Analysis of genotypic variation in genes associated with virulence in Aggregatibacter actinomycetemcomitans clinical isolates

Background and Objective: Although certain serotypes of Aggregatibacter actinomycetemcomitans are associated more with aggressive periodontitis than are other serotypes, the correlation between distinct lineages and virulence traits in this species is poorly understood. This study aimed to evaluate the polymorphism of genes encoding putative virulence factors of clinical isolates, and to correlate these findings with A. actinomycetemcomitans serotypes, genotypes and periodontal status of the hosts. Material and Methods: Twenty-six clinical isolates from diverse geographic populations with different periodontal conditions were evaluated. Genotyping was performed using pulse-field gel electrophoresis. Polymorphisms in the genes encoding leukotoxin, Aae, ApaH and determinants for serotype-specific O polysaccharide were investigated. Results: The isolates were classified into serotypes a-f, and exhibited three apaH genotypes, five aae alleles and 25 macrorestriction profiles. Two serotype b isolates (7.7%), obtained from Brazilian patients with aggressive periodontitis, were associated with the highly leukotoxic genotype; these isolates showed identical fingerprint patterns and aae and apaH genotypes. Serotype c, obtained from various periodontal conditions, was the most prevalent among Brazilian isolates, and isolates were distributed in two aae alleles, but formed a genetically distinct group based on apaH analysis. Cluster analysis showed a close relationship between fingerprinting genotypes and serotypes/apaH genotypes, but not with aae genotypes. Conclusion: Apart from the deletion in the ltx promoter region, no disease-associated markers were identified. Non-JP2-like strains recovered from individuals with periodontal disease exhibited considerable genetic variation regarding aae/apaH genotypes, serotypes and XhoI DNA fingerprints.

Phylogeny of snake trypanosomes inferred by SSU rDNA sequences, their possible transmission by phlebotomines, and taxonomic appraisal by molecular, cross-infection and morphological analysis

Blood examination by microhaematocrit and haemoculture of 459 snakes belonging to 37 species revealed 24% trypanosome prevalence in species of Viperidae (Crotalus durissus and Bothrops jararaca) and Colubridae (Pseudoboa nigra). Trypanosome cultures from C. durissus and P. nigra were behaviourally and morphologically indistinguishable. In addition, the growth and morphological features of a trypanosome from the sand fly Viannaniyia tuberculata were similar to those of snake isolates. Cross-infection experiments revealed a lack of host restriction, as snakes of 3 species were infected with the trypanosome from C. durissus. Phylogeny based on ribosomal sequences revealed that snake trypanosomes clustered together with the sand fly trypanosome, forming a new phylogenetic lineage within Trypanosoma closest to a clade of lizard trypanosomes transmitted by sand flies dagger. The clade of trypanosomes from snakes and lizards suggests an association between the evolutionary histories of these trypanosomes and their squamate hosts. Moreover, data strongly indicated that these trypanosomes are transmitted by sand flies. The flaws of the current taxonomy of snake trypanosomes are discussed, and the need for molecular parameters to be adopted is emphasized. To our knowledge, this is the first molecular phylogenetic study of snake trypanosomes.

Phylogenetic, morphological and behavioural analyses support host switching of Trypanosoma (Herpetosoma) lewisi from domestic rats to primates

We characterized four Brazilian trypanosomes isolated from domestic rats and three from captive nonhuman primates that were morphologically similar to T. lewisi, a considered non-pathogenic species restricted to rodents and transmitted by fleas, despite its potential pathogenicity for infants. These isolates were identified as T. lewisi by barcoding using V7V8 SSU rDNA sequences. In inferred phylogenetic trees, all isolates clustered tightly with reference T. lewisi and T. lewisi-like trypanosomes from Europe, Asia and Africa and despite their high sequence conservation formed a homogeneous clade separate from other species of the subgenus T. (Herpetosoma). With the aim of clearly resolving the relationships between the Brazilian isolates from domestic rats and primates, we compared sequences from more polymorphic ITS rDNA. Results corroborated that isolates from Brazilian rats and monkeys were indeed of the same species and quite close to T. lewisi isolates of humans and rats from different geographical regions. Morphology of the monkey isolates and their behaviour in culture and in experimentally infected rats were also compatible with T. lewisi. However, infection with T. lewisi is rare among monkeys. We have examined more than 200 free-ranging and 160 captive monkeys and found only three infected individuals among the monkeys held in captivity. The findings of this work suggest that proximity of monkeys and infected rats and their exposure to infected fleas may be responsible for the host switching of T. Iewisi from their natural rodent species to primates. This and previous studies reporting T. lewisi in humans suggest that this trypanosome can cause sporadic and opportunistic fleaborne infection in primates. (C) 2010 Elsevier B.V. All rights reserved.

