Urinary pyrophosphate concentration is inversely associated with renal mineralization size in a combined bivariate linear regression analysis of all mice.

<p>All experimental WT and mutant mice from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0180098#pone.0180098.g002" target="_blank">Fig 2</a> (n = 28) for which urine was available were evaluated using linear regression analysis to determine the association of renal mineralization with the urine pyrophosphate concentration (U-PPi) (% calcified area = 100*calcified area/total area <b>A</b> and calcification size = calcified area/number of mineralization <b>B</b>). Data points represent values of individual animals. Results of the linear regression analysis are shown as solid line with 95% confidence interval (stippled lines), R² and p-values.</p

Shifting education’s philosophical imaginaries: relations, affects, bodies, materialities

As Michèle Le Doeuff pointed out in her classic feminist work, The Philosophical Imaginary, images function in philosophical writing to enact certain political and theoretical possibilities and limitations. She draws our attention to the relationship between images and concepts throughout the history of philosophy, and philosophy’s forgetting and occlusion of its own imaginaries. We wonder with Le Doeuff about the image that philosophy gives to itself of what it is to do philosophy. So too we wonder about the images that orient and inflect both educational practice and research. What images do educational researchers give to themselves of education, the practice of education and of research in education? This issue examines the ways in which diverse educational imaginaries operate. It thinks from and with recent feminist work in both philosophy and education

Urine PPi concentration and renal gene expression in <i>Npt2a</i>^<i>-/-</i> mice.

<p>Urine pyrophosphate concentration (U-PPi, <b>A</b>) following an overnight fast and renal gene expression as indicated on the y-axis for <i>ectonucleotide pyrophosphatase/phosphodiesterase 1</i> (<i>Enpp1</i>, <b>B</b>), <i>progressive ankylosis</i> (<i>Ank</i>, <b>C</b>), <i>ectonucleoside triphosphate diphosphohydrolase 5</i> (<i>Entpd5</i>, <b>D</b>), <i>tissue nonspecific alkaline phosphatase</i> (<i>Tnsalp</i>, <b>E</b><i>)</i> in mice fed regular chow for 10 weeks. The data represent mean±SEM of 4–19 mice, p-values shown above the lines of comparisons were calculated by one-way ANOVA using Tukey’s adjustment for multiple comparisons (<b>A</b>) and Student’s t-test (<b>B-E</b>).</p

Intraperitoneal injection of Na-pyrophosphate reduces cortical and medulary renal mineralization in <i>Npt2a</i>^<i>-/-</i> mice.

<p>Light micrographs of 10 um renal sections prepared from paraffin-embedded kidneys, obtained from mice with various genotypes fed regular chow for 10 weeks (<b>A, upper panels:</b> von Kossa, methylene green staining, 4X, and <b>A, lower panels:</b> von Kossa, hematoxylin and eosin staining, 40X); Transmission electron micrographs showing microspheres in double mutant mice on regular chow, inset with larger magnification shown to the right (<b>B</b>); Two weeks old <i>Npt2a</i>^<i>-/-</i> pups treated with i.p. injections of vehicle or sodium pyrophosphate (160 micromole/Kg/day) for two weeks (<b>C</b>); Histomorphometric analysis of renal mineralization (Êlcified area = 100*mineralization area/tissue area, (<b>D)</b>; calcification size = mineralization area/number of calcifications, um², (<b>E</b>), and plasma pyrophosphate levels (<b>F</b>) and urine pyrophosphate (U-PPi) (<b>G</b>) of two weeks old <i>Npt2a</i>^<i>-/-</i> pups treated with i.p. injections of vehicle or sodium pyrophosphate (160 micromole/Kg/day) for two weeks, measured after overnight fast and 18–24 hrs. following the last treatment. The data represent individual animals (closed circles) with the means±SEM, p-values shown above the lines of comparisons were calculated by Student’s t-test.</p

Intraperitoneal pyrophosphate treatment reduces renal calcifications in <i>Npt2a</i> null mice

