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Protein misfolding in neurodegenerative diseases:implications and strategies

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Translational Neurodegeneration 2017年第1期6卷 37-49页

作者： Patrick Sweeney Hyunsun Park Marc Baumann John Dunlop Judith Frydman Ron Kopito Alexander McCampbell gabrielle leblanc Anjli Venkateswaran Antti Nurmi Robert Hodgson Discovery Services Charles Rivers LaboratoriesWilmingtonMAUSA Royal Veterinary College University of LondonLondonUK Health&Life Science Consulting Los AngelesCAUSA Biochemistry and Developmental Biology University of HelsinkiHelsinkiFinland Neuroscience Innovation Medicines Astra ZenecaCambridgeMAUSA Stanford University StanfordCAUSA Neurology Biogen IdecCambridgeMAUSA leblanc Bioscience Consulting BerkeleyCAUSA

A hallmark of neurodegenerative proteinopathies is the formation of misfolded protein aggregates that cause cellular toxicity and contribute to cellular proteostatic *** options are currently being explored that target different steps in the production and processing of proteins implicated in neurodegenerative disease,including synthesis,chaperone-assisted folding and trafficking,and degradation via the proteasome and autophagy *** therapies,like mTOR inhibitors and activators of the heat shock response,can rebalance the entire proteostatic ***,there are major challenges that impact the development of novel therapies,including incomplete knowledge of druggable disease targets and their mechanism of action as well as a lack of biomarkers to monitor disease progression and therapeutic response.A notable development is the creation of collaborative ecosystems that include patients,clinicians,basic and translational researchers,foundations and regulatory agencies to promote scientific rigor and clinical data to accelerate the development of therapies that prevent,reverse or delay the progression of neurodegenerative proteinopathies.

关键词： Neurodegeneration Proteostasis Mouse models Biomarkers Chaperones Drug discovery

Philippine retinoblastoma initiative multi-eye center study 2010-2020

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International Journal of Ophthalmology(English edition) 2024年第1期17卷 144-156页

作者： Roland Joseph D.Tan gary John V.Mercado Patricia E.Cabrera Paulita Pamela P.Astudillo Rolando Enrique D.Domingo Josept Mari S.Poblete Charmaine grace M.Cabebe Adriel Vincent R.Te Melissa Anne S.gonzales Jocelyn g.Sy Beltran Alexis A.Aclan Jayson T.So Fatima g.Regala Kimberley Amanda K.Comia Josemaria M.Castro Mara Augustine S.galang Aldous Dominic C.Cabanlas Benedicto Juan E.Aguilar gabrielle S.Evangelista Jo Michael Maniwan Andrei P.Martin Calvin Y.Martinez John Alfred H.Lim Rena Ivy Bascuna Rachel M.Ng Kevin B.Agsaoay Kris Zanna A.Acluba-Arao Ellaine Rose V.Apostol Beatriz M.Prieto Department of Ophthalmology and Visual Sciences Philippine General HospitalManila 1000Philippines Department of Ophthalmology Baguio General Hospital and Medical CenterBaguio City 2600Philippines Department of Ophthalmology Manila Doctors HospitalManila 1000Philippines Department of Ophthalmology Rizal Medical CenterPasig City 1600Philippines Department of Ophthalmology Jose B.Lingad Memorial Regional HospitalPampanga 2000Philippines Department of Ophthalmology Southern Philippines Medical CenterDavao City 8000Philippines Department of Ophthalmology East Avenue Medical CenterQuezon City 1100Philippines Department of Ophthalmology Northern Mindanao Medical CenterCagayan de Oro City 9000Philippines Department of Ophthalmology Cebu Velez General HospitalCebu City 6000Philippines Legazpi Eye Center Legazpi City 4500Philippines Department of Ophthalmology Cagayan Valley Medical CenterTuguegarao City 3500Philippines

