This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The primary focus of this project is to improve our understanding of the role of iron (particularly iron oxides) in neurodegenerative diseases. This will be accomplished via the development and use of novel techniques for high-resolution mapping of iron anomalies in tissue sections.
Our specific Aim i s to employ synchrotron-based techniques for high-resolution iron mapping and identification of iron phases in neurodegenerative tissue. This work will primarily involve; (i) refinement of sample preparation techniques developed by our group, (ii) the use of X-ray Absorption Fine Structure (XAFS) and X-ray Absorption Near Edge Structure (XANES) to determine which iron compounds are present/dominant (iii)develop the capabilities in microdiffraction to determine the degree of crystallinity of iron anomalies identified by the iron area scans, and (iv) the adaptation of methods we have developed for the examination of avian and transgenic mouse brain tissue to human brain tissue and (iv) determine iron and other biogenic minerals concentration and chemical state as well as locate specific tissue areas to be further examined by other optical and electron- microscopy techniques. It is anticipated that this work will further our knowlege of the biochemistry of a number of neurodegenerative disorders in a manner not possible by any other known analytical technique.
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| Yazdi, Aliakbar Khalili; Vezina, Grant C; Shilton, Brian H (2017) An alternate mode of oligomerization for E. coli SecA. Sci Rep 7:11747 |
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| Liang, Wenguang G; Ren, Min; Zhao, Fan et al. (2015) Structures of human CCL18, CCL3, and CCL4 reveal molecular determinants for quaternary structures and sensitivity to insulin-degrading enzyme. J Mol Biol 427:1345-1358 |
| Zhou, Hao; Li, Shangyang; Badger, John et al. (2015) Modulation of HIV protease flexibility by the T80N mutation. Proteins 83:1929-39 |
| Kathuria, Sagar V; Kayatekin, Can; Barrea, Raul et al. (2014) Microsecond barrier-limited chain collapse observed by time-resolved FRET and SAXS. J Mol Biol 426:1980-94 |
| Skinner, John J; Yu, Wookyung; Gichana, Elizabeth K et al. (2014) Benchmarking all-atom simulations using hydrogen exchange. Proc Natl Acad Sci U S A 111:15975-80 |
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