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61.
Smadja DM Duong-van-Huyen JP Dal Cortivo L Blanchard A Bruneval P Emmerich J Gaussem P 《Cytotherapy》2012,14(2):232-239
Background aimsEndothelial progenitor cells (EPC) have been proposed for autologous angiogenic therapy. The objectives of this study were to quantify EPC in the peripheral blood and bone marrow mononuclear cells (BM-MNC) of patients with critical limb ischemia that had received BM-MNC as a cell therapy product, and to study the putative relationship between the presence of EPC and the process of neovascularization in toe or transmetatarsal amputation specimens.MethodsEarly and late endothelial progenitor cells (CFU-EC and ECFC) were cultivated and quantified according to published methods in peripheral blood and BM-MNC from patients with critical limb ischemia (CLI; n = 11) enrolled in the OPTIPEC trial (http://clinicaltrials.gov/ct2/show/NCT00377897) to receive BM-MNC as a cell therapy product.ResultsEight out of the 11 patients had undergone amputations. Three of the patients displayed a neoangiogenic process that was associated with a higher number of CFU-EC in BM-MNC, while CD3+, CFU-GM and CD34+ in BM-MNC, and EPC in peripheral blood, did not correlate with the appearance of newly formed vessels. As expected, circulating CFU-EC and ECFC counts were significantly lower in CLI patients compared with age-matched controls.ConclusionsIn patients with critical limb ischemia, EPC in peripheral blood were decreased compared with healthy individuals. However, in BM-MNC we found that relative numbers of CFU-EC could be used as an indicator to discriminate patients with neoangiogenic processes. These results need to be confirmed in a randomized study. 相似文献
62.
Alzbeta Trancikova Adamantios Mamais Philip J. Webber Klodjan Stafa Elpida Tsika Liliane Glauser Andrew B. West Rina Bandopadhyay Darren J. Moore 《PloS one》2012,7(10)
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are a common cause of autosomal dominant familial Parkinson''s disease (PD). LRRK2 encodes a multi-domain protein containing GTPase and kinase enzymatic domains. Disease-associated mutations in LRRK2 variably influence enzymatic activity with the common G2019S variant leading to enhanced kinase activity. Mutant LRRK2 induces neuronal toxicity through a kinase-dependent mechanism suggesting that kinase activity is important for mediating the pathogenic effects of LRRK2 mutations. A number of LRRK2 kinase substrates have been identified in vitro but whether they represent authentic physiological substrates in mammalian cells or tissues is not yet clear. The eukaryotic initiation factor 4E (eIF4E)-binding protein, 4E-BP1, was recently identified as a potential substrate of LRRK2 kinase activity in vitro and in Drosophila with phosphorylation occurring at Thr37 and Thr46. Here, we explore a potential interaction of LRRK2 and 4E-BP1 in mammalian cells and brain. We find that LRRK2 can weakly phosphorylate 4E-BP1 in vitro but LRRK2 overexpression is not able to alter endogenous 4E-BP1 phosphorylation in mammalian cells. In mammalian neurons LRRK2 and 4E-BP1 display minimal co-localization, whereas the subcellular distribution, protein complex formation and covalent post-translational modification of endogenous 4E-BP1 are not altered in the brains of LRRK2 knockout or mutant LRRK2 transgenic mice. In the brain, the phosphorylation of 4E-BP1 at Thr37 and Thr46 does not change in LRRK2 knockout or mutant LRRK2 transgenic mice, nor is 4E-BP1 phosphorylation altered in idiopathic or G2019S mutant PD brains. Collectively, our results suggest that 4E-BP1 is neither a major nor robust physiological substrate of LRRK2 in mammalian cells or brain. 相似文献
63.
Granado J Thürig B Kieffer E Petrini L Fliessbach A Tamm L Weibel FP Wyss GS 《Microbial ecology》2008,56(4):720-732
The effects of organic and integrated production systems on the culturable fungal microflora of stored apple fruits from five
matched pairs of certified organic and integrated ‘Golden Delicious’ farms were studied at five representative production
sites in Switzerland. Isolated fungi were identified morphologically. Colonization frequency (percentage of apples colonized),
abundance (colony numbers), and diversity (taxon richness) were assessed for each orchard. The standard quality of the stored
fruits was comparable for both organic and integrated apples and complied with national food hygiene standards. Yeasts (six
taxa) and the yeast-like fungus Aureobasidium pullulans were the dominant epiphytes, filamentous fungi (21 taxa) the dominant endophytes. The most common fungi occurred at all sites
and belonged to the “white” and “pink” yeasts, yeast-like A. pullulans, filamentous fungi Cladosporium spp., Alternaria spp., and sterile filamentous fungi. Canonical correspondence analysis of the total fungal community revealed a clear differentiation
among production systems and sites. Compared to integrated apples, organic apples had significantly higher frequencies of
filamentous fungi, abundance of total fungi, and taxon diversity. The effects of the production system on the fungal microflora
are most likely due to the different plant protection strategies. The incidence of potential mycotoxin producers such as Penicillium and Alternaria species was not different between production systems. We suggest that higher fungal diversity may generally be associated
with organic production and may increase the level of beneficial and antagonistically acting species known for their potential
to suppress apple pathogens, which may be an advantage to organic apples, e.g., in respect to natural disease control. 相似文献
64.
