Participant Characteristics.

<p>CHF- congestive heart failure, DM- diabetes mellitus, COPD- chronic obstructive pulmonary disease, CKD- chronic kidney disease, ESRD- end stage renal disease on dialysis, HTN- hypertension, PUD- peptic ulcer disease, CAD- coronary artery disease, DVT- deep vein thrombosis, PTSD- post traumatic stress disorder.</p

Additional file 1: of SPARC expression in patients with high-risk localized soft tissue sarcoma treated on a randomized phase II trial of neo/adjuvant chemotherapy

Table S1. Multivariate model for OS by SPARC expression, any versus no expression. Table S2. Multivariate model for time to recurrence by SPARC expression, any versus no expression. Table S3. Distribution of SPARC scores. (DOCX 15 kb

Additional file 2 of Transition models of care for type 1 diabetes: a systematic review

Supplementary Material

Calcium-Dependent Interaction of Calmodulin with Human 80S Ribosomes and Polyribosomes

Ribosomes are the protein factories of every living cell. The process of protein translation is highly complex and tightly regulated by a large number of diverse RNAs and proteins. Earlier studies indicate that Ca²⁺ plays a role in protein translation. Calmodulin (CaM), a ubiquitous Ca²⁺-binding protein, regulates a large number of proteins participating in many signaling pathways. Several 40S and 60S ribosomal proteins have been identified to interact with CaM, and here, we report that CaM binds with high affinity to 80S ribosomes and polyribosomes in a Ca²⁺-dependent manner. No binding is observed in buffer with 6 mM Mg²⁺ and 1 mM EGTA that chelates Ca²⁺, suggesting high specificity of the CaM–ribosome interaction dependent on the Ca²⁺ induced conformational change of CaM. The interactions between CaM and ribosomes are inhibited by synthetic peptides comprising putative CaM-binding sites in ribosomal proteins S2 and L14. Using a cell-free <i>in vitro</i> translation system, we further found that these synthetic peptides are potent inhibitors of protein synthesis. Our results identify an involvement of CaM in the translational activity of ribosomes

Additional file 1 of Transition models of care for type 1 diabetes: a systematic review

Supplementary Material

First Genome-Wide Association Study in an Australian Aboriginal Population Provides Insights into Genetic Risk Factors for Body Mass Index and Type 2 Diabetes

<div><p>A body mass index (BMI) >22kg/m² is a risk factor for type 2 diabetes (T2D) in Aboriginal Australians. To identify loci associated with BMI and T2D we undertook a genome-wide association study using 1,075,436 quality-controlled single nucleotide polymorphisms (SNPs) genotyped (Illumina 2.5M Duo Beadchip) in 402 individuals in extended pedigrees from a Western Australian Aboriginal community. Imputation using the thousand genomes (1000G) reference panel extended the analysis to 6,724,284 post quality-control autosomal SNPs. No associations achieved genome-wide significance, commonly accepted as P<5x10^-8. Nevertheless, genes/pathways in common with other ethnicities were identified despite the arrival of Aboriginal people in Australia >45,000 years ago. The top hit (rs10868204 <i>P</i>_genotyped = 1.50x10^-6; rs11140653 P_{imputed_1000G} = 2.90x10^-7) for BMI lies 5’ of <i>NTRK2</i>, the type 2 neurotrophic tyrosine kinase receptor for brain-derived neurotrophic factor (BDNF) that regulates energy balance downstream of melanocortin-4 receptor (MC4R). PIK3C2G (rs12816270 P_genotyped = 8.06x10^-6; rs10841048 P_{imputed_1000G} = 6.28x10^-7) was associated with BMI, but not with T2D as reported elsewhere. BMI also associated with <i>CNTNAP2</i> (rs6960319 P_genotyped = 4.65x10^-5; rs13225016 P_{imputed_1000G} = 6.57x10^-5), previously identified as the strongest gene-by-environment interaction for BMI in African-Americans. The top hit (rs11240074 P_genotyped = 5.59x10^-6, P_{imputed_1000G} = 5.73x10^-6) for T2D lies 5’ of <i>BCL9</i> that, along with <i>TCF7L2</i>, promotes beta-catenin’s transcriptional activity in the WNT signaling pathway. Additional hits occurred in genes affecting pancreatic (<i>KCNJ6</i>, <i>KCNA1</i>) and/or GABA (<i>GABRR1</i>, <i>KCNA1</i>) functions. Notable associations observed for genes previously identified at genome-wide significance in other populations included <i>MC4R</i> (P_genotyped = 4.49x10^-4) for BMI and <i>IGF2BP2</i> P_{imputed_1000G} = 2.55x10^-6) for T2D. Our results may provide novel functional leads in understanding disease pathogenesis in this Australian Aboriginal population.</p></div

Imputation accuracy for 402 genotyped individuals imputed against the 1000G reference panel.

<p>Imputation accuracy is measured as average <i>r</i>² across all autosomes for SNPs of different MAFs (see key).</p

Top GWAS SNP hits in genes of functional relevance for BMI, organized by chromosome.

<p>Results are for GWAS analysis in GenABEL using each individual BMI reading as a separate observation, modelling the correlation between readings via the estimated kinship and using the Genomic Control deflation factor to avoid inflation of the overall distribution of test statistics. Results are for allele-wise tests under an additive model of inheritance for genotyped SNPs and for imputed data. Bold indicates the top hit for BMI based on both genotyped and 1000G imputed data. Full lists of the top 50 hits for genotyped SNPs, and the top 100 SNPs for imputed data, appear in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119333#pone.0119333.s012" target="_blank">S3 Table</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119333#pone.0119333.s015" target="_blank">S6 Table</a>, respectively.</p><p>* Genes separated by forward slash indicate nearest protein coding genes upstream/downstream of the SNP. NCBI37 = bp location on chromosome for NCBI Build 37. A1 = major allele; A2 = minor allele.</p><p>Top GWAS SNP hits in genes of functional relevance for BMI, organized by chromosome.</p

Top GWAS SNP hits in genes of functional interest for T2D, organized by chromosome.

<p>Data analyzed in GenABEL using genotyped or 1000G imputed data for all individuals with doctor-diagnosed T2D. Results are for allele-wise tests under an additive model of inheritance. Bold indicates top hit for T2D based on both genotyped and imputed data. Full lists of the top 50 hits for genotyped SNPs, and the top 100 SNPs for imputed data, appear in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119333#pone.0119333.s014" target="_blank">S5 Table</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119333#pone.0119333.s016" target="_blank">S7 Table</a>, respectively.</p><p>* Genes separated by forward slash indicate nearest protein coding genes upstream/downstream of the SNP. NCBI37 = bp location on chromosome for NCBI Build 37. A1 = major allele; A2 = minor allele.</p><p>Top GWAS SNP hits in genes of functional interest for T2D, organized by chromosome.</p

Regional association plots (LocusZoom [35]) of the signal for BMI association in the region <i>SLC28A3</i> to <i>NTRK2</i> on chromosome 9.

<p>(A) is the plot for genotyped data; and (B) is the plot for 1000G imputed data. The −log₁₀<i>P</i>-values are shown on the upper part of each plot. SNPs are colored (see key) based on their <i>r</i>² with the labeled hit SNP (purple), calculated in the 146 unrelated genotyped individuals. The bottom section of each plot shows the genes marked as horizontal lines. The second Y axis is for recombination rate, as shown in blue on the plot.</p