AIM:To provide a comprehensive and more representative national data on the disease,especially on treatment options and outcomes,and to determine access of retinoblastoma patients from Luzon,Visayas and Mindanao to eye care,and determine if access is associated with delay in consultation,staging and ***:Cohort study of retinoblastoma patients seen in eleven institutions located in the three major areas of the Philippines namely Luzon,Vizayas and Mindanao from ***:Totally 636 patients,involving 821 eyes,were ***(57%)were from Luzon and were seen in institutions in Luzon(72%).Annually,58±10 new cases were seen with 71%having unilateral *** delay of consultation remained long at 9(3,17)mo,longest in patients with unilateral disease(Pging System,only 35%of patients had Stage 1 while 47%already had extraocular *** was the most common treatment received by 484 patients while intravenous chemotherapy was received by *** were 250(39%)patients alive,195(31%)dead,85(13%)abandoned,17(3%)refused and 89(14%)with no ***:This study presents the largest cohort of retinoblastoma patients in the Philippines in terms of patients’and participating institutions’number and geographical location and type of institution(private and public).It also presents more comprehensive data on the treatments used and outcomes(survival,globe salvage,and vision retention rates).Delay in consultation was still long among patients leading to advanced disease stage and lower survival *** increasing capacity to diagnose and manage retinoblastoma in the country,the delay of consultation remains long primarily due to accessibility issues to eye care institutions especially in the Visayas and financial *** delay was still significant that overall survival rate remain low.

关键词： retinoblastoma Philippines clinical profile

Neural stem cell heterogeneity through time and space in the ventricular-subventricular zone

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Frontiers in Biology 2016年第4期11卷 261-284页

作者： gabrielle Rushing Rebecca A. Ihrie Program in Neuroscience Vanderbilt University Nashville TAr 37232 USA Departments of Cancer Biology and Neurological Surgery Vanderbilt University Nashville TN 37232 USA

BACKgROUND： The origin and classification of neural stem cells （NSCs） has been a subject of intense investigation for the past two decades. Efforts to categorize NSCs based on their location, function and expression have established that these cells are a heterogeneous pool in both the embryonic and adult brain. The discovery and additional characterization of adult NSCs has introduced the possibility of using these cells as a source for neuronal and glial replacement following injury or disease. To understand how one could manipulate NSC developmental programs for therapeutic use, additional work is needed to elucidate how NSCs are programmed and how signals during development are interpreted to determine cell fate. OBJECTIVE： This review describes the identification, classification and characterization of NSCs within the large neurogenic niche of the ventricular-subventricular zone （V-SVZ）. METHODS： A literature search was conducted using Pubmed including the keywords ＂ventricular-subventricular zone,＂＂neural stem cell,＂＂heterogeneity,＂＂identity＂ and/or ＂single cell＂ to find relevant manuscripts to include within the review. A special focus was placed on more recent findings using single-cell level analyses on neural stem cells within their niche（s）. RESULTS： This review discusses over 20 research articles detailing findings on V-SVZ NSC heterogeneity, over 25 articles describing fate determinants of NSCs, and focuses on 8 recent publications using distinct single-cell analyses of neural stem cells including fl0w cytometry and RNA-seq. Additionally, over 60 manuscripts highlighting the markers expressed on cells within the NSC lineage are included in a chart divided by cell type. CONCLUSIONS： Investigation of NSC heterogeneity and fate decisions is ongoing. Thus far, much research has been conducted in mice however, findings in human and other mammalian species are also discussed here. Implications of NSC heterogeneity established in the embryo for the properti

关键词： ventricular-subventricular zone neural stem cells positional identity single-cell heterogeneity

Designing and Teaching Pharmacology for an Integrated Program at the University of Canberra

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Designing and Teaching Pharmacology for an Integrated Progra...

Dose of alendronate directly increases trabeculae expansivity without altering bone volume in rat femurs

Satellite Meeting on Pharmacological Teaching & The 15th World Congress of Pharmacology

作者： g.David Lin gabrielle M.Cooper Pharmacy Discipline School of Health SciencesUniversity of CanberraACT 2601Australia Pharmacy Discipline School of Health SciencesUniversity of CanberraACT 2601Australia

＜正＞In response to the shortage of pharmacists in Australia, and the desire of graduates in non-pharmacy fields to become a pharmacist, the University of Canberra pioneered a 2-year integrated Master of Pharmacy by coursework program in 2004. Here we present how pharmacology teaching is designed, developed and implemented. We introduce Pharmacology in

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World Journal of Orthopedics 2018年第10期9卷 190-197页

作者： Suyany g Weiss gabrielle O Kuchar Jennifer T gerber Fernanda Tiboni Carmen Lucia M Storrer Thaís C Casagrande Allan F giovanini Rafaela Scariot School of Health Science Department of Dentistry Positivo University School of Health Science Department of Biotecnology Positivo University

