In Vitro and In Vivo Antiplasmodial Activities of Risedronate and Its Interference with Protein Prenylation in Plasmodium falciparum

The increasing resistance of malarial parasites to almost all available drugs calls for the identification of new compounds and the detection of novel targets. Here, we establish the antimalarial activities of risedronate, one of the most potent bisphosphonates clinically used to treat bone resorption diseases, against blood stages of Plasmodium falciparum (50% inhibitory concentration [IC(50)] of 20.3 +/- 1.0 mu M). We also suggest a mechanism of action for risedronate against the intraerythrocytic stage of P. falciparum and show that protein prenylation seems to be modulated directly by this drug. Risedronate inhibits the transfer of the farnesyl pyrophosphate group to parasite proteins, an effect not observed for the transfer of geranylgeranyl pyrophosphate. Our in vivo experiments further demonstrate that risedronate leads to an 88.9% inhibition of the rodent parasite Plasmodium berghei in mice on the seventh day of treatment; however, risedronate treatment did not result in a general increase of survival rates.

Design and validation of a sheet metal shearing experimental procedure

Throughout the industrial processes of sheet metal manufacturing and refining, shear cutting is widely used for its speed and cost advantages over competing cutting methods. Industrial shears may include some force measurement possibilities, but the force is most likely influenced by friction losses between shear tool and the point of measurement, and are in general not showing the actual force applied to the sheet. Well defined shears and accurate measurements of force and shear tool position are important for understanding the influence of shear parameters. Accurate experimental data are also necessary for calibration of numerical shear models. Here, a dedicated laboratory set-up with well defined geometry and movement in the shear, and high measurability in terms of force and geometry is designed, built and verified. Parameters important to the shear process are studied with perturbation analysis techniques and requirements on input parameter accuracy are formulated to meet experimental output demands. Input parameters in shearing are mostly geometric parameters, but also material properties and contact conditions. Based on the accuracy requirements, a symmetric experiment with internal balancing of forces is constructed to avoid guides and corresponding friction losses. Finally, the experimental procedure is validated through shearing of a medium grade steel. With the obtained experimental set-up performance, force changes as result of changes in studied input parameters are distinguishable down to a level of 1%.

Quantified Interference: Information Theory and Information Flow

The paper investigates which of Shannon’s measures (entropy, conditional entropy, mutual information) is the right one for the task of quantifying information flow in a programming language. We examine earlier relevant contributions from Denning, McLean and Gray and we propose and motivate a specific quantitative definition of information flow. We prove results relating equivalence relations, interference of program variables, independence of random variables and the flow of confidential information. Finally, we show how, in our setting, Shannon’s Perfect Secrecy theorem provides a sufficient condition to determine whether a program leaks confidential information.

Weed interference on maize (Zea mays) under no tillage system

A field trial was carried out in Brazil in March 2002 with the aim to evaluate the effects of different timing and extension of weedy period on maize productivity. The hybrid Pioneer 30K75 was sowed under 7 t ha(-1) mulching promoted by glyphosate spraying. The treatments were divided in two groups: In the first group, weeds were maintained since the maize sowing until different periods in the crop cycle: 0, 14, 28, 42, 56, 70, and 150 days (harvesting time). In the second group, the maize crop was kept weed free for the same periods of the first group. Weed control was done through hand hoeing. A complete randomized blocks experimental design with five replications was used for plots distribution in the field. Nonlinear regression model was used to study the effects of weedy or weedfree periods on maize productivity. Weed community included 13 families and 31 species. Asteraceae, Poaceae, and Euphorbiaceae were the most abundant families. Results showed that under no tillage condition with 7 t ha-1 mulching at sowing time, the maize crop could cohabit with weed community for 54 days without any yield lost. on the other hand, if the crop was kept weed free for 27 days, the weed interference was not enable to reduce maize production. According to these results one weed control measure between 27 and 54 days after crop emergence could be enough to avoid any reduction in maize productivity.

EFFECTS of MINERAL NUTRITION on INTER- and INTRASPECIFIC INTERFERENCE of PEANUT (Arachis hypogaea L.) and HAIRY BEGGARTICKS (Bidens pilosa L.)

The present work was carried out to study the effects of mineral nutrition on peanut (Arachis hypogaea L) cv. IAC Runner-886 and hairy beggarticks (Bidens pilosa L) growth, when submitted to inter- and intraspecific competition. The treatments consisted of two peanut plants per pot, two hairy beggarticks per pot and one plant of each species per pot. The plants were nourished with Hoagland and Arnon (1950) complete solution, or without potassium, or without phosphorus or without nitrogen. Sixty days after planting, no inter- or intraspecific competition effect on growth characteristics of peanut was verified and nutrition was not a limiting factor to the culture. No interaction between competition and nutrition effects was observed for both species. The weed suffered more negative effects from intraspecific competition and nutrition. The absence of N had a pronounced effect compared to the other elements, resulting in a reduction in all the evaluated characteristics. The deficiency of nutrients and competition affected the weed more than the crop, showing that peanut was more competitive than hairy beggarticks.

