Aggretin, a heterodimeric C-type lectin from Calloselasma rhodostoma (malayan pit viper), stimulates platelets by binding to alpha 2beta 1 integrin and glycoprotein Ib, activating Syk and phospholipase Cgamma 2, but does not involve the glycoprotein VI/Fc receptor gamma chain collagen receptor

Aggretin, a potent platelet activator, was isolated from Calloselasma rhodostoma venom, and 30-amino acid N-terminal sequences of both subunits were determined. Aggretin belongs to the heterodimeric snake C-type lectin family and is thought to activate platelets by binding to platelet glycoprotein alpha(2)beta(1). We now show that binding to glycoprotein (GP) Ib is also required. Aggretin-induced platelet activation was inhibited by a monoclonal antibody to GPIb as well as by antibodies to alpha(2)beta(1). Binding of both of these platelet receptors to aggretin was confirmed by affinity chromatography. No binding of other major platelet membrane glycoproteins, in particular GPVI, to aggretin was detected. Aggretin also activates platelets from Fc receptor gamma chain (Fcgamma)-deficient mice to a greater extent than those from normal control mice, showing that it does not use the GPVI/Fcgamma pathway. Platelets from Fcgamma-deficient mice expressed fibrinogen receptors normally in response to collagen, although they did not aggregate, indicating that these platelets may partly compensate via other receptors including alpha(2)beta(1) or GPIb for the lack of the Fcgamma pathway. Signaling by aggretin involves a dose-dependent lag phase followed by rapid tyrosine phosphorylation of a number of proteins. Among these are p72(SYK), p125(FAK), and PLCgamma2, whereas, in comparison with collagen and convulxin, the Fcgamma subunit neither is phosphorylated nor coprecipitates with p72(SYK). This supports an independent, GPIb- and integrin-based pathway for activation of p72(SYK) not involving the Fcgamma receptor.

Bothrops aff. Leucurus (Wagler, 1824) populazio irlatar baten deskribapen morfologikoa: suge populazio irlatar baten morfologia

[EUS] Atrox konplexuko espezieen barruan, Bothrops leucurus (Wagler, 1824) Bahia estatuko oihan atlantikoko sugegorri espezie arruntena da. Polimorfikoa da eta ezaugarri geografikoekin, ontogenikoekin eta sexuarekin erlazionatutako kolore aldakortasuna aurkezten du. Jadanik hainbat ikerketa burutu dira kontinenteko populazioei buruz, baina, oraindik ez da lanik egin BTS badiako populazio uhartetarrekin. Lan honen xedea Bothrops aff. leucurus populazio uhartetarraren deskribapena burutzea izan da, orbanen ereduetan, folidosian eta gorputz tamainan oinarriturik. Lagin tamaina erlatiboki txikia izanik (n=20), Student t testeko emaitzak type II erroreen menpe daude eta kontinenteko eta uharteko populazioen arteko ezberdintasunak estatistikoki ikertu izan ez diren arren, gure datuak garrantzia dute. Izan ere, ikerketa sakonagoetan oinarri bezala erabili ahal izango dira. Biometriari dagokionez, gure populazio uhartetarrean batazbesteko MKL txikiagoa ikusi dugu eta balioen tarteak murritzagoak dira. Ez da sexuen arteko ezberdintasun esangarririk topatu gorputzeko neurrientzat. Folidosian (ezkata zenbateka) lortutako datuak, beste autoreek Bothrops leucurus-entzat deskribatutako parametroekin bat datozen arren, gure laginak ezkata tarte mugatuagoak ageri ditu. Orban ereduak ale guztietan behatu eta irudikatu ostean, oro har bi eredu ezberdindu eta deskribatzea posible izan da. Behatuak izan diren ezberdintasunak, uhartetako baliagai-hornidura mugatuen ondorio gisa uler daitezke, izan ere, halako baldintzetan ale txikiagoak positiboki hautatuak izango liratekeelako.

