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PMC2453137

18565227

1471-2180-8-101-6

Figure 6 Proportion of samples categorized in the motif class (% TP), for each MDR operon, using FFall and a classification threshold of -0.9.

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2022-01-12 14:45:40

BMC Microbiol. 2008 Jun 19; 8:101

PMC2453137

18565227

1471-2180-8-101-7

Figure 7 Proportion of samples categorized in the motif class (% TP), for each MDR operon, using BFall and a classification threshold of -0.9.

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2022-01-12 14:45:40

BMC Microbiol. 2008 Jun 19; 8:101

PMC2453137

18565227

1471-2180-8-101-8

Figure 8 Outline of the inferred regulatory interactions found employing the FFall predictor . There are seven types of regulatory interactions, according to the functional classification of the TF. Slice (a)-(e) in the outer donut chart (bold green) represents the set of relationships where a putative binding of the regulator to the promoter region of the operon exists. Refer to text for more details.

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2022-01-12 14:45:40

BMC Microbiol. 2008 Jun 19; 8:101

PMC2453137

18565227

1471-2180-8-101-9

Figure 9 Outline of the inferred regulatory interactions found employing the BFall predictor . The color scheme is the same as in the one in Figure 8.

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no

2022-01-12 14:45:40

BMC Microbiol. 2008 Jun 19; 8:101

PMC2453138

18578868

1471-2148-8-184-1

Figure 1 Phylogenetic neighbor-joining tree of NPY receptors and closely related GPCRs . Numbers below branches show percent bootstrap support for each node. Nodes with values below 50 have been collapsed. Human bradykinin receptor B1 was used to root the tree.

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2022-01-12 17:11:35

BMC Evol Biol. 2008 Jun 25; 8:184

PMC2453138

18578868

1471-2148-8-184-2

Figure 2 RT-PCR in Takifugu rubripes . Agarose gel showing the expression of the five Takifugu rubripes receptor genes in eleven different tissues. Actin was used as control to verify quality and content of samples.

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2022-01-12 17:11:35

BMC Evol Biol. 2008 Jun 25; 8:184

PMC2453138

18578868

1471-2148-8-184-3

Figure 3 Schematic picture of Takifugu rubripes NPY receptors . Picture depicting the Y4 (panel A), Y8a (panel B) and Y8b (panel C) receptors in Takifugu rubripes , indicating the extended second extracellular loop in Y4, the three extra introns present in the Y8a receptor gene and the alternative splicing of Y8b.

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2022-01-12 17:11:35

BMC Evol Biol. 2008 Jun 25; 8:184

PMC2453138

18578868

1471-2148-8-184-4

Figure 4 A-F – Phylogenetic analysis of neighboring gene families . Examples of the phylogenetic relationship for six neighboring gene families A (ABLIM), B (ADAMTS), C (AP3), D (ZIMP), E (HNRNP) and F (LGI). The trees were constructed using the neighbor-joining method as implemented in MEGA 3.1 with pair-wise deletion of gaps and poisson-corrected distances [ 117 ] All datasets were bootstrapped 1000 times (percent bootstrap support are indicated below each node). Species abbreviations are: Dme ( Drosophila melanogaster ), Cel ( Caenorhabditis elegans ), Cin ( Ciona intestinalis ), Csa ( Ciona savignyi ), Tru ( Takifugu rubripes ), Tni ( Tetraodon nigroviridis ), Dre ( Danio rerio ), Mmu ( Mus musculus ), Hsa ( Homo sapiens ). Numbers refers to chromosome number or scaffold number (ScXX), letters after chromosomal/scaffold number was arbitrarily assigned to family members located on the same chromosome to tell them apart. The scale below every tree indicates numbers of substitutions/site.

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2022-01-12 17:11:35

BMC Evol Biol. 2008 Jun 25; 8:184

PMC2453138

18578868

1471-2148-8-184-5

Figure 5 A-F – Phylogenetic analysis of neighboring gene families . A-F. Examples of the phylogenetic relationship for six additional neighboring gene families A (MAX), B (NKR), C (OGDH), D (PX19), E (SORB) and F (TSPAN). Trees were constructed and visualized in the same way as in Fig. 4.

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no

2022-01-12 17:11:35

BMC Evol Biol. 2008 Jun 25; 8:184

PMC2453138

18578868

1471-2148-8-184-6

Figure 6 Conserved synteny among vertebrate species compared to human chromosome 4 . Conservation of synteny for genes investigated in this study residing on human chromosome 4 compared to mouse, T. rubripes , T. nigroviridis and D. rerio . Numbers above boxes denotes chromosome numbers or scaffold names. Position of the genes (Mega base pairs) is given below each box. Genes are ordered according to their positions on the human chromosome. Genes linked in the other species are indicated with lines above boxes. Species name abbreviations are: Hsa ( Homo sapiens ), Mmu ( Mus musculus ), Tni ( Tetraodon nigroviridis ), Tru ( Takifugu rubripes ) and Dre ( Danio rerio ). The NPY receptors are indicated in darker color while loss of NPY receptor genes are indicated with striped boxes. White boxes indicate genes where the phylogenetic analysis is inconclusive but where position indicates orthology.

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no

2022-01-12 17:11:35

BMC Evol Biol. 2008 Jun 25; 8:184

PMC2453138

18578868

1471-2148-8-184-7

Figure 7 Conserved synteny among vertebrate species compared to human chromosome 5 . Conservation of synteny for genes investigated in this study residing on human chromosome 5 compared to mouse, T. rubripes , T. nigroviridis and D. rerio . Chromosomes, scaffolds, gene positions, gene order and species abbreviations are given in the same way as in Fig. 6.

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no

2022-01-12 17:11:35

BMC Evol Biol. 2008 Jun 25; 8:184

PMC2453138

18578868

1471-2148-8-184-8

Figure 8 Conserved synteny among vertebrate species compared to human chromosomes 8, 2 and 7 . Conservation of synteny for genes investigated in this study residing on human chromosome 8, 2 and 7 compared to mouse, T. rubripes , T. nigroviridis and D. rerio . Chromosomes, scaffolds, gene positions, gene order and species abbreviations are given in the same way as in Fig. 6.

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no

2022-01-12 17:11:35

BMC Evol Biol. 2008 Jun 25; 8:184

PMC2453138

18578868

1471-2148-8-184-9

Figure 9 Conserved synteny among vertebrate species compared to human chromosome 10 . Conservation of synteny for genes investigated in this study residing on human chromosome 10 compared to mouse, T. rubripes , T. nigroviridis and D. rerio . Chromosomes, scaffolds, gene positions, gene order and species abbreviations are given in the same way as in Fig. 6.

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no

2022-01-12 17:11:35

BMC Evol Biol. 2008 Jun 25; 8:184

PMC2453138

18578868

1471-2148-8-184-10

Figure 10 Proposed evolutionary scenario for the NPY receptor gene chromosomes . Schematic picture showing the proposed evolutionary history for 16 gene families located on the same chromosomes as the NPY receptor genes in T. nigroviridis and human. Note that position of genes is shuffled to simplify the picture. Striped boxes indicate gene losses. Position for genes on Hsa2 and Hsa7 is indicated in the boxes.

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no

2022-01-12 17:11:35

BMC Evol Biol. 2008 Jun 25; 8:184

PMC2453139

18593461

1471-2148-8-189-1

Figure 1 Plan view of the choice apparatus . The central arena for the choosing female consisted of a central neutral zone with an opaque plastic cylinder in the middle and four preference zones, which are separated from the central zone by dotted lines. The four tanks for the stimulus males contained the males' nests (N) and were placed perpendicular to the choice chambers. Solid lines represent opaque plastic walls whereas dashed lines represent UV transparent Plexiglas panes. Optical filters were placed horizontally over the four stimulus tanks.

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no

2022-01-12 17:11:35

BMC Evol Biol. 2008 Jul 1; 8:189

PMC2453139

18593461

1471-2148-8-189-2

Figure 2 Transmission of treatment filters . Transmission spectra for the four optical filters used in the stimulus and control experiment (UV-blocking (UV-), short-wave-blocking (SW-), medium-wave-blocking (MW-) and long-wave-blocking (LW-)). Spectra were measured with an Avantes AVS-USB2000 spectrometer connected to an Avantes DH-2000 deuterium-halogen light source. Transmission was determined by attaching the reflection probe at a 90° angle to the measured filter located on a 98% white standard.

