Lack of association of ABCB4 insertion mutation with gallbladder mucoceles in dogs

The etiology of canine gallbladder mucocele (GBM) has not yet been identified. However, several studies have linked GBM in dogs to particular breeds (Shetland Sheepdogs are commonly implicated), concurrent endocrine disease (hyperadrenocorticism and/or hypothyroidism), and a mutation in the canine ABCB4 gene (ABCB4 1583_1584G), particularly in Shetland Sheepdogs. The current study assessed ABCB4 1583_1584G, in a wider sample of dogs with GBM compared with age and breed-matched controls. ABCB4 1583_1584G was identified in 4 of 8 Shetland Sheepdogs and 13 of 28 other breeds with GBM. ABCB4 1583_1584G was also detected in 9 of 12 Shetland Sheepdogs and 23 of 37 other breeds that did not have GBM. No statistically significant association existed between ABCB4 1583_1584G and the presence of GBM for all dogs combined or for Shetland Sheepdogs alone. In contrast to previously reported findings, the current study did not identify a strong association between ABCB4 1583_1584G and GBM in Shetland Sheepdogs or other breeds.This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by Sage Publications. The published article can be found at: http://vdi.sagepub.com/.Keywords: Canine, Mucocele, Gall bladder, ABCB4 gen

An insertion mutation in ABCB4 is associated with gallbladder mucocele formation in dogs

BACKGROUND: ABCB4 functions as a phosphatidylcholine translocater, flipping phosphatidylcholine across hepatocyte canalicular membranes into biliary canaliculi. In people, ABCB4 gene mutations are associated with several disease syndromes including intrahepatic cholestasis of pregnancy, progressive familial intrahepatic cholestasis (type 3), primary biliary cirrhosis, and cholelithiasis. Hepatobiliary disease, specifically gallbladder mucocele formation, has been recognized with increased frequency in dogs during the past decade. Because Shetland Sheepdogs are considered to be predisposed to gallbladder mucoceles, we initially investigated ABCB4 as a candidate gene for gallbladder mucocele formation in that breed, but included affected dogs of other breeds as well. RESULTS: An insertion (G) mutation in exon 12 of canine ABCB4 (ABCB4 1583_1584G) was found to be significantly associated with hepatobiliary disease in Shetland Sheepdogs specifically (P < 0.0001) as well as other breeds (P < 0.0006). ABCB4 1583_1584G results in a frame shift generating four stop codons that prematurely terminate ABCB4 protein synthesis within exon 12, abolishing over half of the protein including critical ATP and a putative substrate binding site. CONCLUSIONS: The finding of a significant association of ABCB4 1583_1584G with gallbladder mucoceles in dogs suggests that this phospholipid flippase may play a role in the pathophysiology of this disorder. Affected dogs may provide a useful model for identifying novel treatment strategies for ABCB4-associated hepatobiliary disease in people

Contributions to arachnid systematics in honor of Willis J. Gertsch, on the occasion of his seventy-fifth birthday. Bulletin of the AMNH ; v. 170, article 1

270 p., [1] leaf of plates : ill. (some col.), maps, ports. ; 26 cm."Scientific publications of Willis J. Gertsch": p. 11-14.Includes bibliographical references and author index.A new species of Mastigoproctus (Thelyphonidae), the first record of Uropygida from Costa Rica / Carlos E. Valerio -- On the Cryptocellus centralis group (Arachnida, Ricinulei) / Norman I. Platnick and Mohammad U. Shadab -- A new genus of troglobitic scorpion from Mexico (Chactoidea, Megacorminae) / Oscar F. Francke -- A new Bothriurus from Bolivia (Scorpiones, Bothriuridae) / Emilio A. Maury -- A study of the syntypes of Diplocentrus keyserlingii (Diplocentridae) / Herbert L. Stahnke -- On Liphistius desultor Schiödte (Araneae, Liphistiidae) / John A. Murphy and Norman I. Platnick -- Three new mygalomorph spiders (Dipluridae, Masteriinae) from Colombia / Robert J. Raven -- The mygalomorph spider genus Microhexura (Araneae, Dipluridae) / Frederick A. Coyle -- Two new species of the mygalomorph spider genus Neocteniza (Araneae, Actinopodidae) / Norman I. Platnick and Mohammad U. Shadab -- Spitting spiders (Araneae, Scytodidae, Scytodes) from Central America / Carlos E. Valerio -- Studies on the Pholcidae. 1, Notes on the genera Artema and Physocyclus / Paolo Marcello Brignoli -- A new genus of spider (Agelenidae) from California exhibiting a third type of leg autospasy / Vincent D. Roth -- Classification of two North American species of Pirata, with a description of a new genus (Araneae, Lycosidae) / Charles D. Dondale and James H. Redner -- Studies on species of Holarctic Pardosa groups (Araneae, Lycosidae). 2, Redescriptions of Pardosa modica (Blackwall), Pardosa labradorensis (Thorell), and Pardosa sinistra (Thorell) / Torbjörn Kronestedt -- A revision of the nigra group of the genus Pardosa in North America (Araneae, Lycosidae) / Donald C. Lowrie and Charles D. Dondale -- The Neotropical spider genera Architis and Staberius (Pisauridae) / James E. Carico -- A new species of Trechalea (Pisauridae) from North America / James E. Carico and Edwin W. Minch -- The Ctenidae of temperate zone North America / William B. Peck -- Color variation in two species of Castianeira (Araneae, Clubionidae) / Jonathan Reiskind -- A new genus of the spider family Gnaphosidae (Arachnida, Araneae) / Norman I. Platnick and Mohammad U. Shadab -- On the spider genus Eilica (Araneae, Gnaphosidae) / Norman I. Platnick and Mohammad U. Shadab -- New species and records of Neotropical Gnaphosidae (Arachnida, Araneae) / Norman I. Platnick and Mohammad U. Shadab -- A revision of the genus Habrocestum (Araneae, Salticidae) in North America / David B. Richman -- A revision of the spider genus Paradamoetas (Araneae, Salticidae) / Bruce Cutler -- Three new species of Salticidae (Araneae) / María Elena Galiano -- New Central and South American Uloboridae (Arachnida, Araneae) / Brent D. Opell -- The Nearctic species of Oreonetides (Araneae, Linyphiidae) / P.J. Van Helsdingen -- The erigonine spiders of North America. Part 5, The genus Satilatlas (Araneae, Linyphiidae) / A.F. Millidge -- More on the genus Araneus from North America / Herbert W. Levi -- Structure of the male palpal organ in Mimetus, Ero, and Gelanor (Araneae, Mimetidae) / William A. Shear -- A textricellid spider from Chile (Araneae, Textricellidae) / Raymond R. Forster and Norman I. Platnick

The Mycobacterium tuberculosis regulatory network and hypoxia

We have taken the first steps towards a complete reconstruction of the Mycobacterium tuberculosis regulatory network based on ChIP-Seq and combined this reconstruction with system-wide profiling of messenger RNAs, proteins, metabolites and lipids during hypoxia and re-aeration. Adaptations to hypoxia are thought to have a prominent role in M. tuberculosis pathogenesis. Using ChIP-Seq combined with expression data from the induction of the same factors, we have reconstructed a draft regulatory network based on 50 transcription factors. This network model revealed a direct interconnection between the hypoxic response, lipid catabolism, lipid anabolism and the production of cell wall lipids. As a validation of this model, in response to oxygen availability we observe substantial alterations in lipid content and changes in gene expression and metabolites in corresponding metabolic pathways. The regulatory network reveals transcription factors underlying these changes, allows us to computationally predict expression changes, and indicates that Rv0081 is a regulatory hub