Backbone RMSF of (a) RXRα and (b) PPARγ DBD residues.

<p>RMSF was measured from a trajectory pooled from the final 400 ns of each replicate simulation, for a total of 1.2 μs of sampling. A least-squares fit of backbone atoms in each DBD was performed prior to calculating the RMSF.</p

The PPARγ-RXRα LBD-LBD interface.

<p>Labels in blue correspond to structural features of PPARγ, while those in red correspond to RXRα. At left is the full complex, including the PPRE DNA sequence. At right is a zoomed-in view of the LBD-LBD interface.</p

Structural properties of PPARγ^*.

<p>Structural properties of PPARγ^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0123984#t002fn001" target="_blank">*</a>}.</p

Summary of the contents of each complex.

<p>Summary of the contents of each complex.</p

Components of the PPARγ-RXRα-DNA ternary complex.

<p>Protein structural domains (DBD, DNA-binding domain and LBD, ligand-binding domain) are indicated. Yellow spheres in the two DBD are Zn²⁺ ions. DNA is shown as a cartoon.</p

Effect of VSL#3 and dietary conjugated linoleic acid (CLA) supplementation on experimental <i>Helicobacter typhlonius</i>-induced colorectal cancer.

<p>Bacterial-free 129/SvEv and IL-10 gene deficient (IL-10−/−) 129/SvEv mice in a 129/SvEv background (n = 60) were treated with the VSL#3 probiotic (n = 20), CLA-supplemented (1 g/100 g) (n = 20) or control diets (n = 20) for 32 days and then were infected with <i>H. typhlonius</i> in order to develop experimental colorectal cancer associated with colitis. The disease activity index, a composite score reflecting clinical signs of the disease, was assessed daily for mice undergoing the DSS challenge (A). Colon, spleen and mesenteric lymph nodes (MLN) (B–D) were macroscopically scored for inflammation. Data are represented as mean ± standard error. Points with an asterisk are significantly different when compared to the control group (<i>P</i><0.05).</p

VSL#3 and conjugated linoleic acid (CLA) modulate colonic gene expression.

<p>C57BL/6J mice (n = 60) were treated with the VSL#3 probiotic (n = 20), CLA-supplemented (1 g/100 g) (n = 20) or control diets (n = 20) for 32 days and challenged i.p. with azoxymethane (10 mg/kg) followed by 2% dextran sodium sulfate (DSS) in the drinking water for 7 days to induce colitis-associated colorectal cancer (CRC). Mice were euthanized on day 68. Expression of CD36 (A), cyclooxygenase 2 (COX2) (B), peroxisome proliferator-activated receptor γ (PPAR γ) (C) and angiostatin (D) were assessed by real-time quantitative PCR. Data are represented as mean ± standard error. Points with an asterisk are significantly different when compared to the control group (<i>P</i><0.05).</p

Free energy surfaces of interfacial dynamics of all complexes studied here.

<p>Three free energy minima are identified in the holo complex simulations, and are labeled by Roman numerals. Images corresponding to representative holo complex conformations of each basin are shown, with the conformations being positioned most closely to the respective basins to which they correspond. Interfacial PPARγ and RXRα helices are in blue and red, respectively, and are labeled in the image nearest to Basin I. Positions along eigenvector 1 (x-axis) and eigenvector 2 (y-axis) are shown in nm for each free energy surface.</p

Movement of the H2’-H3 loop and the BVT.13 ligand in PPARγ complexes.

<p>Positions of the loop in snapshots from the (a) holo complex and (b) phospho complex (red) simulations, (c) heavy-atom RMSD distributions of the BVT.13 ligand in both the holo and phospho complexes, from data pooled over all frames in all trajectories, and (d) representative conformations of the BVT.13 partial agonist in holo (blue) and phospho (red) complexes. In panels (a) and (b), one structure was taken from each of the three replicate simulations to indicate the three different states (indicated by different shades of red and blue). Helices H2 and H3 are labeled, as is the position of Ser245/pSer245. The “crystal” positions of the ligands in panel (d) are from the energy-minimized, equilibrated structures, with hydrogen atoms removed for clarity.</p

Effect of the CLA and VSL#3 treatment on colon histopathology on experimental azoxymethane-induced colorectal cancer.

<p>C57BL/6J mice (n = 60) were treated with the VSL#3 probiotic (n = 20), CLA-supplemented (1 g/100 g) (n = 20) or control diets (n = 20) for 32 days and challenged i.p. with azoxymethane (10 mg/kg) followed by 2% dextran sodium sulfate (DSS) in the drinking water for 7 days to induce colitis-associated colorectal cancer (CRC). Mice were euthanized on day 68. All specimens underwent blinded histological examination and were scored 1–4 on leukocyte infiltration (A), and mucosal wall thickening (B), adenocarcinomas (C) and adenomas (D). Data are represented as mean ± standard error. Points with an asterisk are significantly different when compared to the control group (<i>P</i><0.05).</p