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Research at OU


62  Akita, F.; Chong, K. T.; Tanaka, H.; Yamashita, E.; Miyazaki, N.; Nakaishi, Y.; Suzuki, M.; Namba, K.; Ono, Y.; Tsukihara, T.; Nakagawa. A.
(Institute for Protein Research)
The Crystal Structure of a Virus-like Particle from the Hyperthermophilic Archaeon Pyrococcus furiosus Provides Insight into the Evolution of Viruses
The Journal of Molecular Biology, 368, 1469-1483 (2007)

We solved the atomic structure of a virus-like particle isolated from a hyperthermophle, Pyrococcus furiosus, (PfV) by X-ray crystallography. The coat protein of PfV is encoded in a genome of P. furiosus. The PfV particle showed that it retained T=3 icosahedral symmetry, as is often the case in spherical viruses. An examination of capsid structures suggested strong evolutionary links among PfV and other various virus particles. It provides a previously undescribed example of viral relationships across the three domains of life.

63 Egawa, A.; Fujiwara, T.; Mizoguchi, T.; Kakitani, Y.; Koyama, Y.; Akutsu, H.
(Institute for Protein Research)
Structure of the Light-Harvesting Bacteriochlorophyll c Assembly in Chlorosomes from Chlorobium limicola Determined by Solid-State NMR
Proceedings of the National Academy of Sciences of the United States of America, 104, 790-795 (2007)

64 Hashimoto, R.*1; Hashimoto, H.*1, 2; Shintani, N.*2; Chiba, S.; Hattori, S.; Okada, T.; Nakajima, M.*2; Tanaka, K.*2; Kawagishi, N.*2; Nemoto, K.; Mori, T.; Ohnishi T.; Noguchi, H.; Hori, H.; Suzuki, T.; Iwata, N.; Ozaki, N.; Nakabayashi, T.; Saitoh, O.; Kosuga, A.; Tatsumi, M.; Kamijima, K.; Weinberger, DR.; Kunugi, H.; Baba. A.*2
*1(Graduate School of Medicine)
*2(Graduate School of Pharmaceutical Sciences)
Pituitary Adenylate Cyclase-activating Polypeptide Is Associated with Schizophrenia
Molecular Psychiatry, advance online publication, 27, March 2007 (in press)

We provide evidence that genetic variants of pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide, and its receptor, PAC1, are associated with schizophrenia. The allele of the PACAP gene overrepresented in schizophrenia was associated with reduced hippocampal volume and poorer memory performance, neurobiological traits related to risk for schizophrenia. Abnormal behaviors in PACAP knockout mice, including elevated locomotor activity and deficits in prepulse inhibition, were reversed by an antipsychotic treatment. These data suggest that alterations in PACAP signaling might contribute to the pathogenesis of schizophrenia.

65 Hattori, T.*1; Baba, K.; Matsuzaki, S.*1; Honda, A.; Miyoshi, K.; Inoue, K.*1; Taniguchi, M.*1; Hashimoto, H.*2; Shintani, N.*2; Baba, A.*2; Shimizu, S.*1; Yukioka, F.*1; Kumamoto, N.*1; Yamaguchi, A.; Tohyama, M.*1; Katayama, T.
*1(Graduate School of Medicine)
*2(Graduate School of Pharmaceutical Sciences)
A Novel DISC1-interacting Partner DISC1-Binding Zinc-finger Protein: Implication in the Modulation of DISC1-dependent Neurite Outgrowth
Molecular Psychiatry, 12, 398-407 (2007)

We identified a novel interacting protein of Disrupted-In-Schizophrenia 1 (DISC1), which has relation to major psychiatric disorders, termed DISC1-binding zinc finger protein (DBZ). PACAP caused markedly the dissociation between DISC1 and DBZ in PC12 cells and the inhibition of the DISC1-DBZ dissociation reduced the neurite length in PC12 cells after PACAP stimulation and in primary cultured hippocampal neurons. The present results provide some new molecular insights into the mechanisms of neuronal development and neuropsychiatric disorders.

66 Hayashi, M.; Katou, Y.; Itoh, T.; Tazumi, A.; Yamada, Y.; Takahashi, T.; Nakagawa, T.; Shirahige, K.; Masukata, H.
(Graduate School of Engineering Science)
Genome-wide localization of pre-RC Sites and Identification of Replication Origins in Fission Yeast
The EMBO Journal, 26, 1327-1339 (2007)

67 Hirata, M.; Koreeda, S.; Sakihara, K.; Kato, A.; Yoshimine, T.; Yorifuji, S.
(Graduate School of Medicine)
Effects of the Emotional Connotations in Words on the Frontal Areas - a Spatially Filtered MEG Study
NeuroImage, 35, 420-429 (2007)

Here, we investigated the cerebral oscillatory changes during emotional word reading. We found that the emotional connotations increase the activities in the Broca area and the anterior cingulate area. Negative emotional connotations activate the left prefrontal cortex, whereas positive emotional connotations activate the right. Negative and positive emotional words may be processed by different mechanisms. This is the first report demonstrating with magnetoencephalography how and where the emotional connotations in words effect on the brain.

68 Hishida, T.; Ohya, T.; Kubota, Y.; Kamada, Y.; Shinagawa, H.
(Research Institute for Microbial Diseases)
Functional and Physical Interaction of Yeast Mgs1 with PCNA: Impact on RAD6-dependent DNA Damage Tolerance
Molcullar and Cellular Biolbiology, 26, 5509-5517 (2006)

Current studies indicate that replication arrest is a key factor in genome instability. In eukaryote cells, DNA damage tolerance and homologous recombination pathways play an important role in rescuing stalled replication forks. We demonstrate that Mgs1, Srs2 and SUMO modification of PCNA can modulate the multiple repair pathways and prevent genome instability caused by inappropriate repair of stalled replication forks. The present findings may provide novel insights into the mechanisms determining the mode of action at stalled replication fork.

69 Ikeda, F.; Nishimura, R.; Matsubara, T.; Hata, K.; Reddy, SV.; Yoneda, T.
(Graduate School of Dentistry)
Activation of NFAT Signal In Vivo Leads to Osteopenia Associated with Increased Osteoclastogenesis and Bone-Resorbing Activity
The Journal of Immunology, 177, 2384-2390 (2006)

Others and we identified a transcription factor, NFAT2, as a master regulator of osteoclastogenesis. To further understand the role of NFAT signal in vivo, we generated transgenic mice overexpressing constitutively-active NAFT1, which can mimic osteoclastogenic action of NAFT2, in osteoclast specific lineage. The mice showed high osteoclastogenic and bone resorbing activity in association with activation of c-Src activity.

70 Imada, K.; Minamino, T.; Tahara, A.; Namba, K.
(Graduate School of Frontier Biosciences)
Structural Similarity between the Flagellar Type III ATPase FliI and F1-ATPase Subunits
Proceedings of the National Academy of Sciences of the United States of America, 104, 485-490 (2007)

Construction of the bacterial flagellum in the cell exterior is a highly-ordered process. The component proteins are selectively exported through the central channel of the growing flagellum by the flagellar type III export apparatus in an ATPase-driven manner. We determined the structure of FliI, the ATPase component, at 2.4 Å resolution. The whole structure shows a striking similarity to the subunits of F1-ATPase, implying evolutionary relation between the flagellum and F0F1-ATPsynthase and a similarity in the mechanism between FliI and F1-ATPase.
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