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31.
Barbara Dhooghe Sabrina No?l Caroline Bouzin Ga?tane Behets-Wydemans Teresinha Leal 《PloS one》2013,8(10)
Although lung disease is the major cause of mortality in cystic fibrosis (CF), gastrointestinal (GI) manifestations are the first hallmarks in 15–20% of affected newborns presenting with meconium ileus, and remain major causes of morbidity throughout life. We have previously shown that cGMP-dependent phosphodiesterase type 5 (PDE5) inhibitors rescue defective CF Transmembrane conductance Regulator (CFTR)-dependent chloride transport across the mouse CF nasal mucosa. Using F508del-CF mice, we examined the transrectal potential difference 1 hour after intraperitoneal injection of the PDE5 inhibitor vardenafil or saline to assess the amiloride-sensitive sodium transport and the chloride gradient and forskolin-dependent chloride transport across the GI tract. In the same conditions, we performed immunohistostaining studies in distal colon to investigate CFTR expression and localization. F508del-CF mice displayed increased sodium transport and reduced chloride transport compared to their wild-type littermates. Vardenafil, applied at a human therapeutic dose (0.14 mg/kg) used to treat erectile dysfunction, increased chloride transport in F508del-CF mice. No effect on sodium transport was detected. In crypt colonocytes of wild-type mice, the immunofluorescence CFTR signal was mostly detected in the apical cell compartment. In F508del-CF mice, a 25% reduced signal was observed, located mostly in the subapical region. Vardenafil increased the peak of intensity of the fluorescence CFTR signal in F508del-CF mice and displaced it towards the apical cell compartment. Our findings point out the intestinal mucosa as a valuable tissue to study CFTR transport function and localization and to evaluate efficacy of therapeutic strategies in CF. From our data we conclude that vardenafil mediates potentiation of the CFTR chloride channel and corrects mislocalization of the mutant protein. The study provides compelling support for targeting the cGMP signaling pathway in CF pharmacotherapy. 相似文献
32.
No?l Ndeledje Jérémy Bouyer Frédéric Stachurski Patrice Grimaud Adrien Marie Gaston Belem Fidèle Molélé Mba?ndingatoloum Zakaria Bengaly Idriss Oumar Alfaroukh Guiliano Cecchi Renaud Lancelot 《PloS one》2013,8(6)
Background
In Chad, several species of tsetse flies (Genus: Glossina ) transmit African animal trypanosomoses (AAT), which represents a major obstacle to cattle rearing, and sleeping sickness, which impacts public health. After the failure of past interventions to eradicate tsetse, the government of Chad is now looking for other approaches that integrate cost-effective intervention techniques, which can be applied by the stake holders to control tsetse-transmitted trypanosomoses in a sustainable manner. The present study thus attempted to assess the efficacy of restricted application of insecticides to cattle leg extremities using footbaths for controlling Glossina m. submorsitans, G . tachinoides and G . f . fuscipes in southern Chad.Methodology/Principal Findings
Two sites were included, one close to the historical human African trypanosomiasis (HAT) focus of Moundou and the other to the active foci of Bodo and Moissala. At both sites, a treated and an untreated herd were compared. In the treatment sites, cattle were treated on a regular basis using a formulation of deltamethrin 0.005% (67 to 98 cattle were treated in one of the sites and 88 to 102 in the other one). For each herd, tsetse densities were monthly monitored using 7 biconical traps set along the river and beside the cattle pen from February to December 2009. The impact of footbath treatment on tsetse populations was strong (p < 10-3) with a reduction of 80% in total tsetse catches by the end of the 6-month footbath treatment.Conclusions/Significance
The impact of footbath treatment as a vector control tool within an integrated strategy to manage AAT and HAT is discussed in the framework of the “One Health” concept. Like other techniques based on the treatment of cattle, this technology should be used under controlled conditions, in order to avoid the development of insecticide and acaricide resistance in tsetse and tick populations, respectively. 相似文献33.
Mélanie Chabaud Noémie Paillon Katharina Gaus Claire Hivroz 《Biology of the cell / under the auspices of the European Cell Biology Organization》2020,112(7):196-212
To mount an immune response, T cells must first find rare antigens present at the surface of antigen-presenting cells (APCs). They achieve this by migrating rapidly through the crowded space of tissues and constantly sampling the surface of APCs. Upon antigen recognition, T cells decelerate and polarise towards the APC, ultimately forming a specialised interface known as the immunological synapse. These conjugates form as the result of the interaction between pairs of receptors/ligands that are under mechanical stress due to the continuously reorganising cell cytoskeleton. In this review, we discuss the involvement of mechanical forces during antigen recognition by migrating T cells. We will explore this question from a conceptual and technical perspective, with the aim of providing new insights into the emerging field of mechanobiology. 相似文献
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Luís Roque Noélia Duarte Maria Rosário Bronze Catarina Garcia Julia Alopaeus Jesus Molpeceres 《Biofouling》2013,29(8):880-892
AbstractGlycyrrhiza glabra L. is considered an important source of bioactive compounds. This study aimed at the development of an efficient solution for the treatment of oral candidiasis. Several extracts of Glycyrrhiza glabra L. were prepared using different solvents and their potential in vitro antifungal activity was assessed. Ethanolic extracts showed the most promising results against C. albicans. This extract was incorporated into mucoadhesive nanoparticles (PLA, PLGA and alginate), which were further included in an oral gel, an oral film and a toothpaste, respectively. The results showed that nanoparticles were successfully produced, presenting a mean size among 100–900?nm with high encapsulation efficiency. In vitro studies showed that the most bioadhesive formulation was the oral film with extract-loaded PLGA nanoparticles, followed by the toothpaste with extract-loaded alginate nanoparticles and the oral gel with extract-loaded PLA nanoparticles. 相似文献
38.
