WorldWideScience

Sample records for neurodegeneration electronic resource

  1. Electronic Resource Management Systems

    Directory of Open Access Journals (Sweden)

    Mark Ellingsen

    2004-10-01

    Full Text Available Computer applications which deal with electronic resource management (ERM are quite a recent development. They have grown out of the need to manage the burgeoning number of electronic resources particularly electronic journals. Typically, in the early years of e-journal acquisition, library staff provided an easy means of accessing these journals by providing an alphabetical list on a web page. Some went as far as categorising the e-journals by subject and then grouping the journals either on a single web page or by using multiple pages. It didn't take long before it was recognised that it would be more efficient to dynamically generate the pages from a database rather than to continually edit the pages manually. Of course, once the descriptive metadata for an electronic journal was held within a database the next logical step was to provide administrative forms whereby that metadata could be manipulated. This in turn led to demands for incorporating more information and more functionality into the developing application.

  2. Electronic Resource Management and Design

    Science.gov (United States)

    Abrams, Kimberly R.

    2015-01-01

    We have now reached a tipping point at which electronic resources comprise more than half of academic library budgets. Because of the increasing work associated with the ever-increasing number of e-resources, there is a trend to distribute work throughout the library even in the presence of an electronic resources department. In 2013, the author…

  3. Managing electronic resources a LITA guide

    CERN Document Server

    Weir, Ryan O

    2012-01-01

    Informative, useful, current, Managing Electronic Resources: A LITA Guide shows how to successfully manage time, resources, and relationships with vendors and staff to ensure personal, professional, and institutional success.

  4. Electronic Resources Management Project Presentation 2012

    KAUST Repository

    Ramli, Rindra M.

    2012-11-05

    This presentation describes the electronic resources management project undertaken by the KAUST library. The objectives of this project is to migrate information from MS Sharepoint to Millennium ERM module. One of the advantages of this migration is to consolidate all electronic resources into a single and centralized location. This would allow for better information sharing among library staff.

  5. Implementing CORAL: An Electronic Resource Management System

    Science.gov (United States)

    Whitfield, Sharon

    2011-01-01

    A 2010 electronic resource management survey conducted by Maria Collins of North Carolina State University and Jill E. Grogg of University of Alabama Libraries found that the top six electronic resources management priorities included workflow management, communications management, license management, statistics management, administrative…

  6. Electronic Resources Management System: Recommendation Report 2017

    KAUST Repository

    Ramli, Rindra M.

    2017-01-01

    This recommendation report provides an overview of the selection process for the new Electronic Resources Management System. The library has decided to move away from Innovative Interfaces Millennium ERM module. The library reviewed 3 system

  7. Electronic Resources Management Project Presentation 2012

    KAUST Repository

    Ramli, Rindra M.

    2012-01-01

    This presentation describes the electronic resources management project undertaken by the KAUST library. The objectives of this project is to migrate information from MS Sharepoint to Millennium ERM module. One of the advantages of this migration

  8. PRINCIPLES OF CONTENT FORMATION EDUCATIONAL ELECTRONIC RESOURCE

    Directory of Open Access Journals (Sweden)

    О Ю Заславская

    2017-12-01

    Full Text Available The article considers modern possibilities of information and communication technologies for the design of electronic educational resources. The conceptual basis of the open educational multimedia system is based on the modular architecture of the electronic educational resource. The content of the electronic training module can be implemented in several versions of the modules: obtaining information, practical exercises, control. The regularities in the teaching process in modern pedagogical theory are considered: general and specific, and the principles for the formation of the content of instruction at different levels are defined, based on the formulated regularities. On the basis of the analysis, the principles of the formation of the electronic educational resource are determined, taking into account the general and didactic patterns of teaching.As principles of the formation of educational material for obtaining information for the electronic educational resource, the article considers: the principle of methodological orientation, the principle of general scientific orientation, the principle of systemic nature, the principle of fundamentalization, the principle of accounting intersubject communications, the principle of minimization. The principles of the formation of the electronic training module of practical studies in the article include: the principle of systematic and dose based consistency, the principle of rational use of study time, the principle of accessibility. The principles of the formation of the module for monitoring the electronic educational resource can be: the principle of the operationalization of goals, the principle of unified identification diagnosis.

  9. Electronic Resources Management System: Recommendation Report 2017

    KAUST Repository

    Ramli, Rindra M.

    2017-05-01

    This recommendation report provides an overview of the selection process for the new Electronic Resources Management System. The library has decided to move away from Innovative Interfaces Millennium ERM module. The library reviewed 3 system as potential replacements namely: Proquest 360 Resource Manager, Ex Libris Alma and Open Source CORAL ERMS. After comparing and trialling the systems, it was decided to go for Proquest 360 Resource Manager.

  10. CHALLENGES OF ELECTRONIC INFORMATION RESOURCES IN ...

    African Journals Online (AJOL)

    This paper discusses the role of policy for proper and efficient library services in the electronic era. It points out some of the possible dangers of embarking in electronic resources without a proper focus at hand. Thus, it calls for today's librarians and policy makers to brainstorm and come up with working policies suitable to ...

  11. Library training to promote electronic resource usage

    DEFF Research Database (Denmark)

    Frandsen, Tove Faber; Tibyampansha, Dativa; Ibrahim, Glory

    2017-01-01

    Purpose: Increasing the usage of electronic resources is an issue of concern for many libraries all over the world. Several studies stress the importance of information literacy and instruction in order to increase the usage. Design/methodology/approach: The present article presents the results...

  12. Electronic resource management systems a workflow approach

    CERN Document Server

    Anderson, Elsa K

    2014-01-01

    To get to the bottom of a successful approach to Electronic Resource Management (ERM), Anderson interviewed staff at 11 institutions about their ERM implementations. Among her conclusions, presented in this issue of Library Technology Reports, is that grasping the intricacies of your workflow-analyzing each step to reveal the gaps and problems-at the beginning is crucial to selecting and implementing an ERM. Whether the system will be used to fill a gap, aggregate critical data, or replace a tedious manual process, the best solution for your library depends on factors such as your current soft

  13. use of electronic resources by graduate students of the department

    African Journals Online (AJOL)

    respondent's access electronic resources from the internet via Cybercafé .There is a high ... KEY WORDS: Use, Electronic Resources, Graduate Students, Cybercafé. INTRODUCTION ... Faculty of Education, University of Uyo, Uyo. Olu Olat ...

  14. Use of Electronic Resources in a Private University in Nigeria ...

    African Journals Online (AJOL)

    The study examined awareness and constraints in the use of electronic resources by lecturers and students of Ajayi Crowther University, Oyo, Nigeria. It aimed at justifying the resources expended in the provision of electronic resources in terms of awareness, patronage and factors that may be affecting awareness and use ...

  15. Gender Analysis Of Electronic Information Resource Use: The Case ...

    African Journals Online (AJOL)

    Based on the findings the study concluded that access and use of electronic information resources creates a “social digital divide” along gender lines. The study ... Finally, the library needs to change its marketing strategies on the availability of electronic information resources to increase awareness of these resources.

  16. Electronic Resource Management System. Vernetzung von Lizenzinformationen

    Directory of Open Access Journals (Sweden)

    Michaela Selbach

    2014-12-01

    Full Text Available In den letzten zehn Jahren spielen elektronische Ressourcen im Bereich der Erwerbung eine zunehmend wichtige Rolle: Eindeutig lässt sich hier ein Wandel in den Bibliotheken (fort vom reinen Printbestand zu immer größeren E-Only-Beständen feststellen. Die stetig wachsende Menge an E-Ressourcen und deren Heterogenität stellt Bibliotheken vor die Herausforderung, die E-Ressourcen effizient zu verwalten. Nicht nur Bibliotheken, sondern auch verhandlungsführende Institutionen von Konsortial- und Allianzlizenzen benötigen ein geeignetes Instrument zur Verwaltung von Lizenzinformationen, welches den komplexen Anforderungen moderner E-Ressourcen gerecht wird. Die Deutsche Forschungsgemeinschaft (DFG unterstützt ein Projekt des Hochschulbibliothekszentrums des Landes Nordrhein-Westfalen (hbz, der Universitätsbibliothek Freiburg, der Verbundzentrale des Gemeinsamen Bibliotheksverbundes (GBV und der Universitätsbibliothek Frankfurt, in dem ein bundesweit verfügbares Electronic Ressource Managementsystem (ERMS aufgebaut werden soll. Ein solches ERMS soll auf Basis einer zentralen Knowledge Base eine einheitliche Nutzung von Daten zur Lizenzverwaltung elektronischer Ressourcen auf lokaler, regionaler und nationaler Ebene ermöglichen. Statistische Auswertungen, Rechteverwaltung für alle angeschlossenen Bibliotheken, kooperative Datenpflege sowie ein über standardisierte Schnittstellen geführter Datenaustausch stehen bei der Erarbeitung der Anforderungen ebenso im Fokus wie die Entwicklung eines Daten- und Funktionsmodells. In the last few years the importance of electronic resources in library acquisitions has increased significantly. There has been a shift from mere print holdings to both e- and print combinations and even e-only subscriptions. This shift poses a double challenge for libraries: On the one hand they have to provide their e-resource collections to library users in an appealing way, on the other hand they have to manage these

  17. Electronic human resource management: Enhancing or entrancing?

    Directory of Open Access Journals (Sweden)

    Paul Poisat

    2017-07-01

    Full Text Available Orientation: This article provides an investigation into the current level of development of the body of knowledge related to electronic human resource management (e-HRM by means of a qualitative content analysis. Several aspects of e-HRM, namely definitions of e-HRM, the theoretical perspectives around e-HRM, the role of e-HRM, the various types of e-HRM and the requirements for successful e-HRM, are examined. Research purpose: The purpose of the article was to determine the status of e-HRM and examine the studies that report on the link between e-HRM and organisational productivity. Motivation for the study: e-HRM has the capacity to improve organisational efficiency and leverage the role of human resources (HR as a strategic business partner. Main findings: The notion that the implementation of e-HRM will lead to improved organisational productivity is commonly assumed; however, empirical evidence in this regard was found to be limited. Practical/managerial implications: From the results of this investigation it is evident that more research is required to gain a greater understanding of the influence of e-HRM on organisational productivity, as well as to develop measures for assessing this influence. Contribution: This article proposes additional areas to research and measure when investigating the effectiveness of e-HRM. It provides a different lens from which to view e-HRM assessment whilst keeping it within recognised HR measurement parameters (the HR value chain. In addition, it not only provides areas for measuring e-HRM’s influence but also provides important clues as to how the measurements may be approached.

  18. Utilization of electronic information resources by academic staff at ...

    African Journals Online (AJOL)

    The study investigated the utilization of Electronic Information resources by the academic staff of Makerere University in Uganda. It examined the academic staff awareness of the resources available, the types of resources provided by the Makerere University Library, the factors affecting resource utilization. The study was ...

  19. Oxidative Stress in Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Varsha Shukla

    2011-01-01

    Full Text Available It has been demonstrated that oxidative stress has a ubiquitous role in neurodegenerative diseases. Major source of oxidative stress due to reactive oxygen species (ROS is related to mitochondria as an endogenous source. Although there is ample evidence from tissues of patients with neurodegenerative disorders of morphological, biochemical, and molecular abnormalities in mitochondria, it is still not very clear whether the oxidative stress itself contributes to the onset of neurodegeneration or it is part of the neurodegenerative process as secondary manifestation. This paper begins with an overview of how oxidative stress occurs, discussing various oxidants and antioxidants, and role of oxidative stress in diseases in general. It highlights the role of oxidative stress in neurodegenerative diseases like Alzheimer's, Parkinson's, and Huntington's diseases and amyotrophic lateral sclerosis. The last part of the paper describes the role of oxidative stress causing deregulation of cyclin-dependent kinase 5 (Cdk5 hyperactivity associated with neurodegeneration.

  20. Users satisfaction with electronic information resources and services ...

    African Journals Online (AJOL)

    This study investigated users satisfaction on the use of electronic information resources and services in MTN Net libraries in ABU & UNIBEN. Two objectives and one null hypotheses were formulated and tested with respect to the users' satisfaction on electronic information resources and services in MTN Net libraries in ...

  1. The Role of the Acquisitions Librarian in Electronic Resources Management

    Science.gov (United States)

    Pomerantz, Sarah B.

    2010-01-01

    With the ongoing shift to electronic formats for library resources, acquisitions librarians, like the rest of the profession, must adapt to the rapidly changing landscape of electronic resources by keeping up with trends and mastering new skills related to digital publishing, technology, and licensing. The author sought to know what roles…

  2. Selection and Evaluation of Electronic Resources

    Directory of Open Access Journals (Sweden)

    Doğan Atılgan

    2013-11-01

    Full Text Available Publication boom and issues related to controlling and accession of printed sources have created some problems after World War II. Consequently, publishing industry has encountered the problem of finding possible solution for emerged situation. Industry of electronic publishing has started to improve with the rapid increase of the price of printed sources as well as the problem of publication boom. The first effects of electronic publishing were appeared on the academic and scholarly publications then electronic publishing became a crucial part of all types of publications. As a result of these developments, collection developments and service policies of information centers were also significantly changed. In this article, after a general introduction about selection and evaluation processes of electronic publications, the subscribed databases by a state and a privately owned university in Turkey and their usage were examined.

  3. Neuroinflammation Induces Neurodegeneration.

    Science.gov (United States)

    Kempuraj, D; Thangavel, R; Natteru, P A; Selvakumar, G P; Saeed, D; Zahoor, H; Zaheer, S; Iyer, S S; Zaheer, A

    2016-01-01

    Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Multiple Sclerosis (MS) are characterized by neuronal degeneration and neuronal death in specific regions of the central nervous system (CNS). In AD, neurons of the hippocampus and entorhinal cortex are the first to degenerate, whereas in PD, dopaminergic neurons in the substantia nigra degenerate. MS patients show destruction of the myelin sheath. Once the CNS neurons are damaged, they are unable to regenerate unlike any other tissue in the body. Neurodegeneration is mediated by inflammatory and neurotoxic mediators such as interleukin-1beta (IL-1β), IL-6, IL-8, IL-33, tumor necrosis factor-alpha (TNF-α), chemokine (C-C motif) ligand 2 (CCL2), CCL5, matrix metalloproteinase (MMPs), granulocyte macrophage colony-stimulating factor (GM-CSF), glia maturation factor (GMF), substance P, reactive oxygen species (ROS), reactive nitrogen species (RNS), mast cells-mediated histamine and proteases, protease activated receptor-2 (PAR-2), CD40, CD40L, CD88, intracellular Ca + elevation, and activation of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa-B (NF-kB). Activated microglia, astrocytes, neurons, T-cells and mast cells release these inflammatory mediators and mediate neuroinflammation and neurodegeneration in a vicious manner. Further, immune and inflammatory cells and inflammatory mediators from the periphery cross the defective blood-brain-barrier (BBB) and augment neuroinflammation. Though inflammation is crucial in the onset and the progression of neurodegenerative diseases, anti-inflammatory drugs do not provide significant therapeutic effects in these patients till date, as the disease pathogenesis is not yet clearly understood. In this review, we discuss the possible factors involved in neuroinflammation-mediated neurodegeneration.

  4. Improving Electronic Resources through Holistic Budgeting

    Science.gov (United States)

    Kusik, James P.; Vargas, Mark A.

    2009-01-01

    To establish a more direct link between its collections and the educational goals of Saint Xavier University, the Byrne Memorial Library has adopted a "holistic" approach to collection development. This article examines how traditional budget practices influenced the library's selection of resources and describes how holistic collection…

  5. Page 170 Use of Electronic Resources by Undergraduates in Two ...

    African Journals Online (AJOL)

    undergraduate students use electronic resources such as NUC virtual library, HINARI, ... web pages articles from magazines, encyclopedias, pamphlets and other .... of Nigerian university libraries have Internet connectivity, some of the system.

  6. Utilisation of Electronic Information Resources By Lecturers in ...

    African Journals Online (AJOL)

    This study assesses the use of information resources, specifically, electronic databases by lecturers/teachers in Universities and Colleges of Education in South Western Nigeria. Information resources are central to teachers' education. It provides lecturers/teachers access to information that enhances research and ...

  7. Preservation and conservation of electronic information resources of ...

    African Journals Online (AJOL)

    The major holdings of the broadcast libraries of the Nigerian Television Authority (NTA) are electronic information resources; therefore, providing safe places for general management of these resources have aroused interest in the industry in Nigeria for sometimes. The need to study the preservation and conservation of ...

  8. Using XML Technologies to Organize Electronic Reference Resources

    OpenAIRE

    Huser, Vojtech; Del Fiol, Guilherme; Rocha, Roberto A.

    2005-01-01

    Provision of access to reference electronic resources to clinicians is becoming increasingly important. We have created a framework for librarians to manage access to these resources at an enterprise level, rather than at the individual hospital libraries. We describe initial project requirements, implementation details, and some preliminary results.

  9. Euler European Libraries and Electronic Resources in Mathematical Sciences

    CERN Document Server

    The Euler Project. Karlsruhe

    The European Libraries and Electronic Resources (EULER) Project in Mathematical Sciences provides the EulerService site for searching out "mathematical resources such as books, pre-prints, web-pages, abstracts, proceedings, serials, technical reports preprints) and NetLab (for Internet resources), this outstanding engine is capable of simple, full, and refined searches. It also offers a browse option, which responds to entries in the author, keyword, and title fields. Further information about the Project is provided at the EULER homepage.

  10. Building an electronic resource collection a practical guide

    CERN Document Server

    Lee, Stuart D

    2004-01-01

    This practical book guides information professionals step-by-step through building and managing an electronic resource collection. It outlines the range of electronic products currently available in abstracting and indexing, bibliographic, and other services and then describes how to effectively select, evaluate and purchase them.

  11. Organizational matters of competition in electronic educational resources

    Directory of Open Access Journals (Sweden)

    Ирина Карловна Войтович

    2015-12-01

    Full Text Available The article examines the experience of the Udmurt State University in conducting competitions of educational publications and electronic resources. The purpose of such competitions is to provide methodological support to educational process. The main focus is on competition of electronic educational resources. The technology of such contests is discussed through detailed analysis of the main stages of the contest. It is noted that the main task of the preparatory stage of the competition is related to the development of regulations on competition and the definition of criteria for selection of the submitted works. The paper also proposes a system of evaluation criteria of electronic educational resources developed by members of the contest organizing committee and jury members. The article emphasizes the importance of not only the preparatory stages of the competition, but also measures for its completion, aimed at training teachers create quality e-learning resources.

  12. Metals and Neurodegeneration

    Science.gov (United States)

    Chen, Pan; Miah, Mahfuzur Rahman; Aschner, Michael

    2016-01-01

    Metals play important roles in the human body, maintaining cell structure and regulating gene expression, neurotransmission, and antioxidant response, to name a few. However, excessive metal accumulation in the nervous system may be toxic, inducing oxidative stress, disrupting mitochondrial function, and impairing the activity of numerous enzymes. Damage caused by metal accumulation may result in permanent injuries, including severe neurological disorders. Epidemiological and clinical studies have shown a strong correlation between aberrant metal exposure and a number of neurological diseases, including Alzheimer’s disease, amyotrophic lateral sclerosis, autism spectrum disorders, Guillain–Barré disease, Gulf War syndrome, Huntington’s disease, multiple sclerosis, Parkinson’s disease, and Wilson’s disease. Here, we briefly survey the literature relating to the role of metals in neurodegeneration. PMID:27006759

  13. Peptides Against Autoimmune Neurodegeneration.

    Science.gov (United States)

    Stepanov, Alexey; Lomakin, Yakov; Gabibov, Alexander; Belogurov, Alexey

    2017-01-01

    The mammalian immune system is a nearly perfect defensive system polished by a hundred million years of evolution. Unique flexibility and adaptivity have created a virtually impenetrable barrier to numerous exogenous pathogens that are assaulting us every moment. Unfortunately, triggers that remain mostly enigmatic will sometimes persuade the immune system to retarget against self-antigens. This civil war remains underway, showing no mercy and taking no captives, eventually leading to irreversible pathological changes in the human body. Research that has emerged during the last two decades has given us hope that we may have a chance to overcome autoimmune diseases using a variety of techniques to "reset" the immune system. In this report, we summarize recent advances in utilizing short polypeptides - mostly fragments of autoantigens - in the treatment of autoimmune neurodegeneration. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Why and How to Measure the Use of Electronic Resources

    Directory of Open Access Journals (Sweden)

    Jean Bernon

    2008-11-01

    Full Text Available A complete overview of library activity implies a complete and reliable measurement of the use of both electronic resources and printed materials. This measurement is based on three sets of definitions: document types, use types and user types. There is a common model of definitions for printed materials, but a lot of questions and technical issues remain for electronic resources. In 2006 a French national working group studied these questions. It relied on the COUNTER standard, but found it insufficient and pointed out the need for local tools such as web markers and deep analysis of proxy logs. Within the French national consortium COUPERIN, a new working group is testing ERMS, SUSHI standards, Shibboleth authentication, along with COUNTER standards, to improve the counting of the electronic resources use. At this stage this counting is insufficient and its improvement will be a European challenge for the future.

  15. Access to electronic resources by visually impaired people

    Directory of Open Access Journals (Sweden)

    Jenny Craven

    2003-01-01

    Full Text Available Research into access to electronic resources by visually impaired people undertaken by the Centre for Research in Library and Information Management has not only explored the accessibility of websites and levels of awareness in providing websites that adhere to design for all principles, but has sought to enhance understanding of information seeking behaviour of blind and visually impaired people when using digital resources.

  16. Practical guide to electronic resources in the humanities

    CERN Document Server

    Dubnjakovic, Ana

    2010-01-01

    From full-text article databases to digitized collections of primary source materials, newly emerging electronic resources have radically impacted how research in the humanities is conducted and discovered. This book, covering high-quality, up-to-date electronic resources for the humanities, is an easy-to-use annotated guide for the librarian, student, and scholar alike. It covers online databases, indexes, archives, and many other critical tools in key humanities disciplines including philosophy, religion, languages and literature, and performing and visual arts. Succinct overviews of key eme

  17. Discipline, availability of electronic resources and the use of Finnish National Electronic Library - FinELib

    Directory of Open Access Journals (Sweden)

    Sanna Torma

    2004-01-01

    Full Text Available This study elaborated relations between digital library use by university faculty, users' discipline and the availability of key resources in the Finnish National Electronic Library (FinELib, Finnish national digital library, by using nationwide representative survey data. The results show that the perceived availability of key electronic resources by researchers in FinELib was a stronger predictor of the frequency and purpose of use of its services than users' discipline. Regardless of discipline a good perceived provision of central resources led to a more frequent use of FinELib. The satisfaction with the services did not vary with the discipline, but with the perceived availability of resources.

  18. Access to electronic information resources by students of federal ...

    African Journals Online (AJOL)

    The paper discusses access to electronic information resources by students of Federal Colleges of Education in Eha-Amufu and Umunze. Descriptive survey design was used to investigate sample of 526 students. Sampling technique used was a Multi sampling technique. Data for the study were generated using ...

  19. Electronic Commerce Resource Centers. An Industry--University Partnership.

    Science.gov (United States)

    Gulledge, Thomas R.; Sommer, Rainer; Tarimcilar, M. Murat

    1999-01-01

    Electronic Commerce Resource Centers focus on transferring emerging technologies to small businesses through university/industry partnerships. Successful implementation hinges on a strategic operating plan, creation of measurable value for customers, investment in customer-targeted training, and measurement of performance outputs. (SK)

  20. ANALYTICAL REVIEW OF ELECTRONIC RESOURCES FOR THE STUDY OF LATIN

    Directory of Open Access Journals (Sweden)

    Olena Yu. Balalaieva

    2014-04-01

    Full Text Available The article investigates the current state of development of e-learning content in the Latin language. It is noted that the introduction of ICT in the educational space has expanded the possibility of studying Latin, opened access to digital libraries resources, made it possible to use scientific and educational potential and teaching Latin best practices of world's leading universities. A review of foreign and Ukrainian information resources and electronic editions for the study of Latin is given. Much attention was paid to the didactic potential of local and online multimedia courses of Latin, electronic textbooks, workbooks of interactive tests and exercises, various dictionaries and software translators, databases and digital libraries. Based on analysis of the world market of educational services and products the main trends in the development of information resources and electronic books are examined. It was found that multimedia courses with interactive exercises or workbooks with interactive tests, online dictionaries and translators are the most widely represented and demanded. The noticeable lagging of Ukrainian education and computer linguistics in quantitative and qualitative measures in this industry is established. The obvious drawback of existing Ukrainian resources and electronic editions for the study of Latin is their noninteractive nature. The prospects of e-learning content in Latin in Ukraine are outlined.

  1. Adoption and use of electronic information resources by medical ...

    African Journals Online (AJOL)

    This study investigated the adoption and use of electronic information resources by medical science students of the University of Benin. The descriptive survey research design was adopted for the study and 390 students provided the data. Data collected were analysed with descriptive Statistics(Simple percentage and ...

  2. Modern ICT Tools: Online Electronic Resources Sharing Using Web ...

    African Journals Online (AJOL)

    Modern ICT Tools: Online Electronic Resources Sharing Using Web 2.0 and Its Implications For Library And Information Practice In Nigeria. ... The PDF file you selected should load here if your Web browser has a PDF reader plug-in installed (for example, a recent version of Adobe Acrobat Reader). If you would like more ...

  3. Technical Communicator: A New Model for the Electronic Resources Librarian?

    Science.gov (United States)

    Hulseberg, Anna

    2016-01-01

    This article explores whether technical communicator is a useful model for electronic resources (ER) librarians. The fields of ER librarianship and technical communication (TC) originated and continue to develop in relation to evolving technologies. A review of the literature reveals four common themes for ER librarianship and TC. While the…

  4. MODEL OF AN ELECTRONIC EDUCATIONAL RESOURCE OF NEW GENERATION

    Directory of Open Access Journals (Sweden)

    Anatoliy V. Loban

    2016-01-01

    Full Text Available The mathematical structure of the modular architecture of an electronic educational resource (EER of new generation, which allows to decompose the process of studying the subjects of the course at a hierarchically ordered set of data (knowledge and procedures for manipulating them, to determine the roles of participants of process of training of and technology the development and use of EOR in the study procrate.

  5. Neurodegeneration in the diabetic eye

    DEFF Research Database (Denmark)

    Simó, Rafael; Hernández, Cristina; Bandello, F

    2014-01-01

    Diabetic retinopathy (DR), one of the leading causes of preventable blindness, has been considered a microcirculatory disease of the retina. However, there is emerging evidence to suggest that retinal neurodegeneration is an early event in the pathogenesis of DR, which participates in the develop...

  6. Initiation and propagation of neurodegeneration.

    Science.gov (United States)

    Haass, Christian

    2010-11-01

    Although substantial progress has been made in understanding the molecular and pathological bases of neurodegeneration, there have been few successes in the clinic and a number of fundamental questions remain unanswered. Is this skepticism misplaced, or do the words of Sir Isaac Newton hold true, that "what we know is a drop, what we don't know is an ocean"?

  7. Genetic pathways to Neurodegeneration

    Indian Academy of Sciences (India)

    Renu

    The extensive resource on ataxia has led to the development of a clinico-genetic ... Keywords: Cerebellar ataxias, SCAs, ARCAs, NGS, Gene network, iPSCs, .... Besides, mutations in different regions of the same gene result in different ..... integration with population data can also allow focussed testing/screening in specific.

  8. End-of-life resource recovery from emerging electronic products

    DEFF Research Database (Denmark)

    Parajuly, Keshav; Habib, Komal; Cimpan, Ciprian

    2016-01-01

    Integrating product design with appropriate end-of-life (EoL) processing is widely recognized to have huge potentials in improving resource recovery from electronic products. In this study, we investigate both the product characteristics and EoL processing of robotic vacuum cleaner (RVC), as a case...... of emerging electronic product, in order to understand the recovery fate of different materials and its linkage to product design. Ten different brands of RVC were dismantled and their material composition and design profiles were studied. Another 125 RVCs (349 kg) were used for an experimental trial...... at a conventional ‘shred-and-separate’ type preprocessing plant in Denmark. A detailed material flow analysis was performed throughout the recycling chain. The results show a mismatch between product design and EoL processing, and the lack of practical implementation of ‘Design for EoL’ thinking. In the best...

  9. Analysis of Human Resources Management Strategy in China Electronic Commerce Enterprises

    Science.gov (United States)

    Shao, Fang

    The paper discussed electronic-commerce's influence on enterprise human resources management, proposed and proved the human resources management strategy which electronic commerce enterprise should adopt from recruitment strategy to training strategy, keeping talent strategy and other ways.

  10. Effects of Electronic Information Resources Skills Training for Lecturers on Pedagogical Practices and Research Productivity

    Science.gov (United States)

    Bhukuvhani, Crispen; Chiparausha, Blessing; Zuvalinyenga, Dorcas

    2012-01-01

    Lecturers use various electronic resources at different frequencies. The university library's information literacy skills workshops and seminars are the main sources of knowledge of accessing electronic resources. The use of electronic resources can be said to have positively affected lecturers' pedagogical practices and their work in general. The…

  11. Electronic Resources and Mission Creep: Reorganizing the Library for the Twenty-First Century

    Science.gov (United States)

    Stachokas, George

    2009-01-01

    The position of electronic resources librarian was created to serve as a specialist in the negotiation of license agreements for electronic resources, but mission creep has added more functions to the routine work of electronic resources such as cataloging, gathering information for collection development, and technical support. As electronic…

  12. Electronic Document Management: A Human Resource Management Case Study

    Directory of Open Access Journals (Sweden)

    Thomas Groenewald

    2004-11-01

    Full Text Available This case study serve as exemplar regarding what can go wrong with the implementation of an electronic document management system. Knowledge agility and knowledge as capital, is outlined against the backdrop of the information society and knowledge economy. The importance of electronic document management and control is sketched thereafter. The literature review is concluded with the impact of human resource management on knowledge agility, which includes references to the learning organisation and complexity theory. The intervention methodology, comprising three phases, follows next. The results of the three phases are presented thereafter. Partial success has been achieved with improving the human efficacy of electronic document management, however the client opted to discontinue the system in use. Opsomming Die gevalle studie dien as voorbeeld van wat kan verkeerd loop met die implementering van ’n elektroniese dokumentbestuur sisteem. Teen die agtergrond van die inligtingsgemeenskap en kennishuishouding word kennissoepelheid en kennis as kapitaal bespreek. Die literatuurstudie word afgesluit met die inpak van menslikehulpbronbestuur op kennissoepelheid, wat ook die verwysings na die leerorganisasie en kompleksietydsteorie insluit. Die metodologie van die intervensie, wat uit drie fases bestaan, volg daarna. Die resultate van die drie fases word vervolgens aangebied. Slegs gedeelte welslae is behaal met die verbetering van die menslike doeltreffendheid ten opsigte van elektroniese dokumentbestuur. Die klient besluit egter om nie voort te gaan om die huidige sisteem te gebruik nie.

  13. Temporal dynamics of hippocampal neurogenesis in chronic neurodegeneration

    Science.gov (United States)

    Suzzi, Stefano; Vargas-Caballero, Mariana; Fransen, Nina L.; Al-Malki, Hussain; Cebrian-Silla, Arantxa; Garcia-Verdugo, Jose Manuel; Riecken, Kristoffer; Fehse, Boris; Perry, V. Hugh

    2014-01-01

    The study of neurogenesis during chronic neurodegeneration is crucial in order to understand the intrinsic repair mechanisms of the brain, and key to designing therapeutic strategies. In this study, using an experimental model of progressive chronic neurodegeneration, murine prion disease, we define the temporal dynamics of the generation, maturation and integration of new neurons in the hippocampal dentate gyrus, using dual pulse-chase, multicolour γ-retroviral tracing, transmission electron microscopy and patch-clamp. We found increased neurogenesis during the progression of prion disease, which partially counteracts the effects of chronic neurodegeneration, as evidenced by blocking neurogenesis with cytosine arabinoside, and helps to preserve the hippocampal function. Evidence obtained from human post-mortem samples, of both variant Creutzfeldt-Jakob disease and Alzheimer’s disease patients, also suggests increased neurogenic activity. These results open a new avenue into the exploration of the effects and regulation of neurogenesis during chronic neurodegeneration, and offer a new model to reproduce the changes observed in human neurodegenerative diseases. PMID:24941947

  14. Electronic Safety Resource Tools -- Supporting Hydrogen and Fuel Cell Commercialization

    Energy Technology Data Exchange (ETDEWEB)

    Barilo, Nick F.

    2014-09-29

    The Pacific Northwest National Laboratory (PNNL) Hydrogen Safety Program conducted a planning session in Los Angeles, CA on April 1, 2014 to consider what electronic safety tools would benefit the next phase of hydrogen and fuel cell commercialization. A diverse, 20-person team led by an experienced facilitator considered the question as it applied to the eight most relevant user groups. The results and subsequent evaluation activities revealed several possible resource tools that could greatly benefit users. The tool identified as having the greatest potential for impact is a hydrogen safety portal, which can be the central location for integrating and disseminating safety information (including most of the tools identified in this report). Such a tool can provide credible and reliable information from a trustworthy source. Other impactful tools identified include a codes and standards wizard to guide users through a series of questions relating to application and specific features of the requirements; a scenario-based virtual reality training for first responders; peer networking tools to bring users from focused groups together to discuss and collaborate on hydrogen safety issues; and a focused tool for training inspectors. Table ES.1 provides results of the planning session, including proposed new tools and changes to existing tools.

  15. Controlling user access to electronic resources without password

    Science.gov (United States)

    Smith, Fred Hewitt

    2015-06-16

    Described herein are devices and techniques for remotely controlling user access to a restricted computer resource. The process includes pre-determining an association of the restricted computer resource and computer-resource-proximal environmental information. Indicia of user-proximal environmental information are received from a user requesting access to the restricted computer resource. Received indicia of user-proximal environmental information are compared to associated computer-resource-proximal environmental information. User access to the restricted computer resource is selectively granted responsive to a favorable comparison in which the user-proximal environmental information is sufficiently similar to the computer-resource proximal environmental information. In at least some embodiments, the process further includes comparing user-supplied biometric measure and comparing it with a predetermined association of at least one biometric measure of an authorized user. Access to the restricted computer resource is granted in response to a favorable comparison.

  16. DNA repair deficiency in neurodegeneration

    DEFF Research Database (Denmark)

    Jeppesen, Dennis Kjølhede; Bohr, Vilhelm A; Stevnsner, Tinna V.

    2011-01-01

    Deficiency in repair of nuclear and mitochondrial DNA damage has been linked to several neurodegenerative disorders. Many recent experimental results indicate that the post-mitotic neurons are particularly prone to accumulation of unrepaired DNA lesions potentially leading to progressive...... neurodegeneration. Nucleotide excision repair is the cellular pathway responsible for removing helix-distorting DNA damage and deficiency in such repair is found in a number of diseases with neurodegenerative phenotypes, including Xeroderma Pigmentosum and Cockayne syndrome. The main pathway for repairing oxidative...... base lesions is base excision repair, and such repair is crucial for neurons given their high rates of oxygen metabolism. Mismatch repair corrects base mispairs generated during replication and evidence indicates that oxidative DNA damage can cause this pathway to expand trinucleotide repeats, thereby...

  17. Unconventional neurotransmitters, neurodegeneration and neuroprotection

    Directory of Open Access Journals (Sweden)

    M. Leonelli

    2009-01-01

    Full Text Available Neurotransmitters are also involved in functions other than conventional signal transfer between nerve cells, such as development, plasticity, neurodegeneration, and neuroprotection. For example, there is a considerable amount of data indicating developmental roles for the glutamatergic, cholinergic, dopaminergic, GABA-ergic, and ATP/adenosine systems. In this review, we discuss the existing literature on these "new" functions of neurotransmitters in relation to some unconventional neurotransmitters, such as the endocannabinoids and nitric oxide. Data indicating both transcriptional and post-transcriptional modulation of endocannabinoid and nitrinergic systems after neural lesions are discussed in relation to the non-conventional roles of these neurotransmitters. Knowledge of the roles of neurotransmitters in brain functions other than information transfer is critical for a more complete understanding of the functional organization of the brain and to provide more opportunities for the development of therapeutical tools aimed at minimizing neuronal death.

  18. The Internet School of Medicine: use of electronic resources by medical trainees and the reliability of those resources.

    Science.gov (United States)

    Egle, Jonathan P; Smeenge, David M; Kassem, Kamal M; Mittal, Vijay K

    2015-01-01

    Electronic sources of medical information are plentiful, and numerous studies have demonstrated the use of the Internet by patients and the variable reliability of these sources. Studies have investigated neither the use of web-based resources by residents, nor the reliability of the information available on these websites. A web-based survey was distributed to surgical residents in Michigan and third- and fourth-year medical students at an American allopathic and osteopathic medical school and a Caribbean allopathic school regarding their preferred sources of medical information in various situations. A set of 254 queries simulating those faced by medical trainees on rounds, on a written examination, or during patient care was developed. The top 5 electronic resources cited by the trainees were evaluated for their ability to answer these questions accurately, using standard textbooks as the point of reference. The respondents reported a wide variety of overall preferred resources. Most of the 73 responding medical trainees favored textbooks or board review books for prolonged studying, but electronic resources are frequently used for quick studying, clinical decision-making questions, and medication queries. The most commonly used electronic resources were UpToDate, Google, Medscape, Wikipedia, and Epocrates. UpToDate and Epocrates had the highest percentage of correct answers (47%) and Wikipedia had the lowest (26%). Epocrates also had the highest percentage of wrong answers (30%), whereas Google had the lowest percentage (18%). All resources had a significant number of questions that they were unable to answer. Though hardcopy books have not been completely replaced by electronic resources, more than half of medical students and nearly half of residents prefer web-based sources of information. For quick questions and studying, both groups prefer Internet sources. However, the most commonly used electronic resources fail to answer clinical queries more than half

  19. Developing Humanities Collections in the Digital Age: Exploring Humanities Faculty Engagement with Electronic and Print Resources

    Science.gov (United States)

    Kachaluba, Sarah Buck; Brady, Jessica Evans; Critten, Jessica

    2014-01-01

    This article is based on quantitative and qualitative research examining humanities scholars' understandings of the advantages and disadvantages of print versus electronic information resources. It explores how humanities' faculty members at Florida State University (FSU) use print and electronic resources, as well as how they perceive these…

  20. Electronic resource management practical perspectives in a new technical services model

    CERN Document Server

    Elguindi, Anne

    2012-01-01

    A significant shift is taking place in libraries, with the purchase of e-resources accounting for the bulk of materials spending. Electronic Resource Management makes the case that technical services workflows need to make a corresponding shift toward e-centric models and highlights the increasing variety of e-formats that are forcing new developments in the field.Six chapters cover key topics, including: technical services models, both past and emerging; staffing and workflow in electronic resource management; implementation and transformation of electronic resource management systems; the ro

  1. Mechanism of Neurodegeneration Following Viral Infection

    National Research Council Canada - National Science Library

    Maheshwari, Radha

    2001-01-01

    The long term goal of this proposal is to delineate the mechanism(s) for neurodegeneration and neuropathogenesis following infection with a neurovirulent virus, Venezuelan equine encephalitis virus (VEE...

  2. Electronic resources access and usage among the postgraduates of ...

    African Journals Online (AJOL)

    ... and usage among the postgraduates of a Nigerian University of Technology. ... faced by postgraduates in using e-resources include takes too much time to find, ... Resources, Access, Use, Postgraduat, Students, University, Technology, Nigeria ... By Country · List All Titles · Free To Read Titles This Journal is Open Access.

  3. Strategic Planning for Electronic Resources Management: A Case Study at Gustavus Adolphus College

    Science.gov (United States)

    Hulseberg, Anna; Monson, Sarah

    2009-01-01

    Electronic resources, the tools we use to manage them, and the needs and expectations of our users are constantly evolving; at the same time, the roles, responsibilities, and workflow of the library staff who manage e-resources are also in flux. Recognizing a need to be more intentional and proactive about how we manage e-resources, the…

  4. Natural Products Combating Neurodegeneration: Parkinson's Disease.

    Science.gov (United States)

    Solayman, Md; Islam, Md Asiful; Alam, Fahmida; Khalil, Md Ibrahim; Kamal, Mohammad Amjad; Gan, Siew Hua

    2017-01-01

    Parkinson's disease (PD) is characterized by neurodegeneration and a progressive functional impairment of the midbrain nigral dopaminergic neurons. The cause remains unknown; however, several pathological processes and central factors, such as protein aggregation, mitochondrial dysfunction, iron accumulation, neuroinflammation and oxidative stress, have been reported. The current treatment method primarily targets symptoms by using anti-Parkinson drugs such as levodopa, carbidopa, dopamine (DA) agonists, monoamine oxidase type B inhibitors and anticholinergics to replace DA. When drug therapy is not satisfactory, surgical treatments are recommended. Unfortunately, the existing conventional strategies that target PD are associated with numerous side effects and possess an economic burden. Therefore, novel therapeutic approaches that regulate the pathways leading to neuronal death and dysfunction are necessary. For many years, nature has provided the primary resource for the discovery of potential therapeutic agents. Remarkably, many natural products from medicinal plants, fruits and vegetables have been demonstrated to be efficacious anti-Parkinson agents. These products possess neuroprotective properties as a result of not only their wellrecognized anti-oxidative and anti-inflammatory activities but also their inhibitory roles regarding iron accumulation, protein misfolding and the maintenance of proteasomal degradation, as well as mitochondrial homeostasis. The aim of this review is to report the available anti-Parkinson agents based on natural products and delineate their therapeutic actions, which act on various pathways. Overall, this review emphasizes the types of natural products that are potential future resources in the treatment of PD as novel regimens or supplementary agents. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. impact of the use of electronic resources on research output

    African Journals Online (AJOL)

    manda

    ... Julita Nawe. University of Dar Es Salaam Library, P.O. Box 35092, Dar Es Salaam, Tanzania .... significantly, while 28.3% observed that quality of service to the community had improved .... resources and evaluate them is an important area.

  6. Preservation of and Permanent Access to Electronic Information Resources

    National Research Council Canada - National Science Library

    Hodge, Gail

    2004-01-01

    The rapid growth in the creation and dissemination of electronic information has emphasized the digital environment's speed and ease of dissemination with little regard for its long-term preservation and access...

  7. Electronic conferencing for continuing medical education: a resource survey.

    Science.gov (United States)

    Sternberg, R J

    1986-10-01

    The use of electronic technologies to link participants for education conferences is an option for providers of Continuing Medical Education. In order to profile the kinds of electronic networks currently offering audio- or videoteleconferences for physician audiences, a survey was done during late 1985. The information collected included range of services, fees, and geographic areas served. The results show a broad diversity of providers providing both interactive and didactic programming to both physicians and other health care professionals.

  8. Controlling user access to electronic resources without password

    Science.gov (United States)

    Smith, Fred Hewitt

    2017-08-22

    Described herein are devices and techniques for remotely controlling user access to a restricted computer resource. The process includes obtaining an image from a communication device of a user. An individual and a landmark are identified within the image. Determinations are made that the individual is the user and that the landmark is a predetermined landmark. Access to a restricted computing resource is granted based on the determining that the individual is the user and that the landmark is the predetermined landmark. Other embodiments are disclosed.

  9. Electron beam pasteurised oil palm waste: a potential feed resource

    International Nuclear Information System (INIS)

    Mat Rasol Awang; Hassan Hamdani Mutaat; Tamikazu Kume; Tachibana, H.

    2002-01-01

    Pasteurization of oil palm empty fruit bunch (EFB) was performed using electron beam single sided irradiation. The dose profiles of oil palm EFB samples for different thickness in both directions X and Y were established. The results showed the usual characteristics dose uniformity as sample thickness decreased. The mean average absorbed dose on both sides at the surface and bottom of the samples for different thickness samples lead to establishing depth dose curve. Based on depth dose curve and operation conditions of electron beam machine, the process throughput for pasteurized oil palm EFB were estimated. (Author)

  10. Availability of Electronic Resources for Service Provision in ...

    African Journals Online (AJOL)

    The study also revealed that majority of the University libraries have adequate basic infrastructure for effective electronic information services. ... acquired by the library are put into maximal use by the library clientele, thereby ensuring the achievement of the library's objective which is satisfying the users, information needs.

  11. Utilization of bio-resources by low energy electron beam

    International Nuclear Information System (INIS)

    Kume, Tamikazu

    2003-01-01

    Utilization of bio-resources by radiation has been investigated for recycling the natural resources and reducing the environmental pollution. Polysaccharides such as chitosan and sodium alginate were easily degraded by irradiation and induced various kinds of biological activities, i.g. anti-microbial activity, promotion of plant growth, suppression of heavy metal stress, phytoalexins induction. Radiation degraded chitosan was effective to enhance the growth of plants in tissue culture. It was demonstrated that the liquid sample irradiation system using low energy EB was effective for the preparation of degraded polysaccharides. Methylcellulose (MC) can be crosslinked under certain radiation condition as same as carboxymethylcellulose (CMC) and produced the biodegradable hydrogel for medical and agricultural use. Treatment of soybean seeds by low energy EB enhanced the growth and the number of rhizobia on the root. (author)

  12. Analysis of Pedagogic Potential of Electronic Educational Resources with Elements of Autodidactics

    Directory of Open Access Journals (Sweden)

    Igor A.

    2018-03-01

    Full Text Available Introduction: in recent years didactic properties of electronic educational resources undergo considerable changes, nevertheless, the question of studying of such complete phenomenon as “an electronic educational resource with autodidactics elements” remains open, despite sufficient scientific base of researches of the terms making this concept. Article purpose – determination of essence of electronic educational resources with autodidactics elements. Materials and Methods: the main method of research was the theoretical analysis of the pedagogical and psychological literature on the problem under study. We used the theoretical (analysis, synthesis, comparison and generalization methods, the method of interpretation, pedagogical modeling, and empirical methods (observation, testing, conversation, interview, analysis of students’ performance, pedagogical experiment, peer review. Results: we detected the advantages of electronic educational resources in comparison with traditional ones. The concept of autodidactics as applied to the subject of research is considered. Properties of electronic educational resources with a linear and nonlinear principle of construction are studied.The influence of the principle of construction on the development of the learners’ qualities is shown. We formulated an integral definition of electronic educational resources with elements of autodidactics, namely, the variability, adaptivity and cyclicity of training. A model of the teaching-learning process with electronic educational resources is developed. Discussion and Conclusions: further development of a problem will allow to define whether electronic educational resources with autodidactics elements pedagogical potential for realization of educational and self-educational activity of teachers have, to modify technological procedures taking into account age features of students, their specialties and features of the organization of process of training of

  13. A Study on Developing Evaluation Criteria for Electronic Resources in Evaluation Indicators of Libraries

    Science.gov (United States)

    Noh, Younghee

    2010-01-01

    This study aimed to improve the current state of electronic resource evaluation in libraries. While the use of Web DB, e-book, e-journal, and other e-resources such as CD-ROM, DVD, and micro materials is increasing in libraries, their use is not comprehensively factored into the general evaluation of libraries and may diminish the reliability of…

  14. Managing Selection for Electronic Resources: Kent State University Develops a New System to Automate Selection

    Science.gov (United States)

    Downey, Kay

    2012-01-01

    Kent State University has developed a centralized system that manages the communication and work related to the review and selection of commercially available electronic resources. It is an automated system that tracks the review process, provides selectors with price and trial information, and compiles reviewers' feedback about the resource. It…

  15. Where Do Electronic Books Fit in the College Research Arsenal of Resources?

    Science.gov (United States)

    Barbier, Patricia

    2007-01-01

    Student use of electronic books has become an accepted supplement to traditional resources. Student use and satisfaction was monitored through an online course discussion board. Increased use of electronic books indicate this service is an accepted supplement to the print book collection.

  16. The National Site Licensing of Electronic Resources: An Institutional Perspective

    Directory of Open Access Journals (Sweden)

    Xiaohua Zhu

    2011-06-01

    Full Text Available While academic libraries in most countries are struggling to negotiate with publishers and vendors individually or collaboratively via consortia, a few countries have experimented with a different model, national site licensing (NSL. Because NSL often involves government and large-scale collaboration, it has the potential to solve many problems in the complex licensing world. However, not many nations have adopted it. This study uses historical research approach and the comparative case study research method to explore the seemingly low level of adoption. The cases include the Canadian National Site Licensing Project (CNSLP, the United Kingdom’s National Electronic Site Licensing Initiative (NESLI, and the United States, which has not adopted NSL. The theoretical framework guiding the research design and data collection is W. Richard Scott’s institutional theory, which utilizes three supporting pillars—regulative, normative, and cultural-cognitive—to analyze institutional processes. In this study, the regulative pillar and the normative pillar of NSL adoption— an institutional construction and change—are examined. Data were collected from monographs, research articles, government documents, and relevant websites. Based on the analysis of these cases, a preliminary model is proposed for the adoption of NSL. The factors that support a country’s adoption of NSL include the need for new institutions, a centralized educational policy-making system and funding system, supportive political trends, and the tradition of cooperation. The factors that may prevent a country from adopting NSL include decentralized educational policy and funding, diversity and the large number of institutions, the concern for the “Big Deal,” and the concern for monopoly.

  17. A survey of the use of electronic scientific information resources among medical and dental students

    Directory of Open Access Journals (Sweden)

    Aarnio Matti

    2006-05-01

    Full Text Available Abstract Background To evaluate medical and dental students' utilization of electronic information resources. Methods A web survey sent to 837 students (49.9% responded. Results Twenty-four per cent of medical students and ninteen per cent of dental students searched MEDLINE 2+ times/month for study purposes, and thiry-two per cent and twenty-four per cent respectively for research. Full-text articles were used 2+ times/month by thirty-three per cent of medical and ten per cent of dental students. Twelve per cent of respondents never utilized either MEDLINE or full-text articles. In multivariate models, the information-searching skills among students were significantly associated with use of MEDLINE and full-text articles. Conclusion Use of electronic resources differs among students. Forty percent were non-users of full-text articles. Information-searching skills are correlated with the use of electronic resources, but the level of basic PC skills plays not a major role in using these resources. The student data shows that adequate training in information-searching skills will increase the use of electronic information resources.

  18. Analytical Study of Usage of Electronic Information Resources at Pharmacopoeial Libraries in India

    Directory of Open Access Journals (Sweden)

    Sunil Tyagi

    2014-02-01

    Full Text Available The objective of this study is to know the rate and purpose of the use of e-resource by the scientists at pharmacopoeial libraries in India. Among other things, this study examined the preferences of the scientists toward printed books and journals, electronic information resources, and pattern of using e-resources. Non-probability sampling specially accidental and purposive technique was applied in the collection of primary data through administration of user questionnaire. The sample respondents chosen for the study consists of principle scientific officer, senior scientific officer, scientific officer, and scientific assistant of different division of the laboratories, namely, research and development, pharmaceutical chemistry, pharmacovigilance, pharmacology, pharmacogonosy, and microbiology. The findings of the study reveal the personal experiences and perceptions they have had on practice and research activity using e-resource. The major findings indicate that of the total anticipated participants, 78% indicated that they perceived the ability to use computer for electronic information resources. The data analysis shows that all the scientists belonging to the pharmacopoeial libraries used electronic information resources to address issues relating to drug indexes and compendia, monographs, drugs obtained through online databases, e-journals, and the Internet sources—especially polices by regulatory agencies, contacts, drug promotional literature, and standards.

  19. Parkinson’s disease managing reversible neurodegeneration

    Science.gov (United States)

    Hinz, Marty; Stein, Alvin; Cole, Ted; McDougall, Beth; Westaway, Mark

    2016-01-01

    Traditionally, the Parkinson’s disease (PD) symptom course has been classified as an irreversible progressive neurodegenerative disease. This paper documents 29 PD and treatment-induced systemic depletion etiologies which cause and/or exacerbate the seven novel primary relative nutritional deficiencies associated with PD. These reversible relative nutritional deficiencies (RNDs) may facilitate and accelerate irreversible progressive neurodegeneration, while other reversible RNDs may induce previously undocumented reversible pseudo-neurodegeneration that is hiding in plain sight since the symptoms are identical to the symptoms being experienced by the PD patient. Documented herein is a novel nutritional approach for reversible processes management which may slow or halt irreversible progressive neurodegenerative disease and correct reversible RNDs whose symptoms are identical to the patient’s PD symptoms. PMID:27103805

  20. Considering Point-of-Care Electronic Medical Resources in Lieu of Traditional Textbooks for Medical Education.

    Science.gov (United States)

    Hale, LaDonna S; Wallace, Michelle M; Adams, Courtney R; Kaufman, Michelle L; Snyder, Courtney L

    2015-09-01

    Selecting resources to support didactic courses is a critical decision, and the advantages and disadvantages must be carefully considered. During clinical rotations, students not only need to possess strong background knowledge but also are expected to be proficient with the same evidence-based POC resources used by clinicians. Students place high value on “real world” learning and therefore may place more value on POC resources that they know practicing clinicians use as compared with medical textbooks. The condensed nature of PA education requires students to develop background knowledge and information literacy skills over a short period. One way to build that knowledge and those skills simultaneously is to use POC resources in lieu of traditional medical textbooks during didactic training. Electronic POC resources offer several advantages over traditional textbooks and should be considered as viable options in PA education.

  1. Elektronik Bilgi Kaynaklarının Seçimi / Selection of Electronic Information Resources

    Directory of Open Access Journals (Sweden)

    Pınar Al

    2003-04-01

    Full Text Available For many years, library users have used only from the printed media in order to get the information that they have needed. Today with the widespread use of the Web and the addition of electronic information resources to library collections, the use of information in the electronic environment as well as in printed media is started to be used. In time, such types of information resources as, electronic journals, electronic books, electronic encyclopedias, electronic dictionaries and electronic theses have been added to library collections. In this study, selection criteria that can be used for electronic information resources are discussed and suggestions are provided for libraries that try to select electronic information resources for their collections.

  2. Parkinson’s disease managing reversible neurodegeneration

    Directory of Open Access Journals (Sweden)

    Hinz M

    2016-04-01

    Full Text Available Marty Hinz,1 Alvin Stein,2 Ted Cole,3 Beth McDougall,4 Mark Westaway5 1Clinical Research, NeuroResearch Clinics, Inc., Cape Coral, FL, 2Stein Orthopedic Associates, Plantation, FL, 3Cole Center for Healing, Cincinnati, OH, 4CLEARCenter of Health, Mill Valley, CA, USA; 5Four Pillars Health, Brendale, QLD, Australia Abstract: Traditionally, the Parkinson’s disease (PD symptom course has been classified as an irreversible progressive neurodegenerative disease. This paper documents 29 PD and treatment-induced systemic depletion etiologies which cause and/or exacerbate the seven novel primary relative nutritional deficiencies associated with PD. These reversible relative nutritional deficiencies (RNDs may facilitate and accelerate irreversible progressive neurodegeneration, while other reversible RNDs may induce previously undocumented reversible pseudo-neurodegeneration that is hiding in plain sight since the symptoms are identical to the symptoms being experienced by the PD patient. Documented herein is a novel nutritional approach for reversible processes management which may slow or halt irreversible progressive neurodegenerative disease and correct reversible RNDs whose symptoms are identical to the patient’s PD symptoms. Keywords: Parkinson’s disease, L-dopa, carbidopa, B6, neurodegeneration

  3. Intracellular Cholesterol Trafficking and Impact in Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Fabian Arenas

    2017-11-01

    Full Text Available Cholesterol is a critical component of membrane bilayers where it plays key structural and functional roles by regulating the activity of diverse signaling platforms and pathways. Particularly enriched in brain, cholesterol homeostasis in this organ is singular with respect to other tissues and exhibits a heterogeneous regulation in distinct brain cell populations. Due to the key role of cholesterol in brain physiology and function, alterations in cholesterol homeostasis and levels have been linked to brain diseases and neurodegeneration. In the case of Alzheimer disease (AD, however, this association remains unclear with evidence indicating that either increased or decreased total brain cholesterol levels contribute to this major neurodegenerative disease. Here, rather than analyzing the role of total cholesterol levels in neurodegeneration, we focus on the contribution of intracellular cholesterol pools, particularly in endolysosomes and mitochondria through its trafficking via specialized membrane domains delineated by the contacts between endoplasmic reticulum and mitochondria, in the onset of prevalent neurodegenerative diseases such as AD, Parkinson disease, and Huntington disease as well as in lysosomal disorders like Niemann-Pick type C disease. We dissect molecular events associated with intracellular cholesterol accumulation, especially in mitochondria, an event that results in impaired mitochondrial antioxidant defense and function. A better understanding of the mechanisms involved in the distribution of cholesterol in intracellular compartments may shed light on the role of cholesterol homeostasis disruption in neurodegeneration and may pave the way for specific intervention opportunities.

  4. Use of electronic sales data to tailor nutrition education resources for an ethnically diverse population.

    Science.gov (United States)

    Eyles, H; Rodgers, A; Ni Mhurchu, C

    2010-02-01

    Nutrition education may be most effective when personally tailored. Individualised electronic supermarket sales data offer opportunities to tailor nutrition education using shopper's usual food purchases. The present study aimed to use individualised electronic supermarket sales data to tailor nutrition resources for an ethnically diverse population in a large supermarket intervention trial in New Zealand. Culturally appropriate nutrition education resources (i.e. messages and shopping lists) were developed with the target population (through two sets of focus groups) and ethnic researchers. A nutrient database of supermarket products was developed using retrospective sales data and linked to participant sales to allow tailoring by usual food purchases. Modified Heart Foundation Tick criteria were used to identify 'healthier' products in the database suitable for promotion in the resources. Rules were developed to create a monthly report listing the tailored and culturally targeted messages to be sent to each participant, and to produce automated, tailored shopping lists. Culturally targeted nutrition messages (n = 864) and shopping lists (n = 3 formats) were developed. The food and nutrient database (n = 3000 top-selling products) was created using 12 months of retrospective sales data, and comprised 60%'healthier' products. Three months of baseline sales data were used to determine usual food purchases. Tailored resources were successfully mailed to 123 Māori, 52 Pacific and 346 non-Māori non-Pacific participants over the 6-month trial intervention period. Electronic supermarket sales data can be used to tailor nutrition education resources for a large number of ethnically diverse supermarket shoppers.

  5. REVIEW OF MOODLE PLUGINS FOR DESIGNING MULTIMEDIA ELECTRONIC EDUCATIONAL RESOURCES FROM LANGUAGE DISCIPLINES

    Directory of Open Access Journals (Sweden)

    Anton M. Avramchuk

    2015-09-01

    Full Text Available Today the problem of designing multimedia electronic educational resources from language disciplines in Moodle is very important. This system has a lot of different, powerful resources, plugins to facilitate the learning of students with language disciplines. This article presents an overview and comparative analysis of the five Moodle plugins for designing multimedia electronic educational resources from language disciplines. There have been considered their key features and functionality in order to choose the best for studying language disciplines in the Moodle. Plugins are compared by a group of experts according to the criteria: efficiency, functionality and easy use. For a comparative analysis of the plugins it is used the analytic hierarchy process.

  6. Effects of the Use of Electronic Human Resource Management (EHRM Within Human Resource Management (HRM Functions at Universities

    Directory of Open Access Journals (Sweden)

    Chux Gervase Iwu

    2016-09-01

    Full Text Available This study set out to examine the effect of e-hrm systems in assisting human resource practitioners to execute their duties and responsibilities. In comparison to developed economies of the world, information technology adoption in sub-Saharan Africa has not been without certain glitches. Some of the factors that are responsible for these include poor need identification, sustainable funding, and insufficient skills. Besides these factors, there is also the issue of change management and users sticking to what they already know. Although, the above factors seem negative, there is strong evidence that information systems such as electronic human resource management present benefits to an organization. To achieve this, a dual research approach was utilized. Literature assisted immensely in both the development of the conceptual framework upon which the study hinged as well as in the development of the questionnaire items. The study also made use of an interview checklist to guide the participants. The findings reveal a mix of responses that indicate that while there are gains in adopting e-hrm systems, it is wiser to consider supporting resources as well as articulate the needs of the university better before any investment is made.

  7. The Electron Microscopy Outreach Program: A Web-based resource for research and education.

    Science.gov (United States)

    Sosinsky, G E; Baker, T S; Hand, G; Ellisman, M H

    1999-01-01

    We have developed a centralized World Wide Web (WWW)-based environment that serves as a resource of software tools and expertise for biological electron microscopy. A major focus is molecular electron microscopy, but the site also includes information and links on structural biology at all levels of resolution. This site serves to help integrate or link structural biology techniques in accordance with user needs. The WWW site, called the Electron Microscopy (EM) Outreach Program (URL: http://emoutreach.sdsc.edu), provides scientists with computational and educational tools for their research and edification. In particular, we have set up a centralized resource containing course notes, references, and links to image analysis and three-dimensional reconstruction software for investigators wanting to learn about EM techniques either within or outside of their fields of expertise. Copyright 1999 Academic Press.

  8. Identifying and evaluating electronic learning resources for use in adult-gerontology nurse practitioner education.

    Science.gov (United States)

    Thompson, Hilaire J; Belza, Basia; Baker, Margaret; Christianson, Phyllis; Doorenbos, Ardith; Nguyen, Huong

    2014-01-01

    Enhancing existing curricula to meet newly published adult-gerontology advanced practice registered nurse (APRN) competencies in an efficient manner presents a challenge to nurse educators. Incorporating shared, published electronic learning resources (ELRs) in existing or new courses may be appropriate in order to assist students in achieving competencies. The purposes of this project were to (a) identify relevant available ELR for use in enhancing geriatric APRN education and (b) to evaluate the educational utility of identified ELRs based on established criteria. A multilevel search strategy was used. Two independent team members reviewed identified ELR against established criteria to ensure utility. Only resources meeting all criteria were retained. Resources were found for each of the competency areas and included formats such as podcasts, Web casts, case studies, and teaching videos. In many cases, resources were identified using supplemental strategies and not through traditional search or search of existing geriatric repositories. Resources identified have been useful to advanced practice educators in improving lecture and seminar content in a particular topic area and providing students and preceptors with additional self-learning resources. Addressing sustainability within geriatric APRN education is critical for sharing of best practices among educators and for sustainability of teaching and related resources. © 2014.

  9. USE OF ELECTRONIC EDUCATIONAL RESOURCES WHEN TRAINING IN WORK WITH SPREADSHEETS

    Directory of Open Access Journals (Sweden)

    Х А Гербеков

    2017-12-01

    Full Text Available Today the tools for maintaining training courses based on opportunities of information and communication technologies are developed. Practically in all directions of preparation and on all subject matters electronic textbook and self-instruction manuals are created. Nevertheless the industry of computer educational and methodical materials actively develops and gets more and more areas of development and introduction. In this regard more and more urgent is a problem of development of the electronic educational resources adequate to modern educational requirements. Creation and the organization of training courses with use of electronic educational resources in particular on the basis of Internet technologies remains a difficult methodical task.In article the questions connected with development of electronic educational resources for use when studying the substantial line “Information technologies” of a school course of informatics in particular for studying of spreadsheets are considered. Also the analysis of maintenance of a school course and the unified state examination from the point of view of representation of task in him corresponding to the substantial line of studying “Information technologies” on mastering technology of information processing in spreadsheets and the methods of visualization given by means of charts and schedules is carried out.

  10. From Millennium ERM to Proquest 360 Resource Manager: Implementing a new Electronic Resources Management System ERMS in an International Graduate Research University in Saudi Arabia

    KAUST Repository

    Ramli, Rindra M.

    2017-01-01

    An overview of the Recommendation Study and the subsequent Implementation of a new Electronic Resources Management system ERMS in an international graduate research university in the Kingdom of Saudi Arabia. It covers the timeline, deliverables

  11. Vascular Changes and Neurodegeneration in the Early Stages of Diabetic Retinopathy

    DEFF Research Database (Denmark)

    Jonsson, Karoline Boegeberg; Frydkjaer-Olsen, Ulrik; Grauslund, Jakob

    2016-01-01

    INTRODUCTION: Neurodegeneration is an early component of diabetic retinopathy (DR). It is unclear whether neurodegeneration is an independent factor or a consequence of damaged retinal vasculature. The aims of this study were to review the literature concerning neurodegeneration in diabetic...

  12. Availability, Level of Use and Constraints to Use of Electronic Resources by Law Lecturers in Public Universities in Nigeria

    Science.gov (United States)

    Amusa, Oyintola Isiaka; Atinmo, Morayo

    2016-01-01

    (Purpose) This study surveyed the level of availability, use and constraints to use of electronic resources among law lecturers in Nigeria. (Methodology) Five hundred and fifty-two law lecturers were surveyed and four hundred and forty-two responded. (Results) Data analysis revealed that the level of availability of electronic resources for the…

  13. GUIDELINES FOR EVALUATION OF PSYCHOLOGICAL AND PEDAGOGICAL QUALITY CHARACTERISTICS OF ELECTRONIC EDUCATIONAL RESOURCES

    Directory of Open Access Journals (Sweden)

    Galina P. Lavrentieva

    2014-05-01

    Full Text Available The article highlights the causes of insufficient effective use of electronic learning resources and sets out the guidelines on ways to solve the aforementioned problems. The set of didactic, methodical, psychological, pedagogical, design and ergonomic quality requirements is considered for evaluation, selection and application of information and communication technologies in the educational process. The most appropriate mechanisms for the ICT introduction into the learning process are disclosed as it should meet the specific learning needs of the student and the objectives of the educational process. The guidance for psycho-educational assessment of quality of electronic educational resources is provided. It is argued that the effectiveness of the ICT use is to be improved by means of quality evaluation mechanisms involved into the educational process.

  14. Model of e-learning with electronic educational resources of new generation

    OpenAIRE

    A. V. Loban; D. A. Lovtsov

    2017-01-01

    Purpose of the article: improving of scientific and methodical base of the theory of the е-learning of variability. Methods used: conceptual and logical modeling of the е-learning of variability process with electronic educational resource of new generation and system analysis of the interconnection of the studied subject area, methods, didactics approaches and information and communication technologies means. Results: the formalization complex model of the е-learning of variability with elec...

  15. A systematic review of portable electronic technology for health education in resource-limited settings.

    Science.gov (United States)

    McHenry, Megan S; Fischer, Lydia J; Chun, Yeona; Vreeman, Rachel C

    2017-08-01

    The objective of this study is to conduct a systematic review of the literature of how portable electronic technologies with offline functionality are perceived and used to provide health education in resource-limited settings. Three reviewers evaluated articles and performed a bibliography search to identify studies describing health education delivered by portable electronic device with offline functionality in low- or middle-income countries. Data extracted included: study population; study design and type of analysis; type of technology used; method of use; setting of technology use; impact on caregivers, patients, or overall health outcomes; and reported limitations. Searches yielded 5514 unique titles. Out of 75 critically reviewed full-text articles, 10 met inclusion criteria. Study locations included Botswana, Peru, Kenya, Thailand, Nigeria, India, Ghana, and Tanzania. Topics addressed included: development of healthcare worker training modules, clinical decision support tools, patient education tools, perceptions and usability of portable electronic technology, and comparisons of technologies and/or mobile applications. Studies primarily looked at the assessment of developed educational modules on trainee health knowledge, perceptions and usability of technology, and comparisons of technologies. Overall, studies reported positive results for portable electronic device-based health education, frequently reporting increased provider/patient knowledge, improved patient outcomes in both quality of care and management, increased provider comfort level with technology, and an environment characterized by increased levels of technology-based, informal learning situations. Negative assessments included high investment costs, lack of technical support, and fear of device theft. While the research is limited, portable electronic educational resources present promising avenues to increase access to effective health education in resource-limited settings, contingent

  16. Model of e-learning with electronic educational resources of new generation

    Directory of Open Access Journals (Sweden)

    A. V. Loban

    2017-01-01

    Full Text Available Purpose of the article: improving of scientific and methodical base of the theory of the е-learning of variability. Methods used: conceptual and logical modeling of the е-learning of variability process with electronic educational resource of new generation and system analysis of the interconnection of the studied subject area, methods, didactics approaches and information and communication technologies means. Results: the formalization complex model of the е-learning of variability with electronic educational resource of new generation is developed, conditionally decomposed into three basic components: the formalization model of the course in the form of the thesaurusclassifier (“Author of e-resource”, the model of learning as management (“Coordination. Consultation. Control”, the learning model with the thesaurus-classifier (“Student”. Model “Author of e-resource” allows the student to achieve completeness, high degree of didactic elaboration and structuring of the studied material in triples of variants: modules of education information, practical task and control tasks; the result of the student’s (author’s of e-resource activity is the thesaurus-classifier. Model of learning as management is based on the principle of personal orientation of learning in computer environment and determines the logic of interaction between the lecturer and the student when determining the triple of variants individually for each student; organization of a dialogue between the lecturer and the student for consulting purposes; personal control of the student’s success (report generation and iterative search for the concept of the class assignment in the thesaurus-classifier before acquiring the required level of training. Model “Student” makes it possible to concretize the learning tasks in relation to the personality of the student and to the training level achieved; the assumption of the lecturer about the level of training of a

  17. A ketogenic diet accelerates neurodegeneration in mice with induced mitochondrial DNA toxicity in the forebrain

    DEFF Research Database (Denmark)

    Lauritzen, Knut H.; Hasan-Olive, Md Mahdi; Regnell, Christine E.

    2016-01-01

    neurons. Here, we examine whether severe neurodegeneration in mutUNG1-expressing mice could be rescued by feeding the mice a ketogenic diet, which is known to have beneficial effects in several neurological disorders. The diet increased the levels of superoxide dismutase 2, and mitochondrial mass, enzymes......, and regulators such as SIRT1 and FIS1, and appeared to downregulate N-methyl-D-aspartic acid (NMDA) receptor subunits NR2A/B and upregulate γ-aminobutyric acid A (GABAA) receptor subunits α1. However, unexpectedly, the ketogenic diet aggravated neurodegeneration and mitochondrial deterioration. Electron...... microscopy showed structurally impaired mitochondria accumulating in neuronal perikarya. We propose that aggravation is caused by increased mitochondrial biogenesis of generally dysfunctional mitochondria. This study thereby questions the dogma that a ketogenic diet is unambiguously beneficial...

  18. Review of material recovery from used electric and electronic equipment-alternative options for resource conservation.

    Science.gov (United States)

    Friege, Henning

    2012-09-01

    For waste from electric and electronic equipment, the WEEE Directive stipulates the separate collection of electric and electronic waste. As to new electric and electronic devices, the Restriction of Hazardous Substances (RoHS) Directive bans the use of certain chemicals dangerous for man and environment. From the implementation of the WEEE directive, many unsolved problems have been documented: poor collection success, emission of dangerous substances during collection and recycling, irretrievable loss of valuable metals among others. As to RoHS, data from the literature show a satisfying success. The problems identified in the process can be reduced to some basic dilemmas at the borders between waste management, product policy and chemical safety. The objectives of the WEEE Directive and the specific targets for use and recycling of appliances are not consistent. There is no focus on scarce resources. Extended producer responsibility is not sufficient to guarantee sustainable waste management. Waste management reaches its limits due to problems of implementation but also due to physical laws. A holistic approach is necessary looking at all branch points and sinks in the stream of used products and waste from electric and electronic equipment. This may be done with respect to the general rules for sustainable management of material streams covering the three dimensions of sustainable policy. The relationships between the players in the field of electric and electronic devices have to be taken into account. Most of the problems identified in the implementation process will not be solved by the current amendment of the WEEE Directive.

  19. [Use of internet and electronic resources among Spanish intensivist physicians. First national survey].

