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O-GlcNAcylation negatively regulates phosphorylation of tau:A novel mechanism involved in Alzheimer's disease

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O-GlcNAcylation negatively regulates phosphorylation of tau:...

蛋白磷酸酶抑制剂对离体海马组织tau蛋白磷酸化的影响

2008年全国糖生物学学术会议

作者：刘飞 inge grundke-iqbal Khalid iqbal Jiangsu Key Laboratory of Neuroregeneration Nantong University epartment of Neurochemistry New York State Institute for Basic Research in Developmental Disabilities1050 Forest Hill RoadStaten IslandNew York 10314U.S.A. Department of Neurochemistry New York State Institute for Basic Research in Developmental Disabilities1050 Forest Hill RoadStaten IslandNew York 10314U.S.A.

Microtubule-associated protein tau is abnormally hyperphosphorylated and aggregated into neurofibrillary tangles in brains of individuals with Alzheimer’s disease(AD)and other tauopathies. Tau pathology is critical t...

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中华老年医学杂志 2005年第6期24卷 462-463页

作者：李良 Amittabha Sengupta inge grundke-iqbal Khalid iqbal 首都医科大学病理解剖学教研室北京市100054 美国纽约发育障碍基础研究所

老年变性型痴呆(AD)患者神经元内出现神经原纤维缠结(NFT)、老年斑(SP)的形成及神经元的丢失为其主要病理学改变.NFT的核心是过度磷酸化的tau蛋白.我们于2001年11月至2003年8月年采用离体培养海马片,经用磷酸酶抑制剂冈田酸(okadaic ac... 详细信息

老年变性型痴呆(AD)患者神经元内出现神经原纤维缠结(NFT)、老年斑(SP)的形成及神经元的丢失为其主要病理学改变.NFT的核心是过度磷酸化的tau蛋白.我们于2001年11月至2003年8月年采用离体培养海马片,经用磷酸酶抑制剂冈田酸(okadaic acid)处理后,观察tau蛋白磷酸化的改变及其相关酶的变化,以期寻找一种适于研究的体外AD模型。

关键词： tau蛋白磷酸化蛋白磷酸酶抑制剂海马组织神经原纤维缠结 2003年8月变性型痴呆病理学改变过度磷酸化 2001年离体培养 AD模型神经元老年斑 NFT 海马片冈田酸相关酶

τ蛋白磷酸化位点与其促微管组装及与微管结合活性的体外分析

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中国医学科学院学报 2000年第2期22卷 120-123页

作者：王建枝魏泽兰王群 inge grundke-iqbal Khalidiqbal 同济医科大学病理生理教研室武汉430030

目的　探讨 Alzheimer病 (AD) τ蛋白异常磷酸化位点与其促微管组装及与微管结合活性抑制的关系。方法　采用超速离心和离子交换柱层析法分离制备重组 τ蛋白及 τ蛋白的体外磷酸化 ,以 Fe Cl3亲和柱分离纯化 32 Pτ肽 ,手工 Edman降解... 详细信息

目的　探讨 Alzheimer病 (AD) τ蛋白异常磷酸化位点与其促微管组装及与微管结合活性抑制的关系。方法　采用超速离心和离子交换柱层析法分离制备重组 τ蛋白及 τ蛋白的体外磷酸化 ,以 Fe Cl3亲和柱分离纯化 32 Pτ肽 ,手工 Edman降解和氨基酸自动分析仪鉴定 32 Pτ肽磷酸氨基酸位点。结果　 (1)酪蛋白激酶 - 1(CK- 1)、c AMP依赖性蛋白激酶 (PKA )和糖元合成酶激酶 - 3(GSK- 3)的磷酸化作用可不同程度地抑制τ蛋白的功能 ,CK - 1或 PKA的预处理可明显增强 GSK - 3对τ促微管组装活性的抑制 ,其中 PKA加 GSK- 3的抑制作用最强。 (2 )单纯GSK- 3磷酸化τ蛋白的位点为 :苏氨酸 (Thr) - 181,丝氨酸 (Ser) - 184,Ser- 2 6 2 ,Ser- 35 6和 Ser- 40 0 ,而 GSK- 3对PKA预处理τ蛋白的磷酸化位点为 :Ser- 195 ,Ser- 198,Ser- 199,Ser- 2 0 2 ,Ser- 2 35 ,Ser- 2 6 2 ,Ser- 35 6 ,Ser- 40 4,Thr-2 0 5和 Thr- 2 31。其中 Ser- 198,Ser- 199,Ser- 2 0 2 ,Thr- 2 0 5 ,Thr- 2 31,Ser- 2 35 ,Ser- 2 6 2 ,Ser- 40 0和 Ser- 40 4为 AD患者τ蛋白异常磷酸化位点。此外 ,Ser- 2 6 2磷酸化仅轻度抑制τ蛋白活性 ,而 Ser- 198,Ser- 199,Ser- 2 0 2 ,Thr- 2 31,Ser- 2 35 ,Ser- 40 0和 Ser- 40