Prudent R Moucadel V López-Ramos M Aci S Laudet B Mouawad L Barette C Einhorn J Einhorn C Denis JN Bisson G Schmidt F Roy S Lafanechere L Florent JC Cochet C 《Molecular and cellular biochemistry》2008,316(1-2):71-85
None of the already described CK2 inhibitors did fulfill the requirements for successful clinical settings. In order to find innovative CK2 inhibitors based on new scaffolds, we have performed a high-throughput screening of diverse chemical libraries. We report here the identification and characterization of several classes of new inhibitors. Whereas some share characteristics of previously known CK2 inhibitors, others are chemically unrelated and may represent new opportunities for the development of better CK2 inhibitors. By combining structure-activity relationships with a docking procedure, we were able to determine the binding mode of these inhibitors. Interestingly, beside the identification of several nanomolar ATP-competitive inhibitors, one class of chemical inhibitors displays a non-ATP competitive mode of inhibition, a feature that suggests that CK2 possess distinct druggable binding sites. For the most promising inhibitors, selectivity profiling was performed. We also provide evidence that some chemical compounds are inhibiting CK2 in living cells. Finally, the collected data allowed us to draw the rules about the chemical requirements for CK2 inhibition both in vitro and in a cellular context. 相似文献
65.
Effect of Bacillus thuringiensis Cry1 Toxins in Insect Hemolymph and Their Neurotoxicity in Brain Cells of Lymantria dispar
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Anja Cerstiaens Peter Verleyen Jeroen Van Rie Emmy Van Kerkhove Jean-Louis Schwartz Raynald Laprade Arnold De Loof Liliane Schoofs 《Applied microbiology》2001,67(9):3923-3927
Little information is available on the systemic effects of Bacillus thuringiensis toxins in the hemocoel of insects. In order to test whether B. thuringiensis-activated toxins elicit a toxic response in the hemocoel, we measured the effect of intrahemocoelic injections of several Cry1 toxins on the food intake, growth, and survival of Lymantria dispar (Lepidoptera) and Neobellieria bullata (Diptera) larvae. Injection of Cry1C was highly toxic to the Lymantria larvae and resulted in the complete inhibition of food intake, growth arrest, and death in a dose-dependent manner. Cry1Aa and Cry1Ab (5 μg/0.2 g [fresh weight] [g fresh wt]) also affected growth and food intake but were less toxic than Cry1C (0.5 μg/0.2 g fresh wt). Cry1E and Cry1Ac (5 μg/0.2 g fresh wt) had no toxic effect upon injection. Cry1C was also highly toxic to N. bullata larvae upon injection. Injection of 5 μg/0.2 g fresh wt resulted in rapid paralysis, followed by hemocytic melanization and death. Lower concentrations delayed pupariation or gave rise to malformation of the puparium. Finally, Cry1C was toxic to brain cells of Lymantria in vitro. The addition of Cry1C (20 μg/ml) to primary cultures of Lymantria brain cells resulted in rapid lysis of the cultured neurons. 相似文献
66.
SATB1 Cleavage by Caspase 6 Disrupts PDZ Domain-Mediated Dimerization, Causing Detachment from Chromatin Early in T-Cell Apoptosis
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Sanjeev Galande Liliane A. Dickinson I. Saira Mian Marianna Sikorska Terumi Kohwi-Shigematsu 《Molecular and cellular biology》2001,21(16):5591-5604
SATB1 is expressed primarily in thymocytes and orchestrates temporal and spatial expression of a large number of genes in the T-cell lineage. SATB1 binds to the bases of chromatin loop domains in vivo, recognizing a special DNA context with strong base-unpairing propensity. The majority of thymocytes are eliminated by apoptosis due to selection processes in the thymus. We investigated the fate of SATB1 during thymocyte and T-cell apoptosis. Here we show that SATB1 is specifically cleaved by a caspase 6-like protease at amino acid position 254 to produce a 65-kDa major fragment containing both a base-unpairing region (BUR)-binding domain and a homeodomain. We found that this cleavage separates the DNA-binding domains from amino acids 90 to 204, a region which we show to be a dimerization domain. The resulting SATB1 monomer loses its BUR-binding activity, despite containing both its DNA-binding domains, and rapidly dissociates from chromatin in vivo. We found this dimerization region to have sequence similarity to PDZ domains, which have been previously shown to be involved in signaling by conferring protein-protein interactions. SATB1 cleavage during Jurkat T-cell apoptosis induced by an anti-Fas antibody occurs concomitantly with the high-molecular-weight fragmentation of chromatin of ~50-kb fragments. Our results suggest that mechanisms of nuclear degradation early in apoptotic T cells involve efficient removal of SATB1 by disrupting its dimerization and cleavage of genomic DNA into loop domains to ensure rapid and efficient disassembly of higher-order chromatin structure. 相似文献
67.