    Science.gov (United States)

    Gómez-Tello, V; Latour-Pérez, J; Añón Elizalde, J M; Palencia-Herrejón, E; Díaz-Alersi, R; De Lucas-García, N

    2006-01-01

    Estimate knowledge and use habits of different electronic resources in a sample of Spanish intensivists: Internet, E-mail, distribution lists, and use of portable electronic devices. Self-applied questionnaire. A 50-question questionnaire was distributed among Spanish intensivists through the hospital marketing delegates of a pharmaceutical company and of electronic forums. A total of 682 questionnaires were analyzed (participation: 74%). Ninety six percent of those surveyed used Internet individually: 67% admitted training gap. Internet was the second source of clinical consultations most used (61%), slightly behind consultation to colleagues (65%). The pages consulted most were bibliographic databases (65%) and electronic professional journals (63%), with limited use of Evidence Based Medicine pages (19%). Ninety percent of those surveyed used e-mail regularly in the practice of their profession, although 25% admitted that were not aware of its possibilities. The use of E-mail decreased significantly with increase in age. A total of 62% of the intensivists used distribution lists. Of the rest, 42% were not aware of its existence and 32% admitted they had insufficient training to handle them. Twenty percent of those surveyed had portable electronic devices and 64% considered it useful, basically due to its rapid consultation at bedside. Female gender was a negative predictive factor of its use (OR 0.35; 95% CI 0.2-0.63; p=0.0002). A large majority of the Spanish intensivists use Internet and E-mail. E-mail lists and use of portable devices are still underused resources. There are important gaps in training and infrequent use of essential pages. There are specific groups that require directed educational policies.

  20. Insights into Mechanisms of Chronic Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Abigail B. Diack

    2016-01-01

    Full Text Available Chronic neurodegenerative diseases such as Alzheimer’s disease (AD, Parkinson’s disease (PD, and prion diseases are characterised by the accumulation of abnormal conformers of a host encoded protein in the central nervous system. The process leading to neurodegeneration is still poorly defined and thus development of early intervention strategies is challenging. Unique amongst these diseases are Transmissible Spongiform Encephalopathies (TSEs or prion diseases, which have the ability to transmit between individuals. The infectious nature of these diseases has permitted in vivo and in vitro modelling of the time course of the disease process in a highly reproducible manner, thus early events can be defined. Recent evidence has demonstrated that the cell-to-cell spread of protein aggregates by a “prion-like mechanism” is common among the protein misfolding diseases. Thus, the TSE models may provide insights into disease mechanisms and testable hypotheses for disease intervention, applicable to a number of these chronic neurodegenerative diseases.

  1. Structural neurodegeneration correlates with early diabetic retinopathy

    DEFF Research Database (Denmark)

    Frydkjaer-Olsen, Ulrik; Hansen, Rasmus Søgaard; Peto, Tunde

    2018-01-01

    PURPOSE: To examine differences in structural and functional neurodegenerative measurements between patients with no and early diabetic retinopathy (DR). METHODS: In this cross-sectional study, we examined 103 patients with type 2 diabetes mellitus. In 7-field fundus photographs acquired...... with Topcon TRC-NW6S, a single, certified grader determined the presence of DR according to the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. Retinal neurodegeneration was evaluated by Topcon 3D OCT-2000 spectral domain optical coherence tomography (OCT) and by a RETI-scan multifocal...... electroretinography (mf-ERG) system in rings 1-6. RESULTS: Median age and duration of diabetes were 63.6 and 10 years, respectively, and 46% were men. Median HbA1c was 50 mmol/mol (6.7%), and ETDRS levels were 10 (41.7%, n = 43), 20 (35.0%, n = 36), and 35 (23.3%, n = 24). The duration of diabetes increased...

  2. Near-critical GLUT1 and Neurodegeneration.

    Science.gov (United States)

    Barros, L Felipe; San Martín, Alejandro; Ruminot, Ivan; Sandoval, Pamela Y; Fernández-Moncada, Ignacio; Baeza-Lehnert, Felipe; Arce-Molina, Robinson; Contreras-Baeza, Yasna; Cortés-Molina, Francisca; Galaz, Alex; Alegría, Karin

    2017-11-01

    Recent articles have drawn renewed attention to the housekeeping glucose transporter GLUT1 and its possible involvement in neurodegenerative diseases. Here we provide an updated analysis of brain glucose transport and the cellular mechanisms involved in its acute modulation during synaptic activity. We discuss how the architecture of the blood-brain barrier and the low concentration of glucose within neurons combine to make endothelial/glial GLUT1 the master controller of neuronal glucose utilization, while the regulatory role of the neuronal glucose transporter GLUT3 emerges as secondary. The near-critical condition of glucose dynamics in the brain suggests that subtle deficits in GLUT1 function or its activity-dependent control by neurons may contribute to neurodegeneration. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  3. The Synthesis of the Hierarchical Structure of Information Resources for Management of Electronic Commerce Entities

    Directory of Open Access Journals (Sweden)

    Krutova Anzhelika S.

    2017-06-01

    Full Text Available The aim of the article is to develop the theoretical bases for the classification and coding of economic information and the scientific justification of the content of information resources of an electronic commerce enterprise. The essence of information resources for management of electronic business entities is investigated. It is proved that the organization of accounting in e-commerce systems is advisable to be built on the basis of two circuits: accounting for financial flows and accounting associated with transformation of business factors in products and services as a result of production activities. There presented a sequence of accounting organization that allows to combine the both circuits in a single information system, which provides a possibility for the integrated replenishment and distributed simultaneous use of the e-commerce system by all groups of users. It is proved that the guarantee of efficient activity of the information management system of electronic commerce entities is a proper systematization of the aggregate of information resources on economic facts and operations of an enterprise in accordance with the management tasks by building the hierarchy of accounting nomenclatures. It is suggested to understand nomenclature as an objective, primary information aggregate concerning a certain fact of the economic activity of an enterprise, which is characterized by minimum requisites, is entered into the database of the information system and is to be reflected in the accounting system. It is proposed to build a database of e-commerce systems as a part of directories (constants, personnel, goods / products, suppliers, buyers and the hierarchy of accounting nomenclatures. The package of documents regulating the organization of accounting at an enterprise should include: the provision on the accounting services, the order on the accounting policy, the job descriptions, the schedules of information exchange, the report card and

  4. ELECTRONIC EDUCATIONAL RESOURCES FOR ONLINE SUPPORT OF MODERN CHEMISTRY CLASSES IN SPECIALIZED SCHOOL

    Directory of Open Access Journals (Sweden)

    Maria D. Tukalo

    2013-09-01

    Full Text Available This article contains material of some modern electronic educational resources that can be used via the Internet to support the modern chemistry classes in specialized school. It was drawn attention to the educational chemical experiments as means of knowledge; simulated key motivational characteristics to enhance students interest for learning subjects, their cognitive and practical activity in the formation of self-reliance and self-creative; commented forecasts for creating of conditions to enhance the creative potential of students in a modern learning environment.

  5. THE MODEL OF LINGUISTIC TEACHERS’ COMPETENCY DEVELOPMENT ON DESIGNING MULTIMEDIA ELECTRONIC EDUCATIONAL RESOURCES IN THE MOODLE SYSTEM

    Directory of Open Access Journals (Sweden)

    Anton M. Avramchuk

    2017-10-01

    Full Text Available The article is devoted to the problem of developing the competency of teachers of language disciplines on designing multimedia electronic educational resources in the Moodle system. The concept of "the competence of teachers of language disciplines on designing multimedia electronic educational resources in the Moodle system" is justified and defined. Identified and characterized the components by which the levels of the competency development of teachers of language disciplines on designing multimedia electronic educational resources in the Moodle system should be assessed. Developed a model for the development of the competency of teachers of language disciplines on designing multimedia electronic educational resources in the Moodle system, which is based on the main scientific approaches, used in adult education, and consists of five blocks: target, informative, technological, diagnostic and effective.

  6. A preliminary categorization of end-of-life electrical and electronic equipment as secondary metal resources

    International Nuclear Information System (INIS)

    Oguchi, Masahiro; Murakami, Shinsuke; Sakanakura, Hirofumi; Kida, Akiko; Kameya, Takashi

    2011-01-01

    Highlights: → End-of-life electrical and electronic equipment (EEE) as secondary metal resources. → The content and the total amount of metals in specific equipment are both important. → We categorized 21 EEE types from contents and total amounts of various metals. → Important equipment types as secondary resources were listed for each metal kind. → Collectability and possible collection systems of various EEE types were discussed. - Abstract: End-of-life electrical and electronic equipment (EEE) has recently received attention as a secondary source of metals. This study examined characteristics of end-of-life EEE as secondary metal resources to consider efficient collection and metal recovery systems according to the specific metals and types of EEE. We constructed an analogy between natural resource development and metal recovery from end-of-life EEE and found that metal content and total annual amount of metal contained in each type of end-of-life EEE should be considered in secondary resource development, as well as the collectability of the end-of-life products. We then categorized 21 EEE types into five groups and discussed their potential as secondary metal resources. Refrigerators, washing machines, air conditioners, and CRT TVs were evaluated as the most important sources of common metals, and personal computers, mobile phones, and video games were evaluated as the most important sources of precious metals. Several types of small digital equipment were also identified as important sources of precious metals; however, mid-size information and communication technology (ICT) equipment (e.g., printers and fax machines) and audio/video equipment were shown to be more important as a source of a variety of less common metals. The physical collectability of each type of EEE was roughly characterized by unit size and number of end-of-life products generated annually. Current collection systems in Japan were examined and potentially appropriate collection

  7. Open-Source Electronic Health Record Systems for Low-Resource Settings: Systematic Review.

    Science.gov (United States)

    Syzdykova, Assel; Malta, André; Zolfo, Maria; Diro, Ermias; Oliveira, José Luis

    2017-11-13

    Despite the great impact of information and communication technologies on clinical practice and on the quality of health services, this trend has been almost exclusive to developed countries, whereas countries with poor resources suffer from many economic and social issues that have hindered the real benefits of electronic health (eHealth) tools. As a component of eHealth systems, electronic health records (EHRs) play a fundamental role in patient management and effective medical care services. Thus, the adoption of EHRs in regions with a lack of infrastructure, untrained staff, and ill-equipped health care providers is an important task. However, the main barrier to adopting EHR software in low- and middle-income countries is the cost of its purchase and maintenance, which highlights the open-source approach as a good solution for these underserved areas. The aim of this study was to conduct a systematic review of open-source EHR systems based on the requirements and limitations of low-resource settings. First, we reviewed existing literature on the comparison of available open-source solutions. In close collaboration with the University of Gondar Hospital, Ethiopia, we identified common limitations in poor resource environments and also the main requirements that EHRs should support. Then, we extensively evaluated the current open-source EHR solutions, discussing their strengths and weaknesses, and their appropriateness to fulfill a predefined set of features relevant for low-resource settings. The evaluation methodology allowed assessment of several key aspects of available solutions that are as follows: (1) integrated applications, (2) configurable reports, (3) custom reports, (4) custom forms, (5) interoperability, (6) coding systems, (7) authentication methods, (8) patient portal, (9) access control model, (10) cryptographic features, (11) flexible data model, (12) offline support, (13) native client, (14) Web client,(15) other clients, (16) code

  8. THE MODEL OF LINGUISTIC TEACHERS’ COMPETENCY DEVELOPMENT ON DESIGNING MULTIMEDIA ELECTRONIC EDUCATIONAL RESOURCES IN THE MOODLE SYSTEM

    OpenAIRE

    Anton M. Avramchuk

    2017-01-01

    The article is devoted to the problem of developing the competency of teachers of language disciplines on designing multimedia electronic educational resources in the Moodle system. The concept of "the competence of teachers of language disciplines on designing multimedia electronic educational resources in the Moodle system" is justified and defined. Identified and characterized the components by which the levels of the competency development of teachers of language disciplines on designing ...

  9. Determining the level of awareness of the physicians in using the variety of electronic information resources and the effecting factors.

    Science.gov (United States)

    Papi, Ahmad; Ghazavi, Roghayeh; Moradi, Salimeh

    2015-01-01

    Understanding of the medical society's from the types of information resources for quick and easy access to information is an imperative task in medical researches and management of the treatment. The present study was aimed to determine the level of awareness of the physicians in using various electronic information resources and the factors affecting it. This study was a descriptive survey. The data collection tool was a researcher-made questionnaire. The study population included all the physicians and specialty physicians of the teaching hospitals affiliated to Isfahan University of Medical Sciences and numbered 350. The sample size based on Morgan's formula was set at 180. The content validity of the tool was confirmed by the library and information professionals and the reliability was 95%. Descriptive statistics were used including the SPSS software version 19. On reviewing the need of the physicians to obtain the information on several occasions, the need for information in conducting the researches was reported by the maximum number of physicians (91.9%) and the usage of information resources, especially the electronic resources, formed 65.4% as the highest rate with regard to meeting the information needs of the physicians. Among the electronic information databases, the maximum awareness was related to Medline with 86.5%. Among the various electronic information resources, the highest awareness (43.3%) was related to the E-journals. The highest usage (36%) was also from the same source. The studied physicians considered the most effective deterrent in the use of electronic information resources as being too busy and lack of time. Despite the importance of electronic information resources for the physician's community, there was no comprehensive knowledge of these resources. This can lead to less usage of these resources. Therefore, careful planning is necessary in the hospital libraries in order to introduce the facilities and full capabilities of the

  10. Success criteria for electronic medical record implementations in low-resource settings: a systematic review.

    Science.gov (United States)

    Fritz, Fleur; Tilahun, Binyam; Dugas, Martin

    2015-03-01

    Electronic medical record (EMR) systems have the potential of supporting clinical work by providing the right information at the right time to the right people and thus make efficient use of resources. This is especially important in low-resource settings where reliable data are also needed to support public health and local supporting organizations. In this systematic literature review, our objectives are to identify and collect literature about success criteria of EMR implementations in low-resource settings and to summarize them into recommendations. Our search strategy relied on PubMed queries and manual bibliography reviews. Studies were included if EMR implementations in low-resource settings were described. The extracted success criteria and measurements were summarized into 7 categories: ethical, financial, functionality, organizational, political, technical, and training. We collected 381 success criteria with 229 measurements from 47 articles out of 223 articles. Most papers were evaluations or lessons learned from African countries, published from 1999 to 2013. Almost half of the EMR systems served a specific disease area like human immunodeficiency virus (HIV). The majority of criteria that were reported dealt with the functionality, followed by organizational issues, and technical infrastructures. Sufficient training and skilled personnel were mentioned in roughly 10%. Political, ethical, and financial considerations did not play a predominant role. More evaluations based on reliable frameworks are needed. Highly reliable data handling methods, human resources and effective project management, as well as technical architecture and infrastructure are all key factors for successful EMR implementation. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Impact of Knowledge Resources Linked to an Electronic Health Record on Frequency of Unnecessary Tests and Treatments

    Science.gov (United States)

    Goodman, Kenneth; Grad, Roland; Pluye, Pierre; Nowacki, Amy; Hickner, John

    2012-01-01

    Introduction: Electronic knowledge resources have the potential to rapidly provide answers to clinicians' questions. We sought to determine clinicians' reasons for searching these resources, the rate of finding relevant information, and the perceived clinical impact of the information they retrieved. Methods: We asked general internists, family…

  12. A ketogenic diet accelerates neurodegeneration in mice with induced mitochondrial DNA toxicity in the forebrain.

    Science.gov (United States)

    Lauritzen, Knut H; Hasan-Olive, Md Mahdi; Regnell, Christine E; Kleppa, Liv; Scheibye-Knudsen, Morten; Gjedde, Albert; Klungland, Arne; Bohr, Vilhelm A; Storm-Mathisen, Jon; Bergersen, Linda H

    2016-12-01

    Mitochondrial genome maintenance plays a central role in preserving brain health. We previously demonstrated accumulation of mitochondrial DNA damage and severe neurodegeneration in transgenic mice inducibly expressing a mutated mitochondrial DNA repair enzyme (mutUNG1) selectively in forebrain neurons. Here, we examine whether severe neurodegeneration in mutUNG1-expressing mice could be rescued by feeding the mice a ketogenic diet, which is known to have beneficial effects in several neurological disorders. The diet increased the levels of superoxide dismutase 2, and mitochondrial mass, enzymes, and regulators such as SIRT1 and FIS1, and appeared to downregulate N-methyl-D-aspartic acid (NMDA) receptor subunits NR2A/B and upregulate γ-aminobutyric acid A (GABA A ) receptor subunits α 1 . However, unexpectedly, the ketogenic diet aggravated neurodegeneration and mitochondrial deterioration. Electron microscopy showed structurally impaired mitochondria accumulating in neuronal perikarya. We propose that aggravation is caused by increased mitochondrial biogenesis of generally dysfunctional mitochondria. This study thereby questions the dogma that a ketogenic diet is unambiguously beneficial in mitochondrial disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Resource conservation approached with an appropriate collection and upgrade-remanufacturing for used electronic products.

    Science.gov (United States)

    Zlamparet, Gabriel I; Tan, Quanyin; Stevels, A B; Li, Jinhui

    2018-03-01

    This comparative research represents an example for a better conservation of resources by reducing the amount of waste (kg) and providing it more value under the umbrella of remanufacturing. The three discussed cases will expose three issues already addressed separately in the literature. The generation of waste electrical and electronic equipment (WEEE) interacts with the environmental depletion. In this article, we gave the examples of addressed issues under the concept of remanufacturing. Online collection opportunity eliminating classical collection, a business to business (B2B) implementation for remanufactured servers and medical devices. The material reuse (recycling), component sustainability, reuse (part harvesting), product reuse (after repair/remanufacturing) indicates the recovery potential using remanufacturing tool for a better conservation of resources adding more value to the products. Our findings can provide an overview of new system organization for the general collection, market potential and the technological advantages using remanufacturing instead of recycling of WEEE or used electrical and electronic equipment. Copyright © 2017. Published by Elsevier Ltd.

  14. Phosphatidylinositol transfer protein alpha and its role in neurodegeneration

    NARCIS (Netherlands)

    Bunte, H.

    2007-01-01

    Selective neuronal loss is a prominent feature in neurodegenerative disorders. Recently, a link between neurodegeneration and a deficiency in the protein phosphatidylinositol transfer protein alpha (PI-TPalpha) has been demonstrated. In this context it is of importance that fibroblasts

  15. Electronic theses and dissertations: a review of this valuable resource for nurse scholars worldwide.

    Science.gov (United States)

    Goodfellow, L M

    2009-06-01

    A worldwide repository of electronic theses and dissertations (ETDs) could provide worldwide access to the most up-to-date research generated by masters and doctoral students. Until that international repository is established, it is possible to access some of these valuable knowledge resources. ETDs provide a technologically advanced medium with endless multimedia capabilities that far exceed the print and bound copies of theses and dissertations housed traditionally in individual university libraries. CURRENT USE: A growing trend exists for universities worldwide to require graduate students to submit theses or dissertations as electronic documents. However, nurse scholars underutilize ETDs, as evidenced by perusing bibliographic citation lists in many of the research journals. ETDs can be searched for and retrieved through several digital resources such as the Networked Digital Library of Theses and Dissertations (http://www.ndltd.org), ProQuest Dissertations and Theses (http://www.umi.com), the Australasian Digital Theses Program (http://adt.caul.edu.au/) and through individual university web sites and online catalogues. An international repository of ETDs benefits the community of nurse scholars in many ways. The ability to access recent graduate students' research electronically from anywhere in the world is advantageous. For scholars residing in developing countries, access to these ETDs may prove to be even more valuable. In some cases, ETDs are not available for worldwide access and can only be accessed through the university library from which the student graduated. Public access to university library ETD collections is not always permitted. Nurse scholars from both developing and developed countries could benefit from ETDs.

  16. Epidemiology of neurodegeneration in American-style professional football players

    OpenAIRE

    Lehman, Everett J

    2013-01-01

    The purpose of this article is to review the history of head injuries in relation to American-style football play, summarize recent research that has linked football head injuries to neurodegeneration, and provide a discussion of the next steps for refining the examination of neurodegeneration in football players. For most of the history of football, the focus of media reports and scientific studies on football-related head injuries was on the acute or short-term effects of serious, traumatic...

  17. An improved route to 19-substituted geldanamycins as novel Hsp90 inhibitors ? potential therapeutics in cancer and neurodegeneration? ?Electronic supplementary information (ESI) available. See DOI: 10.1039/c3cc43457e Click here for additional data file. Click here for additional data file.

    OpenAIRE

    Kitson, Russell R. A.; Moody, Christopher J.

    2013-01-01

    19-Substituted geldanamycin derivatives are efficient Hsp90 inhibitors, without the toxicity associated with the other benzoquinone ansamycins, thus giving them potential for use as molecular therapeutics in cancer and neurodegeneration. Here a new method of synthesising these important compounds is reported, eliminating the need for toxic metals and metalloids.

  18. From Millennium ERM to Proquest 360 Resource Manager: Implementing a new Electronic Resources Management System ERMS in an International Graduate Research University in Saudi Arabia

    KAUST Repository

    Ramli, Rindra M.

    2017-05-17

    An overview of the Recommendation Study and the subsequent Implementation of a new Electronic Resources Management system ERMS in an international graduate research university in the Kingdom of Saudi Arabia. It covers the timeline, deliverables and challenges as well as lessons learnt by the Project Team.

  19. Methylenedioxymethamphetamine (MDMA, 'Ecstasy': Neurodegeneration versus Neuromodulation

    Directory of Open Access Journals (Sweden)

    Elena Puerta

    2011-07-01

    Full Text Available The amphetamine analogue 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’ is widely abused as a recreational drug due to its unique psychological effects. Of interest, MDMA causes long-lasting deficits in neurochemical and histological markers of the serotonergic neurons in the brain of different animal species. Such deficits include the decline in the activity of tryptophan hydroxylase in parallel with the loss of 5-HT and its main metabolite 5-hydoxyindoleacetic acid (5-HIAA along with a lower binding of specific ligands to the 5-HT transporters (SERT. Of concern, reduced 5-HIAA levels in the CSF and SERT density have also been reported in human ecstasy users, what has been interpreted to reflect the loss of serotonergic fibers and terminals. The neurotoxic potential of MDMA has been questioned in recent years based on studies that failed to show the loss of the SERT protein by western blot or the lack of reactive astrogliosis after MDMA exposure. In addition, MDMA produces a long-lasting down-regulation of SERT gene expression; which, on the whole, has been used to invoke neuromodulatory mechanisms as an explanation to MDMA-induced 5-HT deficits. While decreased protein levels do not necessarily reflect neurodegeneration, the opposite is also true, that is, neuroregulatory mechanisms do not preclude the existence of 5-HT terminal degeneration.

  20. Electronic tracking of human resource skills and knowledge, just in time training, manageable due diligence

    Energy Technology Data Exchange (ETDEWEB)

    Kolodziej, M.A. [Quick Test International Inc., (Canada). Canadian Technology Human Resource Board; Baker, O. [KeySpan Energy Canada, Calgary, AB (Canada)

    2001-06-01

    KeySpan Energy Canada is in the process of obtaining recognition of various occupational profiles including pipeline operators, inspectors, and field and plant operators from various certifying organizations. The process of allowing individuals to obtain certification is recognized by Canadian Technology Human Resources Board as a step towards national standards for technologists and technicians. Proven competency is a must for workers in todays oil industry in response to increasingly stringent government safety regulations, environmental concerns and high public scrutiny. Quick Test international Inc. has developed a management tool in collaboration with end users at KeySpan Energy Canada. It is an electronic, Internet based competency tool for tracking personal competencies and maintaining continued competency. Response to the tool has been favourable. 2 refs., 4 figs.

  1. Availability, Use and Constraints to Use of Electronic Information Resources by Postgraduates Students at the University of Ibadan

    Directory of Open Access Journals (Sweden)

    Dare Samuel Adeleke

    2017-12-01

    Full Text Available Availability, awareness and use of electronic resources provide access to authoritative, reliable, accurate and timely access to information. The use of electronic information resources (EIRs can enable innovation in teaching and increase timeliness in research of postgraduate students which will eventual result into encouragement of the expected research-led enquiry in this digital age. The study adopted a descriptive survey design. Samples of 300 of postgraduate students within seven out 13 Faculties were randomly selected. Data were collected using questionnaire designed to elicit response from respondents and data were analyzed using descriptive statistics methods percentages, mean, and standard deviation. Results indicated that internet was ranked most available and used in the university. Low level of usage of electronic resources, in particular, full texts data bases is linked to a number of constraints: Interrupted power supply was ranked highest among other factors as speed and capacity of computers, retrieval of records with high recall and low precision, retrieving records relevant to information need, lack of knowledge of search techniques to retrieve information effectively, non possession of requisite IT skills and problems accessing the internet. The study recommended that usage of electronic resources be made compulsory, intensifying awareness campaigns concerning the availability, training on use of electronic resources and the problem of power outage be addressed.

  2. Using mobile electronic devices to deliver educational resources in developing countries.

    Science.gov (United States)

    Mazal, Jonathan Robert; Ludwig, Rebecca

    2015-01-01

    Developing countries have far fewer trained radiography professionals than developed countries, which exacerbates the limited access to imaging services. The lack of trained radiographers reflects, in part, limited availability of radiographer-specific educational resources. Historically, organizations that provided such resources in the developing world faced challenges related to the limited stock of current materials as well as expenses associated with shipping and delivery. Four mobile electronic devices (MEDs) were loaded with educational content (e-books, PDFs, and digital applications) spanning major radiography topics. The MEDs were distributed to 4 imaging departments in Ghana, India, Nepal, and Nigeria based on evidence of need for radiography-specific resources, as revealed by survey responses. A cost comparison of postal delivery vs digital delivery of educational content was performed. The effectiveness of delivering additional content via Wi-Fi transmission also was evaluated. Feedback was solicited on users' experience with the MEDs as a delivery tool for educational content. An initial average per e-book expense of $30.05, which included the cost of the device, was calculated for the MED delivery method compared with $15.56 for postal delivery of printed materials. The cost of the MED delivery method was reduced to an average of $10.05 for subsequent e-book deliveries. Additional content was successfully delivered via Wi-Fi transmission to all recipients during the 3-month follow-up period. Overall user feedback on the experience was positive, and ideas for enhancing the MED-based method were identified. Using MEDs to deliver radiography-specific educational content appears to be more cost effective than postal delivery of printed materials on a long-term basis. MEDs are more efficient for providing updates to educational materials. Customization of content to department needs, and using projector devices could enhance the usefulness of MEDs for

  3. The electronic encapsulation of knowledge in hydraulics, hydrology and water resources

    Science.gov (United States)

    Abbott, Michael B.

    The rapidly developing practice of encapsulating knowledge in electronic media is shown to lead necessarily to the restructuring of the knowledge itself. The consequences of this for hydraulics, hydrology and more general water-resources management are investigated in particular relation to current process-simulation, real-time control and advice-serving systems. The generic properties of the electronic knowledge encapsulator are described, and attention is drawn to the manner in which knowledge 'goes into hiding' through encapsulation. This property is traced in the simple situations of pure mathesis and in the more complex situations of taxinomia using one example each from hydraulics and hydrology. The consequences for systems architectures are explained, pointing to the need for multi-agent architectures for ecological modelling and for more general hydroinformatics systems also. The relevance of these developments is indicated by reference to ongoing projects in which they are currently being realised. In conclusion, some more general epistemological aspects are considered within the same context. As this contribution is so much concerned with the processes of signification and communication, it has been partly shaped by the theory of semiotics, as popularised by Eco ( A Theory of Semiotics, Indiana University, Bloomington, 1977).

  4. Plastics disassembly versus bulk recycling: engineering design for end-of-life electronics resource recovery.

    Science.gov (United States)

    Rios, Pedro; Stuart, Julie Ann; Grant, Ed

    2003-12-01

    Annual plastic flows through the business and consumer electronics manufacturing supply chain include nearly 3 billion lb of high-value engineering plastics derived from petroleum. The recovery of resource value from this stream presents critical challenges in areas of materials identification and recycling process design that demand new green engineering technologies applied together with life cycle assessment and ecological supply chain analysis to create viable plastics-to-plastics supply cycles. The sustainable recovery of potentially high-value engineering plastics streams requires that recyclers either avoid mixing plastic parts or purify later by separating smaller plastic pieces created in volume reduction (shredding) steps. Identification and separation constitute significant barriers in the plastics-to-plastics recycling value proposition. In the present work, we develop a model that accepts randomly arriving electronic products to study scenarios by which a recycler might identify and separate high-value engineering plastics as well as metals. Using discrete eventsimulation,we compare current mixed plastics recovery with spectrochemical plastic resin identification and subsequent sorting. Our results show that limited disassembly with whole-part identification can produce substantial yields in separated streams of recovered engineering thermoplastics. We find that disassembly with identification does not constitute a bottleneck, but rather, with relatively few workers, can be configured to pull the process and thus decrease maximum staging space requirements.

  5. Neurodegeneration and Neuroprotection in Diabetic Retinopathy

    Directory of Open Access Journals (Sweden)

    Abdullah S. Alhomida

    2013-01-01

    Full Text Available Diabetic retinopathy is widely considered to be a neurovascular disease. This is in contrast to its previous identity as solely a vascular disease. Early in the disease progression of diabetes, the major cells in the neuronal component of the retina consist of retinal ganglion cells and glial cells, both of which have been found to be compromised. A number of retinal function tests also indicated a functional deficit in diabetic retina, which further supports dysfunction of neuronal cells. As an endocrinological disorder, diabetes alters metabolism both systemically and locally in several body organs, including the retina. A growing body of evidences indicates increased levels of excitotoxic metabolites, including glutamate, branched chain amino acids and homocysteine in cases of diabetic retinopathy. Also present, early in the disease, are decreased levels of folic acid and vitamin-B12, which are potential metabolites capable of damaging neurons. These altered levels of metabolites are found to activate several metabolic pathways, leading to increases in oxidative stress and decreases in the level of neurotrophic factors. As a consequence, they may damage retinal neurons in diabetic patients. In this review, we have discussed those potential excitotoxic metabolites and their implications in neuronal damage. Possible therapeutic targets to protect neurons are also discussed. However, further research is needed to understand the exact molecular mechanism of neurodegeneration so that effective neuroprotection strategies can be developed. By protecting retinal neurons early in diabetic retinopathy cases, damage of retinal vessels can be protected, thereby helping to ameliorate the progression of diabetic retinopathy, a leading cause of blindness worldwide.

  6. Molecular pathways underpinning ethanol-induced neurodegeneration

    Directory of Open Access Journals (Sweden)

    Dan eGoldowitz*

    2014-07-01

    -induced neurodegeneration.

  7. SAGES: a suite of freely-available software tools for electronic disease surveillance in resource-limited settings.

    Directory of Open Access Journals (Sweden)

    Sheri L Lewis

    Full Text Available Public health surveillance is undergoing a revolution driven by advances in the field of information technology. Many countries have experienced vast improvements in the collection, ingestion, analysis, visualization, and dissemination of public health data. Resource-limited countries have lagged behind due to challenges in information technology infrastructure, public health resources, and the costs of proprietary software. The Suite for Automated Global Electronic bioSurveillance (SAGES is a collection of modular, flexible, freely-available software tools for electronic disease surveillance in resource-limited settings. One or more SAGES tools may be used in concert with existing surveillance applications or the SAGES tools may be used en masse for an end-to-end biosurveillance capability. This flexibility allows for the development of an inexpensive, customized, and sustainable disease surveillance system. The ability to rapidly assess anomalous disease activity may lead to more efficient use of limited resources and better compliance with World Health Organization International Health Regulations.

  8. Electronic Human Resources Management (e-HRM Adoption Studies: Past and Future Research

    Directory of Open Access Journals (Sweden)

    Winarto Winarto

    2018-05-01

    Full Text Available Electronic human resource management (e-HRM systems become more widely used by profit and non-profit organization. However, the field currently lacks sound theoretical frameworks that can be useful in addressing a key issue concerning the implementation of e-HRM systems, in particular to obtain a better understanding of the factors influencing the adoption of e-HRM systems. The objective of this paper is to provide a foundation towards the development of a theoretical framework for the implementation of e-HRM systems and develop a conceptual model that would reflect the nature of e-HRM systems’ adoption through systematic literature review. Adopting Crossan and Apaydin’s procedure of systematic review, this paper investigated 21 empirical papers of electronics human resources management, then categorized them into 4 characteristics which influence the adoption; System and technology characteristics; Organizational characteristics; User/individual characteristics, and Environmental and contextual characteristics. Finally, the e-HRM adoption research framework is drawn and based on the framework; avenues for future research are discussed.   Bahasa Indonesia Abstrak: Manajemen sumber daya manusia elektronik (selanjutnya disebut dengan e-HRM semakin banyak digunakan oleh organisasi profit dan nonprofit. Namun, bidang dan topik ini belum memiliki kerangka teori yang mapan, yang dapat digunakan untuk menganalisis isu-isu terkait penerapan e-HRM, terutama mengenai faktor-faktor yang mempengaruhi adopsi sistem e-HRM. Tujuan penelitian ini adalah untuk memberikan landasan bagi pengembangan kerangka teoritis untuk implementasi sistem e-HRM dan mengembangkan model konseptual yang akan menggambarkan adopsi sistem e-HRM melalui tinjauan literatur sistematis. Mengadopsi prosedur dan metode Crossan dan Apaydin untuk melakukan telaah literatur secara sistematis, paper ini menyelidiki 21 publikasi empiris manajemen sumber daya manusia elektronik dari 2

  9. Impact of Electronic Resources and Usage in Academic Libraries in Ghana: Evidence from Koforidua Polytechnic & All Nations University College, Ghana

    Science.gov (United States)

    Akussah, Maxwell; Asante, Edward; Adu-Sarkodee, Rosemary

    2015-01-01

    The study investigates the relationship between impact of electronic resources and its usage in academic libraries in Ghana: evidence from Koforidua Polytechnic & All Nations University College, Ghana. The study was a quantitative approach using questionnaire to gather data and information. A valid response rate of 58.5% was assumed. SPSS…

  10. Utilization of Electronic Information Resources by Undergraduate Students of University of Ibadan: A Case Study of Social Sciences and Education

    Science.gov (United States)

    Owolabi, Sola; Idowu, Oluwafemi A.; Okocha, Foluke; Ogundare, Atinuke Omotayo

    2016-01-01

    The study evaluated utilization of electronic information resources by undergraduates in the Faculties of Education and the Social Sciences in University of Ibadan. The study adopted a descriptive survey design with a study population of 1872 undergraduates in the Faculties of Education and the Social Sciences in University of Ibadan, from which a…

  11. Systematic review of electronic surveillance of infectious diseases with emphasis on antimicrobial resistance surveillance in resource-limited settings.

    Science.gov (United States)

    Rattanaumpawan, Pinyo; Boonyasiri, Adhiratha; Vong, Sirenda; Thamlikitkul, Visanu

    2018-02-01

    Electronic surveillance of infectious diseases involves rapidly collecting, collating, and analyzing vast amounts of data from interrelated multiple databases. Although many developed countries have invested in electronic surveillance for infectious diseases, the system still presents a challenge for resource-limited health care settings. We conducted a systematic review by performing a comprehensive literature search on MEDLINE (January 2000-December 2015) to identify studies relevant to electronic surveillance of infectious diseases. Study characteristics and results were extracted and systematically reviewed by 3 infectious disease physicians. A total of 110 studies were included. Most surveillance systems were developed and implemented in high-income countries; less than one-quarter were conducted in low-or middle-income countries. Information technologies can be used to facilitate the process of obtaining laboratory, clinical, and pharmacologic data for the surveillance of infectious diseases, including antimicrobial resistance (AMR) infections. These novel systems require greater resources; however, we found that using electronic surveillance systems could result in shorter times to detect targeted infectious diseases and improvement of data collection. This study highlights a lack of resources in areas where an effective, rapid surveillance system is most needed. The availability of information technology for the electronic surveillance of infectious diseases, including AMR infections, will facilitate the prevention and containment of such emerging infectious diseases. Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  12. The Use of Electronic Resources by Academic Staff at the University of Ilorin, Nigeria

    Science.gov (United States)

    Tella, Adeyinka; Orim, Faith; Ibrahim, Dauda Morenikeji; Memudu, Suleiman Ajala

    2018-01-01

    The use of e-resources is now commonplace among academics in tertiary educational institutions the world over. Many academics including those in the universities are exploring the opportunities of e-resources to facilitate teaching and research. As the use of e-resources is increasing particularly among academics at the University of Ilorin,…

  13. Modeling antecedents of electronic medical record system implementation success in low-resource setting hospitals.

    Science.gov (United States)

    Tilahun, Binyam; Fritz, Fleur

    2015-08-01

    With the increasing implementation of Electronic Medical Record Systems (EMR) in developing countries, there is a growing need to identify antecedents of EMR success to measure and predict the level of adoption before costly implementation. However, less evidence is available about EMR success in the context of low-resource setting implementations. Therefore, this study aims to fill this gap by examining the constructs and relationships of the widely used DeLone and MacLean (D&M) information system success model to determine whether it can be applied to measure EMR success in those settings. A quantitative cross sectional study design using self-administered questionnaires was used to collect data from 384 health professionals working in five governmental hospitals in Ethiopia. The hospitals use a comprehensive EMR system since three years. Descriptive and structural equation modeling methods were applied to describe and validate the extent of relationship of constructs and mediating effects. The findings of the structural equation modeling shows that system quality has significant influence on EMR use (β = 0.32, P quality has significant influence on EMR use (β = 0.44, P service quality has strong significant influence on EMR use (β = 0.36, P effect of EMR use on user satisfaction was not significant. Both EMR use and user satisfaction have significant influence on perceived net-benefit (β = 0.31, P mediating factor in the relationship between service quality and EMR use (P effect on perceived net-benefit of health professionals. EMR implementers and managers in developing countries are in urgent need of implementation models to design proper implementation strategies. In this study, the constructs and relationships depicted in the updated D&M model were found to be applicable to assess the success of EMR in low resource settings. Additionally, computer literacy was found to be a mediating factor in EMR use and user satisfaction of

  14. Effects of mild running on substantia nigra during early neurodegeneration.

    Science.gov (United States)

    Almeida, Michael F; Silva, Carolliny M; Chaves, Rodrigo S; Lima, Nathan C R; Almeida, Renato S; Melo, Karla P; Demasi, Marilene; Fernandes, Tiago; Oliveira, Edilamar M; Netto, Luis E S; Cardoso, Sandra M; Ferrari, Merari F R

    2018-06-01

    Moderate physical exercise acts at molecular and behavioural levels, such as interfering in neuroplasticity, cell death, neurogenesis, cognition and motor functions. Therefore, the aim of this study is to analyse the cellular effects of moderate treadmill running upon substantia nigra during early neurodegeneration. Aged male Lewis rats (9-month-old) were exposed to rotenone 1mg/kg/day (8 weeks) and 6 weeks of moderate treadmill running, beginning 4 weeks after rotenone exposure. Substantia nigra was extracted and submitted to proteasome and antioxidant enzymes activities, hydrogen peroxide levels and Western blot to evaluate tyrosine hydroxylase (TH), alpha-synuclein, Tom-20, PINK1, TrkB, SLP1, CRMP-2, Rab-27b, LC3II and Beclin-1 level. It was demonstrated that moderate treadmill running, practiced during early neurodegeneration, prevented the increase of alpha-synuclein and maintained the levels of TH unaltered in substantia nigra of aged rats. Physical exercise also stimulated autophagy and prevented impairment of mitophagy, but decreased proteasome activity in rotenone-exposed aged rats. Physical activity also prevented H 2 O 2 increase during early neurodegeneration, although the involved mechanism remains to be elucidated. TrkB levels and its anterograde trafficking seem not to be influenced by moderate treadmill running. In conclusion, moderate physical training could prevent early neurodegeneration in substantia nigra through the improvement of autophagy and mitophagy.

  15. Genetics Home Reference: fatty acid hydroxylase-associated neurodegeneration

    Science.gov (United States)

    ... Mutat. 2010 Apr;31(4):E1251-60. doi: 10.1002/humu.21205. Citation on PubMed Edvardson S, Hama H, ... Neurol. 2010 Nov;68(5):611-8. doi: 10.1002/ana.22122. Citation on PubMed Schipper HM. Neurodegeneration ...

  16. 4R-cembranoid protects against diisopropylfluorophosphate-mediated neurodegeneration

    OpenAIRE

    Ferchmin, P.A.; Andino, Myrna; Salaman, Rebeca Reyes; Alves, Janaina; Velez-Roman, Joyce; Cuadrado, Brenda; Carrasco, Marimeé; Torres-Rivera, Wilmarie; Segarra, Annabell; Martins, Antonio Henrique; Lee, Jae Eun; Eterovic, Vesna A.

    2014-01-01

    Many organophosphorous esters synthesized for applications in industry, agriculture, or warfare irreversibly inhibit acetylcholinesterase, and acute poisoning with these compounds causes life-threatening cholinergic overstimulation. Following classical emergency treatment with atropine, an oxime, and a benzodiazepine, surviving victims often suffer brain neurodegeneration. Currently, there is no pharmacological treatment to prevent this brain injury. Here we show that a cyclic diterpenoid, (1...

  17. Use and Cost of Electronic Resources in Central Library of Ferdowsi University Based on E-metrics

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Davarpanah

    2012-07-01

    Full Text Available The purpose of this study was to investigate the usage of electronic journals in Ferdowsi University, Iran based on e-metrics. The paper also aimed to emphasize the analysis of cost-benefit and the correlation between the journal impact factors and the usage data. In this study experiences of Ferdowsi University library on licensing and usage of electronic resources was evaluated by providing a cost-benefit analysis based on the cost and usage statistics of electronic resources. Vendor-provided data were also compared with local usage data. The usage data were collected by tracking web-based access locally, and by collecting vender-provided usage data. The data sources were one-year of vendor-supplied e-resource usage data such as Ebsco, Elsevier, Proquest, Emerald, Oxford and Springer and local usage data collected from the Ferdowsi university web server. The study found that actual usage values differ for vendor-provided data and local usage data. Elsevier has got the highest usage degree in searches, sessions and downloads. Statistics also showed that a small number of journals satisfy significant amount of use while the majority of journals were used less frequent and some were never used at all. The users preferred the PDF rather than HTML format. The data in subject profile suggested that the provided e-resources were best suited to certain subjects. There was no correlation between IF and electronic journal use. Monitoring the usage of e-resources gained increasing importance for acquisition policy and budget decisions. The article provided information about local metrics for the six surveyed vendors/publishers, e.g. usage trends, requests per package, cost per use as related to the scientific specialty of the university.

  18. Use and User Perception of Electronic Information Resources: A Case Study of Siva Institute of Frontier Technology, India

    Directory of Open Access Journals (Sweden)

    Velmurugan Chandran

    2013-12-01

    Full Text Available The present study aims to explore the use and user perception of electronic resources in Siva Institute of Frontier Technology, India. A total number of 123 users were taken into account for the study through a questionnaire-based survey method. A well-structured questionnaire was designed and distributed to the selected 200 students and staff members. 123 copies of the questionnaires were returned dully filled in and the overall response rate was 61.50 percent. The questionnaire contained both open- and close-ended questions. The collected data were classified, analyzed, and tabulated by using simple statistical methods. This study covers the impact of electronic resources on students and faculty in their academic pursuit.

  19. Challenges in the implementation of an electronic surveillance system in a resource-limited setting: Alerta, in Peru

    Directory of Open Access Journals (Sweden)

    Soto Giselle

    2008-11-01

    Full Text Available Abstract Background Infectious disease surveillance is a primary public health function in resource-limited settings. In 2003, an electronic disease surveillance system (Alerta was established in the Peruvian Navy with support from the U.S. Naval Medical Research Center Detachment (NMRCD. Many challenges arose during the implementation process, and a variety of solutions were applied. The purpose of this paper is to identify and discuss these issues. Methods This is a retrospective description of the Alerta implementation. After a thoughtful evaluation according to the Centers for Disease Control and Prevention (CDC guidelines, the main challenges to implementation were identified and solutions were devised in the context of a resource-limited setting, Peru. Results After four years of operation, we have identified a number of challenges in implementing and operating this electronic disease surveillance system. These can be divided into the following categories: (1 issues with personnel and stakeholders; (2 issues with resources in a developing setting; (3 issues with processes involved in the collection of data and operation of the system; and (4 issues with organization at the central hub. Some of the challenges are unique to resource-limited settings, but many are applicable for any surveillance system. For each of these challenges, we developed feasible solutions that are discussed. Conclusion There are many challenges to overcome when implementing an electronic disease surveillance system, not only related to technology issues. A comprehensive approach is required for success, including: technical support, personnel management, effective training, and cultural sensitivity in order to assure the effective deployment of an electronic disease surveillance system.

  20. RESEARCH OF INFLUENCE OF QUALITY OF ELECTRONIC EDUCATIONAL RESOURCES ON QUALITY OF TRAINING WITH USE OF DISTANCE TECHNOLOGIES

    Directory of Open Access Journals (Sweden)

    H. M. Kravtsov

    2013-03-01

    Full Text Available Communication improving of educational processes requires today new approaches to the management arrangements and forming of educational policy in the field of distance learning, which is based on the use of modern information and communication technologies. An important step in this process is the continuous monitoring of the development and implementation of information technology and, in particular, the distance learning systems in higher educational establishments. The main objective of the monitoring is the impact assessment on the development of distance learning following the state educational standards, curricula, methodical and technical equipment and other factors; factors revelation that influence the implementation and outcomes of distance learning; results comparison of educational institution functioning and distance education systems in order to determine the most efficient ways of its development. The paper presents the analysis results of the dependence of the quality of educational services on the electronic educational resources. Trends in educational services development was studied by comparing the quality influence of electronic educational resources on the quality of educational services of higher pedagogical educational institutions of Ukraine as of 2009-2010 and 2012-2013. Generally, the analysis of the survey results allows evaluating quality of the modern education services as satisfactory and it can be said that almost 70% of the success of their future development depends on the quality of the used electronic educational resources and distance learning systems in particular.

  1. Tracking the Flow of Resources in Electronic Waste - The Case of End-of-Life Computer Hard Disk Drives.

    Science.gov (United States)

    Habib, Komal; Parajuly, Keshav; Wenzel, Henrik

    2015-10-20

    Recovery of resources, in particular, metals, from waste flows is widely seen as a prioritized option to reduce their potential supply constraints in the future. The current waste electrical and electronic equipment (WEEE) treatment system is more focused on bulk metals, where the recycling rate of specialty metals, such as rare earths, is negligible compared to their increasing use in modern products, such as electronics. This study investigates the challenges in recovering these resources in the existing WEEE treatment system. It is illustrated by following the material flows of resources in a conventional WEEE treatment plant in Denmark. Computer hard disk drives (HDDs) containing neodymium-iron-boron (NdFeB) magnets were selected as the case product for this experiment. The resulting output fractions were tracked until their final treatment in order to estimate the recovery potential of rare earth elements (REEs) and other resources contained in HDDs. The results further show that out of the 244 kg of HDDs treated, 212 kg comprising mainly of aluminum and steel can be finally recovered from the metallurgic process. The results further demonstrate the complete loss of REEs in the existing shredding-based WEEE treatment processes. Dismantling and separate processing of NdFeB magnets from their end-use products can be a more preferred option over shredding. However, it remains a technological and logistic challenge for the existing system.

  2. HELP (INFORMATION ELECTRONIC RESOURCE "CHRONICLE OF ONU: DATES, FACTS, EVENTS": HISTORY OF UNIVERSITY IN INFORMATION SPACE

    Directory of Open Access Journals (Sweden)

    А. М. Гавриленко

    2016-03-01

    Object of research is the help information resource "The chronicle of the Odessa national university of I. I. Mechnikov: dates, facts, events". The main objective of our article – to state the main methodological bases of creation of information resource. One of advantages of information resource is possibility of continuous updating and replenishment by new information. Main objective of creation of this information resource is systematization of material on stories of the Odessa national university of I. I. Mechnikov from the date of his basis to the present, ensuring interactive access to information on the main dates, the most significant events in life of university. The base of research are sources on the history of university, chronology of historical development, formation of infrastructure, cadres and scientific researches. In information resource the main stages of development, functioning and transformation of the Odessa University are analyzed, information on its divisions is collected. For creation of this information resource in Scientific library the method of work was developed, the main selection criteria of data are allocated. This information resource have practical value for all who is interested in history of university, historians, scientists-researchers of history of science and the city of Odessa.

  3. Print and Electronic Resources: Usage Statistics at Guru Gobind Singh Indraprastha University Library

    Science.gov (United States)

    Kapoor, Kanta

    2010-01-01

    Purpose: The purpose of this paper is to quantify the use of electronic journals in comparison with the print collections in the Guru Gobind Singh Indraprastha University Library. Design/methodology/approach: A detailed analysis was made of the use of lending services, the Xerox facility and usage of electronic journals such as Science Direct,…

  4. Understanding intention to use electronic information resources: A theoretical extension of the technology acceptance model (TAM).

    Science.gov (United States)

    Tao, Donghua

    2008-11-06

    This study extended the Technology Acceptance Model (TAM) by examining the roles of two aspects of e-resource characteristics, namely, information quality and system quality, in predicting public health students' intention to use e-resources for completing research paper assignments. Both focus groups and a questionnaire were used to collect data. Descriptive analysis, data screening, and Structural Equation Modeling (SEM) techniques were used for data analysis. The study found that perceived usefulness played a major role in determining students' intention to use e-resources. Perceived usefulness and perceived ease of use fully mediated the impact that information quality and system quality had on behavior intention. The research model enriches the existing technology acceptance literature by extending TAM. Representing two aspects of e-resource characteristics provides greater explanatory information for diagnosing problems of system design, development, and implementation.

  5. Microglial cell dysregulation in brain aging and neurodegeneration

    OpenAIRE

    von Bernhardi, Rommy; Eugen?n-von Bernhardi, Laura; Eugen?n, Jaime

    2015-01-01

    Aging is the main risk factor for neurodegenerative diseases. In aging, microglia undergoes phenotypic changes compatible with their activation. Glial activation can lead to neuroinflammation, which is increasingly accepted as part of the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD). We hypothesize that in aging, aberrant microglia activation leads to a deleterious environment and neurodegeneration. In aged mice, microglia exhibit an increased expression of c...

  6. Multiproteinopathy, neurodegeneration and old age: a case study.

    Science.gov (United States)

    Rojas, Julio C; Stephens, Melanie L; Rabinovici, Gil D; Kramer, Joel H; Miller, Bruce L; Seeley, William W

    2018-02-01

    A complex spectrum of mixed brain pathologies is common in older people. This clinical pathologic conference case study illustrates the challenges of formulating clinicopathologic correlations in late-onset neurodegenerative diseases featuring cognitive-behavioral syndromes with underlying multiple proteinopathy. Studies on the co-existence and interactions of Alzheimer's disease (AD) with neurodegenerative non-AD pathologies in the aging brain are needed to understand the pathogenesis of neurodegeneration and to support the development of diagnostic biomarkers and therapies.

  7. Astrocytic Pathological Calcium Homeostasis and Impaired Vesicle Trafficking in Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Nina Vardjan

    2017-02-01

    Full Text Available Although the central nervous system (CNS consists of highly heterogeneous populations of neurones and glial cells, clustered into diverse anatomical regions with specific functions, there are some conditions, including alertness, awareness and attention that require simultaneous, coordinated and spatially homogeneous activity within a large area of the brain. During such events, the brain, representing only about two percent of body mass, but consuming one fifth of body glucose at rest, needs additional energy to be produced. How simultaneous energy procurement in a relatively extended area of the brain takes place is poorly understood. This mechanism is likely to be impaired in neurodegeneration, for example in Alzheimer’s disease, the hallmark of which is brain hypometabolism. Astrocytes, the main neural cell type producing and storing glycogen, a form of energy in the brain, also hold the key to metabolic and homeostatic support in the central nervous system and are impaired in neurodegeneration, contributing to the slow decline of excitation-energy coupling in the brain. Many mechanisms are affected, including cell-to-cell signalling. An important question is how changes in cellular signalling, a process taking place in a rather short time domain, contribute to the neurodegeneration that develops over decades. In this review we focus initially on the slow dynamics of Alzheimer’s disease, and on the activity of locus coeruleus, a brainstem nucleus involved in arousal. Subsequently, we overview much faster processes of vesicle traffic and cytosolic calcium dynamics, both of which shape the signalling landscape of astrocyte-neurone communication in health and neurodegeneration.

  8. Optic neuropathies: the tip of the neurodegeneration iceberg

    Science.gov (United States)

    Carelli, Valerio; La Morgia, Chiara; Ross-Cisneros, Fred N.; Sadun, Alfredo A.

    2017-01-01

    Abstract The optic nerve and the cells that give origin to its 1.2 million axons, the retinal ganglion cells (RGCs), are particularly vulnerable to neurodegeneration related to mitochondrial dysfunction. Optic neuropathies may range from non-syndromic genetic entities, to rare syndromic multisystem diseases with optic atrophy such as mitochondrial encephalomyopathies, to age-related neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease where optic nerve involvement has, until recently, been a relatively overlooked feature. New tools are available to thoroughly investigate optic nerve function, allowing unparalleled access to this part of the central nervous system. Understanding the molecular pathophysiology of RGC neurodegeneration and optic atrophy, is key to broadly understanding the pathogenesis of neurodegenerative disorders, for monitoring their progression in describing the natural history, and ultimately as outcome measures to evaluate therapies. In this review, the different layers, from molecular to anatomical, that may contribute to RGC neurodegeneration and optic atrophy are tackled in an integrated way, considering all relevant players. These include RGC dendrites, cell bodies and axons, the unmyelinated retinal nerve fiber layer and the myelinated post-laminar axons, as well as olygodendrocytes and astrocytes, looked for unconventional functions. Dysfunctional mitochondrial dynamics, transport, homeostatic control of mitobiogenesis and mitophagic removal, as well as specific propensity to apoptosis may target differently cell types and anatomical settings. Ultimately, we can envisage new investigative approaches and therapeutic options that will speed the early diagnosis of neurodegenerative diseases and their cure. PMID:28977448

  9. Xeroderma Pigmentosum: defective DNA repair causes skin cancer and neurodegeneration

    International Nuclear Information System (INIS)

    Robbins, J.H.

    1988-01-01

    Xeroderma pigmentosum is a rare autosomal recessive disease with numerous malignancies on sun-exposed areas of the skin and eye because of an inability to repair DNA damage inflicted by harmful ultraviolet (UV) radiation of the sun. Because it is the only disease in which cancer is known to result from defective DNA repair, XP has received intense clinical and biochemical study during the last two decades. Furthermore, some patients with XP develop a primary neuronal degeneration, probably due to the inability of nerve cells to repair damage to their DNA caused by intraneuronal metabolites and physicochemical events that mimic the effects of UV radiation. Studies of XP neurodegeneration and DNA-repair defects have led to the conclusion that efficient DNA repair is required to prevent premature death of human nerve cells. Since XP neurodegeneration has similarities to premature death of nerve cells that occurs in such neurodegenerative disorders, XP may be the prototype for these more common neurodegenerations. Recent studies indicate that these degenerations also may have DNA-repair defects

  10. Building and Managing Electronic Resources in Digital Era in India with Special Reference to IUCAA and NIV, Pune: A Comparative Case Study

    Science.gov (United States)

    Sahu, H. K.; Singh, S. N.

    2015-04-01

    This paper discusses and presents a comparative case study of two libraries in Pune, India, Inter-University Centre for Astronomy and Astrophysics and Information Centre and Library of National Institute of Virology (Indian Council of Medical Research). It compares how both libraries have managed their e-resource collections, including acquisitions, subscriptions, and consortia arrangements, while also developing a collection of their own resources, including pre-prints and publications, video lectures, and other materials in an institutional repository. This study illustrates how difficult it is to manage electronic resources in a developing country like India, even though electronic resources are used more than print resources. Electronic resource management can be daunting, but with a systematic approach, various problems can be solved, and use of the materials will be enhanced.

  11. The level of the usage of the human resource information system and electronic recruitment in Croatian companies

    Directory of Open Access Journals (Sweden)

    Snježana Pivac

    2014-12-01

    Full Text Available Performing business according to contemporary requirements influences companies for continuous usage of modern managerial tools, such as a human resource information system (HRIS and electronic recruitment (ER. Human resources have been recognised as curtail resources and the main source of a competitive advantage in creation of successful business performance. In order to attract and select the top employees, companies use quality information software for attracting internal ones, and electronic recruitment for attracting the best possible external candidates. The main aim of this paper is to research the level of the usage of HRIS and ER within medium-size and large Croatian companies. Moreover, the additional aim of this paper is to evaluate the relationship among the usage of these modern managerial tools and the overall success of human resource management within these companies. For the purpose of this paper, primary and secondary research has been conducted in order to reveal the level of the usage of HRIS and ER as well as the overall success of human resource management in Croatian companies. The companies’ classification (HRIS and ER is done by using the non-hierarchical k-means cluster method as well as the nonparametric Kruskal Wallis test. Further, the companies are ranked by the multicriteria PROMETHEE method. Relevant nonparametric tests are used for testing the overall companies’ HRM. Finally, binary logistic regression is estimated, relating binary variable HRM and HRIS development. After detailed research, it can be concluded that large Croatian companies apply HRIS in majority (with a positive relation to HRM performance, but still require certain degrees of its development.

  12. Epidemiology of neurodegeneration in American-style professional football players.

    Science.gov (United States)

    Lehman, Everett J

    2013-01-01

    The purpose of this article is to review the history of head injuries in relation to American-style football play, summarize recent research that has linked football head injuries to neurodegeneration, and provide a discussion of the next steps for refining the examination of neurodegeneration in football players. For most of the history of football, the focus of media reports and scientific studies on football-related head injuries was on the acute or short-term effects of serious, traumatic head injuries. Beginning about 10 years ago, a growing concern developed among neurologists and researchers about the long-term effects that playing professional football has on the neurologic health of the players. Autopsy-based studies identified a pathologically distinct neurodegenerative disorder, chronic traumatic encephalopathy, among athletes who were known to have experienced concussive and subconcussive blows to the head during their playing careers. Football players have been well represented in these autopsy findings. A mortality study of a large cohort of retired professional football players found a significantly increased risk of death from neurodegeneration. Further analysis found that non-line players were at higher risk than line players, possibly because of an increased risk of concussion. Although the results of the studies reviewed do not establish a cause effect relationship between football-related head injury and neurodegenerative disorders, a growing body of research supports the hypothesis that professional football players are at an increased risk of neurodegeneration. Significant progress has been made in the last few years on detecting and defining the pathology of neurodegenerative diseases. However, less progress has been made on other factors related to the progression of those diseases in football players. This review identifies three areas for further research: (a) quantification of exposure - a consensus is needed on the use of clinically

  13. Peroxisome proliferator-activated receptor γ is expressed in hippocampal neurons and its activation prevents β-amyloid neurodegeneration: role of Wnt signaling

    International Nuclear Information System (INIS)

    Inestrosa, Nibaldo C.; Godoy, Juan A.; Quintanilla, Rodrigo A.; Koenig, Cecilia S.; Bronfman, Miguel

    2005-01-01

    The molecular pathogenesis of Alzheimer's disease (AD) involves the participation of the amyloid-β-peptide (Aβ), which plays a critical role in the neurodegeneration that triggers the disease. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors, which are members of the nuclear receptor family. We report here that (1) PPARγ is present in rat hippocampal neurons in culture. (2) Activation of PPARγ by troglitazone and rosiglitazone protects rat hippocampal neurons against Aβ-induced neurodegeneration, as shown by the 3-[4,5 -2yl]-2,5-diphenyltetrazolium bromide (MTT) reduction assay, immunofluorescence using an anti-heavy neurofilament antibody, and quantitative electron microscopy. (3) Hippocampal neurons treated with several PPARγ agonists, including troglitazone, rosiglitazone, and ciglitazone, prevent the excitotoxic Aβ-induced rise in bulk-free Ca 2+ . (4) PPARγ activation results in the modulation of Wnt signaling components, including the inhibition of glycogen synthase kinase-3β (GSK-3β) and an increase of the cytoplasmic and nuclear β-catenin levels. We conclude that the activation of PPARγ prevents Aβ-induced neurodegeneration by a mechanism that may involve a cross talk between neuronal PPARγ and the Wnt signaling pathway. More important, the fact that the activation of PPARγ attenuated Aβ-dependent neurodegeneration opens the possibility to fight AD from a new therapeutic perspective

  14. MendelWeb: An Electronic Science/Math/History Resource for the WWW.

    Science.gov (United States)

    Blumberg, Roger B.

    This paper describes a hypermedia resource, called MendelWeb that integrates elementary biology, discrete mathematics, and the history of science. MendelWeb is constructed from Gregor Menders 1865 paper, "Experiments in Plant Hybridization". An English translation of Mendel's paper, which is considered to mark the birth of classical and…

  15. Helping Patrons Find Locally Held Electronic Resources: An Interlibrary Loan Perspective

    Science.gov (United States)

    Johnston, Pamela

    2016-01-01

    The University of North Texas Libraries provide extensive online access to academic journals through major vendor databases. As illustrated by interlibrary loan borrowing requests for items held in our databases, patrons often have difficulty navigating the available resources. In this study, the Interlibrary Loan staff used data gathered from the…

  16. QR Codes as Finding Aides: Linking Electronic and Print Library Resources

    Science.gov (United States)

    Kane, Danielle; Schneidewind, Jeff

    2011-01-01

    As part of a focused, methodical, and evaluative approach to emerging technologies, QR codes are one of many new technologies being used by the UC Irvine Libraries. QR codes provide simple connections between print and virtual resources. In summer 2010, a small task force began to investigate how QR codes could be used to provide information and…

  17. Defining SNAP by cross-sectional and longitudinal definitions of neurodegeneration

    OpenAIRE

    Wisse, L.E.M.; Das, S.R.; Davatzikos, C.; Dickerson, B.C.; Xie, S.X.; Yushkevich, P.A.; Wolk, D.A.

    2018-01-01

    Introduction: Suspected non-Alzheimer's pathophysiology (SNAP) is a biomarker driven designation that represents a heterogeneous group in terms of etiology and prognosis. SNAP has only been identified by cross-sectional neurodegeneration measures, whereas longitudinal measures might better reflect “active” neurodegeneration and might be more tightly linked to prognosis. We compare neurodegeneration defined by cross-sectional ‘hippocampal volume’ only (SNAP/L−) versus both cross-sectional and ...

  18. Eavesdropping on Electronic Guidebooks: Observing Learning Resources in Shared Listening Environments.

    Science.gov (United States)

    Woodruff, Allison; Aoki, Paul M.; Grinter, Rebecca E.; Hurst, Amy; Szymanski, Margaret H.; Thornton, James D.

    This paper describes an electronic guidebook, "Sotto Voce," that enables visitors to share audio information by eavesdropping on each others guidebook activity. The first section discusses the design and implementation of the guidebook device, key aspects of its user interface, the design goals for the audio environment, the eavesdropping…

  19. Development and evolution of The Knowledge Hub for Pathology and related electronic resources.

    Science.gov (United States)

    Hardwick, David F; Sinard, John; Silva, Fred

    2011-06-01

    The Knowledge Hub for Pathology was created to provide authenticated and validated knowledge for United States and Canadian Academy of Pathology members and pathologists worldwide with access to the Web. Using the material presented at the annual meeting of the United States and Canadian Academy of Pathology with existing selection and review procedures ensured that these criteria were met without added costly procedures. Further submissions for courses and research papers are provided in electronic format and funded by universities and hospitals for their creation; thus, the principal costs borne by the United States and Canadian Academy of Pathology are Web site-posting costs. Use has escalated rapidly from 2 million hits in 2002 to 51 million in 2009 with use by 35,000 pathologists from now a total of 180 countries. This true "freemium" model is a successful process as are more traditional continuing professional development course structures such as Anatomic Pathology Electronic Case Series, a "premium" model for learning electronically also sponsored by the United States and Canadian Academy of Pathology. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. An Exploratory study on the use of LibAnswers to Resolve, Track and Monitor Electronic Resources Issues: The KAUST Library experience

    KAUST Repository

    Ramli, Rindra M.

    2017-01-01

    An Exploratory study on KAUST library use of LibAnswers in resolving electronic resources questions received in LibAnswers. It describes the findings of the questions received in LibAnswers. The author made suggestions based on the findings to improve the reference services in responding to e-resources questions.

  1. An Exploratory study on the use of LibAnswers to Resolve, Track and Monitor Electronic Resources Issues: The KAUST Library experience

    KAUST Repository

    Ramli, Rindra M.

    2017-05-03

    An Exploratory study on KAUST library use of LibAnswers in resolving electronic resources questions received in LibAnswers. It describes the findings of the questions received in LibAnswers. The author made suggestions based on the findings to improve the reference services in responding to e-resources questions.

  2. Designing a model of electronic human resource management’s implementation at the Ministry of Communications and Information Technology

    Directory of Open Access Journals (Sweden)

    Mirali Seyednaghavi

    2017-06-01

    Full Text Available : In the first phase of this study a model for electronic human resource management in government agencies based on new public services was explored by using software MAXQDA, then in the second phase, relationship between the elements of the theory were tested using software Smart PLS2. So the aim of this study is to design a model of electronic human resource management’s implementation at the Ministry of Communications and Information Technology. In this regard, according to Strauss and Corbin’s structured plan, five hypotheses were tested. Quantitative data analysis indicates that the pressures of the policies and global perspectives cause to move toward e-HRM. Among the contextual conditions macro structural mechanisms, considerations of actors, governance considerations have a significant impact on the strategy of new public services and therefore lead to the consequences of its implementation in public organizations. The findings suggest that e-HRM does not have a positive and meaningful impact on new public services, and in our country, although the recent political developments have somehow removed the gap between public policy makers, administrators, and the public, but there is still a long way to go.

  3. Preference and Use of Electronic Information and Resources by Blind/Visually Impaired in NCR Libraries in India

    Directory of Open Access Journals (Sweden)

    Shailendra Kumar

    2013-06-01

    Full Text Available This paper aims to determine the preference and use of electronic information and resources by blind/visually impaired users in the leading National Capital Region (NCR libraries of India. Survey methodology has been used as the basic research tool for data collection with the help of questionnaires. The 125 in total users surveyed in all the five libraries were selected randomly on the basis of willingness of the users with experience of working in digital environments to participate in the survey. The survey results were tabulated and analyzed with descriptive statistics methods using Excel software and 'Stata version 11'. The findings reveal that ICT have a positive impact in the lives of people with disabilities as it helps them to work independently and increases the level of confidence among them. The Internet is the most preferred medium of access to information among the majority of blind/visually impaired users. The 'Complexity of content available on the net' is found as the major challenge faced during Internet use by blind users of NCR libraries. 'Audio books on CDs/DVDs and DAISY books' are the most preferred electronic resources among the majority of blind/visually impaired users. This study will help the library professionals and organizations/institutions serving people with disabilities to develop effective library services for blind/visually impaired users in the digital environment on the basis of findings on information usage behavior in the study.

  4. Brain and Peripheral Atypical Inflammatory Mediators Potentiate Neuroinflammation and Neurodegeneration.

    Science.gov (United States)

    Kempuraj, Duraisamy; Thangavel, Ramasamy; Selvakumar, Govindhasamy P; Zaheer, Smita; Ahmed, Mohammad E; Raikwar, Sudhanshu P; Zahoor, Haris; Saeed, Daniyal; Natteru, Prashant A; Iyer, Shankar; Zaheer, Asgar

    2017-01-01

    Neuroinflammatory response is primarily a protective mechanism in the brain. However, excessive and chronic inflammatory responses can lead to deleterious effects involving immune cells, brain cells and signaling molecules. Neuroinflammation induces and accelerates pathogenesis of Parkinson's disease (PD), Alzheimer's disease (AD) and Multiple sclerosis (MS). Neuroinflammatory pathways are indicated as novel therapeutic targets for these diseases. Mast cells are immune cells of hematopoietic origin that regulate inflammation and upon activation release many proinflammatory mediators in systemic and central nervous system (CNS) inflammatory conditions. In addition, inflammatory mediators released from activated glial cells induce neurodegeneration in the brain. Systemic inflammation-derived proinflammatory cytokines/chemokines and other factors cause a breach in the blood brain-barrier (BBB) thereby allowing for the entry of immune/inflammatory cells including mast cell progenitors, mast cells and proinflammatory cytokines and chemokines into the brain. These peripheral-derived factors and intrinsically generated cytokines/chemokines, α-synuclein, corticotropin-releasing hormone (CRH), substance P (SP), beta amyloid 1-42 (Aβ1-42) peptide and amyloid precursor proteins can activate glial cells, T-cells and mast cells in the brain can induce additional release of inflammatory and neurotoxic molecules contributing to chronic neuroinflammation and neuronal death. The glia maturation factor (GMF), a proinflammatory protein discovered in our laboratory released from glia, activates mast cells to release inflammatory cytokines and chemokines. Chronic increase in the proinflammatory mediators induces neurotoxic Aβ and plaque formation in AD brains and neurodegeneration in PD brains. Glial cells, mast cells and T-cells can reactivate each other in neuroinflammatory conditions in the brain and augment neuroinflammation. Further, inflammatory mediators from the brain can

  5. Huntingtin interacting proteins are genetic modifiers of neurodegeneration.

    Directory of Open Access Journals (Sweden)

    Linda S Kaltenbach

    2007-05-01

    Full Text Available Huntington's disease (HD is a fatal neurodegenerative condition caused by expansion of the polyglutamine tract in the huntingtin (Htt protein. Neuronal toxicity in HD is thought to be, at least in part, a consequence of protein interactions involving mutant Htt. We therefore hypothesized that genetic modifiers of HD neurodegeneration should be enriched among Htt protein interactors. To test this idea, we identified a comprehensive set of Htt interactors using two complementary approaches: high-throughput yeast two-hybrid screening and affinity pull down followed by mass spectrometry. This effort led to the identification of 234 high-confidence Htt-associated proteins, 104 of which were found with the yeast method and 130 with the pull downs. We then tested an arbitrary set of 60 genes encoding interacting proteins for their ability to behave as genetic modifiers of neurodegeneration in a Drosophila model of HD. This high-content validation assay showed that 27 of 60 orthologs tested were high-confidence genetic modifiers, as modification was observed with more than one allele. The 45% hit rate for genetic modifiers seen among the interactors is an order of magnitude higher than the 1%-4% typically observed in unbiased genetic screens. Genetic modifiers were similarly represented among proteins discovered using yeast two-hybrid and pull-down/mass spectrometry methods, supporting the notion that these complementary technologies are equally useful in identifying biologically relevant proteins. Interacting proteins confirmed as modifiers of the neurodegeneration phenotype represent a diverse array of biological functions, including synaptic transmission, cytoskeletal organization, signal transduction, and transcription. Among the modifiers were 17 loss-of-function suppressors of neurodegeneration, which can be considered potential targets for therapeutic intervention. Finally, we show that seven interacting proteins from among 11 tested were able to

  6. Internet and electronic resources for inflammatory bowel disease: a primer for providers and patients.

    Science.gov (United States)

    Fortinsky, Kyle J; Fournier, Marc R; Benchimol, Eric I

    2012-06-01

    Patients with inflammatory bowel disease (IBD) are increasingly turning to the Internet to research their condition and engage in discourse on their experiences. This has resulted in new dynamics in the relationship between providers and their patients, with misinformation and advertising potentially presenting barriers to the cooperative patient-provider partnership. This article addresses important issues of online IBD-related health information and social media activity, such as quality, reliability, objectivity, and privacy. We reviewed the medical literature on the quality of online information provided to IBD patients, and summarized the most commonly accessed Websites related to IBD. We also assessed the activity on popular social media sites (such as Facebook, Twitter, and YouTube), and evaluated currently available applications for use by IBD patients and providers on mobile phones and tablets. Through our review of the literature and currently available resources, we developed a list of recommended online resources to strengthen patient participation in their care by providing reliable, comprehensive educational material. Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.

