2,208 research outputs found
Les WNK kinases et les effets de WNK3 sur l'activiteĢ du canal ENaC
Les WNK kinases sont une famille de seĢrine/threĢonine proteĢines kinases, des enzymes capables de phosphoryler le reĢsidu OH de seĢrine ou threĢonine. Quatre membres (WNK 1-4) ont eĢteĢ identifieĢs, largement distribueĢs dans les cellules et tissus des mammifeĢres et dont les fonctions sont de reĢguler des canaux ioniques et cotransporteurs. Leur particulariteĢ se situe au niveau de leur structure puisque une lysine a eĢteĢ substitueĢe par une cysteĢine dans le domaine catalytique, d'ouĢ leur nom Ā« with-no-lysine kinase Ā» (McCormick and Ellison, 2011).
Leur roĢle dans le bon fonctionnement du rein et plus particulieĢrement dans le controĢle et maintien du bilan hydro-sodeĢ n'est plus aĢ veĢrifier puisque des mutations dans WNK 1 et WNK 4 sont connues pour causer la maladie de l'hypertension familiale ou syndrome de pseudohypoaldosteĢronisme de type 2, aussi appeleĢ syndrome de Gordon (ou Fhht = Familial hyperkalaemic hypertension) (Furgeson and Linas, 2010). Le syndrome de Gordon est une maladie geĢneĢtique autosomale dominante caracteĢriseĢe par une hypertension, une hyperkalieĢmie et une acidose meĢtabolique.
Les WNKs controĢlent de nombreux canaux et transporteurs dans le rein, devenant des acteurs importants dans la reĢgulation du bilan sodique et potassique. Leurs effets sont nombreux et variables et les canaux jouant un roĢle cleĢ dans cette reĢgulation sont ENaC, NCC et ROMK (Kahle et al., 2008).
Dans ce travail, nous commencerons par une partie theĢorique faisant le point sur l'organisation des neĢphrons et la reĢgulation du bilan sodique et les diffeĢrents meĢcanismes entrant en jeu. Nous inteĢgrerons des informations geĢneĢrales concernant les WNKs ainsi qu'une revue plus deĢtailleĢe de leurs effets respectifs dans le neĢphron. Pour terminer, nous aborderons les reĢsultats d'une expeĢrience qui a eĢteĢ reĢaliseĢe en laboratoire sur des oocytes de Xenopus laevis. L'implication de WNK1 et WNK4 dans le controĢle du sodium ayant deĢjaĢ eĢteĢ prouveĢe aĢ de nombreuses reprises, nous nous sommes inteĢresseĢs ici aux effets de WNK3 sur le canal ENaC ainsi que l'implication de Nedd4-2 dans ce proceĢdeĢ
Correction: Hyperbranched phosphorus flame retardants: multifunctional additives for epoxy resins, by Alexander Battig et al., Polym. Chem., 2019, DOI: 10.1039/c9py00737g.
Hyperbranched Rigid Aromatic Phosphorus-Containing Flame Retardants for Epoxy Resins
A rigid aromatic phosphorus-containing hyperbranched flame retardant structure is synthesized from 10-(2,5-dihydroxyphenyl)-10H-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO-HQ), tris(4-hydroxyphenyl)phosphine oxide (THPPO), and 1,4-terephthaloyl chloride (TPC). The resulting poly-(DOPO-HQ/THPPO-terephthalate) (PDTT) is implemented as a flame retardant into an epoxy resin (EP) at a 10 wt% loading. The effects on EP are compared with those of the monomer DOPO-HQ and triphenylphosphine oxide (OPPh3) as low molar mass flame retardants. The glass transition temperature, thermal decomposition, flammability (reaction to small flame), and burning behavior of the thermosets are investigated using differential scanning calorimetry, thermogravimetric analysis, pyrolysis combustion flow calorimetry, UL 94-burning chamber testing, and cone calorimeter measurements. Although P-contents are low at only 0.6 wt%, the study aims not at attaining V-0, but at presenting a proof of principle: Epoxy resinswith PDTT show promising fire performance, exhibiting a 25% reduction in total heat evolved (THE), a 30% reduction in peak heat release rate (PHRR) due to flame inhibition (21% reduction in effective heat of combustion (EHC)), and an increase in T-g at the same time. This study indicates that rigid aromatic hyperbranched polymeric structures offer a promising route toward multifunctional flame retardancy
Molecular Firefighting ā How Modern Phosphorus Chemistry Can Help Solve the Flame Retardancy Task
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A multicenter experience using adipose-derived mesenchymal stem cell therapy for cats with chronic, non-responsive gingivostomatitis.
