Deletion of twenty seven nucleotides within exon 11 of the band 3 gene identified in ovalocytosis in Lombok Island, Indonesia

This study reports the molecular characterization of ovalocytosis in Lombok Island, Indonesia. The analysis of genomic DNA by polymerase chain reaction shows that all 21 ovalocytotic individuals have two amplified products of different size from a region encompassing exon 11 of the band 3 gene. The sequence of the larger product matched perfectly with that of normal individuals. In the sequence of the smaller product, 27 nucleotides within exon 11 were deleted. The heterozygous presence of the deletion identified in other parts of Southeast Asia was confirmed in patients with ovalocytosis in an isolated island of eastern Indonesia.     

Automated Modeling of Three-Dimensional Structural Components Using Irregular Lattices

Abstract:   Irregular lattices are used to model three-dimensional (3D) structural components consisting of a bulk material, curvilinear reinforcement, and their interface. Domain discretization is highly automated and involves the semi-random placement of nodal points within the domain, followed by Voronoi tessellation of the nodal point set. A technique is given for the Voronoi partitioning of nonconvex domains. For discretizing nonconvex domains, and for effective gradation of nodal point density, a minimum allowable distance between nodes is maintained and the domain is saturated with nodes. To accelerate this computationally expensive operation, a partitioned domain search is used during the filling process. Reinforcement, and its interface with the bulk material, are discretely modeled and freely positioned in the domain, irrespective of the geometry of the irregular lattice representing the bulk material. This method of discretization facilitates model construction, results interpretation, and possible revisions to the model. While the focus is on automated domain discretization and the modeling of reinforcement, elastic properties of the model are demonstrated through examples involving nodal stress calculations and deflection analyses of prestressed concrete beams.     

Prevention of potential fracture between two implants using interlocking bipolar cut short GK nail and Enders nail

OBJECTIVE: To evaluate the ocular toxicity of intravitreous octreotide. DESIGN: New Zealand white rabbits weighing approximately 2 kg were given 5 mg (group 1, two eyes), 2 mg (group 2, four eyes), 1 mg (group 3, four eyes), 0.5 mg (group 4, two eyes), 0.3 mg (group 5, two eyes) or 0.1 mg (group 7, two eyes) of octreotide acetate, two doses of 0.3 mg 1 week apart (group 6, four eyes) or 0.1 mL of balanced salt solution (group 8 [control group], two eyes). OUTCOME MEASURES: Findings on clinical examination and electroretinography, performed before and 10 days after injection, and on light microscopy. RESULTS: Cataracts developed in groups 1 and 2. No clinical changes were found in groups 3 to 8. Electroretinography showed various degrees of decrease in the b-wave amplitude in groups 1 and 2; the results were normal in groups 3 to 8. Histologic examination showed macrophage and monocyte infiltration in the vitreous and retina in group 1. No histologic change was seen in the eyes in groups 2 to 8. CONCLUSIONS: Octreotide injected intravitreally is safe at dosages of 1 mg or less.     

An AP-2 binding sequence within exon 1 of human and porcine choline acetyltransferase genes enhances transcription in neural cells

It has been established that GABAA and GABAB receptors can exist separately and/or co-exist in the membrane of dorsal root ganglion neurons. In our previous investigation it has been shown that co-existence of these two kinds of receptors is about 80% of the neurons examined (20/25). The present study was aimed to explore whether the activation of these two kinds of receptors could interact with each other using intracellular and whole-cell patch-clamp recordings. Baclofen, a specific GABAB receptor agonist, was found to exert negative modulatory effects on the responses mediated by GABAA receptor. In experiments with intracellular recording, GABA (0.3-1000 microM)- and muscimol (100-1000 microM)-induced depolarization was attenuated markedly and reversibly by preapplication of baclofen (100 microM) (15/21 and 17/21, respectively). In whole-cell patch-clamp recordings GABA (100 microM) and two specific GABAA receptor agonists, muscimol (10 microM) and isoguvacine (50 microM), activated currents were inhibited markedly by preapplication of baclofen 30 s or more and the inhibition was concentration dependent (1-100 microM baclofen) and reversible. The possible mechanisms underlying the inhibition by baclofen of the responses mediated by GABAA receptor and the physiological significance implicated are discussed.     

Structural instability of uniaxially compressed α-quartz

We report a molecular dynamics simulation study of stress–strain response of single crystal α-quartz under uniaxial compression using the interatomic potential of van Beest et al. [Phys. Rev. Lett. 64 (1990) 1955]. The results at 1073 K shows an abrupt onset of large deformation of 14 GPa and subsequent time-dependent evolution of an “amorphous” structure with near-planar character. We regard this to be a lattice instability leading to structural failure, to be distinguished from a similar instability observed under hydrostatic loading which results in a phase change. The simulation results allow us to suggest new interpretations of experimental observations with regard to the formation of thin zones of isotropic (glassy) material along faults and a possible mechanism for planar fracture.     

