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Modulating Wnt signaling to improve cell replacement therapy for Parkinson＇s disease

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Journal of Molecular Cell Biology 2014年第1期8卷 54-63页

作者： Clare L. parish Lachlan H. Thompson Florey institute of Neuroscience and Mental Health The University of Melbourne Parkville VIC 3010 Australia

Clinical trials have demonstrated the capacity for dopamine neurons, transplanted ectopicaUy into the striatum, to structurally inte- grate, restore dopamine transmission, and induce long-term functional benefits for Parkinson＇s disease （PD） patients. Despite this proof of principle, a number of limitations have hindered the development of cell replacement therapy over the past 20 years, particu- larly tissue availability, graft survival, and adequate reinnervation of the host brain. With a greater understanding of failure in prior clinical trials, increased knowledge of midbrain dopamine development （now including Wnts）, and the development of pluripotent stem cell technologies, we are better equipped than ever to re-address a number of these challenges. This review summarizes the trials, tribulations, and progress in cell replacement therapy for PD. We discuss the prospects of modulating canonical and non-canon- ical Wnt signalingto improve cell therapy based upon their roles in dopamine neural development and the adult brain. This will include the potential of Wnts to （i） expand fetaUy derived tissue in vitro and foUowing transplantation, （ii） promote the differentiation of pluripotent stem cells, （iii） increase graft integration and restoration of neural circuitry, and finally （iv） enhance graft survival.

关键词： Wnt dopamine Parkinson's disease cell transplantation neurogenesis axon growth motor function

stage of readiness for planned activity reveals heart failure patients at higher risk

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Open Journal of Preventive Medicine 2013年第1期3卷 118-127页

作者： Tracie R. parish Maria Kosma Michael A. Welsch Department of Kinesiology and Health studies Southeastern Louisiana University Hammond USA Department of Kinesiology Louisiana State University Baton Rouge USA

Few individuals with chronic heart failure (CHF) engage in regular physical activity. PURPOsE: 1) To examine stage of readiness for planned physical activity;2) To compare estimated self-reported daily physical activity and exercise tolerance/capacity by stage of readiness;and 3) To determine the association between stages of readiness for planned physical activity, self-reported daily physical activity and exercise tolerance, in CHF patients. METHODs: One-hundred eleven CHF patients (Age: 53 ± 14 yrs;New YorkHeart Association class ii/iii) participated. Each participant’s stage of readiness for planned physical activity was assessed. Patients completed a self-reported daily physical activity questionnaire, and performed a six-minute walk test. REsULTs: Average left ventricular ejection fraction (LVEF) was 30.12% ± 10.72%. Twelve patients were in Precontemplation (PC),29 inContemplation (C),30 inPreparation (PR),20 inAction (A), and20 inMaintenance (M). There were no differences in age and LVEF between stages. Those classified in A/M performed more minutes in activities > 3 METs. Average 6MWD was 349 ± 118 meters, with significant differences between stages (PC, C CONCLUsiON: The majority of CHF patients are in pre-action stages of readiness for adoption of planned physical activity. Patients in pre-action are engaged in less daily activity and have lower exercise tolerance/capacity than those in A/M. Lower exercise tolerance/capacity suggests these patients are more fragile and at greater risk for complications and early mortality. Greater emphasis should be placed on strategies to move patients toward A/M.

关键词： Chronic Heart Failure Transtheoretical Model Daily Activity Exercise Tolerance

降胆固醇药辛伐他汀可减少血管疾病或有血管疾病危险因素患者的卒中发生率

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英国医学杂志中文版 2005年第1期8卷 52-53页

作者： Collins R Armitage J parish s 杨颖 Heart Protection study Radcliffe infirmary Oxford UK

方法设计：随机对照试验(心脏保护研究)，分配：隐匿分配，盲法：全盲(患者，医生以及数据监测委员会)，随访时间：5年，地点：英国的69所医院。参加者：20536位患者(平均年龄64岁，75％为男性)，其非快速总胆固醇浓度≥3．5mmol／L(13... 详细信息

