Forever Young: Structural Stability of Telomeric Guanine Quadruplexes in the Presence of Oxidative DNA Lesions**

Human telomeric DNA, in G-quadruplex (G4) conformation, is characterized by a remarkable structural stability that confers it the capacity to resist to oxidative stress producing one or even clustered 8-oxoguanine (8oxoG) lesions. We present a combined experimental/computational investigation, by using circular dichroism in aqueous solutions, cellular immunofluorescence assays and molecular dynamics simulations, that identifies the crucial role of the stability of G4s to oxidative lesions, related also to their biological role as inhibitors of telomerase, an enzyme overexpressed in most cancers associated to oxidative stress

AVPV neurons containing estrogen receptor-beta in adult male rats are influenced by soy isoflavones

BACKGROUND: Isoflavones, the most abundant phytoestrogens in soy foods, are structurally similar to 17beta-estradiol. It is known that 17beta-estradiol induces apoptosis in anteroventral periventricular nucleus (AVPV) in rat brain. Also, there is evidence that consumption of soy isoflavones reduces the volume of AVPV in male rats. Therefore, in this study, we examined the influence of dietary soy isoflavones on apoptosis in AVPV of 150 day-old male rats fed either a soy isoflavone-free diet (Phyto-free) or a soy isoflavone-rich diet (Phyto-600). RESULTS: The occurrence of apoptosis in AVPV was examined by TUNEL staining. The incidence of apoptosis was about 10 times higher in the Phyto-600 group (33.1 ± 1.7%) than in the Phyto-free group (3.6 ± 1.0%). Furthermore, these apoptotic cells were identified as neurons by dual immunofluorescent staining of GFAP and NeuN as markers of astrocytes and neurons, respectively. Then the dopaminergic neurons in AVPV were detected by immunohistochemistry staining of tyrosine hydroxylase (TH). No significant difference in the number of TH neurons was observed between the diet treatment groups. When estrogen receptor (ER) alpha and beta were examined by immunohistochemistry, we observed a 22% reduction of ERbeta-positive cell numbers in AVPV with consumption of soy isoflavones, whereas no significant change in ERalpha-positive cell numbers was detected. Furthermore, almost all the apoptotic cells were ERbeta-immunoreactive (ir), but not ERalpha-ir. Last, subcutaneous injections of equol (a major isoflavone metabolite) that accounts for approximately 70–90% of the total circulating plasma isoflavone levels did not alter the volume of AVPV in adult male rats. CONCLUSION: In summary, these findings provide direct evidence that consumption of soy isoflavones, but not the exposure to equol, influences the loss of ERbeta-containing neurons in male AVPV

a multi scalar approach to long term dynamics spatial relations and economic networks of roman secondary settlements in italy and the ombrone valley system southern tuscany towards a model

In Roman landscapes, the particular sites defined as secondary settlements (also known as vici/villages, minor centres, agglomerations secondaires and/or stationes/mansiones) have played an 'intermediary' role between the cities and other rural structures (villae/farms), linked to medium- and long-distance economic and commercial trajectories. The aim of this paper is to apply a multi-scalar approach to model their long-term spatial relationships and connectivity with the Mediterranean exchange network. On the macro-scale, we have analysed a sample of 219 reviewed sites to understand the diachronic trends and spatial dynamics of attraction/proximity to significant elements of the landscape such as towns, roads, rivers and coastline. The Ombrone Valley (Tuscany, Italy) represents a micro-scale case study of a complex system, in which the imported pottery (amphorae, African Red Slip ware, ingobbiata di rosso) found in the vicus/mansio of Santa Cristina in Caio, the Roman villa of La Befa and the town of Siena (Saena Iulia) provided diagnostic 'macroeconomic' perspectives. The results show how the secondary settlements occupied a nodal position in the Roman landscape in terms of resilience (long period of occupation until the Early Middle Ages) and spatial organization with a close relationship to natural and anthropic infrastructures and trade functions linked to Mediterranean routes

Active site mutagenesis and phospholipid hydroperoxide reductase activity of poplar type II peroxiredoxin

International audienc

Blind identification of FIR MIMO systems driven by cyclostationary inputs in wireless communications using joint block diagonalization

International audienc

Crystal structure of the wild-type and D30A mutant thioredoxin h of Chlamydomonas reinhardtii and implications for the catalytic mechanism

Thioredoxins are ubiquitous proteins which catalyse the reduction of disulphide bridges on target proteins. The catalytic mechanism proceeds via a mixed disulphide intermediate whose breakdown should be enhanced by the involvement of a conserved buried residue, Asp-30, as a base catalyst towards residue Cys-39. We report here the crystal structure of wild-type and D30A mutant thioredoxin h from Chlamydomonas reinhardtii, which constitutes the first crystal structure of a cytosolic thioredoxin isolated from a eukaryotic plant organism. The role of residue Asp-30 in catalysis has been revisited since the distance between the carboxylate OD1 of Asp-30 and the sulphur SG of Cys-39 is too great to support the hypothesis of direct proton transfer. A careful analysis of all available crystal structures reveals that the relative positioning of residues Asp-30 and Cys-39 as well as hydrophobic contacts in the vicinity of residue Asp-30 do not allow a conformational change sufficient to bring the two residues close enough for a direct proton transfer. This suggests that protonation/deprotonation of Cys-39 should be mediated by a water molecule. Molecular-dynamics simulations, carried out either in vacuo or in water, as well as proton-inventory experiments, support this hypothesis. The results are discussed with respect to biochemical and structural data