Mice carrying 100P mutations show layer-specific decreases in proportions of PV+ cells.

<p>(<b>A-D</b>) Decreases occurred in layer IV in fSSp, SSp, vAud and Vis, in layer V in SSp, vAud and Vis and in layer II/III in SSp. (<b>E-H</b>) For GAD67+ cells, the only differences were in layer I in vAud. (n = 3–8 animals; data are means ± sems; * p<0.05, ** p<0.01, *** p<0.001, two-way ANOVA with Dunnet’s multiple comparisons test where applicable). <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0156082#pone.0156082.s004" target="_blank">S3 Table</a> provides the results of ANOVA.</p

Analysis of interneurons in the cortex of wild-type (WT) and mutant mice.

<p>(<b>A</b>) Coronal sections at P21 with regions of interest marked by red boxes: medial prefrontal cortex (MPFC), frontal primary somatosensory cortex (fSSp), primary somatosensory cortex (SSp), ventral auditory cortex (vAud) and primary visual cortex (Vis). (<b>B-K</b>) Representative images of interneuronal marker expression in SSp in WT and 100P/100P mice. Abbreviations: PV, parvalbumin; GAD67, glutamate decarboxylase 67; STT, somatostatin; CLR, calretinin. Cortical layers marked in B and G are in approximately the same positions in the other images. Scale bars: 100μm.</p

100P homozygous mice show overall decrease in proportions of PV-expressing cells in the P21 neocortex.

<p>(<b>A, B</b>) Proportion of PV-expressing cells was significantly decreased in the 100P/100P mouse cortex without any loss in the total interneurons number. (<b>C, D</b>) No difference was observed in other two subpopulations of cortical interneurons: STT- and CLR-positive cells (n = 3–8 animals for each comparison; data are means ± sems; * p<0.05, ** p<0.01, one-way ANOVA with Bonferroni’s multiple comparisons test where applicable). (E-H) No change in the PV, GAD67, CLR and SST was observed in the 31L mutant mice neocortex (n = 3–9 animals, one-way ANOVA). Full ANOVA results are in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0156082#pone.0156082.s002" target="_blank">S1 Table</a>.</p

<i>In utero</i> electroporation of Disc1 and Disc1-100P constructs into wild-type neocortex and analysis at P21.

<p>(<b>A</b>,<b>B</b>) Flag-tagged Disc1 and Disc1-100P coding sequences subcloned into an IRES-NLS-GFP vector as well as the empty IRES-NLS-GFP vector were electroporated at E14.5 into cortical regions whose proportions of PV+ cells are affected in mice carrying 100P mutations. (<b>C</b>) PV cells density was analysed at P21 in in the cortical regions marked. Abbreviations in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0156082#pone.0156082.g001" target="_blank">Fig 1</a>; RSA, retrosplenial area. (<b>D-E”</b>) Expression of the constructs was assessed (<b>D-D''</b>) 2 days after transfection <i>in vitro</i> and (<b>E-E''</b>) at P21 <i>in vivo</i> (<b>F-H''</b>) GFP expression was observed predominantly in layers II/III and IV at P21 as seen in the representative images of the electroporated SSp. Scale bar: for <b>D-D''</b> 50 μm; for <b>E-H''</b> 100μm.</p

Effects of expression of Disc1 or Disc1-100P from constructs electroporated into the cortex on the densities and distributions of PV expressing cells in the P21 mouse cortex.

<p>(<b>A</b>) Cells in layer II/III targeted by the electroporation (<b>B</b>) send their callosal projections to the contralateral side. Scale bar, 150μm. (<b>C,E,G</b>) Effects on densities of PV expressing cells in (C) the electroporated cortical areas and non-electroporated retrosplenial area (RSA) and in (D,E) cortical layers in electroporated SSp and Vis. (<b>D,F.H</b>) Effects on densities of PV expressing cells in (<b>D</b>) the areas contralateral to the electroporated areas and (<b>F,H</b>) cortical layers in areas contralateral to electroporated SSp and Vis (n = 3–10 animals per genotype; multiple comparisons two-way ANOVA with Bonferroni correction: * p<0.05; ** p<0.01; *** p<0.001). <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0156082#pone.0156082.s006" target="_blank">S5 Table</a> provides the results of ANOVA.</p

Mice carrying 100P mutations show region-specific decreases in proportions of PV-expressing cells.

<p>(<b>A</b>) Significant decreases in the proportions of PV+ cells were observed in fSSp, SSp, vAud and in Vis, but not MPFC. (<b>B</b>) Corresponding decreases in the proportions of cells expressing the mRNA for PV were observed in fSSp, SSp and vAud. (<b>C</b>) There were no corresponding changes in the proportions of GAD67+ cells. (<b>D</b>, <b>E</b>) No major change was observed in the proportion of cells expressing calretinin (CLR) or somatostatin (STT) across the mutant cortex (n = 3–8 animals for each comparison; data are means ± sems; * p<0.05, ** p<0.01, two-way ANOVA with Dunnet’s multiple comparisons test where applicable). (<b>F</b>-<b>I</b>) No change in the PV, GAD67, CLR and SST was observed across the cortices of the 31L mutant mice (n = 3–9 animals, two-way ANOVA with Dunnet’s multiple comparisons test where applicable). <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0156082#pone.0156082.s003" target="_blank">S2 Table</a> provides the results of ANOVA.</p

An efficient moments-based inference method for within-host bacterial infection dynamics - Fig 13

<p>Left: Diagram of each model illustrating the relevant compartments, initial conditions, and rates of interest. Right: MDE parameter estimate (blue dot) with box plots of the bootstrapped parameter estimates, and MLE parameter estimate (red cross) with 95% confidence interval (red bars).</p

Image2.JPEG

<p>Multiple signals control the balance between proliferation and differentiation of neural progenitor cells during corticogenesis. A key point of this regulation is the control of G1 phase length, which is regulated by the Cyclin/Cdks complexes. Using genome-wide chromatin immunoprecipitation assay and mouse genetics, we have explored the transcriptional regulation of Cyclin D1 (Ccnd1) during the early developmental stages of the mouse cerebral cortex. We found evidence that SP8 binds to the Ccnd1 locus on exon regions. In vitro experiments show SP8 binding activity on Ccnd1 gene 3′-end, and point to a putative role for SP8 in modulating PAX6-mediated repression of Ccnd1 along the dorso-ventral axis of the developing pallium, creating a medial^Low-lateral^High gradient of neuronal differentiation. Activation of Ccnd1 through the promoter/5′-end of the gene does not depend on SP8, but on βcatenin (CTNNB1). Importantly, alteration of the Sp8 level of expression in vivo affects Ccnd1 expression during early corticogenesis. Our results indicate that Ccnd1 regulation is the result of multiple signals and that SP8 is a player in this regulation, revealing an unexpected and potentially novel mechanism of transcriptional activation.</p

Figures demonstrating the goodness-of-fit of the two models to the respective data sets.

<p>The histogram bars are the bootstrapped estimate of the null distribution of divergences under the model at the estimated parameter values for the respective model. The (blue) vertical dashed-line is the divergence corresponding to the observed data set.</p

Bivariate distributions of replication and killing rates in liver and spleen, for both naive and live-vaccinated groups.

<p>Blue circles are the MDE values, with the blue (solid) ellipses representing the 95% confidence ellipses calculated using the 1000 bootstrap samples (grey points). The red crosses are the MLE values, with red (dashed) ellipse calculated using the hessian evaluated at the MLE.</p