Additional file 1 of Integrating phenotype ontologies with PhenomeNET

Supplementary Information. The supplementary information contains the full evaluation results of the PhenomeNET system and other participating systems for the OAEI challenge 2016. (PDF 26 kb

Abnormal skeletal and cardiac development, cardiomyopathy, muscle atrophy and cataracts in mice with a targeted disruption of the gene-3

Nd 9 days (B, F) in culture showing enhanced cartilage differentiation in -/- cells, with the dashed line in B and F marking the extent of the micromass. Alkaline phosphatase staining after 5 days (C, G) and 9 days (D, H) in culture showing enhanced osteoblast differentiation in -/- cells. I-L: Morphology of monolayer PEF cultures derived from wild type (I, J) and -/- (K,L) embryos with (I, K) and without (J, L) phase contrast. Alkaline phosphatase staining after 10 days in culture (I, J, K, L) showing osteoblast differentiation in the -/- PEFs but not in the wild type PEFs. Scale bar in I-N = 10 μm. M: Semi quantitative RT-PCR of mRNA from wild type (+/+) and -/- PEFs using primers for alkaline phosphatase, collagen I and osteocalcin. Two fold serial dilutions of cDNA were used and normalised to .<p><b>Copyright information:</b></p><p>Taken from "Abnormal skeletal and cardiac development, cardiomyopathy, muscle atrophy and cataracts in mice with a targeted disruption of the () gene"</p><p>http://www.biomedcentral.com/1471-213X/8/18</p><p>BMC Developmental Biology 2008;8():18-18.</p><p>Published online 20 Feb 2008</p><p>PMCID:PMC2275724.</p><p></p

Abnormal skeletal and cardiac development, cardiomyopathy, muscle atrophy and cataracts in mice with a targeted disruption of the gene-7

Sed to confirm targeting by Southern blotting. The TkneopolyA cassette replaces exon 3 in the targeted allele while the HSV TK cassette allows negative selection with Gancyclovir. B. Southern analysis of DNA from wild type, heterozygous and homozygous embryos using 5' and 3' external probes to confirm targeting. Digestion with HI gave a 16 kb wild type band with the 5'external probe and 14 kb targeted allele with the 5' probe, while digestion with RI gave a 14 kb wild type band and 8.5 kb targeted band with the 3' probe. C. Western blotting of whole cell lysates and conditioned media from homozygous and wild type E13.5 PEFs, using an anti-NOV antibody (59.3). Although NOV protein is readily detectable in wild type PEF whole cell lysates, no NOV protein can be detected in homozygous PEFs. Conditioned medium from wild type PEFs contains high levels of secreted NOV, whereas that from -/- PEFs contains trace amounts of mutant NOV protein lacking the VWD domain.<p><b>Copyright information:</b></p><p>Taken from "Abnormal skeletal and cardiac development, cardiomyopathy, muscle atrophy and cataracts in mice with a targeted disruption of the () gene"</p><p>http://www.biomedcentral.com/1471-213X/8/18</p><p>BMC Developmental Biology 2008;8():18-18.</p><p>Published online 20 Feb 2008</p><p>PMCID:PMC2275724.</p><p></p

Abnormal skeletal and cardiac development, cardiomyopathy, muscle atrophy and cataracts in mice with a targeted disruption of the gene-0

Sed to confirm targeting by Southern blotting. The TkneopolyA cassette replaces exon 3 in the targeted allele while the HSV TK cassette allows negative selection with Gancyclovir. B. Southern analysis of DNA from wild type, heterozygous and homozygous embryos using 5' and 3' external probes to confirm targeting. Digestion with HI gave a 16 kb wild type band with the 5'external probe and 14 kb targeted allele with the 5' probe, while digestion with RI gave a 14 kb wild type band and 8.5 kb targeted band with the 3' probe. C. Western blotting of whole cell lysates and conditioned media from homozygous and wild type E13.5 PEFs, using an anti-NOV antibody (59.3). Although NOV protein is readily detectable in wild type PEF whole cell lysates, no NOV protein can be detected in homozygous PEFs. Conditioned medium from wild type PEFs contains high levels of secreted NOV, whereas that from -/- PEFs contains trace amounts of mutant NOV protein lacking the VWD domain.<p><b>Copyright information:</b></p><p>Taken from "Abnormal skeletal and cardiac development, cardiomyopathy, muscle atrophy and cataracts in mice with a targeted disruption of the () gene"</p><p>http://www.biomedcentral.com/1471-213X/8/18</p><p>BMC Developmental Biology 2008;8():18-18.</p><p>Published online 20 Feb 2008</p><p>PMCID:PMC2275724.</p><p></p

Abnormal skeletal and cardiac development, cardiomyopathy, muscle atrophy and cataracts in mice with a targeted disruption of the gene-6

