Human Papillomavirus Infection in a Male Population Attending a Sexually Transmitted Infection Service

Objective

Human Papillomavirus (HPV) infection in men may produce cancer and other major disorders. Men play an important role in the transmission of the virus and act as a reservoir. The aim of this study was to determine the HPV-genotypes and their prevalence in a group of men attending a Sexually Transmitted Infection service.

Patients and Samples

Between July 2002 and June 2011, 1392 balanopreputial, 435 urethral, 123 anal, and 67 condyloma lesions from 1551 men with a mean age of 35.8±11.3 years old (range: 17–87) were collected for HPV-DNA testing.

Methods

A fragment of the L1-gene and a fragment of the E6/E7-genes were amplified by PCR. Positive samples were typed by hybridization.

Results

The HPV genome was detected in 36.9% (486/1318) balanopreputial and in 24.9% (101/405) urethral (p<0.0001) swabs from 38.1% (538) of 1469 men. Co-infections were present in 5.4% (80/1469) of cases. HPV was found in 43.9% (373/850) of men younger than 35 vs. 31.7% (187/589) of men aged >35. HPV was found in 59.4% (104) of 165 men with lesions (macroscopic or positive peniscopy), and in 22.8% (61/267) without clinical alterations. HPV was also detected in 71.4% (40/56) men with condylomata and in 58.7% (64/109) of men with positive peniscopy.

Conclusions

HPV prevalence in men was high and decreased with age. HPV was found more frequently in balanopreputial than in urethral swabs. There was a low rate of co-infections. Low-risk HPV vaccine genotypes were the most recurrent especially in younger. Although HPV has been associated with clinical alterations, it was also found in men without any clinical presentation. Inclusion of men in the national HPV vaccination program may reduce their burden of HPV-related disease and reduce transmission of the virus to non-vaccinated women.     

Unexpected link between metal ion deficiency and autophagy in Aspergillus fumigatus

Autophagy is the major cellular pathway for bulk degradation of cytosolic material and is required to maintain viability under starvation conditions. To determine the contribution of autophagy to starvation stress responses in the filamentous fungus Aspergillus fumigatus, we disrupted the A. fumigatus atg1 gene, encoding a serine/threonine kinase required for autophagy. The ΔAfatg1 mutant showed abnormal conidiophore development and reduced conidiation, but the defect could be bypassed by increasing the nitrogen content of the medium. When transferred to starvation medium, wild-type hyphae were able to undergo a limited amount of growth, resulting in radial expansion of the colony. In contrast, the ΔAfatg1 mutant was unable to grow under these conditions. However, supplementation of the medium with metal ions rescued the ability of the ΔAfatg1 mutant to grow in the absence of a carbon or nitrogen source. Depleting the medium of cations by using EDTA was sufficient to induce autophagy in wild-type A. fumigatus, even in the presence of abundant carbon and nitrogen, and the ΔAfatg1 mutant was severely growth impaired under these conditions. These findings establish a role for autophagy in the recycling of internal nitrogen sources to support conidiophore development and suggest that autophagy also contributes to the recycling of essential metal ions to sustain hyphal growth when exogenous nutrients are scarce.     

LSD1 Overexpression Is Associated with Poor Prognosis in Basal-Like Breast Cancer,and Sensitivity to PARP Inhibition

LSD1, a lysine-specific histone demethylase, is overexpressed in several types of cancers and linked to poor outcomes. In breast cancer, the significance of LSD1 overexpression is not clear. We have performed an in silico analysis to assess the relationship of LSD1 expression to clinical outcome. We demonstrate that LSD1 overexpression is a poor prognostic factor in breast cancer, especially in basal-like breast cancer, a subtype of breast cancer with aggressive clinical features. This link is also observed in samples of triple negative breast cancer. Interestingly, we note that overexpression of LSD1 correlates with down-regulation of BRCA1 in triple negative breast cancer. This phenomenon is also observed in in vitro models of basal-like breast cancer, and is associated with an increased sensitivity to PARP inhibitors. We propose therefore that high expression levels of the demethylase LSD1 is a potential prognostic factor of poor outcome in basal-like breast cancer, and that PARP inhibition may be a therapeutic strategy of interest in this poor prognostic subtype with overexpression of LSD1.     

