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941.
942.
Ortis F Miani M Colli ML Cunha DA Gurzov EN Allagnat F Chariot A Eizirik DL 《FEBS letters》2012,586(7):984-989
The cytokines interleukin (IL)-1β and tumor necrosis factor (TNF)-α induce β-cell death in type 1 diabetes via NF-κB activation. IL-1β induces a more marked NF-κB activation than TNF-α, with higher expression of genes involved in β-cell dysfunction and death. We show here a differential usage of the IKK complex by IL-1β and TNF-α in β-cells. While TNF-α uses IKK complexes containing both IKKα and IKKβ, IL-1β induces complexes with IKKα only; this effect is achieved by induction of IKKβ degradation via the proteasome. Both IKKγ and activation of the TRAF6-TAK1-JNK pathway are involved in IL-1β-induced IKKβ degradation. 相似文献
943.
Yvonne R. Freund Tsutomu Akama M.R.K. Alley Joana Antunes Chen Dong Kurt Jarnagin Richard Kimura James A. Nieman Kirk R. Maples Jacob J. Plattner Fernando Rock Rashmi Sharma Rajeshwar Singh Virginia Sanders Yasheen Zhou 《FEBS letters》2012,586(19):3410-3414
We have used boron-based molecules to create novel, competitive, reversible inhibitors of phosphodiesterase 4 (PDE4). The co-crystal structure reveals a binding configuration which is unique compared to classical catechol PDE4 inhibitors, with boron binding to the activated water in the bimetal center. These phenoxybenzoxaboroles can be optimized to generate submicromolar potency enzyme inhibitors, which inhibit TNF-α, IL-2, IFN-γ, IL-5 and IL-10 activities in vitro and show safety and efficacy for topical treatment of human psoriasis. They provide a valuable new route for creating novel potent anti-PDE4 inhibitors. 相似文献
944.
MS Tada Rde G Ferreira TH Katsuragawa RC Martha JD Costa L Albrecht G Wunderlich LH Silva 《Memórias do Instituto Oswaldo Cruz》2012,107(5):621-629
In this study, we determined whether the treatment of asymptomatic parasites carriers (APCs), which are frequently found in the riverside localities of the Brazilian Amazon that are highly endemic for malaria, would decrease the local malaria incidence by decreasing the overall pool of parasites available to infect mosquitoes. In one village, the treatment of the 19 Plasmodium falciparum-infected APCs identified among the 270 residents led to a clear reduction (Z = -2.39, p = 0.017) in the incidence of clinical cases, suggesting that treatment of APCs is useful for controlling falciparum malaria. For vivax malaria, 120 APCs were identified among the 716 residents living in five villages. Comparing the monthly incidence of vivax malaria in two villages where the APCs were treated with the incidence in two villages where APCs were not treated yielded contradictory results and no clear differences in the incidence were observed (Z = -0.09, p = 0.933). Interestingly, a follow-up study showed that the frequency of clinical relapse in both the treated and untreated APCs was similar to the frequency seen in patients treated for primary clinical infections, thus indicating that vivax clinical immunity in the population is not species specific but only strain specific. 相似文献
945.
The rhizospheres of five different potato cultivars (including a genetically modified cultivar) obtained from a loamy sand
soil and two from a sandy peat soil, next to corresponding bulk soils, were studied with respect to their community structures
and potential function. For the former analyses, we performed bacterial 16S ribosomal RNA gene-based PCR denaturing gradient
gel electrophoresis (PCR-DGGE) on the basis of soil DNA; for the latter, we extracted microbial communities and subjected
these to analyses in phenotype arrays (PM1, PM2, and PM4, Biolog), with a focus on the use of different carbon, sulfur and
phosphorus sources. In addition, we performed bacterial PCR-DGGE on selected wells to assess the structures of these substrate-responsive
communities. Effects of soil type, the rhizosphere, and cultivar on the microbial community structures were clearly observed.
Soil type was the most determinative parameter shaping the functional communities, whereas the rhizosphere and cultivar type
also exerted an influence. However, no genetically modified plant effect was observed. The effects were imminent based on
general community analysis and also single-compound analysis. Utilization of some of the carbon and sulfur sources was specific
per cultivar, and different microbial communities were found as defined by cultivar. Thus, both soil and cultivar type shaped
the potato root-associated bacterial communities that were responsive to some of the substrates in phenotype arrays. 相似文献
946.
Crous KY Zaragoza-Castells J Ellsworth DS Duursma RA Löw M Tissue DT Atkin OK 《Plant, cell & environment》2012,35(5):966-981
We investigated whether the degree of light inhibition of leaf respiration (R) differs among large Eucalyptus saligna grown in whole‐tree chambers and exposed to present and future atmospheric [CO2] and summer drought. Associated with month‐to‐month changes in temperature were concomitant changes in R in the light (Rlight) and darkness (Rdark), with both processes being more temperature dependent in well‐watered trees than under drought. Overall rates of Rlight and Rdark were not significantly affected by [CO2]. By contrast, overall rates of Rdark (averaged across both [CO2]) were ca. 25% lower under drought than in well‐watered trees. During summer, the degree of light inhibition of leaf R was greater in droughted (ca. 80% inhibition) than well‐watered trees (ca. 50% inhibition). Notwithstanding these treatment differences, an overall positive relationship was observed between Rlight and Rdark when data from all months/treatments were combined (R2 = 0.8). Variations in Rlight were also positively correlated with rates of Rubisco activity and nitrogen concentration. Light inhibition resulted in a marked decrease in the proportion of light‐saturated photosynthesis respired (i.e. reduced R/Asat). Collectively, these results highlight the need to account for light inhibition when assessing impacts of global change drivers on the carbon economy of tree canopies. 相似文献
947.
