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141.
Clastre M Goubard A Prel A Mincheva Z Viaud-Massuart MC Bout D Rideau M Velge-Roussel F Laurent F 《Experimental parasitology》2007,116(4):375-384
The apicoplast is a recently discovered, plastid-like organelle present in most apicomplexa. The methylerythritol phosphate (MEP) pathway involved in isoprenoid biosynthesis is one of the metabolic pathways associated with the apicoplast, and is a new promising therapeutic target in Plasmodium falciparum. Here, we check the presence of isoprenoid genes in four coccidian parasites according to genome database searches. Cryptosporidium parvum and C. hominis, which have no plastid genome, lack the MEP pathway. In contrast, gene expression studies suggest that this metabolic pathway is present in several development stages of Eimeria tenella and in tachyzoites of Toxoplasma gondii. We studied the potential of fosmidomycin, an antimalarial drug blocking the MEP pathway, to inhibit E. tenella and T. gondii growth in vitro. The drug was poorly effective even at high concentrations. Thus, both fosmidomycin sensitivity and isoprenoid metabolism differs substantially between apicomplexan species. 相似文献
142.
We have investigated the mechanisms involved in generating hindbrain motoneurone subtypes, focusing on somatic motoneurones, which are confined to the caudal hindbrain within rhombomeres 5-8. Following heterotopic transplantation of rhombomeres along the rostrocaudal axis at various developmental stages, we have found that the capacity of rhombomeres to generate somatic motoneurones is labile at the neural plate stage but becomes fixed just after neural tube closure, at stage 10-11. Grafting of somites or retinoic acid-loaded beads beneath the rostral hindbrain induced the formation of somatic motoneurones in rhombomere 4 only, and Hox genes normally expressed more caudally (Hoxa3, Hoxd4) were induced in this region. Targeted overexpression of Hoxa3 in the rostral hindbrain led to the generation of ectopic somatic motoneurones in ventral rhombomeres 1-4, and was accompanied by the repression of the dorsoventral patterning gene Irx3. Taken together, these observations suggest that the somites, retinoic acid and Hox genes play a role in patterning somatic motoneurones in vivo. 相似文献
143.
Raynaud F Marcilhac A Chebli K Benyamin Y Rossel M 《The International journal of developmental biology》2008,52(4):383-388
Regulation of migration and proliferation by calpain has been shown in various cell types; however, no data are available concerning calpain 2 (capn2) localization in embryonic tissues. Here, we report the expression pattern of capn2 during mouse embryonic development. Expression of the capn2 gene is observed throughout embryonic development. From ES cells and the 8-cell stage to late neurulation stages, CAPN2 is expressed in the cytoplasm and nuclear compartments, with a clear co-localisation with chromatin. Whole-mount in situ hybridization analysis from E8.5 to 14.5 stages indicates high levels of capn2 expression in the nervous system, heart and mesodermal tissues. Up-regulation is maintained during later developmental stages in proliferating cells and in precursor cells involved in muscle (myoblasts) or bone formation (chondrocytes). At later developmental stages, elevated mRNA levels coincided with CAPN2 nuclear localization in these cell types, while differentiated cells maintained cytoplasmic expression. This detailed analysis reveals dynamic expression: nuclear localization was associated either with active cell mitosis in embryonic stem cells and early developmental stages or with precursor cells later during organogenesis. Thus, these data indicate that CAPN2 may represent a key factor in development from the first cell division. 相似文献
144.
