Serum contents of immunoreactive pancreatic secretory trypsin inhibitor and seminal plasma acrosin-trypsin inhibitor in polytraumatized patients

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Strategies in 'snake venomics' aiming at an integrative view of compositional, functional, and immunological characteristics of venoms

This work offers a general overview on the evolving strategies for the proteomic analysis of snake venoms, and discusses how these may be combined through diverse experimental approaches with the goal of achieving a more comprehensive knowledge on the compositional, toxic, and immunological characteristics of venoms. Some recent developments in this field are summarized, highlighting how strategies have evolved from the mere cataloguing of venom components (proteomics/venomics), to a broader exploration of their immunological (antivenomics) and functional (toxicovenomics) characteristics. Altogether, the combination of these complementary strategies is helping to build a wider, more integrative view of the life-threatening protein cocktails produced by venomous snakes, responsible for thousands of deaths every year.Ministerio de Economía y Competitividad/[BFU2013-42833-P]//EspañaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP

Tissue Localization and Extracellular Matrix Degradation by PI, PII and PIII Snake Venom Metalloproteinases: Clues on the Mechanisms of Venom-Induced Hemorrhage

20 páginas, 4 figuras, 3 tablas y 7 tablas en material suplementario.Snake venom hemorrhagic metalloproteinases (SVMPs) of the PI, PII and PIII classes were compared in terms of tissue localization and their ability to hydrolyze basement membrane components in vivo, as well as by a proteomics analysis of exudates collected in tissue injected with these enzymes. Immunohistochemical analyses of co-localization of these SVMPs with type IV collagen revealed that PII and PIII enzymes co-localized with type IV collagen in capillaries, arterioles and post-capillary venules to a higher extent than PI SVMP, which showed a more widespread distribution in the tissue. The patterns of hydrolysis by these three SVMPs of laminin, type VI collagen and nidogen in vivo greatly differ, whereas the three enzymes showed a similar pattern of degradation of type IV collagen, supporting the concept that hydrolysis of this component is critical for the destabilization of microvessel structure leading to hemorrhage. Proteomic analysis of wound exudate revealed similarities and differences between the action of the three SVMPs. Higher extent of proteolysis was observed for the PI enzyme regarding several extracellular matrix components and fibrinogen, whereas exudates from mice injected with PII and PIII SVMPs had higher amounts of some intracellular proteins. Our results provide novel clues for understanding the mechanisms by which SVMPs induce damage to the microvasculature and generate hemorrhage.This work was performed in partial fulfillment of the requirements for the PhD degree for Cristina Herrera at Universidad de Costa Rica.Peer reviewe

Purification and functional characterisation of rhiminopeptidase A, a novel aminopeptidase from the venom of Bitis gabonica rhinoceros

This study describes the discovery and characterisation of a novel aminopeptidase A from the venom of B. g. rhinoceros and highlights its potential biological importance. Similar to mammalian aminopeptidases, rhiminopeptidase A might be capable of playing roles in altering the blood pressure and brain function of victims. Furthermore, it could have additional effects on the biological functions of other host proteins by cleaving their N-terminal amino acids. This study points towards the importance of complete analysis of individual components of snake venom in order to develop effective therapies for snake bites

Computational Biology in Costa Rica: The Role of a Small Country in the Global Context of Bioinformatics

Introduction: The successful development of high throughput methods for DNA sequencing, transcriptomics, proteomics, and other –omics, has contributed to the emergence of novel possibilities for the examination of complex biological systems through computational analysis. These fields have witnessed unprecedented advances in high income countries. Nevertheless, the role of other nations needs to be examined in order to delineate their contribution within the global context of bioinformatics. Previous articles have focused on the expansion of Computational Biology in Brazil and Mexico [1],[2], two of the largest Latin American countries, and which have shown political commitment to foster their scientific development. Costa Rica is a small Central American country with a population of 4 million, with its territory 164 and 38 times smaller than Brazil and Mexico, respectively. Thus, it is interesting to visualize the possibilities and challenges of this low-income country in the context of the global bioinformatics endeavor.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP

Effectiveness of habitat management in the recovery of low-density populations of wild rabbit.

Understanding the relationship between spatial patterns of landscape attributes and population presence and abundance is essential for understanding population processes as well as supporting management and conservation strategies. This study evaluates the influence of three factors: environment, habitat management, and season on the presence and abundance of the wild rabbit (Oryctolagus cuniculus), an important prey species for Mediterranean endangered predator species. To address this issue, we estimated wild rabbit presence and abundance by latrine counting in transects located in 45 plots within a 250×250 m grid from June 2007 until June 2009 in a 1,200 ha hunting area in southern Portugal.We then analyzed how wild rabbit presence and abundance correlatewith the aforementioned factors. Our results showed that the main variable influencing wild rabbit presence and abundance was the distance to the artificial warrens. North and northeast slope directions were negatively related to wild rabbit presence. Conversely, rabbit presence was positively correlated with short distances to ecotone, artificial warrens, and spring. Regarding rabbit abundance, in addition to artificial warrens, soft soils, bushes, and season also had a positive effect. We found that environmental variables, management practices, and season each affect wild rabbit presence and abundance differently at a home range scale in low-density population. Thus, our major recommendations are reducing the distance to artificial warrens and ecotone, ideally to less than 100 m, and promoting habitat quality improvement on slopes with plenty of sun exposure

