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  • Blackwell Science Ltd  (2)
  • Munksgaard International Publishers  (2)
  • American Institute of Physics (AIP)  (1)
  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The enzyme γ-secretase catalyzes the intramembrane proteolytic cleavage that generates the amyloid β-peptide from the β-amyloid precursor protein. The presenilin (PS) protein is one of the four integral membrane protein components of the mature γ-secretase complex. The PS protein is itself subjected to endoproteolytic processing, generating stable N- and C-terminal fragment (NTF and CTF, respectively) heterodimers. Here we demonstrate that coexpression of PS1 NTF and CTF functionally mimics expression of the full-length PS1 protein and restores γ-secretase activity in PS-deficient mammalian cells. The coexpressed fragments re-associate with each other inside the cell, where they also interact with nicastrin, another γ-secretase complex component. Analysis of γ-secretase activity following the expression of mutant forms of NTF and CTF, under conditions bypassing endoproteolysis, indicated that the putatively catalytic Asp257 and Asp385 residues have a direct effect on γ-secretase activity. Moreover, we demonstrate that expression of the wild-type CTF rescues endoproteolytic cleavage of C-terminally truncated PS1 molecules that are otherwise uncleaved and inactive. Recovery of cleavage is critically dependent on the integrity of Asp385. Taken together, our findings indicate that ectopically expressed NTF and CTF restore functional γ-secretase complexes and that the presence of full-length PS1 is not a requirement for proper complex assembly.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The ε4 allele of apolipoprotein E (apoE, protein; APOE, gene) is a major risk factor for Alzheimer's disease (AD). Genetically, the frequency of the ε4 allele is enriched in early-onset sporadic, late-onset familial, and common late-onset sporadic AD. ApoE is found in the extracellular amyloid-β (Aβ) deposits that are characteristic features of AD. In this study, we examined the interaction between Aβ and apoE isoforms. The apoE isoforms used in this study were either produced by stably transfected Chinese hamster ovary cells (CHO) or were from human plasma. We report that when similar concentrations of the apoE isoforms were used, native nonpurified apoE3 from recombinant CHO-derived sources bound Aβ, but apoE4 did not. In fact, in our system, binding of recombinant apoE4 to Aβ was never detectable, even after incubation for 4 days. Furthermore, using the same assay conditions, native apoE2, like apoE3, binds Aβ avidly. Furthermore, when human plasma apoE isoforms are tested in Aβ binding experiments, apoE3 bound Aβ more avidly than apoE4, and a major apoE/Aβ complex (the 40-kDa form) was observed with plasma apoE3 but not apoE4. These data extend our understanding of apoE isoform-dependent binding of Aβ by associating apoE2 with efficient apoE/Aβ complex formation and demonstrate that native apoE3 (whether recombinant or derived from human plasma) forms sodium dodecyl sulfate-stable apoE/Aβ complexes more readily than native apoE4. The different Aβ-binding properties of native apoE4 versus native apoE3 provide insight into the molecular mechanisms by which the APOE ε4 allele exerts its risk factor effects in AD.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 64 (1988), S. 5230-5233 
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The distribution of excess carriers in the three dimensions of a semiconductor in closely packed sensing arrays is analytically derived using a novel three-dimensional simulation. In addition to the introduction of lateral transport, the results show significant deviation from the distribution obtained out of the one-dimensional model, both in magnitude and gradients. Thus, the net flow of carriers is drastically different than previously predicted. The technical implications of the exact three-dimensional distribution on quantum efficiency and crosstalk is visualized. The effects of physical parameters such as absorption coefficient, diffusion length, array geometry, and detector structure are thoroughly investigated.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1600-051X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Aim: To evaluate whether bone formation under Teflon capsules may be enhanced by concomitant implantation of recombinant human platelet-derived growth factor-BB/insulin-like growth factor-I (rhPDGF-BB/IGF-I) incorporated into a methyl cellulose gel.Materials and Methods: Fifty-five male 6-month-old albino rats of the Wistar strain were used in the study. The lateral aspect of the mandibular ramus was exposed on both sides of the jaw. In 70 sites, the periosteum was removed from the ramus, leaving the bone denuded, while in 35 sites, it was preserved. On 10 non-periosteal (P−) sites and five periosteal (P+) sites, an empty rigid teflon capsule (d=7 mm), serving as control, was placed on the ramus. In the 40 test animals, the capsule placed on the one side of the jaw was filled at random with one of three different concentrations (1200, 600, 150 μg/ml) of rhPDGF-BB/IGF-I gel. The capsules placed on the contralateral side of the jaw contained a placebo methyl cellulose gel. Each growth factor group, defined according to the gel concentration, and the placebo group contained 10 capsules placed on the P− side and five capsules placed on the P+ side. Two months after surgery, all animals were sacrificed.Results: Histologic analysis revealed that in the non-filled control capsules, the amount of new bone including the bone marrow was 29.9% and 39.7% of the capsule area on the P− and P+ sides, respectively. In the test capsules with the growth factor gel and placed on the P−sides, the amounts of new bone ranged from 5.6% to 6.3%, which were similar (p〉0.05) to that formed in the capsules filled with the methyl cellulose gel (5.5%). New bone formation was larger in the capsules on the P+ sides than in those on the P− sides but was similar in the capsules with different growth factor concentrations (range 17.9–19.6%) and in those with placebo gel (21.0%). In all groups, the carrier gel was poorly absorbed and occupied most of the capsules.Conclusion: Local application of a methyl cellulose gel obstructed bone formation under Teflon capsules placed adjacent to uninjured cortical bone in the mandibular ramus of rats. These data suggest that another material should be utilized to deliver growth factors under Teflon membranes for guided bone regeneration.
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  • 5
    ISSN: 1600-051X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Aim: To investigate the effect of Bio-Oss® with and without the local application of recombinant human platelet-derived growth factor (rhPDGF-BB) on bone formation under Teflon capsules.Materials and Methods: Eight male, 6-month-old, Wistar strain rats were used in the study. In each animal, the lateral aspect of the mandibular ramus was exposed and small perforations were produced in the bone. A rigid, non-porous hemispherical teflon capsule (diameter 7 mm) was placed on the ramus in both sides of the animals. The capsule placed on the one side of the jaw was filled with Bio-Oss® granules soaked in a solution of PDGF-BB (20 μg/capsule) and autogenous blood prior to placement. The capsules placed on the other side of the jaw were filled with Bio-Oss® granules soaked in autogenous blood only (controls). Four rats were sacrificed after 3 months and the remaining four after 5 months. Undecalcified sections containing the capsule and surrounding tissues were prepared and analysed in the microscope.Results: Histologic analysis revealed limited amounts of bone formation. Most of the space underneath the capsules was occupied by Bio-Oss® particles surrounded by fibrovascular connective tissue. Given the small sample size statistical analysis was not possible, however, the mean amount of mineralized new bone in the control group (20.8%) appeared to be larger than that in the test group (6.7%). After 5 months the amount of newly formed bone appeared similar in the two groups (23.0% test, 26.0% controls). The Bio-Oss® particles occupied between 31.4% and 41.1% of the capsule area at 3 months and between 34.0% and 34.7% at 5 months. Only particles adjacent to the mandibular ramus were incorporated in newly formed bone.Conclusion: Limited bone formation was present in the capsules grafted with Bio-Oss® with or without the growth factor.
    Type of Medium: Electronic Resource
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