Disulfide-linked head-to-head multimerization in the mechanism of ion channel clustering by PSD-95

The PSD-95/SAP90 family of PDZ-containing proteins is directly involved in the clustering of specific ion channels at synapses. We report that channel clustering depends on a conserved N-terminal domain of PSD-95 that mediates multimerization and disulfide linkage of PSD-95 protomers. This N-terminal multimerization domain confers channel clustering activity on a single PDZ domain. Thus, channel clustering depends on aggregation of PDZ domains achieved by head-to-head multimerization of PSD-95, rather than by concatenation of PDZ domains in PSD-95 monomers. This mechanism predicts that PSD-95 can organize heterogeneous membrane protein clusters via differential binding specificities of its three PDZ domains. PSD-95 and its relative chapsyn-110 exist as disulfide-linked complexes in rat brain, consistent with head-to-head multimerization of these proteins in vivo.     

Reappraisal of the role of vegetables in the vitamin A status of mothers in Central Java, Indonesia

Food-based approaches for controlling vitamin A deficiency and its consequences, such as increased mortality, more severe morbidity, and anemia, have become increasingly important, thus prompting a reassessment of the relation between vitamin A intake and status. A nutrition surveillance system in Central Java, Indonesia, assessed the vitamin A intake and serum retinol concentration of women with a child < or =24 mo old with a semiquantitative 24-h recall method that categorized vitamin A-containing foods into 3 categories of plant foods and into 2 categories of animal foods and identified portions as small, medium, or large. Median vitamin A intake was 335 retinol equivalents (RE)/d (n = 600) and vitamin A intake from plant foods was 8 times higher than from animal foods. Serum retinol concentration was related to vitamin A intake in a dose-response manner. The multiple logistic regression model for predicting the chance for a serum retinol concentration greater than the observed median (> or = 1.37 micromol/L) included physiologic factors, vitamin A intake from plant [odds ratio (95% CI) per quartile: 1st, 1.00: 2nd, 1.23 (0.75, 2.02); 3rd, 1.60 (0.97, 2.63); and 4th, 2.06 (1.25, 3.40)] and animal [1st and 2nd, 1.00; 3rd, 1.31 (0.86, 2.02); and 4th, 2.18 (1.40. 3.42)] foods, home gardening [(no, 1.00; yes, 1.71 (1.12, 2.60)], and woman's education level [< or =primary school, 1.00; > or =secondary school, 1.51 (1.02, 2.22)]. Despite the fact that plant foods contributed 8 times as much vitamin A as did animal foods, serum retinol concentrations did not reflect this large difference. Home gardening and woman's education level seemed to reflect longer-term consumption of vitamin A-rich plant and animal foods, respectively.     

Cleavage efficiency of the novel aspartic protease yapsin 1 (Yap3p) enhanced for substrates with arginine residues flanking the P1 site: correlation with electronegative active-site pockets predicted by molecular modeling

Yapsin 1, a novel aspartic protease with unique specificity for basic residues, was shown to cleave CCK13-33 at Lys23. Molecular modeling of yapsin 1 identified the active-site cleft to have negative residues close to or within the S6, S3, S2, S1, S1', S2', and S3' pockets and is more electronegative than rhizopuspepsin or endothiapepsin. In particular, the S2' subsite has three negative charges in and close to this pocket that can provide strong electrostatic interactions with a basic residue. The model, therefore, predicts that substrates with a basic residue in the P1 position would be favored with additional basic residues binding to the other electronegative pockets. A deletion of six residues close to the S1 pocket in yapsin 1, relative to rhizopuspepsin and other aspartic proteases of known 3D structure, is likely to affect its specificity. The model was tested using CCK13-33 analogues. We report that yapsin 1 preferentially cleaves a CCK13-33 substrate with a basic residue in the P1 position since the substrates with Ala in P1 were not cleaved. Furthermore, the cleavage efficiency of yapsin 1 was enhanced for CCK13-33 analogues with arginine residues flanking the P1 position. An alanine residue, substituting for the arginine residue in the P6 position in CCK13-33, resulted in a 50% reduction in the cleavage efficiency. Substitution with arginine residues downstream of the cleavage site at the P2', P3', or P6' position increased the cleavage efficiency by 21-, 3- and 7-fold, respectively. Substitution of Lys23 in CCK13-33 with arginine resulted not only in cleavage after the substituted arginine residue, but also forced a cleavage after Met25, suggesting that an arginine residue in the S2' pocket is so favorable that it can affect the primary specificity of yapsin 1. These results are consistent with the predictions from the molecular model of yapsin 1.