Search results for "PTEN"
showing 10 items of 211 documents
Tradition et culte d'Hildegarde
1987
International audience; La tradition d'Hildegarde est diverse. Elle est conservée par quelques monastères, Saint-Arnould de Metz, et d'autres situés en Souabe. L'un de ceux-ci, Kempten, surclassant Saint-Arnould, accapara littéralement le souvenir de Hildegarde à des fins très précises et tenta même de faire reconnaître officiellement sa sainteté vers la fin du XVe siècle. L'affaire échoua. Aussi faut-il dire dès maintenant qu'Hildegarde n'est pas sainte bien qu'elle ait été, dans une zone étroitement délimitée, l'objet d'un culte très réduit qui autorise à la placer parmi les bienheureux. Ce culte doit être considéré comme la conséquence de la tradition d'Hildegarde, que l'on envisagera su…
Mitochondrial dynamics in type 2 diabetes: Pathophysiological implications
2017
Mitochondria play a key role in maintaining cellular metabolic homeostasis. These organelles have a high plasticity and are involved in dynamic processes such as mitochondrial fusion and fission, mitophagy and mitochondrial biogenesis. Type 2 diabetes is characterised by mitochondrial dysfunction, high production of reactive oxygen species (ROS) and low levels of ATP. Mitochondrial fusion is modulated by different proteins, including mitofusin-1 (MFN1), mitofusin-2 (MFN2) and optic atrophy (OPA-1), while fission is controlled by mitochondrial fission 1 (FIS1), dynamin-related protein 1 (DRP1) and mitochondrial fission factor (MFF). PARKIN and (PTEN)-induced putative kinase 1 (PINK1) partici…
PTEN Deletion in Adult Mice Induces Hypoinsulinemia With Concomitant Low Glucose Levels
2022
The PI3K/AKT pathway, negatively regulated by PTEN, plays a paramount role in glucose metabolism regulation due to its activation by the insulin receptor signaling pathway. We generated a PTEN-KO mouse to evaluate the systemic effect of the overactivation of the PI3K/AKT pathway in insulin signaling and glucose homeostasis. Our results demonstrate that PTEN-KO mice show very low glucose levels in the fasted state, which poorly respond to glucose and pyruvate administration. Insulinemia decreased without alterations in pancreatic islets. Among the possible reasons, we uncover the deregulation of the expression of proximal tubule glucose transporter and consequent glycosuria. Moreover, we evi…
Click chemistry-assisted bioconjugates for hapten immunodiagnostics
2020
Bioorthogonal reactions have revolutionized the way low molecular weight compounds are coupled to biomolecules. Organic chemistry, polymer science, and chemical biology are among the disciplines that are benefited the most from this breakthrough. Despite the reliability of the click chemistry concept for the efficient and chemoselective functionalization of biomacromolecules with haptens at preferred positions, the fact that azide–alkyne cycloaddition reactions originate new chemical moieties as part of the linker may have delayed their application in the immunodiagnostic field. Using the mycotoxin ochratoxin A as a model compound, we herein demonstrate for the first time that bioconjugates…
Synthesis of site-heterologous haptens for high-affinity anti-pyraclostrobin antibody generation.
2011
The design and synthesis of functional chemical derivatives of small organic molecules is usually a key step for the intricate production of a variety of bioconjugates. In this respect, the derivatization site at which the spacer arm is introduced in immunizing conjugates constitutes a highly critical parameter for the generation of high-affinity and selective antibodies. However, due to the usual complexity of the required synthetic procedures, the appropriate comparison of alternative tethering positions has often been neglected. In the present study, meticulous strategies were followed to prepare synthetic derivatives of pyraclostrobin with the same linkers located at diverse rationally-…
Design and development of heterologous competitive immunoassays for the determination of boscalid residues
2014
Boscalid is a modern agrochemical belonging to the so-called chemical class of succinate dehydrogenase inhibitor fungicides. With the aim of developing rapid analytical screening methods for this relevant compound, we herein report the synthesis of new boscalid mimics and the study of their suitability for the production of polyclonal antibodies. Aliphatic spacer arms equivalent in length and composition were tethered at two different aromatic rings of the target molecular structure. These haptens, besides being used for immunization, were employed in the development of heterologous competitive enzyme-linked immunosorbent assays (cELISAs) in order to improve assay detectability. Direct and …
Small-angle X-ray Scattering-based Three-dimensional Reconstruction of the Immunogen KLH1 Reveals Different Oxygen-dependent Conformations
2003
For decades the respiratory protein keyhole limpet hemocyanin (KLH1) from the marine gastropod Megathura crenulata has been used widely as a potent immunostimulant, useful hapten carrier, and valuable agent in the treatment of bladder carcinoma. Although much information on the immunological properties of KLH1 is available, biochemical and structural data are still incomplete. Small-angle x-ray scattering revealed the existence of two conformations, an oxy state being slightly more compact than the deoxy state. Based on small-angle scattering curves, a newly developed Monte Carlo algorithm delivered a surface representation of proteins. The massive changes of the surfaces of reconstructed d…
Design, synthesis, and biological evaluation of novel disubstituted dibenzosuberones as highly potent and selective inhibitors of p38 mitogen activat…
2012
Synthesis, biological testing, structure-activity relationships (SARs), and selectivity of novel disubstituted dibenzosuberone derivatives as p38 MAP kinase inhibitors are described. Hydrophilic moieties were introduced at the 7-, 8-, and 9-position of the 2-phenylamino-dibenzosuberones, improving physicochemical properties as well as potency. Extremely potent inhibitors were obtained, with half-maximal inhibitory concentration (IC(50)) values in the low nM range in a whole blood assay measuring the inhibition of cytokine release. The high potency of the target compounds together with the outstanding selectivity of this novel class of compounds toward p38 mitogen activated protein (MAP) kin…
Quenching of fluorescein-conjugated lipids by antibodies. Quantitative recognition and binding of lipid-bound haptens in biomembrane models, formatio…
1992
Three model biomembrane systems, monolayers, micelles, and vesicles, have been used to study the influence of chemical and physical variables of hapten presentation at membrane interfaces on antibody binding. Hapten recognition and binding were monitored for the anti-fluorescein monoclonal antibody 4–4-20 generated against the hapten, fluorescein, in these membrane models as a function of fluorescein-conjugated lipid architecture. Specific recognition and binding in this system are conveniently monitored by quenching of fluorescein emission upon penetration of fluorescein into the antibody's active site. Lipid structure was shown to play a large role in affecting antibody quenching. Interes…
Novel Domino Oxidative Coupling: C−C Bond Formation Sequence to Highly Functionalized Dibenzo[a,c]cycloheptenes
2011
A domino sequence involving various MoCl(5)-mediated oxidations followed by trapping and supposed [3,3]-sigmatropic rearrangement provides a fast access to the full carbon skeleton of metasequirin-B. A variety of different moieties R(1) and R(2) are tolerated.