Biology

Miyazono, S. ^*1 ; Shimauchi-Matsukawa, Y.; Tachibanaki, S. ^{*1, 2} ; Kawamura, S. ^{*1, 2}
^*1 (Graduate School of Frontier Biosciences)
^*2 (Graduate School of Science)
Highly Efficient Retinal Metabolism in Cones
Proceedings of the National Academy of Sciences of the United States of America, 105(41), 16051-16056 (2008)

After visual pigment bleaching, all-trans retinal is reduced to all-trans retinol. This reducing activity was >30 times higher in cones than in rods. A novel oxidation pathway was found in cones to convert 11- cis retinol to 11- cis retinal, the required step to regenerate the pigment: this conversion was coupled with reduction of all-trans retinal to all-trans retinol. The oxidation was >50 times more effective than the reaction previously known. These effective reactions would be requisite for cones to function during daytime.

Nin, F.; Hibino, H.; Doi, K.; Suzuki, T.; Hisa, Y.; Kurachi, Y.
(Graduate School of Medicine)
The Endocochlear Potential Depends on Two K ⁺ Diffusion Potentials and an Electrical Barrier in the Stria Vascularis of the Inner Ear
Proceedings of the National Academy of Sciences of the United States of America, 105(5), 1751-1756 (2008)

Endocochlear potential (EP) of +80 mV in cochlear endolymph is essential for hearing. The EP seems to mainly originate from positive potential detected in stria vascularis comprising two epithelial layers. However, the precise mechanism underlying generation of the EP has remained uncertain. We have found that the high potential in stria vascularis is attributed to a K ⁺ diffusion dominating in one layer and electrical barrier function of the stria. A K ⁺ diffusion potential occurring in the other layer also contributes to the EP.

Ogura, H. ^{*1, 2} ; Murakami, M. ^{*1, 2} ; Okuyama, Y. ^{*1, 2} ; Tsuruoka, M. ^{*1, 2} ; Kitabayashi, C. ^{*1, 2} ; Kanamoto, M. ^{*1, 2} ; Nishihara, M. ^{*1, 2} ; Iwakura, Y.; Hirano, T. ^{*1, 2}
^*1 (Graduate School of Medicine)
^*2 (Immunology Frontier Research Center)
Interleukin-17 Promotes Autoimmunity by Triggering a Positive-Feedback Loop via Interleukin-6 Induction
Immunity, 29, 628-636 (2008)

Okada, K.; Toyama, K.; Inoue, Y.; Isa, T.; Kobayashi, Y.
(Graduate School of Frontier Biosciences)
Different Pedunculopontine Tegmental Neurons Signal Predicted and Actual Task Rewards
The Journal of Neuroscience, 29, 4858-4870 (2009)

Reinforcement learning is accomplished by choosing behaviors expected to elicit the maximum reward and revising those predictions to minimize reward prediction error, the difference between predicted and actual reward signal. The most essential question of the learning mechanism, which neural structures provide the signals, remains elusive. We recorded neuronal activity of the brainstem in reward-seeking animals. Two different groups of these neurons selectively signal the predicted and actual reward, the necessary information for computation of reward prediction error.

Oshino, S.; Kato, A.; Hirata, M.; Kishima, H.; Saitoh, Y.; Fujinaka, T.; Yoshimine, T.
(Graduate School of Medicine)
Ipsilateral Motor-related Hyperactivity in Patients with Cerebral Occlusive Vascular Disease
Stroke, 39, 2769-2775 (2008)

Cortical oscillatory changes during unilateral hand movement was evaluated quantitatively using magnetoencephalography in patients with cerebral occlusive vascular disease. Although the patients showed no motor symptoms, abnormal ipsilateral hyperactivity was detected significantly in those with atherosclerotic lesion during the motor task with contra-lesional hand. This phenomenon, related to the higher age and severe morphological changes in magnetic resonance images, would reflect subclinical functional alteration accompanying cerebral ischemia due to atherosclerosis.