关键词： τ蛋白磷酸化蛋白激酶早老性痴呆微管结合

Expression and phosphorylation of neurofilament protein in different neuronal tissues

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中国病理生理杂志 2001年第8期 91-91页

作者： WANG Yi-pen WANG Jian-zhi WEI Ze-lan XIA Ruo-han WANG Qun inge grundke-iqbal Khalid iqbal Department of Pathophysiology Tongji Medical University Wuhan 430030 China Department of Chemical Neuropathology NYS Institute for Basic Research Staten Island New York NY 10314 USA

The neurofilament proteins (NFPs) from different neuronal tissues including Alzheimer and Huntington disease gray matter, rat brain gray, white matter and spinal cord were separated biochemically into two major fractions. A systematic investigation on the distribution, expression and phosphorylation of NFPs in those fractions was undertaken in the present study. It was found that only non-phosphorylated NF-H and NF-M, but not NF-L subunit were detected in Alzheimer brain gray matter high speed supernatant, whereas all neurofilament subunits including non-phosphorylated and phosphorylated were measured in high speed pellet fraction of the same tissue. The hyperphosphorylation of NF-H and NF-M in Alzheimer brain was shown by phosphorylation dependent monoclonal antibodies SMI31 and SMI34. This hyperphosphorylation was confirmed by non-phosphorylation dependent antibody SMI32 with dephosphosphorylation of the samples. Furthermore, an increased amount of NF-H, NH-M and NF-L, detected by SMI33 and NR4 respectively, was also observed in Alzheimer samples, in which the elevation in NF-L was significant. A significantly different immunoblot patterns in distribution, expression and phosphorylation were determined in various position of the neural system and alternative fractions. To our best knowledge, this is the first data shown definite abnormality of NFPs in Alzheimer disease. The information obtained in the present study will be extremely valuable in further study of the proteins both in physiological and pathological conditions.

关键词： Expression and phosphorylation of neurofilament protein in different neuronal tissues

蛋白磷酸酯酶在Alzheimer氏病tau蛋白异常磷酸化中的作用

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基础医学与临床 1999年第4期19卷 74-78页

作者：王建枝 Iqba.,IG 同济医科大学病理生理教研室武汉武汉430030 美国纽约州立基础研究所化学病理实验室

用蛋白磷酸酯酸PP-2A、-2B和-1型分别处理的Alzheimer病（AD）异常磷酸化tau蛋白可不同程度恢复其促微管聚集和组装功能。PP－2A的恢复作用比PP－2B和PP－1更强．PP－2A，PP－2B和PP－1使异常tau蛋白水解释放磷酸的量分别为其总量的57％... 详细信息

用蛋白磷酸酯酸PP-2A、-2B和-1型分别处理的Alzheimer病（AD）异常磷酸化tau蛋白可不同程度恢复其促微管聚集和组装功能。PP－2A的恢复作用比PP－2B和PP－1更强．PP－2A，PP－2B和PP－1使异常tau蛋白水解释放磷酸的量分别为其总量的57％，36％和30％。tau蛋白Ser－235位的磷酸化不是决定其功能的关键位点，而Thr－231的磷酸化可能与微管组装早期的成核聚集作用有关。该研究证明：体内蛋白磷酸酯酶PP－2A，PP－2B和PP－1可能参与tau蛋白异常磷酸化过程，保持这些磷酸酯酶的活性有可能抑制AD神经原纤维退化．

关键词：蛋白磷酸酯酶去磷酸化作用 tau蛋白早老性痴呆

A chromosome-level genome of electric catfish(Malapterurus electricus)provided new insights into order Siluriformes evolution

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Marine Life Science & Technology 2024年第1期6卷 1-14页

