Papel da proteína de reparo XPC na regulação das proteínas de reparo APE1, OGG1 e PARP-1 em células humanas e de camundongos

studies using UV as a source of DNA damage. However, even though unrepaired UV-induced DNA damages are related to mutagenesis, cell death and tumorigenesis, they do not explain phenotypes such as neurodegeneration and internal tumors observed in patients with syndromes like Xeroderma Pigmentosum (XP) and Cockayne Syndrome (CS) that are associated with NER deficiency. Recent evidences point to a role of NER in the repair of 8-oxodG, a typical substrate of Base Excision Repair (BER). Since deficiencies in BER result in genomic instability, neurodegenerative diseases and cancer, it was investigated in this research the impact of XPC deficiency on BER functions in human cells. It was analyzed both the expression and the cellular localization of APE1, OGG1 e PARP-1, the mainly BER enzymes, in different NER-deficient human fibroblasts. The endogenous levels of these enzymes are reduced in XPC deficient cells. Surprisingly, XP-C fibroblasts were more resistant to oxidative agents than the other NER deficient fibroblasts, despite presenting the highest of 8-oxodG. Furthermore, subtle changes in the nuclear and mitochondrial localization of APE1 were detected in XP-C fibroblasts. To confirm the impact of XPC deficiency in the regulation of APE1 and OGG1 expression and activity, we constructed a XPC-complemented cell line. Although the XPC complementation was only partial, we found that XPC-complemented cells presented increased levels of OGG1 than XPC-deficient cells. The extracts from XPC-complemented cells also presented an elevated OGG1 enzimatic activity. However, it was not observed changes in APE1 expression and activity in the XPCcomplemented cells. In addition, we found that full-length APE1 (37 kDa) and OGG1- α are in the mitochondria of XPC-deficient fibroblasts and XPC-complemented fibroblasts before and after induction of oxidative stress. On the other hand, the expression of APE1 and PARP-1 are not altered in brain and liver of XPC knockout mice. However, XPC deficiency changed the APE1 localization in hypoccampus and hypothalamus. We also observed a physical interaction between XPC and APE1 proteins in human cells. In conclusion, the data suggest that XPC protein has a role in the regulation of OGG1 expression and activity in human cells and is involved mainly in the regulation of APE1 localization in mice. Aditionally, the response of NER deficient cells under oxidative stress may not be only associated to the NER deficiency per se, but it may include the new functions of NER enzymes in regulation of expression and cell localization of BER proteins

Estudo dos genes do complexo do antígeno leucocitário humano (hla) associados à susceptibilidade ao diabetes mellitus tipo 1

Of all of the genes associated with the development of Diabetes mellitus type 1 (T1D), the largest contribution comes from the genes in the Human Leukocyte Antigen (HLA) region, mostly the class II DR e DQ genes. Specific combinations of alleles DRB1, DQA1 and DQB1 constituting haplotypes, and further, a combination of more than one haplotype, providing multilocus genotypes are associated with susceptibility, protection and neutrality to DM1. Thus, the aim of present study was to verified the association of polymorphisms of HLA genes class II with susceptibility to type 1 diabetes mellitus (T1D). Ninety-two patients with T1D and 100 individuals normoglycemics (NG) aged between 6 and 20 years were studied. Genomic DNA was obtained from peripheral whole blood, collected in EDTA tube, using the extraction kit Illustra Triple Prep®, GE Healthcare. For HLA typing was used DNA LABType system by One Lambda kit applying Luminex® technology to the method of PCRSSO typing reverse. The alleles DRB1*03:01, *04:05, *04:01, *04:02, DQA1*03:01g, *05:01g, DQB1*02:01g, *03:02, the haplotypes DRB1*03:01-DQA1*05:01-DQB1*02:01, DRB1*04:05-DQA1*03:01g-DQB1*03:02, DRB1*04:02-DQA1*03:01g-DQB1*03:02, DRB1*04:01-DQA1*03:01g-DQB1*03:02 and DR3-DQ2/DR4-DQ8 genotype were significantly associated with the chance of developing T1D. The alleles DRB1*11:01, *15:03, *15:01, *13:01, DQA1*01:02, *04:01g, *01:03, DQB1*06:02, *03:01g, *06:03, *04:02, the haplotypes DRB1*11:01-DQA1*05:01-DQB1*03:01, DRB1*13:01-DQA1*01:03-DQB1*06:03 and DRX-DQX/DRX-DQX genotype, formed by other than the DR3-DQ2 or DR4-DQ8 haplotypes, were significantly associated with T1D protection Despite the major racial Brazilian, even at the regional level, these results are similar to the majority of alleles, genotypes and haplotypes of HLA class II-related susceptibility or resistance to T1D, extensively described in the literature for Caucasian population. Children with age at diagnosis less than 5 years of age had significantly higher frequency of the heterozygous genotype DR3-DQ2/DR4-DQ8 compared to children with age at diagnosis than 5 years old. These results also demonstrate strong association of the genetic profile of the class II HLA for this age group, possibly associated with the severity and rapid progression to the onset of T1D. The knowledge of HLA class II genes may be useful in genetic screens that allow the prediction of T1D

