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91.
Stefano Crosignani Agnes Bombrun David Covini Maurizio Maio Delphine Marin Anna Quattropani Dominique Swinnen Don Simpson Wolfgang Sauer Bernard Françon Thierry Martin Yves Cambet Anthony Nichols Isabelle Martinou Fabienne Burgat-Charvillon Delphine Rivron Cristina Donini Olivier Schott Valerie Eligert Laurence Novo-Perez Jean-François Arrighi 《Bioorganic & medicinal chemistry letters》2010,20(5):1516-1519
The discovery of a novel series of S1P1 agonists is described. Starting from a micromolar HTS positive, iterative optimization gave rise to several single-digit nanomolar S1P1 agonists. The compounds were able to induce internalization of the S1P1 receptor, and a selected compound was shown to be able to induce lymphopenia in mice after oral dosing. 相似文献
92.
Dispersal mood revealed by shifts from routine to direct flights in the meadow brown butterfly Maniola jurtina 总被引:1,自引:0,他引:1
Thomas Delattre Françoise Burel Antoine Humeau Virginie M. Stevens Philippe Vernon Michel Baguette 《Oikos》2010,119(12):1900-1908
A comprehensive mechanistic approach to dispersal requires the translation of the whole mobility register of the target organism into movement rules that could subsequently be used to model its displacements. According to the optimality paradigm, this procedure implies a cost–benefit analysis of mobility patterns taking into account not only movements, but also their external context and the internal state of the moving individuals. Using this framework, we detected a ‘dispersal mood’ in some individuals of the meadow brown butterfly Maniola jurtina. These adopted a direct flight strategy, which was topologically different from the previously documented foray search strategy. Those individuals that used the direct flight strategy moved straighter as soon as they left the habitat and avoided heading back to their patch of origin, which is the best inter‐patch search strategy when dispersal risks and costs are high. The direct flight strategy was conditional to sex: females used it twice as much as males. We suggest that this sex bias was due to female investment in offspring, which is maximized by male avoidance and spatial bet hedging. Inter‐patch dispersal of gravid females is crucial for the persistence of M. jurtina populations in spatially and temporally unpredictable environments. 相似文献
93.
94.
Delphine Benaitreau Esther Dos Santos Marie-Christine Leneveu Philippe De Mazancourt René Pecquery Marie-Noëlle Dieudonné 《Reproductive biology and endocrinology : RB&E》2010,8(1):128
Background
In human pregnancy, a correct placentation depends on trophoblast proliferation, differentiation, migration and invasion. These processes are highly regulated by placental hormones, growth factors and cytokines. Recently, we have shown that adiponectin, an adipokine, has anti-proliferative effects on trophoblastic cells. Here, we complete this study by demonstrating that adiponectin modulates BeWo and human villous cytotrophoblast cell differentiation. 相似文献95.
Vincent Corvest Darren A. Murrey Delphine G. Bernard David B. Knaff Bernard Guiard Patrice P. Hamel 《Genetics》2010,186(2):561-571
The electron transport chains in the membranes of bacteria and organelles generate proton-motive force essential for ATP production. The c-type cytochromes, defined by the covalent attachment of heme to a CXXCH motif, are key electron carriers in these energy-transducing membranes. In mitochondria, cytochromes c and c1 are assembled by the cytochrome c heme lyases (CCHL and CC1HL) and by Cyc2p, a putative redox protein. A cytochrome c1 mutant with a CAPCH heme-binding site instead of the wild-type CAACH is strictly dependent upon Cyc2p for assembly. In this context, we found that overexpression of CC1HL, as well as mutations of the proline in the CAPCH site to H, L, S, or T residues, can bypass the absence of Cyc2p. The P mutation was postulated to shift the CXXCH motif to an oxidized form, which must be reduced in a Cyc2p-dependent reaction before heme ligation. However, measurement of the redox midpoint potential of apocytochrome c1 indicates that neither the P nor the T residues impact the thermodynamic propensity of the CXXCH motif to occur in a disulfide vs. dithiol form. We show instead that the identity of the second intervening residue in the CXXCH motif is key in determining the CCHL-dependent vs. CC1HL-dependent assembly of holocytochrome c1. We also provide evidence that Cyc2p is dedicated to the CCHL pathway and is not required for the CC1HL-dependent assembly of cytochrome c1.THE c-type cytochromes, also referred to as cytochrome c, represent a universal class of heme-containing proteins that function as electron carriers in the energy-transducing pathways of bacteria, plastids, and mitochondria (Thöny-Meyer 1997; Nakamoto et al. 2000; Bonnard et al. 2010). Because cytochromes c carry a heme covalently attached to a CXXCH motif, they constitute an attractive object of study to address the question of cofactor protein assembly. The biochemical requirements for cytochrome c assembly were deduced from in vivo and in vitro studies, and the conclusion is that both apocytochromes c and heme are transported independently across at least one biological membrane and maintained as reduced prior to catalysis of the heme attachment reaction (Allen et al. 2003; Hamel et al. 2009; Kranz et al. 2009; Sanders et al. 2010). Bacterial cytochromes c are assembled in the periplasmic space, a compartment where cysteine pairs in proteins form disulfide bonds in reactions catalyzed by dedicated enzymes (Inaba 2009; Kadokura and Beckwith 2010). The current thinking holds that a c-type apocytochrome is a substrate of the disulfide bond-forming pathway, which