Effect of cadmium on cytosine hydroxymethylation in gastropod hepatopancreas

5-Hydroxymethylcytosine (5hmC) is an important, yet poorly understood epigenetic DNA modification, especially in invertebrates. Aberrant genome-wide 5hmC levels have been associated with cadmium (Cd) exposure in humans, but such information is lacking for invertebrate bioindicators. Here, we aimed to determine whether this epigenetic mark is present in DNA of the hepatopancreas of the land snail Cantareus aspersus and is responsive to Cd exposure. Adult snails were reared under laboratory conditions and exposed to graded amounts of dietary cadmium for 14 days. Weight gain was used as a sublethal endpoint, whereas survival as a lethal endpoint. Our results are the first to provide evidence for the presence of 5hmC in DNA of terrestrial mollusks; 5hmC levels are generally low with the measured values falling below 0.03%. This is also the first study to investigate the interplay of Cd with DNA hydroxymethylation levels in a non-human animal study system. Cadmium retention in the hepatopancreas of C. aspersus increased from a dietary Cd dose of 1 milligram per kilogram dry weight (mg/kg d. wt). For the same treatment, we identified the only significant elevation in percentage of samples with detectable 5hmC levels despite the lack of significant mortalities and changes in weight gain among treatment groups. These findings indicate that 5hmC is an epigenetic mark that may be responsive to Cd exposure, thereby opening a new aspect to invertebrate environmental epigenetics

Identification of IGF1, SLC4A4, WWOX, and SFMBT1 as Hypertension Susceptibility Genes in Han Chinese with a Genome-Wide Gene-Based Association Study

Hypertension is a complex disorder with high prevalence rates all over the world. We conducted the first genome-wide gene-based association scan for hypertension in a Han Chinese population. By analyzing genome-wide single-nucleotide-polymorphism data of 400 matched pairs of young-onset hypertensive patients and normotensive controls genotyped with the Illumina HumanHap550-Duo BeadChip, 100 susceptibility genes for hypertension were identified and also validated with permutation tests. Seventeen of the 100 genes exhibited differential allelic and expression distributions between patient and control groups. These genes provided a good molecular signature for classifying hypertensive patients and normotensive controls. Among the 17 genes, IGF1, SLC4A4, WWOX, and SFMBT1 were not only identified by our gene-based association scan and gene expression analysis but were also replicated by a gene-based association analysis of the Hong Kong Hypertension Study. Moreover, cis-acting expression quantitative trait loci associated with the differentially expressed genes were found and linked to hypertension. IGF1, which encodes insulin-like growth factor 1, is associated with cardiovascular disorders, metabolic syndrome, decreased body weight/size, and changes of insulin levels in mice. SLC4A4, which encodes the electrogenic sodium bicarbonate cotransporter 1, is associated with decreased body weight/size and abnormal ion homeostasis in mice. WWOX, which encodes the WW domain-containing protein, is related to hypoglycemia and hyperphosphatemia. SFMBT1, which encodes the scm-like with four MBT domains protein 1, is a novel hypertension gene. GRB14, TMEM56 and KIAA1797 exhibited highly significant differential allelic and expressed distributions between hypertensive patients and normotensive controls. GRB14 was also found relevant to blood pressure in a previous genetic association study in East Asian populations. TMEM56 and KIAA1797 may be specific to Taiwanese populations, because they were not validated by the two replication studies. Identification of these genes enriches the collection of hypertension susceptibility genes, thereby shedding light on the etiology of hypertension in Han Chinese populations

Fluctuations at the edges of the spectrum of the full rank deformed GUE

5 figures, 44 pagesInternational audienceWe consider a full rank deformation of the GUE $W_N+A_N$ where $A_N$ is a full rank Hermitian matrix of size $N$ and $W_N$ is a GUE. The empirical eigenvalue distribution $\mu_{A_N}$ of $A_N$ converges to a probability distribution $\nu$. We identify all the possible limiting eigenvalue statistics at the edges of the spectrum, including outliers, edges and merging points of connected components of the limiting spectrum. The results are stated in terms of a deterministic equivalent of the empirical eigenvalue distribution of $W_N+A_N$, namely the free convolution of the semi-circle distribution and the empirical eigenvalues distribution of $A_N$

Nutrigenomics as strategy for neuronal health

Nutrigenomics through gene expression and epigenetic remodeling can program adult health. Diet during pregnancy and lactation (the first 1000 days of life) can modulate offspring’s epigenome leading to tissue specific variations during cell differentiation processes, and may define epigenetic marks associated with longterm effects on offspring neuronal health. Being epigenetics reversible, a healthy diet represents a fundamental opportunity, even after the first 1000 days of life, for maintaining cellular homeostasis. The positive impact of food (i.e. maternal milk, oily fish, fruit and vegetables, curcumin, tea) with its dietary flavonoids (i.e. sulforaphane, quercetin, lutein, resveratrol, carotenoids) and other bioactive compounds (i.e. docosahexanoic acid, melatonin etc.), will be reflected on chromatin structure modulation and DNA methylation which are associated with switching on/off of genes. An anti-inflammatory diet during early-life and across the whole life may represent a key strategy for influencing brain plasticity and for building an “epigenetic memory” useful in developing neuronal resilience against early-life stressors and to prevent age-related neurodegeneration