Granular C3 Dermatosis

There has been no previous systematic study of bullous skin diseases with granular basement membrane zone deposition exclusively of C3. In this study we collected 20 such patients, none of whom showed cutaneous vasculitis histopathologically. Oral dapsone and topical steroids were effective. Various serological tests detected no autoantibodies or autoantigens. Direct immunofluorescence for various complement components revealed deposition only of C3 and C5?C9, indicating that no known complement pathways were involved. Studies of in situ hybridization and micro-dissection with quantitative RT-PCR revealed a slight reduction in expression of C3 in patient epidermis. These patients may represent a new disease entity, for which we propose the term “granular C3 dermatosis”. The mechanism for granular C3 deposition in these patients is unknown, but it is possible that the condition is caused by autoantibodies to skin or aberrant C3 expression in epidermal keratinocytes

Conservation and lineage-specific rearrangements in the GOBP/PBP gene complex of distantly related ditrysian Lepidoptera.

General odorant binding proteins (GOBPs) and pheromone binding proteins (PBPs) form a monophyletic subfamily of insect odorant binding proteins (OBPs) specific for Lepidoptera, butterflies and moths. The GOBP/PBP genes include six subgroups (GOBP1-2, PBP-A-D) previously reported to form a complex arrayed in a conserved order in representative moths (superfamily Bombycoidea) and butterflies (Nymphalidae). Although our knowledge of lepidopteran genomes has increased greatly recently, the structure of the GOBP/PBP complex has been studied only for species that represent limited lineages of the highly diverged Ditrysia. To understand the evolution of this functionally important gene complex, we determined 69-149 kb genomic sequences that include GOBP2 and five PBP genes in three Ostrinia moths (Pyraloidea), O. nubilalis, O. furnacalis, and O. latipennis, using bacterial artificial chromosome (BAC) and fosmid clones. The structure of the GOBP2/PBP gene cluster was well conserved despite the different sex pheromone composition utilized by the three moths. Five expressed PBP genes in Ostrinia moths were the result of two duplications of PBP-A genes. Surprisingly, an allele containing a fusion gene between tandemly arrayed PBP-A genes was observed in O. nubilalis. We also revealed duplication and intra-chromosomal translocation of the GOBP1 gene in P. xylostella by fluorescence in situ hybridization (FISH) analysis. Additionally, we compared the structure of the GOBP/PBP gene complex of seventeen species covering six superfamilies and twelve families of the lepidopteran clade, Ditrysia, and found the gene order was basically conserved despite the frequent occurrence of lineage-specific gains, losses, inversions and translocations of these genes, compared with their neighboring genes. Our findings support the hypothesis that the structure of the GOBP/PBP gene complex was already established in the common ancestor of Ditrysia

Diurnal expression of MRP4 in bone marrow cells underlies the dosing-time dependent changes in the oxaliplatin-induced myelotoxicity

Abstract The expression and function of some xenobiotic transporters varies according to the time of day, causing the dosing time-dependent changes in drug disposition and toxicity. Multidrug resistance-associated protein-4 (MRP4), an ATP­binding cassette (ABC) efflux transporter encoded by the Abcc4 gene, is highly expressed in bone marrow cells (BMCs) and protects them against xenobiotics, including chemotherapeutic drugs. In this study, we demonstrated that MRP4 was responsible for the extrusion of oxaliplatin (L-OHP), a platinum (Pt)-based chemotherapeutic drug, from BMCs of mice, and that the efflux transporter expression exhibited significant diurnal variation. Therefore, we investigated the relevance of the diurnal expression of MRP4 in BMCs for L-OHP-induced myelotoxicity in mice maintained under standardized light/dark cycle conditions. After intravenous injection of L-OHP, the Pt content in BMCs varied according to the injection time. Lower Pt accumulation in BMCs was detected in mice after injection of L-OHP at the mid-dark phase, during which the expression levels of MRP4 increased. Consistent with these observations, the myelotoxic effects of L-OHP were attenuated when mice were injected with L-OHP during the dark phase. This dosing schedule also alleviated the L-OHP-induced reduction of the peripheral white blood cell count. The present results suggest that the myelotoxicity of L-OHP is attenuated by optimizing the dosing schedule. Diurnal expression of MRP4 in BMCs is associated with the dosing time-dependent changes in L-OHP-induced myelotoxicity

Expression inferred from RPKMs of conserved genes and CDSs of the PBP/GOBP complex in <i>O</i>. <i>furnacalis</i> adult antennae.

