Host Cell Poly(ADP-Ribose) Glycohydrolase Is Crucial for Trypanosoma cruzi Infection Cycle

Trypanosoma cruzi, etiological agent of Chagas’ disease, has a complex life cycle which involves the invasion of mammalian host cells, differentiation and intracellular replication. Here we report the first insights into the biological role of a poly(ADP-ribose) glycohydrolase in a trypanosomatid (TcPARG). In silico analysis of the TcPARG gene pointed out the conservation of key residues involved in the catalytic process and, by Western blot, we demonstrated that it is expressed in a life stage-dependant manner. Indirect immunofluorescence assays and electron microscopy using an anti-TcPARG antibody showed that this enzyme is localized in the nucleus independently of the presence of DNA damage or cell cycle stage. The addition of poly(ADP-ribose) glycohydrolase inhibitors ADP-HPD (adenosine diphosphate (hydroxymethyl) pyrrolidinediol) or DEA (6,9-diamino-2-ethoxyacridine lactate monohydrate) to the culture media, both at a 1 µM concentration, reduced in vitro epimastigote growth by 35% and 37% respectively, when compared to control cultures. We also showed that ADP-HPD 1 µM can lead to an alteration in the progression of the cell cycle in hydroxyurea synchronized cultures of T. cruzi epimastigotes. Outstandingly, here we demonstrate that the lack of poly(ADP-ribose) glycohydrolase activity in Vero and A549 host cells, achieved by chemical inhibition or iRNA, produces the reduction of the percentage of infected cells as well as the number of amastigotes per cell and trypomastigotes released, leading to a nearly complete abrogation of the infection process. We conclude that both, T. cruzi and the host, poly(ADP-ribose) glycohydrolase activities are important players in the life cycle of Trypanosoma cruzi, emerging as a promising therapeutic target for the treatment of Chagas’ disease.     

Alterations of Choroidal Blood Flow Regulation in Young Healthy Subjects with Complement Factor H Polymorphism

A common polymorphism in the complement factor H gene (rs1061170, Y402H) is associated with a high risk of age-related macular degeneration (AMD). In the present study we hypothesized that healthy young subjects homozygous for the high-risk haplotype (CC) show abnormal choroidal blood flow (ChBF) regulation decades before potentially developing the disease. A total of 100 healthy young subjects were included in the present study, of which 4 subjects were excluded due to problems with genotyping or blood flow measurements. ChBF was measured continuously using laser Doppler flowmetry while the subjects performed isometric exercise (squatting) for 6 minutes. The increase in ChBF was less pronounced than the response in ocular perfusion pressure (OPP), indicating for some degree of choroidal blood flow regulation. Eighteen subjects were homozygous for C, 47 subjects were homozygous for T and 31 subjects were heterozygous (CT). The increase in OPP during isometric exercise was not different between groups. By contrast the increase in ChBF was more pronounced in subjects homozygous for the high risk C allele (p = 0.041). This was also evident from the pressure/flow relationship, where the increase in ChBF in homozygous C carriers started at lower OPPs as compared to the other groups. Our data indicate that the regulation of ChBF is abnormal in rs1061170 CC carriers. So far this polymorphism has been linked to age related macular degeneration (AMD) mainly via inflammatory pathways associated with the complement system dysfunction. Our results indicate that it could also be related to vascular factors that have been implicated in AMD pathogenesis.     

Exploring the global decline of music education

This article seeks to explain the disjuncture between the decline of music education in schools and the importance music has in popular youth culture and in creativity within the new knowledge economy. The data discussed in this article have been derived from analyses of major documents on curriculum reform as well as e-mail responses from music educators around the world. This analysis reveals that these music educators agree with the perception of a demise in music education around the world, as well as the significance of the disjuncture alluded to. The four major reasons found for the decline in music education are: (1) the model of curriculum supported in educational reforms; (2) an emphasis on standardized evaluation; (3) less resources available; and (4) a wrong approach on music advocacy.     

