Time kinetic of body weight and food intake in wild-type versus mdr1ab^-/- mice.

<p>The weights were recorded weekly from weaning to 35-weeks of age for male (Fig. 1A) or female (Fig. 1B) wild-type (open symbols) and mdr1ab^-/- (close symbols) mice fed a standard chow diet. Results are means ± s.e.m of 5 to 10 animals. Differences are considered significant when *, <i>p</i><0.05; **, <i>p</i><0.01; ***, <i>p</i><0.001. Daily food intakes of males (Fig. 1C) and females (Fig. 1D) were calculated weekly by monitoring the total food consumption for wild-type (open symbols) and mdr1ab^-/- (close symbols) mice, measured as mean food consumption for two to three mice caged together. Results are expressed per gram of body weight and are the means of 3 values per subgroup.</p

Influence of high fat diet (HFD) on hepatic triglyceride concentrations in wild-type and mdr1ab^-/- mice.

<p>Mice were fed with HFD during 25 weeks. Triglycerides have been quantified in liver samples from 15- or 25-week old wild-type (open bars) and mdr1ab^-/- (solid bars) mice. Results are expressed as nmol per mg of liver and are means ± s.e.m of 3 values at 15-week old and 5 at 25-week old. Differences are considered significant when *, <i>p</i><0.05; **, <i>p</i><0.01.</p

Morphological comparison and liver lipid content in wild type and mdr1ab^-/- males.

<p>2A. Whole body. 2B. Respective livers at 35 weeks of age. 2C. Oil red O staining of liver sections. Livers were collected from 25- or 35-week old mice and kept frozen in OCT at −80°C until analysis. 2D. Lipid content of liver. Total cholesterol (upper histogram) and triglycerides (lower histogram) in liquid-frozen liver samples from 25- and 35- week old mice, were quantified by liquid chromatography in wild-type (open bars) and mdr1ab^-/- (solid bars) males. Results are expressed as means ± s.e.m of 5 to 7 mice. Differences are considered significant when <i>p<</i>0.05. ***, <i>p</i><0.001.</p

Analysis of lipids and xenobiotics target genes expression in the liver.

<p>Relative gene expressions of <i>scd-1</i>, <i>fasn</i>, <i>cd36</i>, <i>acox</i>, <i>cyp2B10</i> and <i>cyp3A11</i> were quantified in liver samples from 12-week old (Fig. 5A) and 25-week old (Fig. 5B) mice by real-time time PCR. Similarly, <i>scd-1, cyp7a1</i> and <i>pltp</i> expressions were quantified in 35-week old mice (Fig. 5C); wild-type (open bars) and mdr1ab-/- (solid bars). Values were normalized to TBP gene and expressed as arbitrary unit. Values shown are means ± s.e.m (n = 3). Differences are considered significant when <i>p</i><0.05. *, <i>p</i><0.05; **, <i>p</i><0.01; ***, <i>p</i><0.001.</p

Liver and adipose tissue contributions to the body weight in wild-type versus mdr1ab^-/- mice.

<p>Mice were sacrificed at 25 and 35 weeks of age and discrete fat pads from five anatomical sites were dissected and weighed. WAT refers to white adipose tissue. Total WAT weight represents the sum of the data reported for the four WAT sites considered in the study. Body weight is expressed in gram and tissue weights are expressed as percentage of body weight. F is the ratio of mdr1ab^-/- versus wild-type. Results are means ± s.e.m. Statistical relevance of data is assessed by <i>p</i> values.</p>a<p><i>p</i><0.05;</p>b<p><i>p</i><0.01.</p

Lipid content in bile of wild-type and mdr1ab^-/- mice.

<p>Cholesterol and bile acids were quantified in bile in wild-type (open bars) and mdr1ab^-/- (solid bars) 35-week old male mice. Results are expressed as means ± s.e.m of 5 mice. Differences are considered significant when *, <i>p</i><0.05; **, <i>p</i><0.01; ***, <i>p</i><0.001.</p

Plateau spectra for the three volcanic centers dated.

<p>Uncertainties are given at the 2σ level. Plateau steps are plotted at the 1σ level.</p

The Chauvet-Pont d’Arc cave and the Bas-Vivarais volcanic field.

<p>(A) Digital elevation model of France (Courtesy NASA/JPL-Caltech) showing the MIS 2–3 active volcanoes and the Chauvet-Pont d’Arc cave; C.P: Chaîne de Puys; B.V: Bas-Vivarais. (B) Digital elevation model of the Bas-Vivarais and Ardèche (Courtesy NASA/JPL-Caltech). The volcanic centers investigated are highlighted in bold italic fonts. (C) Detail of the spray-shape sign engraving from the Megaloceros panel. (D) View from the plateau above the Chauvet-Pont d’Arc cave showing several strombolian cones located 35 km Northwest (Courtesy NASA/JPL-Caltech).</p

Volcanic centers ⁴⁰Ar/³⁹Ar ages and spray-shape sign TL and ¹⁴C AMS dates.

<p>In red: ⁴⁰Ar/³⁹Ar ages of the three volcanic centers studied; blue: TL age on reddened limestone in the Megaloceros Gallery [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0146621#pone.0146621.ref026" target="_blank">26</a>]; ¹⁴C AMS dates correspond to the first occupation of the Megaloceros Gallery in the Chauvet-Pont d’Arc cave [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0146621#pone.0146621.ref005" target="_blank">5</a>]. The ¹⁴C AMS in green corresponds to the date obtained for the sample taken from the rump of the Megaloceros [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0146621#pone.0146621.ref008" target="_blank">8</a>]. Uncertainties are reported at the 2σ level excluding TL age where uncertainty is an estimated standard deviation [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0146621#pone.0146621.ref026" target="_blank">26</a>].</p

Example of a spray-shape sign from Chauvet-Pont d’Arc cave compared to the oldest known depictions of volcanic eruptions.

<p>(A) Map of the Chauvet-Pont d’Arc cave. (B) General view of the Megaloceros panel. The green dot marks the location of the ¹⁴C AMS date [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0146621#pone.0146621.ref008" target="_blank">8</a>] (picture credit D. Genty). (C) Detail of the Megaloceros panel chronological succession [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0146621#pone.0146621.ref008" target="_blank">8</a>] (pictures credit V. Feruglio-D. Baffier). (D) Petroglyphs depicting the Porak volcano eruption and dated from the 5^th millennium BC in the Syunik region of Armenia [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0146621#pone.0146621.ref003" target="_blank">3</a>]. The figure is similar to [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0146621#pone.0146621.ref003" target="_blank">3</a>] but not identical to the original image, and is therefore for illustrative purposes only. (E) Çatalhöyük mural painting (Turkey) considered the oldest depiction of a volcanic eruption dated from the 8^th/7^th millennium BC [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0146621#pone.0146621.ref001" target="_blank">1</a>].</p