  7. Cerebrospinal fluid biomarkers of neurodegeneration are decreased or normal in narcolepsy

    DEFF Research Database (Denmark)

    Jennum, Poul Jørgen; Pedersen, Lars Østergaard; Bahl, Justyna Maria Czarna

    2017-01-01

    OBJECTIVES: To investigate whether cerebrospinal fluid (CSF) biomarkers of neurodegeneration are altered in narcolepsy in order to evaluate whether the hypocretin deficiency and abnormal sleep-wake pattern in narcolepsy leads to neurodegeneration. METHODS: Twenty-one patients with central...... that hypocretin deficiency and an abnormal sleep-wake pattern alter the turnover of these proteins in CNS....

  8. Autophagy and Microglia: Novel Partners in Neurodegeneration and Aging.

    Science.gov (United States)

    Plaza-Zabala, Ainhoa; Sierra-Torre, Virginia; Sierra, Amanda

    2017-03-09

    Autophagy is emerging as a core regulator of Central Nervous System (CNS) aging and neurodegeneration. In the brain, it has mostly been studied in neurons, where the delivery of toxic molecules and organelles to the lysosome by autophagy is crucial for neuronal health and survival. However, we propose that the (dys)regulation of autophagy in microglia also affects innate immune functions such as phagocytosis and inflammation, which in turn contribute to the pathophysiology of aging and neurodegenerative diseases. Herein, we first describe the basic concepts of autophagy and its regulation, discuss key aspects for its accurate monitoring at the experimental level, and summarize the evidence linking autophagy impairment to CNS senescence and disease. We focus on acute, chronic, and autoimmunity-mediated neurodegeneration, including ischemia/stroke, Alzheimer's, Parkinson's, and Huntington's diseases, and multiple sclerosis. Next, we describe the actual and potential impact of autophagy on microglial phagocytic and inflammatory function. Thus, we provide evidence of how autophagy may affect microglial phagocytosis of apoptotic cells, amyloid-β, synaptic material, and myelin debris, and regulate the progression of age-associated neurodegenerative diseases. We also discuss data linking autophagy to the regulation of the microglial inflammatory phenotype, which is known to contribute to age-related brain dysfunction. Overall, we update the current knowledge of autophagy and microglia, and highlight as yet unexplored mechanisms whereby autophagy in microglia may contribute to CNS disease and senescence.

  9. Impact of aging immune system on neurodegeneration and potential immunotherapies.

    Science.gov (United States)

    Liang, Zhanfeng; Zhao, Yang; Ruan, Linhui; Zhu, Linnan; Jin, Kunlin; Zhuge, Qichuan; Su, Dong-Ming; Zhao, Yong

    2017-10-01

    The interaction between the nervous and immune systems during aging is an area of avid interest, but many aspects remain unclear. This is due, not only to the complexity of the aging process, but also to a mutual dependency and reciprocal causation of alterations and diseases between both the nervous and immune systems. Aging of the brain drives whole body systemic aging, including aging-related changes of the immune system. In turn, the immune system aging, particularly immunosenescence and T cell aging initiated by thymic involution that are sources of chronic inflammation in the elderly (termed inflammaging), potentially induces brain aging and memory loss in a reciprocal manner. Therefore, immunotherapeutics including modulation of inflammation, vaccination, cellular immune therapies and "protective autoimmunity" provide promising approaches to rejuvenate neuroinflammatory disorders and repair brain injury. In this review, we summarize recent discoveries linking the aging immune system with the development of neurodegeneration. Additionally, we discuss potential rejuvenation strategies, focusing aimed at targeting the aging immune system in an effort to prevent acute brain injury and chronic neurodegeneration during aging. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Electronic medical records in diabetes consultations: participants' gaze as an interactional resource.

    Science.gov (United States)

    Rhodes, Penny; Small, Neil; Rowley, Emma; Langdon, Mark; Ariss, Steven; Wright, John

    2008-09-01

    Two routine consultations in primary care diabetes clinics are compared using extracts from video recordings of interactions between nurses and patients. The consultations were chosen to present different styles of interaction, in which the nurse's gaze was either primarily toward the computer screen or directed more toward the patient. Using conversation analysis, the ways in which nurses shift both gaze and body orientation between the computer screen and patient to influence the style, pace, content, and structure of the consultation were investigated. By examining the effects of different levels of engagement between the electronic medical record and the embodied patient in the consultation room, we argue for the need to consider the contingent nature of the interface of technology and the person in the consultation. Policy initiatives designed to deliver what is considered best-evidenced practice are modified in the micro context of the interactions of the consultation.

  11. Granulometric composition study of mineral resources using opto-electronic devices and Elsieve software system

    Directory of Open Access Journals (Sweden)

    Kaminski Stanislaw

    2016-01-01

    Full Text Available The use of mechanical sieves has a great impact on measurement results because occurrence of anisometric particles causes undercounting the average size. Such errors can be avoided by using opto-electronic measuring devices that enable measurement of particles from 10 μm up to a few dozen millimetres in size. The results of measurement of each particle size fraction are summed up proportionally to its weight with the use of Elsieve software system and for every type of material particle-size distribution can be obtained. The software allows further statistical interpretation of the results. Beam of infrared radiation identifies size of particles and counts them precisely. Every particle is represented by an electronic impulse proportional to its size. Measurement of particles in aqueous suspension that replaces the hydrometer method can be carried out by using the IPS L analyser (range from 0.2 to 600 μm. The IPS UA analyser (range from 0.5 to 2000 μm is designed for measurement in the air. An ultrasonic adapter enables performing measurements of moist and aggregated particles from 0.5 to 1000 μm. The construction and software system allow to determine second dimension of the particle, its shape coefficient and specific surface area. The AWK 3D analyser (range from 0.2 to 31.5 mm is devoted to measurement of various powdery materials with subsequent determination of particle shape. The AWK B analyser (range from 1 to 130 mm measures materials of thick granulation and shape of the grains. The presented method of measurement repeatedly accelerates and facilitates study of granulometric composition.

  12. Timing of neurodegeneration and beta-amyloid (Abeta) peptide deposition in the brain of aging kokanee salmon.

    Science.gov (United States)

    Maldonado, Tammy A; Jones, Richard E; Norris, David O

    2002-10-01

    Brains of kokanee salmon (Oncorhynchus nerka kennerlyi) in one of four reproductive stages (sexually immature, maturing, sexually mature, and spawning) were stained with cresyl violet and silver stain to visualize neurodegeneration. These reproductive stages correlate with increasing somatic aging of kokanee salmon, which die after spawning. Twenty-four regions of each brain were examined. Brains of sexually immature fish exhibited low levels of neurodegeneration, whereas neurodegeneration was more marked in maturing fish and greatest in spawning fish. Neurodegeneration was present in specific regions of the telencephalon, diencephalon, mesencephalon, and rhombencephalon. Pyknotic neurons were observed in all regions previously reported to be immunopositive for A beta. Regions that did not exhibit neurodegeneration during aging included the magnocellular vestibular nucleus, the nucleus lateralis tuberis of the hypothalamus, and Purkinje cells of the cerebellum, all of which also lack A beta; perhaps these regions are neuroprotected. In 14 of 16 brain areas for which data were available on both the increase in A beta deposition and pyknosis, neurodegeneration preceded or appeared more or less simultaneously with A beta production, whereas in only two regions did A beta deposition precede neurodegeneration. This information supports the hypothesis that A beta deposition is a downstream product of neurodegeneration in most brain regions. Other conclusions are that the degree of neurodegeneration varies among brain regions, neurodegeneration begins in maturing fish and peaks in spawning fish, the timing of neurodegeneration varies among brain regions, and some regions do not exhibit accelerated neurodegeneration during aging. Copyright 2002 Wiley Periodicals, Inc.

  13. Green Supply Chain Collaboration for Fashionable Consumer Electronics Products under Third-Party Power Intervention—A Resource Dependence Perspective

    Directory of Open Access Journals (Sweden)

    Jiuh-Biing Sheu

    2014-05-01

    Full Text Available Under third-party power intervention (TPPI, which increases uncertainty in task environments, complex channel power interplays and restructuring are indispensable among green supply chain members as they move toward sustainable collaborative relationships for increased viability and competitive advantage. From the resource dependence perspective, this work presents a novel conceptual model to investigate the influence of political and social power on channel power restructuring and induced green supply chain collaboration in brander-retailer bidirectional green supply chains of fashionable consumer electronics products (FCEPs. An FCEP refers to the consumer electronics product (e.g., personal computers, mobile phones, computer notebooks, and game consoles with the features of a well-known brand associated, a short product lifecycle, timely and fashionable design fit for market trends, and quick responsiveness to the variations of market demands. The proposed model is tested empirically using questionnaire data obtained from retailers in the FCEP brander-retailer distribution channels. Analytical results reveal that as an extension of political and social power, TPPI positively affects the reciprocal interdependence of dyadic members and reduces power asymmetry, thereby enhancing the collaborative relationship of dyadic members and leading to improved green supply chain performance. Therein, reciprocal interdependence underlying collaborative relationship is the key to reducing the external environmental uncertainties in the TPPI context.

  14. The management of online resources and long-term saving of electronic documents by transfer into the digital space

    Directory of Open Access Journals (Sweden)

    Marius Daniel MAREŞ

    2011-12-01

    The electronic archive refers to the electronic storage system, along with the totality of electronic-type stored documents, while using as storage support any environment that can support storing and from which an electronic document can be presented.

  15. Age-Related Neurodegeneration and Memory Loss in Down Syndrome

    Directory of Open Access Journals (Sweden)

    Jason P. Lockrow

    2012-01-01

    Full Text Available Down syndrome (DS is a condition where a complete or segmental chromosome 21 trisomy causes variable intellectual disability, and progressive memory loss and neurodegeneration with age. Many research groups have examined development of the brain in DS individuals, but studies on age-related changes should also be considered, with the increased lifespan observed in DS. DS leads to pathological hallmarks of Alzheimer's disease (AD by 40 or 50 years of age. Progressive age-related memory deficits occurring in both AD and in DS have been connected to degeneration of several neuronal populations, but mechanisms are not fully elucidated. Inflammation and oxidative stress are early events in DS pathology, and focusing on these pathways may lead to development of successful intervention strategies for AD associated with DS. Here we discuss recent findings and potential treatment avenues regarding development of AD neuropathology and memory loss in DS.

  16. Metals and Neurodegeneration [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Pan Chen

    2016-03-01

    Full Text Available Metals play important roles in the human body, maintaining cell structure and regulating gene expression, neurotransmission, and antioxidant response, to name a few. However, excessive metal accumulation in the nervous system may be toxic, inducing oxidative stress, disrupting mitochondrial function, and impairing the activity of numerous enzymes. Damage caused by metal accumulation may result in permanent injuries, including severe neurological disorders. Epidemiological and clinical studies have shown a strong correlation between aberrant metal exposure and a number of neurological diseases, including Alzheimer’s disease, amyotrophic lateral sclerosis, autism spectrum disorders, Guillain–Barré disease, Gulf War syndrome, Huntington’s disease, multiple sclerosis, Parkinson’s disease, and Wilson’s disease. Here, we briefly survey the literature relating to the role of metals in neurodegeneration.

  17. Deep Brain Stimulation for Pantothenate Kinase-Associated Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Pedro J. Garcia-Ruiz

    2015-01-01

    Full Text Available Pantothenate kinase-associated neurodegeneration (PKAN is usually associated with dystonia, which is typically severe and progressive over time. Pallidal stimulation (GPi DBS has been carried out in selected cases of PKAN with drug-resistant dystonia with variable results. We report a 30-month follow-up study of a 30-year-old woman with PKAN-related dystonia treated with GPi DBS. Postoperatively, the benefit quickly became evident, as the patient exhibited a marked improvement in her dystonia, including her writing difficulty. This result has been maintained up to the present. GPi DBS should be considered in dystonic PKAN patients provided fixed contractures and/or pyramidal symptoms are not present.

  18. Neuronal matrix metalloproteinase-9 is a determinant of selective neurodegeneration.

    Science.gov (United States)

    Kaplan, Artem; Spiller, Krista J; Towne, Christopher; Kanning, Kevin C; Choe, Ginn T; Geber, Adam; Akay, Turgay; Aebischer, Patrick; Henderson, Christopher E

    2014-01-22

    Selective neuronal loss is the hallmark of neurodegenerative diseases. In patients with amyotrophic lateral sclerosis (ALS), most motor neurons die but those innervating extraocular, pelvic sphincter, and slow limb muscles exhibit selective resistance. We identified 18 genes that show >10-fold differential expression between resistant and vulnerable motor neurons. One of these, matrix metalloproteinase-9 (MMP-9), is expressed only by fast motor neurons, which are selectively vulnerable. In ALS model mice expressing mutant superoxide dismutase (SOD1), reduction of MMP-9 function using gene ablation, viral gene therapy, or pharmacological inhibition significantly delayed muscle denervation. In the presence of mutant SOD1, MMP-9 expressed by fast motor neurons themselves enhances activation of ER stress and is sufficient to trigger axonal die-back. These findings define MMP-9 as a candidate therapeutic target for ALS. The molecular basis of neuronal diversity thus provides significant insights into mechanisms of selective vulnerability to neurodegeneration. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Chromosome 13 dementia syndromes as models of neurodegeneration

    DEFF Research Database (Denmark)

    Ghiso, J.; Revesz, T.; Holton, J.

    2001-01-01

    Two hereditary conditions, familial British dementia (FBD) and familial Danish dementia (FDD), are associated with amyloid deposition in the central nervous system and neurodegeneration. The two amyloid proteins, ABri and ADan, are degradation products of the same precursor molecule BriPP bearing......-terminus. Neurofibrillary tangles containing the classical paired helical filaments as well as neuritic components in many instances co-localize with the amyloid deposits. In both disorders, the pattern of hyperphosphorylatedtau immunoreactivity is almost indistinguishable from that seen in Alzheimer's disease....... These issues argue for the primary importance of the amyloid deposits in the mechanism(s) of neuronal cell loss. We propose FBD and FDD, the chromosome 13 dementia syndromes, as models to study the molecular basis of neurofibrillary degeneration, cell death and amyloid formation in the brain....

  20. Strategies for clinical approach to neurodegeneration in Amyotrophic lateral sclerosis.

    Science.gov (United States)

    Carlesi, Cecilia; Pasquali, Livia; Piazza, Selina; Lo Gerfo, Annalisa; Caldarazzo Ienco, Elena; Alessi, Rosaria; Fornai, Francesco; Siciliano, Gabriele

    2011-03-01

    Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and ultimately fatal neurodegenerative disorder of unknown aetiology that involves the loss of upper and lower motor neurons in the cerebral cortex, brainstem and spinal cord. Significant progress in understanding the cellular mechanisms of motor neuron degeneration in ALS has not been matched with the development of therapeutic strategies to prevent disease progression, and riluzole remains the only available therapy, with only marginal effects on disease survival. More recently alterations of mRNA processing in genetically defined forms of ALS, as those related to TDP-43 and FUS-TLS gene mutations have provided important insights into the molecular networks implicated in the disease pathogenesis. Here we review some of the recent progress in promoting therapeutic strategies for neurodegeneration.

  1. Autophagy and Neurodegeneration: Pathogenic Mechanisms and Therapeutic Opportunities.

    Science.gov (United States)

    Menzies, Fiona M; Fleming, Angeleen; Caricasole, Andrea; Bento, Carla F; Andrews, Stephen P; Ashkenazi, Avraham; Füllgrabe, Jens; Jackson, Anne; Jimenez Sanchez, Maria; Karabiyik, Cansu; Licitra, Floriana; Lopez Ramirez, Ana; Pavel, Mariana; Puri, Claudia; Renna, Maurizio; Ricketts, Thomas; Schlotawa, Lars; Vicinanza, Mariella; Won, Hyeran; Zhu, Ye; Skidmore, John; Rubinsztein, David C

    2017-03-08

    Autophagy is a conserved pathway that delivers cytoplasmic contents to the lysosome for degradation. Here we consider its roles in neuronal health and disease. We review evidence from mouse knockout studies demonstrating the normal functions of autophagy as a protective factor against neurodegeneration associated with intracytoplasmic aggregate-prone protein accumulation as well as other roles, including in neuronal stem cell differentiation. We then describe how autophagy may be affected in a range of neurodegenerative diseases. Finally, we describe how autophagy upregulation may be a therapeutic strategy in a wide range of neurodegenerative conditions and consider possible pathways and druggable targets that may be suitable for this objective. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Implications of mitochondrial dynamics on neurodegeneration and on hypothalamic dysfunction

    Directory of Open Access Journals (Sweden)

    Antonio eZorzano

    2015-06-01

    Full Text Available Mitochondrial dynamics is a term that encompasses the movement of mitochondria along the cytoskeleton, regulation of their architecture, and connectivity mediated by tethering and fusion/fission. The importance of these events in cell physiology and pathology has been partially unraveled with the identification of the genes responsible for the catalysis of mitochondrial fusion and fission. Mutations in two mitochondrial fusion genes (MFN2 and OPA1 cause neurodegenerative diseases, namely Charcot-Marie Tooth type 2A and autosomal dominant optic atrophy. Alterations in mitochondrial dynamics may be involved in the pathophysiology of prevalent neurodegenerative conditions. Moreover, impairment of the activity of mitochondrial fusion proteins dysregulates the function of hypothalamic neurons, leading to alterations in food intake and in energy homeostasis. Here we review selected findings in the field of mitochondrial dynamics and their relevance for neurodegeneration and hypothalamic dysfunction.

  3. Microglial cell dysregulation in Brain Aging and Neurodegeneration.

    Directory of Open Access Journals (Sweden)

    Rommy eVon Bernhardi

    2015-07-01

    Full Text Available Aging is the main risk factor for neurodegenerative diseases. In aging, microglia undergo phenotypic changes compatible with their activation. Glial activation can lead to neuroinflammation, which is increasingly accepted as part of the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD. We hypothesize that in aging, aberrant microglia activation leads to a deleterious environment and neurodegeneration. In aged mice, microglia exhibit an increased expression of cytokines and an exacerbated inflammatory response to pathological changes. Whereas LPS increases nitric oxide secretion in microglia from young mice, induction of reactive oxygen species (ROS predominates in older mice. Furthermore, there is accumulation of DNA oxidative damage in mitochondria of microglia during aging, and also an increased intracellular ROS production. Increased ROS activates the redox-sensitive nuclear factor kappa B, which promotes more neuroinflammation, and can be translated in functional deficits, such as cognitive impairment. Mitochondria-derived ROS and cathepsin B, are also necessary for the microglial cell production of interleukin-1β, a key inflammatory cytokine. Interestingly, whereas the regulatory cytokine TGFβ1 is also increased in the aged brain, neuroinflammation persists. Assessing this apparent contradiction, we have reported that TGFβ1 induction and activation of Smad3 signaling after inflammatory stimulation are reduced in adult mice. Other protective functions, such as phagocytosis, although observed in aged animals, become not inducible by inflammatory stimuli and TGFβ1. Here, we discuss data suggesting that mitochondrial and endolysosomal dysfunction could at least partially mediate age-associated microglial cell changes, and, together with the impairment of the TGFβ1-Smad3 pathway, could result in a reduction of protective activation and a facilitation of cytotoxic activation of microglia, resulting in the

  4. The multiple sclerosis visual pathway cohort: understanding neurodegeneration in MS.

    Science.gov (United States)

    Martínez-Lapiscina, Elena H; Fraga-Pumar, Elena; Gabilondo, Iñigo; Martínez-Heras, Eloy; Torres-Torres, Ruben; Ortiz-Pérez, Santiago; Llufriu, Sara; Tercero, Ana; Andorra, Magi; Roca, Marc Figueras; Lampert, Erika; Zubizarreta, Irati; Saiz, Albert; Sanchez-Dalmau, Bernardo; Villoslada, Pablo

    2014-12-15

    Multiple Sclerosis (MS) is an immune-mediated disease of the Central Nervous System with two major underlying etiopathogenic processes: inflammation and neurodegeneration. The latter determines the prognosis of this disease. MS is the main cause of non-traumatic disability in middle-aged populations. The MS-VisualPath Cohort was set up to study the neurodegenerative component of MS using advanced imaging techniques by focusing on analysis of the visual pathway in a middle-aged MS population in Barcelona, Spain. We started the recruitment of patients in the early phase of MS in 2010 and it remains permanently open. All patients undergo a complete neurological and ophthalmological examination including measurements of physical and disability (Expanded Disability Status Scale; Multiple Sclerosis Functional Composite and neuropsychological tests), disease activity (relapses) and visual function testing (visual acuity, color vision and visual field). The MS-VisualPath protocol also assesses the presence of anxiety and depressive symptoms (Hospital Anxiety and Depression Scale), general quality of life (SF-36) and visual quality of life (25-Item National Eye Institute Visual Function Questionnaire with the 10-Item Neuro-Ophthalmic Supplement). In addition, the imaging protocol includes both retinal (Optical Coherence Tomography and Wide-Field Fundus Imaging) and brain imaging (Magnetic Resonance Imaging). Finally, multifocal Visual Evoked Potentials are used to perform neurophysiological assessment of the visual pathway. The analysis of the visual pathway with advance imaging and electrophysilogical tools in parallel with clinical information will provide significant and new knowledge regarding neurodegeneration in MS and provide new clinical and imaging biomarkers to help monitor disease progression in these patients.

  5. Development of an Electronic Medical Record Based Alert for Risk of HIV Treatment Failure in a Low-Resource Setting

    Science.gov (United States)

    Puttkammer, Nancy; Zeliadt, Steven; Balan, Jean Gabriel; Baseman, Janet; Destiné, Rodney; Domerçant, Jean Wysler; France, Garilus; Hyppolite, Nathaelf; Pelletier, Valérie; Raphael, Nernst Atwood; Sherr, Kenneth; Yuhas, Krista; Barnhart, Scott

    2014-01-01

    Background The adoption of electronic medical record systems in resource-limited settings can help clinicians monitor patients' adherence to HIV antiretroviral therapy (ART) and identify patients at risk of future ART failure, allowing resources to be targeted to those most at risk. Methods Among adult patients enrolled on ART from 2005–2013 at two large, public-sector hospitals in Haiti, ART failure was assessed after 6–12 months on treatment, based on the World Health Organization's immunologic and clinical criteria. We identified models for predicting ART failure based on ART adherence measures and other patient characteristics. We assessed performance of candidate models using area under the receiver operating curve, and validated results using a randomly-split data sample. The selected prediction model was used to generate a risk score, and its ability to differentiate ART failure risk over a 42-month follow-up period was tested using stratified Kaplan Meier survival curves. Results Among 923 patients with CD4 results available during the period 6–12 months after ART initiation, 196 (21.2%) met ART failure criteria. The pharmacy-based proportion of days covered (PDC) measure performed best among five possible ART adherence measures at predicting ART failure. Average PDC during the first 6 months on ART was 79.0% among cases of ART failure and 88.6% among cases of non-failure (pART initiation were added to PDC, the risk score differentiated between those who did and did not meet failure criteria over 42 months following ART initiation. Conclusions Pharmacy data are most useful for new ART adherence alerts within iSanté. Such alerts offer potential to help clinicians identify patients at high risk of ART failure so that they can be targeted with adherence support interventions, before ART failure occurs. PMID:25390044

  6. Development of an electronic medical record based alert for risk of HIV treatment failure in a low-resource setting.

    Directory of Open Access Journals (Sweden)

    Nancy Puttkammer

    Full Text Available The adoption of electronic medical record systems in resource-limited settings can help clinicians monitor patients' adherence to HIV antiretroviral therapy (ART and identify patients at risk of future ART failure, allowing resources to be targeted to those most at risk.Among adult patients enrolled on ART from 2005-2013 at two large, public-sector hospitals in Haiti, ART failure was assessed after 6-12 months on treatment, based on the World Health Organization's immunologic and clinical criteria. We identified models for predicting ART failure based on ART adherence measures and other patient characteristics. We assessed performance of candidate models using area under the receiver operating curve, and validated results using a randomly-split data sample. The selected prediction model was used to generate a risk score, and its ability to differentiate ART failure risk over a 42-month follow-up period was tested using stratified Kaplan Meier survival curves.Among 923 patients with CD4 results available during the period 6-12 months after ART initiation, 196 (21.2% met ART failure criteria. The pharmacy-based proportion of days covered (PDC measure performed best among five possible ART adherence measures at predicting ART failure. Average PDC during the first 6 months on ART was 79.0% among cases of ART failure and 88.6% among cases of non-failure (p<0.01. When additional information including sex, baseline CD4, and duration of enrollment in HIV care prior to ART initiation were added to PDC, the risk score differentiated between those who did and did not meet failure criteria over 42 months following ART initiation.Pharmacy data are most useful for new ART adherence alerts within iSanté. Such alerts offer potential to help clinicians identify patients at high risk of ART failure so that they can be targeted with adherence support interventions, before ART failure occurs.

  7. Innovative direct energy conversion systems using electronic adiabatic processes of electron fluid in solid conductors: new plants of electrical power and hydrogen gas resources without environmental pollutions

    International Nuclear Information System (INIS)

    Kondoh, Y.; Kondo, M.; Shimoda, K.; Takahashi, T.

    2001-07-01

    It is shown that using a novel recycling process of the environmental thermal energy, innovative permanent auto-working direct energy converter systems (PA-DEC systems) from the environmental thermal to electrical and/or chemical potential (TE/CP) energies, abbreviated as PA-TE/CP-DEC systems, can be used for new auto-working electrical power plants and the plants of the compressible and conveyable hydrogen gas resources at various regions in the whole world, with contributions to the world peace and the economical development in the south part of the world. It is shown that the same physical mechanism by free electrons and electrical potential determined by temperature in conductors, which include semiconductors, leads to the Peltier effect and the Seebeck one. It is experimentally clarified that the long distance separation between two π type elements of the heat absorption (HAS) and the production one (HPS) of the Peltier effect circuit system or between the higher temperature side (HTS) and the lower one (LTS) of the Seebeck effect circuit one does not change in the whole for the both effects. By using present systems, we do not need to use petrified fuels such as coals, oils, and natural gases in order to decrease the greenhouse effect by the CO 2 surrounding the earth. Furthermore, we do not need plats of nuclear fissions that left radiating wastes, i.e., with no environmental pollutions. The PA-TE/CP-DEC systems can be applicable for several km scale systems to the micro ones, such as the plants of the electrical power, the compact transportable hydrogen gas resources, a large heat energy container, which can be settled at far place from thermal energy absorbing area, the refrigerators, the air conditioners, home electrical apparatuses, and further the computer elements. It is shown that the simplest PA-TE/CP-DEC system can be established by using only the Seebeck effect components and the resolving water ones. It is clarified that the externally applied

  8. Consumer reports [electronic resource

    National Research Council Canada - National Science Library

    1942-01-01

    ... only. A limited number of selected reports, advice on product selection and safety alerts are freely available, as are a five year listing of product recalls, a listing of major consumer product...

  9. Dystonia in neurodegeneration with brain iron accumulation : outcome of bilateral pallidal stimulation

    NARCIS (Netherlands)

    Timmermann, L.; Pauls, K. A. M.; Wieland, K.; Jech, R.; Kurlemann, G.; Sharma, N.; Gill, S. S.; Haenggeli, C. A.; Hayflick, S. J.; Hogarth, P.; Leenders, K. L.; Limousin, P.; Malanga, C. J.; Moro, E.; Ostrem, J. L.; Revilla, F. J.; Santens, P.; Schnitzler, A.; Tisch, S.; Valldeoriola, F.; Vesper, J.; Volkmann, J.; Woitalla, D.; Peker, S.

    Neurodegeneration with brain iron accumulation encompasses a heterogeneous group of rare neurodegenerative disorders that are characterized by iron accumulation in the brain. Severe generalized dystonia is frequently a prominent symptom and can be very disabling, causing gait impairment, difficulty

  10. The electronic Rothamsted Archive (e-RA), an online resource for data from the Rothamsted long-term experiments.

    Science.gov (United States)

    Perryman, Sarah A M; Castells-Brooke, Nathalie I D; Glendining, Margaret J; Goulding, Keith W T; Hawkesford, Malcolm J; Macdonald, Andy J; Ostler, Richard J; Poulton, Paul R; Rawlings, Christopher J; Scott, Tony; Verrier, Paul J

    2018-05-15

    The electronic Rothamsted Archive, e-RA (www.era.rothamsted.ac.uk) provides a permanent managed database to both securely store and disseminate data from Rothamsted Research's long-term field experiments (since 1843) and meteorological stations (since 1853). Both historical and contemporary data are made available via this online database which provides the scientific community with access to a unique continuous record of agricultural experiments and weather measured since the mid-19 th century. Qualitative information, such as treatment and management practices, plans and soil information, accompanies the data and are made available on the e-RA website. e-RA was released externally to the wider scientific community in 2013 and this paper describes its development, content, curation and the access process for data users. Case studies illustrate the diverse applications of the data, including its original intended purposes and recent unforeseen applications. Usage monitoring demonstrates the data are of increasing interest. Future developments, including adopting FAIR data principles, are proposed as the resource is increasingly recognised as a unique archive of data relevant to sustainable agriculture, agroecology and the environment.

  11. Principles of formation of the content of an educational electronic resource on the basis of general and didactic patterns of learning

    Directory of Open Access Journals (Sweden)

    Ольга Юрьевна Заславская

    2018-12-01

    Full Text Available The article considers the influence of the development of technical means of teaching on the effectiveness of educational and methodical resources. Modern opportunities of information and communication technologies allow creating electronic educational resources that represent educational information that automates the learning process, provide information assistance, if necessary, collect and process statistical information on the degree of development of the content of the school material by schoolchildren, set an individual trajectory of learning, and so on. The main principle of data organization is the division of the training course into separate sections on the thematic elements and components of the learning process. General regularities include laws that encompass the entire didactic system, and in specific (particular cases, those whose actions extend to a separate component (aspect of the system. From the standpoint of the existence of three types of electronic training modules in the aggregate content of the electronic learning resource - information, control and module of practical classes - the principles of the formation of the electronic learning resource, in our opinion, should regulate all these components. Each of the certain principles is considered in the groups: scientific orientation, methodological orientation, systemic nature, accounting of interdisciplinary connections, fundamentalization, systematic and dosage sequence, rational use of study time, accessibility, minimization, operationalization of goals, unified identification diagnosis.

  12. The module of methodical support in system of electronic educational resources as the innovative element of the modern maintenance of formation

    Directory of Open Access Journals (Sweden)

    Ольга Николаевна Крылова

    2009-06-01

    Full Text Available The article introduces some results of research, which were devoted to evaluation of tearches' mobility to introduce innovations in the contents of education. The author considers innovative potential of modules of the methodical support for system of electronic educational resources.

  13. Charting a Course through CORAL: Texas A&M University Libraries' Experience Implementing an Open-Source Electronic Resources Management System

    Science.gov (United States)

    Hartnett, Eric; Beh, Eugenia; Resnick, Taryn; Ugaz, Ana; Tabacaru, Simona

    2013-01-01

    In 2010, after two previous unsuccessful attempts at electronic resources management system (ERMS) implementation, Texas A&M University (TAMU) Libraries set out once again to find an ERMS that would fit its needs. After surveying the field, TAMU Libraries selected the University of Notre Dame Hesburgh Libraries-developed, open-source ERMS,…

  14. Ethanol-Induced Neurodegeneration and Glial Activation in the Developing Brain

    Directory of Open Access Journals (Sweden)

    Mariko Saito

    2016-08-01

    Full Text Available Ethanol induces neurodegeneration in the developing brain, which may partially explain the long-lasting adverse effects of prenatal ethanol exposure in fetal alcohol spectrum disorders (FASD. While animal models of FASD show that ethanol-induced neurodegeneration is associated with glial activation, the relationship between glial activation and neurodegeneration has not been clarified. This review focuses on the roles of activated microglia and astrocytes in neurodegeneration triggered by ethanol in rodents during the early postnatal period (equivalent to the third trimester of human pregnancy. Previous literature indicates that acute binge-like ethanol exposure in postnatal day 7 (P7 mice induces apoptotic neurodegeneration, transient activation of microglia resulting in phagocytosis of degenerating neurons, and a prolonged increase in glial fibrillary acidic protein-positive astrocytes. In our present study, systemic administration of a moderate dose of lipopolysaccharides, which causes glial activation, attenuates ethanol-induced neurodegeneration. These studies suggest that activation of microglia and astrocytes by acute ethanol in the neonatal brain may provide neuroprotection. However, repeated or chronic ethanol can induce significant proinflammatory glial reaction and neurotoxicity. Further studies are necessary to elucidate whether acute or sustained glial activation caused by ethanol exposure in the developing brain can affect long-lasting cellular and behavioral abnormalities observed in the adult brain.

  15. LINGO-1 and Neurodegeneration: Pathophysiologic Clues for Essential Tremor?

    Directory of Open Access Journals (Sweden)

    Zhou Zhi-dong

    2012-03-01

    Full Text Available Essential tremor (ET, one of the most common adult-onset movement disorders, has been associated with cerebellar Purkinje cell degeneration and formation of brainstem Lewy bodies. Recent findings suggest that genetic variants of the leucine-rich repeat and Ig domain containing 1 (LINGO-1 gene could be risk factors for ET. The LINGO-1 protein contains both leucine-rich repeat (LRR and immunoglobulin (Ig-like domains in its extracellular region, as well as a transmembrane domain and a short cytoplasmic tail. LINGO-1 can form a ternary complex with Nogo-66 receptor (NgR1 and p75. Binding of LINGO-1 with NgR1 can activate the NgR1 signaling pathway, leading to inhibition of oligodendrocyte differentiation and myelination in the central nervous system. LINGO-1 has also been found to bind with epidermal growth factor receptor (EGFR and induce downregulation of the activity of EGFR–PI3K–Akt signaling, which might decrease Purkinje cell survival. Therefore, it is possible that genetic variants of LINGO-1, either alone or in combination with other genetic or environmental factors, act to increase LINGO-1 expression levels in Purkinje cells and confer a risk to Purkinje cell survival in the cerebellum. Here, we provide a concise summary of the link between LINGO-1 and neurodegeneration and discuss various hypotheses as to how this could be potentially relevant to ET pathogenesis.

  16. Molecular Mechanisms of Neurodegeneration in Spinal Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Saif Ahmad

    2016-01-01

    Full Text Available Spinal muscular atrophy (SMA is an autosomal recessive motor neuron disease with a high incidence and is the most common genetic cause of infant mortality. SMA is primarily characterized by degeneration of the spinal motor neurons that leads to skeletal muscle atrophy followed by symmetric limb paralysis, respiratory failure, and death. In humans, mutation of the Survival Motor Neuron 1 (SMN1 gene shifts the load of expression of SMN protein to the SMN2 gene that produces low levels of full-length SMN protein because of alternative splicing, which are sufficient for embryonic development and survival but result in SMA. The molecular mechanisms of the (a regulation of SMN gene expression and (b degeneration of motor neurons caused by low levels of SMN are unclear. However, some progress has been made in recent years that have provided new insights into understanding of the cellular and molecular basis of SMA pathogenesis. In this review, we have briefly summarized recent advances toward understanding of the molecular mechanisms of regulation of SMN levels and signaling mechanisms that mediate neurodegeneration in SMA.

  17. Brain aging and neurodegeneration: from a mitochondrial point of view.

    Science.gov (United States)

    Grimm, Amandine; Eckert, Anne

    2017-11-01

    Aging is defined as a progressive time-related accumulation of changes responsible for or at least involved in the increased susceptibility to disease and death. The brain seems to be particularly sensitive to the aging process since the appearance of neurodegenerative diseases, including Alzheimer's disease, is exponential with the increasing age. Mitochondria were placed at the center of the 'free-radical theory of aging', because these paramount organelles are not only the main producers of energy in the cells, but also to main source of reactive oxygen species. Thus, in this review, we aim to look at brain aging processes from a mitochondrial point of view by asking: (i) What happens to brain mitochondrial bioenergetics and dynamics during aging? (ii) Why is the brain so sensitive to the age-related mitochondrial impairments? (iii) Is there a sex difference in the age-induced mitochondrial dysfunction? Understanding mitochondrial physiology in the context of brain aging may help identify therapeutic targets against neurodegeneration. This article is part of a series "Beyond Amyloid". © 2017 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.

  18. Application of medical cannabis in patients with the neurodegeneration disorders

    Directory of Open Access Journals (Sweden)

    Lidia Kotuła

    2014-04-01

    Full Text Available Medical cannabis is the dried flowers of the female Cannabis sativa L. plant. Cannabis contains a number of active elements, including dronabinol (THC and cannabidiol (CBD. Dronabinol is usually the main ingredient. The body’s own cannabinoid system has been identified. The discovery of this system, which comprises endocannabinoids and receptors, confirmed that cannabis has a positive effect on certain illnesses and conditions. Two types of cannabinoid receptors have been identified: CB1 and CB2 receptors. The first type CB1 is mostly found in the central nervous system, modulate pain. It also has an anti-emetic effect, and has influence on the memory and the motor system. The second type of receptors CB2 is peripheral, and it is primarily found in immune system cells and it is responsible for the immunomodulatory effects of cannabinoids. Medical cannabis can help in cases of the neurodegeneration disorders, for example Parkinson’s disease, Huntington’s Disease, Amyotrophic Lateral Sclerosis. Patients generally tolerate medical cannabis well.

  19. Oxidative damage and neurodegeneration in manganese-induced neurotoxicity

    International Nuclear Information System (INIS)

    Milatovic, Dejan; Zaja-Milatovic, Snjezana; Gupta, Ramesh C.; Yu, Yingchun; Aschner, Michael

    2009-01-01

    Exposure to excessive manganese (Mn) levels results in neurotoxicity to the extrapyramidal system and the development of Parkinson's disease (PD)-like movement disorder, referred to as manganism. Although the mechanisms by which Mn induces neuronal damage are not well defined, its neurotoxicity appears to be regulated by a number of factors, including oxidative injury, mitochondrial dysfunction and neuroinflammation. To investigate the mechanisms underlying Mn neurotoxicity, we studied the effects of Mn on reactive oxygen species (ROS) formation, changes in high-energy phosphates (HEP), neuroinflammation mediators and associated neuronal dysfunctions both in vitro and in vivo. Primary cortical neuronal cultures showed concentration-dependent alterations in biomarkers of oxidative damage, F 2 -isoprostanes (F 2 -IsoPs) and mitochondrial dysfunction (ATP), as early as 2 h following Mn exposure. Treatment of neurons with 500 μM Mn also resulted in time-dependent increases in the levels of the inflammatory biomarker, prostaglandin E 2 (PGE 2 ). In vivo analyses corroborated these findings, establishing that either a single or three (100 mg/kg, s.c.) Mn injections (days 1, 4 and 7) induced significant increases in F 2 -IsoPs and PGE 2 in adult mouse brain 24 h following the last injection. Quantitative morphometric analyses of Golgi-impregnated striatal sections from mice exposed to single or three Mn injections revealed progressive spine degeneration and dendritic damage of medium spiny neurons (MSNs). These findings suggest that oxidative stress, mitochondrial dysfunction and neuroinflammation are underlying mechanisms in Mn-induced neurodegeneration.

  20. Cerebellar neurodegeneration in the absence of microRNAs

    Science.gov (United States)

    Schaefer, Anne; O'Carroll, Dónal; Tan, Chan Lek; Hillman, Dean; Sugimori, Mutsuyuki; Llinas, Rodolfo; Greengard, Paul

    2007-01-01

    Genome-encoded microRNAs (miRNAs) are potent regulators of gene expression. The significance of miRNAs in various biological processes has been suggested by studies showing an important role of these small RNAs in regulation of cell differentiation. However, the role of miRNAs in regulation of differentiated cell physiology is not well established. Mature neurons express a large number of distinct miRNAs, but the role of miRNAs in postmitotic neurons has not been examined. Here, we provide evidence for an essential role of miRNAs in survival of differentiated neurons. We show that conditional Purkinje cell–specific ablation of the key miRNA-generating enzyme Dicer leads to Purkinje cell death. Deficiency in Dicer is associated with progressive loss of miRNAs, followed by cerebellar degeneration and development of ataxia. The progressive neurodegeneration in the absence of Dicer raises the possibility of an involvement of miRNAs in neurodegenerative disorders. PMID:17606634

  1. Kynurenine 3-monooxygenase inhibition in blood ameliorates neurodegeneration

    Science.gov (United States)

    Zwilling, Daniel; Huang, Shao-Yi; Sathyasaikumar, Korrapati V.; Notarangelo, Francesca M.; Guidetti, Paolo; Wu, Hui-Qiu; Lee, Jason; Truong, Jennifer; Andrews-Zwilling, Yaisa; Hsieh, Eric W.; Louie, Jamie Y.; Wu, Tiffany; Scearce-Levie, Kimberly; Patrick, Christina; Adame, Anthony; Giorgini, Flaviano; Moussaoui, Saliha; Laue, Grit; Rassoulpour, Arash; Flik, Gunnar; Huang, Yadong; Muchowski, Joseph M.; Masliah, Eliezer; Schwarcz, Robert; Muchowski, Paul J.

    2011-01-01

    SUMMARY Metabolites in the kynurenine pathway of tryptophan degradation are thought to play an important role in neurodegenerative disorders such as Alzheimer’s disease and Huntington’s disease. Metabolites that cause glutamate receptor-mediated excitotoxicity and free radical formation are elevated in the blood and vulnerable brain regions in these diseases, while levels of the neuroprotective metabolite kynurenic acid are often decreased. Here we describe the synthesis and characterization of JM6, a novel small-molecule pro-drug inhibitor of kynurenine 3-monooxygenase (KMO). JM6 raises kynurenic acid and reduces extracellular glutamate in the brain after chronic oral administration by inhibiting KMO in blood. In a transgenic mouse model of Alzheimer’s disease, JM6 prevented spatial memory deficits, anxiety-related behavior, and synaptic loss. JM6 also extended life span, prevented synaptic loss, and decreased microglial activation in a mouse model of Huntington’s disease. These findings support a critical link between blood cells and neurodegeneration that is mediated by KMO and the kynurenine pathway. PMID:21640374

  2. Progressing neurobiological strategies against proteostasis failure: Challenges in neurodegeneration.

    Science.gov (United States)

    Amanullah, Ayeman; Upadhyay, Arun; Joshi, Vibhuti; Mishra, Ribhav; Jana, Nihar Ranjan; Mishra, Amit

    2017-12-01

    Proteins are ordered useful cellular entities, required for normal health and organism's survival. The proteome is the absolute set of cellular expressed proteins, which regulates a wide range of physiological functions linked with all domains of life. In aging cells or under unfavorable cellular conditions, misfolding of proteins generates common pathological events linked with neurodegenerative diseases and aging. Current advances of proteome studies systematically generates some progress in our knowledge that how misfolding of proteins or their accumulation can contribute to the impairment or depletion of proteome functions. Still, the underlying causes of this unrecoverable loss are not clear that how such unsolved transitions give rise to multifactorial challengeable degenerative pathological conditions in neurodegeneration. In this review, we specifically focus and systematically summarize various molecular mechanisms of proteostasis maintenance, as well as discuss progressing neurobiological strategies, promising natural and pharmacological candidates, which can be useful to counteract the problem of proteopathies. Our article emphasizes an urgent need that now it is important for us to recognize the fundamentals of proteostasis to design a new molecular framework and fruitful strategies to uncover how the proteome defects are associated with aging and neurodegenerative diseases. A enhance understanding of progress link with proteome and neurobiological challenges may provide new basic concepts in the near future, based on pharmacological agents, linked with impaired proteostasis and neurodegenerative diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Electronics

    Science.gov (United States)

    2001-01-01

    International Acer Incorporated, Hsin Chu, Taiwan Aerospace Industrial Development Corporation, Taichung, Taiwan American Institute of Taiwan, Taipei, Taiwan...Singapore and Malaysia .5 - 4 - The largest market for semiconductor products is the high technology consumer electronics industry that consumes up...Singapore, and Malaysia . A new semiconductor facility costs around $3 billion to build and takes about two years to become operational

  4. Defining SNAP by cross-sectional and longitudinal definitions of neurodegeneration.

    Science.gov (United States)

    Wisse, L E M; Das, S R; Davatzikos, C; Dickerson, B C; Xie, S X; Yushkevich, P A; Wolk, D A

    2018-01-01

    Suspected non-Alzheimer's pathophysiology (SNAP) is a biomarker driven designation that represents a heterogeneous group in terms of etiology and prognosis. SNAP has only been identified by cross-sectional neurodegeneration measures, whereas longitudinal measures might better reflect "active" neurodegeneration and might be more tightly linked to prognosis. We compare neurodegeneration defined by cross-sectional 'hippocampal volume' only (SNAP/L-) versus both cross-sectional and longitudinal 'hippocampal atrophy rate' (SNAP/L+) and investigate how these definitions impact prevalence and the clinical and biomarker profile of SNAP in Mild Cognitive Impairment (MCI). 276 MCI patients from ADNI-GO/2 were designated amyloid "positive" (A+) or "negative" (A-) based on their florbetapir scan and neurodegeneration 'positive' or 'negative' based on cross-sectional hippocampal volume and longitudinal hippocampal atrophy rate. 74.1% of all SNAP participants defined by the cross-sectional definition of neurodegeneration also met the longitudinal definition of neurodegeneration, whereas 25.9% did not. SNAP/L+ displayed larger white matter hyperintensity volume, a higher conversion rate to dementia over 5 years and a steeper decline on cognitive tasks compared to SNAP/L- and the A- CN group. SNAP/L- had more abnormal values on neuroimaging markers and worse performance on cognitive tasks than the A- CN group, but did not show a difference in dementia conversion rate or longitudinal cognition. Using a longitudinal definition of neurodegeneration in addition to a cross-sectional one identifies SNAP participants with significant cognitive decline and a worse clinical prognosis for which cerebrovascular disease may be an important driver.

  5. m-AAA proteases, mitochondrial calcium homeostasis and neurodegeneration.

    Science.gov (United States)

    Patron, Maria; Sprenger, Hans-Georg; Langer, Thomas

    2018-03-01

    The function of mitochondria depends on ubiquitously expressed and evolutionary conserved m-AAA proteases in the inner membrane. These ATP-dependent peptidases form hexameric complexes built up of homologous subunits. AFG3L2 subunits assemble either into homo-oligomeric isoenzymes or with SPG7 (paraplegin) subunits into hetero-oligomeric proteolytic complexes. Mutations in AFG3L2 are associated with dominant spinocerebellar ataxia (SCA28) characterized by the loss of Purkinje cells, whereas mutations in SPG7 cause a recessive form of hereditary spastic paraplegia (HSP7) with motor neurons of the cortico-spinal tract being predominantly affected. Pleiotropic functions have been assigned to m-AAA proteases, which act as quality control and regulatory enzymes in mitochondria. Loss of m-AAA proteases affects mitochondrial protein synthesis and respiration and leads to mitochondrial fragmentation and deficiencies in the axonal transport of mitochondria. Moreover m-AAA proteases regulate the assembly of the mitochondrial calcium uniporter (MCU) complex. Impaired degradation of the MCU subunit EMRE in AFG3L2-deficient mitochondria results in the formation of deregulated MCU complexes, increased mitochondrial calcium uptake and increased vulnerability of neurons for calcium-induced cell death. A reduction of calcium influx into the cytosol of Purkinje cells rescues ataxia in an AFG3L2-deficient mouse model. In this review, we discuss the relationship between the m-AAA protease and mitochondrial calcium homeostasis and its relevance for neurodegeneration and describe a novel mouse model lacking MCU specifically in Purkinje cells. Our results pledge for a novel view on m-AAA proteases that integrates their pleiotropic functions in mitochondria to explain the pathogenesis of associated neurodegenerative disorders.

  6. Evaluation of three electronic report processing systems for preparing hydrologic reports of the U.S Geological Survey, Water Resources Division

    Science.gov (United States)

    Stiltner, G.J.

    1990-01-01

    In 1987, the Water Resources Division of the U.S. Geological Survey undertook three pilot projects to evaluate electronic report processing systems as a means to improve the quality and timeliness of reports pertaining to water resources investigations. The three projects selected for study included the use of the following configuration of software and hardware: Ventura Publisher software on an IBM model AT personal computer, PageMaker software on a Macintosh computer, and FrameMaker software on a Sun Microsystems workstation. The following assessment criteria were to be addressed in the pilot studies: The combined use of text, tables, and graphics; analysis of time; ease of learning; compatibility with the existing minicomputer system; and technical limitations. It was considered essential that the camera-ready copy produced be in a format suitable for publication. Visual improvement alone was not a consideration. This report consolidates and summarizes the findings of the electronic report processing pilot projects. Text and table files originating on the existing minicomputer system were successfully transformed to the electronic report processing systems in American Standard Code for Information Interchange (ASCII) format. Graphics prepared using a proprietary graphics software package were transferred to all the electronic report processing software through the use of Computer Graphic Metafiles. Graphics from other sources were entered into the systems by scanning paper images. Comparative analysis of time needed to process text and tables by the electronic report processing systems and by conventional methods indicated that, although more time is invested in creating the original page composition for an electronically processed report , substantial time is saved in producing subsequent reports because the format can be stored and re-used by electronic means as a template. Because of the more compact page layouts, costs of printing the reports were 15% to 25

  7. Electronic resources of the rare books and valuable editions department of the Central Scientific Library of the V.N. Karazin Kharkiv National University: open access for research

    Directory of Open Access Journals (Sweden)

    І. К. Журавльова

    2014-12-01

    Full Text Available The article describes tasks that electronic collections of rare books fulfill: broad access for readers to rare and valuable editions providing, preservation of ensuring of the original. On the example of the electronic collection of the Central Scientific Library of the V.N. Karazin Kharkiv National University – «eScriptorium: electronic archive of rare books and manuscripts for research and education» the possibility of the full-text resources of the valuable editions using is shown. The principles of creation, structure, chronological frameworks, directions of adding the documents to the archive are represented. The perspectives of the project development are outlined as well as examples of the digital libraries of the European countries and Ukraine are provided, the actual task of preserving the originals of the rare books of the country is raised, the innovative approaches to serving users with electronic resources are considered. The evidences of cooperation of the Central Scientific Library of the V.N. Karazin Kharkiv National University with the largest world digital libraries: World Digital Library and Europeana are provided.

  8. The use of quality benchmarking in assessing web resources for the dermatology virtual branch library of the National electronic Library for Health (NeLH).

    Science.gov (United States)

    Kamel Boulos, M N; Roudsari, A V; Gordon, C; Muir Gray, J A

    2001-01-01

    In 1998, the U.K. National Health Service Information for Health Strategy proposed the implementation of a National electronic Library for Health to provide clinicians, healthcare managers and planners, patients and the public with easy, round the clock access to high quality, up-to-date electronic information on health and healthcare. The Virtual Branch Libraries are among the most important components of the National electronic Library for Health. They aim at creating online knowledge based communities, each concerned with some specific clinical and other health-related topics. This study is about the envisaged Dermatology Virtual Branch Libraries of the National electronic Library for Health. It aims at selecting suitable dermatology Web resources for inclusion in the forthcoming Virtual Branch Libraries after establishing preliminary quality benchmarking rules for this task. Psoriasis, being a common dermatological condition, has been chosen as a starting point. Because quality is a principal concern of the National electronic Library for Health, the study includes a review of the major quality benchmarking systems available today for assessing health-related Web sites. The methodology of developing a quality benchmarking system has been also reviewed. Aided by metasearch Web tools, candidate resources were hand-selected in light of the reviewed benchmarking systems and specific criteria set by the authors. Over 90 professional and patient-oriented Web resources on psoriasis and dermatology in general are suggested for inclusion in the forthcoming Dermatology Virtual Branch Libraries. The idea of an all-in knowledge-hallmarking instrument for the National electronic Library for Health is also proposed based on the reviewed quality benchmarking systems. Skilled, methodical, organized human reviewing, selection and filtering based on well-defined quality appraisal criteria seems likely to be the key ingredient in the envisaged National electronic Library for

  9. Forever young: SIRT3 a shield against mitochondrial meltdown, aging, and neurodegeneration

    Directory of Open Access Journals (Sweden)

    Brad eKincaid

    2013-09-01

    Full Text Available Caloric restriction, fasting, and exercise have long been recognized for their neuroprotective and lifespan-extending properties; however, the underlying mechanisms of these phenomena remain elusive. Such extraordinary benefits might be linked to the activation of sirtuins. In mammals, the sirtuin family has seven members (SIRT1-7, which diverge in tissue distribution, subcellular localization, enzymatic activity and targets. SIRT1, SIRT2, and SIRT3 have deacetylase activity. Their dependence on NAD+ directly links their activity to the metabolic status of the cell. High NAD+ levels convey neuroprotective effects, possibly via activation of sirtuin family members. Mitochondrial sirtuin 3 (SIRT3 has received much attention for its role in metabolism and aging. Specific small nucleotide polymorphisms (SNPs in Sirt3 are linked to increased human lifespan. SIRT3 mediates the adaptation of increased energy demand during caloric restriction, fasting and exercise to increased production of energy equivalents. SIRT3 deacetylates and activates mitochondrial enzymes involved in fatty acid β-oxidation, amino acid metabolism, the electron transport chain, and antioxidant defenses. As a result, the mitochondrial energy metabolism increases. In addition, SIRT3 prevents apoptosis by lowering reactive oxygen species (ROS and inhibiting components of the mitochondrial permeability transition pore. Mitochondrial deficits associated with aging and neurodegeneration might therefore be slowed or even prevented by SIRT3 activation. In addition, upregulating SIRT3 activity by dietary supplementation of sirtuin activating compounds might promote the beneficial effects of this enzyme. The goal of this review is to summarize emerging data supporting a neuroprotective action of SIRT3 against Alzheimer’s disease (AD, Huntington’s disease (HD, Parkinson’s disease (PD and amyotrophic lateral sclerosis (ALS.

  10. Barriers to electronic access and delivery of educational information in resource constrained public schools: a case of Greater Tubatse Municipality

    CSIR Research Space (South Africa)

    Pholotho, T

    2016-05-01

    Full Text Available Information and Communication Technologies (ICTs) are capable of expanding access to quality education, educational resources and provide teachers with new skills. Nevertheless, a majority of rural public schools have limited ICTs, mainly due...

  11. Electronic Grey Literature in Accelerator Science and Its Allied Subjects : Selected Web Resources for Scientists and Engineers

    CERN Document Server

    Rajendiran, P

    2006-01-01

    Grey literature Web resources in the field of accelerator science and its allied subjects are collected for the scientists and engineers of RRCAT (Raja Ramanna Centre for Advanced Technology). For definition purposes the different types of grey literature are described. The Web resources collected and compiled in this article (with an overview and link for each) specifically focus on technical reports, preprints or e-prints, which meet the main information needs of RRCAT users.

  12. A Patient with Beta-Propeller Protein-Associated Neurodegeneration: Treatment with Iron Chelation Therapy

    Directory of Open Access Journals (Sweden)

    Shen-Yang Lim

    2018-05-01

    Full Text Available We present a case of beta-propeller protein-associated neurodegeneration, a form of neurodegeneration with brain iron accumulation. The patient harbored a novel mutation in the WDR45 gene. A detailed video and description of her clinical condition are provided. Her movement disorder phenomenology was characterized primarily by limb stereotypies and gait dyspraxia. The patient’s disability was advanced by the time iron-chelating therapy with deferiprone was initiated, and no clinical response in terms of cognitive function, behavior, speech, or movements were observed after one year of treatment.

  13. Disruption of microvascular flow-patterns in Alzheimer's disease correlates with neurodegeneration and cognitive decline

    DEFF Research Database (Denmark)

    Nielsen, Rune Bæksager; Egefjord, Lærke; Eskildsen, Simon Fristed

    and neurodegeneration in AD. METHOD: 24 patients diagnosed with AD were assessed at inclusion and after six months. Using perfusion magnetic resonance imaging (MRI), we estimated CTH, flow-normalized CTH termed relative transit time heterogeneity (RTH), OEFmax and relative cerebral blood flow (rCBF). Neurodegeneration...... was quantified as cortical thickness utilizing structural MRI, while cognitive abilities were tested with brief cognitive status exam (BCSE). Low BCSE-score indicates worse symptoms. Regional means were extracted from atrophic cortical grey matter (A-CGM), defined using MRIs from the ADNI-database. Correlation...

  14. Prenatal exposure to a novel antipsychotic quetiapine: impact on neuro-architecture, apoptotic neurodegeneration in fetal hippocampus and cognitive impairment in young rats.

    Science.gov (United States)

    Singh, K P; Tripathi, Nidhi

    2015-05-01

    Reports on prenatal exposure to some of the first generation antipsychotic drugs like, haloperidol, their effects on fetal neurotoxicity and functional impairments in the offspring, are well documented. But studies on in utero exposure to second generation antipsychotics, especially quetiapine, and its effects on fetal neurotoxicity, apoptotic neurodegeneration, postnatal developmental delay and neurobehavioral consequences are lacking. Therefore, the present study was undertaken to evaluate the effect of prenatal administration to equivalent therapeutic doses of quetiapine on neuro-architectural abnormalities, neurohistopathological changes, apoptotic neurodegeneration in fetal hippocampus, and postnatal development and growth as well as its long-lasting imprint on cognitive impairment in young-adult offspring. Pregnant Wistar rats (n=24) were exposed to selected doses (55 mg, 80 mg and 100mg/kg) of quetiapine, equivalent to human therapeutic doses, from gestation day 6 to 21 orally with control subjects. Half of the pregnant subjects of each group were sacrificed at gestation day 21 for histopathological, confocal and electron microscopic studies and rest of the dams were allowed to deliver naturally. Their pups were reared postnatally up to 10 weeks of age for neurobehavioral observations. In quetiapine treated groups, there was significant alterations in total and differential thickness of three typical layers of hippocampus associated with neuronal cells deficit and enhanced apoptotic neurodegeneration in the CA1 area of fetal hippocampus. Prenatally drug treated rat offspring displayed post-natal developmental delay till postnatal day 70, and these young-adult rats displayed cognitive impairment in Morris water maze and passive avoidance regimes as long-lasting impact of the drug. Therefore, quetiapine should be used with cautions considering its developmental neurotoxicological and neurobehavioral potential in animal model, rat. Copyright © 2015 Elsevier

  15. Relative importance of redox buffers GSH and NAD(P)H in age-related neurodegeneration and Alzheimer disease-like mouse neurons.

    Science.gov (United States)

    Ghosh, Debolina; Levault, Kelsey R; Brewer, Gregory J

    2014-08-01

    Aging, a major risk factor in Alzheimer's disease (AD), is associated with an oxidative redox shift, decreased redox buffer protection, and increased free radical reactive oxygen species (ROS) generation, probably linked to mitochondrial dysfunction. While NADH is the ultimate electron donor for many redox reactions, including oxidative phosphorylation, glutathione (GSH) is the major ROS detoxifying redox buffer in the cell. Here, we explored the relative importance of NADH and GSH to neurodegeneration in aging and AD neurons from nontransgenic and 3xTg-AD mice by inhibiting their synthesis to determine whether NADH can compensate for the GSH loss to maintain redox balance. Neurons stressed by either depleting NAD(P)H or GSH indicated that NADH redox control is upstream of GSH levels. Further, although depletion of NAD(P)H or GSH correlated linearly with neuron death, compared with GSH depletion, higher neurodegeneration was observed when NAD(P)H was extrapolated to zero, especially in old age, and in the 3xTg-AD neurons. We also observed an age-dependent loss of gene expression of key redox-dependent biosynthetic enzymes, NAMPT (nicotinamide phosphoribosyltransferase), and NNT (nicotinamide nucleotide transhydrogenase). Moreover, age-related correlations between brain NNT or NAMPT gene expression and NADPH levels suggest that these genes contribute to the age-related declines in NAD(P)H. Our data indicate that in aging and more so in AD-like neurons, NAD(P)H redox control is upstream of GSH and an oxidative redox shift that promotes neurodegeneration. Thus, NAD(P)H generation may be a more efficacious therapeutic target upstream of GSH and ROS. © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  16. Clinical Heterogeneity of Atypical Pantothenate Kinase-Associated Neurodegeneration in Koreans

    Directory of Open Access Journals (Sweden)

    Jae-Hyeok Lee

    2016-01-01

    Full Text Available Objective Neurodegeneration with brain iron accumulation (NBIA represents a group of inherited movement disorders characterized by iron accumulation in the basal ganglia. Recent advances have included the identification of new causative genes and highlighted the wide phenotypic variation between and within the specific NBIA subtypes. This study aimed to investigate the current status of NBIA in Korea. Methods We collected genetically confirmed NBIA patients from twelve nationwide referral hospitals and from a review of the literature. We conducted a study to describe the phenotypic and genotypic characteristics of Korean adults with atypical pantothenate kinase-associated neurodegeneration (PKAN. Results Four subtypes of NBIA including PKAN (n = 30, PLA2G6-related neurodegeneration (n = 2, beta-propeller protein-associated neurodegeneration (n = 1, and aceruloplasminemia (n = 1 have been identified in the Korean population. The clinical features of fifteen adults with atypical PKAN included early focal limb dystonia, parkinsonism-predominant feature, oromandibular dystonia, and isolated freezing of gait (FOG. Patients with a higher age of onset tended to present with parkinsonism and FOG. The p.R440P and p.D378G mutations are two major mutations that represent approximately 50% of the mutated alleles. Although there were no specific genotype-phenotype correlations, most patients carrying the p.D378G mutation had a late-onset, atypical form of PKAN. Conclusions We found considerable phenotypic heterogeneity in Korean adults with atypical PKAN. The age of onset may influence the presentation of extrapyramidal symptoms.

  17. Metallothionein prevents neurodegeneration and central nervous system cell death after treatment with gliotoxin 6-aminonicotinamide

    DEFF Research Database (Denmark)

    Penkowa, Milena; Quintana, Albert; Carrasco, Javier

    2004-01-01

    Transgenic expression of interleukin-6 (IL-6) in the CNS under the control of the glial fibrillary acidic protein (GFAP) gene promoter (GFAP-IL6 mice) induces significant inflammation and neurodegeneration but also affords neuroprotection against acute traumatic brain injury. This neuroprotection...

  18. Mechanisms of neurodegeneration : Towards a cure for Alzheimer’s disease

    NARCIS (Netherlands)

    Dumbacher, M.|info:eu-repo/dai/nl/372628737

    2018-01-01

    Neurodegeneration in Alzheimer’s disease (AD) entails dysregulated signalling in and between neurons. As such, the search for new therapies capable of normalising these signalling dysfunctions in AD is a promising strategy to treat the disease. Therefore we set out to validate an in-house

  19. Thiamine Deficiency and Neurodegeneration: the Interplay Among Oxidative Stress, Endoplasmic Reticulum Stress, and Autophagy.

    Science.gov (United States)

    Liu, Dexiang; Ke, Zunji; Luo, Jia

    2017-09-01

    Thiamine (vitamin B1) is an essential nutrient and indispensable for normal growth and development of the organism due to its multilateral participation in key biochemical and physiological processes. Humans must obtain thiamine from their diet since it is synthesized only in bacteria, fungi, and plants. Thiamine deficiency (TD) can result from inadequate intake, increased requirement, excessive deletion, and chronic alcohol consumption. TD affects multiple organ systems, including the cardiovascular, muscular, gastrointestinal, and central and peripheral nervous systems. In the brain, TD causes a cascade of events including mild impairment of oxidative metabolism, neuroinflammation, and neurodegeneration, which are commonly observed in neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Thiamine metabolites may serve as promising biomarkers for neurodegenerative diseases, and thiamine supplementations exhibit therapeutic potential for patients of some neurodegenerative diseases. Experimental TD has been used to model aging-related neurodegenerative diseases. However, to date, the cellular and molecular mechanisms underlying TD-induced neurodegeneration are not clear. Recent research evidence indicates that TD causes oxidative stress, endoplasmic reticulum (ER) stress, and autophagy in the brain, which are known to contribute to the pathogenesis of various neurodegenerative diseases. In this review, we discuss the role of oxidative stress, ER stress, and autophagy in TD-mediated neurodegeneration. We propose that it is the interplay of oxidative stress, ER stress, and autophagy that contributes to TD-mediated neurodegeneration.

  20. The GluR2 hypothesis: Ca(++)-permeable AMPA receptors in delayed neurodegeneration

    NARCIS (Netherlands)

    Bennett, M. V.; Pellegrini-Giampietro, D. E.; Gorter, J. A.; Aronica, E.; Connor, J. A.; Zukin, R. S.

    1996-01-01

    Increased glutamate-receptor-mediated Ca++ influx is considered an important factor underlying delayed neurodegeneration following ischemia or seizures. Until recently, the NMDA receptor was the only glutamate receptor known to be Ca(++)-permeable. It is now well established that glutamate receptors

  1. Trace elements monitored with neutron activation analysis durig neurodegeneration in brains of mutant mice

    Czech Academy of Sciences Publication Activity Database

    Kranda, Karel; Kučera, Jan; Bäurle, J.

    2006-01-01

    Roč. 269, č. 3 (2006), s. 555-559 ISSN 0236-5731 Institutional research plan: CEZ:AV0Z10480505 Keywords : trace elements * neutron activation analysis * brain neurodegeneration * mutant mice Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 0.509, year: 2006

  2. 3-NP-induced neurodegeneration studies in experimental models of Huntington's disease.

    NARCIS (Netherlands)

    Vis, J.C.

    2005-01-01

    This thesis investigates the possible role of apoptosis, or programmed cell death, in Huntington's disease (HD). HD is caused by an expanded CAG repeat in the N-terminal region of the huntingtin protein leading to specific neostriatal neurodegeneration. The sequence of events that leads to this

  3. Relationship between brainstem neurodegeneration and clinical impairment in traumatic spinal cord injury

    Directory of Open Access Journals (Sweden)

    Patrick Grabher

    2017-01-01

    Conclusion: Neurodegeneration, indicated by volume loss and myelin reductions, is evident in major brainstem pathways and nuclei following traumatic SCI; the magnitude of these changes relating to clinical impairment. Thus, quantitative MRI protocols offer new targets, which may be used as neuroimaging biomarkers in treatment trials.

  4. Evaluation of Amyloid Protective Factors and Alzheimer Disease Neurodegeneration Protective Factors in Elderly Individuals.

    Science.gov (United States)

    Vemuri, Prashanthi; Knopman, David S; Lesnick, Timothy G; Przybelski, Scott A; Mielke, Michelle M; Graff-Radford, Jonathan; Murray, Melissa E; Roberts, Rosebud O; Vassilaki, Maria; Lowe, Val J; Machulda, Mary M; Jones, David T; Petersen, Ronald C; Jack, Clifford R

    2017-06-01

    While amyloid and neurodegeneration are viewed together as Alzheimer disease pathophysiology (ADP), the factors that influence amyloid and AD-pattern neurodegeneration may be considerably different. Protection from these ADP factors may be important for aging without significant ADP. To identify the combined and independent protective factors for amyloid and AD-pattern neurodegeneration in a population-based sample and to test the hypothesis that "exceptional agers" with advanced ages do not have significant ADP because they have protective factors for amyloid and neurodegeneration. This cohort study conducted a prospective analysis of 942 elderly individuals (70-≥90 years) with magnetic resonance imaging and Pittsburgh compound B-positron emission tomography scans enrolled in the Mayo Clinic Study of Aging, a longitudinal population-based study of cognitive aging in Olmsted County, Minnesota. We operationalized "exceptional aging" without ADP by considering individuals 85 years or older to be without significant evidence of ADP. We evaluated predictors including demographics, APOE, intellectual enrichment, midlife risk factors (physical inactivity, obesity, smoking, diabetes, hypertension, and dyslipidemia), and the total number of late-life cardiac and metabolic conditions. We used multivariate linear regression models to identify the combined and independent protective factors for amyloid and AD-pattern neurodegeneration. Using a subsample of the cohort 85 years of age or older, we computed Cohen d-based effect size estimations to compare the quantitative strength of each predictor variable in their contribution with exceptional aging without ADP. The study participants included 423 (45%) women and the average age of participants was 79.7 (5.9) years. Apart from demographics and the APOE genotype, only midlife dyslipidemia was associated with amyloid deposition. Obesity, smoking, diabetes, hypertension, and cardiac and metabolic conditions, but not

  5. Clinician‐selected Electronic Information Resources do not Guarantee Accuracy in Answering Primary Care Physicians’ Information Needs. A review of: McKibbon, K. Ann, and Douglas B. Fridsma. “Effectiveness of Clinician‐selected Electronic Information Resources for Answering Primary Care Physicians’ Information Needs.” Journal of the American Medical Informatics Association 13.6 (2006: 653‐9.

    Directory of Open Access Journals (Sweden)

    Martha Ingrid Preddie

    2008-03-01

    Full Text Available Objective – To determine if electronic information resources selected by primary care physicians improve their ability to answer simulated clinical questions.Design – An observational study utilizing hour‐long interviews and think‐aloud protocols.Setting – The offices and clinics of primary care physicians in Canada and the United States.Subjects – Twenty‐five primary care physicians of whom 4 were women, 17 were from Canada, 22 were family physicians,and 24 were board certified.Methods – Participants provided responses to 23 multiple‐choice questions. Each physician then chose two questions and looked for the answers utilizing information resources of their own choice. The search processes, chosen resources and search times were noted. These were analyzed along with data on the accuracy of the answers and certainties related to the answer to each clinical question prior to the search.Main results – Twenty‐three physicians sought answers to 46 simulated clinical questions. Utilizing only electronic information resources, physicians spent a mean of 13.0 (SD 5.5 minutes searching for answers to the questions, an average of 7.3(SD 4.0 minutes for the first question and 5.8 (SD 2.2 minutes to answer the second question. On average, 1.8 resources were utilized per question. Resources that summarized information, such as the Cochrane Database of Systematic Reviews, UpToDate and Clinical Evidence, were favored 39.2% of the time, MEDLINE (Ovid and PubMed 35.7%, and Internet resources including Google 22.6%. Almost 50% of the search and retrieval strategies were keyword‐based, while MeSH, subheadings and limiting were used less frequently. On average, before searching physicians answered 10 of 23 (43.5% questions accurately. For questions that were searched using clinician‐selected electronic resources, 18 (39.1% of the 46 answers were accurate before searching, while 19 (42.1% were accurate after searching. The difference of

  6. Self-Paced Interactive Multimedia Courseware: A Learning Support Resource for Enhancing Electronic Theses and Dissertations Development

    Science.gov (United States)

    Essel, Harry Barton; Osei-Poku, Patrick; Tachie-Menson, Akosua; Opoku-Asare, Nana Afia

    2016-01-01

    Submission of Electronic Theses and Dissertations (ETDs) by postgraduate students has become a common phenomenon in learning environments globally. The purpose of ETDs is to train postgraduate students as knowledge workers in online publishing and also extend their skills beyond word processing. The challenge however, is that many postgraduate…

  7. Web Accessibility Issues for Higher & Further Education. EDNER (Formative Evaluation of the Distributed National Electronic Resource) Project. Issues Paper.

    Science.gov (United States)

    Manchester Metropolitan Univ. (England).

    This issues paper, sixth in a series of eight, is intended to distill formative evaluation questions on topics that are central to the development of the higher and further education information environment in the United Kingdom. In undertaking formative evaluation studies, the Formative Evaluation of the Distributed National Electronic Resource…

  8. Analyzing the Academic Research Trends by Using University Digital Resources: A Bibliometric Study of Electronic Commerce in China

    Science.gov (United States)

    Fatima, Anam; Abbas, Asad; Ming, Wan; Zaheer, Ahmad Nawaz; Akhtar, Masood-ul-Hassan

    2017-01-01

    Technology plays a vital role in every field of life especially in business and education. Electronic commerce (EC) begins in the year of 1991 right after internet was introduced for commercial use. It is known to be the 12th five years' plan (2011 to 2015) of Chinese Ministry of Industry and Information Technology. The main "objective"…

  9. Green Supply Chain Collaboration for Fashionable Consumer Electronics Products under Third-Party Power Intervention—A Resource Dependence Perspective

    OpenAIRE

    Jiuh-Biing Sheu

    2014-01-01

    Under third-party power intervention (TPPI), which increases uncertainty in task environments, complex channel power interplays and restructuring are indispensable among green supply chain members as they move toward sustainable collaborative relationships for increased viability and competitive advantage. From the resource dependence perspective, this work presents a novel conceptual model to investigate the influence of political and social power on channel power restructuring and induced ...

