of cartilage components. As a first step, aggrecan is cleaved by an unidentified MMP along the edges of the channel walls, as detected by an antiserum directed to a cleavage fragment retained in the tissue; the presence of an active MMP at the channel edge is confirmed by the binding of a recombinant MMP inhibitor, TIMP-2. Second, using histozymography, the collagen component of cartilage is degraded by another MMP, identified as gelatinase B by inhibition studies, at similar channel sites. Thus, two proteinases combine their efforts to produce the resorption associated with channel invasion preceding the appearance of the secondary ossification center in the rat tibial epiphysis.

A finite-element model of the cat middle ear was modified to include a shell representation of the incudostapedial joint. A low-frequency, uniform sound pressure was applied to the eardrum. Joint stiffness was varied from very low to very high. The resulting displacements of the stapedial footplate, incudostapedial joint, manubrium and eardrum were examined. The footplate tilts both anteroposteriorly and inferosuperiorly for almost all Young's modulus values. The in-plane rotation of the footplate is greatest when the incudostapedial joint is effectively rigid. The joint compresses most when it is extremely flexible and less as the joint becomes less flexible. The joint compression is greater than the joint shear. The displacement pattern of the eardrum is relatively insensitive to changes in the joint stiffness.