Crystal structure of a novel myotoxic Arg49 phospholipase A(2) homolog (zhaoermiatoxin) from Zhaoermia mangshanensis snake venom: Insights into Arg49 coordination and the role of Lys122 in the polarization of the C-terminus

The venom of Zhaoermia mangshanensis, encountered solely in Mt Mang in China's Hunan Province, exhibits coagulant, phosphodiesterase, L-amino acid oxidase, kallikrein, phospholipase A(2) and myotoxic activities. The catalytically inactive PLA(2) homolog referred to as zhaoermiatoxin is highly myotoxic and displays high myonecrotic and edema activities. Zhaoermiatoxin possesses a molecular weight of 13,972 Da, consists of 121 amino-acid residues crosslinked by seven disulfide bridges and shares high sequence homology with Lys49-PLA(2)s from the distantly related Asian pitvipers. However, zhaoermiatoxin possesses an arginine residue at position 49 instead of a lysine, thereby suggesting a secondary Lys49 -> Arg substitution which results in a catalytically inactive protein. We have determined the first crystal structure of zhaoermiatoxin, an Arg49-PLA(2), from Zhaoermia mangshanensis venom at 2.05 A resolution, which represents a novel member of phospholipase A(2) family. In this structure, unlike the Lys49 PLA(2)s, the C-terminus is well ordered and an unexpected non-polarized state of the putative calcium-binding loop due to the flip of Lys122 towards the bulk solvent is observed. The orientation of the Arg-49 side chain results in a similar binding mode to that observed in the Lys49 PLA(2)s; however, the guadinidium group is tri-coordinated by carbonyl oxygen atoms of the putative calcium-binding loop, whereas the N zeta atom of lysine is tetra-coordinated as a result of the different conformation adopted by the putative calcium-binding loop. (c) 2008 Elsevier Ltd. All rights reserved.

SEM analysis of the in situ early bacterial colonization on two novel feldspathic ceramics submitted to different types of glazing

Aim: The aim of this study was to evaluate in situ, the early bacterial colonization on feldspar-ceramics submitted to different glazing. Methods and Materials: Fourteen standardized disc specimens (diameter: 5 mm, thickness: 1.5 mm) of each of two micro-particulate feldspathic ceramics (VM7 and VM13, Vita) were produced according to manufacturers' specifications for a total of 28 specimens (24 for the analysis of biofilm and 4 for topographic analysis analyzing the ceramic surfaces). Specimens from each type of ceramic were submitted to two different glazing methods composing four groups: VM7 glazed using glazing liquid Vita Akzent® 25 (G1) and glaze firing (G2), VM13 glazed using glazing liquid (G3) and glaze firing (G4). Six individuals (n=6) wore oral appliances with four ceramic specimens, fixed on the buccal face of the appliances. After 8 hours, each sample was evaluated for the presence (1) or absence (0) of bacterial colonization under a scanning electron microscope (SEM) on five randomly selected fields. The value for each sample was cumulative of the results observed in the fields. One sample from each group was evaluated under a SEM to verify the topographic pattern. Results: There was no difference with regard to bacterial colonization between the feldspar-ceramics and between the glazing types (Kruskal-Wallis non-parametric test). Conclusion: Feldspar-ceramics submitted to firing or glaze firing with Vita Akzent® 25 present a similar condition for in situ bacterial colonization. The similar topographic pattern of the ceramic surfaces seems to have influenced the bacterial colonization.

A novel device with 36 channels for imaging and signal acquisition of the gastrointestinal tract based on AC biosusceptometry

The alternate current biosusceptometry (ACB) is a biomagnetic technique used to study some physiological parameters associated with gastrointestinal (GI) tract. For this purpose it applies an AC magnetic field and measures the response originating from magnetic marks or tracers. This paper presents an equipment based on the ACB which uses anisotropic magnetoresistive (AMR) sensors and an inexpensive electronic support. The ACB-AMR developed consists of a square array of 6x6 sensors arranged in a firstorder gradiometer configuration with one reference sensor. The equipment was applied to capture magnetic images of different phantoms and to acquire gastric contraction activity of healthy rats. The results show a reasonable sensitivity and spatial-temporal resolution, so that it may be applied for imaging of phantoms and signal acquisition of the GI tract of small animals. © 2010 IEEE.