  10. Multiple sclerosis deep grey matter: the relation between demyelination, neurodegeneration, inflammation and iron.

    Science.gov (United States)

    Haider, Lukas; Simeonidou, Constantina; Steinberger, Günther; Hametner, Simon; Grigoriadis, Nikolaos; Deretzi, Georgia; Kovacs, Gabor G; Kutzelnigg, Alexandra; Lassmann, Hans; Frischer, Josa M

    2014-12-01

    In multiple sclerosis (MS), diffuse degenerative processes in the deep grey matter have been associated with clinical disabilities. We performed a systematic study in MS deep grey matter with a focus on the incidence and topographical distribution of lesions in relation to white matter and cortex in a total sample of 75 MS autopsy patients and 12 controls. In addition, detailed analyses of inflammation, acute axonal injury, iron deposition and oxidative stress were performed. MS deep grey matter was affected by two different processes: the formation of focal demyelinating lesions and diffuse neurodegeneration. Deep grey matter demyelination was most prominent in the caudate nucleus and hypothalamus and could already be seen in early MS stages. Lesions developed on the background of inflammation. Deep grey matter inflammation was intermediate between low inflammatory cortical lesions and active white matter lesions. Demyelination and neurodegeneration were associated with oxidative injury. Iron was stored primarily within oligodendrocytes and myelin fibres and released upon demyelination. In addition to focal demyelinated plaques, the MS deep grey matter also showed diffuse and global neurodegeneration. This was reflected by a global reduction of neuronal density, the presence of acutely injured axons, and the accumulation of oxidised phospholipids and DNA in neurons, oligodendrocytes and axons. Neurodegeneration was associated with T cell infiltration, expression of inducible nitric oxide synthase in microglia and profound accumulation of iron. Thus, both focal lesions as well as diffuse neurodegeneration in the deep grey matter appeared to contribute to the neurological disabilities of MS patients. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  11. Share and share alike: encouraging the reuse of academic resources through the Scottish electronic Staff Development Library

    Directory of Open Access Journals (Sweden)

    Lorna M. Campbell

    2001-12-01

    Full Text Available The Scottish electronic Staff Development Library (http://www.sesdl.scotcit.acuk is an ongoing collaborative project involving the Universities of Edinburgh, Paisley and Strathclyde which has been funded by SHEFC as part of their current ScotCIT Programme (http:llwww.scotcit.ac.uk. This project is being developed in response to the increasing demand for flexible, high-quality staff development materials.

  12. Success factors for implementing and sustaining a mature electronic medical record in a low-resource setting: a case study of iSanté in Haiti.

    Science.gov (United States)

    deRiel, E; Puttkammer, N; Hyppolite, N; Diallo, J; Wagner, S; Honoré, J G; Balan, J G; Celestin, N; Vallès, J S; Duval, N; Thimothé, G; Boncy, J; Coq, N R L; Barnhart, S

    2018-03-01

    Electronic health information systems, including electronic medical records (EMRs), have the potential to improve access to information and quality of care, among other things. Success factors and challenges for novel EMR implementations in low-resource settings have increasingly been studied, although less is known about maturing systems and sustainability. One systematic review identified seven categories of implementation success factors: ethical, financial, functionality, organizational, political, technical and training. This case study applies this framework to iSanté, Haiti's national EMR in use in more than 100 sites and housing records for more than 750 000 patients. The author group, consisting of representatives of different agencies within the Haitian Ministry of Health (MSPP), funding partner the Centers for Disease Control and Prevention (CDC) Haiti, and implementing partner the International Training and Education Center for Health (I-TECH), identify successes and lessons learned according to the seven identified categories, and propose an additional cross-cutting category, sustainability. Factors important for long-term implementation success of complex information systems are balancing investments in hardware and software infrastructure upkeep, user capacity and data quality control; designing and building a system within the context of the greater eHealth ecosystem with a plan for interoperability and data exchange; establishing system governance and strong leadership to support local system ownership and planning for system financing to ensure sustainability. Lessons learned from 10 years of implementation of the iSanté EMR system are relevant to sustainability of a full range of increasingly interrelated information systems (e.g. for laboratory, supply chain, pharmacy and human resources) in the health sector in low-resource settings. © The Author 2017. Published by Oxford University Press in association with The London School of Hygiene

  13. Selection and Evaluation of Electronic Resources Elektronik Kaynakların Seçimi ve Değerlendirilmesi

    Directory of Open Access Journals (Sweden)

    Doğan Atılgan

    2009-12-01

    Full Text Available Publication boom and issues related to controlling and accession of printed sources have created some problems after World War II. Consequently, publishing industry has encountered the problem of finding possible solution for emerged situation. Industry of electronic publishing has started to improve with the rapid increase of the price of printed sources as well as the problem of publication boom. The first effects of electronic publishing were appeared on the academic and scholarly publications then electronic publishing became a crucial part of all types of publications. As a result of these developments, collection developments and service policies of information centers were also significantly changed. In this article, after a general introduction about selection and evaluation processes of electronic publications, the subscribed databases by a state and a privately owned university in Turkey and their usage were examined. İkinci dünya savaşından sonra görülen yayın patlaması, basılı kaynakların denetim ve erişiminde sorunlar yaşanmasına neden olmuştur. Bu da yayıncılık sektöründe yeni arayışlara yol açmıştır. 1980’li yıllardan sonra basılı yayın fiyatlarındaki hızlı artış da bu etmenlere eklenince elektronik yayıncılık sektörü gelişmeye başlamıştır. Öncelikle bilimsel ve akademik yayınlarla başlayan elektronik yayın günümüzde tüm yayın türlerini kapsamaktadır. Yayıncılıktaki bu gelişim bilgi merkezlerinin derme geliştirme ve hizmet politikalarını da önemli ölçüde değiştirmiştir. Bu çalışmada elektronik yayınların seçim, değerlendirme ve sağlama konularında genel bir girişten sonra bir devlet üniversitesinin bir de özel üniversitenin abone olduğu veritabanları ve bu veri tabanlarının kullanımının değerlendirilmesi yapılmaktadır.

  14. Landolphia owariensis Attenuates Alcohol-induced Cerebellar Neurodegeneration: Significance of Neurofilament Protein Alteration in the Purkinje Cells

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    Oyinbo Charles A.

    2016-12-01

    Full Text Available Background: Alcohol-induced cerebellar neurodegeneration is a neuroadaptation that is associated with chronic alcohol abuse. Conventional drugs have been largely unsatisfactory in preventing neurodegeneration. Yet, multimodal neuro-protective therapeutic agents have been hypothesised to have high therapeutic potential for the treatment of CNS conditions; there is yet a dilemma of how this would be achieved. Contrarily, medicinal botanicals are naturally multimodal in their mechanism of action.

  15. Resveratrol Attenuates Neurodegeneration and Improves Neurological Outcomes after Intracerebral Hemorrhage in Mice

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    Frederick Bonsack

    2017-08-01

    Full Text Available Intracerebral hemorrhage (ICH is a devastating type of stroke with a substantial public health impact. Currently, there is no effective treatment for ICH. The purpose of the study was to evaluate whether the post-injury administration of Resveratrol confers neuroprotection in a pre-clinical model of ICH. To this end, ICH was induced in adult male CD1 mice by collagenase injection method. Resveratrol (10 mg/kg or vehicle was administered at 30 min post-induction of ICH and the neurobehavioral outcome, neurodegeneration, cerebral edema, hematoma resolution and neuroinflammation were assessed. The Resveratrol treatment significantly attenuated acute neurological deficits, neurodegeneration and cerebral edema after ICH in comparison to vehicle treated controls. Further, Resveratrol treated mice exhibited improved hematoma resolution with a concomitant reduction in the expression of proinflammatory cytokine, IL-1β after ICH. Altogether, the data suggest the efficacy of post-injury administration of Resveratrol in improving acute neurological function after ICH.

  16. Neurodegeneration in Alzheimer Disease: Role of Amyloid Precursor Protein and Presenilin 1 Intracellular Signaling

    Directory of Open Access Journals (Sweden)

    Mario Nizzari

    2012-01-01

    Full Text Available Alzheimer disease (AD is a heterogeneous neurodegenerative disorder characterized by (1 progressive loss of synapses and neurons, (2 intracellular neurofibrillary tangles, composed of hyperphosphorylated Tau protein, and (3 amyloid plaques. Genetically, AD is linked to mutations in few proteins amyloid precursor protein (APP and presenilin 1 and 2 (PS1 and PS2. The molecular mechanisms underlying neurodegeneration in AD as well as the physiological function of APP are not yet known. A recent theory has proposed that APP and PS1 modulate intracellular signals to induce cell-cycle abnormalities responsible for neuronal death and possibly amyloid deposition. This hypothesis is supported by the presence of a complex network of proteins, clearly involved in the regulation of signal transduction mechanisms that interact with both APP and PS1. In this review we discuss the significance of novel finding related to cell-signaling events modulated by APP and PS1 in the development of neurodegeneration.

  17. Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration

    Science.gov (United States)

    Pearson, Brandon L.; Simon, Jeremy M.; McCoy, Eric S.; Salazar, Gabriela; Fragola, Giulia; Zylka, Mark J.

    2016-01-01

    Environmental factors, including pesticides, have been linked to autism and neurodegeneration risk using retrospective epidemiological studies. Here we sought to prospectively identify chemicals that share transcriptomic signatures with neurological disorders, by exposing mouse cortical neuron-enriched cultures to hundreds of chemicals commonly found in the environment and on food. We find that rotenone, a pesticide associated with Parkinson's disease risk, and certain fungicides, including pyraclostrobin, trifloxystrobin, famoxadone and fenamidone, produce transcriptional changes in vitro that are similar to those seen in brain samples from humans with autism, advanced age and neurodegeneration (Alzheimer's disease and Huntington's disease). These chemicals stimulate free radical production and disrupt microtubules in neurons, effects that can be reduced by pretreating with a microtubule stabilizer, an antioxidant, or with sulforaphane. Our study provides an approach to prospectively identify environmental chemicals that transcriptionally mimic autism and other brain disorders. PMID:27029645

  18. Anaesthetic management of a child with panthothenate kinase-associated neurodegeneration

    Directory of Open Access Journals (Sweden)

    Renu Sinha

    2015-01-01

    Full Text Available Panthothenate kinase-associated neurodegeneration (PKAN (Hallervorden-Spatz disease is a rare autosomal recessive chromosomal disorder characterised by progressive neuroaxonal dystrophy. The characteristic features include involuntary movements, rigidity, mental retardation, seizures, emaciation. The anaesthetic concerns include difficult airway, aspiration pneumonia, dehydration, and post-operative respiratory, and renal insufficiency. We report successful anaesthetic management of a 9-year-old intellectually disabled male child with PKAN, scheduled for ophthalmic surgery under general anaesthesia.

  19. Insulin resistance and neurodegeneration: Roles of obesity, type 2 diabetes mellitus and non-alcoholic steatohepatitis

    OpenAIRE

    de la Monte, Suzanne M; Longato, Lisa; Tong, Ming; Wands, Jack R

    2009-01-01

    Recent studies have linked obesity, type 2 diabetes mellitus (T2DM) or non-alcoholic steatohepatitis (NASH) to insulin resistance in the brain, cognitive impairment and neurodegeneration. Insulin resistance compromises cell survival, metabolism and neuronal plasticity, and increases oxidative stress, cytokine activation and apoptosis. T2DM/NASH has been demonstrated to be associated with increased ceramide generation, suggesting a mechanistic link between peripheral insulin resistance and neu...

  20. Compensatory mechanisms in genetic models of neurodegeneration: are the mice better than humans?

    OpenAIRE

    Kreiner, Grzegorz

    2015-01-01

    Neurodegenerative diseases are one of the main causes of mental and physical disabilities. Neurodegeneration has been estimated to begin many years before the first clinical symptoms manifest, and even a prompt diagnosis at this stage provides very little advantage for a more effective treatment as the currently available pharmacotherapies are based on disease symptomatology. The etiology of the majority of neurodegenerative diseases remains unknown, and even for those diseases caused by iden...

  1. Novel Mechanism for Reducing Acute and Chronic Neurodegeneration After Traumatic Brain Injury

    Science.gov (United States)

    2017-07-01

    Award Number: W81XWH-14-1-0195 TITLE: Novel Mechanism for Reducing Acute and Chronic Neurodegeneration after Traumatic Brain Injury...Purpose: The purpose of this project is to develop a radically different strategy to reduce brain glutamate excitotoxicity and treat TBI. We will...objective of reducing blood levels of glutamate. This will produce a brain -to-blood gradient of glutamate which will enhance the removal of excess

  2. Ablation of ferroptosis regulator glutathione peroxidase 4 in forebrain neurons promotes cognitive impairment and neurodegeneration

    Directory of Open Access Journals (Sweden)

    William Sealy Hambright

    2017-08-01

    Full Text Available Synaptic loss and neuron death are the underlying cause of neurodegenerative diseases such as Alzheimer's disease (AD; however, the modalities of cell death in those diseases remain unclear. Ferroptosis, a newly identified oxidative cell death mechanism triggered by massive lipid peroxidation, is implicated in the degeneration of neurons populations such as spinal motor neurons and midbrain neurons. Here, we investigated whether neurons in forebrain regions (cerebral cortex and hippocampus that are severely afflicted in AD patients might be vulnerable to ferroptosis. To this end, we generated Gpx4BIKO mouse, a mouse model with conditional deletion in forebrain neurons of glutathione peroxidase 4 (Gpx4, a key regulator of ferroptosis, and showed that treatment with tamoxifen led to deletion of Gpx4 primarily in forebrain neurons of adult Gpx4BIKO mice. Starting at 12 weeks after tamoxifen treatment, Gpx4BIKO mice exhibited significant deficits in spatial learning and memory function versus Control mice as determined by the Morris water maze task. Further examinations revealed that the cognitively impaired Gpx4BIKO mice exhibited hippocampal neurodegeneration. Notably, markers associated with ferroptosis, such as elevated lipid peroxidation, ERK activation and augmented neuroinflammation, were observed in Gpx4BIKO mice. We also showed that Gpx4BIKO mice fed a diet deficient in vitamin E, a lipid soluble antioxidant with anti-ferroptosis activity, had an expedited rate of hippocampal neurodegeneration and behavior dysfunction, and that treatment with a small-molecule ferroptosis inhibitor ameliorated neurodegeneration in those mice. Taken together, our results indicate that forebrain neurons are susceptible to ferroptosis, suggesting that ferroptosis may be an important neurodegenerative mechanism in diseases such as AD. Keywords: Ferroptosis, Neurodegeneration, Cognitive impairment, Alzheimer's disease, Glutathione peroxidase 4, Transgenic mice

  3. Therapeutic effect of mesenchymal multipotent stromal cells on memory in animals with Alzheimer-type neurodegeneration.

    Science.gov (United States)

    Bobkova, N V; Poltavtseva, R A; Samokhin, A N; Sukhikh, G T

    2013-11-01

    Transplantation of human mesenchymal multipotent stromal cells improved spatial memory in bulbectomized mice with Alzheimer-type neurodegeneration. The positive effect was observed in 1 month after intracerebral transplantation and in 3 months after systemic injection of mesenchymal multipotent stromal cells. No cases of malignant transformation were noted. These findings indicate prospects of using mesenchymal multipotent stromal cells for the therapy of Alzheimer disease and the possibility of their systemic administration for attaining the therapeutic effect.

  4. The db/db mouse: a useful model for the study of diabetic retinal neurodegeneration.

    Directory of Open Access Journals (Sweden)

    Patricia Bogdanov

    Full Text Available BACKGROUND: To characterize the sequential events that are taking place in retinal neurodegeneration in a murine model of spontaneous type 2 diabetes (db/db mouse. METHODS: C57BLKsJ-db/db mice were used as spontaneous type 2 diabetic animal model, and C57BLKsJ-db/+ mice served as the control group. To assess the chronological sequence of the abnormalities the analysis was performed at different ages (8, 16 and 24 weeks. The retinas were evaluated in terms of morphological and functional abnormalities [electroretinography (ERG]. Histological markers of neurodegeneration (glial activation and apoptosis were evaluated by immunohistochemistry. In addition glutamate levels and glutamate/aspartate transporter (GLAST expression were assessed. Furthermore, to define gene expression changes associated with early diabetic retinopathy a transcriptome analyses was performed at 8 week. Furthermore, an additional interventional study to lower blood glucose levels was performed. RESULTS: Glial activation was higher in diabetic than in non diabetic mice in all the stages (p<0.01. In addition, a progressive loss of ganglion cells and a significant reduction of neuroretinal thickness were also observed in diabetic mice. All these histological hallmarks of neurodegeneration were less pronounced at week 8 than at week 16 and 24. Significant ERG abnormalities were present in diabetic mice at weeks 16 and 24 but not at week 8. Moreover, we observed a progressive accumulation of glutamate in diabetic mice associated with an early downregulation of GLAST. Morphological and ERG abnormalities were abrogated by lowering blood glucose levels. Finally, a dysregulation of several genes related to neurotransmission and oxidative stress such as UCP2 were found at week 8. CONCLUSIONS: Our results suggest that db/db mouse reproduce the features of the neurodegenerative process that occurs in the human diabetic eye. Therefore, it seems an appropriate model for investigating the

  5. Early intranasal insulin therapy halts progression of neurodegeneration: progress in Alzheimer’s disease therapeutics

    OpenAIRE

    de la Monte, Suzanne M.

    2012-01-01

    Evaluation of Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, et al. Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment: A Pilot Clinical Trial. Arch Neurol. 2011 Sep 12. Alzheimer’s disease is associated with brain insulin deficiency and insulin resistance, similar to the problems in diabetes. If insulin could be supplied to the brain in the early stages of Alzheimer’s, subsequent neurodegeneration might be prevented. ...

  6. Virulence test using nematodes to prescreen Nocardia species capable of inducing neurodegeneration and behavioral disorders

    Directory of Open Access Journals (Sweden)

    Claire Bernardin Souibgui

    2017-10-01

    Full Text Available Background Parkinson’s disease (PD is a disorder characterized by dopaminergic neuron programmed cell death. The etiology of PD remains uncertain—some cases are due to selected genes associated with familial heredity, others are due to environmental exposure to toxic components, but over 90% of cases have a sporadic origin. Nocardia are Actinobacteria that can cause human diseases like nocardiosis. This illness can lead to lung infection or central nervous system (CNS invasion in both immunocompromised and immunocompetent individuals. The main species involved in CNS are N. farcinica, N. nova, N. brasiliensis and N. cyriacigeorgica. Some studies have highlighted the ability of N. cyriacigeorgica to induce Parkinson’s disease-like symptoms in animals. Actinobacteria are known to produce a large variety of secondary metabolites, some of which can be neurotoxic. We hypothesized that neurotoxic secondary metabolite production and the onset of PD-like symptoms in animals could be linked. Methods Here we used a method to screen bacteria that could induce dopaminergic neurodegeneration before performing mouse experiments. Results The nematode Caenorhabditis elegans allowed us to demonstrate that Nocardia strains belonging to N. cyriacigeorgica and N. farcinica species can induce dopaminergic neurodegeneration. Strains of interest involved with the nematodes in neurodegenerative disorders were then injected in mice. Infected mice had behavioral disorders that may be related to neuronal damage, thus confirming the ability of Nocardia strains to induce neurodegeneration. These behavioral disorders were induced by N. cyriacigeorgica species (N. cyriacigeorgica GUH-2 and N. cyriacigeorgica 44484 and N. farcinica 10152. Discussion We conclude that C. elegans is a good model for detecting Nocardia strains involved in neurodegeneration. This model allowed us to detect bacteria with high neurodegenerative effects and which should be studied in mice to

  7. Reduced synaptic vesicle protein degradation at lysosomes curbs TBC1D24/sky-induced neurodegeneration.

    Science.gov (United States)

    Fernandes, Ana Clara; Uytterhoeven, Valerie; Kuenen, Sabine; Wang, Yu-Chun; Slabbaert, Jan R; Swerts, Jef; Kasprowicz, Jaroslaw; Aerts, Stein; Verstreken, Patrik

    2014-11-24

    Synaptic demise and accumulation of dysfunctional proteins are thought of as common features in neurodegeneration. However, the mechanisms by which synaptic proteins turn over remain elusive. In this paper, we study Drosophila melanogaster lacking active TBC1D24/Skywalker (Sky), a protein that in humans causes severe neurodegeneration, epilepsy, and DOOR (deafness, onychdystrophy, osteodystrophy, and mental retardation) syndrome, and identify endosome-to-lysosome trafficking as a mechanism for degradation of synaptic vesicle-associated proteins. In fly sky mutants, synaptic vesicles traveled excessively to endosomes. Using chimeric fluorescent timers, we show that synaptic vesicle-associated proteins were younger on average, suggesting that older proteins are more efficiently degraded. Using a genetic screen, we find that reducing endosomal-to-lysosomal trafficking, controlled by the homotypic fusion and vacuole protein sorting (HOPS) complex, rescued the neurotransmission and neurodegeneration defects in sky mutants. Consistently, synaptic vesicle proteins were older in HOPS complex mutants, and these mutants also showed reduced neurotransmission. Our findings define a mechanism in which synaptic transmission is facilitated by efficient protein turnover at lysosomes and identify a potential strategy to suppress defects arising from TBC1D24 mutations in humans. © 2014 Fernandes et al.

  8. Intranasal Insulin Therapy for Cognitive Impairment and Neurodegeneration: Current State of the Art

    Science.gov (United States)

    de la Monte, Suzanne M.

    2015-01-01

    Introduction Growing evidence supports the concept that insulin resistance plays an important role in the pathogenesis of cognitive impairment and neurodegeneration, including in Alzheimer's disease (AD). The metabolic hypothesis has led to the development and utilization of insulin- and insulin agonist-based treatments. Therapeutic challenges faced include the ability to provide effective treatments that do not require repeated injections and also minimize potentially hazardous off-target effects. Areas covered This review covers the role of intra-nasal insulin therapy for cognitive impairment and neurodegeneration, particularly Alzheimer's disease. The literature reviewed focuses on data published within the past 5 years as this field is evolving rapidly. The author provides evidence that brain insulin resistance is an important and early abnormality in Alzheimer's disease, and that increasing brain supply and utilization of insulin improves cognition and memory. Emphasis was placed on discussing outcomes of clinical trials and interpreting discordant results to clarify the benefits and limitations of intranasal insulin therapy. Expert Opinion Intranasal insulin therapy can efficiently and directly target the brain to support energy metabolism, myelin maintenance, cell survival, and neuronal plasticity, which begin to fail in the early stages of neurodegeneration. Efforts must continue toward increasing the safety, efficacy, and specificity of intranasal insulin therapy. PMID:24215447

  9. Gallic acid and p-coumaric acid attenuate type 2 diabetes-induced neurodegeneration in rats.

    Science.gov (United States)

    Abdel-Moneim, Adel; Yousef, Ahmed I; Abd El-Twab, Sanaa M; Abdel Reheim, Eman S; Ashour, Mohamed B

    2017-08-01

    The brain of diabetics revealed deterioration in many regions, especially the hippocampus. Hence, the present study aimed to evaluate the effects of gallic acid and p-coumaric acid against the hippocampal neurodegeneration in type 2 diabetic rats. Adult male albino rats were randomly allocated into four groups: Group 1 served as control ones and others were induced with diabetes. Group 2 considered as diabetic, and groups 3 and 4 were further orally treated with gallic acid (20 mg/kg b.wt./day) and p-coumaric acid (40 mg/kg b.wt./day) for six weeks. Diabetic rats revealed significant elevation in the levels of serum glucose, blood glycosylated hemoglobin and serum tumor necrosis factor-α, while the level of serum insulin was significantly declined. Furthermore, the brain of diabetic rats showed a marked increase in oxidative stress and a decrease of antioxidant parameters as well as upregulation the protein expression of Bax and downregulation the protein expression of Bcl-2 in the hippocampus. Treatment of diabetic rats with gallic acid and p-coumaric acid significantly ameliorated glucose tolerance, diminished the brain oxidative stress and improved antioxidant status, declined inflammation and inhibited apoptosis in the hippocampus. The overall results suggested that gallic acid and p-coumaric acid may inhibit hippocampal neurodegeneration via their potent antioxidant, anti-inflammatory and anti-apoptotic properties. Therefore, both compounds can be recommended as hopeful adjuvant agents against brain neurodegeneration in diabetics.

  10. Mutations in the Heme Exporter FLVCR1 Cause Sensory Neurodegeneration with Loss of Pain Perception.

    Science.gov (United States)

    Chiabrando, Deborah; Castori, Marco; di Rocco, Maja; Ungelenk, Martin; Gießelmann, Sebastian; Di Capua, Matteo; Madeo, Annalisa; Grammatico, Paola; Bartsch, Sophie; Hübner, Christian A; Altruda, Fiorella; Silengo, Lorenzo; Tolosano, Emanuela; Kurth, Ingo

    2016-12-01

    Pain is necessary to alert us to actual or potential tissue damage. Specialized nerve cells in the body periphery, so called nociceptors, are fundamental to mediate pain perception and humans without pain perception are at permanent risk for injuries, burns and mutilations. Pain insensitivity can be caused by sensory neurodegeneration which is a hallmark of hereditary sensory and autonomic neuropathies (HSANs). Although mutations in several genes were previously associated with sensory neurodegeneration, the etiology of many cases remains unknown. Using next generation sequencing in patients with congenital loss of pain perception, we here identify bi-allelic mutations in the FLVCR1 (Feline Leukemia Virus subgroup C Receptor 1) gene, which encodes a broadly expressed heme exporter. Different FLVCR1 isoforms control the size of the cytosolic heme pool required to sustain metabolic activity of different cell types. Mutations in FLVCR1 have previously been linked to vision impairment and posterior column ataxia in humans, but not to HSAN. Using fibroblasts and lymphoblastoid cell lines from patients with sensory neurodegeneration, we here show that the FLVCR1-mutations reduce heme export activity, enhance oxidative stress and increase sensitivity to programmed cell death. Our data link heme metabolism to sensory neuron maintenance and suggest that intracellular heme overload causes early-onset degeneration of pain-sensing neurons in humans.

  11. Drugs of abuse in pregnancy, poor neonatal development, and future neurodegeneration. Is oxidative stress the culprit?

    Science.gov (United States)

    Neri, Margherita; Bello, Stefania; Turillazzi, Emanuela; Riezzo, Irene

    2015-01-01

    The abuse of licit and illicit drugs is a worldwide issue that is a cause for concern in pregnant women. It may lead to complications in pregnancy that may affect the mother, fetus, and /or neonate. The effects of any substance on the developing embryo and fetus are dependent upon dosing, timing, duration of drug exposure, and the extent of drug distribution. Teratogenic effects have been described when exposure takes place during the embryonic stage; however drugs have subtle effects, including abnormal growth and/or maturation, alterations in neurotransmitters and their receptors, and brain organization. The mechanisms by which intrauterine exposure to many substances may result in neuronal injury have not been completely elucidated. Oxidative stress and epigenetic changes have been recently implicated in the pathogenesis of long - term adverse health sequelae, and neuro-developmental impairment in the offspring of addicted mothers. Transgenerational epigenetics may also explain the alarming datum that developmental abnormalities, impairment in learning and memory, and attention deficit can occur even in the absence of direct fetal exposure, when drugs are consumed prior to conception. There is a growing body of evidence demonstrating a link between redox state unbalance, epigenetic markers, developmental anomalies, and neurodegeneration. The reviewed literature data uphold redox homeostasis disruption as an important factor in the pathogenesis of drug of abuse- induced neurodegeneration, and highlight the potential for new therapies that could prevent neurodegeneration through antioxidant and epigenetic modulatory mechanisms. This therefore reveals important targets for novel neuroprotective strategies.

  12. SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis.

    Science.gov (United States)

    Kim, Dohoon; Nguyen, Minh Dang; Dobbin, Matthew M; Fischer, Andre; Sananbenesi, Farahnaz; Rodgers, Joseph T; Delalle, Ivana; Baur, Joseph A; Sui, Guangchao; Armour, Sean M; Puigserver, Pere; Sinclair, David A; Tsai, Li-Huei

    2007-07-11

    A progressive loss of neurons with age underlies a variety of debilitating neurological disorders, including Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), yet few effective treatments are currently available. The SIR2 gene promotes longevity in a variety of organisms and may underlie the health benefits of caloric restriction, a diet that delays aging and neurodegeneration in mammals. Here, we report that a human homologue of SIR2, SIRT1, is upregulated in mouse models for AD, ALS and in primary neurons challenged with neurotoxic insults. In cell-based models for AD/tauopathies and ALS, SIRT1 and resveratrol, a SIRT1-activating molecule, both promote neuronal survival. In the inducible p25 transgenic mouse, a model of AD and tauopathies, resveratrol reduced neurodegeneration in the hippocampus, prevented learning impairment, and decreased the acetylation of the known SIRT1 substrates PGC-1alpha and p53. Furthermore, injection of SIRT1 lentivirus in the hippocampus of p25 transgenic mice conferred significant protection against neurodegeneration. Thus, SIRT1 constitutes a unique molecular link between aging and human neurodegenerative disorders and provides a promising avenue for therapeutic intervention.

  13. SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis

    Science.gov (United States)

    Kim, Dohoon; Nguyen, Minh Dang; Dobbin, Matthew M; Fischer, Andre; Sananbenesi, Farahnaz; Rodgers, Joseph T; Delalle, Ivana; Baur, Joseph A; Sui, Guangchao; Armour, Sean M; Puigserver, Pere; Sinclair, David A; Tsai, Li-Huei

    2007-01-01

    A progressive loss of neurons with age underlies a variety of debilitating neurological disorders, including Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), yet few effective treatments are currently available. The SIR2 gene promotes longevity in a variety of organisms and may underlie the health benefits of caloric restriction, a diet that delays aging and neurodegeneration in mammals. Here, we report that a human homologue of SIR2, SIRT1, is upregulated in mouse models for AD, ALS and in primary neurons challenged with neurotoxic insults. In cell-based models for AD/tauopathies and ALS, SIRT1 and resveratrol, a SIRT1-activating molecule, both promote neuronal survival. In the inducible p25 transgenic mouse, a model of AD and tauopathies, resveratrol reduced neurodegeneration in the hippocampus, prevented learning impairment, and decreased the acetylation of the known SIRT1 substrates PGC-1alpha and p53. Furthermore, injection of SIRT1 lentivirus in the hippocampus of p25 transgenic mice conferred significant protection against neurodegeneration. Thus, SIRT1 constitutes a unique molecular link between aging and human neurodegenerative disorders and provides a promising avenue for therapeutic intervention. PMID:17581637

  14. The Kynurenine Pathway Modulates Neurodegeneration in a Drosophila Model of Huntington’s Disease

    Science.gov (United States)

    Campesan, Susanna; Green, Edward W.; Breda, Carlo; Sathyasaikumar, Korrapati V.; Muchowski, Paul J.; Schwarcz, Robert; Kyriacou, Charalambos P.; Giorgini, Flaviano

    2014-01-01

    Summary Neuroactive metabolites of the kynurenine pathway (KP) of tryptophan degradation have been implicated in the pathophysiology of neurodegenerative disorders, including Huntington’s disease (HD) [1]. A central hallmark of HD is neurodegeneration caused by a polyglutamine expansion in the huntingtin (htt) protein [2]. Here we exploit a transgenic Drosophila melanogaster model of HD to interrogate the therapeutic potential of KP manipulation. We observe that genetic and pharmacological inhibition of kynurenine 3-monooxygenase (KMO) increases levels of the neuroprotective metabolite kynurenic acid (KYNA) relative to the neurotoxic metabolite 3-hydroxykynurenine (3-HK) and ameliorates neurodegeneration. We also find that genetic inhibition of tryptophan 2,3-dioxygenase (TDO), the first and rate-limiting step in the pathway, leads to a similar neuroprotective shift toward KYNA synthesis. Importantly, we demonstrate that the feeding of KYNA and 3-HK to HD model flies directly modulates neurodegeneration, underscoring the causative nature of these metabolites. This study provides the first genetic evidence that inhibition of KMO and TDO activity protects against neurodegenerative disease in an animal model, indicating that strategies targeted at two key points within the KP may have therapeutic relevance in HD, and possibly other neurodegenerative disorders. PMID:21636279

  15. Neuroprotective Effects of Citicoline in in Vitro Models of Retinal Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Andrea Matteucci

    2014-04-01

    Full Text Available In recent years, citicoline has been the object of remarkable interest as a possible neuroprotectant. The aim of this study was to investigate if citicoline affected cell survival in primary retinal cultures and if it exerted neuroprotective activity in conditions modeling retinal neurodegeneration. Primary retinal cultures, obtained from rat embryos, were first treated with increasing concentrations of citicoline (up to 1000 µM and analyzed in terms of apoptosis and caspase activation and characterized by immunocytochemistry to identify neuronal and glial cells. Subsequently, excitotoxic concentration of glutamate or High Glucose-containing cell culture medium (HG was administered as well-known conditions modeling neurodegeneration. Glutamate or HG treatments were performed in the presence or not of citicoline. Neuronal degeneration was evaluated in terms of apoptosis and loss of synapses. The results showed that citicoline did not cause any damage to the retinal neuroglial population up to 1000 µM. At the concentration of 100 µM, it was able to counteract neuronal cell damage both in glutamate- and HG-treated retinal cultures by decreasing proapoptotic effects and contrasting synapse loss. These data confirm that citicoline can efficiently exert a neuroprotective activity. In addition, the results suggest that primary retinal cultures, under conditions inducing neurodegeneration, may represent a useful system to investigate citicoline neuroprotective mechanisms.

  16. Mapping and reconstruction of domoic acid-induced neurodegeneration in the mouse brain.

    Science.gov (United States)

    Colman, J R; Nowocin, K J; Switzer, R C; Trusk, T C; Ramsdell, J S

    2005-01-01

    Domoic acid, a potent neurotoxin and glutamate analog produced by certain species of the marine diatom Pseudonitzschia, is responsible for several human and wildlife intoxication events. The toxin characteristically damages the hippocampus in exposed humans, rodents, and marine mammals. Histochemical studies have identified this, and other regions of neurodegeneration, though none have sought to map all brain regions affected by domoic acid. In this study, mice exposed (i.p.) to 4 mg/kg domoic acid for 72 h exhibited behavioral and pathological signs of neurotoxicity. Brains were fixed by intracardial perfusion and processed for histochemical analysis. Serial coronal sections (50 microm) were stained using the degeneration-sensitive cupric silver staining method of DeOlmos. Degenerated axons, terminals, and cell bodies, which stained black, were identified and the areas of degeneration were mapped onto Paxinos mouse atlas brain plates using Adobe Illustrator CS. The plates were then combined to reconstruct a 3-dimensional image of domoic acid-induced neurodegeneration using Amira 3.1 software. Affected regions included the olfactory bulb, septal area, and limbic system. These findings are consistent with behavioral and pathological studies demonstrating the effects of domoic acid on cognitive function and neurodegeneration in rodents.

  17. The Drosophila carbonyl reductase sniffer prevents oxidative stress-induced neurodegeneration.

    Science.gov (United States)

    Botella, Jose A; Ulschmid, Julia K; Gruenewald, Christoph; Moehle, Christoph; Kretzschmar, Doris; Becker, Katja; Schneuwly, Stephan

    2004-05-04

    A growing body of evidence suggests that oxidative stress is a common underlying mechanism in the pathogenesis of neurodegenerative disorders such as Alzheimer's, Huntington's, Creutzfeld-Jakob and Parkinson's diseases. Despite the increasing number of reports finding a causal relation between oxidative stress and neurodegeneration, little is known about the genetic elements that confer protection against the deleterious effects of oxidation in neurons. We have isolated and characterized the Drosophila melanogaster gene sniffer, whose function is essential for preventing age-related neurodegeneration. In addition, we demonstrate that oxidative stress is a direct cause of neurodegeneration in the Drosophila central nervous system and that reduction of sniffer activity leads to neuronal cell death. The overexpression of the gene confers neuronal protection against oxygen-induced apoptosis, increases resistance of flies to experimental normobaric hyperoxia, and improves general locomotor fitness. Sniffer belongs to the family of short-chain dehydrogenase/reductase (SDR) enzymes and exhibits carbonyl reductase activity. This is the first in vivo evidence of the direct and important implication of this enzyme as a neuroprotective agent in the cellular defense mechanisms against oxidative stress.

  18. Mutations in the Heme Exporter FLVCR1 Cause Sensory Neurodegeneration with Loss of Pain Perception.

    Directory of Open Access Journals (Sweden)

    Deborah Chiabrando

    2016-12-01

    Full Text Available Pain is necessary to alert us to actual or potential tissue damage. Specialized nerve cells in the body periphery, so called nociceptors, are fundamental to mediate pain perception and humans without pain perception are at permanent risk for injuries, burns and mutilations. Pain insensitivity can be caused by sensory neurodegeneration which is a hallmark of hereditary sensory and autonomic neuropathies (HSANs. Although mutations in several genes were previously associated with sensory neurodegeneration, the etiology of many cases remains unknown. Using next generation sequencing in patients with congenital loss of pain perception, we here identify bi-allelic mutations in the FLVCR1 (Feline Leukemia Virus subgroup C Receptor 1 gene, which encodes a broadly expressed heme exporter. Different FLVCR1 isoforms control the size of the cytosolic heme pool required to sustain metabolic activity of different cell types. Mutations in FLVCR1 have previously been linked to vision impairment and posterior column ataxia in humans, but not to HSAN. Using fibroblasts and lymphoblastoid cell lines from patients with sensory neurodegeneration, we here show that the FLVCR1-mutations reduce heme export activity, enhance oxidative stress and increase sensitivity to programmed cell death. Our data link heme metabolism to sensory neuron maintenance and suggest that intracellular heme overload causes early-onset degeneration of pain-sensing neurons in humans.

  19. VDAC1 as pharmacological target in cancer and neurodegeneration: focus on its role in apoptosis.

    Science.gov (United States)

    Magrì, Andrea; Reina, Simona; De Pinto, Vito

    2018-04-01

    Cancer and neurodegeneration are different classes of diseases that share the involvement of mitochondria in their pathogenesis. Whereas the high glycolytic rate (the so-called Warburg metabolism) and the suppression of apoptosis are key elements for the establishment and maintenance of cancer cells, mitochondrial dysfunction and increased cell death mark neurodegeneration. As a main actor in the regulation of cell metabolism and apoptosis, VDAC may represent the common point between these two broad families of pathologies. Located in the outer mitochondrial membrane, VDAC forms channels that control the flux of ions and metabolites across the mitochondrion thus mediating the organelle's cross-talk with the rest of the cell. Furthermore, the interaction with both pro-apoptotic and anti-apoptotic factors makes VDAC a gatekeeper for mitochondria-mediated cell death and survival signaling pathways. Unfortunately, the lack of an evident druggability of this protein, since it has no defined binding or active sites, makes the quest for VDAC interacting molecules a difficult tale. Pharmacologically active molecules of different classes have been proposed to hit cancer and neurodegeneration. In this work, we provide an exhaustive and detailed survey of all the molecules, peptides and microRNAs that exploit VDAC in the treatment of the two examined classes of pathologies. The mechanism of action and the potential or effectiveness of each compound are discussed.

  20. The Regulatory Machinery of Neurodegeneration in In Vitro Models of Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Burcin Ikiz

    2015-07-01

    Full Text Available Neurodegenerative phenotypes reflect complex, time-dependent molecular processes whose elucidation may reveal neuronal class-specific therapeutic targets. The current focus in neurodegeneration has been on individual genes and pathways. In contrast, we assembled a genome-wide regulatory model (henceforth, “interactome”, whose unbiased interrogation revealed 23 candidate causal master regulators of neurodegeneration in an in vitro model of amyotrophic lateral sclerosis (ALS, characterized by a loss of spinal motor neurons (MNs. Of these, eight were confirmed as specific MN death drivers in our model of familial ALS, including NF-κB, which has long been considered a pro-survival factor. Through an extensive array of molecular, pharmacological, and biochemical approaches, we have confirmed that neuronal NF-κB drives the degeneration of MNs in both familial and sporadic models of ALS, thus providing proof of principle that regulatory network analysis is a valuable tool for studying cell-specific mechanisms of neurodegeneration.

  1. Utility of the electronic information resource UpToDate for clinical decision-making at bedside rounds.

    Science.gov (United States)

    Phua, J; See, K C; Khalizah, H J; Low, S P; Lim, T K

    2012-02-01

    Clinical questions often arise at daily hospital bedside rounds. Yet, little information exists on how the search for answers may be facilitated. The aim of this prospective study was, therefore, to evaluate the overall utility, including the feasibility and usefulness of incorporating searches of UpToDate, a popular online information resource, into rounds. Doctors searched UpToDate for any unresolved clinical questions during rounds for patients in general medicine and respiratory wards, and in the medical intensive care unit of a tertiary teaching hospital. The nature of the questions and the results of the searches were recorded. Searches were deemed feasible if they were completed during the rounds and useful if they provided a satisfactory answer. A total of 157 UpToDate searches were performed during the study period. Questions were raised by all ranks of clinicians from junior doctors to consultants. The searches were feasible and performed immediately during rounds 44% of the time. Each search took a median of three minutes (first quartile: two minutes, third quartile: five minutes). UpToDate provided a useful and satisfactory answer 75% of the time, a partial answer 17% of the time and no answer 9% of the time. It led to a change in investigations, diagnosis or management 37% of the time, confirmed what was originally known or planned 38% of the time and had no effect 25% of the time. Incorporating UpToDate searches into daily bedside rounds was feasible and useful in clinical decision-making.

  2. Searching for neurodegeneration in multiple sclerosis at clinical onset: Diagnostic value of biomarkers.

    Science.gov (United States)

    Novakova, Lenka; Axelsson, Markus; Malmeström, Clas; Imberg, Henrik; Elias, Olle; Zetterberg, Henrik; Nerman, Olle; Lycke, Jan

    2018-01-01

    Neurodegeneration occurs during the early stages of multiple sclerosis. It is an essential, devastating part of the pathophysiology. Tools for measuring the degree of neurodegeneration could improve diagnostics and patient characterization. This study aimed to determine the diagnostic value of biomarkers of degeneration in patients with recent clinical onset of suspected multiple sclerosis, and to evaluate these biomarkers for characterizing disease course. This cross-sectional study included 271 patients with clinical features of suspected multiple sclerosis onset and was the baseline of a prospective study. After diagnostic investigations, the patients were classified into the following disease groups: patients with clinically isolated syndrome (n = 4) or early relapsing remitting multiple sclerosis (early RRMS; n = 93); patients with relapsing remitting multiple sclerosis with disease durations ≥2 years (established RRMS; n = 39); patients without multiple sclerosis, but showing symptoms (symptomatic controls; n = 89); and patients diagnosed with other diseases (n = 46). In addition, we included healthy controls (n = 51) and patients with progressive multiple sclerosis (n = 23). We analyzed six biomarkers of neurodegeneration: cerebrospinal fluid neurofilament light chain levels; cerebral spinal fluid glial fibrillary acidic protein; cerebral spinal fluid tau; retinal nerve fiber layer thickness; macula volume; and the brain parenchymal fraction. Except for increased cerebral spinal fluid neurofilament light chain levels, median 670 ng/L (IQR 400-2110), we could not find signs of early degeneration in the early disease group with recent clinical onset. However, the intrathecal immunoglobin G production and cerebral spinal fluid neurofilament light chain levels showed diagnostic value. Moreover, elevated levels of cerebral spinal fluid glial fibrillary acidic protein, thin retinal nerve fiber layers, and low brain parenchymal fractions were associated with

  3. Comprehensive evaluation of electronic medical record system use and user satisfaction at five low-resource setting hospitals in ethiopia.

    Science.gov (United States)

    Tilahun, Binyam; Fritz, Fleur

    2015-05-25

    Electronic medical record (EMR) systems are increasingly being implemented in hospitals of developing countries to improve patient care and clinical service. However, only limited evaluation studies are available concerning the level of adoption and determinant factors of success in those settings. The objective of this study was to assess the usage pattern, user satisfaction level, and determinants of health professional's satisfaction towards a comprehensive EMR system implemented in Ethiopia where parallel documentation using the EMR and the paper-based medical records is in practice. A quantitative, cross-sectional study design was used to assess the usage pattern, user satisfaction level, and determinant factors of an EMR system implemented in Ethiopia based on the DeLone and McLean model of information system success. Descriptive statistical methods were applied to analyze the data and a binary logistic regression model was used to identify determinant factors. Health professionals (N=422) from five hospitals were approached and 406 responded to the survey (96.2% response rate). Out of the respondents, 76.1% (309/406) started to use the system immediately after implementation and user training, but only 31.7% (98/309) of the professionals reported using the EMR during the study (after 3 years of implementation). Of the 12 core EMR functions, 3 were never used by most respondents, and they were also unaware of 4 of the core EMR functions. It was found that 61.4% (190/309) of the health professionals reported over all dissatisfaction with the EMR (median=4, interquartile range (IQR)=1) on a 5-level Likert scale. Physicians were more dissatisfied (median=5, IQR=1) when compared to nurses (median=4, IQR=1) and the health management information system (HMIS) staff (median=2, IQR=1). Of all the participants, 64.4% (199/309) believed that the EMR had no positive impact on the quality of care. The participants indicated an agreement with the system and information

  4. Paraquat and maneb co-exposure induces noradrenergic locus coeruleus neurodegeneration through NADPH oxidase-mediated microglial activation

    International Nuclear Information System (INIS)

    Hou, Liyan; Zhang, Cong; Wang, Ke; Liu, Xiaofang; Wang, Hongwei; Che, Yuning; Sun, Fuqiang; Zhou, Xueying; Zhao, Xiulan; Wang, Qingshan

    2017-01-01

    Highlights: • Microglial activation induced by paraquat and maneb precedes noradrenergic neurodegeneration in locus coeruleus. • NADPH oxidase activation contributes to microglia-mediated neuroinflammation and related noradrenergic neurodegeneration. • Inhibition of NADPH oxidase by apocynin protects noradrenergic neurons against paraquat and maneb-induced toxicity. - Abstract: Co-exposure to paraquat (PQ) and maneb (Mb) has been shown to increase the risk of Parkinson’s disease (PD) and dopaminergic (DA) neurodegeneration in the substantia nigra pars compacta (SNpc) is observed in PQ and Mb-treated experimental animals. The loss of noradrenergic locus coeruleus (LC/NE) neurons in brainstem is a common feature shared by multiple neurodegenerative diseases, including PD. However, whether PQ and Mb is able to damage LC/NE neurons remains undefined. In this study, mice treated with combined PQ and Mb displayed progressive LC/NE neurodegeneration. Time course studies revealed that the activation of microglia preceded LC/NE neurodegeneration. Mechanistically, the activation of NADPH oxidase contributed to microglial activation and subsequent LC/NE neurodegeneration. We found that PQ and Mb co-exposure induced activation of NADPH oxidase as shown by increased superoxide production and membrane translocation of p47 phox , a cytosolic subunit of NADPH oxidase. Inhibition of NADPH oxidase by apocynin, a widely used NADPH oxidase inhibitor, suppressed microglial activation and gene expressions of proinflammatory factors. Furthermore, reduced activation of nuclear factor-κB (NF-κB) pathway was observed in apocynin-treated mice. More importantly, inhibition of NADPH oxidase by apocynin afforded LC/NE neuroprotection against PQ and Mb-induced neurotoxicity. Thus, our findings revealed the critical role NADPH oxidase-mediated microglial activation in driving LC/NE neurodegeneration induced by PQ and Mb, providing new insights into the pathogenesis of environmental

  5. Randomized Controlled Trial of Electronic Care Plan Alerts and Resource Utilization by High Frequency Emergency Department Users with Opioid Use Disorder

    Directory of Open Access Journals (Sweden)

    Niels Rathlev, MD

    2016-01-01

    Full Text Available Introduction: There is a paucity of literature supporting the use of electronic alerts for patients with high frequency emergency department (ED use. We sought to measure changes in opioid prescribing and administration practices, total charges and other resource utilization using electronic alerts to notify providers of an opioid-use care plan for high frequency ED patients. Methods: This was a randomized, non-blinded, two-group parallel design study of patients who had 1 opioid use disorder and 2 high frequency ED use. Three affiliated hospitals with identical electronic health records participated. Patients were randomized into “Care Plan” versus “Usual Care groups”. Between the years before and after randomization, we compared as primary outcomes the following: 1 opioids (morphine mg equivalents prescribed to patients upon discharge and administered to ED and inpatients; 2 total medical charges, and the numbers of; 3 ED visits, 4 ED visits with advanced radiologic imaging (computed tomography [CT] or magnetic resonance imaging [MRI] studies, and 5 inpatient admissions. Results: A total of 40 patients were enrolled. For ED and inpatients in the “Usual Care” group, the proportion of morphine mg equivalents received in the post-period compared with the pre-period was 15.7%, while in the “Care Plan” group the proportion received in the post-period compared with the pre-period was 4.5% (ratio=0.29, 95% CI [0.07-1.12]; p=0.07. For discharged patients in the “Usual Care” group, the proportion of morphine mg equivalents prescribed in the post-period compared with the pre-period was 25.7% while in the “Care Plan” group, the proportion prescribed in the post-period compared to the pre-period was 2.9%. The “Care Plan” group showed an 89% greater proportional change over the periods compared with the “Usual Care” group (ratio=0.11, 95% CI [0.01-0.092]; p=0.04. Care plans did not change the total charges, or, the numbers

  6. There is a Relationship between Resource Expenditures and Reference Transactions in Academic Libraries. A Review of: Dubnjakovic, A. (2012. Electronic resource expenditure and the decline in reference transaction statistics in academic libraries. Journal of Academic Librarianship, 38(2, 94-100. doi:10.1016/j.acalib.2012.01.001

    Directory of Open Access Journals (Sweden)

    Annie M. Hughes

    2013-03-01

    Full Text Available Objective – To provide an analysis of the impact of expenditures on electronic resourcesand gate counts on the increase or decrease in reference transactions.Design – Analysis of results of existing survey data from the National Center for Educational Statistics (NCES 2006 Academic Library Survey(ALS.Setting – Academic libraries in the United States.Subjects – 3925 academic library respondents.Methods – The author chose to use survey data collected from the 2006 ALS conducted bythe NCES. The survey included data on various topics related to academic libraries, but in the case of this study, the author chose to analyze three of the 193 variables included. The three variables: electronic books expenditure, computer hardware and software, and expenditures on bibliographic utilities, were combined into one variable called electronic resource expenditure. Gate counts were also considered as a variable. Electronic resource expenditure was also split as a variable into three groups: low, medium, and high. Multiple regression analysis and general linear modeling, along with tests of reliability, were employed. Main Results – The author determined that low, medium, and high spenders with regard to electronic resources exhibited differences in gate counts, and gate counts have an effect on reference transactions in any given week. Gate counts tend to not have much of an effect on reference transactions for the higher spenders, and higher spenders tend to have a higher number of reference transactions overall. Low spenders have lower gate counts and also a lower amount of reference transactions.Conclusion – The findings from this study show that academic libraries spending more on electronic resources also tend to have an increase with regard to reference transactions. The author also concludes that library spaces are no longer the determining factor with regard to number of reference transactions. Spending more on electronic resources is

  7. Global application of disorders of sex development-related electronic resources: e-learning, e-consultation and e-information sharing.

    Science.gov (United States)

    Muscarella, Miriam; Kranenburg-van Koppen, Laura; Grijpink-van den Biggelaar, Kalinka; Drop, Stenvert L S

    2014-01-01

    The past 20 years have seen proliferation of electronic (e) resources that promote improved understanding of disorders of sex development (DSD): e-learning for physicians and trainees, e-consultation between clinicians, and e-information for families and affected individuals. Recent e-learning advances have emerged from the European Society for Pediatric Endocrinology's online learning portal for current physicians and trainees. Developed with attention to developing clinical competencies incorporating learning theory, and presenting material that represents international best practice, this e-learning portal offers advances in training, making information more accessible for clinicians and trainees. Multiple levels of instruction, authentic case examples, collaborative forums for physicians and trainees, individualized feedback and user-friendly tools represent advances in trainee and physician learning that can take place in any location. e-consultation is an emerging tool that aims to connect physicians with specialists experienced in DSD care. Although it faces logistical challenges, e-consultation carries the potential to improve DSD care, especially in remote areas with limited access to DSD specialists. e-information for families and patients of all ages is widely accessible online, often with focus on DSD biology, medical care, and psychological and social support. e-information tools aid self-management and support of those affected by DSD. Efforts to improve these resources should aim to map information to individual users, incorporate optimally clear nomenclature, and continue as a 'shared enterprise' of clinicians, affected individuals, families and researchers. Improving the quality of DSD-related e-learning and e-information and developing e-consultation carries the potential to transform DSD care and support for patients, families and physicians worldwide. © 2014 S. Karger AG, Basel.

  8. Ranking Medical Terms to Support Expansion of Lay Language Resources for Patient Comprehension of Electronic Health Record Notes: Adapted Distant Supervision Approach.

    Science.gov (United States)

    Chen, Jinying; Jagannatha, Abhyuday N; Fodeh, Samah J; Yu, Hong

    2017-10-31

    Medical terms are a major obstacle for patients to comprehend their electronic health record (EHR) notes. Clinical natural language processing (NLP) systems that link EHR terms to lay terms or definitions allow patients to easily access helpful information when reading through their EHR notes, and have shown to improve patient EHR comprehension. However, high-quality lay language resources for EHR terms are very limited in the public domain. Because expanding and curating such a resource is a costly process, it is beneficial and even necessary to identify terms important for patient EHR comprehension first. We aimed to develop an NLP system, called adapted distant supervision (ADS), to rank candidate terms mined from EHR corpora. We will give EHR terms ranked as high by ADS a higher priority for lay language annotation-that is, creating lay definitions for these terms. Adapted distant supervision uses distant supervision from consumer health vocabulary and transfer learning to adapt itself to solve the problem of ranking EHR terms in the target domain. We investigated 2 state-of-the-art transfer learning algorithms (ie, feature space augmentation and supervised distant supervision) and designed 5 types of learning features, including distributed word representations learned from large EHR data for ADS. For evaluating ADS, we asked domain experts to annotate 6038 candidate terms as important or nonimportant for EHR comprehension. We then randomly divided these data into the target-domain training data (1000 examples) and the evaluation data (5038 examples). We compared ADS with 2 strong baselines, including standard supervised learning, on the evaluation data. The ADS system using feature space augmentation achieved the best average precision, 0.850, on the evaluation set when using 1000 target-domain training examples. The ADS system using supervised distant supervision achieved the best average precision, 0.819, on the evaluation set when using only 100 target

  9. Mechanisms of AD neurodegeneration may be independent of Aβ and its derivatives.

    Science.gov (United States)

    Robakis, Nikolaos K

    2011-03-01

    Alzheimer's disease (AD) is the most common cause of dementia in the aged population. Most cases are sporadic although a small percent are familial (FAD) linked to genetic mutations. AD is caused by severe neurodegeneration in the hippocampus and neocortical regions of the brain but the cause of this neuronal loss is unclear. A widely discussed theory posits that amyloid depositions of Aβ peptides or their soluble forms are the causative agents of AD. Extensive research in the last 20 years however, failed to produce convincing evidence that brain amyloid is the main cause of AD neurodegeneration. Moreover, a number of observations, including absence of correlations between amyloid deposits and cognition, detection in normal individuals of amyloid loads similar to AD, and animal models with behavioral abnormalities independent of amyloid, are inconsistent with this theory. Other theories propose soluble Aβ peptides or their oligomers as agents that promote AD. These peptides, however, are normal components of human CSF and serum and there is little evidence of disease-associated increases in soluble Aβ and oligomers. That mutants of amyloid precursor protein (APP) and presenilin (PS) promote FAD suggests these proteins play crucial roles in neuronal function and survival. Accordingly, PS regulates production of signaling peptides and cell survival pathways while APP functions in cell death and may promote endosomal abnormalities. Evidence that FAD mutations inhibit the biological functions of PS combined with absence of haploinsufficiency mutants, support a model of allelic interference where inactive FAD mutant alleles promote autosomal dominant neurodegeneration by also inhibiting the functions of wild type alleles. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Loss of circadian clock accelerates aging in neurodegeneration-prone mutants.

    Science.gov (United States)

    Krishnan, Natraj; Rakshit, Kuntol; Chow, Eileen S; Wentzell, Jill S; Kretzschmar, Doris; Giebultowicz, Jadwiga M

    2012-03-01

    Circadian clocks generate rhythms in molecular, cellular, physiological, and behavioral processes. Recent studies suggest that disruption of the clock mechanism accelerates organismal senescence and age-related pathologies in mammals. Impaired circadian rhythms are observed in many neurological diseases; however, it is not clear whether loss of rhythms is the cause or result of neurodegeneration, or both. To address this important question, we examined the effects of circadian disruption in Drosophila melanogaster mutants that display clock-unrelated neurodegenerative phenotypes. We combined a null mutation in the clock gene period (per(01)) that abolishes circadian rhythms, with a hypomorphic mutation in the carbonyl reductase gene sniffer (sni(1)), which displays oxidative stress induced neurodegeneration. We report that disruption of circadian rhythms in sni(1) mutants significantly reduces their lifespan compared to single mutants. Shortened lifespan in double mutants was coupled with accelerated neuronal degeneration evidenced by vacuolization in the adult brain. In addition, per(01)sni(1) flies showed drastically impaired vertical mobility and increased accumulation of carbonylated proteins compared to age-matched single mutant flies. Loss of per function does not affect sni mRNA expression, suggesting that these genes act via independent pathways producing additive effects. Finally, we show that per(01) mutation accelerates the onset of brain pathologies when combined with neurodegeneration-prone mutation in another gene, swiss cheese (sws(1)), which does not operate through the oxidative stress pathway. Taken together, our data suggest that the period gene may be causally involved in neuroprotective pathways in aging Drosophila. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Neurodegeneration Alters Metabolic Profile and Sirt 1 Signaling in High-Fat-Induced Obese Mice.

    Science.gov (United States)

    Lima, Leandro Ceotto Freitas; Saliba, Soraya Wilke; Andrade, João Marcus Oliveira; Cunha, Maria Luisa; Cassini-Vieira, Puebla; Feltenberger, John David; Barcelos, Lucíola Silva; Guimarães, André Luiz Sena; de-Paula, Alfredo Mauricio Batista; de Oliveira, Antônio Carlos Pinheiro; Santos, Sérgio Henrique Sousa

    2017-07-01

    Different factors may contribute to the development of neurodegenerative diseases. Among them, metabolic syndrome (MS), which has reached epidemic proportions, has emerged as a potential element that may be involved in neurodegeneration. Furthermore, studies have shown the importance of the sirtuin family in neuronal survival and MS, which opens the possibility of new pharmacological targets. This study investigates the influence of sirtuin metabolic pathways by examining the functional capacities of glucose-induced obesity in an excitotoxic state induced by a quinolinic acid (QA) animal model. Mice were divided into two groups that received different diets for 8 weeks: one group received a regular diet, and the other group received a high-fat diet (HF) to induce MS. The animals were submitted to a stereotaxic surgery and subdivided into four groups: Standard (ST), Standard-QA (ST-QA), HF and HF-QA. The QA groups were given a 250 nL quinolinic acid injection in the right striatum and PBS was injected in the other groups. Obese mice presented with a weight gain of 40 % more than the ST group beyond acquiring an insulin resistance. QA induced motor impairment and neurodegeneration in both ST-QA and HF-QA, although no difference was observed between these groups. The HF-QA group showed a reduction in adiposity when compared with the groups that received PBS. Therefore, the HF-QA group demonstrated a commitment-dependent metabolic pathway. The results suggest that an obesogenic diet does not aggravate the neurodegeneration induced by QA. However, the excitotoxicity induced by QA promotes a sirtuin pathway impairment that contributes to metabolic changes.

  12. Minocycline Rescues from Zinc-Induced Nigrostriatal Dopaminergic Neurodegeneration: Biochemical and Molecular Interventions.

    Science.gov (United States)

    Kumar, Vinod; Singh, Brajesh Kumar; Chauhan, Amit Kumar; Singh, Deepali; Patel, Devendra Kumar; Singh, Chetna

    2016-07-01

    Accumulation of zinc (Zn) in dopaminergic neurons is implicated in Parkinson's disease (PD), and microglial activation plays a critical role in toxin-induced Parkinsonism. Oxidative stress is accused in Zn-induced dopaminergic neurodegeneration; however, its connection with microglial activation is still not known. This study was undertaken to elucidate the role and underlying mechanism of microglial activation in Zn-induced nigrostriatal dopaminergic neurodegeneration. Male Wistar rats were treated intraperitoneally with/without zinc sulphate (20 mg/kg) in the presence/absence of minocycline (30 mg/kg), a microglial activation inhibitor, for 2-12 weeks. While neurobehavioral and biochemical indexes of PD and number of dopaminergic neurons were reduced, the number of microglial cells was increased in the substantia nigra of the Zn-exposed animals. Similarly, Zn elevated lipid peroxidation (LPO) and activities of superoxide dismutase (SOD) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase; however, catalase activity was reduced. Besides, Zn increased an association of NADPH oxidase subunit p67(phox) with membrane, cytochrome c release from the mitochondria and cleavage of pro-caspase 3. Zn attenuated the expression of tyrosine hydroxylase (TH) and vesicular monoamine transporter-2 (VMAT-2) while augmented the expression of dopamine transporter (DAT) and heme oxygenase-1 (HO-1). Minocycline alleviated Zn-induced behavioural impairments, loss of TH-positive neurons, activated microglial cells and biochemical indexes and modulated the expression of studied genes/proteins towards normalcy. The results demonstrate that minocycline reduces the number of activated microglial cells and oxidative stress, which rescue from Zn-induced changes in the expression of monoamine transporter and nigrostriatal dopaminergic neurodegeneration.

  13. Progranulin: A Proteolytically Processed Protein at the Crossroads of Inflammation and Neurodegeneration*

    Science.gov (United States)

    Cenik, Basar; Sephton, Chantelle F.; Kutluk Cenik, Bercin; Herz, Joachim; Yu, Gang

    2012-01-01

    GRN mutations cause frontotemporal lobar degeneration with TDP-43-positive inclusions. The mechanism of pathogenesis is haploinsufficiency. Recently, homozygous GRN mutations were detected in two patients with neuronal ceroid lipofuscinosis, a lysosomal storage disease. It is unknown whether the pathogenesis of these two conditions is related. Progranulin is cleaved into smaller peptides called granulins. Progranulin and granulins are attributed with roles in cancer, inflammation, and neuronal physiology. Cell surface receptors for progranulin, but not granulin peptides, have been reported. Revealing the cell surface receptors and the intracellular functions of granulins and progranulin is crucial for understanding their contributions to neurodegeneration. PMID:22859297

  14. Neurodegeneration with inflammation is accompanied by accumulation of iron and ferritin in microglia and neurons.

    Science.gov (United States)

    Thomsen, Maj Schneider; Andersen, Michelle Vandborg; Christoffersen, Pia Rægaard; Jensen, Malene Duedal; Lichota, Jacek; Moos, Torben

    2015-09-01

    Chronic inflammation in the substantia nigra (SN) accompanies conditions with progressive neurodegeneration. This inflammatory process contributes to gradual iron deposition that may catalyze formation of free-radical mediated damage, hence exacerbating the neurodegeneration. This study examined proteins related to iron-storage (ferritin) and iron-export (ferroportin) (aka metal transporter protein 1, MTP1) in a model of neurodegeneration. Ibotenic acid injected stereotactically into the striatum leads to loss of GABAergic neurons projecting to SN pars reticulata (SNpr), which subsequently leads to excitotoxicity in the SNpr as neurons here become vulnerable to their additional glutamatergic projections from the subthalamic nucleus. This imbalance between glutamate and GABA eventually led to progressive shrinkage of the SNpr and neuronal loss. Neuronal cell death was accompanied by chronic inflammation as revealed by the presence of cells expressing ED1 and CD11b in the SNpr and the adjacent white matter mainly denoted by the crus cerebri. The SNpr also exhibited changes in iron metabolism seen as a marked accumulation of inflammatory cells containing ferric iron and ferritin with morphology corresponding to macrophages and microglia. Ferritin was detected in neurons of the lesioned SNpr in contrast to the non-injected side. Compared to non-injected rats, surviving neurons of the SNpr expressed ferroportin at unchanged level. Analyses of dissected SNpr using RT-qPCR showed a rise in ferritin-H and -L transcripts with increasing age but no change was observed in the lesioned side compared to the non-lesioned side, indicating that the increased expression of ferritin in the lesioned side occurred at the post-transcriptional level. Hepcidin transcripts were higher in the lesioned side in contrast to ferroportin mRNA that remained unaltered. The continuous entry of iron-containing inflammatory cells into the degenerating SNpr and their subsequent demise is probably

  15. Frontal lobe neurodegeneration - Use of songs in the music therapy setting

    DEFF Research Database (Denmark)

    Ridder, Hanne Mette Ochsner

    2005-01-01

    .g. in vascular or frontotemporal dementia) it is difficult to avoid secondary symptoms of the brain damage that is caused by missing communicative abilities and difficulties in fulfilment of psychosocial needs. Songs are used to build up the music therapy setting with this client group. The songs function......When the frontal lobes are damaged by neurodegeneration certain qualities of psychosocial functioning are changed. The person might show lack of initiative, poor social judgment, and loss of personal and social awareness. When these symptoms co-occur with other cortical degeneration (e...

  16. Impact of two interventions on timeliness and data quality of an electronic disease surveillance system in a resource limited setting (Peru: a prospective evaluation

    Directory of Open Access Journals (Sweden)

    Quispe Jose A

    2009-03-01

    Full Text Available Abstract Background A timely detection of outbreaks through surveillance is needed in order to prevent future pandemics. However, current surveillance systems may not be prepared to accomplish this goal, especially in resource limited settings. As data quality and timeliness are attributes that improve outbreak detection capacity, we assessed the effect of two interventions on such attributes in Alerta, an electronic disease surveillance system in the Peruvian Navy. Methods 40 Alerta reporting units (18 clinics and 22 ships were included in a 12-week prospective evaluation project. After a short refresher course on the notification process, units were randomly assigned to either a phone, visit or control group. Phone group sites were called three hours before the biweekly reporting deadline if they had not sent their report. Visit group sites received supervision visits on weeks 4 & 8, but no phone calls. The control group sites were not contacted by phone or visited. Timeliness and data quality were assessed by calculating the percentage of reports sent on time and percentage of errors per total number of reports, respectively. Results Timeliness improved in the phone group from 64.6% to 84% in clinics (+19.4 [95% CI, +10.3 to +28.6]; p Conclusion Regular phone reminders significantly improved timeliness of reports in clinics and ships, whereas supervision visits led to improved data quality only among clinics. Further investigations are needed to establish the cost-effectiveness and optimal use of each of these strategies.

  17. Mitochondrial Complex 1 Activity Measured by Spectrophotometry Is Reduced across All Brain Regions in Ageing and More Specifically in Neurodegeneration.

    Science.gov (United States)

    Pollard, Amelia Kate; Craig, Emma Louise; Chakrabarti, Lisa

    2016-01-01

    Mitochondrial function, in particular complex 1 of the electron transport chain (ETC), has been shown to decrease during normal ageing and in neurodegenerative disease. However, there is some debate concerning which area of the brain has the greatest complex 1 activity. It is important to identify the pattern of activity in order to be able to gauge the effect of age or disease related changes. We determined complex 1 activity spectrophotometrically in the cortex, brainstem and cerebellum of middle aged mice (70-71 weeks), a cerebellar ataxic neurodegeneration model (pcd5J) and young wild type controls. We share our updated protocol on the measurements of complex1 activity and find that mitochondrial fractions isolated from frozen tissues can be measured for robust activity. We show that complex 1 activity is clearly highest in the cortex when compared with brainstem and cerebellum (p<0.003). Cerebellum and brainstem mitochondria exhibit similar levels of complex 1 activity in wild type brains. In the aged brain we see similar levels of complex 1 activity in all three-brain regions. The specific activity of complex 1 measured in the aged cortex is significantly decreased when compared with controls (p<0.0001). Both the cerebellum and brainstem mitochondria also show significantly reduced activity with ageing (p<0.05). The mouse model of ataxia predictably has a lower complex 1 activity in the cerebellum, and although reductions are measured in the cortex and brain stem, the remaining activity is higher than in the aged brains. We present clear evidence that complex 1 activity decreases across the brain with age and much more specifically in the cerebellum of the pcd5j mouse. Mitochondrial impairment can be a region specific phenomenon in disease, but in ageing appears to affect the entire brain, abolishing the pattern of higher activity in cortical regions.

  18. Insulin and Insulin-Sensitizing Drugs in Neurodegeneration: Mitochondria as Therapeutic Targets

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    Paula I. Moreira

    2009-12-01

    Full Text Available Insulin, besides its glucose lowering effects, is involved in the modulation of lifespan, aging and memory and learning processes. As the population ages, neurodegenerative disorders become epidemic and a connection between insulin signaling dysregulation, cognitive decline and dementia has been established. Mitochondria are intracellular organelles that despite playing a critical role in cellular metabolism are also one of the major sources of reactive oxygen species. Mitochondrial dysfunction, oxidative stress and neuroinflammation, hallmarks of neurodegeneration, can result from impaired insulin signaling. Insulin-sensitizing drugs such as the thiazolidinediones are a new class of synthetic compounds that potentiate insulin action in the target tissues and act as specific agonists of the peroxisome proliferator-activated receptor gamma (PPAR-γ. Recently, several PPAR agonists have been proposed as novel and possible therapeutic agents for neurodegenerative disorders. Indeed, the literature shows that these agents are able to protect against mitochondrial dysfunction, oxidative damage, inflammation and apoptosis. This review discusses the role of mitochondria and insulin signaling in normal brain function and in neurodegeneration. Furthermore, the potential protective role of insulin and insulin sensitizers in Alzheimer´s, Parkinson´s and Huntington´s diseases and amyotrophic lateral sclerosis will be also discussed.

  19. Chronic Progressive Neurodegeneration in a transgenic mouse model of Prion disease

    Directory of Open Access Journals (Sweden)

    Nina Fainstein

    2016-11-01

    Full Text Available Neurodegenerative diseases present pathologically with progressive structural destruction of neurons and accumulation of mis-folded proteins specific for each condition leading to brain atrophy and functional disability. Many animal models exert deposition of pathogenic protein without accompanying neurodegeneration pattern. The lack of a comprehensive model hinders the efforts to develop treatment. We performed longitudinal quantification of cellular, neuronal and synaptic density, as well as of neurogenesis in brains of mice, mimicking for genetic Creutzfeldt-Jacob disease as compared to age matched wild type mice. Mice exhibited a neurodegenerative process indicated by progressive reduction in cortical neurons and synapses, starting at age of 4-6 months, in accordance with neurologic disability. This was accompanied by significant decrease in subventricular/subependymal zone neurogenesis. Although increased hippocampal neurogenesis was detected in mice, a neurodegenerative process of CA1 and CA3 regions associated with impaired hippocampal-dependent memory function was observed. In conclusion, mice exhibit pathological neurodegeneration concomitant with progressive neurological disease, indicating these mice can serve as a model for neurodegenerative diseases.

