PARP-1 Regulates Metastatic Melanoma through Modulation of Vimentin-induced Malignant Transformation

PARP inhibition can induce anti-neoplastic effects when used as monotherapy or in combination with chemo- or radiotherapy in various tumor settings; however, the basis for the anti-metastasic activities resulting from PARP inhibition remains unknown. PARP inhibitors may also act as modulators of tumor angiogenesis. Proteomic analysis of endothelial cells revealed that vimentin, an intermediary filament involved in angiogenesis and a specific hallmark of EndoMT (endothelial to mesenchymal transition) transformation, was down-regulated following loss of PARP-1 function in endothelial cells. VE-cadherin, an endothelial marker of vascular normalization, was up-regulated in HUVEC treated with PARP inhibitors or following PARP-1 silencing; vimentin over-expression was sufficient to drive to an EndoMT phenotype. In melanoma cells, PARP inhibition reduced pro-metastatic markers, including vasculogenic mimicry. We also demonstrated that vimentin expression was sufficient to induce increased mesenchymal/pro-metastasic phenotypic changes in melanoma cells, including ILK/GSK3-β-dependent E-cadherin down-regulation, Snail1 activation and increased cell motility and migration. In a murine model of metastatic melanoma, PARP inhibition counteracted the ability of melanoma cells to metastasize to the lung. These results suggest that inhibition of PARP interferes with key metastasis-promoting processes, leading to suppression of invasion and colonization of distal organs by aggressive metastatic cells.     

A novel cellular automata approach: seed input/output of the alien species Leucaena leucocephala in the soil and the effects of climate changes

The potential impact of the soil seed bank of a given species and subsequent population persistence will depend on the robustness of the seeds against depletion. Invasiveness is frequently linked to this behavior and successful control of invasive species depends on reducing the size of their seed banks. We propose a hybrid model that simulates the seed bank dynamics in association with their physical dormancy (PD) based on experimental data on seed bank depletion of a Leucaena leucocephala population during the dispersal phase. The hybrid model uses cellular automata (CA) and Monte Carlo techniques. The sensitivity analysis revealed that the model delivers reproducible and reliable results. Then, we discuss the ability of the hybrid model to predict the effect of seasonal climate change. A 2.0 °C increase in temperature was enough to cause a considerable impact in the seed depletion curve, and after 1 year, ~?75% of the seeds had already disappeared from the seed bank. The proposed hybrid CA model can be used to study soil-stored seed banks with physical dormancy, and could be applied to other Fabaceae species with similar seed traits. We believe that this computational model contributes to a better understanding of seed bank dynamics and will aid in the control of invasive species and for testing different scenarios to reduce or eliminate seed banks that have already been formed.

     

Postnatal exposure to finasteride causes different effects on the prostate of male and female gerbils

The development and maintenance of prostate function depend on a fine balance between oestrogen and androgen levels. Finasteride inhibits 5α‐reductase, which is responsible for the conversion of testosterone into its most active form, dihydrotestosterone. Enzymes that metabolize these hormones have a highly relevant role in both the normal prostate metabolism and in the occurrence of pathological conditions. There are few studies on the impact of finasteride on male prostate development and fewer studies on the female prostate and possible intersexual differences. Therefore, we treated male and female gerbils from 7 to 14 days in postnatal life with a high dose of finasteride (500 μg/kg/day); the prostate complexes were then removed and submitted to immunohistochemistry, immunofluorescence and three‐dimensional reconstruction. In addition, hormonal serum dosages were administered. Treatment with finasteride resulted in an increased thickness of the periductal smooth musculature in the prostate of both male and female gerbils, such as well as a reduction in the thickness of developing prostate alveoli in both sexes. In addition, intersexual differences were observed as increased epithelial proliferation and decreases in the number of developing alveoli in females. Together, the data indicate that postnatal exposure to finasteride causes greater changes in the female gerbil prostate than in the male.     

Characterization,Toxicity, and Optimization for the Growth and Production of Bacteriocin-like Substances by Lactobacillus curvatus

Probiotics and Antimicrobial Proteins - This study aimed to characterize, evaluate toxicity and optimize the conditions for the growth and production of bacteriocin-like substances by Lactobacillus...     

A standardized assessment of forest mammal communities reveals consistent functional composition and vulnerability across the tropics

The understanding of global diversity patterns has benefitted from a focus on functional traits and how they relate to variation in environmental conditions among assemblages. Distant communities in similar environments often share characteristics, and for tropical forest mammals, this functional trait convergence has been demonstrated at coarse scales (110–200 km resolution), but less is known about how these patterns manifest at fine scales, where local processes (e.g. habitat features and anthropogenic activities) and biotic interactions occur. Here, we used standardized camera trapping data and a novel analytical method that accounts for imperfect detection to assess how the functional composition of terrestrial mammal communities for two traits – trophic guild and body mass – varies across 16 protected areas in tropical forests and three continents, in relation to the extent of protected habitat and anthropogenic pressures. We found that despite their taxonomic differences, communities generally have a consistent trophic guild composition, and respond similarly to these factors. Insectivores were found to be sensitive to the size of protected habitat and surrounding human population density. Body mass distribution varied little among communities both in terms of central tendency and spread, and interestingly, community average body mass declined with proximity to human settlements. Results indicate predicted trait convergence among assemblages at the coarse scale reflects consistent functional composition among communities at the local scale, suggesting that broadly similar habitats and selective pressures shaped communities with similar trophic strategies and responses to drivers of change. These similarities provide a foundation for assessing assemblages under anthropogenic threats and sharing conservation measures.