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Search Results: 1 - 10 of 91 matches for " Shirou Mohri "
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A Rapid Bioassay for Classical and L-Type Bovine Spongiform Encephalopathies  [PDF]
Yuichi Matsuura, Yukiko Ishikawa, Robert A. Somerville, Takashi Yokoyama, Ken’ichi Hagiwara, Yoshio Yamakawa, Tetsutaro Sata, Tetsuyuki Kitamoto, Shirou Mohri
Open Journal of Veterinary Medicine (OJVM) , 2013, DOI: 10.4236/ojvm.2013.31013

The rapid detection of infectivity of several agents that cause Creutzfeldt-Jakob disease has previously been achieved by assaying for deposits of abnormal prion protein (PrPSc) in follicular dendritic cells in the spleens of transgenic mice carrying the human prion protein gene. In this study, transgenic mice expressing the bovine prion protein were inoculated intraperitoneally with classical (C-type) or atypical L-type bovine spongiform encephalopathies (BSE). Proteinase-resistant PrPSc were detected in the spleens of all transgenic mice at 75 days after inoculation with both types of BSE. Infectivity in PrPSc-positive spleens of the transgenic mice revealed that prions of C- and L-type BSE replicated. These results suggest that bioassay system by the transgenic mice could be useful for the rapid detection of BSE infectivity with discriminating between C- and L-type BSEs.

Heterogeneity of the Abnormal Prion Protein (PrPSc) of the Chandler Scrapie Strain
Kazuo Kasai,Yoshifumi Iwamaru,Kentaro Masujin,Morikazu Imamura,Shirou Mohri,Takashi Yokoyama
Pathogens , 2013, DOI: 10.3390/pathogens2010092
Abstract: The pathological prion protein, PrP Sc, displays various sizes of aggregates. In this study, we investigated the conformation, aggregation stability and proteinase K (PK)-sensitivity of small and large PrP Sc aggregates of mouse-adapted prion strains. We showed that small PrP Sc aggregates, previously thought to be PK-sensitive, are resistant to PK digestion. Furthermore, we showed that small PrP Sc aggregates of the Chandler scrapie strain have greater resistance to PK digestion and aggregation-denaturation than large PrP Sc aggregates of this strain. We conclude that this strain consists of heterogeneous PrP Sc.
Prion Protein Binds to Aldolase A Produced by Bovine Intestinal M Cells  [PDF]
Yuya Nagasawa, Yu Takahashi, Wataru Itani, Hitoshi Watanabe, Yusuke Hidaka, Shotaro Morita, Kei Suzuki, Kouichi Watanabe, Shyuichi Ohwada, Haruki Kitazawa, Morikazu Imamura, Takashi Yokoyama, Motohiro Horiuchi, Suehiro Sakaguchi, Shirou Mohri, Michael T. Rose, Tomonori Nochi, Hisashi Aso
Open Journal of Veterinary Medicine (OJVM) , 2015, DOI: 10.4236/ojvm.2015.53007
Abstract: Microfold (M) cells are a kind of intestinal epithelial cell in the follicle-associated epithelium (FAE) of Peyer’s patches. They can transport antigens and microorganisms to lymphoid tissues. Bovine spongiform encephalopathy (BSE) is a fatal neurodegenerative disorder in cattle. It is linked to variant Creutzfeldt-Jakob disease in humans. Although it is thought that M cells transport the BSE agent, the exact mechanism by which it crosses the intestinal barrier is not clear. We have bovine intestinal epithelial cell line (BIE cells), which can differentiate into the M cell type in vitro after stimulation, and which is able to transport the BSE agent. We show here that M cells are able to incorporate large numbers of PrP coated magnetic particles into intracellular vesicles, which we collected. The results of 2-DE show a specific protein associated with the PrP-coated particles, compared with non-coated particles. This protein was identified as aldolase A, a glycolytic pathway enzyme, using LC-MS/MS analysis. Aldolase A was synthesized and secreted by BIE cells, and increased during M cell differentiation. In the villi of the bovine intestine, aldolase A was detected on the surface of the epithelium and in the mucus droplet of goblet cells. In the FAE of bovine jejunal and ileal Peyer’s patches, aldolase A was localized on the surface and the apical part of the M cells. The binding of rbPrP to aldolase A was clearly detected and inhibited by pre-treatment of anti-aldolase A antibody. Aldolase A was co-stained with incorporated PrPSc in M-BIE cells. These results suggest that bovine M cells and goblet cells synthesize aldolase A, and that aldolase A may have the ability to bind PrP and associate with PrP in cellular vesicles. Therefore, aldolase A-positive M cells may play a key role in the invasion of BSE into the body.