  20. Network Neurodegeneration in Alzheimer’s Disease via MRI based Shape Diffeomorphometry and High Field Atlasing

    Directory of Open Access Journals (Sweden)

    Michael I Miller

    2015-05-01

    Full Text Available This paper examines MRI analysis of neurodegeneration in Alzheimer’s Disease (AD in a network of structures within the medial temporal lobe using diffeomorphometry methods coupled with high-field atlasing in which the entorhinal cortex is partitioned into nine subareas. The morphometry markers for three groups of subjects (controls, preclinical AD and symptomatic AD are indexed to template coordinates measured with respect to these nine subareas. The location and timing of changes are examined within the subareas as it pertains to the classic Braak and Braak staging by comparing the three groups. We demonstrate that the earliest preclinical changes in the population occur in the lateral most sulcal extent in the entorhinal cortex (alluded to as trans entorhinal cortex by Braak and Braak, and then proceeds medially which is consistent with the Braak and Braak staging. We use high field 11T atlasing to demonstrate that the network changes are occurring at the junctures of the substructures in this medial temporal lobe network. Temporal progression of the disease through the network is also examined via changepoint analysis demonstrating earliest changes in entorhinal cortex. The differential expression of rate of atrophy with progression signaling the changepoint time across the network is demonstrated to be signaling in the intermediate caudal subarea of the entorhinal cortex, which has been noted to be proximal to the hippocampus. This coupled to the findings of the nearby basolateral involvement in amygdala demonstrates the selectivity of neurodegeneration in early AD.

  1. Forced swimming stress does not affect monoamine levels and neurodegeneration in rats.

    Science.gov (United States)

    Abbas, Ghulam; Naqvi, Sabira; Mehmood, Shahab; Kabir, Nurul; Dar, Ahsana

    2011-10-01

    The current study was aimed to investigate the correlations between immobility time in the forced swimming test (FST, a behavioral indicator of stress level) and hippocampal monoamine levels (markers of depression), plasma adrenalin level (a peripheral marker of stress) as well as fluoro-jade C staining (a marker of neurodegeneration). Male Sprague-Dawley rats were subjected to acute, sub-chronic (7 d) or chronic (14 d) FSTs and immobility time was recorded. Levels of noradrenalin, serotonin and dopamine in the hippocampus, and adrenalin level in the plasma were quantified by high-performance liquid chromatography with electrochemical detection. Brain sections from rats after chronic forced swimming or rotenone treatment (3 mg/kg subcutaneously for 4 d) were stained with fluoro-jade C. The rats subjected to swimming stress (acute, sub-chronic and chronic) showed long immobility times [(214 +/- 5), (220 +/- 4) and (231 +/- 7) s, respectively], indicating that the animals were under stress. However, the rats did not exhibit significant declines in hippocampal monoamine levels, and the plasma adrenalin level was not significantly increased compared to that in unstressed rats. The rats that underwent chronic swimming stress did not manifest fluoro-jade C staining in brain sections, while degenerating neurons were evident after rotenone treatment. The immobility time in the FST does not correlate with markers of depression (monoamine levels) and internal stress (adrenalin levels and neurodegeneration), hence this parameter may not be a true indicator of stress level.

  2. Evolution of Neurodegeneration Imaging Biomarkers from Clinically Normal to Dementia in the Alzheimer Disease Spectrum

    Science.gov (United States)

    Knopman, David S.; Jack, Clifford R.; Lundt, Emily S.; Weigand, Stephen D.; Vemuri, Prashanthi; Lowe, Val J.; Kantarci, Kejal; Gunter, Jeffrey L.; Senjem, Matthew L.; Mielke, Michelle M.; Machulda, Mary M.; Roberts, Rosebud O.; Boeve, Bradley F.; Jones, David T.; Petersen, Ronald C.

    2016-01-01

    The availability of antemortem biomarkers for Alzheimer’s Disease (AD) enables monitoring the evolution of neurodegenerative processes in real time. Pittsburgh compound B (PIB) positron emission tomography (PET) was used to select participants in the Mayo Clinic Study of Aging and the Mayo Alzheimer’s Disease Research Center with elevated β-amyloid, designated as “A+,” and hippocampal volume and 18fluorodeoxyglucose (FDG) positron emission tomography were used to characterize participants as having evidence of neurodegeneration (“N+”) at the baseline evaluation. There were 145 clinically normal (CN) A+ individuals, 62 persons with mild cognitive impairment (MCI) who were A+ and 20 with A+ AD dementia. Over a period of 1–6 years, MCI A+N+ individuals showed declines in medial temporal, lateral temporal, lateral parietal, and to a lesser extent, medial parietal regions for both FDG standardized uptake value ratio (SUVR) and grey matter (GM) volume that exceeded declines seen in the CN A+N+ group. The AD dementia group showed declines in the same regions on FDG SUVR and GM volume with rates that exceeded that in MCI A+N+. Expansion of regional involvement and faster rate of neurodegeneration characterizes progression in the AD pathway. PMID:27460147

  3. Evolution of neurodegeneration-imaging biomarkers from clinically normal to dementia in the Alzheimer disease spectrum.

    Science.gov (United States)

    Knopman, David S; Jack, Clifford R; Lundt, Emily S; Weigand, Stephen D; Vemuri, Prashanthi; Lowe, Val J; Kantarci, Kejal; Gunter, Jeffrey L; Senjem, Matthew L; Mielke, Michelle M; Machulda, Mary M; Roberts, Rosebud O; Boeve, Bradley F; Jones, David T; Petersen, Ronald C

    2016-10-01

    The availability of antemortem biomarkers for Alzheimer's disease (AD) enables monitoring the evolution of neurodegenerative processes in real time. Pittsburgh compound B (PIB) positron emission tomography (PET) was used to select participants in the Mayo Clinic Study of Aging and the Mayo Alzheimer's Disease Research Center with elevated β-amyloid, designated as "A+," and hippocampal volume and (18)fluorodeoxyglucose (FDG) positron emission tomography were used to characterize participants as having evidence of neurodegeneration ("N+") at the baseline evaluation. There were 145 clinically normal (CN) A+ individuals, 62 persons with mild cognitive impairment (MCI) who were A+ and 20 with A+ AD dementia. Over a period of 1-6 years, MCI A+N+ individuals showed declines in medial temporal, lateral temporal, lateral parietal, and to a lesser extent, medial parietal regions for both FDG standardized uptake value ratio and gray matter volume that exceeded declines seen in the CN A+N+ group. The AD dementia group showed declines in the same regions on FDG standardized uptake value ratio and gray matter volume with rates that exceeded that in MCI A+N+. Expansion of regional involvement and faster rate of neurodegeneration characterizes progression in the AD pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Tryptophan-2,3-dioxygenase (TDO) inhibition ameliorates neurodegeneration by modulation of kynurenine pathway metabolites.

    Science.gov (United States)

    Breda, Carlo; Sathyasaikumar, Korrapati V; Sograte Idrissi, Shama; Notarangelo, Francesca M; Estranero, Jasper G; Moore, Gareth G L; Green, Edward W; Kyriacou, Charalambos P; Schwarcz, Robert; Giorgini, Flaviano

    2016-05-10

    Metabolites of the kynurenine pathway (KP) of tryptophan (TRP) degradation have been closely linked to the pathogenesis of several neurodegenerative disorders. Recent work has highlighted the therapeutic potential of inhibiting two critical regulatory enzymes in this pathway-kynurenine-3-monooxygenase (KMO) and tryptophan-2,3-dioxygenase (TDO). Much evidence indicates that the efficacy of KMO inhibition arises from normalizing an imbalance between neurotoxic [3-hydroxykynurenine (3-HK); quinolinic acid (QUIN)] and neuroprotective [kynurenic acid (KYNA)] KP metabolites. However, it is not clear if TDO inhibition is protective via a similar mechanism or if this is instead due to increased levels of TRP-the substrate of TDO. Here, we find that increased levels of KYNA relative to 3-HK are likely central to the protection conferred by TDO inhibition in a fruit fly model of Huntington's disease and that TRP treatment strongly reduces neurodegeneration by shifting KP flux toward KYNA synthesis. In fly models of Alzheimer's and Parkinson's disease, we provide genetic evidence that inhibition of TDO or KMO improves locomotor performance and ameliorates shortened life span, as well as reducing neurodegeneration in Alzheimer's model flies. Critically, we find that treatment with a chemical TDO inhibitor is robustly protective in these models. Consequently, our work strongly supports targeting of the KP as a potential treatment strategy for several major neurodegenerative disorders and suggests that alterations in the levels of neuroactive KP metabolites could underlie several therapeutic benefits.

  5. Chronic Progressive Neurodegeneration in a Transgenic Mouse Model of Prion Disease.

    Science.gov (United States)

    Fainstein, Nina; Dori, Dvir; Frid, Kati; Fritz, Alexa T; Shapiro, Ilona; Gabizon, Ruth; Ben-Hur, Tamir

    2016-01-01

    Neurodegenerative diseases present pathologically with progressive structural destruction of neurons and accumulation of mis-folded proteins specific for each condition leading to brain atrophy and functional disability. Many animal models exert deposition of pathogenic proteins without an accompanying neurodegeneration pattern. The lack of a comprehensive model hinders efforts to develop treatment. We performed longitudinal quantification of cellular, neuronal and synaptic density, as well as of neurogenesis in brains of mice mimicking for genetic Creutzfeldt-Jacob disease as compared to age-matched wild-type mice. Mice exhibited a neurodegenerative process of progressive reduction in cortical neurons and synapses starting at age of 4-6 months, in accord with neurologic disability. This was accompanied by significant decrease in subventricular/subependymal zone neurogenesis. Although increased hippocampal neurogenesis was detected in mice, a neurodegenerative process of CA1 and CA3 regions associated with impaired hippocampal-dependent memory function was observed. In conclusion, mice exhibit pathological neurodegeneration concomitant with neurological disease progression, indicating these mice can serve as a model for neurodegenerative diseases.

  6. Common defects of mitochondria and iron in neurodegeneration and diabetes (MIND): A paradigm worth exploring

    Science.gov (United States)

    Stroh, Matthew; Swerdlow, Russell H.; Zhu, Hao

    2014-01-01

    A popular, if not centric, approach to the study of an event is to first consider that of the simplest cause. When dissecting the underlying mechanisms governing idiopathic diseases, this generally takes the form of an ab initio genetic approach. To date, this genetic ‘smoking gun’ has remained elusive in diabetes mellitus and for many affected by neurodegenerative diseases. With no single gene, or even subset of genes, conclusively causative in all cases, other approaches to the etiology and treatment of these diseases seem reasonable, including the correlation of a systems’ predisposed sensitivity to particular influence. In the cases of diabetes mellitus and neurodegenerative diseases, overlapping themes of mitochondrial influence or dysfunction and iron dyshomeostasis are apparent and relatively consistent. This mini-review discusses the influence of mitochondrial function and iron homeostasis on diabetes mellitus and neurodegenerative disease, namely Alzheimer’s disease. Also discussed is the incidence of diabetes accompanied by neuropathy and neurodegeneration along with neurodegenerative disorders prone to development of diabetes. Mouse models containing multiple facets of this overlap are also described alongside current molecular trends attributed to both diseases. As a way of approaching the idiopathic and complex nature of these diseases we are proposing the consideration of a MIND (mitochondria, iron, neurodegeneration, and diabetes) paradigm in which systemic metabolic influence, iron homeostasis, and respective genetic backgrounds play a central role in the development of disease. PMID:24361914

  7. Uncoupling of Protein Aggregation and Neurodegeneration in a Mouse Amyotrophic Lateral Sclerosis Model.

    Science.gov (United States)

    Lee, Joo-Yong; Kawaguchi, Yoshiharu; Li, Ming; Kapur, Meghan; Choi, Su Jin; Kim, Hak-June; Park, Song-Yi; Zhu, Haining; Yao, Tso-Pang

    2015-01-01

    Aberrant accumulation of protein aggregates is a pathological hallmark of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Although a buildup of protein aggregates frequently leads to cell death, whether it is the key pathogenic factor in driving neurodegenerative disease remains controversial. HDAC6, a cytosolic ubiquitin-binding deacetylase, has emerged as an important regulator of ubiquitin-dependent quality control autophagy, a lysosome-dependent degradative system responsible for the disposal of misfolded protein aggregates and damaged organelles. Here, we show that in cell models HDAC6 plays a protective role against multiple disease-associated and aggregation-prone cytosolic proteins by facilitating their degradation. We further show that HDAC6 is required for efficient localization of lysosomes to protein aggregates, indicating that lysosome targeting to autophagic substrates is regulated. Supporting a critical role of HDAC6 in protein aggregate disposal in vivo, genetic ablation of HDAC6 in a transgenic SOD1G93A mouse, a model of ALS, leads to dramatic accumulation of ubiquitinated SOD1G93A protein aggregates. Surprisingly, despite a robust buildup of SOD1G93A aggregates, deletion of HDAC6 only moderately modified the motor phenotypes. These findings indicate that SOD1G93A aggregation is not the only determining factor to drive neurodegeneration in ALS, and that HDAC6 likely modulates neurodegeneration through additional mechanisms beyond protein aggregate clearance. © 2015 S. Karger AG, Basel.

  8. The human epilepsy mutation GABRG2(Q390X) causes chronic subunit accumulation and neurodegeneration.

    Science.gov (United States)

    Kang, Jing-Qiong; Shen, Wangzhen; Zhou, Chengwen; Xu, Dong; Macdonald, Robert L

    2015-07-01

    Genetic epilepsy and neurodegenerative diseases are two common neurological disorders that are conventionally viewed as being unrelated. A subset of patients with severe genetic epilepsies who have impaired development and often go on to die of their disease respond poorly to anticonvulsant drug therapy, suggesting a need for new therapeutic targets. Previously, we reported that multiple GABAA receptor epilepsy mutations result in protein misfolding and abnormal receptor trafficking. We have now developed a model of a severe human genetic epileptic encephalopathy, the Gabrg2(+/Q390X) knock-in mouse. We found that, in addition to impairing inhibitory neurotransmission, mutant GABAA receptor γ2(Q390X) subunits accumulated and aggregated intracellularly, activated caspase 3 and caused widespread, age-dependent neurodegeneration. These findings suggest that the fundamental protein metabolism and cellular consequences of the epilepsy-associated mutant γ2(Q390X) ion channel subunit are not fundamentally different from those associated with neurodegeneration. Our results have far-reaching relevance for the identification of conserved pathological cascades and mechanism-based therapies that are shared between genetic epilepsies and neurodegenerative diseases.

  9. C19orf12 mutations in neurodegeneration with brain iron accumulation mimicking juvenile amyotrophic lateral sclerosis.

    Science.gov (United States)

    Deschauer, M; Gaul, C; Behrmann, C; Prokisch, H; Zierz, S; Haack, T B

    2012-11-01

    Mutations in C19orf12 have been recently identified as the molecular genetic cause of a subtype of neurodegeneration with brain iron accumulation (NBIA). Given the mitochondrial localization of the gene product the new NBIA subtype was designated mitochondrial membrane protein-associated neurodegeneration. Frequent features in the patients described so far included extrapyramidal signs and pyramidal tract involvement. Here, we report three C19orf12-mutant patients from two families presenting with predominant upper and lower motor neuron dysfunction mimicking amyotrophic lateral sclerosis with juvenile onset. While extrapyramidal signs were absent, all patients showed neuropsychological abnormalities with disinhibited or impulsive behavior. Optic atrophy was present in the simplex case. T2-weighted cranial MRI showed hypointensities suggestive of iron accumulation in the globi pallidi and the midbrain in all patients. Sequence analysis of C19orf12 revealed a novel mutation, p.Gly66del, compound heterozygous with known mutations in all patients. These patients highlight that C19orf12 defects should be considered as a differential diagnosis in patients with juvenile onset motor neuron diseases. Patients have to be examined carefully for neuropsychological abnormalities, optic neuropathy, and signs of brain iron accumulation in MRI.

  10. The P66Shc/Mitochondrial Permeability Transition Pore Pathway Determines Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Costanza Savino

    2013-01-01

    Full Text Available Mitochondrial-mediated oxidative stress and apoptosis play a crucial role in neurodegenerative disease and aging. Both mitochondrial permeability transition (PT and swelling of mitochondria have been involved in neurodegeneration. Indeed, knockout mice for cyclophilin-D (Cyc-D, a key regulatory component of the PT pore (PTP that triggers mitochondrial swelling, resulted to be protected in preclinical models of multiple sclerosis (MS, Parkinson’s disease (PD, and amyotrophic lateral sclerosis (ALS. However, how neuronal stress is transduced into mitochondrial oxidative stress and swelling is unclear. Recently, the aging determinant p66Shc that generates H2O2 reacting with cytochrome c and induces oxidation of PTP and mitochondrial swelling was found to be involved in MS and ALS. To investigate the role of p66Shc/PTP pathway in neurodegeneration, we performed experimental autoimmune encephalomyelitis (EAE experiments in p66Shc knockout mice (p66Shc−/−, knock out mice for cyclophilin-D (Cyc-D−/−, and p66Shc Cyc-D double knock out (p66Shc/Cyc-D−/− mice. Results confirm that deletion of p66Shc protects from EAE without affecting immune response, whereas it is not epistatic to the Cyc-D mutation. These findings demonstrate that p66Shc contributes to EAE induced neuronal damage most likely through the opening of PTP suggesting that p66Shc/PTP pathway transduces neurodegenerative stresses.

  11. Moderate exercise prevents neurodegeneration in D-galactose-induced aging mice

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    Li Li

    2016-01-01

    Full Text Available D-galactose has been widely used in aging research because of its efficacy in inducing senescence and accelerating aging in animal models. The present study investigated the benefits of exercise for preventing neurodegeneration, such as synaptic plasticity, spatial learning and memory abilities, in mouse models of aging. D-galactose-induced aging mice were administered daily subcutaneous injections of D-galactose at the base of the neck for 10 consecutive weeks. Then, the mice were subjected to exercise training by running on a treadmill for 6 days a week. Shortened escape latency in a Morris water maze test indicated that exercise improved learning and memory in aging mice. The ameliorative changes were likely induced by an upregulation of Bcl-2 and brain-derived neurotrophic factor, the repression of apoptosis factors such as Fas and Bax, and an increase in the activity of glucose transporters-1 and 4. The data suggest moderate exercise may retard or inhibit neurodegeneration in D-galactose-induced aging mice.

  12. Assaying locomotor, learning, and memory deficits in Drosophila models of neurodegeneration.

    Science.gov (United States)

    Ali, Yousuf O; Escala, Wilfredo; Ruan, Kai; Zhai, R Grace

    2011-03-11

    Advances in genetic methods have enabled the study of genes involved in human neurodegenerative diseases using Drosophila as a model system. Most of these diseases, including Alzheimer's, Parkinson's and Huntington's disease are characterized by age-dependent deterioration in learning and memory functions and movement coordination. Here we use behavioral assays, including the negative geotaxis assay and the aversive phototaxic suppression assay (APS assay), to show that some of the behavior characteristics associated with human neurodegeneration can be recapitulated in flies. In the negative geotaxis assay, the natural tendency of flies to move against gravity when agitated is utilized to study genes or conditions that may hinder locomotor capacities. In the APS assay, the learning and memory functions are tested in positively-phototactic flies trained to associate light with aversive bitter taste and hence avoid this otherwise natural tendency to move toward light. Testing these trained flies 6 hours post-training is used to assess memory functions. Using these assays, the contribution of any genetic or environmental factors toward developing neurodegeneration can be easily studied in flies.

  13. Online Resources

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Online Resources. Journal of Genetics. Online Resources. Volume 97. 2018 | Online resources. Volume 96. 2017 | Online resources. Volume 95. 2016 | Online resources. Volume 94. 2015 | Online resources. Volume 93. 2014 | Online resources. Volume 92. 2013 | Online resources ...

  14. Interactive Electronic Decision Trees for the Integrated Primary Care Management of Febrile Children in Low Resource Settings - Review of existing tools.

    Science.gov (United States)

    Keitel, Kristina; D'Acremont, Valérie

    2018-04-20

    The lack of effective, integrated diagnostic tools pose a major challenge to the primary care management of febrile childhood illnesses. These limitations are especially evident in low-resource settings and are often inappropriately compensated by antimicrobial over-prescription. Interactive electronic decision trees (IEDTs) have the potential to close these gaps: guiding antibiotic use and better identifying serious disease. This narrative review summarizes existing IEDTs, to provide an overview of their degree of validation, as well as to identify gaps in current knowledge and prospects for future innovation. Structured literature review in PubMed and Embase complemented by google search and contact with developers. Six integrated IEDTs were identified: three (eIMCI, REC, and Bangladesh digital IMCI) based on Integrated Management of Childhood Illnesses (IMCI); four (SL eCCM, MEDSINC, e-iCCM, and D-Tree eCCM) on Integrated Community Case Management (iCCM); two (ALMANACH, MSFeCARE) with a modified IMCI content; and one (ePOCT) that integrates novel content with biomarker testing. The types of publications and evaluation studies varied greatly: the content and evidence-base was published for two (ALMANACH and ePOCT), ALMANACH and ePOCT were validated in efficacy studies. Other types of evaluations, such as compliance, acceptability were available for D-Tree eCCM, eIMCI, ALMANACH. Several evaluations are still ongoing. Future prospects include conducting effectiveness and impact studies using data gathered through larger studies to adapt the medical content to local epidemiology, improving the software and sensors, and Assessing factors that influence compliance and scale-up. IEDTs are valuable tools that have the potential to improve management of febrile children in primary care and increase the rational use of diagnostics and antimicrobials. Next steps in the evidence pathway should be larger effectiveness and impact studies (including cost analysis) and

  15. Library resources on the Internet

    Science.gov (United States)

    Buchanan, Nancy L.

    1995-07-01

    Library resources are prevalent on the Internet. Library catalogs, electronic books, electronic periodicals, periodical indexes, reference sources, and U.S. Government documents are available by telnet, Gopher, World Wide Web, and FTP. Comparatively few copyrighted library resources are available freely on the Internet. Internet implementations of library resources can add useful features, such as full-text searching. There are discussion lists, Gophers, and World Wide Web pages to help users keep up with new resources and changes to existing ones. The future will bring more library resources, more types of library resources, and more integrated implementations of such resources to the Internet.

  16. A lesion model of envy and Schadenfreude: legal, deservingness and moral dimensions as revealed by neurodegeneration

    Science.gov (United States)

    Santamaría-García, Hernando; Baez, Sandra; Reyes, Pablo; Santamaría-García, José A; Santacruz-Escudero, José M; Matallana, Diana; Arévalo, Analía; Sigman, Mariano; García, Adolfo M; Ibáñez, Agustín

    2017-01-01

    Abstract The study of moral emotions (i.e. Schadenfreude and envy) is critical to understand the ecological complexity of everyday interactions between cognitive, affective, and social cognition processes. Most previous studies in this area have used correlational imaging techniques and framed Schadenfreude and envy as unified and monolithic emotional domains. Here, we profit from a relevant neurodegeneration model to disentangle the brain regions engaged in three dimensions of Schadenfreude and envy: deservingness, morality, and legality. We tested a group of patients with behavioural variant frontotemporal dementia (bvFTD), patients with Alzheimer’s disease, as a contrastive neurodegeneration model, and healthy controls on a novel task highlighting each of these dimensions in scenarios eliciting Schadenfreude and envy. Compared with the Alzheimer’s disease and control groups, patients with bvFTD obtained significantly higher scores on all dimensions for both emotions. Correlational analyses revealed an association between envy and Schadenfreude scores and greater deficits in social cognition, inhibitory control, and behaviour disturbances in bvFTD patients. Brain anatomy findings (restricted to bvFTD and controls) confirmed the partially dissociable nature of the moral emotions’ experiences and highlighted the importance of socio-moral brain areas in processing those emotions. In all subjects, an association emerged between Schadenfreude and the ventral striatum, and between envy and the anterior cingulate cortex. In addition, the results supported an association between scores for moral and legal transgression and the morphology of areas implicated in emotional appraisal, including the amygdala and the parahippocampus. By contrast, bvFTD patients exhibited a negative association between increased Schadenfreude and envy across dimensions and critical regions supporting social-value rewards and social-moral processes (dorsolateral prefrontal cortex, angular

  17. A lesion model of envy and Schadenfreude: legal, deservingness and moral dimensions as revealed by neurodegeneration.

    Science.gov (United States)

    Santamaría-García, Hernando; Baez, Sandra; Reyes, Pablo; Santamaría-García, José A; Santacruz-Escudero, José M; Matallana, Diana; Arévalo, Analía; Sigman, Mariano; García, Adolfo M; Ibáñez, Agustín

    2017-12-01

    The study of moral emotions (i.e. Schadenfreude and envy) is critical to understand the ecological complexity of everyday interactions between cognitive, affective, and social cognition processes. Most previous studies in this area have used correlational imaging techniques and framed Schadenfreude and envy as unified and monolithic emotional domains. Here, we profit from a relevant neurodegeneration model to disentangle the brain regions engaged in three dimensions of Schadenfreude and envy: deservingness, morality, and legality. We tested a group of patients with behavioural variant frontotemporal dementia (bvFTD), patients with Alzheimer's disease, as a contrastive neurodegeneration model, and healthy controls on a novel task highlighting each of these dimensions in scenarios eliciting Schadenfreude and envy. Compared with the Alzheimer's disease and control groups, patients with bvFTD obtained significantly higher scores on all dimensions for both emotions. Correlational analyses revealed an association between envy and Schadenfreude scores and greater deficits in social cognition, inhibitory control, and behaviour disturbances in bvFTD patients. Brain anatomy findings (restricted to bvFTD and controls) confirmed the partially dissociable nature of the moral emotions' experiences and highlighted the importance of socio-moral brain areas in processing those emotions. In all subjects, an association emerged between Schadenfreude and the ventral striatum, and between envy and the anterior cingulate cortex. In addition, the results supported an association between scores for moral and legal transgression and the morphology of areas implicated in emotional appraisal, including the amygdala and the parahippocampus. By contrast, bvFTD patients exhibited a negative association between increased Schadenfreude and envy across dimensions and critical regions supporting social-value rewards and social-moral processes (dorsolateral prefrontal cortex, angular gyrus and

  18. Novel neuroprotective function of apical-basal polarity gene crumbs in amyloid beta 42 (aβ42 mediated neurodegeneration.

    Directory of Open Access Journals (Sweden)

    Andrew M Steffensmeier

    Full Text Available Alzheimer's disease (AD, OMIM: 104300, a progressive neurodegenerative disorder with no cure to date, is caused by the generation of amyloid-beta-42 (Aβ42 aggregates that trigger neuronal cell death by unknown mechanism(s. We have developed a transgenic Drosophila eye model where misexpression of human Aβ42 results in AD-like neuropathology in the neural retina. We have identified an apical-basal polarity gene crumbs (crb as a genetic modifier of Aβ42-mediated-neuropathology. Misexpression of Aβ42 caused upregulation of Crb expression, whereas downregulation of Crb either by RNAi or null allele approach rescued the Aβ42-mediated-neurodegeneration. Co-expression of full length Crb with Aβ42 increased severity of Aβ42-mediated-neurodegeneration, due to three fold induction of cell death in comparison to the wild type. Higher Crb levels affect axonal targeting from the retina to the brain. The structure function analysis identified intracellular domain of Crb to be required for Aβ42-mediated-neurodegeneration. We demonstrate a novel neuroprotective role of Crb in Aβ42-mediated-neurodegeneration.

  19. Alzheimer Disease Signature Neurodegeneration and APOE Genotype in Mild Cognitive Impairment With Suspected Non-Alzheimer Disease Pathophysiology.

    Science.gov (United States)

    Schreiber, Stefanie; Schreiber, Frank; Lockhart, Samuel N; Horng, Andy; Bejanin, Alexandre; Landau, Susan M; Jagust, William J

    2017-06-01

    There are conflicting results claiming that Alzheimer disease signature neurodegeneration may be more, less, or similarly advanced in individuals with β-amyloid peptide (Aβ)-negative (Aβ-) suspected non-Alzheimer disease pathophysiology (SNAP) than in Aβ-positive (Aβ+) counterparts. To examine patterns of neurodegeneration in individuals with SNAP compared with their Aβ+ counterparts. A longitudinal cohort study was conducted among individuals with mild cognitive impairment (MCI) and cognitively normal individuals receiving care at Alzheimer's Disease Neuroimaging Initiative sites in the United States and Canada for a mean follow-up period of 30.5 months from August 1, 2005, to June 30, 2015. Several neurodegeneration biomarkers and longitudinal cognitive function were compared between patients with distinct SNAP (Aβ- and neurodegeneration-positive [Aβ-N+]) subtypes and their Aβ+N+ counterparts. Participants were classified according to the results of their florbetapir F-18 (Aβ) positron emission tomography and their Alzheimer disease-associated neurodegeneration status (temporoparietal glucose metabolism determined by fluorodeoxyglucose F 18 [FDG]-labeled positron emission tomography and/or hippocampal volume [HV] determined by magnetic resonance imaging: participants with subthreshold HV values were regarded as exhibiting hippocampal volume atrophy [HV+], while subthreshold mean FDG values were considered as FDG hypometabolism [FDG+]). The study comprised 265 cognitively normal individuals (135 women and 130 men; mean [SD] age, 75.5 [6.7] years) and 522 patients with MCI (225 women and 297 men; mean [SD] age, 72.6 [7.8] years). A total of 469 individuals with MCI had data on neurodegeneration biomarkers; of these patients, 107 were Aβ-N+ (22.8%; 63 FDG+, 82 HV+, and 38 FDG+HV+) and 187 were Aβ+N+ (39.9%; 135 FDG+, 147 HV+, and 95 FDG+HV+ cases). A total of 209 cognitively normal participants had data on neurodegeneration biomarkers; of these, 52 were

  20. Neurodegeneration in drop-dead mutant drosophila melanogaster is associated with the respiratory system but not with Hypoxia.

    Directory of Open Access Journals (Sweden)

    Christine Lynn Sansone

    Full Text Available Mutations in the gene drop-dead (drd cause diverse phenotypes in adult Drosophila melanogaster including early lethality, neurodegeneration, tracheal defects, gut dysfunction, reduced body mass, and female sterility. Despite the identification of the drd gene itself, the causes of early lethality and neurodegeneration in the mutant flies remain unknown. To determine the pattern of drd expression associated with the neurodegenerative phenotype, knockdown of drd with various Gal4 drivers was performed. Early adult lethality and neurodegeneration were observed upon knockdown of drd in the tracheal system with two independent insertions of the breathless-Gal4 driver and upon knockdown in the tracheal system and elsewhere with the DJ717-Gal4 driver. Surprisingly, rescue of drd expression exclusively in the tracheae in otherwise mutant flies rescued the neurodegenerative phenotype but not adult lethality. Gut dysfunction, as measured by defecation rate, was not rescued in these flies, and gut function appeared normal upon tracheal-specific knockdown of drd. Finally, the hypothesis that tracheal dysfunction in drd mutants results in hypoxia was tested. Hypoxia-sensitive reporter transgenes (LDH-Gal4 and LDH-LacZ were placed on a drd mutant background, but enhanced expression of these reporters was not observed. In addition, manipulation of drd expression in the tracheae did not affect expression of the hypoxia-induced genes LDH, tango, and similar. Overall, these results indicate that there are at least two causes of adult lethality in drd mutants, that gut dysfunction and neurodegeneration are independent phenotypes, and that neurodegeneration is associated with tracheal expression of drd but not with hypoxia.

  1. Alpha-Synuclein Toxicity in the Early Secretory Pathway: How it Drives Neurodegeneration in Parkinsons Disease

    Directory of Open Access Journals (Sweden)

    Ting eWang

    2015-11-01

    Full Text Available Alpha-synuclein is a predominant player in the pathogenesis of Parkinson’s Disease. However, despite extensive study for two decades, its physiological and pathological mechanisms remain poorly understood. Alpha-synuclein forms a perplexing web of interactions with lipids, trafficking machinery, and other regulatory factors. One emerging consensus is that synaptic vesicles are likely the functional site for alpha-synuclein, where it appears to facilitate vesicle docking and fusion. On the other hand, the disfunctions of alpha-synuclein are more dispersed and numerous; when mutated or over-expressed, alpha-synuclein affects several membrane trafficking and stress pathways, including exocytosis, ER-to-Golgi transport, ER stress, Golgi homeostasis, endocytosis, autophagy, oxidative stress and others. Here we examine recent developments in alpha-synuclein’s toxicity in the early secretory pathway placed in the context of emerging themes from other affected pathways to help illuminate its underlying pathogenic mechanisms in neurodegeneration.

  2. Cp/Heph mutant mice have iron-induced neurodegeneration diminished by deferiprone

    Science.gov (United States)

    Zhao, Liangliang; Hadziahmetovic, Majda; Wang, Chenguang; Xu, Xueying; Song, Ying; Jinnah, H.A.; Wodzinska, Jolanta; Iacovelli, Jared; Wolkow, Natalie; Krajacic, Predrag; Weissberger, Alyssa Cwanger; Connelly, John; Spino, Michael; Lee, Michael K.; Connor, James; Giasson, Benoit; Harris, Z. Leah; Dunaief, Joshua L.

    2016-01-01

    Brain iron accumulates in several neurodegenerative diseases and can cause oxidative damage, but mechanisms of brain iron homeostasis are incompletely understood. Patients with mutations in the cellular iron-exporting ferroxidase ceruloplasmin (Cp) have brain iron accumulation causing neurodegeneration. Here, we assessed the brains of mice with combined mutation of Cp and its homolog hephaestin. Compared to single mutants, brain iron accumulation was accelerated in double mutants in the cerebellum, substantia nigra, and hippocampus. Iron accumulated within glia, while neurons were iron deficient. There was loss of both neurons and glia. Mice developed ataxia and tremor, and most died by 9 months. Treatment with the oral iron chelator deferiprone diminished brain iron levels, protected against neuron loss, and extended lifespan. Ferroxidases play important, partially overlapping roles in brain iron homeostasis by facilitating iron export from glia, making iron available to neurons. PMID:26303407

  3. Obesity and the Ageing Brain: Could Leptin Play a Role in Neurodegeneration?

    Directory of Open Access Journals (Sweden)

    G. H. Doherty

    2011-01-01

    Full Text Available Obesity and ageing are both characteristics of the human population that are on the increase across the globe. It has long been established that ageing is the major risk factor for neurodegenerative conditions such as Alzheimer's disease, and it is becoming increasingly evident that obesity is another such factor. Leptin resistance or insensitivity has been uncovered as a cause of obesity, and in addition the leptin signalling system is less potent in the elderly. Taken together, these findings reveal that this molecule may be a link between neurodegeneration and obesity or ageing. It is now known that leptin has beneficial effects on both the survival and neurophysiology of the neurons that are lost in Alzheimer's disease suggesting that it may be an important research target in the quest for strategies to prevent, halt, or cure this condition.

  4. Exome sequencing and SNP analysis detect novel compound heterozygosity in fatty acid hydroxylase-associated neurodegeneration

    Science.gov (United States)

    Pierson, Tyler Mark; Simeonov, Dimitre R; Sincan, Murat; Adams, David A; Markello, Thomas; Golas, Gretchen; Fuentes-Fajardo, Karin; Hansen, Nancy F; Cherukuri, Praveen F; Cruz, Pedro; Blackstone, Craig; Tifft, Cynthia; Boerkoel, Cornelius F; Gahl, William A

    2012-01-01

    Fatty acid hydroxylase-associated neurodegeneration due to fatty acid 2-hydroxylase deficiency presents with a wide range of phenotypes including spastic paraplegia, leukodystrophy, and/or brain iron deposition. All previously described families with this disorder were consanguineous, with homozygous mutations in the probands. We describe a 10-year-old male, from a non-consanguineous family, with progressive spastic paraplegia, dystonia, ataxia, and cognitive decline associated with a sural axonal neuropathy. The use of high-throughput sequencing techniques combined with SNP array analyses revealed a novel paternally derived missense mutation and an overlapping novel maternally derived ∼28-kb genomic deletion in FA2H. This patient provides further insight into the consistent features of this disorder and expands our understanding of its phenotypic presentation. The presence of a sural nerve axonal neuropathy had not been previously associated with this disorder and so may extend the phenotype. PMID:22146942

  5. Correlated Inflammatory Responses and Neurodegeneration in Peptide-Injected Animal Models of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    James G. McLarnon

    2014-01-01

    Full Text Available Animal models of Alzheimer’s disease (AD which emphasize activation of microglia may have particular utility in correlating proinflammatory activity with neurodegeneration. This paper reviews injection of amyloid-β (Aβ into rat brain as an alternative AD animal model to the use of transgenic animals. In particular, intrahippocampal injection of Aβ1-42 peptide demonstrates prominent microglial mobilization and activation accompanied by a significant loss of granule cell neurons. Furthermore, pharmacological inhibition of inflammatory reactivity is demonstrated by a broad spectrum of drugs with a common endpoint in conferring neuroprotection in peptide-injected animals. Peptide-injection models provide a focus on glial cell responses to direct peptide injection in rat brain and offer advantages in the study of the mechanisms underlying neuroinflammation in AD brain.

  6. ER stress signaling and neurodegeneration: At the intersection between Alzheimer's disease and Prion-related disorders.

    Science.gov (United States)

    Torres, Mauricio; Matamala, José Manuel; Duran-Aniotz, Claudia; Cornejo, Victor Hugo; Foley, Andrew; Hetz, Claudio

    2015-09-02

    Alzheimer's and Prion diseases are two neurodegenerative conditions sharing different pathophysiological characteristics. Disease symptoms are associated with the abnormal accumulation of protein aggregates, which are generated by the misfolding and oligomerization of specific proteins. Recent functional studies uncovered a key role of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) in the occurrence of synaptic dysfunction and neurodegeneration in Prion-related disorders and Alzheimer's disease. Here we review common pathological features of both diseases, emphasizing the link between amyloid formation, its pathogenesis and alterations in ER proteostasis. The potential benefits of targeting the UPR as a therapeutic strategy is also discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Advanced glycation end products and RAGE: a common thread in aging, diabetes, neurodegeneration, and inflammation.

    Science.gov (United States)

    Ramasamy, Ravichandran; Vannucci, Susan J; Yan, Shirley Shi Du; Herold, Kevan; Yan, Shi Fang; Schmidt, Ann Marie

    2005-07-01

    The products of nonenzymatic glycation and oxidation of proteins and lipids, the advanced glycation end products (AGEs), accumulate in a wide variety of environments. AGEs may be generated rapidly or over long times stimulated by a range of distinct triggering mechanisms, thereby accounting for their roles in multiple settings and disease states. A critical property of AGEs is their ability to activate receptor for advanced glycation end products (RAGE), a signal transduction receptor of the immunoglobulin superfamily. It is our hypothesis that due to such interaction, AGEs impart a potent impact in tissues, stimulating processes linked to inflammation and its consequences. We hypothesize that AGEs cause perturbation in a diverse group of diseases, such as diabetes, inflammation, neurodegeneration, and aging. Thus, we propose that targeting this pathway may represent a logical step in the prevention/treatment of the sequelae of these disorders.

  8. Early intranasal insulin therapy halts progression of neurodegeneration: progress in Alzheimer's disease therapeutics.

    Science.gov (United States)

    de la Monte, Suzanne M

    Evaluation of Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, et al. Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment: A Pilot Clinical Trial. Arch Neurol . 2011 Sep 12. Alzheimer's disease is associated with brain insulin deficiency and insulin resistance, similar to the problems in diabetes. If insulin could be supplied to the brain in the early stages of Alzheimer's, subsequent neurodegeneration might be prevented. Administering systemic insulin to elderly non-diabetics poses unacceptable risks of inadvertant hypoglycemia. However, intranasal delivery directs the insulin into the brain, avoiding systemic side-effects. This pilot study demonstrates both efficacy and safety of using intranasal insulin to treat early Alzheimer's and mild cognitive impairment, i.e. the precursor to Alzheimer's. Significant improvements in learning, memory, and cognition occured within a few months, but without intranasal insulin, brain function continued to deteriorate in measurable degrees. Intranasal insulin therapy holds promise for halting progression of Alzheimer's disease.

  9. Minocycline reduces neuroinflammation but does not ameliorate neuron loss in a mouse model of neurodegeneration

    Science.gov (United States)

    Cheng, Shanshan; Hou, Jinxing; Zhang, Chen; Xu, Congyu; Wang, Long; Zou, Xiaoxia; Yu, Huahong; Shi, Yun; Yin, Zhenyu; Chen, Guiquan

    2015-01-01

    Minocycline is a broad-spectrum tetracycline antibiotic. A number of preclinical studies have shown that minocycline exhibits neuroprotective effects in various animal models of neurological diseases. However, it remained unknown whether minocycline is effective to prevent neuron loss. To systematically evaluate its effects, minocycline was used to treat Dicer conditional knockout (cKO) mice which display age-related neuron loss. The drug was given to mutant mice prior to the occurrence of neuroinflammation and neurodegeneration, and the treatment had lasted 2 months. Levels of inflammation markers, including glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule1 (Iba1) and interleukin6 (IL6), were significantly reduced in minocycline-treated Dicer cKO mice. In contrast, levels of neuronal markers and the total number of apoptotic cells in Dicer cKO mice were not affected by the drug. In summary, inhibition of neuroinflammation by minocycline is insufficient to prevent neuron loss and apoptosis. PMID:26000566

  10. Herpes - resources

    Science.gov (United States)

    Genital herpes - resources; Resources - genital herpes ... following organizations are good resources for information on genital herpes : March of Dimes -- www.marchofdimes.org/complications/sexually- ...

  11. Tobacco Smoke Exposure Impairs Brain Insulin/IGF Signaling: Potential Co-Factor Role in Neurodegeneration.

    Science.gov (United States)

    Deochand, Chetram; Tong, Ming; Agarwal, Amit R; Cadenas, Enrique; de la Monte, Suzanne M

    2016-01-01

    Human studies suggest tobacco smoking is a risk factor for cognitive impairment and neurodegeneration, including Alzheimer's disease (AD). However, experimental data linking tobacco smoke exposures to underlying mediators of neurodegeneration, including impairments in brain insulin and insulin-like growth factor (IGF) signaling in AD are lacking. This study tests the hypothesis that cigarette smoke (CS) exposures can impair brain insulin/IGF signaling and alter expression of AD-associated proteins. Adult male A/J mice were exposed to air for 8 weeks (A8), CS for 4 or 8 weeks (CS4, CS8), or CS8 followed by 2 weeks recovery (CS8+R). Gene expression was measured by qRT-PCR analysis and proteins were measured by multiplex bead-based or direct binding duplex ELISAs. CS exposure effects on insulin/IGF and insulin receptor substrate (IRS) proteins and phosphorylated proteins were striking compared with the mRNA. The main consequences of CS4 or CS8 exposures were to significantly reduce insulin R, IGF-1R, IRS-1, and tyrosine phosphorylated insulin R and IGF-1R proteins. Paradoxically, these effects were even greater in the CS8+R group. In addition, relative levels of S312-IRS-1, which inhibits downstream signaling, were increased in the CS4, CS8, and CS8+R groups. Correspondingly, CS and CS8+R exposures inhibited expression of proteins and phosphoproteins required for signaling through Akt, PRAS40, and/or p70S6K, increased AβPP-Aβ, and reduced ASPH protein, which is a target of insulin/IGF-1 signaling. Secondhand CS exposures caused molecular and biochemical abnormalities in brain that overlap with the findings in AD, and many of these effects were sustained or worsened despite short-term CS withdrawal.

  12. Ninjin'yoeito and ginseng extract prevent oxaliplatin-induced neurodegeneration in PC12 cells.

    Science.gov (United States)

    Suzuki, Toshiaki; Yamamoto, Ayano; Ohsawa, Masahiro; Motoo, Yoshiharu; Mizukami, Hajime; Makino, Toshiaki

    2015-10-01

    Ninjin'yoeito (NYT) is a formula of Japanese traditional kampo medicine composed of 12 crude drugs, and is designed to improve the decline in constitution after recovery from disease, fatigue, anemia, anorexia, perspiration during sleep, cold limbs, slight fever, chills, persistent cough, malaise, mental disequilibrium, insomnia, and constipation. Oxaliplatin (L-OHP) is a platinum-based anticancer drug used to treat colorectal, pancreatic, and stomach cancers. However, it often causes acute and chronic peripheral neuropathies including cold allodynia and mechanical hyperalgesia. In this study, we investigated the preventive effects of NYT on neuronal degeneration caused by L-OHP using PC12 cells, which are derived from the rat adrenal medulla and differentiate into nerve-like cells after exposure to nerve growth factor. L-OHP treatment decreased the elongation of neurite-like projection outgrowths in differentiated PC12 cells. When PC12 cells were treated with NYT hot water extract, neurodegeneration caused by L-OHP was significantly prevented in a concentration-dependent manner. Among the 12 crude drugs composing NYT, the extract of Ginseng (the root of Panax ginseng) exhibited the strongest preventive effects on neurodegeneration in differentiated PC12 cells. By activity-guided fractionation, we found that the fraction containing ginsenosides displayed preventive activity and, among several ginsenosides, ginsenoside F2 exhibited significant preventive effects on L-OHP-induced decreases in neurite-like outgrowths in differentiated PC12 cells. These results suggest that NYT and ginseng are promising agents for preventing L-OHP-induced neuropathies and present ginsenoside F2 as one of the active ingredients in ginseng.

  13. Mössbauer spectroscopy and the understanding of the role of iron in neurodegeneration

    Science.gov (United States)

    Friedman, A.; Galazka-Friedman, J.

    2017-11-01

    The possible role of iron in neurodegeneration may be related to the oxidative stress, triggered by Fenton reaction. In this reaction hydroxyl free radical production is generated by divalent iron. Motor symptoms of Parkinson's disease depend on the destruction of substantia nigra (SN). As the substantive questions were: 1/ what is the concentration of iron in the samples, 2/ what is the proportion of divalent vs. trivalent iron in the samples, and 3/ what is the iron-binding compound, it seemed appropriate to use Mössbauer spectroscopy to answer those questions. We found no difference in the concentration of total iron between PD and control, with the ratio of iron in PD vs. control being 1.00 ± 0.13. The divalent iron could not exceed 5% of the total iron. The main iron-binding compound in SN, both in PD and control is ferritin. Our further studies of ferritin in parkinsonian SN demonstrated a decrease, compared to control, of L-ferritin involved in the storage of iron within ferritin. This could allow an efflux of iron from the ferritin shell and an increase of non-ferritin iron in PD SN, which was confirmed by us. Mössbauer studies in Alzheimer showed slightly higher concentration of iron in hippocampal cortex with significantly higher concentrations of L and H ferritins compared to control. In atypical parkinsonism, progressive supranuclear palsy, higher concentration of iron was found in globus pallidus and SN compared to control. Mössbauer spectroscopy may play crucial role in further studies of human neurodegeneration.

  14. Age and neurodegeneration imaging biomarkers in persons with Alzheimer disease dementia.

    Science.gov (United States)

    Knopman, David S; Jack, Clifford R; Wiste, Heather J; Weigand, Stephen D; Vemuri, Prashanthi; Lowe, Val J; Kantarci, Kejal; Gunter, Jeffrey L; Senjem, Matthew L; Mielke, Michelle M; Machulda, Mary M; Roberts, Rosebud O; Boeve, Bradley F; Jones, David T; Petersen, Ronald C

    2016-08-16

    To examine neurodegenerative imaging biomarkers in Alzheimer disease (AD) dementia from middle to old age. Persons with AD dementia and elevated brain β-amyloid with Pittsburgh compound B (PiB)-PET imaging underwent [(18)F]-fluorodeoxyglucose (FDG)-PET and structural MRI. We evaluated 3 AD-related neurodegeneration biomarkers: hippocampal volume adjusted for total intracranial volume (HVa), FDG standardized uptake value ratio (SUVR) in regions of interest linked to AD, and cortical thickness in AD-related regions of interest. We examined associations of each biomarker with age and evaluated age effects on cutpoints defined by the 90th percentile in AD dementia. We assembled an age-, sex-, and intracranial volume-matched group of 194 similarly imaged clinically normal (CN) persons. The 97 participants with AD dementia (aged 49-93 years) had PiB SUVR ≥1.8. A nonlinear (inverted-U) relationship between FDG SUVR and age was seen in the AD group but an inverse linear relationship with age was seen in the CN group. Cortical thickness had an inverse linear relationship with age in AD but a nonlinear (flat, then inverse linear) relationship in the CN group. HVa showed an inverse linear relationship with age in both AD and CN groups. Age effects on 90th percentile cutpoints were small for FDG SUVR and cortical thickness, but larger for HVa. In persons with AD dementia with elevated PiB SUVR, values of each neurodegeneration biomarker were associated with age. Cortical thickness had the smallest differences in 90th percentile cutpoints from middle to old age, and HVa the largest differences. © 2016 American Academy of Neurology.

  15. Differentiated NSC-34 motoneuron-like cells as experimental model for cholinergic neurodegeneration.

    Science.gov (United States)

    Maier, Oliver; Böhm, Julia; Dahm, Michael; Brück, Stefan; Beyer, Cordian; Johann, Sonja

    2013-06-01

    Alpha-motoneurons appear to be exceedingly affected in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Morphological and physiological degeneration of this neuronal phenotype is typically characterized by a marked decrease of neuronal markers and by alterations of cholinergic metabolism such as reduced choline acetyltransferase (ChAT) expression. The motoneuron-like cell line NSC-34 is a hybrid cell line produced by fusion of neuroblastoma with mouse motoneuron-enriched primary spinal cord cells. In order to further establish this cell line as a valid model system to investigate cholinergic neurodegeneration, NSC-34 cells were differentiated by serum deprivation and additional treatment with all-trans retinoic acid (atRA). Cell maturation was characterized by neurite outgrowth and increased expression of neuronal and cholinergic markers, including MAP2, GAP-43 and ChAT. Subsequently, we used differentiated NSC-34 cells to study early degenerative responses following exposure to various neurotoxins (H2O2, TNF-α, and glutamate). Susceptibility to toxin-induced cell death was determined by means of morphological changes, expression of neuronal marker proteins, and the ratio of pro-(Bax) to anti-(Bcl-2) apoptotic proteins. NSC-34 cells respond to low doses of neurotoxins with increased cell death of remaining undifferentiated cells with no obvious adverse effects on differentiated cells. Thus, the different vulnerability of differentiated and undifferentiated NSC-34 cells to neurotoxins is a key characteristic of NSC-34 cells and has to be considered in neurotoxic studies. Nonetheless, application of atRA induced differentiation of NSC-34 cells and provides a suitable model to investigate molecular events linked to neurodegeneration of differentiated neurons. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Zinc Improves Cognitive and Neuronal Dysfunction During Aluminium-Induced Neurodegeneration.

    Science.gov (United States)

    Singla, Neha; Dhawan, D K

    2017-01-01

    Metals are considered as important components of a physiologically active cell, and imbalance in their levels can lead to various diseased conditions. Aluminium (Al) is an environmental neurotoxicant, which is etiologically related to several neurodegenerative disorders like Alzheimer's, whereas zinc (Zn) is an essential trace element that regulates a large number of metabolic processes in the brain. The objective of the present study was to understand whether Zn provides any physiological protection during Al-induced neurodegeneration. Male Sprague Dawley rats weighing 140-160 g received either aluminium chloride (AlCl 3 ) orally (100 mg/kg b.wt./day), zinc sulphate (ZnSO 4 ) in drinking water (227 mg/L) or combined treatment of aluminium and zinc for 8 weeks. Al treatment resulted in a significant decline in the cognitive behaviour of rats, whereas zinc supplementation caused an improvement in various neurobehavior parameters. Further, Al exposure decreased (p ≤ 0.001) the levels of neurotransmitters, acetylcholinesterase activity, but increased (p ≤ 0.001) the levels of L-citrulline as well as activities of nitric oxide and monoamine oxidase in the brain. However, zinc administration to Al-treated animals increased the levels of neurotransmitters and regulated the altered activities of brain markers. Western blot of tau, amyloid precursor protein (APP), glial fibrillary acidic protein (GFAP), ubiquitin, α-synuclein and Hsp 70 were also found to be elevated after Al exposure, which however were reversed following Zn treatment. Al treatment also revealed alterations in neurohistoarchitecture in the form of loss of pyramidal and Purkinje cells, which were improved upon zinc co-administration. Therefore, the present study demonstrates that zinc improves cognitive functions by regulating α-synuclein and APP-mediated molecular pathways during aluminium-induced neurodegeneration.

  17. Increased RhoA prenylation in the loechrig (loe mutant leads to progressive neurodegeneration.

    Directory of Open Access Journals (Sweden)

    Mandy Cook

    Full Text Available The Drosophila mutant loechrig (loe shows age-dependent degeneration of the nervous system and is caused by the loss of a neuronal isoform of the AMP-activated protein kinase (AMPK γ-subunit (also known as SNF4Aγ. The trimeric AMPK complex is activated by low energy levels and metabolic insults and regulates multiple important signal pathways that control cell metabolism. A well-known downstream target of AMPK is hydroxyl-methylglutaryl-CoA reductase (HMGR, a key enzyme in isoprenoid synthesis, and we have previously shown that HMGR genetically interacts with loe and affects the severity of the degenerative phenotype. Prenylation of proteins like small G-proteins is an important posttranslational modification providing lipid moieties that allow the association of these proteins with membranes, thereby facilitating their subsequent activation. Rho proteins have been extensively studied in neuronal outgrowth, however, much less is known about their function in neuronal maintenance. Here we show that the loe mutation interferes with isoprenoid synthesis, leading to increased prenylation of the small GTPase Rho1, the fly orthologue of vertebrate RhoA. We also demonstrate that increased prenylation and Rho1 activity causes neurodegeneration and aggravates the behavioral and degenerative phenotypes of loe. Because we cannot detect defects in the development of the central nervous system in loe, this suggests that loe only interferes with the function of the RhoA pathway in maintaining neuronal integrity during adulthood. In addition, our results show that alterations in isoprenoids can result in progressive neurodegeneration, supporting findings in vertebrates that prenylation may play a role in neurodegenerative diseases like Alzheimer's Disease.

  18. The Effects of Meditation on Grey Matter Atrophy and Neurodegeneration: A Systematic Review.

    Science.gov (United States)

    Last, Nicole; Tufts, Emily; Auger, Leslie E

    2017-01-01

    The present systematic review is based on the premise that a variety of neurodegenerative diseases are accompanied by grey matter atrophy in the brain and meditation may impact this. Given that age is a major risk factor for many of these progressive and neurodegenerative diseases and that the percentage of the population over the age of 65 is quickly increasing, there is an obvious need for prompt treatment and prevention advances in research. As there is currently no cure for Alzheimer's disease and other neurodegenerative diseases, many are seeking non-pharmacological treatment options in attempts to offset the disease-related cognitive and functional declines. On the basis of a growing body of research suggesting that meditation is effective in increasing grey matter volume in healthy participants, this paper systematically reviewed the literature regarding the effects of meditation on restoring grey matter volume in healthy individuals and those affected by neurodegeneration. This review searched PubMed, CINAHL, and APA PsycNET to identify original studies that included MRI imaging to measure grey matter volume in meditators and post-mindfulness-based intervention participants compared to controls. Thirteen studies were considered eligible for review and involved a wide variety of meditation techniques and included participants with and without cognitive impairment. All studies reported significant increases in grey matter volume in the meditators/intervention group, albeit in assorted regions of the brain. Limited research exists on the mechanisms through which meditation affects disease-related neurodegeneration, but preliminary evidence suggests that it may offset grey matter atrophy.

  19. The Use of Quality Benchmarking in Assessing Web Resources for the Dermatology Virtual Branch Library of the National electronic Library for Health (NeLH)

    OpenAIRE

    Boulos, MN Kamel; Roudsari, AV; Gordon, C; Gray, JA Muir

    2001-01-01

    Background In 1998, the U.K. National Health Service Information for Health Strategy proposed the implementation of a National electronic Library for Health to provide clinicians, healthcare managers and planners, patients and the public with easy, round the clock access to high quality, up-to-date electronic information on health and healthcare. The Virtual Branch Libraries are among the most important components of the National electronic Library for Health . They aim at creating online kno...

  20. Functional and Structural Findings of Neurodegeneration in Early Stages of Diabetic Retinopathy. Cross-sectional Analyses of Baseline Data of the EUROCONDOR project

    DEFF Research Database (Denmark)

    Santos, Ana Rita; Ribeiro, Luisa; Bandello, Francesco

    2017-01-01

    Cross-sectional study evaluating the relationship between: a) functional and structural measurements of neurodegeneration in initial stages of diabetic retinopathy (DR); and b) presence of neurodegeneration and early microvascular impairment. We analyzed baseline data of patients with type 2...... diabetes (n=449) enrolled in the EUROCONDOR study (NCT01726075). Functional studies by multifocal ERG (mfERG) evaluated neurodysfunction and structural measurements using spectral domain optical-coherence tomography (SD-OCT) evaluated neurodegeneration. The mfERG P1 amplitude was more sensitive than the P1...

  1. Analysis on Current Situation and Countermeasure of Domestic Electronic Commerce Logistics in the Internet Age——Based on Resource Dependence Theory

    Directory of Open Access Journals (Sweden)

    Zhang Jiapeng

    2017-01-01

    Full Text Available This paper analyzes the status of electric business logistics in the current Internet era in China, and combines the SWOT analysis with AHP to do the empirical analysis, then puts forward the countermeasure that the electric business logistics resource should be shared based on the resource dependence theory. Through the empirical analysis, it is found that the disadvantages and opportunities of the logistics status are important in the Internet era.The resource sharing strategy based on the resource dependence theory is more scientific. The rational use of Internet technology in electric business logistics industry can achieve “sharing”. It is of great significance for its balanced development, intelligent development and optimization and development.

  2. Clinical and Imaging Presentation of a Patient with Beta-Propeller Protein-Associated Neurodegeneration, a Rare and Sporadic form of Neurodegeneration with Brain Iron Accumulation (NBIA).

    Science.gov (United States)

    Hattingen, Elke; Handke, Nikolaus; Cremer, Kirsten; Hoffjan, Sabine; Kukuk, Guido Matthias

    2017-12-01

    Neurodegeneration with brain iron accumulation (NBIA) is a heterogeneous group of inherited neurologic disorders with iron accumulation in the basal ganglia, which share magnetic resonance (MR) imaging characteristics, histopathologic and clinical features. According to the affected basal nuclei, clinical features include extrapyramidal movement disorders and varying degrees of intellectual disability status. The most common NBIA subtype is caused by pathogenic variants in PANK2. The hallmark of MR imaging in patients with PANK2 mutations is an eye-of-the-tiger sign in the globus pallidus. We report a 33-year-old female with a rare subtype of NBIA, called beta-propeller protein-associated neurodegeneration (BPAN) with a hitherto unknown missense variant in WDR45. She presented with BPAN's particular biphasic course of neurological symptoms and with a dominant iron accumulation in the midbrain that enclosed a spotty T2-hyperintensity.

  3. Pantethine treatment is effective in recovering the disease phenotype induced by ketogenic diet in a pantothenate kinase-associated neurodegeneration mouse model

    NARCIS (Netherlands)

    Brunetti, Dario; Dusi, Sabrina; Giordano, Carla; Lamperti, Costanza; Morbin, Michela; Fugnanesi, Valeria; Marchet, Silvia; Fagiolari, Gigliola; Sibon, Ody; Moggio, Maurizio; d'Amati, Giulia; Tiranti, Valeria

    Pantothenate kinase-associated neurodegeneration, caused by mutations in the PANK2 gene, is an autosomal recessive disorder characterized by dystonia, dysarthria, rigidity, pigmentary retinal degeneration and brain iron accumulation. PANK2 encodes the mitochondrial enzyme pantothenate kinase type 2,

  4. Dementia, preclinical studies in neurodegeneration and its potential for translational medicine in SouthAmerica

    Directory of Open Access Journals (Sweden)

    Gloria Patricia Cardona Gomez

    2016-12-01

    Full Text Available Latin-American people with dementia will increase in a 368% in 2050, higher than USA and Europe. In addition, to sporadic dementia type Alzheimer and vascular dementia progression after Cerebrovascular disease, the statistics are increased in Colombia by specific populations affected with pure neurodegenerative and vascular dementias like autosomical dominant familial Alzheimer´s disease and CADASIL. In spite of the enormous human and economical effort and investment, neither sporadic nor genetic kinds of dementia progression have been prevented or blocked yet. Currently, exist several animal models that partially solve the understanding of the neurodegenerative etiopathogenesis and its treatment. However, when the potential therapies are translated to humans, those do not work or present a limited action. Main difficulties are the diverse comorbility associated to the cause and/or several affected brain regions, reducing the efficacy of some therapies which are limited to a tissue-specific action or modulating a kind of neurotransmission. Global investigation suggests that a general prevention could be achieved with the improvement in the quality of lifestyle, including healthy diet, physical and mental activity, and avoiding mechanical or chemical pro-inflammatory events in an early stage in the most of non-communicable diseases. In this review, we present some molecular targets and preclinical studies in animal models to propose strategies that could be useful in a future translation to prevent or block neurodegeneration: One is gene therapy silencing pathogenic genes in critical brain areas where excitotoxicity arise and spread. Another is to take advantage of the natural source and its wide biodiversity of natural products some of them identified by the blocking and prevention of neurodegeneration. On the other side, the casuistic of pure dementias in the Latin-American region give an exceptional opportunity to understand the pathogenesis

  5. Dopamine receptor D3 expressed on CD4+ T cells favors neurodegeneration of dopaminergic neurons during Parkinson's disease.

    Science.gov (United States)

    González, Hugo; Contreras, Francisco; Prado, Carolina; Elgueta, Daniela; Franz, Dafne; Bernales, Sebastián; Pacheco, Rodrigo

    2013-05-15

    Emerging evidence has demonstrated that CD4(+) T cells infiltrate into the substantia nigra (SN) in Parkinson's disease (PD) patients and in animal models of PD. SN-infiltrated CD4(+) T cells bearing inflammatory phenotypes promote microglial activation and strongly contribute to neurodegeneration of dopaminergic neurons. Importantly, altered expression of dopamine receptor D3 (D3R) in PBLs from PD patients has been correlated with disease severity. Moreover, pharmacological evidence has suggested that D3R is involved in IFN-γ production by human CD4(+) T cells. In this study, we examined the role of D3R expressed on CD4(+) T cells in neurodegeneration of dopaminergic neurons in the SN using a mouse model of PD. Our results show that D3R-deficient mice are strongly protected against loss of dopaminergic neurons and microglial activation during 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. Notably, D3R-deficient mice become susceptible to MPTP-induced neurodegeneration and microglial activation upon transfer of wild-type (WT) CD4(+) T cells. Furthermore, RAG1 knockout mice, which are devoid of T cells and are resistant to MPTP-induced neurodegeneration, become susceptible to MPTP-induced loss of dopaminergic neurons when reconstituted with WT CD4(+) T cells but not when transferred with D3R-deficient CD4(+) T cells. In agreement, experiments analyzing activation and differentiation of CD4(+) T cells revealed that D3R favors both T cell activation and acquisition of the Th1 inflammatory phenotype. These findings indicate that D3R expressed on CD4(+) T cells plays a fundamental role in the physiopathology of MPTP-induced PD in a mouse model.

  6. Ferrous Iron Up-regulation in Fibroblasts of Patients with Beta Propeller Protein-Associated Neurodegeneration (BPAN).

    OpenAIRE

    Ingrassia, Rosaria; Memo, Maurizio; Garavaglia, Barbara

    2017-01-01

    Mutations in WDR45 gene, coding for a beta-propeller protein, have been found in patients affected by Neurodegeneration with Brain Iron Accumulation, NBIA5 (also known as BPAN). BPAN is a movement disorder with Non Transferrin Bound Iron (NTBI) accumulation in the basal ganglia as common hallmark between NBIA classes (Hayflick et al., 2013). WDR45 has been predicted to have a role in autophagy, while the impairment of iron metabolism in the different NBIA subclasses has not currently been cla...

  7. Neuroprotective Effect of Fisetin Against Amyloid-Beta-Induced Cognitive/Synaptic Dysfunction, Neuroinflammation, and Neurodegeneration in Adult Mice.

    Science.gov (United States)

    Ahmad, Ashfaq; Ali, Tahir; Park, Hyun Young; Badshah, Haroon; Rehman, Shafiq Ur; Kim, Myeong Ok

    2017-04-01

    Alzheimer's disease (AD) is a devastating and progressive neurodegenerative disease and is characterized pathologically by the accumulation of amyloid beta (Aβ) and the hyperphosphorylation of tau proteins in the brain. The deposition of Aβ aggregates triggers synaptic dysfunction, hyperphosphorylation of tau, and neurodegeneration, which lead to cognitive disorders. Here, we investigated the neuroprotective effect of fisetin in the Aβ 1-42 mouse model of AD. Single intracerebroventricular injections of Aβ 1-42 (3 μl/5 min/mouse) markedly induced memory/synaptic deficits, neuroinflammation, and neurodegeneration. Intraperitoneal injections of fisetin at a dose of 20 mg/kg/day for 2 weeks starting 24 h after Aβ 1-42 injection significantly decreased the Aβ 1-42 -induced accumulation of Aβ, BACE-1 expression, and hyperphosphorylation of tau protein at serine 413. Fisetin treatment also markedly reversed Aβ 1-42 -induced synaptic dysfunction by increasing the levels of both presynaptic (SYN and SNAP-25) and postsynaptic proteins (PSD-95, SNAP-23, p-GluR1 (Ser 845), p-CREB (Ser 133) and p-CAMKII (Thr 286) and ultimately improved mouse memory, as observed in the Morris water maze test. Fisetin significantly activated p-PI3K, p-Akt (Ser 473), and p-GSK3β (Ser 9) expression in Aβ 1-42 -treated mice. Moreover, fisetin prevented neuroinflammation by suppressing various activated neuroinflammatory mediators and gliosis; it also suppressed the apoptotic neurodegeneration triggered by Aβ 1-42 injections in the mouse hippocampus. Fluorojade-B and immunohistochemical staining for caspase-3 revealed that fisetin prevented neurodegeneration in Aβ 1-42 -treated mice. Our results suggest that fisetin has a potent neuroprotective effect against Aβ 1-42 -induced neurotoxicity. These results demonstrate that polyphenolic flavonoids such as fisetin could be a beneficial, effective and safe neuroprotective agent for preventing neurological disorders such as AD.

  8. Increased CDK5 expression in HIV encephalitis contributes to neurodegeneration via tau phosphorylation and is reversed with Roscovitine.

    Science.gov (United States)

    Patrick, Christina; Crews, Leslie; Desplats, Paula; Dumaop, Wilmar; Rockenstein, Edward; Achim, Cristian L; Everall, Ian P; Masliah, Eliezer

    2011-04-01

    Recent treatments with highly active antiretroviral therapy (HAART) regimens have been shown to improve general clinical status in patients with human immunodeficiency virus (HIV) infection; however, the prevalence of cognitive alterations and neurodegeneration has remained the same or has increased. These deficits are more pronounced in the subset of HIV patients with the inflammatory condition known as HIV encephalitis (HIVE). Activation of signaling pathways such as GSK3β and CDK5 has been implicated in the mechanisms of HIV neurotoxicity; however, the downstream mediators of these effects are unclear. The present study investigated the involvement of CDK5 and tau phosphorylation in the mechanisms of neurodegeneration in HIVE. In the frontal cortex of patients with HIVE, increased levels of CDK5 and p35 expression were associated with abnormal tau phosphorylation. Similarly, transgenic mice engineered to express the HIV protein gp120 exhibited increased brain levels of CDK5 and p35, alterations in tau phosphorylation, and dendritic degeneration. In contrast, genetic knockdown of CDK5 or treatment with the CDK5 inhibitor roscovitine improved behavioral performance in the water maze test and reduced neurodegeneration, abnormal tau phosphorylation, and astrogliosis in gp120 transgenic mice. These findings indicate that abnormal CDK5 activation contributes to the neurodegenerative process in HIVE via abnormal tau phosphorylation; thus, reducing CDK5 might ameliorate the cognitive impairments associated with HIVE. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  9. Towards an Integrative Understanding of tRNA Aminoacylation–Diet–Host–Gut Microbiome Interactions in Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Elena L. Paley

    2018-03-01

    Full Text Available Transgenic mice used for Alzheimer’s disease (AD preclinical experiments do not recapitulate the human disease. In our models, the dietary tryptophan metabolite tryptamine produced by human gut microbiome induces tryptophanyl-tRNA synthetase (TrpRS deficiency with consequent neurodegeneration in cells and mice. Dietary supplements, antibiotics and certain drugs increase tryptamine content in vivo. TrpRS catalyzes tryptophan attachment to tRNAtrp at initial step of protein biosynthesis. Tryptamine that easily crosses the blood–brain barrier induces vasculopathies, neurodegeneration and cell death via TrpRS competitive inhibition. TrpRS inhibitor tryptophanol produced by gut microbiome also induces neurodegeneration. TrpRS inhibition by tryptamine and its metabolites preventing tryptophan incorporation into proteins lead to protein biosynthesis impairment. Tryptophan, a least amino acid in food and proteins that cannot be synthesized by humans competes with frequent amino acids for the transport from blood to brain. Tryptophan is a vulnerable amino acid, which can be easily lost to protein biosynthesis. Some proteins marking neurodegenerative pathology, such as tau lack tryptophan. TrpRS exists in cytoplasmic (WARS and mitochondrial (WARS2 forms. Pathogenic gene variants of both forms cause TrpRS deficiency with consequent intellectual and motor disabilities in humans. The diminished tryptophan-dependent protein biosynthesis in AD patients is a proof of our model-based disease concept.

  10. The Role of S-Nitrosylation and S-Glutathionylation of Protein Disulphide Isomerase in Protein Misfolding and Neurodegeneration

    Directory of Open Access Journals (Sweden)

    M. Halloran

    2013-01-01

    Full Text Available Neurodegenerative diseases involve the progressive loss of neurons, and a pathological hallmark is the presence of abnormal inclusions containing misfolded proteins. Although the precise molecular mechanisms triggering neurodegeneration remain unclear, endoplasmic reticulum (ER stress, elevated oxidative and nitrosative stress, and protein misfolding are important features in pathogenesis. Protein disulphide isomerase (PDI is the prototype of a family of molecular chaperones and foldases upregulated during ER stress that are increasingly implicated in neurodegenerative diseases. PDI catalyzes the rearrangement and formation of disulphide bonds, thus facilitating protein folding, and in neurodegeneration may act to ameliorate the burden of protein misfolding. However, an aberrant posttranslational modification of PDI, S-nitrosylation, inhibits its protective function in these conditions. S-nitrosylation is a redox-mediated modification that regulates protein function by covalent addition of nitric oxide- (NO- containing groups to cysteine residues. Here, we discuss the evidence for abnormal S-nitrosylation of PDI (SNO-PDI in neurodegeneration and how this may be linked to another aberrant modification of PDI, S-glutathionylation. Understanding the role of aberrant S-nitrosylation/S-glutathionylation of PDI in the pathogenesis of neurodegenerative diseases may provide insights into novel therapeutic interventions in the future.

  11. Towards an Integrative Understanding of tRNA Aminoacylation-Diet-Host-Gut Microbiome Interactions in Neurodegeneration.

