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RNAi-mediated knock-down of Dab and Numb attenuate Ab levels via g-secretase mediated APP processing

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Translational Neurodegeneration 2012年第1期1卷 45-54页

作者： Zhongcong Xie Yuanlin Dong Uta Maeda Weiming Xia rudolph e tanzi Department of Neurology Genetics and Aging Research UnitMassGeneral Institute for Neurodegenerative DiseaseMassachusetts General Hospital and Harvard Medical SchoolCharlestownMA 02129-2060USA Department of Anesthesia and Critical Care Geriatric Anesthesia Research UnitMassachusetts General Hospital and Harvard Medical SchoolCharlestownMA 02129-2060USA Center for Neurological Diseases Harvard Institute of Medicine and Harvard Medical SchoolBostonMA 02115USA Graduate student Department of PsychologyUniversity of Southern CaliforniaLos AngelesCA 90089USA.

Amyloid-b-protein(Ab),the key component of senile plaques in Alzheimer’s disease(AD)brain,is produced from amyloid precursor protein(APP)by cleavage of b-secretase and then *** adaptor proteins with phosphotyrosine-binding(PTB)domains,including Dab(gene:DAB)and Numb(gene:NUMB),can bind to and interact with the conserved YeNPTY-motif in the APP *** we describe,for the first time,the effects of RNAi knock-down of Dab and Numb expression on APP processing and Ab *** knock-down of Dab and Numb in H4 human neuroglioma cells stably transfected to express either FL-APP(H4-FL-APP cells)or APP-C99(H4-APP-C99 cells)increased levels of APP-C-terminal fragments(APP-CTFs)and lowered Ab levels in both cell lines by inhibiting g-secretase cleavage of ***,RNAi knock-down of APP also reduced levels of Numb in H4-APP *** findings suggest that pharmacologically blocking interaction of APP with Dab and Numb may provide novel therapeutic strategies of *** notion of attenuating g-secretase cleavage of APP via the APP adaptor proteins,Dab and Numb,is particularly attractive with regard to therapeutic potential,given that side effects of gsecretase inhibition owing to impaired proteolysis of other g-secretase substrates,***,might be avoided.

关键词： APP impaired attractive

Curcumin Decreases Amyloidβ-peptide Levels by Attenuating the Maturation of Amyloid-βPrecursor Protein

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Curcumin Decreases Amyloidβ-peptide Levels by Attenuating t...

Development of a potential PeT probe for HDAC6 imaging in Alzheimer's disease

2011全国老年痴呆与衰老相关疾病学术会议第三届山东省神经内科医师（学术）论坛

作者： rudolph e.tanzi Genetics and Aging Research Unit MassGeneral Institute for Neurodegenerative Disease Department of Neurology Massachusetts General Hospital and Harvard Medical School Charlestown MA 02129-2060

Background:Alzheimer s disease(AD) is a devastating neurodegenerative disease with no *** is clinically characterized by insidious deterioration of memory and cognitive function,progressive impairment of daily living activities,and several neuropsychiatric *** genetic,biochemical and molecular biological evidence suggests that the excessive accumulation of a small peptide,Aβ,is

关键词： Alzheimer’s disease Curcumin APP Aβ Curcumin-like derivative

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Acta Pharmaceutica Sinica B 2022年第10期12卷 3891-3904页

作者： Ping Bai Prasenjit Mondal Frederick A.Bagdasarian Nisha Rani Yan Liu Ashley Gomm Darcy R.Tocci Se Hoon Choi Hsiao-Ying Wey rudolph e.tanzi Can Zhang Changning Wang Athinoula A.Martinos Center for Biomedical Imaging Department of RadiologyMassachusetts General HospitalHarvard Medical SchoolCharlestownMA 02129USA Genetics and Aging Research Unit McCance Center for Brain HealthMassGeneral Institute for Neurodegenerative DiseaseDepartment of NeurologyMassachusetts General HospitalHarvard Medical SchoolCharlestownMA 02129USA

