When destruction comes first: Two new species of Hypostomus Lacépède, 1803 (Siluriformes: Loricariidae) from a deeply-impacted river in the Rio São Francisco basin in Brazil

Environmental disasters affecting Brazilian rivers have been frequent recently, especially involving mining activities. Two recent dam-rupture events suddenly released millions of cubic meters of iron tailings downstream into two major Brazilian watersheds. These events generated major losses to the environment and human life. Additionally, the biodiversity in both watersheds was still incompletely known. Two new species of the armoured catfish genus Hypostomus were discovered in the Rio Paraopeba and surrounding rivers of the Rio São Francisco Basin. The species share some main characteristics including a depressed body, large dark spots on a clearer background and the absence of keels on flanks. However, while one species (Hypostomus freirei sp. n.) has a large mandibular ramus and numerous slender teeth, the other (Hypostomus guajupia sp. n.) has a shorter mandibular ramus and few robust teeth. The discovery of these two new mid-sized fish species emphasizes the presumption that the effects of major environmental disasters cannot be fully estimated as local biodiversity is not completely known. This discovery in a recently devastated area also shows that tough environmental laws for the protection, supervision and mitigation of major impacts are urgently needed in developing countries.     

Human-derived NLS enhance the gene transfer efficiency of chitosan

Nuclear import is considered as one of the major limitations for non-viral gene delivery systems and the incorporation of nuclear localization signals (NLS) that mediate nuclear intake can be used as a strategy to enhance internalization of exogenous DNA.In this work, human-derived endogenous NLS peptides based on insulin growth factor binding proteins (IGFBP), namely IGFBP-3 and IGFBP-5, were tested for their ability to improve nuclear translocation of genetic material by non-viral vectors. Several strategies were tested to determine their effect on chitosan mediated transfection efficiency: co-administration with polyplexes, co-complexation at the time of polyplex formation, and covalent ligation to chitosan. Our results show that co-complexation and covalent ligation of the NLS peptide derived from IGFBP-3 to chitosan polyplexes yields a 2-fold increase in transfection efficiency, which was not observed for NLS peptide derived from IGFBP-5.These results indicate that the integration of IGFBP-NLS-3 peptides into polyplexes has potential as a strategy to enhance the efficiency of non-viral vectors.     

Autophagy modulates SNCA/α-synuclein release,thereby generating a hostile microenvironment

SNCA/α-synuclein aggregation plays a crucial role in synucleinopathies such as Parkinson disease and dementia with Lewy bodies. Aggregating and nonaggregating SNCA species are degraded by the autophagy-lysosomal pathway (ALP). Previously, we have shown that the ALP is not only responsible for SNCA degradation but is also involved in the intracellular aggregation process of SNCA. An additional role of extracellular SNCA in the pathology of synucleinopathies substantiating a prion-like propagation hypothesis has been suggested since released SNCA species and spreading of SNCA pathology throughout neural cells have been observed. However, the molecular interplay between intracellular pathways, SNCA aggregation, release, and response of the local microenvironment remains unknown. Here, we attributed SNCA-induced toxicity mainly to secreted species in a cell culture model of SNCA aggregation and in SNCA transgenic mice: We showed that ALP inhibition by bafilomycinA₁ reduced intracellular SNCA aggregation but increased secretion of smaller oligomers that exacerbated microenvironmental response including uptake, inflammation, and cellular damage. Low-aggregated SNCA was predominantly released by exosomes and RAB11A-associated pathways whereas high-aggregated SNCA was secreted by membrane shedding. In summary, our study revealed a novel role of the ALP by linking protein degradation to nonclassical secretion for toxic SNCA species. Thus, impaired ALP in the diseased brain not only limits intracellular degradation of misfolded proteins, but also leads to a detrimental microenvironmental response due to enhanced SNCA secretion. These findings suggest that the major toxic role of SNCA is related to its extracellular species and further supports a protective role of intracellular SNCA aggregation.     

