DW-MRI as a Biomarker to Compare Therapeutic Outcomes in Radiotherapy Regimens Incorporating Temozolomide or Gemcitabine in Glioblastoma

The effectiveness of the radiosensitizer gemcitabine (GEM) was evaluated in a mouse glioma along with the imaging biomarker diffusion-weighted magnetic resonance imaging (DW-MRI) for early detection of treatment effects. A genetically engineered murine GBM model [Ink4a-Arf−/− PtenloxP/loxP/Ntv-a RCAS/PDGF(+)/Cre(+)] was treated with gemcitabine (GEM), temozolomide (TMZ) +/− ionizing radiation (IR). Therapeutic efficacy was quantified by contrast-enhanced MRI and DW-MRI for growth rate and tumor cellularity, respectively. Mice treated with GEM, TMZ and radiation showed a significant reduction in growth rates as early as three days post-treatment initiation. Both combination treatments (GEM/IR and TMZ/IR) resulted in improved survival over single therapies. Tumor diffusion values increased prior to detectable changes in tumor volume growth rates following administration of therapies. Concomitant GEM/IR and TMZ/IR was active and well tolerated in this GBM model and similarly prolonged median survival of tumor bearing mice. DW-MRI provided early changes to radiosensitization treatment warranting evaluation of this imaging biomarker in clinical trials

Preference for male traits differ in two female morphs of the tree lizard, Urosaurus ornatus.

Non-random female mating preferences may contribute to the maintenance of phenotypic variation in color polymorphic species. However, the effect of female preference depends on the types of male traits used as signals by receptive females. If preference signals derive from discrete male traits (i.e., morph-specific), female preferences may rapidly fix to a morph. However, female preference signals may also include condition-dependent male traits. In this scenario, female preference may differ depending on the social context (i.e., male morph availability). Male tree lizards (Urosaurus ornatus) exhibit a dewlap color polymorphism that covaries with mating behavior. Blue morph males are aggressive and defend territories, yellow males are less aggressive and defend smaller territories, and orange males are typically nomadic. Female U. ornatus are also polymorphic in dewlap color, but the covariation between dewlap color and female behavior is unknown. We performed an experiment to determine how female mate choice depends on the visual and chemical signals produced by males. We also tested whether female morphs differ in their preferences for these signals. Female preferences involved both male dewlap color and size of the ventral color patch. However, the female morphs responded to these signals differently and depended on the choice between the types of male morphs. Our experiment revealed that females may be capable of distinguishing among the male morphs using chemical signals alone. Yellow females exhibit preferences based on both chemical and visual signals, which may be a strategy to avoid ultra-dominant males. In contrast, orange females may prefer dominant males. We conclude that female U. ornatus morphs differ in mating behavior. Our findings also provide evidence for a chemical polymorphism among male lizards in femoral pore secretions

Preference of female <i>Urosaurus ornatus</i> when presented with orange and yellow males (visual experiment).

<p>Preference by yellow (light grey) and orange (dark grey) morph females refers to a greater number of visits towards one male over another and bars are mean+1.0 standard error (SE). Both yellow and orange females preferred yellow over orange morph males (see Results).</p

Yellow female <i>Urosaurus ornatus</i> preference for chemical signals of yellow and orange males.

<p>Preference refers to the number of visits by yellow females to either tile in the Y-O dyad. Bars are mean+1.0 standard error (SE). Yellow females preferred tiles scented with yellow male secretions (see Results).</p

Component loadings of the first axis of two Principle Components Analyses (PCAs) performed on dewlap and ventral color patch color properties, respectively.

<p>We used PCA to describe dewlap and ventral patch hue, chroma, and brightness as an independent color score (based on the first PCA axis, PC1) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0101515#pone.0101515-Endler1" target="_blank">[36]</a>. Factor loadings indicate the relative direction and magnitude of contribution by each color component to a score.</p

Dewlap color differences among male tree lizard (<i>Urosaurus ornatus</i>) morphs.

<p>Dewlap color refers to scores from the first principal component axis derived from hue, chroma, and brightness data collected from male dewlaps (n = 29 males, see Materials and Methods for color procedure). Male lizards are grouped by morph: blue, orange, or yellow (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0101515#pone.0101515.s001" target="_blank">Figure S1</a>). Values are mean ±1.0 standard error (SE).</p

Strength of preference for male <i>Urosaurus ornatus</i> by the two female morphs.

<p>Strength of preference (absolute difference in number of visits) for both yellow (A) and orange (B) morph female <i>U. ornatus</i> in each dyad. Bars are shaded by experiment (grey: visual, white: chemical) and are mean+1.0 standard error (SE).</p

Relationship between male <i>Urosaurus ornatus</i> ventral patch size and yellow female preference (visual experiment).

<p>Preference refers to the number of visits by yellow females to males that differ in ventral patch size (mm²) in the B-O dyad. The grey shaded region denotes 95% confidence intervals around predicted values from a poisson regression.</p