Antioxidant Supplementation in the Treatment of Aging-Associated Diseases

Oxidative stress is generally considered as the consequence of an imbalance between pro- and antioxidants species, which often results into indiscriminate and global damage at the organismal level. Elderly people are more susceptible to oxidative stress and this depends, almost in part, from a decreased performance of their endogenous antioxidant system. As many studies reported an inverse correlation between systemic levels of antioxidants and several diseases, primarily cardiovascular diseases, but also diabetes and neurological disorders, antioxidant supplementation has been foreseen as an effective preventive and therapeutic intervention for aging-associated pathologies. However, the expectations of this therapeutic approach have often been partially disappointed by clinical trials. The interplay of both endogenous and exogenous antioxidants with the systemic redox system is very complex and represents an issue that is still under debate. In this review a selection of recent clinical studies concerning antioxidants supplementation and the evaluation of their influence in aging-related diseases is analyzed. The controversial outcomes of antioxidants supplementation therapies, which might partially depend from an underestimation of the patient specific metabolic demand and genetic background, are presented

Bethe approximation for self-interacting lattice trees

In this paper we develop a Bethe approximation, based on the cluster variation method, which is apt to study lattice models of branched polymers. We show that the method is extremely accurate in cases where exact results are known as, for instance, in the enumeration of spanning trees. Moreover, the expressions we obtain for the asymptotic number of spanning trees and lattice trees on a graph coincide with analogous expressions derived through different approaches. We study the phase diagram of lattice trees with nearest-neighbour attraction and branching energies. We find a collapse transition at a tricritical theta point, which separates an expanded phase from a compact phase. We compare our results for the theta transition in two and three dimensions with available numerical estimates.Comment: 10 pages, 3 figures, to be published in Europhysics Letter

The Phase Diagram of Random Heteropolymers

We propose a new analytic approach to study the phase diagram of random heteropolymers, based on the cavity method. For copolymers we analyze the nature and phenomenology of the glass transition as a function of sequence correlations. Depending on these correlations, we find that two different scenarios for the glass transition can occur. We show that, beside the much studied possibility of an abrupt freezing transition at low temperature, the system can exhibit, upon cooling, a first transition to a soft glass phase with fully broken replica symmetry and a continuously growing degree of freezing as the temperature is lowered.Comment: 4 pages, 3 figures; published versio

Simulation study of the inhomogeneous Olami-Feder-Christensen model of earthquakes

Statistical properties of the inhomogeneous version of the Olami-Feder-Christensen (OFC) model of earthquakes is investigated by numerical simulations. The spatial inhomogeneity is assumed to be dynamical. Critical features found in the original homogeneous OFC model, e.g., the Gutenberg-Richter law and the Omori law are often weakened or suppressed in the presence of inhomogeneity, whereas the characteristic features found in the original homogeneous OFC model, e.g., the near-periodic recurrence of large events and the asperity-like phenomena persist.Comment: Shortened from the first version. To appear in European Physical Journal

Regulation of ATR activity via the RNA polymerase II associated factors CDC73 and PNUTS-PP1

© The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.Ataxia telangiectasia mutated and Rad3-related (ATR) kinase is a key factor activated by DNA damage and replication stress. An alternative pathway for ATR activation has been proposed to occur via stalled RNA polymerase II (RNAPII). However, how RNAPII might signal to activate ATR remains unknown. Here, we show that ATR signaling is increased after depletion of the RNAPII phosphatase PNUTS-PP1, which dephosphorylates RNAPII in its carboxy-terminal domain (CTD). High ATR signaling was observed in the absence and presence of ionizing radiation, replication stress and even in G1, but did not correlate with DNA damage or RPA chromatin loading. R-loops were enhanced, but overexpression of EGFP-RNaseH1 only slightly reduced ATR signaling after PNUTS depletion. However, CDC73, which interacted with RNAPII in a phospho-CTD dependent manner, was required for the high ATR signaling, R-loop formation and for activation of the endogenous G2 checkpoint after depletion of PNUTS. In addition, ATR, RNAPII and CDC73 co-immunoprecipitated. Our results suggest a novel pathway involving RNAPII, CDC73 and PNUTS-PP1 in ATR signaling and give new insight into the diverse functions of ATR.Norwegian Cancer Society [3367910]; South-Eastern Norway Health Authorities [2014035, 2013017]; Norwegian Research Council [275918]; EEA Czech-Norwegian Research Programme (Norwegian Financial Mechanism 2009–2014 and the Ministry of Education, Youth and Sports [Project Contract no. MSMT-22477/2014 (7F14061)]. Funding for open access charge: Norwegian Research Council.info:eu-repo/semantics/publishedVersio

