クラスリン被覆小孔の構成分子との会合がμオピオイド受容体下流のβアレスチンを介したMAPK経路のシグナル伝達を制御する

京都大学新制・課程博士博士(医学)甲第24525号医博第4967号新制||医||1065(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 渡邊 直樹, 教授 中川 一路, 教授 秋山 芳展学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Minimum Supersymmetric Standard Model on the Noncommutative Geometry

We have obtained the supersymmetric extension of spectral triple which specify a noncommutative geometry(NCG). We assume that the functional space H constitutes of wave functions of matter fields and their superpartners included in the minimum supersymmetric standard model(MSSM). We introduce the internal fluctuations to the Dirac operator on the manifold as well as on the finite space by elements of the algebra A in the triple. So, we obtain not only the vector supermultiplets which meditate SU(3)xSU(2)xU(1)_Y gauge degrees of freedom but also Higgs supermultiplets which appear in MSSM on the same standpoint. Accoding to the supersymmetric version of the spectral action principle, we calculate the square of the fluctuated total Dirac operator and verify that the Seeley-DeWitt coeffients give the correct action of MSSM. We also verify that the relation between coupling constants of $SU(3)$,$SU(2)$ and $U(1)_Y$ is same as that of SU(5) unification theory

Supersymmetric Yang-Mills Theory on the Noncommutative Geometry

Recently, we found the supersymmetric counterpart of the spectral triple. When we restrict the representation space to the fermionic functions of matter fields, the counterpart which we name "the triple" reduces to the original spectral triple which defines noncommutative geometry. We see that the fluctuation to the supersymmetric Dirac operator induced by algebra in the triple generates vector supermultiplet which mediates gauge interaction. Following the supersymmetric version of spectral action principle, we calculate the heat kernel expansion of the square of fluctuated Dirac operator and obtain the correct supersymmetric Yang-Mills action with U(N) gauge symmetry.Comment: arXiv admin note: text overlap with arXiv:1201.344

Retinal Angiomatous Proliferation in an Eye with Cuticular Drusen

Purpose: To report the presence of retinal angiomatous proliferation (RAP) in an eye with cuticular drusen detected by fluorescein and indocyanine green angiography by confocal scanning laser ophthalmoscopy and by spectral-domain optical coherence tomography (SD-OCT). Methods: Case report of a 65-year-old Japanese woman with cuticular drusen. Results: At her first ophthalmic examination, her visual acuity was 20/20 in both eyes. An ophthal-moscopy showed many small subretinal pigment epithelial deposits in both eyes. These de-posits had a ‘saw-tooth pattern’ in the SD-OCT images. During the follow-up examination, retinal hemorrhages were observed, and fluorescein angiography showed a ‘stars-in-the-sky’ appearance and intraretinal neovascularization. The patient was diagnosed with cuticular drusen associated with RAP. Conclusion: We suggest that the cuticular drusen were associ-ated with RAP, so periodic follow-up examinations are needed for patients with cuticular drusen for the early detection and treatment of RAP

Displacement of fovea toward optic disk after macular hole surgery with internal limiting membrane peeling

PURPOSE:The purpose of this study was to demonstrate a displacement of the foveal depression toward the optic disk after idiopathic macular hole (MH) surgery with internal limiting membrane (ILM) peeling.METHODS:Two patients with a unilateral MH developed an MH in the fellow eyes. Vitrectomy with ILM peeling was performed on the fellow eye to close the MH. Images of spectral-domain optical coherence tomography (SD-OCT) were used to measure the disk-to-fovea distances pre MH formation, after MH formation, and 6 months after the closure of the MH.RESULTS:The disk-to-fovea　distance was shorter at 6 months than after the development of the MH (4,109 µm and 4,174 µm in Case 1 and 4,001 µm and 4,051 µm in Case 2).CONCLUSION:These results indicate that the fovea moves nasally after the MH surgery with ILM peeling

Transient Increase of Retinal Nerve Fiber Layer Thickness after Vitrectomy with ILM Peeling for Idiopathic Macular Hole

Purpose. The purpose of this study was to determine the long-term changes in the circumpapillary retinal nerve fiber layer (RNFL) thickness following macular hole surgery with internal limiting membrane (ILM) peeling combined with phacoemulsification. Methods. Thirty-eight eyes of 37 patients who had pars plana vitrectomy (n = 36) between 2010 and 2014 were studied. The average thicknesses of the global and the six sectors of the RNFL were determined before and at 1, 3, 6, 12, and 24 (n = 22) months (M) after the surgery by spectral-domain optical coherent tomography. The postoperative mean RNFL thickness at each time was compared to that before the surgery by paired t-tests. Results. The RNFL of the operated eyes was significantly thicker at 1 month (1 M) and 3 M in all but the inferior-nasal sectors. The significant increase remained until 12 M in the superior-temporal and superior-nasal sectors. In addition, the RNFL was also significantly thicker in the temporal-inferior sector at 12 M based on the findings in 38 eyes. Conclusions. The postoperative RNFL was thicker in all but the nasal-inferior sector for at least 12 M after surgery. This prolonged increase of the RNFL thickness may indicate damage and mild edema of the RNFL

Neuregulin 1 Type II-ErbB Signaling Promotes Cell Divisions Generating Neurons from Neural Progenitor Cells in the Developing Zebrafish Brain.

Post-mitotic neurons are generated from neural progenitor cells (NPCs) at the expense of their proliferation. Molecular and cellular mechanisms that regulate neuron production temporally and spatially should impact on the size and shape of the brain. While transcription factors such as neurogenin1 (neurog1) and neurod govern progression of neurogenesis as cell-intrinsic mechanisms, recent studies show regulatory roles of several cell-extrinsic or intercellular signaling molecules including Notch, FGF and Wnt in production of neurons/neural progenitor cells from neural stem cells/radial glial cells (NSCs/RGCs) in the ventricular zone (VZ). However, it remains elusive how production of post-mitotic neurons from neural progenitor cells is regulated in the sub-ventricular zone (SVZ). Here we show that newborn neurons accumulate in the basal-to-apical direction in the optic tectum (OT) of zebrafish embryos. While neural progenitor cells are amplified by mitoses in the apical ventricular zone, neurons are exclusively produced through mitoses of neural progenitor cells in the sub-basal zone, later in the sub-ventricular zone, and accumulate apically onto older neurons. This neurogenesis depends on Neuregulin 1 type II (NRG1-II)-ErbB signaling. Treatment with an ErbB inhibitor, AG1478 impairs mitoses in the sub-ventricular zone of the optic tectum. Removal of AG1478 resumes sub-ventricular mitoses without precedent mitoses in the apical ventricular zone prior to basal-to-apical accumulation of neurons, suggesting critical roles of ErbB signaling in mitoses for post-mitotic neuron production. Knockdown of NRG1-II impairs both mitoses in the sub-basal/sub-ventricular zone and the ventricular zone. Injection of soluble human NRG1 into the developing brain ameliorates neurogenesis of NRG1-II-knockdown embryos, suggesting a conserved role of NRG1 as a cell-extrinsic signal. From these results, we propose that NRG1-ErbB signaling stimulates cell divisions generating neurons from neural progenitor cells in the developing vertebrate brain