Hydrolysis of Tay-Sachs ganglioside by beta-hexosaminidase A of human liver and urine.
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Biomedical subjects
Publications and source records attributed to S C Li.
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Transmembrane (TM) segments of integral membrane proteins are putatively alpha-helical in conformation, yet their primary sequences are rich in residues known in globular proteins as helix-breakers (Gly) and beta-sheet promoters (Ile, Val, Thr). To examine the specific 2 degrees structure propensities of such residues in membrane environments, we have now designed and synthesized a series of model 20-residue peptides with "guest" hydrophobia segments embedded in "host" N- and C-terminal hydrophilic matrices. Molecular design was based on the prototypical sequence NH2-(Ser-Lys)2-Ala5-Leu6-x7-Ala8-Leu9-y10-Trp 11-Ala12-Leu13-z14-(Lys-Ser)3-OH. The 10-residue hydrophobic mid-segment 5-14 is expected to act as ca. three turns of an alpha-helix. In the present work, we compare the 20-residue peptide having three "helix-forming" Ala residues [x = y = z = Ala (peptide 3A)] to the corresponding peptide 3G (x = y = z = Gly) which contains three "helix-breaking" Gly residues. Trp was inserted to provide a measure of aromatic character typical of TM segments; Ser and Lys enhanced solubility in aqueous media. Circular dichroism studies in water, in a membrane-mimetic [sodium dodecylsulfate (SDS)], medium, and in methanol solutions, demonstrated the exquisite sensitivity of the conformations of these peptides to environment, and proved that despite its backbone flexibility, Gly can be accommodated as readily as Ala into a hydrophobic alpha-helix in a membrane. Nevertheless, the relative stability of Ala- vs. Gly-containing helices emerged in methanol solvent titration and temperature dependence experiments in SDS.(ABSTRACT TRUNCATED AT 250 WORDS)
To determine the prevalence of major neurologic disorders, a door-to-door survey was conducted in six cities of the People's Republic of China during 1983 in a well-defined population of 63,195. The survey included a complete census and a screening interview together with an examination having high sensitivity for detecting individuals with frequently occurring neurologic disorders, including epilepsy. All individuals with responses or findings suggesting neurologic disease were examined by senior neurologists using standardized diagnostic criteria. There was 100% cooperation among the study subjects. Two hundred eighty-nine individuals alive on prevalence day (January 1, 1983) were identified as having epilepsy, yielding a lifetime age-adjusted (to the 1960 U.S. population) point prevalence ratio of 4.4/1,000. There were 16 people who developed epilepsy in the sample population during 1982, providing an age-adjusted incidence rate of 35/100,000 per year. The most frequent type identified was generalized convulsive seizures. Brain injury, intracranial infection, and cerebrovascular disease, in that order, were the leading putative causes of epilepsy.