Mall white colouration in the wild type eye is an artefact due to reflected light. C-F: Haematoxylin and Eosin stained sections of wild type (C,E) and -/- (D,F) adult eyes showing degeneration of the mutant lens, with vacuolation and loss of surface epithelium. Scale bars in E,F = 5 μm; C,D = 15 μm.<p><b>Copyright information:</b></p><p>Taken from "Abnormal skeletal and cardiac development, cardiomyopathy, muscle atrophy and cataracts in mice with a targeted disruption of the () gene"</p><p>http://www.biomedcentral.com/1471-213X/8/18</p><p>BMC Developmental Biology 2008;8():18-18.</p><p>Published online 20 Feb 2008</p><p>PMCID:PMC2275724.</p><p></p

Abnormal skeletal and cardiac development, cardiomyopathy, muscle atrophy and cataracts in mice with a targeted disruption of the gene-4

A subset of cells near the origins of the great vessels at E16.5. C-F: Haematoxylin and Eosin stained sections of wild type (C,D) and -/- (E,F) E13.5 embryonic hearts showing abnormal expansion of the endocardial cushions (EC) and delay in fusion of the septum (S) in the mutant mouse (arrow). G-M: Haematoxylin and Eosin stained sections of wild type (G, J) and -/- (H, I, K) adult hearts, showing accumulation of blood in the sub-endothelial space between the right ventricle and septum (H) and hypertrophy of the septum near the origins of the great vessels, (H, I, K). Areas of calcification on the septal wall of the right ventricle (K, L), stain with Von Kossa (M). There is no associated fibrosis. Scale bars in A,D,F = 20 μm; B,L = 10 μm; C,E = 50 μm; G,H,I = 1 mm; J,K = 50 μm; M = 5 μm.<p><b>Copyright information:</b></p><p>Taken from "Abnormal skeletal and cardiac development, cardiomyopathy, muscle atrophy and cataracts in mice with a targeted disruption of the () gene"</p><p>http://www.biomedcentral.com/1471-213X/8/18</p><p>BMC Developmental Biology 2008;8():18-18.</p><p>Published online 20 Feb 2008</p><p>PMCID:PMC2275724.</p><p></p

Discovery of a Potent, Selective, and Orally Bioavailable Acidic 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1) Inhibitor: Discovery of 2-[(3<i>S</i>)-1-[5-(Cyclohexylcarbamoyl)-6-propylsulfanylpyridin-2-yl]-3-piperidyl]acetic Acid (AZD4017)

Inhibition of 11β-HSD1 is an attractive mechanism for the treatment of obesity and other elements of the metabolic syndrome. We report here the discovery of a nicotinic amide derived carboxylic acid class of inhibitors that has good potency, selectivity, and pharmacokinetic characteristics. Compound <b>11i</b> (AZD4017) is an effective inhibitor of 11β-HSD1 in human adipocytes and exhibits good druglike properties and as a consequence was selected for clinical development

Circumventing Seizure Activity in a Series of G Protein Coupled Receptor 119 (GPR119) Agonists

Agonism of GPR119 is viewed as a potential therapeutic approach for the treatment of type II diabetes and other elements of metabolic syndrome. During progression of a previously disclosed candidate <b>1</b> through mice toxicity studies, we observed tonic–clonic convulsions in several mice at high doses. An in vitro hippocampal brain slice assay was used to assess the seizure liability of subsequent compounds, leading to the identification of an aryl sulfone as a replacement for the 3-cyano pyridyl group. Subsequent optimization to improve the overall profile, specifically with regard to hERG activity, led to alkyl sulfone <b>16</b>. This compound did not cause tonic–clonic convulsions in mice, had a good pharmacokinetic profile, and displayed in vivo efficacy in murine models. Importantly, it was shown to be effective in wild-type (WT) but not GPR119 knockout (KO) animals, consistent with the pharmacology observed being due to agonism of GPR119

Use of Small-Molecule Crystal Structures To Address Solubility in a Novel Series of G Protein Coupled Receptor 119 Agonists: Optimization of a Lead and in Vivo Evaluation

G protein coupled receptor 119 (GPR119) is viewed as an attractive target for the treatment of type 2 diabetes and other elements of the metabolic syndrome. During a program toward discovering agonists of GPR119, we herein describe optimization of an initial lead compound, <b>2</b>, into a development candidate, <b>42</b>. A key challenge in this program of work was the insolubility of the lead compound. Small-molecule crystallography was utilized to understand the intermolecular interactions in the solid state and resulted in a switch from an aryl sulphone to a 3-cyanopyridyl motif. The compound was shown to be effective in wild-type but not knockout animals, confirming that the biological effects were due to GPR119 agonism