Low-Resolution Molecular Models Reveal the Oligomeric State of the PPAR and the Conformational Organization of Its Domains in Solution

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

Tax performance and reform in the Organization of Eastern Caribbean States (OECS)

Includes bibliography

School inclusion: analyzing the establishment and organization of a special needs education service in a brazilian municipality

The present research integrates a network of studies called National Monitoring Center for Special Education (NMCSE) which studies the Multi-purpose Feature Rooms (MFRs) in regular schools. We aim to investigate whether the service offered by such rooms, maintained by the Department of Education of the Municipality of Araraquara, in São Paulo State, Brazil, is being successful at supporting the education of children and youth with special needs, pervasive developmental disorders and high skilled/gifted individuals. We have also investigated the limits and possibilities of such rooms concerning the set of services offered to their participants. In order to conduct the present research, we have performed: an interview with the Special Education Program manager from the abovementioned Department of Education; and the analysis of a Training Program that MFRs teachers must take. The training program consists of ten morning and afternoon shift meetings. The analyzed data leads us to conclude that the policy of implementation of MFRs, even in this relatively restricted universe is seen from different perspectives. Some interpretations are still permeated by the clinical model, considering individual action. The challenges observed in the classrooms show that the cooperation among teachers still occur randomly and, among other difficulties raised by them, is the selection of the right placement methods to identify eligible students who will benefit from the Specialized Educational Service (SES). In addition, teaching evaluation was considered fragile, as well as the training and the general requirements demanded in order to achieve the expected results.

CHALLENGES TO THE ORGANIZATION OF A CERVICAL CANCER SCREENING PROGRAM IN MANAUS-AM

The purpose was to investigate sociodemographic characteristics of women who underwent a Pap smear test in Manaus, Amazonas, Brazil, and identify the reasons why the women had the test. This exploratory study was performed with 281 women who had taken the Pap smear test within the last five years in Manaus. Most participants were between 18 to 34 years old (54%), had 5 to 11 years of education (54.4%), had a monthly income of less than three minimum wage salaries (84.3%) and were in a stable relationship (72.2%), with an onset of sexual activity between the ages of 15 to 19 years (69.4%). The reasons for their taking the Pap test were personal choice (66.2%), recommendation by a physician (23.5%) and gynecological symptoms (10.3%). Women who received information about the Pap test from health professionals had a greater chance of being tested within the last three years (p=0.008). Women choosing to have the exam (personal choice) are prevalent, and the opportunistic service is provided to younger women, thus not reaching the group at greater risk for cancer. It is necessary to implement active recruitment strategies to reach women in situations of socioeconomic disadvantage.

Repertoire, Genealogy and Genomic Organization of Cruzipain and Homologous Genes in Trypanosoma cruzi, T. cruzi-Like and Other Trypanosome Species

Trypanosoma cruzi, the agent of Chagas disease, is a complex of genetically diverse isolates highly phylogenetically related to T. cruzi-like species, Trypanosoma cruzi marinkellei and Trypanosoma dionisii, all sharing morphology of blood and culture forms and development within cells. However, they differ in hosts, vectors and pathogenicity: T. cruzi is a human pathogen infective to virtually all mammals whilst the other two species are non-pathogenic and bat restricted. Previous studies suggest that variations in expression levels and genetic diversity of cruzipain, the major isoform of cathepsin L-like (CATL) enzymes of T. cruzi, correlate with levels of cellular invasion, differentiation, virulence and pathogenicity of distinct strains. In this study, we compared 80 sequences of genes encoding cruzipain from 25 T. cruzi isolates representative of all discrete typing units (DTUs TcI-TcVI) and the new genotype Tcbat and 10 sequences of homologous genes from other species. The catalytic domain repertoires diverged according to DTUs and trypanosome species. Relatively homogeneous sequences are found within and among isolates of the same DTU except TcV and TcVI, which displayed sequences unique or identical to those of TcII and TcIII, supporting their origin from the hybridization between these two DTUs. In network genealogies, sequences from T. cruzi clustered tightly together and closer to T. c. marinkellei than to T. dionisii and largely differed from homologues of T. rangeli and T. b. brucei. Here, analysis of isolates representative of the overall biological and genetic diversity of T. cruzi and closest T. cruzi-like species evidenced DTU- and species-specific polymorphisms corroborating phylogenetic relationships inferred with other genes. Comparison of both phylogenetically close and distant trypanosomes is valuable to understand host-parasite interactions, virulence and pathogenicity. Our findings corroborate cruzipain as valuable target for drugs, vaccine, diagnostic and genotyping approaches.

