NIH Blueprint Research Articles

Neuregulin‐1β and neuregulin‐1α differentially affect the migration and invasion of malignant peripheral nerve sheath tumor cells

Malignant peripheral nerve sheath tumors (MPNSTs), the most common malignancy associated with neurofibromatosis type 1 (NF1), aggressively invade adjacent nerve and soft tissue. MPNSTs express neuregulin‐1 (NRG‐1) β, which promotes Schwann cell migration during development, and NRG‐1α, whose effects on Schwann cells are unknown. We hypothesized that NRG‐1β and/or NRG‐1α promote MPNST invasion. We found that NRG‐1β promoted MPNST migration in a substrate‐specific manner. The NRG‐1 receptors erbB4 and erbB3 were present in MPNSTs, colocalized with focal adhesion kinase and the laminin receptor β1‐integrin and coimmunoprecipitated with β1‐integrin. NRG‐1β stimulated human and murine MPNST cell migration in a concentration‐dependent manner, acting as a chemotactic factor. Both baseline and NRG‐1β induced migration and invasion were erbB‐dependent and required the action of MEK 1/2, SAPK/JNK, PI3K, Src kinases and ROCK‐I/II. In contrast, NRG‐1α had no effect on the migration of some lines and inhibited the migration of others. While NRG‐1β activated Erk 1/2, SAPK/JNK, Akt and Src family kinases, NRG‐1α did not activate Akt and activated other kinases in a kinetically distinct manner. These findings suggest that NRG‐1β enhances MPNST migration and that NRG‐1β and NRG‐1α differentially modulate this process. Supported by NIH grant NS048353, CA122804 and NIH Blueprint grant NS57098.

Article 7: Filling the National Institutes of Health's Toolbox: Defining Priorities and Selecting Measures for a Uniform Assessment Battery of Neurologic and Behavioral Function

Objective: To determine the critical assessment characteristics, functional domains, and performance-based measures to include in the National Institutes of Health's (NIH) Toolbox, a uniform assessment battery being developed under the aegis of the NIH's Blueprint for Neuroscience Research for use in clinical trials and cohort studies. Design: Online surveys, in-depth interviews, and systematic evidence-based literature review. Setting: More than 15 collaborating academic and clinical research centers. Participants: 191 experts in clinical and epidemiologic research (Internet survey, n=147; expert interviews, n=44). Interventions: Not applicable. Main Outcome Measures: Survey data were analyzed descriptively using t tests and 1-way analysis of variance to determine assessment priorities and core constructs. Descriptive analysis of expert interview rankings coupled with findings from the evidence-based literature reviews were used to identify appropriate outcomes measures. Results: The full Toolbox should: take less than 2 hours to administer; be precise and accurate across the range of normal function for people aged 3 to 85 years; be easy to administer, score, and interpret; and involve minimal cost. 54 construct areas and appropriate measures for each were identified across 4 core domains of motor function, cognition, sensation, and emotional health. Modifications to standard measures and development of new ones are recommended to meet the Toolbox's inclusion criteria. Implications for rehabilitation research are discussed using the motor and cognitive domains as exemplars. Conclusions: The NIH Toolbox will set the standard for measurement in NIH-funded research; will enable quick, precise measurement of key functional domains; and will facilitate cross-study comparisons.

The Neuroscience Information Framework: A Data and Knowledge Environment for Neuroscience

With support from the Institutes and Centers forming the NIH Blueprint for Neuroscience Research, we have designed and implemented a new initiative for integrating access to and use of Web-based neuroscience resources: the Neuroscience Information Framework. The Framework arises from the expressed need of the neuroscience community for neuroinformatic tools and resources to aid scientific inquiry, builds upon prior development of neuroinformatics by the Human Brain Project and others, and directly derives from the Society for Neuroscience's Neuroscience Database Gateway. Partnered with the Society, its Neuroinformatics Committee, and volunteer consultant-collaborators, our multi-site consortium has developed: (1) a comprehensive, dynamic, inventory of Web-accessible neuroscience resources, (2) an extended and integrated terminology describing resources and contents, and (3) a framework accepting and aiding concept-based queries. Evolving instantiations of the Framework may be viewed at http://nif.nih.gov , http://neurogateway.org , and other sites as they come on line.

Terminology for Neuroscience Data Discovery: Multi-tree Syntax and Investigator-Derived Semantics

The Neuroscience Information Framework (NIF), developed for the NIH Blueprint for Neuroscience Research and available at http://nif.nih.gov and http://neurogateway.org , is built upon a set of coordinated terminology components enabling data and web-resource description and selection. Core NIF terminologies use a straightforward syntax designed for ease of use and for navigation by familiar web interfaces, and readily exportable to aid development of relational-model databases for neuroscience data sharing. Datasets, data analysis tools, web resources, and other entities are characterized by multiple descriptors, each addressing core concepts, including data type, acquisition technique, neuroanatomy, and cell class. Terms for each concept are organized in a tree structure, providing is-a and has-a relations. Broad general terms near each root span the category or concept and spawn more detailed entries for specificity. Related but distinct concepts (e.g., brain area and depth) are specified by separate trees, for easier navigation than would be required by graph representation. Semantics enabling NIF data discovery were selected at one or more workshops by investigators expert in particular systems (vision, olfaction, behavioral neuroscience, neurodevelopment), brain areas (cerebellum, thalamus, hippocampus), preparations (molluscs, fly), diseases (neurodegenerative disease), or techniques (microscopy, computation and modeling, neurogenetics). Workshop-derived integrated term lists are available Open Source at http://brainml.org ; a complete list of participants is at http://brainml.org/workshops.

