Investigation of the relationship between the structure and function of Ts2, a neurotoxin from Tityus serrulatus venom

Scorpion toxins targeting voltage-gated sodium (NaV) channels are peptides that comprise 6076 amino acid residues cross-linked by four disulfide bridges. These toxins can be divided in two groups (a and beta toxins), according to their binding properties and mode of action. The scorpion a-toxin Ts2, previously described as a beta-toxin, was purified from the venom of Tityus serrulatus, the most dangerous Brazilian scorpion. In this study, seven mammalian NaV channel isoforms (rNaV1.2, rNaV1.3, rNaV1.4, hNaV1.5, mNaV1.6, rNaV1.7 and rNaV1.8) and one insect NaV channel isoform (DmNaV1) were used to investigate the subtype specificity and selectivity of Ts2. The electrophysiology assays showed that Ts2 inhibits rapid inactivation of NaV1.2, NaV1.3, NaV1.5, NaV1.6 and NaV1.7, but does not affect NaV1.4, NaV1.8 or DmNaV1. Interestingly, Ts2 significantly shifts the voltage dependence of activation of NaV1.3 channels. The 3D structure of this toxin was modeled based on the high sequence identity (72%) shared with Ts1, another T. serrulatus toxin. The overall fold of the Ts2 model consists of three beta-strands and one a-helix, and is arranged in a triangular shape forming a cysteine-stabilized a-helix/beta-sheet (CSa beta) motif.

The Influence of Osteoblast Differentiation Stage on Bone Formation in Autogenously Implanted Cell-Based Poly(Lactide-Co-Glycolide) and Calcium Phosphate Constructs

We tested the hypothesis that the osteoblast differentiation status of bone marrow stem cells (BMSCs) combined with a three-dimensional (3D) structure modulates bone formation when autogenously implanted. Rat BMSCs were aspirated, expanded, and seeded into a 3D composite of poly(lactide-co-glycolide) and calcium phosphate (PLGA/CaP) to produce a hybrid biomaterial. Calvarial defects were implanted with (1) scaffold without cells (SC/NC), (2) scaffold and BMSCs (SC + BMSC), (3) scaffold and osteoblasts differentiated for 7 days (SC + OB7), and (4) for 14 days (SC + OB14). After 4 weeks, there was more bone formation in groups combining scaffold and cells, SC + BMSC and SC + OB7. A nonsignificant higher amount of bone formation was observed on SC + OB14 compared with SC/NC. Additionally, more blood vessels were counted within all hybrid biomaterials, without differences among them, than into SC/NC. These findings provide evidences that the cell differentiation status affects in vivo bone formation in autogenously implanted cell-based constructs. Undifferentiated BMSCs or osteoblasts in early stage of differentiation combined with PLGA/CaP scaffold favored bone formation compared with plain scaffold and that one associated with more mature osteoblasts.

Quantum Mechanics Insight into the Microwave Nucleation of SrTiO3 Nanospheres

An extensive investigation of strontium titanate, SrTiO3 (STO), nanospheres synthesized via a microwave-assisted hydrothermal (MAH) method has been conducted to gain a better insight into thermodynamic, kinetic, and reaction phenomena involved in STO nucleation and crystal growth processes. To this end, quantum chemical modeling based on the density functional theory and periodic super cell models were done. Several experimental techniques were employed to get a deep characterization of structural and optical features of STO nanospheres. A possible formation mechanism was proposed, based on dehydration of titanium and strontium clusters followed by mesoscale transformation and a self-assembly process along an oriented attachment mechanism resulting in spherical like shape. Raman and XANES analysis renders a noncentrosymmetric environment for the octahedral titanium, while infrared and first order Raman modes reveal OH groups which are unsystematically incorporated into uncoordinated superficial sites. These results seem to indicate that the key component is the presence of distorted TiO6 clusters to engender a luminescence property. Analysis of band structure, density Of states, and charge map shows that there is a close relationship among local broken symmetry, polarization, and energy split of the 3d orbitals of titanium. The interplay among these electronic and structural features provides necessary conditions to evaluate its luminescent properties under two energy excitation.

