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51.
Partial Sperm beta1 Integrin Subunit Deletion Proves Its Involvement in Mouse Gamete Adhesion/Fusion
Virginie Barraud-Lange Cme Ialy-Radio Cline Chalas Isabelle Holtzmann Jean-Philippe Wolf Sandrine Barbaux Ahmed Ziyyat 《International journal of molecular sciences》2020,21(22)
We have previously shown, using antibodies, that the sperm alpha6beta1 integrin is involved in mouse gamete fusion in vitro. Here we report the conditional knockdown of the sperm Itgb1 gene. It induced a drastic failure of sperm fusogenic ability with sperm accumulation in the perivitelline space of in vitro inseminated oocytes deleted or not for the Itgb1 gene. These data demonstrate that sperm, but not oocyte, beta1 integrin subunit is involved in gamete adhesion/fusion. Curiously, knockdown males were fertile in vivo probably because of the incomplete Cre-mediated deletion of the sperm Itgb1 floxed gene. Indeed, this was shown by Western blot analysis and confirmed by both the viability and litter size of pups obtained by mating partially sperm Itgb1 deleted males with females producing completely deleted Itgb1 oocytes. Because of the total peri-implantation lethality of Itgb1 deletion in mice, we assume that sperm that escaped the Itgb1 excision seemed to be preferentially used to fertilize in vivo. Here, we showed for the first time that the deletion, even partial, of the sperm Itgb1 gene makes the sperm unable to normally fertilize oocytes. However, to elucidate the question of the essentiality of its role during fertilization, further investigations using a mouse expressing a recombinase more effective in male germ cells are necessary. 相似文献
52.
Mach UR Hackling AE Perachon S Ferry S Wermuth CG Schwartz JC Sokoloff P Stark H 《Chembiochem : a European journal of chemical biology》2004,5(4):508-518
Based on N-alkylated 1,2,3,4-tetrahydroisoquinoline derivatives, which are structurally related to the partial agonist BP 897, a series of novel, selective dopamine D3 receptor antagonists has been synthesised. Derivatisation included changes in the arylamide moiety and the tetrahydroisoquinoline substructure leading to compounds with markedly improved selectivities and affinities in the low nanomolar concentration range. From the 55 structures presented here, (E)-3-(4-iodophenyl)-N-(4-(1,2,3,4-tetrahydroisoquinolin-2-yl)butyl)acrylamide (51) has high affinity (Ki(hD3)=12 nM) and a 123-fold preference for the D3 receptor relative to the D2 receptor subtype. Its pharmacological profile offers the prospect of a novel radioligand as a tool for various dopamine D3-receptor-related in vitro and in vivo investigations. 相似文献
53.
Sandrine Hönig Dietmar Koch Steffen Weber Simon Etzold Thorsten Tonnesen Rainer Telle Nicolas Traon 《International Journal of Applied Ceramic Technology》2019,16(5):1723-1733
The determination of elastic properties at application temperature is fundamental for the design of fibre reinforced ceramic composite components. An attractive method to characterize the flexural modulus at room and high temperature under specific atmosphere is the nondestructive Resonant Frequency Damping Analysis (RFDA). The objective of this paper was to evaluate and validate the modulus measurement via RFDA for orthotropic C/C-SiC composites at the application temperature. At room temperature flexural moduli of C/C-SiC with 0/90° reinforcement were measured under quasi-static 4-point bending loads and compared with dynamic moduli measured via RFDA longitudinally to fibre direction. The dynamic modulus of C/C-SiC was then measured via RFDA up to 1250°C under flowing inert gas and showed an increase with temperature which fitted with literature values. The measured fundamental frequencies were finally compared to those resulting from numerical modal analyses. Dynamic and quasi-static flexural moduli are comparable and the numerical analyses proved that bending modes are correctly modeled by means of dynamic modulus measured via RFDA. The nondestructive RFDA as well as the numerical modeling approach are suitable for evaluation of C/C-SiC and may be transferred to other fibre reinforced ceramic composite materials. 相似文献
54.
Mass spectrometry in metabolome analysis 总被引:12,自引:0,他引:12
55.
