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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.
Human T-cell leukemia virus type I (HTLV-I) infection is emerging as an important complication in HIV infection and AIDS in injecting drug users. HIV-1 and HTLV-I share a common host in CD4+ T lymphocytes. However, the result of HIV-1 infection is the decimation of this cell population, whereas a hallmark of HTLV-I infection is the inappropriate proliferation of infected cells. Combined epidemiologic data suggest that HTLV-I infection is enhanced during concurrent HIV-1/HTLV-I infection; however, there are currently no in vitro studies focusing on the effects of drugs of abuse on retrovirus coinfection. We have found that in an in vitro coinfection system (HIV-1 + HTLV-I), morphine treatment further enhanced the levels of HTLV-I p19. In addition, indicators of in vitro infection by cell-free HIV-1 were reduced by morphine treatment in both single and dual in vitro infection experiments. Interleukin 2 levels in the affected cultures were found to increase with combined HTLV-I infection and morphine treatment. These in vitro results indicate the need to further explore the activity of HTLV-I within opiate-treated cells, as this oncoretrovirus appears to be especially sensitive to morphine-induced alterations to its host cell environment. 相似文献
3.
Noguchi T Chen Z Bell SP Nyland L LeWinter MM 《American journal of physiology. Heart and circulatory physiology》2003,285(4):H1428-H1434
The effects of endothelin (ET) receptor blockade on energy utilization in heart failure (HF) are unknown. We administered ET type A (ETA), ET type B (ETB), and ETA/ETB antagonists to isolated hearts from Dahl salt-sensitive (DS) rats with HF and controls. Contractile efficiency was assessed as slope-1 of myocardial O consumption (VO2)-pressure-volume area relation. In HF, ETA and ETA/ETB but not ETB blockade decreased the contractility index (Emax)(-15 +/- 3% and -17 +/- 2%, P < 0.05), excitation-contraction (E-C) coupling VO2 (-39 +/- 4% and -37 +/- 5%, P < 0.01), and efficiency (-15 +/- 4% and -17 +/- 2%, P < 0.05). Despite decreased efficiency, ETA and ETA/ETB blockade decreased total VO2 (-24 +/- 3% and -22 +/- 2%, P < 0.05). Na+/H+ exchanger inhibition decreased Emax and E-C coupling VO2 similar to ETA and ETA/ETB blockade, but did not alter efficiency. In HF, endogenous ET-1 maintains contractility at expense of increased VO2 through ETA receptor activation, likely mediated by Na+/H+ exchange. 相似文献
4.
Morphology and transverse stiffness of Drosophila myofibrils measured by atomic force microscopy 下载免费PDF全文
Atomic force microscopy was used to investigate the surface morphology and transverse stiffness of myofibrils from Drosophila indirect flight muscle exposed to different physiologic solutions. I- and A-bands were clearly observed, and thick filaments were resolved along the periphery of the myofibril. Interfilament spacings correlated well with estimates from previous x-ray diffraction studies. Transverse stiffness was measured by using a blunt tip to indent a small section of the myofibrillar surface in the region of myofilament overlap. At 10 nm indention, the effective transverse stiffness (K( perpendicular)) of myofibrils in rigor solution (ATP-free, pCa 4.5) was 10.3 +/- 5.0 pN nm(-1) (mean +/- SEM, n = 8); in activating solution (pCa 4.5), 5.9 +/- 3.1 pN nm(-1); and in relaxing solution (pCa 8), 4.4 +/- 2.0 pN nm(-1). The apparent transverse Young's modulus (E( perpendicular)) was 94 +/- 41 kPa in the rigor state and 40 +/- 17 kPa in the relaxed state. The value of E( perpendicular) for calcium-activated myofibrils (55 +/- 29 kPa) was approximately a tenth that of Young's modulus in the longitudinal direction, a difference that at least partly reflects the transverse flexibility of the myosin molecule. 相似文献
5.
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6.