方法设计：随机对照试验(心脏保护研究)，分配：隐匿分配，盲法：全盲(患者，医生以及数据监测委员会)，随访时间：5年，地点：英国的69所医院。参加者：20536位患者(平均年龄64岁，75％为男性)，其非快速总胆固醇浓度≥3．5mmol／L(135mg／dl)，并伴有脑血管病、冠心病、及其他闭塞性血管病或糖尿病或高血压治疗后年龄≥65岁的男性患者。排除标准：有明确的他汀药的适应证和禁忌证；卒中，心肌梗死或6个月内因心绞痛而住院者；慢性肝病；严重肾病；炎症性肌病；同时服用环孢菌素、贝特类或大剂量烟酸、可能妊娠；严重心衰或威胁生命的疾病。干预措施：辛伐他汀400mg／日(n=10 269)或匹配的安慰剂(n=10267)，治疗5年。结果测定指标：首次主要血管事件(例如，非致死性心肌梗死或冠状动脉疾病死亡、卒中或血管重建手术)，次级结果包括所有。(非致死和致死性)卒中、假定的缺血性卒中和出血性卒中。随访：99．7％的患者完成5年的随访(意向性治疗分析)(心脏保护研究协作组．Lancet 2002：360:7—22．)。主要结果辛伐他汀组在第5年发生首次主要血管事件和卒中者比安慰剂组明显减少(附表)，二组出血性卒中发生率无差异(0．5％比0．5％)。结论降胆固醇药辛伐他汀减少血管疾病或有血管疾病高危因素者卒中发生率。

关键词：出血性卒中辛伐他汀患者发生率血管疾病安慰剂首次附表测定指标分配

inVitro Activation of Human Heparanase:Evidence for Proteolytic Post-transational Processing

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InVitro Activation of Human Heparanase:Evidence for Proteoly...

Eosinophil MBP Extract Modulates Oncogene Expression in Prostate Tumor Cells: A Preliminary study with Monolayer Cultures

Asian-Pacific Conference of Tumor Biology 2001

作者： CraigFreeman MarkD.Hulett Rosssteven KarenJakobsen AnnaBrowne ChristopherR.parish Division of lmmunology and Cell Biology John Cutin School of Medical Research The Australian National University CanberraACT2601Australia Division of lmmunology and Cell Biology John Cutin School of Medical Research The Australian National University CanberraACT2601Australia Division of lmmunology and Cell Biology John Cutin School of Medical Research The Australian National University CanberraACT2601Australia Division of lmmunology and Cell Biology John Cutin School of Medical Research The Australian National University CanberraACT2601Australia Division of lmmunology and Cell Biology John Cutin School of Medical Research The Australian National University CanberraACT2601Australia Division of lmmunology and Cell Biology John Cutin School of Medical Research The Australian National University CanberraACT2601Australia

＜正＞Heparanase,a key enzyme involved in many pathological and physiological processes including tumormetastasis and inflammation,has recently been *** has been suggested that like many other bioac-tive molecules,the biosynthesis of heparanase is subject to post-translational proteolytic modifiction ofthe inactive pro-enzyme to yield the mature and functional *** date,there has been little evi-dence about the nature of the specific protease（s）involved in the heparanase proteolytic post-transla-tional processing and *** now report in vitro activation of the heparanase pre-enzyme from the

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Journal of Cancer Therapy 2015年第6期6卷 482-492页

作者： Christine A. Clarke Michael A. smith ibrahim Laniyan Theresa R. Vaughn Debra parish-Gause William Green Paulette M. Furbert-Harris Department of Microbiology Howard University College of Medicine Washington DC USA Howard University Cancer Center Howard University College of Medicine Washington DC USA Carolina’s Hospital system Marion Mullins SC USA Department of Pathology Howard University College of Medicine Washington DC USA National Human Genome Center at Howard University Howard University College of Medicine Washington DC USA