    Science.gov (United States)

    Paley, Elena L; Perry, George

    2018-03-26

    Transgenic mice used for Alzheimer's disease (AD) preclinical experiments do not recapitulate the human disease. In our models, the dietary tryptophan metabolite tryptamine produced by human gut microbiome induces tryptophanyl-tRNA synthetase (TrpRS) deficiency with consequent neurodegeneration in cells and mice. Dietary supplements, antibiotics and certain drugs increase tryptamine content in vivo. TrpRS catalyzes tryptophan attachment to tRNA trp at initial step of protein biosynthesis. Tryptamine that easily crosses the blood-brain barrier induces vasculopathies, neurodegeneration and cell death via TrpRS competitive inhibition. TrpRS inhibitor tryptophanol produced by gut microbiome also induces neurodegeneration. TrpRS inhibition by tryptamine and its metabolites preventing tryptophan incorporation into proteins lead to protein biosynthesis impairment. Tryptophan, a least amino acid in food and proteins that cannot be synthesized by humans competes with frequent amino acids for the transport from blood to brain. Tryptophan is a vulnerable amino acid, which can be easily lost to protein biosynthesis. Some proteins marking neurodegenerative pathology, such as tau lack tryptophan. TrpRS exists in cytoplasmic (WARS) and mitochondrial (WARS2) forms. Pathogenic gene variants of both forms cause TrpRS deficiency with consequent intellectual and motor disabilities in humans. The diminished tryptophan-dependent protein biosynthesis in AD patients is a proof of our model-based disease concept.

  12. How Students Learn: Ways of Thinking about "Good Learning" in HE. EDNER (Formative Evaluation of the Distributed National Electronic Resource) Project. Issues Paper.

    Science.gov (United States)

    Manchester Metropolitan Univ. (England).

    This issues paper, one of a series of eight, is intended to distill formative evaluation questions on topics that are central to the development of the higher and further education information environment in the United Kingdom. The topic of this first issues paper is a conceptual framework that can help members of a project (information resource)…

  13. Neuronal dark matter: The emerging role of microRNAs in neurodegeneration

    Directory of Open Access Journals (Sweden)

    Emily Frances Goodall

    2013-10-01

    Full Text Available MicroRNAs (miRNAs are small, abundant RNA molecules that constitute part of the cell’s non-coding RNA dark matter. In recent years, the discovery of miRNAs has revolutionised the traditional view of gene expression and our understanding of miRNA biogenesis and function has expanded. Altered expression of miRNAs is increasingly recognised as a feature of many disease states, including neurodegeneration. Here, we review the emerging role for miRNA dysfunction in Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and Huntington’s disease pathogenesis. We emphasise the complex nature of gene regulatory networks and the need for systematic studies, with larger sample cohorts than have so far been reported, to reveal the most important miRNA regulators in disease. Finally, miRNA diversity and their potential to target multiple pathways, offers novel clinical applications for miRNAs as biomarkers and therapeutic agents in neurodegenerative diseases.

  14. Brain network alterations and vulnerability to simulated neurodegeneration in breast cancer.

    Science.gov (United States)

    Kesler, Shelli R; Watson, Christa L; Blayney, Douglas W

    2015-08-01

    Breast cancer and its treatments are associated with mild cognitive impairment and brain changes that could indicate an altered or accelerated brain aging process. We applied diffusion tensor imaging and graph theory to measure white matter organization and connectivity in 34 breast cancer survivors compared with 36 matched healthy female controls. We also investigated how brain networks (connectomes) in each group responded to simulated neurodegeneration based on network attack analysis. Compared with controls, the breast cancer group demonstrated significantly lower fractional anisotropy, altered small-world connectome properties, lower brain network tolerance to systematic region (node), and connection (edge) attacks and significant cognitive impairment. Lower tolerance to network attack was associated with cognitive impairment in the breast cancer group. These findings provide further evidence of diffuse white matter pathology after breast cancer and extend the literature in this area with unique data demonstrating increased vulnerability of the post-breast cancer brain network to future neurodegenerative processes. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Switch-Like Roles for Polycomb Proteins from Neurodevelopment to Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Anke Hoffmann

    2017-12-01

    Full Text Available Polycomb Group (PcG proteins are best-known for maintaining repressive or active chromatin states that are passed on across multiple cell divisions, and thus sustain long-term memory of gene expression. PcG proteins engage different, partly gene- and/or stage-specific, mechanisms to mediate spatiotemporal gene expression during central nervous system development. In the course of this, PcG proteins bind to various cis-regulatory sequences (e.g., promoters, enhancers or silencers and coordinate, as well the interactions between distantly separated genomic regions to control chromatin function at different scales ranging from compaction of the linear chromatin to the formation of topological hubs. Recent findings show that PcG proteins are involved in switch-like changes in gene expression states of selected neural genes during the transition from multipotent to differentiating cells, and then to mature neurons. Beyond neurodevelopment, PcG proteins sustain mature neuronal function and viability, and prevent progressive neurodegeneration in mice. In support of this view, neuropathological findings from human neurodegenerative diseases point to altered PcG functions. Overall, improved insight into the multiplicity of PcG functions may advance our understanding of human neurodegenerative diseases and ultimately pave the way to new therapies.

  16. New isatin derivative inhibits neurodegeneration by restoring insulin signaling in brain.

    Science.gov (United States)

    Aftab, Meha Fatima; Afridi, Shabbir Khan; Mughal, Uzma Rasool; Karim, Aneela; Haleem, Darakhshan Jabeen; Kabir, Nurul; Khan, Khalid M; Hafizur, Rahman M; Waraich, Rizwana S

    2017-04-01

    Diabetes is associated with neurodegeneration. Glycation ensues in diabetes and glycated proteins cause insulin resistance in brain resulting in amyloid plaques and NFTs. Also glycation enhances gliosis by promoting neuroinflammation. Currently there is no therapy available to target neurodegenration in brain therefore, development of new therapy that offers neuroprotection is critical. The objective of this study was to evaluate mechanistic effect of isatin derivative URM-II-81, an anti-glycation agent for improvement of insulin action in brain and inhibition of neurodegenration. Methylglyoxal induced stress was inhibited by treatment with URM-II-81. Also, Ser473 and Ser9 phosphorylation of Akt and GSK-3β respectively were restored by URM-II-81. Effect of URM-II-81 on axonal integrity was studied by differentiating Neuro2A using retinoic acid. URM-II-81 restored axonal length in MGO treated cells. Its effects were also studied in high fat and low dose streptozotocin induced diabetic mice where it reduced RBG levels and inhibited glycative stress by reducing HbA1c. URM-II-81 treatment also showed inhibition of gliosis in hippocampus. Histological analysis showed reduced NFTs in CA3 hippocampal region and restoration of insulin signaling in hippocampii of diabetic mice. Our findings suggest that URM-II-81 can be developed as a new therapeutic agent for treatment of neurodegenration. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Cystathionine γ-lyase deficiency mediates neurodegeneration in Huntington’s disease

    Science.gov (United States)

    Paul, Bindu D.; Sbodio, Juan I.; Xu, Risheng; Vandiver, M. Scott; Cha, Jiyoung Y.; Snowman, Adele M.; Snyder, Solomon H.

    2015-01-01

    Huntington’s disease is an autosomal dominant disease associated with a mutation in the gene encoding huntingtin (Htt) leading to expanded polyglutamine repeats of mutant Htt (mHtt) that elicit oxidative stress, neurotoxicity, and motor and behavioural changes1. Huntington’s disease is characterized by highly selective and profound damage to the corpus striatum, which regulates motor function. Striatal selectivity of Huntington’s disease may reflect the striatally selective small G protein Rhes binding to mHtt and enhancing its neurotoxicity2. Specific molecular mechanisms by which mHtt elicits neurodegeneration have been hard to determine. Here we show a major depletion of cystathionine γ-lyase (CSE), the biosynthetic enzyme for cysteine, in Huntington’s disease tissues, which may mediate Huntington’s disease pathophysiology. The defect occurs at the transcriptional level and seems to reflect influences of mHtt on specificity protein 1, a transcriptional activator for CSE. Consistent with the notion of loss of CSE as a pathogenic mechanism, supplementation with cysteine reverses abnormalities in cultures of Huntington’s disease tissues and in intact mouse models of Huntington’s disease, suggesting therapeutic potential. PMID:24670645

  18. Compensatory mechanisms in genetic models of neurodegeneration: are the mice better than humans?

    Directory of Open Access Journals (Sweden)

    Grzegorz eKreiner

    2015-03-01

    Full Text Available Neurodegenerative diseases are one of the main causes of mental and physical disabilities. Neurodegeneration has been estimated to begin many years before the first clinical symptoms manifest, and even a prompt diagnosis at this stage provides very little advantage for a more effective treatment as the currently available pharmacotherapies are based on disease symptomatology. The etiology of the majority of neurodegenerative diseases remains unknown, and even for those diseases caused by identified genetic mutations, the direct pathways from gene alteration to final cell death have not yet been fully elucidated. Advancements in genetic engineering have provided many transgenic mice that are used as an alternative to pharmacological models of neurodegenerative diseases. Surprisingly, even the models reiterating the same causative mutations do not fully recapitulate the inevitable neuronal loss, and some fail to even show phenotypic alterations, which suggests the possible existence of compensatory mechanisms. A better evaluation of these mechanisms may not only help us to explain why neurodegenerative diseases are mostly late-onset disorders in humans but may also provide new markers and targets for novel strategies designed to extend neuronal function and survival. The aim of this mini-review is to draw attention to this under-explored field in which investigations may reasonably contribute to unveiling hidden reserves in the organism.

  19. Neurodegeneration caused by expression of human truncated tau leads to progressive neurobehavioural impairment in transgenic rats.

    Science.gov (United States)

    Hrnkova, Miroslava; Zilka, Norbert; Minichova, Zuzana; Koson, Peter; Novak, Michal

    2007-01-26

    Human truncated tau protein is an active constituent of the neurofibrillary degeneration in sporadic Alzheimer's disease. We have shown that modified tau protein, when expressed as a transgene in rats, induced AD characteristic tau cascade consisting of tau hyperphosphorylation, formation of argyrophilic tangles and sarcosyl-insoluble tau complexes. These pathological changes led to the functional impairment characterized by a variety of neurobehavioural symptoms. In the present study we have focused on the behavioural alterations induced by transgenic expression of human truncated tau. Transgenic rats underwent a battery of behavioural tests involving cognitive- and sensorimotor-dependent tasks accompanied with neurological assessment at the age of 4.5, 6 and 9 months. Behavioural examination of these rats showed altered spatial navigation in Morris water maze resulting in less time spent in target quadrant (popen field was not influenced by transgene expression. However beam walking test revealed that transgenic rats developed progressive sensorimotor disturbances related to the age of tested animals. The disturbances were most pronounced at the age of 9 months (p<0.01). Neurological alterations indicating impaired reflex responses were other added features of behavioural phenotype of this novel transgenic rat. These results allow us to suggest that neurodegeneration, caused by the non-mutated human truncated tau derived from sporadic human AD, result in the neuronal dysfunction consequently leading to the progressive neurobehavioural impairment.

  20. Bifenthrin causes neurite retraction in the absence of cell death: a model for pesticide associated neurodegeneration.

    Science.gov (United States)

    Nandi, Avishek; Chandil, Daljit; Lechesal, Rethabile; Pryor, Stephen C; McLaughlin, Ashlea; Bonventre, Josephine A; Flynnx, Katherine; Weeks, Benjamin S

    2006-05-01

    Bifenthrin is a synthetic pyrethroid insecticide derivative of naturally occurring pyrethrins from chrysanthemum flowers. Bifenthrin is considered relatively safe and therefore incorporated as the active ingredient in preparations sold over the counter for household use. Recent studies have raised concern that chronic exposure to pesticides in the home setting may increase the risk for neurodegenerative diseases. To address this concer, in the present study, bifenthrin is added to pre-differentiated PC12 and effect of bifenthrin on the retraction of existing neurites is observed a model for neurodegeneration. PC12 cells were differentiated with nerve growth factor for twenty-four hours and then treated with what was determined to be a sublethal dose of bifenthrin for up to an additional 48 hours. The percent of cells with neurites was assessed at various times before and after nerve growth factor treatment. Bifenthrin toxicity was determined using trypan blue exclusion. Bifenthrin was not toxic to PC12 cells at concentrations ranging from 1 x 10(-10) M to 1 x 10(-4) M. Twenty-four hours after nerve growth factor treatment, a maximum percent of cells had formed neurites and with a treatment of 1 x 10(-5) M bifenthrin, approximately 80% of these neurites retracted in within 12 additional hours and almost all neurites had retracted within 48 hours. Trypan exclusion showed that these cells were viable. These data show that bifenthrin can stimulate the retraction of neurites in the absence of frank toxicity.

  1. Neurodegeneration after mild and repetitive traumatic brain injury: Chronic traumatic encepalopathy

    Directory of Open Access Journals (Sweden)

    Stanescu Ioana

    2015-09-01

    Full Text Available Repetitive brain trauma is associated with a progressive neurological deterioration, now termed as chronic traumatic encephalopathy (CTE. Although research on the long-term effects of TBI is advancing quickly, the incidence and prevalence of post-traumatic neurodegeneration and CTE are unknown. The incidence and prevalence of chronic traumatic encephalopathy and the genetic risk factors critical to its development are currently under research. CTE can be diagnosed only by post mortem neuropathological examination of the brain. Great efforts are being made to better understand the clinical signs and symptoms of CTE, obtained in most cases retrospectively from families of affected persons.Patients with CTE are described as having behavioral, mood, cognitive and motor impairments, occurring after a long latency from the traumatic events. Recent pathogenetic studies have provided new insights to CTE mechanisms, offering important clues in understanding neurodegenerative process and relations between physical factors and pathologic protein deposition. Further research is needed to better identify the genetic and environmental risk factors for CTE, as well as rehabilitation and treatment strategies.

  2. Use of Okadaic Acid to Identify Relevant Phosphoepitopes in Pathology: A Focus on Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Jesús Avila

    2013-05-01

    Full Text Available Protein phosphorylation is involved in the regulation of a wide variety of physiological processes and is the result of a balance between protein kinase and phosphatase activities. Biologically active marine derived compounds have been shown to represent an interesting source of novel compounds that could modify that balance. Among them, the marine toxin and tumor promoter, okadaic acid (OA, has been shown as an inhibitor of two of the main cytosolic, broad-specificity protein phosphatases, PP1 and PP2A, thus providing an excellent cell-permeable probe for examining the role of protein phosphorylation, and PP1 and PP2A in particular, in any physiological or pathological process. In the present work, we review the use of okadaic acid to identify specific phosphoepitopes mainly in proteins relevant for neurodegeneration. We will specifically highlight those cases of highly dynamic phosphorylation-dephosphorylation events and the ability of OA to block the high turnover phosphorylation, thus allowing the detection of modified residues that could be otherwise difficult to identify. Finally, its effect on tau hyperhosphorylation and its relevance in neurodegenerative pathologies such as Alzheimer’s disease and related dementia will be discussed.

  3. KCa2 and KCa3 channels in learning and memory processes, and neurodegeneration

    Directory of Open Access Journals (Sweden)

    Els F. E. Kuiper

    2012-06-01

    Full Text Available Calcium-activated potassium (KCa channels are present throughout the central nervous system as well as many peripheral tissues. Activation of KCa channels is essential for maintenance of the neuronal membrane potential and was shown to underlie the afterhyperpolarization (AHP that regulates action potential firing and limits the firing frequency of repetitive action potentials. Different subtypes of KCa channels were anticipated on the basis of their physiological and pharmacological profiles, and cloning revealed two well defined but phylogenetic distantly related groups of channels. The group subject of this review includes both the small-conductance KCa2 channels (KCa2.1, KCa2.2, and KCa2.3 and the intermediate-conductance (KCa3.1 channel. These channels are activated by submicromolar intracellular Ca2+ concentrations and are voltage independent. Of all KCa channels only the KCa2 channels can be potently but differentially blocked by the bee-venom apamin. In the past few years modulation of KCa channel activation revealed new roles for KCa2 channels in controlling dendritic excitability, synaptic functioning and synaptic plasticity. Furthermore, KCa2 channels appeared to be involved in neurodegeneration, and learning and memory processes. In this review, we focus on the role of KCa2 and KCa3 channels in these latter mechanisms with emphasis on learning and memory, Alzheimer’s disease and on the interplay between neuroinflammation and different neurotransmitters/neuromodulators, their signalling components and KCa channel activation.

  4. Sirtuin-2 Protects Neural Cells from Oxidative Stress and Is Elevated in Neurodegeneration

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    Preeti Singh

    2017-01-01

    Full Text Available Sirtuins are highly conserved lysine deacetylases involved in ageing, energy production, and lifespan extension. The mammalian SIRT2 has been implicated in Parkinson’s disease (PD where studies suggest SIRT2 promotes neurodegeneration. We therefore evaluated the effects of SIRT2 manipulation in toxin treated SH-SY5Y cells and determined the expression and activity of SIRT2 in postmortem brain tissue from patients with PD. SH-SY5Y viability in response to oxidative stress induced by diquat or rotenone was measured following SIRT2 overexpression or inhibition of deacetylase activity, along with α-synuclein aggregation. SIRT2 in human tissues was evaluated using Western blotting, immunohistochemistry, and fluorometric activity assays. In SH-SY5Y cells, elevated SIRT2 protected cells from rotenone or diquat induced cell death and enzymatic inhibition of SIRT2 enhanced cell death. SIRT2 protection was mediated, in part, through elevated SOD2 expression. SIRT2 reduced the formation of α-synuclein aggregates but showed minimal colocalisation with α-synuclein. In postmortem PD brain tissue, SIRT2 activity was elevated compared to controls but also elevated in other neurodegenerative disorders. Results from both in vitro work and brain tissue suggest that SIRT2 is necessary for protection against oxidative stress and higher SIRT2 activity in PD brain may be a compensatory mechanism to combat neuronal stress.

  5. Retinal Vascular Fractals Correlate With Early Neurodegeneration in Patients With Type 2 Diabetes Mellitus

    DEFF Research Database (Denmark)

    Frydkjaer-Olsen, Ulrik; Soegaard Hansen, Rasmus; Pedersen, Knud

    2015-01-01

    . In a randomly selected eye of each patient, Fd was calculated using SIVA-Fractal, a specialized semiautomatic software. Retinal neurodegeneration was evaluated by Topcon 3D OCT-2000 spectral-domain optical coherence tomography (OCT) and by a RETI-scan multifocal ERG (mf-ERG) system in rings one to six. Level...... were 10 (42.7%), 20 (35.0%), and 35 (22.3%), respectively. Fd correlated inversely with mf-ERG implicit time of ring one (r = -0.25, P = 0.01) and present diabetic neuropathy (P = 0.02), and positively with OCT ganglion cell layer (GCL) thickness (r = 0.20, P = 0.04). In a multivariable linear...... regression model, Fd was associated with mf-ERG implicit time of ring one (coefficient -0.0021/ms, P = 0.040) and the presence of diabetic neuropathy (coefficient -0.0209 for neuropathy present versus absent, P = 0.041). Conclusions: In patients with T2DM and no or minimal DR, independent correlations were...

  6. AP-1 proteins in the adult brain: facts and fiction about effectors of neuroprotection and neurodegeneration.

    Science.gov (United States)

    Herdegen, T; Waetzig, V

    2001-04-30

    Jun and Fos proteins are induced and activated following most physiological and pathophysiological stimuli in the brain. Only few data allow conclusions about distinct functions of AP-1 proteins in neurodegeneration and neuroregeneration, and these functions mainly refer to c-Jun and its activation by JNKs. Apoptotic functions of activated c-Jun affect hippocampal, nigral and primary cultured neurons following excitotoxic stimulation and destruction of the neuron-target-axis including withdrawal of trophic molecules. The inhibition of JNKs might exert neuroprotection by subsequent omission of c-Jun activation. Besides endogenous neuronal functions, the c-Jun/AP-1 proteins can damage the nervous system by upregulation of harmful programs in non-neuronal cells (e.g. microglia) with release of neurodegenerative molecules. In contrast, the differentiation with neurite extension and maturation of neural cells in vitro indicate physiological and potentially neuroprotective functions of c-Jun and JNKs including sensoring for alterations in the cytoskeleton. This review summarizes the multiple molecular interfunctions which are involved in the shift from the physiological role to degenerative effects of the Jun/JNK-axis such as cell type-specific expression and intracellular localization of scaffold proteins and upstream activators, antagonistic phosphatases, interaction with other kinase systems, or the activation of transcription factors competing for binding to JNK proteins and AP-1 DNA elements.

  7. Puzzles in modern biology. IV. Neurodegeneration, localized origin and widespread decay [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Steven A. Frank

    2016-10-01

    Full Text Available The motor neuron disease amyotrophic lateral sclerosis (ALS typically begins with localized muscle weakness. Progressive, widespread paralysis often follows over a few years. Does the disease begin with local changes in a small piece of neural tissue and then spread? Or does neural decay happen independently across diverse spatial locations? The distinction matters, because local initiation may arise by local changes in a tissue microenvironment, by somatic mutation, or by various epigenetic or regulatory fluctuations in a few cells. A local trigger must be coupled with a mechanism for spread. By contrast, independent decay across spatial locations cannot begin by a local change, but must depend on some global predisposition or spatially distributed change that leads to approximately synchronous decay. This article outlines the conceptual frame by which one contrasts local triggers and spread versus parallel spatially distributed decay. Various neurodegenerative diseases differ in their mechanistic details, but all can usefully be understood as falling along a continuum of interacting local and global processes. Cancer provides an example of disease progression by local triggers and spatial spread, setting a conceptual basis for clarifying puzzles in neurodegeneration. Heart disease also has crucial interactions between global processes, such as circulating lipid levels, and local processes in the development of atherosclerotic plaques. The distinction between local and global processes helps to understand these various age-related diseases.

  8. A saposin deficiency model in Drosophila: Lysosomal storage, progressive neurodegeneration and sensory physiological decline.

    Science.gov (United States)

    Hindle, Samantha J; Hebbar, Sarita; Schwudke, Dominik; Elliott, Christopher J H; Sweeney, Sean T

    2017-02-01

    Saposin deficiency is a childhood neurodegenerative lysosomal storage disorder (LSD) that can cause premature death within three months of life. Saposins are activator proteins that promote the function of lysosomal hydrolases that mediate the degradation of sphingolipids. There are four saposin proteins in humans, which are encoded by the prosaposin gene. Mutations causing an absence or impaired function of individual saposins or the whole prosaposin gene lead to distinct LSDs due to the storage of different classes of sphingolipids. The pathological events leading to neuronal dysfunction induced by lysosomal storage of sphingolipids are as yet poorly defined. We have generated and characterised a Drosophila model of saposin deficiency that shows striking similarities to the human diseases. Drosophila saposin-related (dSap-r) mutants show a reduced longevity, progressive neurodegeneration, lysosomal storage, dramatic swelling of neuronal soma, perturbations in sphingolipid catabolism, and sensory physiological deterioration. Our data suggests a genetic interaction with a calcium exchanger (Calx) pointing to a possible calcium homeostasis deficit in dSap-r mutants. Together these findings support the use of dSap-r mutants in advancing our understanding of the cellular pathology implicated in saposin deficiency and related LSDs. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  9. REM Sleep Behavior Disorder and Prodromal Neurodegeneration - Where are We Headed?

    Directory of Open Access Journals (Sweden)

    Ronald B. Postuma

    2013-04-01

    Full Text Available Rapid eye movement (REM sleep behavior disorder (RBD is characterized by loss of normal atonia during REM sleep, such that patients appear to act out their dreams. The most important implication of research into this area is that patients with idiopathic RBD are at very high risk of developing synucleinmediated neurodegenerative disease (Parkinson's disease [PD], dementia with Lewy bodies [DLB], and multiple system atrophy, with risk estimates that approximate 40–65% at 10 years. Thus, RBD disorder is a very strong feature of prodromal synucleinopathy. This provides several opportunities for future research. First, patients with REM sleep behavior disorder can be studied to test other predictors of disease, which could potentially be applied to the general population. These studies have demonstrated that olfactory loss, decreased color vision, slowing on quantitative motor testing, and abnormal substantia nigra neuroimaging findings can predict clinical synucleinopathy. Second, prospectively studying patients with RBD allows a completely unprecedented opportunity to directly evaluate patients as they transition into clinical neurodegenerative disease. Studies assessing progression of markers of neurodegeneration in prodromal PD are beginning to appear. Third, RBD are very promising subjects for neuroprotective therapy trials because they have a high risk of disease conversion with a sufficiently long latency, which provides an opportunity for early intervention. As RBD research expands, collaboration between centers will become increasingly essential.

  10. Autophagy and Neurodegeneration: Insights from a Cultured Cell Model of ALS

    Directory of Open Access Journals (Sweden)

    Francesca Navone

    2015-08-01

    Full Text Available Autophagy plays a major role in the elimination of cellular waste components, the renewal of intracellular proteins and the prevention of the build-up of redundant or defective material. It is fundamental for the maintenance of homeostasis and especially important in post-mitotic neuronal cells, which, without competent autophagy, accumulate protein aggregates and degenerate. Many neurodegenerative diseases are associated with defective autophagy; however, whether altered protein turnover or accumulation of misfolded, aggregate-prone proteins is the primary insult in neurodegeneration has long been a matter of debate. Amyotrophic lateral sclerosis (ALS is a fatal disease characterized by selective degeneration of motor neurons. Most of the ALS cases occur in sporadic forms (SALS, while 10%–15% of the cases have a positive familial history (FALS. The accumulation in the cell of misfolded/abnormal proteins is a hallmark of both SALS and FALS, and altered protein degradation due to autophagy dysregulation has been proposed to contribute to ALS pathogenesis. In this review, we focus on the main molecular features of autophagy to provide a framework for discussion of our recent findings about the role in disease pathogenesis of the ALS-linked form of the VAPB gene product, a mutant protein that drives the generation of unusual cytoplasmic inclusions.

  11. Missense variants in AIMP1 gene are implicated in autosomal recessive intellectual disability without neurodegeneration.

    Science.gov (United States)

    Iqbal, Zafar; Püttmann, Lucia; Musante, Luciana; Razzaq, Attia; Zahoor, Muhammad Yasir; Hu, Hao; Wienker, Thomas F; Garshasbi, Masoud; Fattahi, Zohreh; Gilissen, Christian; Vissers, Lisenka E L M; de Brouwer, Arjan P M; Veltman, Joris A; Pfundt, Rolph; Najmabadi, Hossein; Ropers, Hans-Hilger; Riazuddin, Sheikh; Kahrizi, Kimia; van Bokhoven, Hans

    2016-03-01

    AIMP1/p43 is a multifunctional non-catalytic component of the multisynthetase complex. The complex consists of nine catalytic and three non-catalytic proteins, which catalyze the ligation of amino acids to their cognate tRNA isoacceptors for use in protein translation. To date, two allelic variants in the AIMP1 gene have been reported as the underlying cause of autosomal recessive primary neurodegenerative disorder. Here, we present two consanguineous families from Pakistan and Iran, presenting with moderate to severe intellectual disability, global developmental delay, and speech impairment without neurodegeneration. By the combination of homozygosity mapping and next generation sequencing, we identified two homozygous missense variants, p.(Gly299Arg) and p.(Val176Gly), in the gene AIMP1 that co-segregated with the phenotype in the respective families. Molecular modeling of the variants revealed deleterious effects on the protein structure that are predicted to result in reduced AIMP1 function. Our findings indicate that the clinical spectrum for AIMP1 defects is broader than witnessed so far.

  12. Missense variants in AIMP1 gene are implicated in autosomal recessive intellectual disability without neurodegeneration

    Science.gov (United States)

    Iqbal, Zafar; Püttmann, Lucia; Musante, Luciana; Razzaq, Attia; Zahoor, Muhammad Yasir; Hu, Hao; Wienker, Thomas F; Garshasbi, Masoud; Fattahi, Zohreh; Gilissen, Christian; Vissers, Lisenka ELM; de Brouwer, Arjan PM; Veltman, Joris A; Pfundt, Rolph; Najmabadi, Hossein; Ropers, Hans-Hilger; Riazuddin, Sheikh; Kahrizi, Kimia; van Bokhoven, Hans

    2016-01-01

    AIMP1/p43 is a multifunctional non-catalytic component of the multisynthetase complex. The complex consists of nine catalytic and three non-catalytic proteins, which catalyze the ligation of amino acids to their cognate tRNA isoacceptors for use in protein translation. To date, two allelic variants in the AIMP1 gene have been reported as the underlying cause of autosomal recessive primary neurodegenerative disorder. Here, we present two consanguineous families from Pakistan and Iran, presenting with moderate to severe intellectual disability, global developmental delay, and speech impairment without neurodegeneration. By the combination of homozygosity mapping and next generation sequencing, we identified two homozygous missense variants, p.(Gly299Arg) and p.(Val176Gly), in the gene AIMP1 that co-segregated with the phenotype in the respective families. Molecular modeling of the variants revealed deleterious effects on the protein structure that are predicted to result in reduced AIMP1 function. Our findings indicate that the clinical spectrum for AIMP1 defects is broader than witnessed so far. PMID:26173967

  13. Endosomal sorting complexes required for ESCRTing cells toward death during neurogenesis, neurodevelopment and neurodegeneration.

    Science.gov (United States)

    Kaul, Zenia; Chakrabarti, Oishee

    2018-03-25

    The endosomal sorting complexes required for transport (ESCRT) proteins help in the recognition, sorting and degradation of ubiquitinated cargoes from the cell surface, long-lived proteins or aggregates, and aged organelles present in the cytosol. These proteins take part in the endo-lysosomal system of degradation. The ESCRT proteins also play an integral role in cytokinesis, viral budding and mRNA transport. Many neurodegenerative diseases are caused by toxic accumulation of cargo in the cell, which causes stress and ultimately leads to neuronal death. This accumulation of cargo occurs because of defects in the endo-lysosomal degradative pathway-loss of function of ESCRTs has been implicated in this mechanism. ESCRTs also take part in many survival processes, lack of which can culminate in neuronal cell death. While the role played by the ESCRT proteins in maintaining healthy neurons is known, their role in neurodegenerative diseases is still poorly understood. In this review, we highlight the importance of ESCRTs in maintaining healthy neurons and then suggest how perturbations in many of the survival mechanisms governed by these proteins could eventually lead to cell death; quite often these correlations are not so obviously laid out. Extensive neuronal death eventually culminates in neurodegeneration. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Phosphatidylinositol-glycan-phospholipase D is involved in neurodegeneration in prion disease.

    Directory of Open Access Journals (Sweden)

    Jae-Kwang Jin

    Full Text Available PrPSc is formed from a normal glycosylphosphatidylinositol (GPI-anchored prion protein (PrPC by a posttranslational modification. Most GPI-anchored proteins have been shown to be cleaved by GPI phospholipases. Recently, GPI-phospholipase D (GPI-PLD was shown to be a strictly specific enzyme for GPI anchors. To investigate the involvement of GPI-PLD in the processes of neurodegeneration in prion diseases, we examined the mRNA and protein expression levels of GPI-PLD in the brains of a prion animal model (scrapie, and in both the brains and cerebrospinal fluids (CSF of sporadic and familial Creutzfeldt-Jakob disease (CJD patients. We found that compared with controls, the expression of GPI-PLD was dramatically down-regulated in the brains of scrapie-infected mice, especially in the caveolin-enriched membrane fractions. Interestingly, the observed decrease in GPI-PLD expression levels began at the same time that PrPSc began to accumulate in the infected brains and this decrease was also observed in both the brain and CSF of CJD patients; however, no differences in expression were observed in either the brains or CSF specimens from Alzheimer's disease patients. Taken together, these results suggest that the down-regulation of GPI-PLD protein may be involved in prion propagation in the brains of prion diseases.

  15. Mitochondrial deficiency: a double-edged sword for ageing and neurodegeneration

    Directory of Open Access Journals (Sweden)

    Daniele eBano

    2012-11-01

    Full Text Available For decades, ageing was considered the inevitable result of the accumulation of damaged macromolecules due to environmental factors and intrinsic processes. Our current knowledge clearly supports that ageing is a complex biological process influenced by multiple evolutionary conserved molecular pathways. With the advanced age, loss of cellular homeostasis severely affects the structure and function of various tissues, especially those highly sensitive to stressful conditions like the central nervous system. In this regard, the age-related regression of neural circuits and the consequent poor neuronal plasticity have been associated with metabolic dysfunctions, in which the decline of mitochondrial activity significantly contributes. Interestingly, while mitochondrial lesions promote the onset of degenerative disorders, mild mitochondrial manipulations delay some of the age-related phenotypes and, more importantly, increase the lifespan of organisms ranging from invertebrates to mammals. Here, we survey the insulin/IGF-1 and the TOR signaling pathways and review how these two important longevity determinants regulate mitochondrial activity. Furthermore, we discuss the contribution of slight mitochondrial dysfunction in the engagement of pro-longevity processes and the opposite role of strong mitochondrial dysfunction in neurodegeneration.

  16. The m-AAA Protease Associated with Neurodegeneration Limits MCU Activity in Mitochondria.

    Science.gov (United States)

    König, Tim; Tröder, Simon E; Bakka, Kavya; Korwitz, Anne; Richter-Dennerlein, Ricarda; Lampe, Philipp A; Patron, Maria; Mühlmeister, Mareike; Guerrero-Castillo, Sergio; Brandt, Ulrich; Decker, Thorsten; Lauria, Ines; Paggio, Angela; Rizzuto, Rosario; Rugarli, Elena I; De Stefani, Diego; Langer, Thomas

    2016-10-06

    Mutations in subunits of mitochondrial m-AAA proteases in the inner membrane cause neurodegeneration in spinocerebellar ataxia (SCA28) and hereditary spastic paraplegia (HSP7). m-AAA proteases preserve mitochondrial proteostasis, mitochondrial morphology, and efficient OXPHOS activity, but the cause for neuronal loss in disease is unknown. We have determined the neuronal interactome of m-AAA proteases in mice and identified a complex with C2ORF47 (termed MAIP1), which counteracts cell death by regulating the assembly of the mitochondrial Ca 2+ uniporter MCU. While MAIP1 assists biogenesis of the MCU subunit EMRE, the m-AAA protease degrades non-assembled EMRE and ensures efficient assembly of gatekeeper subunits with MCU. Loss of the m-AAA protease results in accumulation of constitutively active MCU-EMRE channels lacking gatekeeper subunits in neuronal mitochondria and facilitates mitochondrial Ca 2+ overload, mitochondrial permeability transition pore opening, and neuronal death. Together, our results explain neuronal loss in m-AAA protease deficiency by deregulated mitochondrial Ca 2+ homeostasis. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. The Role of Microglia in Diabetic Retinopathy: Inflammation, Microvasculature Defects and Neurodegeneration

    Science.gov (United States)

    Altmann, Christine

    2018-01-01

    Diabetic retinopathy is a common complication of diabetes mellitus, which appears in one third of all diabetic patients and is a prominent cause of vision loss. First discovered as a microvascular disease, intensive research in the field identified inflammation and neurodegeneration to be part of diabetic retinopathy. Microglia, the resident monocytes of the retina, are activated due to a complex interplay between the different cell types of the retina and diverse pathological pathways. The trigger for developing diabetic retinopathy is diabetes-induced hyperglycemia, accompanied by leukostasis and vascular leakages. Transcriptional changes in activated microglia, mediated via the nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) and extracellular signal–regulated kinase (ERK) signaling pathways, results in release of various pro-inflammatory mediators, including cytokines, chemokines, caspases and glutamate. Activated microglia additionally increased proliferation and migration. Among other consequences, these changes in microglia severely affected retinal neurons, causing increased apoptosis and subsequent thinning of the nerve fiber layer, resulting in visual loss. New potential therapeutics need to interfere with these diabetic complications even before changes in the retina are diagnosed, to prevent neuronal apoptosis and blindness in patients. PMID:29301251

  18. Retinal neurodegeneration may precede microvascular changes characteristic of diabetic retinopathy in diabetes mellitus.

    Science.gov (United States)

    Sohn, Elliott H; van Dijk, Hille W; Jiao, Chunhua; Kok, Pauline H B; Jeong, Woojin; Demirkaya, Nazli; Garmager, Allison; Wit, Ferdinand; Kucukevcilioglu, Murat; van Velthoven, Mirjam E J; DeVries, J Hans; Mullins, Robert F; Kuehn, Markus H; Schlingemann, Reinier Otto; Sonka, Milan; Verbraak, Frank D; Abràmoff, Michael David

    2016-05-10

    Diabetic retinopathy (DR) has long been recognized as a microvasculopathy, but retinal diabetic neuropathy (RDN), characterized by inner retinal neurodegeneration, also occurs in people with diabetes mellitus (DM). We report that in 45 people with DM and no to minimal DR there was significant, progressive loss of the nerve fiber layer (NFL) (0.25 μm/y) and the ganglion cell (GC)/inner plexiform layer (0.29 μm/y) on optical coherence tomography analysis (OCT) over a 4-y period, independent of glycated hemoglobin, age, and sex. The NFL was significantly thinner (17.3 μm) in the eyes of six donors with DM than in the eyes of six similarly aged control donors (30.4 μm), although retinal capillary density did not differ in the two groups. We confirmed significant, progressive inner retinal thinning in streptozotocin-induced "type 1" and B6.BKS(D)-Lepr(db)/J "type 2" diabetic mouse models on OCT; immunohistochemistry in type 1 mice showed GC loss but no difference in pericyte density or acellular capillaries. The results suggest that RDN may precede the established clinical and morphometric vascular changes caused by DM and represent a paradigm shift in our understanding of ocular diabetic complications.

  19. Moringa oleifera Mitigates Memory Impairment and Neurodegeneration in Animal Model of Age-Related Dementia

    Directory of Open Access Journals (Sweden)

    Chatchada Sutalangka

    2013-01-01

    Full Text Available To date, the preventive strategy against dementia is still essential due to the rapid growth of its prevalence and the limited therapeutic efficacy. Based on the crucial role of oxidative stress in age-related dementia and the antioxidant and nootropic activities of Moringa oleifera, the enhancement of spatial memory and neuroprotection of M. oleifera leaves extract in animal model of age-related dementia was determined. The possible underlying mechanism was also investigated. Male Wistar rats, weighing 180–220 g, were orally given M. oleifera leaves extract at doses of 100, 200, and 400 mg/kg at a period of 7 days before and 7 days after the intracerebroventricular administration of AF64A bilaterally. Then, they were assessed memory, neuron density, MDA level, and the activities of SOD, CAT, GSH-Px, and AChE in hippocampus. The results showed that the extract improved spatial memory and neurodegeneration in CA1, CA2, CA3, and dentate gyrus of hippocampus together with the decreased MDA level and AChE activity but increased SOD and CAT activities. Therefore, our data suggest that M. oleifera leaves extract is the potential cognitive enhancer and neuroprotectant. The possible mechanism might occur partly via the decreased oxidative stress and the enhanced cholinergic function. However, further explorations concerning active ingredient(s are still required.

  20. Grey matter alterations in patients with Pantothenate Kinase-Associated Neurodegeneration (PKAN).

    Science.gov (United States)

    Rodriguez-Raecke, Rea; Roa-Sanchez, Pedro; Speckter, Herwin; Fermin-Delgado, Rafael; Perez-Then, Eddy; Oviedo, Jairo; Stoeter, Peter

    2014-09-01

    Pantothenate Kinase-Associated Neurodegeneration (PKAN) is a rare heritable disease marked by dystonia and loss of movement control. In contrast to the well-known "Eye-of-the-Tiger" sign affecting the globus pallidus, little is known about other deviations of brain morphology, especially about grey matter changes. We investigated 29 patients with PKAN and 29 age-matched healthy controls using Magnet Resonance Imaging and Voxel-Based Morphometry. As compared to controls, children with PKAN showed increased grey matter density in the putamen and nucleus caudatus and adults with PKAN showed increased grey matter density in the ventral part of the anterior cingulate cortex. A multiple regression analysis with dystonia score as predictor showed grey matter reduction in the cerebellum, posterior cingulate cortex, superior parietal lobule, pars triangularis and small frontal and temporal areas and an analysis with age as predictor showed grey matter decreases in the putamen, nucleus caudatus, supplementary motor area and anterior cingulate cortex. The grey matter increases may be regarded as a secondary phenomenon compensating the increased activity of the motor system due to a reduced inhibitory output of the globus pallidus. With increasing age, the grey matter reduction of cortical midline structures however might contribute to the progression of dystonic symptoms due to loss of this compensatory control. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Whey protein concentrate supplementation protects rat brain against aging-induced oxidative stress and neurodegeneration.

    Science.gov (United States)

    Garg, Geetika; Singh, Sandeep; Singh, Abhishek Kumar; Rizvi, Syed Ibrahim

    2018-05-01

    Whey protein concentrate (WPC) is a rich source of sulfur-containing amino acids and is consumed as a functional food, incorporating a wide range of nutritional attributes. The purpose of this study is to evaluate the neuroprotective effect of WPC on rat brain during aging. Young (4 months) and old (24 months) male Wistar rats were supplemented with WPC (300 mg/kg body weight) for 28 days. Biomarkers of oxidative stress and antioxidant capacity in terms of ferric reducing antioxidant potential (FRAP), lipid hydroperoxide (LHP), total thiol (T-SH), protein carbonyl (PC), reactive oxygen species (ROS), nitric oxide (NO), and acetylcholinesterase (AChE) activity were measured in brain of control and experimental (WPC supplemented) groups. In addition, gene expression and histopathological studies were also performed. The results indicate that WPC augmented the level of FRAP, T-SH, and AChE in old rats as compared with the old control. Furthermore, WPC-treated groups exhibited significant reduction in LHP, PC, ROS, and NO levels in aged rats. WPC supplementation also downregulated the expression of inflammatory markers (tumor necrosis factor alpha, interleukin (IL)-1β, IL-6), and upregulated the expression of marker genes associated with autophagy (Atg3, Beclin-1, LC3B) and neurodegeneration (neuron specific enolase, Synapsin-I, MBP-2). The findings suggested WPC to be a potential functional nutritional food supplement that prevents the progression of age-related oxidative damage in Wistar rats.

  2. Neurodegeneration and functional impairments associated with glycogen synthase accumulation in a mouse model of Lafora disease.

    Science.gov (United States)

    Valles-Ortega, Jordi; Duran, Jordi; Garcia-Rocha, Mar; Bosch, Carles; Saez, Isabel; Pujadas, Lluís; Serafin, Anna; Cañas, Xavier; Soriano, Eduardo; Delgado-García, José M; Gruart, Agnès; Guinovart, Joan J

    2011-11-01

    Lafora disease (LD) is caused by mutations in either the laforin or malin gene. The hallmark of the disease is the accumulation of polyglucosan inclusions called Lafora Bodies (LBs). Malin knockout (KO) mice present polyglucosan accumulations in several brain areas, as do patients of LD. These structures are abundant in the cerebellum and hippocampus. Here, we report a large increase in glycogen synthase (GS) in these mice, in which the enzyme accumulates in LBs. Our study focused on the hippocampus where, under physiological conditions, astrocytes and parvalbumin-positive (PV(+)) interneurons expressed GS and malin. Although LBs have been described only in neurons, we found this polyglucosan accumulation in the astrocytes of the KO mice. They also had LBs in the soma and some processes of PV(+) interneurons. This phenomenon was accompanied by the progressive loss of these neuronal cells and, importantly, neurophysiological alterations potentially related to impairment of hippocampal function. Our results emphasize the relevance of the laforin-malin complex in the control of glycogen metabolism and highlight altered glycogen accumulation as a key contributor to neurodegeneration in LD. Copyright © 2011 EMBO Molecular Medicine.

  3. 大學圖書館電子資源之需求分析與行銷策略之研究 A Study of Demands Analysis and Marketing Strategy of Electronic Resources in University Library

    Directory of Open Access Journals (Sweden)

    Huang-Yu Liu

    2008-03-01

    Full Text Available 電子資源的出現,使得知識載體有了新的突破,提高了使用者的便利性與即時性。對於圖書館而言,如何使電子資源的使用效益達到最高,必須思考一套有效的行銷策略。電子資源行銷概念應以讀者為導向,尊重讀者的資訊需求,並利用各種宣傳技巧,行銷電子資源,使圖書館能提供更完善的服務。本研究之目的旨在探討讀者的使用需求及電子資源的推廣策略,以獲致最有效益的行銷方式。研究對象以開南大學日間部四學院(商學院、運輸觀光學院、資訊學院、人文社會學院)學生為樣本,佐以缺口分析模型為分析架構,藉以找出個案中讀者/學生對於電子資源使用的真實需求,並進而歸納出提供服務的大學圖書館在其推廣或行銷服務上可有的因應策略。The emergence of electronic resources has made new breakthrough in knowledge carriers because of their ease of use, instant availability, and the characteristic of no time and space constraints. For public libraries to achieve maximum efficiency in its electronic resources, it is necessary to seek the most effective marketing strategies. Therefore, the marketing concept of the electronic resources should be reader oriented, such as respecting and understanding library user’s information needs. Libraries also need to utilize various media and techniques to market the electronic resources, so that more comprehensive services and experiences can be provided to readers. The purpose of this study is to investigate library user’s needs and promotion strategies of electronic resources in order to identify the most effective ways of marketing. This study focuses on the students of the four colleges (College of Business, College of Tourism, College of Information, and College of Humanities and Social Science in Kainan University as subjects in the survey questionnaire. It uses the Gap Analysis

  4. Application of electronic learning tools for training of specialists in the field of information technologies for enterprises of mineral resources sector

    Directory of Open Access Journals (Sweden)

    Е. В. Катунцов

    2017-08-01

    Full Text Available The article shows the advantages of using modern electronic learning tools in the training of specialists for the mineral and raw materials complex and considers the basic principles of organizing training using these tools. The experience of using electronic learning tools using foreign teaching materials and involving foreign professors is described. A special attention is given to the electronic learning environment of the Cisco Networking Academy – Cisco NetAcad. The experience of teaching at the Networking Academy of the Saint-Petersburg Mining University is described. Details are given to modern virtual environments for laboratory work, such as Cisco Packet Tracer, GNS3 and Emulated Virtual Environment. The experience of using electronic learning technologies at the University of Economics of Bratislava is considered. It actively cooperates with a number of universities of other countries, such as the University of International Business (Almaty, the Eurasian National University named after LN Gumilyov (Astana and the Institute of Social and Humanitarian Knowledge (Kazan.

  5. An operational utility assessment [electronic resource]: measuring the effectiveness of the Joint Concept Technology Demonstration (JCTD), Joint Forces Protection Advance Security System (JFPASS)

    OpenAIRE

    McGovern, Mark; Mayor, Jeffrey D.; Symmes, Joseph

    2008-01-01

    MBA Professional Report Planning modern military operations requires an accurate intelligence assessment of potential threats, combined with a detailed assessment of the physical theater of operations. This information can then be combined with equipment and manpower resources to set up a logistically supportable operation that mitigates as much of the enemy threat as possible. Given such a daunting challenge, military planners often turn to intelligent software agents to support their...

  6. Positive Perceptions of Access to Online Library Resources Correlates with Quality and Quantity of Scholarly Publications among Finnish Academics. A Review of: Vakkari, Pertti. “Perceived Influence of the Use of Electronic Information Resources on Scholarly Work and Publication Productivity.” Journal of the American Society for Information Science and Technology 59.4 (Feb. 15, 2008: 602-12.

    Directory of Open Access Journals (Sweden)

    Scott Marsalis

    2008-12-01

    Full Text Available Objective – To investigate the relationship between academics’ use of library electronic resources and their opinions regarding how these resources have impacted their work, and to investigate the association between this perceived influence and publication productivity during the previous two years.Design – Two specific questions added to an annual online user-survey questionnaire; additional data mined from surveySetting – Twenty-two Finnish Universities served by FinELib, the Finnish Electronic Library.Subjects – Seven hundred and sixty seven academic staff and full-time doctoral students.Methods – A questionnaire was posted in April 2007 on FinELib’s homepage and advertised on each university library’s mainpage, and focused on respondents’ experience in the previous two years. Participants selected answers either from a list of category choices, or, when measuring perceptions, by rating agreement with statements along a four-point scale. Controlled variables measured were the respondents’ academic position, their discipline, membership in a research group, whether their literature use was discipline-specific or interdisciplinary, and their perception of the availability online of the relevant core literature. The independent variable measured was the scholars’ perception of the impact of the use of electronic library resources on their work. The dependent variable measured was the scholars’ self-reported publications in the two years preceding the survey.Main Results – Participants reported a positive impact on the efficiency of their work, most strongly in areas of ease of access, with lesser impacts in the range of materials available to them and the ease with which they can keep up-to-date in their field. To a lesser extent, the scholars perceived a positive impact on the quality of their work. Upon analysis, the study found that access to online library resources improved scholars’ work by the interconnected

  7. Protective effects of Erigeron breviscapus Hand.- Mazz. (EBHM) extract in retinal neurodegeneration models.

    Science.gov (United States)

    Zhu, Jingyuan; Chen, Li; Qi, Yun; Feng, Jing; Zhu, Li; Bai, Yujing; Wu, Huijuan

    2018-01-01

    To investigate the neuroprotective effects of scutellarin, an active component of the multifunctional traditional Chinese herb Erigeron breviscapus (vant.) Hand.-Mazz. (EBHM), which has been used as a neuroprotective therapy for cerebrovascular diseases. We performed the experiments using in vitro and in vivo models of retinal neurodegeneration. In the in vitro experiments, we exposed BV-2 cells to low oxygen levels in an incubator for 24 and 48 h to generate hypoxia models. We then treated these cells with scutellarin at concentrations of 2, 10, and 50 µM. Cell viability was measured using an enzyme-linked immunosorbent assay (ELISA). The levels of the components of the nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 (NLRP3) inflammasome signaling pathway, including NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), cleaved caspase-1, interleukin-18 (IL-18), and IL-1β were analyzed using western blots and ELISAs. In the in vivo study, we raised the intraocular pressure of Brown Norway rats to 60 mmHg for 30 min to generate a high intraocular pressure (HIOP) model, that is, an acute glaucoma model. The rats were then treated with scutellarin via oral gavage for 2 consecutive weeks. The relevant components of the NLRP3 inflammasome signaling pathway were analyzed with western blots and ELISAs. Retinal ganglion cells (RGCs) were retrogradely labeled using 4% Fluoro-Gold, and then the numbers of cells were calculated. Retinal microglial cells were labeled using immunofluorescence, and then the morphological changes were observed. In the in vitro cell viability experiments, 50 µM scutellarin statistically significantly enhanced the viability rate when compared to 2 µM and 10 µM scutellarin (hypoxia + 50 µM EBHM group: 94.01±2.130% and 86.02±2.520% after 24 and 48 h, respectively; hypoxia model group: 74.98±3.860% and 64.41±4.890% after 24 and 48 h, respectively; for all

  8. Protective effects of Erigeron breviscapus Hand.– Mazz. (EBHM) extract in retinal neurodegeneration models

    Science.gov (United States)

    Zhu, Jingyuan; Chen, Li; Qi, Yun; Feng, Jing; Zhu, Li; Bai, Yujing

    2018-01-01

    Purpose To investigate the neuroprotective effects of scutellarin, an active component of the multifunctional traditional Chinese herb Erigeron breviscapus (vant.) Hand.-Mazz. (EBHM), which has been used as a neuroprotective therapy for cerebrovascular diseases. We performed the experiments using in vitro and in vivo models of retinal neurodegeneration. Methods In the in vitro experiments, we exposed BV-2 cells to low oxygen levels in an incubator for 24 and 48 h to generate hypoxia models. We then treated these cells with scutellarin at concentrations of 2, 10, and 50 µM. Cell viability was measured using an enzyme-linked immunosorbent assay (ELISA). The levels of the components of the nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 (NLRP3) inflammasome signaling pathway, including NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), cleaved caspase-1, interleukin-18 (IL-18), and IL-1β were analyzed using western blots and ELISAs. In the in vivo study, we raised the intraocular pressure of Brown Norway rats to 60 mmHg for 30 min to generate a high intraocular pressure (HIOP) model, that is, an acute glaucoma model. The rats were then treated with scutellarin via oral gavage for 2 consecutive weeks. The relevant components of the NLRP3 inflammasome signaling pathway were analyzed with western blots and ELISAs. Retinal ganglion cells (RGCs) were retrogradely labeled using 4% Fluoro-Gold, and then the numbers of cells were calculated. Retinal microglial cells were labeled using immunofluorescence, and then the morphological changes were observed. Results In the in vitro cell viability experiments, 50 µM scutellarin statistically significantly enhanced the viability rate when compared to 2 µM and 10 µM scutellarin (hypoxia + 50 µM EBHM group: 94.01±2.130% and 86.02±2.520% after 24 and 48 h, respectively; hypoxia model group: 74.98±3.860% and 64.41±4.890% after 24 and 48 h

  9. Power Electronics

    DEFF Research Database (Denmark)

    Iov, Florin; Ciobotaru, Mihai; Blaabjerg, Frede

    2008-01-01

    is to change the electrical power production sources from the conventional, fossil (and short term) based energy sources to renewable energy resources. The other is to use high efficient power electronics in power generation, power transmission/distribution and end-user application. This paper discuss the most...... emerging renewable energy sources, wind energy, which by means of power electronics are changing from being a minor energy source to be acting as an important power source in the energy system. Power electronics is the enabling technology and the presentation will cover the development in wind turbine...... technology from kW to MW, discuss which power electronic solutions are most feasible and used today....

  10. Multivariate profiling of neurodegeneration-associated changes in a subcellular compartment of neurons via image processing

    Directory of Open Access Journals (Sweden)

    Kumarasamy Saravana K

    2008-11-01

    differentiates all three bchs phenotypes (loss of function as well as overexpression from the wild type. Conclusion Our model demonstrates that neurodegeneration-associated endolysosomal defects can be detected, analyzed, and classified rapidly and accurately as a diagnostic imaging-based screening tool.

  11. Presymptomatic and longitudinal neuroimaging in neurodegeneration--from snapshots to motion picture: a systematic review.

    Science.gov (United States)

    Schuster, Christina; Elamin, Marwa; Hardiman, Orla; Bede, Peter

    2015-10-01

    Recent quantitative neuroimaging studies have been successful in capturing phenotype and genotype-specific changes in dementia syndromes, amyotrophic lateral sclerosis, Parkinson's disease and other neurodegenerative conditions. However, the majority of imaging studies are cross-sectional, despite the obvious superiority of longitudinal study designs in characterising disease trajectories, response to therapy, progression rates and evaluating the presymptomatic phase of neurodegenerative conditions. The aim of this work is to perform a systematic review of longitudinal imaging initiatives in neurodegeneration focusing on methodology, optimal statistical models, follow-up intervals, attrition rates, primary study outcomes and presymptomatic studies. Longitudinal imaging studies were identified from 'PubMed' and reviewed from 1990 to 2014. The search terms 'longitudinal', 'MRI', 'presymptomatic' and 'imaging' were utilised in combination with one of the following degenerative conditions; Alzheimer's disease, amyotrophic lateral sclerosis/motor neuron disease, frontotemporal dementia, Huntington's disease, multiple sclerosis, Parkinson's disease, ataxia, HIV, alcohol abuse/dependence. A total of 423 longitudinal imaging papers and 103 genotype-based presymptomatic studies were identified and systematically reviewed. Imaging techniques, follow-up intervals and attrition rates showed significant variation depending on the primary diagnosis. Commonly used statistical models included analysis of annualised percentage change, mixed and random effect models, and non-linear cumulative models with acceleration-deceleration components. Although longitudinal imaging studies have the potential to provide crucial insights into the presymptomatic phase and natural trajectory of neurodegenerative processes a standardised design is required to enable meaningful data interpretation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under

  12. Presence of insoluble Tau following rotenone exposure ameliorates basic pathways associated with neurodegeneration

    Directory of Open Access Journals (Sweden)

    Rodrigo S. Chaves

    2016-12-01

    aggregation might exert protective cellular effects, at least briefly, when neurons are facing neurodegeneration stimulus. We believe that our data add more complexity for the understanding of protein aggregation role in AD etiology.

  13. Protection of DFP-induced oxidative damage and neurodegeneration by antioxidants and NMDA receptor antagonist

    International Nuclear Information System (INIS)

    Zaja-Milatovic, Snjezana; Gupta, Ramesh C.; Aschner, Michael; Milatovic, Dejan

    2009-01-01

    Prophylactic agents acutely administered in response to anticholinesterases intoxication can prevent toxic symptoms, including fasciculations, seizures, convulsions and death. However, anticholinesterases also have long-term unknown pathophysiological effects, making rational prophylaxis/treatment problematic. Increasing evidence suggests that in addition to excessive cholinergic stimulation, organophosphate compounds such as diisopropylphosphorofluoridate (DFP) induce activation of glutamatergic neurons, generation of reactive oxygen (ROS) and nitrogen species (RNS), leading to neurodegeneration. The present study investigated multiple affectors of DFP exposure critical to cerebral oxidative damage and whether antioxidants and NMDA receptor antagonist memantine provide neuroprotection by preventing DFP-induced biochemical and morphometric changes in rat brain. Rats treated acutely with DFP (1.25 mg/kg, s.c.) developed onset of toxicity signs within 7-15 min that progressed to maximal severity of seizures and fasciculations within 60 min. At this time point, DFP caused significant (p 2 -isoprostanes, F 2 -IsoPs; and F 4 -neuroprostanes, F 4 -NeuroPs), RNS (citrulline), and declines in high-energy phosphates (HEP) in rat cerebrum. At the same time, quantitative morphometric analysis of pyramidal neurons of the hippocampal CA1 region revealed significant (p 2 -IsoPs, F 4 -NeuroPs, citrulline, and depletion of HEP were noted. Furthermore, attenuation in oxidative damage following antioxidants or memantine pretreatment was accompanied by rescue from dendritic degeneration of pyramidal neurons in the CA1 hippocampal area. These findings closely associated DFP-induced lipid peroxidation with dendritic degeneration of pyramidal neurons in the CA1 hippocampal area and point to possible interventions to limit oxidative injury and dendritic degeneration induced by anticholinesterase neurotoxicity.

  14. First successful trial of preimplantation genetic diagnosis for pantothenate kinase-associated neurodegeneration.

    Science.gov (United States)

    Trachoo, Objoon; Satirapod, Chonthicha; Panthan, Bhakbhoom; Sukprasert, Matchuporn; Charoenyingwattana, Angkana; Chantratita, Wasun; Choktanasiri, Wicharn; Hongeng, Suradej

    2017-01-01

    We aim to present a case of a healthy infant born after intracytoplasmic sperm injection-in vitro fertilization (ICSI-IVF) with a preimplantation genetic diagnosis (PGD) for pantothenate kinase-associated neurodegeneration (PKAN) due to PANK2 mutation. ICSI-IVF was performed on a Thai couple, 34-year-old female and 33-year-old male, with a family history of PKAN in their first child. Following fertilization, each of the embryos were biopsied in the cleavage stage and subsequently processed for whole-genome amplification. Genetic status of the embryos was diagnosed by linkage analysis and direct mutation testing using primer extension-based mini-sequencing. Comprehensive chromosomal aneuploidy screening was performed using a next-generation sequencing-based strategy. Only a single cycle of ICSI-IVF was processed. There were seven embryos from this couple-two were likely affected, three were likely carriers, one was likely unaffected, and one failed in target genome amplification. Aneuploidy screening was performed before making a decision on embryo transfer, and only one unaffected embryo passed the screening. That embryo was transferred in a frozen thawed cycle, and the pregnancy was successful. The diagnosis was confirmed by amniocentesis, which presented with a result consistent with PGD. At 38 weeks of gestational age, a healthy male baby was born. Postnatal genetic confirmation was also consistent with PGD and the prenatal results. At the age of 24 months, the baby presented with normal growth and development lacking any neurological symptoms. We report the first successful trial of PGD for PKAN in a developing country using linkage analysis and mini-sequencing in cleavage stage embryos.

  15. Estimating Memory Deterioration Rates Following Neurodegeneration and Traumatic Brain Injuries in a Hopfield Network Model

    Directory of Open Access Journals (Sweden)

    Melanie Weber

    2017-11-01

    Full Text Available Neurodegenerative diseases and traumatic brain injuries (TBI are among the main causes of cognitive dysfunction in humans. At a neuronal network level, they both extensively exhibit focal axonal swellings (FAS, which in turn, compromise the information encoded in spike trains and lead to potentially severe functional deficits. There are currently no satisfactory quantitative predictors of decline in memory-encoding neuronal networks based on the impact and statistics of FAS. Some of the challenges of this translational approach include our inability to access small scale injuries with non-invasive methods, the overall complexity of neuronal pathologies, and our limited knowledge of how networks process biological signals. The purpose of this computational study is three-fold: (i to extend Hopfield's model for associative memory to account for the effects of FAS, (ii to calibrate FAS parameters from biophysical observations of their statistical distribution and size, and (iii to systematically evaluate deterioration rates for different memory-recall tasks as a function of FAS injury. We calculate deterioration rates for a face-recognition task to account for highly correlated memories and also for a discrimination task of random, uncorrelated memories with a size at the capacity limit of the Hopfield network. While it is expected that the performance of any injured network should decrease with injury, our results link, for the first time, the memory recall ability to observed FAS statistics. This allows for plausible estimates of cognitive decline for different stages of brain disorders within neuronal networks, bridging experimental observations following neurodegeneration and TBI with compromised memory recall. The work lends new insights to help close the gap between theory and experiment on how biological signals are processed in damaged, high-dimensional functional networks, and towards positing new diagnostic tools to measure cognitive

  16. Curcumin confers neuroprotection against alcohol-induced hippocampal neurodegeneration via CREB-BDNF pathway in rats.

    Science.gov (United States)

    Motaghinejad, Majid; Motevalian, Manijeh; Fatima, Sulail; Hashemi, Hajar; Gholami, Mina

    2017-03-01

    Alcohol abuse causes severe damage to the brain neurons. Studies have reported the neuroprotective effects of curcumin against alcohol-induced neurodegeneration. However, the precise mechanism of action remains unclear. Seventy rats were equally divided into 7 groups (10 rats per group). Group 1 received normal saline (0.7ml/rat) and group 2 received alcohol (2g/kg/day) for 21days. Groups 3, 4, 5 and 6 concurrently received alcohol (2g/kg/day) and curcumin (10, 20, 40 and 60mg/kg, respectively) for 21days. Animals in group 7 self- administered alcohol for 21days. Group 8 treated with curcumin (60mg/kg, i.p.) alone for 21days. Open Field Test (OFT) was used to investigate motor activity in rats. Hippocampal oxidative, antioxidative and inflammatory factors were evaluated. Furthermore, brain cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) and brain derived neurotrophic factor (BDNF) levels were studied at gene level by reverse transcriptase polymerase chain reaction (RT-PCR). In addition, protein expression for BDNF, CREB, phosphorylated CREB (CREB-P), Bax and Bcl-2 was determined by western blotting. Voluntary and involuntary administration of alcohol altered motor activity in OFT, and curcumin treatment inhibited this alcohol-induced motor disturbance. Also, alcohol administration augmented lipid peroxidation, mitochondrial oxidized glutathione (GSSG), interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and Bax levels in isolated hippocampal tissues. Furthermore, alcohol-induced significant reduction were observed in reduced form of glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) activities and CREB, BDNF and Bcl-2 levels. Also curcumin alone did not change the behavior and biochemical and molecular parameters. Curcumin can act as a neuroprotective agent against neurodegenerative effects of alcohol abuse, probably via activation of CREB-BDNF signaling pathway

  17. Protective effect of pyruvate against ethanol-induced apoptotic neurodegeneration in the developing rat brain.

    Science.gov (United States)

    Ullah, Najeeb; Naseer, Muhammad Imran; Ullah, Ikram; Lee, Hae Young; Koh, Phil Ok; Kim, Myeong Ok

    2011-12-01

    Exposure to alcohol during the early stages of brain development can lead to neurological disorders in the CNS. Apoptotic neurodegeneration due to ethanol exposure is a main feature of alcoholism. Exposure of developing animals to alcohol (during the growth spurt period in particular) elicits apoptotic neuronal death and causes fetal alcohol effects (FAE) or fetal alcohol syndrome (FAS). A single episode of ethanol intoxication (at 5 g/kg) in a seven-day-old developing rat can activate the apoptotic cascade, leading to widespread neuronal death in the brain. In the present study, we investigated the potential protective effect of pyruvate against ethanol-induced neuroapoptosis. After 4h, a single dose of ethanol induced upregulation of Bax, release of mitochondrial cytochrome-c into the cytosol, activation of caspase-3 and cleavage of poly (ADP-ribose) polymerase (PARP-1), all of which promote apoptosis. These effects were all reversed by co-treatment with pyruvate at a well-tolerated dosage (1000 mg/kg). Histopathology performed at 24 and 48 h with Fluoro-Jade-B and cresyl violet stains showed that pyruvate significantly reduced the number of dead cells in the cerebral cortex, hippocampus and thalamus. Immunohistochemical analysis at 24h confirmed that ethanol-induced cell death is both apoptotic and inhibited by pyruvate. These findings suggest that pyruvate treatment attenuates ethanol-induced neuronal cell loss in the developing rat brain and holds promise as a safe therapeutic and neuroprotective agent in the treatment of neurodegenerative disorders in newborns and infants. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Mito-Nuclear Interactions Affecting Lifespan and Neurodegeneration in a Drosophila Model of Leigh Syndrome.

    Science.gov (United States)

    Loewen, Carin A; Ganetzky, Barry

    2018-04-01

    Proper mitochondrial activity depends upon proteins encoded by genes in the nuclear and mitochondrial genomes that must interact functionally and physically in a precisely coordinated manner. Consequently, mito-nuclear allelic interactions are thought to be of crucial importance on an evolutionary scale, as well as for manifestation of essential biological phenotypes, including those directly relevant to human disease. Nonetheless, detailed molecular understanding of mito-nuclear interactions is still lacking, and definitive examples of such interactions in vivo are sparse. Here we describe the characterization of a mutation in Drosophila ND23 , a nuclear gene encoding a highly conserved subunit of mitochondrial complex 1. This characterization led to the discovery of a mito-nuclear interaction that affects the ND23 mutant phenotype. ND23 mutants exhibit reduced lifespan, neurodegeneration, abnormal mitochondrial morphology, and decreased ATP levels. These phenotypes are similar to those observed in patients with Leigh syndrome, which is caused by mutations in a number of nuclear genes that encode mitochondrial proteins, including the human ortholog of ND23 A key feature of Leigh syndrome, and other mitochondrial disorders, is unexpected and unexplained phenotypic variability. We discovered that the phenotypic severity of ND23 mutations varies depending on the maternally inherited mitochondrial background. Sequence analysis of the relevant mitochondrial genomes identified several variants that are likely candidates for the phenotypic interaction with mutant ND23 , including a variant affecting a mitochondrially encoded component of complex I. Thus, our work provides an in vivo demonstration of the phenotypic importance of mito-nuclear interactions in the context of mitochondrial disease. Copyright © 2018 by the Genetics Society of America.

  19. Estimating Memory Deterioration Rates Following Neurodegeneration and Traumatic Brain Injuries in a Hopfield Network Model

    Science.gov (United States)

    Weber, Melanie; Maia, Pedro D.; Kutz, J. Nathan

    2017-01-01

    Neurodegenerative diseases and traumatic brain injuries (TBI) are among the main causes of cognitive dysfunction in humans. At a neuronal network level, they both extensively exhibit focal axonal swellings (FAS), which in turn, compromise the information encoded in spike trains and lead to potentially severe functional deficits. There are currently no satisfactory quantitative predictors of decline in memory-encoding neuronal networks based on the impact and statistics of FAS. Some of the challenges of this translational approach include our inability to access small scale injuries with non-invasive methods, the overall complexity of neuronal pathologies, and our limited knowledge of how networks process biological signals. The purpose of this computational study is three-fold: (i) to extend Hopfield's model for associative memory to account for the effects of FAS, (ii) to calibrate FAS parameters from biophysical observations of their statistical distribution and size, and (iii) to systematically evaluate deterioration rates for different memory-recall tasks as a function of FAS injury. We calculate deterioration rates for a face-recognition task to account for highly correlated memories and also for a discrimination task of random, uncorrelated memories with a size at the capacity limit of the Hopfield network. While it is expected that the performance of any injured network should decrease with injury, our results link, for the first time, the memory recall ability to observed FAS statistics. This allows for plausible estimates of cognitive decline for different stages of brain disorders within neuronal networks, bridging experimental observations following neurodegeneration and TBI with compromised memory recall. The work lends new insights to help close the gap between theory and experiment on how biological signals are processed in damaged, high-dimensional functional networks, and towards positing new diagnostic tools to measure cognitive deficits. PMID

  20. Merge of terminological resources

    DEFF Research Database (Denmark)

    Henriksen, Lina; Braasch, Anna

    2012-01-01

    In our globalized world, the amount of cross-national communication increases rapidly, which also calls for easy access to multi-lingual high quality terminological resources. Sharing of terminology resources is currently becoming common practice, and efficient strategies for integration...... – or merging – of terminology resources are strongly needed. This paper discusses prerequisites for successful merging with the focus on identification of candidate duplicates of a subject domain found in the resources to be merged, and it describes automatic merging strategies to be applied to such duplicates...... in electronic terminology resources. Further, some perspectives of manual, supplementary assessment methods supporting the automatic procedures are sketched. Our considerations are primarily based on experience gained in the IATE and EuroTermBank projects, as merging was a much discussed issue in both projects....

  1. Renewable energy resources

    DEFF Research Database (Denmark)

    Ellabban, Omar S.; Abu-Rub, Haitham A.; Blaabjerg, Frede

    2014-01-01

    Electric energy security is essential, yet the high cost and limited sources of fossil fuels, in addition to the need to reduce greenhouse gasses emission, have made renewable resources attractive in world energy-based economies. The potential for renewable energy resources is enormous because...... they can, in principle, exponentially exceed the world's energy demand; therefore, these types of resources will have a significant share in the future global energy portfolio, much of which is now concentrating on advancing their pool of renewable energy resources. Accordingly, this paper presents how...... renewable energy resources are currently being used, scientific developments to improve their use, their future prospects, and their deployment. Additionally, the paper represents the impact of power electronics and smart grid technologies that can enable the proportionate share of renewable energy...

  2. Altered expression of the Cdk5 activator-like protein, Cdk5α, causes neurodegeneration, in part by accelerating the rate of aging

    Directory of Open Access Journals (Sweden)

    Joshua Spurrier

    2018-03-01

    Full Text Available Aging is the greatest risk factor for neurodegeneration, but the connection between the two processes remains opaque. This is in part for want of a rigorous way to define physiological age, as opposed to chronological age. Here, we develop a comprehensive metric for physiological age in Drosophila, based on genome-wide expression profiling. We applied this metric to a model of adult-onset neurodegeneration, increased or decreased expression of the activating subunit of the Cdk5 protein kinase, encoded by the gene Cdk5α, the ortholog of mammalian p35. Cdk5α-mediated degeneration was associated with a 27-150% acceleration of the intrinsic rate of aging, depending on the tissue and genetic manipulation. Gene ontology analysis and direct experimental tests revealed that affected age-associated processes included numerous core phenotypes of neurodegeneration, including enhanced oxidative stress and impaired proteostasis. Taken together, our results suggest that Cdk5α-mediated neurodegeneration results from accelerated aging, in combination with cell-autonomous neuronal insults. These data fundamentally recast our picture of the relationship between neurodegeneration and its most prominent risk factor, natural aging.

