Citrus flavanones enhance carotenoid uptake by human intestinal Caco-2 cells

The health benefit of a diet rich in fruits and vegetables could be attributed to the complex mixture of phytochemicals. It is now widely believed that the actions of the antioxidant microconstituents is a result of additive and/or synergistic effects of these phytochemicals present in whole food. Because citrus juices are considered as a rich source of antioxidants including ascorbic acid (or vitamin C), phenolics compounds, and carotenoids, these different molecules may affect bioavailability or intestinal absorption of each other microconstituent. For these reasons, our study focused on effects of flavonoids and acid ascorbic on intestinal carotenoid uptake. This study was conducted using the differentiated Caco-2 cellline as experimental in vitro model and interactions of different flavanones such as hesperidin (HES-G) and hesperetin (HES) with carotenoid uptake were examined. Effect of ascorbic acid (AA) added to HES-G was also investigated. The data showed an enhancing effect of HES-G and HES on ?-carotene (b-C) and ?-cryptoxanthin (b-CX) uptake. For instance, at 5h incubation in presence of a mixture b-C:b-CX, HES-G and HES significantly increased total carotenoid uptake by 1.7 and 1.6-fold, respectively. Moreover, AA was able to cancel the enhancing effect of HES-G by decreasing significantly the cellular uptake of carotenoids from 48.2 to 39.8 % (P<0.05). In order to attribute the enhancing effect of HES-G to its already known iron-chelating effect, another experiment was conducted by incubating cells with b-CX in presence of either iron or a metal chelator (deferoxamine). b-CX uptake decreases in presence of iron and increases in presence of deferoxamine In sum, the results indicate that citrus flavanones enhance the carotenoid uptake by intestinal cells and that iron inhibits this process. Thus, the present data suggest that the citrus polyphenols could act through their iron-chelating properties. (Texte intégral

The cognitive deficits responsible for developmental dyslexia: Review of evidence for a visual attentional deficit hypothesis.

International audienceThere is strong converging evidence suggesting that developmental dyslexia stems from a phonological processing deficit. However, this hypothesis has been challenged by the widely admitted heterogeneity of the dyslexic population, and by several reports of dyslexic individuals with no apparent phonological deficit. In this paper, we discuss the hypothesis that a phonological deficit may not be the only core deficit in developmental dyslexia and critically examine several alternative proposals. To establish that a given cognitive deficit is causally related to dyslexia, at least two conditions need to be fulfilled. First, the hypothesised deficit needs to be associated with developmental dyslexia independently of additional phonological deficits. Second, the hypothesised deficit must predict reading ability, on both empirical and theoretical grounds. While most current hypotheses fail to fulfil these criteria, we argue that the visual attentional deficit hypothesis does. Recent studies providing evidence for the independence of phonological and visual attentional deficits in developmental dyslexia are reviewed together with empirical data showing that phonological and visual attentional processing skills contribute independently to reading performance. A theoretical model of reading is outlined in support of a causal link between a visual attentional disorder and a failure in reading acquisition

Developmental dyslexia: The visual attention span deficit hypothesis

International audienceThe visual attention (VA) span is defined as the amount of distinct visual elements which can be processed in parallel in a multi-element array. Both recent empirical data and theoretical accounts suggest that a VA span deficit might contribute to developmental dyslexia, independently of a phonological disorder. In this study, this hypothesis was assessed in two large samples of French and British dyslexic children whose performance was compared to that of chronological-age matched control children. Results of the French study show that the VA span capacities account for a substantial amount of unique variance in reading, as do phonological skills. The British study replicates this finding and further reveals that the contribution of the VA span to reading performance remains even after controlling IQ, verbal fluency, vocabulary and single letter identification skills, in addition to phoneme awareness. In both studies, most dyslexic children exhibit a selective phonological or VA span disorder. Overall, these findings support a multi-factorial view of developmental dyslexia. In many cases, developmental reading disorders do not seem to be due to phonological disorders. We propose that a VA span deficit is a likely alternative underlying cognitive deficit in dyslexia

TRF1 and TRF2 binding to telomeres is modulated by nucleosomal organization

The ends of eukaryotic chromosomes need to be protected from the activation of a DNA damage response that leads the cell to replicative senescence or apoptosis. In mammals, protection is accomplished by a six-factor complex named shelterin, which organizes the terminal TTAGGG repeats in a still ill-defined structure, the telomere. The stable interaction of shelterin with telomeres mainly depends on the binding of two of its components, TRF1 and TRF2, to double-stranded telomeric repeats. Tethering of TRF proteins to telomeres occurs in a chromatin environment characterized by a very compact nucleosomal organization. In this work we show that binding of TRF1 and TRF2 to telomeric sequences is modulated by the histone octamer. By means of in vitro models, we found that TRF2 binding is strongly hampered by the presence of telomeric nucleosomes, whereas TRF1 binds efficiently to telomeric DNA in a nucleosomal context and is able to remodel telomeric nucleosomal arrays. Our results indicate that the different behavior of TRF proteins partly depends on the interaction with histone tails of their divergent N-terminal domains. We propose that the interplay between the histone octamer and TRF proteins plays a role in the steps leading to telomere deprotection

