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PS C 13 12 (BSE) HS. 1. HCV 1 DDX1 (HCV) ATPase/RNA DDX1 HCV DDX1 HCV N DDX1 ATPase HCV 16 28 12 GLP 17 3 31 2 C C Huh7 1

[ ] [ ( ): ( )] PrP sc neuro 2a ScN2a 2. PrP sc PrP sc 100 Glial Fibrilary Acidic Protein (GFAP) vacuolar ATPase A-subunit PrP sc CRMP-2 (Collapsin response mediator protein-2) PrP sc [ ] 24- U18666A PrP C PrP sc ED50 25nM ED50 1/20 1/40 U18666A ScN2a HMG-CoA mrna 24- PrP sc U18666A PrP sc U18666A BSE II (BSE) PrP BSE P9FD PrP sc BSE PrP BSE PrP BSE PrP BSE 1/1000 BSE ScN2a P9FD PrP sc 14 15 P9FD PrP sc P9FD P9FD P9FD 168 4 PrP sc 60 P9FD 174 5 PrP sc 2

120 P9FD 181 5 P9FD PrP sc [ ] 2. A Toll-like receptor PmrC A Toll-like receptor. 1. LPS LPS lipid A monophosphoryl lipid A PmrC A TLR4 A NF- B [ ] MPL LPS LPS Caspase-1 MPL Caspase-1 caspase-1 lipid A MPL caspase-1 caspase-11 lipid A MPL MPL TLR-4 MyD88/NF B LPS caspase-1 THP-1 MPL caspase-1 IL-1beta LPS TLR-4 MPL. 1. 1-1. 1 PS PSS PSS1 PSS2 PS CHO PS PS [ ] [ ] 2 SINV 3

PS SINV PS lacz SINV RNA CHO PS RNA SINV RNA PS PS RNA RNA PS CERT CERT CERT C5-DMB- 1:1 200 nm (LPS) CERT LPS [] RNA RNA PS [ ] CERT (1R,3R)-HPA12 CERT CHO -SM (1R,3R)-HPA12 CERT cdna 1-2. CERT (SM) SM CHO CERT CERT -SM (1R,3R)-HPA12 (1R,3R)-HPA12 CERT HPA12 (1R,3R)-HPA12 CERT [ ] CERT CERT (1) D-erythoro- (2) SM (3) [] CERT FFAT VAP FFAT CERT VAP CERT VAP CERT CERT FFAT CERT - FFAT FFAT CERT VAP - 4

[] CCKR CCKR CCK (PDT) PDT CCK CCKR [ ; Kaleeckal G. Harikumar, Vishwajeet Puri, Raman Deep Singh, Richard E. Pagano, and Laurence J. Miller ( )] PDT PDT [ ; Vladislav Dolgachev, M. Sharjeel Farooqui, Olga I. Kulaeva, Michael Tainsky, Biserka Nagy, Duska Separovic( )]] [; Bjørn Spilsberg, Kirsten Sandvig ( )] CB1 1-3. CHO CoA [; Arkaitz Carracedo, María Diez, Manuel Guzman, and Guillermo Velasco ( ) Math J.H. Geelen ( )] (CCK) CCKR G (IPC) IPC IPCS 5

IPCS [ 3 H]C2-96 TLC 96 GLUT1 T HTLV-1) GLUT1 [ ] Far Eastern Blotting MALDI-QIT-TOF-MS (matrix-assisted laser desorption/ ionization quadrupole ion trap IPCS (SMS) (SMS-1, SMS-2) (PC) SM IPCS IPCS/SMS SMS-1 SMS-2 C6-NBD- IPCS SMS IPCS [] time-of-flight mass spectrometry) MALDI-QIT-TOF-MS Far Eastern Blotting ( ) (TLC) PVDF MS TLC [ (. ) ] 10 GLUT) 12 GLUT1 GLUT3 GLUT1 F- GLUT1 MALDI-QIT-TOF-MS MALDI-QIT-TOF-MS DHBA 6

