222 research outputs found
Etude in vitro de l’effet des tanins de Newbouldia laevis et de Zanthoxylum zanthoxyloïdes sur la migration des larves infestantes de Haemonchus contortus
Dans le but d’aborder le mécanisme d’action des extraits acétoniques et éthanoliques de Newbouldia laevis (Bignoniaceae) et de Zanthoxylum zanthoxyloïdes (Rutaceae), leur effet inhibiteur a été évalué in vitro sur la migration larvaire de Haemonchus contortus. Le test d’inhibition de la migration larvaire (LMI) a été appliqué sur les larves infestantes (L3), âgées de 2 à 3 mois incubées avec des extraits végétaux à différentes concentrations : 150, 300, 600 et 1200 μg/mL mis ou non en contact avec la polyvinylpolypyrrolidone (PVPP). Un témoin négatif (tampon PBS) a été inclus dans chaque test. L’observation sous microscope et le dénombrement des L3 ayant migré par rapport au nombre total de larves déposées dans l’insert ont permis de calculer le taux de la migration larvaire. Les extraits de Newbouldia laevis et de Zanthoxylum zanthoxyloïdes inhibent in vitro la migration larvaire de Haemonchus contortus. Cet effet est dose-dépendant (p<0,001). Les extraits hydroéthanoliques ont eu plus d’effet surtout aux fortes doses. Le contact des extraits des plantes avec la polyvinylpolypyrrolidone (PVPP) annule tout ou une partie de l’effet anthelminthique des extraits. Ces résultats suggèrent que l’inhibition de la migration larvaire est en partie due à l’action des tanins. Le pourcentage d’inhibition dû aux tanins est de 28,60% quel que soit la plante et quel que soit le solvant d’extraction.Keywords: Haemonchus contortus, migration larvaire, tanins, Zanthoxylum zanthoxyloïdes, Newbouldia laevis, Béni
The Multifunctional Sorting Protein PACS-2 Controls Mitophagosome Formation in Human Vascular Smooth Muscle Cells through Mitochondria-ER Contact Sites.
Mitochondria-associated ER membranes (MAMs) are crucial for lipid transport and synthesis, calcium exchange, and mitochondrial functions, and they also act as signaling platforms. These contact sites also play a critical role in the decision between autophagy and apoptosis with far reaching implications for cell fate. Vascular smooth muscle cell (VSMC) apoptosis accelerates atherogenesis and the progression of advanced lesions, leading to atherosclerotic plaque vulnerability and medial degeneration. Though the successful autophagy of damaged mitochondria promotes VSMC survival against pro-apoptotic atherogenic stressors, it is unknown whether MAMs are involved in VSMC mitophagy processes. Here, we investigated the role of the multifunctional MAM protein phosphofurin acidic cluster sorting protein 2 (PACS-2) in regulating VSMC survival following a challenge by atherogenic lipids. Using high-resolution confocal microscopy and proximity ligation assays, we found an increase in MAM contacts as in PACS-2-associated MAMs upon stimulation with atherogenic lipids. Correspondingly, the disruption of MAM contacts by PACS-2 knockdown impaired mitophagosome formation and mitophagy, thus potentiating VSMC apoptosis. In conclusion, our data shed new light on the significance of the MAM modulatory protein PACS-2 in vascular cell physiopathology and suggest MAMs may be a new target to modulate VSMC fate and favor atherosclerotic plaque stability
Re-evaluating early breast neoplasia
Historically, histomorphological and epidemiological data suggested that atypical ductal hyperplasia and ductal carcinoma in situ are the earliest recognizable neoplastic stages of breast cancer progression. Over the past several years, detailed high-throughput molecular genetic, gene expression and epigenetic analyses have enhanced our understanding of these early neoplastic lesions and have re-shaped our view of human breast cancer progression to include multiple distinct pathways of evolution
Smooth extensions of functions on separable Banach spaces
Let be a Banach space with a separable dual . Let be
a closed subspace, and a -smooth function. Then we
show there is a extension of to .Comment: 19 pages. This version fixes a gap in the previous proof of Theorem 1
by providing a sharp version of Lemma
Rubredoxin from Clostridium thermosaccharolyticum. Amino acid sequence, mass-spectrometric and preliminary crystallographic data
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A BRCA1 deficient-like signature is enriched in breast cancer brain metastases and predicts DNA damage-induced poly (ADP-ribose) polymerase inhibitor sensitivity