68.
Liliane Didierjean Rosanne Wrench Jean H. Saurat 《Differentiation; research in biological diversity》1982,23(1-3):250-255
Abstract. An unusual example of two different types of epidermal differentiation occurs side by side in adult mouse tail. The neonate shows only orthokeratotic differentiation, but develops parakeratotic scales in precise patterns over the first two weeks of life, retaining orthokeratotic differentiation at the necks of hair follicles. Certain human IgG antibodies from patients receiving bone marrow transplants bind only to cytoplasmic components of orthokeratotic epithelium. As markers of orthokeratotic differentiation in indirect immunofluorescent studies, these antibodies allowed the timing and location of the change in epidermal differentiation. A specific loss of 'orthokeratotic' antigens in the natural switch from orthokeratosis to parakeratosis was demonstrated. The sequence of the orthokeratotic antigens disappearance suggested that the switch to parakeratotic differentation occurred at a supra-basal level. 相似文献
69.
Flaviana Mouawad Lamine Aoudjit Ruihua Jiang Katalin Szaszi Tomoko Takano 《The Journal of biological chemistry》2014,289(7):4206-4218
Visceral glomerular epithelial cells (GEC), also known as podocytes, are vital for the structural and functional integrity of the glomerulus. The actin cytoskeleton plays a central role in maintaining GEC morphology. In a rat model of experimental membranous nephropathy (passive Heymann nephritis (PHN)), complement C5b-9-induced proteinuria was associated with the activation of the actin regulator small GTPase, RhoA. The mechanisms of RhoA activation, however, remained unknown. In this study, we explored the role of the epithelial guanine nucleotide exchange factor, GEF-H1, in complement-induced RhoA activation. Using affinity precipitation to monitor GEF activity, we found that GEF-H1 was activated in glomeruli isolated from rats with PHN. Complement C5b-9 also induced parallel activation of GEF-H1 and RhoA in cultured GEC. In GEC in which GEF-H1 was knocked down, both basal and complement-induced RhoA activity was reduced. On the other hand, GEF-H1 knockdown augmented complement-mediated cytolysis, suggesting a role for GEF-H1 and RhoA in protecting GEC from cell death. The MEK1/2 inhibitor, U0126, and mutation of the ERK-dependent phosphorylation site (T678A) prevented complement-induced GEF-H1 activation, indicating a role for the ERK pathway. Further, complement induced GEF-H1 and microtubule accumulation in the perinuclear region. However, both the perinuclear accumulation and the activation of GEF-H1 were independent of microtubules and myosin-mediated contractility, as shown using drugs that interfere with microtubule dynamics and myosin II activity. In summary, we have identified complement-induced ERK-dependent GEF-H1 activation as the upstream mechanism of RhoA stimulation, and this pathway has a protective role against cell death. 相似文献
70.
Résumé L’introduction de corps étrangers dans les larves de lépidoptères entra?ne une augmentation parfois considérable du taux de
lysozyme dans l’hémolymphe. L’efficacité inductrice de diverses substances varie dans de larges mesures. L’action de l’Actinomycine
D et de la Cycloheximide sur la production du lysozyme induit a été recherchée chez des larves deGalleria mellonella L. recevant un stimulus peu spécifique (chlorure de sodium) ou plus spécifique (Micrococcus luteus vivants). L’action de ces inhibiteurs sur la quantité de lysozyme présente dans l’hémolymphe 24 h après induction, indique
que les variations du taux de l’enzyme sont sous le contr?le d’un mécanisme unique indépendant de la spécificité des stimuli
inducteurs. L’augmentation du taux de lysozyme chez les larves deG. mellonella induites, fait suite à une synthèse protéique et non à la libération d’enzyme préformé.
Summary Foreign bodies introduced into lepidopteran larvae induce an increase, often considerable, in amount of lysozyme in the hemolymph. The efficiency of various substances to elicit the release of lysozyme in the larvae varies to a great extent. The effect of Actinomycin D and Cycloheximide introduced in theGalleria mellonella L. larvae stimulated to produce lysozyme by injection of saline or liveMicrococcus luteus was studied. The action of these metabolic inhibitors on the quantity of lysozyme in the hemolymph, 24 h after injection of the inducers, showed that the variations of the amount of the enzyme are under the control of only one mechanism which is not affected by the nature of the inducers. The increase in lysozyme amount of the hemolymph of the inducedG. mellonella larvae is due to the protein synthesis; it does not result from the release of a preformed enzyme as it was demonstrated in other animal species.相似文献