introduces an intramolecular disulfide between the two cysteines of the CXXCH sequence (Allen et al. 2003; Sanders et al. 2010). This disulfide needs to be reduced to a dithiol to provide free sulfhydryls for the heme ligation. Consistent with this view is the fact that groups of specific oxido-reductases that constitute a transmembrane dithiol-disulfide relay from the cytosol to the periplasmic space have been shown to function as c-type cytochrome assembly factors (Allen et al. 2003; Kadokura et al. 2003; Mapller and Hederstedt 2006; Sanders et al. 2010). The proposal that the components of this pathway control the in vivo redox status of the CXXCH sulfhydryls has been inferred from the presence of motifs in their protein sequences that are consistent with a function in redox chemistry and also from the demonstration that their recombinant forms participate in dithiol–disulfide exchange reactions (Monika et al. 1997; Setterdahl et al. 2000). Moreover, the ability of exogenous thiol compounds to bypass the lack of these factors in vivo substantiates the view that the redox components have a disulfide-reducing activity in the pathway (e.g., Sambongi and Ferguson 1994; Fabianek et al. 1998; Beckett et al. 2000; Deshmukh et al. 2000; Bardischewsky and Friedrich 2001; Erlendsson and Hederstedt 2002; Erlendsson et al. 2003; Feissner et al. 2005; Turkarslan et al. 2008).While the role of these pathways is well established in bacteria, much less is known about the components that catalyze thiol/disulfide chemistry in the mitochondrial intermembrane space (IMS), which is topologically equivalent to the bacterial periplasm. By analogy with the bacterial pathways, the participation of redox-active factors that catalyze thiol formation is expected, as the mitochondrial IMS houses two c-type cytochromes, the soluble cytochrome c and the membrane-bound cytochrome c1, both of which function in respiration. In fungi, heme attachment to apocytochromes c and c1 is dependent upon the IMS resident cytochrome c and c1 heme lyases, CCHL and CC1HL, although the exact role of these lyases in the assembly process is still unclear (Dumont et al. 1987; Zollner et al. 1992). Conversion of apocytochrome to holocytochrome c depends only on CCHL, while apocytochrome c1 can be acted upon by both CCHL and CC1HL (Matner and Sherman 1982; Dumont et al. 1987; Stuart et al. 1990; Zollner et al. 1992; Bernard et al. 2003). In animals, apoforms of cytochromes c and c1 are assembled by a unique heme lyase, HCCS, which carries both the CCHL and CC1HL activities (Prakash et al. 2002; Schwarz and Cox 2002; Bernard et al. 2003).Cyc2p, a component first described as a mitochondrial biogenesis factor in yeast (Matner and Sherman 1982; Dumont et al. 1993; Pearce et al. 1998; Sanchez et al. 2001), was recently rediscovered in the context of cytochrome c1 maturation (Bernard et al. 2003). Cyc2p is located at the mitochondrial inner membrane with its C-terminal domain containing a non-covalently bound FAD exposed to the IMS (Bernard et al. 2005). A redox function for Cyc2p is likely based on the finding that a recombinant form of the molecule exhibits a NAD(P)H-dependent reductase activity (Bernard et al. 2005). However, as Cyc2p activity is not essential for the maturation process, a functional redundancy was postulated based on the fact that a cyc2-null mutant still assembles holoforms of cytochromes c and c1 (Bernard et al. 2005). The absolute requirement of Cyc2p was revealed via genetic analysis of the cyc2-null cyt1-34 combination that displays a synthetic respiratory-deficient phenotype with loss of holocytochrome c1 assembly (Bernard et al. 2005). The cyt1-34 mutation maps to the gene encoding cytochrome c1 and results in a CAPCH heme-binding site replacing the wild-type CAACH site (Bernard et al. 2005). The synthetic interaction is specific for the cyt1-34 allele carrying the A-to-P mutation and is not observed in a cyc2-null cyt1-48 strain carrying an A-to-D mutation at the heme-binding site of apocytochrome c1 (Bernard et al. 2005). The fact that Cyc2p becomes essential when the cytochrome c1 heme-binding site carries an A-to-P mutation suggests that the CXXCH motif could be the target of Cyc2p action in vivo. One possible interpretation for this observation is that the P residue alters the reactivity of the cysteinyl thiols to redox chemistry so that the apocytochrome c1 CAPCH heme-binding site occurs in an oxidized (disulfide) form, which must be reduced in a Cyc2p-dependent reaction before heme attachment can occur.In this article, we have undertaken a genetic approach to elucidate this pathway and searched for suppressors that alleviate the respiratory deficiency of the cyc2-null cyt1-34 strain. Either overexpression of CC1HL or replacement of the P mutation in the heme-binding site by H, L, S, or T residues restore the assembly of holocytochrome c1. In vitro measurement of redox potential of apoforms of CA(A/P/T)CH cytochrome c1 indicates that there is no change in the thermodynamic stability of the disulfide at the CXXCH motif that could account for the Cyc2p-dependent assembly of cytochrome c1. Genetic studies reveal that the replacement of the second A residue at the CAACH motif by H, L, P, S, and T residues is key in determining the conversion of apocytochrome c1 to its corresponding holoform via the CCHL and/or CC1HL-dependent pathway. We also demonstrate that Cyc2p is a component dedicated to the CCHL pathway and is not required for the CC1HL-dependent assembly of cytochrome c1. We propose that the CAPCH cytochrome c1 is strictly dependent upon CCHL and Cyc2p for its assembly but becomes a substrate of CC1HL upon overexpression of CC1HL or in the presence of H, L, S, or T mutations. 相似文献
96.
