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Posttranslational modifications of α-tubulin in alzheimer disease

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Translational Neurodegeneration 2015年第1期4卷 59-67页

作者： Fan Zhang Bo Su chunyu Wang sandra L.Siedlak Siddhartha mondragon-Rodriguez Hyoung-gon Lee Xinglong Wang George Perry Xiongwei Zhu Department of Pathology Case Western Reserve UniversityClevelandOH 44121USA Department of Neurosurgery Shandong Provincial HospitalShandong UniversityJinan 250012China Department of Neurobiology Shandong UniversityJinan 250012China Department of Neurology the Second Xiangya HospitalCentral South UniversityChangshaHunan 410011China Departamento de Neurobiología del Desarrollo y Neurofisiología Instituto de NeurobiologíaUniversidad Nacional Autónoma de México QuerétaroQuerétaro MéxicoD.F.Mexico The University of Texas at San Antonio One UTSA CircleSan AntonioTX 78249USA 2103 cornell Road ClevelandOH 44106USA

Background:In Alzheimer disease(AD),hyperphosphorylation of tau proteins results in microtubule destabilization and cytoskeletal *** prior ultra-morphometric studies documented a clear reduction in microtubules in pyramidal neurons in AD compared to controls,however,this reduction did not coincide with the presence of paired helical *** latter suggests the presence of compensatory mechanism(s)that stabilize microtubule dynamics despite the loss of tau binding and *** are composed of tubulin dimers which are subject to posttranslational modifications that affect the stability and function of ***:In this study,we performed a detailed analysis on changes in the posttranslational modifications in tubulin in postmortem human brain tissues from AD patients and age-matched controls by immunoblot and ***:consistent with our previous study,we found decreased levels ofα-tubulin in AD *** of tubulin with various posttranslational modifications such as polyglutamylation,tyrosination,and detyrosination were also proportionally reduced in AD brain,but,interestingly,there was an increase in the proportion of the acetylatedα-tubulin in the remainingα-*** distribution was changed from predominantly in the processes to be more accumulated in the cell *** number of processes containing polyglutamylated tubulin was well preserved in AD *** there was a cell autonomous detrimental effect of NFTs on tubulin,this is likely a gradual and slow process,and there was no selective loss of acetylated or polyglutamylated tubulin in NFT-bearing ***:Overall,we suggest that the specific changes in tubulin modification in AD brain likely represent a compensatory response.

关键词： Acetylation Alzheimer disease Polyglutamylation Tau Tubulin

The Role of Eumelanin in Generating Reactive Oxygen and Reactive Nitrogen in Solution: Possible Relevance to Keloid Formation

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Open Journal of Physical chemistry 2013年第4期3卷 157-162页

作者： Julian m. menter comnuan Nokkaew Danita Eatman Aquilla Sprewell Natalia Silvestrov Abrienne m. Patta sandra Harris-Hooker Analytical Laboratory Department of Pharmacology and Toxicology Morehouse School of Medicine Atlanta USA Department of microbiology Biochemistry and Immunology Morehouse School of Medicine Atlanta USA Office of Sponsored Research Department of Pathology Morehouse School of Medicine Atlanta USA

Recently, nitric oxide (NO) has been implicated as an epigenetic factor in keloids, a scarring disease occurring primarily in dark skinned people who have relatively high amounts of pigment melanin. In this work, we tested whether a melanin-mediated redox reaction involving adsorbed NO and O2 can couple NO oxidation with O2 reduction to form reactive oxygen species (ROS) or reactive nitrogen species (RNS) in vitro at pH 7.4. We measured the formation of reactive species that oxidize dihydrorhodamine123 (DHR) to fluorescent rhodamine123 in the presence and absence of sepia melanin. In separate experiments, we monitored NO concentration with 4,5-diaminofluorescein (DAF) by measuring the highly fluorescent NO-adduct, DAF-2T. We attempted to detect peroxynitrite with 5 μm 3-methyl-1,2-cyclopentanedione (mcP), a selective scavenger of peroxynitrite (Ic50 = 3.6 μm for ONOO- vs. 63.8 μm and >> 100 μm for NO and O2- respectively). However, mcP itself oxidized DHR. We found that in the absence of NO, melanin itself oxidizes DHR, with no loss of DAF-fluorescence (i.e. no net consumption of NO). In the presence of NO, there was a ~ 57% loss of DAF fluorescence, indicating that NOx is formed at the expense of NO. The data provided good fit (r2 = 0.94) to a Langmuir adsorption isotherm, with pseudo first order rate k' = 8.2 × 107) s-1 and adsorption coefficient Kad = 4.04 m-1. Both of these parameters are consistent with a facile chemisorption reaction between NO and O2 on the melanin surface. Possible reactions are a) NO and O2- → ONOO- and/or b) 2NO + O2 → 2NO2. The latter reaction is disfavored in solution but is significantly accelerated on the melanin surface via an entropy effect.

