751 resultados para lytic activity and cooperativity
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There is a growing consensus that the eleven year modulation of galactic cosmic rays (GCRs) resulting from solar activity is related to interplanetary propagating diffusive barriers (PDBs). The source of these PDBs is not well understood and numerical models describing GCR modulation simulate their effect by scaling the diffusion tensor to the interplanetary magnetic field strength (IMF). The implications of a century-scale change in solar wind speed and open solar flux, for numerical modelling of GCR modulation and the reconstruction of GCR variations over the last hundred years are discussed. The dominant role of the solar non-axisymmetric magnetic field in both forcing longitudinal solar wind speed fluctuations at solar maximum and in increasing the IMF is discussed in the context of a long-term rise in the open solar magnetic flux.
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The orientation of the Interplanetary Magnetic Field (IMF) during transient bursts of ionospheric flow and auroral activity in the dayside auroral ionosphere is studied, using data from the EISCAT radar, meridian-scanning photometers, and an all-sky TV camera, in conjunction with simultaneous observations of the interplanetary medium by the IMP-8 satellite. It is found that the ionospheric flow and auroral burst events occur regularly (mean repetition period equal to 8.3 ± 0.6 min) during an initial period of about 45 min when the IMF is continuously and strongly southward in GSM coordinates, consistent with previous observations of the occurrence of transient dayside auroral activity. However, in the subsequent 1.5 h, the IMF was predominantly northward, and only made brief excursions to a southward orientation. During this period, the mean interval between events increased to 19.2 ± 1.7 min. If it is assumed that changes in the North-South component of the IMF are aligned with the IMF vector in the ecliptic plane, the delays can be estimated between such a change impinging upon IMP-8 and the response in the cleft ionosphere within the radar field-of-view. It is found that, to within the accuracy of this computed lag, each transient ionospheric event during the period of predominantly northward IMF can be associated with a brief, isolated southward excursion of the IMF, as observed by IMP-8. From this limited period of data, we therefore suggest that transient momentum exchange between the magnetosheath and the ionosphere occurs quasi-periodically when the IMF is continuously southward, with a mean period which is strikingly similar to that for Flux Transfer Events (FTEs) at the magnetopause. During periods of otherwise northward IMF, individual momentum transfer events can be triggered by brief swings to southward IMF. Hence under the latter conditions the periodicity of the events can reflect a periodicity in the IMF, but that period will always be larger than the minimum value which occurs when the IMF is strongly and continuously southward.
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Combined observations by meridian-scanning photometers and the EISCAT radar show that the "midday-auroral breakup" phenomenon is associated with major increases in ionospheric flow. A sequence of nine events is observed in the early afternoon MLT sector during a period when the IMF is strongly southward with a large positive By component. Each auroral structure is seen at both 630 and 557.7nm and initially moves westward, accompanied by an increase in potential of 30-60kV across the north-south dimension of the EISCAT field-of-view. After a few minutes the arc (or arc fragment) moves into the polar cap and fades, and the velocities observed by the radar swing from westward toward northward. We conclude that dayside auroral breakup is closely associated with momentum transfer across the magnetopause which occurs in a series of events 5-15 minutes apart. The largest of the observed events has dimensions of about 300km (in the direction of westward motion) by 700km, is bounded on its poleward edge by a 5kR arc and is associated with a potential of at least 80kV.
