Exocrine Proteins Including Trypsin(ogen) as a Key Biomarker in Type 1 Diabetes

   Objective Proteomic profiling can identify useful biomarkers. Monozygotic(MZ) twins, discordant for a condition represent an ideal test population. We aimed to investigate and validate proteomic profiling in twins with type 1 diabetes and in other well characterised cohorts. Research Design and Methods A broad, multiplex analysis of 4068 proteins in sera from MZ twins concordant (n=43) and discordant for type 1 diabetes (n=27) identified major differences which were subsequently validated by a trypsin(ogen) assay in MZ pairs concordant (n=39) and discordant (n=42) for type 1 diabetes, individuals at-risk (n=195) and with type 1 diabetes (n=990), as well as with non-insulin requiring adult-onset diabetes diagnosed as either autoimmune (n=96) or type 2 (n=291). Results Proteomic analysis identified major differences between exocrine enzyme levels in discordant MZ twin pairs despite strong correlation between twins, whether concordant or discordant for type 1 diabetes (p Conclusions Type 1 diabetes is associated with altered exocrine function, even before onset. Twin data suggest roles for genetic and non-genetically determined factors. Exocrine/endocrine interactions are important under-investigated factors in type 1 diabetes.</p

Additional file 3: of Optimization of late gadolinium enhancement cardiovascular magnetic resonance imaging of post-ablation atrial scar: a cross-over study

Figure S2. Impact of scan parameters on scar apparent signal to noise ratio. Paired acquisitions at 10, 20 and 30 min post GBCA injection, for control subjects (top left), half GBCA dose (top right), half slice thickness (bottom left) and 3 T scanner (bottom right). Scan 1 (standard acquisition, circle) and scan 2 (experimental acquisition, square) are linked for each subject. P-values are for two-way repeated measures ANOVA: at the top of each plot is the p-value for variance with time, and to the right is the p-value for variance with acquisition parameter. Unpaired acquisitions are shown as unlinked circle or square, and were not included in statistical analyses. (JPEG 286 kb

Additional file 2: of Optimization of late gadolinium enhancement cardiovascular magnetic resonance imaging of post-ablation atrial scar: a cross-over study

Figure S1. Impact of scan parameters on blood pool apparent signal to noise ratio. Paired acquisitions at 10, 20 and 30 min post GBCA injection, for control subjects (top left), half GBCA dose (top right), half slice thickness (bottom left) and 3 T scanner (bottom right). Scan 1 (standard acquisition, circle) and scan 2 (experimental acquisition, square) are linked for each subject. P-values are for two-way repeated measures ANOVA: at the top of each plot is the p-value for variance with time, and to the right is the p-value for variance with acquisition parameter. Unpaired acquisitions are shown as unlinked circle or square, and were not included in statistical analyses. (JPEG 268 kb

Additional file 1: of Optimization of late gadolinium enhancement cardiovascular magnetic resonance imaging of post-ablation atrial scar: a cross-over study

Details of acquisition and analysis techniques. (DOCX 26 kb

Additional file 1: of The reproducibility of late gadolinium enhancement cardiovascular magnetic resonance imaging of post-ablation atrial scar: a cross-over study

Reproducibility of Post-ablation atrial scar imaging- Supplementary Data. (DOCX 889 kb

Microscale High-Throughput Experimentation as an Enabling Technology in Drug Discovery: Application in the Discovery of (Piperidinyl)pyridinyl‑1<i>H</i>‑benzimidazole Diacylglycerol Acyltransferase 1 Inhibitors

Miniaturization and parallel processing play an important role in the evolution of many technologies. We demonstrate the application of miniaturized high-throughput experimentation methods to resolve synthetic chemistry challenges on the frontlines of a lead optimization effort to develop diacylglycerol acyltransferase (DGAT1) inhibitors. Reactions were performed on ∼1 mg scale using glass microvials providing a miniaturized high-throughput experimentation capability that was used to study a challenging S_<i>N</i>Ar reaction. The availability of robust synthetic chemistry conditions discovered in these miniaturized investigations enabled the development of structure–activity relationships that ultimately led to the discovery of soluble, selective, and potent inhibitors of DGAT1