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.     

Pragmatic data and observations related to the epidemiology of Chagas disease

Chagas' disease or American trypanosomiasis is a parasitic zoonosis which constitutes and important public health problem in most of the Latin American countries. According to the development of socio-political events in the world, it is possible at present to speak of rural-periurban Chagas' disease and urban Chagas' disease. Rural-periurban Chagas' disease. In its endemo-enzootic condition it is distributed in vast areas from Mexico in the north and Argentina and Chile in the south. It is calculated that the population at risk is about 90 million persons, not less than 16-18 million are Trypanosoma cruzi infected and approximately 38% of these present or have presented pathology caused by the parasite. Organs most frequently affected: heart, esophagus and colon. The corresponding biological vectors are hematophagus triatomid bugs, with greater than 100 species synantropic (st) or sylvatic (sv), existing between parallels 41 N. and 46 S., but only about 36, which have been found infected, have some relationship with man because their adaptation to human dwelling. The human parasitose is less extended due to the fact that the vectors of the region are predominantly sv. The known reservoirs are more than 180 species of terrestrial mammals: domestic, st and sv. Man is possibly the most important. Some available relevant epidemiological information is summarized as follows: Additionally, some autochthonous cases of T. cruzi human infection have been registered in the United States, Trinidad-Tobago, Guyana and Belize. Moreover, infected vectors and/or sv reservoirs have been observed in almost a dozen of Caribbean countries. Urban Chagas' disease. As a consequence of possible better salaries and many other motivations, in the last decades there have been significant and constant migrations from rural to urban areas in many Latin American countries. This situation has facilitated the dissemination of T. cruzi infection through infected reservoirs--mostly humans--and/or passively transported infected vectors. In most of the cases these rural-urban migrations occur in chagasic endemic areas within a same country or in neighbouring ones; in others, the migration can involve countries where Chagas' disease does not exist, transmission being via blood transfusion or placental. According to some estimates, with a mean rate of 1.5% chagasic infected blood donors the minimum risk of T. cruzi transmission is nearly 12.5-25.0% when the volumen of transfused blood is 500 ml.(ABSTRACT TRUNCATED AT 400 WORDS)     

Partial Evaluation of Autochthonous Probiotic Potential of the Gut Microbiota of Seriola lalandi

Seriola lalandi is an economically important species that is globally distributed in temperate and subtropical marine waters. Aquaculture production of this species has had problems associated with intensive fish farming, such as disease outbreaks or nutritional deficiencies causing high mortality. Intestinal microbiota are involved in many processes that benefit a host, such as disease control, stimulation of the immune response, and the promotion of nutrient metabolism. The aim of this study is to evaluate the in vitro probiotic properties of bacteria isolated from the intestinal content of wild Seriola lalandi. The probiotic potential was evaluated in terms of (i) the antimicrobial activity against vibrios causing outbreaks in farmed fish; (ii) the ability to stimulate genes related to an innate immune response in fish; and (iii) antibiotic resistance. Nineteen isolates identified as Pseudomonas, Shewanella, Psychrobacter, and Acinetobacter showed antimicrobial activity and significant relative expression of cytokines, serum amyloid A protein (SAA), hepcidin, and lysozyme. A positive correlation was observed between the levels of expression and the bacterial load after 24 h of exposure. Pseudomonas isolates showed a level of antibiotic resistance. In conclusion, isolates of the genera Shewanella, Psychrobacter, and Acinetobacter could serve as potential probiotics in S. lalandi culture.

     

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.     

A model for gain of function in superoxide dismutase

Studies have found that mutant, misfolded superoxide dismutase [Cu–Zn] (SOD1) can convert wild type SOD1 (wtSOD1) in a prion-like fashion, and that misfolded wtSOD1 can be propagated by release and uptake of protein aggregates. In developing a prion-like mechanism for this propagation of SOD1 misfolding we have previously shown how enervation of the SOD1 electrostatic loop (ESL), caused by the formation of transient non-obligate SOD1 oligomers, can lead to an experimentally observed gain of interaction (GOI) that results in the formation of SOD1 amyloid-like filaments. It has also been shown that freedom of ESL motion is essential to catalytic function. This work investigates the possibility that restricting ESL mobility might not only compromise superoxide catalytic activity but also serve to promote the peroxidase activity of SOD1, thus implicating the formation of SOD1 oligomers in both protein misfolding and in protein oxidation.