Dynamics Determine Signaling in a Multicomponent System Associated with Rheumatoid Arthritis

Strategies that target multiple components are usually required for treatment of diseases originating from complex biological systems. The multicomponent system consisting of the DR4 major histocompatibility complex type II molecule, the glycopeptide CII259–273 from type II collagen, and a T-cell receptor is associated with development of rheumatoid arthritis (RA). We introduced non-native amino acids and amide bond isosteres into CII259–273 and investigated the effect on binding to DR4 and the subsequent T-cell response. Molecular dynamics simulations revealed that complexes between DR4 and derivatives of CII259–273 were highly dynamic. Signaling in the overall multicomponent system was found to depend on formation of an appropriate number of dynamic intramolecular hydrogen bonds between DR4 and CII259–273, together with the positioning of the galactose moiety of CII259–273 in the DR4 binding groove. Interestingly, the system tolerated modifications at several positions in CII259–273, indicating opportunities to use analogues to increase our understanding of how rheumatoid arthritis develops and for evaluation as vaccines to treat RA

Dynamics Determine Signaling in a Multicomponent System Associated with Rheumatoid Arthritis

Strategies that target multiple components are usually required for treatment of diseases originating from complex biological systems. The multicomponent system consisting of the DR4 major histocompatibility complex type II molecule, the glycopeptide CII259–273 from type II collagen, and a T-cell receptor is associated with development of rheumatoid arthritis (RA). We introduced non-native amino acids and amide bond isosteres into CII259–273 and investigated the effect on binding to DR4 and the subsequent T-cell response. Molecular dynamics simulations revealed that complexes between DR4 and derivatives of CII259–273 were highly dynamic. Signaling in the overall multicomponent system was found to depend on formation of an appropriate number of dynamic intramolecular hydrogen bonds between DR4 and CII259–273, together with the positioning of the galactose moiety of CII259–273 in the DR4 binding groove. Interestingly, the system tolerated modifications at several positions in CII259–273, indicating opportunities to use analogues to increase our understanding of how rheumatoid arthritis develops and for evaluation as vaccines to treat RA

Peer Effects and Voluntary Green Building Certification

Empirical evidence is provided to show that peer effects have statistically significant and positive impacts on the diffusion of green building certificates. Application and approval records of green certificates by commercial buildings in NY and AZ are used. The challenge of self-selection is addressed by the usage of fixed effects and the challenge of reflection is addressed by the time lag delay between a building’s application and its approval. Empirical results show that an additional approved LEED certificate within a zip code will increase the probability of a commercial building in the same zip code to apply for a LEED certificate by 3–4 percentage points; an additional approved Energy Star certificate within a zip code will increase the probability of a commercial building in the same zip code to apply for an Energy Star certificate by 1–2 percentage points

Additional file 3: of The influence of menstrual cycle and endometriosis on endometrial methylome

Differentially methylated regions between different menstrual cycle phases. The methylation data of each menstrual cycle phase was compared to other phases. (XLSX 2676 kb

Additional file 7: of The influence of menstrual cycle and endometriosis on endometrial methylome

Menstrual cycle phase specific genes. The list of late-secretory and menstrual phase specific hyper- and hypomethylated genes. (XLSX 28 kb

風俗 金魚傳 第二編

An Edo-period illustrated novel of the gesaku genre.Dimensions: 7 x 4⅝ x ⅛ in. (17.78 x 11.75 x 0.32 cm)Gift of Barry Rosenstee

Additional file 6: of The influence of menstrual cycle and endometriosis on endometrial methylome

Venn diagrams of differentially methylated genes. Diagrams show the total number of hypo- and hypermethylated genes identified in each comparison. (TIF 3142 kb

Prospective study design and data analysis in UK Biobank

Population-based prospective studies, such as UK Biobank, are valuable for generating and testing hypotheses about the potential causes of human disease. We describe how UK Biobank’s study design, data access policies, and approaches to statistical analysis can help to minimize error and improve the interpretability of research findings, with implications for other population-based prospective studies being established worldwide.</p

Enrichment of variance and gene <i>×</i> environment interaction nominally significant results with GWAS-derived loci.

<p>Enrichment of variance and gene <i>×</i> environment interaction nominally significant results with GWAS-derived loci.</p

Data flow-chart.

<p>Three sources of genome-wide results were used: i) meta-analysis of Levene’s test results for between-genotype heterogeneity of phenotypic variances; ii) published results for marginal effects genome-wide association studies undertaken by the GIANT and GLGC consortia; iii) published results for SNP <b>×</b> physical activity and SNP <b>×</b> smoking in BMI (from the GIANT consortium).</p