902 resultados para phosphorylated Tau
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Kerodon rupestris (rock cavy, mocó) is an endemic caviidae of Brazilian northeast that inhabits rocky places in the semi arid region. The aim of this study was to characterize the activity/rest rhythm of the rock cavy under 12:12 h LD cycle and continuous light. In the first stage, seven animals were submitted to two light intensities (LD; 250:0 lux and 400:0 lux; 40 days each intensity). In the second stage four males were kept for 40 days in LD (470:<1 lux), for 18 days in LL 470 lux (LL470) and for 23 days in red dim light below 1 lux (LL<1). In the third stage three males were initially kept in LD 12:12 h (450:<1 lux) and after that in LL with gradual increase in light intensity each 21 days (<1 lux LL<1; 10 lux-LL10; 160 lux LL160; 450 lux LL450). In the fourth stage it was analyzed the motor activity of 16 animals in the first 10 days in LD. Motor activity was continuously recorded by passive infrared movement sensors connected to a computer and totaled in 5 min bins. The activity showed circadian and ultradian rhythms and activity peaks at phase transitions. The activity and the rest occurred in the light as well as in the dark phase, with activity mean greater in the light phase for most of the animals. The light intensity influenced the activity/rest rhythm in the first three stages and in the first stage the activity in 400 lux increased in four animals and decreases in two. In the second stage, the tau for 3 animals in LL470 was greater than 24 h; in LL<1 it was greater than 24 h for one and lower for two. In the third stage the tau decreased with the light intensity increase for animal 8. During the first days in the experimental room, the animals did not synchronize to the LD cycle with activity and rest occurring in both phases. The results indicate that the activity/rest rhythm of Kerodon rupestris can be affected by light intensity and that the synchronization to the LD cycle results from entrainment as well as masking probably as a consequence of the action of two or more oscillators with low coupling strength
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This study aims to analyze tourist information provided by the official websites of the 2014 FIFA World Cup host cities. The framework developed by Díaz (2005) was applied to analyze different aspects, such as: local tourist information, tourist services distribution, communication and interaction between website and users, and website foreign language versions. This dissertation describes how society and tourism are related by analyzing the consequences of technological evolution in the travel and tourism sector, showing the importance of the use of information and communication technology to provide accurate, upto- date and low-cost information to tourist destinations. Because of the nature of the study, the research subjects are the 12 Brazilian host cities represented by their respective official webpages (cities, states and convention bureaus), and also Brazil s official website, totalizing 36 elements to be analyzed. The methodology has been characterized as descriptive and exploratory with quantitative analysis, and also using desk research and survey literature review. In order to analyze the data collected, parametric and nonparametric statistics tests were used, such as: variance analysis (ANOVA and KRUSKAL-WALLIS) to measure means variance between groups combined with multiple comparison tests (Tukey and Games Howell); nonparametric correlations tests (Kendall s Tau b); and cluster analyses. Finally, Microsoft Excel was used to collect data and SPSS for managing data through quantitative analyses tests. Overall, the websites of the south region showed better results than the other Brazilian regions. Despite this result, the data analysis demonstrated that the available tourist information are incomplete as it was verified that tourist host cities websites are unable to provide all the information needed for the web visitors to organize and plan their journey. This means that visitors have to look for more information in other sources
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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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The studied area is geologically located in the Northern Domain of the Borborema Province (Northeast Brazil), limited to the south by the Patos shear zone. Terranes of the Jaguaribeano system are dominant, flanked by the Piranhas (E and S sides) and Central Ceará (NE side) terranes. Its basement comprises gneiss -migmatite terrains of Paleoproterozoic to Archean age (2.6 to 1.9 Ga old), overprinted by neoproterozoic to cambrian tectonotherma l events. Narrow supracrustal belts ( schist belts) display a 1.6 to 1.8 Ga age, as shown by whole - rock Rb-Sr and zircon U-Pb and Pb/Pb dates in acid metavolcanics which dominate in the lower section of these sequences, and in coeval metaplutonics (granitic augen gneisses). From the stratigraphic point of view, three Staterian belts are recognized: 1. Orós Belt - made up by the Orós Group, subdivided in the Santarém (predominantly pure to impure quartzites, micaschists and metacarbonates) and Campo Alegre (metandesites, metabasalts, metarhyolites and metarhyodacites, interlayered with metatuffs and metasediments) formations, and by the Serra do Deserto Magmatic Suite (granitic augen gneisses). 