The ruthenium complexes cis-(dichloro)tetramineruthenium(III) chloride and cis-tetraammine(oxalato)ruthenium(III) dithionate overcome resistance inducing apoptosis on human lung carcinoma cells (A549)

Lung cancer is one of the leading causes of death in the world, and non-small cell lung carcinoma accounts for approximately 75–85 % of all lung cancers. In the present work, we studied the antitumor activity of the compound cis-(dichloro)tetramineruthenium(III) chloride {cis-[RuCl₂(NH₃)₄]Cl} against human lung carcinoma tumor cell line A549. The present study aimed to investigate the relationship between the expression of MDR1 and CYP450 genes in human lung carcinoma cell lines A549 treated with cisCarboPt, cisCRu(III) and cisDRu(III). The ruthenium-based coordinated complexes presented low cytotoxic and antiproliferative activities, with high IC₅₀ values, 196 (±15.49), 472 (±20.29) and 175 (±1.41) for cisCarboPt, cisCRu(III) and cisDRu(III), respectively. The tested compounds induced apoptosis in A549 tumor cells as evidenced by caspase 3 activation, but only at high concentrations. Results also revealed that the amplification of P-gp gene is greater in A549 cells exposed to cisCarboPt and cisCRu(III) than cisDRu(III). Taken together all these results strongly demonstrate that MDR-1 over-expression in A549 cells could be associated to a MDR phenotype of these cells and moreover, it is also contributing to the platinum, and structurally-related compound, resistance in these cells. The identification and characterization of novel mechanisms of drug resistance will enable the development of a new generation of anti-cancer drugs that increase cancer sensitivity and/or represent more effective chemotherapeutic agents.     

Cellular interplay in pulmonary arterial hypertension: Implications for new therapies

Pulmonary arterial hypertension (PAH) is a complex and multifactorial disease characterized by vascular remodeling, vasoconstriction, inflammation and thrombosis. Although the available therapies have resulted in improvements in morbidity and survival, PAH remains a severe and devastating disease with a poor prognosis and a high mortality, justifying the need of novel therapeutic targets. An increasing number of studies have demonstrated that endothelial cells (ECs), smooth muscle cells (SMCs) and fibroblasts of the pulmonary vessel wall, as well as platelets and inflammatory cells have a role in PAH pathogenesis. This review aims to integrate the interplay among different types of cells, during PAH development and progression, and the impact of current therapies in cellular modulation. The interplay among endothelial cells, smooth muscle cells and fibroblasts present in pulmonary vessels wall, platelets and inflammatory cells is regulated by several mediators produced by these cells, contributing to the pathophysiologic features of PAH. Current therapies are mainly focused in the pulmonary vascular tone and in the endothelial dysfunction. However, once they have not been effective, novel therapies targeting other PAH features, such as inflammation and platelet dysfunction are emerging. Further understanding of the interplay among different vascular cell types involved in PAH development and progression can contribute to find novel therapeutic targets, decreasing PAH mortality and morbidity in the future.     

Cell cultures of Maytenus ilicifolia Mart. are richer sources of quinone-methide triterpenoids than plant roots in natura

The quinone-methide triterpenoids (QMTs) are chemotaxonomic markers of the family Celastraceae and many compounds of this class possess important anticancer and anti-inflammatory activities. However, the levels of QMTs in the roots of Celastraceous species are typically very low (ca. 0.0003 %) and commercial production by extraction from such tissues would not be commercially viable. With the aim of determining if cells cultured in vitro might provide alternative sources of these bioactive triterpenoids, we have quantified and compared the concentrations of QMTs accumulated by the roots of plants of Maytenus ilicifolia Mart. ex Reissek (Celastraceae) aged 0.5–10 years, and in callus and suspension cultures derived from a cell line that had been subcultured over a period of 10 years. Comparing plants cultivated in natura, the highest levels of QMTs were detected in the root bark of 5-year old specimens. However, cell suspensions derived from the long-term cell line retained their capacity to synthesize and accumulate QMTs, and presented levels of maytenin, 22β-hydroxymaytenin, celastrol and pristimerin that were, respectively, 1.96-, 2.48-, 8.85- and 3.29-times higher than those in the roots of 5-year old plants. The results presented herein open up new possibilities for the large-scale production of QMTs and for the development of novel pharmaceuticals.     