Fairweather D Frisancho-Kiss S Njoku DB Nyland JF Kaya Z Yusung SA Davis SE Frisancho JA Barrett MA Rose NR 《Journal of immunology (Baltimore, Md. : 1950)》2006,176(6):3516-3524
Complement and complement receptors (CR) play a central role in immune defense by initiating the rapid destruction of invading microorganisms, amplifying the innate and adaptive immune responses, and mediating solubilization and clearance of immune complexes. Defects in the expression of C or CR have been associated with loss of tolerance to self proteins and the development of immune complex-mediated autoimmune diseases such as systemic lupus erythematosus. In this study, we examined the role of CR on coxsackievirus B3 (CVB3)-induced myocarditis using mice deficient in CR1/2. We found that CR1/2 deficiency significantly increased acute CVB3 myocarditis and pericardial fibrosis resulting in early progression to dilated cardiomyopathy and heart failure. The increase in inflammation was not due to increased viral replication, which was not significantly altered in the hearts of CR1/2-deficient mice, but was associated with increased numbers of macrophages, IL-1beta levels, and immune complex deposition in the heart. The complement regulatory protein, CR1-related gene/protein Y (Crry), was increased on cardiac macrophage populations, while immature B220(low) B cells were increased in the spleen of CR1/2-deficient mice during acute CVB3-induced myocarditis. These results show that expression of CR1/2 is not necessary for effective clearance of CVB3 infection, but prevents immune-mediated damage to the heart. 相似文献
7.
8.
Nyland Cecilia Askham Modahl Ingunn Saur Raadal Hanne Lerche Hanssen Ole Jørgen 《The International Journal of Life Cycle Assessment》2003,8(6):331-336
Aim, Scope and Background When materials are recycled they are made available for use for several future life cycles and can therefore replace virgin
material more than just once. In order to analyse the optimal waste management system for a given material, the authors have
analysed the material flows in a life cycle perspective. It is important to distinguish this approach for material flow analysis
for a given material from life cycle analysis of products. A product life cycle analysis analyses the product system from
cradle to grave, but uses some form of allocation in order to separate the life cycle of one product from another in cases
where component materials are recycled. This paper does not address allocation of burdens between different product systems,
but rather focuses on methodology for decision making for waste management systems where the optimal waste management system
for a given material is analysed. The focus here is the flow of the given material from cradle (raw material extraction) to
grave (the material, or its inherent energy, is no longer available for use). The limitation on the number of times materials
can be recycled is set by either the recycling rate, or the technical properties of the recycled material.
Main Features This article describes a mathematical geometric progression approach that can be used to expand the system boundaries and
allow for recycling a given number of times. Case studies for polyethylene and paperboard are used to illustrate the importance
of including these aspects when part of the Goal and Scope for the LCA study is to identify which waste management treatment
options are best for a given material. The results and discussion examine the different conclusions that can be reached about
which waste management option is most environmentally beneficial when the higher burdens and benefits of recycling several
times are taken into account.
Results In order to assess the complete picture of the burdens and benefits arising from recycling the system boundaries must be expanded
to allow for recycling many times. A mathematical geometric progression approach manages to take into account the higher burdens
and benefits arising from recycling several times. If one compares different waste management systems, e.g. energy recovery
with recycling, without expanding the system to include the complete effects of material recycling one can reach a different
conclusion about which waste management option is preferred.
Conclusions When the purpose of the study is to compare different waste management options, it is important that the system boundaries
are expanded in order to include several recycling loops where this is a physical reality. The equations given in this article
can be used to include these recycling loops. The error introduced by not expanding the system boundaries can be significant.
This error can be large enough to change the conclusions of a comparative study, such that material recycling followed by
incineration is a much better option than waste incineration directly.
Recommendations and Outlook When comparing waste management solutions, where material recycling is a feasible option, it is important to include the relevant
number of recycling loops to ensure that the benefits of material recycling are not underestimated. The methodology presented
in this article should be used in future comparative studies for strategic decision-making for waste management. The approach
should not be used for LCAs for product systems without due care, as this could lead to double counting of the benefits of
recycling (depending on the goal and scope of the analysis). For materials where the material cycle is more of a closed loop
and one cannot truly say that recycled materials replace virgin materials, a more sophisticated approach will be required,
taking into account the fact that recycled materials will only replace a certain proportion of virgin materials. 相似文献
9.
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10.