What's the Problem? Cultural Capability and Learning from Historical Performance

Contains the cis-eQTLs with P value < 5 % for T-cells obtained from early undifferentiated arthritis patients. (TXT 1162 kb

Genetic association of seven SNPs with the response to treatment with anti-tumor necrosis factor agents in patients with RA from Crete.

<p>Genetic association of seven SNPs with the response to treatment with anti-tumor necrosis factor agents in patients with RA from Crete.</p

Risk of developing RA for combinations of the <i>HLA-DRB1</i> SE and rs3087456 alleles in Swedish.

<p>British. Dutch and Norwegian cohorts.</p><p>Results for additive (add.) and multiplicative (mult.) interaction is displayed as significance (P value) of deviation from expected risk given no interaction. AP = attributable proportion; SE = shared epitope; OR = odds ratio; ACPA+ = anti citrullinated protein antibody positive RA patients; CI = confidence interval.</p

Summary data for interaction analysis between <i>CIITA</i> rs4781019 and <i>HLA-DRB1</i> SE.

<p>The table presents the best result after analysis of interaction between the <i>CIITA</i> locus and <i>HLA-DRB1</i>. Dominant and recessive (for the risk allele) genetic models were tested for each SNP, see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032861#pone.0032861.s004" target="_blank">Table S4</a> for complete results. AP = attributable proportion; SE = shared epitope; ACPA+ = anti citrullinated protein antibody positive RA patients.</p

Additional file 2: of Capture Hi-C identifies a novel causal gene, IL20RA, in the pan-autoimmune genetic susceptibility region 6q23

Contains the cis-eQTLs with P value < 5 % for CD4+ T-cells obtained from NRHV participants. (TXT 405 kb

Results from initial (GRACE only) meta-analysis.

<p>SNPs allocated to group 1, 2 or 3 based on previously published evidence. The SNPs^† in group 2 do not reach genome-wide significance in Stahl et al used in meta-analysis <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0066456#pone.0066456-Stahl1" target="_blank">[6]</a> (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0066456#pone-0066456-t002" target="_blank">Table 2</a>), but have in prior publications <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0066456#pone.0066456-Gregersen1" target="_blank">[4]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0066456#pone.0066456-Raychaudhuri1" target="_blank">[5]</a>. Het <i>P</i> = meta-analysis heterogeneity χ²<i>P</i> value, OR = odds ratio calculated using fixed or random* effects meta-analysis.</p

Discovery of Imidazo[1,2‑<i>a</i>]pyridine Ethers and Squaramides as Selective and Potent Inhibitors of Mycobacterial Adenosine Triphosphate (ATP) Synthesis

The approval of bedaquiline to treat tuberculosis has validated adenosine triphosphate (ATP) synthase as an attractive target to kill Mycobacterium tuberculosis (Mtb). Herein, we report the discovery of two diverse lead series imidazo­[1,2-<i>a</i>]­pyridine ethers (IPE) and squaramides (SQA) as inhibitors of mycobacterial ATP synthesis. Through medicinal chemistry exploration, we established a robust structure–activity relationship of these two scaffolds, resulting in nanomolar potencies in an ATP synthesis inhibition assay. A biochemical deconvolution cascade suggested cytochrome c oxidase as the potential target of IPE class of molecules, whereas characterization of spontaneous resistant mutants of SQAs unambiguously identified ATP synthase as its molecular target. Absence of cross resistance against bedaquiline resistant mutants suggested a different binding site for SQAs on ATP synthase. Furthermore, SQAs were found to be noncytotoxic and demonstrated efficacy in a mouse model of tuberculosis infection