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no

2022-01-12 17:11:35

BMC Evol Biol. 2008 Jul 1; 8:189

PMC2453139

18593461

1471-2148-8-189-3

Figure 3 Female filter preference . (A) Mean relative time ± SEM spent by 12 females within the preference zones in front of males under the ultraviolet-blocking (UV-), short-wave-blocking (SW-), medium-wave-blocking (MW-) and long-wave-blocking (LW-) treatment filters during the 10 min test phase of the stimulus experiment. (B) Mean relative time ± SEM spent by eight females within the preference zones in front of empty tanks under the UV-, SW-, MW- and LW- treatment filters during the 10 min test phase of the control experiment.

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no

2022-01-12 17:11:35

BMC Evol Biol. 2008 Jul 1; 8:189

PMC2453139

18593461

1471-2148-8-189-4

Figure 4 Male body reflectance, quantal catches for the different light treatments and irradiance of unfiltered light . Mean reflectance of (A I ) the background, (A II ) cheek region, (A III ) the abdominal region and (A IV ) the ventral spine of male sticklebacks. (B I -B IV ) Relative quantal catches calculated for the four stickleback cone classes (UV, S, M, L) affected by the reflectance of the experimental background and each male body region under fullspectrum illumination (Natural) and under the four treatment filters (UV-, SW-, MW-, LW-). Quantal catches are calculated relative to the excitation of the four cone types by the stimulus background under unfiltered light (C) Relative irradiance (log quantal flux) of the True Light tubes used in the experiment and visual modelling. Irradiance was measured with an Avantes AVS-USB2000 connected to an Avantes CC-UV/VIS cosine corrector located in the stimulus tank centre with filters removed. Irradiance calibration was performed versus an Avantes NIST traceable irradiance application standard.

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no

2022-01-12 17:11:35

BMC Evol Biol. 2008 Jul 1; 8:189

PMC2453140

18570671

1471-2407-8-176-1

Figure 1 Rapamycin induces growth delay of Wnt-1 tumors . Growth of Wnt-1 tumors implanted subcutaneously (S.C.) (A) or into MFP (B and C) of irradiated and bone marrow reconstituted (XRT, n = 10/group) (A and B) or naïve (no XRT, n = 5/group) mice (C). D. Summary of the effect of irradiation and bone marrow reconstitution on the growth of Wnt-1 tumors implanted subcutaneously (S.C.) or into MFP. Data are presented as tumor volume at day 60 for s.c. and at day 50 for MFP after implantation. Mice were treated with 1.5 mg/kg of Rapamycin for 30 days in s.c. groups (A and D) or 20 days in MFP groups (B, C and D) starting the day after tumor implantation (arrows). Tumor size was calculated as described in Methods.

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no

2022-01-12 14:45:40

BMC Cancer. 2008 Jun 21; 8:176

PMC2453140

18570671

1471-2407-8-176-2

Figure 2 Effect of Rapamycin on immune cells in vivo . A. Cell number in lymphoid organs of mice implanted with Wnt-1 tumor and treated with Rapamycin in vivo for 7 and 20 days (n = 5/group). B and C. Spontaneous apoptosis in splenocytes from mice treated for 7 days with Rapamycin (B) or control mice (C). D. Cytokine production by CD3/CD28 stimulated splenocytes from control and in vivo Rapamycin treated mice at days 7 and 20 post treatment.

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no

2022-01-12 14:45:40

BMC Cancer. 2008 Jun 21; 8:176

PMC2453140

18570671

1471-2407-8-176-3

Figure 3 Effects of T1Rapa cells on Wnt-1 tumor growth in vivo . A. Tumor growth in lethally irradiated and BM reconstituted mice implanted s.c. with Wnt-1 tumor cells (2 × 10 5 /mouse). T1Rapa cells (7 × 10 6 /mouse, 1:1 of CD4:CD8) were injected intravenously at day 5 or 20 after tumor implantation (shown with arrows). B. Tumor growth in lethally irradiated and BM reconstituted mice implanted with Wnt-1 tumor cells (10 5 /mouse) into MFP and treated with Rapamycin from day 0 to day 20. T1Rapamycin cells (7 × 10 6 /mouse, 1:1 of CD4:CD8) were injected intravenously at day 21 after tumor implantation (shown with an arrow).

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no

2022-01-12 14:45:40

BMC Cancer. 2008 Jun 21; 8:176

PMC2453140

18570671

1471-2407-8-176-4

Figure 4 Rapamycin inhibits Wnt-1 tumor cell proliferation . A and B. Morphology (A) and epithelial marker Ep-CAM expression (B) in primary Wnt-1 tumor cells. C and D. Proliferation of normal CD3/28 activated splenocytes (pooled from 5 mice) (C) or primary Wnt-1 cells from 3 different tumors (D). Cells were incubated with 1 μM of Rapamycin for 72 hours and proliferation was measured by 3 H-thymidine incorporation.

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no

2022-01-12 14:45:40

BMC Cancer. 2008 Jun 21; 8:176

PMC2453140

18570671

1471-2407-8-176-5

Figure 5 Effect of Rapamycin on mTOR signalling in Wnt-1 cells . A. Cells from Wnt-1 cultured for 3–4 days were trypsinyzed, seeded into flasks in complete medium and incubated overnight. Rapamycin (1 μM) was added for additional 24 hours. Western blots of cellular extracts were stained with specific antibodies to phosphorelated forms of TOR pathway messengers. B. Western blots of cell extracts from Wnt-1 cell lines, W1308 and W1204.

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no

2022-01-12 14:45:40

BMC Cancer. 2008 Jun 21; 8:176

PMC2453140

18570671

1471-2407-8-176-6

Figure 6 Rapamycin induces apoptosis of splenocytes but not Wnt-1 cells . A and B. Intact splenocytes (A) and cells from primary Wnt-1 cultures (B) were incubated with or without 1 μM Rapamycin for 24 hours, labeled with DiOC 6 and stained with annexinV-APC. Representative contour plots for splenocytes and Wnt-1 culture are shown. Apoptotic cells are gated in a square in each panel. C. Percent of apoptotic cells (mean ± SD) is shown for 5 spleens and 6 Wnt-1 cultures. D and E. Expression of Fas on Wnt-1 cells (D) or activated splenocytes (E).

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no

2022-01-12 14:45:40

BMC Cancer. 2008 Jun 21; 8:176

PMC2453140

18570671

1471-2407-8-176-7

Figure 7 Rapamycin induces cell cycle arrest in activated splenocytes, but not Wnt-1 cells . Normal spleen cells stimulated with CD3/CD28 magnetic beads or primary cultures of Wnt-1 tumor cells were incubated for 72 hours with or without 1 μM of Rapamycin. Wnt-1 cells were incubated overnight to achieve adherent state before Rapamycin addition. Average percent of cells in G1, G2, and S phases from 3 independent experiments is shown. Significant differences (p < 0.02) are indicated by the bars.

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no

2022-01-12 14:45:40

BMC Cancer. 2008 Jun 21; 8:176

PMC2453141

18588674

1471-2407-8-180-1

Figure 1 Relative increases in bone and cartilage degradation markers and ratio between these as a function of the extent of skeletal involvement assessed in 132 breast and prostate cancer patients. Relative increases are expressed as percentage of levels in patients with Soloway score 0. Asterisks indicate significant difference compared to the level at score 0.

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no

2022-01-12 14:45:40

BMC Cancer. 2008 Jun 27; 8:180

PMC2453141

18588674

1471-2407-8-180-2

Figure 2 Release of CTXI and CTXII by osteoclastic resorption of human cortical bone at day 28.

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no

2022-01-12 14:45:40

BMC Cancer. 2008 Jun 27; 8:180

PMC2453141

18588674

1471-2407-8-180-3

Figure 3 Release of CTXI and CTXII from cathepsin K treated human cortical bone.