Saitoh, T. ^{*1, 2} ; Fujita, N. ^*2 ; Jang, M. H. ^*1 ; Uematsu, S. ^{*1, 2} ; Yang, B.-G. ^{*1, 2} ; Satoh, T. ^{*1, 2} ; Omori, H. ^*2 ; Noda, T. ^*2 ; Yamamoto, N.; Komatsu, M.; Tanaka, K.; Kawai, T. ^{*1, 2} ; Tsujimura, T.; Takeuchi, O. ^{*1, 2} ; Yoshimori, T. ^*2 ; Akira, S. ^{*1, 2}
^*1 (Immunology Frontier Research Center)
^*2 (Research Institute for Microbial Deseases)
Loss of the Autophagy Protein Atg16L1 Enhances Endotoxin-induced IL-1beta Production
Nature, 456(13), 264-269 (2008)

Takeda, Y. ^*1 ; He, P. ^*1 ; Tachibana, I. ^*1 ; Zhou, B. ^*1 ; Miyado, K. ^*2 ; Kaneko, H.; Suzuki, M. ^*1 ; Minami, S. ^*1 ; Iwasaki, T. ^*1 ; Goya, S. ^*1 ; Kijima, T. ^*1 ; Kumagai, T. ^*1 ; Yoshida, M. ^*1 ; Osaki, T. ^*1 ; Komori, T. ^*1 ; Mekada, E. ^*2 ; Kawase, I. ^*1
^*1 (Graduate School of Medicine)
^*2 (Research Institute for Microbial Deseases)
Double Deficiency of Tetraspanins CD9 and CD81 Alters Cell Motility and Protease Production of Macrophages and Causes Chronic Obstructive Pulmonary Disease-like Phenotype in Mice
The Journal of Biological Chemistry, 283(38), 26089-26097 (2008)

Chronic obstructive lung disease (COPD) is expected to be the third most common cause of death by 2020. Tetraspanins are membrane-spaning proteins that function as the organizers of membrane microdomains. CD9 and CD81, closely correlated tetraspanins, are down-regulated by smoking-related stimuli in macrophages and ablation of their function suppresses cell motility and increases the production of MMPs. Surprisingly, CD9/CD81 double-null mice spontaneously develops pulmonary emphysema and osteoporosis, a phenotype akin to human COPD. This mouse could be a new mouse model to provide some clues to clarify the pathogenesis of COPD.

Tanaka, H.; Kato, K.; Yamashita, E.; Sumizawa, T.; Zhou, Y.; Yao, M.; Iwasaki, K.; Yoshimura, M.; Tsukihara, T.
(Institute for Protein Research)
The Structure of Rat Liver Vault at 3.5 Angstrom Resolution
Science, 323, 384-388 (2009)

Vaults are among the largest cytoplasmic ribonucleoprotein particles and are found in numerous eukaryotic species. Although roles in multidrug resistance and innate immunity have been suggested, the cellular function remains unclear. We have determined the X-ray structure of rat liver vault at 3.5 Å resolution. A vault particle shell was composed of 78 MVP ( M ajor v ault p rotein) chains with 39-fold dihedral symmetry. The shoulder domain of MVP is structurally similar to SPFH ( s tomatin/ p rohibitin/ f lotillin/ H flK/C) domain involved in lipid raft association. These results will be breakthrough in the elucidation of vault function.