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The study of decaying organisms and death assemblages is referred to as forensic taphonomy, or more simply the study of graves. This field is dominated by the fields of entomology, anthropology and archaeology. Forensic taphonomy also includes the study of the ecology and chemistry of the burial environment. Studies in forensic taphonomy often require the use of analogues for human cadavers or their component parts. These might include animal cadavers or skeletal muscle tissue. However, sufficient supplies of cadavers or analogues may require periodic freezing of test material prior to experimental inhumation in the soil. This study was carried out to ascertain the effect of freezing on skeletal muscle tissue prior to inhumation and decomposition in a soil environment under controlled laboratory conditions. Changes in soil chemistry were also measured. In order to test the impact of freezing, skeletal muscle tissue (Sus scrofa) was frozen (−20 °C) or refrigerated (4 °C). Portions of skeletal muscle tissue (∼1.5 g) were interred in microcosms (72 mm diameter × 120 mm height) containing sieved (2 mm) soil (sand) adjusted to 50% water holding capacity. The experiment had three treatments: control with no skeletal muscle tissue, microcosms containing frozen skeletal muscle tissue and those containing refrigerated tissue. The microcosms were destructively harvested at sequential periods of 2, 4, 6, 8, 12, 16, 23, 30 and 37 days after interment of skeletal muscle tissue. These harvests were replicated 6 times for each treatment. Microbial activity (carbon dioxide respiration) was monitored throughout the experiment. At harvest the skeletal muscle tissue was removed and the detritosphere soil was sampled for chemical analysis. Freezing was found to have no significant impact on decomposition or soil chemistry compared to unfrozen samples in the current study using skeletal muscle tissue. However, the interment of skeletal muscle tissue had a significant impact on the microbial activity (carbon dioxide respiration) and chemistry of the surrounding soil including: pH, electroconductivity, ammonium, nitrate, phosphate and potassium. This is the first laboratory controlled study to measure changes in inorganic chemistry in soil associated with the decomposition of skeletal muscle tissue in combination with microbial activity.
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Proanthocyanidins (PAC) are a class of plant secondary metabolites commonly found in the diet that have shown potential to control gastrointestinal nematode infections. The anti-parasitic mechanism(s) of PAC remain obscure, however the protein-binding properties of PAC suggest that disturbance of key enzyme functions may be a potential mode of action. Glutathione-S-transferases (GSTs) are essential for parasite detoxification and have been investigated as drug and vaccine targets. Here, we show that purified PAC strongly inhibit the activity of both recombinant and native GSTs from the parasitic nematode Ascaris suum. As GSTs are involved in detoxifying xenobiotic substances within the parasite, we hypothesised that this inhibition may render parasites hyper-susceptible to anthelmintic drugs. Migration inhibition assays with A. suum larvae demonstrated that the potency of levamisole (LEV) and ivermectin (IVM) were significantly increased in the presence of PAC purified from pine bark (4.6-fold and 3.2-fold reduction in IC50 value for LEV and IVM, respectively). Synergy analysis revealed that the relationship between PAC and LEV appeared to be synergistic in nature, suggesting a specific enhancement of LEV activity, whilst the relationship between PAC and IVM was additive rather than synergistic, suggesting independent actions. Our results demonstrate that these common dietary compounds may increase the efficacy of synthetic anthelmintic drugs in vitro, and also suggest one possible mechanism for their well-known anti-parasitic activity.
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The inhibitory effects of mate tea (MT), a beverage produced with leaves from Ilex paraguariensis, in vitro lipase activity and on obesity in obese mice models were examined. For the in vitro experiment, porcine and human pancreatic lipase (PL) activities were determined by measuring the rate of release of oleic acid from hydrolysis of olive oil emulsified with taurocholate, phospholipids, gum arabic, or polyvinyl alcohol. For the in vivo experiments, animals were fed with a standard diet (SD, n = 10) or high-fat diet (HFD, n = 30) for 16 weeks. After the first 8 weeks on the HFD, the animals were treated with 1 and 2 g/kg of body weight of MT. The time course of the body weight and obesity-related biochemical parameters were evaluated. The results showed that MT inhibited both porcine and human PL (half-maximal inhibitory concentration = 1.5 mg MT/ml) and induced a strong inhibition of the porcine lipase activity in the hydrolysis of substrate emulsified with taurocholate + phosphatidylcholine (PC) (83 +/- 3.8%) or PC alone (62 +/- 4.3%). MT suppressed the increases in body weight (P < 0.05) and decreased the serum triglycerides and low-density lipoprotein (LDL)-cholesterol concentrations at both doses (from 190.3 +/- 5.7 to 135.0 +/- 8.9 mg/dl, from 189.1 +/- 7.3 to 129.3 +/- 17.6 mg/dl; P < 0.05, respectively) after they had been increased by the HFD. The liver lipid content was also decreased by the diet containing MT (from 132.6 +/- 3.9 to 95.6 +/- 6.1 mg/g of tissue; P < 0.05). These results suggest that MT could be a potentially therapeutic alternative in the treatment of obesity caused by a HFD.