Measurement of the underlying event activity in pp collisions at √s = 0.9 and 7 TeV with the novel jet-area/median approach

The first measurement of the charged component of the underlying event using the novel jet-area/median approach is presented for proton-proton collisions at centre-of-mass energies of 0.9 and 7 TeV. The data were recorded in 2010 with the CMS experiment at the LHC. A new observable, sensitive to soft particle production, is introduced and investigated inclusively and as a function of the event scale defined by the transverse momentum of the leading jet. Various phenomenological models are compared to data, with and without corrections for detector effects. None of the examined models describe the data satisfactorily. © 2012 SISSA.

Structure-function relationships of the peptide Paulistine: A novel toxin from the venom of the social wasp Polybia paulista

Background: The peptide Paulistine was isolated from the venom of wasp Polybia paulista. This peptide exists under a natural equilibrium between the forms: oxidised - with an intra-molecular disulphide bridge; and reduced - in which the thiol groups of the cysteine residues do not form the disulphide bridge. The biological activities of both forms of the peptide are unknown up to now. Methods: Both forms of Paulistine were synthesised and the thiol groups of the reduced form were protected with the acetamidemethyl group [Acm-Paulistine] to prevent re-oxidation. The structure/activity relationships of the two forms were investigated, taking into account the importance of the disulphide bridge. Results: Paulistine has a more compact structure, while Acm-Paulistine has a more expanded conformation. Bioassays reported that Paulistine caused hyperalgesia by interacting with the receptors of lipid mediators involved in the cyclooxygenase type II pathway, while Acm-Paullistine also caused hyperalgesia, but mediated by receptors involved in the participation of prostanoids in the cyclooxygenase type II pathway. Conclusion: The acetamidemethylation of the thiol groups of cysteine residues caused small structural changes, which in turn may have affected some physicochemical properties of the Paulistine. Thus, the dissociation of the hyperalgesy from the edematogenic effect when the actions of Paulistine and Acm-Paulistine are compared to each other may be resulting from the influence of the introduction of Acm-group in the structure of Paulistine. General significance: The peptides Paulistine and Acm-Paulistine may be used as interesting tools to investigate the mechanisms of pain and inflammation in future studies. © 2013 Elsevier B.V.

Novel anthraquinone derivatives produced by Pestalotiopsis guepinii, an endophytic of the medicinal plant Virola michelii (Myristicaceae)

Um novo derivado de antraquinona, denominado guepinone (1), juntamente com as conhecidas substâncias isossulocrina (2) e cloroissosulocrina (3) foram isolados de uma cultura em arroz de Pestalotiopsis guepinii, um fungo endofitico de Virola michelii. Os compostos foram identificados pela análise de seus dados espectrométricos de RMN 1D e 2D e EM. A atividade antimicrobiana dos compostos isolados foi avaliada e a cloroisossulcrina (3) foi a mais ativa.

Reproductive cycle of the Neotropical cichlid yellow peacock bass Cichla kelberi: A novel pattern of testicular development

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

Biotechnology of polyketides: new breath of life for the novel antibiotic genetic pathways discovery through metagenomics

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

Identification of two novel cytolysins from the hydrozoan Olindias sambaquiensis (Cnidaria)

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

Spontaneous osteonecrosis of the jaws in the maxilla of mice on antiresorptive treatment: A novel ONJ mouse model

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

Novel estimation of the humification degree of soil organic matter by laser-induced breakdown spectroscopy