A random fatigue of mechanize titanium abutment studied with Markoff chain and stochastic finite element formulation

To measure fatigue in dental implants and in its components, it is necessary to use a probabilistic analysis since the randomness in the output depends on a number of parameters (such as fatigue properties of titanium and applied loads, unknown beforehand as they depend on mastication habits). The purpose is to apply a probabilistic approximation in order to predict fatigue life, taking into account the randomness of variables. More accuracy on the results has been obtained by taking into account different load blocks with different amplitudes, as happens with bite forces during the day and allowing us to know how effects have different type of bruxism on the piece analysed.     

Guaraná (Paullinia cupana) as a commercial crop in Brazilian Amazonia

Guaraná (Paullinia cupana) is a woody vine or sprawling shrub native to the central Amazon Basin. The seeds are commercially produced on some 6,000 ha in the state of Amazonas near Manaus. The principal article of commerce is an amber-colored, carbonated soft drink. It is also widely used as a high caffeine stimulant and in local medicines. The plant is monoecious and is damaged by a number of diseases, the most severe being anthracnose. Prospects are excellent for greatly expanded international markets.     

Synthesis and structure-activity relationship of 2-(aminoalkyl)-2,3,3a,8-tetrahydrodibenzo[c,f]isoxazolo[2,3-a]azepine derivatives: a novel series of 5-HT(2A/2C) receptor antagonists. Part 2.

Following the programme started at Janssen Research Foundation searching for 5-HT(2A/2C) antagonists, we now report on the synthesis of a series of substituted 2-(Dimethylaminomethyl)-2,3,3a,8-tetrahydrodibenzo[c,f]isoxazolo[2,3-a]azepine derivatives. The 5-HT(2A), 5-HT(2C) and H(1) receptor affinities as well as the mCPP antagonistic activity of the compounds synthesised is described.     

Changes in fish condition and mercury vary by region,not Bythotrephes invasion: a result of climate change?

We compared changes in body condition (relative weight) and mercury concentrations ([Hg]) in two species of coregonid fish (lake herring Coregonus artedi, lake whitefish C. clupeaformis) among discrete populations in Ontario between 1967 and 2006. Temporal comparisons among populations were made to determine whether 1) the establishment of Bythotrephes longimanus had affected coregonid populations, or 2) if changes in body condition or [Hg] were related to regional differences in the degree of climate change during the time period investigated. Climate data from northwestern, northeastern and southern Ontario showed a general warming trend in all regions over the period of study. However, greater temporal changes in climate were observed in the northwest where growing degree days >5°C (GDD) increased and precipitation declined over the study period compared with relatively little change in southern or northeastern Ontario. Correspondingly, northwestern Ontario coregonid populations demonstrated significantly greater declines in body condition relative to those from northeastern or southern Ontario. Declines in [Hg] of both species were also greater among northwestern populations compared with those from northeastern or southern Ontario but only significantly so for lake herring. These declines were independent of the invasion of non‐native Bythotrephes, and declines in [Hg] were opposite predictions based on the hypothesis that Bythotrephes invasion lengthened aquatic food chains. Based on our findings and further evidence from the literature, we propose that warming regional climates are capable of contributing to declines in both condition and [Hg] of fishes. Because fish condition affects both reproductive success and overwinter survival, observed condition declines of the magnitude reported here could have profound implications for the structure of future aquatic ecosystems in a warming climate.     

Effects of lateral amygdala lesions on the responses to novelty in mice

Bilateral electrolytic lesions restricted to the lateral, basolateral and basomedial amygdaloid nuclei in mice produced a lack of avoidance responses towards novel stimuli. While controls showed avoidance and burying reactions to a novel object introduced into their familiar environment, lesioned mice displayed a high number of approach responses and a low level of burying reactions. Furthermore, when given the opportunity to move around freely in simultaneously presented novel and familiar places, control mice at first exhibited avoidance reactions to the novel environment before showing novelty preference. There were no avoidance reactions in lesioned mice. These data are consistent with the hypothesis that amygdala plays a specific role in the regulation of defensive reactions.