关键词： melanin Nitric Oxide NOx Redox

Imaging biomarkers in Parkinson’s disease and Parkinsonian syndromes:current and emerging concepts

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Translational Neurodegeneration 2017年第1期6卷 67-91页

作者： Usman Saeed Jordana compagnone Richard I.Aviv Antonio P.Strafella sandra E.Black Anthony E.Lang mario masellis Institute of medical Science Faculty of MedicineUniversity of TorontoTorontoCanada Lc campbell cognitive Neurology Research Unit Sunnybrook Research InstituteTorontoCanada Department of medical Imaging University of Toronto and Division of NeuroradiologySunnybrook Health Sciences CentreTorontoCanada Research Imaging centre Centre for Addiction and Mental HealthTorontoCanada Division of Brain Imaging&Behaviour-Systems NeuroscienceToronto Western HospitalTorontoCanada Division of Neurology Department of MedicineUniversity of TorontoTorontoCanada Heart&Stroke Foundation canadian Partnership for Stroke Recovery Sunnybrook Health Sciences CentreTorontoCanada movement Disorders centre Toronto Western HospitalTorontoCanada Edmond J.Safra Program in Parkinson’s Disease University Health NetworkTorontoCanada cognitive&movement Disorders clinic Sunnybrook Health Sciences Centre2075 Bayview Ave.Room A4-55TorontoOntario M4N 3 M5Canada

Two centuries ago in 1817,James Parkinson provided the first medical description of Parkinson’s disease,later refined by Jean-martin charcot in the mid-to-late 19th century to include the atypical parkinsonian variants(also termed,Parkinson-plus syndromes).Today,Parkinson’s disease represents the second most common neurodegenerative disorder with an estimated global prevalence of over 10 ***,atypical parkinsonian syndromes encompass a group of relatively heterogeneous disorders that may share some clinical features with Parkinson’s disease,but are uncommon distinct clinicopathological *** of scientific advancements have vastly improved our understanding of these disorders,including improvements in in vivo imaging for biomarker *** imaging for the visualization of structural and functional brain changes is especially important,as it allows a‘window’into the underlying pathophysiological *** this article,we first present an overview of the cardinal clinical and neuropathological features of,1)synucleinopathies:Parkinson’s disease and other Lewy body spectrum disorders,as well as multiple system atrophy,and 2)tauopathies:progressive supranuclear palsy,and corticobasal degeneration.A comprehensive presentation of wellestablished and emerging imaging biomarkers for each disorder are then *** for the following imaging modalities are reviewed:1)structural magnetic resonance imaging(mRI)using T1,T2,and susceptibilityweighted sequences for volumetric and voxel-based morphometric analyses,as well as mRI derived visual signatures,2)diffusion tensor mRI for the assessment of white matter tract injury and microstructural integrity,3)proton magnetic resonance spectroscopy for quantifying proton-containing brain metabolites,4)single photon emission computed tomography for the evaluation of nigrostriatal integrity(as assessed by presynaptic dopamine transporters and postsynaptic dopamine D2 receptors),a

关键词： Biomarkers Parkinson’s disease Atypical parkinsonian syndrome mRI PET SPEcT Diffusion tensor imaging molecular imaging myocardial scintigraphy Transcranial sonography

Bioactive compounds and Insecticidal Activity of Hysterionica pinifolia, a Native South American Plant

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American Journal of Plant Sciences 2022年第6期13卷 815-832页

作者： Ingrid m. cufre Lucas E. Fabián sandra V. clemente Arnaldo L. Bandoni Adriana m. Broussalis Facultad de Farmacia y Bioquímica Catedra de Farmacognosia Universidad de Buenos Aires Buenos Aires Argentina cONIcET Instituto de la Química y Metabolismo del Fármaco (IQUIMEFA) Buenos Aires Argentina Facultad de Farmacia y Bioquímica Catedra de Química Medicinal Universidad de Buenos Aires Buenos Aires Argentina Facultad de Agronomía área de Producción Vegetal Orgánica Universidad de Buenos Aires Buenos Aires Argentina

