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Search Results: 1 - 10 of 12583 matches for " Weiming Xia "
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Brain amyloid β protein and memory disruption in Alzheimer’s disease
Weiming Xia
Neuropsychiatric Disease and Treatment , 2010,
Abstract: Weiming XiaCenter for Neurologic Diseases, Department of Neurology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USAAbstract: The development of amyloid-containing neuritic plaques is an invariable characteristic of Alzheimer’s diseases (AD). The conversion from monomeric amyloid β protein (Aβ) to oligomeric Aβ and finally neuritic plaques is highly dynamic. The specific A species that is correlated with disease severity remains to be discovered. Oligomeric Aβ has been detected in cultured cells, rodent and human brains, as well as human cerebrospinal fluid. Synthetic, cell, and brain derived Aβ oligomers have been found to inhibit hippocampal long-term potentiation (LTP) and this effect can be suppressed by the blockage of Aβ oligomer formation. A large body of evidence suggests that Aβ oligomers inhibit N-methyl-D-aspartate receptor dependent LTP; additional receptors have also been found to elicit downstream pathways upon binding to Aβ oligomers. Amyloid antibodies and small molecular compounds that reduce brain Aβ levels and block Aβ oligomer formation are capable of reversing synaptic dysfunction and these approaches hold a promising therapeutic potential to rescue memory disruption.Keywords: Alzheimer, amyloid, oligomer, long-term potentiation, NMDA
Engineering Antibody Fragment with the Quantum Dot in Cancer Cell Imaging and Diagnosis  [PDF]
Lizhi Liu, Weiming Xu
Engineering (ENG) , 2012, DOI: 10.4236/eng.2012.410B033
Abstract:
The conjugates of monoclonal antibodies and nanoparticles, including quantum-dot(QD), offer significant advantages over conventional fluorescent probes to image and study biological processes. The extend stability, intense fluorescence and low toxicity of QDs are well suited for biological applications. In the present study, we used QD-conjugated anti-glucose-regulated protein 78(GRP78) antibody to examine the gene expression in prostate cancer cells under the unfolded protein response (UPR). QDs have got unique, simple and fast properties over current diagnostic techniques such as peroxidase-based immunohistochemical staining procedures, therefore the nanocarrier-conjugated antibody fragment has potential to become a new therapeutic tool for cancer diagnosis and treatment.
Analysis of the Influence Factors of Grain Supply-Demand Gap in China  [PDF]
Bingjun Li, Weiming Yang
Agricultural Sciences (AS) , 2018, DOI: 10.4236/as.2018.97062
Abstract: Based on the analysis of the grain supply and demand gap’s current situation in China, this paper establishes an indicator system for the influence factors of grain supply and demand gap. Then this paper calculates the correlation degree between the main grain varieties’ supply and demand gap and its influence factors. The results show that sown area and unit yield have the greatest impact on wheat supply and demand gap; per capita disposable income and unit yield have the greatest impact on corn supply and demand gap; per capita disposable income and agricultural mechanization level have the greatest impact on the supply and demand gap of soybean and rice. From the analysis results, we can obtain the difference between the factors affecting the grain supply and demand gap, and provide a certain theoretical basis and new ideas for the balance of grain supply and demand in China.
