Identification and estimation algorithm for stochastic neural system. II

The algorithm for identifying the stochastic neural system and estimating the system process which reflects the dynamics of the neural network are presented in this papar. The analogous algorithm has been proposed in our preceding paper (Nakao et al., 1984), which was based on the randomly missed observations of a system process only. Since the previous algorithm mentioned above was subject to an unfavorable effect of consecutively missed observations, to reduce such an effect the algorithm proposed here is designed additionally to observe an intensity process in a neural spike train as the information for the estimation.The algorithm is constructed with the extended Kalman filters because it is naturally expected that a nonlinear and time variant structure is necessary for the filters to realize the observation of an intensity process by means of mapping from a system process to an intensity process. The performance of the algorithm is examined by applying it to some artificial neural systems and also to cat's visual nervous systems. The results in these applications are thought to prove the effectiveness of the algorithm proposed here and its superiority to the algorithm proposed previously.     

Chemical reactivity of labile sulfur of iron-sulfur proteins The reaction of triphenyl phosphine

The reaction of triphenyl phosphine to iron-sulfur proteins from adrenal cortex mitochondria, spinach chloroplasts, and Clostridium pasteurianum was investigated. As ethanol concentrations in the reaction mixture increased, the rate of the reaction decreased. In the simultaneous presence of 1 M KCl and 5 M urea, the reaction rate reached at maximum. Under these conditions the initial rates of the decolorization reaction by the phosphine were found to be 8.7, 0.88, and 1.8 nmol of ferrodoxin per min at 25°C for adrenal, spinach, and clostridial ferredoxins, respectively. The kinetic curves for the reaction of the phosphine sulfide formation, the loss of labile sulfur, and the deterioriation of visible absorption showed a similar pattern with a comparable rate. During this reaction, the complete reduction of ferric ions present in ferredoxin was observed with a fast rate under either aerobic or anaerobic conditions.These results suggest that the iron atoms in ferredoxin are first reduced by the intramolecular reductants in the presence of triphenyl phosphine with the concomitant formation of S₂^2?, which then reacts with triphenyl phosphine resulting in the formation of triphenyl phosphine sulfide.     

Localization of the gene encoding myelin basic protein to mouse chromosome 18E3----4 and rat chromosome 1p11----p12.

The location of a gene encoding myelin basic protein in rat (MBP) and mouse (Mbp) was determined by in situ hybridization using the mouse Mbp cDNA labeled with biotin-11-dUTP as a specific probe. The localization of biotin signals in the mouse was found on Chromosome 18E2----3. The result is consistent with the previous report that the Mbp gene is located on the distal half of Chromosome 18. In the rat, the signals localized on chromosome 1p11----p12, suggesting homology between mouse Chromosome 18 and the short arm of rat chromosome 1.     

Effect of sodium butyrate on actin distribution in rat 3Y1 fibroblasts in monolayer culture

We studied the effect of sodium butyrate, a potent G1/G2-arresting agent, on actin distribution in rat 3Y1 fibroblasts in monolayer culture by fluorescence microscopy of cells stained with 7-nitrobenz-2-oxa-1, 3-diazole phallacidine (NBD-Ph). When randomly proliferating cells were arrested mainly in G1 phase with butyrate, a reversible overaccumulation of cellular net protein occurred. In the G1-arrested cells, actin markedly accumulated at the margin of cells, and a network structure of actin stress fibers appeared. When density-arrested cells were replated sparsely and rearrested in the G1, early S, and G2 phases with butyrate or hydroxyurea, the actin network was observed extensively in the cells arrested in the G1 and G2 phases with butyrate. These results agree with our previous results indicating the existence of some physiological similarity between cells in the G1 and G2 phases and suggest that actin distribution somehow depends on the phases of the cell cycle. The actin profiles observed by the NBD-Ph staining were confirmed by transmission electronmicroscopy (TEM) of negatively stained whole cells. TEM further revealed that electron-dense amorphous materials were present at crossing points in the network but rarely present on interconnecting microfilament bundles.     

