Responses of Plasma Acetate Metabolism to Hop (Humulus lupulus L.) in Sheep

An isotope dilution method using [1-13C]sodium (Na) acetate was conducted to determine the effect of feeding hop (Humulus lupulus L.) residues on plasma acetate metabolism in six adult crossbred sheep. The sheep were fed 63 g/kg BW0.75/d of either mixed hay (MH-diet) of orchardgrass (Dactylis glomerata L.) and reed canarygrass (Phalaris arundinacea L.) at a 60:40 ratio or MH-diet and hop-residues (Hop-diet) at 85:15 ratio with a crossover design for each of 3 week period. The isotope dilution method using single injection of [1-13C]Na acetate was performed thrice; before feeding (BF), 2 h after feeding (2F) and 4 h after feeding (4F), on the 21st day of each dietary treatment. Plasma acetate concentration tended to increase (P= 0.06) and turnover rate was numerically higher (P= 0.16) for MH-diet than Hop-diet. Plasma glucose, NEFA, VFA and lactic acid concentrations were similar between dietary treatments. In both the diets, although plasma concentration of acetate did not change, turnover rate increased significantly (P= 0.02) 2F than BF. Hop-residues did not show any negative impacts on acetate metabolism as well as physiology of animals in the present experimental conditions, hence thereby it could be used as an alternative to MH-diet for rearing sheep

Aging effect on microstructure of cold groove-rolled α′-type Ti-12 mass%V-2 mass%Al alloys studied by transmission electron microscopy

Microstructure and phase decomposition of hexagonal α′ martensite in cold groove rolled (CGR) Ti-12 mass% V-2 mass% Al alloys have been studied by transmission electron microscopy and electron diffraction. Acicular structure of the α′ martensite changes into equiaxed α′ grains by CGR with a cold reduction of 75%. After aging at 573K for 500 h, local Moiré fringes disappear and diffraction rings become sharp due to recovery. However, Vickers hardness also increased in spite of the recovery. Partitioning of solute atoms and/or formation of fine precipitates can be possible cause for the observed age-hardening. Although a CGR alloy is characterized by a microstructure with polycrystalline equiaxed grains, following orientation relationship is locally observed between β precipitates and α grains after aging at 673 K: (101)β // (011̄1̄)α, [010]β // (101̄1)α. Electron tomography revealed a heterogeneous nucleation and growth of β precipitates in the deformed α′ matrix. © 2014 The Japan Institute of Metals and Materials

Pigment-dispersing activities and cortisol-releasing activities of melanocortins and their receptors in xanthophores and head kidneys of the goldfish Carassius auratus

The five subtypes of melanocortin receptors (MCRs) mediate the functions of α-melanocyte-stimulating hormone (α-MSH) and adrenocorticotropic hormone (ACTH). In fish, these hormones are involved in pigment dispersion and cortisol release, respectively. α-MSH-related peptides exhibit ACTH-like activity in certain fishes. We recently found that multiple Mcr transcripts are expressed in some cell types in the barfin flounder, which is related to regulation of α-MSH activities. Similar results were also observed for the cortisol-releasing activity of α-MSH-related peptides in the head kidney. The present study was undertaken to assess relationship between the expression of multiply expressed Mcrs and α-MSH activities using goldfish. We also determined if α-MSH-related peptides exhibit ACTH-like activity in goldfish. The transcripts of Mc1r, but not those of other subtypes, were observed in xanthophores. α-MSH, which has an acetyl group at the N-terminus, was found to disperse pigment in a dose-dependent manner in xanthophores. This potency was found to be slightly greater than that of desacetyl-α-MSH. These results support our findings that MCR has a higher affinity for α-MSH when single Mcr subtype is expressed. On the other hand, transcripts of Mc2r, but not those of other subtypes, were observed in the head kidney. ACTH1-24-stimulated cortisol release was observed in a dose-dependent manner, while α-MSH-related peptides showed no activity. It therefore appears that MC2R also acts as an ACTH-specific receptor in goldfish and that association of α-MSH-related peptides upon release of cortisol is uncommon in fishes. © 2011 Elsevier Inc.Peer Reviewe

Membrane-Type 1 Matrix Metalloproteinase Cleaves Cd44 and Promotes Cell Migration