Phytochemical investigation of the purified fractions of the active dichloromethane extract of Hysterionica pinifolia (Poir.) Baker led to the identification of five compounds. New acetylenic alcohol (E)-undec-3-en-5,7-diyne-1-ol (1) and three other compounds (3), (4), and (5) were reported for the first time in this species. Furthermore, forty-six components from the volatile fraction of H. pinifolia were identified. These compounds were elucidated using 1D and 2D NmR spectroscopy as well as mS-ESI and Gc-FID-mS experiments. The dichloromethane extract, its fractions, and the methanolic extract were tested for insecticidal activity against Tribolium castaneum under laboratory conditions. The dichloromethane extract and the fraction F2 were found to be active, showing high larval mortality. The dichloromethane extract was also active against T. castaneum adults. The results have shown that H. pinifolia could be considered, in a near future, as a potential source for the development of a botanical insecticide for pest control.

关键词： Hysterionica pinifolia Bioactive compounds Polyacetylene compounds (E)-undec-3-en-5 7-diyne-1-ol Insecticidal Activity

Hyperhomocysteinemia and hypercoagulability in primary biliary cirrhosis

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World Journal of Gastroenterology 2006年第10期12卷 1607-1612页

作者： maria Rosa Biagini Alessandro Tozzi Rossella marcucci Rita Paniccia sandra Fedi Stefano milani Andrea Galli Elisabetta ceni marco capanni Raffaele manta Rosanna Abbate calogero Surrenti Department of clinical Pathophysiology Gastroenterology Unit University of FlorenceAOU CareggiFlorenceItaly Thrombosis center Department of critical Area University of FlorenceAOU CareggiFlorenceItaly

AIm： To assess the hypercoagulability in PBc and its relationship with homocysteine （HcY） and various components of the haemostatic system. mETHODS： We investigated 51 PBc patients （43F/8m; mean age： 63±13.9 yr） and 102 healthy subjects （86 women/16 men, 63±13 yr）, and evaluated the haemostatic process in whole blood by the Sonoclot analysis and the platelet function by PFA-100 device. We then measured HcY （fasting and after methionine loading）, tissue factor （TF）, thrombin-antithrombin complexes （TAT）, D-dimer （D-D）, thrombomodulin （TH）, folic acid, vitamin B6 and B12 plasma levels. c677T 5,10-methylenetetrahydrofolate reductase （HTHFR） polymorphism was analyzed. RESULTS： Sonoclot RATE values of patients were significantly （P〈 0.001） higher than those of controls. Sonoclot time to peak values and PFA-100 closure times were comparable in patients and controls. TAT, TF and HcY levels, both in the fasting and post-methionine loading, were significantly （P〈0.001） higher in patients than in controls. Vitamin deficiencies were detected in 45/51 patients （88.2%）. The prevalence of the homozygous TT677 mTHFR genotype was significantly higher in patients （31.4%） than in controls （17.5%）（P〈 0.05）. Sonodot RATE values correlated significantly with HcY levels and TF.cONcLUSION： In PBc, hyper-HcY is related to hypovitaminosis and genetic predisposing factors. Increased TF and HcY levels and signs of endothelial activation areassociated with hypercoagulability and may have an important role in blood clotting activation.

关键词： Homocysteinemia Hypercoagulability Primary biliary cirrhosis Tissue factor Folic acid

Physicochemical, Nutritional, Organoleptic characteristics and Food Applications of Four mango (<i>mangifera indica</i>) Varieties

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Food and Nutrition Sciences 2015年第2期6卷 242-253页

作者： Emy Njoh Ellong sandra Adenet Katia Rochefort P&ocircle Agroalimentaire Régional de martinique (P. A. R. m.) Lamentin Martinique (F.W.I.) France

Physicochemical characteristics of four varieties of mango (Julie, Bassignac, Green and moussache) from martinique (F.W.I.) were examined at three ripening stages. All ripening protocols studied showed an evolution in parameters between the harvesting and the expandable stage. Fruit and pulp firmness, starch and vitamin c contents decreased whereas pulp pH and carotenoids content increased. Only fruit size and polyphenols content were the same during the ripening. Bassignac and Julie varieties were richer in vitamin c, polyphenols and carotenoids. moussache variety was the most energetic with important carbohydrates content. The Green variety differed significantly with a light-coloured pulp, low fruity odour and mango flavour, and a specific slightly sweet, very sour, bitter and astringent taste. moussache and Bassignac varieties had a very sweet taste unlike the Julie variety with a specific slightly sweeter taste. Different processing methods were tested for each variety. mangoes technological ability processing had been validated.