作者： Meiru Liu Yue Song Suyu Zhang Lili Yu Zengbao Yuan Hengjia Yang Mengqi Zhang Zhuocheng Zhou inge Seim Shanshan Liu Guangyi Fan Huanming Yang College of Life Sciences University of Chinese Academy of SciencesBeijing 100049China BGI-Qingdao BGI-ShenzhenQingdao 266555China BGI-Shenzhen Shenzhen 518083China Professional Committee of Native Aquatic Organisms and Water Ecosystem of China Fisheries Association Beijing 100125China Integrative Biology Laboratory College of Life SciencesNanjing Normal UniversityNanjing 210023China State Key Laboratory of Agricultural Genomics BGI-ShenzhenShenzhen 518083China

The electric catfish(Malapterurus electricus),belonging to the family Malapteruridae,order Siluriformes(Actinopterygii:Ostariophysi),is one of the six branches that has independently evolved electrical *** assembled a 796.75 Mb *** genome and anchored 88.72%sequences into 28 *** family analysis revealed 295 expanded gene families that were enriched on functions related to glutamate *** evolutionary analyses of electric organs among different lineage of electric fishes further revealed that the coding gene of rho guanine nucleotide exchange factor 4-like(arhgef4),which is associated with G-protein coupled receptor(GPCR)signaling pathway,underwent adaptive parallel *** identification suggests visual degradation in catfishes,and an important role for taste in environmental *** findings fill in the genomic data for a branch of electric fish and provide a relevant genetic basis for the adaptive evolution of Siluriformes.

关键词： Electric fish Karyotype analysis Convergent evolution Environmental adaptation Historical effective population size

Protective and Regenerative Efficacy of a Plant Oil-Based Day and Night Cream: Investigated by a Novel Approach to Reveal the Impact of Blue Light Irradiation on Epidermal Barrier Integrity and Lipid Matrix

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Journal of Cosmetics, Dermatological Sciences and Applications 2024年第3期14卷 227-241页

作者： Dorothee Dähnhardt Stephan Dähnhardt-Pfeiffer Isabel Simon Dana Ditgen inge Holland Dörte Segger Peter Staib Microscopy Services Dhnhardt GmbH Flintbek Germany Research & Development and Regulatory Affairs Kneipp GmbH Wuerzburg Germany SGS INSTITUT FRESENIUS GmbH Hamburg Germany

In recent years, the harmful effects of blue light (400 - 500 nm) as a component of visible light (400 - 700 nm) have increasingly gained attention of science, industry, and consumers. To date, only a few in vivo test methods for measuring the effects of blue light on the skin have been described. A direct measurement method that can detect the immediate effects of blue light on the epidermal permeability barrier (EPB) is still lacking. In this study, we present a new methodological approach that can be used to investigate both the protective and regenerative effects of cosmetic products on the EPB after blue light irradiation. In a study with 14 female volunteers, it was investigated whether the regular application of an O/W emulsion (day cream) can strengthen and protect the epidermal barrier against damaging blue light radiation of 60 J/cm2 (protective study design) and also whether a disruption of the epidermal barrier caused by blue light radiation is restored faster and better by the regular application of another O/W emulsion (night cream) than in product-untreated skin (regenerative study design). The two O/W emulsions are different in plant oil, active ingredient composition and texture. The seven-day treatment with the day cream initially led to a significant increase in the normalized lipid lamellae length in the intercellular space, whereas the irradiation with blue light after 24 hours led to a significant decrease in the lipid lamellae length in the untreated test area, but not in the area previously treated with the product. Regarding the regenerative study design, a two-day treatment with the night cream was able to restore a blue-light-induced decrease in lipid lamellae length in the intercellular space. In summary, with the study designs presented here, the protective and regenerative effect of two cosmetic products could be demonstrated for the first time on the integrity of the EPB after blue light irradiation and the data showed that the Lipbarv

关键词： Skin Care Blue Light Irradiation Skin Barrier Intercellular Lipid Lamellae Electron Microscopy

Circulating microRNA expression and nonalcoholic fatty liver disease in adolescents with severe obesity

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World Journal of Gastroenterology 2024年第4期30卷 332-345页