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no

2022-01-12 14:45:40

BMC Cancer. 2008 Jun 27; 8:180

PMC2453142

18505553

1471-2105-9-248-1

Figure 1 Parameters effecting thermodynamic consensus RNA structure predictions. As a basic parameter set we used equal base frequencies of 0.25, a transition/transversion rate ratio κ = 1, and the following tree ((A:0.09,B:0.09):0.09,(C:0.09,D:0.09):0.09) One parameter was varied at a time while others were kept constant. If necessary branch lengths were adjusted to keep a mean pairwise sequence identity (MPI) of 0.75 ± 0.01. 1000 alignments of length 80 were simulated under each condition. Cumulative histograms for the RNAalifold consensus folding energies are shown. Please note that we plot negative minimum free energies, i.e. higher values correspond to more stable folds. ( A ) Base frequencies were varied to get high and low G+C content. ( B ) Two specific dinucleotide frequencies were elevated 3-fold while the mononucleotide content was kept constant. ( C ) Branch lengths were equally scaled to produce alignments with lower or higher MPI identity than for the basic tree. ( D ) The transition/transversion rate ratio was varied. κ = 1 means equal rates, while κ > 1 gives more transition than transversions. ( E ) The alignment of size 80 was divided into a central block of 40 and two anking regions of 20. We set 100% conservation in the central block and low conservation in the anks (rate "high-low-high") and the other way round ("low-high-low"). The total average MPI was always 0.75. ( F ) We tested all possible topologies of this 4 taxa tree and adjusted the branch lengths to give a MPI of 0.75. For one given topology, all the branch lengths were of the same length.

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no

2022-01-12 14:45:40

BMC Bioinformatics. 2008 May 27; 9:248

PMC2453142

18505553

1471-2105-9-248-2

Figure 2 Site dependencies for overlapping dinucleotides (red-gray): The substitution process of a given nucleotide x k at site k by another one depends on the states x k -1 , x k , x k +1 , the subsequence s k . Q k has the dimension 64 × 64, where only one mutation is allowed at the current site k . The substitution rate for the whole sequence q ( x ) is the sum of each rate q ( k ) = Q k ( s k , s k ) multiplied with a site-specific scaling factor f k , with k = 1, ..., l .

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no

2022-01-12 14:45:40

BMC Bioinformatics. 2008 May 27; 9:248

PMC2453142

18505553

1471-2105-9-248-3

Figure 3 Key concepts of the algorithm shown on an example alignment of 5.8S rRNA. ( A ) Distribution of dinucleotide frequencies of 1000 simulated alignments are shown as box-plots (the line in the box indicates the median, the borders of the box the 25th and 75th quartile, and the dotted lines 1.5× the interquartile range). Red circles show the frequencies observed in the original alignment. ( B ) Relationship between the number of substitutions and observed differences empirically determined by sampling of 25 points. Each point shows the average of 10 simulations. Note that the short distances are sampled more densely. These settings are the default values in our program and used throughout the paper. ( C ) Distribution of mean pairwise identities for 1000 random samples. The MPI of the original alignment is shown in red. ( D ) Comparison of site-wise MPIs in the original alignment and the average of the corresponding sites of 1000 random alignments.

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no

2022-01-12 14:45:40

BMC Bioinformatics. 2008 May 27; 9:248

PMC2453142

18505553

1471-2105-9-248-4

Figure 4 Overview of the algorithm. Left: The steps of the randomization procedure are shown. Right: In combination with RNAalifold consensus folding the randomization procedure can be used to calculate z -scores and to predict significant RNA structures. See text for details.

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no

2022-01-12 14:45:40

BMC Bioinformatics. 2008 May 27; 9:248

PMC2453142

18505553

1471-2105-9-248-5

Figure 5 Example of randomized alignments. Part of the example alignment used in Fig. 3 are shown. The grey bars indicate the level of local conservation. Exactly conserved sites are marked by asterisks.

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no

2022-01-12 14:45:40

BMC Bioinformatics. 2008 May 27; 9:248

PMC2453142

18505553

1471-2105-9-248-6

Figure 6 Dinucleotide frequencies of genomic alignments. 1000 vertebrate genome alignments were randomized using three different methods. The dinucleotide frequency of the native and randomized data is shown as box-plots.

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no

2022-01-12 14:45:40

BMC Bioinformatics. 2008 May 27; 9:248

PMC2453142

18505553

1471-2105-9-248-7

Figure 7 Mean pairwise identity in randomized genomic alignments. The distribution of the difference of the mean pairwise identity between the original genomic alignments and the simulated ones (dinucleotide model) is shown.

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no

2022-01-12 14:45:40

BMC Bioinformatics. 2008 May 27; 9:248

PMC2453142

18505553

1471-2105-9-248-8

Figure 8 Influence of the randomization procedure on RNA predictions. ( A ) Cumulative frequency distribution of RNAalifold consensus folding energies for the native and randomized alignments. ( B ) Cumulative frequency distribution of RNAz scores. The "decision-value" is the result of the support vector machine classification. Positive values indicate a potential functional RNA while negative values indicate no significant fold. The positive tail is magnified.

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no

2022-01-12 14:45:40

BMC Bioinformatics. 2008 May 27; 9:248

PMC2453142

18505553

1471-2105-9-248-9

Figure 9 Accuracy of z -score based classification of structured RNAs. As positive examples, alignments from eight different classes of structural RNAs were used. As negative examples, random locations from genome wide vertebrate alignments were chosen. ROC curves are shown in dependence on the null model used. In addition, the results of the RNAz support vector machine are shown. The region of high specificity which is of special interest is magnified.

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no

2022-01-12 14:45:40

BMC Bioinformatics. 2008 May 27; 9:248

PMC2453145

18538026

1471-2105-9-269-1

Figure 1 Cox-Snell residuals obtained from fitting various survival models to the Barrier data . The upper left panel shows the Cox-Snell residuals of a semiparametric Cox model vs. the Nelson-Aalen estimate of their cumulative hazard function. Estimates were obtained from fitting a Cox proportional hazards model to the Barrier data via maximization of the partial log likelihood. The 14 most differentially expressed genes between the disease and the disease-free group were used as predictor variables. The other panels show the Cox-Snell residuals (together with their cumulative hazard function) obtained from fitting various parametric AFT models to the same data via maximum likelihood estimation. Obviously, the lines corresponding to the Cox-Snell residuals of the log-logistic and lognormal models are closest to the line through the origin, indicating that these models fit the data best. By contrast, the Cox model and the Weibull model (which both assume proportional hazards) do not seem to fit the data well, indicating that the proportional hazards assumption is violated.

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no

2022-01-12 14:45:40

BMC Bioinformatics. 2008 Jun 6; 9:269

PMC2453145

18538026

1471-2105-9-269-2

Figure 2 Estimated log cumulative hazard functions obtained from fitting a stratified Cox model to the Barrier data . Estimates were obtained via maximization of the stratified partial log likelihood. The strata were generated by splitting the expression values of the most overexpressed gene in the disease group (202500_at) at their median. The remaining 13 of the 14 most differentially expressed genes were used as predictor variables in the stratified Cox model.

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no

2022-01-12 14:45:40

BMC Bioinformatics. 2008 Jun 6; 9:269

PMC2453145

18538026

1471-2105-9-269-3

Figure 3 Boxplots of the Weibull parameter estimates when 5 informative covariates are present . Boxplots of the estimates of β = (0.5, 0.25, -0.25, -0.5, 0.5) ⊤ , as obtained from the 50 Weibull-distributed samples following Model (10). Grey boxplots correspond to boosting estimates, white boxplots correspond to maximum likelihood estimates. Similar results were obtained for the log-logistic and lognormal models.

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no

2022-01-12 14:45:40

BMC Bioinformatics. 2008 Jun 6; 9:269

PMC2453145

18538026

1471-2105-9-269-4

Figure 4 Boxplots of the Weibull parameter estimates when 5 informative and 15 additional non-informative covariates are present . Boxplots of the estimates of β 1 ,..., β 20 , as obtained from the 50 Weibull-distributed samples following Model (10). Grey boxplots correspond to boosting estimates, white boxplots correspond to maximum likelihood estimates. Similar results were obtained for the log-logistic and lognormal models.