Charge-charge interactions are key determinants of the pK values of ionizable groups in ribonuclease Sa (pI=3.5) and a basic variant (pI=10.2)

The pK values of the titratable groups in ribonuclease Sa (RNase Sa) (pI=3.5), and a charge-reversed variant with five carboxyl to lysine substitutions, 5K RNase Sa (pI=10.2), have been determined by NMR at 20 degrees C in 0.1M NaCl. In RNase Sa, 18 pK values and in 5K, 11 pK values were measured. The carboxyl group of Asp33, which is buried and forms three intramolecular hydrogen bonds in RNase Sa, has the lowest pK (2.4), whereas Asp79, which is also buried but does not form hydrogen bonds, has the most elevated pK (7.4). These results highlight the importance of desolvation and charge-dipole interactions in perturbing pK values of buried groups. Alkaline titration revealed that the terminal amine of RNase Sa and all eight tyrosine residues have significantly increased pK values relative to model compounds.A primary objective in this study was to investigate the influence of charge-charge interactions on the pK values by comparing results from RNase Sa with those from the 5K variant. The solution structures of the two proteins are very similar as revealed by NMR and other spectroscopic data, with only small changes at the N terminus and in the alpha-helix. Consequently, the ionizable groups will have similar environments in the two variants and desolvation and charge-dipole interactions will have comparable effects on the pK values of both. Their pK differences, therefore, are expected to be chiefly due to the different charge-charge interactions. As anticipated from its higher net charge, all measured pK values in 5K RNase are lowered relative to wild-type RNase Sa, with the largest decrease being 2.2 pH units for Glu14. The pK differences (pK(Sa)-pK(5K)) calculated using a simple model based on Coulomb's Law and a dielectric constant of 45 agree well with the experimental values. This demonstrates that the pK differences between wild-type and 5K RNase Sa are mainly due to changes in the electrostatic interactions between the ionizable groups. pK values calculated using Coulomb's Law also showed a good correlation (R=0.83) with experimental values. The more complex model based on a finite-difference solution to the Poisson-Boltzmann equation, which considers desolvation and charge-dipole interactions in addition to charge-charge interactions, was also used to calculate pK values. Surprisingly, these values are more poorly correlated (R=0.65) with the values from experiment. Taken together, the results are evidence that charge-charge interactions are the chief perturbant of the pK values of ionizable groups on the protein surface, which is where the majority of the ionizable groups are positioned in proteins.     

Oxidative Stress Predicts All-Cause Mortality in HIV-Infected Patients

ObjectiveWe aimed to assess whether oxidative stress is a predictor of mortality in HIV-infected patients.MethodsWe conducted a nested case-control study in CoRIS, a contemporary, multicentre cohort of HIV-infected patients, antiretroviral-naïve at entry, launched in 2004. Cases were patients who died with available stored plasma samples collected. Two age and sex-matched controls for each case were selected. We measured F2-isoprostanes (F₂-IsoPs) and malondialdehyde (MDA) plasma levels in the first blood sample obtained after cohort engagement.Results54 cases and 93 controls were included. Median F₂-IsoPs and MDA levels were significantly higher in cases than in controls. When adjustment was performed for age, HIV-transmission category, CD4 cell count and HIV viral load at cohort entry, and subclinical inflammation measured with highly-sensitive C-reactive protein (hsCRP), the association of F₂-IsoPs with mortality remained significant (adjusted OR per 1 log₁₀ increase, 2.34 [1.23–4.47], P = 0.009). The association of MDA with mortality was attenuated after adjustment: adjusted OR (95% CI) per 1 log₁₀ increase, 2.05 [0.91–4.59], P = 0.080. Median hsCRP was also higher in cases, and it also proved to be an independent predictor of mortality in the adjusted analysis: OR (95% CI) per 1 log₁₀ increase, 1.39 (1.01–1.91), P = 0.043; and OR (95% CI) per 1 log₁₀ increase, 1.46 (1.07–1.99), P = 0.014, respectively, when adjustment included F₂-IsoPs and MDA.ConclusionOxidative stress is a predictor of all-cause mortality in HIV-infected patients. For plasma F₂-IsoPs, this association is independent of HIV-related factors and subclinical inflammation.     