作者： Yi-Jie Li Brittney O Baumert Nikos Stratakis Jesse A Goodrich Hao-Tian Wu Jing-Xuan He Yin-Qi Zhao Max T Aung Hong-Xu Wang Sandrah P Eckel Douglas I Walker Damaskini Valvi Michele A La Merrill Justin R Ryder Thomas H inge Todd Jenkins Stephanie Sisley Rohit Kohli Stavra A Xanthakos Andrea A Baccarelli Rob McConnell David V Conti Lida Chatzi Department of Population and Public Health Sciences Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90032United States Barcelona Institute of Global Health Barcelona Institute of Global HealthBarcelona 08036Spain Department of Environmental Health Sciences Mailman School of Public HealthColumbia UniversityNew YorkNY 10032United States Gangarosa Department of Environmental Health Rollins School of Public HealthEmory UniversityAtlantaGA 30329United States Department of Environmental Medicine and Public Health Icahn School of Medicine at Mount SinaiNew YorkNY 10029United States Department of Environmental Toxicology University of CaliforniaDavisCA 95616United States Department of Surgery Lurie Children’s Hospital of ChicagoChicagoIL 60611United States Northwestern University Feinberg School of Medicine Northwestern UniversityChicagoIL 60611United States Division of Biostatistics and Epidemiology Cincinnati Children's Hospital Medical CenterCincinnatiOH 45229United States Department of Pediatrics University of Cincinnati College of MedicineCincinnatiOH 45229United States Department of Pediatrics Children’s Nutrition Research Center USDA/ARSBaylor College of MedicineHoustonTX 77030United States Department of Gastroenterology Children’s Hospital Los AngelesLos AngelesCA 90027United States Division of Gastroenterology Hepatology and NutritionCincinnati Children's Hospital Medical CenterCincinnatiOH 45229United States

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases in children and *** ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis(NASH),wherein hepatocellular inflammation and/or fibrosis coexist with *** microRNA(miRNA)levels have been suggested to be altered in NAFLD,but the extent to which miRNA are related to NAFLD features remains *** analysis tested the hypothesis that plasma miRNAs are significantly associated with histological features of NAFLD in *** To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with *** This study included 81 adolescents diagnosed with NAFLD and 54 adolescents without NAFLD from the Teen-Longitudinal Assessment of Bariatric Surgery ***-operative core liver biopsies were collected from participants and used to characterize histological features of *** samples were collected during surgery for miRNA profiling.A total of 843 plasma miRNAs were profiled using the HTG EdgeSeq *** examined associations of plasma miRNAs and NAFLD features using logistic regression after adjusting for age,sex,race,and other key *** Pathways Analysis was used to identify biological functions of miRNAs that were associated with multiple histological features of *** We identified 16 upregulated plasma miRNAs,including miR-193a-5p and miR-193b-5p,and 22 downregulated plasma miRNAs,including miR-1282 and miR-6734-5p,in adolescents with ***,52,16,15,and 9 plasma miRNAs were associated with NASH,fibrosis,ballooning degeneration,and lobular inflammation,***,16 miRNAs were associated with two or more histological features of *** those miRNAs,miR-411-5p was downregulated in NASH,ballooning,and fibrosis,while miR-122-5p,miR-1343-5p,miR-193a-5p,miR-193b-5p,and miR-7845-5p were consistently and posi

关键词： MicroRNA Nonalcoholic fatty liver disease Non-alcoholic steatohepatitis Liver fibrosis Lobular inflammation Ballooning degeneration

Crushed rocks stabilized with organosilane and lignosulfonate in pavement unbound layers:Repeated load triaxial tests

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Frontiers of Structural and Civil Engineering 2021年第2期15卷 412-424页

作者： Diego Maria BARBIERI inge HOFF Chun-Hsing HO Department of Civil and Environmental Engineering Norwegian University of Science and TechnologyTrondheimTrøndelag7491Norway Department of Civil and Environmental Engineering Northern Arizona UniversityFlagstaffAZ86011USA

The creation of the new“Ferry-Free Coastal Highway Route E39”in southwest Norway entails the production of a remarkable quantity of crushed *** resources could be beneficially employed as aggregates in the unbound courses of the highway itself or other road pavements present *** innovative stabilizing agents,organosilane and lignosulfonate,can significantly enhance the key properties,namely,resilient modulus and resistance against permanent deformation,of the aggregates that are excessively weak in their natural *** beneficial effect offered by the additives was thoroughly evaluated by performing repeated load triaxial *** study adopted the most common numerical models to describe these two key mechanical *** increase in the resilient modulus and reduction in the accumulated vertical permanent deformation show the beneficial impact of the ***,a finite element model was created to simulate the repeated load triaxial test by implementing nonlinear elastic and plastic constitutive relationships.

关键词： organosilane lignosulfonate crushed rocks pavement unbound layers repeated load triaxial test finite element analysis