AIM To evaluate the effects of sodium alendronate on bone repair in fractures created in appendicular bones. METHODS Wistar rats(n = 36) were allocated into three distinct groups: group C(control), group B1(received 1 mg/kg of alendronate), and group B2(received 3 mg/kg of alendronate). The rats underwent femoral transversal linear fracture surgery using stable internal fixation with a 2.0 mm plate and screw system. Each animal randomly received intraperitoneal applications of sodium alendronate at a dose corresponding to group B1 or B2 three times a week, while the control group received a 0.9% saline solution. Drug administration was performed until euthanasia at 45 d. The femurs were removed and each surgical piece was sent for radiographic, tomographic and microtomographic analysis. Data were submitted to descriptive and inferential statistical analysis(95% confidence interval).RESULTS Quantitative evaluations of bone neoformation did not show differences among the groups in the radiographic(P = 0.341), microtomographic(P = 0.581) and tomographic evaluations(P = 0.171). In the qualitative microtomographic analysis, a smaller distance was observed between the internal bone trabeculae in the groups that used alendronate(P = 0.05). On the other hand, group B2 had a higher amount of bone trabeculae per unit length when compared to the other groups(P = 0.04).CONCLUSION It is likely that the use of alendronate did not have a direct influence on the amount of bone neoformation, however it did influence the bone quality in a dosedependent manner, ultimately affecting the distance and quantity of the trabeculae.

关键词： Alendronate Bone regeneration Fracture Femur Bisphosphonates

Leontiasis Ossea about a Case Treated at Chu Owendo

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Open Journal of Stomatology 2023年第5期13卷 167-173页

作者： Alain Patrick Makungu gabrielle Atsame Mohamed Roukaya Sidonie Nguisi Ogoula gabrielle Kenguej Department of Stomatology and Maxillofacial Surgery University Hospital Center (CHU) Owendo Libreville Gabon Department of Anatomy Pathology USS School of Medecine Libreville Gabon

Introduction: Leontiasis ossea is the most severe bone complication of the maxillae of chronic renal failure. The objective of this work is to determine the clinical, paraclinical and therapeutic aspects of this condition. Observation: A 42-year-old patient with chronic anuric terminal renal failure dialysis for 12 years had consulted for multiple maxillo-mandibular swelling evolving for 2 years deforming the face with discomfort to chewing. The biological assessment was: PTH: 5252 pg/mL, Ca2+: 2.86 mmol/L, free T3: 4.16 pmol/L, free T4: 6.55 pmol/L, TSH: 3.13 U/mL, serum protein: 61 g/L, Creatinine: 835 μmol/L. The maxillofacial CT noted heterogeneous diffuse thickening of the cranial vault and bones of the facial massif evoking leontiasis ossea with right mandibular brown tumor. The biopsy diagnosed fibrous gingival epulis. The patient had undergone modeling surgery, under general anesthesia after dialysis, of the right mandibular tumor whose histological result was Leontiasis ossea. Conclusion: Treatment is modeling surgery under hemostatic control.

关键词： eontiasis Ossea Hyperparathyroidism CKD Bone Hypertrophy

Inhibiting WNT secretion reduces high bone mass caused by Sost loss-of-function or gain-of-function mutations in Lrp5

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骨研究:英文版 2023年第3期11卷 595-606页

作者： Cassandra R.Diegel Ina Kramer Charles Moes gabrielle E.Foxa Mitchell J.McDonald Zachary B.Madaj Sabine guth Jun Liu Jennifer L.Harris Michaela Kneissel Bart O.Williams Department of Cell Biology Van Andel Institute333 Bostwick Ave.NEGrand RapidsMI 49503USA Diseases of Aging and Regenerative Medicine Novartis Institutes for Biomedical ResearchCH-4002 BaselSwitzerland Bioinformatics and Biostatistics Core Van Andel Institute333 Bostwick Ave.NEGrand RapidsMI 49503USA Oncology Novartis Institutes for Biomedical ResearchSan DiegoCA 92121USA

Proper regulation of Wnt signaling is critical for normal bone development and *** in several Wnt signaling components,which increase the activity of the pathway in the skeleton,cause high bone mass in human subjects and mouse *** bone mass is often accompanied by severe headaches from increased intracranial pressure,which can lead to fatality and loss of vision or hearing due to the entrapment of cranial *** addition,progressive forehead bossing and mandibular overgrowth occur in almost all *** that would provide symptomatic relief in these subjects are ***-mediated palmitoylation is necessary for Wnt secretion and binding to the frizzled *** inhibition of porcupine is a highly selective method of Wnt signaling *** treated three different mouse models of high bone mass caused by aberrant Wnt signaling,including homozygosity for loss-of-function in Sost,which models sclerosteosis,and two strains of mice carrying different point mutations in Lrp5(equivalent to human g171V and A214V),at 3 months of age with porcupine inhibitors for 5–6 *** significantly reduced both trabecular and cortical bone mass in all three *** demonstrates that porcupine inhibition is potentially therapeutic for symptomatic relief in subjects who suffer from these disorders and further establishes that the continued production of Wnts is necessary for sustaining high bone mass in these models.