关键词： mango Ripening Stage Physicochemical characteristics Nutritional composition Fruit Processing

应用SSR和SRAP标记分析番木瓜种质资源遗传多样性及其亲缘关系

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应用SSR和SRAP标记分析番木瓜种质资源遗传多样性及其亲缘关系

作者： Onyedinma sandra Adaolisa 福建农林大学

学位级别：硕士

木瓜(carica papaya L.)也称番木瓜,是世界上主要的热带水果作物之一,在世界各地大部分地区广泛种植和消费。据研究,番木瓜产量高且具有营养学和药用功效,因此成为世界范围内具有重用应用前景的水果。过去几年,全球木瓜产量大幅增加,已... 详细信息

木瓜(carica papaya L.)也称番木瓜,是世界上主要的热带水果作物之一,在世界各地大部分地区广泛种植和消费。据研究,番木瓜产量高且具有营养学和药用功效,因此成为世界范围内具有重用应用前景的水果。过去几年,全球木瓜产量大幅增加,已经成为发展中国家重要的出口创汇农产品,已成为亚洲和拉丁美洲成千上万人的经济支柱,因此选育高产优质的木瓜品种具有重要意义。过去,由于木瓜在生长发育的幼苗期难以分辨出雌雄株,加上木瓜病害及品种间遗传多样性狭窄等因素的影响,严重阻碍了木瓜的育种进程。近年来,随着新的研究技术不断进步和发展,这些问题逐步得到了成功的解决。然而,对木瓜的遗传多样性研究的报道却很少。分子标记技术在木瓜上日益广泛的应用为木瓜育种和生产的长足进展铺平了道路。目前,简单重复序列(SSRs)标记由于具有多态性信息含量高和操作简便等优点,已成为木瓜遗传多样性研究上应用最多的分子标记方法。另一方面,序列相关扩增扩增多态性标记(SRAP)是一种在木瓜研究上未得到广泛应用的新型分子标记技术。对于中国和尼日利亚木瓜遗传来说,研究主要集中在抗性品种的选育、性别相关标记的鉴定和形态多样性等方面,而关于中国和尼日利亚木瓜品种的遗传多样性则缺乏相关信息。本研究的目的弥补这一空白,增加木瓜研究可用的遗传资源及方法。对收集于中国和尼日利亚这两个不同地理区域木瓜品种的遗传关系进行了研究,并与已有的形态学数据进行了比较。首先利用54个分子标记(SSR和SRAP)分析了在野外收集到的60份(其中40份来自中国,16份来自尼日利亚)木瓜种质资源的遗传多样性及亲缘关系,利用木瓜鲜叶提取DNA后,根据不同分子标记的方法对其进行了扩增。利用SDS-PAGE电泳技术对扩增产物进行检测分析,通过NTSYSpc(2.10e版)软件确定了多态性信息含量值,并计算了遗传多样性,将木瓜种质资源分为三组,分别是中国组、尼日利亚组和中国-尼日利亚组。SSR标记共扩增到34个,29个和31个等位基因,平均每个位点等位基因数分别是3.78,3.22和3.44,平均多态信息量分别为0.76,0.73和0.61,尼日利亚和中国的木瓜种质资源等位基因数在每个分组中的变化范围是1-6个。其中标记SSR02和SSR21具有最高的多态性信息含量值,因此这两个标记最适合用于分析中国和尼日利亚木瓜种质资源遗传多样性,而SSR49获得的多态性信息含量值最低。SRAP分子标记分别检测到88个,25个和67个等位基因,平均每个位点的等位基因数分别是1.96,1.47和1.76。每个分组的多态性信息量分别是0.49,0.37和0.47。m9E1和m2E16两个标记扩增到的多态性信息含量最多,表明这两个引物组合是可用于同类分析的高多态性信息量引物。利用SSR-SRAP结合方法同时扩增来自中国和尼日利亚的木瓜种质资源,可获得121个,54个和98个等位基因,平均每个位点的等位基因数分别是4.4个,2.07个和2个,多态性信息量分别是0.52,0.5和0.5。利用SSR-SRAP综合引物和SSR引物在每个位点至少可以检测到一个等位基因,可有效区分木瓜种质资源,而SRAP标记每个位点上检测到的等位基因数在不同区组间有所变化。SSR标记获得的平均多态性信息量最高,因此表明SSR标记比SSR-SRAP综合标记或单独使用SRAP引物可获得更多的等位基因多态性含量,这也解释了为什么SSR标记或许是目前可用于木瓜研究的最佳选择。SRAP-SSR、SSR、SRAP扩增结果的聚类分析表明,木瓜种质资源具有丰富遗传多态性,其遗传相似系数(GS)分别是0.65、0.59和0.66。根据地理来源不同可将每大类木瓜种质资源再分为两个亚类,表明中国和尼日利亚的木瓜具有较高的遗传差异性。而且在第一大类中,尼日利亚木瓜资源根据地理来源被分为不同的亚类,说明不同地理来源的木瓜具有遗传多样性。综上所述,SSR标记更适合于进行木瓜种质资源亲缘关系和遗传多样性研究。