Targeting αvβ3 and α5β1 for gene delivery to proliferating VSMCs: synergistic effect of TGF-β1

TGF-beta1 levels increase after vascular injury and promote vascular smooth muscle cell (VSMC) proliferation. We define a nonviral gene delivery system that targets alphavbeta3 and alpha5beta1 integrins that are expressed on proliferating VSMCs and strongly induced by TGF-beta1. A 15-amino acid RGDNP-containing peptide from American Pit Viper venom was linked to a Lys(16) peptide as vector (molossin vector) and complexed with Lipofectamine or fusogenic peptide for delivery of luciferase or beta-galactosidase reporter genes to primary cultures of human, rabbit, and rat VSMCs. Preincubation of VSMCs with TGF-beta1 for 24 h, but not with PDGF-BB, interferon-gamma, TNF-alpha, nor PMA, increased alphavbeta3 and alpha5beta1 expressions on VSMCs and enhanced gene delivery of molossin vector. Thus beta-galactosidase activity increased from 35 +/- 5% (controls) to 75 +/- 5% after TGF-beta1 treatment, and luciferase activity increased fourfold over control values. Potential use of this system in vessel bypass surgery was examined in an ex vivo rat aortic organ culture model after endothelial damage. Molossin vector system delivered beta-galactosidase to VSMCs in the vessel wall that remained for up to 12 days posttransfection. The molossin vector system, when combined with TGF-beta1, enhances gene delivery to proliferating VSMCs and might have clinical applications for certain vasculoproliferative diseases.

Enhancement of the citrulline-nitric oxide cycle in astroglioma cells by the proline-rich peptide-10c from Bothrops jararaca venom

The biological activity of the proline rich decapeptde Bj PRO 10c a processing product of the C type natriuretic peptide precursor protein, expressed in the brain and the venom gland of the pit viper Bothrops jararaca, was originally attributed to the inhibition of the somatic angiotensm converting enzyme activity with subsequent ant hypertensive effect However recent results suggest broader biological activity may also be involved in the cardiovascular effects of this peptide Here we show that Bj PRO 10c enhances and sustains the generation of nitric made (NO) by regulating argininosuccinate synthase activity and thereby velocity of the citrulline NO cycle Bj PRO 10c-mediated effects not restricted to the cardiovascular system since NO production was also induced in cells of astroglial origin Bj PRO 10c was internalized by C6 astroglioma cells where it induces NO production and upregulation of the citrulline NO cycle cells in a dose dependent fashion In view of that, astroglial cells function as L arginine pool for NO production in neighboring neurons, we suggest a regulatory function for Bj PRO-10c on the metabolism of this gaseous neurotransmitter in the CNS Moreover, proliferation of astroglial cells was reduced in the presence of Bj PRO 10c however, cell death was not induced Since NO donors have been studied for the treatment of solid cancers Bj PRO 10c may serve as structural model for developing drugs to improve the effects of cancer therapy based on the peptide`s ability to augment NO production (C) 2010 Elsevier B V All rights reserved

The Central Nervous System as Target for Antihypertensive Actions of a Proline-Rich Peptide from Bothrops jararaca Venom

Pyroglutamyl proline-rich oligopeptides, present in the venom of the pit viper Bothrops jararaca (Bj-PROs), are the first described naturally occurring inhibitors of the angiotensin I-converting enzyme (ACE). The inhibition of ACE by the decapeptide Bj-PRO-10c (

Cloning and Identification of a Complete cDNA Coding for a Bactericidal and Antitumoral Acidic Phospholipase A(2) from Bothrops jararacussu Venom

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Temperature and thermal regime effects on the specific dynamic action of Bothrops alternatus (Serpentes, Viperidae)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Court cleaning behavior of the white-bearded manakin (manacus manacus) and a test of the anti-predation hypothesis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Venomics Profiling of Thamnodynastes strigatus Unveils Matrix Metalloproteinases and Other Novel Proteins Recruited to the Toxin Arsenal of Rear-Fanged Snakes