The neuroimaging informatics tools and resources clearinghouse (NITRC)

Event Abstract Back to Event The neuroimaging informatics tools and resources clearinghouse (NITRC) David Kennedy1* 1 NYU, United States Introduction: We report on the use of a new neuroimaging informatics knowledge environment for MRI entitled: Neuroimaging Informatics Tools and Resources Clearinghouse (NITRC). Initiated in October 2006 through the NIH Blueprint for Neuroscience Research (1,2), NITRC’s mission is to create a user-friendly knowledge environment for the functional magnetic resonance imaging (fMRI) and associated structural analysis community. Through the identification of existing tools and resources valuable to this community, NITRC’s goal is to develop a knowledge environment to enhance, adopt, distribute, and contribute to the evolution of neuroimaging tools and resources. Located on the web at www.nitrc.org, this site promotes tools and resources, vocabularies, and databases, thereby extending the impact of previously funded, neuroimaging informatics contributions to a broader community. It is anticipated that this will give fMRI researchers greater and more efficient access to the tools and resources they need, better categorize and organize existing tools and resources, facilitate interactions between researchers and developers, promote better use through enhanced documentation and tutorials—all while keeping the set of resources up-to-date with the most recent resource upgrades and updates. Approach: To meet the disparate needs of resource developers and users, NITRC requires functionality like that found in platforms such as Source Forge, Bugzilla, CVS, Wiki, etc. To unify such functionality, we have chosen to design the knowledge environment using the open-source GForge project (3). Within the NITRC environment a ‘project’ is created for each tool or resource that is to be represented. Each project will have independent descriptive content (as projects do currently at IATR, (4)), as well as Wiki, CVS, bug tracking, news forums, and discussion lists associated with it. Descriptions can be housed on the NITRC servers themselves, passed through to an external, preexisting site for content management. The site was formally launched to the public on Oct. 1, 2007. There are currently 72 hosted projects, and 295 registered users, and these numbers are increasing daily. NITRC encourages feedback, through surveys of its users to make the site as accessible as possible. Summary: NITRC, a new neuroimaging knowledge environment, is now online. We encourage the fMRI community to try it out and provide feedback on its design, tools, resources, and content. NITRC is a knowledge environment for the fMRI community where tools and resources are presented in a coherent and synergistic environment for the advancement of MRI-based neuroscience research. Acknowledgement: This work is supported by Contract No.: N02-EB-6-4281 under the auspices of the NIH Blueprint for Neuroscience Research. Conference: Neuroinformatics 2008, Stockholm, Sweden, 7 Sep - 9 Sep, 2008. Presentation Type: Oral Presentation Topic: Live Demonstrations Citation: Kennedy D (2008). The neuroimaging informatics tools and resources clearinghouse (NITRC). Front. Neuroinform. Conference Abstract: Neuroinformatics 2008. doi: 10.3389/conf.neuro.11.2008.01.122 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 28 Jul 2008; Published Online: 28 Jul 2008. * Correspondence: David Kennedy, NYU, Boston, United States, dave@cma.mgh.harvard.edu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers David Kennedy Google David Kennedy Google Scholar David Kennedy PubMed David Kennedy Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

EHPnet: National Institute of Neurological Disorders and Stroke

More than 600 disorders affect the nervous system, and neurological disorders strike an estimated 50 million Americans annually. The National Institute of Neurological Disorders and Stroke (NINDS) is the NIH institute charged with overseeing research on these conditions. The NINDS website at http://www.ninds.nih.gov/ provides the latest news concerning the institute, its programs, and neurological science in general, as well as a resource on the entire spectrum of neurological diseases. At the top of the homepage is a Disorder Index of the many neurological conditions that the NINDS addresses. Selecting one of the hundreds of disorders takes visitors to in-depth information about the disorder’s symptoms, methods of diagnosis, treatment options, research being done on the disorder, organizations devoted to the disorder, related NINDS publications (including information in Spanish) and additional resources from MedlinePlus. The site’s homepage features the latest news about neurological diseases, with an archive of older items. The homepage also includes a section listing studies that are seeking subjects. Here, visitors can learn more about what clinical trials really are; those who wish to participate in a clinical trial can choose from an extensive list of neurological conditions, from ADHD to Zellweger syndrome, to see what research is in progress or coming up at the NINDS and elsewhere across the country. Two sections of the homepage allow researchers to find out about funding opportunities. Under the Funding Opportunities header, visitors can retrieve lists of NINDS opportunities either for the last 60 days or all current opportunities. This section also has information on electronic submission of grant applications and answers questions potential grantees may have about new government requirements for submitting grant applications online. Under the Funding Newsletters header, visitors can sign up for the free NINDS Notes newsletter, published three times a year, which contains information on grant applications, requests for applications, and studies that need volunteers. The most current newsletter, plus links to previous editions, are available on the site. The Neuroscience at NIH section of the homepage contains three sections. The Research at NINDS (Intramural) section contains links to information about NINDS faculty, research facilities, events, and training programs such as summer programs and fellowships. The NIH Blueprint section contains an overview of and link to an NIH framework “to enhance cooperative activities among fifteen NIH Institutes and Centers that support research on the nervous system.” This section also has links to requests for information and requests for applications related to the blueprint. Finally, the Neuroscience@NIH section contains information about NIH neuroscience faculty, areas of research interest, seminars, interest groups, and postdoctoral openings.