Background Acute pancreatitis (AP) is associated with a high death rate in dogs, but accurate predictors of early death are still lacking. Objectives To develop a scoring system for prediction of short‐term case fatality in dogs with AP. Animals One hundred sixty‐nine dogs with AP including 138 dogs in the training cohort and 31 dogs in the validation cohort. Methods Multicenter, retrospective cohort study. Survival analysis was used to assess the associations with short‐term death (within 30 days after admission). Independent predictors of death were identified by a stepwise selection method and used for the score calculation. Results Death rate within 30 days after admission was 33% in the training cohort. Four independent risk factors for short‐term death were identified in the training cohort: presence of systemic inflammatory response syndrome, coagulation disorders, increased creatinine and ionized hypocalcemia. Canine Acute Pancreatitis Severity (CAPS) score was developed to predict short‐term death, integrating these 4 factors in a weighted way. A simplified version of CAPS score (sCAPS) including respiratory rate instead of SIRS was also assessed. The area under the receiver‐operating characteristic curve (AUC) of CAPS and sCAPS scores was 0.92 in the training cohort with an optimal cutoff of 11 (sensitivity, 89%; specificity, 90%) and 6 (sensitivity, 96%; specificity, 77%), respectively. CAPS and sCAPS score were validated in the validation cohort with respective AUC of 0.91 and 0.96. Conclusions and Clinical Importance We propose 2 scoring systems that allow early and accurate prediction of short‐term death in dogs with AP.

Neuronal ceroid lipofuscinoses (NCLs) represent the most common group of inherited progressive encephalopathies in children. They are characterized by progressive loss of vision, mental and motor deterioration, epileptic seizures, and premature death. Rare adult forms of NCL with late onset are known as Kufs’ disease. Loci underlying these adult forms remain unknown due to the small number of patients and genetic heterogeneity. Here we confirm that a late-onset form of NCL recessively segregates in US and French pedigrees of American Staffordshire Terrier (AST) dogs. Through combined association, linkage, and haplotype analyses, we mapped the disease locus to a single region of canine chromosome 9. We eventually identified a worldwide breed-specific variant in exon 2 of the Arylsulfatase G ( ARSG ) gene, which causes a p.R99H substitution in the vicinity of the catalytic domain of the enzyme. In transfected cells or leukocytes from affected dogs, the missense change leads to a 75% decrease in sulfatase activity, providing a functional confirmation that the variant might be the NCL-causing mutation. Our results uncover a protein involved in neuronal homeostasis, identify a family of candidate genes to be screened in patients with Kufs' disease, and suggest that a deficiency in sulfatase is part of the NCL pathogenesis.

The phosphatidylinositol 3-kinase-mammalian target of rapamycin (PI3K-mTOR) pathway plays pivotal roles in cell survival, growth, and proliferation downstream of growth factors. Its perturbations are associated with cancer progression, type 2 diabetes, and neurological disorders. To better understand the mechanisms of action and regulation of this pathway, we initiated a large scale yeast two-hybrid screen for 33 components of the PI3K-mTOR pathway. Identification of 67 new interactions was followed by validation by co-affinity purification and exhaustive literature curation of existing information. We provide a nearly complete, functionally annotated interactome of 802 interactions for the PI3K-mTOR pathway. Our screen revealed a predominant place for glycogen synthase kinase-3 (GSK3) A and B and the AMP-activated protein kinase. In particular, we identified the deformed epidermal autoregulatory factor-1 (DEAF1) transcription factor as an interactor and in vitro substrate of GSK3A and GSK3B. Moreover, GSK3 inhibitors increased DEAF1 transcriptional activity on the 5-HT1A serotonin receptor promoter. We propose that DEAF1 may represent a therapeutic target of lithium and other GSK3 inhibitors used in bipolar disease and depression. Molecular & Cellular Proteomics 9:1578 -1593, 2010.The phosphatidylinositol 3-kinases (PI3Ks) 1 are a conserved family of lipid kinases that phosphorylate phosphatidylinositol on phosphoinositide 3Ј-hydroxyl group, forming second messengers. Class IA PI3K (hereafter "PI3K") is activated by growth factor receptor tyrosine kinases, and upon stimulation by insulin or IGF1, PI3K triggers the formation of phosphatidylinositol 3,4,5-trisphosphate, which recruits and From the ‡UMR5239