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The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute of Neurological Disorders and Stroke (NINDS), the National Eye Institute (NEI), the National Institute of Nursing Research (NINR), and the National Heart, Lung, and Blood Institute (NHLBI) seek research to understand racial/ethnic disparities in the development of the microvascular (nephropathy, retinopathy, and neuropathy), and macrovascular (cardiovascular disease and stroke) complications of diabetes.

Dystonia is defined clinically as involuntary, often sustained, co- contraction of agonist and antagonist muscles causing abnormal and often painful postures or movements. It is generally believed to be centrally mediated. Dystonia occurs due to many different etiologies. Although the prevalence and disease burden of this group of disorders is not well known, it is estimated by some sources that this debilitating movement disorder affects over 500,000 individuals in the USA. Some forms of dystonia are associated with specific genetic and/or environmental risk factors, but the underlying pathophysiological pathways remain elusive. The purpose of this program announcement is to solicit applications for new studies on the underlying causes of human dystonia, secondary consequences of these movement disorders, and potential therapeutic strategies for treating these conditions.

The purpose of this program announcement (PA) is to encourage the submission of applications for research to enhance animal stem cells as model biological systems. Research to isolate, characterize and identify totipotent and multipotent stem cells from nonhuman biomedical research animal models, as well as to generate reagents and techniques to characterize and separate those stem cells from other cell types is encouraged. Innovative approaches to the problems of making multipotent stem cells available from a variety of nonhuman sources, and to creating reagents that will identify those stem cells across species and allow for separation of multipotent stem cells from differentiated cell types, will be stressed. Studies involving human subjects are not allowed under this PA. This PA supersedes PA-01-076 issued earlier by the NCRR.

This Program Announcement (PA) is to encourage investigator-initiated applications for research designed to exploit the power of mutagenesis screening in zebrafish in order to detect and characterize genes, pathways, and phenotypes of interest in development and aging, organ formation, behavior, and disease processes. Applications that propose to advance the technologies associated with such phenotyping also are welcome. A secondary goal of this PA is to ensure that tools developed under this initiative are widely available to the research community. This PA is a continuation of the program initiated by RFA HD-00-004, "Mutagenesis Screens/Phenotyping Tools for Zebrafish" (http://grants.nih.gov/grants/guide/rfa-files/RFA-HD-00-004.html), and incorporates an earlier PA, "Development of Zebrafish Mutagenesis and Screening Tools" (http://grants.nih.gov/grants/guide/pa-files/PA-01-070.html). This effort stems from an NIH initiative with participation of the Institutes and Centers listed above, working though the Trans-NIH Zebrafish Coordinating Committee (TZCC; http://www.nih.gov/science/models/zebrafish/) under the co-chairmanship of NICHD and NIDDK. Since its formation in 1997, the committee has played an active role as an advocate for the zebrafish as an important model for development and disease research.

Recent discoveries across a broad range of research areas in the neurosciences offer promising opportunities for treatment of neurological disorders. As part of its mission to reduce the burden of neurological disease, NINDS is committed to encouraging the "translation" of these discoveries into new treatments. The goal of this PA is to implement a program of cooperative agreements that will support milestone-driven projects focused on the identification and pre-clinical testing of new therapeutics. The program will facilitate the effective review and research administration of translational research projects and will accelerate the translation of discoveries in basic research to treatment in the clinic.

Recent discoveries across a broad range of research areas in the neurosciences offer promising opportunities for improved therapies for neurological disorders. As part of its mission to reduce the burden of neurological disease, NINDS is committed to encouraging the "translation" of these basic discoveries into new treatments. The goal of this PA is to announce a career development opportunity for new investigators to build a program of translational research in neurological disorders under the guidance of an experienced mentor.

NINDS encourages translational research projects that focus on neurological disorders. This PA requests applications for exploratory/developmental projects intended to discover potential targets for therapeutic intervention, to identify candidate therapeutics, or to develop assays, animal models, devices, or technologies for screening or developing therapeutics. Such projects, if successful, should lead directly to a therapy development project for a particular neurological disorder.

Biomedical research laboratories occasionally undertake a software development project to solve a problem the laboratory faces. These software packages sometimes evolve into a well-designed system that can be easily extended and that is useful to a much broader community other than the members of the originating laboratory. The goal of this PA is to support the continued development, maintenance, testing and evaluation of existing software. The proposed work should apply best practices and proven methods for software design, construction and implementation to extend the applicability of existing bioinformatics/computational biology software to a broader biomedical research community.

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute on Aging (NIA), the National Institute of Child Health and Human Development (NICHD) and the National Institute of Neurological Disorders and Stroke (NINDS) encourage investigator-initiated research grant applications to isolate, characterize and identify precursor cells required for normal growth and repair of injured, aged, or diseased muscle. Goals include determining factors responsible for migration, proliferation, and differentiation of precursor cells following muscle injury or increased exercise. This includes characterizing molecular controls responsible for the quiescence of muscle satellite cells and determining metabolic and motile properties of satellite cells while they are quiescent. Researchers are encouraged to develop strategies using muscle satellite and stem cells in therapies for human disease and enhanced repair of muscle injury and as cellular vectors of genes.

Pharmacological compounds have the potential to enhance functional recovery in rehabilitation, especially when used in conjunction with behavioral and physical therapy. This Request for Applications (RFA) supports studies relevant to the treatment of neurological conditions such as stroke, brain trauma, spinal cord injury, neurodevelopmental and neurodegenerative disorders, infections, and neurosurgery. Applications in response to this RFA must focus on rehabilitative strategies rather than the reduction of acute pathology. They may include studies involving synaptic plasticity, neurotransmitter interactions, neurotrophic mechanisms, pain or fatigue, or any other neurological mechanisms that accelerate the recovery process, enhance function or reduce disability. Studies in validated animal models may be proposed, provided they include appropriate functional outcomes. Pilot clinical trials in humans may also be considered.