Hokkaido University

About: Hokkaido University is a education organization based out in Sapporo, Hokkaidô, Japan. It is known for research contribution in the topics: Population & Catalysis. The organization has 53925 authors who have published 115403 publications receiving 2651647 citations. The organization is also known as: Hokudai & Hokkaidō daigaku.

ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid synthesis

Abstract: Very long-chain fatty acids (VLCFAs) exert a variety of cellular functions and are associated with numerous diseases. However, the precise pathway behind their elongation has remained elusive. Moreover, few regulatory mechanisms for VLCFAs synthesis have been identified. Elongases catalyze the first of four steps in the VLCFA elongation cycle; mammals have seven elongases (ELOVL1–7). In the present study, we determined the precise substrate specificities of all the ELOVLs by in vitro analyses. Particularly notable was the high activity exhibited by ELOVL1 toward saturated and monounsaturated C20- and C22-CoAs, and that it was essential for the production of C24 sphingolipids, which are unique in their capacity to interdigitate within the membrane as a result of their long chain length. We further established that ELOVL1 activity is regulated with the ceramide synthase CERS2, an enzyme essential for C24 sphingolipid synthesis. This regulation may ensure that the production of C24-CoA by elongation is coordinated with its utilization. Finally, knockdown of ELOVL1 caused a reduction in the activity of the Src kinase LYN, confirming that C24-sphingolipids are particularly important in membrane microdomain function.

Firefly bioluminescence quantum yield and colour change by pH-sensitive green emission

Abstract: Firefly bioluminescence1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19 is the most well-known ideal photo-emitter system in biophotonics, known in particular for its extremely high quantum yield, 88 ± 25% (refs 2,3) or higher4,5,6, and its magnificent pH-dependent emission-colour change3,7 between yellow-green and red, modelled as the chemical equilibrium between two corresponding states8,9,10,11,12,13,14 However, the need for re-examination has also been discussed4,5,6 In this letter we quantify quantum yields and colour changes using our new total-photon-flux spectrometer20,21 We determine the highest quantum yield to be 410 ± 74% (1 standard deviation (sd) estimate, coverage factor k = 1), and find that bioluminescence spectra are systematically decomposed into one pH-sensitive and two pH-insensitive gaussian components There is no intensity conversion between yellow-green and red emissions through pH equilibrium, but simple intensity variation of the pH-sensitive gaussian peak at 22 eV causes the changes in emission colours This represents a paradigm shift in the concept of colour determination from long-standing interpretation based on pH equilibrium

A genome-wide screen identifies a single β-defensin gene cluster in the chicken: implications for the origin and evolution of mammalian defensins

Abstract: Defensins comprise a large family of cationic antimicrobial peptides that are characterized by the presence of a conserved cysteine-rich defensin motif. Based on the spacing pattern of cysteines, these defensins are broadly divided into five groups, namely plant, invertebrate, α-, β-, and θ-defensins, with the last three groups being mostly found in mammalian species. However, the evolutionary relationships among these five groups of defensins remain controversial. Following a comprehensive screen, here we report that the chicken genome encodes a total of 13 different β-defensins but with no other groups of defensins being discovered. These chicken β-defensin genes, designated as Gallinacin 1–13, are clustered densely within a 86-Kb distance on the chromosome 3q3.5-q3.7. The deduced peptides vary from 63 to 104 amino acid residues in length sharing the characteristic defensin motif. Based on the tissue expression pattern, 13 β-defensin genes can be divided into two subgroups with Gallinacin 1–7 being predominantly expressed in bone marrow and the respiratory tract and the remaining genes being restricted to liver and the urogenital tract. Comparative analysis of the defensin clusters among chicken, mouse, and human suggested that vertebrate defensins have evolved from a single β-defensin-like gene, which has undergone rapid duplication, diversification, and translocation in various vertebrate lineages during evolution. We conclude that the chicken genome encodes only β-defensin sequences and that all mammalian defensins are evolved from a common β-defensin-like ancestor. The α-defensins arose from β-defensins by gene duplication, which may have occurred after the divergence of mammals from other vertebrates, and θ-defensins have arisen from α-defensins specific to the primate lineage. Further analysis of these defensins in different vertebrate lineages will shed light on the mechanisms of host defense and evolution of innate immunity.

Endothelial cells as target for antiphospholipid antibodies : Human polyclonal and monoclonal anti-β2-glycoprotein I antibodies react in vitro with endothelial cells through adherent β2-glycoprotein I and induce endothelial activation

Abstract: Objective To investigate the ability of human anti-beta 2-glycoprotein I (anti-beta 2 GPI) antibodies to recognize the cofactor adherent on endothelial cells (EC) and to modulate endothelial functions. Methods Six human affinity-purified polyclonal anti-beta 2 GPI IgG and 2 IgM monoclonal antibodies (MAb) were obtained from patients with the antiphospholipid syndrome. The antibodies were tested for their ability to 1) bind to endothelial monolayers through the adherent beta 2 GPI and 2) modulate endothelial adhesion molecule expression and interleukin-6 (IL-6) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) secretion. Results The affinity-purified IgG and the MAb with anti-beta 2 GPI activity, but not the respective controls, displayed EC binding, which declined on cells incubated in serum-free medium and was restored in a dose-dependent manner by exogenous human beta 2 GPI. After EC binding, both polyclonal and monoclonal antibodies up-regulated adhesion molecule expression. Anti-beta 2 GPI MAb also significantly increased IL-6 and 6-keto-PGF1 alpha secretion. Conclusion These findings support the hypothesis that anti-beta 2 GPI antibodies bind and activate EC through the adherent cofactor beta 2 GPI, likely leading to a procoagulant state.