Weed interference on coffee fruit production during a four-year investigation after planting

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

Modeling of weeds interference periods in bean

Objetivou-se com este trabalho determinar o período de convivência anterior à interferência das plantas daninhas (PAI) e o período anterior ao dano no rendimento econômico (PADRE) na cultura do feijão, em diferentes espaçamentos (0,45 e 0,60 m) e densidade de plantas (10 e 15 plantas m-1). Os tratamentos foram constituídos de períodos de convivência entre a cultura e as plantas daninhas (0 a 10, 0 a 20, 0 a 30, 0 a 40, 0 a 50, 0 a 60, 0 a 70 e 0 a 80 dias), mais uma testemunha sem convívio com as plantas daninhas. Adotou-se o delineamento experimental de blocos casualizados, com quatro repetições. Os períodos anteriores à interferência (PAI) da cultura foram de 23, 27, 13 e 19 dias após emergência, e os períodos anteriores ao dano no rendimento econômico (PADRE), de 10, 9, 8 e 8 dias, para os tratamentos com espaçamento de 0,45 m e densidades de semeadura de 10 e 15 plantas m-1 e para aqueles com espaçamento de 0,60 m e densidades de semeadura de 10 e 15 plantas m-1, respectivamente, o que reduziu a produtividade de grãos em 63, 50, 42 e 57%, respectivamente, com a presença das plantas daninhas durante todo o ciclo do feijoeiro.

Interference effects in nonplanar wires with a two-dimensional electron gas

We have studied the universal conductance fluctuations (UCF) due to quantum interface in a two-dimensional electron gas (2DEG) grown on the substrates with pre-patterned, sub-micron wires. The dependence of UCF on the angle between the direction of the magnetic field and the substrate has been investigated. We found, that magnetoresistance traces for different angles are completely uncorrelated. A non-planar character of electron motion is responsible for these angular conductance fluctuations. We compared the experimental results with a simple geometrical model.

Occurrence of pneumocystis pneumonia in HIV-infected patients and the interference of the highly active antiretroviral therapy

From the beginning of the AIDS epidemic, pneumocystis pneumonia ( PCP) has been distinguished as one of the most frequent opportunistic diseases with high morbid-mortality. As from 1996, the advent of the highly active antiretroviral therapy ( HAART) has changed the characteristics of such epidemic by reducing its related diseases and, as a result, AIDS-related mortality. With the purpose to estimate PCP occurrence and HAART interference, 376 HIV-infected or AIDS patients were studied from January 1992 to December 2002. Among them, 58 ( 15.5%) PCP cases were found. There was a higher occurrence of PCP in the group of patients in which HAART was not used, with 40 ( 69.0%) of the episodes. As regards the studied period, a tendency to a linear reduction in annual PCP incidence was observed. The mean of T CD4+ lymphocytes in the patients with PCP ( 117 cells/mm(3)) was significantly lower when compared to that of the other individuals ( 325 cells/mm(3)). Therefore, this study suggests a temporal reduction in PCP occurrence related to HAART use with higher T CD4+ lymphocyte counts. Nevertheless, this opportunistic infection still shows significant incidence in AIDS patients. ( NCT00516581).

Vaccine immune response and interference of colostral antibodies in calves vaccinated against rabies at 2, 4 and 6 months of age born from antirabies revaccinated females

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

Morphological evidences indicate that the interference of cimetidine on the peritubular components is responsible for detachment and apoptosis of Sertoli cells

Cimetidine, referred as antiandrogenic agent, has caused alterations in the seminiferous tubules, including alterations in the peritubular tissue and death of myoid cells by apoptosis. Regarding the structural and functional importance of the peritubular tissue for the maintenance of Sertoli cells (SC), we purpose to investigate the SC-basement membrane interface, focusing the morphological features of SC and their interaction with the basement membrane in the affected tubules by cimetidine. Ten animals were distributed into two groups, control (CG) and cimetidine (CmG) which received saline solution and 50 mg of cimetidine per kg of body weight, respectively, for 52 days. The testes were fixed, dehydrated and embedded for analyses under light and transmission electron microscopy. Paraffin sections were submitted to the TUNEL method; sections of testes embedded in glycol methacrylate were submitted to PAS method and stained by H&E for morphological and quantitative analyses of Sertoli Cells. In the CmG, the SC nuclei were positive to the TUNEL method and showed typical morphological alterations of cell death by apoptosis (from early to advanced stages). A significant reduction in the number of Sertoli Cells was probably due to death of these cells by apoptosis. A close relationship between SC nuclear alterations (including a high frequency of dislocated nuclei from the basal portion) and damage in the peritubular tissue was observed. The ultrastructural analysis showed a parallelism between the gradual advancement of apoptotic process in SC and detachment of the anchoring sites (hemidesmosomes) of SC plasma membrane from the lamina densa. The presence of portions of lamina densa underlying the detached hemidesmosomes indicates a continuous deposition of lamina densa, resulting in the thickening of the basal lamina. The results indicate a possible disarrangement of the SC cytoskeleton, including the focal adhesion structure. These alterations are related to SC apoptosis and probably result from disturbs induced by cimetidine on the peritubular tissue.

Strand Analysis, a free online program for the computational identification of the best RNA interference (RNAi) targets based on Gibbs free energy

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