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There is worldwide recognition that the burden of noncommunicable diseases (NCDs) and obesity-related health problems is rapidly increasing in low- and middle-income countries. Environmental determinants of obesity are likely to differ between countries, particularly in those undergoing rapid socioeconomic and nutrition transitions such as Brazil. This study aims to describe some built environment and local food environment variables and to explore their association with the overweight rate and diet and physical activity area-level aggregated indicators of adults living in the city of Sao Paulo, the largest city in Brazil. This formative study includes an ecological analysis of environmental factors associated with overweight across 31 submunicipalities of the city of Sao Paulo using statistical and spatial analyses. Average prevalence of overweight was 41.69% (95% confidence interval 38.74, 44.64), ranging from 27.14% to 60.75% across the submunicipalities. There was a wide geographical variation of both individual diet and physical activity, and indicators of food and built environments, favoring wealthier areas. After controlling for area socioeconomic status, there was a positive correlation between regular fruits and vegetables (FV) intake and density of FV specialized food markets (r = 0.497; p < 0.001), but no relationship between fast-food restaurant density and overweight prevalence was found. A negative association between overweight prevalence and density of parks and public sport facilities was seen (r = -0.527; p < 0.05). Understanding the relationship between local neighborhood environments and increasing rates of poor diet, physical activity, and obesity is essential in countries undergoing rapid economic and urban development, such as Brazil, in order to provide insights for policies to reduce increasing rates of NCDs and food access and health inequalities.
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Pteridium aquilinum (bracken fern) is one of the most common plants. Epidemiological studies have revealed a higher risk of certain types of cancers (i.e., esophageal, gastric) in people who consume bracken fern directly ( as crosiers or rhizomes) or indirectly through the consumption of milk from livestock that fed on the plant. In animals, evidence exists regarding the associations between chronic bracken fern intoxication, papilloma virus infection, and the development of carcinomas. While it is possible that some carcinogens in bracken fern could be responsible for these cancers in both humans and animals, it is equally plausible that the observed increases in cancers could be related to induction of an overall immunosuppression by the plant/its various constituents. Under the latter scenario, normal tumor surveillance responses against nascent (non-bracken-induced) cancers or responses against viral infections ( specifically those linked to induction of cancers) might be adversely impacted by continuous dietary exposure to this plant. Therefore, the overall objective of this study was to evaluate the immunomodulatory effects of bracken fern following daily ingestion of its extract by a murine host over a period of 14 ( or up to 30) days. In C57BL/6 mice administered ( by gavage) the extract, histological analyses revealed a significant reduction in splenic white pulp area. Among a variety of immune response parameters/functions assessed in these hosts and isolated cells, both delayed-type hypersensitivity (DTH) analysis and evaluation of IFN gamma. production by NK cells during T(H)1 priming were also reduced. Lastly, the innate response in these hosts-assessed by analysis of NK cell cytotoxic functionality-was also diminished. The results here clearly showed the immunosuppressive effects of P. aquilinum and that many of the functions that were modulated could contribute to the increased risk of cancer formation in exposed hosts.
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Brachycephalus hermogenesi is an endemic leaf litter inhabitant of the Atlantic forest of southeastern Brazil, whose original distribution included a restricted area near the boundaries of the States of Sao Paulo and Rio de Janeiro. We were surprised to find out, while conducting herpetofaunal surveys at Estacao Biologica de Boraceia (EBB), that the background forest insect-like sound we have been searching for corresponded to calling individuals of the species. Males call during the day at high densities, hidden under the leaf litter. Individuals do not answer playback, seem to move very infrequently, and seem to ignore nearby calling activity. We gathered data on annual and daily vocal activity of the species at EBB, observing a total of 1,549 calls given by 31 focal individuals in November 2003 and 2005. The call varies from short single note calls to calls composed of groups of two to seven similar notes emitted at regular intervals. We also extend the known distribution of the species southward to the State of Sao Paulo.
