Association of polymorphisms in genes coding for antioxidant enzymes and human male infertility

This is the peer reviewed version of the following article: Annals of Human Genetics 83.1 (2019): 63-72, which has been published in final form at https://doi.org/10.1111/ahg.12286. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsPurpose: Although oxidative stress is thought to be an important cause of male infertility, primarily due to DNA and cell membrane damage, little is known about the genetic causes underlying suboptimal function of the seminal enzymatic antioxidant system. The aim of this study was to investigate the relationship of four potentially functional polymorphisms associated with oxidative stress pathway genes (superoxide dismutase—SOD2 lle58Thr and SOD2 rs4880, catalase—CAT C-262T, glutathione peroxidase 1—GPX1 Pro200Leu) and two null variants of the glutathione S transferase (GSTT and GSTM) genes and infertility risk. Methods: A case control study was conducted on 313 infertile patients and 80 fertile donors. Each ejaculate was subjected to a seminal analysis that included the classical parameters seminal volume, sperm concentration, sperm motility, and sperm morphology, as well as sperm DNA fragmentation (patients only). Polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) and PCR multiplex methods were carried out for genotyping. Results: Statistically significant differences were found between fertile donors and infertile patients for SNP CAT C-262T; the CC genotype was related with a twofold increased risk of infertility (odds ratio [OR] = 2.262; 95% confidence interval [CI] = 1.369–3.733; P = 0.001), whereas the CT genotype was associated with a protective effect (OR = 0.401; 95% CI = 0.241–0.667; P = 0.001). Surprisingly, the SOD2 Ile58ssThr SNP was not represented in the sample population, so its frequency in the current population frequenting fertility clinics in Madrid may be very low. Conclusions: Our results suggest that the CAT SNP C-262T is potentially associated with an increased risk of male infertilityThe Ministry of Economy, Industry and Competitiveness of Spain supported this stud

Cumulus Cell DNA damage as an index of human oocyte competence

The determination of oocyte quality is crucial for achieving effective syngamy post-sperm injection and embryonic development. Cumulus cells (CCs) have been proposed as biomarkers of oocyte quality because of their close bio-dynamic relationship with the oocyte. To determine the quality of the oocyte, CCs were sampled during oocyte preparation for ICSI to determine a CC DNA fragmentation index (CCDFI) of each individual oocyte using a variant of the chromatin dispersion test. One hundred and thirty oocytes were selected and studied from two Spanish fertility clinics, 90 of which were fertilized and developed to embryos. Significant differences were found between the CCDFI of unfertilized and fertilized oocytes (p <.001) and between the CCDFI of embryos that were discarded and those that developed suitable for transfer or cryopreservation (p <.001). Oocyte quality was negatively correlated with CCDFI (Spearman’s rho = − 0.45; p <.001). Receiver operator characteristics curves (ROC) suggested that a cut-off value of 24% CCDFI was able to discriminate the capacity of the gametes to result in syngamy with a sensitivity and specificity of 75.6% and 65%, respectively. This cut-off supports the application of CCDFI as potential index for the evaluation of the reproductive potential of oocytes prior to fertilizatio

Patterns of coral-reef finfish species disappearances inferred from fishers' knowledge in global epicentre of marine shorefish diversity

In the Philippines, very high fishing pressure coincides with the globally greatest number of shorefish species, yet no long-term fisheries data are available to explore species-level changes that may have occurred widely in the most species rich and vulnerable marine ecosystem, namely coral reefs. Through 2655 face-to-face interviews conducted between August 2012 and July 2014, we used fishers' recall of past catch rates of reef-associated finfish to infer species disappearances from catches in five marine key biodiversity areas (Lanuza Bay, Danajon Bank, Verde Island Passage, Polillo Islands and Honda Bay). We modeled temporal trends in perceived catch per unit effort (CPUE) based on fishers' reports of typical good days' catches using Generalized Linear Mixed Modelling. Fifty-nine different finfish disappeared from catches between the 1950s and 2014; 42 fish were identified to species level, two to genus, seven to family and eight to local name only. Five species occurring at all sites with the greatest number of fishers reporting zero catches were the green bumphead parrotfish (Bolbometopon muricatum), humphead wrasse (Cheilinus undulatus), African pompano (Alectis ciliaris), giant grouper (Epinephelus lanceolatus) and mangrove red snapper (Lutjanus argentimaculatus). Between the 1950s and 2014, the mean perceived CPUE of bumphead parrotfish declined by 88%, that of humphead wrasse by 82%, African pompano by 66%, giant grouper by 74% and mangrove red snapper by 64%. These declines were mainly associated with excess and uncontrolled fishing, fish life-history traits like maximum body size and socio-economic factors like access to market infrastructure and services, and overpopulation. The fishers' knowledge is indicative of extirpations where evidence for these losses was otherwise lacking. Our models provide information as basis for area-based conservation and regional resource management particularly for the more vulnerable, once common, large, yet wide-ranging reef finfish species

