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41.
42.
Cleide G da Silva César A J Ribeiro Guilhian Leipnitz Carlos S Dutra-Filho Angela T S Wyse AT Clóvis M D Wannmacher Jo?o J F Sarkis Cornelis Jakobs Moacir Wajner 《Biochimica et biophysica acta》2002,1586(1):81-91
L-2-Hydroxyglutaric (LGA) and D-2-hydroxyglutaric (DGA) acids are the characteristic metabolites accumulating in the neurometabolic disorders known as L-2-hydroxyglutaric aciduria and D-2-hydroxyglutaric aciduria, respectively. Although these disorders are predominantly characterized by severe neurological symptoms, the neurotoxic mechanisms of brain damage are virtually unknown. In this study we have evaluated the role of LGA and DGA at concentrations ranging from 0.01 to 5.0 mM on various parameters of energy metabolism in cerebral cortex slices and homogenates of 30-day-old Wistar rats, namely glucose uptake, CO(2) production and the respiratory chain enzyme activities of complexes I to IV. DGA significantly decreased glucose utilization (2.5 and 5.0 mM) by brain homogenates and CO(2) production (5 mM) by brain homogenates and slices, whereas LGA had no effect on either measurement. Furthermore, DGA significantly inhibited cytochrome c oxidase activity (complex IV) (EC 1.9.3.1) in a dose-dependent manner (35-95%) at doses as low as 0.5 mM, without compromising the other respiratory chain enzyme activities. In contrast, LGA did not interfere with these activities. Our results suggest that the strong inhibition of cytochrome c oxidase activity by increased levels of DGA could be related to the neurodegeneration of patients affected by D-2-hydroxyglutaric aciduria. 相似文献
43.
Xiaofang Wang Darren J. Creek Charles E. Schiaffo Yuxiang Dong Jacques Chollet Christian Scheurer Sergio Wittlin Susan A. Charman Patrick H. Dussault James K. Wood Jonathan L. Vennerstrom 《Bioorganic & medicinal chemistry letters》2009,19(16):4542-4545
These data suggest that iron(II) reactivity for a set of homologous spiroadamantyl 1,2,4-trioxolane, 1,2,4-trioxane, and 1,2,4-trioxepane peroxide heterocycles is a necessary, but insufficient, property of animalarial peroxides. Heme alkylation efficiency appears to give a more accurate prediction of antimalarial activity than FeSO4-mediated reaction rates, suggesting that antimalarial activity is not merely dependent on peroxide bond cleavage, but also on the ability of reactive intermediates to alkylate heme or other proximal targets. 相似文献
44.
Odhran S. O'sullivan Mary A. Heskel Peter B. Reich Mark G. Tjoelker Lasantha K. Weerasinghe Aurore Penillard Lingling Zhu John J. G. Egerton Keith J. Bloomfield Danielle Creek Nur H. A. Bahar Kevin L. Griffin Vaughan Hurry Patrick Meir Matthew H. Turnbull Owen K. Atkin 《Global Change Biology》2017,23(1):209-223
High‐temperature tolerance in plants is important in a warming world, with extreme heat waves predicted to increase in frequency and duration, potentially leading to lethal heating of leaves. Global patterns of high‐temperature tolerance are documented in animals, but generally not in plants, limiting our ability to assess risks associated with climate warming. To assess whether there are global patterns in high‐temperature tolerance of leaf metabolism, we quantified Tcrit (high temperature where minimal chlorophyll a fluorescence rises rapidly and thus photosystem II is disrupted) and Tmax (temperature where leaf respiration in darkness is maximal, beyond which respiratory function rapidly declines) in upper canopy leaves of 218 plant species spanning seven biomes. Mean site‐based Tcrit values ranged from 41.5 °C in the Alaskan arctic to 50.8 °C in lowland tropical rainforests of Peruvian Amazon. For Tmax, the equivalent values were 51.0 and 60.6 °C in the Arctic and Amazon, respectively. Tcrit and Tmax followed similar biogeographic patterns, increasing linearly (?8 °C) from polar to equatorial regions. Such increases in high‐temperature tolerance are much less than expected based on the 20 °C span in high‐temperature extremes across the globe. Moreover, with only modest high‐temperature tolerance despite high summer temperature extremes, species in mid‐latitude (~20–50°) regions have the narrowest thermal safety margins in upper canopy leaves; these regions are at the greatest risk of damage due to extreme heat‐wave events, especially under conditions when leaf temperatures are further elevated by a lack of transpirational cooling. Using predicted heat‐wave events for 2050 and accounting for possible thermal acclimation of Tcrit and Tmax, we also found that these safety margins could shrink in a warmer world, as rising temperatures are likely to exceed thermal tolerance limits. Thus, increasing numbers of species in many biomes may be at risk as heat‐wave events become more severe with climate change. 相似文献
45.
