Transcription factors are presented with boldfacing and connected to the respective target genes with gray lines

The connections shown between transcription factors and their target genes are based on compilations in Yeast Proteome Database [][] and on the transcription factor binding network by Young and co-workers []. Expression of the genes presented in white boxes with black text was highest in the glucose derepressed cells (Derep.) and lowest in the glucose repressed cells (Rep.). Expression of the genes presented in black boxes with white text was highest in the glucose repressed cells and lowest in the glucose derepressed cells. Expression of the genes presented in dark gray boxes with black text was highest in the xylose-grown cells and lowest in the glucose derepressed cells. Expression of the genes presented in light gray boxes with black text was highest in the xylose-grown cells and lowest in the glucose repressed cells. Expression of the genes presented in gray boxes with white text was lowest in the xylose-grown cells. In addition to the genes shown in the figure, 89% of the genes (31 out of 35) annotated to GO category "Oxidative phosphorylation" and its daughter categories [] had highest expression in the glucose derepressed cells, lowest expression in the glucose repressed cells and intermediate expression in the cells grown on xylose (data not shown).<p><b>Copyright information:</b></p><p>Taken from "Regulation of xylose metabolism in recombinant "</p><p>http://www.microbialcellfactories.com/content/7/1/18</p><p>Microbial Cell Factories 2008;7():18-18.</p><p>Published online 4 Jun 2008</p><p>PMCID:PMC2435516.</p><p></p

The y-axis corresponds to the difference of a gene relative to the mean expression of the gene in all samples on a log-scale (values above zero-level represent up-regulation and below it down-regulation)

The red lines represent the average expression pattern of each cluster. The x-axes are the 5 h and 24 h glucose and 72 h xylose samples (Glc5h, Glc24h and Xyl72h, respectively). The total number of genes in each cluster was: 484, 514, 127, 182, 22, 22, 34 and 54 for clusters 1 to 8, respectively.<p><b>Copyright information:</b></p><p>Taken from "Regulation of xylose metabolism in recombinant "</p><p>http://www.microbialcellfactories.com/content/7/1/18</p><p>Microbial Cell Factories 2008;7():18-18.</p><p>Published online 4 Jun 2008</p><p>PMCID:PMC2435516.</p><p></p

Mouse plasma IgM binding to apoptotic T lymphocytes after <i>P. gingivalis</i> immunization.

<p>C57BL/6 mice were immunized with heat-killed Pg and controls received sterile saline (n = 8 per group). Mouse plasma (1∶70) IgM binding to UV-irradiated Jurkat T cells was measured with flow cytometry. A, B) Apoptotic T cell population (R1) was verified with propidium iodide (PI) staining. C) Plasma IgM binding in gate R2 of preimmune (black) and postimmune (blue) plasma samples, and competition of IgM binding with 250 µg/ml MDA-LDL (green) or native LDL (red). Inset plots (in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0034910#pone-0034910-g006" target="_blank">Fig. 6C</a>) represent the secondary antibody control (2°Ab control) and plasma IgM binding to apoptotic cells in a Pg-immunized mouse (post). D) IgM binding to Jurkat cells was determined for each mouse in Pg-immunized and control group as geometric mean value in R2 subtracted by the 2°Ab control. Box-plot graphs represent the distribution of sample means calculated for two repeated assays. **P<0.01 and *P<0.05.</p

Weight gain and plasma lipids of LDLR^−/− mice.

*<p>Female LDLR^−/− mice were immunized with killed <i>P. gingivalis</i> (n = 7) and controls (n = 8) received PBS. Mean ± SD is shown.</p>†<p>Plasma lipids were measured from EDTA-plasma samples collected immediately after sacrifice at the end of HFD. Concentration of LDL cholesterol was estimated using the formula of Friedewald.</p

Association between human serum IgM to <i>P. gingivalis</i> and MDA-LDL, and competitive binding with recombinant gingipain domains.

<p>Sera from 29 healthy adults were analyzed for IgM (A) and IgG (B) binding to Pg and MDA-LDL by chemiluminescence immunoassay. Associations between antibody levels were analyzed with Spearman rank correlation test. Human sera were pre-incubated with recombinant gingipain domains Rgp44, Rgp15–27, RgpCAT (C, D) in a competitive immunoassay detecting IgM binding to immobilized MDA-LDL. The ratio of serum IgM binding (B/B₀) to MDA-LDL with and without competitor (175 µg/ml) in 29 human serum samples (C) and dose-dependent competition assays of one sample (D). Reciprocal competition assay was performed to analyze human serum IgM binding to Pg antigen competed with MDA-LDL, nLDL and PC-BSA in a representative sample (E). RU, relative units.</p

Antibodies to recombinant gingipain in <i>P. gingivalis</i> immunized mice.

<p>Recombinant proteins of the arginine specific gingipain protease of <i>P. gingivalis</i> were produced in <i>E.coli</i>: two proteins in the hemagglutinin/adhesion domain, Rgp44 and Rgp15–27, and the catalytic domain, RgpCAT, which were used in chemiluminescence immunoassay to determine mouse plasma (1∶500) IgM and IgG binding in <i>P. gingivalis</i> immunized (Pg) and control (Co) groups in both A) C57BL/6 and B) LDLR^−/− mice. A) For C57BL/6 immunized and control mice the samples (n = 8 each) were determined as duplicate before (pre) and after (post) immunization. Box-plots represent the distribution of the means of the sample duplicates. B) Two plasma samples within the group were pooled for immunized (black bars) and control (hatched bars) LDLR^−/− mice and measured in duplicate. Samples were collected before (pre), after the second booster immunization (imm) and at the end of HFD (end). Columns represent the mean ± SD of pooled samples in each group. **P<0.01 and *P<0.05.</p

Mouse plasma IgM and IgG binding to MDA-LDL after immunization with <i>P. gingivalis</i>.