2. Jaguaribe Belt - its lithostratigrahic-lithodemic framework is similar to the one of the Orós Belt, however with a greater expression of the volcano -plutonic components (Campo Alegre Formation and Serra do Deserto Magmatic Suite). The Peixe Gordo Sequence, separately described, is also related to this belt and contain s metasedimentary, metavolcanic (with subordinated volcanoclastics) and metaplutonic units. The first one correlated to the Orós Group and the latter the Serra do Deserto Magmatic Suite. 3. Western Potiguar Belt - represented by the Serra de São José Gro up, subdivided in the Catolezinho (biotite -amphibole gneisses with intercalations of metacarbonates, calcsilicate rocks, amphibolites and quartzite beds to the top) and Minhuins (quartzites, micaschists, metaconglomerates, calcsilicate rocks, acid to the b asic metavolcanics and metatuffs) formations. Its late Paleoproterozoic (Staterian) age was established by a Pb/Pb date on zircons from a granitic orthogneiss of the Catolezinho Formation. The petrographic characteristics and sedimentary structures of the Santarém Formation of the Orós Group point to deltaic to shallow marine depositional systems, overlain by deep water deposits (turbidites). The geodynamic setting of this region encompassed a large depositional basin, probably extending to the east of the Portalegre shear zone and west of the Senador Pompeu shear zone, with possible equivalents in the Jucurutu Formation of the Seridó Belt and in the Ceará Group of central Ceará. The Arneiróz Belt, west Ceará, displays some stratigraphic features and granito ids geochemically akin to the ones of the Orós Belt. The evolutionary setting started with an extensional phase which was more active in the eastern part of this domain (Western Potiguar and part of the Jaguaribe belts), where the rudite and psamite sedime ntation relates to a fluviatile rift environment which evolved to a prograding deltaic system to the west (Orós Group). The basaltic andesitic and rhyolitic volcanics were associated to this extensional phase. During this magmatic event, acid magmas also crystallized at plutonic depths. The Orós Group illustrates the environmental conditions in the western part of this domain. Later on, after a large time gap (1.6 to 1.1 Ga), the region was subjected to an extensional deformational episode marked by 900 Ma old (Sm-Nd data) basic rocks, possibly in connection with the deposition of the Cachoeirinha Group south of the Patos shear zone. In the 800 to 500 Ma age interval, the region was affected by important deformational and metamorphic events coupled with in trusion of granitic rocks of variable size (dykes to batholiths), related to the Brasiliano/Pan -African geotectonic cycle. These events produced structural blocks which differentiate, one from the other, according to the importance of anatectic mobilizatio n, proportion of high-grade supracrustals and the amount of neoproterozoic -cambrian granitoid intrusions. On this basis, a large portion of the Jaguaretama Block/Terrane is relatively well preserved from this late overprint. The border belts of the Jagua retama Block (Western Potiguar and Arneiroz) display kyanite-bearing (medium pressure) mineral associations, while in the inner part of the block there is a north-south metamorphic zoning marked by staurolite or sillimanite peak metamorphic conditions. Regarding the deformations of the Staterian supracrustal rocks, second and third phases were the most important, diagnosed as having developed in a progressive tectonic process. In the general, more vigorous conditions of PT are related to the interval tardi - phase 2 early-phase 3, whose radiometric ages and regional structuring indicators places it in the Brasiliano/Pan-African Cycle. In the Staterian geodynamic setting of Brazilian Platform , these sequences are correlated to the lower Espinhaço Supergroup (p.ex., Rio dos Remédios and Paraguaçu groups, a paleproterozoic rift system in the São Francisco Craton), the Araí and Serra da Mesa groups (north of Goiás, in the so -called Goiás Central Massif), and the Uatumã Group (in the Amazonian Craton). Granitic ( augen gneisses) plutonics are also known from these areas, as for example the A-type granites intrusive in the Araí and Serra da Mesa groups, dated at 1.77 Ga. Gravimetric and geological data place the limits of the Jaguaribeano System (terranes) along the Senador Pompeu Shear Zone (western border) and the Portalegre- Farias Brito shear zone (eastern and southern). However, the same data area not conclusive as regards the interpretation of those structures as suture of the terrane docking process. The main features of those shear zones and of involved lothological associations, appear to favour an intracontinental transpressional -transcurrent regime, during Neoproterozoic-Cambrian times, marking discontinuities along which different crustal blocks were laterally dispersed. Inside of this orogenic system and according to the magnetic data (total field map), the most important terrane boundary appears to be the Jaguaribe shear zone. The geochronological data, on some tectonostratigraphic associations (partly represented by the Ceará and Jucurutu groups), still at a preliminary level, besides the lack of granitic zonation and other petrotectonic criteria, do not allow to propose tectonic terrane assembly diagrams for the studied area