Soil organic matter (SOM) constitutes an important reservoir of terrestrial carbon and can be considered an alternative for atmospheric carbon storage, contributing to global warming mitigation. Soil management can favor atmospheric carbon incorporation into SUM or its release from SOM to atmosphere. Thus, the evaluation of the humification degree (HD), which is an indication of the recalcitrance of SOM, can provide an estimation of the capacity of carbon sequestration by soils under various managements. The HD of SOM can be estimated by using various analytical techniques including fluorescence spectroscopy. In the present work, the potential of laser-induced breakdown spectroscopy (LIBS) to estimate the HD of SUM was evaluated for the first time. Intensities of emission lines of Al, Mg and Ca from LIBS spectra showing correlation with fluorescence emissions determined by laser-induced fluorescence spectroscopy (LIFS) reference technique were used to obtain a multivaried calibration model based on the k-nearest neighbor (k-NN) method. The values predicted by the proposed model (A-LIBS) showed strong correlation with LIFS results with a Pearson's coefficient of 0.87. The HD of SUM obtained after normalizing A-LIBS by total carbon in the sample showed a strong correlation to that determined by LIFS (0.94), thus suggesting the great potential of LIBS for this novel application. (C) 2014 Elsevier B.V. All rights reserved.

Novel bioassay for the discovery of inhibitors of the 2-C-Methyl-D-erythritol 4-Phosphate (MEP) and terpenoid pathways leading to carotenoid biosynthesis

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Structural characterization of novel chemotactic and mastoparan peptides from the venom of the social wasp Agelaia pallipes pallipes by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Analysis of linearity and frequency response of a novel piezoelectric flextensional actuator using a homodyne interferometer and the J(1)-J(4) method

Piezoelectric transducers are widely used in high-resolution positioning systems. This paper reports the experimental analysis of a novel piezoelectric flextensional actuator (PFA), which is designed by using the topology-optimization method through a low-cost homodyne Michelson interferometer. By applying the J(1) - J(4) method for signal demodulation, which provides a linear and direct measurement of dynamic optical phase shift independent of fading, the nanometric displacements of the PFA were determined. Linearity and frequency response of the PFA were evaluated up to 50 kHz. PFA calibration factor and amplification rate were determined for the PFA operating in the quasi-static regime. To confirm the observed frequencies of resonance, an impedance analyzer is also utilized to measure the magnitude and phase of the PFA admittance.

Lufaxin, a Novel Factor Xa Inhibitor From the Salivary Gland of the Sand Fly Lutzomyia longipalpis Blocks Protease-Activated Receptor 2 Activation and Inhibits Inflammation and Thrombosis In Vivo

Objective-Blood-sucking arthropods' salivary glands contain a remarkable diversity of antihemostatics. The aim of the present study was to identify the unique salivary anticoagulant of the sand fly Lutzomyia longipalpis, which remained elusive for decades. Methods and Results-Several L. longipalpis salivary proteins were expressed in human embryonic kidney 293 cells and screened for inhibition of blood coagulation. A novel 32.4-kDa molecule, named Lufaxin, was identified as a slow, tight, noncompetitive, and reversible inhibitor of factor Xa (FXa). Notably, Lufaxin's primary sequence does not share similarity to any physiological or salivary inhibitors of coagulation reported to date. Lufaxin is specific for FXa and does not interact with FX, Dansyl-Glu-Gly-Arg-FXa, or 15 other enzymes. In addition, Lufaxin blocks prothrombinase and increases both prothrombin time and activated partial thromboplastin time. Surface plasmon resonance experiments revealed that FXa binds Lufaxin with an equilibrium constant approximate to 3 nM, and isothermal titration calorimetry determined a stoichiometry of 1:1. Lufaxin also prevents protease-activated receptor 2 activation by FXa in the MDA-MB-231 cell line and abrogates edema formation triggered by injection of FXa in the paw of mice. Moreover, Lufaxin prevents FeCl3-induced carotid artery thrombus formation and prolongs activated partial thromboplastin time ex vivo, implying that it works as an anticoagulant in vivo. Finally, salivary gland of sand flies was found to inhibit FXa and to interact with the enzyme. Conclusion-Lufaxin belongs to a novel family of slow-tight FXa inhibitors, which display antithrombotic and anti-inflammatory activities. It is a useful tool to understand FXa structural features and its role in prohemostatic and proinflammatory events. (Arterioscler Thromb Vasc Biol. 2012;32:2185-2196.)