Effect of Dopants on Zirconia Stabilization—An X-ray Absorption Study: I, Trivalent Dopants

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65562/1/j.1151-2916.1994.tb06964.x.pd

O-Glycosylation Modulates Proprotein Convertase Activation of Angiopoietin-like Protein 3: POSSIBLE ROLE OF POLYPEPTIDE GalNAc-TRANSFERASE-2 IN REGULATION OF CONCENTRATIONS OF PLASMA LIPIDS*

The angiopoietin-like protein 3 (ANGPTL3) is an important inhibitor of the endothelial and lipoprotein lipases and a promising drug target. ANGPTL3 undergoes proprotein convertase processing (RAPR224↓TT) for activation, and the processing site contains two potential GalNAc O-glycosylation sites immediately C-terminal (TT226). We developed an in vivo model system in CHO ldlD cells that was used to show that O-glycosylation in the processing site blocked processing of ANGPTL3. Genome-wide SNP association studies have identified the polypeptide GalNAc-transferase gene, GALNT2, as a candidate gene for low HDL and high triglyceride blood levels. We hypothesized that the GalNAc-T2 transferase performed critical O-glycosylation of proteins involved in lipid metabolism. Screening of a panel of proteins known to affect lipid metabolism for potential sites glycosylated by GalNAc-T2 led to identification of Thr226 adjacent to the proprotein convertase processing site in ANGPTL3. We demonstrated that GalNAc-T2 glycosylation of Thr226 in a peptide with the RAPR224↓TT processing site blocks in vitro furin cleavage. The study demonstrates that ANGPTL3 activation is modulated by O-glycosylation and that this step is probably controlled by GalNAc-T2

Structure of GeO2−P2O5GeO_{2}-P_{2}O_{5} glasses studied by x-ray and neutron diffraction

The structures of three xGeO(2)-(1- x)P(2)O(5) glasses, where x = 0.98,0.88, and 0.81, have been studied by neutron and x-ray diffraction experiments that yield well resolved P-O and Ge-O bond distances. The Ge-O coordination number (N(GeO)) increased from 4.0 ± 0.2 to 4.5 ± 0.2 with the decrease in x from 0.98 to 0.81. The increase in N(GeO) is consistent with a structural model that assumes that all oxygen form Ge-O-Ge and P-O-Ge linkages between Ge polyhedra and P tetrahedra and that new GeO(5) or GeO(6) polyhedra are formed with isolated PO(4) units when P(2)O(5) is added to GeO(2). The bond valencies in the P-O bonds of the PO(4) tetrahedra are greater than unity and are balanced in P-O-Ge bridges with underbonded Ge-O links in the GeO(5) or GeO(6) polyhedra. Mixed site connections are expected for the GeO(5) (or GeO(6)) and PO(4) units in glasses with relatively low (<20 mol%) P(2)O(5) content due to the overwhelming fraction of GeO(4) tetrahedra. The structural changes are compared with those reported for alkali germanate glasses. Several features indicate different characteristics for the compositional dependence of N(GeO) for the GeO(2)-P(2)O(5) and alkali germanate glasses. However, the distributions of the first-neighbour Ge-O distances are found to be nearly identical for the GeO(2)-P(2)O(5) and K(2)O-GeO(2) glasses of equimolar K(2)O and P(2)O(5) content

Short-range order and dynamics in crystalline α-TeO2

The short-range order and dynamics in crystalline α-TeO2 have been investigated by neutron and X-ray total scattering and by Rietveld refinement of neutron diffraction data. The true lengths of the two bonds in a Te–O–Te bridge are 1.882(1) and 2.117(1) Å, and the high valence, 1.293, of the strong, short bond is balanced by the low valence, 0.686, of the weak, long bond. The root-mean-square (rms) thermal variation, 0.083(1) Å, in the long bond length is nearly twice the rms thermal variation, 0.048(1) Å, in the short bond length because the largest motion of both Te and O atoms is perpendicular to the short bonds. A bond-valence model for the thermal variation in bond lengths, in which both the average and the instantaneous positions of the atoms conform to bond-valence requirements, accounts closely for the observed distribution of Te–O distances in α-TeO2. This has important implications for the interpretation of diffraction experiments on tellurite glasses

Effect of Dopants on Zirconia Stabilization—An X-ray Absorption Study: II, Tetravalent Dopants

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65957/1/j.1151-2916.1994.tb05403.x.pd

Diagnostic value of post-heparin lipase testing in detecting common genetic variants in the LPL and LIPC genes

Post-heparin lipoprotein lipase and hepatic lipase activities are used to identify primary disorders of triglyceride and HDL-cholesterol metabolism. Their ability to identify common variants in the lipoprotein lipase (LPL) and hepatic lipase (LIPC) genes is unclear. To investigate the ability of lipase testing to detect common lipase gene variants, we included 183 patients who had undergone post-heparin lipase testing and genotyped the LPL D9N, N291S, PvuII, HindIII, and S447X and the LIPC-514CT, V73M, V133V, and N193S polymorphisms. Allele frequencies were compared with 163 controls. Polymorphisms with different allele frequencies in patients and controls or influencing lipids, were analyzed further. The diagnostic value of post-heparin lipase testing was assessed using logistic regression and receiver operating characteristic curves. We found that lipase activities did not predict the LPL D9N and N291S polymorphisms, but predicted the LPL S447X and LIPC-514CT polymorphisms. Adjusted for covariates, the area under the receiver operating characteristic curves was 0.643, 0.478, 0.686, and 0.657 for LPL D9N, N291S S447X and LIPC-514CT, respectively. On the basis of these findings, we conclude that high-LPL and low-HL activities associate with the LPL S447X and LIPC-514CT polymorphisms, but low-LPL activity was not related to LPL polymorphisms. Overall, the discriminative ability of post-heparin lipase tests in identifying carriers of common variants in the LPL and LIPC genes was limited. This indicates that conclusions on the genetic causes of lipase activities outside of the normal range should be drawn with caution