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It is presently assumed that the Borborema Province resulted from a complex collisional process associated with the convergent movement of plates, possibly involving amalgamation and accretion of microplates. This process was consolidated at the end of the Brasiliano event. It is investigated the possible limits for the tectonostratigraphic terranes in the northern portion of the province based on an integrated study of geological and gravity data. The study area comprises the portion of the Borborema Province located north of the Patos Lineament, limited by longitudes 33º00 W and 43º29 44"W and latitudes 1º36 S and 8º00 S. A revision of the regional geology allowed to identify areas presenting contrasting geological attributes, possibly representing different terranes whose limits are always shear zones of Brasiliano-age. The Sobral-Pedro II shear zone is the only one undoubtedly presenting geological attributes of sutures zones. The other shear zones are very likely associated with a geodinymic context of accretion, involving oblique collisions (docking), transcurrent and/or transforming sutures, and deep intracrustal shear zones. The gravity data contributed as a tool to identify strong lateral contrasts of density inside the upper crust possibly associated with crustal blocks tectonically juxtaposed. The dominant long wavelength anomaly in the Bouguer anomaly map is an expressive gradient, grossly parallel to the continental margin, caused by density variation across the crust-mantle interface in the transition from the continental crust to the oceanic crust originated by the separation between South America and Africa. Medium to small wavelength anomalies are due to intracrustal heterogeneities such as different Precambrian crustal blocks, Brasiliano-age granites and Mesozoic sedimentary basins. A regional-residual separation of the Bouguer anomaly map was performed in order to enhance in the residual map the effect due to intracrustal heterogeneities. The methodology used for this separation was a robust polinomial fitting. The inversion of residual gravity field resulted in a density contrast map (Δρ), in an equivalent layer that provided more accurated anomalies contours and consolidated the model which the sources of residual anomalies are located in the upper part of the present crust. Based on the coincidence of gravity lineaments in the residual map and Brasiliano shear zones, and using additional geological information, the following shear zones are proposed as limits between terranes: Patos shear zone, Sobral-Pedro II shear zone, Picuí-João Câmara shear zone, Remígio-Pocinhos shear zone, Senador Pompeu shear zone, Tauá shear zone, and Portalegre shear zone. Based on the geological/geophysical information it is attributed a higher level of confidence to the first three proposed limits(Patos, Sobral Pedro II, and Picuí-João Câmara shear zones). From west to east, these shear zones individualize the following terranes: Northwest of Ceará terrane, Central Ceará terrane, Tauá terrane, Orós-Jaguaribe terrane, Seridó terrane, and São José de Campestre terrane. In our study, the Rio Piranhas and Patos terranes are questioned because their previously proposed limits do not present good geological and gravimetric evidences. On the other hand, the previously proposed Cearense terrane is now subdivided into Central Ceará and Tauá terranes. Two residual gravity profiles located in the Seridó belt were interpreted using 2 ½ D direct gravity modeling. The main result of the modeling process is that all anomalies, with the exception of one, can be explained by outcroppring bodies, therefore restricted to the upper part of the present crust
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Aim: Inflammation is as an important factor in ovulation with the active participation of leucocytes and their inflammatory mediators. The present study was performed to compare the activity of the inflammatory enzymes myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) in patients with endometriosis-related infertility and in normally ovulating women undergoing intracytoplasmic sperm injection (ICSI).Material and Methods: This prospective study included infertile women undergoing ICSI treatment. These women were divided into two groups: endometriosis anovulation (n = 18) and normally ovulating (n = 20). NAG and MPO activity was evaluated colorimetrically in serum and in follicular fluids obtained at the time of oocyte retrieval.Results: There was a significant correlation between the serum and follicular fluid activities of NAG and MPO (tau = 0.256, P = 0.025; and tau = -0.234, P = 0.041; respectively). Both serum and follicular fluid NAG activities were higher in patients with endometriosis compared to the control group (P < 0.001). MPO follicular fluid activity was lower in patients with endometriosis compared to normally ovulating women (P = 0.016).Conclusion: Infertile patients with endometriosis show a distinct pattern of serum and follicular fluid macrophage/neutrophil activation compared to normally ovulating women undergoing ICSI, which may reflect the role of immune and inflammatory alterations in endometriosis-related infertility.
