Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic neuropeptide that belongs to the secretin/glucagon/vasoactive intestinal peptide (VIP) family. PACAP prevents ischemic delayed neuronal cell death (apoptosis) in the hippocampus. PACAP inhibits the activity of the mitogen-activated protein kinase (MAPK) family, especially JNK/SAPK and p38, thereby protecting against apoptotic cell death. After the ischemia-reperfusion, both pyramidal cells and astrocytes increased their expression of the PACAP receptor (PAC1-R). Reactive astrocytes increased their expression of PAC1-R, released interleukin-6 (IL-6) that is a proinflammatory cytokine with both differentiation and growth-promoting effects for a variety of target cell types, and thereby protected neurons from apoptosis. These results suggest that PACAP itself and PACAP-stimulated secretion of IL-6 synergistically inhibit apoptotic cell death in the hippocampus. The PAC1-R is expressed in the neuroepithelial cells from early developmental stages and in various brain regions during development. We have recently found that PACAP, at physiological concentrations, induces differentiation of mouse neural stem cells into astrocytes. Neural stem cells were prepared from the telencephalon of mouse embryos and cultured with basic fibroblast growth factor. The PAC1-R immunoreactivity was demonstrated in the neural stem cells. When neural stem cells were exposed to PACAP, about half of these cells showed glial fibrillary acidic protein (GFAP) immunoreactivity. This phenomenon was significantly antagonized by a PAC1-R antagonist (PACAP6-38), indicating that PACAP induces differentiation of neural stem cell into astrocytes. Other our physiological studies have demonstrated that PACAP acts on PAC1-R in mouse neural stem cells and its signal is transmitted to the PAC1-R-coupled G protein Gq but not to Gs. These findings strongly suggest that PACAP plays very important roles in neuroprotection in adult brain as well as astrocyte differentiation during development.

N-Vanillyl-acylamides (NVAs) naturally occur as capsaicinoids in Capsicum plants. NVAs with a longer chain acyl moiety (LCNVAs) have been developed as attractive tools for medicinal usage because of their capsaicin-like bioactive and physiological properties, without harmful irritancy. In this study, we isolated four LCNVAs from Capsicum oleoresin. Their structures were determined to be N-vanillyl-hexadecanamide (palvanil, 2), N-vanillyl-octadecanamide (stevanil, 3), N-vanillyl-9E-octadecenamide (olvanil, 4), and N-vanillyl-9E,12E-octadecadienamide (livanil, 5) by spectroscopic analysis and gas chromatography-mass spectrometry analysis of their methanolysis products. Furthermore, the existence of two LCNVAs in oleoresin, N-vanillyl-tetradecanamide (myrvanil, 1) and N-vanillyl-9E,12E,15E-octadecatrienamide (linvanil, 6), was suggested. The contents of these LCNVAs and the major capsaicinoids-capsaicin and dihydrocapsaicin-in three Capsicum oleoresins and the fresh fruits of two hot peppers were measured by a liquid chromatography-tandem mass spectrometry system. The content ratios of the total LCNVAs, except for myrvanil, versus the capsaicin in the oleoresins (0.1-41%) was significantly larger than that in fresh fruits (<0.01%). The composition of these LCNVAs in each oleoresin was similar to that of fatty acids in the oil fraction of each oleoresin. We observed no relationship between the composition of these LCNVAs in the fresh fruits.

ABSTRACT. To investigate the genetic characteristics of phosphoprotein (P) and matrix protein (M) genes of variable rabies virus (RV) prevalent in Brazil, the authors genetically characterized the P and M genes from 30 Brazilian RV field isolates. Phylogenetic analysis based on the P and M genes revealed the presence of six RV variants that consisted primarily of three insectivorous bats, the vampire bat, dog and fox in Brazil. Specific amino acid substitutions corresponding to these phylogenetic lineages were observed, with Asp 42 and Glu 62 in the P protein found to be characteristic of Brazilian chiroptera-and carnivora-related RVs, respectively. Amino acid sequence motifs predicted to associate with a viral function in the P and M proteins were conserved among Brazilian RV variants. KEY WORDS: Brazil, genetic analysis, matrix protein, phosphoprotein, rabies virus.J. Vet. Med. Sci. 69(11): 1145-1154 Rabies virus (RV) is a member of the Lyssavirus genus, which belongs to the Rhabdoviridae family. Lyssavirus is characterized as having seven genotypes (GTs) comprising, rabies virus (GT 1), Lagos bat virus (GT 2), Mokola virus (GT 3), Duvenhage virus (GT 4), European bat lyssavirus type (EBL) 1 (GT 5), EBL 2 (GT 6) and Australian bat lyssavirus (GT 7). Lyssaviruses have approximately 12-kb of unsegmented negative-stranded genomic RNA for encoding the genes of the nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G) and polymerase (L).RV has an almost global distribution and infects a wide range of mammalian species in which it causes a lethal form of encephalopathy. In Brazil, the principal RV transmitters to humans and domestic animals -dogs and vampire batshave caused serious problems in the public health sector and the livestock industry [6,19]. In addition, RVs have been isolated from other animal species [8]. Previously, phylogenetic analyses targeting the N and G genes revealed that there were several RV variants which varied depending on the host species, which included vampire bats, insectivorous bats, dogs and foxes. Furthermore, RV isolates from cattle and frugivorous bats (Artibeus (A.) sp.) have frequently been typed as vampire bat-related RVs in Brazil [19,25,26,41,42,44,45]. Variability has also been reported in the G protein, a major contributor to the pathogenicity of the virus, in which several amino acid substitutions at antigenic sites associated with the pathogenicity and immunogenicity of the virus have been identified in Brazilian RV variants [41]. However, differences in the pathogenicity and antigenic characteristics of these Brazilian RV variants are not yet known. Recently, in addition to the G protein, both P and M proteins have also been reported to be associated with the pathogenicity of the virus [43]. The P protein forms a ribonucleoprotein (RNP) with N and L proteins, which then wraps around the viral RNA, and plays an important role in transcription and replication in conjunction with the L protein [3,5,11]. In addition, the P protein acts to counteract the ...

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