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The effect of glucose on the intracellular pH (pH(i)) recovery rate (dpH(i)/dt) and Na(+)-glucose transporter (SGLT) localization was investigated in HEK-293 cells, a cell line that expresses endogenous NHE1, NHE3, SGLT1, and SGLT2 proteins. The activity of the Na(+)/H(+) exchangers (NHEs) was evaluated by using fluorescence microscopy. The total and membrane protein expression levels were analyzed by immunoblotting. In cells cultivated in 5 mM glucose, the pH(i) recovery rate was 0.169 +/- A 0.020 (n = 6). This value did not change in response to the acute presence of glucose at 2 or 10 mM, but decreased with 25 mM glucose, an effect that was not observed with 25 mM mannitol. Conversely, the chronic effect of high glucose (25 mM) increased the pH(i) recovery rate (similar to 40%, P < 0.05), without changes in the total levels of NHE1, NHE3, or SGLT1 expression, but increasing the total cellular (similar to 50%, P < 0.05) and the plasma membrane (similar to 100%, P < 0.01) content of SGLT2. Treatment with H-89 (10(-6) M) prevented the stimulatory effect of chronic glucose treatment on the pH(i) recovery rate and SGLT2 expression in the plasma membrane. Our results indicate that the effect of chronic treatment with a high glucose concentration is associated with increased NHEs activity and plasma membrane expression of SGLT2 in a protein kinase A-dependent way. The present results reveal mechanisms of glucotoxicity and may contribute to understanding the diabetes-induced damage of this renal epithelial cell.
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Adolescents differ from adults in their acute sensitivity to several drugs of abuse, but little is known about the long-term neurobehavioral effects of adolescent drug exposure. To explore this further, we evaluated the locomotor responses to repeated cocaine administration in adolescent and adult male DBA/2J mice and alterations in extracellular levels of dopamine (DA) and glutamate (GLU) in the nucleus accumbens (NAc) in response to a subsequent cocaine challenge. Adolescent and adult mice were treated daily with saline or cocaine (10 mg/kg, i.p) for 9 consecutive days. Ten days following the last injection, animals were implanted with microdialysis probes and 24 h later microdialysis samples were collected before and after an acute cocaine challenge. Adolescents but not adults demonstrated development of behavioral sensitization to cocaine. Microdialysis procedures revealed that cocaine-treated mice displayed greater peak increases in extracellular DA in response to a subsequent cocaine challenge as compared to saline-treated mice, in contrast with lower peak increases in extracellular GLU. While adults exhibited greater peaks in extracellular DA in response to cocaine than adolescents did, adolescent mice presented a more rapid onset of peak extracellular DA levels than adults. Our results indicate differences in the behavioral and neurochemical responses to cocaine in adolescent versus adult mice, which may be relevant to the increased risk of developing addiction in humans who are exposed to drugs of abuse during adolescence. (C) 2007 Elsevier B.V. All rights reserved.
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Antimicrobial peptides (AMPs) are essential for the innate immune system of eukaryotes, imparting protection against pathogens and their proliferation in host organisms. The recent interest in AMPs as active materials in bionanostructures is due to the properties shown by these biological molecules, such as the presence of an alpha-helix structure and distribution of positive charges along the chain. In this study the antimicrobial peptide dermaseptin 01 (DS 01), from the skin secretion of Phyllomedusa hypochondrialis frogs was immobilized in nanostructured layered films in conjunction with nickel tetrasulfonated phthalocyanines. The leishmanicidal activity of DS 01 was confirmed using kinetic essays, in which DS 01 promoted death of all metacyclic promastigote cells in 45 minutes. Surprisingly, the immobilized DS 01 molecules displayed electroactivity, as revealed by electrochemical experiments, in which an oxidation peak at about 0.61 V was observed for a DS 01 monolayer deposited on top of a conductive electrode. Such electroactivity was used to investigate the sensing abilities of the nanostructured films toward Leishmania. We observed an increase in the oxidation current as a function of number of Leishmania cells in the electrolytic solution at concentrations down to 10(3) cells/mL. The latter is indicative that the use of AMPs immobilized in electroactive nanostructured films may be of interest for applications in the pharmaceutical industry and diagnosis.
