Cartilage oligomeric matrix protein-deficient mice have normal skeletal development.

Cartilage oligomeric matrix protein (COMP) belongs to the thrombospondin family and is a homopentamer primarily expressed in cartilage. Mutations in the COMP gene result in the autosomal dominant chondrodysplasias pseudoachondroplasia (PSACH) and some types of multiple epiphyseal dysplasia (MED), which are characterized by mild to severe short-limb dwarfism and early-onset osteoarthritis. We have generated COMP-null mice to study the role of COMP in vivo. These mice show no anatomical, histological, or ultrastructural abnormalities and show none of the clinical signs of PSACH or MED. Northern blot analysis and immunohistochemical analysis of cartilage indicate that the lack of COMP is not compensated for by any other member of the thrombospondin family. The results also show that the phenotype in PSACH/MED cartilage disorders is not caused by the reduced amount of COMP

The role of leucine-rich repeat glycoproteins/proteoglycans in the assembly of collagen matrices

The properties of different connective tissues depend on the synthesis and assembly of macromolecular structures composed of collagen and other extracellular matrix components. Mechanisms modulating these events play important roles in the formation of a functional tissue. We have studied the role of collagen-binding extracellular matrix leucine-rich repeat glycoproteins/proteoglycans in the formation of collagen matrices. A region in decorin with high affinity for collagen type I was identified. Using a mammalian cell expression system we produced recombinant chimeric proteoglycans consisting of decorin sequences fused with biglycan sequences. Biglycan is closely related to decorin but does not bind to collagen type I. The collagen-binding properties of the proteoglycans and the proteoglycan chimeras were investigated in collagen fibril formation/sedimentation assays. The chimeric proteoglycan consisting of biglycan, substituted with leucine-rich repeats 4-5 from decorin, bound collagen type I. This region represents 13% of the amino acid sequence of decorin and contains a major collagen binding site. To study the function of fibromodulin in vivo, a mouse strain lacking the expression of this proteoglycan was generated by gene targeting. These mice phenotypically showed abnormal collagen fibrils in tendons, suggesting a role for fibromodulin in collagen fibrillogenesis. Moreover, these fibromodulin-null mice showed an increased lumican deposition in tendons. Using both recombinant fibromodulin and lumican in collagen fibril formation/sedimentation assays, we showed that fibromodulin and the closely related lumican share a binding region on collagen type I fibrils. The binding of fibromodulin to collagen occurs with higher affinity than the binding of lumican

Quantification of myocardial perfusion defects using three different software packages.

Software packages are widely used for quantification of myocardial perfusion defects. The quantification is used to assist the physician in his/her interpretation of the study. The purpose of this study was to compare the quantification of reversible perfusion defects by three different commercially available software packages. We included 50 consecutive patients who underwent myocardial perfusion single-photon emission tomography (SPET) with a 2-day technetium-99m tetrofosmin protocol. Two experienced technologists processed the studies using the following three software packages: Cedars Quantitative Perfusion SPECT, Emory Cardiac Toolbox and 4D-MSPECT. The same sets of short axis slices were used as input to all three software packages. Myocardial uptake was scored in 20 segments for both the rest and the stress studies. The summed difference score (SDS) was calculated for each patient and the SDS values were classified into: normal (13). All three software packages were in agreement that 21 patients had a normal SDS, four patients had a mildly abnormal SDS and one patient had a severely abnormal SDS. In the remaining 24 patients (48%) there was disagreement between the software packages regarding SDS classification. A difference in classification of more than one step between the highest and lowest scores, for example from normal to moderately abnormal or from mildly to severely abnormal, was found in six of these 24 patients. Widely used software packages commonly differ in their quantification of myocardial perfusion defects. The interpreting physician should be aware of these differences when using scoring systems

The crystal structure of staphylococcal enterotoxin H : Implications for binding properties to MHC class II and TcR molecules

The X-ray structure of the superantigen staphylococcal enterotoxin H (SEH) has been determined at 1.69 Å resolution. In this paper we present two structures of zinc-free SEH (apoSEH) and one zinc-loaded form of SEH (ZnSEH). SEH exhibits the conventional superantigen (SAg) fold with two characteristic domains. In ZnSEH one zinc ion per SEH molecule is bound to the C-terminal β-sheet in the region implicated for major histocompatibility complex class II (MHC class II) binding in SEA, SED and SEE. Surprisingly, the zinc ion has only two ligating amino acid residues His206 and Asp208. The other ligands to the zinc ion are two water molecules. An extensive packing interaction between two symmetry-related molecules in the crystal, 834 Å2/molecule, forms a cavity that buries the zinc ions of the molecules. This dimer-like interaction is found in two crystal forms. Nevertheless, zinc-dependent dimerisation is not observed in solution, as seen in the case of SED. A unique feature of SEH as compared to other staphylococcal enterotoxins is a large negatively charged surface close to the Zn2+ site. The interaction of SEH with MHC class II is the strongest known among the staphylococcal enterotoxins. However, SEH seems to lack a SEB-like MHC class II binding site, since the side-chain properties of structurally equivalent amino acid residues in SEH and those in SEB-binding MHC class II differ dramatically. There is also a structural flexibility between the domains of SEH. The domains of two apoSEH structures are related by a 5°rotation leading to at most 3 Å difference in C(α) positions. Since the T-cell receptor probably interacts with both domains, SEH by this rotation may modulate its binding to different TcR Vβ-chains. (C) 2000 Academic Press

F#ck Your Family!: The Visual Jurisprudence of Automobility

This paper considers the popular visual jurisprudence of bumper stickers. Drawing upon a sample sticker/driver/vehicle assemblages observed at the Gold Coast, Australia in 2014, we argue that the meanings and messages projected by the assemblages have a significant legal dimension. The argument is located at the intersection of past research into bumper stickers, increased scholarly interest in the relation of law to automobility and especially recent considerations of the popular visual jurisprudence of the motor vehicle, its cultures and semiotics. In particular we argue that the sticker/driver/vehicle assemblage represents an engagement with law and legality. We suggest this goes beyond immediate denotations of brands with intellectual property or flags and the sovereign nation state to more essential engagement with consumer capitalisms law of the image, the friend/enemy distinction, the ouroboros of rights and the essential legality of living in a polis.Arts, Education & Law Group, School of Criminology and Criminal JusticeNo Full Tex