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951.
Burgarella C Navascués M Zabal-Aguirre M Berganzo E Riba M Mayol M Vendramin GG González-Martínez SC 《Molecular ecology》2012,21(12):3006-3021
Taxanes are defensive metabolites produced by Taxus species (yews) and used in anticancer therapies. Despite their medical interest, patterns of natural diversity in taxane-related genes are unknown. We examined variation at five main genes of Taxus baccata in the Iberian Peninsula, a region where unique yew genetic resources are endangered. We looked at several gene features and applied complementary neutrality tests, including diversity/divergence tests, tests solely based on site frequency spectrum (SFS) and Zeng's compound tests. To account for specific demography, microsatellite data were used to infer historical changes in population size based on an Approximate Bayesian Computation (ABC) approach. Polymorphism-divergence tests pointed to positive selection for genes TBT and TAT and balancing selection for DBAT. In addition, neutrality tests based on SFS found that while a recent reduction in population size may explain most statistics' values, selection may still be in action in genes TBT and DBAT, at least in some populations. Molecular signatures on taxol genes suggest the action of frequent selective waves with different direction or intensity, possibly related to varying adaptive pressures produced by the host-enemy co-evolution on defence-related genes. Such natural selection processes may have produced taxane variants still undiscovered. 相似文献
952.
Adela González-Megías Rosa Menéndez 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2012,367(1606):3115-3124
Individual species respond to climate change by altering their abundance, distribution and phenology. Less is known, however, about how climate change affects multitrophic interactions, and its consequences for food-web dynamics. Here, we investigate the effect of future changes in rainfall patterns on detritivore–plant–herbivore interactions in a semiarid region in southern Spain by experimentally manipulating rainfall intensity and frequency during late spring–early summer. Our results show that rain intensity changes the effect of below-ground detritivores on both plant traits and above-ground herbivore abundance. Enhanced rain altered the interaction between detritivores and plants affecting flower and fruit production, and also had a direct effect on fruit and seed set. Despite this finding, there was no net effect on plant reproductive output. This finding supports the idea that plants will be less affected by climatic changes than by other trophic levels. Enhanced rain also affected the interaction between detritivores and free-living herbivores. The effect, however, was apparent only for generalist and not for specialist herbivores, demonstrating a differential response to climate change within the same trophic level. The complex responses found in this study suggest that future climate change will affect trophic levels and their interactions differentially, making extrapolation from individual species'' responses and from one ecosystem to another very difficult. 相似文献
953.
López-Cortés LF Ruiz-Valderas R Jimenez-Jimenez L González-Escribano MF Torres-Cornejo A Mata R Rivero A Pineda JA Marquez-Solero M Viciana P;Grupo para el Estudio de las Hepatitis Víricas 《PloS one》2012,7(1):e28115
Background
Data on which to base definitive recommendations on the doses and duration of therapy for genotype 3 HCV/HIV-coinfected patients are scarce. We evaluated the efficacy of a lower peginterferon-α 2a dose and a shorter duration of therapy than the current standard of care in genotype 3 HCV/HIV-coinfected patients.Methods and Findings
Pilot, open-label, single arm clinical trial which involved 58 Caucasian HCV/HIV-coinfected patients who received weekly 135 µg peginterferon-α 2a plus ribavirin 400 mg twice daily during 20 weeks after attaining undetectable viremia. The relationships between baseline patient-related variables, including IL28B genotype, plasma HCV-RNA, ribavirin dose/kg, peginterferon-α 2a and ribavirin levels with virological responses were analyzed.Only 4 patients showed lack of response and 5 patients dropped out due to adverse events related to the study medication. Overall, sustained virologic response (SVR) rates were 58.3% by intention-to-treat and 71.4% by per protocol analysis, respectively. Among patients with rapid virologic response (RVR), SVR and relapses rates were 92.6% and 7.4%, respectively. No relationships were observed between viral responses and ribavirin dose/kg, peginterferon-α 2a concentrations, ribavirin levels or rs129679860 genotype.Conclusions
Weekly 135 µg pegIFN-α 2a could be as effective as the standard 180 µg dose, with a very low incidence of severe adverse events. A 24-week treatment duration appears to be appropriate in patients achieving RVR, but extending treatment up to just 20 weeks beyond negativization of viremia is associated with a high relapse rate in those patients not achieving RVR. There was no influence of IL28B genotype on the virological responses.Trial Registration:
ClinicalTrials.gov NCT00553930相似文献954.
Previous works have demonstrated that protein rigidity is related to thermodynamic stability, especially under conditions that favor formation of native structure. Mechanical network rigidity properties of a single conformation are efficiently calculated using the integer body-bar Pebble Game (PG) algorithm. However, thermodynamic properties require averaging over many samples from the ensemble of accessible conformations to accurately account for fluctuations in network topology. We have developed a mean field Virtual Pebble Game (VPG) that represents the ensemble of networks by a single effective network. That is, all possible number of distance constraints (or bars) that can form between a pair of rigid bodies is replaced by the average number. The resulting effective network is viewed as having weighted edges, where the weight of an edge quantifies its capacity to absorb degrees of freedom. The VPG is interpreted as a flow problem on this effective network, which eliminates the need to sample. Across a nonredundant dataset of 272 protein structures, we apply the VPG to proteins for the first time. Our results show numerically and visually that the rigidity characterizations of the VPG accurately reflect the ensemble averaged [Formula: see text] properties. This result positions the VPG as an efficient alternative to understand the mechanical role that chemical interactions play in maintaining protein stability. 相似文献
955.