Prostate cancer is the second leading cause of cancer deaths in the United states and remains a significant health concern for men throughout the world. Despite the discovery of promising immunotherapeutic strategies, curative outcomes remain elusive. We have investigated eosinophils as potential anti-cancer effector cells, and have reported the ability of their toxic granular proteins (MBP, EPO, ECP, EDN) to inhibit prostate tumor cell growth?in vitro. This study investigates the effect of eosinophil MBP extract on the expression of oncogenes p53, bcl-xl, bax, and c-myc, which modulate tumor growth, proliferation, and apoptosis. Briefly, granular proteins were differentially extracted from GRC.014.22 and GRC.014.24, eosinophilic cell lines established in our laboratory from a patient with moderate asthma. Protein extracts were fractionated on sephadex G-50 columns, and prostate tumor cell lines DU-145, LNCaP, PC-3, and HPC8L (established in our laboratory from a tumor resected from an African American patient) were treated with MBP extracts from the pooled third peaks. Colony formation and monolayer cell growth inhibition assays were used to evaluate the protein’s growth inhibitory activity against prostate tumor cells;and gene expression analyses, to determine p53, bcl-xl, bax, and c-myc oncogene expression. We show that the granular proteins were potent in their action on HPC8L, inhibiting colony formation in a dose-dependent manner. Treated prostate tumor cell lines trended toward apoptosis-induction, as evident in bcl-xl/bax ratios increased p53 expression, and up or downregulation of c-myc. These preliminary results demonstrate the growth inhibitory potential of eosinophil granular proteins and strongly support the hypothesis that eosinophils modulate the expression of oncogenes associated with prostate tumor proliferation and apoptosis. More importantly, this study offers insights into possible applications of eosinophilic mediators in oncogenic-targeted

关键词： Eosinophils Major Basic Protein (MBP) Prostate Cancer HPC8L Oncogenes

sendai Framework’s Global Targets A and B: Opinions from the Global Platform for Disaster Risk Reduction’s ignite stage 2019

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international Journal of Disaster Risk science 2022年第5期13卷 651-663页

作者： Nibedita s.Ray-Bennett Krishna Clarke Daniel Mendez school of Business University of LeicesterLeicester LE17RHUK Avoidable Deaths Network University of LeicesterLeicester LE17RHUK Office of the President saint Michael Parish of Saint MichaelCaribbean Development BankBridgetown 11000Barbados

The sendai Framework for Disaster Risk Reduction 2015-2030 set seven global targets of which the first two targets are to reduce disaster deaths(target A) and diminish the number of affected people globally(target B)by *** realize these targets,the United Nations General Assembly’s Expert Working Group provided indicators to measure progress as well as terminologies for these targets in *** around these targets is *** article contributes to the understanding of the targets by exploring:(1) what are the conditions that may hinder achieving targets,as well as those that may accelerate their achievement at the national and local levels;and(2) which types of organizations should lead a country’s effort to reduce disaster deaths?These questions were answered by opinion survey research carried out at the sixth session of the Global Platform for Disaster Risk *** participants identified disaster risk reduction efforts,early warning systems,awareness,finance and investment(among others) as the important facilitating factors to achieve targets A and *** investment in human security,lack of response and coordination,uncertainty of climate change,poor information,lack of campaigns and low budget allocation(among others) are considered as the important hindering factors for these targets by the *** findings also suggest that the facilitating and hindering variables of targets A and B are interconnected with global target E(disaster risk governance and capacity building).The majority of the participants thought that it is the national government who should lead in a country’s effort to reduce disaster *** on these findings,a few recommendations have been made to improve policy and practice related to the indicators as well as to reimagine theories so that targets A and B can be realized in alignment with target E at the national and local levels by 2030.

关键词： Disaster deaths Disaster risk reduction Global Platform for Disaster Risk Reduction HealthEDRM Health system sendai Framework’s targets A and B

A Novel Approach to Measuring spatiotemporal Changes in social Vulnerability at the Local Level in Portugal

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international Journal of Disaster Risk science 2022年第6期13卷 842-861页