Sexual orientation and mental health: a review [Orientation sexuelle et santé mentale : une revue de la littérature ]

International audienceBACKGROUND: The aim of this paper is to review available knowledge on sexual orientation and mental health, especially for women. METHODS: Papers published in English or French, between 1997 and 2007, were selected in PubMed using the following keywords "homosexuality/sexual orientation and mental health/depression/suicide". To be retained, papers had to contain findings from quantitative surveys comparing homosexual and heterosexual adults. In all, this review analyses 22 papers including two that are based on the same survey. RESULTS: This review found a general pattern of poorer mental health for homosexuals and even more so for bisexuals compared to heterosexuals. Results are especially consistent regarding elevated risk of suicide attempts

TRF2 controls telomeric nucleosome organization in a cell cycle phase-dependent manner

Mammalian telomeres stabilize chromosome ends as a result of their assembly into a peculiar form of chromatin comprising a complex of non-histone proteins named shelterin. TRF2, one of the shelterin components, binds to the duplex part of telomeric DNA and is essential to fold the telomeric chromatin into a protective cap. Although most of the human telomeric DNA is organized into tightly spaced nucleosomes, their role in telomere protection and how they interplay with telomere-specific factors in telomere organization is still unclear. In this study we investigated whether TRF2 can regulate nucleosome assembly at telomeres.By means of chromatin immunoprecipitation (ChIP) and Micrococcal Nuclease (MNase) mapping assay, we found that the density of telomeric nucleosomes in human cells was inversely proportional to the dosage of TRF2 at telomeres. This effect was not observed in the G1 phase of the cell cycle but appeared coincident of late or post-replicative events. Moreover, we showed that TRF2 overexpression altered nucleosome spacing at telomeres increasing internucleosomal distance. By means of an in vitro nucleosome assembly system containing purified histones and remodeling factors, we reproduced the short nucleosome spacing found in telomeric chromatin. Importantly, when in vitro assembly was performed in the presence of purified TRF2, nucleosome spacing on a telomeric DNA template increased, in agreement with in vivo MNase mapping.Our results demonstrate that TRF2 negatively regulates the number of nucleosomes at human telomeres by a cell cycle-dependent mechanism that alters internucleosomal distance. These findings raise the intriguing possibility that telomere protection is mediated, at least in part, by the TRF2-dependent regulation of nucleosome organization

NPHS2 mutation analysis shows genetic heterogeneityof steroid-resistant nephrotic syndrome and lowpost-transplant recurrence

NPHS2 mutation analysis shows genetic heterogeneity of steroid-resistant nephrotic syndrome and low post-transplant recurrence.BackgroundMutations of NPHS2 are causative in familial autosomal-recessive (AR) and sporadic steroid-resistant nephrotic syndrome (SRNS). This study aimed to determine the spectrum of NPHS2 mutations and to establish genotype-phenotype correlations.MethodsNPHS2 mutation analysis was performed in 338 patients from 272 families with SRNS: 81 families with AR SRNS, 172 patients with sporadic SRNS, and 19 patients with diffuse mesangial sclerosis (DMS).ResultsTwenty-six different pathogenic NPHS2 mutations were detected, including 13 novel mutations. The mutation detection rate was 43% for familial AR and 10.5% for sporadic SRNS, confirming genetic heterogeneity. No pathogenic NPHS2 mutations were found in DMS patients. Age at onset in patients with two pathogenic mutations was earlier, especially in cases with frameshift, truncating, and the R138Q missense mutations. Patients with only one NPHS2 mutation or variant had late-onset NS. Triallelic inheritance was observed in one patient with a homozygous R138Q mutation and a de novo NPHS1 mutation. Among 32 patients with two NPHS2 mutations who underwent kidney transplantation, only one developed late recurrence of focal segmental glomerulosclerosis (FSGS). Among 25 patients with sporadic SRNS and post-transplantation recurrence, we detected a heterozygous NPHS2 mutation in one case, and heterozygous variants/polymorphisms in 3 cases.ConclusionPatients with two pathogenic NPHS2 mutations present with early-onset SRNS and very low incidence of post-transplantation recurrence. Heterozygous NPHS2 variants may play a role in atypical cases with mild, late-onset course, and recurrence after transplantation