Self-reported history of Pap-smear in HIV-positive women in Northern Italy: a cross-sectional study

BACKGROUND: The incidence of invasive cervical cancer in HIV-positive women is higher than in the general population. There is evidence that HIV-positive women do not participate sufficiently in cervical cancer screening in Italy, where cervical cancer is more than 10-fold higher in women with AIDS than in the general population. The aim of the present study was to evaluate the history of Pap-smear in HIV-positive women in Italy in recent years. We also examined the sociodemographic, clinical, and organizational factors associated with adherence to cervical cancer screening.METHODS: A cross-sectional study was conducted between July 2006 and June 2007 in Emilia-Romagna region (Northern Italy). All HIV-positive women who received a follow-up visit in one of the 10 regional infectivology units were invited to participate. History of Pap-smear, including abnormal smears and subsequent treatment, was investigated through a self-administered anonymous questionnaire. The association between lack of Pap-smear in the year preceding the interview and selected characteristics was assessed by means of odds ratios (OR) and 95% confidence intervals adjusted for study centre and age.RESULTS: A total of 1,002 HIV-positive women were interviewed. Nine percent reported no history of Pap-smear, and 39% had no Pap-smear in the year prior to the date of questionnaire (last year). The lack of Pap-smear in the last year was significantly associated with age <35 years (OR = 1.4, compared to age > or =45 years), lower education level (OR = 1.3), first HIV-positive test in the last 2 years (OR = 1.4), and CD4 count <200 cells/microl (OR = 1.6). Conversely, when women were advised by a gynecologist rather than other health workers to undergo screening, it significantly increased adherence. Non-significantly higher proportions of lack of Pap-smear in the last year were found in women born in Central-Eastern Europe (OR = 1.8) and Africa (OR = 1.3). No difference in history of Pap-smear emerged by mode of HIV-acquisition or AIDS status.Three hundred five (34%) women reported a previous abnormal Pap-smear, and of the 178 (58%) referred for treatment, 97% complied.CONCLUSIONS: In recent years the self-reported history of Pap-smear in HIV-positive women, in some public clinics in Italy, is higher than previously reported, but further efforts are required to make sure cervical cancer screening is accessible to all HIV-positive women

COIL: a methodology for evaluating malarial complexity of infection using likelihood from single nucleotide polymorphism data.

International audienceComplex malaria infections are defined as those containing more than one genetically distinct lineage of Plasmodium parasite. Complexity of infection (COI) is a useful parameter to estimate from patient blood samples because it is associated with clinical outcome, epidemiology and disease transmission rate. This manuscript describes a method for estimating COI using likelihood, called COIL, from a panel of bi-allelic genotyping assays. COIL assumes that distinct parasite lineages in complex infections are unrelated and that genotyped loci do not exhibit significant linkage disequilibrium. Using the population minor allele frequency (MAF) of the genotyped loci, COIL uses the binomial distribution to estimate the likelihood of a COI level given the prevalence of observed monomorphic or polymorphic genotypes within each sample. COIL reliably estimates COI up to a level of three or five with at least 24 or 96 unlinked genotyped loci, respectively, as determined by in silico simulation and empirical validation. Evaluation of COI levels greater than five in patient samples may require a very large collection of genotype data, making sequencing a more cost-effective approach for evaluating COI under conditions when disease transmission is extremely high. Performance of the method is positively correlated with the MAF of the genotyped loci. COI estimates from existing SNP genotype datasets create a more detailed portrait of disease than analyses based simply on the number of polymorphic genotypes observed within samples. The capacity to reliably estimate COI from a genome-wide panel of SNP genotypes provides a potentially more accurate alternative to methods relying on PCR amplification of a small number of loci for estimating COI. This approach will also increase the number of applications of SNP genotype data, providing additional motivation to employ SNP barcodes for studies of disease epidemiology or control measure efficacy. The COIL program is available for download from GitHub, and users may also upload their SNP genotype data to a web interface for simple and efficient determination of sample COI