<p>C57BL/6 mice were immunized with heat-killed <i>P. gingivalis</i> ATCC33277 (Pg; n = 8) and controls received saline (Co; n = 8). Plasma IgM (A) and IgG (B) to MDA-LDL before (pre) and after immunization (post) were determined with chemiluminescence immunoassay. Each C57BL/6 plasma sample (1∶500) was measured in duplicate and an average for each individual was calculated. LDLR^−/− mice were immunized with killed <i>P. gingivalis</i> (3 strains mixed) (Pg; n = 7) and controls received PBS (Co; n = 8). Plasma IgM (C) and IgG (D) to MDA-LDL after the second booster immunization (imm) and after the HFD (end) were determined. Each LDLR^−/− plasma sample (1∶1000) was measured in duplicate and an average for each individual in two repeated assays was calculated. Additionally, mouse plasma IgM binding to CuOx-LDL (E, G) and PC-BSA (F, H) was determined. For C57BL/6 mice (E, F) this was done similarly as described for panel A. Plasma samples of LDLR^−/− mice (G, H) were pooled between three or four mice (1∶1000) for a single assay, in which the mean ± SD within a group is shown.</p

Quantification of atherosclerosis in LDLR^−/− mice immunized with <i>P. gingivalis</i>.

<p>LDLR^−/− mice (n = 7) were immunized without adjuvant with killed <i>P. gingivalis</i> (3 strains mixed) (Pg) followed by high fat diet (HFD). Controls (PBS, n = 8) received PBS. A) The extent of atherosclerotic plaque development was determined after HFD by <i>en face</i> analysis of the Sudan IV -stained aortas. B) Lesions at the aortic origin were measured on histological sections as percentage of plaque area in the aorta cross-sectional area. Representative pictures of aortas and cross-sections are shown for each group. * P<0.05.</p

Identification of <i>P. gingivalis</i> epitopes for anti-MDA-LDL-IgM.

<p>A) Schematic presentation of arg-gingipain (RgpA) functional domains cloned and produced in a recombinant system <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0034910#pone.0034910-Inagaki1" target="_blank">[41]</a>. B) Proteins of <i>P. gingivalis</i> were separated on SDS-PAGE (Pg, gel). Fragments recognized by MDmAb (45, 40 and 32 kDa, black arrows) were identified by mass spectrometry as arginine-specific gingipain or hemagglutinin A of <i>P. gingivalis</i>. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0034910#pone.0034910.s001" target="_blank">Figures S1</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0034910#pone.0034910.s002" target="_blank">S2</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0034910#pone.0034910.s003" target="_blank">S3</a> contain the Mascot results of the database searches and the MSMS spectrum showing the matching amino acids in the peptide sequence. Three domains of the recombinant arg-specific gingipain, RgpCAT, Rgp44 and Rgp15–27 were produced in <i>E. coli</i> and analyzed for recognition by MDmAb and anti-PC-IgM control antibody (α-PC-mAb). C) Specific binding of MDmAb to recombinant gingipain domains Rgp15–27, Rgp44 and RgpCAT was tested with a competitive immunoassay. D) Reciprocally, soluble MDA-LDL, nLDL and PC-BSA were used as competitors for MDmAb binding to Rgp44. B/B₀ indicates the ratio of IgM binding with and without a competitor. MW, molecular weight. PC-BSA, phosphocholine-conjugated bovine serum albumin.</p

Table1.XLSX

<p>The heart of a newborn mouse has an exceptional capacity to regenerate from myocardial injury that is lost within the first week of its life. In order to elucidate the molecular mechanisms taking place in the mouse heart during this critical period we applied an untargeted combinatory multiomics approach using large-scale mass spectrometry-based quantitative proteomics, metabolomics and mRNA sequencing on hearts from 1-day-old and 7-day-old mice. As a result, we quantified 1.937 proteins (366 differentially expressed), 612 metabolites (263 differentially regulated) and revealed 2.586 differentially expressed gene loci (2.175 annotated genes). The analyses pinpointed the fructose-induced glycolysis-pathway to be markedly active in 1-day-old neonatal mice. Integrated analysis of the data convincingly demonstrated cardiac metabolic reprogramming from glycolysis to oxidative phosphorylation in 7-days old mice, with increases of key enzymes and metabolites in fatty acid transport (acylcarnitines) and β-oxidation. An upsurge in the formation of reactive oxygen species and an increase in oxidative stress markers, e.g., lipid peroxidation, altered sphingolipid and plasmalogen metabolism were also evident in 7-days mice. In vitro maintenance of physiological fetal hypoxic conditions retained the proliferative capacity of cardiomyocytes isolated from newborn mice hearts. In summary, we provide here a holistic, multiomics view toward early postnatal changes associated with loss of a tissue regenerative capacity in the neonatal mouse heart. These results may provide insight into mechanisms of human cardiac diseases associated with tissue regenerative incapacity at the molecular level, and offer a prospect to discovery of novel therapeutic targets.</p