<div><p>Mutations in the proximal tubular sodium-dependent phosphate co-transporters <i>NPT2a</i> and <i>NPT2c</i> have been reported in patients with renal stone disease and nephrocalcinosis, however the relative contribution of genotype, dietary calcium and phosphate, and modifiers of mineralization such as pyrophosphate (PPi) to the formation of renal mineral deposits is unclear. In the present study, we used <i>Npt2a</i>^<i>-/-</i> mice to model the renal calcifications observed in these disorders. We observed elevated urinary excretion of PPi in <i>Npt2a</i>^<i>-/-</i> mice when compared to WT mice. Presence of two hypomorphic <i>Extracellular nucleotide pyrophosphatase phosphodiesterase 1</i> (<i>Enpp1</i>^{<i>asj/asj</i>}) alleles decreased urine PPi and worsened renal calcifications in <i>Npt2a</i>^<i>-/-</i> mice. These studies suggest that PPi is a thus far unrecognized factor protecting <i>Npt2a</i>^<i>-/-</i> mice from the development of renal mineral deposits. Consistent with this conclusion, we next showed that renal calcifications in these mice can be reduced by intraperitoneal administration of sodium pyrophosphate. If confirmed in humans, urine PPi could therefore be of interest for developing new strategies to prevent the nephrocalcinosis and nephrolithiasis seen in phosphaturic disorders.</p></div

The hypomorphic <i>Enpp1</i>^<i>asj</i> allele worsens renal mineralization area seen in <i>Npt2a</i>^<i>-/-</i> mice on regular chow.

<p>Histomorphometric analysis of renal mineralization (Êlcified area = 100*mineralization area/tissue area, <b>A</b>; calcification size = mineralization area/number of calcifications, um², <b>B</b>) in 10 um sections of kidneys from mice fed regular chow for 10 weeks. The data represent individual animals (closed circles) with the means±SEM, p-values shown above the lines of comparisons were calculated by one-way ANOVA using Tukey’s adjustment for multiple comparisons, no significant differences were detected between groups in panel <b>B</b>.</p

Two-way ANOVA analysis.

<p>Two-way ANOVA analysis.</p

Biochemical parameters.

<p>Serum phosphorus (S-P), serum calcium (S-Ca), serum 1,25(OH)₂-vitamin D (1,25-D), plasma intact PTH (PTH), plasma c-terminal FGF23 (cFGF23), serum blood urea nitrogen (S-BUN), phosphate excretion index (U-Pi/(S-Pi*u-creatinine)(PEI), calcium excretion index (U-Ca/(S-Ca*U-creatinine) (CEI), citrate (U-citrate), oxalate (U-oxalate) and anion gap (U-AG). 8 weeks old mice were placed for 10 weeks on special egg-white based diets: HPC diet (High phosphate and calcium diet; 20% lactate, 2% calcium, 1.25% phosphate); HP diet (High phosphate diet; 0.6% calcium, 1.20% phosphate); CO diet (Control diet; 0.6% calcium, 0.3% phosphate); WT: wild type; Npt2a: <i>Npt2a</i>^<i>-/-</i> mice. The data represent mean±SEM; p-values were obtained by ANOVA and Tukey’s test to correct for multiple comparison, selected comparisons shown here, see complete list of p-values in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0176232#pone.0176232.s004" target="_blank">S1 Table</a>.</p

Renal mineralization is increased in <i>Npt2a</i>^<i>-/-</i> mice on high phosphate/high calcium diet.

<p>Histomorphometric analysis of renal mineralization (Êlcified area = 100*mineralization area/tissue area) in 10 um sections of kidneys from mice feed different diets for 10 weeks (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0176232#pone.0176232.s001" target="_blank">S1 Fig</a> for layout and legend of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0176232#pone.0176232.t002" target="_blank">Table 2</a> for composition of diets). The data represent individual animals (closed circles) and the mean±SEM; p-values were obtained by ANOVA and Tukey’s test to correct for multiple comparison.</p

Cortical and medulary renal mineralization.

<p>Light micrographs of 10 um renal sections, prepared from paraffin-embedded kidneys, of mice were fed different diets. WT (<b>a-c</b>), <i>Npt2a</i>^<i>-/-</i> (<b>d-f</b>), von Kossa&methylene green, 4X; <i>Npt2a</i>^<i>-/-</i> on CO diet, renal cortex (<b>g</b>) and medulla (<b>h</b>), von Kossa&hematoxin&eosin, 40X. Transmission electron micrographs showing microspheres in <i>Npt2a</i>^<i>-/-</i> on CO diet (<b>i</b>), inset with larger magnification shown in (<b>j</b>).</p