Complex, 3D strain patterns in a synkinematic tonalite batholith from the Aracuai Neoproterozoic orogen (Eastern Brazil): Evidence from combined magnetic and isotopic chronology studies

This work combines structural and geochronological data to improve our understanding of the mechanical behaviour of continental crust involving large amount of magma or partially melted material in an abnormally hot collisional belt. We performed a magnetic and geochronological (U/Pb) study on a huge tonalitic batholith from the Neoproterozoic Aracual belt of East Brazil to determine the strain distribution through space and time. Anisotropy of magnetic susceptibility, combined with rock magnetism investigations, supports that the magnetic fabric is a good proxy of the structural fabric. Field measurements together with the magnetic fabrics highlight the presence in the batholith of four domains characterized by contrasted magmatic flow patterns. The western part is characterized by a gently dipping, orogen-parallel (similar to NS) magmatic foliation that bears down-dip lineations, in agreement with westward thrusting onto the Sao Francisco craton. Eastward, the magmatic foliation progressively turns sub-vertical with a lineation that flips from sub-horizontal to sub-vertical over short distances. This latter domain involves an elongated corridor in which the magmatic foliation is sub-horizontal and bears an orogen-parallel lineation. Finally the fourth, narrow domain displays sub-horizontal lineations on a sub-vertical magmatic foliation oblique (similar to N150 degrees E) to the trend of the belt. U/Pb dating of zircons from the various domains revealed homogeneity in age for all samples. This, together with the lack of solid-state deformation suggests that: 1) the whole batholith emplaced during a magmatic event at similar to 580 Ma, 2) the deformation occurred before complete solidification. and 3) the various fabrics are roughly contemporaneous. The complex structural pattern mapped in the studied tonalitic batholith suggests a 3D deformation of a slowly cooling, large magmatic body and its country rock. We suggest that the development of the observed 3D flow field was promoted by the low viscosity of the middle crust that turned gravitational force as an active tectonic force combining with the East-West convergence between the Sao Francisco and Congo cratons. (C) 2012 Elsevier Ltd. All rights reserved.

Investigation of the Goias Alkaline Province, Central Brazil: Application of gravity and magnetic methods

We investigate the strong magnetic and gravity anomalies of the Goias Alkaline Province (GAP), a region of Late Cretaceous alkaline magmatism along the northern border of the Parana Basin, Brazil. The alkaline complexes (eight of which are present in outcrops, two others inferred from magnetic signals) are characterized by a series of small intrusions forming almost circular magnetic and gravimetric anomalies varying from -4000 to +6000 nT and from -10 to +40 mGal, respectively. We used the Aneuler method and Analytical Signal Amplitude to obtain depth and geometry for mapped sources from the magnetic anomaly data. These results were used as the reference models in the 3D gravity inversion. The 3D inversion results show that the alkaline intrusions have depths of 10-12 km. The intrusions in the northern GAP follow two alignments and have different sizes. In the anomaly magnetic map, dominant guidelines correlate strongly with the extensional regimes that correlate with the rise of alkaline magmatism. The emplacement of these intrusions marks mechanical discontinuities and zones of weakness in the upper crust. According to the 3D inversion results, those intrusions are located within the upper crust (from the surface to 18 km depth) and have spheres as the preferable geometry. Such spherical shapes are more consistent with magmatic chambers instead of plug intrusions. The Registro do Araguaia anomaly (similar to 15 by 25 km) has a particular magnetic signature that indicates that the top is deeper than 1500 m. North of this circular anomaly are lineaments with structural indices indicating contacts on their edges and dikes/sills in the interiors. Results of 3D inversion of magnetic and gravity data suggest that the Registro do Araguaia is the largest body in the area, reaching 18 km depth and indicating a circular layered structure. (C) 2011 Elsevier Ltd. All rights reserved.