The Trophic Effect of Ouabain on Retinal Ganglion Cell is Mediated by EGF Receptor and PKC δ Activation

It was already shown that ouabain treatment can stimulate PKC isoenzymes leading to the activation of intracellular pathways involved in cell survival, growth and proliferation. We have previously demonstrated that ouabain or PMA treatment increases retinal ganglion cell survival, an effect mediated by PKC activation. The aim of this work was to investigate the role of EGF receptors in the ouabain effect and also to study which PKC isoform is activated by treatment with ouabain and PMA. Our results show that 2.5 μM tyrphostin, 1.0 μM PP1, 4.0 μM U73122, 1.0 μM JNK inhibitor V and 2.0 μM rottlerin blocked the ouabain effect indicating an involvement of receptors for EGF, Src, PLC, JNK and PKC δ respectively. The effect of PMA was only abolished when cultures were treated with rottlerin or with the JNK inhibitor suggesting the involvement of PKC δ and JNK. These results indicate that PKC δ could be a key regulator of retinal ganglion cell survival.     

The effect of terrestrial effluents on the incidence of Aeromonas spp. in coastal waters

The numbers of Aeromonas species were monitored for one year at 18 stations on the Barcelona coast. Their concentrations exceed those of faecal coliforms and faecal streptococci in all samples, both on the shoreline and at 500 m from the coast. The mean values of the three bacterial counts reflected the proximity of the terrestrial effluents. There was a positive correlation between aeromonads and faecal indicators on the shoreline but not at 500 m offshore. This reflected their common origin and different survival rates in seawater. When sterile sea water was inoculated with A. hydrophila ATCC 7966, the numbers decreased initially by three orders of magnitude before they began to multiply. The final count was related to the concentration of organic matter in the water.     

Size Matters: Metastatic Cluster Size and Stromal Recruitment in the Establishment of Successful Prostate Cancer to Bone Metastases

Prostate cancer (PCa) impacts over 180,000 men every year in the USA alone, with 26,000 patients expected to succumb to the disease (cancer.gov). The primary cause of death is metastasis, with secondary lesions most commonly occurring in the skeleton. Prostate cancer to bone metastasis is an important, yet poorly understood, process that is difficult to explore with experimental techniques alone. To this end we have utilized a hybrid (discrete–continuum) cellular automaton model of normal bone matrix homeostasis that allowed us to investigate how metastatic PCa can disrupt the bone microenvironment. Our previously published results showed that PCa cells can recruit mesenchymal stem cells (MSCs) that give rise to bone-building osteoblasts. MSCs are also thought to be complicit in the establishment of successful bone metastases (Lu, in Mol Cancer Res 4(4):221–233, 2006). Here we have explored the aspects of early metastatic colonization and shown that the size of PCa clusters needs to be within a specific range to become successfully established: sufficiently large to maximize success, but not too large to risk failure through competition among cancer and stromal cells for scarce resources. Furthermore, we show that MSC recruitment can promote the establishment of a metastasis and compensate for relatively low numbers of PCa cells seeding the bone microenvironment. Combined, our results highlight the utility of biologically driven computational models that capture the complex and dynamic dialogue between cells during the initiation of active metastases.     

The role of landscape change and paleoclimatic events in shaping the evolutionary history of the Polioptila gnatcatchers (Passeriformes,Polioptilidae) with emphasis on species associated with open habitats

We conducted a large‐scale phylogenetic and biogeographical inference of the Poliptila gnatcatchers and investigated the evolutionary history of two closely related neotropical bird species linked to open habitats, Polioptila dumicola and Polioptila plumbea. A Bayesian inference was employed based on the NADH subunit 2 gene to reconstruct the phylogenetic relationship of the gnatcatchers, and ancestral area reconstructions were estimated using BioGeoBEARS. For the phylogeographic analysis, we analyzed two mitochondrial genes, cytochrome b and ND2, of 102 individuals from P. dumicola and P. plumbea distributed throughout the complete range of both species. To reconstruct the dates related to the splitting events, we included a subset of sequences from the nuclear gene beta‐fibrinogen intron‐7. A striking result was the recovery of the sister relationship between the lineages of P. dumicola /plumbea and the paraphyly among the subspecies of P. plumbea: the first group was formed by P. dumicola, P. p. plumbea, P. p. parvirostris, P. p. atricapilla and P. lactea, occurring mainly on the Brazilian shield; while the second group consisted of lineages from north of the Amazon, west of the Andes, and Central America, and included P. maior, P. p. cinericia, P. p. bilineata and P. p. innotata. Significant phylogeographic structure was evident within lineages attributed to P. plumbea, with high levels of differentiation in the well‐defined clades according to all phylogenetic analyses. Our biogeographic analyses support distinct evolutionary histories related to founder events and vicariance, occurring during the late Pliocene and early Pleistocene. Several dispersal episodes between North/Central America and South America led to the establishment of populations which became differentiated due to landscape changes, such as the establishment of riverine barriers, the uplift of the Andes and the formation of the Panama Isthmus.     