Ação da β-1,3 glucana no sistema imune de camundongos com sepse por Candida albicans

The frequency of disseminated candidiasis caused by yeast has enhancing in intensive care unit. Despite the availability of new antifungal drugs, C. albicans sepsis mortality causes can be as high as 30-40%. So, it has been needed to looking for a new therapeutic medicament that helps in treatment and prevention of this infection. Previous data that demonstrated that particulated β-glucan stimulates the immune system and experiments of this work were conducted to investigating if β-glucan extracted from Saccharomices cerevisiae, could modified the evolution of mouse model C. albicans systemic infection. Balb/c mice with sepsis and β-1,3 glucan treated or not were analyzed the influence of β-1,3 glucan in survival of the animals, in the fungal burdens in kidney, in the production of urea and TNF even in the histopathology of kidney. The experiments shown that the infected animals a nd glucan treated had great survival (p<0,05), less unit form colony in kidney and normal levels of urea. In the kidney histopathology of not glucan treated animals it has seen more lesions when compared with treated animals. So we conclude that β-1,3 glucan could stimulate the immune system against disseminated C. albicans

O dia mais feliz da minha vida: a entrada na universidade segundo os alunos recém-ingressos no curso de Pedagogia da UFRN(2004.1)

The present work, based on the methodological principles of the Comprehensive Discourse Analysis, aimed, through the speech of twelve newly arrived students at the Pedagogy course of the Federal University of Rio Grande do Norte, to understand the moment students start university. It also aimed to analyze the relationship between the schools they were coming from and university entrance as well as the relationship between university and their new students. In the first part of the work, which focused on school knowledge, a comprehensive listening of the speeches of the students led primarily to a distinction, established by the students, between public and private schools, a distinction especially based on the view of superiority of private schools against public ones. The abovementioned interpretation is found in the discussion of the structural duality of Brazilian education which, historically, offers different pedagogical appliances among students of more priviledged social classes and those who come from lower levels of society. The overcome of this duality, aspired by the Brazilian Constitution of 1988, was stopped by the advent of a new economic model neoliberalism, which reinforced the differences between public and private when it prioritized the market on the economic, political and social relations, including educational projects. Impoverishment of public institutions and pauperization of the work of professors affected also the relationship between teachers and studens at the current institution. This is how the teacher becomes the greatest villain at the public management system. All of these references concerning differences in the quality of teaching at public and private schools, expressed by the students interviewed, however, were centered in the preparation for the entrance exam, called vestibular, thus showing a view that the relationship between the student and the school he came from is of a propedeutic kind and even so, reduced to a preparation for an entrance exam. In the second part of the work, which analyzed the relationship between newly arrived students and their university, it was noticed that the latter represents a whole new world. This world is seen as the change at the student´s social statute for now he is grown, takes more responsibilities and is socially respected. This change of attitude established by society and the discovery of a new world which requires more independence from the students, creates in them feelings of pride and fear and they feel insecure when it comes to making decision in the campus because now their decisions deliver a greater load of responsibility. This is when students understand they need to develop autonomy, which is seen, in this work, as the capacity to make conscious decisions. Nevertheless students expressed an understanding of autonomy as something that comes as a gift for those who enter university and not as a process that is constructed from social experiences. For these students, the need to be autonomous refers to the relationships with their teachers and the search for information. This search, however, is also related, according to interviews, to public school financial cuts, which penalize university, and to the lack of employers

Levels of digestible threonine for male broilers from 1 to 7 days of age

The influence of threonine has been studied in broilers; however, information concerning the phase from 1 to 7 d is lacking. In this study, we evaluated the effects on performance and body composition and the relationship with other amino acids with respect to digestible lysine and total glycine + glycine. Research on the initial 7-d phase of broiler growth is still poorly studied, even though it is important, especially in nutrition. It was found that threonine had a great influence on the broilers at that phase and nutritional recommendations need constant evaluation. In conclusion, the digestible threonine: digestible lysine ratio and digestible threonine: total glycine + serine ratio recommended for better performance and body composition are 0.68 and 0.40, respectively. The levels of digestible threonine and total glycine + serine that provide the best results are 0.864 and 2.192%, respectively.

