Fujino K.,Kyoto University |
Fujino K.,Azabu University |
Horie M.,Kyoto University |
Horie M.,Kagoshima University |
And 4 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2014
Animal genomes contain endogenous viral sequences, such as endogenous retroviruses and retrotransposons. Recently, we and others discovered that nonretroviral viruses also have been endogenized in many vertebrate genomes. Bornaviruses belong to the Mononegavirales and have left endogenous fragments, called "endogenous bornavirus-like elements " (EBLs), in the genomes of many mammals. The striking features of EBLs are that they contain relatively long ORFs which have high sequence homology to the extant bornavirus proteins. Furthermore, some EBLs derived from bornavirus nucleoprotein (EBLNs) have been shown to be transcribed as mRNA and probably are translated into proteins. These features lead us to speculate that EBLs may function as cellular coopted genes. An EBLN element in the genome of the thirteen-lined ground squirrel (Ictidomys tridecemlineatus), itEBLN, encodes an ORF with 77% amino acid sequence identity to the current bornavirus nucleoprotein. In this study, we cloned itEBLN from the ground squirrel genome and investigated its involvement in Borna disease virus (BDV) replication. Interestingly, itEBLN, but not a human EBLN, colocalized with the viral factory in the nucleus and appeared to affect BDV polymerase activity by being incorporated into the viral ribonucleoprotein. Our data show that, as do certain endogenous retroviruses, itEBLN potentially may inhibit infection by related exogenous viruses in vivo.
Blood-Brain Barrier (BBB) pharmacoproteomics: Reconstruction of in vivo brain distribution of 11 P-glycoprotein substrates based on the BBB transporter protein concentration, in vitro intrinsic transport activity, and unbound fraction in plasma and brain in mice
Uchida Y.,Tohoku University |
Ohtsuki S.,Tohoku University |
Kamiie J.,Azabu University |
Terasaki T.,Tohoku University
Journal of Pharmacology and Experimental Therapeutics | Year: 2011
The purpose of this study was to examine whether in vivo drug distribution to the brain can be reconstructed by integrating P-glycoprotein (P-gp)/mdr1a expression levels, P-gp in vitro activity, and drug unbound fractions in mouse plasma and brain. For 11 P-gp substrates, in vitro P-gp transport activities were determined by measuring transcellular transport across monolayers of mouse P-gptransfected LLC-PK1 (L-mdr1a) and parental cells. P-gp expression amounts were determined by quantitative targeted absolute proteomics. Unbound drug fractions in plasma and brain were obtained from the literature and by measuring brain slice uptake, respectively. Brain-to-plasma concentration ratios (K p brain) and its ratios between wild-type and mdr1a/1b(-/-) mice (K p brain ratio) were obtained from the literature or determined by intravenous constant infusion. Unbound brain-to-plasma concentration ratios (K p,uu,brain) were estimated from K p brain and unbound fractions. Based on pharmacokinetic theory, K p brain ratios were reconstructed from in vitro P-gp transport activities and P-gp expression amounts in L-mdr1a cells and mouse brain capillaries. All reconstructed K p brain ratios were within a 1.6-fold range of observed values. K p brain then was reconstructed from the reconstructed K p brain ratios and unbound fractions. K p,uu,brain was reconstructed as the reciprocal of the reconstructed K p brain ratios. For quinidine, loperamide, risperidone, indinavir, dexamethasone, paclitaxel, verapamil, loratadine, and diazepam, the reconstructed K p brain and K p,uu,brain agreed with observed and estimated in vivo values within a 3-fold range, respectively. Thus, brain distributions of P-gp substrates can be reconstructed from P-gp expression levels, in vitro activity, and drug unbound fractions. Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics.
Nagasawa M.,Azabu University
The Journal of veterinary medical science / the Japanese Society of Veterinary Science | Year: 2011
In order to introduce the Canine Behavioral Assessment and Research Questionnaire (C-BARQ), which is a standardized system for evaluating the behavioral traits of dogs, to Japan, where the environment with respect to dog ownership is thought to differ from those of the United States and Europe, we compared demographic information on dogs in the United States and Japan and examined whether similar factors could be extracted from both countries using questionnaire items of the C-BARQ. The C-BARQ was completed by 11,410, and 734 dog owners respectively in the United States and Japan, and some demographic differences were found, such as breed and neuter status. Data from completed questionnaires were subjected to factor analysis, and the resulting factors were tested for reliability. In the United States, factor analysis yielded 11 factors from 63 items that accounted for 52.9% of the common variance. In Japan, 15 factors were extracted, and these accounted for 57.0% of the common variance. The present factors for the United States were almost identical to the factors identified in a previous study, and similar factors were extracted in both countries. Therefore, the C-BARQ can function effectively as a fundamental behavioral evaluation system for dogs in Japan.
Sakata R.,Azabu University
Meat Science | Year: 2010
This review starts by introducing the history and underlying culture of meat production and consumption in Japan since early times, and the effects of social change on these parameters. Meat processing in Japan is described, and certain other related papers are also introduced. Automatic machines for meat cutting have been developed by the Japanese food industry and are currently being used throughout the world, particularly in Europe. Soft meat products specially produced for the elderly, along with diet meat products low in salt and calorie content for middle aged persons have recently gone into production. The intensification of color formation of meat using naturally occurring materials, and tenderization of sausage casing are discussed. © 2010 The American Meat Science Association.
Kubo M.O.,University of Tokyo |
Takatsuki S.,Azabu University
Evolutionary Biology | Year: 2015
Using Japanese sika deer from boreal and subtropical forests, we investigated the effects of environmental factors on body size variation and tested the following ecological hypotheses pertaining to Bergmann’s rule in mammals: (1) heat conservation, (2) heat dissipation, (3) starvation resistance, (4) food availability and (5) insularity. Data on body sizes and habitats of sika deer from 31 populations on the Japanese archipelago were collected. Body mass and cranial greatest length (CGL; reflecting skeletal body size) were measured and analysed separately among gender groups. Path analyses were used to clarify inter-variable relationships and estimate direct and indirect effects of environmental variables on body size. Consistent with Bergmann’s rule, a clear latitudinal cline of body size was found for sika deer. Subsequent path analyses showed that the abiotic factors, specifically mean annual temperature and annual precipitation, had significant negative effects on body size, and annual temperature had the greatest effect among tested environmental variables. Winter severity and food availability during spring were significantly associated with body mass but not with CGL. Both heat conservation and dissipation hypotheses were accepted and food availability and starvation resistance hypotheses were applicable to variation of body mass but not to CGL, indicating that phenotypic changes in fat reserves strongly influence variation in body mass. Path diagram modelling of inter-variable relationships fit well for females but not for males, and unexplained variation of male body size suggested the presence of unidentified factors. Variation in mating systems among populations may effect body size variation of the male sika deer. © 2015, Springer Science+Business Media New York.