Noëlle Richard-Mercier Myriam Bettane-Casanova Marc Fellous Hélène Charniaux-Cotton 《Invertebrate reproduction & development.》2013,57(3):243-252
Summary The Daudi cell line, a male human line from Burkitt's lymphoma, possesses the peculiarity of releasing H-Y antigen into its culture medium. Daudi-conditioned medium was injected into Colorado potato beetles either during the blastoderm stage, when individualization of the pole cells occurs, or later, during gonadal differentiation. Ovarian and testicular sections examined at hatching showed that only ovarian differentiation was affected by the Daudi conditioned medium, which, irrespective of the day of injection, reduced the number of the terminal filaments of the future lateral ovarioles. Furthermore, in some cases sexual differentiation was blocked altogether. When H-Y antigen was precipitated from the conditioned medium with specific H-Y antisera, the effectiveness of Daudi-conditioned medium was partially destroyed. These results suggest that mammalian H-Y antigen inhibits morphogenetic events leading to ovarian differentiation in the Colorado potato beetle. 相似文献
39.
Jean‐Noël Octave Nathalie Pierrot Susana Ferao Santos Natalia N. Nalivaeva Anthony J. Turner 《Journal of neurochemistry》2013,126(2):183-190
Despite intensive studies of the secretase‐mediated processing of the amyloid precursor protein (APP) to form the amyloid β‐peptide (Aβ), in relation to Alzheimer's disease (AD), no new therapeutic agents have reached the clinics based on reducing Aβ levels through the use of secretase inhibitors or immunotherapy. Furthermore, the normal neuronal functions of APP and its various metabolites still remain under‐investigated and unclear. Here, we highlight emerging areas of APP function that may provide new insights into synaptic development, cognition, and gene regulation. By modulating expression levels of endogenous APP in primary cortical neurons, the frequency and amplitude of calcium oscillations is modified, implying a key role for APP in maintaining neuronal calcium homeostasis essential for synaptic transmission. Disruption of this homeostatic mechanism predisposes to aging and AD. Synaptic spine loss is a feature of neurogeneration resulting in learning and memory deficits, and emerging evidence indicates a role for APP, probably mediated via one or more of its metabolites, in spine structure and functions. The intracellular domain of APP (AICD) has also emerged as a key epigenetic regulator of gene expression controlling a diverse range of genes, including APP itself, the amyloid‐degrading enzyme neprilysin, and aquaporin‐1. A fuller understanding of the physiological and pathological actions of APP and its metabolic network could provide new opportunities for therapeutic intervention in AD. 相似文献
40.
Maja Martic Ida Noémi Jakab-Simon Lærke Tvedebrink Haahr Wilfred Raymond Hagen Hans Erik Mølager Christensen 《Journal of biological inorganic chemistry》2013,18(2):261-276
Heterometallic [AgFe3S4] iron–sulfur clusters assembled in wild-type Pyrococcus furiosus ferredoxin and two variants, D14C and D14H, are characterized. The crystal structure of the [AgFe3S4] D14C variant shows that the silver(I) ion is indeed part of the cluster and is coordinated to the thiolate group of residue 14. Cyclic voltammetry shows one redox pair with a reduction potential of +220 mV versus the standard hydrogen electrode which is assigned to the [AgFe3S4]2+/+ couple. The oxidized form of the [AgFe3S4] D14C variant is stable in the presence of dioxygen, whereas the oxidized forms of the [AgFe3S4] wild type and D14H variants convert to the [Fe3S4] ferredoxin form. The monovalent d 10 silver(I) ion stabilizes the [Fe3S4]+/0 cluster fragment, as opposed to divalent d 10 metal ions, resulting in more than 0.4 V difference in reduction potentials between the silver(I) and, e.g., zinc(II) heterometallic [MFe3S4] ferredoxins. The trend in reduction potentials for the variants containing the [AgFe3S4] cluster is wild type ≤ D14C < D14H and shows the same trend as reported for the variants containing the [Fe3S4] cluster, but is different from the D14C < D14H < wild type trend reported for the [Fe4S4] ferredoxin. The similarity in the reduction potential trend for the variants containing the heterometallic [AgFe3S4] cluster and the [Fe3S4] cluster can be rationalized in terms of the electrostatic influence of the residue 14 side chains, rather than the dissociation constant of this residue, as is the case for [Fe4S4] ferredoxins. The trends in reduction potentials are in line with there being no electronic coupling between the silver(I) ion and the Fe3S4 fragment. 相似文献