The Thyroid Hormone Receptor (TR) beta-Selective Agonist GC-1 Inhibits Proliferation But Induces Differentiation and TR beta mRNA Expression in Mouse and Rat Osteoblast-Like Cells

Previous studies showed anabolic effects of GC-1, a triiodothyronine (T3) analogue that is selective for both binding and activation functions of thyroid hormone receptor (TR) beta 1 over TR alpha 1, on bone tissue in vivo. The aim of this study was to investigate the responsiveness of rat (ROS17/2.8) and mouse (MC3T3-E1) osteoblast-like cells to GC-1. As expected, T3 inhibited cellular proliferation and stimulated mRNA expression of osteocalcin or alkaline phosphatase in both cell lineages. Whereas equimolar doses of T3 and GC-1 equally affected these parameters in ROS17/2.8 cells, the effects of GC-1 were more modest compared to those of T3 in MC3T3-E1 cells. Interestingly, we showed that there is higher expression of TR alpha 1 than TR beta 1 mRNA in rat (similar to 20-90%) and mouse (similar to 90-98%) cell lineages and that this difference is even higher in mouse cells, which highlights the importance of TR alpha 1 to bone physiology and may partially explain the modest effects of GC-1 in comparison with T3 in MC3T3-E1 cells. Nevertheless, we showed that TR beta 1 mRNA expression increases (similar to 2.8- to 4.3-fold) as osteoblastic cells undergo maturation, suggesting a key role of TR beta 1 in mediating T3 effects in the bone forming cells, especially in mature osteoblasts. It is noteworthy that T3 and GC-1 induced TR beta 1 mRNA expression to a similar extent in both cell lineages (similar to 2- to 4-fold), indicating that both ligands may modulate the responsiveness of osteoblasts to T3. Taken together, these data show that TR beta selective T3 analogues have the potential to directly induce the differentiation and activity of osteoblasts.

Trypanosoma cruzi maxicircle heterogeneity in Chagas disease patients from Brazil

The majority of individuals in the chronic phase of Chagas disease are asymptomatic (indeterminate form, IF). Each year, similar to 3% of them develop lesions in the heart or gastrointestinal tract. Cardiomyopathy (CCHD) is the most severe manifestation of Chagas disease. The factors that determine the outcome of the infection are unknown, but certainly depend on complex interactions amongst the genetic make-up of the parasite, the host immunogenetic background and environment. In a previous study we verified that the maxicircle gene NADH dehydrogenase (mitochondrial complex 1) subunit 7 (ND7) from IF isolates had a 455 bp deletion compared with the wild type (WT) ND7 gene from CCHD strains. We proposed that ND7 could constitute a valuable target for PCR assays in the differential diagnosis of the infective strain. In the present study we evaluated this hypothesis by examination of ND7 structure in parasites from 75 patients with defined pathologies, from Southeast Brazil. We also analysed the structure of additional mitochondrial genes (ND4/CR4, COIII and COII) since the maxicircle is used for clustering Trypanosoma cruzi strains into three clades/haplogroups. We conclude that maxicircle genes do not discriminate parasite populations which induce IF or CCHD forms. Interestingly, the great majority of the analysed isolates belong to T cruzi 11 (discrete typing unit, (DTU) IIb) genotype. This scenario is at variance with the prevalence of hybrid (DTU IId) human isolates in Bolivia, Chile and Argentina. The distribution of WT and deleted ND7 and ND4 genes in T cruzi strains suggests that mutations in the two genes occurred in different ancestrals in the T cruzi 11 cluster, allowing the identification of at least three mitochondrial sub-lineages within this group. The observation that T. cruzi strains accumulate mutations in several genes coding for complex I subunits favours the hypothesis that complex I may have a limited activity in this parasite. (C) 2009 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Aminoacetone, a putative endogenous source of methylglyoxal, causes oxidative stress and death to insulin-producing RINm5f cells