Critical Issues For Understanding Particle Acceleration in Impulsive Solar Flares

This paper, a review of the present status of existing models for particle acceleration during impulsive solar flares, was inspired by a week-long workshop held in the Fall of 1993 at NASA Goddard Space Flight Center. Recent observations from Yohkoh and the Compton Gamma Ray Observatory, and a reanalysis of older observations from the Solar Maximum Mission, have led to important new results concerning the location, timing, and efficiency of particle acceleration in flares. These are summarized in the first part of the review. Particle acceleration processes are then discussed, with;particular emphasis on new developments in stochastic acceleration by magnetohydrodynamic waves and direct electric field acceleration by both sub- and super-Dreicer electric fields. Finally, issues that arise when these mechanisms are incorporated into the large-scale flare structure are considered. Stochastic and super-Dreicer acceleration may occur either in a single large coronal reconnection site or at multiple \u27\u27fragmented\u27\u27 energy release sites. Sub-Dreicer acceleration requires a highly filamented coronal current pattern. A particular issue that needs to be confronted by all theories is the apparent need for large magnetic field strengths in the flare energy release region

The INTEGRAL/IBIS AGN catalogue I: X-ray absorption properties versus optical classification

In this work we present the most comprehensive INTEGRAL AGN sample which lists 272 objects. Here we mainly use this sample to study the absorption properties of active galaxies, to probe new AGN classes and to test the AGN unification scheme. We find that half (48%) of the sample is absorbed while the fraction of Compton thick AGN is small (~7%). In line with our previous analysis, we have however shown that when the bias towards heavily absorbed objects which are lost if weak and at large distance is removed, as it is possible in the local Universe, the above fractions increase to become 80% and 17%. We also find that absorption is a function of source luminosity, which implies some evolution in the obscuration properties of AGN. Few peculiar classes, so far poorly studied in the hard X-ray band, have been detected and studied for the first time such as 5 XBONG, 5 type 2 QSOs and 11 LINERs. In terms of optical classification, our sample contains 57% of type 1 and 43% of type 2 AGN; this subdivision is similar to that found in X-rays if unabsorbed versus absorbed objects are considered, suggesting that the match between optical and X-ray classification is overall good. Only a small percentage of sources (12%) does not fulfill the expectation of the unified theory as we find 22 type 1 AGN which are absorbed and 10 type 2 AGN which are unabsorbed. Studying in depth these outliers we found that most of the absorbed type 1 AGN have X-ray spectra characterized by either complex or warm/ionized absorption more likely due to ionized gas located in an accretion disk wind or in the biconical structure associated to the central nucleus, therefore unrelated to the toroidal structure. Among 10 type 2 AGN which resulted to be unabsorbed, at most 3-4% is still eligible to be classified as a "true" type 2 AGN.Comment: 21 pages, 6 figures, 5 tables. Accepted for publication on MNRAS. arXiv admin note: text overlap with arXiv:0709.2077 by other author

