142 research outputs found
The Ilha Anchieta Quartz Monzonite: the southernmost expression of ca. 500 Ma post-collisional magmatism in the Ribeira Belt
Pluton emplacement in a releasing bend in a transpressive regime: the arrozal granite in the Paraíba do Sul shear belt, Rio de Janeiro
A novel case of human visceral leishmaniasis from the urban area of the city of Rio de Janeiro: autochthonous or imported from Spain ?
The Trypanosoma cruzi vitamin C dependent peroxidase confers protection against oxidative stress but is not a determinant of virulence.
BACKGROUND: The neglected parasitic infection Chagas disease is rapidly becoming a globalised public health issue due to migration. There are only two anti-parasitic drugs available to treat this disease, benznidazole and nifurtimox. Thus it is important to identify and validate new drug targets in Trypanosoma cruzi, the causative agent. T. cruzi expresses an ER-localised ascorbate-dependent peroxidase (TcAPx). This parasite-specific enzyme has attracted interest from the perspective of targeted chemotherapy. METHODOLOGY/PRINCIPAL FINDINGS: To assess the importance of TcAPx in protecting T. cruzi from oxidative stress and to determine if it is essential for virulence, we generated null mutants by targeted gene disruption. Loss of activity was associated with increased sensitivity to exogenous hydrogen peroxide, but had no effect on susceptibility to the front-line Chagas disease drug benznidazole. This suggests that increased oxidative stress in the ER does not play a significant role in its mechanism of action. Homozygous knockouts could proceed through the entire life-cycle in vitro, although they exhibited a significant decrease in their ability to infect mammalian cells. To investigate virulence, we exploited a highly sensitive bioluminescence imaging system which allows parasites to be monitored in real-time in the chronic stage of murine infections. This showed that depletion of enzyme activity had no effect on T. cruzi replication, dissemination or tissue tropism in vivo. CONCLUSIONS/SIGNIFICANCE: TcAPx is not essential for parasite viability within the mammalian host, does not have a significant role in establishment or maintenance of chronic infections, and should therefore not be considered a priority for drug design
Numerical analysis of different heating systems for warm sheet metal forming
The main goal of this study is to present an analysis
of different heating methods frequently used in laboratory
scale and in the industrial practice to heat blanks at warm
temperatures. In this context, the blank can be heated inside
the forming tools (internal method) or using a heating system
(external method). In order to perform this analysis, a finite
element model is firstly validated with the simulation of the
direct resistance system used in a Gleeble testing machine.
The predicted temperature was compared with the temperature
distribution recorded experimentally and a good agreement
was found. Afterwards, a finite element model is used to
predict the temperature distribution in the blank during the
heating process, when using different heating methods. The
analysis also includes the evaluation of a cooling phase associated
to the transport phase for the external heating methods.
The results of this analysis show that neglecting the heating
phase and a transport phase could lead to inaccuracies in the
simulation of the forming phase.The authors gratefully acknowledge the financial
support of the Portuguese Foundation for Science and Technology (FCT)
under project PTDC/EMS-TEC/1805/2012 and by FEDER funds
through the program COMPETE—Programa Operacional Factores de
Competitividade, under the project CENTRO-07-0224-FEDER-002001
(MT4MOBI). The authors would like to thank Prof. A. Andrade-Campos
for helpful contributions on the development of the finite element code
presented in this work.info:eu-repo/semantics/publishedVersio
Antimalarial Activity and Mechanisms of Action of Two Novel 4-Aminoquinolines against Chloroquine-Resistant Parasites
Chloroquine (CQ) is a cost effective antimalarial drug with a relatively good safety profile (or therapeutic index). However, CQ is no longer used alone to treat patients with Plasmodium falciparum due to the emergence and spread of CQ-resistant strains, also reported for P. vivax. Despite CQ resistance, novel drug candidates based on the structure of CQ continue to be considered, as in the present work. One CQ analog was synthesized as monoquinoline (MAQ) and compared with a previously synthesized bisquinoline (BAQ), both tested against P. falciparum in vitro and against P. berghei in mice, then evaluated in vitro for their cytotoxicity and ability to inhibit hemozoin formation. Their interactions with residues present in the NADH binding site of P falciparum lactate dehydrogenase were evaluated using docking analysis software. Both compounds were active in the nanomolar range evaluated through the HRPII and hypoxanthine tests. MAQ and BAQ derivatives were not toxic, and both compounds significantly inhibited hemozoin formation, in a dose-dependent manner. MAQ had a higher selectivity index than BAQ and both compounds were weak PfLDH inhibitors, a result previously reported also for CQ. Taken together, the two CQ analogues represent promising molecules which seem to act in a crucial point for the parasite, inhibiting hemozoin formation
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