Rear-fanged and aglyphous snakes are usually considered not dangerous to humans because of their limited capacity of injecting venom. Therefore, only a few studies have been dedicated to characterizing the venom of the largest parcel of snake fauna. Here, we investigated the venom proteome of the rear-fanged snake Thamnodynastes strigatus, in combination with a transcriptomic evaluation of the venom gland. About 60% of all transcripts code for putative venom components. A striking finding is that the most abundant type of transcript (similar to 47%) and also the major protein type in the venom correspond to a new kind of matrix metalloproteinase (MMP) that is unrelated to the classical snake venom metalloproteinases found in all snake families. These enzymes were recently suggested as possible venom components, and we show here that they are proteolytically active and probably recruited to venom from a MMP-9 ancestor. Other unusual proteins were suggested to be venom components: a protein related to lactadherin and an EGF repeat-containing transcript. Despite these unusual molecules, seven toxin classes commonly found in typical venomous snakes are also present in the venom. These results support the evidence that the arsenals of these snakes are very diverse and harbor new types of biologically important molecules.

Strategic project evaluation for open pit mining ventures using real options and allied econometric techniques

Open pit mine operations are complex businesses that demand a constant assessment of risk. This is because the value of a mine project is typically influenced by many underlying economic and physical uncertainties, such as metal prices, metal grades, costs, schedules, quantities, and environmental issues, among others, which are not known with much certainty at the beginning of the project. Hence, mining projects present a considerable challenge to those involved in associated investment decisions, such as the owners of the mine and other stakeholders. In general terms, when an option exists to acquire a new or operating mining project, , the owners and stock holders of the mine project need to know the value of the mining project, which is the fundamental criterion for making final decisions about going ahead with the venture capital. However, obtaining the mine project’s value is not an easy task. The reason for this is that sophisticated valuation and mine optimisation techniques, which combine advanced theories in geostatistics, statistics, engineering, economics and finance, among others, need to be used by the mine analyst or mine planner in order to assess and quantify the existing uncertainty and, consequently, the risk involved in the project investment. Furthermore, current valuation and mine optimisation techniques do not complement each other. That is valuation techniques based on real options (RO) analysis assume an expected (constant) metal grade and ore tonnage during a specified period, while mine optimisation (MO) techniques assume expected (constant) metal prices and mining costs. These assumptions are not totally correct since both sources of uncertainty—that of the orebody (metal grade and reserves of mineral), and that about the future behaviour of metal prices and mining costs—are the ones that have great impact on the value of any mining project. Consequently, the key objective of this thesis is twofold. The first objective consists of analysing and understanding the main sources of uncertainty in an open pit mining project, such as the orebody (in situ metal grade), mining costs and metal price uncertainties, and their effect on the final project value. The second objective consists of breaking down the wall of isolation between economic valuation and mine optimisation techniques in order to generate a novel open pit mine evaluation framework called the ―Integrated Valuation / Optimisation Framework (IVOF)‖. One important characteristic of this new framework is that it incorporates the RO and MO valuation techniques into a single integrated process that quantifies and describes uncertainty and risk in a mine project evaluation process, giving a more realistic estimate of the project’s value. To achieve this, novel and advanced engineering and econometric methods are used to integrate financial and geological uncertainty into dynamic risk forecasting measures. The proposed mine valuation/optimisation technique is then applied to a real gold disseminated open pit mine deposit to estimate its value in the face of orebody, mining costs and metal price uncertainties.

Bi-2223 precursor billets for pit wire production

High temperature superconductor precursor billets (feed rods) have been developed for loading into silver tubes. The billets are loaded prior to rolling or drawing operations in PIT wire manufacture. Investigations have shown that wires and tapes prepared from feed rod loaded tubes show enhanced uniformity of electrical transport properties when compared with conventional powder packing, especially in wires drawn to long lengths. Analysis on production feed rods have shown carbon content to be as low as 110 ppm. © 1999 IEEE.

A short-term production scheduling methodology for open-pit mines

A multi-resource multi-stage scheduling methodology is developed to solve short-term open-pit mine production scheduling problems as a generic multi-resource multi-stage scheduling problem. It is modelled using essential characteristics of short-term mining production operations such as drilling, sampling, blasting and excavating under the capacity constraints of mining equipment at each processing stage. Based on an extended disjunctive graph model, a shifting-bottleneck-procedure algorithm is enhanced and applied to obtain feasible short-term open-pit mine production schedules and near-optimal solutions. The proposed methodology and its solution quality are verified and validated using a real mining case study.