Fitness of transgenic Anopheles stephensi mosquitoes expressing the SM1 peptide under the control of a vitellogenin promoter

Three transgenic Anopheles stephensi lines were established that strongly inhibit transmission of the mouse malaria parasite Plasmodium berghei. Fitness of the transgenic mosquitoes was assessed based on life table analysis and competition experiments between transgenic and wild-type mosquitoes. Life table analysis indicated low fitness load for the 2 single-insertion transgenic mosquito lines VD35 and VD26 and no load for the double-insertion transgenic mosquito line VD9. However, in cage experiments, where each of the 3 homozygous transgenic mosquitoes was mixed with nontransgenic mosquitoes, transgene frequency of all 3 lines decreased with time. Further experiments suggested that reduction of transgene frequency is a consequence of reduced mating success, reduced reproductive capacity, and/or insertional mutagenesis, rather than expression of the transgene itself. Thus, for transgenic mosquitoes released in the field to be effective in reducing malaria transmission, a driving mechanism will be required.

Only subtle protein conformational adaptations are required for ligand binding to thyroid hormone receptors: Simulations using a novel multipoint steered molecular dynamics approach

Thyroid hormone receptors (TR) are hormone-dependent transcription regulators that play a major role in human health, development, and metabolic functions. The thyroid hormone resistance syndrome, diabetes, obesity, and some types of cancer are just a few examples of important diseases that are related to TR malfunctioning, particularly impaired hormone binding. Ligand binding to and dissociation from the receptor ultimately control gene transcription and, thus, detailed knowledge of binding and release mechanisms are fundamental for the comprehension of the receptor`s biological function and development of pharmaceuticals. In this work, we present the first computational study of ligand entry into the ligand binding domain (LBD) of a nuclear receptor. We report molecular dynamics simulations of ligand binding to TRs using a generalization of the steered molecular dynamics technique designed to perform single-molecule pulling simulations along arbitrarily nonlinear driving pathways. We show that only gentle protein movements and conformational adaptations are required for ligand entry into the LBDs and that the magnitude of the forces applied to assist ligand binding are of the order of the forces involved in ligand dissociation. Our simulations suggest an alternative view for the mechanisms ligand binding and dissociation of ligands from nuclear receptors in which ligands can simply diffuse through the protein surface to reach proper positioning within the binding pocket. The proposed picture indicates that the large-amplitude protein motions suggested by the apo- and holo-RXR alpha crystallographic structures are not required, reconciling conformational changes of LBDs required for ligand entry with other nuclear receptors apo-structures that resemble the ligand-bound LBDs.

Mineralogy and trace-element geochemistry of the high-grade iron ores of the Aguas Claras Mine and comparison with the Capao Xavier and Tamandua iron ore deposits, Quadrilahero Ferrifero, Brazil

Several major iron deposits occur in the Quadrilatero Ferrifero (QF), southeastern region of Brazil, where metamorphosed and heterogeneously deformed banded iron formation (BIF) of the Caue Formation, regionally called itabirite, was transformed into high- (Fe >64%) and lowgrade (30%elements. The high-grade ores at the Aguas Claras Mine have at least a dual origin, involving hypogene and supergene processes. The occurrence of the hard, massive high-grade ore within ""fresh"" dolomitic itabirite is evidence of its hypogene origin. Despite the contention about the origin of the dolomitic itabirite (if this rock is a carbonate-rich facies of the Caue Formation or a hematite-carbonate precursor of the soft high-grade ore), mineralogical and geochemical features of the soft high-grade ore indicate that it was formed by leaching of dolomite from the dolomitic itabirite by meteoric water. The comparison of the Aguas Claras, Capao Xavier and Tamandua orebodies shows that the original composition of the itabiritic protore plays a major role in the genesis of high- and low-grade soft ores in the QF. Under the same weathering and structural conditions, the dolomitic itabirite is the more favorable to form high-grade deposits than siliceous itabirite. Field relations at the Aguas Claras and Capao Xavier deposits suggest that it is not possible to form huge soft high-grade supergene deposits from siliceous itabirite, unless another control, such as impermeable barriers, had played an important role. The occurrence in the Tamandua Mine of a large, soft, high-grade orebody formed from siliceous itabirite and closely associated with hypogene hard ore suggests that large, soft, high-grade orebodies of the Quadrilatero Ferrifero, which occur within siliceous itabirite, have a hypogene contribution in their formation.

Trace element impurity determination in aspirin tablets by INAA

Instrumental neutron activation analysis (INAA) was applied to assess trace element concentrations in six samples of aspirin tablets acquired in SA o pound Paulo city, Brazil. Concentrations of the elements Br, Ca, Co, Cr, Fe, K, La, Na, Sc and Zn were determined. Comparisons were made between the results obtained with published data for aspirins from foreign countries. Certified reference materials, INCT-MPH-2 Mixed Polish Herbs were analyzed for quality control of the analytical results.