Expression of UDP-glucuronosyltransferase cDNA in Saccharomyces cerevisiae as a membrane-bound and as a cytosolic form

The mouse clone UDPGTm-1 encodes a UDP-glucuronosyltransferase enzyme which was isolated from a lambda gt11 cDNA library constructed with phenobarbital-induced liver mRNA [Kimura, T., & Owens, I. S. (1987) Eur. J. Biochem. 168, 515-521]. In order to establish substrate specificity, UDPGTm-1 was inserted into the yeast vector pEVP11 and expressed in Saccharomyces cerevisiae strain AH22. Cells transformed with the expression unit pUDPGTm-1c (insert in correct orientation with respect to promoter) stably transcribe the transferase cDNA. Consistent with the presence of mRNA, pUDPGTm-1c-transformed AH22 cells synthesize a transferase protein with Mr congruent to 51,000 by Western immunoblot analysis. The membrane-bound transferase expressed in yeast in glycosylated as indicated by its enhanced electrophoretic mobility in a SDS-polyacrylamide gel following endoglycosidase H treatment and detection by Western immunoblot analysis. A survey, using 12 aglycons in an assay with microsomes from cells which express the protein, shows preferential glucuronidation of naphthol and estrone followed by p-nitrophenol. Testosterone, phenolphthalein, dihydrotestosterone, androsterone, and 4-methylumbelliferone are conjugated at an intermediate level. There is barely detectable glucuronidation of 3-hydroxy- and 9-hydroxybenzo[a]pyrene and no detectable conversion of morphine or lithocholic acid. The truncated cDNA (lacking the putative membrane-insertion signal-peptide coding sequence, but with a newly adapted translation-start codon) is ligated into pAAH5 and is expressed as a cytosolic transferase form in the protease-deficient ZA521 strain of S. cerevisiae. The Mr congruent to 51,000-52,000 is similar to that seen in microsomes from AH22 cells where the protein is presumably processed as it is inserted into the membrane.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fine-Scale Genetic Structure and Demographic History in the Miyako Islands of the Ryukyu Archipelago

The Ryukyu Archipelago is located in the southwest of the Japanese islands and is composed of dozens of islands, grouped into the Miyako Islands, Yaeyama Islands, and Okinawa Islands. Based on the results of principal component analysis on genome-wide single-nucleotide polymorphisms, genetic differentiation was observed among the island groups of the Ryukyu Archipelago. However, a detailed population structure analysis of the Ryukyu Archipelago has not yet been completed. We obtained genomic DNA samples from 1,240 individuals living in the Miyako Islands, and we genotyped 665,326 single-nucleotide polymorphisms to infer population history within the Miyako Islands, including Miyakojima, Irabu, and Ikema islands. The haplotype-based analysis showed that populations in the Miyako Islands were divided into three subpopulations located on Miyakojima northeast, Miyakojima southwest, and Irabu/Ikema. The results of haplotype sharing and the D statistics analyses showed that the Irabu/Ikema subpopulation received gene flows different from those of the Miyakojima subpopulations, which may be related with the historically attested immigration during the Gusuku period (900 − 500 BP). A coalescent-based demographic inference suggests that the Irabu/Ikema population firstly split away from the ancestral Ryukyu population about 41 generations ago, followed by a split of the Miyako southwest population from the ancestral Ryukyu population (about 16 generations ago), and the differentiation of the ancestral Ryukyu population into two populations (Miyako northeast and Okinawajima populations) about seven generations ago. Such genetic information is useful for explaining the population history of modern Miyako people and must be taken into account when performing disease association studies.     

N-type Calcium Channel in the Pathogenesis of Experimental Autoimmune Encephalomyelitis

One of the family of voltage-gated calcium channels (VGCC), the N-type Ca²⁺ channel, is located predominantly in neurons and is associated with a variety of neuronal responses, including neurodegeneration. A precise mechanism for how the N-type Ca²⁺ channel plays a role in neurodegenerative disease, however, is unknown. In this study, we immunized N-type Ca²⁺ channel α_1B-deficient (α_1B^−/−) mice and their wild type (WT) littermates with myelin oligodendrocyte glycoprotein 35–55 and analyzed the progression of experimental autoimmune encephalomyelitis (EAE). The neurological symptoms of EAE in the α_1B^−/− mice were less severe than in the WT mice. In conjunction with these results, sections of the spinal cord (SC) from α_1B^−/− mice revealed a reduction in both leukocytic infiltration and demyelination compared with WT mice. No differences were observed in the delayed-type hypersensitivity response, spleen cell proliferation, or cytokine production from splenocytes between the two genotypes. On the other hand, Western blot array analysis and RT-PCR revealed that a typical increase in the expression of MCP-1 in the SC showed a good correlation with the infiltration of leukocytes into the SC. Likewise, immunohistochemical analysis showed that the predominant source of MCP-1 was activated microglia. The cytokine-induced production of MCP-1 in primary cultured microglia from WT mice was significantly higher than that from α_1B^−/− mice and was significantly inhibited by a selective N-type Ca²⁺ channel antagonist, ω-conotoxin GVIA or a withdrawal of extracellular Ca²⁺. These results suggest that the N-type Ca²⁺ channel is involved in the pathogenesis of EAE at least in part by regulating MCP-1 production by microglia.