The regulatory NEMO (NF-κB essential modulator) protein has a crucial role in the canonical NF-κB signaling pathway notably involved in immune and inflammatory responses, apoptosis and oncogenesis. The regulatory domain is located in the C-terminal half of NEMO and contains a classical CCHC-type zinc finger (ZF). We have investigated the structural and functional effects of a cysteine to phenylalanine point mutation (C417F) in the ZF motif, identified in patients with anhidrotic ectodermal dysplasia with immunodeficiency. The solution structures of the wild type and mutant ZF were determined by NMR. Remarkably, the mutant adopts a global ββα fold similar to that of the wild type and retains thermodynamic stability, i.e., the ability to bind zinc with a native-like affinity, although the last zinc-chelating residue is missing. However, the mutation induces enhanced dynamics in the motif and leads to an important loss of stability. A detailed analysis of the wild type solution structure and experimental evidences led to the identification of two possible protein-binding surfaces that are largely destabilized in the mutant. This is sufficient to alter NEMO function, since functional complementation assays using NEMO-deficient pre-B and T lymphocytes show that full-length C417F pathogenic NEMO leads to a partial to strong defect in LPS, IL-1β and TNF-α-induced NF-κB activation, respectively, as compared to wild type NEMO. Altogether, these results shed light onto the role of NEMO ZF as a protein-binding motif and show that a precise structural integrity of the ZF should be preserved to lead to a functional protein-recognition motif triggering full NF-κB activation. 相似文献
145.
Freeman Bradley D.; Quezado Zenaide; Zeni Fabrice; Natanson Charles; Danner Robert L.; Banks Steven; Quezado Marcello; Fitz Yvonne; Bacher John; Eichacker Peter Q. 《Journal of applied physiology》1997,83(5):1467-1475
Freeman, Bradley D., Zenaide Quezado, Fabrice Zeni, CharlesNatanson, Robert L. Danner, Steven Banks, Marcello Quezado, YvonneFitz, John Bacher, and Peter Q. Eichacker. rG-CSF reduces endotoxemia and improves survival during E. coli pneumonia. J. Appl.Physiol. 83(5): 1467-1475, 1997.We investigatedthe effects of recombinant granulocyte colony-stimulating factor(rG-CSF) during canine bacterial pneumonia. Beagles with chronictracheostomies received daily subcutaneous rG-CSF (5 µg/kg body wt)or placebo for 14 days, beginning 9 days before intrabronchialinoculation with E. coli. Animalsreceived antibiotics and fluid support; a subset received humidifiedoxygen (fractional inspired O20.40). Compared with controls, rG-CSF increased circulating neutrophil counts (57.4 vs. 11.0 × 103/mm3,day 1 after infection;P = 0.0001), decreased plasmaendotoxin (7.5 vs. 1.1 EU/ml at 8 h; P < 0.01) and serum tumor necrosis factor- (3,402 vs.729 pg/ml at 2 h; P = 0.01) levels,and prolonged survival (relative risk of death = 0.45, 95% confidenceinterval 0.21-0.97; P = 0.038).Also, rG-CSF attenuated sepsis-associated myocardial dysfunction(P < 0.001). rG-CSF had no effect onpulmonary function or on blood and lung bacteria counts (allP = not significant). Other animalschallenged with endotoxin (4 mg/kg iv) after similar treatment withrG-CSF had lower serum endotoxin levels (7.62 vs. 5.81 log EU/ml at 6 h; P < 0.01) and less cardiovasculardysfunction (P < 0.05 to < 0.002)but similar tumor necrosis factor- levels (P = not significant) compared withcontrols. Thus prophylactic rG-CSF sufficient to increase circulatingneutrophils during bacterial pneumonia may improve cardiovascularfunction and survival by mechanisms that in part enhance the clearanceof bacterial toxins but do not improve lung function. 相似文献
146.
Cornille Fabrice Martin Loïc Lenoir Christine Cussac Didier Roques Bernard P. Fournié-Zaluski Marie-Claude 《International journal of peptide research and therapeutics》1997,4(4-6):207-212
Summary The light chain of tetanus neurotoxin (TeNTL chain) has been shown to be endowed with zine endopeptidase activity, selectively
directed towards the Gln76-Phe77 bond of synaptobrevin, a vesicle-associated membrane protein critically involved in neuroexocytosis. In previous reports,
truncations at the NH2- and COOH-terminus of synaptobrevin have shown that the sequence 39–88 of synaptobrevin is the minimum substrate of TeNT,
suggesting either the requirement of a well-defined three-dimensional structure of synaptobrevin or a role in the mechanism
of substrate hydrolysis for residues distal from the cleavage site. In this study, the addition of NH2- and COOH-terminal peptides of synaptobrevin, S 27–55 (S1) and S 82–93 (S2), to the synaptobrevin fragment S 56–81 allowed the cleavage of this latter peptide by TeNT to occur. This appears to result
from an activation process mediated by the simultaneous binding of S1 and S2 with complementary sites present on TeNT as shown by surface plasmon resonance experiments. All these results favor an exosite-controlled
hydrolysis of synaptobrevin by TeNT probably involving a conformational change of the toxin. This could accound for the high
degree of substrate specificity of TeNT and, probably, botulinum neurotoxins. 相似文献
147.