<p>Expression inferred from RPKMs of conserved genes and CDSs of the PBP/GOBP complex in <i>O</i>. <i>furnacalis</i> adult antennae.</p

Comparison of the <i>OnubPBP2</i> (solid squares) and <i>OnubPBP3</i> (open squares) gene structures between the two BAC clones, 25F18 and 28N16.

<p>Arrows represent locations of primer pairs used to analyze the gene fusion.</p

Phylogenetic relationships among GOBP/PBP genes of crambid and non- crambid species.

<p>Arcs represent six clades of GOBP/PBP genes; the color-code is the same as <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0192762#pone.0192762.g004" target="_blank">Fig 4</a>. Shaded circles represent clusters comprising crambid PBP-A genes exclusively. Numbers near nodes show bootstrap values. Amino acid sequences used for phylogenetic analysis are listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0192762#pone.0192762.s010" target="_blank">S1 File</a>. Alignments are shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0192762#pone.0192762.s011" target="_blank">S2 File</a>. Abbreviations of crambid species names (in magenta): Csup, <i>Chilo suppressalis</i>; Cmed, <i>C</i>. <i>medinalis</i>; Dind, <i>D</i>. <i>indica</i>; Ofur, <i>O</i>. <i>furnacalis</i>; Olat, <i>O</i>. <i>latipennis</i>; Onub, <i>O</i>. <i>nubilalis</i>; butterfly species names (in blue): Bany, <i>B</i>. <i>anynana</i>; Ccec, <i>C</i>. <i>cecrops</i>; Dple, <i>D</i>. <i>plexippus</i>; Lacc, <i>L</i>. <i>accius</i>; Psen, <i>Phoebis sennae</i>; Pxut, <i>Papilio xuthus</i>; Pyralidae species names (in orange) Atra, <i>A</i>. <i>transitella</i>; Pint, <i>P</i>. <i>interpunctella</i>; Bombycoidea species names (in green): Bmor, <i>B</i>. <i>mori</i>; Msex, <i>M</i>. <i>sexta</i>; other moth species (in black): Obru, <i>O</i>. <i>brumata</i>; Pxyl, <i>P</i>. <i>xylostella</i>; Slit, <i>S</i>. <i>littoralis</i>.</p

Schematic representation of the order and transcriptional orientation of CDSs located within and sourrrounding the GOBP/PBP complex of seventeen lepidopteran species.

<p>Arrowheads represent CDSs for which transcriptional orientation is identified. Squares represent CDSs for which transcriptional orientation is not identified. Closed arrowheads and squares represent lineage-specific gains or inversions. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0192762#pone.0192762.s008" target="_blank">S3 Table</a> for details. brown, GOBP1; green, GOBP2; magenta, PBP-A; blue, PBP-B; orange, PBP-C; purple, PBP-D.</p

BAC-FISH mapping of two <i>P</i>. <i>xylostella GOBP1</i> genes.

<p>Signals on <i>P</i>. <i>xylostella</i> chromosome 19 are pseudocolored and probe names are shown to the right of the FISH images (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0192762#pone.0192762.s009" target="_blank">S4 Table</a> for details). Left-side bars represent syntenic <i>B</i>. <i>mori</i> chromosome 19. Locations of <i>B</i>. <i>mori</i> orthologs are adopted from Kaikobase. Scale bar, 2.5 μm.</p