Armando Cavalcante Franco Dias Michele de Cassia Pereira e Silva Simone Raposo Cotta Francisco Dini-Andreote Fábio Lino Soares Jr. Joana Falc?o Salles Jo?o Lúcio Azevedo Jan Dirk van Elsas Fernando Dini Andreote 《Applied and environmental microbiology》2012,78(22):7960-7967
Although mangroves represent ecosystems of global importance, the genetic diversity and abundance of functional genes that are key to their functioning scarcely have been explored. Here, we present a survey based on the nifH gene across transects of sediments of two mangrove systems located along the coast line of São Paulo state (Brazil) which differed by degree of disturbance, i.e., an oil-spill-affected and an unaffected mangrove. The diazotrophic communities were assessed by denaturing gradient gel electrophoresis (DGGE), quantitative PCR (qPCR), and clone libraries. The nifH gene abundance was similar across the two mangrove sediment systems, as evidenced by qPCR. However, the nifH-based PCR-DGGE profiles revealed clear differences between the mangroves. Moreover, shifts in the nifH gene diversities were noted along the land-sea transect within the previously oiled mangrove. The nifH gene diversity depicted the presence of nitrogen-fixing bacteria affiliated with a wide range of taxa, encompassing members of the Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria, Firmicutes, and also a group of anaerobic sulfate-reducing bacteria. We also detected a unique mangrove-specific cluster of sequences denoted Mgv-nifH. Our results indicate that nitrogen-fixing bacterial guilds can be partially endemic to mangroves, and these communities are modulated by oil contamination, which has important implications for conservation strategies. 相似文献
948.
Cunha TF Moreira JB Paixão NA Campos JC Monteiro AW Bacurau AV Bueno CR Ferreira JC Brum PC 《Journal of applied physiology (Bethesda, Md. : 1985)》2012,112(11):1839-1846
Aerobic exercise training (AET) is an important mechanical stimulus that modulates skeletal muscle protein turnover, leading to structural rearrangement. Since the ubiquitin-proteasome system (UPS) and calpain system are major proteolytic pathways involved in protein turnover, we aimed to investigate the effects of intensity-controlled AET on the skeletal muscle UPS and calpain system and their association to training-induced structural adaptations. Long-lasting effects of AET were studied in C57BL/6J mice after 2 or 8 wk of AET. Plantaris cross-sectional area (CSA) and capillarization were assessed by myosin ATPase staining. mRNA and protein expression levels of main components of the UPS and calpain system were evaluated in plantaris by real-time PCR and Western immunoblotting, respectively. No proteolytic system activation was observed after 2 wk of AET. Eight weeks of AET resulted in improved running capacity, plantaris capillarization, and CSA. Muscle RING finger-1 mRNA expression was increased in 8-wk-trained mice. Accordingly, elevated 26S proteasome activity was observed in the 8-wk-trained group, without accumulation of ubiquitinated or carbonylated proteins. In addition, calpain abundance was increased by 8 wk of AET, whereas no difference was observed in its endogenous inhibitor calpastatin. Taken together, our findings indicate that skeletal muscle enhancements, as evidenced by increased running capacity, plantaris capillarization, and CSA, occurred in spite of the upregulated UPS and calpain system, suggesting that overactivation of skeletal muscle proteolytic systems is not restricted to atrophying states. Our data provide evidence for the contribution of the UPS and calpain system to metabolic turnover of myofibrillar proteins and skeletal muscle adaptations to AET. 相似文献
949.
950.
Oliveira-Filho JP Badial PR Cunha PH Peiró JR Araújo JP Divers TJ Winand NJ Borges AS 《Innate immunity》2012,18(3):438-446
Hepcidin has been found to be the key regulator of iron metabolism that leads to hypoferremia during inflammation. Recent work has shown that equine hepcidin is predominantly expressed in the liver of horses. In this study, hepcidin gene expression was determined in the liver and bone marrow of six healthy horses after iv infusion of Escherichia coli O55:B5 LPS. The IL-6 gene expression was also determined in liver and bone marrow samples. Clinical and laboratory evaluations were measured at multiple time points between 0 and 240?h post-LPS infusion (PI). Liver and bone marrow biopsies were taken immediately before (baseline) and at 6 and 18?h PI. In response to endotoxin infusion, all horses showed characteristic clinical signs of endotoxemia. Plasma iron concentration was decreased significantly from the pre-infusion level at 8?h PI. Hypoferremia peak was observed at 12?h and returned to normal levels at 30?h PI. Relative real-time RT-PCR analysis showed that liver hepcidin and IL-6 mRNA expression was up-regulated at 6?h PI. Bone marrow hepcidin relative expression was not influenced by LPS infusion. In another experiment, equine monocyte cultures were stimulated with LPS (1?μg/ml). Monocyte hepcidin and IL-6 gene expression was significantly induced after 2?h of LPS stimulus and returned to baseline levels thereafter. The present study describes that, in horses, LPS infusion up-regulates hepatic hepcidin mRNA expression resulting in early observed hypoferremia and suggests that hepcidin may act as an acute-phase protein in horses. 相似文献