CC BY

no

2022-01-12 14:45:40

BMC Bioinformatics. 2008 Jun 6; 9:269

PMC2453145

18538026

1471-2105-9-269-5

Figure 5 Boxplots of the predictive Weibull log likelihood estimates . Boxplots of the predictive Weibull log likelihood estimates, as obtained from the 50 Weibull-distributed test samples following Model (10). The predictive log likelihood values of the null model were obtained via maximum likelihood estimation with no covariates and an intercept only. Similar results were obtained for the log-logistic and lognormal models.

CC BY

no

2022-01-12 14:45:40

BMC Bioinformatics. 2008 Jun 6; 9:269

PMC2453145

18538026

1471-2105-9-269-6

Figure 6 Analysis of the Barrier stage II colon cancer data – prediction error curves for various parametric AFT models . Prediction error curves obtained from boosting with the negative log-logistic log likelihood, boosting with the negative Weibull log likelihood, and boosting with the negative lognormal log likelihood.

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no

2022-01-12 14:45:40

BMC Bioinformatics. 2008 Jun 6; 9:269

PMC2453145

18538026

1471-2105-9-269-7

Figure 7 Analysis of the Barrier stage II colon cancer data – prediction error curves for parametric and semiparametric AFT models . Prediction error curves obtained from boosting with the negative log-logistic log likelihood, L 2 Boosting for semiparametric AFT models, and L 1 penalized estimation for semiparametric AFT models (Lasso).

CC BY

no

2022-01-12 14:45:40

BMC Bioinformatics. 2008 Jun 6; 9:269

PMC2453145

18538026

1471-2105-9-269-8

Figure 8 Analysis of the Barrier stage II colon cancer data – prediction error curves for various survival models . Prediction error curves obtained from boosting with the negative log-logistic log likelihood, boosting with the negative Cox partial log likelihood, L 1 penalized estimation of a Cox proportional hazards model (CoxPath), and nonparametric estimation via the Kaplan-Meier estimator.

CC BY

no

2022-01-12 14:45:40

BMC Bioinformatics. 2008 Jun 6; 9:269

PMC2453145

18538026

1471-2105-9-269-9

Figure 9 Analysis of the Barrier stage II colon cancer data – Cox-Snell residuals for various boosting methods . The upper left panel shows the Cox-Snell residuals of a semiparametric Cox model vs. the Nelson-Aalen estimate of their cumulative hazard function. Estimates were obtained from boosting with the negative Cox partial log likelihood. The other panels show the Cox-Snell residuals (together with their cumulative hazard function) obtained from fitting various parametric AFT models to the same data via boosting with the corresponding negative log likelihood loss. Similar to Fig. 1, we see that the line corresponding to the Cox-Snell residuals of the log-logistic model is close to the line through the origin. The Cox model does not seem to fit the data well, indicating that the proportional hazards assumption is violated.

CC BY

no

2022-01-12 14:45:40

BMC Bioinformatics. 2008 Jun 6; 9:269

PMC2453146

18577234

1742-4690-5-52-1

Figure 1 Phylogenetic tree of peptide receptors belonging to the GPCR family . The phylogenetic tree for 20 CKRs and 16 GPCRs related to CKRs was constructed by the ClustalW program [ 72 ] according to the methods described in the DDBJ website (National Institute of Genetics, Center for Information Biology and DNA Databank of Japan, ). FPRL1 is indicated by the arrow. GPCRs reported to function as HIV/SIV coreceptors are indicated by "*".

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no

2022-01-12 14:45:40

Retrovirology. 2008 Jun 25; 5:52

PMC2453146

18577234

1742-4690-5-52-2

Figure 2 Expression of GPCR mRNA in various types of human cells detected by RT-PCR . (A) Relative amount of mRNA expression for CCR5, CXCR4, FPRL1 and GPR1 in NP-2/CD4 cells expressing the coreceptors. RT-PCR was done using serially diluted (1:1, 1:10, 1:100, 1:1000, and 1:10000) cDNA reverse-transcribed from the total RNA. As a control, the expression level of GAPDH mRNA in each cDNA preparation was determined by RT-PCR. (B) mRNA expression for four GPCRs in 11 kinds of human cells as detected by RT-PCR using the specific primers. As a control, the expression level of GAPDH mRNA in each cDNA preparation was determined by RT-PCR. The PCR primers amplify 1,377 (CD4), 1,059 (CCR5 and CXCR4), 1,056 (FPRL1), 1,068 (GPR1), and 1,008 (GAPDH) base-pair DNA fragments when these genes are expressed in the cells. Expression level, (-~++) were determined by intensities of amplified DNA bands compared to those of the corresponding controls (GAPDH).

CC BY

no

2022-01-12 14:45:40

Retrovirology. 2008 Jun 25; 5:52

PMC2453146

18577234

1742-4690-5-52-3

Figure 3 Use of FPRL1, CCR5, CXCR4 or GPR1 as a coreceptor by various cell line-adapted HIV-1 strains . Cells were inoculated with nine HIV-1 strains. The susceptibilities of the cells were determined by IFA six days after viral inoculation. The coreceptor uses of these HIV-1 strains are summarized (see Additional file 2 ). NP-2/CD4 cells were also tested up to eight days after inoculation and were completely resistant to all the HIV-1 strains examined.

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2022-01-12 14:45:40

Retrovirology. 2008 Jun 25; 5:52

PMC2453146

18577234

1742-4690-5-52-4

Figure 4 Use of FPRL1, CCR5, CXCR4 or GPR1 as a coreceptor by various primary HIV-1 isolates . The susceptibilities of cells to HIV-1 isolates were determined by IFA six days after viral inoculation. NP-2/CD4 cells were completely resistant to all these HIV-1 isolates (E). The origins and subtypes of these primary isolates are summarized (see Additional file 2 ).

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2022-01-12 14:45:40

Retrovirology. 2008 Jun 25; 5:52

PMC2453146

18577234

1742-4690-5-52-5

Figure 5 The susceptibilities of NP-2/CD4/GPCR cells to HIV-1 strains . Cells were infected with two primary HIV-1 isolates, AG204 and mSTD104, and a cell line-adapted strain, Ba-L. Six days after infection, cells positive for HIV-1 antigens were detected by IFA using a fluorescence microscope. Percentage of cells judged to be positive for IFA are shown.

CC BY

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2022-01-12 14:45:40

Retrovirology. 2008 Jun 25; 5:52

PMC2453146

18577234

1742-4690-5-52-6

Figure 6 Use of FPRL1, CCR5, CXCR4 or GPR1 as a coreceptor by HIV-2 and SIV strains . The susceptibilities of cells to four HIV-2 strains and two SIV strains were determined by IFA six days after viral inoculation. NP-2/CD4 cells were completely resistant to these HIV-2 strains (E). These results are summarized (see Additional file 2 ).

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no

2022-01-12 14:45:40

Retrovirology. 2008 Jun 25; 5:52

PMC2453146

18577234

1742-4690-5-52-7

Figure 7 Effects of anti-CD4 MoAb, the fMLF peptide, and RANTES on the susceptibility of cells to HIV/SIV strains . NP-2/CD4/CCR5 (open symbols) and NP-2/CD4/FPRL1 (closed symbols) cells were pretreated with anti-CD4 MoAb Nu-TH/I (A), the fMLF peptide (B) or RANTES for two hours at 37°C (C), and then inoculated with two HIV-1 strains, GUN-7WT (○ and ●) and HCM342 (□ and ■), HIV-2 CBL23 strain (△ and ▲), and SIV mndGB-1 strain (◇ and ◆). Six days after infection, cells positive for HIV-1 antigens were detected by IFA using a fluorescence microscope.

CC BY

no

2022-01-12 14:45:40

Retrovirology. 2008 Jun 25; 5:52

PMC2453147

18559081

1476-4598-7-57-1

Figure 1 Diagram representing the rationale of CoMet . (A) The intracellular level of a metabolite X is predicted to be increased in cancer cells when enzymes that produce X are upregulated and/or enzymes that consume X are downregulated in cancer cells. (B) The intracellular level of a metabolite X is predicted to be decreased in cancer cells when enzymes that produce X are downregulated and/or enzymes that consume X are upregulated in cancer cells. See Material and Methods for a complete description of the rules.