Effects of habitat simplification on assemblages of cavity nesting bees and wasps in a semiarid neotropical conservation area

Habitat complexity is directly correlated to insect diversity in most natural environments. Structural complexity reflects an increase in vertical stratification and plant diversity and often leads to a greater availability of floral resources and nesting sites. Efficient conservation strategies require understanding of how changes in habitat structure affect insects that provide essential ecosystem services. We analyzed how the diversity and species composition of bees and wasps that nest in pre-existing cavities is affected by habitat complexity. Our study was developed in the semiarid region of northeastern Brazil, in the Ubajara National Park and surrounding area. Four types of habitats within two physiognomies were sampled for two consecutive years. We used 120 trap-nest (9000 cavities) distributed in 40 sample points. Overall, 657 cavities were occupied by 11 species of bees, nine of wasps, and six of cleptoparasitic/parasitoids. Bees and wasp diversity increases with habitat complexity. While species richness was higher in more complex physiognomies, abundance was higher in disturbed areas. Species composition also varied with habitat structure. Habitat simplification has adverse effects on the diversity and composition of assemblages. These effects are stronger in more complex habitats indicating that conservation of humid habitats within semiarid areas is essential to maintain bee and wasp regional diversity.     

Identification of new promising <Emphasis Type="Italic">Plasmodium falciparum</Emphasis> superoxide dismutase allosteric inhibitors through hierarchical pharmacophore-based virtual screening and molecular dynamics

Malaria is the world’s most widespread protozoan infection, being responsible for more than 445,000 annual deaths. Among the malaria parasites, Plasmodium falciparum is the most prevalent and lethal. In this context, the search for new antimalarial drugs is urgently needed. P. falciparum superoxide dismutase (PfSOD) is an important enzyme involved in the defense mechanism against oxidative stress. The goal of this study was to identify through hierarchical screening on pharmacophore models and molecular dynamics (MD), promising allosteric PfSOD inhibitors that do not show structural requirements for human inhibition. MD simulations of 1000 ps were performed on PfSOD using GROMACS 5.1.2. For this, the AMBER99SB-ILDN force field was adapted to describe the metal-containing system. The simulations indicated stability in the developed system. Therefore, a covariance matrix was generated, in which it was possible to identify residues with correlated and anticorrelated movements with the active site. These results were associated with the results found in the predictor of allosteric sites, AlloSitePro, which affirmed the ability of these residues to delimit an allosteric site. Then, after successive filtering of the Sigma-Aldrich® compounds database for HsSOD1 and PfSOD pharmacophores, 152 compounds were selected, also obeying Lipinski’s rule of 5. Further filtering of those compounds based on molecular docking results, toxicity essays, availability, and price filtering led to the selection of a best compound, which was then submitted to MD simulations of 20,000 ps on the allosteric site. The study concludes that the ZINC00626080 compound could be assayed against SODs.

Open image in new window

Graphical Abstract Plasmodium falciparum superoxide dismutase

     

Loss of Paneth Cell Autophagy Causes Acute Susceptibility to Toxoplasma gondii-Mediated Inflammation

1. Download high-res image (165KB)
2. Download full-size image

     

Behavioral and Biochemical Effects of N-Acetylcysteine in Zebrafish Acutely Exposed to Ethanol

Neurochemical Research - Alcohol hangover refers to unpleasant symptoms experienced as a direct consequence of a binge drinking episode. The effects observed in this condition are related to the...