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81.
Background
Although being situated in a niche, research on parasite aquaporins is a lively field that has provided new insight into basic aquaporin structure–function relationships and physiological roles of water and solute transport. Moreover, it bears the potential to find novel approaches to antiparasitic chemotherapy.Scope of review
Here, we summarize the current knowledge about the structure and substrate selectivity of aquaporins from protozoan and helminth parasites, review the current views on their physiological roles, and discuss their potency for chemotherapy.Major conclusions
Parasite aquaporins fulfill highly diverse tasks in the physiology of the various organisms, yet their general protein structure is well conserved. Aquaporins are directly (antimonials) and indirectly (melarsoprol, pentamidine) linked to the uptake of antiparasitic drugs. Unfortunately, drug-like aquaporin inhibitors are still missing.General significance
Aquaporins expression levels determine the degree of parasite resistance against certain drugs. Further studies on parasite aquaporins may provide data about overcoming drug resistance mechanisms or even spark novel treatments. This article is part of a Special Issue entitled Aquaporins. 相似文献82.
A novel class of organic nanoparticles as biolabels that can generate an instant visible signal was applied to immunodipsticks. A new principle for signal generation based on hydrolysis of colourless signal precursor molecules to produce coloured signal molecules followed by signal precipitation and localization was demonstrated. The nanoparticle biolabels were applied to sandwich immunoassays for the detection of mouse immunoglobulin G (M IgG). In the presence of M IgG, a nanoparticle-immunocomplex was formed and bound on the test zone immobilized with goat anti M IgG (Gt α M IgG). A blue line was developed on the test zone upon the addition of a signal developing reagent. An optical signal could be simply assessed using naked eyes or quantified using a reading device. The lowest visible signal that could be observed using naked eyes was found to be 1.25 μg L(-1) M IgG. The nanoparticle biolabel also showed a better sensitivity (signal-to-noise ratio) compared with the conventional colloidal gold biolabel. This novel class of organic nanoparticles offers an alternative biolabel system for the development of point-of-care immunodipsticks. 相似文献
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Podosomes are transient cell surface structures essential for degradation of extracellular matrix during cell invasion. Protein kinase C (PKC) is involved in the regulation of podosome formation; however, the roles of individual PKC isoforms in podosome formation and proteolytic function are largely unknown. Recently, we reported that PDBu, a PKC activator, induced podosome formation in normal human bronchial epithelial cells. Here, we demonstrate that phorbol-12,13-dibutyrate (PDBu)-induced podosome formation is mainly mediated through redistribution of conventional PKCs, especially PKCα, from the cytosol to the podosomes. Interestingly, although blocking atypical PKCζ did not affect PDBu-induced podosome formation, it significantly reduced matrix degradation at podosomes. Inhibition of PKCζ reduced recruitment of matrix metalloprotease 9 (MMP-9) to podosomes and its release and activation. Downregulation of MMP-9 by small interfering RNA (siRNA) or neutralization antibody also significantly reduced matrix degradation. The regulatory effects of PKCζ on matrix degradation and recruitment of MMP-9 to podosomes were PKCζ kinase activity dependent. PDBu-induced recruitment of PKCζ and MMP-9 to podosomes was blocked by inhibition of novel PKC with rottlerin or PKCδ siRNA. Our data suggest that multiple PKC isozymes form a signaling cascade that controls podosome formation and dynamics and MMP-9 recruitment, release, and activation in a coordinated fashion. 相似文献
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Scanlan BJ Tuft B Elfrey JE Smith A Zhao A Morimoto M Chmielinska JJ Tejero-Taldo MI Mak IuT Weglicki WB Shea-Donohue T 《Molecular and cellular biochemistry》2007,306(1-2):59-69
The aim of this study was to determine the effect of magnesium deficiency on small intestinal morphology and function. Rats
were assigned to 4 groups and placed on magnesium sufficient or deficient diet for 1 or 3 weeks. Infiltration of neutrophils
and mucosal injury were assessed in stained sections of small intestine. Magnesium deficiency alone induced a significant
increase in neutrophil infiltration and increased vascular ICAM-1 expression, in the absence of changes in mucosal injury
or expression of proinflammatory mediators. Magnesium deficiency was associated with hyposecretory epithelial cell responses
and vascular macromolecular leak in the small intestine and lung, which was attributed partly to reduced expression of NOS-3.
To determine the effect of hypomagnesmia on the intestinal responses to a known oxidative stress, groups of rats were randomized
to either sham operation or superior mesenteric artery occlusion for 10 (non-injurious) or 30 (injurious) minutes followed
by a 1- or 4-hour reperfusion period. In response to mesenteric ischemia/reperfusion, deficient rats showed exaggerated PMN
influx, but similar mucosal injury. Intestinal ischemia in sufficient animals induced vascular macromolecular leak in the
small intestine and lung at 4 hours of reperfusion, with levels similar to those observed in untreated deficient rats. Acute
magnesium repletion of deficient rats 24 h before surgery attenuated the exaggerated inflammation in deficient rats. These
data show that magnesium deficiency induced a subclinical inflammation in the small intestine in the absence of mucosal injury,
but with significant functional changes in local and remote organs and increased sensitivity to oxidative stress.
The opinions contained herein are those of the authors and are not to be construed as official policy or reflecting the views
of the Department of Defense 相似文献
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Characterization of Environmental Sources of the Human and Animal Pathogen Cryptococcus gattii in British Columbia, Canada, and the Pacific Northwest of the United States 下载免费PDF全文
Sarah E. Kidd Yat Chow Sunny Mak Paxton J. Bach Huiming Chen Adrian O. Hingston James W. Kronstad Karen H. Bartlett 《Applied microbiology》2007,73(5):1433-1443
Cryptococcus gattii has recently emerged as a primary pathogen of humans and wild and domesticated animals in British Columbia, particularly on Vancouver Island. C. gattii infections are typically infections of the pulmonary and/or the central nervous system, and the incidence of infection in British Columbia is currently the highest reported globally. Prior to this emergence, the environmental distribution of and the extent of colonization by C. gattii in British Columbia were unknown. We characterized the environmental sources and potential determinants of colonization in British Columbia. C. gattii was isolated from tree surfaces, soil, air, freshwater, and seawater, and no seasonal prevalence was observed. The C. gattii concentrations in air samples were significantly higher during the warm, dry summer months, although potentially infectious propagules (<3.3 μm in diameter) were present throughout the year. Positive samples were obtained from many different areas of British Columbia, and some locations were colonization “hot spots.” C. gattii was generally isolated from acidic soil, and geographic differences in soil pH may influence the extent of colonization. C. gattii soil colonization also was associated with low moisture and low organic carbon contents. Most of the C. gattii isolates recovered belonged to the VGIIa genetic subtype; however, sympatric colonization by the VGIIb strain was observed at most locations. At one sampling site, VGIIa, VGIIb, VGI, and the Cryptococcus neoformans serotype AD hybrid all were coisolated. Our findings indicate extensive colonization by C. gattii within British Columbia and highlight an expansion of the ecological niche of this pathogen. 相似文献