Anti-Prion Activity of Brilliant Blue G
Yoshifumi Iwamaru, Takato Takenouchi, Yuichi Murayama, Hiroyuki Okada, Morikazu Imamura, Yoshihisa Shimizu, Makoto Hashimoto, Shirou Mohri, Takashi Yokoyama, Hiroshi Kitani
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0037896
Abstract: Background Prion diseases are fatal neurodegenerative disorders with no effective therapy currently available. Accumulating evidence has implicated over-activation of P2X7 ionotropic purinergic receptor (P2X7R) in the progression of neuronal loss in several neurodegenerative diseases. This has led to the speculation that simultaneous blockade of this receptor and prion replication can be an effective therapeutic strategy for prion diseases. We have focused on Brilliant Blue G (BBG), a well-known P2X7R antagonist, possessing a chemical structure expected to confer anti-prion activity and examined its inhibitory effect on the accumulation of pathogenic isoforms of prion protein (PrPres) in a cellular and a mouse model of prion disease in order to determine its therapeutic potential. Principal Findings BBG prevented PrPres accumulation in infected MG20 microglial and N2a neural cells at 50% inhibitory concentrations of 14.6 and 3.2 μM, respectively. Administration of BBG in vivo also reduced PrPres accumulation in the brains of mice with prion disease. However, it did not appear to alleviate the disease progression compared to the vehicle-treated controls, implying a complex role of P2X7R on the neuronal degeneration in prion diseases. Significance These results provide novel insights into the pathophysiology of prion diseases and have important implications for the treatment.
Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits
Hiroyuki Okada, Yoshifumi Iwamaru, Morikazu Imamura, Kentaro Masujin, Yuichi Matsuura, Yoshihisa Shimizu, Kazuo Kasai, Shirou Mohri, Takashi Yokoyama, Stefanie Czub
Veterinary Research , 2011, DOI: 10.1186/1297-9716-42-79
Abstract: Bovine spongiform encephalopathy (BSE), which belongs to a group of diseases called transmissible spongiform encephalopathies (TSE), is a fatal neurodegenerative disorder of cattle. BSE was first identified in the United Kingdom in 1986 [1], then spread to European as well as North American countries and Japan, and has affected more than 190 000 cattle in the world. The infectious agent responsible for TSE is the disease-associated prion protein (PrPSc), which is thought to be a post-translationally modified form of the host-encoded membrane glycoprotein (PrPC) [2]. According to the protein-only hypothesis, PrPSc is the principal component of the infectious agent.On the basis of uniform pathology and biochemical profile of the protease-resistant prion protein (PrPres) among BSE-affected cattle, it is assumed that BSE in cattle is caused by only one prion strain. Since 2003, variants of BSE (named atypical BSE) have been detected in Japan, Europe, and North America and classified in at least two groups, namely, H-type and L-type BSE, according to the molecular mass of PrPres, compared with those of the classical BSE (named C-type BSE) [3]. H-type BSE was first identified in France [4], and L-type BSE, called bovine amyloidotic spongiform encephalopathy (BASE), was first detected in Italy [5]. It is accepted that C-type BSE is caused by the consumption of BSE-contaminated feed, whereas the origins of H-type and L-type BSE remain enigmatic. Hypotheses for the origin of atypical BSE include (1) infection of cattle with different BSE agents; (2) infection of cattle with a non-bovine source or unrecognized forms of infectious TSE agents; (3) genetic mutations in the prion protein gene; and (4) spontaneous or so-called sporadic forms of TSE in cattle, limited to old age, like the sporadic form of human Creutzfeldt-Jakob disease (CJD) [6-10]. However, only one genetic mutation has been found in an H-type BSE case [11]. Sequence analysis of the open reading frame (ORF) of th
Insect Cell-Derived Cofactors Become Fully Functional after Proteinase K and Heat Treatment for High-Fidelity Amplification of Glycosylphosphatidylinositol-Anchored Recombinant Scrapie and BSE Prion Proteins
Morikazu Imamura, Nobuko Kato, Hiroyuki Okada, Miyako Yoshioka, Yoshifumi Iwamaru, Yoshihisa Shimizu, Shirou Mohri, Takashi Yokoyama, Yuichi Murayama
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0082538