关键词： SSR SRAP 遗传多样性木瓜

Optimization of Nitrogen, Phosphorus and Salt for Lipid Accumulation of microalgae: Towards the Viability of microalgae Biodiesel

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Natural Science 2016年第12期8卷 557-573页

作者： carolina T. miranda Daniel V. N. de Lima Georgia c. Atella Paula F. de Aguiar sandra m. F. O. Azevedo Biophysics Institute carlos chagas Filho Federal University of Rio de Janeiro Rio de Janeiro RJ Brasil medical Biochemistry Institute Leopoldo De meis Federal University of Rio de Janeiro Rio de Janeiro RJ Brasil chemistry Institute Federal University of Rio de Janeiro Rio de Janeiro RJ Brasil

In recent years, microalgae biodiesel has attracted expressive attention and investment, once it was considered a potential resource for energy. Although the wide use of microalgae biodiesel is restricted by its high production cost. For cost-efficient and sustainable production of biodiesel from microalgae, a proper understanding of the variables and their impacts on physiology of the strains is required. In this study, a simple factorial design 23 was used to find optimal conditions for the cultivation of Ankistrodesmus sp. and chlamydomonas sp. in batch culture. The three components considered were nitrate, phosphate and sodium chloride, used to assess the metabolic versatility of the strains in brackish conditions. The results showed that culture medium with 0.04 g·L?1 nitrate, 0.01 g·L?1 phosphate and 5.0 g·L?1 sodium chloride resulted to be the most effective condition to growth and fatty acids accumulation. Using this optimal condition, Ankistrodesmus sp. and chlamydomonas sp. increased in 2.1 and 2.4 folds their fatty acids yield, respectively. Importantly, this protocol reduced 75% of the nitrate and phosphate concentrations of the original medium (ASm-1). Additionally, fatty acids analysis found that these strains were mainly constituted of c16-c18, in accordance with the requirements for biodiesel production. The simple factorial design applied here proved to be an important tool towards a better understanding of synergistic effects of tested factors on microalgae metabolism, and the resulting information could be used effectively to improve microalgae cultivation.

关键词： Optimization microalgae Lipids Ankistrodesmus chlamydomonas Experimental Design

An Alkali Activated Binder for High chemical Resistant Self-Leveling mortar

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Open Journal of composite materials 2016年第4期6卷 132-142页

作者： Henrik L. Funke sandra Gelbrich Lothar Kroll Institute of Lightweight Structures Technische Universitat Chemnitz Chemnitz Germany

This paper reports the development of an Alkali Activated Binder (AAB) with an emphasis on the performance and the durability of the AAB-matrix. For the development of the matrix, the reactive components granulated slag and coal fly ash were used, which were alkali activated with a mixture of sodium hydroxide (2 - 10 mol/l) and aqueous sodium silicate solution (SiO2/Na2O molar ratio: 2.1) at ambient temperature. A sodium hydroxide concentration of 5.5 mol/l revealed the best compromise between setting time and mechanical strengths of the AAB. With this sodium hydroxide concentration, the compressive and the 3-point bending tensile strength of the hardened AAB were 53.4 and 5.5 mPa respectively after 14 days. As a result of the investigation of the acid resistance, the AAB-matrix showed a very high acid resistance in comparison to ordinary Portland cement concrete. In addition, the AAB had a high frost resistance, which had been validated by the capillary suction, internal damage and freeze thaw test with a relative dynamic E-modulus of 93% and a total amount of scaled material of 30 g/m2 after 28 freeze-thaw cycles (exposure class: XF3).

关键词： Alkali Activated Binder Geopolymer Durability chemical Resistance