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62.
Neurochemical Research - Methylmercury (MeHg) exposure and its harmful effects on the developing brain continue to be a global environmental health concern. Decline in mitochondrial function is...  相似文献   
63.
Hundreds of millions of people worldwide are affected by Chagas’ disease caused by Trypanosoma cruzi. Since the current treatment lack efficacy, specificity, and suffers from several side-effects, novel therapeutics are mandatory. Natural products from endophytic fungi have been useful sources of lead compounds. In this study, three lactones isolated from an endophytic strain culture were in silico evaluated for rational guidance of their bioassay screening. All lactones displayed in vitro activity against T. cruzi epimastigote and trypomastigote forms. Notably, the IC50 values of (+)-phomolactone were lower than benznidazole (0.86 vs. 30.78 μM against epimastigotes and 0.41 vs. 4.88 μM against trypomastigotes). Target-based studies suggested that lactones displayed their trypanocidal activities due to T. cruzi glyceraldehyde-3-phosphate dehydrogenase (TcGAPDH) inhibition, and the binding free energy for all three TcGAPDH-lactone complexes suggested that (+)-phomolactone has a lower score value (−3.38), corroborating with IC50 assays. These results highlight the potential of these lactones for further anti-T. cruzi drug development.  相似文献   
64.
Microtubule plus-end depolymerization rate is a potentially important target of physiological regulation, but it has been challenging to measure, so its role in spatial organization is poorly understood. Here we apply a method for tracking plus ends based on time difference imaging to measure depolymerization rates in large interphase asters growing in Xenopus egg extract. We observed strong spatial regulation of depolymerization rates, which were higher in the aster interior compared with the periphery, and much less regulation of polymerization or catastrophe rates. We interpret these data in terms of a limiting component model, where aster growth results in lower levels of soluble tubulin and microtubule-associated proteins (MAPs) in the interior cytosol compared with that at the periphery. The steady-state polymer fraction of tubulin was ∼30%, so tubulin is not strongly depleted in the aster interior. We propose that the limiting component for microtubule assembly is a MAP that inhibits depolymerization, and that egg asters are tuned to low microtubule density.  相似文献   
65.
The relationship between surface electromyography (SEMG) amplitude and the ventilatory threshold has been extensively studied. However, previous studies of muscle fiber conduction velocity (MFCV) are scarce and present insufficient evidence concerning the relationship between MFCV and metabolic responses during cycling. Based on that fact, the purpose of this study is twofold: (1) to investigate the existence of a MFCV threshold (MFCVT) during cycling and (2) to verify if this possible breakpoint is correlated with the ventilatory threshold (VT) and the SEMG threshold (SEMGT). Eight trained male cyclists (age 36.0 ± 9.7 years) performed an incremental cycling test with initial workload of 150 W gradually incremented by 20 W min?1 until the exhaustion. Gas analyses were conducted using a breath-by-breath open-circuit spirometry and SEMG were registered from vastus lateralis in each pedaling cycle with a linear array of electrodes. A bi-segmental linear regression computer algorithm was used to estimate VT, MFCVT and SEMGT respectively in the carbon dioxide production (VCO2), MFCV and electromyography root mean square (EMG RMS) curves. The one way ANOVA for repeated measures did not reveal any significant difference among VT (77.1 ± 7.5% of VO2max), MFCVT (80.3 ± 10.4% of VO2max) and SEMGT (81.9 ± 11.7% of VO2max). The Bland and Altman procedure confirmed a good concordance between SEMGT and VT (Bias = 5.5 of %VO2max) as well as MFCVT and VT (Bias = 5.2 of %VO2max). The present findings suggest that muscle fiber conduction velocity threshold is a valid and reliable non-invasive tool to obtain information about ventilatory threshold in trained cyclists.  相似文献   
66.
Tropical dry forest tree species are recognized for their high resprouting ability after disturbance. We tested whether species that commonly produce root and stem suckers can be propagated by large stem and root cuttings, a useful method for landscape restoration programs. We performed four experiments: (1) In a greenhouse, we tested the propagation of six species using large stem cuttings collected from early successional sites. We used the following treatments: (i) dry season collection and planting; (ii) dry season collection, storage in humid soil, and wet season planting; (iii) wet season collection and planting; and (iv) wet season collection and planting after treatment with commercial NAA auxin. (2) Stem cuttings of Myracrodruon urundeuva were planted in a pasture during the rainy season after either NAA, IBA, or no auxin treatment. (3) As a control experiment, we also planted cuttings of Spondias mombin, a species known for successfully regenerating from cuttings. (4) Root cuttings of six species were collected in recently plowed pastures and planted in the greenhouse with and without treatment with NAA auxin. No root cuttings rooted. Only M. urundeuva and Astronium fraxinifolium stem cuttings rooted. Maximum success was obtained for stem cuttings collected and planted in the dry season (23%). Only 13% of M. urundeuva had sprouted by the 15th month of the field experiment. As a result, large cuttings are not recommended for propagation of the studied species. Future studies should include development of suitable methods of root harvesting and prospection of traditional knowledge for species selection.  相似文献   
67.