Species discrimination in Sisyrinchium (Iridaceae): assessment of DNA barcodes in a taxonomically challenging genus

DNA barcoding aims to develop an efficient tool for species identification based on short and standardized DNA sequences. In this study, the DNA barcode paradigm was tested among the genera of the tribe Sisyrinchieae (Iridoideae). Sisyrinchium, with more than 77% of the species richness in the tribe, is a taxonomically complex genus. A total of 185 samples belonging to 98 species of Sisyrinchium, Olsynium, Orthrosanthus and Solenomelus were tested using matK, trnH‐psbA and internal transcribed spacer (ITS). Candidate DNA barcodes were analysed either as single markers or in combination. Detection of a barcoding gap, similarity‐based methods and tree‐based analyses were used to assess the discrimination efficiency of DNA barcodes. The levels of species identification obtained from plastid barcodes were low and ranged from 17.35% to 20.41% for matK and 5.11% to 7.14% for trnH‐psbA. The ITS provided better results with 30.61–38.78% of species identified. The analyses of the combined data sets did not result in a significant improvement in the discrimination rate. Among the tree‐based methods, the best taxonomic resolution was obtained with Bayesian inference, particularly when the three data sets were combined. The study illustrates the difficulties for DNA barcoding to identify species in evolutionary complex lineages. Plastid markers are not recommended for barcoding Sisyrinchium due to the low discrimination power observed. ITS gave better results and may be used as a starting point for species identification.     

Toxoplasma gondii 70 kDa Heat Shock Protein: Systemic Detection Is Associated with the Death of the Parasites by the Immune Response and Its Increased Expression in the Brain Is Associated with Parasite Replication

The heat shock protein of Toxoplasma gondii (TgHSP70) is a parasite virulence factor that is expressed during T. gondii stage conversion. To verify the effect of dexamethasone (DXM)-induced infection reactivation in the TgHSP70-specific humoral immune response and the presence of the protein in the mouse brain, we produced recombinant TgHSP70 and anti-TgHSP70 IgY antibodies to detect the protein, the specific antibody and levels of immune complexes (ICs) systemically, as well as the protein in the brain of resistant (BALB/c) and susceptible (C57BL/6) mice. It was observed higher TgHSP70-specific antibody titers in serum samples of BALB/c compared with C57BL/6 mice. However, the susceptible mice presented the highest levels of TgHSP70 systemically and no detection of specific ICs. The DXM treatment induced increased parasitism and lower inflammatory changes in the brain of C57BL/6, but did not interfere with the cerebral parasitism in BALB/c mice. Additionally, DXM treatment decreased the serological TgHSP70 concentration in both mouse lineages. C57BL/6 mice presented high expression of TgHSP70 in the brain with the progression of infection and under DXM treatment. Taken together, these data indicate that the TgHSP70 release into the bloodstream depends on the death of the parasites mediated by the host immune response, whereas the increased TgHSP70 expression in the brain depends on the multiplication rate of the parasite.     

A Regional-Scale Ocean Health Index for Brazil

Brazil has one of the largest and fastest growing economies and one of the largest coastlines in the world, making human use and enjoyment of coastal and marine resources of fundamental importance to the country. Integrated assessments of ocean health are needed to understand the condition of a range of benefits that humans derive from marine systems and to evaluate where attention should be focused to improve the health of these systems. Here we describe the first such assessment for Brazil at both national and state levels. We applied the Ocean Health Index framework, which evaluates ten public goals for healthy oceans. Despite refinements of input data and model formulations, the national score of 60 (out of 100) was highly congruent with the previous global assessment for Brazil of 62. Variability in scores among coastal states was most striking for goals related to mariculture, protected areas, tourism, and clean waters. Extractive goals, including Food Provision, received low scores relative to habitat-related goals, such as Biodiversity. This study demonstrates the applicability of the Ocean Health Index at a regional scale, and its usefulness in highlighting existing data and knowledge gaps and identifying key policy and management recommendations. To improve Brazil''s ocean health, this study suggests that future actions should focus on: enhancing fisheries management, expanding marine protected areas, and monitoring coastal habitats.     

Limits and Trade-Offs of Topological Network Robustness

We investigate the trade-off between the robustness against random and targeted removal of nodes from a network. To this end we utilize the stochastic block model to study ensembles of infinitely large networks with arbitrary large-scale structures. We present results from numerical two-objective optimization simulations for networks with various fixed mean degree and number of blocks. The results provide strong evidence that three different blocks are sufficient to realize the best trade-off between the two measures of robustness, i.e. to obtain the complete front of Pareto-optimal networks. For all values of the mean degree, a characteristic three block structure emerges over large parts of the Pareto-optimal front. This structure can be often characterized as a core-periphery structure, composed of a group of core nodes with high degree connected among themselves and to a periphery of low-degree nodes, in addition to a third group of nodes which is disconnected from the periphery, and weakly connected to the core. Only at both extremes of the Pareto-optimal front, corresponding to maximal robustness against random and targeted node removal, a two-block core-periphery structure or a one-block fully random network are found, respectively.