BackgroundThe ability of mesenchymal stem cells (MSCs) to modulate immune responses inspired a series of clinical trials addressing oral mucosal inflammation. We previously reported on the safety and efficacy of fresh, allogeneic and autologous, adipose-derived mesenchymal stem cells (ASCs) to treat feline gingivostomatitis (FCGS), an oral mucosal inflammatory disease that shares similarities with human oral lichen planus.MethodsTo meet clinical demand and goals for future commercialization, we determined the feasibility of shipping fresh ASCs to distant clinics and extended our pilot studies to expand safety and efficacy data for shipped and non-shipped ASCs in a cohort of 18 FCGS cats enrolled locally and at a few different locations within the USA.ResultsWe found that ASCs retained their viability, phenotype, and function after shipment. ASCs administered systemically resulted in a 72% positive response rate, identical to that noted in our previous studies. Cats that responded to ASC therapy had a significant decrease in circulating globulin concentration and histological evidence of decreased CD3+ T cells and CD20+ B cells in the oral mucosa. Responder cats also had significantly decreased percentages of CD8lo cells in blood prior to and at 3āmonths post-ASC therapy. CD8lo cells may serve as a potential "predictor" for response to systemic ASC therapy.ConclusionFresh feline ASCs can be successfully shipped and administered to cats with FCGS. ASCs modulate the immune response and demonstrate efficacy for chronic oral mucosal inflammatory lesions that are characterized by CD8+ T cell inflammation and T cell activation. FCGS is a potentially useful naturally occurring large animal model of human oral inflammatory diseases
On mikusinski's operators of fractional integration
In the field F of convolution quotients,Ā bā is the operator of integration of fractional order ā and bā fĀ Ā Is the Riemann - Liouville integral of orderĀ Ā ā of f. In this paper we give a generalization of this operator, which is denoted as bā,va . Some particular cases are mentioned and the inverse operator is obtained
Antiplasmodial Activity and In Vivo Bio-Distribution of Chloroquine Molecules Released with a 4-(4-Ethynylphenyl)-Triazole Moiety from Organometallo-Cobalamins
We have explored the possibility of using organometallic derivatives of cobalamin as a scaffold for the delivery of the same antimalarial drug to both erythro- and hepatocytes. This hybrid molecule approach, intended as a possible tool for the development of multi-stage antimalarial agents, pivots on the preparation of azide-functionalized drugs which, after coupling to the vitamin, are released with a 4-(4-ethynylphenyl)-triazole functionality. Three chloroquine and one imidazolopiperazine derivative (based on the KAF156 structure) were selected as model drugs. One hybrid chloroquine conjugate was extensively studied via fluorescent labelling for in vitro and in vivo bio-distribution studies and gave proof-of-concept for the design. It showed no toxicity in vivo (zebrafish model) as well as no hepatotoxicity, no cardiotoxicity or developmental toxicity of the embryos. All 4-(4-ethynylphenyl)-triazole derivatives of chloroquine were equally active against chloroquine-resistant (CQR) and chloroquine-sensitive (CQS) Plasmodium falciparum strains
Comparison of successive and simultaneous methods of pair presentation in paired-associate learning
Pneumococcal Gene Complex Involved in Resistance to Extracellular Oxidative Stress
Streptococcus pneumoniae is a Gram-positive bacterium which is a member of the normal human nasopharyngeal flora but can also cause serious disease such as pneumonia, bacteremia, and meningitis. Throughout its life cycle, S. pneumoniae is exposed to significant oxidative stress derived from endogenously produced hydrogen peroxide (H2O2) and from the host through the oxidative burst. How S. pneumoniae, an aerotolerant anaerobic bacterium that lacks catalase, protects itself against hydrogen peroxide stress is still unclear. Bioinformatic analysis of its genome identified a hypothetical open reading frame belonging to the thiol-specific antioxidant (TlpA/TSA) family, located in an operon consisting of three open reading frames. For all four strains tested, deletion of the gene resulted in an approximately 10-fold reduction in survival when strains were exposed to external peroxide stress. However, no role for this gene in survival of internal superoxide stress was observed. Mutagenesis and complementation analysis demonstrated that all three genes are necessary and sufficient for protection against oxidative stress. Interestingly, in a competitive index mouse pneumonia model, deletion of the operon had no impact shortly after infection but was detrimental during the later stages of disease. Thus, we have identified a gene complex involved in the protection of S. pneumoniae against external oxidative stress, which plays an important role during invasive disease.
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