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no

2022-01-12 14:45:40

Mol Cancer. 2008 Jun 17; 7:57

PMC2453147

18559081

1476-4598-7-57-2

Figure 2 Effect of endogenous metabolites on the proliferation of Jurkat cells . The percentage of surviving cells is given as a percentage of the number of control cells after 72 h of incubation in the presence of the tested metabolite at a concentration of 100 μmol/L. Effect of metabolites predicted to be lowered (A), increased (B) or unchanged (C) in Jurkat cells when compared with normal lymphoblasts, on the proliferation of Jurkat cells (2 biological replicates, each with 4 analytical replicates). MQ = menaquinone; HS = α-hydroxystearic acid; DE = dehydroepiandrosterone; SU = 3-sulfino-L-alanine; DM = 5,6-dimethylbenzimidazole; SE = seleno-L-methionine; RB = riboflavin; TN = tryptamine; HA = hydroxyacetone; BR = bilirubin; AT = androsterone; HV = homovanillic acid; VA = vanillylmandelic acid; AA = N-acetyl-L-aspartate; TA = taurocholic acid, CA = citric acid; PA = pantothenic acid; GA = β-D-galactose; FA = folic acid; CH = cholesterol. Error bars represent standard error of mean.

CC BY

no

2022-01-12 14:45:40

Mol Cancer. 2008 Jun 17; 7:57

PMC2453150

18629304

ehp0116-000845f1

Figure 1 Chemical formulas of phthalates.

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2022-01-12 17:58:09

Environ Health Perspect. 2008 Jul 31; 116(7):845-853

PMC2453150

18629304

ehp0116-000845f2

Figure 2 A framework for causal inference illustrating a relevant source–emission–concentration–exposure–effect pathway.

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2022-01-12 17:58:09

Environ Health Perspect. 2008 Jul 31; 116(7):845-853

PMC2453151

18629305

ehp0116-000854f1

Figure 1 Effect of Cd 2+ on cell viability and apoptosis in HEI-OC1 cells. Abbreviations: FL2, red fluorescence; M1, first mitosis; M2, second mitosis. ( A ) Viability of cells (mean ± SE) evaluated by MTT colorimetric assay as a function of Cd 2+ concentration and exposure time. ( B ) Apoptosis in cells as indicated by cell-cycle analysis. * p < 0.05 compared with untreated control cells.

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2022-01-12 17:58:09

Environ Health Perspect. 2008 Jul 26; 116(7):854-862

PMC2453151

18629305

ehp0116-000854f2

Figure 2 Effect of Cd 2+ on MMP in HEI-OC1 cells. FL1-H, green fluorescence. ( A ) MMP level measured by flow cytometry using the DiOC6 fluorescent probe; Cd 2+ incubation (20 μM) resulted in a left shift of the cell distribution, indicating reduced MMP. ( B ) Mean fluorescence intensity (± SE) of traces shown in ( A ). * p < 0.05 compared with untreated control cells.

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2022-01-12 17:58:09

Environ Health Perspect. 2008 Jul 26; 116(7):854-862

PMC2453151

18629305

ehp0116-000854f3

Figure 3 Effect of Cd 2+ on the level of ROS production in HEI-OC1 cells. FL1-H, green fluorescence. ( A ) Fluorescence measured by flow cytometry using DiOC6 in cells exposed to Cd 2+ (20 μM) for 2, 8, or 12 hr; the right shift of cell distribution to the high fluorescence area indicates an increase of ROS production. ( B ) ROS levels (mean ± SE) in cells were also measured using the DCFH-DA fluorescent probe and a spectrofluorometer; the relative fluorescence levels were measured and plotted as a function of Cd 2+ exposure time. * p < 0.05 compared with untreated control cells.

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Environ Health Perspect. 2008 Jul 26; 116(7):854-862

PMC2453151

18629305

ehp0116-000854f4

Figure 4 Effect of Cd 2+ on cyt c and ERK in HEI-COI cells and the involvement of different signaling pathways in Cd 2+ toxicity. ( A ) Protein extracts assayed for cyt c by Western blot analysis; β-actin was used as internal control in the cytosolic marker, and voltage-dependent anion channel (VDAC) was used as the mitochondrial marker. ( B ) Relative levels of cytosolic and mitochondrial cyt c quantitated by densitometry; the relative intensity of cytosolic cyt c was calculated between the band f cyt c and β-actin, and relative intensity of mitochondrial cyt c was calculated by the ratio between cyt c and VDAC. The change was Cd 2+ exposure–time dependent. ( C ) Cd 2+ -induced reduction of cell viability, evaluated by MTT colorimetric assay, was partially blocked by preadministration of inhibitors of ERK, JNK, and p38, but the ERK inhibitor was more effective than the others. ( D ) Effect of Cd 2+ on activation of ERK, showing a dose-dependent activation. Values shown are mean ± SE. * p < 0.05 compared with untreated control cells. # p < 0.05 compared with Cd 2+ alone.

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Environ Health Perspect. 2008 Jul 26; 116(7):854-862

PMC2453151

18629305

ehp0116-000854f5

Figure 5 Effect of Cd 2+ on caspase activities in HEI-COI cells. FL1-H, green fluorescence. ( A ) Cell viability, as evaluated by MTT colorimetric assay, of cells pre-treated with caspase inhibitors (2 μM) for 1 hr and then treated with Cd 2+ (20 μM) for 8 hr. ( B ) Protective effect of caspase-3 and caspase-9 inhibitors on MMP (right shift), analyzed by flow cytometry using the DiOC6 fluorescent probe. ( C ) Western blot analysis of procaspase-3 and procaspase-9 after Cd 2+ exposure in a dose-dependent manner. ( D ) Relative levels of the procaspase-3 and procaspase-9 quantitated by densitometry as a function of Cd 2+ concentration. ( E ) Activities of caspase-3, caspase-8, and caspase-9 as a function of Cd 2+ concentration, determined using a colorimetric kit. Values shown are mean ± SE. * p < 0.05 compared with untreated control cells. # p < 0.05 compared with Cd 2+ alone.

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Environ Health Perspect. 2008 Jul 26; 116(7):854-862

PMC2453151

18629305

ehp0116-000854f6

Figure 6 Effect of antioxidants (50 μM NAC or 20 μM ebselen) on the toxic effect of Cd 2+ (20 μM) in HEI-COI cells. Abbreviations: FL1, green fluorescence; FL2, red fluorescence; M1, first mitosis; M2, second mitosis. ( A ) Cell viability, determined by MTT colorimetric assay and flow cytometry, after exposure to Cd 2+ (20 μM) or Cd 2+ plus antioxidant. ( B ) Change in MMP level shown by flow cytometry; note the increase of MMP in cells treated with Cd 2+ plus antioxidant compared with those treated with Cd 2+ alone. ( C ) Effect of antioxidants on caspase-9 activation by Cd 2+ exposure. ( D, E ) Effect of antioxidants on Cd 2+ -induced reduction of procaspase-9 shown by Western blot analysis ( D ) and relative intensity; NAC appears to have more protective effect on Cd 2+ toxicity than does ebselen. ( F ) Effect of NAC on Cd 2+ -induced ERK activation. Values shown are mean ± SE. # p < 0.05 compared with Cd 2+ alone.

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Environ Health Perspect. 2008 Jul 26; 116(7):854-862

PMC2453151

18629305

ehp0116-000854f7

Figure 7 Toxic effect of Cd 2+ on explants of rat organ of Corti. ( A ) TRITC-conjugated phalloidin (red) and TUNEL (green) staining in organ of Corti explants from rats. Bar = 50 μm. ( B ) Percentage of apoptotic cells (mean ± SE) presented as a function of Cd 2+ exposure time. Cells were counted from five fields per well (×100) using optical microscopy. * p < 0.05.

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Environ Health Perspect. 2008 Jul 26; 116(7):854-862

PMC2453151

18629305

ehp0116-000854f8

Figure 8 NAC protection against Cd 2+ damage in sections of cochlear explants from rats. ( A ) Sections of explants from apical, middle, and basal turns of rat cochlea incubated with Cd 2+ alone or Cd 2+ + NAC and stained with TRITC-conjugated phalloidin. NAC treatment showed a protective effect against the Cd 2+ toxic effect. ( B ) Sections of basal turns of cochlea explants stained with TRITC-conjugated phalloidin (red), DAPI (blue), and TUNEL (green) and examined at a magnification of 100×. In ( A ) and ( B ), bar = 50 μm. ( C ) Percentages of TUNEL-positive cells in different groups of cells. * p < 0.05 compared with untreated control explants. # p < 0.05 compared with Cd 2+ alone.