Background
Spinal cord injury is a major cause of long-term disability and has no current clinically accepted treatment. Leptin, an adipocyte-derived hormone, is best known as a regulator of food intake and energy expenditure. Interestingly, several studies have demonstrated that leptin has significant effects on proliferation and cell survival in different neuropathologies. Here, we sought to evaluate the role of leptin after spinal cord injury.Findings
Based on its proposed neuroprotective role, we have evaluated the effects of a single, acute intraparenchymal injection of leptin in a clinically relevant animal model of spinal cord injury. As determined by quantitative Real Time-PCR, endogenous leptin and the long isoform of the leptin receptor genes show time-dependent variations in their expression in the healthy and injured adult spinal cord. Immunohistochemical analysis of post-injury tissue showed the long isoform of the leptin receptor expression in oligodendrocytes and, to a lesser extent, in astrocytes, microglia/macrophages and neurons. Moreover, leptin administered after spinal cord injury increased the expression of neuroprotective genes, reduced caspase-3 activity and decreased the expression of pro-inflammatory molecules. In addition, histological analysis performed at the completion of the study showed that leptin treatment reduced microglial reactivity and increased caudal myelin preservation, but it did not modulate astroglial reactivity. Consequently, leptin improved the recovery of sensory and locomotor functioning.Conclusions
Our data suggest that leptin has a prominent neuroprotective and anti-inflammatory role in spinal cord damage and highlights leptin as a promising therapeutic agent. 相似文献956.
Rodríguez ES Pose AG Moltó MP Espinoza AS Zamora PA Pedroso MS 《Biotechnology journal》2012,7(8):1049-1053
The production of recombinant proteins in the milk of non-transgenic goats can be achieved by transducing the mammary gland with recombinant adenoviral vectors. However, this process involves several regulatory issues. The current study evaluates the biosafety of this production system. We present a preliminary biosafety profile based on detection of adenoviral particles in different body fluids and the antibody response after adenoviral transduction of the goat mammary gland. In addition, two methods of adenoviral inactivation in milk were tested. Although adenoviral particles were detected in the milk until day 4 after transduction, they were absent in serum, saliva, urine and feces. Anti-adenovirus antibodies were detected in serum and milk. The virus inactivation methods neutralized adenoviral particles and preserved the immunological identity of the recombinant protein. These results support the idea of a safe production of recombinant proteins using adenoviral vectors. 相似文献
957.
González JF Degrassi G Devescovi G De Vleesschauwer D Höfte M Myers MP Venturi V 《Journal of Proteomics》2012,75(18):5911-5919
Xanthomonas oryzae pv. oryzae (Xoo) is the second most important rice pathogen, causing a disease called bacterial leaf blight. Xoo colonizes and infects the vascular tissue resulting in tissue necrosis and wilting causing significant yield losses worldwide. In this study Xoo infected vascular fluid (xylem sap) was recovered and analyzed for secreted Xoo proteins. Three independent experiments resulted in the identification of 324 different proteins, 64 proteins were found in all three samples which included many of the known virulence-associated factors. In addition, 10 genes encoding for the identified proteins were inactivated and one mutant displayed statistically a significant loss in virulence when compared to the wild type Xoo, suggesting that a new virulence-associated factor has been revealed. The usefulness of this approach in understanding the lifestyle and unraveling the virulence-associated factors of phytopathogenic vascular bacteria is discussed. 相似文献
958.
959.
FA Carvalho O Koren JK Goodrich ME Johansson I Nalbantoglu JD Aitken Y Su B Chassaing WA Walters A González JC Clemente TC Cullender N Barnich A Darfeuille-Michaud M Vijay-Kumar R Knight RE Ley AT Gewirtz 《Cell host & microbe》2012,12(2):139-152
Colitis results from breakdown of homeostasis between intestinal microbiota and the mucosal immune system, with both environmental and genetic influencing factors. Flagellin receptor TLR5-deficient mice (T5KO) display elevated intestinal proinflammatory gene expression and colitis with incomplete penetrance, providing a genetically sensitized system to study the contribution of microbiota to driving colitis. Both colitic and noncolitic T5KO exhibited transiently unstable microbiotas, with lasting differences in colitic T5KO, while their noncolitic siblings stabilized their microbiotas to resemble wild-type mice. Transient high levels of proteobacteria, especially enterobacteria species including E.?coli, observed in close proximity to the gut epithelium were a striking feature of colitic microbiota. A Crohn's disease-associated E.?coli strain induced chronic colitis in T5KO, which persisted well after the exogenously introduced bacterial species had been eliminated. Thus, an innate immune deficiency can result in unstable gut microbiota associated with low-grade inflammation, and harboring proteobacteria can drive and/or instigate chronic colitis. 相似文献
960.
ABSTRACT: Centrally necrotizing carcinoma is a rare subtype of breast carcinoma, which is characterized by an extensive central necrotic zone accounting for at least 70% of the cross-sectional area of the neoplasm. This central necrotic zone, in turn, is surrounded by a narrow rim of proliferative viable tumor cells. We report an unusual clinical situation in which a patient whose evident breast mass suggested an ipsilateral local recurrence and for which numerous attempts to confirm the histological diagnosis had failed. The patient was treated with a radical mastectomy based on clinical suspicion of breast cancer recurrence after an undesirable delay. In this case, the narrow rim of viable malignant tissue had a thickness of 0.5 to 8 mm, and the centrally necrotizing carcinoma had a central zone with a predominance of fibrosis. The special features of this case led to a misdiagnosis and to an evident clinical local recurrence. 相似文献