Vidu A Dufau L Bannwarth L Soulier JL Sicsic S Piarulli U Reboud-Ravaux M Ongeri S 《ChemMedChem》2010,5(11):1899-1906
Herein we describe the synthesis and HIV-1 protease (PR) inhibitory activity of 16 new peptidomimetic molecular tongs with a naphthalene scaffold. Their peptidic character was progressively decreased. Two of these molecules exhibited the best dimerization inhibition activity toward HIV-1 wild-type and multimutated ANAM-11 proteases obtained to date for this class of molecules (~40?nM for wild-type PR and 100?nM for ANAM-11 PR). Although the peptidic character of one molecular tong was completely suppressed, the mechanism of inhibition and inhibitory potency toward both proteases were maintained. 相似文献
56.
Vial S Mansuy C Sagan S Irinopoulou T Burlina F Boudou JP Chassaing G Lavielle S 《Chembiochem : a European journal of chemical biology》2008,9(13):2113-2119
Nanodiamonds that were prepared by high pressure/high temperature were functionalized with biomolecules for biological applications. Nanodiamonds (NDs, < or =35 nm) that were coated by silanization or with polyelectrolyte layers were grafted with a fluorescent thiolated peptide via a maleimido function; this led to an aqueous colloidal suspension that was stable for months. These substituted NDs were not cytotoxic for CHO cells. Their capacity to enter mammalian cells, and their localisation inside were ascertained after labelling the nucleus and actin, by examining the cells by confocal, reflected light and fluorescence microscopy. 相似文献
57.
The fatty acid composition of the seeds from Agathis robusta, an Australian gymnosperm (Araucariaceae), was determined by a combination of chromatographic and spectrometric techniques.
These enabled the identification of small amounts of arachidonic (5,8,11,14–20∶4) and eicosapentaenoic (5,8,11,14,17–20∶5)
acid for the first time in the seed oil of a higher plant. They were apparently derived from γ-linolenic (6,9,12–18∶3) and
stearidonic (6,9,12,15–18∶4) acids, which were also present, via chain elongation and desaturation, together with other expected biosynthetic intermediates [bis-homo-γ-linolenic (8,11,14–20∶3)
and bishomo-stearidonic (8,11,14,17–20∶4) acids]. Also present were a number of C20 fatty acids, known to occur in most gymnosperm families, i.e., 5,11–20∶2, 11,14–20∶2 (bishomo-linoleic), 5,11,14–20∶3 (sciadonic),
11,14,17–20∶3 (bishomo-α-linolenic), and 5,11,14,17–20∶4 (juniperonic) acids. In contrast to most other gymnosperm seed lipids
analyzed so far, A. robusta seed lipids did not contain C18 Δ5-desaturated acids [i.e., 5,9–18∶2 (taxoleic), 5,9,12–18∶3 (pinolenic), or 5,9,12,15–18∶4 (coniferonic)]. These structures
support the simultaneous existence of Δ6- and Δ5-desaturase activities in A. robusta seeds. The Δ6-ethylenic bond is apparently introduced into C18 polyunsaturated acids, whereas the Δ5-ethylenic bond is introduced into C20 polyunsaturated acids. A general metabolic pathway for the biosynthesis of unsaturated fatty acids in gymnosperm seeds is
proposed. When compared to Bryophytes, Pteridophytes (known to contain arachidonic and eicosapentaenoic acids), and species
from other gymnosperm families (without such acids), A. robusta appears as an “intermediate,” with the C18 Δ6-desaturase/C18→C20 elongase/C20 Δ5-desaturase system in common with the former subphyla, and the unsaturated C18→C20 elongase/C20 Δ5-desaturase system specific to gymnosperms. The following hypothetical evolutionary sequence for the C18 Δ6/Δ5-desaturase class in gymnosperm seeds is suggested: Δ6 (initial)→Δ6/Δ5 (intermediate)→Δ5 (final). 相似文献
58.
Stéphane Mathieu Lionel Aranda Léo Portebois Sandrine Mathieu Michel Vilasi 《Oxidation of Metals》2018,90(1-2):43-63
The short-term oxidation behaviour of RA 602CA, Inconel 693, Manaurite 40XO and Sumitomo 696, which are four alloys recommended for hydrocarbon processing, was studied both in air and in Ar–H2O to determine the conditions of pre-oxidation treatments. Regardless of the considered material, the oxidation rate at 950 °C was systematically higher in Ar–H2O than in dry air. Surface examination of the Al-containing alloys indicated that they were not uniformly oxidized all over the surface. All Al-containing alloys (from 1.6 to 3.2% wt) formed an external protective alumina scale and behaved as alumina-forming alloys in dry air at 950 °C. In contrast, these alloys developed a rate-controlling chromia scale and severe internal oxidation in a H2O-containing atmosphere. Compared with their oxidation behaviour in air + H2O, the phenomenon was significantly enhanced in the atmosphere that coupled water vapour with a low oxygen pressure. Consequently, the Al-containing alloys should not be pre-oxidized in a water vapour atmosphere prior to long exposure to a corrosive atmosphere. In contrast, the chromia-forming Al-free 696 alloy exhibited identical oxidation behaviour in both atmospheres, demonstrating that the degradation of this alloy was not significantly affected by water vapour. 相似文献
59.