[ ] Golgi stack. Mol. Biol. Cell, 15, 1506-1518, 2004 09) M. Fukasawa, O. Varlamov, W. S. Eng, T. H. Sollner, and J. E. Rothman: Localization and activity of the SNARE Ykt6 determined by its regulatory domain and palmitoylation. Proc. Natl Acad Sci U S A, 101, 4815-4820, 2004 10) Y. Kondo, J. Hamada, C. Kobayashi, R. Nakamura, Y. Suzuki, R. Kimata, T. Nishimura, T. Kitagawa, N. Imura I. 1. 01) V. Dolgachev, M. Sharjeel Farooqui, O. I. Kulaeva, M. Tainsky, B. Nagy, K. Hanada, and D. Separovic: De novo ceramide accumulation due to inhibition of its conversion to complex sphingolipids in apoptotic photosensitized cells. J. Biol. Chem., 279, 23238-23249, 2004 02) A. Carracedo, M.J.H. Geelen, M. Diez, K. Hanada, M. Guzmán, and G. Velasco: Ceramide sensitizes astrocytes to oxidative stress: protective role of cannabinoids. Biochem..J., 380, 435-440, 2004 03) Y. Tanaka, M. Takizawa, S. Igimi, and F. Amano: Enhanced release of prostaglandin D 2 during re-incubation of RAW 264.7 macrophage-like cells after treatment of both lipopolysaccharide and non-steroidal anti-inflammatory drugs. Biol. Pharm. Bull., 27, 985-991, 2004 04) K. Kawasaki, R. K. Ernst, and S. I. Miller: 3-O-deacylation of lipid A by PagL, a PhoP/PhoQ-regulated deacylase of Salmonella typhimurium, modulates signaling through Toll-like receptor 4. J. Biol. Chem., 279, 20044-20048, 2004 07) K. Kawasaki, R. K. Ernst, and S. I. Miller: Deacylation and palmitoylation of lipid A by Salmonellae outer membrane enzymes modulate host signaling through Toll-like receptor 4. J. Endotoxin Res., 10, 439-444, 2004 08) A. Volchuk, M. Ravazzola, A. Perrelet, W. S. Eng, M. De Liberto, O. Varlamov, M. Fukasawa, T. Engel, T. H. Söllner, J. E. Rothman, and L. Orci: Countercurrent distribution of two distinct SNARE complexes mediating transport within the and S. Hara: Overexpression of hypoxia-inducible factor 1α in renal and bladder cancer cells increases tumorigenic potency, J. Urology, 173, 1762-1766, 2005 11) Y. Inoue, Y. Yamakawa, A. Sakudo, T. Kinumi, Y. Nakamura, Y. Matsumoto, K. Saeki, T. Kamiyama, T. Onodera, M. Nishijima: Infection route-independent accumulation of splenic abnormal prion protein. Jpn J Infect Dis., 58(2), 78-82, 2005 12) H. Furuoka, A. Yabuzoe, M. Horiuchi, Y. Tagawa, T. Yokoyama, Y. Yamakawa, M. Shinagawa and T. Sata: Effective antigen-retrieval for immunohistochemical detection of abnormal isoform of prion protein in animals. Acta NeuroPathol., 109, 263-271, 2005 13 K. G. Harikumar, V. Puri, R. D. Singh, K. Hanada, R. E. Pagano, and L. J. Miller: Differential effects of modification of membrane cholesterol and sphingolipids on the conformation, function, and trafficking of the G protein-coupled cholecystokinin receptor. J. Biol. Chem., 280, 2176-2185, 2005 14) K. Kumagai, S. Yasuda, K. Okemoto, M. Nishijima, S. Kobayashi, and K. Hanada: CERT mediates intermembrane transfer of various molecular species of ceramides. J. Biol. Chem., 280, 6488-6495, 2005 15) B. Spilsberg, K. Hanada, and K. Sandvig: Diphtheria toxin translocation across cellular membranes is regulated by sphingolipids. Biochem. Biophys. Res. Commun., 329, 465-473, 2005 16) H. Kishida, Y. Sakasegawa, K. Watanabe, Y. Yamakawa, M. Nishijima, Y. Kuroiwa, N. S. Hachiya, and K. Kaneko: Non-glycosylphosphatidylinositol(GPI)-anchored recombinant prion protein with dominant-negative mutation inhibits PrP sc replication in vitro. J. Protein Folding Disord, 11, 14-20, 2004 7

