Osteoprotegerin mRNA is expressed in primary human osteoblast-like cells: down-regulation by glucocorticoids

Oryzacystatins (OCs) are protease inhibitors (PIs) that inhibit Colorado potato beetle (CPB) digestive proteases, and transgenic potato plants containing these PIs are currently under test. However, OCs could interfere with the digestive system of beneficial insects. Protease activity and susceptibility to class-specific protease inhibitors were studied in protein extracts of Perillus bioculatus, a stinkbug predator that has shown potential for biological control of the CPB. At physiological pH, the analysis of protease activity showed that up to 90% of P. bioculatus protease activity is of the cysteine type. All active life stages of the predator were tested, and electrophoretic characterization detected no major qualitative variation in protease pattern between stages. Protease activity in extracts of P. bioculatus nymphs was significantly reduced, up to 70%, by the two recombinant cystatins from rice (OCI and OCII), and by stefin A, a PI encoded by a human gene. These results clearly indicate that cysteine PIs are active not only against the CPB digestive protease complex, but also against proteases of one of its most important natural predators.     

Knee osteoarthritis after meniscectomy: prevalence of radiographic changes after twenty-one years, compared with matched controls

Aggrecan, a large aggregating proteoglycan, is one of the major structural components of cartilage. Its core protein contains three glubular domains and two glycosaminoglycan-attachment domains. These domains play various roles to maintain cartilage structure and function. An N-terminal globular domain binds hyaluronan and link protein to form huge aggregates. The chondroitin sulfate (CS) chains attach to the CS domain and provide a hydrated, viscous gel that absorbs compressive load. Two autosomal recessive chondrodysplasias, cartilage matrix deficiency (cmd) in mice and nanomelia in chicken are both caused by aggrecan gene mutations. Cmd homozygotes die shortly after birth, while the heterozygotes are born normal. However, cmd heterozygotes develop late onset of spinal disorder, which suggests aggrecan as a candidate gene predisposing individuals to spinal problems. Nanomelia is a useful model to elucidate intracellular trafficking of proteoglycans. Further studies on aggrecan will lead to prophylaxis and treatment of joint destructive diseases such as osteoarthrosis and to elucidation of cartilage development, which is essential for skeletal formation.     

Crystal structure of carbonic anhydrase from Neisseria gonorrhoeae and its complex with the inhibitor acetazolamide

The crystal structure of carbonic anhydrase from Neisseria gonorrhoeae has been solved to a resolution of 1.78 A by molecular replacement using human carbonic anhydrase II as a template. After refinement the R factor was 17.8% (Rfree=23.2%). There are two molecules per asymmetric unit (space group P21), but they have essentially identical structures. The fold of the N. gonorrhoeae enzyme is very similar to that of human isozyme II; 192 residues, 74 of which are identical in the two enzymes, have equivalent positions in the three-dimensional structures. This corresponds to 85% of the entire polypeptide chain of the bacterial enzyme. The only two cysteine residues in the bacterial enzyme, which has a periplasmic location in the cell, are connected by a disulfide bond. Most of the secondary structure elements present in human isozyme II are retained in N. gonorrhoeae carbonic anhydrase, but there are also differences, particularly in the few helical regions. Long deletions in the bacterial enzyme relative to human isozyme II have resulted in a considerable shortening of three surface loops. One of these deletions, corresponding to residues 128 to 139 in the human enzyme, leads to a widening of the entrance to the hydrophobic part of the active site cavity. Practically all the amino acid residues in the active site of human isozyme II are conserved in the N. gonorrhoeae enzyme and have similar structural positions. However, the imidazole ring of a histidine residue, which has been shown to function as a proton shuttle in the catalytic mechanism of the human enzyme, interacts with an extraneous entity, which has tentatively been identified as a 2-mercaptoethanol molecule from the crystallization medium. When this entity is removed by soaking the crystal in a different medium, the side-chain of His66 becomes quite mobile. The structure of a complex with the sulfonamide inhibitor, acetazolamide, has also been determined. Its position in the active site is very similar to that observed in human carbonic anhydrase II.     

Family dissolution, family reconstitution, and children's educational careers: recent evidence for Sweden

Both longitudinal and cross-sectional analyses on a large and recent Swedish data set demonstrate that, compared to children in intact families, children who have experienced family dissolution or reconstitution show lower educational attainment at age 16. Time constraints do not seem to be an important mechanism behind the negative effect of separation. Economic deprivation affects children's attainment negatively, but downward social mobility appears to be an even more important causal mechanism: Losing the parent with the higher social position probably reduces social capital and aspirations. When we control for socioeconomic characteristics, a small net effect of separation and reconstitution remains.     

