Modifications at the N-terminal tails of nucleosomal histones are required for efficient transcription in vivo. We analyzed how H3 histone methylation and demethylation control expression of estrogen-responsive genes and show that a DNA-bound estrogen receptor directs transcription by participating in bending chromatin to contact the RNA polymerase II recruited to the promoter. This process is driven by receptor-targeted demethylation of H3 lysine 9 at both enhancer and promoter sites and is achieved by activation of resident LSD1 demethylase. Localized demethylation produces hydrogen peroxide, which modifies the surrounding DNA and recruits 8-oxoguanine–DNA glycosylase 1 and topoisomeraseIIβ, triggering chromatin and DNA conformational changes that are essential for estrogen-induced transcription. Our data show a strategy that uses controlled DNA damage and repair to guide productive transcription.

Molecular mechanisms involved in pathogenesis of malignant melanoma have been widely studied and novel therapeutic treatments developed in recent past years. Molecular targets for therapy have mostly been recognized in the RAS-RAF-MEK-ERK and PI3K-AKT signaling pathways; small-molecule inhibitors were drawn to specifically target key kinases. Unfortunately, these inhibitors may display intrinsic or acquired resistance and various evidences suggest that targeting a single component in pathogenetic signaling pathways could not yield significant anti-tumor responses. Therefore, knowledge of the multiple altered signaling events involved in response and resistance to targeted treatments will allow to speed up the development of more effective combination therapies. In this review, we summarize the known molecular mechanisms underlying either intrinsic and acquired drug resistance either alternative roads to melanoma pathogenesis, which may become targets for innovative anticancer approaches.

Uric acid nephrolithiasis (UAN) is a common disease with an established genetic component that presents a complex mode of inheritance. While studying an ancient founder population in Talana, a village in Sardinia, we recently identified a susceptibility locus of approximately 2.5 cM for UAN on 10q21-q22 in a relatively small sample that was carefully selected through genealogical information. To refine the critical region and to identify the susceptibility gene, we extended our analysis to severely affected subjects from the same village. We confirm the involvement of this region in UAN through identical-by-descent sharing and autozygosity mapping, and we refine the critical region to an interval of approximately 67 kb associated with UAN by linkage-disequilibrium mapping. After inspecting the genomic sequences available in public databases, we determined that a novel gene overlaps this interval. This gene is divided into 15 exons, spanning a region of approximately 300 kb and generating at least four different proteins (407, 333, 462, and 216 amino acids). Interestingly, the last isoform was completely included in the 67-kb associated interval. Computer-assisted analysis of this isoform revealed at least one membrane-spanning domain and several N- and O-glycosylation consensus sites at N-termini, suggesting that it could be an integral membrane protein. Mutational analysis shows that a coding nucleotide variant (Ala62Thr), causing a missense in exon 12, is in strong association with UAN (P=.0051). Moreover, Ala62Thr modifies predicted protein secondary structure, suggesting that it may have a role in UAN etiology. The present study underscores the value of our small, genealogically well-characterized, isolated population as a model for the identification of susceptibility genes underlying complex diseases. Indeed, using a relatively small sample of affected and unaffected subjects, we identified a candidate gene for multifactorial UAN.

The aim of this paper was to study the polyphenols of peel and pulp of three Citrus taxa—Citrus medica, Citrus bergamia, and Citrus medica cv. Salò—cultivated in the Cosenza province, Southern Italy, and to evaluate their antioxidant and antibacterial activity, performed against Escherichia coli, Listeria monocytogenes, Pseudomonas aeruginosa, Staphylococcus aureus, and Pectobacterium carotovorum. Furthermore, we assessed the inhibitory effect of the extracts on bacterial capacity to form biofilm, and on the metabolic activity of the cells present therein. The results indicated that such extracts could find new potential applications in the field of natural antioxidant and anti-bacterial agents in pharmaceutics, agriculture, and food fields.

Common beans (Phaseolus vulgaris) are a good source of nutrients and phenolic compounds with versatile health benefits. Polyphenol-rich extracts of six ecotypes of P. vulgaris were analysed to determine their phenolic profiles and assayed in vitro for inhibitory effects on digestive enzymes relevant to carbohydrates and lipids metabolism. The extracts inhibited enzyme activities in a dose-dependent manner. IC 50 values ranged from 69 ± 1.9 to 126 ± 3.2 μg/mL and from 107.01 ± 4.5 to 184.20 ± 5.7 μg/mL, before and after cooking, for α-amylase, from 39.3 ± 4.4 to 74.13 ± 6.9 μg/mL and from 51 ± 7.7 to 122.1 ± 5.2 μg/mL for α-glucosidase and from 63.11 ± 7.5 to 103.2 ± 5.9 μg/mL and from 92.0 ± 6.3 to 128.5 ± 7.4 μg/mL for lipase. Results suggest encouraging their consumption, being natural sources of enzyme inhibitors important for type-2 diabetes and obesity prevention/control. Well-monitored in vivo studies would help to establish their beneficial effects, making them worthwhile of further consideration as functional foods.

Analyses of antioxidant and in vitro antimicrobial and anti-proliferative activities of anthocyanin-rich extracts from purple potatoes, Solanum tuberosum L. cv Vitelotte noire (Solanaceae), were performed by simulating both a domestic cooking process and human digestion. Extracts of crude and cooked purple potato did not exhibit antimicrobial activity against the tester strains: Bacillus cereus, Escherichia coli and Pseudomonas aeruginosa. The behaviour changed after the simulated gastrointestinal transit, when an inhibition halo was observed against all tester strains used, ranging from 0.53 cm against B. cereus to 0.82 cm against E. coli. In addition antioxidant activity exhibited, before and after the simulated gastrointestinal digestion (5.96 mg/mL ± 0.92; 28 mg/mL ± 0 .13, respectively) and the persistence of anti-proliferative activity against the colon cancer cells Caco-2, SW48 and MCF7, MDA-MB-231 breast cancer cells, after the simulated digestion, (EC50 = 0.21; 1.13 μg/mL), suggest that vitelotte consumption might bring tangible benefits for human health.