Duarte Gouveia Lucia Grenga Jean‐Charles Gaillard Fabrice Gallais Laurent Bellanger Olivier Pible Jean Armengaud 《Proteomics》2020,20(14)
Detection of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a crucial tool for fighting the COVID‐19 pandemic. This dataset brief presents the exploration of a shotgun proteomics dataset acquired on SARS‐CoV‐2 infected Vero cells. Proteins from inactivated virus samples were extracted, digested with trypsin, and the resulting peptides were identified by data‐dependent acquisition tandem mass spectrometry. The 101 peptides reporting for six viral proteins were specifically analyzed in terms of their analytical characteristics, species specificity and conservation, and their proneness to structural modifications. Based on these results, a shortlist of 14 peptides from the N, S, and M main structural proteins that could be used for targeted mass‐spectrometry method development and diagnostic of the new SARS‐CoV‐2 is proposed and the best candidates are commented. 相似文献
148.
Makelele Isaac Ahanamungu Bauters Marijn Verheyen Kris Barthel Matti Six Johan Rütting Tobias Bodé Samuel Cizungu Ntaboba Landry Mujinya Bazirake Basile Boyemba Bosela Faustin Kimbesa Fabrice Ewango Corneille Boeckx Pascal 《Plant and Soil》2022,476(1-2):743-753
Plant and Soil - Many applied disciplines have recognized problems related to the practice of data analysis within their own communities. Some of them have even declared the existence of a... 相似文献
149.
Camont L Collin F Couturier M Thérond P Jore D Gardès-Albert M Bonnefont-Rousselot D 《Biochimie》2012,94(3):741-747
trans-Resveratrol (RVT) (3,5,4'-trihydroxystilbene), a polyphenolic constituent of red wine, is thought to be beneficial in reducing the incidence of cardiovascular diseases, partly via its antioxidant properties. However, the mechanism of action by which trans-resveratrol displays its antioxidant effect has not been totally unravelled. This study aimed at establishing a comprehensive scheme of the reaction mechanisms of the direct scavenging of HO(*) and O(2)(*-) radicals generated by water gamma radiolysis. Aerated aqueous solutions of trans-RVT (from 10 to 100μmolL(-1)) were irradiated with increasing radiation doses (from 25 to 400Gy) and further analyzed by UV-visible absorption spectrophotometry for detection of trans-RVT oxidation products. Separation and quantification of RVT and its four oxidation products previously identified by mass spectrometry, i.e., piceatannol (PCT), 3,5-dihydroxybenzoic acid (3,5-DHBA), 3,5-dihydroxybenzaldehyde (3,5-DHB) and para-hydroxybenzaldehyde (PHB), were performed by HPLC/UV-visible spectrophotometry. Determination of the radiolytic yields of trans-RVT consumption and oxidation product formation has allowed us to establish balance between trans-RVT disappearance and the sum of oxidation products formation. Under our conditions, O(2)(-) radicals seemed to poorly initiate oxidation of trans-RVT, whereas the latter, whatever its initial concentration, quantitatively reacted with HO() radicals, via a dismutation mechanism. Two reaction pathways involving HO()-induced trans-RVT primary radicals have been proposed to explain the formation of the oxidation end-products of trans-RVT. 相似文献
150.
Fran?oise Lazarini Marc-André Mouthon Gilles Gheusi Fabrice de Chaumont Jean-Christophe Olivo-Marin Stéphanie Lamarque Djoher Nora Abrous Fran?ois D. Boussin Pierre-Marie Lledo 《PloS one》2009,4(9)