Pauline V. Marck Marco T. Pessoa Yunhui Xu Laura C. Kutz Dominic M. Collins Yanling Yan Cierra King Xiaoliang Wang Qiming Duan Liquan Cai Jeffrey X. Xie Jerry B. Lingrel Zijian Xie Jiang Tian Sandrine V. Pierre 《International journal of molecular sciences》2021,22(7)
The Na/K-ATPase is the specific receptor for cardiotonic steroids (CTS) such as ouabain and digoxin. At pharmacological concentrations used in the treatment of cardiac conditions, CTS inhibit the ion-pumping function of Na/K-ATPase. At much lower concentrations, in the range of those reported for endogenous CTS in the blood, they stimulate hypertrophic growth of cultured cardiac myocytes through initiation of a Na/K-ATPase-mediated and reactive oxygen species (ROS)-dependent signaling. To examine a possible effect of endogenous concentrations of CTS on cardiac structure and function in vivo, we compared mice expressing the naturally resistant Na/K-ATPase α1 and age-matched mice genetically engineered to express a mutated Na/K-ATPase α1 with high affinity for CTS. In this model, total cardiac Na/K-ATPase activity, α1, α2, and β1 protein content remained unchanged, and the cardiac Na/K-ATPase dose–response curve to ouabain shifted to the left as expected. In males aged 3–6 months, increased α1 sensitivity to CTS resulted in a significant increase in cardiac carbonylated protein content, suggesting that ROS production was elevated. A moderate but significant increase of about 15% of the heart-weight-to-tibia-length ratio accompanied by an increase in the myocyte cross-sectional area was detected. Echocardiographic analyses did not reveal any change in cardiac function, and there was no fibrosis or re-expression of the fetal gene program. RNA sequencing analysis indicated that pathways related to energy metabolism were upregulated, while those related to extracellular matrix organization were downregulated. Consistent with a functional role of the latter, an angiotensin-II challenge that triggered fibrosis in the α1r/rα2s/s mouse failed to do so in the α1s/sα2s/s. Taken together, these results are indicative of a link between circulating CTS, Na/K-ATPase α1, ROS, and physiological cardiac hypertrophy in mice under baseline laboratory conditions. 相似文献
60.
Alfonso Martín-Bernab Josep Tarrag-Celada Valrie Cunin Sylvie Michelland Roldn Corts Johann Poignant Cyril Boyault Walid Rachidi Sandrine Bourgoin-Voillard Marta Cascante Michel Seve 《International journal of molecular sciences》2021,22(7)
Growing evidence is showing that acetylation plays an essential role in cancer, but studies on the impact of KDAC inhibition (KDACi) on the metabolic profile are still in their infancy. Here, we analyzed, by using an iTRAQ-based quantitative proteomics approach, the changes in the proteome of KRAS-mutated non-small cell lung cancer (NSCLC) A549 cells in response to trichostatin-A (TSA) and nicotinamide (NAM) under normoxia and hypoxia. Part of this response was further validated by molecular and biochemical analyses and correlated with the proliferation rates, apoptotic cell death, and activation of ROS scavenging mechanisms in opposition to the ROS production. Despite the differences among the KDAC inhibitors, up-regulation of glycolysis, TCA cycle, oxidative phosphorylation and fatty acid synthesis emerged as a common metabolic response underlying KDACi. We also observed that some of the KDACi effects at metabolic levels are enhanced under hypoxia. Furthermore, we used a drug repositioning machine learning approach to list candidate metabolic therapeutic agents for KRAS mutated NSCLC. Together, these results allow us to better understand the metabolic regulations underlying KDACi in NSCLC, taking into account the microenvironment of tumors related to hypoxia, and bring new insights for the future rational design of new therapies. 相似文献