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51.
Ippokratis Messaritakis Vasiliki Christodoulou Apostolos Mazeris Eleni Koutala Antonia Vlahou Sevasti Papadogiorgaki Maria Antoniou 《PloS one》2013,8(6)
Resistance of pathogens to drugs is a growing concern regarding many diseases. Parasites like Leishmania, Plasmodium and Entamoeba histolytica; and neoplastic cells, present the multidrug-resistant phenotype rendering chemotherapy ineffective. The acquired resistance of Leishmania to antimony has generated intense research on the mechanisms involved but the question has not yet been resolved. To test the hypothesis that drug efflux in Leishmania, as measured by flow cytometry using the fluorescent dye Rhodamine-123, is largely dependent on the number of efflux pumps an isolate can express, the amount of Pgp 170 molecules was assessed in ten field isolates (5 “resistant” and 5 “susceptible”) using: Western Blotting, Confocal and Transmission Electron Microscopy, and proteomics. Their survival after exposure to three antileishmanial drugs, in vitro, was evaluated and clinical data were compared to the in vitro results. All isolates were resistant to Glucantime but susceptible to Miltefosine, whilst Amphotericin B was more effective on the “susceptible” isolates. The MDR gene, expressing the transmembrane efflux pump Pgp 170, appears to play a key role in the phenomenon of drug resistance. When “susceptible” versus “resistant” parasites were compared, it was shown that the higher the number of Pgp 170 molecules the higher the Rhodamine-123 efflux from the parasite body and, when exposed to the drug, the number of efflux pumps increased. However, the rate of this increase was not linear and it is possible that there is a maximum number of Pgp 170 molecules an isolate can express. Nevertheless, the phenomenon is a complex one and other factors and proteins are involved in which the HSP-70 group proteins, detected in the “resistant” isolates, may play a significant role. 相似文献
52.
Quantification of Bacterial Groups within Human Fecal Flora by Oligonucleotide Probe Hybridization 总被引:11,自引:4,他引:11 下载免费PDF全文
Abdelghani Sghir Genevieve Gramet Antonia Suau Violaine Rochet Philippe Pochart Joel Dore 《Applied microbiology》2000,66(5):2263-2266
To investigate the population structure of the predominant phylogenetic groups within the human adult fecal microbiota, a new oligonucleotide probe designated S-G-Clept-1240-a-A-18 was designed, validated, and used with a set of five 16S rRNA-targeted oligonucleotide probes. Application of the six probes to fecal samples from 27 human adults showed additivity of 70% of the total 16S rRNA detected by the bacterial domain probe. The Bacteroides group-specific probe accounted for 37% ± 16% of the total rRNA, while the enteric group probe accounted for less than 1%. Clostridium leptum subgroup and Clostridium coccoides group-specific probes accounted for 16% ± 7% and 14% ± 6%, respectively, while Bifidobacterium and Lactobacillus groups made up less than 2%. 相似文献
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Noll GA Müller B Ernst AM Rüping B Groscurth S Twyman RM Kawchuk LM Prüfer D 《Bioengineered bugs》2011,2(2):111-114
Forisomes are protein bodies found exclusively in the phloem of the Fabaceae (legumes). In response to wounding, the influx of Ca ( 2+) induces a conformational change from a condensed to a dispersed state which plugs the sieve tubes and prevents the loss of photoassimilates. This reversible, ATP-independent reaction can be replicated with purified forisomes in vitro by adding divalent cations or electrically inducing changes in pH, making forisomes ideal components of technical devices. Although native forisomes comprise several subunits, we recently showed that functional homomeric forisomes with distinct properties can be expressed in plants and yeast, providing an abundant supply of forisomes with tailored properties. Forisome subunits MtSEO-F1 and MtSEO-F4 can each assemble into homomeric artificial forisomes, which indicates functional redundancy. However, we provide further evidence that both proteins are subunits of the native heteromeric forisome body in planta. We also show that the properties of artificial forisomes can be modified by immobilization, which is a prerequisite for their incorporation into technical devices. 相似文献
56.
Production of microcystins in calcareous Mediterranean streams: The Alharabe River,Segura River basin in south-east Spain 总被引:1,自引:0,他引:1
Marina?AboalEmail author M.?ángeles?Puig Antonia?D.?Asencio 《Journal of applied phycology》2005,17(3):231-243
The development of epilithic cyanobacteria communities in a Mediterranean calcareous stream in the province of Murcia (SE Spain) was studied during the course of one year in an attempt to clarify the environmental variables that influence the production of microcystins. The predominant cyanobacteria were species of Rivularia, which formed conspicuous colonies throughout the year. Seasonally, other species were abundant: Schizothrix fasciculata, Tolypothrix distorta and Phormidium splendidum. All the species collected produced microcystins to a varying degree (up to five varieties), while the benthic community as a whole produced concentrations as high as 20.45 mg m−2. At the same time, the presence of microcystins dissolved in water was confirmed. Among environmental variables, air temperature and silicate content were positively and strongly correlated with total microcystins, while nitrite, nitrate, orthophosphate, calcium and flow were negatively correlated with them. Dissolved microcystins were negatively correlated with microcystin LR, P.A.R. and total phosphorus and positively with rainfall. The production of microcystin YR seems to be regulated by different factors from those regulating the other main varieties (microcystin LR and microcystin RR). The data obtained indicate that all the tested benthic cyanobacteria produced microcystins in this shallow calcareous stream, which may contribute to their predominance in the prevailing conditions. The accumulation of microcystins in mucilaginous colonies of other groups of algae poses new questions concerning the possible ecological function of these compounds and needs further study. 相似文献
57.
