Genetic polymorphisms of MMP1, MMP3 and MMP7 gene promoter and risk of colorectal adenoma

BACKGROUND: Matrix metalloproteinases (MMP) have been shown to play a role in colorectal cancer (CRC). More recently, MMP1, MMP3 and MMP7 functional gene promoter polymorphisms have been found to be associated with CRC occurrence and prognosis. To document the role of MMP polymorphisms in the early step of colorectal carcinogenesis, we investigated their association with colorectal adenoma risk in a case-control study comprising 295 patients with large adenomas (LA), 302 patients with small adenomas (SA) and 568 polyp-free (PF) controls. METHODS: Patients were genotyped using automated fragment analysis for MMP1 -1607 ins/del G and MMP3 -1612 ins/delA (MMP3.1) polymorphisms and allelic discrimination assay for MMP3 -709 A/G (MMP3.2) and MMP7 -181 A/G polymorphisms. Association between MMP genotypes and colorectal adenomas was first tested for each polymorphism separately and then for combined genotypes using the combination test. Adjustment on relevant variables and estimation of odds ratios were performed using unconditional logistic regression. RESULTS: No association was observed between the polymorphisms and LA when compared to PF or SA. When comparing SA to PF controls, analysis revealed a significant association between MMP3 -1612 ins/delA polymorphism and SA with an increased risk associated with the 6A/6A genotype (OR = 1.67, 95%CI: 1.20–2.34). Using the combination test, the best association was found for MMP3.1-MMP1 (p = 0.001) with an OR of 1.88 (95%CI: 1.08–3.28) for the combined genotype 2G/2G-6A/6A estimated by logistic regression. CONCLUSION: These data show a relation between MMP1 -1607 ins/del G and MMP3 -1612 ins/delA combined polymorphisms and risk of SA, suggesting their potential role in the early steps of colorectal carcinogenesis

DNA methylation and histone acetylation: genotypic variations in hybrid poplars, impact of water deficit and relationships with productivity

Several reports on annual plants have already shown the involvement of epigenetic modifiers such as DNA methylation in their adaptation to abiotic stresses. Nevertheless, the genotypic variations of epigenetic modifiers, their possible correlations with morphological traits and the impact of water deficit have not been described for perennial plants. Six genotypes of Populus deltoides × P. nigra were subjected or not to a moderate water deficit treatment. Various morphological traits such as the height of the plants, their biomass and the total leaf area were measured to characterize the productivity in both conditions. Levels of DNA methylation, histone acetylation and the activities and isoform accumulation of the corresponding enzymes were measured at the shoot apex, the site of morphogenesis. Genotypic variation was observed for the morphological traits and the epigenetic variables and correlations were established among them. Genotypic variation for DNA methylation was detected in hybrid poplars. A positive correlation was demonstrated between DNA methylation percentage and productivity under well watered conditions. While there was a general decrease of growth for all genotypes in response to a moderate water deficit, genotypic dependant variations of DNA methylation were found suggesting different strategies among hybrids.Plusieurs études sur des plantes annuelles ont déjà montré l’implication des modifications épigénétiques telles que la méthylation de l’ADN dans la plasticité de leurs réponses aux contraintes abiotiques. Néanmoins, les variations génotypiques de ces modifications épigénétiques, leur possible corrélation avec des variables de croissance et l’impact d’un déficit hydrique n’ont pas été décrits sur une plante pérenne. Six génotypes de Populus deltoïdes × P. nigra ont été soumis ou non à un déficit hydrique modéré et plusieurs variables de croissance ont été mesurées afin de caractériser leur productivité. Les niveaux de méthylation de l’ADN, d’acétylation des histones, les activités enzymatiques et l’accumulation des isoformes correspondantes ont été mesurés sur des apex caulinaires, site de la morphogenèse. Des variations génotypiques ont été observées pour les variables de croissance et épigénétiques. Une corrélation positive a été mise en évidence entre la méthylation de l’ADN et la productivité en condition hydrique favorable. Bien qu’il y ait une diminution générale de la croissance de tous les génotypes en réponse à un déficit hydrique modéré, des variations génotype-dépendant de la méthylation de l’ADN ont été trouvées suggérant différentes stratégies entre hybrides

Structure-based optimization of a PDZ binding motif within a viral peptide stimulates neurite outgrowth

International audienceProtection of neuronal homeostasis is a major goal in the management of neurodegenerative diseases. Microtubule-associated Ser/Thre kinase 2 (MAST2), inhibits neurite outgrowth, and its inhibition therefore represents a potential therapeutic strategy. We previously reported that a viral protein (G-protein from rabies virus) capable of interfering with protein-protein interactions between the PDZ domain of MAST2 and the C-terminal moieties of its cellular partners counteracts MAST2-mediated suppression of neurite outgrowth. Here, we designed peptides derived from the native viral protein to increase the affinity of these peptides for the MAST2 PDZ domain. Our strategy involved modifying the length and flexibility of the non-interacting sequence linking the two subsites anchoring the peptide to the PDZ domain. Three peptides, Neurovita1 (NV1), NV2, and NV3, were selected, and we found that they all had increased affinities for the MAST2 PDZ domain, with Kd values decreasing from 1300 to 60 nM, while target selectivity was maintained. A parallel biological assay evaluating neurite extension and branching in cell cultures revealed that the NV peptides gradually improved neural activity, with the efficacies of these peptides for stimulating neurite outgrowth mirroring their affinities for MAST2-PDZ. We also show that NVs can be delivered into the cytoplasm of neurons as a gene or peptide. In summary, our findings indicate that virus-derived peptides targeted to MAST2-PDZ stimulate neurite outgrowth in several neuron types, opening up promising avenues for potentially using NVs in the management of neurodegenerative diseases

Ultra-High-Field 67 Zn and 33 S NMR Studies Coupled with DFT Calculations Reveal the Structure of ZnS Nanoplatelets Prepared by an Organometallic Approach

Herein, we report the successful characterization of sulfur vacancies in ZnS nanoplatelets by in-depth high-field and DNP-enhanced solid-state NMR of 33S and 67Zn nuclei and DFT modeling. This two-dimensional 1 nm-thick nanomaterial was obtained by reacting a dicyclohexyl zinc complex, ZnCy2, with (TMS)2S as the S source under mild conditions (45 °C) in dodecylamine. The joint experimental and theoretical studies on these nanoplatelets evidenced that a large fraction of the Zn and S atoms are located near the surface covered by dodecylamine and that the deviation from stoichiometry (agreeing with energy gap and photoluminescence properties of non-stoichiometric material) is due to sulfur vacancies. Additionally, this work reports the first 33S DNP-NMR spectrum reported in the literature alongside several ultra-high-field 33S and 67Zn solid-state NMR spectra

Function of the fires of the cave Chauvet-Pont d’Arc: contributions of the experiment and the digital simulation

International audienc