Aminoacetone (AA), triose phosphates, and acetone are putative endogenous sources of potentially cytotoxic and genotoxic methylglyoxal (MG), which has been reported to be augmented in the plasma of diabetic patients. In these patients, accumulation of MG derived from aminoacetone, a threonine and glycine catabolite, is inferred from the observed concomitant endothelial overexpression of circulating semicarbazide-sensitive amine oxidases. These copper-dependent enzymes catalyze the oxidation of primary amines, such as AA and methylamine, by molecular oxygen, to the corresponding aldehydes, NH4+ ion and H2O2. We recently reported that AA aerobic oxidation to MG also takes place immediately upon addition of catalytic amounts of copper and iron ions. Taking into account that (i) MG and H2O2 are reportedly cytotoxic to insulin-producing cell lineages such as RINm5f and that (ii) the metal-catalyzed oxidation of AA is propagated by O-2(center dot-) radical anion, we decided to investigate the possible pro-oxidant action of AA on these cells taken here as a reliable model system for pancreatic beta-cells. Indeed, we show that AA (0.10-5.0 mM) administration to RINm5f cultures induces cell death. Ferrous (50-300 mu M) and Fe3+ ion (100 mu M) addition to the cell cultures had no effect, whereas Cu2+ (5.0-100 mu M) significantly increased cell death. Supplementation of the AA- and Cu2+-containing culture medium with antioxidants, such as catalase (5.0 mu M), superoxide dismutase (SOD, 50 U/mL), and N-acetylcysteine (NAC, 5.0 mM) led to partial protection. mRNA expression of MnSOD, CuZnSOD, glutathione peroxidase, and glutathione reductase, but not of catalase, is higher in cells treated with AA (0.50-1.0 mM) plus Cu2+ ions (10-50 mu M) relative to control cultures. This may imply higher activity of antioxidant enzymes C, in RINm5f AA-treated cells. In addition, we have found that AA (0.50-1.0 mM) Plus Cu2+ (100 mu M) (i) increase RINm5f cytosolic calcium; (ii) promote DNA fragmentation; and (iii) increase the pro-apoptotic (Bax)/antiapoptotic (Bcl-2) ratio at the level of mRNA expression. In conclusion, although both normal and pathological concentrations of AA are probably much lower than those used here, it is tempting to propose that excess AA in diabetic patients may drive oxidative damage and eventually the death of pancreatic beta-cells.

Network genealogy of 195-bp satellite DNA supports the superimposed hybridization hypothesis of Trypanosoma cruzi evolutionary pattern

Trypanosoma cruzi is highly diverse genetically and has been partitioned into six discrete typing units (DTUs), recently re-named T. cruzi I-VI. Although T. cruzi reproduces predominantly by binary division, accumulating evidence indicates that particular DTUs are the result of hybridization events. Two major scenarios for the origin of the hybrid lineages have been proposed. It is accepted widely that the most heterozygous TcV and TcVI DTUs are the result of genetic exchange between TcII and TcIII strains. On the other hand, the participation of a TcI parental in the current genome structure of these hybrid strains is a matter of debate. Here, sequences of the T. cruzi-specific 195-bp satellite DNA of TcI, TcII, Tat, TcV, and TcVI strains have been used for inferring network genealogies. The resulting genealogy showed a high degree of reticulation, which is consistent with more than one event of hybridization between the Tc DTUs. The data also strongly suggest that Tat is a hybrid with two distinct sets of satellite sequences, and that genetic exchange between TcI and TcII parentals occurred within the pedigree of the TcV and TcVI DTUs. Although satellite DNAs belong to the fast-evolving portion of eukaryotic genomes, in >100 satellite units of nine T. cruzi strains we found regions that display 100% identity. No DTU-specific consensus motifs were identified, inferring species-wide conservation. (C) 2010 Elsevier B.V. All rights reserved.

