S. C. Meredith

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Methods for the quantitative derivatization of amino acids with phenylisothiocyanate and for the separation and quantitation of the resulting phenylthiocarbamyl derivatives by reverse-phase high-performance liquid chromatography are described. Phenylthiocarbamylation of amino acids proceeds smoothly in 5 to 10 min at room temperature. Coupling solvents,(More)
In vitro, β-amyloid (Aβ) peptides form polymorphic fibrils, with molecular structures that depend on growth conditions, plus various oligomeric and protofibrillar aggregates. Here, we investigate structures of human brain-derived Aβ fibrils, using seeded fibril growth from brain extract and data from solid-state nuclear magnetic resonance and electron(More)
The genetic lesion underlying familial British dementia (FBD), an autosomal dominant neurodegenerative disorder, is a T-A transversion at the termination codon of the BRI gene. The mutant gene encodes BRI-L, the precursor of ABri peptides that accumulate in amyloid deposits in FBD brain. We now report that both BRI-L and its wild-type counterpart, BRI, were(More)
To explain why solid cancers grow or are rejected, we examined how the tumor stroma affected the level of antigen expression necessary to induce an immune response. We applied a tamoxifen-regulated Cre-loxP system to induce a model SIYRYYGL antigen recognized by the 2C T cell receptor. Solid tumors expressing the antigen at lower levels grew, whereas solid(More)
The pathognomonic plaques of Alzheimer's disease are composed primarily of the 39- to 43-aa beta-amyloid (Abeta) peptide. Crosslinking of Abeta peptides by tissue transglutaminase (tTg) indicates that Gln15 of one peptide is proximate to Lys16 of another in aggregated Abeta. Here we report how the fibril structure is resolved by mapping interstrand(More)
-This paper outlines a methodology to measure the ability of a schizophrenic patient to saccade against a presented stimulus by tracking the patient’s electrooculographic (EOG) activity. The overall goal is to investigate a deficit in this anti-saccade task as a cognitive endophenotype for schizophrenia. A portable system for performing this test and a(More)
CD1 molecules function to present lipid-based antigens to T cells. Here we present the crystal structure of CD1c at 2.5 Å resolution, in complex with the pathogenic Mycobacterium tuberculosis antigen mannosyl-β1-phosphomycoketide (MPM). CD1c accommodated MPM's methylated alkyl chain exclusively in the A' pocket, aided by a unique exit portal underneath the(More)
Polyglutamine (poly(Q)) expansion is associated with protein aggregation into beta-sheet amyloid fibrils and neuronal cytotoxicity. In the mutant poly(Q) protein huntingtin, associated with Huntington's disease, both aggregation and cytotoxicity may be abrogated by a polyproline (poly(P)) domain flanking the C terminus of the poly(Q) region. To understand(More)
Solid-state NMR measurements have been reported for four peptides derived from beta-amyloid peptide Abeta(1-42): Abeta(1-40), Abeta(10-35), Abeta(16-22), and Abeta(34-42). Of these, the first two are predicted to be amphiphilic and were reported to form parallel beta-sheets, whereas the latter two peptides appear nonamphiphilic and adopt an antiparallel(More)
Insulin-degrading enzyme (IDE) is a zinc metalloprotease that hydrolyzes amyloid-beta (Abeta) and insulin, which are peptides associated with Alzheimer disease (AD) and diabetes, respectively. Our previous structural analysis of substrate-bound human 113-kDa IDE reveals that the N- and C-terminal domains of IDE, IDE-N and IDE-C, make substantial contact to(More)