Delphine Martire Sarah Garnier Sébastien Sagnol Annick Bourret Stéphane Marchal Norbert Chauvet Amandine Guérin Dominique Forgues Dominique Berrebi Christophe Chardot Marc Bellaiche John Rendu Nicolas Kalfa Sandrine Faure Pascal de Santa Barbara 《Journal of cellular and molecular medicine》2021,25(8):4028-4039
Smooth Muscle Cells (SMC) are unique amongst all muscle cells in their capacity to modulate their phenotype. Indeed, SMCs do not terminally differentiate but instead harbour a remarkable capacity to dedifferentiate, switching between a quiescent contractile state and a highly proliferative and migratory phenotype, a quality often associated to SMC dysfunction. However, phenotypic plasticity remains poorly examined in the field of gastroenterology in particular in pathologies in which gut motor activity is impaired. Here, we assessed SMC status in biopsies of infants with chronic intestinal pseudo-obstruction (CIPO) syndrome, a life-threatening intestinal motility disorder. We showed that CIPO-SMCs harbour a decreased level of contractile markers. This phenotype is accompanied by an increase in Platelet-Derived Growth Factor Receptor-alpha (PDGFRA) expression. We showed that this modulation occurs without origin-related differences in CIPO circular and longitudinal-derived SMCs. As we characterized PDGFRA as a marker of digestive mesenchymal progenitors during embryogenesis, our results suggest a phenotypic switch of the CIPO-SMC towards an undifferentiated stage. The development of CIPO-SMC culture and the characterization of SMC phenotypic switch should enable us to design therapeutic approaches to promote SMC differentiation in CIPO. 相似文献
97.
Resonance Raman experiments were performed on different green bacteria. With blue excitation, i.e. under Soret resonance or preresonance conditions, resonance Raman contributions were essentially arising from the chlorosome pigments. By comparing these spectra and those of isolated chlorosomes, it is possible to evaluate how the latter retain their native structure during the isolation procedures. The structure of bacteriochlorophyll oligomers in chlorosomes was interspecifically compared, in bacteriochlorophyllc- and bacteriochlorophylle- synthesising bacteria. It appears that interactions assumed by the 9-keto carbonyl group are identical inChlorobium limicola, Chlorobium tepidum, andChlorobium phaeobacteroides. In the latter strain, the 3-formyl carbonyl group of bacteriochlorophylle is kept free from intermolecular interactions. By contrast, resonance Raman spectra unambiguously indicate that the structure of bacteriochlorophyll oligomers is slightly different in chlorosomes fromChloroflexus auranticus, either isolated or in the whole bacteria. 相似文献
98.
Clémentine Thabuis Frédéric Destaillats Jean-François Landrier Delphine Tissot-Favre Jean-Charles Martin 《The Journal of nutritional biochemistry》2010,21(10):922-928
Oleoylethanolamide (OEA) has been previously reported to regulate food intake and body weight gain when administered intraperitoneally. Nevertheless, little information is available with regard to oral administration. To assess whether oral OEA can also exert a similar effect on body fat, we fed C3H mice a high-fat diet supplemented with either 10 or 100 mg/kg body weight OEA for 4 weeks. OEA supplementation significantly lowered food intake over the 4 weeks and decreased adipose tissue mass. Plasma triglyceride levels were also significantly decreased by OEA treatment. In order to identify the potential molecular targets of OEA action, we screened the expression levels of 44 genes related to body fat mass and food intake in peripheral tissues. Adipose tissue fatty acid amide hydrolase (FAAH), intestinal fatty acid transporter/cluster of differentiation 36 and the OEA receptor G-protein-coupled receptor 119 (GPR119) were among the most OEA-responsive genes. They were also associated with reduced body fat pads regardless of the dose. Adipose FAAH was found to be primarily associated with a decrease in food intake. Our data suggest that the anti-obesity activity of OEA partially relies on modulation of the FAAH pathway in adipose tissue. Another mechanism might involve modulation of the newly discovered GPR119 OEA signaling pathway in the proximal intestine. In conclusion, our study indicates that oral administration of OEA can effectively decrease obesity in the mouse model and that modulation of the endocannabinoid fatty acid ethanolamide pathway seems to play an important role both in adipose tissue and in small intestine. 相似文献
99.
100.