Disease Gene Interaction Pathways: A Potential Framework for How Disease Genes Associate by Disease-Risk Modules
Lina Chen, Wan Li, Liangcai Zhang, Hong Wang, Weiming He, Jingxie Tai, Xu Li, Xia Li
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0024495
Abstract: Background Disease genes that interact cooperatively play crucial roles in the process of complex diseases, yet how to analyze and represent their associations is still an open problem. Traditional methods have failed to represent direct biological evidences that disease genes associate with each other in the pathogenesis of complex diseases. Molecular networks, assumed as ‘a form of biological systems’, consist of a set of interacting biological modules (functional modules or pathways) and this notion could provide a promising insight into deciphering this topic. Methodology/Principal Findings In this paper, we hypothesized that disease genes might associate by virtue of the associations between biological modules in molecular networks. Then we introduced a novel disease gene interaction pathway representation and analysis paradigm, and managed to identify the disease gene interaction pathway for 61 known disease genes of coronary artery disease (CAD), which contained 46 disease-risk modules and 182 interaction relationships. As demonstrated, disease genes associate through prescribed communication protocols of common biological functions and pathways. Conclusions/Significance Our analysis was proved to be coincident with our primary hypothesis that disease genes of complex diseases interact with their neighbors in a cooperative manner, associate with each other through shared biological functions and pathways of disease-risk modules, and finally cause dysfunctions of a series of biological processes in molecular networks. We hope our paradigm could be a promising method to identify disease gene interaction pathways for other types of complex diseases, affording additional clues in the pathogenesis of complex diseases.
Phenotypic analysis of images of zebrafish treated with Alzheimer's γ-secretase inhibitors
Dilyara Arslanova, Ting Yang, Xiaoyin Xu, Stephen T Wong, Corinne E Augelli-Szafran, Weiming Xia
BMC Biotechnology , 2010, DOI: 10.1186/1472-6750-10-24
Abstract: We have developed a method to examine live zebrafish that were each treated with γ-secretase inhibitors (GSI), DAPT {N- [N-(3,5-Difluorophenacetyl-L-alanyl)]-S-phenylglycine t-Butyl Ester}, Gleevec, or fragments of Gleevec. These compounds were first tested in a cell-based assay and the effective concentrations of these compounds that blocked Aβ generation were quantitated. The mortality of zebrafish, as a result of exposure to different doses of compound, was assessed, and any apoptotic processes were examined by TUNEL staining. We then used conventional and automatic microscopes to acquire images of zebrafish and applied algorithms to automate image composition and processing. Zebrafish were treated in 96- or 384-well plates, and the phenotypes were analyzed at 2, 3 and 5 days post fertilization (dpf). We identified that AD95, a fragment of Gleevec, effectively blocks Aβ production and causes specific phenotypes that were different from those treated with DAPT. Finally, we validated the specificity of two Notch phenotypes (pigmentation and the curvature of tail/trunk) induced by DAPT in a dose-dependent manner. These phenotypes were examined in embryos treated with GSIs or AD95 at increasing concentrations. The expression levels of Notch target gene her6 were also measured by in situ hybridization and the co-relationship between the levels of Notch inhibition by DAPT and AD95 and the severity of phenotypes were determined.The results reported here of the effects on zebrafish suggest that this newly developed method may be used to screen novel GSIs and other leads for a variety of therapeutic indications.High throughput screening in invertebrate animals has emerged as a powerful tool for drug discovery, but whole vertebrate animal-based high throughput screening has yet to be developed and refined. The zebrafish is one of the most cost-effective vertebrates that can be used for high throughput and high content screens. Phenotype-based small molecule screening in ze
Quantification of gamma-secretase modulation differentiates inhibitor compound selectivity between two substrates Notch and amyloid precursor protein
Ting Yang, Dilyara Arslanova, Yongli Gu, Corinne Augelli-Szafran, Weiming Xia