Water availability affects seasonal CO2‐induced photosynthetic enhancement in herbaceous species in a periodically dry woodland 下载免费PDF全文
Varsha S. Pathare Kristine Y. Crous Julia Cooke Danielle Creek Oula Ghannoum David S. Ellsworth 《Global Change Biology》2017,23(12):5164-5178
Elevated atmospheric CO2 (eCO2) is expected to reduce the impacts of drought and increase photosynthetic rates via two key mechanisms: first, through decreased stomatal conductance (gs) and increased soil water content (VSWC) and second, through increased leaf internal CO2 (Ci) and decreased stomatal limitations (Slim). It is unclear if such findings from temperate grassland studies similarly pertain to warmer ecosystems with periodic water deficits. We tested these mechanisms in three important C3 herbaceous species in a periodically dry Eucalyptus woodland and investigated how eCO2‐induced photosynthetic enhancement varied with seasonal water availability, over a 3 year period. Leaf photosynthesis increased by 10%–50% with a 150 μmol mol?1 increase in atmospheric CO2 across seasons. This eCO2‐induced increase in photosynthesis was a function of seasonal water availability, given by recent precipitation and mean daily VSWC. The highest photosynthetic enhancement by eCO2 (>30%) was observed during the most water‐limited period, for example, with VSWC <0.07 in this sandy surface soil. Under eCO2 there was neither a significant decrease in gs in the three herbaceous species, nor increases in VSWC, indicating no “water‐savings effect” of eCO2. Periods of low VSWC showed lower gs (less than ≈ 0.12 mol m?2 s?1), higher relative Slim (>30%) and decreased Ci under the ambient CO2 concentration (aCO2), with leaf photosynthesis strongly carboxylation‐limited. The alleviation of Slim by eCO2 was facilitated by increasing Ci, thus yielding a larger photosynthetic enhancement during dry periods. We demonstrated that water availability, but not eCO2, controls gs and hence the magnitude of photosynthetic enhancement in the understory herbaceous plants. Thus, eCO2 has the potential to alter vegetation functioning in a periodically dry woodland understory through changes in stomatal limitation to photosynthesis, not by the “water‐savings effect” usually invoked in grasslands. 相似文献
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Background
Plasmodium falciparum antigenic diversity and polymorphism confuses the issue of antimalarial vaccine development. Merozoite surface protein (MSP)-1 and -2 are two highly polymorphic vaccine candidates. Characterisation of their precise polymorphism in endemic regions may facilitate the design of an effective vaccine.Methods
Isolates obtained in 52 Gabonese children presenting with uncomplicated malaria were genotyped by nested-PCR of msp -1 block 2, and msp -2 block 3, to analyze both parasite population polymorphism and clone fluctuations.Results
Twenty-five and 19 different alleles were respectively obtained for msp-1 and msp-2 loci, the RO33 family of msp-1 being poorly polymorphic. Four cases of non-random distribution of alleles were reported of the FC27, and/or 3D7 families of msp-2. All but two isolates were composed of more than one genotype, and the multiplicity of infection (MOI) was 4.0. Neither parasite density nor age was related to MOI. Clone fluctuations were studied for ten subjects who were sampled again at reappearance of parasites in blood. Disappearance and reappearance of alleles were observed following treatment, suggesting difficulties in assessing polymorphism and in distinguishing reinfection from recrudescence.Conclusion
P. falciparum polymorphism is extensive in Southeast Gabon, and most of infections are composed of multiple clones. The fluctuation of clones contributes to parasite diversity. 相似文献48.