Pro-premiär eller pro-president? : Om distinktionen mellan parlamentarism, presidentialism och semi-presidentialism

Propremiar or pro-president? On the distinction between parliamentarism, presitentialism and semi-presidentialism. From comparative research on the constitutional development in Central and Eastern Europe and also from the longstanding debate on whether parliamentarism or presidentialism best facilitates democracy, it is apparent that there has been and continues to be, a certain degree of confusion concerning the concepts of semi-presidentialism and presidentialism. Different scholars mean different things by the terms and therefore classify countries differently. In this article I argue that the conceptual dichotomy between pro-premiär (premier-presidentialism) and pro-president systems (presidentparliamentary systems) provide the best solution to several of the problems related to categorising constitutional types, most importantly perhaps to the presidential power dilemma. I, furthermore, employ these concepts on the post-communist constitutional systems and try to reveal patterns with regard to presidential power, geographical region and democratisation.

Demokrati eller presidentdiktatur? : Konstitutionella vägval i postkommunistiska länder

While authoritarian presidents prevail under heavily president-oriented constitutions throughout the post-Soviet region, democracy along parliamentary lines triumphs in Central Europe. This article discusses the constitutional pattern among the post-communist countries on the basis of two general questions: First, how can we explain why strong presidential constitutions dominate throughout the post-Soviet region whereas constrained presidencies and governments anchored in parliament have become the prevailing option in Central Europe? Second, and interlinked with the first question, why have so many post-communist countries (in the post-Soviet region as well as in Central Europe) chosen neither parliamentarism nor presidentialism, but instead semi-presidential arrangements whereby a directly elected president is provided with considerable powers and coexists with a prime minister? The analysis indicates that both historical-institutional and actor-oriented factors are relevant here. Key factors have been regime transition, pre-communist era constitutions and leaders, as well as short-term economic and political considerations. With differing strengths and in partly different ways, these factors seem to have affected the actors’ preferences and final constitutional compromises.

Ukrainas konstitutionella sicksackande : Regimförändring och partiutveckling under semipresidentialism

Ukraine has repeatedly shifted between the two sub-types of semi-presidentialism, i.e. between premier-presidentialism and president-parliamentarism. The aim of this article is to discuss to what extent theoretical arguments against premier-presidential and president-parliamentary systems are relevant for understanding the shifting directions of the Ukrainian regime. As a point of departure, I formulate three main claims from the literature: 1) “President-parliamentarism is less conducive to democratization than premier-presidentialism.”; 2) “Semi-presidentialism in both its variants have built-in incitements for intra-executive conflict between the president and the prime minister.”; 3) “Semi-presidentialism in general, and president-parliamentarism in particular, encourages presidentialization of political parties.” I conclude from the study’s empirical overview that the president-parliamentary system– the constitutional arrangement with the most dismal record of democratization – has been instrumental in strengthening presidential dominance and authoritarian tendencies. The premier-presidential period 2006–2010 was by no means smooth and stable, but the presidential dominance weakened and the survival of the government was firmly anchored in the parliament. During this period, there were also indications of a gradual strengthening of institutional capacity among the main political parties and the parliament began to emerge as a significant political arena.

The “Lunatic Fringe” -- Barry Goldwater and the Conservative Revolution of the 1960s --

How did conservatives, who had become effectively ostracized by their party following the Great Depression and the societal reforms of the New Deal, regain leverage within the GOP during the 1960s? My hypothesis is two-fold. First, I contend that a small group of conservative activists led by F. Clifton White, in spite of a dearth of resources and manpower, managed to infiltrate Republican infrastructure and “hijack” the delegate- selection process. The distinctly conservative and recalcitrant disposition of the Goldwater delegates demonstrates that these activists succeeded. Second, I argue that in addition to temporarily overpowering the national convention in 1964, conservatives thereafter retained control of the party insofar as subsequent GOP candidates were obliged to garner the support of conservative pockets of the country in order to win the presidential nomination. The resulting rightward shift of the Republican Party following the 1960s is a direct corollary of the conservative takeover outlined in this study.

