? Core B This Core has been a critical component of this Program since its beginning, providing to the Projects all human tissue specimens and performing initial tissue processing of those specimens, as well as animal specimens. Irrespective of its consistent value, Core B has been reconfigured over various funding periods to reflect changes in the manner of participation by the team members based in the United Kingdom and the contributions made by those resources to the overall goals of the Program. The organization of Core B has also been adapted to evolving goals in this renewal application. Notably, the collections maintained at Imperial College ? London by will be incorporated into Core B, and this greatly expands availability of diverse, well- characterized human tissue specimens. As a consequence, the Core will no longer need to collect material from new autopsies, as the combined resources of the two institutions provide sufficient material for the needsof Program investigators. One important resource remains the 3D-dissected discrete structures, e.g., olfactory,hippocampus, etc., flash-frozen in for molecular and biochemical analysis in Projects 1, 2 and 3. Other Core B deliverables include: i) 3D dissection of the fresh left half of each animal brain for use by Projects; and ii) collection of blocks from the formalin-fixed right half of either human or animal brains that will be sectioned,immunohistologically reacted, digitally imaged, and image-captured according to investigator requirements. Providing these Core services will enhance and facilitate achievement of the aims of each Project as consistent dissections and staining techniques are supplied, allowing among other things, comparisons across the various Projects. Standardized protocols, record keeping, and primary data analysis? hallmarks of the work of Core's traditions?are vital for successful completion of the specific aims of the Projects in this Program.
? Core B We are taking a new path for Core B in order to streamline our services and foster core-project interactions. The first change is Dr. Gentleman will join Core B rather than having a standalone project. This decision was made for the benefit of the Program goals, as we seek to determine whether the changes that we identify and characterize in experimental model settings are present in corresponding diseases and conditions that our model systems endeavor to mimic. Dr. Gentleman?s role in Core B greatly expands our access to very large collections of well characterized human tissue such as approximately 500 AD and 600 PD, 60 AD/PD, 30 Lewy body dementia (LBD), 33 Down?s (DS), 800 chronic epilepsy, 500 Huntington?s (HD), 14 chronic traumatic encephalopathy (CTE), and 2000 neurologically and neuropathologically normal cases. The second change is related in that, between the collections available to Dr. Gentleman and those in our UAMS Brain Bank housed in and managed by Core B, we have sufficient material for the needs of our investigators and for those of non- program investigators on request. Core B at UAMS holds tissue from 698 autopsies that include fixed tissue blocks and sections from 23 separate brain regions from AD, PD, AD/PD, LBD, HD, and neurologically and neuropathologically normal cases. Over and above these, we have tissue blocks from 68 DS, and 92 blocks of tissues collected at surgery for drug resistant, intractable epilepsy. All have representative sections stained with Nissl/H&E and with Campbell-Switzer and Bielschowsky-Sevier-Munger, are stored and cataloged along with photomicrographic data that is accessible on our secure server. Moreover, Dr. Mrak, who evaluated all of the tissue in our UAMS bank, will continue as our collaborator. Importantly, Core B houses discreet 3-D- dissected, flash frozen structures, e.g., olfactory bulb, hippocampus, etc., for molecular analysis in Core C. The availability of these large collections along with data available on our database, together with the collections available to Dr. Gentleman, will allow our Program investigators to focus on brain regions spanning the gamut of affected locales and to facilitate identification and characterization of pathways that give rise to either successful aging or decline into disease. Core B deliverables include: i) discreet 3-D dissected nuclei and regions from the left side of brain for use by Core C personnel; and ii) Nissl/H&E/silver stains, light and fluorescence immunohistochemistry, digital imaging, image capture, and preliminary analyses of fixed tissue sections according to investigator request; and iii) precise detection of protein-protein proximity in tissues and cells is now offered by the core via Duolink proximity ligation assays (PLA). These core services favor successful completion of aims of each Project. Standardized protocols, record keeping, and primary data analysis?hallmarks of the work of Drs. Griffin and Gentleman?are vital for successful completion of the specific aims of the projects in this Program.
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