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71.
72.
Marek Jindra Mirka Uhlirova Jean-Philippe Charles Vlastimil Smykal Ronald J. Hill 《PLoS genetics》2015,11(7)
Juvenile hormones (JHs) play a major role in controlling development and reproduction in insects and other arthropods. Synthetic JH-mimicking compounds such as methoprene are employed as potent insecticides against significant agricultural, household and disease vector pests. However, a receptor mediating effects of JH and its insecticidal mimics has long been the subject of controversy. The bHLH-PAS protein Methoprene-tolerant (Met), along with its Drosophila melanogaster paralog germ cell-expressed (Gce), has emerged as a prime JH receptor candidate, but critical evidence that this protein must bind JH to fulfill its role in normal insect development has been missing. Here, we show that Gce binds a native D. melanogaster JH, its precursor methyl farnesoate, and some synthetic JH mimics. Conditional on this ligand binding, Gce mediates JH-dependent gene expression and the hormone''s vital role during development of the fly. Any one of three different single amino acid mutations in the ligand-binding pocket that prevent binding of JH to the protein block these functions. Only transgenic Gce capable of binding JH can restore sensitivity to JH mimics in D. melanogaster Met-null mutants and rescue viability in flies lacking both Gce and Met that would otherwise die at pupation. Similarly, the absence of Gce and Met can be compensated by expression of wild-type but not mutated transgenic D. melanogaster Met protein. This genetic evidence definitively establishes Gce/Met in a JH receptor role, thus resolving a long-standing question in arthropod biology. 相似文献
73.
Eliane Berrou Alexandre Kauskot Frédéric Adam Amélie Harel Paulette Legendre Cécile Lavenu Bombled Chantal Rothschild Nicolas Prevost Olivier D. Christophe Peter J. Lenting Cécile V. Denis Jean-Philippe Rosa Marijke Bryckaert 《PloS one》2015,10(12)
Thrombocytopenia and increased platelet clearance observed in von Willebrand disease-type 2B (VWD-2B) may be explained by platelet apoptosis triggered by the constitutive binding of VWF to its receptor, glycoprotein Ib (GPIb). Apoptosis was assessed in platelets from two patients with a severe VWD-2B mutation VWF/p.V1316M and from mice transiently expressing VWF/p.V1316M. We now report that the VWD-2B mutation VWF/p.V1316M which binds spontaneously to its receptor GPIbα does not induce apoptosis. In 2 unrelated patients (P1 and P2) exhibiting different VWF plasma levels (70% and 36%, respectively, compared with normal pooled human plasma given as 100%), inner transmembrane depolarization of mitochondria, characteristic of apoptotic events was undetectable in platelets, whether washed or in whole blood. No or a moderate phosphatidyl serine (PS) exposure as measured by annexin-V staining was observed for P1 and P2, respectively. Expression of pro-apoptotic proteins Bak and Bax, and caspase-3 activity were similar to control platelets. In the VWD-2B mouse model expressing high levels of mVWF/p.V1316M (423%), similar to what is found in inflammatory pathologies, no significant difference was observed between mice expressing mVWF/WT and mVWF/p.V1316M. These results strongly argue against apoptosis as a mechanism for the thrombocytopenia of severe VWD-2B exhibiting the VWF/p.V1316M mutation. 相似文献
74.
75.
76.
Mathieu Muller Dominique Patureau Jean-Jacques Godon Jean-Philippe Delgenès Guillermina Hernandez-Raquet 《Applied microbiology and biotechnology》2010,85(3):691-701
The biodegradation of estradiol (E2), estrone (E1), and ethinylestradiol (EE2) was investigated using mixed bacterial cultures
enriched from activated sludge. Enrichments were carried out on E2 or EE2 in batch conditions with acetonitrile as additional
carbon source. Degradation experiments were performed both using hormones as sole carbon source or with an additional source.
The hormones were completely degraded by these cultures. Estradiol was rapidly converted to E1 within 24 h. Thereafter, E1
degradation began, displaying a lag phase ranging from 3 to 4 days. Estrone depletion took from 48 h to more than 6 days,
depending on the culture conditions. For EE2 degradation, when it was the sole carbon source, the lag phase and the time required
for its complete removal (7 and 15 days, respectively) were shorter that in cultures with a supplementary carbon source. The
specific degradation rates observed for E2 both with and without an additional carbon source were similar. By contrast, the
specific degradation rates for E1 and EE2 were, respectively, seven and 20 times faster when these hormones were supplied
as the sole carbon source. The bacterial community structure of each culture was characterized by molecular and cultural methods.