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Financiamento para o subdesenvolvimento, o Brasil e o segundo consenso de Washington

While in the social and in the ethical realms the Cardoso administration was successful, its economic outcomes were frustrating. In this administration’s eight years the investment rate did not increase and income per capita growth lagged, while the public debt and the foreign debt increased substantially. This poor economic performance may be explained by three chained causes: a mistake in agenda setting, the adoption of the Second Washington Consensus, and the alienation of elites. The decision of setting high inflation as the major problem to be tackled instead of achieving equilibrium in foreign accounts represented a major macroeconomic mistake, which can be explained by the Second Washington Consensus. This consensus proposed in the 1990s that highly indebted countries should grow counting on foreign savings, although this is not the experience among OECD countries. The outcome was to evaluate the real, to increase artificially wages and consumption, so that instead of growth what we have been increased indebtedness. Why this flopped strategy was adopted? Rich countries’ interests are not difficult to guess. On the part of Brazil, the only explanation is Brazilian elites’ alienation in relation to the country’s national interest. As a final outcome, the Cardoso administration ends with another balance of payments crisis, which was empowered by the coming presidential elections. Yet, the solvency situation of the Brazilian economy have been improving since the 1999 successful floatation of the real, so that I believe that, adopted a policy that deepens fiscal adjustment, while lowers the interest rate, and avoids new evaluation of the real, the country will eventually be able to avoid default.

Mudanças institucionais, receitas cumulativas do governo federal e exportações no Brasil entre 1982 e 2001

Desde o início dos anos oitenta, o governo federal brasileiro passou a substituir a receitas de impostos tradicionais por receita de contribuições sociais (cumulativas) na composição da sua receita total (mudança de gestão). Alega-se que este procedimento é uma conseqüência das regras de compartilhamento estabelecidas (receitas de impostos do governo federal são compartilhadas com estados e municípios enquanto que receitas de contribuição não o são).Existem argumentos na literatura mostrando que este processo de descentralização das receitas teve sua origem na mudança de regime político (militar para democrático), outros com a nova Constituição de 1988 e, por último, outros afirmando que ele só foi possível porque a ineficiência das contribuições foi encoberta pela ineficiência alocativa da inflação. Por outro lado, fatos ocorridos no mesmo período, embora não citados na literatura, poderiam explicar ou ajudar na explicação deste comportamento. Entre eles, a fragmentação do poder executivo a partir de 1989 com a primeira eleição presidencial e/ou o processo de abertura da economia a partir dos anos noventa. Usando a técnica de OLS, observou-se que a Nova Constituição e a abertura da economia explicariam esta mudança de gestão. De qualquer forma, independente do que esteja explicando esta mudança, ela é apontada como altamente prejudicial a competitividade das exportações brasileiras. Existem várias proxies tentando medir este efeito, nenhuma delas considerando uma medida de gestão. Resolvemos realizar esta tentativa. Como tínhamos desconfiança da exogeneidade da variável representativa da abertura da economia no teste anterior, tratamos a questão com o instrumental de séries de tempo. No longo prazo, descobrimos que a mudança de gestão afeta negativamente as exportações e positivamente a abertura da economia por ser menos punitiva com as importações em termos de competitividade (as contribuições incidem apenas na comercialização dos produtos importados). JEL classification: H27; H77, H87.

A agenda da transformação: a grande imprensa e a hegemonia neoliberal no Brasil (a imprensa paulista e a 'nova república')

Este trabalho objetiva analisar os posicionamentos da grande imprensa diária paulista os jornais Folha de S. Paulo e O Estado de S. Paulo no tocante à disputa pela transformação da Agenda política e econômica no Brasil entre 1986 e 1989. Neste período, os fracassos dos Planos de estabilização econômica, a elaboração da nova Constituição (com implicações na relação entre Estado e mercado) e a campanha presidencial foram alvos de um intenso embate político/ideológico, no contexto de profundas mudanças internacionais, relacionadas sobretudo ao ocaso do socialismo e à hegemonia da visão neoliberal. A imprensa, em razão de sua capacidade de espraiar idéias, atua como aparelho privado de hegemonia através da formulação de imagens e da utilização da retórica, o que a torna um ator político privilegiado, pois, além do mais, formula e retransmite conteúdos fortemente ideológicos.