González-Yanes C Serrano A Bermúdez-Silva FJ Hernández-Dominguez M Páez-Ochoa MA Rodríguez de Fonseca F Sánchez-Margalet V 《American journal of physiology. Endocrinology and metabolism》2005,289(5):E923-E929
Oleylethanolamide (OEA) is a lipid mediator that inhibits food intake and body weight gain and also exhibits hypolipemiant actions. OEA exerts its anorectic effects peripherally through the stimulation of C-fibers. OEA is synthesized in the intestine in response to feeding, increasing its levels in portal blood after the meal. Moreover, OEA is produced by adipose tissue, and a lipolytic effect has been found. In this work, we have examined the effect of OEA on glucose metabolism in rats in vivo and in isolated adipocytes. In vivo studies showed that acute administration (30 min and 6 h) of OEA produced glucose intolerance without decreasing insulin levels. Ex vivo, we found that 10 min of preincubation with OEA inhibited 30% insulin-stimulated glucose uptake in isolated adipocytes. Maximal effect was achieved at 1 microM OEA. The related compounds palmitylethanolamide and oleic acid had no effect, suggesting a specific mechanism. Insulin-stimulated GLUT4 translocation was not affected, but OEA promoted Ser/Thr phosphorylation of GLUT4, which may impair transport activity. This phosphorylation may be partly mediated by p38 and JNK kinases, since specific inhibitors (SB-203580 and SP-600125) partly reverted the inhibitory effect of OEA on insulin-stimulated glucose uptake. These results suggest that the lipid mediator OEA inhibits insulin action in the adipocyte, impairing glucose uptake via p38 and JNK kinases, and these effects may at least in part explain the glucose intolerance produced in rats in vivo. These effects of OEA may contribute to the anorectic effects induced by this mediator, and they might be also relevant for insulin resistance in adipose tissue. 相似文献
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A complex formation between hemin and a congruous oligonucleotide not only greatly enhances the former’s peroxidative activity
but also results in a biocatalyst (DNAzyme) with a novel specificity. Herein substrate, regio-, enantiomeric, and diastereomeric
selectivities of heme, the DNAzyme, and the enzyme horseradish peroxidase are comparatively examined. 相似文献
60.
Oualid Sbai Mehdi Djelloul Antonia Auletta Alessandro Ieraci Carlo Vascotto L. Perrone 《Cell death & disease》2022,13(4)
Alzheimer’s disease (AD) is the most common form of dementia characterized by progressive memory loss and cognitive decline. Although neuroinflammation and oxidative stress are well-recognized features of AD, their correlations with the early molecular events characterizing the pathology are not yet well clarified. Here, we characterize the role of RAGE–TXNIP axis in neuroinflammation in relation to amyloid-beta (Aβ) burden in both in vivo and in vitro models. In the hippocampus of 5xFAD mice microglial activation, cytokine secretion, and glial fibrillary acidic protein-enhanced expression are paralleled with increased TXNIP expression. TXNIP silencing or its pharmacological inhibition prevents neuroinflammation in those mice. TXNIP is also associated with RAGE and Aβ. In particular, RAGE–TXNIP axis is required for targeting Aβ in mitochondria, leading to mitochondrial dysfunction and oxidative stress. Silencing of TXNIP or inhibition of RAGE activation reduces Aβ transport from the cellular surface to mitochondria, restores mitochondrial functionality, and mitigates Aβ toxicity. Furthermore, Aβ shuttling into mitochondria promotes Drp1 activation and exacerbates mitochondrial dysfunction, which induces NLRP3 inflammasome activation, leading to secretion of IL-1β and activation of the pyroptosis-associated protein Gasdermin D (GSDMD). Downregulation of RAGE–TXNIP axis inhibits Aβ-induced mitochondria dysfunction, inflammation, and induction of GSDMD. Herein we unveil a new pathway driven by TXNIP that links the mitochondrial transport of Aβ to the activation of Drp1 and the NLRP3 inflammasome, promoting the secretion of IL-1β and the pyroptosis pathway associated with GSDMD cleavage. Altogether these data shed new light on a novel mechanism of action of RAGE–TXNIP axis in microglia, which is intertwined with Aβ and ultimately causes mitochondria dysfunction and NLRP3 inflammasome cascade activation, suggesting TXNIP as a druggable target to be better deepened for AD.Subject terms: Cellular neuroscience, Inflammasome 相似文献