Molecular Brain , 2008, DOI: 10.1186/1756-6606-1-15
Abstract: To explore selective γ-secretase inhibitors, a combination of five methods was used to systematically determine these inhibitors' profiles on the γ-secretase cleavage of APP and Notch. When two potent γ-secretase inhibitors, compound E (cpd E) and DAPT, were used in a conventional in vitro γ-secretase activity assay, cpd E completely blocked Aβ generation from the cleavage of substrate APP C100, but only had a minor effect on Notch cleavage and NICD generation. Next, cpd E and DAPT were applied to HEK293 cells expressing a truncated Notch substrate NotchΔE. Both cpd E and DAPT were more potent in blocking Aβ generation than NICD generation. Third, a reporter construct was created that carried the NICD targeting promoter with three Su(H) binding sequences followed by the luciferase gene. We found that the inhibition of NICD generation by cpd E and DAPT was consistent with the reduced expression of luciferase gene driven by this Notch targeting promoter. Fourth, levels of "Notch-Aβ-like" (Nβ*) peptide derived from two previously reported chimeric APP with its transmembrane domain or the juxtamembrane portion replaced by the Notch sequence were quantified. Measurement of Nβ* peptides by ELISA confirmed that EC50's of cpd E were much higher for Nβ* than Aβ. Finally, the expression levels of Notch target gene her6 in cpd E or DAPT-treated zebrafish were correlated with the degree of tail curvature due to defective somitogenesis, a well characterized Notch phenotype in zebrafish.Our ELISA-based quantification of Aβ and Nβ* in combination with the test in zebrafish provides a novel approach for efficient cell-based screening and in vivo validation of APP selective γ-secretase inhibitors.Genetic and neuropathologic evidence suggests that Alzheimer's disease (AD) is caused partly by the overproduction and lack of clearance of the amyloid β peptide (Aβ) [1]. This Aβ peptide is generated by sequential cleavages of the amyloid precursor protein (APP) by β-secretase, which gener
Dissembled DJ-1 high molecular weight complex in cortex mitochondria from Parkinson's disease patients
Hikmet Nural, Ping He, Thomas Beach, Lucia Sue, Weiming Xia, Yong Shen
Molecular Neurodegeneration , 2009, DOI: 10.1186/1750-1326-4-23
Abstract: Parkinson's disease (PD), affecting 1% of the population over 65, is one of the most common neurodegenerative disorders characterized with selective loss of dopaminergic neurons in the substantia nigra [1-3]. Although molecular mechanism of disease is not fully known, studies indicate that mitochondrial dysfunction and oxidative stress could play a role in neuronal loss [4]. Three mutated genes – Parkin, DJ-1, and PINK1 – implicated in mitochondria and oxidative stress-related survival pathways are typically present in the brain with Parkinson's disease (PD) with apparent autosomal recessive inheritance. Two other genes – α -Synuclein and LRRK2 – are present in an autosomal dominant pattern and are associated with prominent intracellular protein inclusions [5,6]. A number of pathogenic mutations identified in the DJ-1 gene are linked to early onset familial Parkinson's disease (PD) [7-11]. Mechanistically, the DJ-1 protein has been reported to be sensitive to oxidative stress and it may function as an anti-oxidant protein [12-15].DJ-1 is a small protein composing 189 amino acids and it is expressed in variety of tissues including brain [16,17]. Although its precise biochemical function is not fully known, recent studies indicate that it has been involved in many diverse biological processes including protease, chaperone and antioxidant activities [13,18-20]. Crystal structure and biochemical data show that DJ-1 forms dimers (37 KD) [18,20-23]. In addition to dimer formation, DJ-1 also tends to form high molecular weight (HMW) complexes (250–700 kD) during normal condition [21,24-26] It is possible that DJ-1 and other DJ-1 interacting proteins might form these HMW complexes. Although presence of α-synuclein is controversial [21,24,27], Parkin has been associated with DJ-1 HMW complex [21] However, whether the DJ-1 HMW complex remains intact in brains with sporadic PD is not clear. Regulation of the formation and distribution of the DJ-1 HMW complexes remains largely
RNAi-mediated knock-down of Dab and Numb attenuate Aβ levels via γ-secretase mediated APP processing
Zhongcong Xie, Yuanlin Dong, Uta Maeda, Weiming Xia, Rudolph E Tanzi