关键词： homeostasis function mass

SHui, an EU-Chinese cooperative project to optimize soil and water management in agricultural areas in the ⅩⅪ century

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International Soil and Water Conservation Research 2020年第1期8卷 1-14页

作者： José A.gómez Alon Ben-gal Juan J.Alarcón gabrielle De Lannoy Shannon de Roos Tomá(s)Dostál Elias Fereres Diego S.Intrigliolo Josef Krása Andreas Klik gunther Liebhard Reinhard Nolz Aviva Peeters Elke Plaas John N.Quinton Rui Miao Peter Strauss Weifeng Xu Zhiqiang Zhang Funing Zhong David Zumr Ian C.Dodd Institute for Sustainable Agriculture IASCSICAvda Menendez Pidal S/NCordobaSpain Agricultural Research Organization Gilat Research CenterIsrael Centro de Edafología y Biología Aplicada Del Segura(CSIC) Dept.RiegoMurciaSpain Department of Earth and Environmental Sciences KU LeuvenHeverleeBelgium Czech Technical University in Prague Faculty of Civil Engineering.CVUTPragueCzech Republic Agronomy Department University of CordobaCordobaSpain University of Agricultural Sciences Vienna(BOKU) ViennaAustria TerraVision Lab Midreshet Ben-GurionIsrael georg-August-Universitat gottingen Germany Centre for Sustainable Agriculture Lancaster Environment CentreLancaster UniversityUK Center for Plant Water-Use and Nutrition Regulation and College of Life Sciences Joint International Research Laboratory of Water and Nutrient in CropsFujian Agriculture and Forestry UniversityFuzhouChina Institute for Land and Water Management Research Federal Agency for Water ManagementPetzenkirchenAustria College of Soil and Water Conservation Beijing Forestry UniversityBeijingChina College of Economics and Management Nanjing Agricultural UniversityNAUNanjingChina

This article outlines the major scientific objectives of the SHui project that seeks to optimize soil and water use in agricultural systems in the EU and China,by considering major current scientific challenges in this ***(for Soil Hydrology research platform underpinning innovation to manage water scarcity in European and Chinese cropping systems)is large cooperative project that aims to provide significant advances through transdisciplinary research at multiple scales(plot,field,catchment and region).This paper explains our research platform of long-term experiments established at plot scale,approaches taken to integrate crop and hydrological models at field scale;coupled crop models and satellite-based observations at regional scales;decision support systems for specific farming situations;and the integration of these technologies to provide policy recommendations through socio-economic analysis of the impact of soil and water saving *** also outlines the training of stake-holders to develop a basic common curriculum despite the subject being distributed across different disciplines and *** such,this article provides a review of major challenges for improving soil and water use in EU and China as well as information about the potential to access information made available by SHui,and to allow others to engage with the project.

关键词： Yield Sustainability Cropping Cooperation

有前途的β测试版:IBM C Set++ 3.0 for OS/2

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个人电脑 1995年第7期1卷 100-101页

作者： gabrielle gagnon

IBM正在将C Set++推向企业。为了将C Set++移植到多种平台并且能在公司所有的g++产品之上提供一个公共的API,IBM公司对该产品进行了较大的修改。我们使用了早期的β版,发现它已经相当不错了。Workframe/2,即IBM用于管理应用开发工具的环... 详细信息

IBM正在将C Set++推向企业。为了将C Set++移植到多种平台并且能在公司所有的g++产品之上提供一个公共的API,IBM公司对该产品进行了较大的修改。我们使用了早期的β版,发现它已经相当不错了。Workframe/2,即IBM用于管理应用开发工具的环境,已经被彻底改写成了一个Workplace Shell应用程序。C Set++拥有了一个重要的新可视化工具,即Visual Builder。该软件包还包含了一个可编程编辑器、链接器和类浏览器。编译器提供了新的优化、修改过的ANSI支持以及预编译头文件支持。

关键词： β测试 OS/2 编译器 C/C++ Windows HighC 链接器交叉平台编辑器油布