Abstract: The central event in prion infection is the conformational conversion of host-encoded cellular prion protein (PrPC) into the pathogenic isoform (PrPSc). Diverse mammalian species possess the cofactors required for in vitro replication of PrPSc by protein-misfolding cyclic amplification (PMCA), but lower organisms, such as bacteria, yeasts, and insects, reportedly lack the essential cofactors. Various cellular components, such as RNA, lipids, and other identified cofactor molecules, are commonly distributed in both eukaryotes and prokaryotes, but the reasons for the absence of cofactor activity in lower organisms remain to be elucidated. Previously, we reported that brain-derived factors were necessary for the in vitro replication of glycosylphosphatidylinositol-anchored baculovirus-derived recombinant PrP (Bac-PrP). Here, we demonstrate that following protease digestion and heat treatment, insect cell lysates had the functional cofactor activity required for Bac-PrP replication by PMCA. Mammalian PrPSc seeds and Bac-PrPSc generated by PMCA using Bac-PrP and insect cell-derived cofactors showed similar pathogenicity and produced very similar lesions in the brains of inoculated mice. These results suggested that the essential cofactors required for the high-fidelity replication of mammalian PrPSc were present in the insect cells but that the cofactor activity was masked or inhibited in the native state. We suggest that not only RNA, but also DNA, are the key components of PMCA, although other cellular factors were necessary for the expression of the cofactor activity of nucleic acids. PMCA using only insect cell-derived substances (iPMCA) was highly useful for the ultrasensitive detection of PrPSc of some prion strains.
Intraspecies Prion Transmission Results in Selection of Sheep Scrapie Strains
Takashi Yokoyama,Kentaro Masujin,Mary Jo Schmerr,Yujing Shu,Hiroyuki Okada,Yoshifumi Iwamaru,Morikazu Imamura,Yuichi Matsuura,Yuichi Murayama,Shirou Mohri
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0015450
Abstract: Sheep scrapie is caused by multiple prion strains, which have been classified on the basis of their biological characteristics in inbred mice. The heterogeneity of natural scrapie prions in individual sheep and in sheep flocks has not been clearly defined.
Sulfated Dextrans Enhance In Vitro Amplification of Bovine Spongiform Encephalopathy PrPSc and Enable Ultrasensitive Detection of Bovine PrPSc
Yuichi Murayama,Miyako Yoshioka,Kentaro Masujin,Hiroyuki Okada,Yoshifumi Iwamaru,Morikazu Imamura,Yuichi Matsuura,Shigeo Fukuda,Sadao Onoe,Takashi Yokoyama,Shirou Mohri
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0013152
Abstract: Prions, infectious agents associated with prion diseases such as Creutzfeldt-Jakob disease in humans, bovine spongiform encephalopathy (BSE) in cattle, and scrapie in sheep and goats, are primarily comprised of PrPSc, a protease-resistant misfolded isoform of the cellular prion protein PrPC. Protein misfolding cyclic amplification (PMCA) is a highly sensitive technique used to detect minute amounts of scrapie PrPSc. However, the current PMCA technique has been unsuccessful in achieving good amplification in cattle. The detailed distribution of PrPSc in BSE-affected cattle therefore remains unknown.
F theory Vacua in Four Dimensions and Toric Threefolds
Kenji Mohri
Physics , 1997, DOI: 10.1142/S0217751X99000415
Abstract: We investigate D=4, N=1 F theory models realized by type IIB string compactification on toric threefolds. Massless spectra, gauge symmetries, phase transitions associated with divisor contractions and flops, and non-perturbative superpotentials are analyzed using elementary toric methods.
$N=2$ super $W$ algebra in half-twisted Landau-Ginzburg model
Kenji Mohri
Physics , 1993, DOI: 10.1142/S0217751X94002065
Abstract: We investigate $N=2$ extended superconformal symmetry, using the half-twisted Landau-Ginzburg models. The first example is the $D_{2n+2}$ -type minimal model. It has been conjectured that this model has a spin $n$ super $W$ current. We checked this by the direct computations of the BRS cohomology class up to $n=4$. We observe for $n\le 3$ the super W currents generate the ring isomorphic to the chiral ring of the model with respect to the classical product. We thus conjecture that this isomorphism holds for any $n$. The next example is $ CP_{n}$ coset model. In this case we find a sort of Miura transformation which gives the simple formula for the super W currents of spin \{1,2,...,n\} in terms of the chiral superfields. Explicit form of the super W currents and their Poisson brackets are obtained for $CP_{2},CP_{3}$ case. We also conjecture that as long as the classical product is concerned, these super W currents generate the ring isomorphic to the chiral ring of the model and this is checked for $CP_2$ model.
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