The mixed cultures were made up of species belonging to Alcaligenes faecalis, Pusillimonas sp., Denitrobacter sp., and Brevundimonas diminuta or related to uncultured Bacteroidetes. The isolated strain B. diminuta achieved the conversion of E2 to E1. 相似文献
77.
Denis Monneret Jean-Louis Pepin Diane Godin-Ribuot Veronique Ducros Jean-Philippe Baguet Patrick Levy Patrice Faure 《Free radical biology & medicine》2010,48(4):619-625
Obstructive sleep apnea (OSA) is characterized by recurrent apnea during sleep that may unbalance oxidative stress, increasing atherosclerosis. Among oxidative stress markers, 15-F2t-isoprostane is considered one of the most sensitive and specific metabolites of lipid peroxidation. To explore the relationship between urinary 15-F2t-isoprostane with sleep apnea severity and carotid modifications in nonobese OSA patients, 31 nonobese sleep apnea patients were studied, along with 10 lean subjects without OSA. Patients were assessed by polysomnography, blood pressure measurement, and ultrasonography to determine the carotid intima–media thickness (IMT). Urinary 15-F2t-isoprostanes were measured by liquid chromatography–tandem mass spectrometry. Urinary 15-F2t-isoprostane concentrations were increased in severe OSA patients compared to control subjects (20.2 ± 7.3 vs 12.3 ± 2.8 ng/mmol creatinine; P = 0.020). Mean carotid IMT was correlated with 15-F2t-isoprostane (r = 0.532; P < 0.001) and with the apnea–hypopnea index (r = 0.345; P = 0.029). 15-F2t-Isoprostane level was related to the night time spent at SaO2 < 90% (r = 0.478; P = 0.002), the apnea–hypopnea index (r = 0.465; P = 0.003), and the mean nocturnal SaO2 (r = ? 0.424; P = 0.007). These results showed a relationship between lipid peroxidation, carotid intima–media thickness, and intermittent hypoxia in nonobese OSA patients, thus reinforcing the hypothesis that oxidative stress could be involved in the early atherosclerotic process. 相似文献
78.
79.
Fichet G Comoy E Dehen C Challier L Antloga K Deslys JP McDonnell G 《Journal of microbiological methods》2007,70(3):511-518
Prions are unique infectious agents which have been shown to be transmitted iatrogenically through contaminated surfaces. Surface contamination is a concern on reusable medical devices and various industrial surfaces, but there is currently no standard, accepted model to evaluate surface prion decontamination. In this report, a set of both in vitro and in vivo methods were investigated based on the contamination of surface through artificial exposure to infected brain. An in vitro surface contamination protocol was developed with subsequent biochemical detection of the prion protein (PrPres). In parallel, the in vivo investigations included the contamination of different types of surface materials (stainless steel or plastic wires) with different prion strains (scrapie strain adapted to hamsters 263K or bovine spongiform encephalopathy strain adapted to mouse 6PB1). The in vivo models with various prion strains and brain homogenate dilutions reproducibly transmitted the disease and a relationship was established between the infectivity titre, the transmission rate and the incubation period. Moreover, the in vivo models were studied for their ability to demonstrate the efficacy of heat and chemical-based decontamination methods, with similar results. The in vivo scrapie method described is proposed as a standard to evaluate existing and developing prion decontamination technologies. 相似文献
80.
Activation of a dimeric metabotropic glutamate receptor by intersubunit rearrangement 总被引:1,自引:0,他引:1
Brock C Oueslati N Soler S Boudier L Rondard P Pin JP 《The Journal of biological chemistry》2007,282(45):33000-33008
Although many G protein-coupled receptors (GPCRs) can form dimers, a possible role of this phenomenon in their activation remains elusive. A recent and exciting proposal is that a dynamic intersubunit interplay may contribute to GPCR activation. Here, we examined this possibility using dimeric metabotropic glutamate receptors (mGluRs). We first developed a system to perfectly control their subunit composition and show that mGluR dimers do not form larger oligomers. We then examined an mGluR dimer containing one subunit in which the extracellular agonist-binding domain was uncoupled from the G protein-activating transmembrane domain. Despite this uncoupling in one protomer, agonist stimulation resulted in symmetric activation of either transmembrane domain in the dimer with the same efficiency. This, plus other data, can only be explained by an intersubunit rearrangement as the activation mechanism. Although well established for other types of receptors such as tyrosine kinase and guanylate cyclase receptors, this is the first clear demonstration that such a mechanism may also apply to GPCRs. 相似文献