Avaliação da desadaptação das selas de próteses parciais removíveis após 1 a 5 anos de uso

The non-adaptation of the removable partial prosthesis (RPP) base to fibromucosal tissue is caused by resorption of residual ridges (RRR). The onset of bone resorption, which occurs after tooth extraction and continues throughout life, is accelerated by local or systemic factors. Aim: Assess the degree of non-adaptation of removable partial prosthesis saddles and the factors that influence it. Methodology: A sectional study was conducted with 81 patients using RPP who had their prostheses installed between 2003 and 2007 (1 to 5 years of use) at the Faculty of Dentistry of the Universidade Federal do Rio Grande do Norte (UFRN). After anamnese and clinical examination, a cast was made with polyether-based material, using the base of the prosthesis to make the impression. The base of the saddle was loaded with the casting material and positioned in the mouth, applying pressure on the supports. After polymerization, the material was removed from the saddle and measurements were taken at 3 different points using a pachymeter. Results: The non-adaptation of the saddle increased significantly with years of use (p = 0.005). The tooth-tissue supported prostheses obtained higher mean non-adaptation values than those of tooth supported prostheses (p < 0.001). Flaccid mucosa showed the worst non-adaptation results, which were statistically different from resilient mucosa (p < 0.001). The greater the extension of the saddle, the greater the non-adaptation (p < 0.001). The natural tooth antagonistic arch yielded better results than did RPP and total prosthesis (p < 0.001). Saddle non-adaptation at the free end was less near the pillar tooth and greater in the more posterior region (p < 0.001). When adaptation of the supports to the niches was poor, greater saddle non-adaptation occurred than when it was good or fair (p < 0.001). Saddles located in the posterior region of the arch had greater non-adaptation than those in the anterior region (p = 0.023). Conclusion: The mean non-adaptation of the saddle to the residual ridges was 0.27 mm. It can be concluded that, even with the use of RPP, bone height reduction was slight within the 1-5-year period of use. The following are factors that influence adaptation of the RPP saddle base: years of use, age, force transmission path to the alveolar bone, location of the toothless area, antagonistic arch, type of mucosa, adaptation of supports to the niche and extension of the saddle

A experiência de adolescentes portadores de diabetes Mellitus Tipo 1: seus significados e sentido

Worldwide, the diabetes mellitus is considered a serious problem of public health; it also involves high costs for its treatment and its complications. Even though the onset of diabetes mellitus type 1 is on 5% to 10% of the diabetic population, it is the most aggressive type of anifestation; furthermore, it is the commonest chronic disease in childhood and adolescence. Such data show the importance of understanding the development of this disease from the moment the individual perceives it, according to their experience, observing the complexity of the phenomenon thoroughly. This study aimed to comprehend the experience of the adolescent with onset of diabetes mellitus type 1 in order to learn how these young individuals perceive and reason their place in the world when they experience this illness. The methodological strategy was based on qualitative research of phenomenological inspiration. We applied the main ideas of heideggerian ontology and some concepts of existential phenomenological psychology to guide our reflexive path. The participants were 10 young individuals (06 female and 04 male), ages between 15 and 18, under treatment in the city of Recife, Pernambuco. The methodological resource was the narrative, which allowed us access to the adolescents experience. The comprehension of the reports was based on the heideggerian hermeneutics, whose priority is the interpretation of the meaning expressed by the participants speech. The results showed that factors such as social, family, economic and cultural context greatly influence the perception and the way the individuals deal with, perceive and reason their experience. We noticed that the diabetes type 1 may often represent a limitation, but it does not make it impossible to be part of the world with others. The data show a significant affective ambivalence regarding the content more directly related to the disease. This demonstrates the unique way which each one gives meaning and reasons their condition of existence. This research points out the need to understand the complexity of this phenomenon in a more complete manner, considering the adolescent in their timely and historical context. We believe we can encourage thinking that may become actions which are more fit to the reality researched regarding all the parties involved with the subject, such as health professionals, adolescents, family, support programs and public health policies

alpha(1)-Adrenoceptors in proximal segments of tail arteries from control and reserpinised rats

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

Effects of indoramin in rat vas deferens and aorta: concomitant alpha(1)-adrenoceptor and neuronal uptake blockade

