Synthesis and characterization of styrylchromone derivatives as beta-amyloid imaging agents

Several promising agents have been synthesized and evaluated for in vivo imaging probes of beta-amyloid plaques in Alzheimer's disease (AD) brain. Recently, we have developed flavone derivatives, which possess the basic structure of the 2-phenylchromone, as useful candidates for amyloid imaging agents. In an attempt to further develop novel tracers, we synthesized and evaluated a series of 2-styrylchromone derivatives, which replace the 2-phenyl substituent of flavone backbone with the 2-styryl. A series of radioiodinated styrylchromone derivatives were designed and synthesized. The binding affinities for amyloid plaques were assessed by in vitro binding assay using pre-formed synthetic Abeta(1-40) aggregates. The new series of styrylchromone derivatives showed high binding affinity to Abeta aggregates at the K(d) values of 32.0, 17.5 and 8.7nM for [(125)I]6, [(125)I]9, and [(125)I]12, respectively. In biodistribution studies using normal mice, [(125)I]6 and [(125)I]9 examined in normal mice displayed high brain uptakes with 4.9 and 2.8%ID/g at 2min post injection. The radioactivity washed out from the brain rapidly (1.6 and 1.0%ID/g at 60min post injection for [(125)I]6 and [(125)I]9, respectively). But [(125)I]12 did not show marked brain uptake, and the washout rate from the brain was relatively slow throughout the time course (1.1 and 1.4%ID/g at 2 and 30min post injection, respectively). Although additional modifications are necessary to improve the brain uptake and rapid clearance of non-specifically bound radiotracer, the styrylchromone backbone may be useful as a backbone structure to develop novel beta-amyloid imaging agents.     

Development of skin structure and cutaneous water loss in nestling desert house sparrows from Saudi Arabia

The outer layer of the epidermis, the stratum corneum (SC), contains lipids and corneocytes, which together form layers that limit cutaneous water loss (CWL). We examined the development of structure of the SC and CWL in nestling House Sparrows (Passer domesticus) from Saudi Arabia. We measured CWL of nestlings, and characterized development of their epidermis using electron microscopy. We tested two antagonistic hypotheses, that CWL decreases as nestlings age, a response to increased thickness of SC, and an opposite idea that CWL increases as nestlings age even though the number of layers of the SC remains constant. CWL of nestling House Sparrows varied with developmental stages, in a non-linear fashion, but not significantly so. CWL of nestlings averaged 7.31+/-1.5 g H(2)O/(m(2) h), whereas for adults it was 4.95 g/(m(2) h); adult CWL was 67.7% that of nestlings. We found that morphology of the SC did not change linearly with age, but seemed to vary with developmental stage. CWL decreased as the SC thickness increased and as the total thickness of the corneocytes increased. Further, we found that CWL decreased as the thickness of the extracellular space increased, number of corneocytes increased, and proportion of the SC that is extracellular space increased.     

Identification of the putative proton donor residue of lacto-N-biose phosphorylase (EC 2.4.1.211)

Two lacto-N-biose phosphorylase (LNBP) isozyme genes were cloned from Bifidobacterium bifidum JCM1254. Alignment of the amino acid sequences of LNBP and its homologs identified 24 completely conserved acidic amino acid residues. All single mutants of Bifidobacterium longum LNBP at residues other than D313N retained considerable activity, suggesting that Asp313 is the putative proton donor residue in LNBP.     

Effects of adiponectin on the renal sympathetic nerve activity and blood pressure in rats

Adiponectin is an adipocytokine that modulates energy homeostasis and glucose metabolism. Here, we examined the effects of acute intravenous (iv) and lateral cerebral ventricular (LCV) injections of adiponectin on the renal sympathetic nerve activity (RSNA) and blood pressure (b/p) in urethane-anesthetized rats. Both iv and LCV injections of adiponectin induced dose-dependent suppressions of RSNA and b/p. Moreover, we found that bilateral lesions of the hypothalamic suprachiasmatic nucleus (SCN) abolished the effects of iv injection of adiponectin on RSNA and b/p. These findings suggest that adiponectin decreases the RSNA and b/p in a dose-dependent manner and that the SCN is implicated in mechanism of adiponectin actions on RSNA and b/p. These findings also suggest that the hypotensive-action activity of adiponectin is realized, at least partially, via changes in activities of autonomic nerves activity.     

N-terminal region of chitinase I of Bacillus circulans KA-304 contained new chitin-biding domain

Chitinase I (CHI1) of Bacillus circulans KA-304 forms protoplasts from Schizophyllum commune mycelia when the enzyme is combined with α-1,3-glucanase of B. circulans KA-304. CHI1 consists of an N-terminal unknown region and a C-terminal catalytic region classified into the glycoside hydrolase family-19 type. An N-terminal region-truncated mutant of CHI 1 (CatCHI1), which was expressed in Escherichia coli Rosetta-gami B (DE3), lost colloidal chitin- and powder chitin-binding activities. The colloidal chitin- and the powder chitin-hydrolyzing activities of CatCHI1 were lower than those of CHI1, and CatCHI1 was not effective in forming the protoplast. A fusion protein of the N-terminal region of CHI1 and green fluorescent protein (Nterm-GFP) was expressed in E. coli, and the fusion protein was adsorbed to colloidal chitin, powder chitin, and chitosan. Fluorescence microscopy analysis showed that Nterm-GFP bound to the S. commune cell-wall.