Translational Neurodegeneration , 2012, DOI: 10.1186/2047-9158-1-8
Abstract: Amyloid-β-protein (Aβ), the key component of senile plaques in Alzheimer's disease (AD) neuropathology, was first isolated from meningovascular amyloid deposits in AD and Down's syndrome [1,2], and has also been reported to be the subunit of the plaque amyloid [2-4]. The current amyloid hypothesis of AD states that the imbalance between Aβ generation and Aβ clearance is the basis of AD neuropathogenesis. Aβ is generated from amyloid precursor protein (APP). Specifically, APP is first hydrolyzed by β-secretase to generate a 99-residue membrane-associated C-terminus fragment (APP-C99) [5-8]. APP-C99 is further cleaved to release a ~4-kDa peptide, Aβ, and the amyloid precursor protein intracellular domain (AICD). This cleavage is achieved by an unusual form of proteolysis in which the protein is cleaved within the transmembrane domain (at residue +40 or +42) by γ-secretase [9-11]. α-secretase cleaves the majority of APP in the middle of the Aβ region of APP. This cleavage will preclude Aβ generation, lead to the release of a large ectodomain (α-APPs), and leave behind a carboxy-terminus fragment of 83 amino acids (APP-C83) in the membrane. γ-Secretase cleaves APP-C83 to produce p3, an amino-terminally truncated form of Aβ [12,13], [see review in [14]].The cleavage of the APP cytoplasmic tail by γ-secretase generates AICD, which contains the strongly conserved YENPTY-motif. The YENPTY-sequence is a consensus motif for the binding of adaptor proteins that possess a phosphotyrosine-binding domain (PTB) present in several APP adaptor proteins, such as X11, Fe65, ShcC, Numb, Dab and JIP families [see review in [15]]. We have previously reported that RNAi knock-down of X11α, ShcC and Fe65 in H4 human neuroglioma cells lower Aβ levels [16,17].Dab (encoded by gene DAB), the PTB-containing APP adaptor protein, can bind to and interact with the YENPTY-motif of APP [18,19]. Dab has been reported to function as an adaptor molecule in signal transduction process [20,21]. Numb (enco
EFFECT OF MICROSTRUCTURE ON CORROSION RESISTANCE OF ELECTROLYTIC AISi7Mg0.3 ALLOYS
电解AlSi7Mg0.3合金组织结构对其耐蚀性能的影响

YUAN Xiangkai,XIA Weiming,
袁象恺
,夏维明

腐蚀科学与防护技术 , 2002,
Abstract: The effect of microstructure on corrosion morphology of ZL101 alloy,Electrolytic ZL101 alloy and A356 alloy in a simulated atmospheric environment with moisture is studied.The experimental results on microstructure and corrosion morphology by SEM and chemical composition analysis by WDS indicate that the excellent corrosion resistance of electrolytic Al-Si alloy is related to both the homogeneity of chemical composition and the fine microstructure of alloy.The results of XDA indicate that less amount of impurity phase in A356 is responsible for its better corrosion resistance.
Study on Abrasive Resistance of Ni-Based Coatings Containing WC Hard Phase
含碳化钨硬相镍基涂层耐磨粒磨损性能研究

Wang Hui,Xia Weiming,Jin Yuansheng,
王慧
,夏为民

摩擦学学报 , 1995,
Abstract: To improve the wear resistance of piston ring and cylinder liner,and extend the servicelife of the engine for the automobiles in desert area applications,friction and wear performanceshave been tested for three Ni-based composite coatings containing varied contents of WC particles ashard phase.Scanning electron microscope(SEM)has been used for observing the surfaces of thecomposite coatings,and wear mechanisms of the coatings have been discussed on the basis of theobservation.The results obtained from Falex test showed that the composite coatings with WC hardphase have improved abrasive wear resistance in comparison with current ring/cylinder materlals.The laser remelting processing, applied to the Ni60+60%WC sprayed coatings,was provedbeneficial to produce an uniform and dense metallographic structure,form a new complex carbidephase containing various elements such as W,Ni,Cr,Si,etc.,and lead to a further improvementin abrasive wear resistance. The excellent abrasive resistance of the composite coatings with WCparticles were found related to three major factors:enhanced bulk hardness,compact metallographicstru cture a nd strong bon d between matrix and ha rd phase,as well as a load supportin g systemconstru cted by hard phase structure.As for as the friction coefficient is concerned,no significantdifferen ces are found betwee n traditional materials and Ni-based WC compooite coatings.
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