Large θ13ν\theta_{13}^\nu and Unified Description of Quark and Lepton Mixing Matrices

We present a revised version of the so-called "yukawaon model", which was proposed for the purpose of a unified description of the lepton mixing matrix $U_{PMNS}$ and the quark mixing matrix $V_{CKM}$. It is assumed from a phenomenological point of view that the neutrino Dirac mass matrix $M_D$ is given with a somewhat different structure from the charged lepton mass matrix $M_e$, although $M_D=M_e$ was assumed in the previous model. As a result, the revised model predicts a reasonable value $\sin^2 2\theta_{13} \sim 0.07$ with keeping successful results for other parameters in $U_{PMNS}$ as well as $V_{CKM}$ and quark and lepton mass ratios.Comment: 13 pages, 3 figures, version accepted by EPJ

Abnormal Structure of Fermion Mixings in a Seesaw Quark Mass Matrix Model

It is pointed out that in a seesaw quark mass matrix model which yields a singular enhancement of the top-quark mass, the right-handed fermion-mixing matrix U_R^u for the up-quark sector has a peculiar structure in contrast to the left-handed one U_L^u. As an example of the explicit structures of U_L^u and U_R^u, a case in which the heavy fermion mass matrix M_F is given by a form [(unit matrix)+(rank-one matrix)] is investigated. As a consequence, one finds observable signatures at projected high energy accelerators like the production of a fourth heavy quark family.Comment: 17 pages (Latex

Neutrino Masses and Mixings in a Universal Seesaw Mass Matrix Model

Neutrino masses and mixings are investigated on the basis of a universal seesaw mass matrix model, in which quark (except for top) and charged lepton mass matrices M_f and neutrino mass matrix M_\nu are given by M_f \simeq m_L M_F^{-1} m_R and M_\nu \simeq m_L M_F^{-1} m_L^T (F=N), respectively. For a simple model which can successfully describe quark masses and mixings, we find that the observed neutrino data (except for the solar neutrino data) are favor to the intermediate mass scales O(m_R) = 10^{11} GeV and O(M_F)= 10^{13} GeV together with O(m_L)= 10^2 GeV. In spite of the largesse of O(m_R), the observed top quark mass can be consistently understood from the would-be seesaw mass matrix with these mass scales.Comment: 19 pages (Latex file

Coupling Constants Evolution in a Universal Seesaw Mass Matrix Model

Stimulated by a universal seesaw mass matrix model which can successfully give quark masses and CKM matrix elements in terms of charged lepton masses, the evolution of the seesaw mass matrices is investigated. Especially, an investigation is made as to whether the evolution can constrain the necessary intermediate scales in these types of models and its viability.Comment: LaTex, 21 pages, 3 Postscript figures. Title was change

Elimination of Hepatitis C Virus from Hepatocytes by a Selective Activation of Therapeutic Molecules

To eliminate hepatitis C virus (HCV) from infected hepatocytes, we generated two therapeutic molecules specifically activated in cells infected with HCV. A dominant active mutant of interferon (IFN) regulatory factor 7 (IRF7) and a negative regulator of HCV replication, VAP-C (Vesicle-associated membrane protein-associated protein subtype C), were fused with the C-terminal region of IPS-1 (IFNβ promoter stimulator-1), which includes an HCV protease cleavage site that was modified to be localized on the ER membrane, and designated cIRF7 and cVAP-C, respectively. In cells expressing the HCV protease, cIRF7 was cleaved and the processed fragment was migrated into the nucleus, where it activated various IFN promoters, including promoters of IFNα6, IFNβ, and IFN stimulated response element. Activation of the IFN promoters and suppression of viral RNA replication were observed in the HCV replicon cells and in cells infected with the JFH1 strain of HCV (HCVcc) by expression of cIRF7. Suppression of viral RNA replication was observed even in the IFN-resistant replicon cells by the expression of cIRF7. Expression of the cVAP-C also resulted in suppression of HCV replication in both the replicon and HCVcc infected cells. These results suggest that delivery of the therapeutic molecules into the liver of hepatitis C patients, followed by selective activation of the molecules in HCV-infected hepatocytes, is a feasible method for eliminating HCV

Production and degradation of extracellular matrix in reversible glomerular lesions in rat model of habu snake venom-induced glomerulonephritis

We investigated the mechanism of development and repair process of glomerular injury in a rat model of habu snake (Trimeresurus flavoviridis) venom (HSV)-induced glomerulonephritis. Glomerulonephritis was induced in rats by intravenously injecting HSV at 3 mg/kg. Renal tissue was isolated and subjected to immunohistochemical analysis for expression levels of type IV collagen, heat shock protein 47 (HSP47), transforming growth factor-β (TGF-β), and matrix metalloproteinase-3 (MMP-3), as well as its transcription factor Ets-1. Expression levels of HSP47, TGF-β, and type IV collagen began to increase in the mesangial area starting from day 14 and peaked on day 21, followed by a gradual decrease. Expression levels of MMP-3 and Ets-1 started to increase coinciding with peak production of mesangial matrix on day 21, peaking on day 35, followed by gradual decrease. Expression of MMP-3 and Ets-1 persisted until day 63, whereas that of HSP47 and type IV collagen returned to baseline level at this time point. Time-course changes of extracellular matrix (ECM) accumulation in glomeruli in the HSV-induced glomerulonephritis model were correlated with those of factors involved in both ECM production and degradation systems. Continued expression of factors in the degradation system seems particularly important for the repair process. These findings might lead to new therapies that prevent and repair glomerular injury

Targeting of alpha(v) integrin identifies a core molecular pathway that regulates fibrosis in several organs

Myofibroblasts are the major source of extracellular matrix components that accumulate during tissue fibrosis, and hepatic stellate cells (HSCs) are the major source of myofibroblasts in the liver. To date, robust systems to genetically manipulate these cells have not existed. We report that Pdgfrb-Cre inactivates genes in murine HSCs with high efficiency. We used this system to delete the αv integrin subunit because of the suggested role of multiple αv integrins as central mediators of fibrosis in multiple organs. Depletion of the αv integrin subunit in HSCs protected mice from CCl(4)-induced hepatic fibrosis, whereas global loss of αvβ3, αvβ5 or αvβ6 or conditional loss of αvβ8 on HSCs did not. Pdgfrb-Cre effectively targeted myofibroblasts in multiple organs, and depletion of αv integrins using this system was also protective in models of pulmonary and renal fibrosis. Critically, pharmacological blockade of αv integrins by a novel small molecule (CWHM 12) attenuated both liver and lung fibrosis, even when administered after fibrosis was established. These data identify a core pathway that regulates fibrosis, and suggest that pharmacological targeting of all αv integrins may have clinical utility in the treatment of patients with a broad range of fibrotic diseases