Accumulation of 5-aminolevulinic acid (ALA) is an event characteristic of porphyrias that may contribute to their pathological manifestations. To investigate effects of ALA independent of porphyrin accumulation we treated rats with the methyl ester of succinylacetone, an inhibitor of 5-aminolevulinic acid dehydratase that accumulates in the porphyric-like syndrome hereditary tyrosinemia. Acute 2-day treatment of fasted rats with succinylacetone methyl ester (SAME) promoted a 27% increase in plasma ALA. This increase in plasma ALA was accompanied by augmentation of the level of total nonheme iron in liver (37%) and brain (20%). Mobilization of iron was also indicated by 49% increase in plasma iron and a 77% increase in plasma transferrin saturation. Liver responded with a mild (12%) increase in ferritin. Under these acute conditions, some indications of oxidative stress were evident: a 15% increase in liver reactive protein carbonyls, and a 42% increase in brain subcellular membrane TBARS. Brain also showed a 44% increase in CuZnSOD activity, consistent with observations in treatment with ALA. Overall, the data indicate that SAME promotes ALA-driven changes in iron metabolism that could lead to increased production of free radicals. The findings support other evidence that accumulation of ALA in porphyrias and hereditary tyrosinemia may induce iron-dependent biological damage that contributes to neuropathy and hepatoma.  相似文献   
68.
The excessive production of reactive oxygen species (ROS) associated with inflammation leads to oxidative stress, which is involved with the high mortality from several diseases such as endotoxic shock and can be controlled to a certain degree by antioxidants. The immune cells use ROS in order to support their functions and, therefore, need adequate levels of antioxidant defenses in order to avoid the harmful effect of an excessive ROS production. In the present work, the effect of the administration of the antioxidant N-acetylcysteine (NAC) on the redox state of peritoneal macrophages and lymphocytes from mice with lethal endotoxic shock (100 mg/kg i.p. of lipopolysaccharide, LPS), was studied. In both types of immune cells at 0, 2, 4, 12 and 24 h after LPS injection, an increase of ROS, of the proinflammatory cytokine tumor necrosis factor alpha (TNFα), the lipid peroxidation (malonaldehyde levels, MDA), inducible nitric oxide synthase (iNOS) expression and the oxidized/reduced glutathione (GSSG/GSH) ratio, as well as a decrease of enzymatic antioxidant defenses, such as superoxide dismutase (SOD) and catalase (CAT) activity, was observed. The injection of NAC (150 mg/kg i.p. at 30 min after LPS injection) decreased the ROS, the TNFα the MDA levels, iNOS expression and the GSSG/GSH ratio, and increased the antioxidant defenses in both macrophages and lymphocytes. Moreover, the NAC treatment prevented the activation of nuclear translocation of the nuclear factor κB (NF-κB), which regulates ROS, inflammatory cytokines and antioxidant levels. Our present results provide evidence that both cell types have a relevant role in the pathogenesis of endotoxic shock, and that NAC, by improving the redox state of these immune cells, could increase mouse survival. Thus, antioxidants could offer an alternative treatment of human endotoxic shock.  相似文献   
69.
The amyloid β‐peptide with a sequence of 42 amino acids is the major constituent of extracellular amyloid deposits in Alzheimer's disease plaques. The control of the peptide self‐assembly is difficult to achieve because the process is fast and is affected by many variables. In this paper, we describe the effect of different charged and non‐charged surfactants on Aβ(1‐42) fibrillation to define common alternate aggregation pathways. The characterization of the peptide‐surfactant interactions by ultra‐structural analysis, thioflavin T assay and secondary structure analysis, suggested that charged surfactants interact with Aβ(1‐42) through electrostatic interactions. Charged micelles slow down the aggregation process and stabilize the peptide in the oligomeric state, whereas non‐charged surfactants promote the Aβ(1‐42) fibril formation. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.  相似文献   
70.
Because of the high adaptive capacity of mosquitoes, studies that focus on transitional environments become very important, such as those in rural areas, which are considered as bridges between wild diseases and human populations of urban areas. In this study, a survey of the existing species of mosquitoes was performed in an Atlantic Forest area of the city of Santa Bárbara d'Oeste, São Paulo state, Brazil, using traps for immatures and analyzing the frequency and distribution of these insects over the sampling months. Five mosquito species were found: Aedes albopictus (the most frequent species), Aedes aegypti, Aedes fluviatilis, Culex quinquefasciatus, and Toxorhynchites theobaldi. The 4,524 eggs collected in ovitraps showed the presence of the tribe Aedini. Aedes aegypti and Ae. albopictus were identified after larval hatching in the laboratory, with different spatial distributions: the first of which coincides with the area of greatest diversity calculated using the Simpson index, while the second does not. The association of ecological analysis of spatial diversity with simple methods of data collection enables the identification of possible epidemiological risk situations and is a strategy that may be implemented to monitor ecological processes resulting from the interaction among different species of mosquitoes.  相似文献   
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