Introduction: There is an unmet clinical need for biomarkers to identify breast cancer patients at an increased risk of developing brain metastases. The objective is to identify gene signatures and biological pathways associated with human epidermal growth factor receptor 2-positive (HER2+) brain metastasis. Methods: We combined laser capture microdissection and gene expression microarrays to analyze malignant epithelium from HER2+ breast cancer brain metastases with that from HER2+ nonmetastatic primary tumors. Differential gene expression was performed including gene set enrichment analysis (GSEA) using publicly available breast cancer gene expression data sets. Results: In a cohort of HER2+ breast cancer brain metastases, we identified a gene expression signature that anti-correlates with overexpression of BRCA1. Sequence analysis of the HER2+ brain metastases revealed no pathogenic mutations of BRCA1, and therefore the aforementioned signature was designated BRCA1 Deficient-Like (BD-L). Evaluation of an independent cohort of breast cancer metastases demonstrated that BD-L values are significantly higher in brain metastases as compared to other metastatic sites. Although the BD-L signature is present in all subtypes of breast cancer, it is significantly higher in BRCA1 mutant primary tumors as compared with sporadic breast tumors. Additionally, BD-L signature values are significantly higher in HER2-/ER- primary tumors as compared with HER2+/ER + and HER2-/ER + tumors. The BD-L signature correlates with breast cancer cell line pharmacologic response to a combination of poly (ADP-ribose) polymerase (PARP) inhibitor and temozolomide, and the signature outperformed four published gene signatures of BRCA1/2 deficiency. Conclusions: A BD-L signature is enriched in HER2+ breast cancer brain metastases without pathogenic BRCA1 mutations. Unexpectedly, elevated BD-L values are found in a subset of primary tumors across all breast cancer subtypes. Evaluation of pharmacological sensitivity in breast cancer cell lines representing all breast cancer subtypes suggests the BD-L signature may serve as a biomarker to identify sporadic breast cancer patients who might benefit from a therapeutic combination of PARP inhibitor and temozolomide and may be indicative of a dysfunctional BRCA1-associated pathway
Spectroscopic investigations of a semi-synthetic [FeFe] hydrogenase with propane di-selenol as bridging ligand in the binuclear subsite: comparison to the wild type and propane di-thiol variants
[FeFe] Hydrogenases catalyze the reversible conversion of H2 into electrons and protons. Their catalytic site, the H-cluster, contains a generic [4Fe–4S]H cluster coupled to a [2Fe]H subsite [Fe2(ADT)(CO)3(CN)2]2−, ADT = µ(SCH2)2NH. Heterologously expressed [FeFe] hydrogenases (apo-hydrogenase) lack the [2Fe]H unit, but this can be incorporated through artificial maturation with a synthetic precursor [Fe2(ADT)(CO)4(CN)2]2−. Maturation with a [2Fe] complex in which the essential ADT amine moiety has been replaced by CH2 (PDT = propane-dithiolate) results in a low activity enzyme with structural and spectroscopic properties similar to those of the native enzyme, but with simplified redox behavior. Here, we study the effect of sulfur-to-selenium (S-to-Se) substitution in the bridging PDT ligand incorporated in the [FeFe] hydrogenase HydA1 from Chlamydomonas reinhardtii using magnetic resonance (EPR, NMR), FTIR and spectroelectrochemistry. The resulting HydA1-PDSe enzyme shows the same redox behavior as the parent HydA1-PDT. In addition, a state is observed in which extraneous CO is bound to the open coordination site of the [2Fe]H unit. This state was previously observed only in the native enzyme HydA1-ADT and not in HydA1-PDT. The spectroscopic features and redox behavior of HydA1-PDSe, resulting from maturation with [Fe2(PDSe)(CO)4(CN)2]2−, are discussed in terms of spin and charge density shifts and provide interesting insight into the electronic structure of the H-cluster. We also studied the effect of S-to-Se substitution in the [4Fe–4S] subcluster. The reduced form of HydA1 containing only the [4Fe–4Se]H cluster shows a characteristic S = 7/2 spin state which converts back into the S = 1/2 spin state upon maturation with a [2Fe]–PDT/ADT complex
An unusual occurrence of Kleine-Levin syndrome in a man with refractory immune thrombocytopenic purpura: a case report
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