Low-Resolution Molecular Models Reveal the Oligomeric State of the PPAR and the Conformational Organization of Its Domains in Solution

The peroxisome proliferator-activated receptors (PPARs) regulate genes involved in lipid and carbohydrate metabolism, and are targets of drugs approved for human use. Whereas the crystallographic structure of the complex of full length PPAR gamma and RXR alpha is known, structural alterations induced by heterodimer formation and DNA contacts are not well understood. Herein, we report a small-angle X-ray scattering analysis of the oligomeric state of hPPAR gamma alone and in the presence of retinoid X receptor (RXR). The results reveal that, in contrast with other studied nuclear receptors, which predominantly form dimers in solution, hPPAR gamma remains in the monomeric form by itself but forms heterodimers with hRXR alpha. The low-resolution models of hPPAR gamma/RXR alpha complexes predict significant changes in opening angle between heterodimerization partners (LBD) and extended and asymmetric shape of the dimer (LBD-DBD) as compared with X-ray structure of the full-length receptor bound to DNA. These differences between our SAXS models and the high-resolution crystallographic structure might suggest that there are different conformations of functional heterodimer complex in solution. Accordingly, hydrogen/deuterium exchange experiments reveal that the heterodimer binding to DNA promotes more compact and less solvent-accessible conformation of the receptor complex.

Frog oocytes to unveil the structure and supramolecular organization of human transport proteins

Structural analyses of heterologously expressed mammalian membrane proteins remain a great challenge given that microgram to milligram amounts of correctly folded and highly purified proteins are required. Here, we present a novel method for the expression and affinity purification of recombinant mammalian and in particular human transport proteins in Xenopus laevis frog oocytes. The method was validated for four human and one murine transporter. Negative stain transmission electron microscopy (TEM) and single particle analysis (SPA) of two of these transporters, i.e., the potassium-chloride cotransporter 4 (KCC4) and the aquaporin-1 (AQP1) water channel, revealed the expected quaternary structures within homogeneous preparations, and thus correct protein folding and assembly. This is the first time a cation-chloride cotransporter (SLC12) family member is isolated, and its shape, dimensions, low-resolution structure and oligomeric state determined by TEM, i.e., by a direct method. Finally, we were able to grow 2D crystals of human AQP1. The ability of AQP1 to crystallize was a strong indicator for the structural integrity of the purified recombinant protein. This approach will open the way for the structure determination of many human membrane transporters taking full advantage of the Xenopus laevis oocyte expression system that generally yields robust functional expression.

Statement by H. E. Manuel Trucco Ambassador of Chile to the Organization of American States, with reference to the OAS' acceptance of Chile's invitation to hold the sixth general assembly in Santiago /

On cover: Original: Spanish.

Extending diplomatic privileges to permanent observers to the Organization of American States. Hearing, Ninety-third Congress, first session.

Mode of access: Internet.

The International conferences of American states, 1889-1928; a collection of the conventions, recommendations, resolutions, reports, and motions adopted by the first six International conferences of the American states, and documents relating to the organization of the conferences,

Bibliography: p. xli-xliv.

To investigate executive agencies : hearings before the Special committee to investigate executive agencies, House of Representatives, Seventy-eighth Congress, first session : pursuant to H. Res. 102, a resolution establishing a select committee to investigate the acts of executive agencies beyond the scope of their authority.

Howard W, chairman. Smith.

Manual for organization of an AEC card catalog.

"June 1955."

The Organization of the Petroleum Exporting Countries (OPEC): a list of research materials in the Library of Congress and other American libraries /

Caption title.