Which Factors Determine Spatial Segregation in the South American Opossums (Didelphis aurita and D. albiventris)? An Ecological Niche Modelling and Geometric Morphometrics Approach

Didelphis albiventris and D. aurita are Neotropical marsupials that share a unique evolutionary history and both are largely distributed throughout South America, being primarily allopatric throughout their ranges. In the Araucaria moist forest of Southern Brazil these species are sympatric and they might potentially compete having similar ecology. For this reason, they are ideal biological models to address questions about ecological character displacement and how closely related species might share their geographic space. Little is known about how two morphologically similar species of marsupials may affect each other through competition, if by competitive exclusion and competitive release. We combined ecological niche modeling and geometric morphometrics to explore the possible effects of competition on their distributional ranges and skull morphology. Ecological niche modeling was used to predict their potential distribution and this method enabled us to identify a case of biotic exclusion where the habit generalist D. albiventris is excluded by the presence of the specialist D. aurita. The morphometric analyses show that a degree of shape discrimination occurs between the species, strengthened by allometric differences, which possibly allowed them to occupy marginally different feeding niches supplemented by behavioral shift in contact areas. Overlap in skull morphology is shown between sympatric and allopatric specimens and a significant, but weak, shift in shape occurs only in D. aurita in sympatric areas. This could be a residual evidence of a higher past competition between both species, when contact zones were possibly larger than today. Therefore, the specialist D. aurita acts a biotic barrier to D. albiventris when niche diversity is not available for coexistence. On the other hand, when there is niche diversification (e.g. habitat mosaic), both species are capable to coexist with a minimal competitive effect on the morphology of D. aurita

RAN Nucleo-Cytoplasmic Transport and Mitotic Spindle Assembly Partners XPO7 and TPX2 Are New Prognostic Biomarkers in Serous Epithelial Ovarian Cancer

<div><p>Purpose</p><p>Epithelial ovarian cancer has the highest mortality rate of all gynecological malignancies. We have shown that high RAN expression strongly correlates with high-grade and poor patient survival in epithelial ovarian cancer. However, as RAN is a small GTPase involved in two main biological functions, nucleo-cytoplasmic transport and mitosis, it is still unknown which of these functions associate with poor prognosis.</p><p>Methods</p><p>To examine the biomarker value of RAN network components in serous epithelial ovarian cancer, protein expression of six specific RAN partners was analyzed by immunohistochemistry using a tissue microarray representing 143 patients associated with clinical parameters. The RAN GDP/GTP cycle was evaluated by the expression of RANBP1 and RCC1, the mitotic function by TPX2 and IMPβ, and the nucleo-cytoplasmic trafficking function by XPO7, XPOT and IMPβ.</p><p>Results</p><p>Based on Kaplan-Meier analyses, RAN, cytoplasmic XPO7 and TPX2 were significantly associated with poor overall patient survival, and RAN and TPX2 were associated with lower disease free survival in patients with high-grade serous carcinoma. Cox regression analysis revealed that RAN and TPX2 expression were independent prognostic factors for both overall and disease free survival, and that cytoplasmic XPO7 expression was a prognostic factor for overall patient survival.</p><p>Conclusions</p><p>In this systematic study, we show that RAN and two protein partners involved in its nucleo-cytoplasmic and mitotic functions (XPO7 and TPX2, respectively) can be used as biomarkers to stratify patients based on prognosis. In particular, we reported for the first time the clinical relevance of the exportin XPO7 and showed that TPX2 expression had the strongest prognostic value. These findings suggest that protein partners in each of RAN’s functions can discriminate between different outcomes in high-grade serous epithelial ovarian cancer patients. Furthermore, these proteins point to cellular processes that may ultimately be targeted to improve the survival in serous epithelial ovarian cancer.</p></div

RAN, XPO7 and TPX2 expressions are associated with poor survival in high-grade serous epithelial ovarian cancer.

<p>Expression of RAN network proteins was evaluated as prognostic indicators in only the high-grade serous carcinomas by Kaplan–Meier analysis. Survival was defined as the time from surgery to death from ovarian cancer or last follow-up. The log-rank test was used to define statistical difference between groups. For panels A–H, low staining (blue line) defined by values <1, medium staining (green line) defined by = 1<2 and high staining (pink line) defined as ≥2. For panel I, samples are scored as negative (black line) or positive (grey line) for TPX2 staining. In A–I, p denotes significance among all groups. For panels J–K, negative TPX2 staining with low staining intensity of RAN (J –black line) or XPO7 (K – black line); negative TPX2 staining with medium+high staining of RAN (J – cyan line) or XPO7 (K – violet line); positive TPX2 staining with medium+high staining of RAN (J – grey line) or XPO7 (K – grey line). In J–K, p (top right hand corner) is calculated for black versus cyan (RAN, panel J) or violet (XPO7, panel K). In J–K, p (bottom left hand corner) is calculated for grey versus cyan (RAN, panel J) or violet (XPO7, panel K). A–K, p<0.05 are indicated in bold letters.</p

Univariate and multivariate Cox regression analyses. Statistical association between the expression of RAN or its partners and HG serous patient outcomes.

<p>*Overall survival is the time from the date of primary resection until either death due to ovarian cancer or last follow-up.</p><p>**Disease free survival is the time from the first resection of the primary tumor until the first event of recurrence.</p><p>Residual disease = amount of residual disease at time of primary resection of the ovarian tumor.</p><p>p = p-value. HR = hazard ratio. Bold fonts denote significant values.</p

Intensity of RAN network proteins in low-grade and high-grade serous epithelial ovarian cancer.

<p>For each protein, the staining intensity was defined as 0 (no staining), 1 (weak staining), 2 (moderate staining) or 3 (dark staining) within the epithelial compartment by two independent observers. The mean of the staining intensity for each protein was compared between low grade (white bars) and high grade tumors (grey bars) using a Student test. *p<0.05 **p≤0.005.</p