Tokunaga, F. ^*1 ; Sakata, S. ^*1 ; Saeki, Y.; Satomi, Y. ^*4 ; Kirisako, T.; Kamei, K. ^*1 ; Nakagawa, T. ^*1 ; Kato, M.; Murata, S.; Yamaoka, S.; Yamamoto, M. ^*1 ; Akira, S. ^*3 ; Takao, T. ^*4 ; Tanaka, K.; Iwai, K. ^{*1, 2}
^*1 (Graduate School of Medicine)
^*2 (Graduate School of Frontier Biosciences)
^*3 (Immunology Frontier Research Center)
^*4 (Institute for Protein Research)
Involvement of Linear Polyubiquitylation of NEMO in NF-κB Activation
Nature Cell Biology, 11(2), 123-132 (2009)

Tsuda, H. ^*1 ; Aoki, T.; Oku, N.; Kimura, Y.; Hatazawa, J. ^*2 ; Kinoshita, H. ^*2
^*1 (Graduate School of Human Sciences)
^*2 (Graduate School of Medicine)
Functional Brain Areas Associated with Manipulation of a Prehensile Tool: a PET Study
Human Brain Mapping, 2009 Jan 26. [Epub ahead of print]

Using PET, Brain areas representing the use of a well-learned tool (chopsticks) were investigated in 10 normal common users. The experimental task was to hold the tool in their right hand and use it to pick up and transport a small pin from a table. Data for the same task performed using only the fingers were also obtained as a control. The results showed an extensive overlap in activated areas with and without the use of the tool. The tool-use prehension, compared to the finger prehension, was associated with higher activities in the caudal-ventral premotor, dorsal premotor, superior parietal, posterior intraparietal, middle temporal gyrus, and primary sensory, occipital cortices and the cerebellum. These are thus considered to be the human cortical and subcortical substrates representing the use of the tool studied.

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Yamaguchi, M.; Terao, Y.; Mori, Y.; Hamada, S.; Kawabata, S.
(Graduate School of Dentistry)
PfbA, a Novel Plasmin- and Fibronectin-binding Protein of Streptococcus pneumoniae Contributes to Fibronectin-dependent Adhesion and Antiphagocytosis
The Journal of Biological Chemistry, 283(52), 36272-36279 (2008)

Streptococcus pneumoniae is a major pathogen of community-acquired pneumonia. We identified a novel fibronectin- and plasmin-binding protein on the pneumococcal surface and named PfbA. PfbA worked as an adhesin and occured the bacterial adhesion to and invasion of human epithelial cells. We also showed that PfbA contributed to anti-phagocytosis. These present findings suggest that PfbA is an important factor in the development of pneumococcal infections and might represent a new candidate for a pneumococcal vaccine.

Yamauchi, K. ^*1 ; Mizushima, S. ^*1 ; Tamada, A.; Yamamoto, N. ^*1 ; Takashima, S. ^*2 ; Murakami, F. ^*1
^*1 (Graduate School of Frontier Biosciences)
^*2 (Graduate School of Medicine)
FGF8 Signaling Regulates Growth of Midbrain Dopaminergic Axons by Inducing Semaphorin 3F
The Journal of Neuroscience, 29(13), 4044-4055 (2009)

A fundamental question in neural development is how the polarized growth of axons is achieved. In this report, we demonstrated that FGF8, a molecule known as a patterning molecule and expressed at the midbrain-hindbrain boundary signaling center regulates the rostrocaudal growth polarity of midbrain dopaminergic axons by inducing an axon guidance molecule, sema3F. Our study demonstrates that the rostrocaudal growth polarities of axons are controlled by activities of signaling centers.

Yokota, T.; Oritani, K.; Butz, S.; Kokame, K.; Kincade, P. W.; Miyata, T.; Vestweber, D.; Kanakura, Y.
(Graduate School of Medicine)
The Endothelial Antigen ESAM Marks Primitive Hematopoietic Progenitors throughout Life in Mice
Blood, 113(13), 2914-2923 (2009)

We defined endothelial cell-selective adhesion molecule (ESAM) as a novel marker of murine hematopoietic stem cells (HSC). High levels of ESAM expression could be used as means to isolate long-term reconstituting HSC in the fetal liver. Developing HSC in earlier embryos also expressed high levels of ESAM. Furthermore, ESAM expression in adult bone marrow was detected on primitive progenitors within the HSC-enriched fraction. Our findings will likely benefit both basic studies for hematopoiesis and efficient HSC-based therapies including regenerative medicine.

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