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Biochemical responses in bivalve mollusks are commonly employed in environmental studies as biomarkers of aquatic contamination. The present study evaluated the possible influence of salinity (35, 25,15 and 9 ppt) in the biomarker responses of Crassostrea gigas oysters exposed to diesel at different nominal concentrations (0.01, 0.1 and 1 mLL(-1)) using a semi-static exposure system. Salinity alone did not resulted in major changes in the gill`s catalase activity (CAT), glutathione S-transferase activity (GST) and lipid peroxidation levels (measured as malondialdehyde. MDA), but influenced diesel related responses. At 25 ppt salinity, but not at the other salinity levels, oysters exposed to diesel showed a strikingly positive concentration-dependent GST response. At 25 ppt and 1 mLL(-1) diesel, the GST activity in the gills remained elevated, even after one week of depuration in clean water. The increased MDA levels in the oysters exposed to diesel comparing to control groups at 9, 15 and 35 ppt salinities suggest the occurrence of lipid peroxidation in those salinities, but not at 25 ppt salinity. The MDA quickly returned to basal levels after 24 h of depuration. CAT activity was unaltered by the treatments employed. High toxicity for 1 mLL(-1) diesel was observed only at 35 ppt salinity, but not in the other salinities. Results from this study strongly suggest that salinity influences the diesel related biomarker responses and toxicity in C. gigas, and that some of those responses remain altered even after depuration. (C) 2011 Elsevier B.V. All rights reserved.
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High fat diets are extensively associated with health complications within the spectrum of the metabolic syndrome. Some of the most prevalent of these pathologies, often observed early in the development of high-fat dietary complications, are non-alcoholic fatty liver diseases. Mitochondrial bioenergetics and redox state changes are also widely associated with alterations within the metabolic syndrome. We investigated the mitochondrial effects of a high fat diet leading to non-alcoholic fatty liver disease in mice. We found that the diet does not substantially alter respiratory rates, ADP/O ratios or membrane potentials of isolated liver mitochondria. However, H(2)O(2) release using different substrates and ATP-sensitive K(+) transport activities are increased in mitochondria from animals on high fat diets. The increase in H(2)O(2) release rates was observed with different respiratory substrates and was not altered by modulators of mitochondrial ATP-sensitive K(+) channels, indicating it was not related to an observed increase in K(+) transport. Altogether, we demonstrate that mitochondria from animals with diet-induced steatosis do not present significant bioenergetic changes, but display altered ion transport and increased oxidant generation. This is the first evidence, to our knowledge, that ATP-sensitive K(+) transport in mitochondria can be modulated by diet.
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The aim of this study was to identify a candidate drug for the development of anti-tuberculosis therapy from previously synthesized compounds based on the thiosemicarbazones, semicarbazones, dithio-carbazates and hydrazide/hydrazones compounds. The minimal inhibitory concentration (MIC) of these compounds against Mycobacterium tuberculosis was determined. Their in vitro cytotoxicity to J774 cells (IC(50)) was determined to establish a selectivity index (SI) (SI = IC(50)/MIC). The best compounds were the thiosemicarbazones (2, 3 and 4) and the hydrazide/hydrazones (14, 15, 16 and 18). The results are comparable to or better than those of ""first line"" or ""second line"" drugs commonly used to treat TB, suggesting these compounds as anti-TB drug candidates. (C) 2010 Elsevier Masson SAS. All rights reserved.