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Environ Health Perspect. 2008 Jul 26; 116(7):854-862

PMC2453151

18629305

ehp0116-000854f9

Figure 9 Effect of Cd 2+ exposure on activation of ERK in mouse cochlea and the protective effect of NAC. ( A ) Western blot analysis showing the effect of Cd 2+ exposure on p-ERK and the effect of NAC on ERK activation. ( B ) Immunohistochemical staining for p-ERK of outer hair cells and inner hair cells in the organ of Corti. ( C ) Fluorescence micrographs of cochlear sections stained for anti-p-ERK, showing Cd 2+ -induced activation of ERK in the organ of Corti, the stria vascularis, and the limbus in mice cochlea [DAPI (blue) and p-ERK (green)]. ( D ) Immunohistochemical staining for p-ERK (green) and DAPI (blue) in the rat cochlear explants treated with Cd 2+ (10 μM) for 4 hr showing positive staining of p-ERK; Cd 2+ -activated ERK was blocked with pretreatment with NAC (50 μM for 1 hr). Bars in ( B ) and ( C ) = 10 μm; bar in ( D ) = 50 μm. * p < 0.05 compared with untreated controls. # p < 0.05 compared with Cd 2+ alone.

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Environ Health Perspect. 2008 Jul 26; 116(7):854-862

PMC2453151

18629305

ehp0116-000854f10

Figure 10 ABR thresholds (mean ± SE) showing effects of Cd 2+ -induced shift at 32 kHz and protective effect of NAC. * p < 0.05 compared with the untreated control.

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2022-01-12 17:58:09

Environ Health Perspect. 2008 Jul 26; 116(7):854-862

PMC2453152

18629306

ehp0116-000863f1

Figure 1 Measured diesel engine emission and on-road aerosol particle size distributions. ISO, data from International Standards Organization (2001) . D p , particle diameter; N, normalized particle concentration in size bin ΔlogD p ; N T , normalized particle total concentration.

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2022-01-12 17:58:09

Environ Health Perspect. 2008 Jul 26; 116(7):863-866

PMC2453152

18629306

ehp0116-000863f2

Figure 2 Measured in-cabin particle number concentration with time for a Toyota Camry and a Saab 93 while driving in heavy traffic, with the air ventilation system in recirculation mode. Dotted lines, experimental data. Solid lines, data fit using the developed empirical model. For comparison, the aerosol particle number concentration measured in a typical office is shown (4,000 particles/cm 3 ).

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2022-01-12 17:58:09

Environ Health Perspect. 2008 Jul 26; 116(7):863-866

PMC2453152

18629306

ehp0116-000863f3

Figure 3 Measured variations in particle size distribution inside a Toyota Camry, with the air ventilation system in recirculation mode and the air filter in place. D p , particle diameter; N, particle number concentration in size bin ΔlogD p .

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2022-01-12 17:58:09

Environ Health Perspect. 2008 Jul 26; 116(7):863-866

PMC2453152

18629306

ehp0116-000863f4

Figure 4 Measured particle number concentration in an enclosed room containing a source of silver nanoparticles with time, while recirculating air through an HVAC filter at 50,970 L/min. Dotted lines, experimental data. Solid lines, data fit using the developed empirical model. For comparison, the aerosol particle number concentration measured in a typical office is shown (4,000 particles/cm 3 ).

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2022-01-12 17:58:09

Environ Health Perspect. 2008 Jul 26; 116(7):863-866

PMC2453153

18629307

ehp0116-000867f1

Figure 1 3-D serial section reconstruction of accessory reproductive organs in male PND1 Long Evans rats after systemic and developmental in utero exposure to 7.0 mg/kg bw 4-MBC. Abbreviations: DT, distal tip; PD, proximal duct, VMP, ventral mesenchymal pad. ( A ) Right lateral view of the surface-rendered anatomical reconstruction of the UGS and ASG structures in a control male. Individual structures are identified by color. ( B ) Reconstruction of the right lateral and cranial views of the UGS from a 4-MBC–treated male and untreated control male illustrating the significant regional growth differences in ducts of the caudal dorsal prostate and branching morphogenesis development in the ventral region. ( C ) Additional anatomical views of the prostatic ducts of a control male and a 4-MBC treated male showing the regional growth patterns. ( D ) Representative histological views of distal-tip budding in the ventral prostate region. Initial bifurcation is the primary feature of the control male, whereas extensive secondary branching morphogenesis has occurred in the 4-MBC–treated male (stained with hematoxylin and eosin; bar = 100 μm). ( E ) Anatomical view of the UGS, ventral ducts, and VMP showing that the distal tips of the ducts in the control male have made initial contact with the VMP. In the 4-MBC–treated male, the distal tips have penetrated the mesenchymal tissue and undergone later stages of branching morphogenesis. ( F ) Lateral and dorsal view of the UGS. Shape of the UGS (gray arrow) and bladder neck region of the urethra (black arrow) are changed in the 4-MBC–treated male.

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Environ Health Perspect. 2008 Jul 25; 116(7):867-872

PMC2453153

18629307

ehp0116-000867f2

Figure 2 Comparative volume analyses of individual and combined regions of the ASGs in PND1 males after prenatal exposure to various doses of UV filter compounds. Significant effects were observed only in the 7.0 mg/kg bw–treated males. Values shown are mean ± SE ( n = 4 for all groups). * p < 0.05, ** p < 0.01, # p < 0.005, and ## p < 0.001 compared with control males.

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Environ Health Perspect. 2008 Jul 25; 116(7):867-872

PMC2453153

18629307

ehp0116-000867f3

Figure 3 Comparative volume analyses of specific regions of the developing prostate in PND1 males after prenatal exposure to various doses of UV filter compounds. Significant effects were observed only in the dorsal and ventral regions of the 7.0 mg/kg bw–treated males. Values shown are mean ± SE ( n = 4 for all groups). * p < 0.05, and ** p < 0.01 compared with control males.

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2022-01-12 17:58:09

Environ Health Perspect. 2008 Jul 25; 116(7):867-872

PMC2453153

18629307

ehp0116-000867f4

Figure 4 Effects of prenatal exposure to UV filter compounds on prostate duct development in PND1 males. A significant increase in the number of developing ducts was observed in the combined dorsolateral prostate region (DLP). This increase was due specifically to an increase in the number of ducts in the caudal region of the dorsal prostate. Values shown are mean ± SE ( n = 4 for all groups). * p < 0.05 compared with control males.

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2022-01-12 17:58:09

Environ Health Perspect. 2008 Jul 25; 116(7):867-872

PMC2453153

18629307

ehp0116-000867f5

Figure 5 Effect of prenatal exposure to 4-MBC (7.0 mg/kg bw) on VMP tissue volume in PND1 males. Values shown are mean ± SE ( n = 4 for all groups). * p < 0.05 compared with control males.

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2022-01-12 17:58:09

Environ Health Perspect. 2008 Jul 25; 116(7):867-872

PMC2453154

18629308

ehp0116-000873f1

Figure 1 Dose-dependent effects of iAs on the expression of K16 in HaCaT cells maintained in serum-free medium for 24 hr and then treated with iAs at various concentrations for 6 or 24 hr ( A ) or 6, 10, or 24 hr ( B ). Con, control. ( A ) After iAs treatment, total RNA was extracted from the cells, and 1-μg aliquots were amplified by semiquantitative RT-PCR using K16 primers; GAPDH was amplified as an internal control. ( B ) Equal amounts of total protein extracts from the cells were subjected to Western blot analysis for K16; β-actin expression was analyzed as a loading control.