Although the epigenetic regulatory protein histone deacetylase 6(HDAC6)has been recently implicated in the etiology of Alzheimer’s disease(AD),little is known about the role of HDAC6 in the etiopathogenesis of AD and whether HDAC6 can be a potential therapeutic target for ***,we performed positron emission tomography(PeT)imaging in combination with histopathological analysis to better understand the underlying pathomechanisms of HDAC6 in *** first developed[^(18)F]PB118 which was demonstrated as a valid HDAC6 radioligand with excellent brain penetration and high specificity to *** studies of[^(18)F]PB118 in 5xFAD mice showed significantly increased radioactivity in the brain compared to WT animals,with more pronounced changes identified in the cortex and *** translatability of this radiotracer for AD in a potential human use was supported by additional studies,including similar uptake profiles in non-human primates,an increase of HDAC6 in ADrelated human postmortem hippocampal tissues by Western blotting protein analysis,and our ex vivo histopathological analysis of HDAC6 in postmortem brain tissues of our ***,our findings show that HDAC6 may lead to AD by mechanisms that tend to affect brain regions particularly susceptible to AD through an association with amyloid pathology.

关键词： HDAC6 Alzheimer’s disease Radiotracer PeT imaging epigenetic

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超级基因

作者： (美) 迪帕克·乔普拉 (Deepak Chopra) (美) 鲁道夫·e.坦齐 (rudolph e.tanzi)

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失窃的灵魂中老年痴呆症的致病基因解码

常用吸入麻醉剂异氟烷诱导凋亡和增加淀粉样β蛋白的水平

丛书名：科学新视野v16

2004年

作者：（美）鲁道夫·谭兹（rudolph e.tanzi）（美）安妮·帕尔森（Ann B.Parson）庄雅婷范嘉榕译

本书是关于中老年痴呆症的科普读物，以科学故事为主线，讨论失智症的致病原因，描述致病基因的寻找及快速筛选自动分析的方式等。

ISBN: (数字)7810365991

ISBN: (纸本)7810365991

本书是关于中老年痴呆症的科普读物，以科学故事为主线，讨论失智症的致病原因，描述致病基因的寻找及快速筛选自动分析的方式等。

关键词：痴呆

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麻醉与监护论坛 2007年第4期14卷 273-273页

作者： Zhongcong Xie Yuanlin Dong Uta Maeda Paui Alfille Deborah J.Culley Gregory Crosby rudolph e.tanzi

背景：β淀粉样蛋白（Aβ）的过度蓄积是阿尔茨海默病的发病机制之一。异氟烷是一种常用的吸入麻醉药，曾经有异氟烷可增加嗜铬细胞瘤细胞内Aβ的寡聚化反应和细胞毒性的报道。为了探讨异氟烷在AD发病机制和术后认知障碍（POCD）中的可... 详细信息

背景：β淀粉样蛋白（Aβ）的过度蓄积是阿尔茨海默病的发病机制之一。异氟烷是一种常用的吸入麻醉药，曾经有异氟烷可增加嗜铬细胞瘤细胞内Aβ的寡聚化反应和细胞毒性的报道。为了探讨异氟烷在AD发病机制和术后认知障碍（POCD）中的可能作用，我们研究了异氟烷在临床应用浓度（2％）下是否能诱导过度表达人APP的人H4神经胶质瘤细胞凋亡、改变APP加工处理过程和增加Aβ的生成。

关键词：异氟烷淀粉样β蛋白吸入麻醉剂诱导凋亡 AD发病机制阿尔茨海默病 β淀粉样蛋白术后认知障碍

A phase inversion polymer coating to prevent swelling and spalling of clay fines in coal seam gas wells

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International Journal of Coal Science & Technology 2018年第2期5卷 179-190页

作者： Lei Ge Christopher Hamilton Rahmah Tasha Febrina Victor rudolph Thomas e. Rufford School of Chemical engineering The University of Queensland Saint Lucia QLD 4072 Australia Centre for Future Materials University of Southern Queensland Springfield Central QLD 4300 Australia