  3. Pantethine treatment is effective in recovering the disease phenotype induced by ketogenic diet in a pantothenate kinase-associated neurodegeneration mouse model

    Science.gov (United States)

    Brunetti, Dario; Dusi, Sabrina; Giordano, Carla; Lamperti, Costanza; Morbin, Michela; Fugnanesi, Valeria; Marchet, Silvia; Fagiolari, Gigliola; Sibon, Ody; Moggio, Maurizio; d’Amati, Giulia

    2014-01-01

    Pantothenate kinase-associated neurodegeneration, caused by mutations in the PANK2 gene, is an autosomal recessive disorder characterized by dystonia, dysarthria, rigidity, pigmentary retinal degeneration and brain iron accumulation. PANK2 encodes the mitochondrial enzyme pantothenate kinase type 2, responsible for the phosphorylation of pantothenate or vitamin B5 in the biosynthesis of co-enzyme A. A Pank2 knockout (Pank2−/−) mouse model did not recapitulate the human disease but showed azoospermia and mitochondrial dysfunctions. We challenged this mouse model with a low glucose and high lipid content diet (ketogenic diet) to stimulate lipid use by mitochondrial beta-oxidation. In the presence of a shortage of co-enzyme A, this diet could evoke a general impairment of bioenergetic metabolism. Only Pank2−/− mice fed with a ketogenic diet developed a pantothenate kinase-associated neurodegeneration-like syndrome characterized by severe motor dysfunction, neurodegeneration and severely altered mitochondria in the central and peripheral nervous systems. These mice also showed structural alteration of muscle morphology, which was comparable with that observed in a patient with pantothenate kinase-associated neurodegeneration. We here demonstrate that pantethine administration can prevent the onset of the neuromuscular phenotype in mice suggesting the possibility of experimental treatment in patients with pantothenate kinase-associated neurodegeneration. PMID:24316510

  4. Anthocyanins protect against LPS-induced oxidative stress-mediated neuroinflammation and neurodegeneration in the adult mouse cortex.

    Science.gov (United States)

    Khan, Muhammad Sohail; Ali, Tahir; Kim, Min Woo; Jo, Myeung Hoon; Jo, Min Gi; Badshah, Haroon; Kim, Myeong Ok

    2016-11-01

    Several studies provide evidence that reactive oxygen species (ROS) are key mediators of various neurological disorders. Anthocyanins are polyphenolic compounds and are well known for their anti-oxidant and neuroprotective effects. In this study, we investigated the neuroprotective effects of anthocyanins (extracted from black soybean) against lipopolysaccharide (LPS)-induced ROS-mediated neuroinflammation and neurodegeneration in the adult mouse cortex. Intraperitoneal injection of LPS (250 μg/kg) for 7 days triggers elevated ROS and oxidative stress, which induces neuroinflammation and neurodegeneration in the adult mouse cortex. Treatment with 24 mg/kg/day of anthocyanins for 14 days in LPS-injected mice (7 days before and 7 days co-treated with LPS) attenuated elevated ROS and oxidative stress compared to mice that received LPS-injection alone. The immunoblotting results showed that anthocyanins reduced the level of the oxidative stress kinase phospho-c-Jun N-terminal Kinase 1 (p-JNK). The immunoblotting and morphological results showed that anthocyanins treatment significantly reduced LPS-induced-ROS-mediated neuroinflammation through inhibition of various inflammatory mediators, such as IL-1β, TNF-α and the transcription factor NF- k B. Anthocyanins treatment also reduced activated astrocytes and microglia in the cortex of LPS-injected mice, as indicated by reductions in GFAP and Iba-1, respectively. Anthocyanins also prevent overexpression of various apoptotic markers, i.e., Bax, cytosolic cytochrome C, cleaved caspase-3 and PARP-1. Immunohistochemical fluoro-jade B (FJB) and Nissl staining indicated that anthocyanins prevent LPS-induced neurodegeneration in the mouse cortex. Our results suggest that dietary flavonoids, such as anthocyanins, have antioxidant and neuroprotective activities that could be beneficial to various neurological disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. PARP Inhibition Prevents Ethanol-Induced Neuroinflammatory Signaling and Neurodegeneration in Rat Adult-Age Brain Slice Cultures

    Science.gov (United States)

    Tajuddin, Nuzhath; Kim, Hee-Yong

    2018-01-01

    Using rat adult-age hippocampal-entorhinal cortical (HEC) slice cultures, we examined the role of poly [ADP-ribose] polymerase (PARP) in binge ethanol’s brain inflammatory and neurodegenerative mechanisms. Activated by DNA strand breaks, PARP (principally PARP1 in the brain) promotes DNA repair via poly [ADP-ribose] (PAR) products, but PARP overactivation triggers regulated neuronal necrosis (e.g., parthanatos). Previously, we found that brain PARP1 levels were upregulated by neurotoxic ethanol binges in adult rats and HEC slices, and PARP inhibitor PJ34 abrogated slice neurodegeneration. Binged HEC slices also exhibited increased Ca+2-dependent phospholipase A2 (PLA2) isoenzymes (cPLA2 IVA and sPLA2 IIA) that mobilize proinflammatory ω6 arachidonic acid (ARA). We now find in 4-day–binged HEC slice cultures (100 mM ethanol) that PARP1 elevations after two overnight binges precede PAR, cPLA2, and sPLA2 enhancements by 1 day and high-mobility group box-1 (HMGB1), an ethanol-responsive alarmin that augments proinflammatory cytokines via toll-like receptor-4 (TLR4), by 2 days. After verifying that PJ34 effectively blocks PARP activity (↑PAR), we demonstrated that, like PJ34, three other PARP inhibitors—olaparib, veliparib, and 4-aminobenzamide—provided neuroprotection from ethanol. Importantly, PJ34 and olaparib also prevented ethanol’s amplification of the PLA2 isoenzymes, and two PLA2 inhibitors were neuroprotective—thus coupling PARP to PLA2, with PLA2 activity promoting neurodegeneration. Also, PJ34 and olaparib blocked ethanol-induced HMGB1 elevations, linking brain PARP induction to TLR4 activation. The results provide evidence in adult brains that induction of PARP1 may mediate dual neuroinflammatory pathways (PLA2→phospholipid→ARA and HMGB1→TLR4→proinflammatory cytokines) that are complicit in binge ethanol-induced neurodegeneration. PMID:29339456

  6. Neurodegeneration severity can be predicted from early microglia alterations monitored in vivo in a mouse model of chronic glaucoma

    Directory of Open Access Journals (Sweden)

    Alejandra Bosco

    2015-05-01

    Full Text Available Microglia serve key homeostatic roles, and respond to neuronal perturbation and decline with a high spatiotemporal resolution. The course of all chronic CNS pathologies is thus paralleled by local microgliosis and microglia activation, which begin at early stages of the disease. However, the possibility of using live monitoring of microglia during early disease progression to predict the severity of neurodegeneration has not been explored. Because the retina allows live tracking of fluorescent microglia in their intact niche, here we investigated their early changes in relation to later optic nerve neurodegeneration. To achieve this, we used the DBA/2J mouse model of inherited glaucoma, which develops progressive retinal ganglion cell degeneration of variable severity during aging, and represents a useful model to study pathogenic mechanisms of retinal ganglion cell decline that are similar to those in human glaucoma. We imaged CX3CR1+/GFP microglial cells in vivo at ages ranging from 1 to 5 months by confocal scanning laser ophthalmoscopy (cSLO and quantified cell density and morphological activation. We detected early microgliosis at the optic nerve head (ONH, where axonopathy first manifests, and could track attenuation of this microgliosis induced by minocycline. We also observed heterogeneous and dynamic patterns of early microglia activation in the retina. When the same animals were aged and analyzed for the severity of optic nerve pathology at 10 months of age, we found a strong correlation with the levels of ONH microgliosis at 3 to 4 months. Our findings indicate that live imaging and monitoring the time course and levels of early retinal microgliosis and microglia activation in glaucoma could serve as indicators of future neurodegeneration severity.

  7. Neurodegeneration in Autoimmune Optic Neuritis Is Associated with Altered APP Cleavage in Neurons and Up-Regulation of p53.

    Directory of Open Access Journals (Sweden)

    Sabine Herold

    Full Text Available Multiple Sclerosis (MS is a chronic autoimmune inflammatory disease of the central nervous system (CNS. Histopathological and radiological analysis revealed that neurodegeneration occurs early in the disease course. However, the pathological mechanisms involved in neurodegeneration are poorly understood. Myelin oligodendrocyte glycoprotein (MOG-induced experimental autoimmune encephalomyelitis (EAE in Brown Norway rats (BN-rats is a well-established animal model, especially of the neurodegenerative aspects of MS. Previous studies in this animal model indicated that loss of retinal ganglion cells (RGCs, the neurons that form the axons of the optic nerve, occurs in the preclinical phase of the disease and is in part independent of overt histopathological changes of the optic nerve. Therefore, the aim of this study was to identify genes which are involved in neuronal cell loss at different disease stages of EAE. Furthermore, genes that are highly specific for autoimmune-driven neurodegeneration were compared to those regulated in RGCs after optic nerve axotomy at corresponding time points. Using laser capture micro dissection we isolated RNA from unfixed RGCs and performed global transcriptome analysis of retinal neurons. In total, we detected 582 genes sequentially expressed in the preclinical phase and 1150 genes in the clinical manifest EAE (P 1.5. Furthermore, using ingenuity pathway analysis (IPA, we identified amyloid precursor protein (APP as a potential upstream regulator of changes in gene expression in the preclinical EAE but neither in clinical EAE, nor at any time point after optic nerve transection. Therefore, the gene pathway analysis lead to the hypothesis that altered cleavage of APP in neurons in the preclinical phase of EAE leads to the enhanced production of APP intracellular domain (AICD, which in turn acts as a transcriptional regulator and thereby initiates an apoptotic signaling cascade via up-regulation of the target gene p

  8. Exacerbation of CNS inflammation and neurodegeneration by systemic LPS treatment is independent of circulating IL-1 beta and IL-6

    LENUS (Irish Health Repository)

    Murray, Carol L

    2011-05-17

    Abstract Background Chronic neurodegeneration comprises an inflammatory response but its contribution to the progression of disease remains unclear. We have previously shown that microglial cells are primed by chronic neurodegeneration, induced by the ME7 strain of prion disease, to synthesize limited pro-inflammatory cytokines but to produce exaggerated responses to subsequent systemic inflammatory insults. The consequences of this primed response include exaggerated hypothermic and sickness behavioural responses, acute neuronal death and accelerated progression of disease. Here we investigated whether inhibition of systemic cytokine synthesis using the anti-inflammatory steroid dexamethasone-21-phosphate was sufficient to block any or all of these responses. Methods ME7 animals, at 18-19 weeks post-inoculation, were challenged with LPS (500 μg\\/kg) in the presence or absence of dexamethasone-21-phosphate (2 mg\\/kg) and effects on core-body temperature and systemic and CNS cytokine production and apoptosis were examined. Results LPS induced hypothermia and decreased exploratory activity. Dexamethasone-21-phosphate prevented this hypothermia, markedly suppressed systemic IL-1β and IL-6 secretion but did not prevent decreased exploration. Furthermore, robust transcription of cytokine mRNA occurred in the hippocampus of both ME7 and NBH (normal brain homogenate) control animals despite the effective blocking of systemic cytokine synthesis. Microglia primed by neurodegeneration were not blocked from the robust synthesis of IL-1β protein and endothelial COX-2 was also robustly synthesized. We injected biotinylated LPS at 100 μg\\/kg and even at this lower dose this could be detected in blood plasma. Apoptosis was acutely induced by LPS, despite the inhibition of the systemic cytokine response. Conclusions These data suggest that LPS can directly activate the brain endothelium even at relatively low doses, obviating the need for systemic cytokine stimulation to

  9. Caffeine prevents d-galactose-induced cognitive deficits, oxidative stress, neuroinflammation and neurodegeneration in the adult rat brain.

    Science.gov (United States)

    Ullah, Faheem; Ali, Tahir; Ullah, Najeeb; Kim, Myeong Ok

    2015-11-01

    d-galactose has been considered a senescent model for age-related neurodegenerative disease. It induces oxidative stress which triggers memory impairment, neuroinflammation and neurodegeneration. Caffeine act as anti-oxidant and has been used in various model of neurodegenerative disease. Nevertheless, the effect of caffeine against d-galactose aging murine model of age-related neurodegenerative disease elucidated. Here, we investigated the neuroprotective effect of caffeine against d-galactose. We observed that chronic treatment of caffeine (3 mg/kg/day intraperitoneally (i.p) for 60 days) improved memory impairment and synaptic markers (Synaptophysin and PSD95) in the d-galactose treated rats. Chronic caffeine treatment reduced the oxidative stress via the reduction of 8-oxoguanine through immunofluorescence in the d-galactose-treated rats. Consequently caffeine treatment suppressed stress kinases p-JNK. Additionally, caffeine treatment significantly reduced the d-galactose-induced neuroinflammation through alleviation of COX-2, NOS-2, TNFα and IL-1β. Furthermore we also analyzed that caffeine reduced cytochrome C, Bax/Bcl2 ratio, caspase-9, caspase-3 and PARP-1 level. Moreover by evaluating the immunohistochemical results of Nissl and Fluro-Jade B staining showed that caffeine prevented the neurodegeneration in the d-galactose-treated rats. Our results showed that caffeine prevents the d-galactose-induced oxidative stress and consequently alleviated neuroinflammation and neurodegeneration; and synaptic dysfunction and memory impairment. Therefore, we could suggest that caffeine might be a dietary anti-oxidant agent and a good candidate for the age-related neurodegenerative disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Cerebrospinal fluid neurofilament light chain as a biomarker of neurodegeneration in the Tg4510 and MitoPark mouse models

    DEFF Research Database (Denmark)

    Clement, Amalie; Mitchelmore, Cathy; Andersson, Daniel

    2017-01-01

    examined whether changes in NF-L levels in brain, plasma, and CSF reflect the changing disease status of preclinical models of neurodegeneration. Using Western Blot and ELISA we characterized NF-L and disease-related proteins in brain, CSF and plasma samples from Tg4510 mice (tauopathy/AD), MitoPark mice...... (PD), and their age-matched control littermates. We found that CSF NF-L clearly discriminates Tg4510 from control littermates, which was not observed for the MitoPark model. However, both Tg4510 and MitoPark showed altered expression and solubilization of NFs compared to control littermates. We found...

  11. Role of Ca+2 and other second messengers in excitatory amino acid receptor mediated neurodegeneration: clinical perspectives

    DEFF Research Database (Denmark)

    Schousboe, A; Belhage, B; Frandsen, A

    1997-01-01

    Neurodegeneration associated with neurological disorders such as epilepsy, Huntington's Chorea, Alzheimer's disease, and olivoponto cerebellar atrophy or with energy failure such as ischemia, hypoxia, and hypoglycemia proceeds subsequent to overexposure of neurons to excitatory amino acids of which...... glutamate and aspartate may be quantitatively the most important. The toxic action of glutamate and aspartate is mediated through activation of glutamate receptors of the N-methyl-D-aspartate (NMDA) and non-NMDA subtypes. Antagonists for these receptors can act as neuroprotectants both in in vitro model...

  12. Diabetes and overexpression of proNGF cause retinal neurodegeneration via activation of RhoA pathway.

    Directory of Open Access Journals (Sweden)

    Mohammed M H Al-Gayyar

    Full Text Available Our previous studies showed positive correlation between accumulation of proNGF, activation of RhoA and neuronal death in diabetic models. Here, we examined the neuroprotective effects of selective inhibition of RhoA kinase in the diabetic rat retina and in a model that stably overexpressed the cleavage-resistance proNGF plasmid in the retina. Male Sprague-Dawley rats were rendered diabetic using streptozotocin or stably express cleavage-resistant proNGF plasmid. The neuroprotective effects of the intravitreal injection of RhoA kinase inhibitor Y27632 were examined in vivo. Effects of proNGF were examined in freshly isolated primary retinal ganglion cell (RGC cultures and RGC-5 cell line. Retinal neurodegeneration was assessed by counting TUNEL-positive and Brn-3a positive retinal ganglion cells. Expression of proNGF, p75(NTR, cleaved-PARP, caspase-3 and p38MAPK/JNK were examined by Western-blot. Activation of RhoA was assessed by pull-down assay and G-LISA. Diabetes and overexpression of proNGF resulted in retinal neurodegeneration as indicated by 9- and 6-fold increase in TUNEL-positive cells, respectively. In vitro, proNGF induced 5-fold cell death in RGC-5 cell line, and it induced >10-fold cell death in primary RGC cultures. These effects were associated with significant upregulation of p75(NTR and activation of RhoA. While proNGF induced TNF-α expression in vivo, it selectively activated RhoA in primary RGC cultures and RGC-5 cell line. Inhibiting RhoA kinase with Y27632 significantly reduced diabetes- and proNGF-induced activation of proapoptotic p38MAPK/JNK, expression of cleaved-PARP and caspase-3 and prevented retinal neurodegeneration in vivo and in vitro. Taken together, these results provide compelling evidence for a causal role of proNGF in diabetes-induced retinal neurodegeneration through enhancing p75(NTR expression and direct activation of RhoA and p38MAPK/JNK apoptotic pathways.

  13. EFFECTIVE ELECTRONIC TUTORIAL

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    Andrei A. Fedoseev

    2014-01-01

    Full Text Available The article analyzes effective electronic tutorials creation and application based on the theory of pedagogy. Herewith the issues of necessary electronic tutorial functional, ways of the educational process organization with the use of information and communication technologies and the logistics of electronic educational resources are touched upon. 

  14. Brain Renin-Angiotensin System and Microglial Polarization: Implications for Aging and Neurodegeneration

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    Jose L. Labandeira-Garcia

    2017-05-01

    , such as estrogens, Rho kinase (ROCK, insulin-like growth factor-1 (IGF-1, tumor necrosis factor α (TNF-α, iron, peroxisome proliferator-activated receptor gamma, and toll-like receptors (TLRs. Metabolic reprogramming has recently been involved in the regulation of the neuroinflammatory response. Interestingly, we have recently observed a mitochondrial RAS, which is altered in aged brains. In conclusion, dysregulation of brain RAS plays a major role in aging-related changes and neurodegeneration by exacerbation of oxidative stress (OS and neuroinflammation, which may be attenuated by pharmacological manipulation of RAS components.

  15. Developmental toxicity of toluene in male rats: effects on semen quality, testis morphology, and apoptotic neurodegeneration

    Energy Technology Data Exchange (ETDEWEB)

    Dalgaard, M.; Hossaini, A.; Hass, U.; Ladefoged, O. [Inst. of Food Safety and Toxicology, Danish Veterinary and Food Administration, Soborg (Denmark); Hougaard, K.S. [National Inst. of Occupational Health, Copenhagen (Denmark)

    2001-04-01

    In one study, pregnant Wistar rats were exposed to 1200 ppm toluene by inhalation 6 h a day from gestational day (GD) 7 to postnatal day (PND) 18. Sperm analysis was performed in the adult male offspring at PND 110 by using computer-assisted sperm analysis. Toluene did not affect the semen quality of exposed rats. In another study, pregnant rats were exposed to 1800 ppm from GD 7 to GD 20, and the male offspring were killed at PND 11, 21 or 90. Paired testes weight, histopathology and immunoexpression of vimentin in Sertoli cells were used as markers of testis toxicity. In the brain, the number of apoptotic cells in the hippocampus and cerebellum were counted after visualisation by means of the TUNEL assay. Mean body weight in pups of exposed dams was lower than in pups from control litters. This decrease was still statistically significant at PND 11, but at PND 21 and 90 the body weight of toluene-exposed males tended to approach that of the controls. Absolute and relative testes weights were reduced in all three age groups, although not to a statistically significant degree. Histopathological examinations of the testis and immuno-expression of vimentin did not reveal any differences between toluene-exposed animals and control animals. In the hippocampus, almost no apoptosis was observed in any age group, and there were no differences in apoptotic neurodegeneration between male rats exposed to 1800 ppm and control animals at PND 11, 21 or 90. Generally, a marked increase in number of apoptotic cells was observed in cerebellar granule cells at PND 21 compared with the other age groups. Toluene induced a statistically significant increase in the number of apoptotic cells in the cerebellar granule layer at PND 21. The mean was increased from 37 in the control group to 71 in the toluene-exposed group. Thus, the granular cell layer in cerebellum is a highly relevant tissue with which to study toluene-induced apoptosis, because of the continuous migration of neurons and

  16. Serum neurofilament light in familial Alzheimer disease: A marker of early neurodegeneration.

    Science.gov (United States)

    Weston, Philip S J; Poole, Teresa; Ryan, Natalie S; Nair, Akshay; Liang, Yuying; Macpherson, Kirsty; Druyeh, Ronald; Malone, Ian B; Ahsan, R Laila; Pemberton, Hugh; Klimova, Jana; Mead, Simon; Blennow, Kaj; Rossor, Martin N; Schott, Jonathan M; Zetterberg, Henrik; Fox, Nick C

    2017-11-21

    To investigate whether serum neurofilament light (NfL) concentration is increased in familial Alzheimer disease (FAD), both pre and post symptom onset, and whether it is associated with markers of disease stage and severity. We recruited 48 individuals from families with PSEN1 or APP mutations to a cross-sectional study: 18 had symptomatic Alzheimer disease (AD) and 30 were asymptomatic but at 50% risk of carrying a mutation. Serum NfL was measured using an ultrasensitive immunoassay on the single molecule array (Simoa) platform. Cognitive testing and MRI were performed; 33 participants had serial MRI, allowing calculation of atrophy rates. Genetic testing established mutation status. A generalized least squares regression model was used to compare serum NfL among symptomatic mutation carriers, presymptomatic carriers, and noncarriers, adjusting for age and sex. Spearman coefficients assessed associations between serum NfL and (1) estimated years to/from symptom onset (EYO), (2) cognitive measures, and (3) MRI measures of atrophy. Nineteen of the asymptomatic participants were mutation carriers (mean EYO -9.6); 11 were noncarriers. Compared with noncarriers, serum NfL concentration was higher in both symptomatic ( p < 0.0001) and presymptomatic mutation carriers ( p = 0.007). Across all mutation carriers, serum NfL correlated with EYO (ρ = 0.81, p < 0.0001) and multiple cognitive and imaging measures, including Mini-Mental State Examination (ρ = -0.62, p = 0.0001), Clinical Dementia Rating Scale sum of boxes (ρ = 0.79, p < 0.0001), baseline brain volume (ρ = -0.62, p = 0.0002), and whole-brain atrophy rate (ρ = 0.53, p = 0.01). Serum NfL concentration is increased in FAD prior to symptom onset and correlates with measures of disease stage and severity. Serum NfL may thus be a feasible biomarker of early AD-related neurodegeneration. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

  17. Dual Role of Vitamin C on the Neuroinflammation Mediated Neurodegeneration and Memory Impairments in Colchicine Induced Rat Model of Alzheimer Disease.

    Science.gov (United States)

    Sil, Susmita; Ghosh, Tusharkanti; Gupta, Pritha; Ghosh, Rupsa; Kabir, Syed N; Roy, Avishek

    2016-12-01

    The neurodegeneration in colchicine induced AD rats (cAD) is mediated by cox-2 linked neuroinflammation. The importance of ROS in the inflammatory process in cAD has not been identified, which may be deciphered by blocking oxidative stress in this model by a well-known anti-oxidant vitamin C. Therefore, the present study was designed to investigate the role of vitamin C on colchicine induced oxidative stress linked neuroinflammation mediated neurodegeneration and memory impairments along with peripheral immune responses in cAD. The impairments of working and reference memory were associated with neuroinflammation and neurodegeneration in the hippocampus of cAD. Administration of vitamin C (200 and 400 mg/kg BW) in cAD resulted in recovery of memory impairments, with prevention of neurodegeneration and neuroinflammation in the hippocampus. The neuroinflammation in the hippocampus also influenced the peripheral immune responses and inflammation in the serum of cAD and all of these parameters were also recovered at 200 and 400 mg dose of vitamin C. However, cAD treated with 600 mg dose did not recover but resulted in increase of memory impairments, neurodegeneration and neuroinflammation in hippocampus along with alteration of peripheral immune responses in comparison to cAD of the present study. Therefore, the present study showed that ROS played an important role in the colchicine induced neuroinflammation linked neurodegeneration and memory impairments along with alteration of peripheral immune responses. It also appears from the results that vitamin C at lower doses showed anti-oxidant effect and at higher dose resulted in pro-oxidant effects in cAD.

  18. Patient Affected by Beta-Propeller Protein-Associated Neurodegeneration: A Therapeutic Attempt with Iron Chelation Therapy

    Directory of Open Access Journals (Sweden)

    Mattia Fonderico

    2017-08-01

    Full Text Available Here, we report the case of a 36-year-old patient with a diagnosis of de novo mutation of the WDR45 gene, responsible for beta-propeller protein-associated neurodegeneration, a phenotypically distinct, X-linked dominant form of Neurodegeneration with Brain Iron Accumulation. The clinical history is characterized by a relatively stable intellectual disability and a hypo-bradykinetic and hypertonic syndrome with juvenile onset. Genetic investigations and T1 and T2-weighted MR images align with what is described in literature. The patient was also subjected to PET with 18-FDG investigation and DaT-Scan study. In reporting relevant clinical data, we want to emphasize the fact that the patient received a chelation therapy with deferiprone (treatment already used in other forms of NBIA with encouraging results, which, however, had to be interrupted because the parkinsonian symptoms worsened. Conversely, the patient has benefited from non-drug therapies and, in particular, from an adapted motor activity with assisted pedaling (method in the process of validation in treatments of parkinsonian syndromes, which started before the treatment with deferiprone and still continues.

  19. Gene Expression Profiling as a Tool to Investigate the Molecular Machinery Activated during Hippocampal Neurodegeneration Induced by Trimethyltin (TMT Administration

    Directory of Open Access Journals (Sweden)

    Maria Concetta Geloso

    2013-08-01

    Full Text Available Trimethyltin (TMT is an organotin compound exhibiting neurotoxicant effects selectively localized in the limbic system and especially marked in the hippocampus, in both experimental animal models and accidentally exposed humans. TMT administration causes selective neuronal death involving either the granular neurons of the dentate gyrus or the pyramidal cells of the Cornu Ammonis, with a different pattern of localization depending on the different species studied or the dosage schedule. TMT is broadly used to realize experimental models of hippocampal neurodegeneration associated with cognitive impairment and temporal lobe epilepsy, though the molecular mechanisms underlying the associated selective neuronal death are still not conclusively clarified. Experimental evidence indicates that TMT-induced neurodegeneration is a complex event involving different pathogenetic mechanisms, probably acting differently in animal and cell models, which include neuroinflammation, intracellular calcium overload, and oxidative stress. Microarray-based, genome-wide expression analysis has been used to investigate the molecular scenario occurring in the TMT-injured brain in different in vivo and in vitro models, producing an overwhelming amount of data. The aim of this review is to discuss and rationalize the state-of-the-art on TMT-associated genome wide expression profiles in order to identify comparable and reproducible data that may allow focusing on significantly involved pathways.

  20. Neurodegeneration and unfolded-protein response in mice expressing a membrane-tethered flexible tail of PrP.

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    Paolo Dametto

    Full Text Available The cellular prion protein (PrPC consists of a flexible N-terminal tail (FT, aa 23-128 hinged to a membrane-anchored globular domain (GD, aa 129-231. Ligation of the GD with antibodies induces rapid neurodegeneration, which is prevented by deletion or functional inactivation of the FT. Therefore, the FT is an allosteric effector of neurotoxicity. To explore its mechanism of action, we generated transgenic mice expressing the FT fused to a GPI anchor, but lacking the GD (PrPΔ141-225, or "FTgpi". Here we report that FTgpi mice develop a progressive, inexorably lethal neurodegeneration morphologically and biochemically similar to that triggered by anti-GD antibodies. FTgpi was mostly retained in the endoplasmic reticulum, where it triggered a conspicuous unfolded protein response specifically activating the PERK pathway leading to phosphorylation of eIF2α and upregulation of CHOP ultimately leading to neurodegeration similar to what was observed in prion infection.

  1. NF-κB Immunity in the Brain Determines Fly Lifespan in Healthy Aging and Age-Related Neurodegeneration.

    Science.gov (United States)

    Kounatidis, Ilias; Chtarbanova, Stanislava; Cao, Yang; Hayne, Margaret; Jayanth, Dhruv; Ganetzky, Barry; Ligoxygakis, Petros

    2017-04-25

    During aging, innate immunity progresses to a chronically active state. However, what distinguishes those that "age well" from those developing age-related neurological conditions is unclear. We used Drosophila to explore the cost of immunity in the aging brain. We show that mutations in intracellular negative regulators of the IMD/NF-κB pathway predisposed flies to toxic levels of antimicrobial peptides, resulting in early locomotor defects, extensive neurodegeneration, and reduced lifespan. These phenotypes were rescued when immunity was suppressed in glia. In healthy flies, suppressing immunity in glial cells resulted in increased adipokinetic hormonal signaling with high nutrient levels in later life and an extension of active lifespan. Thus, when levels of IMD/NF-κB deviate from normal, two mechanisms are at play: lower levels derepress an immune-endocrine axis, which mobilizes nutrients, leading to lifespan extension, whereas higher levels increase antimicrobial peptides, causing neurodegeneration. Immunity in the fly brain is therefore a key lifespan determinant. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  2. NF-κB Immunity in the Brain Determines Fly Lifespan in Healthy Aging and Age-Related Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Ilias Kounatidis

    2017-04-01

    Full Text Available During aging, innate immunity progresses to a chronically active state. However, what distinguishes those that “age well” from those developing age-related neurological conditions is unclear. We used Drosophila to explore the cost of immunity in the aging brain. We show that mutations in intracellular negative regulators of the IMD/NF-κB pathway predisposed flies to toxic levels of antimicrobial peptides, resulting in early locomotor defects, extensive neurodegeneration, and reduced lifespan. These phenotypes were rescued when immunity was suppressed in glia. In healthy flies, suppressing immunity in glial cells resulted in increased adipokinetic hormonal signaling with high nutrient levels in later life and an extension of active lifespan. Thus, when levels of IMD/NF-κB deviate from normal, two mechanisms are at play: lower levels derepress an immune-endocrine axis, which mobilizes nutrients, leading to lifespan extension, whereas higher levels increase antimicrobial peptides, causing neurodegeneration. Immunity in the fly brain is therefore a key lifespan determinant.

  3. Mithramycin is a gene-selective Sp1 inhibitor that identifies a biological intersection between cancer and neurodegeneration.

    Science.gov (United States)

    Sleiman, Sama F; Langley, Brett C; Basso, Manuela; Berlin, Jill; Xia, Li; Payappilly, Jimmy B; Kharel, Madan K; Guo, Hengchang; Marsh, J Lawrence; Thompson, Leslie Michels; Mahishi, Lata; Ahuja, Preeti; MacLellan, W Robb; Geschwind, Daniel H; Coppola, Giovanni; Rohr, Jürgen; Ratan, Rajiv R

    2011-05-04

    Oncogenic transformation of postmitotic neurons triggers cell death, but the identity of genes critical for degeneration remain unclear. The antitumor antibiotic mithramycin prolongs survival of mouse models of Huntington's disease in vivo and inhibits oxidative stress-induced death in cortical neurons in vitro. We had correlated protection by mithramycin with its ability to bind to GC-rich DNA and globally displace Sp1 family transcription factors. To understand how antitumor drugs prevent neurodegeneration, here we use structure-activity relationships of mithramycin analogs to discover that selective DNA-binding inhibition of the drug is necessary for its neuroprotective effect. We identify several genes (Myc, c-Src, Hif1α, and p21(waf1/cip1)) involved in neoplastic transformation, whose altered expression correlates with protective doses of mithramycin or its analogs. Most interestingly, inhibition of one these genes, Myc, is neuroprotective, whereas forced expression of Myc induces Rattus norvegicus neuronal cell death. These results support a model in which cancer cell transformation shares key genetic components with neurodegeneration.

  4. Binge Alcohol Exposure Transiently Changes the Endocannabinoid System: A Potential Target to Prevent Alcohol-Induced Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Daniel J. Liput

    2017-11-01

    Full Text Available Excessive alcohol consumption leads to neurodegeneration, which contributes to cognitive decline that is associated with alcohol use disorders (AUDs. The endocannabinoid system has been implicated in the development of AUDs, but little is known about how the neurotoxic effects of alcohol impact the endocannabinoid system. Therefore, the current study investigated the effects of neurotoxic, binge-like alcohol exposure on components of the endocannabinoid system and related N-acylethanolamines (NAEs, and then evaluated the efficacy of fatty acid amide hydrolase (FAAH inhibition on attenuating alcohol-induced neurodegeneration. Male rats were administered alcohol according to a binge model, which resulted in a transient decrease in [3H]-CP-55,940 binding in the entorhinal cortex and hippocampus following two days, but not four days, of treatment. Furthermore, binge alcohol treatment did not change the tissue content of the three NAEs quantified, including the endocannabinoid and anandamide. In a separate study, the FAAH inhibitor, URB597 was administered to rats during alcohol treatment and neuroprotection was assessed by FluoroJade B (FJB staining. The administration of URB597 during binge treatment did not significantly reduce FJB+ cells in the entorhinal cortex or hippocampus, however, a follow up “target engagement” study found that NAE augmentation by URB597 was impaired in alcohol intoxicated rats. Thus, potential alcohol induced alterations in URB597 pharmacodynamics may have contributed to the lack of neuroprotection by FAAH inhibition.

  5. Pantothenate kinase-associated neurodegeneration: altered mitochondria membrane potential and defective respiration in Pank2 knock-out mouse model.

    Science.gov (United States)

    Brunetti, Dario; Dusi, Sabrina; Morbin, Michela; Uggetti, Andrea; Moda, Fabio; D'Amato, Ilaria; Giordano, Carla; d'Amati, Giulia; Cozzi, Anna; Levi, Sonia; Hayflick, Susan; Tiranti, Valeria

    2012-12-15

    Neurodegeneration with brain iron accumulation (NBIA) comprises a group of neurodegenerative disorders characterized by high brain content of iron and presence of axonal spheroids. Mutations in the PANK2 gene, which encodes pantothenate kinase 2, underlie an autosomal recessive inborn error of coenzyme A metabolism, called pantothenate kinase-associated neurodegeneration (PKAN). PKAN is characterized by dystonia, dysarthria, rigidity and pigmentary retinal degeneration. The pathogenesis of this disorder is poorly understood and, although PANK2 is a mitochondrial protein, perturbations in mitochondrial bioenergetics have not been reported. A knock-out (KO) mouse model of PKAN exhibits retinal degeneration and azoospermia, but lacks any neurological phenotype. The absence of a clinical phenotype has partially been explained by the different cellular localization of the human and murine PANK2 proteins. Here we demonstrate that the mouse Pank2 protein localizes to mitochondria, similar to its human orthologue. Moreover, we show that Pank2-defective neurons derived from KO mice have an altered mitochondrial membrane potential, a defect further corroborated by the observations of swollen mitochondria at the ultra-structural level and by the presence of defective respiration.

  6. Real-world health outcomes in adults with moderate-to-severe psoriasis in the United States: a population study using electronic health records to examine patient-perceived treatment effectiveness, medication use, and healthcare resource utilization.

    Science.gov (United States)

    Armstrong, April W; Foster, Shonda A; Comer, Brian S; Lin, Chen-Yen; Malatestinic, William; Burge, Russel; Goldblum, Orin

    2018-06-28

    Little is known regarding real-world health outcomes data among US psoriasis patients, but electronic health records (EHR) that collect structured data at point-of-care may provide opportunities to investigate real-world health outcomes among psoriasis patients. Our objective was to investigate patient-perceived treatment effectiveness, patterns of medication use (duration, switching, and/or discontinuation), healthcare resource utilization, and medication costs using real-world data from psoriasis patients. Data for adults (≥18-years) with a dermatology provider-given diagnosis of psoriasis from 9/2014-9/2015 were obtained from dermatology practices using a widely used US dermatology-specific EHR containing over 500,000 psoriasis patients. Disease severity was captured by static physician's global assessment and body surface area. Patient-perceived treatment effectiveness was assessed by a pre-defined question. Treatment switching and duration were documented. Reasons for discontinuations were assessed using pre-defined selections. Healthcare resource utilization was defined by visit frequency and complexity. From 82,621 patients with psoriasis during the study period, patient-perceived treatment effectiveness was investigated in 2200 patients. The proportion of patients reporting "strongly agree" when asked if their treatment was effective was highest for biologics (73%) and those reporting treatment adherence (55%). In 16,000 patients who received oral systemics and 21,087 patients who received biologics, median treatment duration was longer for those who received biologics (160 vs. 113 days, respectively). Treatment switching was less frequent among patients on systemic monotherapies compared to those on combination therapies. The most common reason for discontinuing biologics was loss of efficacy; the most common reason for discontinuing orals was side effects. In 28,754 patients, higher disease severity was associated with increased healthcare resource

  7. Water Resources

    International Nuclear Information System (INIS)

    Abira, M.A.

    1997-01-01

    Water is essential for life and ecological sustenance; its availability is essential component of national welfare and productivity.The country's socio-economic activities are largely dependent on the natural endowment of water resources. Kenya's water resources comprises of surface waters (rivers, lakes and wetlands) and ground water. Surface water forms 86% of total water resources while the rest is ground water Geological, topographical and climatic factors influence the natural availability and distribution of water with the rainfall distribution having the major influence. Water resources in Kenya are continuously under threat of depletion and quality degradation owing to rising population, industrialization, changing land use and settlement activities as well as natural changes. However, the anticipated climate change is likely to exacerbate the situation resulting in increased conflict over water use rights in particular, and, natural resource utilisation in general. The impacts of climate change on the water resources would lead to other impacts on environmental and socio-economic systems

  8. Retinal neurodegeneration in patients with type 1 diabetes mellitus: the role of glycemic variability.

    Science.gov (United States)

    Picconi, Fabiana; Parravano, Mariacristina; Ylli, Dorina; Pasqualetti, Patrizio; Coluzzi, Sara; Giordani, Ilaria; Malandrucco, Ilaria; Lauro, Davide; Scarinci, Fabio; Giorno, Paola; Varano, Monica; Frontoni, Simona

    2017-05-01

    Recent studies have identified neuroretinal abnormalities in persons affected by diabetes mellitus, before the onset of microvascular alterations. However, the role of glycemic variability (GV) on early retinal neurodegeneration is still not clarified. To explore the relationship between glycemic control and neuroretinal characteristics, 37 persons with Type 1 diabetes mellitus (Type 1 DM) divided into two groups with no signs (noRD) and with mild non-proliferative diabetic retinopathy (NPDR) compared to 13 healthy control participants (C) were recruited. All persons underwent an optical coherence tomography with automatic segmentation of all neuroretinal layers. Measurements of mean of nasal (N)/temporal (T)/superior (S)/inferior (I) macular quadrants for individual layer were also calculated. Metabolic control was evaluated by glycated hemoglobin (HbA1c), and indexes of GV were calculated from continuous glucose monitoring. The difference among the three groups in terms of RNFL thickness was significantly dependent on quadrant (F(6;132) = 2.315; p = 0.037). This interaction was due to a specific difference in RNFL-N thickness, where both Type 1 DM groups showed a similar reduction versus C (-3.9 for noDR and -4.9 for NPDR), without any relevant difference between them (-1.0). Inner nuclear layer (INL) was increased in all quadrants in the two Type 1 DM groups compared to C (mean difference = 7.73; 95% CI: 0.32-15.14, p = 0.043; mean difference = 7.74; 95% CI: 0.33-15.15, p = 0.043, respectively). A negative correlation between RNFL-N and low blood glucose index (r = -0.382, p = 0.034) and positive correlation between INL and continuous overall net glycemic action -1, -2, -4 h (r = 0.40, p = 0.025; r = 0.39, p = 0.031; r = 0.41, p = 0.021, respectively) were observed in Type 1 DM patients. The triglycerides were positively and significantly correlated to INL (r = 0.48, p = 0.011), in Type 1 DM subjects. GV and triglycerides

  9. Clinical phenotype and genetic mutation of fatty acid hydroxylase - associated neurodegeneration: analysis of four cases

    Directory of Open Access Journals (Sweden)

    Xiao-jun HUANG

    2017-07-01

    Full Text Available Objective To report 4 cases of fatty acid hydroxylase - associated neurodegeneration (FAHN and to summarize the clinical and genetic characteristics of FAHN by literatures review.  Methods Four cases of FAHN patients' clinical and family data were collected in detail. The gDNA of patients and their parents were extracted from peripheral blood. FA2H gene was conducted and followed by Sanger sequencing.  Results Among the 4 cases, 3 cases (Case 2, Case 3, Case 4 presented typical manifestations of FAHN while the other (Case 1 was atypical. Genetic sequencing showed FA2H gene mutation in all affected patients. Compound heterozygous mutation c.461G > A (p.Arg154His and c.794T > G (p.Phe265Cys were seen in Case 1. In Case 2, only one documented heterozygous mutation c.703C > T (p.Arg235Cys was found, and dificit mutation was not found in single nucleotide polymorphism (SNP chip test of the patient and her mother. Compound heterozygous mutation c.688G > A (p.Glu230Lys and insertion mutation c.172_173insGGGCCAGGAC (p.Ile58ArgfsX47 were presented in Case 3. In Case 4, compound heterozygous mutation c.688G > A (p.Glu230Lys, c.968C > A (p.Pro323Gln and c.976G > A (p. Gly326Asp were seen, while his father was the carrier of c.688G > A (p.Glu230Lys mutation and his mother was the carrier of c.968C > A (p.Pro323Gln and c.976G > A (p.Gly326Asp mutation. According to the standard of American College of Medical Genetics and Genomics (ACMG, c.461G > A (p.Arg154His and c.794T > G (p.Phe265Cys in Case 1, and c.703C > T (p.Arg235Cys in Case 2 were considered as "likely pathogenic", while FA2H gene compound heterozygous mutation c.688G > A (p.Glu230Lys, insertion mutation c.172_173insGGGCCAGGAC (p.Ile58ArgfsX47 in Case 3 was as "pathogenic", and in Case 4, the FA2H gene mutation c.688G > A (p.Glu230Lys and c.968C > A (p.Pro323Gln were "pathogenic" and c.976G > A (p.Gly326Asp was "likely pathogenic".  Conclusions FAHN has highly clinical and genetic

  10. Aralia elata inhibits neurodegeneration by downregulating O-GlcNAcylation of NF-κB in diabetic mice

    Directory of Open Access Journals (Sweden)

    Seong-Jae Kim

    2017-08-01

    Full Text Available AIM: To investigate the role of O-GlcNAcylation of nuclear factor-kappa B (NF-κB in retinal ganglion cell (RGC death and analysedthe effect of Aralia elata (AE on neurodegeneration in diabetic mice. METHODS: C57BL/6mice with streptozotocin-induced diabetes were fed daily with AE extract or control (CTL diet at the onset of diabetes mellitus (DM. Two months after injection of streptozotocin or saline, the degree of cell death and the expression of O-GlcNAc transferase (OGT, N-acetyl-b-D-glucosaminidase (OGA, O-GlcNAcylated proteins, and O-GlcNAcylation of NF-κB were examined. RESULTS: AE did not affect the metabolic status of diabetic mice. The decrease in the inner retinal thickness (P<0.001 vs CTL, P<0.01 vs DM and increases in RGCs with terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (P<0.001 vs CTL, P<0.0001 vs DM, glial activation, and active caspase-3 (P<0.0001 vs CTL, P<0.0001 vs DM were blocked in diabetic retinas of AE extract-fed mice. Expression levels of protein O-GlcNAcylation and OGT were increased in diabetic retinas (P<0.0001 vs CTL, and the level of O-GlcNAcylation of the NF-κB p65 subunit was higher in diabetic retinas than in controls (P<0.0001 vs CTL. AE extract downregulated O-GlcNAcylation of NF-κB and prevented neurodegeneration induced by hyperglycemia (P<0.0001 vs DM. CONCLUSION: O-GlcNAcylation of NF-κB is concerned in neuronal degeneration and that AE prevents diabetes-induced RGC apoptosis via downregulation of NF-κB O-GlcNAcylation. Hence, O-GlcNAcylation may be a new object for the treatment of DR, and AE may have therapeutic possibility to prevent diabetes-induced neurodegeneration.

  11. Electronics and electronic systems

    CERN Document Server

    Olsen, George H

    1987-01-01

    Electronics and Electronic Systems explores the significant developments in the field of electronics and electronic devices. This book is organized into three parts encompassing 11 chapters that discuss the fundamental circuit theory and the principles of analog and digital electronics. This book deals first with the passive components of electronic systems, such as resistors, capacitors, and inductors. These topics are followed by a discussion on the analysis of electronic circuits, which involves three ways, namely, the actual circuit, graphical techniques, and rule of thumb. The remaining p

  12. Data on pharmacological applications and hypothermia protection against in vitro oxygen-glucose-deprivation-related neurodegeneration of adult rat CA1 region

    Directory of Open Access Journals (Sweden)

    Pınar Öz

    2017-02-01

    Here, the use CA1sp width measurements on Nissl-stained hippocampal slices is introduced as a valid and affordable method for detecting the level of neurodegeneration and neuroprotection on hippocampal slices. The protective effect of hypothermia was found to be more pronounced compared to other agents.

  13. Uranium resources

    International Nuclear Information System (INIS)

    Gangloff, A.

    1978-01-01

    It is first indicated how to evaluate the mining resources as a function of the cost of production and the degree of certainty in the knowledge of the deposit. A table is given of the world resources (at the beginning 1977) and resources and reserves are compared. There is a concordance between requirements and possible production until 1990. The case of France is examined: known reserves, present and future prospection, present production (In 1978 2200 T of U metal will be produced from 3 French processing plants), production coming from Cogema. A total production of 2000 T in 1980 and 10.000 in 1985 is expected [fr

  14. Nitrosamine exposure exacerbates high fat diet-mediated type 2 diabetes mellitus, non-alcoholic steatohepatitis, and neurodegeneration with cognitive impairment

    Directory of Open Access Journals (Sweden)

    de la Monte Suzanne M

    2009-12-01

    Full Text Available Abstract Background The current epidemics of type 2 diabetes mellitus (T2DM, non-alcoholic steatohepatitis (NASH, and Alzheimer's disease (AD all represent insulin-resistance diseases. Previous studies linked insulin resistance diseases to high fat diets or exposure to streptozotocin, a nitrosamine-related compound that causes T2DM, NASH, and AD-type neurodegeneration. We hypothesize that low-level exposure to nitrosamines that are widely present in processed foods, amplifies the deleterious effects of high fat intake in promoting T2DM, NASH, and neurodegeneration. Methods Long Evans rat pups were treated with N-nitrosodiethylamine (NDEA by i.p. Injection, and upon weaning, they were fed with high fat (60%; HFD or low fat (5%; LFD chow for 6 weeks. Rats were evaluated for cognitive impairment, insulin resistance, and neurodegeneration using behavioral, biochemical, molecular, and histological methods. Results NDEA and HFD ± NDEA caused T2DM, NASH, deficits in spatial learning, and neurodegeneration with hepatic and brain insulin and/or IGF resistance, and reductions in tau and choline acetyltransferase levels in the temporal lobe. In addition, pro-ceramide genes, which promote insulin resistance, were increased in livers and brains of rats exposed to NDEA, HFD, or both. In nearly all assays, the adverse effects of HFD+NDEA were worse than either treatment alone. Conclusions Environmental and food contaminant exposures to low, sub-mutagenic levels of nitrosamines, together with chronic HFD feeding, function synergistically to promote major insulin resistance diseases including T2DM, NASH, and AD-type neurodegeneration. Steps to minimize human exposure to nitrosamines and consumption of high-fat content foods are needed to quell these costly and devastating epidemics.

  15. Loss of Dendritic Complexity Precedes Neurodegeneration in a Mouse Model with Disrupted Mitochondrial Distribution in Mature Dendrites

    Directory of Open Access Journals (Sweden)

    Guillermo López-Doménech

    2016-10-01

    Full Text Available Correct mitochondrial distribution is critical for satisfying local energy demands and calcium buffering requirements and supporting key cellular processes. The mitochondrially targeted proteins Miro1 and Miro2 are important components of the mitochondrial transport machinery, but their specific roles in neuronal development, maintenance, and survival remain poorly understood. Using mouse knockout strategies, we demonstrate that Miro1, as opposed to Miro2, is the primary regulator of mitochondrial transport in both axons and dendrites. Miro1 deletion leads to depletion of mitochondria from distal dendrites but not axons, accompanied by a marked reduction in dendritic complexity. Disrupting postnatal mitochondrial distribution in vivo by deleting Miro1 in mature neurons causes a progressive loss of distal dendrites and compromises neuronal survival. Thus, the local availability of mitochondrial mass is critical for generating and sustaining dendritic arbors, and disruption of mitochondrial distribution in mature neurons is associated with neurodegeneration.

  16. A Novel Drug Delivery Vesicle Development to Reverse Neurodegeneration: Analysis of the Interactions among Protein, Graphene Oxide and Liposome

    Science.gov (United States)

    Miraz, Md Alamin

    In this study, Liposome was decorated with graphene oxide (GO) to synthesize fully-biocompatible theranostic vesicle that can carry bovine serum albumin (BSA) as a model protein. Graphene oxide has been studied as one of the most promising platforms for promoting the growth and repair of neurons. Our graphene oxide based structure could account for the high efficiency of protein loading and deliver to the damaged neuron cell which can reverse the neurodegeneration associated with Alzheimer's disease. The resultant vesicle exhibited high stability in aqueous solution. We investigated the protein adsorption capacity and protein interaction to carbon-based nanomaterials. The Liposome, graphene oxide and bovine serum albumin (BSA) are all biocompatible and hence will not trigger an immune response in vivo.

  17. Seaweed resources

    Digital Repository Service at National Institute of Oceanography (India)

    Deshmukhe, G.V.; Dhargalkar, V.K.; Untawale, A.G.

    The chapter summarizes our present knowledge of the seaweed resources of the Indian Ocean region with regard to the phytogeographical distribution, composition, biomass, utilization, cultivation, conservation and management. The voluminous data...

  18. Arthritis - resources

    Science.gov (United States)

    Resources - arthritis ... The following organizations provide more information on arthritis : American Academy of Orthopaedic Surgeons -- orthoinfo.aaos.org/menus/arthritis.cfm Arthritis Foundation -- www.arthritis.org Centers for Disease Control and Prevention -- www. ...

  19. Mineral resources

    Digital Repository Service at National Institute of Oceanography (India)

    Valsangkar, A.B.

    (placers), biogenous (ooze, limestone) or chemogenous (phosphorites and polymetallic nodules) type. In recent years, hydrothermal deposits, cobalt crust and methane gas hydrates are considered as frontier resources. Their distribution depends upon proximity...

  20. Depression - resources

    Science.gov (United States)

    Resources - depression ... Depression is a medical condition. If you think you may be depressed, see a health care provider. ... following organizations are good sources of information on depression : American Psychological Association -- www.apa.org/topics/depression/ ...

  1. Hemophilia - resources

    Science.gov (United States)

    Resources - hemophilia ... The following organizations provide further information on hemophilia : Centers for Disease Control and Prevention -- www.cdc.gov/ncbddd/hemophilia/index.html National Heart, Lung, and Blood Institute -- www.nhlbi.nih.gov/ ...

  2. Diabetes - resources

    Science.gov (United States)

    Resources - diabetes ... The following sites provide further information on diabetes: American Diabetes Association -- www.diabetes.org Juvenile Diabetes Research Foundation International -- www.jdrf.org National Center for Chronic Disease Prevention and Health Promotion -- ...

  3. Andrographolide - A promising therapeutic agent, negatively regulates glial cell derived neurodegeneration of prefrontal cortex, hippocampus and working memory impairment.

    Science.gov (United States)

    Das, Sudeshna; Mishra, K P; Ganju, Lilly; Singh, S B

    2017-12-15

    Over activation of glial cell derived innate immune factors induces neuro-inflammation that results in neurodegenerative disease, like working memory impairment. In this study, we have investigated the role of andrographolide, a major constituent of Andrographis paniculata plant, in reduction of reactive glial cell derived working memory impairment. Real time PCR, Western bloting, flow cytometric and immunofluorescence studies demonstrated that andrographolide inhibited lipopolysaccharide (LPS)-induced overexpression of HMGB1, TLR4, NFκB, COX-2, iNOS, and release of inflammatory mediators in primary mix glial culture, adult mice prefrontal cortex and hippocampus region. Active microglial and reactive astrocytic makers were also downregulated after andrographolide treatment. Andrographolide suppressed overexpression of microglial MIP-1α, P2X7 receptor and its downstream signaling mediators including-inflammasome NLRP3, caspase1 and mature IL-1β. Furthermore, in vivo maze studies suggested that andrographolide treatment reversed LPS-induced behavioural and working memory disturbances including regulation of expression of protein markers like PKC, p-CREB, amyloid beta, APP, p-tau, synapsin and PSD-95. Andrographolide, by lowering expression of pro apoptotic genes and enhancing the expression of anti-apoptotic gene showed its anti-apoptotic nature that in turn reduces neurodegeneration. Morphology studies using Nissl and FJB staining also showed the neuroprotective effect of andrographolide in the prefrontal cortex region. The above studies indicated that andrographolide prevented neuroinflammation-associated neurodegeneration and improved synaptic plasticity markers in cortical as well as hippocampal region which suggests that andrographolide could be a novel pharmacological countermeasure for the treatment of neuroinflammation and neurological disorders related to memory impairment. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. A new in vivo model of pantothenate kinase-associated neurodegeneration reveals a surprising role for transcriptional regulation in pathogenesis.

    Directory of Open Access Journals (Sweden)

    Varun ePandey

    2013-09-01

    Full Text Available Pantothenate Kinase-Associated Neurodegeneration (PKAN is a neurodegenerative disorder with a poorly understood molecular mechanism. It is caused by mutations in Pantothenate Kinase, the first enzyme in the Coenzyme A (CoA biosynthetic pathway. Here, we developed a Drosophila model of PKAN (tim-fbl flies that allows us to continuously monitor the modeled disease in the brain. In tim-fbl flies, downregulation of fumble, the Drosophila PanK homologue in the cells containing a circadian clock results in characteristic features of PKAN such as developmental lethality, hypersensitivity to oxidative stress, and diminished life span. Despite quasi-normal circadian transcriptional rhythms, tim-fbl flies display brain-specific aberrant circadian locomotor rhythms, and a unique transcriptional signature. Comparison with expression data from flies exposed to paraquat demonstrates that, as previously suggested, pathways others than oxidative stress are affected by PANK downregulation. Surprisingly we found a significant decrease in the expression of key components of the photoreceptor recycling pathways, which could lead to retinal degeneration, a hallmark of PKAN. Importantly, these defects are not accompanied by changes in structural components in eye genes suggesting that changes in gene expression in the eye precede and may cause the retinal degeneration. Indeed tim-fbl flies have diminished response to light transitions, and their altered day/night patterns of activity demonstrates defects in light perception. This suggest that retinal lesions are not solely due to oxidative stress and demonstrates a role for the transcriptional response to CoA deficiency underlying the defects observed in dPanK deficient flies. Moreover, in the present study we developed a new fly model that can be applied to other diseases and that allows the assessment of neurodegeneration in the brains of living flies.

  5. Pharmacologic antagonism of dopamine receptor D3 attenuates neurodegeneration and motor impairment in a mouse model of Parkinson's disease.

    Science.gov (United States)

    Elgueta, Daniela; Aymerich, María S; Contreras, Francisco; Montoya, Andro; Celorrio, Marta; Rojo-Bustamante, Estefanía; Riquelme, Eduardo; González, Hugo; Vásquez, Mónica; Franco, Rafael; Pacheco, Rodrigo

    2017-02-01

    Neuroinflammation involves the activation of glial cells, which is associated to the progression of neurodegeneration in Parkinson's disease. Recently, we and other researchers demonstrated that dopamine receptor D3 (D3R)-deficient mice are completely refractory to neuroinflammation and consequent neurodegeneration associated to the acute intoxication with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In this study we examined the therapeutic potential and underlying mechanism of a D3R-selective antagonist, PG01037, in mice intoxicated with a chronic regime of administration of MPTP and probenecid (MPTPp). Biodistribution analysis indicated that intraperitoneally administered PG01037 crosses the blood-brain barrier and reaches the highest concentration in the brain 40 min after the injection. Furthermore, the drug was preferentially distributed to the brain in comparison to the plasma. Treatment of MPTPp-intoxicated mice with PG01037 (30 mg/kg, administrated twice a week for five weeks) attenuated the loss of dopaminergic neurons in the substantia nigra pars compacta, as evaluated by stereological analysis, and the loss of striatal dopaminergic terminals, as determined by densitometric analyses of tyrosine hydroxylase and dopamine transporter immunoreactivities. Accordingly, the treatment resulted in significant improvement of motor performance of injured animals. Interestingly, the therapeutic dose of PG01037 exacerbated astrogliosis and resulted in increased ramification density of microglial cells in the striatum of MPTPp-intoxicated mice. Further analyses suggested that D3R expressed in astrocytes favours a beneficial astrogliosis with anti-inflammatory consequences on microglia. Our findings indicate that D3R-antagonism exerts a therapeutic effect in parkinsonian animals by reducing the loss of dopaminergic neurons in the nigrostriatal pathway, alleviating motor impairments and modifying the pro-inflammatory phenotype of glial cells. Copyright

  6. XY sex chromosome complement, compared with XX, in the CNS confers greater neurodegeneration during experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Du, Sienmi; Itoh, Noriko; Askarinam, Sahar; Hill, Haley; Arnold, Arthur P; Voskuhl, Rhonda R

    2014-02-18

    Women are more susceptible to multiple sclerosis (MS) and have more robust immune responses than men. However, men with MS tend to demonstrate a more progressive disease course than women, suggesting a disconnect between the severity of an immune attack and the CNS response to a given immune attack. We have previously shown in an MS model, experimental autoimmune encephalomyelitis, that autoantigen-sensitized XX lymph node cells, compared with XY, are more encephalitogenic. These studies demonstrated an effect of sex chromosomes in the induction of immune responses, but did not address a potential role of sex chromosomes in the CNS response to immune-mediated injury. Here, we examined this possibility using XX versus XY bone marrow chimeras reconstituted with a common immune system of one sex chromosomal type. We found that experimental autoimmune encephalomyelitis mice with an XY sex chromosome complement in the CNS, compared with XX, demonstrated greater clinical disease severity with more neuropathology in the spinal cord, cerebellum, and cerebral cortex. A candidate gene on the X chromosome, toll-like receptor 7, was then examined. Toll-like receptor 7 expression in cortical neurons was higher in mice with XY compared with mice with XX CNS, consistent with the known neurodegenerative role for toll-like receptor 7 in neurons. These results suggest that sex chromosome effects on neurodegeneration in the CNS run counter to effects on immune responses, and may bear relevance to the clinical enigma of greater MS susceptibility in women but faster disability progression in men. This is a demonstration of a direct effect of sex chromosome complement on neurodegeneration in a neurological disease.

  7. In vivo treatment with diphenyl ditelluride induces neurodegeneration in striatum of young rats: Implications of MAPK and Akt pathways

    Energy Technology Data Exchange (ETDEWEB)

    Heimfarth, Luana; Loureiro, Samanta Oliveira; Dutra, Márcio Ferreira; Andrade, Cláudia; Pettenuzzo, Letícia; Guma, Fátima T. Costa Rodrigues; Gonçalves, Carlos Alberto Saraiva [Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS (Brazil); Batista Teixeira da Rocha, João [Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, RS Brazil (Brazil); Pessoa-Pureur, Regina, E-mail: rpureur@ufrgs.br [Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS (Brazil)

    2012-10-15

    In the present report 15 day-old Wistar rats were injected with 0.3 μmol of diphenyl ditelluride (PhTe){sub 2}/kg body weight and parameters of neurodegeneration were analyzed in slices from striatum 6 days afterwards. We found hyperphosphorylation of intermediate filament (IF) proteins from astrocyte (glial fibrillary acidic protein—GFAP and vimentin) and from neuron (low-, medium- and high molecular weight neurofilament subunits: NF-L, NF-M and NF-H, respectively) and increased MAPK (Erk, JNK and p38MAPK) as well as PKA activities. The treatment induced reactive astrogliosis in the striatum, evidenced by increased GFAP and vimentin immunocontent as well as their mRNA overexpression. Also, (PhTe){sub 2} significantly increased the propidium iodide (PI) positive cells in NeuN positive population without altering PI incorporation into GFAP positive cells, indicating that in vivo exposure to (PhTe){sub 2} provoked neuronal damage. Immunohistochemistry showed a dramatic increase of GFAP staining characteristic of reactive astrogliosis. Moreover, increased caspase 3 in (PhTe){sub 2} treated striatal slices suggested apoptotic cell death. (PhTe){sub 2} exposure decreased Akt immunoreactivity, however phospho-GSK-3-β (Ser9) was unaltered, suggesting that this kinase is not directly implicated in the neurotoxicity of this compound. Therefore, the present results shed light into the mechanisms of (PhTe){sub 2}-induced neurodegeneration in rat striatum, evidencing a critical role for the MAPK and Akt signaling pathways and disruption of cytoskeletal homeostasis, which could be related with apoptotic neuronal death and astrogliosis. -- Highlights: ► Diphenyl ditelluride causes apoptotic neuronal death in the striatum of young rats. ► Diphenyl ditelluride causes reactive astrogliosis in the striatum of rats. ► Diphenyl ditelluride disrupts the homeostasis of the cytoskeleton of the striatum. ► The actions of diphenyl ditelluride are mediated by MAPK and Akt

  8. Forest Resources

    Energy Technology Data Exchange (ETDEWEB)

    None

    2016-06-01

    Forest biomass is an abundant biomass feedstock that complements the conventional forest use of wood for paper and wood materials. It may be utilized for bioenergy production, such as heat and electricity, as well as for biofuels and a variety of bioproducts, such as industrial chemicals, textiles, and other renewable materials. The resources within the 2016 Billion-Ton Report include primary forest resources, which are taken directly from timberland-only forests, removed from the land, and taken to the roadside.

  9. Teaching Resources

    Science.gov (United States)

    Physics?" Poster Pamphlets/Books/SPIN-UP Resources Making and Sustaining Changes in Undergraduate AAPT.org - American Association of Physics Teachers Skip to content Skip to navigation Skip to local navigation AAPT - American Association of Physics Teachers Go Sign In / Online Services Join

  10. Resource Mobilization

    International Development Research Centre (IDRC) Digital Library (Canada)

    constitute endorsement of the product and is given only for information. ..... point where they could significantly impact an organization's financial viability. This alternative ... putting in place internal systems and processes that enable the resource .... control over the incorporation of non-profit organizations. ..... Accounting.

  11. Resource Mobilization

    International Development Research Centre (IDRC) Digital Library (Canada)

    Annex 1: The Scoping Study on Donor Funding for. Development Research in ... publication of the Resource Mobilization: A Practical Guide for Research .... applied the concept or technique, which validates the practical application of ... some other staff member would write up a grant application addressed to one, two, or a ...

  12. Chemical dependence - resources

    Science.gov (United States)

    Substance use - resources, Drug abuse - resources; Resources - chemical dependence ... are a good resource for information on drug dependence: National Council on Alcoholism and Drug Dependence -- ncadd. ...

  13. Algae Resources

    Energy Technology Data Exchange (ETDEWEB)

    None

    2016-06-01

    Algae are highly efficient at producing biomass, and they can be found all over the planet. Many use sunlight and nutrients to create biomass, which contain key components—including lipids, proteins, and carbohydrates— that can be converted and upgraded to a variety of biofuels and products. A functional algal biofuels production system requires resources such as suitable land and climate, sustainable management of water resources, a supplemental carbon dioxide (CO2) supply, and other nutrients (e.g., nitrogen and phosphorus). Algae can be an attractive feedstock for many locations in the United States because their diversity allows for highpotential biomass yields in a variety of climates and environments. Depending on the strain, algae can grow by using fresh, saline, or brackish water from surface water sources, groundwater, or seawater. Additionally, they can grow in water from second-use sources such as treated industrial wastewater; municipal, agricultural, or aquaculture wastewater; or produced water generated from oil and gas drilling operations.

  14. Uranium resources

    International Nuclear Information System (INIS)

    1976-01-01

    This is a press release issued by the OECD on 9th March 1976. It is stated that the steep increases in demand for uranium foreseen in and beyond the 1980's, with doubling times of the order of six to seven years, will inevitably create formidable problems for the industry. Further substantial efforts will be needed in prospecting for new uranium reserves. Information is given in tabular or graphical form on the following: reasonably assured resources, country by country; uranium production capacities, country by country; world nuclear power growth; world annual uranium requirements; world annual separative requirements; world annual light water reactor fuel reprocessing requirements; distribution of reactor types (LWR, SGHWR, AGR, HWR, HJR, GG, FBR); and world fuel cycle capital requirements. The information is based on the latest report on Uranium Resources Production and Demand, jointly issued by the OECD's Nuclear Energy Agency (NEA) and the International Atomic Energy Agency. (U.K.)

  15. Functional and Structural Findings of Neurodegeneration in Early Stages of Diabetic Retinopathy: Cross-sectional Analyses of Baseline Data of the EUROCONDOR Project.

    Science.gov (United States)

    Santos, Ana Rita; Ribeiro, Luísa; Bandello, Francesco; Lattanzio, Rosangela; Egan, Catherine; Frydkjaer-Olsen, Ulrik; García-Arumí, José; Gibson, Jonathan; Grauslund, Jakob; Harding, Simon P; Lang, Gabriele E; Massin, Pascale; Midena, Edoardo; Scanlon, Peter; Aldington, Stephen J; Simão, Sílvia; Schwartz, Christian; Ponsati, Berta; Porta, Massimo; Costa, Miguel Ângelo; Hernández, Cristina; Cunha-Vaz, José; Simó, Rafael

    2017-09-01

    This cross-sectional study evaluated the relationship between 1 ) functional and structural measurements of neurodegeneration in the initial stages of diabetic retinopathy (DR) and 2 ) the presence of neurodegeneration and early microvascular impairment. We analyzed baseline data of 449 patients with type 2 diabetes enrolled in the European Consortium for the Early Treatment of Diabetic Retinopathy (EUROCONDOR) study (NCT01726075). Functional studies by multifocal electroretinography (mfERG) evaluated neurodysfunction, and structural measurements using spectral domain optical coherence tomography (SD-OCT) evaluated neurodegeneration. The mfERG P1 amplitude was more sensitive than the P1 implicit time and was lower in patients with Early Treatment of Diabetic Retinopathy Study (ETDRS) level 20-35 than in patients with ETDRS level <20 ( P = 0.005). In 58% of patients, mfERG abnormalities were present in the absence of visible retinopathy. Correspondence between SD-OCT thinning and mfERG abnormalities was shown in 67% of the eyes with ETDRS <20 and in 83% of the eyes with ETDRS level 20-35. Notably, 32% of patients with ETDRS 20-35 presented no abnormalities in mfERG or SD-OCT. We conclude that there is a link between mfERG and SD-OCT measurements that increases with the presence of microvascular impairment. However, a significant proportion of patients in our particular study population (ETDRS ≤35) had normal ganglion cell-inner plexiform layer thickness and normal mfERG findings. We raise the hypothesis that neurodegeneration may play a role in the pathogenesis of DR in many but not in all patients with type 2 diabetes. © 2017 by the American Diabetes Association.

  16. Dystrophic (senescent) rather than activated microglial cells are associated with tau pathology and likely precede neurodegeneration in Alzheimer?s disease

    OpenAIRE

    Streit, Wolfgang J.; Braak, Heiko; Xue, Qing-Shan; Bechmann, Ingo

    2009-01-01

    The role of microglial cells in the pathogenesis of Alzheimer’s disease (AD) neurodegeneration is unknown. Although several works suggest that chronic neuroinflammation caused by activated microglia contributes to neurofibrillary degeneration, anti-inflammatory drugs do not prevent or reverse neuronal tau pathology. This raises the question if indeed microglial activation occurs in the human brain at sites of neurofibrillary degeneration. In view of the recent work demonstrating presence of d...

  17. Water resources

    International Nuclear Information System (INIS)

    2002-01-01

    The report entitled Climate Change Impacts and Adaptation : A Canadian Perspective, presents a summary of research regarding the impacts of climate change on key sectors over the past five years as it relates to Canada. This chapter on water resources describes how climate change will affect the supply of water in Canada. Water is one of Canada's greatest resources, which contributes about $7.5 to 23 billion per year to the Canadian economy. The decisions taken to adapt to climate change within the water resources sector will have profound implications in many other areas such as agriculture, human health, transportation and industry. The water related problems include water quality issues that relate to water shortages from droughts, or excesses from floods. The Intergovernmental Panel on Climate Change forecasts an increase in global average surface air temperatures of 1.4 to 5.8 degrees C by 2100. Such a change would impact the hydrological cycle, affecting runoff, evaporation patterns, and the amount of water stored in glaciers, lakes, wetlands and groundwater. The uncertainty as to the magnitude of these changes is due to the difficulty that climate models have in projecting future changes in regional precipitation patterns and extreme events. This chapter presents potential impacts of climate change on water resources in the Yukon, British Columbia, the Prairies, the Great Lakes basin, the Atlantic provinces, and the Arctic and Subarctic. The associated concerns for each region were highlighted. Adaptation research has focused on the impacts of supply and demand, and on options to adapt to these impacts. 60 refs., 2 tabs., 1 fig

  18. Resource Abundance and Resource Dependence in China

    NARCIS (Netherlands)

    Ji, K.; Magnus, J.R.; Wang, W.

    2010-01-01

    This paper reconsiders the ‘curse of resources’ hypothesis for the case of China, and distinguishes between resource abundance, resource rents, and resource dependence. Resource abundance and resource rents are shown to be approximately equivalent, and their association with resource dependence

  19. An Overview of Culinary and Medicinal Mushrooms in Neurodegeneration and Neurotrauma Research.

    Science.gov (United States)

    Wong, Kah-Hui; Ng, Chai-Chee; Kanagasabapathy, Gowri; Yow, Yoon-Yen; Sabaratnam, Vikineswary

    2017-01-01

    Culinary and medicinal mushrooms have been appreciated since prehistoric times as valuable resources for food and medicine. Edible mushrooms represent an untapped source of nutraceuticals and valuable palatable food. Long considered tonics, they are now treasured as functional foods that can improve human health and quality of life. Numerous studies have provided insights into the neuroprotective effects of edible mushrooms, which are attributed to their antioxidant, antineuroinflammatory, and cholinesterase inhibitory properties, and their ability to prevent neuronal death. Here we review the recent literature on the role of culinary and medicinal mushrooms in the management of neurodegenerative diseases and neurotrauma. We highlight some of the molecular mechanisms for how these alternative medicines provide health benefits that could help us to harness their neuroprotective effects.

  20. Internet and Electronic Information Management

    Science.gov (United States)

    2004-12-01

    centers to form consortia and share electronic information sources. Although traditional resource sharing arrangements encouraged competition rather...outside world, through public relations and through marketing information products or services, to its own competitive advantage (Davenport 1997: 193-217... electronic information sources are a challenge for electronic information managers. Libraries and information centers are no longer “the only game in town

  1. Nicotinamide Inhibits Ethanol-Induced Caspase-3 and PARP-1 Over-activation and Subsequent Neurodegeneration in the Developing Mouse Cerebellum.

    Science.gov (United States)

    Ieraci, Alessandro; Herrera, Daniel G

    2018-06-01

    Fetal alcohol spectrum disorder (FASD) is the principal preventable cause of mental retardation in the western countries resulting from alcohol exposure during pregnancy. Ethanol-induced massive neuronal cell death occurs mainly in immature neurons during the brain growth spurt period. The cerebellum is one of the brain areas that are most sensitive to ethanol neurotoxicity. Currently, there is no effective treatment that targets the causes of these disorders and efficient treatments to counteract or reverse FASD are desirable. In this study, we investigated the effects of nicotinamide on ethanol-induced neuronal cell death in the developing cerebellum. Subcutaneous administration of ethanol in postnatal 4-day-old mice induced an over-activation of caspase-3 and PARP-1 followed by a massive neurodegeneration in the developing cerebellum. Interestingly, treatment with nicotinamide, immediately or 2 h after ethanol exposure, diminished caspase-3 and PARP-1 over-activation and reduced ethanol-induced neurodegeneration. Conversely, treatment with 3-aminobenzadine, a specific PARP-1 inhibitor, was able to completely block PARP-1 activation, but not caspase-3 activation or ethanol-induced neurodegeneration in the developing cerebellum. Our results showed that nicotinamide reduces ethanol-induced neuronal cell death and inhibits both caspase-3 and PARP-1 alcohol-induced activation in the developing cerebellum, suggesting that nicotinamide might be a promising and safe neuroprotective agent for treating FASD and other neurodegenerative disorders in the developing brain that shares similar cell death pathways.