Kim AT Verheijden Linette EM Willemsen Saskia Braber Thea Leusink-Muis Dianne JM Delsing Johan Garssen Aletta D Kraneveld Gert Folkerts 《Respiratory research》2015,16(1)
Background
Allergic asthma is strongly associated with the exposure to house dust mite (HDM) and is characterized by eosinophilic pulmonary inflammation and airway hyperresponsiveness (AHR). Recently, there is an increased interest in using dietary oligosaccharides, also known as prebiotics, as a novel strategy to prevent the development of, or reduce, symptoms of allergy.Aim
We investigated the preventive capacity of dietary galacto-oligosaccharides (GOS) compared to an intra-airway therapeutic treatment with budesonide on the development of HDM-induced allergic asthma in mice.Methods
BALB/c mice were intranasally sensitized with 1 μg HDM on day 0 followed by daily intranasal challenge with PBS or 10 μg HDM on days 7 to 11. Two weeks prior to the first sensitization and throughout the experiment mice were fed a control diet or a diet containing 1% GOS. Reference mice were oropharyngeally instilled with budesonide (500 μg/kg) on days 7, 9, 11, and 13, while being fed the control diet. On day 14, AHR was measured by nebulizing increasing doses of methacholine into the airways. At the end of the experiment, bronchoalveolar lavage fluid (BALF) and lungs were collected.Results
Sensitization and challenge with HDM resulted in AHR. In contrast to budesonide, dietary intervention with 1% GOS prevented the development of AHR. HDM sensitization and challenge resulted in a significant increase in BALF leukocytes numbers, which was suppressed by budesonide treatment and dietary intervention with 1% GOS. Moreover, HDM sensitization and challenge resulted in significantly enhanced concentrations of IL-6, CCL17, IL-33, CCL5 and IL-13 in lung tissue. Both dietary intervention with 1% GOS or budesonide treatment significantly decreased the HDM-induced increased concentrations of CCL5 and IL-13 in lung tissue, while budesonide also reduced the HDM-enhanced concentrations of IL-6 and CCL17 in lung tissue.Conclusion
Not only did dietary intervention with 1% GOS during sensitization and challenge prevent the induction of airway eosinophilia and Th2-related cytokine and chemokine concentrations in the lung equally effective as budesonide treatment, it also prevented AHR development in HDM-allergic mice. GOS might be useful for the prevention and/or treatment of symptoms in asthmatic disease.Electronic supplementary material
The online version of this article (doi:10.1186/s12931-015-0171-0) contains supplementary material, which is available to authorized users. 相似文献49.
Jennifer L Percival-Alwyn Elizabeth England Benjamin Kemp Laura Rapley Nicola HE Davis Grant R McCarthy Jayesh B Majithiya Dominic J Corkill Sarah Welsted Kevin Minton E Suzanne Cohen Matthew J Robinson Claire Dobson Trevor CI Wilkinson Tristan J Vaughan Maria AT Groves Natalie J Tigue 《MABS-AUSTIN》2015,7(1):129-137
Immunization of mice or rats with a "non-self" protein is a commonly used method to obtain monoclonal antibodies, and relies on the immune system''s ability to recognize the immunogen as foreign. Immunization of an antigen with 100% identity to the endogenous protein, however, will not elicit a robust immune response. To develop antibodies to mouse proteins, we focused on the potential for breaking such immune tolerance by genetically fusing two independent T-cell epitope-containing sequences (from tetanus toxin (TT) and diphtheria toxin fragment A (DTA)) to a mouse protein, mouse ST2 (mST2). Wild-type CD1 mice were immunized with three mST2 tagged proteins (Fc, TT and DTA) and the specific serum response was determined. Only in mice immunized with the T-cell epitope-containing antigens were specific mST2 serum responses detected; hybridomas generated from these mice secreted highly sequence-diverse IgGs that were capable of binding mST2 and inhibiting the interaction of mST2 with its ligand, mouse interleukin (IL)-33 (mIL-33). Of the hundreds of antibodies profiled, we identified five potent antibodies that were able to inhibit IL-33 induced IL-6 release in a mast cell assay; notably one such antibody was sufficiently potent to suppress IL-5 release and eosinophilia infiltration in an Alternaria alternata challenge mouse model of asthma. This study demonstrated, for the first time, that T-cell epitope-containing tags have the ability to break tolerance in wild-type mice to 100% conserved proteins, and it provides a compelling argument for the broader use of this approach to generate antibodies against any mouse protein or conserved ortholog. 相似文献
50.
Saman Rasoul Jan Paul Ottervanger Jan-Henk E Dambrink Menko-Jan de Boer Jan CA Hoorntje AT Marcel Gosselink Felix Zijlstra Harry Suryapranata Arnoud WJ van't Hof 《BMC cardiovascular disorders》2007,7(1):1-7