Mechanisms of Vascular Damage by Hemorrhagic Snake Venom Metalloproteinases: Tissue Distribution and In Situ Hydrolysis

Snakebite accidents by vipers cause a massive disturbance in hemostasis and tissue damage at the snakebite area. The systemic effects are often prevented by antivenom therapy. However, the local symptoms are not neutralized by antivenoms and are related to the temporary or permanent disability observed in many patients. Although the mechanisms involved in coagulation or necrotic disturbances induced by snake venoms are well known, the disruption of capillary vessels by SVMPs leading to hemorrhage and consequent local tissue damage is not fully understood. In our study, we reveal the mechanisms involved in hemorrhage induced by SVMPs by comparing the action of high and low hemorrhagic toxins isolated from Bothrops venoms, in mouse skin. We show remarkable differences in the tissue distribution and hydrolysis of collagen within the hemorrhagic lesions induced by high and low hemorrhagic metalloproteinases. According to our data, tissue accumulation of hemorrhagic toxins near blood vessel walls allowing the hydrolysis of basement membrane components, preferably collagen IV. These observations unveil new mechanistic insights supporting the local administration of metalloproteinases inhibitors as an alternative to improve snakebite treatment besides antivenom therapy

Diversity of metalloproteinases in Bothrops neuwiedi snake venom transcripts: evidences for recombination between different classes of SVMPs

<p>Abstract</p> <p>Background</p> <p>Snake venom metalloproteinases (SVMPs) are widely distributed in snake venoms and are versatile toxins, targeting many important elements involved in hemostasis, such as basement membrane proteins, clotting proteins, platelets, endothelial and inflammatory cells. The functional diversity of SVMPs is in part due to the structural organization of different combinations of catalytic, disintegrin, disintegrin-like and cysteine-rich domains, which categorizes SVMPs in 3 classes of precursor molecules (PI, PII and PIII) further divided in 11 subclasses, 6 of them belonging to PII group. This heterogeneity is currently correlated to genetic accelerated evolution and post-translational modifications.</p> <p>Results</p> <p>Thirty-one SVMP cDNAs were full length cloned from a single specimen of <it>Bothrops neuwiedi </it>snake, sequenced and grouped in eleven distinct sequences and further analyzed by cladistic analysis. Class P-I and class P-III sequences presented the expected tree topology for fibrinolytic and hemorrhagic SVMPs, respectively. In opposition, three distinct segregations were observed for class P-II sequences. P-IIb showed the typical segregation of class P-II SVMPs. However, P-IIa grouped with class P-I cDNAs presenting a 100% identity in the 365 bp at their 5' ends, suggesting post-transcription events for interclass recombination. In addition, catalytic domain of P-IIx sequences segregated with non-hemorrhagic class P-III SVMPs while their disintegrin domain grouped with other class P-II disintegrin domains suggesting independent evolution of catalytic and disintegrin domains. Complementary regions within cDNA sequences were noted and may participate in recombination either at DNA or RNA levels. Proteins predicted by these cDNAs show the main features of the correspondent classes of SVMP, but P-IIb and P-IIx included two additional cysteines cysteines at the C-termini of the disintegrin domains in positions not yet described.</p> <p>Conclusions</p> <p>In <it>B. neuwiedi </it>venom gland, class P-II SVMPs were represented by three different types of transcripts that may have arisen by interclass recombination with P-I and P-III sequences after the divergence of the different classes of SVMPs. Our observations indicate that exon shuffling or post-transcriptional mechanisms may be driving these recombinations generating new functional possibilities for this complex group of snake toxins.</p

Antiproliferative and anti-inflammatory activity from aerial parts of Psychotria cupularis (Rubiaceae) / Atividade antiproliferativa e anti-inflamatória das partes aéreas de Psychotria cupularis (Rubiaceae)

The crude extract and fractions of aerial parts from Psychotria cupularis, collected at Camacan (Brazil), were tested for anti-inflammatory and antiproliferative activity. A phytochemical screening indicated the presence of tannins, anthraquinones, triterpenes, steroids and flavonoids. The crude extract and fractions inhibited the ear oedema in mice between 50.2 to 87.2% and the myeloperoxidase enzyme activity between 51.6 to 97.1%. The butanolic and ethyl acetate fractions was active against glioma, breast, ovary, kidney, colon and leukaemia cell line (IG50 = 4.3 to 16.9 ?g/mL). 

Genomic history of coastal societies from eastern South America

Sambaqui (shellmound) societies are among the most intriguing archaeological phenomena in pre-colonial South America, extending from approximately 8,000 to 1,000 years before present (yr bp) across 3,000 km on the Atlantic coast. However, little is known about their connection to early Holocene hunter-gatherers, how this may have contributed to different historical pathways and the processes through which late Holocene ceramists came to rule the coast shortly before European contact. To contribute to our understanding of the population history of indigenous societies on the eastern coast of South America, we produced genome-wide data from 34 ancient individuals as early as 10,000 yr bp from four different regions in Brazil. Early Holocene hunter-gatherers were found to lack shared genetic drift among themselves and with later populations from eastern South America, suggesting that they derived from a common radiation and did not contribute substantially to later coastal groups. Our analyses show genetic heterogeneity among contemporaneous Sambaqui groups from the southeastern and southern Brazilian coast, contrary to the similarity expressed in the archaeological record. The complex history of intercultural contact between inland horticulturists and coastal populations becomes genetically evident during the final horizon of Sambaqui societies, from around 2,200 yr bp, corroborating evidence of cultural change

Multidisciplinary Scientific Cruises for Environmental Characterization in the Santos Basin – Methods and Sampling Design

The Santos Basin (SB) is the main petroliferous basin in the Brazilian continental margin and one of the most studied marine areas in Brazil. However, historical data suggest that new efforts should be carried out to acquire quantitative biological data, especially in the deep sea, to establish the baseline of essential ocean variables in different ecosystems for future monitoring programs. The Brazilian energy company Petrobras planned and executed 24 oceanographic cruises over a period of 2 years to assess the benthic (SANSED cruise) and pelagic (SANAGU cruise) systems of the SB (356 days at sea in 2019 and 2021/2022). These efforts were part of the Santos Project, which comprised a comprehensive environmental study aimed at investigating benthic and pelagic variables to characterize ecology, biogeochemistry, thermohaline properties of water masses, and ocean circulation patterns, geomorphology, and sedimentology, as well as organic and inorganic chemistry. Here we present the detailed sampling designs and the field methods employed on board, during the SB scientific cruises. All sampling protocols were based on standardized approaches. For the benthos analyses, triplicate sediment samples were performed using a GOMEX-type box corer (0.25 m²) or a large modified Van Veen grab (0.75 m²) at 100 stations ranging from 25 to 2400 m depth. At each station, 25 geochemical and physico-chemical parameters were analyzed in addition to micro-, meio-, and macrofauna and living foraminifera samples. For the pelagic system, 60 stations were selected to investigate the plankton community, ranging in size from pico- to macroplankton, through vertical, horizontal, and oblique net hauls (20, 200, and 500 μm mesh size), as well as 25 biogeochemical parameters collected with an aid of a CTD-rosette sampler. Part of this scientific information also serves the Regional Environmental Characterization Project (PCR-BS) in support of Petrobras’ Santos Basin drilling licensing process led by the Brazilian Environmental Agency – IBAMA. This project contributes to the sustainable development of the SB, in line with the guidelines of the United Nations Decade of Ocean Science for Sustainable Development