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排序方式: 共有94条查询结果,搜索用时 15 毫秒
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Smith MJ Kwok JB McLean CA Kril JJ Broe GA Nicholson GA Cappai R Hallupp M Cotton RG Masters CL Schofield PR Brooks WS 《Annals of neurology》2001,49(1):125-129
A variant form of Alzheimer's disease (AD), in which spastic paraparesis (SP) precedes dementia, is characterised by large, noncored, weakly neuritic Abeta-amyloid plaques resembling cotton wool balls and is caused by genomic deletion of presenilin 1 exon 9. A pedigree with a 5.9 kb exon 9 deletion shows a phenotypic spectrum including subjects with typical AD or with SP and numerous cotton wool plaques. In SP subjects, dementia onset is delayed and modified. This phenotypic variation suggests that modifying factors are associated with exon 9 deletions. 相似文献
63.
Prion Protein-Deficient Neurons Reveal Lower Glutathione Reductase Activity and Increased Susceptibility to Hydrogen Peroxide Toxicity
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Anthony R. White Steven J. Collins Fran Maher Michael F. Jobling Leanne R. Stewart James M. Thyer Konrad Beyreuther Colin L. Masters Roberto Cappai 《The American journal of pathology》1999,155(5):1723-1730
The prion protein (PrP) has a central role in the pathogenesis of transmissible spongiform encephalopathies (TSE). Accumulating evidence suggests that normal cellular PrP (PrP(c)) may be involved in copper homeostasis and modulation of copper/zinc superoxide dismutase (Cu/ZnSOD) activity in neurons. Hydrogen peroxide (H(2)O(2)) is a toxic reactive oxygen species generated through normal cellular respiration, and neurons contain two important peroxide detoxifying systems (glutathione pathway and catalase). To determine whether PrP expression affects neuronal resistance to H(2)O(2), we exposed primary cerebellar granule neuron cultures derived from PrP knockout (PrP(-/-)) and wild-type (WT) mice to H(2)O(2) for 3, 6, and 24 hours. The PrP(-/-) neurons were significantly more susceptible to H(2)O(2) toxicity than WT neurons after 6 and 24 hours' exposure. The increased H(2)O(2) toxicity may be related to a significant decrease in glutathione reductase activity measured in PrP(-/-) neurons both in vitro and in vivo. This was supported by the finding that inhibition of GR activity with 1,3-bis(2-chloroethyl)-1-nitrosurea (BCNU) increased H(2)O(2) toxicity in WT neurons over the same exposure period. The PrP toxic peptide PrP106-126 significantly reduced neuronal glutathione reductase activity and increased susceptibility to H(2)O(2) toxicity in neuronal cultures suggesting that PrP toxicity in vivo may involve altered glutathione reductase activity. Our results suggest the pathophysiology of prion diseases may involve perturbed PrP(c) function with increased vulnerability to peroxidative stress. 相似文献
64.
CREST staining of micronuclei from free-living rodents to detect environmental contamination in situ. 总被引:1,自引:0,他引:1
F Degrassi C Tanzarella L A Ieradi J Zima A Cappai A Lascialfari F Allegra M Cristaldi 《Mutagenesis》1999,14(4):391-396
In this work immunofluorescent antikinetochore (CREST) staining was used to analyse bone marrow micronuclei (MN) from free-living animals belonging to four different rodent species. Yellow-necked mice (Apodemus flavicollis) and bank voles (Clethrionomys glareolus) were trapped in the Czech Republic, Algerian mice (Mus spretus) in Spain and house mice (Mus musculus domesticus) in Italy. Animals were collected in areas displaying low or high environmental pollution in order to investigate the sensitivity of CREST analysis on bone marrow MN as a biomarker of environmental stress in situ. Differences in total MN frequencies between animals collected in control or contaminated areas were statistically significant for two species, whereas the differences in CREST+ MN were statistically significant for three species. Interestingly, the percentages of CREST+ MN in animals collected in the control areas were very low (3. 2-8.7%), suggesting that activities inducing alterations in the distribution of chromosomes are very rare in natural conditions. The increased frequencies of CREST+ MN observed in areas with high environmental impact indicate that activities producing loss of chromosomes at mitosis may be characteristic of anthropogenic environments such as industrial settlements around petrochemical factories. Our data suggest that the analysis of CREST+ MN may represent a sensitive end-point for the detection of environmental contamination by genotoxic xenobiotics, offering the advantage of providing information on the mechanism of action of environmental contaminants. 相似文献