The GPIIIA PlA2 polymorphism is associated with an increased risk of cardiovascular adverse events

<p>Abstract</p> <p>Background</p> <p>The clinical impact of PlA2 polymorphism has been investigated in several diseases, but the definition of its specific role on thrombotic cardiovascular complications has been challenging. We aimed to explore the effect of PlA2 polymorphism on outcome in patients with atherosclerosis.</p> <p>Methods</p> <p>We studied 400 consecutive patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention. A replication study was conducted in 74 hypertensive patients with cerebrovascular events while a group of 100 healthy subjects was included as control population. PlA genotype was determined by PCR-RFLP on genomic DNA from peripheral blood cells. Major adverse cardiac events (MACE), were considered as end points, and recorded at a mean follow up of 24 ± 4.3 months.</p> <p>Results</p> <p>The frequencies of PlA2 polymorphism was similar between groups and genotype distribution was in Hardy-Weinberg equilibrium. In patients with CAD, the presence of PlA2 allele was associated with higher incidence of cardiac death (13.1% vs. 1.5%, p = 0.0001), myocardial infarction (10.7% vs. 2.6%, p = 0.004) and needs of new revascularization (34.8% vs. 17.7%, p = 0.010). Accordingly, the Kaplan-Meier analysis for event free survival in patients harboring the PlA2 allele showed worse long-term outcome for these patients (p = 0.015). Cox regression analysis identified the presence of PlA2 as an independent predictor of cardiac death (OR: 9.594, 95% CI: 2.6 to 35.3, p = 0.002) and overall MACE (OR: 1.829, 95% CI: 1.054 to 3.176, p = 0.032). In the replication study, the PlA2 polymorphism increased the risk of stroke (OR: 4.1, 95% CI: 1.63-12.4, p = 0.02) over TIA and was identified as an independent risk factor for stroke (B:-1.39; Wald: 7.15; p = 0.001).</p> <p>Conclusions</p> <p>Our study demonstrates that in patients with severe atherosclerosis the presence of PlA2 allele is associated with thrombotic cardiovascular complications.</p

Structure of a lectin from Canavalia gladiata seeds: new structural insights for old molecules

<p>Abstract</p> <p>Background</p> <p>Lectins are mainly described as simple carbohydrate-binding proteins. Previous studies have tried to identify other binding sites, which possible recognize plant hormones, secondary metabolites, and isolated amino acid residues. We report the crystal structure of a lectin isolated from <it>Canavalia gladiata </it>seeds (CGL), describing a new binding pocket, which may be related to pathogen resistance activity in ConA-like lectins; a site where a non-protein amino-acid, α-aminobutyric acid (Abu), is bound.</p> <p>Results</p> <p>The overall structure of native CGL and complexed with α-methyl-mannoside and Abu have been refined at 2.3 Å and 2.31 Å resolution, respectively. Analysis of the electron density maps of the CGL structure shows clearly the presence of Abu, which was confirmed by mass spectrometry.</p> <p>Conclusion</p> <p>The presence of Abu in a plant lectin structure strongly indicates the ability of lectins on carrying secondary metabolites. Comparison of the amino acids composing the site with other legume lectins revealed that this site is conserved, providing an evidence of the biological relevance of this site. This new action of lectins strengthens their role in defense mechanisms in plants.</p

Snake Envenoming: A Disease of Poverty

Every year snake envenoming kills more people in the tropics than some of the world's recognised neglected tropical diseases (NTDs), including schistosomiasis and leishmaniasis. While lacking the epidemic potential of an infectious/vector-borne disease, snake envenoming in rural tropical communities has as great a medical mortality, if not morbidity, as the NTDs. The recent categorisation of snake envenoming as an NTD is an important advance that hopefully will result in the wider recognition and allocation of resources, particularly since death from snake envenoming is preventable; antivenom is very effective when the appropriate antivenom is correctly administered. Snake envenoming urgently requires international support to instigate the epidemiological, health education, and effective treatment initiatives that proved so potent in addressing the medical burden of NTDs such as leprosy and dracunculosis. All the global estimates of snake envenoming and deaths from snakebite indicate that mortality is highest in the world's tropical countries. Here we examined associations between the globally available data on (i) snakebite-induced mortality and (ii) socioeconomic markers of poverty. Our data unequivocally establishes that snake envenoming is globally associated with poverty, a distinctive characteristic of the neglected tropical diseases

KSHV gB associated RGD interactions promote attachment of cells by inhibiting the potential migratory signals induced by the disintegrin-like domain

Background: Kaposi's sarcoma-associated herpesvirus (KSHV) glycoprotein B (gB) is not only expressed on the envelope of mature virions but also on the surfaces of cells undergoing lytic replication. Among herpesviruses, KSHV gB is the only glycoprotein known to possess the RGD (Arg-Gly-Asp) binding integrin domain critical to mediating cell attachment. Recent studies described gB to also possess a disintegrin-like domain (DLD) said to interact with non-RGD binding integrins. We wanted to decipher the roles of two individually distinct integrin binding domains (RGD versus DLD) within KSHV gB in regulating attachment of cells over cell migration