1 the actions of the alpha(1)-adrenoceptor antagonist indoramin have been examined against the contractions induced by noradrenaline in the rat vas deferens and aorta taking into account a putative neuronal uptake blocking activity of this antagonist which could. result in self-cancelling actions.2 Indoramin behaved as a simple competitive antagonist of the contractions induced by noradrenaline in the vas deferens and aorta yielding pA(2) values of 7.38 +/- 0.05 (slope = 0.98 +/- 0.03) and 6.78 +/- 0.14 (slope = 1.08 +/- 0.06), respectively.3 When the experiments were repeated in the presence of cocaine (6 mu M) the potency (pA(2)) of indoramin in antagonizing the contractions of the vas deferens to noradrenaline was increased to 8.72 +/- 0.07 (slope = 1.10 +/- 0.05) while its potency remained unchanged in the aorta (pA(2) = 6.69 +/- 0.12; slope = 1.04 +/- 0.05).4 In denervated vas deferens, indoramin antagonized the contractions to noradrenaline with a potency similar to that found in the presence of cocaine (8.79 +/- 0.07; slope = 1.09 +/- 0.06).5 It is suggested that indoramin blocks alpha(1)-adrenoceptors and neuronal uptake in rat vas deferens resulting in Schild plots with slopes not different from unity even in the absence of selective inhibition of neuronal uptake. As a major consequence of this double mechanism of action, the pA(2) values for this antagonist are underestimated when calculated in situations where the neuronal uptake is active, yielding spurious pK(B) values.

Structural characterization of 0.5PbMg(1/3)Nb(2/3)O(3)-0.5Ba(x)Pb((1-x))TiO(3) powders

The present work reports the effects caused by barium on phase formation, morphology and sintering of lead magnesium niobate-lead titanate (PMN-50PT). Ab initio study of 0.5PbMg(1/3)Nb(2/3)O(3)-0.5Ba(x)Pb((1-x))TiO(3) ceramic powders, with x = 0, 0.20, and 0.40 was proposed, considering that the partial substitution of lead by barium can reestablish the equilibrium of monoclinic-tetragonal phases in the system. It was verified that even for 40 mol% of barium, it was possible to obtain pyrochlore-free PMN-PT powders. The increase of the lattice parameters of PMN-PT doped-powders confirmed dopant incorporation into the perovskite phase. The presence of barium improved the reactivity of the powders, with an average particle size of 120 nm for 40 mol% of barium against 167 mn for the pure sample. Although high barium content (40 mol%) was deleterious for a dense ceramic, contents up to 20 mol% allowed 95% density when sintered at 1100 degrees C for 4 h. (c) 2007 Elsevier Ltd. All rights reserved.

Crystallographic structure of PNP from Mycobacterium tuberculosis at 1.9 angstrom resolution

Even being a bacterial purine nucleoside phosphorylase (PNP), which normally shows hexameric folding, the Mycobacterium tuberculosis PNP (MtPNP) resembles the mammalian trimeric structure. The crystal structure of the MtPNP apoenzyme was solved at 1.9 Angstrom resolution. The present work describes the first structure of MtPNP in complex with phosphate. In order to develop new insights into the rational drug design, conformational changes were profoundly analyzed and discussed. Comparisons over the binding sites were specially studied to improve the discussion about the selectivity of potential new drugs. (C) 2004 Elsevier B.V. All rights reserved.

Shikimate Kinase (EC 2.7.1.71) from Mycobacterium tuberculosis: Kinetics and Structural Dynamics of a Potential Molecular Target for Drug Development

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

3-3-1 models at electroweak scale

We show that in 3-3-1 models there exist a natural relation among the SU(3)(L) coupling constant g, the electroweak mixing angle theta(W), the mass of the W, and one of the vacuum expectation values, which implies that those models can be realized at low energy scales and, in particular, even at the electroweak scale. So that, being that symmetries realized in Nature, new physics may be really just around the corner. (c) 2006 Elsevier B.V. All rights reserved.

Spontaneous breaking of the lepton number and invisible majoron in a 3-3-1 model

In this work we implement the spontaneous breaking of lepton number in version II of the 3-3-1 models and study their phenomenological consequences. The main result of this work is that our majoron is invisible even though it belongs to a triplet representation by the 3-3-1 symmetry.

Relativistic particle dynamics in D=2+1

We propose a SUSY variant of the action for a massless spinning particles via the inclusion of twistor variables. The action is constructed to be invariant under SUSY transformations and tau-reparametrizations even when an interaction field is including. The constraint analysis is achieved and the equations of motion are derived. The commutation relations obtained for the commuting spinor variables lambda(alpha) show that the particle states have fractional statistics and spin. At once we introduce a possible massive term for the non-interacting model.