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In order to determine if patients with a history of previous urothelial cell carcinoma (UCC) but with current normal urinary cytology have DNA damage in urothelial cells, the single-cell gel electrophoresis (comet) assay was conducted with cells obtained by urinary bladder washings from 44 patients (28 with a history of previous UCC). Increased DNA damage was observed in cytologically normal urothelial cells of patients with a history of UCC when compared with referents with no similar history and after correcting the data for smoking status and age (P < 0.018). Increased DNA damage also correlated with the highest tumor grade, irrespective of time or course of the disease after clinical intervention (Kendall tau correlation, 0.37, P = 0.016). Moreover, aneuploidy, as assessed by DNA content ratio (DCR; 75th/25th percentile of total DNA fluorescence of 50 comets/patient) was unaltered by smoking status, but increased with UCC grade: 1.39 +/- 0.12 (median +/- 95% confidence interval; referents); 1.43 +/- 0.11 (Grade I UCC; P = 0.264, against referents); 1.49 +/- 0.16 (Grade II UCC; P = 0.057); 1.57 +/- 0.16 (Grade III UCC; P = 0.003). Micronucleated urothelial cells (MNC) were also scored on Giemsa-stained routine cytological smears and were found not to correlate with DNA damage or DCR. MNC frequencies were higher for patients with a history of UCC and/or smoking than referents with neither history, but there was no statistical difference between groups. Taken together, these results suggest that the normal-appearing urothelium of patients resected for UCC still harbor genetically unstable cells. (C) 2002 Wiley-Liss, Inc.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Actinobacillus actinomycetemcomitans plays a major role in the pathogenesis of aggressive periodontitis. Lipopolysaccharide (LPS) derived from A. actinomycetemcomitans is a key factor in inflammatory cytokine generation within periodontal tissues. In this study, we identify major mitogen-activated protein kinase (MAPK) signaling pathways induced by A. actinomycetemcomitans LPS, Escherichia coli LPS and interleukin-1 beta (IL-1 beta) in a murine periodontal ligament (mPDL) fibroblast cell line. Immunoblot analysis was used to assess the phosphorylated forms of p38, extracellular-regulated kinase (ERK) and c-jun N-terminal kinase (JNK) MAPK following stimulation with A. actinomycetemcomitans LPS, E. coli LPS and IL-1 beta. IL-6 mRNA induction was detected via reverse transcription-polymerase chain reaction, while protein levels were quantified via enzyme-linked immunosorbent assays (ELISA). We utilized biochemical inhibitors of p38, ERK and JNK MAPK to identify the MAPK signaling pathways needed for IL-6 expression. Additional use of stable mPDL cell lines containing dominant negative mutant constructs of MAPK kinase-3 and -6 (MKK-3/6) and p38 null mutant mouse embryonic fibroblast (MEF) cells were used to substantiate the biochemical inhibitor data. Blocking p38 MAPK with SB203580 reduced the induction of IL-6 mRNA by A. actinomycetemcomitans LPS, E. coli LPS and IL-1 beta by > 70%, > 95% and similar to 60%, respectively. IL-6 ELISA indicated that blocking p38 MAPK reduced the IL-6 protein levels induced by A. actinomycetemcomitans LPS, E. coli LPS and IL-1 beta by similar to 60%, similar to 50% and similar to 70%, respectively. All MAPK inhibitors significantly reduced the IL-6 protein levels induced by A. actinomycetemcomitans LPS, E. coli LPS and IL-1 beta whereas only p38 inhibitors consistently reduced the A. actinomycetemcomitans LPS, E. coli LPS and IL-1 beta induction of IL-6 mRNA steady-state levels. The contribution of p38 MAPK LPS-induced IL-6 expression was confirmed using MKK-3/6 dominant negative stable mPDL cell lines. Wild-type and p38 alpha(-/-) MEF cells provided additional evidence to support the role of p38 alpha MAPK in A. actinomycetemcomitans LPS-stimulated IL-6. Our results indicate that induction of IL-6 by E. coli LPS, IL-1 beta and A. actinomycetemcomitans LPS requires signaling through MKK-3-p38 alpha ERK, JNK and p38 MAPK in mPDL cells.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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The nuclear import of simian-virus-40 large T-antigen (tumour antigen) is enhanced via phosphorylation by the protein kinase CK2 at Ser(112) in the vicinity of the NLS (nuclear localization sequence). To determine the structural basis of the effect of the sequences flanking the basic cluster KKKRK, and the effect of phosphorylation on the recognition of the NLS by the nuclear import factor importin-alpha (Impalpha), we co-crystallized non-autoinhibited Impalpha with peptides corresponding to the phosphorylated and non-phosphorylated forms of the NLS, and determined the crystal structures of the complexes. The structures show that