We report a phase inversion polymer coating as a novel concept with potential to prevent clay swelling and fines generation in coal seam gas, or other petroleum, wellbores. Our approach uses polyethersulfone （PeS） with N-methyl-2- pyrrolidone （NMP） as a water-soluble solvent to form a dense, low-porosity film across the clay-rich interburden layers, but a porous and permeable membrane on coal seams. This contrasting behaviour occurs because the coal contains much more free water than the clay-rich interburden layers. We demonstrate the efficacy of the method to prevent clay spalling in immersion tests and under a flow of fresh water in a visual swell test apparatus. The clay-rich rocks studied were mudstone and siltstone, and these were dip coated in the PeS/NMP solution. The uncoated mudstone swelled and broke apart quickly in the immersion test and visual flow test, but the PeS coated rock samples were stable for 30 days. The coated rock and coal samples were characterised by X-ray diffraction, Fourier transform infrared spectroscopy and scanning electron microscopy. The morphology of coated mudstone and coated coal samples showed that the polymer formed a dense layer across the low-permeability mudstone, but an open porous structure on the coal surface. The effect of the coating on the permeability of KCl brine through coal was measured in a core-flood apparatus. Although the permeability of the coal showed some deterioration after coating, from （0.58 ± 0.12） mD to （0.3 ±0.03） mD, these results demonstrate the potential of a smart polymer coating to prevent clay swelling while remaining permeable to gas and water on coal layers.

关键词： Coal bed methane Formation damage Smectite Wellbore stability

evaluation of host resistance and fungicide application as tools for the management of root rot of field pea caused by Aphanomyces euteiches

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The Crop Journal 2019年第1期7卷 38-48页

作者： Longfei Wu Kan-Fa Chang Sheau-Fang Hwang Robert Conner rudolph Fredua-Agyeman David Feindel Stephen e.Strelkov Department of Agricultural Food and Nutritional Science University of Alberta Crop Diversification Centre North Alberta Agriculture and Forestry Agriculture and Agri-Food Canada Morden Research and Development Centre

Aphanomyces root rot(ARR) of field pea(Pisum sativum), caused by Aphanomyces euteiches, can cause severe root damage, wilting, and large yield losses under wet soil conditions. To identify ways to manage this disease, the effect of A. euteiches inoculum density on field pea was studied under greenhouse and field conditions in 2015 and 2016. Increases in inoculum density reduced seedling emergence, root nodulation, and plant vigor, and resulted in increased root rot severity in both field and greenhouse tests. Seed treatments with the fungicides Apron Advance(thiabendazole + fludioxonil + metalaxyl) + Vibrance(difenoconazole + metalaxylM + sedaxane), INTeGO Solo(ethaboxam), BAS 516F(boscalid + pyraclostrobin), BAS 720F(metalaxyl + pyraclostrobin + fluxapyroxad), and BAS 516F + BAS 720F(3:1) were evaluated for their efficacy against ARR. All seed treatments except Apron Advance + Vibrance reduced root rot severity under controlled conditions. BAS 516F, BAS 720F and INTeGO Solo improved plant vigor and all treatments reduced seedling blight to varying degrees under greenhouse conditions, but not in the field. A collection of 22 pea genotypes was evaluated for resistance to root rot in field plot experiments. Line 00–2067 showed the least severe root rot symptoms,whereas ‘Spring D' showed the lowest reduction in yield. The results suggest that there may be an opportunity to combine partial host resistance and fungicidal seed treatments to adequately manage ARR of field pea.

关键词： Aphanomyces euteiches Field pea Fungicides Inoculum density Resistance

enhancing perianal disease management with integrated physical and psychological approaches

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World Journal of Clinical Cases 2025年第2期13卷 59-63页

作者： Uchenna e Okpete Haewon Byeon Department of Digital Anti-aging Healthcare(BK21) Inje UniversityGimhae 50834South Korea

This article provides a comprehensive analysis of the study by Hou et al,focusing on the complex interplay between psychological and physical factors in the postoperative recovery(POR)of patients with perianal *** study sheds light on how illness perception,anxiety,and depression significantly influence recovery *** et al developed a predictive model that demonstrated high accuracy in identifying patients at risk of poor *** article explores the critical role of pre-operative psychological assessment,highlighting the need for mental health support and personalized recovery plans in enhancing POR quality.A multidisciplinary approach,integrating mental health professionals with surgeons,anesthesiologists,and other specialists,is emphasized to ensure comprehensive care for *** study’s findings serve as a call to integrate psychological care into surgical practice to optimize outcomes for patients with perianal diseases.

关键词： Perianal disease Post-operative recovery Anxiety Depression Pain management emotional well-being Multidisciplinary approach