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2022-01-12 17:58:09

Environ Health Perspect. 2008 Jul 12; 116(7):873-879

PMC2453154

18629308

ehp0116-000873f2

Figure 2 Response of the K16 regulatory region to iAs using a luciferase reporter gene assay, with relative luciferase activities normalized for pRL-CMV activity and calculated as a percentage of the promoter activity in HaCaT cells without iAs exposure (control). Abbreviations: +, presence; –, absence; Con, control. ( A ) Transcriptional activation of K16 gene by iAs (left) and the luciferase reporter gene construct harboring the –515-bp K16 gene promoter region (pXK-1; right). ( B ) Luciferase activity of the iAs responsive region in the K16 gene promoter in cells cotransfected with individual reporter constructs harboring various deletions of the 5′-flanking region of the K16 gene promoter (left) and normalized for pRL-CMV, and the luciferase reporter gene constructs for individual promoter regions (right). See “Materials and Methods” for details of experiments. The values shown indicate the ratio of the luciferase activities in untreated cells and in cells treated with 20 μM iAs for 6 hr; luciferase activity with no treatment was defined as 100%. Values represent the mean ± SD of five to eight independent experiments, each run in triplicate. Each p -value was obtained by t -test following logarithmic transformation of normalized values. * p < 0.01, and ** p < 0.001 compared with the untreated group.

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2022-01-12 17:58:09

Environ Health Perspect. 2008 Jul 12; 116(7):873-879

PMC2453154

18629308

ehp0116-000873f3

Figure 3 Effects of iAs on the expression of AP-1 transcription factors in HaCaT cells maintained in serum-free medium for 24 hr and then treated with iAs. Con, control. ( A ) Expression of c- Jun , c- Fos , and GAPDH genes examined by semiquantitative RT-PCR at 6 and 24 hr; GAPDH gene expression was analyzed as a loading control. ( B ) Western blot analysis of nuclear extracts from cells 6, 10, or 24 hr after iAs treatment using c-Jun and β-actin antibodies. Equal protein loading was confirmed by β-actin expression. Results were obtained from three independent experiments.

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2022-01-12 17:58:09

Environ Health Perspect. 2008 Jul 12; 116(7):873-879

PMC2453154

18629308

ehp0116-000873f4

Figure 4 iAs potently stimulates the ARE and induces production and translocation of NRF2 into the nucleus of HaCaT cells. Abbreviations: +, presence; –, absence; Con, control. ( A ) Effect of iAs on ARE-driven promoter activity determined using cotransfection of the p3xARE/Luc reporter gene construct (shown schematically in the lower panel), containing three copies of the ARE, into HaCaT cells with the pRL-TK vector encoding Renilla luciferase. See “Materials and Methods” for details. Values shown indicate the ratio of the luciferase activities in untreated cells and in cells treated with 20 μM iAs for 6 hr; luciferase activity with no treatment was defined as 100%. Values represent the mean ± SD of three independent experiments, each run in triplicate. ( B ) Results of EMSA analyses performed using iAs-stimulated nuclear extracts and a biotinylated consensus ARE probe. The arrow indicates the consensus ARE probe-nuclear protein band shifts; an unlabeled consensus ARE probe was used as a competitor oligo. ( C ) EMSA of nuclear extracts prepared from cells treated with iAs for 6 hr using a biotinylated WT-K16ARE probe (5′-GGGGAACCT GGAGTCAGC AGTTAGGA-3′, with the wild-type ARE sequence found in the K16 promoter from –157 to –132 bp underlined). An unlabeled WT-K16ARE probe was used as a competitor. To determine the binding specificity of ARE, an unlabeled AP-1 oligonucleotide was added to the iAs-treated nuclear extracts before the addition of the labeled WT-K16ARE probe. The arrow indicates shifted K16ARE-nuclear protein complexes. ( D ) Nuclear accumulation of NRF2 stimulated by iAs in HaCaT cells maintained in serum-free medium for 24 hr and then treated with iAs for 3 or 6 hr. Cytoplasmic and nuclear extracts were then prepared and subjected to Western blot analysis using polyclonal NRF2 antibodies; results shown represent three independent experiments. ( E ) Regulation of the ARE site within the K16 gene promoter after iAs treatment. The WT-K16ARE probe was incubated with nuclear extracts prepared from cells cultured in the absence (–) or presence (+) of 20 μM iAs for 6 hr. For supershift EMSA analysis, the nuclear extracts were incubated with either an anti-NRF2 or anti-c-Jun antibody before the addition of labeled probe. The binding specificity was confirmed by the addition of excess unlabeled WT-K16ARE probe. The arrow indicates shifted complexes, and double arrowheads indicate supershifted K16ARE-NRF2 complexes. ( F ) In a similar experiment to the one shown in ( E ), either a WT-K16ARE or Mut-K16ARE probe was incubated with nuclear extracts of cells cultured in the presence of 20 μM iAs for 6 hr. The GC box of Mut-K16ARE was substituted with AA as indicated. Anti-NRF2 antibody was used in the supershift assays. The arrows and double arrowheads indicate shifted and supershifted complexes, respectively. a Nonspecific band.

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Environ Health Perspect. 2008 Jul 12; 116(7):873-879

PMC2453154

18629308

ehp0116-000873f5

Figure 5 iAs enhances the stability of the NRF2 protein. Abbreviations: +, presence; –, absence; Con, control. ( A ) Expression levels of KEAP1 and GAPDH mRNA determined by semiquantitative RT-PCR in HaCaT cells cultured in serum-free medium for 24 hr and then treated with iAs for 3 or 6 hr (upper panels); cytoplasmic extracts from iAs-treated cells were subjected to Western blot analysis for KEAP1 and β-actin (lower panels). ( B ) Posttranscriptional regulation of both the steady-state level and half-life of NRF2 protein shown by Western blot analysis (see “Materials and Methods” for details). β-Actin was used as an internal control. Similar results were obtained from three independent experiments.

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Environ Health Perspect. 2008 Jul 12; 116(7):873-879

PMC2453154

18629308

ehp0116-000873f6

Figure 6 NRF2 directly induces the K16 gene in HaCaT cells. Abbreviations: +, presence; –, absence; Con, control. ( A ) Cells were transiently transfected with empty vector pcDNA3.1 (control) or expression vector WT-NRF2 as described in “Materials and Methods,” and the expression of TXN , K16 , and GAPDH was examined by semiquantitative RT-PCR using GAPDH expression levels as an internal control. ( B ) Cells were transfected with WT-NRF2, together with the pXK-5–1 and the Renilla luciferase vector pRL-TK (the pXK-5-1 luciferase vector is shown schematically in the lower panel). Transfected cells were incubated for 48 hr and then analyzed for luciferase activity as described in “Materials and Methods.” Luciferase activity in cells transfected with pcDNA3.1 was set as 100%. The values represent the mean ± SD of four independent transfection experiments, each run in triplicate. We obtained p -values by t -tests following logarithmic transformation of normalized values. ** p < 0.01 compared with the control group (pcDNA3.1).

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Environ Health Perspect. 2008 Jul 12; 116(7):873-879

PMC2453157

18629311

ehp0116-000893f1

Figure 1 LSGM concentrations of BP-3 (in micrograms per liter) by age and race/ethnicity: ( A ) children and adolescents and ( B ) adults. Error bars indicate 95% CIs.

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Environ Health Perspect. 2008 Jul 21; 116(7):893-897

PMC2453158

18629312

ehp0116-000898f1

Figure 1 Relationships of biomarkers of inflammation to outdoor air pollutants (adjusted coefficient and 95% CI). ( A ) CRP (ng/mL). ( B ) IL-6 (pg/mL). ( C ) sTNF-RII (pg/mL). Expected change in the biomarker corresponds to an interquartile range change in the air pollutant ( Table 3 ). Abbreviations: ave, average; Est coef, estimated coefficient.

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Environ Health Perspect. 2008 Jul 26; 116(7):898-906

PMC2453158

18629312

ehp0116-000898f2

Figure 2 Relationships of biomarkers of inflammation to indoor air pollutants (adjusted coefficient and 95% CI). ( A ) CRP (ng/mL). ( B ) IL-6 (pg/mL). ( C ) sTNF-RII (pg/mL). Abbreviations: ave, average; Est coef, estimated coefficient; o_o, indoor concentrations of outdoor origin. Expected change in the biomarker corresponds to an interquartile range change in the air pollutant ( Table 3 ).

