Biology

93	Shigemura, N.; Sawa, Y. ; Mizuno, S.; Ono, M.; Minami, M.; Okumura, M.; Nakamura, T.; Kaneda, Y.; Matsuda, H. (Graduate School of Medicine) Induction of Compensatory Lung Growth in Pulmonary Emphysema Improves Surgical Outcomes in Rats American Journal of Respiratory and Critical Care Medicine, 171, 1237-1245 (2005) Although lung volume reduction surgery (LVRS) has been widely used as a therapeutic strategy for pulmonary emphysema, the procedure carries still significant disadvantages such as high operative mortality and a limited duration of effective response. The present results showed that emphysema-induced hypoxia may down-regulate HGF gene expression and the induction of compensatory growth by the regenerative factors following LVRS may overcome those limitations through enhancement of alveolar regeneration and angiogenesis in the remaining lung. This is the first report demonstrating successful use of a therapeutic strategy for emphysema with surgery and supplementation of growth factors as a combined technique in thoracic surgery.

94	Kotera, I. 1; Sekimoto, T. 1; Miyamoto, Y. 2; Saiwaki, T. 1; Nagoshi, E. 1; Sakagami, H.; Kondo, H.; Yoneda, Y. 2 1 (Graduate School of Medicine) 2(Graduate School of Frontier Biosciences) Importin α Transports CaMKIV to the Nucleus without Utilizing Importin β EMBO Journal, 24, 942-951 (2005) Ca2 ⁺ /calmodulin-dependent protein kinase IV (CaMKIV) plays an essential role in the transcriptional activation of cAMP response element-binding protein mediated signaling pathways. In this study, we revealed that nuclear import of CaMKIV is mediated by importin α without utilizing the classical importin β dependent transport system. This is a first report to demonstrate definitely that importin α can act as a nuclear import carrier like importin β family molecule.

95	Fujito, T.; Ikeda, W.; Kakunaga, S.; Minami, Y.; Kajita, M.; Sakamoto, Y.; Monden, M.; Takai, Y. (Graduate School of Medicine) Inhibition of Cell Movement and Proliferation by Cell-Cell Contact-induced Interaction of Necl-5 with Nectin-3 The Journal of Cell Biology, 171, 165-173 (2005) Cells stop moving and proliferating upon cell-cell contact. This phenomenon is known as contact inhibition of cell movement and proliferation. We have found that Necl-5 localizes at leading edges of moving cells and enhances cell movement and proliferation. This paper shows that Necl-5 is down-regulated by its trans -interaction with nectin-3 upon cell-cell contact, resulting in reduction of cell movement and proliferation. Nectin-3 then initiates cell-cell adhesion cooperatively with cadherin. Thus, Necl-5 and nectin-3 play roles in the contact inhibition.

96	Takemoto, T. ; Uchikawa, M.; Kamachi, Y.; Kondoh, H. (Graduate School of Frontier Biosciences) Convergence of Wnt and FGF Signals in the Genesis of Posterior Neural Plate through Activation of the Sox2 Enhancer N-1 Development, 133, 297-306 (2006)

97	Matsuno, K.; Kumano, M.; Kubota, Y.; Hashimoto, Y.; Takisawa, H. (Graduate School of Science) The N-Terminal Noncatalytic Region of Xenopus RecQ4 Is Required for Chromatin Binding of DNA Polymerase α in the Initiation of DNA Replication Molecular and Cellular Biology, 26, 4843-4852 (2006) Recruitment of DNA polymerases onto replication origins is a crucial step in the assembly of eukaryotic replication machinery. We isolated Xenopus RecQ4 as an essential replication protein for chromatin binding of DNA polymerase α. N-terminal fragments of RecQ4 physically interacted with Cut5, and their ability to bind to Cut5 closely correlated with their ability to rescue the replication activity of the depleted extracts. Our data suggest that RecQ4 performs an essential role in the assembly of replication machinery through interaction with Cut5 in vertebrates.

98	Terao, Y. ; Okamoto, S.; Kataoka, K.; Hamada, S.; Kawabata, S. (Graduate School of Dentistry) Protective Immunity against Streptococcus pyogenes Challenge in Mice after Immunization with Fibronectin-binding Protein The Journal of Infectious Diseases, 192, 2081-2091 (2005)
99	Saeki, H. ; Ohsumi, K.; Aihara, H.; Ito, T.; Hirose, S.; Ura, K. ; Kaneda, Y. (Graduate School of Medicine) Linker Histone Variants Control Chromatin Dynamics during Early Embryogenesis Proceedings of the National Academy of Science of the United States of America, 102, 5697-5702 (2005) Linker histones comprise divergent subtypes and change their types during early embryogenesis in higher organisms. In this study, we revealed that maternal histone B4 allows chromatin to be remodeled by ATP-dependent chromatin remodeling factor, whereas somatic histone H1 prevents this remodeling. Structural analysis shows that histone B4 does not significantly restrict the accessibility of linker DNA. These results provide direct molecular evidence for the functional significance of maternally expressed linker histones with respect to embryonic totipotency.

100	Hata, K.; Nishimura, R.; Ueda, M.; Ikeda, F.; Matsubara, T.; Ichida, F.; Hisada, K.; Nokubi, T.; Yamaguchi, A.; Yoneda, T. (Graduate School of Dentistry) A CCAAT/Enhancer Binding Protein β Isoform, Liver-Enriched Inhibitory Protein, Regulates Commitment of Osteoblasts and Adipocytes Molecular and Cellular Biology, 25, 1971-1979 (2005) Here, we investigated the role of transcription factor C/EBPβ and its isoform, LIP, in the regulation of balance between osteoblast and adipocyte differentiation. We found that CEBP/β promotes osteoblast differentiation in cooperation with Runx2, an essential transcription factor for osteogenesis. LIP also physically binds to Runx2 and stimulates transcriptional activity and osteogenic action of Runx2, whereas it inhibits adipogenesis. These data provide new insights into the molecular mechanism of the regulation of osteoblast and adipocyte commitment of mesenchymal stem cells.

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