作者： Pedro Pinto santos JoséLuís Zêzere susana Pereira Jorge Rocha Alexandre Oliveira Tavares Centre for Geographical studies Institute of Geography and Spatial PlanningTERRAUniversity of Lisbon(CEG-IGOT-ULisboa)1600-276 LisboaLAPortugal Centre for social studies Earth Science DepartmentScience and Technology FacultyUniversity of Coimbra(CES/DCT-FCT-UCoimbra)3000-995 CoimbraPortugal

social vulnerability,as one of the risk components,partially explains the magnitude of the impacts observed after a *** this study,a spatiotemporally comparable assessment of social vulnerability and its drivers was conducted in Portugal,at the civil parish level,for three census *** first challenging step consisted of the selection of meaningful and consistent variables over *** were normalized using the Adjusted Mazziotta-Pareto index(AMPi)to obtain comparable adimensional-normalized values.A joint principal component analysis(PCA)was applied,resulting in a robust set of variables,interpretable from the point of view of their self-grouping around vulnerability drivers.A separate PCA for each census was also conducted,which proved to be useful in analyzing changes in the composition and type of drivers,although only the joint PCA allows the monitoring of spatiotemporal changes in social vulnerability scores and drivers from 1991 to 2011.A general improvement in social vulnerability was observed for *** two main drivers are the economic condition(PC1),and aging and depopulation(PC2).The remaining drivers highlighted are uprooting and internal mobility,and daily *** data proved their value in the territorial,social,and demographic characterization of the country,to support medium-and long-term disaster risk reduction measures.

关键词： AMPi normalization Portugal social vulnerability spatiotemporal changes

Effects of storage time on DNA profiling success from archived latent fingerprint samples using an optimised workflow

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Forensic sciences Research 2022年第1期7卷 61-68页

作者： sydney i.Menchhoff April D.solomon Jordan O.Cox Madison E.Hytinen Marilyn T.Miller Tracey Dawson Cruz Department of Forensic science Virginia Commonwealth UniversityRichmondVirginiaUSA Jefferson parish sheriff’s Office Regional DNA Laboratory HarveyLouisianaUSA

Due to recent improvements in forensic DNA testing kit sensitivity,there has been an increased demand in the criminal justice community to revisit past convictions or cold *** of these cases have little biological evidence other than touch DNA in the form of archived latent fingerprint lift *** this study,a previously developed optimised workflow for this sample type was tested on aged fingerprints to determine if improved short tandem repeat(sTR)profiles could be ***-year-old samples processed with the optimised workflow produced an average of approximately five more sTR alleles per profile over the traditional *** optimised workflow also produced detectable alleles in samples aged out to 28 *** the methods tested,the optimised workflow resulted in the most informative profiles from evidence samples more representative of the forensic *** workflow is recommended for use with archived latent fingerprint samples,regardless of the archival time.

关键词： Forensic sciences forensic genetics low template DNA touch DNA aged samples archived latent fingerprints optimised workflow

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3D双时相全心MRi的心脏容积定量分析

国际医学放射学杂志 2008年第5期31卷 406-406页

作者： s.Uribe T.Tangchaoren V.parish i.Wolf R.Razavi G.Greil 郭雪梅 Division of imaging sciences King’s College LondonBHF Centre London SE1 7EH England.

本研究经地区伦理委员会批准并取得所有志愿者及病人的知情同意。本研究目的是在一次自由呼吸MRi检查时，采用收缩末期和舒张末期的3D全心MR数据评价心室容积。5位健康志愿者和10例病人在MRi检查时采集了3D双时相心脏数据、屏气短轴位... 详细信息

本研究经地区伦理委员会批准并取得所有志愿者及病人的知情同意。本研究目的是在一次自由呼吸MRi检查时，采用收缩末期和舒张末期的3D全心MR数据评价心室容积。5位健康志愿者和10例病人在MRi检查时采集了3D双时相心脏数据、屏气短轴位多层影像和大血管层面间流动影像。在这些数据中，用统计学分析比较了收缩、收缩末期和舒张末期的左室（LV）和右室（RV）容积。结果表明，屏气多层影像方式、流动测量方式和新的双时相3D方式均可得到有可比性的心脏容积和功能结果。这些方法之间进行比较时．相关系数高于0．95，且收缩、收缩末期和舒张末期的左室（LV）和右室（RV）容积之间均无显著性差异。

关键词： MRi检查心脏容积定量分析时相收缩末期健康志愿者舒张末期伦理委员会