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Environ Health Perspect. 2008 Jul 26; 116(7):898-906

PMC2453158

18629312

ehp0116-000898f3

Figure 3 Relationship of sP-selectin to outdoor and indoor air pollutants (adjusted coefficient and 95% CI). ( A ) Outdoor air pollutants. ( B ) Indoor air pollutants. Abbreviations: ave, average; Est coef, estimated coefficient; o_o, indoor concentrations of outdoor origin. Expected change in sP-selectin (ng/mL) corresponds to an interquartile range change in the air pollutant ( Table 3 ).

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Environ Health Perspect. 2008 Jul 26; 116(7):898-906

PMC2453158

18629312

ehp0116-000898f4

Figure 4 Relationship of Cu,Zn-SOD to outdoor and indoor air pollutants (adjusted coefficient and 95% CI). ( A ) Outdoor air pollutants. ( B ) Indoor air pollutants. o_o, indoor concentrations of outdoor origin; Est Coef, estimated coefficient. Expected change in Cu,Zn-SOD (U/g Hb) corresponds to an interquartile range change in the air pollutant ( Table 3 ).

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Environ Health Perspect. 2008 Jul 26; 116(7):898-906

PMC2453159

18629313

ehp0116-000907f1

Figure 1 Map of study area showing Shenyang City (green circle), the capital of Liaoning Province (blue), China. Arrows note the approximate locations of the urban households (in Shenyang city) and rural households (in Liaozhong County). Liaozhong County is approximately 69 km southwest of Shenyang City.

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2022-01-12 17:58:09

Environ Health Perspect. 2008 Jul 24; 116(7):907-914

PMC2453159

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Figure 2 Study participant with the personal monitor in a rural setting: using biomass to fuel the stove ( A ) and cooking ( B ).

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Environ Health Perspect. 2008 Jul 24; 116(7):907-914

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Figure 3 Box plots of hourly measurements from PM 10 stationary monitors (mg/m 3 ). SRM, sitting room. An outlier value for urban kitchen 1 took place during indoor construction.

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Environ Health Perspect. 2008 Jul 24; 116(7):907-914

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Figure 4 Time–activity budgets of three rural cooks ( A ), two rural noncooks ( B ), three urban cooks ( C ), and two urban noncooks ( D ).

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Environ Health Perspect. 2008 Jul 24; 116(7):907-914

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Figure 5 Variations of personal PM 2.5 in a rural cook, based on second-by-second concentrations. Horizontal lines reflect the average for each cooking period.

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Figure 1 Effect of QDs on cell death in cultured control and QD-treated hippocampal neurons. ( A ) Cell viability measured by MTT assay; data represent mean ± SE of three independent experiments. ( B ) Percentage of surviving neurons (mean ± SE) evaluated using the DAPI staining method. * p < 0.05 compared with control.

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Environ Health Perspect. 2008 Jul 31; 116(7):915-922

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Figure 2 Effect of QD exposure on sustained elevation of cytoplasmic calcium concentration in cultured control QD-treated hippocampal neurons. In each experiment, the images were obtained under calcium fluorescence before QD exposure ( A1 – D1 ) and 5 min after QD exposure ( A2–D2 ); bar = 20 μM. ( E ) Traces show mean ± SE of calcium fluorescence ratios (ΔF/F 0 ) before and after QD exposure; 10 nM and 20 nM QD exposure significantly elevated calcium fluorescence.

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Environ Health Perspect. 2008 Jul 31; 116(7):915-922

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Figure 3 Extracellular calcium influx and internal calcium release involvement in QD-induced elevation of cytoplasmic calcium concentration in cultured hippocampal neurons. Images [( A ; control) and ( B; calcium free); ( C ; control) and ( D; thapsigargin); ( E ; control) and ( F ; calcium free and thapsigargin)] were obtained under calcium fluorescence before QD exposure ( A1 – F1 ) and 5 min after 10 nM QD exposure ( A2 – F2 ). See “Materials and Methods” for details; bar = 20 μM. ( G–J ) Effect of 10 nM QD exposure on calcium fluorescence (ΔF/F 0 ratio; mean ± SE) in ( G ) calcium-free external solutions, ( H ) thapsigargin-preincubated external solutions, ( I ) thapsigargin-preincubated calcium-free external solutions, and ( J ) standard external solutions, calcium-free external solutions, thapsigargin-preincubated external solutions, and thapsigargin-preincubated calcium-free external solutions.

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Environ Health Perspect. 2008 Jul 31; 116(7):915-922

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Figure 4 Effects of QDs on I Na activation in cultured control and QD-treated hippocampal neurons. ( A ) Representative traces of activation of I Na in control and 10nM QDs (I Na was activated by a series of 50-msec voltage steps between −70 and +30 mV from the holding potential −80 mV; the increment was 10 mV except from −60 to −30 mV, where the increment was 5 mV). ( B ) Current-voltage relationships of I Na in control, 1 nM QDs, 10 nM QDs, and 20 nM QDs ( n = 8 per group); current amplitudes were normalized to the maximal I Na peak value of each group. ( C ) Steady-state activation of I Na in control, 1 nM QDs, 10 nM QDs, and 20 nM QDs ( n = 8 per group). I Na peak current values (I) were transformed into conductances (G) according to the equation G = I/(V m −V rev ), where V rev is the Na + reversal potential and V m is the membrane potential at which the current was recorded. The reversal potentials (V rev ) were calculated from the crossing between the prolongation of the current-voltage curves and the horizontal axis: 55.7, 53.3, 54.3, and 56.5 mV, respectively, for control, 1 nM, 10 nM, and 20 nM QDs (not shown). Normalized peak conductances (G/G max ) were fitted with a Boltzmann function G/G max = {1+exp[(V 1/2 −V m )/V c ]} −1 , where G max is the maximal conductance; V m is the command voltage; V 1/2 is the potential of half-maximal activation; and V c is proportional to the slope at V 1/2 .

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Environ Health Perspect. 2008 Jul 31; 116(7):915-922

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Figure 5 Effect of QDs on time course of I Na in control QD-treated hippocampal neurons ( n = 8 per group). ( A ) Time to peak of I Na against the command voltage. ( B ) Time to peak at the command voltage of −30 mV plotted into histograms. ( C ) Time constants of fitted I Na decay plotted into histograms. Insets are representative traces of I Na , whose decay phases were fitted with a single exponential function. * p < 0.05 compared with control.

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Figure 6 Effects of QDs on I Na steady-state inactivation in cultured control and QD-treated hippocampal neurons. ( A ) Representative traces of steady-state inactivation of I Na with 250-msec conditioning prepulses stepped from −120 to −30 mV and the membrane potential depolarized to a fixed test pulse of −30 mV to evoke inward I Na . ( B ) Normalized currents (I/I max ) plotted against the voltages of conditioning pulses ( n = 8) and fitted with a Boltzmann function I/I max = {1+exp[(V 1/2 –V m )/V c ]} −1 , where I max is the maximal current, V m is the conditioning voltage, V 1/2 is the potential of half-maximal inactivation, and V c is proportional to the slope at V 1/2 .

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Environ Health Perspect. 2008 Jul 31; 116(7):915-922

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Figure 7 Effect of QDs on I Na recovery in cultured control and QD-treated hippocampal neurons. ( A ) Representative traces of I Na recovery. After a 30-msec conditioning pulse from the holding potential of −80 mV to −30 mV and a various interpulse interval of −80 mV ranging from 2 msec to 100 msec, a test pulse to −30 mV was subsequently applied. ( B ) Percentage of peak current recovery (I 2 /I 1 ) against the time course of the interpulse interval ( n = 8). The curves were well fitted with a single exponential function.

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Environ Health Perspect. 2008 Jul 31; 116(7):915-922

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Figure 8 Effects of QDs on I Na fraction of activated channels in cultured control and QD-treated hippocampal neurons. ( A ) Representative traces in control and 10 nM QDs; a conditioning pulse of various duration from 20 to 120 msec was first applied to modulate the level of Na + channel inactivation and was followed by a 30-msec interval and subsequent test pulse. ( B ) Plots I 2 /I 1 against the duration of the conditioning pulse ( n = 8).

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Environ Health Perspect. 2008 Jul 31; 116(7):915-922