17) T. Ohsawa, M. Nishijima, and O. Kuge: Functional analysis of Chinese hamster phosphatidylserine synthase 1 ( ),,, 28-34, 2004 through systematic alanine mutagenesis. Biochem. J., 381, 853-859, 2004 18) Q. Lao, O. Kuge, T. Fukamachi, T. Kakegawa, H. Saito, M. Nishijima, and H. Kobayashi: An IκB-β COOH Terminal Region Protein Is Essential for the Proliferation of CHO Cells Under Acidic Stress. J. Cell. Physiol., 203, 186-192, 2005 19) K. Kawasaki, R. K. Ernst, and S. I. Miller: Inhibition of Salmonella enterica serovar Typhimurium lipopolysaccharide deacylation by aminoarabinose membrane modification. J. Bacteriol., in press 20) K. Kawasaki, R. K. Ernst, and S. I. Miller: Purification and characterization of deacylated and/or palmitoylated lipid A species unique to Salmonella typhimurium. J. Endotoxin Res., in press 21) Q. Lao, T. Fukamachi, H. Saito, O. Kuge, M. Nishijima, II. 1. 01) K. Hanada: Nonvesicular ER-to-Golgi trafficking of ceramide by CERT having a PI4P- recognising PH domain, The 3rd Japanese Biochemical society Biofrontier Symposium, New Aspect of Phospholipid Biology 2004, 2004.5.12, Kamakura, Japan 02) K. Hanada: Molecular machinery for intracellular trafficking of ceramide, American Society for Biochemistry and Molecular Biology 2004 Annual Meeting, 2004.6.15, Boston, USA 03) K. Hanada: Pickup and delivery of ceramide by CERT, Sapporo Sphingolipid Symposium, 2004.7.22, Sapporo, Japan 04) K. Hanada: Molecular machinery for non-vesicular and H. Kobayashi: Requirement of an IκB-β COOH trafficking of ceramide in mammalian cells, Gordon Research terminal region protein for acidic-adaptation in CHO cells. J. Cell. Physiol., in press Conference on Glycolipid and Sphingolipid Biology, 2004.7.26, Hyogo, Japan 05) K. Hanada: Discovery of the molecular machinery CERT 1) : : CERT,, 22, 966-969, 2004 2) : CERT,, 76, 562-570, 2004 3) :,, 40, 640-644, 2004 4) : ( ),,, 132-136, 2004 5), : BSE, 34(3), 44-46, 2004 6), : :,, 23, 828-834, 2005 7), : MD-2,, 7, 123-128, 2004 8) :, for ER-to-Golgi trafficking of ceramide, 5th International Conference on Lipid Binding Proteins, 2004.9.28, Zao, Japan 06) K. Hanada: Molecular machinery for intracellular trafficking of ceramide, The 8th Membrane Forum, 2004.11.24, Nagoya, Japan 07) K. Kawasaki, R. K. Ernst, and S. I. Miller: Lipid A deacylation by PagL: regulation of TLR4 signaling, 8th Biennial Conference of the International Endotoxin Society, 2004.11, Kyoto Japan 08) K. Okemoto, K. Kawasaki, and M. Nishijima: Dephosphorylation of lipid A selectively reduces its activity to induce IL-1β production, 8th Biennial Conference of the International Endotoxin Society, 2004.11.15-18, Kyoto, Japan 09) Y. Yamakawa, K. Hagiwara, K. Nohtomi, Y. Nakamura, Y. Higuchi, Y. Sato, T. Sata, and Expert Committee for BSE Diagnosis, Ministry of Health, Labour and Welfare of Japan: BSE inspection in Japan and finding of atypical PK-resistant prion protein (PrPRES) in an apparently healthy 23-month-old-holstein steer in Japan: First International 8

Conference of the European Network of Excellence NeuroPrion Prion 2004 2004.5.24-28, Paris 10) M. Fukasawa, S. Sato, Y. Yamakawa, T. Natsume, T. Suzuki, I. Shoji, H. Aizaki, T. Miyamura, and M. Nishijima: Proteomic profiling of lipid droplet proteins in HCV core-expressing hepatoma cell lines, 11th International Symposium on Hepatitis C Virus and Related Viruses, 2004.10.5, Heidelberg, Germany 11) M. Shirakura, I. Shoji, T. Ichimura, R. Suzuki, T. Suzuki, Y. Sugiyama, T. Shimoji, K. Murakami, S. Sato, M. Fukasawa, Y. Yamakawa, M. Nishijima, and T. Miyamura: Proteomic analysis of Hepatitis C virus core-interacting proteins using a novel tandem affinity purification tag and mass spectrometry, 11th International Symposium on Hepatitis C virus and Related Viruses, 2004.10.5, Heidelberg, Germany 09),, : CERT 77 2004.10.15 10),,,,,, : Neuroblastoma N2a cells stably expressing MHM2-tagged prion protein (PrP) for the analysis of the conformational conversion of PrP, 77, 2004.10.15 11), O. Varlamov, W. S. Eng, T. H. Sollner, J. E. Rothman: Localization and Activity of the SNARE Ykt6 Determined by its Regulatory Domain and Palmitoylation SNARE Ykt6 ), 77, 2004.10.15 12) : LPS 2. 01) : 26 2004.5.20 02) : 2004.5.28 03) : BSE,, 2004.6.18, 04) : 13 2004.6.26 05) : : 2 2004.8.25 06) : :, 3 HTLV/ATL,,, 2004.9 ( ) 07),, :, 26, 2004.10 ( ) 08) : Molecular machinery for intracellular trafficking of the lipid ceramide 77 2004.10.14, 77 2004.10.16 13) 2005.2.14 14),,,, : Mycoplasma penetrans,, 2005.3.5-6 ( ) 15) : C,, 2005.3.15 16),,,,,,,,, : C, 125, 2005.3.29 17),, :, 125, 2005.3.30 18) :, 125, 2005.3.30 ( ) 19),,, : 9

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