Performance simulations of twin-screw compressors with economizer

In a compressor refrigeration plant with an economizer system, the regular expansion valve is replaced by two valves and an intermediate pressure vessel. The refrigerant which is vaporized after the first valve is injected via the compressor economizer inlet to a thread under compression. The economizer arrangement increases the refrigeration capacity and improves the coefficient of performance (COP). In this paper a performance simulation computer program for twin-screw compressors with an economizer arrangement is presented. Comparisons of economizer performance for different arrangements are often difficult to carry out if real tests have not been run, as the performance is dependent on the intermediate pressure and this pressure is not the same for different arrangements. Such comparisons can be made with the simulation program. Examples are presented for an economizer arrangement combined with external liquid subcooling and for a two-stage economizer arrangement.     

Transfer of human serum IgG to nonobese diabetic Igmu null mice reveals a role for autoantibodies in the loss of secretory function of exocrine tissues in Sj?gren's syndrome

The NOD (nonobese diabetic) mouse has been studied as an animal model for autoimmune insulin-dependent diabetes and Sj?gren's syndrome. NOD.Igmu null mice, which lack functional B lymphocytes, develop progressive histopathologic lesions of the submandibular and lachrymal glands similar to NOD mice, but in the absence of autoimmune insulitis and diabetes. Despite the focal appearance of T cells in salivary and lachrymal tissues, NOD.Igmu null mice fail to lose secretory function as determined by stimulation of the muscarinic/cholinergic receptor by the agonist pilocarpine, suggesting a role for B cell autoantibodies in mediating exocrine dryness. Infusion of purified serum IgG or F(ab')2 fragments from parental NOD mice or human primary Sj?gren's syndrome patients, but not serum IgG from healthy controls, alters stimulated saliva production, an observation consistent with antibody binding to neural receptors. Furthermore, human patient IgG fractions competitively inhibited the binding of the muscarinic receptor agonist, [3H]quinuclidinyl benzilate, to salivary gland membranes. This autoantibody activity is lost after preadsorption with intact salivary cells. These findings indicate that autoantibodies play an important part in the functional impairment of secretory processes seen in connection with the autoimmune exocrinopathy of Sj?gren's syndrome.     

Homozygous protein C deficiency can be detected by prenatal diagnosis

Homozygous protein C deficiency (HPCD) with purpura fulminans is a rare condition with an estimated incidence of 1-2 per 400,000 births. About 20 case reports have appeared since the first one was published in 1983. HPCD provides an excellent illustration of the fundamental importance of the protein C anticoagulant pathway. This severe coagulopathy results in serious organ damage, often already in utero, and without treatment it is incompatible with life. The treatment options include fresh frozen plasma and protein C concentrate in the acute phase, followed by oral anticoagulant therapy. Over 160 different point mutations in the protein C gene have been identified in recent years, offering new possibilities for prenatal diagnosis. The article describes the case of a family who lost two children with congenital HPCD. But where the specific point mutation was identified thus enabling prenatal diagnosis to be performed in a subsequent pregnancy.     

Effect of Al on High-Temperature Oxidation of Cr–W Alloys

The effect of Al on the high temperature oxidation behavior of Cr–10 wt.%W alloy was investigated using a cyclical oxidation test at 1,000 °C in dry air. First, Al was added into the Cr–W alloy as an alloying element up to 8 weight percent. Although alloying with Al reduced the spalling, it did not eliminate it. Secondly, Al was applied to the surface using an aluminizing process. Forming an Al–Cr layer on the Cr–W alloy reduced oxidation rate significantly and eliminated spalling completely.     

Effect of spherical pores on the strength of a polycrystalline ceramic

Bending tests on a ceramic material, lead zirconate-titanate, with varying amounts of porosity, show that the decrease in strength due to spherical pores is much less than would be expected from the stress concentration factor. Using the Weibull probabilistic approach to brittle strength, it is shown that reasonable predictions may be made for the median strength for porosity up to about ten percent.

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Résumé Les essais de flexion sur un matériau céramique: zirconate-titanate de plomb, avec des quantités variables de porosités, montrent que la diminution de la résistance due à la porosité est plus faible que celle donnée par le facteur de concentration de contraintes. En utilisant la méthode statistique de Weibull pour la résistance fragile, il est montré que des prévisions raisonables peuvent être faites pour déterminer la résistance médiane pour une porosité jusqu'aux environs de dix pourcents.