the amino acids N-terminally flanking the basic cluster make specific contacts with the receptor that are distinct from the interactions between bipartite NLSs and Impalpha. We confirm the important role of flanking sequences using binding assays. Unexpectedly, the regions of the peptides containing the phosphorylation site do not make specific contacts with the receptor. Binding assays confirm that phosphorylation does not increase the affinity of the T-antigen NLS to Impalpha. We conclude that the sequences flanking the basic clusters in NLSs play a crucial role in nuclear import by modulating the recognition of the NLS by Impalpha, whereas phosphorylation of the T-antigen enhances nuclear import by a mechanism that does not involve a direct interaction of the phosphorylated residue with Impalpha.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Background/Aims: To investigate the effect of taurine on cardiac remodeling induced by smoking. Methods: In the first step, rats were allocated into two groups: Group C (n=14): control; Group T (n=14): treated with taurine (3% in drinking water), for three months. In the second step, rats were allocated into two groups: Group ETS (n=9): rats exposed to tobacco smoke; Group ETS-T (n=9): rats exposed to tobacco smoke and treated with taurine for two months. Results: After three months, taurine presented no effects on morphological or functional variables of normal rats assessed by echocardiogram. on the other hand, after two months, ETS-T group presented higher LV wall thickness (ETS=1.30 (1.20-1.42); ETS-T=1.50 (1.40-1.50); p=0.029), E/A ratio (ETS=1.13 +/- 0.13; ETS-T=1.37 +/- 0.26; p=0.028), and isovolumetric relaxation time normalized for heart rate (ETS=53.9 +/- 4.33; ETS-T=72.5 +/- 12.0; p<0.001). The cardiac activity of the lactate dehydrogenase was higher in the ETS-T group (ETS=204 +/- 14 nmol/mg protein; ETS-T=232 +/- 12 nmol/mg protein; p<0.001). ETS-T group presented lower levels of phospholamban (ETS=1.00 +/- 0.13; ETS-T=0.82 +/- 0.06; p=0.026), phosphorylated phospholamban at Ser16 (ETS=1.00 +/- 0.14;ETS-T=0.63 +/- 0.10;p=0.003), and phosphorylated phosfolamban/phospholamban ratio (ETS=1.01 +/- 0.17; ETS-T=0.77 +/- 0.11; p=0.050). Conclusion: In normal rats, taurine produces no effects on cardiac morphological or functional variables. on the other hand, in rats exposed to cigarette smoke, taurine supplementation increases wall thickness and worsens diastolic function, associated with alterations in calcium handling protein and cardiac energy metabolism. Copyright (C) 2011 S. Karger AG, Basel
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Background: Acute pancreatitis is an inflammatory disease characterized by local tissue injury and systemic inflammatory response leading to massive nitric oxide (NO) production and haemodynamic disturbances. Therefore, the aim of this work was to evaluate the vascular reactivity of pulmonary and mesenteric artery rings from rats submitted to experimental pancreatitis.Male Wistar rats were divided into three groups: saline (SAL); tauracholate (TAU) and phospholipase A(2) (PLA(2)). Pancreatitis was induced by administration of TAU or PLA(2) from Naja mocambique mocambique into the common bile duct of rats, and after 4 h of duct injection the animals were sacrificed. Concentration-response curves to acetylcholine (ACh), sodium nitroprusside (SNP) and phenylephrine (PHE) in isolated mesenteric and pulmonary arteries were obtained. Potency (pEC(50)) and maximal responses (E(MAX)) were determined. Blood samples were collected for biochemical analysis.Results: In mesenteric rings, the potency for ACh was significantly decreased from animals treated with TAU (about 4.2-fold) or PLA(2) (about 6.9-fold) compared to saline group without changes in the maximal responses. Neither pEC(50) nor E(MAX) values for Ach were altered in pulmonary rings in any group. Similarly, the pEC(50) and the E(MAX) values for SNP were not changed in both preparations in any group. The potency for PHE was significantly decreased in rat mesenteric and pulmonary rings from TAU group compared to SAL group (about 2.2- and 2.69-fold, for mesenteric and pulmonary rings, respectively). No changes were seen in the E(MAX) for PHE. The nitrite/nitrate (NO(x)(-)) levels were markedly increased in animals submitted to acute pancreatitis as compared to SAL group, approximately 76 and 68% in TAU and PLA(2) protocol, respectively.Conclusion: Acute pancreatitis provoked deleterious effects in endothelium-dependent relaxing response for ACh in mesenteric rings that were strongly associated with high plasma NO(x)(-) levels as consequence of intense inflammatory responses. Furthermore, the subsensitivity of contractile response to PHE in both mesenteric and pulmonary rings might be due to the complications of this pathological condition in the early stage of pancreatitis.