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Stefano Cappai Ileana Baldi Pietro Desini Antonio Pintore Daniele Denurra Marcella Cherchi Sandro Rolesu Daniela Mandas Giulia Franzoni Mariangela Stefania Fiori Annalisa Oggiano Francesco Feliziani Vittorio Guberti Federica Loi 《Viruses》2022,14(7)
African swine fever (ASF) is a devastating disease, resulting in the high mortality of domestic and wild pigs, spreading quickly around the world. Ensuring the prevention and early detection of the disease is even more crucial given the absence of licensed vaccines. As suggested by the European Commission, those countries which intend to provide evidence of freedom need to speed up passive surveillance of their wild boar populations. If this kind of surveillance is well-regulated in domestic pig farms, the country-specific activities to be put in place for wild populations need to be set based on wild boar density, hunting bags, the environment, and financial resources. Following the indications of the official EFSA opinion 2021, a practical interpretation of the strategy was implemented based on the failure probabilities of wrongly declaring the freedom of an area even if the disease is still present but undetected. This work aimed at providing a valid, applicative example of an exit strategy based on two different approaches: the first uses the wild boar density to estimate the number of carcasses need to complete the exit strategy, while the second estimates it from the number of wild boar hunted and tested. A practical free access tool, named WBC-Counter, was developed to automatically calculate the number of needed carcasses. The practical example was developed using the ASF data from Sardinia (Italian island). Sardinia is ASF endemic from 43 years, but the last ASFV detection dates back to 2019. The island is under consideration for ASF eradication declaration. The subsequent results provide a practical example for other countries in approaching the EFSA exit strategy in the best choices for its on-field application. 相似文献
67.
Peter J. Crouch Lin Wai Hung Paul A. Adlard Mikhalina Cortes Varsha Lal Gulay Filiz Keyla A. Perez Milawaty Nurjono Aphrodite Caragounis Tai Du Katrina Laughton Irene Volitakis Ashley I. Bush Qiao-Xin Li Colin L. Masters Roberto Cappai Robert A. Cherny Paul S. Donnelly Anthony R. White Kevin J. Barnham 《Proceedings of the National Academy of Sciences of the United States of America》2009,106(2):381-386
Cognitive decline in Alzheimer's disease (AD) involves pathological accumulation of synaptotoxic amyloid-β (Aβ) oligomers and hyperphosphorylated tau. Because recent evidence indicates that glycogen synthase kinase 3β (GSK3β) activity regulates these neurotoxic pathways, we developed an AD therapeutic strategy to target GSK3β. The strategy involves the use of copper-bis(thiosemicarbazonoto) complexes to increase intracellular copper bioavailability and inhibit GSK3β through activation of an Akt signaling pathway. Our lead compound CuII(gtsm) significantly inhibited GSK3β in the brains of APP/PS1 transgenic AD model mice. CuII(gtsm) also decreased the abundance of Aβ trimers and phosphorylated tau, and restored performance of AD mice in the Y-maze test to levels expected for cognitively normal animals. Improvement in the Y-maze correlated directly with decreased Aβ trimer levels. This study demonstrates that increasing intracellular copper bioavailability can restore cognitive function by inhibiting the accumulation of neurotoxic Aβ trimers and phosphorylated tau. 相似文献
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Li QX Mok SS Laughton KM McLean CA Cappai R Masters CL Culvenor JG Horne MK 《Experimental neurology》2007,204(2):583-588
Alpha-synuclein (alphaSN) is implicated in Parkinson's disease (PD) and is the major component of Lewy bodies (LBs). Although alphaSN is mainly expressed in neuronal cells and exists as a cytoplasmic protein, it has been found in body fluids including cerebrospinal fluid and blood. This study explored plasma alphaSN as a diagnostic marker for PD. Western blot analysis was used to characterize plasma alphaSN compared to brain alphaSN. Plasma alphaSN of 16 kDa migrates with the same mobility as its brain counterpart and recombinant alphaSN on denatured polyacrylamide gels and reacted with three different antibodies against the C-terminal and NAC regions of the alphaSN protein. The alphaSN levels in plasma from PD subjects are significantly lower than that in age-matched controls (p=0.001), and the alphaSN levels in patients with early-onset PD are lower than that in both late-onset PD and controls. This initial study indicates that measurement of alphaSN in plasma can provide support for a clinical diagnosis of Parkinson's disease and warrants further study in a larger population. 相似文献
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