XIPE: the X-ray Imaging Polarimetry Explorer

X-ray polarimetry, sometimes alone, and sometimes coupled to spectral and temporal variability measurements and to imaging, allows a wealth of physical phenomena in astrophysics to be studied. X-ray polarimetry investigates the acceleration process, for example, including those typical of magnetic reconnection in solar flares, but also emission in the strong magnetic fields of neutron stars and white dwarfs. It detects scattering in asymmetric structures such as accretion disks and columns, and in the so-called molecular torus and ionization cones. In addition, it allows fundamental physics in regimes of gravity and of magnetic field intensity not accessible to experiments on the Earth to be probed. Finally, models that describe fundamental interactions (e.g. quantum gravity and the extension of the Standard Model) can be tested. We describe in this paper the X-ray Imaging Polarimetry Explorer (XIPE), proposed in June 2012 to the first ESA call for a small mission with a launch in 2017 but not selected. XIPE is composed of two out of the three existing JET-X telescopes with two Gas Pixel Detectors (GPD) filled with a He-DME mixture at their focus and two additional GPDs filled with pressurized Ar-DME facing the sun. The Minimum Detectable Polarization is 14 % at 1 mCrab in 10E5 s (2-10 keV) and 0.6 % for an X10 class flare. The Half Energy Width, measured at PANTER X-ray test facility (MPE, Germany) with JET-X optics is 24 arcsec. XIPE takes advantage of a low-earth equatorial orbit with Malindi as down-link station and of a Mission Operation Center (MOC) at INPE (Brazil).Comment: 49 pages, 14 figures, 6 tables. Paper published in Experimental Astronomy http://link.springer.com/journal/1068

Body size adaptation alters perception of test stimuli, not internal body image

Recent studies have reported that adaptation to extreme body types produces aftereffects on judgments of body normality and attractiveness, and also judgments of the size and shape of the viewer’s own body. This latter effect suggests that adaptation could constitute an experimental model of media influences on body image. Alternatively, adaptation could affect perception of test stimuli, which should produce the same aftereffects for judgments about participant’s own body or someone else’s body. Here, we investigated whether adaptation similarly affects judgments about one’s body and other bodies. We were interested in participants’ own body image judgements, i.e. we wanted to measure the mental representations to which the test stimuli were compared to and not the perception of test stimuli per se. Participants were adapted to pictures of thin or fat bodies and then rated whether bodies were fatter or thinner than either: their own body, an average body (Experiment 1) or the body of another person (Experiments 2-3). By keeping the visual stimuli constant but changing the task/type of judgement, i.e. the internal criterion participants are asked to judge the bodies against, we investigated how adaptation affects different stored representations of bodies, specifically. own body image vs representations of others. After adaptation, a classic aftereffect was found, with judgments biased away from the adapting stimulus. Critically, aftereffects were nearly identical for judgments of one’s own body and for other people’s bodies. These results suggest that adaptation affects body representations in a generic way and may not be specific to the own body image

SN 2012ec: Mass of the progenitor from PESSTO follow-up of the photospheric phase

We present the results of a photometric and spectroscopic monitoring campaign of SN 2012ec, which exploded in the spiral galaxy NGC 1084, during the photospheric phase. The photometric light curve exhibits a plateau with luminosity L = 0.9 × 1042 erg s−1 and duration ∼90 d, which is somewhat shorter than standard Type II-P supernovae (SNe). We estimate the nickel mass M(56Ni) = 0.040 ± 0.015 M from the luminosity at the beginning of the radioactive tail of the light curve. The explosion parameters of SN 2012ec were estimated from the comparison of the bolometric light curve and the observed temperature and velocity evolution of the ejecta with predictions from hydrodynamical models. We derived an envelope mass of 12.6 M, an initial progenitor radius of 1.6 × 1013 cm and an explosion energy of 1.2 foe. These estimates agree with an independent study of the progenitor star identified in pre-explosion images, for which an initial mass of M = 14−22 M was determined. We have applied the same analysis to two other Type II-P SNe (SNe 2012aw and 2012A), and carried out a comparison with the properties of SN 2012ec derived in this paper. We find a reasonable agreement between the masses of the progenitors obtained from pre-explosion images and masses derived from hydrodynamical models. We estimate the distance to SN 2012ec with the standardized candle method (SCM) and compare it with other estimates based on other primary and secondary indicators. SNe 2012A, 2012aw and 2012ec all follow the standard relations for the SCM for the use of Type II-P SNe as distance indicators

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer.

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM -/- patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors