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1.
Michael J Stobart Debra Parchaliuk Sharon LR Simon Jillian LeMaistre Jozef Lazar Richard Rubenstein J David Knox 《Molecular neurodegeneration》2007,2(1):1-13
Background
Alzheimer's disease (AD) is characterized by a decline in cognitive function and accumulation of amyloid-β peptide (Aβ) in extracellular plaques. Mutations in amyloid precursor protein (APP) and presenilins alter APP metabolism resulting in accumulation of Aβ42, a peptide essential for the formation of amyloid deposits and proposed to initiate the cascade leading to AD. However, the role of Aβ40, the more prevalent Aβ peptide secreted by cells and a major component of cerebral Aβ deposits, is less clear. In this study, virally-mediated gene transfer was used to selectively increase hippocampal levels of human Aβ42 and Aβ40 in adult Wistar rats, allowing examination of the contribution of each to the cognitive deficits and pathology seen in AD.Results
Adeno-associated viral (AAV) vectors encoding BRI-Aβ cDNAs were generated resulting in high-level hippocampal expression and secretion of the specific encoded Aβ peptide. As a comparison the effect of AAV-mediated overexpression of APPsw was also examined. Animals were tested for development of learning and memory deficits (open field, Morris water maze, passive avoidance, novel object recognition) three months after infusion of AAV. A range of impairments was found, with the most pronounced deficits observed in animals co-injected with both AAV-BRI-Aβ40 and AAV-BRI-Aβ42. Brain tissue was analyzed by ELISA and immunohistochemistry to quantify levels of detergent soluble and insoluble Aβ peptides. BRI-Aβ42 and the combination of BRI-Aβ40+42 overexpression resulted in elevated levels of detergent-insoluble Aβ. No significant increase in detergent-insoluble Aβ was seen in the rats expressing APPsw or BRI-Aβ40. No pathological features were noted in any rats, except the AAV-BRI-Aβ42 rats which showed focal, amorphous, Thioflavin-negative Aβ42 deposits.Conclusion
The results show that AAV-mediated gene transfer is a valuable tool to model aspects of AD pathology in vivo, and demonstrate that whilst expression of Aβ42 alone is sufficient to initiate Aβ deposition, both Aβ40 and Aβ42 may contribute to cognitive deficits. 相似文献2.
Claudia G Petersen Fabiana C Massaro Ana L Mauri Joao BA Oliveira Ricardo LR Baruffi Jose G FrancoJr 《Reproductive biology and endocrinology : RB&E》2010,8(1):149
Background
The present study aimed to evaluate the efficacy of the hyaluronic acid (HA) binding assay in the selection of motile spermatozoa with normal morphology at high magnification (8400x). 相似文献3.
4.
Stephen LR Ellison Claire A English Malcolm J Burns Jacquie T Keer 《BMC biotechnology》2006,6(1):33-11
Background
Accurate quantification of DNA using quantitative real-time PCR at low levels is increasingly important for clinical, environmental and forensic applications. At low concentration levels (here referring to under 100 target copies) DNA quantification is sensitive to losses during preparation, and suffers from appreciable valid non-detection rates for sampling reasons. This paper reports studies on a real-time quantitative PCR assay targeting a region of the human SRY gene over a concentration range of 0.5 to 1000 target copies. The effects of different sample preparation and calibration methods on quantitative accuracy were investigated. 相似文献5.
6.
The 18S ribosomal RNAs of 21 tetrapods were sequenced and aligned with five
published tetrapod sequences. When the coelacanth was used as an outgroup,
Lissamphibia (living amphibians) and Amniota (amniotes) were found to be
statistically significant monophyletic groups. Although little resolution
was obtained among the lissamphibian taxa, the amniote sequences support a
sister-group relationship between birds and mammals. Portions of the 28S
ribosomal RNA (rRNA) molecule in 11 tetrapods also were sequenced, although
the phylogenetic results were inconclusive. In contrast to previous
studies, deletion or down- weighting of base-paired sites were found to
have little effect on phylogenetic relationships. Molecular evidence for
amniote relationships is reviewed, showing that three genes
(beta-hemoglobin, myoglobin, and 18S rRNA) unambiguously support a
bird-mammal relationship, compared with one gene (histone H2B) that favors
a bird- crocodilian clade. Separate analyses of four other genes (alpha-
crystallin A, alpha-hemoglobin, insulin, and 28S rRNA) and a combined
analysis of all sequence data are inconclusive, in that different groups
are defined in different analyses and none are strongly supported. It is
suggested that until sequences become available from a broader array of
taxa, the molecular evidence is best evaluated at the level of individual
genes, with emphasis placed on those studies with the greatest number of
taxa and sites. When this is done, a bird-mammal relationship is most
strongly supported. When regarded in combination with the morphological
evidence for this association, it must be considered at least as plausible
as a bird-crocodilian relationship.
相似文献
7.
Luzianina AA Goriacheva AS Semin IuA Izmest'eva OS Deĭgin VI Saenko AS Zhavoronkov LP 《Radiatsionnaia biologiia, radioecologiia / Rossi?skaia akademiia nauk》2012,52(3):257-260
Our work was aimed at researching into the influence of dipeptide (gamma-dGlu-dTrp) "Timodepressin" and this dipeptide-based tripeptides on the colony-forming ability of the irradiated in vitro bone marrow and hemopoietic stem cells of the normal organism. Also studied was the effect of various doses (1-1000 microg/kg) of one oftripeptides (dAla-gammadGlu-dTrp) on the output of exogenous splenic colonies in the case of its introduction 48 hours before irradiation. It is shown that the mode of influence of the preparations produced on the basis ofdipeptides dGlu-dTrp and gamma-dGlu-dTrp on the initial stages ofa hemopoiesis in the normal and irradiated organism depends on the nature of the additional amino-acid residue and its optical orientation. 相似文献
8.
Izmest'eva OS Zhavoronkov LP Semin IuA Posadskaia VM Glushakova VS Luzianina AA Shevchenko AS 《Radiatsionnaia biologiia, radioecologiia / Rossi?skaia akademiia nauk》2012,52(1):39-43
The prolonged ionizing radiation exposure at the absorbed doze rate of 2.6 mGy/hour and the total accumulated doze of about 20 cGy during different periods of the intrauterine development caused disorders of a coordinated development of organs and the decrease of endurance in physical activity in the postnatal ontogenesis of the irradiated posterity. The results obtained are comparable to the consequences of irradiation exposure of the fetus at the accumulated doze of 125 cGy during all stages of pregnancy and give grounds for considering radiation exposure at the above-mentioned rate (20 cGy) as a biologically significant factor. 相似文献
9.
Kaplan MA Zhavoronkov LP Krivosheev IaV Lagoda TS Filimonova MV Izmest'eva OS Izmest'ev VI 《Radiatsionnaia biologiia, radioecologiia / Rossi?skaia akademiia nauk》1999,39(6):701-706
The immediate and the remote effects of the total one-time uniform irradiation with arsenid-hallium laser (wavelength 0.89 mu, pulse power 450 W, pulsed mode 80-3000 Hz) on the new-born Wistar rats have been examined. The complex of tests illustrated the biotropical effects of used laser regimes. The stimulating or braking of the animal's growth was observed in accodanse with the laser regime. 相似文献
10.
Kate L E Phillips Neil Chiverton Anthony LR Michael Ashley A Cole Lee M Breakwell Gail Haddock Rowena AD Bunning Alison K Cross Christine L Le Maitre 《Arthritis research & therapy》2013,15(6):R213