ISL1 Directly Regulates FGF10 Transcription during Human Cardiac Outflow Formation

The LIM homeodomain gene Islet-1 (ISL1) encodes a transcription factor that has been associated with the multipotency of human cardiac progenitors, and in mice enables the correct deployment of second heart field (SHF) cells to become the myocardium of atria, right ventricle and outflow tract. Other markers have been identified that characterize subdomains of the SHF, such as the fibroblast growth factor Fgf10 in its anterior region. While functional evidence of its essential contribution has been demonstrated in many vertebrate species, SHF expression of Isl1 has been shown in only some models. We examined the relationship between human ISL1 and FGF10 within the embryonic time window during which the linear heart tube remodels into four chambers. ISL1 transcription demarcated an anatomical region supporting the conserved existence of a SHF in humans, and transcription factors of the GATA family were co-expressed therein. In conjunction, we identified a novel enhancer containing a highly conserved ISL1 consensus binding site within the FGF10 first intron. ChIP and EMSA demonstrated its direct occupation by ISL1. Transcription mediated by ISL1 from this FGF10 intronic element was enhanced by the presence of GATA4 and TBX20 cardiac transcription factors. Finally, transgenic mice confirmed that endogenous factors bound the human FGF10 intronic enhancer to drive reporter expression in the developing cardiac outflow tract. These findings highlight the interest of examining developmental regulatory networks directly in human tissues, when possible, to assess candidate non-coding regions that may be responsible for congenital malformations

Notes de lecture

Pinson Daniel, De Tapia Stéphane. Notes de lecture. In: Revue européenne des migrations internationales, vol. 9, n°2,1993. pp. 137-139

L’appel à projets urbains « 50 000 logements » à Bordeaux : la mise en échec de la métropole stratège

Article de revue en ligneLes appels à projets urbains se développent au-delà du Grand Paris, comme à Bordeaux, où la démarche est mobilisée dès le début des années 2010. En décrivant la genèse et la mise en œuvre de ce dispositif, cet article souligne les difficultés qu’il génère dans la conduite d’une stratégie métropolitaine

Utility of 18F-FDG PET with a Semi-Quantitative Index in the Detection of Sarcomatous Transformation in Patients with Neurofibromatosis Type 1

International audienceBackground: Malignant peripheral nerve sheath tumors (MPNSTs) are a serious complications of neurofibromatosis type 1 associated with poor prognosis and deeper lesions can be difficult to diagnose. 18-FDG PET improves the detection of malignancies. However, the criteria for malignancy, notably the SUVmax threshold, are not standardized. Therefore, the aim of the study was to evaluate a semi-quantitative index for the reproducible detection of MPNST with FDG PET.Methods: It is a multicenter retrospective study conducted between 2000 to 2012. All patients with NF1 referred for suspected MPNST underwent PET. Since SUVmax was not available until 2004 in our centers, we had to settle for the semi-quantitative method used at that time, the uptake ratio between the tumor and the normal liver (T/L ratio) with 1.5 as the cut-off for malignancy. When dedicated PET with SUVmax became available, the semi-quantitative analysis of PET images remained, along with SUVmax.Results: 113 patients with 145 tumors were included. PET assessment revealed 65 suspected lesions with T/L >1.5 and among these, 40 were MPNSTs. 80 tumors were classified as non-suspicious, and 79 were benign. The 1.5 T/L cut-off had a negative predictive value (NPV) of 98,8% and a positive predictive value of 61,5%. The positive likelihood ratio (LR) was 4,059, the negative LR was 0,032 with 97% sensitivity and 76% specificity.Conclusions: This study, which is among the largest published, confirms the utility of PET for detecting NF1-associated MPNSTs. A semi-quantitative index, the T/L ratio with a cut-off of 1.5, allowed sensitive and specific differentiation of malignant from benign tumors better than SUVmax. When T/L was 1.5, there was a strong suspicion of malignancy. This semi-quantitative analytical method is as simple as SUVmax, but is more sensitive, more reproducible and non-user-dependen

Bioguided isolation, characterization, and biotransformation by Fusarium verticillioides of maize kernel compounds that inhibit fumonisin production

Fusarium verticillioides infects maize ears, causing ear rot disease and contamination of grain with fumonisin mycotoxins. This contamination can be reduced by the presence of bioactive compounds in kernels that are able to inhibit fumonisin biosynthesis. To identify such compounds, we used kernels from a maize genotype with moderate susceptibility to F. verticillioides, harvested at the milk-dough stage (i.e., when fumonisin production initiates in planta), and applied a bioguided fractionation approach. Chlorogenic acid was the most abundant compound in the purified active fraction and its contribution to fumonisin inhibitory activity was up to 70%. Moreover, using a set of maize genotypes with different levels of susceptibility, chlorogenic acid was shown to be significantly higher in immature kernels of the moderately susceptible group. Altogether, our data indicate that chlorogenic acid may considerably contribute to either maize resistance to Fusarium ear rot, fumonisin accumulation, or both. We further investigated the mechanisms involved in the inhibition of fumonisin production by chlorogenic acid and one of its hydrolyzed products, caffeic acid, by following their metabolic fate in supplemented F. verticillioides broths. Our data indicate that F. verticillioides was able to biotransform these phenolic compounds and that the resulting products can contribute to their inhibitory activity.Pesticide Use-and-risk Reduction in European farming systems with Integrated Pest Managemen

The UMD-APC Database, a Model of Nation-Wide Knowledge Base: Update with Data from 3,581 Variations

International audienceFamilial adenomatous polyposis (FAP) is a rare autosomal-inherited disease that highly predisposes to colorectal cancer, characterized by a diffuse duodenal and colorectal polyposis associated with various extradigestive tumors and linked to germline mutations within the APC gene. A French consortium of laboratories involved in APC mutation screening has progressively improved the description of the variation spectrum, inferred functional significance of nontruncating variations, and delineated phenotypic characteristics of the disease. The current version of the UMD-APC database is described here. The total number of variations has risen to 5,453 representing 1,473 distinct variations. The published records initially registered into the database were extended with 3,581 germline variations found through genetic testing performed by the eight licensed laboratories belonging to the French APC network. Sixty six of 149 variations of previously unknown significance have now been classified as (likely) causal or neutral. The database is available on the Internet (http://www.umd.be/APC/) and updated twice per year according to the consensus rules of the network. The UMD-APC database is thus expected to facilitate functional classification of rare synonymous, nonsynonymous, and intronic mutations and consequently improve genetic counseling and medical care in FAP families