Migratory cells including invasive tumor cells frequently express CD44, a major receptor for hyaluronan and membrane-type 1 matrix metalloproteinase (MT1-MMP) that degrades extracellular matrix at the pericellular region. In this study, we demonstrate that MT1-MMP acts as a processing enzyme for CD44H, releasing it into the medium as a soluble 70-kD fragment. Furthermore, this processing event stimulates cell motility; however, expression of either CD44H or MT1-MMP alone did not stimulate cell motility. Coexpression of MT1-MMP and mutant CD44H lacking the MT1-MMP–processing site did not result in shedding and did not promote cell migration, suggesting that the processing of CD44H by MT1-MMP is critical in the migratory stimulation. Moreover, expression of the mutant CD44H inhibited the cell migration promoted by CD44H and MT1-MMP in a dominant-negative manner. The pancreatic tumor cell line, MIA PaCa-2, was found to shed the 70-kD CD44H fragment in a MT1-MMP–dependent manner. Expression of the mutant CD44H in the cells as well as MMP inhibitor treatment effectively inhibited the migration, suggesting that MIA PaCa-2 cells indeed use the CD44H and MT1-MMP as migratory devices. These findings revealed a novel interaction of the two molecules that have each been implicated in tumor cell migration and invasion

Effect of CYP3A5*3 genetic variant on the metabolism of direct-acting antivirals in vitro : a different effect on asunaprevir versus daclatasvir and beclabuvir

Direct-acting antivirals, asunaprevir (ASV), daclatasvir (DCV), and beclabuvir (BCV) are known to be mainly metabolized by CYP3A enzymes; however, the differences in the detailed metabolic activities of CYP3A4 and CYP3A5 on these drugs are not well clarified. The aim of the present study was to elucidate the relative contributions of CYP3A4 and CYP3A5 to the metabolism of ASV, DCV, and BCV, as well as the effect of CYP3A5*3 genetic variant in vitro. The amount of each drug and their major metabolites were determined using LC-MS/MS. Recombinant CYP3As and CYP3A5*3-genotyped human liver microsomes (CYP3A5 expressers or non-expressers) were used for the determination of their metabolic activities. The contribution of CYP3A5 to ASV metabolism was considerable compared to that of CYP3A4. Consistently, ASV metabolic activity in CYP3A5 expressers was higher than those in CYP3A5 non-expresser. Moreover, CYP3A5 expression level was significantly correlated with ASV metabolism. In contrast, these observations were not found in DCV and BCV metabolism. To our knowledge, this is the first study to directly demonstrate the effect of CYP3A5*3 genetic variants on the metabolism of ASV. The findings of the present study may provide basic information on ASV, DCV, and BCV metabolisms

Extragalactic Science, Cosmology and Galactic Archaeology with the Subaru Prime Focus Spectrograph (PFS)

The Subaru Prime Focus Spectrograph (PFS) is a massively-multiplexed fiber-fed optical and near-infrared 3-arm spectrograph (N_fiber=2400, 380<lambda<1260nm, 1.3 degree diameter FoV), offering unique opportunities in survey astronomy. Here we summarize the science case feasible for a survey of Subaru 300 nights. We describe plans to constrain the nature of dark energy via a survey of emission line galaxies spanning a comoving volume of 9.3 (Gpc/h)^3 in the redshift range 0.8<z<2.4. In each of 6 redshift bins, the cosmological distances will be measured to 3% precision via BAO, and redshift-space distortions will be used to constrain structure growth to 6% precision. In the GA program, radial velocities and chemical abundances of stars in the Milky Way and M31 will be used to infer the past assembly histories of spiral galaxies and the structure of their dark matter halos. Data will be secured for 10^6 stars in the Galactic thick-disk, halo and tidal streams as faint as V~22, including stars with V < 20 to complement the goals of the Gaia mission. A medium-resolution mode with R = 5000 to be implemented in the red arm will allow the measurement of multiple alpha-element abundances and more precise velocities for Galactic stars, elucidating the detailed chemo-dynamical structure and evolution of each of the main stellar components of the Milky Way Galaxy and of its dwarf spheroidal galaxies. For the extragalactic program, our simulations suggest the wide avelength range will be powerful in probing the galaxy population and its clustering over a wide redshift range. We propose to conduct a color-selected survey of 1<z<2 galaxies and AGN over 16 deg^2 to J~23.4, yielding a fair sample of galaxies with stellar masses above ~10^{10}Ms at z~2. A two-tiered survey of higher redshift LBGs and LAEs will quantify the properties of early systems close to the reionization epoch.Comment: This document describes the scientific program and requirements for the Subaru Prime Focus Spectrograph (PFS) project. Made significant revision based on studies for the Preliminary Design Review (PRD) held in Feb 2013. The higher-resolution paper file is available from http://member.ipmu.jp/masahiro.takada/pfs_astroph_rv.pd