  2. Short-term exposure to dim light at night disrupts rhythmic behaviors and causes neurodegeneration in fly models of tauopathy and Alzheimer's disease.

    Science.gov (United States)

    Kim, Mari; Subramanian, Manivannan; Cho, Yun-Ho; Kim, Gye-Hyeong; Lee, Eunil; Park, Joong-Jean

    2018-01-08

    The accumulation and aggregation of phosphorylated tau proteins in the brain are the hallmarks for the onset of Alzheimer's disease (AD). In addition, disruptions in circadian rhythms (CRs) with altered sleep-wake cycles, dysregulation of locomotion, and increased memory defects have been reported in patients with AD. Drosophila flies that have an overexpression of human tau protein in neurons exhibit most of the symptoms of human patients with AD, including locomotion defects and neurodegeneration. Using the fly model for tauopathy/AD, we investigated the effects of an exposure to dim light at night on AD symptoms. We used a light intensity of 10 lux, which is considered the lower limit of light pollution in many countries. After the tauopathy flies were exposed to the dim light at night for 3 days, the flies showed disrupted CRs, altered sleep-wake cycles due to increased pTau proteins and neurodegeneration, in the brains of the AD flies. The results indicate that the nighttime exposure of tauopathy/AD model Drosophila flies to dim light disrupted CR and sleep-wake behavior and promoted neurodegeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Automotive electronics design fundamentals

    CERN Document Server

    Zaman, Najamuz

    2015-01-01

    This book explains the topology behind automotive electronics architectures and examines how they can be profoundly augmented with embedded controllers. These controllers serve as the core building blocks of today’s vehicle electronics. Rather than simply teaching electrical basics, this unique resource focuses on the fundamental concepts of vehicle electronics architecture, and details the wide variety of Electronic Control Modules (ECMs) that enable the increasingly sophisticated "bells & whistles" of modern designs.  A must-have for automotive design engineers, technicians working in automotive electronics repair centers and students taking automotive electronics courses, this guide bridges the gap between academic instruction and industry practice with clear, concise advice on how to design and optimize automotive electronics with embedded controllers.

  4. S113R mutation in SLC33A1 leads to neurodegeneration and augmented BMP signaling in a mouse model

    Directory of Open Access Journals (Sweden)

    Pingting Liu

    2017-01-01

    Full Text Available The S113R mutation (c.339T>G (MIM #603690.0001 in SLC33A1 (MIM #603690, an ER membrane acetyl-CoA transporter, has been previously identified in individuals with hereditary spastic paraplegia type 42 (SPG42; MIM #612539. SLC33A1 has also been shown to inhibit the bone morphogenetic protein (BMP signaling pathway in zebrafish. To better understand the function of SLC33A1, we generated and characterized Slc33a1S113R knock-in mice. Homozygous Slc33a1S113R mutant mice were embryonic lethal, whereas heterozygous Slc33a1 mutant mice (Slc33a1wt/mut exhibited behavioral abnormalities and central neurodegeneration, which is consistent with hereditary spastic paraplegia (HSP phenotypes. Importantly, we found an upregulation of BMP signaling in the nervous system and mouse embryonic fibroblasts of Slc33a1wt/mut mice. Using a sciatic nerve crush injury model in vivo and dorsal root ganglion (DRG culture in vitro we showed that injury-induced axonal regeneration in Slc33a1wt/mut mice was accelerated and mediated by upregulated BMP signaling. Exogenous addition of BMP signaling antagonist, noggin, could efficiently alleviate the accelerated injury-induced axonal regrowth. These results indicate that SLC33A1 can negatively regulate BMP signaling in mice, further supporting the notion that upregulation of BMP signaling is a common mechanism of a subset of hereditary spastic paraplegias.

  5. Clinical assessment of dysphagia in neurodegeneration (CADN): development, validity and reliability of a bedside tool for dysphagia assessment.

    Science.gov (United States)

    Vogel, Adam P; Rommel, Natalie; Sauer, Carina; Horger, Marius; Krumm, Patrick; Himmelbach, Marc; Synofzik, Matthis

    2017-06-01

    Screening assessments for dysphagia are essential in neurodegenerative disease. Yet there are no purpose-built tools to quantify swallowing deficits at bedside or in clinical trials. A quantifiable, brief, easy to administer assessment that measures the impact of dysphagia and predicts the presence or absence of aspiration is needed. The Clinical Assessment of Dysphagia in Neurodegeneration (CADN) was designed by a multidisciplinary team (neurology, neuropsychology, speech pathology) validated against strict methodological criteria in two neurodegenerative diseases, Parkinson's disease (PD) and degenerative ataxia (DA). CADN comprises two parts, an anamnesis (part one) and consumption (part two). Two-thirds of patients were assessed using reference tests, the SWAL-QOL symptoms subscale (part one) and videofluoroscopic assessment of swallowing (part two). CADN has 11 items and can be administered and scored in an average of 7 min. Test-retest reliability was established using correlation and Bland-Altman plots. 125 patients with a neurodegenerative disease were recruited; 60 PD and 65 DA. Validity was established using ROC graphs and correlations. CADN has sensitivity of 79 and 84% and specificity 71 and 69% for parts one and two, respectively. Significant correlations with disease severity were also observed (p dysphagia symptomatology and risk of aspiration. The CADN is a reliable, valid, brief, quantifiable, and easily deployed assessment of swallowing in neurodegenerative disease. It is thus ideally suited for both clinical bedside assessment and future multicentre clinical trials in neurodegenerative disease.

  6. Garcinia kola aqueous suspension prevents cerebellar neurodegeneration in long-term diabetic rat - a type 1 diabetes mellitus model.

    Science.gov (United States)

    Farahna, Mohammed; Seke Etet, Paul F; Osman, Sayed Y; Yurt, Kıymet K; Amir, Naheed; Vecchio, Lorella; Aydin, Isınsu; Aldebasi, Yousef H; Sheikh, Azimullah; Chijuka, John C; Kaplan, Süleyman; Adem, Abdu

    2017-01-04

    The development of compounds able to improve metabolic syndrome and mitigate complications caused by inappropriate glycemic control in type 1 diabetes mellitus is challenging. The medicinal plant with established hypoglycemic properties Garcinia kola Heckel might have the potential to mitigate diabetes mellitus metabolic syndrome and complications. We have investigated the neuroprotective properties of a suspension of G. kola seeds in long-term type 1 diabetes mellitus rat model. Wistar rats, made diabetic by single injection of streptozotocin were monitored for 8 months. Then, they were administered with distilled water or G. kola oral aqueous suspension daily for 30 days. Body weight and glycemia were determined before and after treatment. After sacrifice, cerebella were dissected out and processed for stereological quantification of Purkinje cells. Histopathological and immunohistochemical analyses of markers of neuroinflammation and neurodegeneration were performed. Purkinje cell counts were significantly increased, and histopathological signs of apoptosis and neuroinflammation decreased, in diabetic animals treated with G. kola compared to diabetic rats given distilled water. Glycemia was also markedly improved and body weight restored to non-diabetic control values, following G. kola treatment. These results suggest that G. kola treatment improved the general condition of long-term diabetic rats and protected Purkinje cells partly by improving the systemic glycemia and mitigating neuroinflammation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Pacific Ciguatoxin Induces Excitotoxicity and Neurodegeneration in the Motor Cortex Via Caspase 3 Activation: Implication for Irreversible Motor Deficit.

    Science.gov (United States)

    Asthana, Pallavi; Zhang, Ni; Kumar, Gajendra; Chine, Virendra Bhagawan; Singh, Kunal Kumar; Mak, Yim Ling; Chan, Leo Lai; Lam, Paul Kwan Sing; Ma, Chi Him Eddie

    2018-01-18

    Consumption of fish containing ciguatera toxins or ciguatoxins (CTXs) causes ciguatera fish poisoning (CFP). In some patients, CFP recurrence occurs even years after exposure related to CTXs accumulation. Pacific CTX-1 (P-CTX-1) is one of the most potent natural substances known that causes predominantly neurological symptoms in patients; however, the underlying pathogenies of CFP remain unknown. Using clinically relevant neurobehavioral tests and electromyography (EMG) to assess effects of P-CTX-1 during the 4 months after exposure, recurrent motor strength deficit occurred in mice exposed to P-CTX-1. We detected irreversible motor strength deficits accompanied by reduced EMG activity, demyelination, and slowing of motor nerve conduction, whereas control unexposed mice fully recovered in 1 month after peripheral nerve injury. Finally, to uncover the mechanism underlying CFP, we detected reduction of spontaneous firing rate of motor cortical neurons even 6 months after exposure and increased number of glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes. Increased numbers of motor cortical neuron apoptosis were detected by dUTP-digoxigenin nick end labeling assay along with activation of caspase 3. Taken together, our study demonstrates that persistence of P-CTX-1 in the nervous system induces irreversible motor deficit that correlates well with excitotoxicity and neurodegeneration detected in the motor cortical neurons.

  8. Synthesis of new heterocyclic compounds based on pyrazolopyridine scaffold and evaluation of their neuroprotective potential in MPP+-induced neurodegeneration.

    Science.gov (United States)

    Jouha, Jabrane; Loubidi, Mohammed; Bouali, Jamila; Hamri, Salha; Hafid, Abderrafia; Suzenet, Franck; Guillaumet, Gérald; Dagcı, Taner; Khouili, Mostafa; Aydın, Fadime; Saso, Luciano; Armagan, Güliz

    2017-03-31

    Neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, and Huntington's disease affect millions of people in the world. Thus several new approaches to treat brain disorders are under development. The aim of the present study is to synthesize potential neuroprotective heterocyclic compounds based on pyrazolopyridine derivatives and then to evaluate their effects in MPP + -induced neurodegeneration in human neuroblastoma cell line (SH-SY5Y cells). The effects of the compounds on cell viability were measured by MTT assay and the changes in apoptosis-related proteins including bax, Bcl-2, Bcl-xl and caspase-3 were investigated by western blot technique. Based on the cell viability results obtained by MTT assay, the percentage of neuroprotection-induced by compounds against MPP + -induced neurotoxicity in SH-SY5Y cells was between 20% and 30% at 5 μM concentrations of all synthesized compounds. Moreover, the downregulation in pro-apoptotic proteins including bax and caspase-3 were found following the novel synthesized compounds treatments and these effects were observed in a dose-dependent manner. Our results provide an evidence that these heterocyclic compounds based on pyrazolopyridine derivatives may have a role on dopaminergic neuroprotection via antiapoptotic pathways. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. Targeting PERK signaling with the small molecule GSK2606414 prevents neurodegeneration in a model of Parkinson's disease.

    Science.gov (United States)

    Mercado, Gabriela; Castillo, Valentina; Soto, Paulina; López, Nélida; Axten, Jeffrey M; Sardi, Sergio P; Hoozemans, Jeroen J M; Hetz, Claudio

    2018-04-01

    Parkinson's disease (PD) is the second most common neurodegenerative disorder, leading to the progressive decline of motor control due to the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Accumulating evidence suggest that altered proteostasis is a salient feature of PD, highlighting perturbations to the endoplasmic reticulum (ER), the main compartment involved in protein folding and secretion. PERK is a central ER stress sensor that enforces adaptive programs to recover homeostasis through a block of protein translation and the induction of the transcription factor ATF4. In addition, chronic PERK signaling results in apoptosis induction and neuronal dysfunction due to the repression in the translation of synaptic proteins. Here we confirmed the activation of PERK signaling in postmortem brain tissue derived from PD patients and three different rodent models of the disease. Pharmacological targeting of PERK by the oral administration of GSK2606414 demonstrated efficient inhibition of the pathway in the SNpc after experimental ER stress stimulation. GSK2606414 protected nigral-dopaminergic neurons against a PD-inducing neurotoxin, improving motor performance. The neuroprotective effects of PERK inhibition were accompanied by an increase in dopamine levels and the expression of synaptic proteins. However, GSK2606414 treated animals developed secondary effects possibly related to pancreatic toxicity. This study suggests that strategies to attenuate ER stress levels may be effective to reduce neurodegeneration in PD. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Ferrous Iron Up-regulation in Fibroblasts of Patients with Beta Propeller Protein-Associated Neurodegeneration (BPAN).

    Science.gov (United States)

    Ingrassia, Rosaria; Memo, Maurizio; Garavaglia, Barbara

    2017-01-01

    Mutations in WDR45 gene, coding for a beta-propeller protein, have been found in patients affected by Neurodegeneration with Brain Iron Accumulation, NBIA5 (also known as BPAN). BPAN is a movement disorder with Non Transferrin Bound Iron (NTBI) accumulation in the basal ganglia as common hallmark between NBIA classes (Hayflick et al., 2013). WDR45 has been predicted to have a role in autophagy, while the impairment of iron metabolism in the different NBIA subclasses has not currently been clarified. We found the up-regulation of the ferrous iron transporter (-)IRE/Divalent Metal Transporter1 and down-regulation of Transferrin receptor in the fibroblasts of two BPAN affected patients with splicing mutations 235+1G>A (BPAN1) and 517_519ΔVal 173 (BPAN2). The BPAN patients showed a concomitant increase of intracellular ferrous iron after starvation. An altered pattern of iron transporters with iron overload is highlighted in BPAN human fibroblasts, supporting for a role of DMT1 in NBIA. We here present a novel element, about iron accumulation, to the existing knowledge in field of NBIA. Attention is focused to a starvation-dependent iron overload, possibly accounting for iron accumulation in the basal ganglia. Further investigation could clarify iron regulation in BPAN.

  11. Identification of Novel Compound Mutations in PLA2G6-Associated Neurodegeneration Patient with Characteristic MRI Imaging.

    Science.gov (United States)

    Guo, Sen; Yang, Liu; Liu, Huijie; Chen, Wei; Li, Jinchen; Yu, Ping; Sun, Zhong Sheng; Chen, Xiang; Du, Jie; Cai, Tao

    2017-08-01

    Neurodegeneration with brain iron accumulation comprises a heterogeneous group of disorders characterized clinically by progressive motor dysfunction. Accurate identification of de novo and rare inherited mutations is important for determining causative genes of undiagnosed neurological diseases. In the present study, we report a unique case with cerebellar ataxia symptoms and social communication difficulties in an intermarriage family. MRI showed a marked cerebellar atrophy and the "eye-of-the-tiger"-like sign in the medial globus pallidus. Potential genetic defects were screened by whole-exome sequencing (WES) for the patient and four additional family members. A previously undescribed de novo missense mutation (c.1634A>G, p.K545R) in the exon 12 of the PLA2G6 gene was identified. A second rare variant c.1077G>A at the end of exon 7 was also identified, which was inherited from the mother, and resulted in a frame-shift mutation (c.1074_1077del.GTCG) due to an alternative splicing. In conclusion, the identification of the "eye-of-the-tiger"-like sign in the globus pallidus of the patient expands the phenotypic spectrum of PLA2G6-associated disorders and reveals its value in differential diagnosis of PLA2G6-associated disorders.

  12. Parkinson phenotype in aged PINK1-deficient mice is accompanied by progressive mitochondrial dysfunction in absence of neurodegeneration.

    Directory of Open Access Journals (Sweden)

    Suzana Gispert

    Full Text Available BACKGROUND: Parkinson's disease (PD is an adult-onset movement disorder of largely unknown etiology. We have previously shown that loss-of-function mutations of the mitochondrial protein kinase PINK1 (PTEN induced putative kinase 1 cause the recessive PARK6 variant of PD. METHODOLOGY/PRINCIPAL FINDINGS: Now we generated a PINK1 deficient mouse and observed several novel phenotypes: A progressive reduction of weight and of locomotor activity selectively for spontaneous movements occurred at old age. As in PD, abnormal dopamine levels in the aged nigrostriatal projection accompanied the reduced movements. Possibly in line with the PARK6 syndrome but in contrast to sporadic PD, a reduced lifespan, dysfunction of brainstem and sympathetic nerves, visible aggregates of alpha-synuclein within Lewy bodies or nigrostriatal neurodegeneration were not present in aged PINK1-deficient mice. However, we demonstrate PINK1 mutant mice to exhibit a progressive reduction in mitochondrial preprotein import correlating with defects of core mitochondrial functions like ATP-generation and respiration. In contrast to the strong effect of PINK1 on mitochondrial dynamics in Drosophila melanogaster and in spite of reduced expression of fission factor Mtp18, we show reduced fission and increased aggregation of mitochondria only under stress in PINK1-deficient mouse neurons. CONCLUSION: Thus, aging Pink1(-/- mice show increasing mitochondrial dysfunction resulting in impaired neural activity similar to PD, in absence of overt neuronal death.

  13. Uranium resource processing. Secondary resources

    International Nuclear Information System (INIS)

    Gupta, C.K.; Singh, H.

    2003-01-01

    This book concentrates on the processing of secondary sources for recovering uranium, a field which has gained in importance in recent years as it is environmental-friendly and economically in tune with the philosophy of sustainable development. Special mention is made of rock phosphate, copper and gold tailings, uranium scrap materials (both natural and enriched) and sea water. This volume includes related area of ore mineralogy, resource classification, processing principles involved in solubilization followed by separation and safety aspects

  14. Energy resources

    CERN Document Server

    Simon, Andrew L

    1975-01-01

    Energy Resources mainly focuses on energy, including its definition, historical perspective, sources, utilization, and conservation. This text first explains what energy is and what its uses are. This book then explains coal, oil, and natural gas, which are some of the common energy sources used by various industries. Other energy sources such as wind, solar, geothermal, water, and nuclear energy sources are also tackled. This text also looks into fusion energy and techniques of energy conversion. This book concludes by explaining the energy allocation and utilization crisis. This publ

  15. Loss of thymidine kinase 2 alters neuronal bioenergetics and leads to neurodegeneration.

    Science.gov (United States)

    Bartesaghi, Stefano; Betts-Henderson, Joanne; Cain, Kelvin; Dinsdale, David; Zhou, Xiaoshan; Karlsson, Anna; Salomoni, Paolo; Nicotera, Pierluigi

    2010-05-01

    Mutations of thymidine kinase 2 (TK2), an essential component of the mitochondrial nucleotide salvage pathway, can give rise to mitochondrial DNA (mtDNA) depletion syndromes (MDS). These clinically heterogeneous disorders are characterized by severe reduction in mtDNA copy number in affected tissues and are associated with progressive myopathy, hepatopathy and/or encephalopathy, depending in part on the underlying nuclear genetic defect. Mutations of TK2 have previously been associated with an isolated myopathic form of MDS (OMIM 609560). However, more recently, neurological phenotypes have been demonstrated in patients carrying TK2 mutations, thus suggesting that loss of TK2 results in neuronal dysfunction. Here, we directly address the role of TK2 in neuronal homeostasis using a knockout mouse model. We demonstrate that in vivo loss of TK2 activity leads to a severe ataxic phenotype, accompanied by reduced mtDNA copy number and decreased steady-state levels of electron transport chain proteins in the brain. In TK2-deficient cerebellar neurons, these abnormalities are associated with impaired mitochondrial bioenergetic function, aberrant mitochondrial ultrastructure and degeneration of selected neuronal types. Overall, our findings demonstrate that TK2 deficiency leads to neuronal dysfunction in vivo, and have important implications for understanding the mechanisms of neurological impairment in MDS.

  16. Electronic technology

    International Nuclear Information System (INIS)

    Kim, Jin Su

    2010-07-01

    This book is composed of five chapters, which introduces electronic technology about understanding of electronic, electronic component, radio, electronic application, communication technology, semiconductor on its basic, free electron and hole, intrinsic semiconductor and semiconductor element, Diode such as PN junction diode, characteristic of junction diode, rectifier circuit and smoothing circuit, transistor on structure of transistor, characteristic of transistor and common emitter circuit, electronic application about electronic equipment, communication technology and education, robot technology and high electronic technology.

  17. Mineral resources

    International Nuclear Information System (INIS)

    1991-09-01

    This paper reports that to prevent the concentration of control over federal oil and gas resources in a few companies or individuals, Congress has limited the number of acres of oil and gas leases that one party may control in a single state. An exception to this limitation involves lease acreage within the boundaries of development contracts. These contracts permit oil and gas lease operators and pipeline companies to contract with enough lessees to economically justify large-scale drilling operations for the production and transportation of oil and gas, subject to approval by the Secretary of the Interior, who must find that such contracts are in the public interest. Since 1986 Interior has entered into or approved 10 contracts with 12 lease operators for exploration of largely unleased federal lands-ranging from about 180,000 to 3.5 million acres in four western states-and has designated them as developmental contracts. GAO believes that the 10 contracts do not satisfy the legal requirements for development contracts because they are for oil and gas exploration on largely unleased federal lands, rather than for developing existing leases. By designating the 10 contracts as development contracts, Interior has enabled nine of the 12 contract parties to accumulate lease acreage that vastly exceeds the statutory acreage limitation. All nine of the contract parties were major or large independent oil companies. As a result, other parties who wish to participate in developing federal oil and gas resources within the four states may be adversely affected because the parties to Interior's contracts have been able to compete for and obtain lease acreage beyond the statutory acreage limitation. Although Interior believes that the Secretary has the discretion under law to use development contracts in the current manner, in April 1989 it ceased issuing these contracts pending completion of GAO's review

  18. The Electron

    Energy Technology Data Exchange (ETDEWEB)

    Thomson, George

    1972-01-01

    Electrons are elementary particles of atoms that revolve around and outside the nucleus and have a negative charge. This booklet discusses how electrons relate to electricity, some applications of electrons, electrons as waves, electrons in atoms and solids, the electron microscope, among other things.

  19. Hard electronics; Hard electronics

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    Hard material technologies were surveyed to establish the hard electronic technology which offers superior characteristics under hard operational or environmental conditions as compared with conventional Si devices. The following technologies were separately surveyed: (1) The device and integration technologies of wide gap hard semiconductors such as SiC, diamond and nitride, (2) The technology of hard semiconductor devices for vacuum micro- electronics technology, and (3) The technology of hard new material devices for oxides. The formation technology of oxide thin films made remarkable progress after discovery of oxide superconductor materials, resulting in development of an atomic layer growth method and mist deposition method. This leading research is expected to solve such issues difficult to be easily realized by current Si technology as high-power, high-frequency and low-loss devices in power electronics, high temperature-proof and radiation-proof devices in ultimate electronics, and high-speed and dense- integrated devices in information electronics. 432 refs., 136 figs., 15 tabs.

  20. Organophosphate-Induced Changes in the PKA Regulatory Function of Swiss Cheese/NTE Lead to Behavioral Deficits and Neurodegeneration

    Science.gov (United States)

    Kretzschmar, Doris

    2014-01-01

    Organophosphate-induced delayed neuropathy (OPIDN) is a Wallerian-type axonopathy that occurs weeks after exposure to certain organophosphates (OPs). OPs have been shown to bind to Neuropathy Target Esterase (NTE), thereby inhibiting its enzymatic activity. However, only OPs that also induce the so-called aging reaction cause OPIDN. This reaction results in the release and possible transfer of a side group from the bound OP to NTE and it has been suggested that this induces an unknown toxic function of NTE. To further investigate the mechanisms of aging OPs, we used Drosophila, which expresses a functionally conserved orthologue of NTE named Swiss Cheese (SWS). Treating flies with the organophosporous compound tri-ortho-cresyl phosphate (TOCP) resulted in behavioral deficits and neurodegeneration two weeks after exposure, symptoms similar to the delayed effects observed in other models. In addition, we found that primary neurons showed signs of axonal degeneration within an hour after treatment. Surprisingly, increasing the levels of SWS, and thereby its enzymatic activity after exposure, did not ameliorate these phenotypes. In contrast, reducing SWS levels protected from TOCP-induced degeneration and behavioral deficits but did not affect the axonopathy observed in cell culture. Besides its enzymatic activity as a phospholipase, SWS also acts as regulatory PKA subunit, binding and inhibiting the C3 catalytic subunit. Measuring PKA activity in TOCP treated flies revealed a significant decrease that was also confirmed in treated rat hippocampal neurons. Flies expressing additional PKA-C3 were protected from the behavioral and degenerative phenotypes caused by TOCP exposure whereas primary neurons were not. In addition, knocking-down PKA-C3 caused similar behavioral and degenerative phenotypes as TOCP treatment. We therefore propose a model in which OP-modified SWS cannot release PKA-C3 and that the resulting loss of PKA-C3 activity plays a crucial role in developing

  1. NEW ROLES FOR FC RECEPTORS IN NEURODEGENERATION-THE IMPACT ON IMMUNOTHERAPY FOR ALZHEIMER’S DISEASE

    Directory of Open Access Journals (Sweden)

    James P. Fuller

    2014-08-01

    Full Text Available There are an estimated 18 million Alzheimer’s disease (AD sufferers worldwide and with no disease modifying treatment currently available, development of new therapies represents an enormous unmet clinical need. AD is characterised by episodic memory loss followed by severe cognitive decline and is associated with many neuropathological changes. AD is characterised by deposits of amyloid beta (Aβ, neurofibrillary tangles, and neuroinflammation. Active immunisation or passive immunisation against Aβ leads to the clearance of deposits in transgenic mice expressing human Aβ. This clearance is associated with reversal of associated cognitive deficits, but these results have failed to translate to humans, with both active and passive immunotherapy failing to improve memory loss. One explanation for these observations is that certain anti-Aβ antibodies mediate damage to the cerebral vasculature limiting the top dose and potentially reducing efficacy. Fc gamma receptors (Fcγ are a family of immunoglobulin like receptors which bind to the Fc portion of IgG, and mediate the response of effector cells to immune complexes. Data from both mouse and human studies suggest that cross-linking Fc receptors by therapeutic antibodies and the subsequent pro-inflammatory response mediates the vascular side effects seen following immunotherapy. Increasing evidence is emerging that Fc receptor expression on CNS resident cells, including microglia and neurons, is increased during aging and functionally involved in the pathogenesis of age-related neurodegenerative diseases. We propose that increased expression and ligation of Fc receptors in the CNS, either by endogenous IgG or therapeutic antibodies, has the potential to induce vascular damage and exacerbate neurodegeneration. To produce safe and effective immunotherapies for AD and other neurodegenerative diseases it will be vital to understand the role of Fc receptors in the healthy and diseased brain.

  2. Neuroinflammation and J2 prostaglandins: linking impairment of the ubiquitin-proteasome pathway and mitochondria to neurodegeneration

    Directory of Open Access Journals (Sweden)

    Maria Emilia Figueiredo-Pereira

    2015-01-01

    Full Text Available The immune response of the CNS is a defense mechanism activated upon injury to initiate repair mechanisms while chronic over-activation of the CNS immune system (termed neuroinflammation may exacerbate injury. The latter is implicated in a variety of neurological and neurodegenerative disorders such as Alzheimer and Parkinson diseases, amyotrophic lateral sclerosis, multiple sclerosis, traumatic brain injury, HIV dementia and prion diseases. Cyclooxygenases (COX -1 and COX-2, which are key enzymes in the conversion of arachidonic acid into bioactive prostanoids, play a central role in the inflammatory cascade. J2 prostaglandins are endogenous toxic products of cyclooxygenases, and because their levels are significantly increased upon brain injury, they are actively involved in neuronal dysfunction induced by pro-inflammatory stimuli. In this review, we highlight the mechanisms by which J2 prostaglandins (1 exert their actions, (2 potentially contribute to the transition from acute to chronic inflammation and to the spreading of neuropathology, (3 disturb the ubiquitin-proteasome pathway and mitochondrial function, and (4 contribute to neurodegenerative disorders such as Alzheimer and Parkinson diseases, and amyotrophic lateral sclerosis, as well as stroke, traumatic brain injury, and demyelination in Krabbe disease. We conclude by discussing the therapeutic potential of targeting the J2 prostaglandin pathway to prevent/delay neurodegeneration associated with neuroinflammation. In this context, we suggest a shift from the traditional view that cyclooxygenases are the most appropriate targets to treat neuroinflammation, to the notion that J2 prostaglandin pathways and other neurotoxic prostaglandins downstream from cyclooxygenases, would offer significant benefits as more effective therapeutic targets to treat chronic neurodegenerative diseases, while minimizing adverse side effects.

  3. Fisetin as a caloric restriction mimetic protects rat brain against aging induced oxidative stress, apoptosis and neurodegeneration.

    Science.gov (United States)

    Singh, Sandeep; Singh, Abhishek Kumar; Garg, Geetika; Rizvi, Syed Ibrahim

    2018-01-15

    In the present study, attempts have been made to evaluate the potential role of fisetin, a caloric restriction mimetic (CRM), for neuroprotection in D-galactose (D-gal) induced accelerated and natural aging models of rat. Fisetin was supplemented (15mg/kg b.w., orally) to young, D-gal induced aged (D-gal 500mg/kg b.w subcutaneously) and naturally aged rats for 6weeks. Standard protocols were employed to measure pro-oxidants, antioxidants and mitochondrial membrane potential in brain tissues. Gene expression analysis with reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to assess the expression of autophagy, neuronal, aging as well as inflammatory marker genes. We have also evaluated apoptotic cell death and synaptosomal membrane-bound ion transporter activities in brain tissues. Our data demonstrated that fisetin significantly decreased the level of pro-oxidants and increased the level of antioxidants. Furthermore, fisetin also ameliorated mitochondrial membrane depolarization, apoptotic cell death and impairments in the activities of synaptosomal membrane-bound ion transporters in aging rat brain. RT-PCR data revealed that fisetin up-regulated the expression of autophagy genes (Atg-3 and Beclin-1), sirtuin-1 and neuronal markers (NSE and Ngb), and down-regulated the expression of inflammatory (IL-1β and TNF-α) and Sirt-2 genes respectively in aging brain. The present study suggests that fisetin supplementation may provide neuroprotection against aging-induced oxidative stress, apoptotic cell death, neuro-inflammation, and neurodegeneration in rat brain. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Social Studies Online Resources. Media Corner.

    Science.gov (United States)

    Wilson, Jeri, Ed.

    1995-01-01

    Maintains that three types of social studies activities are found on the information highway: (1) electronic mail; (2) information; and (3) conferencing. Describes examples of each. Discusses commercial services and resource materials and provides references to online services. (CFR)

  5. The Biomedical Resource Ontology (BRO) to enable resource discovery in clinical and translational research.

    Science.gov (United States)

    Tenenbaum, Jessica D; Whetzel, Patricia L; Anderson, Kent; Borromeo, Charles D; Dinov, Ivo D; Gabriel, Davera; Kirschner, Beth; Mirel, Barbara; Morris, Tim; Noy, Natasha; Nyulas, Csongor; Rubenson, David; Saxman, Paul R; Singh, Harpreet; Whelan, Nancy; Wright, Zach; Athey, Brian D; Becich, Michael J; Ginsburg, Geoffrey S; Musen, Mark A; Smith, Kevin A; Tarantal, Alice F; Rubin, Daniel L; Lyster, Peter

    2011-02-01

    The biomedical research community relies on a diverse set of resources, both within their own institutions and at other research centers. In addition, an increasing number of shared electronic resources have been developed. Without effective means to locate and query these resources, it is challenging, if not impossible, for investigators to be aware of the myriad resources available, or to effectively perform resource discovery when the need arises. In this paper, we describe the development and use of the Biomedical Resource Ontology (BRO) to enable semantic annotation and discovery of biomedical resources. We also describe the Resource Discovery System (RDS) which is a federated, inter-institutional pilot project that uses the BRO to facilitate resource discovery on the Internet. Through the RDS framework and its associated Biositemaps infrastructure, the BRO facilitates semantic search and discovery of biomedical resources, breaking down barriers and streamlining scientific research that will improve human health. Copyright © 2010 Elsevier Inc. All rights reserved.

  6. Electron radiography

    Science.gov (United States)

    Merrill, Frank E.; Morris, Christopher

    2005-05-17

    A system capable of performing radiography using a beam of electrons. Diffuser means receive a beam of electrons and diffuse the electrons before they enter first matching quadrupoles where the diffused electrons are focused prior to the diffused electrons entering an object. First imaging quadrupoles receive the focused diffused electrons after the focused diffused electrons have been scattered by the object for focusing the scattered electrons. Collimator means receive the scattered electrons and remove scattered electrons that have scattered to large angles. Second imaging quadrupoles receive the collimated scattered electrons and refocus the collimated scattered electrons and map the focused collimated scattered electrons to transverse locations on an image plane representative of the electrons' positions in the object.

  7. Information resources

    Science.gov (United States)

    Friend, Milton; Franson, J. Christian; Friend, Milton; Gibbs, Samantha E.J.; Wild, Margaret A.

    2015-10-19

    During recent decades, natural resources agency personnel and others involved with the management and stewardship of wildlife have experienced an increasing need to access information and obtain technical assistance for addressing a diverse array of wildlife disease issues. This Chapter provides a broad overview of selected sources for obtaining supplemental information and technical assistance for addressing wildlife disease issues in North America. Specifically, examples of existing major wildlife disease programs focusing on free-ranging wildlife populations are highlighted; training opportunities for enhancing within-agency wildlife disease response are identified; a selected reading list of wildlife disease references is provided; and selected Web sites providing timely information on wildlife disease are highlighted. No attempt is made to detail all the North American programs and capabilities that address disease in free-ranging wildlife populations. Instead, this Chapter is focused on enhancing awareness of the types of capabilities that exist as potential sources for assistance and collaboration between wildlife conservation agency personnel and others in addressing wildlife disease issues.

  8. GENDER ANALYSIS OF ELECTRONIC INFORMATION

    African Journals Online (AJOL)

    use of internet Search engines such as google, yahoo and other free internet resources was found ... empirical studies are undertaken to examine the influence of gender ... H3: Perceived ease of use is positively related to the use of electronic.

  9. Total Lignans of Schisandra chinensis Ameliorates Aβ1-42-Induced Neurodegeneration with Cognitive Impairment in Mice and Primary Mouse Neuronal Cells.

    Directory of Open Access Journals (Sweden)

    Xu Zhao

    Full Text Available Lignan compounds extracted from Schisandra chinensis (Turcz. Baill. have been reported to possess various biological activities, and have potential in the treatment of Alzheimer's disease. This study was designed to investigate the effects of total lignans of Schisandra chinensis (TLS on cognitive function and neurodegeneration in the model of AD induced by Aβ1-42 in vivo and in vitro. It was found that intragastric infusion with TLS (50 and 200 mg/kg to Aβ1-42-induced mice significantly increased the number of avoidances in the shuttle-box test and swimming time in the target quadrant in the Morris water maze test. TLS at dose of 200 mg/kg significantly restored the activities of total antioxidant capacity (T-AOC, as well as the level of malondialdehyde (MDA both in the hippocampus and cerebral cortex in mice. Results of histopathological examination indicated that TLS noticeably ameliorated the neurodegeneration in the hippocampus in mice. On the other hand, TLS (100 μM could protect the Aβ1-42-induced primary mouse neuronal cells by blocking the decrease of mitochondrial membrane potential (MMP, change the expressions of Bcl-2 (important regulator in the mitochondria apoptosis pathway. Moreover, TLS also decreased the activity of β-secretase 1 (BACE1, crucial protease contributes to the hydrolysis of amyloid precursor protein (APP, and inhibited the expression of JKN/p38, which involved in the MAPKs signaling pathways in both mice and primary mouse neuronal cells. In summary, TLS might protect against cognitive deficits and neurodegeneration by releasing the damage of oxidative stress, inhibiting the expression of BACE1 and the MAPKs inflammatory signaling pathways.

  10. Pituitary adenylate cyclase-activating polypeptide (PACAP has a neuroprotective function in dopamine-based neurodegeneration in rat and snail parkinsonian models

    Directory of Open Access Journals (Sweden)

    Gabor Maasz

    2017-02-01

    Full Text Available Pituitary adenylate cyclase-activating polypeptide (PACAP rescues dopaminergic neurons from neurodegeneration and improves motor changes induced by 6-hydroxy-dopamine (6-OHDA in rat parkinsonian models. Recently, we investigated the molecular background of the neuroprotective effect of PACAP in dopamine (DA-based neurodegeneration using rotenone-induced snail and 6-OHDA-induced rat models of Parkinson's disease. Behavioural activity, monoamine (DA and serotonin, metabolic enzyme (S-COMT, MB-COMT and MAO-B and PARK7 protein concentrations were measured before and after PACAP treatment in both models. Locomotion and feeding activity were decreased in rotenone-treated snails, which corresponded well to findings obtained in 6-OHDA-induced rat experiments. PACAP was able to prevent the behavioural malfunctions caused by the toxins. Monoamine levels decreased in both models and the decreased DA level induced by toxins was attenuated by ∼50% in the PACAP-treated animals. In contrast, PACAP had no effect on the decreased serotonin (5HT levels. S-COMT metabolic enzyme was also reduced but a protective effect of PACAP was not observed in either of the models. Following toxin treatment, a significant increase in MB-COMT was observed in both models and was restored to normal levels by PACAP. A decrease in PARK7 was also observed in both toxin-induced models; however, PACAP had a beneficial effect only on 6-OHDA-treated animals. The neuroprotective effect of PACAP in different animal models of Parkinson's disease is thus well correlated with neurotransmitter, enzyme and protein levels. The models successfully mimic several, but not all etiological properties of the disease, allowing us to study the mechanisms of neurodegeneration as well as testing new drugs. The rotenone and 6-OHDA rat and snail in vivo parkinsonian models offer an alternative method for investigation of the molecular mechanisms of neuroprotective agents, including PACAP.

  11. Induction of Neuron-Specific Degradation of Coenzyme A Models Pantothenate Kinase-Associated Neurodegeneration by Reducing Motor Coordination in Mice.

    Directory of Open Access Journals (Sweden)

    Stephanie A Shumar

    Full Text Available Pantothenate kinase-associated neurodegeneration, PKAN, is an inherited disorder characterized by progressive impairment in motor coordination and caused by mutations in PANK2, a human gene that encodes one of four pantothenate kinase (PanK isoforms. PanK initiates the synthesis of coenzyme A (CoA, an essential cofactor that plays a key role in energy metabolism and lipid synthesis. Most of the mutations in PANK2 reduce or abolish the activity of the enzyme. This evidence has led to the hypothesis that lower CoA might be the underlying cause of the neurodegeneration in PKAN patients; however, no mouse model of the disease is currently available to investigate the connection between neuronal CoA levels and neurodegeneration. Indeed, genetic and/or dietary manipulations aimed at reducing whole-body CoA synthesis have not produced a desirable PKAN model, and this has greatly hindered the discovery of a treatment for the disease.Cellular CoA levels are tightly regulated by a balance between synthesis and degradation. CoA degradation is catalyzed by two peroxisomal nudix hydrolases, Nudt7 and Nudt19. In this study we sought to reduce neuronal CoA in mice through the alternative approach of increasing Nudt7-mediated CoA degradation. This was achieved by combining the use of an adeno-associated virus-based expression system with the synapsin (Syn promoter. We show that mice with neuronal overexpression of a cytosolic version of Nudt7 (scAAV9-Syn-Nudt7cyt exhibit a significant decrease in brain CoA levels in conjunction with a reduction in motor coordination. These results strongly support the existence of a link between CoA levels and neuronal function and show that scAAV9-Syn-Nudt7cyt mice can be used to model PKAN.

  12. Oscillator clustering in a resource distribution chain

    DEFF Research Database (Denmark)

    Postnov, D.; Sosnovtseva, Olga; Mosekilde, Erik

    2005-01-01

    separate the inherent dynamics of the individual oscillator from the properties of the coupling network. Illustrated by examples from microbiological population dynamics, renal physiology, and electronic oscillator theory, we show how competition for primary resources in a resource distribution chain leads...

  13. Pantothenate kinase 2 mutation with classic pantothenate-kinase-associated neurodegeneration without 'eye-of-the-tiger' sign on MRI in a pair of siblings

    International Nuclear Information System (INIS)

    Zolkipli, Zarazuela; Surtees, Robert; Dahmoush, Hisham; Saunders, Dawn E.; Kling Chong, W.K.

    2006-01-01

    It has been postulated that all patients with pantothenate kinase 2 (PANK2) mutations causing pantothenate-kinase-associated neurodegeneration (PKAN) are associated with the 'eye-of-the-tiger' sign on MRI. We report a pair of siblings who presented with dystonia and who have been found to be homozygous for 104C>A, S35X mutation, confirming the diagnosis of PKAN. They do not have the typical iron deposition in the globi pallida or substantia nigra on MR imaging. (orig.)

  14. Correlation between Retinal Vessel Calibre and Neurodegeneration in Patients with Type 2 Diabetes Mellitus in the European Consortium for the Early Treatment of Diabetic Retinopathy (EUROCONDOR)

    DEFF Research Database (Denmark)

    Frydkjaer-Olsen, Ulrik; Soegaard Hansen, Rasmus; Simó, Rafael

    2016-01-01

    .04). In a multivariable linear regression model, CRAE was associated with macular ganglion cell layer thickness (coefficient 0.27 per micrometre, p correlated with macular retinal thickness (coefficient -0.07 per micrometre, p = 0.04) and retinal nerve fibre layer thickness at the optic disc......PURPOSE: To investigate the correlation between retinal vessel calibre and measurements of neurodegeneration in patients with type 2 diabetes (T2D) and no or early diabetic retinopathy (DR). METHODS: Baseline data on 440 patients with T2D from the EUROCONDOR clinical trial were used. DR was graded...... (coefficient 0.32 per micrometre, p

  15. Shaping the Electronic Library--The UW-Madison Approach.

    Science.gov (United States)

    Dean, Charles W., Ed.; Frazier, Ken; Pope, Nolan F.; Gorman, Peter C.; Dentinger, Sue; Boston, Jeanne; Phillips, Hugh; Daggett, Steven C.; Lundquist, Mitch; McClung, Mark; Riley, Curran; Allan, Craig; Waugh, David

    1998-01-01

    This special theme section describes the University of Wisconsin-Madison's experience building its Electronic Library. Highlights include integrating resources and services; the administrative framework; the public electronic library, including electronic publishing capability and access to World Wide Web-based and other electronic resources;…

  16. Pathological changes in hippocampal neuronal circuits underlie age-associated neurodegeneration and memory loss: positive clue toward SAD.

    Science.gov (United States)

    Moorthi, P; Premkumar, P; Priyanka, R; Jayachandran, K S; Anusuyadevi, M

    2015-08-20

    defect in neuronal-circuits of hippocampus (DG-CA4-CA1-Sub) that were significantly damaged leading to memory impairment. Interestingly, RSV was observed to culminate pathological events in the hippocampal neuronal circuit during aging, proving them as potent therapeutic drug against age-associated neurodegeneration and memory loss. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. 17β-trenbolone, an anabolic–androgenic steroid as well as an environmental hormone, contributes to neurodegeneration

    International Nuclear Information System (INIS)

    Ma, Fucui; Liu, Daicheng

    2015-01-01

    Both genetic and environmental factors contribute to neurodegenerative disorders. In a large number of neurodegenerative diseases (for example, Alzheimer's disease (AD)), patients do not carry the mutant genes. Other risk factors, for example the environmental factors, should be evaluated. 17β-trenbolone is a kind of environmental hormone as well as an anabolic–androgenic steroid. 17β-trenbolone is used as a growth promoter for livestock in the USA. Also, a large portion of recreational exercisers inject 17β-trenbolone in large doses and for very long time to increase muscle and strength. 17β-trenbolone is stable in the environment after being excreted. In the present study, 17β-trenbolone was administered to adult and pregnant rats and the primary hippocampal neurons. 17β-trenbolone's distribution and its effects on serum hormone levels and Aβ42 accumulation in vivo and its effects on AD related parameters in vitro were assessed. 17β-trenbolone accumulated in adult rat brain, especially in the hippocampus, and in the fetus brain. It altered Aβ42 accumulation. 17β-trenbolone induced apoptosis of primary hippocampal neurons in vitro and resisted neuroprotective function of testosterone. Presenilin-1 protein expression was down-regulated while β-amyloid peptide 42 (Aβ42) production and caspase-3 activities were increased. Both androgen and estrogen receptors mediated the processes. 17β-trenbolone played critical roles in neurodegeneration. Exercisers who inject large doses of trenbolone and common people who are exposed to 17β-trenbolone by various ways are all influenced chronically and continually. Identification of such environmental risk factors will help us take early prevention measure to slow down the onset of neurodegenerative disorders. - Highlights: • The widely used anabolic–androgenic steroid 17β-trenbolone has neurotoxicity. • 17β-trenbolone crosses the blood brain barrier and placental barrier. • Rat has high level of

  18. Dystrophic (senescent) rather than activated microglial cells are associated with tau pathology and likely precede neurodegeneration in Alzheimer's disease.

    Science.gov (United States)

    Streit, Wolfgang J; Braak, Heiko; Xue, Qing-Shan; Bechmann, Ingo

    2009-10-01

    The role of microglial cells in the pathogenesis of Alzheimer's disease (AD) neurodegeneration is unknown. Although several works suggest that chronic neuroinflammation caused by activated microglia contributes to neurofibrillary degeneration, anti-inflammatory drugs do not prevent or reverse neuronal tau pathology. This raises the question if indeed microglial activation occurs in the human brain at sites of neurofibrillary degeneration. In view of the recent work demonstrating presence of dystrophic (senescent) microglia in aged human brain, the purpose of this study was to investigate microglial cells in situ and at high resolution in the immediate vicinity of tau-positive structures in order to determine conclusively whether degenerating neuronal structures are associated with activated or with dystrophic microglia. We used a newly optimized immunohistochemical method for visualizing microglial cells in human archival brain together with Braak staging of neurofibrillary pathology to ascertain the morphology of microglia in the vicinity of tau-positive structures. We now report histopathological findings from 19 humans covering the spectrum from none to severe AD pathology, including patients with Down's syndrome, showing that degenerating neuronal structures positive for tau (neuropil threads, neurofibrillary tangles, neuritic plaques) are invariably colocalized with severely dystrophic (fragmented) rather than with activated microglial cells. Using Braak staging of Alzheimer neuropathology we demonstrate that microglial dystrophy precedes the spread of tau pathology. Deposits of amyloid-beta protein (Abeta) devoid of tau-positive structures were found to be colocalized with non-activated, ramified microglia, suggesting that Abeta does not trigger microglial activation. Our findings also indicate that when microglial activation does occur in the absence of an identifiable acute central nervous system insult, it is likely to be the result of systemic infectious

  19. Squamosamide derivative FLZ protects dopaminergic neurons against inflammation-mediated neurodegeneration through the inhibition of NADPH oxidase activity

    Directory of Open Access Journals (Sweden)

    Wilson Belinda

    2008-05-01

    Full Text Available Abstract Background Inflammation plays an important role in the pathogenesis of Parkinson's disease (PD through over-activation of microglia, which consequently causes the excessive production of proinflammatory and neurotoxic factors, and impacts surrounding neurons and eventually induces neurodegeneration. Hence, prevention of microglial over-activation has been shown to be a prime target for the development of therapeutic agents for inflammation-mediated neurodegenerative diseases. Methods For in vitro studies, mesencephalic neuron-glia cultures and reconstituted cultures were used to investigate the molecular mechanism by which FLZ, a squamosamide derivative, mediates anti-inflammatory and neuroprotective effects in both lipopolysaccharide-(LPS- and 1-methyl-4-phenylpyridinium-(MPP+-mediated models of PD. For in vivo studies, a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-(MPTP- induced PD mouse model was used. Results FLZ showed potent efficacy in protecting dopaminergic (DA neurons against LPS-induced neurotoxicity, as shown in rat and mouse primary mesencephalic neuronal-glial cultures by DA uptake and tyrosine hydroxylase (TH immunohistochemical results. The neuroprotective effect of FLZ was attributed to a reduction in LPS-induced microglial production of proinflammatory factors such as superoxide, tumor necrosis factor-α (TNF-α, nitric oxide (NO and prostaglandin E2 (PGE2. Mechanistic studies revealed that the anti-inflammatory properties of FLZ were mediated through inhibition of NADPH oxidase (PHOX, the key microglial superoxide-producing enzyme. A critical role for PHOX in FLZ-elicited neuroprotection was further supported by the findings that 1 FLZ's protective effect was reduced in cultures from PHOX-/- mice, and 2 FLZ inhibited LPS-induced translocation of the cytosolic subunit of p47PHOX to the membrane and thus inhibited the activation of PHOX. The neuroprotective effect of FLZ demonstrated in primary neuronal

  20. Neurovascular-neuroenergetic coupling axis in the brain: master regulation by nitric oxide and consequences in aging and neurodegeneration.

    Science.gov (United States)

    Lourenço, Cátia F; Ledo, Ana; Barbosa, Rui M; Laranjinha, João

    2017-07-01

    The strict energetic demands of the brain require that nutrient supply and usage be fine-tuned in accordance with the specific temporal and spatial patterns of ever-changing levels of neuronal activity. This is achieved by adjusting local cerebral blood flow (CBF) as a function of activity level - neurovascular coupling - and by changing how energy substrates are metabolized and shuttled amongst astrocytes and neurons - neuroenergetic coupling. Both activity-dependent increase of CBF and O 2 and glucose utilization by active neural cells are inextricably linked, establishing a functional metabolic axis in the brain, the neurovascular-neuroenergetic coupling axis. This axis incorporates and links previously independent processes that need to be coordinated in the normal brain. We here review evidence supporting the role of neuronal-derived nitric oxide ( • NO) as the master regulator of this axis. Nitric oxide is produced in tight association with glutamatergic activation and, diffusing several cell diameters, may interact with different molecular targets within each cell type. Hemeproteins such as soluble guanylate cyclase, cytochrome c oxidase and hemoglobin, with which • NO reacts at relatively fast rates, are but a few of the key in determinants of the regulatory role of • NO in the neurovascular-neuroenergetic coupling axis. Accordingly, critical literature supporting this concept is discussed. Moreover, in view of the controversy regarding the regulation of catabolism of different neural cells, we further discuss key aspects of the pathways through which • NO specifically up-regulates glycolysis in astrocytes, supporting lactate shuttling to neurons for oxidative breakdown. From a biomedical viewpoint, derailment of neurovascular-neuroenergetic axis is precociously linked to aberrant brain aging, cognitive impairment and neurodegeneration. Thus, we summarize current knowledge of how both neurovascular and neuroenergetic coupling are compromised in

  1. 17β-trenbolone, an anabolic–androgenic steroid as well as an environmental hormone, contributes to neurodegeneration

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Fucui, E-mail: mafucui@hotmail.com [Wenzhou Institute of Biomaterials and Engineering, No. 16 Xinshan Road, Hi-tech Industry Park, Wenzhou (China); Key Laboratory of Animal Resistance, College of Life Science, Shandong Normal University, 88 East Wenhua Road, Jinan 250014 (China); Liu, Daicheng, E-mail: liudch@sdnu.edu.cn [Key Laboratory of Animal Resistance, College of Life Science, Shandong Normal University, 88 East Wenhua Road, Jinan 250014 (China)

    2015-01-01

    Both genetic and environmental factors contribute to neurodegenerative disorders. In a large number of neurodegenerative diseases (for example, Alzheimer's disease (AD)), patients do not carry the mutant genes. Other risk factors, for example the environmental factors, should be evaluated. 17β-trenbolone is a kind of environmental hormone as well as an anabolic–androgenic steroid. 17β-trenbolone is used as a growth promoter for livestock in the USA. Also, a large portion of recreational exercisers inject 17β-trenbolone in large doses and for very long time to increase muscle and strength. 17β-trenbolone is stable in the environment after being excreted. In the present study, 17β-trenbolone was administered to adult and pregnant rats and the primary hippocampal neurons. 17β-trenbolone's distribution and its effects on serum hormone levels and Aβ42 accumulation in vivo and its effects on AD related parameters in vitro were assessed. 17β-trenbolone accumulated in adult rat brain, especially in the hippocampus, and in the fetus brain. It altered Aβ42 accumulation. 17β-trenbolone induced apoptosis of primary hippocampal neurons in vitro and resisted neuroprotective function of testosterone. Presenilin-1 protein expression was down-regulated while β-amyloid peptide 42 (Aβ42) production and caspase-3 activities were increased. Both androgen and estrogen receptors mediated the processes. 17β-trenbolone played critical roles in neurodegeneration. Exercisers who inject large doses of trenbolone and common people who are exposed to 17β-trenbolone by various ways are all influenced chronically and continually. Identification of such environmental risk factors will help us take early prevention measure to slow down the onset of neurodegenerative disorders. - Highlights: • The widely used anabolic–androgenic steroid 17β-trenbolone has neurotoxicity. • 17β-trenbolone crosses the blood brain barrier and placental barrier. • Rat has high level of

  2. Alterations in the Interplay between Neurons, Astrocytes and Microglia in the Rat Dentate Gyrus in Experimental Models of Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Daniele Lana

    2017-09-01

    the different susceptibility of the DG in comparison to the CA1 and CA3 hippocampal areas to neurodegeneration during aging and inflammation.

  3. Electrons, Electronic Publishing, and Electronic Display.

    Science.gov (United States)

    Brownrigg, Edwin B.; Lynch, Clifford A.

    1985-01-01

    Provides a perspective on electronic publishing by distinguishing between "Newtonian" publishing and "quantum-mechanical" publishing. Highlights include media and publishing, works delivered through electronic media, electronic publishing and the printed word, management of intellectual property, and recent copyright-law issues…

  4. 研究/電子資源使用統計標準與規範之探討/陳雪華;許嘉珍;朱雅琦 | Study of the Electronic Resources Usage Statistics Standards and Guidelines/ Hsueh-Hua Chen;Chia-Chen Hsu;Ya-Chi Chu

    Directory of Open Access Journals (Sweden)

    陳雪華、許嘉珍、朱雅琦

    2007-04-01

    Full Text Available

    近年來,由於資訊科技的進步,圖書館中的電子資源數量快速增加,所佔預算金額比例也大幅增長。圖書館希望能夠透過評鑑電子資源的使用,以便能夠在電 子資源館藏發展等方面做出正確的決策。由於體認到電子資源使用統計之重要性,圖書館界與相關組織紛紛發展或修訂圖書館統計標準,增列電子資源使用統計的項 目以充分反映圖書館電子資源使用之狀況。本文主要採用文獻分析法以及內容分析法,收集探討並比較近軍來國內外電子資源使用統計之相關規範及標準,包含 ISO 2789、 ICOLC Guidelines、州ANSI/NISO Z39.7、CNS13151、ARL E-Metrlcs、E-Measures Project、以及Project COUNTER等。

    Recently, due to the advances of information technology, electronic resources are gradually replacing print resources as the largest consumer of library acquisition budgets. Logically, libraries want to evaluate the usage of electronic resources and incorporate the results into their decision making regarding electronic resource acquisition. Over these years, there is a general awareness among libraries to develop statistics standards and guidelines for library electronic resources usage. In this paper, literature review and content analysis methods are used to compare several library statistics standards, including: ISO 2789 、ICOLC Guidelines、ANSI/NISO Z39.7、CNS13151、ARL E-Metrics、E-Measures Project、and Project COUNTER etc.

    頁次:89-102

  5. Brain aging and Aβ₁₋₄₂ neurotoxicity converge via deterioration in autophagy-lysosomal system: a conditional Drosophila model linking Alzheimer's neurodegeneration with aging.

    Science.gov (United States)

    Ling, Daijun; Salvaterra, Paul M

    2011-02-01

    Aging is known to be the most prominent risk factor for Alzheimer's disease (AD); however, the underlying mechanism linking brain aging with AD pathogenesis remains unknown. The expression of human amyloid beta 42 peptide (Aβ₁₋₄₂), but not Aβ₁₋₄₀ in Drosophila brain induces an early onset and progressive autophagy-lysosomal neuropathology. Here we show that the natural process of brain aging also accompanies a chronic and late-onset deterioration of neuronal autophagy-lysosomal system. This process is characterized by accumulation of dysfunctional autophagy-lysosomal vesicles, a compromise of these vesicles leading to damage of intracellular membranes and organelles, necrotic-like intraneuronal destruction and neurodegeneration. In addition, conditional activation of neuronal autophagy in young animals is protective while late activation is deleterious for survival. Intriguingly, conditional Aβ₁₋₄₂ expression limited to young animals exacerbates the aging process to a greater extent than Aβ₁₋₄₂ expression in old animals. These data suggest that the neuronal autophagy-lysosomal system may shift from a functional and protective state to a pathological and deleterious state either during brain aging or via Aβ₁₋₄₂ neurotoxicity. A chronic deterioration of the neuronal autophagy-lysosomal system is likely to be a key event in transitioning from normal brain aging to pathological aging leading to Alzheimer's neurodegeneration.

  6. Nebula/DSCR1 upregulation delays neurodegeneration and protects against APP-induced axonal transport defects by restoring calcineurin and GSK-3β signaling.

    Directory of Open Access Journals (Sweden)

    Jillian L Shaw

    Full Text Available Post-mortem brains from Down syndrome (DS and Alzheimer's disease (AD patients show an upregulation of the Down syndrome critical region 1 protein (DSCR1, but its contribution to AD is not known. To gain insights into the role of DSCR1 in AD, we explored the functional interaction between DSCR1 and the amyloid precursor protein (APP, which is known to cause AD when duplicated or upregulated in DS. We find that the Drosophila homolog of DSCR1, Nebula, delays neurodegeneration and ameliorates axonal transport defects caused by APP overexpression. Live-imaging reveals that Nebula facilitates the transport of synaptic proteins and mitochondria affected by APP upregulation. Furthermore, we show that Nebula upregulation protects against axonal transport defects by restoring calcineurin and GSK-3β signaling altered by APP overexpression, thereby preserving cargo-motor interactions. As impaired transport of essential organelles caused by APP perturbation is thought to be an underlying cause of synaptic failure and neurodegeneration in AD, our findings imply that correcting calcineurin and GSK-3β signaling can prevent APP-induced pathologies. Our data further suggest that upregulation of Nebula/DSCR1 is neuroprotective in the presence of APP upregulation and provides evidence for calcineurin inhibition as a novel target for therapeutic intervention in preventing axonal transport impairments associated with AD.

  7. Nebula/DSCR1 upregulation delays neurodegeneration and protects against APP-induced axonal transport defects by restoring calcineurin and GSK-3β signaling.

    Science.gov (United States)

    Shaw, Jillian L; Chang, Karen T

    2013-01-01

    Post-mortem brains from Down syndrome (DS) and Alzheimer's disease (AD) patients show an upregulation of the Down syndrome critical region 1 protein (DSCR1), but its contribution to AD is not known. To gain insights into the role of DSCR1 in AD, we explored the functional interaction between DSCR1 and the amyloid precursor protein (APP), which is known to cause AD when duplicated or upregulated in DS. We find that the Drosophila homolog of DSCR1, Nebula, delays neurodegeneration and ameliorates axonal transport defects caused by APP overexpression. Live-imaging reveals that Nebula facilitates the transport of synaptic proteins and mitochondria affected by APP upregulation. Furthermore, we show that Nebula upregulation protects against axonal transport defects by restoring calcineurin and GSK-3β signaling altered by APP overexpression, thereby preserving cargo-motor interactions. As impaired transport of essential organelles caused by APP perturbation is thought to be an underlying cause of synaptic failure and neurodegeneration in AD, our findings imply that correcting calcineurin and GSK-3β signaling can prevent APP-induced pathologies. Our data further suggest that upregulation of Nebula/DSCR1 is neuroprotective in the presence of APP upregulation and provides evidence for calcineurin inhibition as a novel target for therapeutic intervention in preventing axonal transport impairments associated with AD.

  8. Recent progress on curcumin-based therapeutics: a patent review (2012-2016). Part II: curcumin derivatives in cancer and neurodegeneration.

    Science.gov (United States)

    Di Martino, Rita Maria Concetta; Bisi, Alessandra; Rampa, Angela; Gobbi, Silvia; Belluti, Federica

    2017-08-01

    Curcumin, the main bioactive compound found in the rhizome of Curcuma longa L., is considered a 'privileged structure', due to its ability to modulate different signaling pathways involved in the pathogenesis of several diseases. Unfortunately, its poor pharmacodynamic and pharmacokinetic properties, mainly related to chemical instability, low solubility and rapid metabolism, greatly reduce its therapeutic potential. In the last years a number of derivatives were developed and patented, aimed both at improving its multifaceted biological profile and overcoming its undesired effects. Areas covered: This review summarizes the patent literature of the last five years dealing with synthetic curcumin-related compounds in cancer and neurodegeneration, properly designed in order to avoid the so-called 'dark side of curcumin', and to take advantage of the beneficial properties of this molecule, worth to be further exploited to obtain effective therapeutics. Expert opinion: Due to the synergistic binding to several networked targets, curcumin turned out to be suitable for polypharmacological approaches, and its 'privileged structure' could also provide the key scaffold to develop novel multipotent drugs useful for treating multifactiorial pathologic conditions such as cancer and neurodegeneration.

  9. Genetic Correction of SOD1 Mutant iPSCs Reveals ERK and JNK Activated AP1 as a Driver of Neurodegeneration in Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Akshay Bhinge

    2017-04-01

    Full Text Available Summary: Although mutations in several genes with diverse functions have been known to cause amyotrophic lateral sclerosis (ALS, it is unknown to what extent causal mutations impinge on common pathways that drive motor neuron (MN-specific neurodegeneration. In this study, we combined induced pluripotent stem cells-based disease modeling with genome engineering and deep RNA sequencing to identify pathways dysregulated by mutant SOD1 in human MNs. Gene expression profiling and pathway analysis followed by pharmacological screening identified activated ERK and JNK signaling as key drivers of neurodegeneration in mutant SOD1 MNs. The AP1 complex member JUN, an ERK/JNK downstream target, was observed to be highly expressed in MNs compared with non-MNs, providing a mechanistic insight into the specific degeneration of MNs. Importantly, investigations of mutant FUS MNs identified activated p38 and ERK, indicating that network perturbations induced by ALS-causing mutations converge partly on a few specific pathways that are drug responsive and provide immense therapeutic potential. : In this article, Bhinge, Stanton, and colleagues use genome editing of patient-derived iPSCs to model ALS phenotypic defects in vitro. Transcriptomic analysis of disease MNs reveals activation of MAPK, AP1, WNT, cell-cycle, and p53 signaling in ALS MNs. Pharmacological screening uncovers activated ERK and JNK signaling as therapeutic targets in ALS. Keywords: ALS, SOD1, FUS, CRISPR-Cas9, p38, ERK, JNK, WNT, TP53, JUN

  10. Long-chain polyunsaturated fatty acids (LCPUFA) from genesis to senescence: the influence of LCPUFA on neural development, aging, and neurodegeneration.

    Science.gov (United States)

    Janssen, Carola I F; Kiliaan, Amanda J

    2014-01-01

    Many clinical and animal studies demonstrate the importance of long-chain polyunsaturated fatty acids (LCPUFA) in neural development and neurodegeneration. This review will focus on involvement of LCPUFA from genesis to senescence. The LCPUFA docosahexaenoic acid and arachidonic acid are important components of neuronal membranes, while eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid also affect cardiovascular health and inflammation. In neural development, LCPUFA deficiency can lead to severe disorders like schizophrenia and attention deficit hyperactivity disorder. Perinatal LCPUFA supplementation demonstrated beneficial effects in neural development in humans and rodents resulting in improved cognition and sensorimotor integration. In normal aging, the effect of LCPUFA on prevention of cognitive impairment will be discussed. LCPUFA are important for neuronal membrane integrity and function, and also contribute in prevention of brain hypoperfusion. Cerebral perfusion can be compromised as result of obesity, cerebrovascular disease, hypertension, or diabetes mellitus type 2. Last, we will focus on the role of LCPUFA in most common neurodegenerative diseases like Alzheimer's disease and Parkinson's disease. These disorders are characterized by impaired cognition and connectivity and both clinical and animal supplementation studies have shown the potential of LCPUFA to decrease neurodegeneration and inflammation. This review shows that LCPUFA are essential throughout life. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Dopaminergic expression of the Parkinsonian gene LRRK2-G2019S leads to non-autonomous visual neurodegeneration, accelerated by increased neural demands for energy

    Science.gov (United States)

    Hindle, Samantha; Afsari, Farinaz; Stark, Meg; Middleton, C. Adam; Evans, Gareth J.O.; Sweeney, Sean T.; Elliott, Christopher J.H.

    2013-01-01

    Parkinson's disease (PD) is associated with loss of dopaminergic signalling, and affects not just movement, but also vision. As both mammalian and fly visual systems contain dopaminergic neurons, we investigated the effect of LRRK2 mutations (the most common cause of inherited PD) on Drosophila electroretinograms (ERGs). We reveal progressive loss of photoreceptor function in flies expressing LRRK2-G2019S in dopaminergic neurons. The photoreceptors showed elevated autophagy, apoptosis and mitochondrial disorganization. Head sections confirmed extensive neurodegeneration throughout the visual system, including regions not directly innervated by dopaminergic neurons. Other PD-related mutations did not affect photoreceptor function, and no loss of vision was seen with kinase-dead transgenics. Manipulations of the level of Drosophila dLRRK suggest G2019S is acting as a gain-of-function, rather than dominant negative mutation. Increasing activity of the visual system, or of just the dopaminergic neurons, accelerated the G2019S-induced deterioration of vision. The fly visual system provides an excellent, tractable model of a non-autonomous deficit reminiscent of that seen in PD, and suggests that increased energy demand may contribute to the mechanism by which LRRK2-G2019S causes neurodegeneration. PMID:23396536

  12. Grape powder consumption affects the expression of neurodegeneration-related brain proteins in rats chronically fed a high-fructose-high-fat diet.

    Science.gov (United States)

    Liao, Hsiang; Chou, Liang-Mao; Chien, Yi-Wen; Wu, Chi-Hao; Chang, Jung-Su; Lin, Ching-I; Lin, Shyh-Hsiang

    2017-05-01

    Abnormal glucose metabolism in the brain is recognized to be associated with cognitive decline. Because grapes are rich in polyphenols that produce antioxidative and blood sugar-lowering effects, we investigated how grape consumption affects the expression and/or phosphorylation of neurodegeneration-related brain proteins in aged rats fed a high-fructose-high-fat (HFHF) diet. Wistar rats were maintained on the HFHF diet from the age of 8 weeks to 66 weeks, and then on an HFHF diet containing either 3% or 6% grape powder as an intervention for 12 weeks. Western blotting was performed to measure the expression/phosphorylation levels of several cortical and hippocampal proteins, including amyloid precursor protein (APP), tau, phosphatidylinositol-3-kinase (PI3K), extracellular signal-regulated kinase (ERK), receptor for advanced glycation end products (RAGEs), erythroid 2-related factor 2 (Nrf2) and brain-derived neurotrophic factor (BDNF). Inclusion of up to 6% grape powder in the diet markedly reduced RAGE expression and tau hyperphosphorylation, but upregulated the expression of Nrf2 and BDNF, as well as the phosphorylation of PI3K and ERK, in the brain tissues of aged rats fed the HFHF diet. Thus, grape powder consumption produced beneficial effects in HFHF-diet-fed rats, exhibiting the potential to ameliorate changes in neurodegeneration-related proteins in the brain. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Neuroglia in neurodegeneration

    Czech Academy of Sciences Publication Activity Database

    Heneka, M. T.; Rodríguez Arellano, Jose Julio; Verkhratsky, Alexei

    2010-01-01

    Roč. 63, 1-2 (2010), s. 189-211 ISSN 0165-0173 R&D Projects: GA ČR GA309/09/1696; GA ČR GA305/08/1384 Institutional research plan: CEZ:AV0Z50390703 Keywords : Glia * Astrocyte * Microglia Subject RIV: FH - Neurology Impact factor: 8.842, year: 2010

  14. Electron detector

    International Nuclear Information System (INIS)

    Hashimoto, H.; Mogami, A.

    1975-01-01

    A device for measuring electron densities at a given energy level in an electron beam or the like having strong background noise, for example, in the detection of Auger electric energy spectrums is described. An electron analyzer passes electrons at the given energy level and at the same time electrons of at least one adjacent energy level. Detecting means associated therewith produce signals indicative of the densities of the electrons at each energy level and combine these signals to produce a signal indicative of the density of the electrons of the given energy level absent background noise

  15. World resources: engineering solutions

    Energy Technology Data Exchange (ETDEWEB)

    1976-01-01

    The proceedings include 10 papers that contribute to population environment; fossil fuel resources and energy conservation; nuclear and solar power; production of ores and manufacture and use of metallic resources; resources of manufactured and natural nonmetallic materials; water as a reusable resource; and timber as a replaceable resource.

  16. Electron/electron acoustic instability

    International Nuclear Information System (INIS)

    Gary, S.P.

    1987-01-01

    The electron acoustic wave becomes a normal mode of an unmagnetized collisionless plasma in the presence of two electron components with similar densities, but strongly disparate temperatures. The characteristic frequency of this mode is the plasma frequency of the cooler electron component. If these two electron components have a relative drift speed several times the thermal speed of the cooler component, the electron/electron acoustic instability may arise. This paper describes the parametric dependences of the threshold drift speed and maximum growth rate of this instability, and compares these with the same properties of the electron/ion acoustic instability. Under the condition of zero current, the electron/ion acoustic instability typically has the lower threshold drift speed, so that observation of the electron/electron acoustic instability is a strong indication of the presence of an electrical current in the plasma

  17. Innovations in electronic services

    Directory of Open Access Journals (Sweden)

    Dagmara Wach

    2011-12-01

    Full Text Available Summarry Existence in electronic business has become increasingly difficult. High competition and considerable financial resources needed to enter electronic market are the problems of most micro and small sized enterprises, starting or developing their business. Nevertheless, there is a market niche for them, which can ensure success and grant partial financing of the business. This niche are small web projects, providing the customer with personalized service, hitting his tastes and meeting immediate needs. A projects that large websites are unable to perform. Financial sourcing of those projects comes from EU subsidies, in the framework of the Działanie 8.1. PO IG, 2007-2013.

  18. Electronic emission and electron guns

    International Nuclear Information System (INIS)

    Roy, Amitava

    2010-01-01

    This paper reviews the process of electron emission from metal surface. Although electrons move freely in conductors like metals, they normally do not leave the metal without some manipulation. In fact, heating and bombardment are the two primary ways in which electrons are emitted through the use of a heating element behind the cathode (termed thermionic emission) or as a result of bombardment with a beam of electrons, ions, or metastable atoms (termed secondary emission). Another important emission mechanism called Explosive Electron Emission (EEE) is also often used in various High Voltage Pulse Power Systems to generate very high current (few hundreds of kA) pulsed electron beams. The electron gun is the device in that it shoots off a continuous (or pulsed) stream of electrons. A brief idea about the evolution of the electron gun components and their basis of functioning are also discussed. (author)

  19. Sticker electronics

    KAUST Repository

    Hussain, Muhammad Mustafa; Torres Sevilla, Galo Andres; Diaz Cordero, Marlon Steven

    2017-01-01

    Electronic stickers may be manufactured on flexible substrates (110, 120, 130) as layers and packaged together. The package may then have an adhesive applied to one side to provide capability for sticking the electronic devices to surfaces

  20. ELECTRONIC SIGNATURES

    African Journals Online (AJOL)

    10332324

    "[to] promote the understanding and, acceptance of and growth in the number of electronic transactions .... Chapter III of the ECT Act is based on the UNCITRAL Model Law on Electronic. Commerce ... Communications Technology Law 146. 22.