High contrast imaging at the LBT: the LEECH exoplanet imaging survey

In Spring 2013, the LEECH (LBTI Exozodi Exoplanet Common Hunt) survey began its $\sim$130-night campaign from the Large Binocular Telescope (LBT) atop Mt Graham, Arizona. This survey benefits from the many technological achievements of the LBT, including two 8.4-meter mirrors on a single fixed mount, dual adaptive secondary mirrors for high Strehl performance, and a cold beam combiner to dramatically reduce the telescope's overall background emissivity. LEECH neatly complements other high-contrast planet imaging efforts by observing stars at L' (3.8 $\mu$m), as opposed to the shorter wavelength near-infrared bands (1-2.4 $\mu$m) of other surveys. This portion of the spectrum offers deep mass sensitivity, especially around nearby adolescent ($\sim$0.1-1 Gyr) stars. LEECH's contrast is competitive with other extreme adaptive optics systems, while providing an alternative survey strategy. Additionally, LEECH is characterizing known exoplanetary systems with observations from 3-5$\mu$m in preparation for JWST.Comment: 12 pages, 5 figures. Proceedings of the SPIE, 9148-2

The LEECH Exoplanet Imaging Survey: Limits on Planet Occurrence Rates Under Conservative Assumptions

We present the results of the largest $L^{\prime}$ ($3.8~\mu$m) direct imaging survey for exoplanets to date, the Large Binocular Telescope Interferometer (LBTI) Exozodi Exoplanet Common Hunt (LEECH). We observed 98 stars with spectral types from B to M. Cool planets emit a larger share of their flux in $L^{\prime}$ compared to shorter wavelengths, affording LEECH an advantage in detecting low-mass, old, and cold-start giant planets. We emphasize proximity over youth in our target selection, probing physical separations smaller than other direct imaging surveys. For FGK stars, LEECH outperforms many previous studies, placing tighter constraints on the hot-start planet occurrence frequency interior to $\sim20$ au. For less luminous, cold-start planets, LEECH provides the best constraints on giant-planet frequency interior to $\sim20$ au around FGK stars. Direct imaging survey results depend sensitively on both the choice of evolutionary model (e.g., hot- or cold-start) and assumptions (explicit or implicit) about the shape of the underlying planet distribution, in particular its radial extent. Artificially low limits on the planet occurrence frequency can be derived when the shape of the planet distribution is assumed to extend to very large separations, well beyond typical protoplanetary dust-disk radii ($\lesssim50$ au), and when hot-start models are used exclusively. We place a conservative upper limit on the planet occurrence frequency using cold-start models and planetary population distributions that do not extend beyond typical protoplanetary dust-disk radii. We find that $\lesssim90\%$ of FGK systems can host a 7 to 10 $M_{\mathrm{Jup}}$ planet from 5 to 50 au. This limit leaves open the possibility that planets in this range are common.Comment: 31 pages, 13 figures, accepted to A

First direct detection of an exoplanet by optical interferometry; Astrometry and K-band spectroscopy of HR8799 e

To date, infrared interferometry at best achieved contrast ratios of a few times $10^{-4}$ on bright targets. GRAVITY, with its dual-field mode, is now capable of high contrast observations, enabling the direct observation of exoplanets. We demonstrate the technique on HR8799, a young planetary system composed of four known giant exoplanets. We used the GRAVITY fringe tracker to lock the fringes on the central star, and integrated off-axis on the HR8799e planet situated at 390 mas from the star. Data reduction included post-processing to remove the flux leaking from the central star and to extract the coherent flux of the planet. The inferred K band spectrum of the planet has a spectral resolution of 500. We also derive the astrometric position of the planet relative to the star with a precision on the order of 100$\,\mu$as. The GRAVITY astrometric measurement disfavors perfectly coplanar stable orbital solutions. A small adjustment of a few degrees to the orbital inclination of HR 8799 e can resolve the tension, implying that the orbits are close to, but not strictly coplanar. The spectrum, with a signal-to-noise ratio of $\approx 5$ per spectral channel, is compatible with a late-type L brown dwarf. Using Exo-REM synthetic spectra, we derive a temperature of $1150\pm50$\,K and a surface gravity of $10^{4.3\pm0.3}\,$cm/s$^{2}$. This corresponds to a radius of $1.17^{+0.13}_{-0.11}\,R_{\rm Jup}$ and a mass of $10^{+7}_{-4}\,M_{\rm Jup}$, which is an independent confirmation of mass estimates from evolutionary models. Our results demonstrate the power of interferometry for the direct detection and spectroscopic study of exoplanets at close angular separations from their stars.Comment: published in A&