Xanthophyllomyces dendrorhous for the industrial production of astaxanthin

Astaxanthin is a red xanthophyll (oxygenated carotenoid) with large importance in the aquaculture, pharmaceutical, and food industries. The green alga Haematococcus pluvialis and the heterobasidiomycetous yeast Xanthophyllomyces dendrorhous are currently known as the main microorganisms useful for astaxanthin production at the industrial scale. The improvement of astaxanthin titer by microbial fermentation is a requirement to be competitive with the synthetic manufacture by chemical procedures, which at present is the major source in the market. In this review, we show how the isolation of new strains of X. dendrorhous from the environment, the selection of mutants by the classical methods of random mutation and screening, and the rational metabolic engineering, have provided improved strains with higher astaxanthin productivity. To reduce production costs and enhance competitiveness from an industrial point of view, low-cost raw materials from industrial and agricultural origin have been adopted to get the maximal astaxanthin productivity. Finally, fermentation parameters have been studied in depth, both at flask and fermenter scales, to get maximal astaxanthin titers of 4.7 mg/g dry cell matter (420 mg/l) when X. dendrorhous was fermented under continuous white light. The industrial scale-up of this biotechnological process will provide a cost-effective method, alternative to synthetic astaxanthin, for the commercial exploitation of the expensive astaxanthin (about $2,500 per kilogram of pure astaxanthin).     

Landscape fragmentation affects responses of avian communities to climate change

Forecasting the consequences of climate change is contingent upon our understanding of the relationship between biodiversity patterns and climatic variability. While the impacts of climate change on individual species have been well‐documented, there is a paucity of studies on climate‐mediated changes in community dynamics. Our objectives were to investigate the relationship between temporal turnover in avian biodiversity and changes in climatic conditions and to assess the role of landscape fragmentation in affecting this relationship. We hypothesized that community turnover would be highest in regions experiencing the most pronounced changes in climate and that these patterns would be reduced in human‐dominated landscapes. To test this hypothesis, we quantified temporal turnover in avian communities over a 20‐year period using data from the New York State Breeding Atlases collected during 1980–1985 and 2000–2005. We applied Bayesian spatially varying intercept models to evaluate the relationship between temporal turnover and temporal trends in climatic conditions and landscape fragmentation. We found that models including interaction terms between climate change and landscape fragmentation were superior to models without the interaction terms, suggesting that the relationship between avian community turnover and changes in climatic conditions was affected by the level of landscape fragmentation. Specifically, we found weaker associations between temporal turnover and climatic change in regions with prevalent habitat fragmentation. We suggest that avian communities in fragmented landscapes are more robust to climate change than communities found in contiguous habitats because they are comprised of species with wider thermal niches and thus are less susceptible to shifts in climatic variability. We conclude that highly fragmented regions are likely to undergo less pronounced changes in composition and structure of faunal communities as a result of climate change, whereas those changes are likely to be greater in contiguous and unfragmented habitats.     

Altered expression of Bcl-2 and Bax in follicles within dehydroepiandrosterone-induced polycystic ovaries in rats

PCOS (polycystic ovary syndrome) is a heterogeneous disease characterized by hyperandrogenaemia, hirsutism, oligo- or amenorrhea, insulin resistance and anovulation. The aim of the present study was to evaluate if the balance between the ovarian expression of Bax (proapoptotic protein) and Bcl-2 (antiapoptotic protein) is altered in a PCOS model developed in rats by DHEA (dehydroepiandrosterone) administration. In addition, the ovarian morphology and the circulating progesterone levels were evaluated. Histological studies confirmed the presence of follicular cysts, atretic follicles and the absence of corpora lutea in the ovaries from the PCOS group and a significant decrease in circulating progesterone levels. Immunohistochemical studies showed that the expression of Bcl-2 and Bax were mainly localized in granulosa cells of AFs (antral follicles) in both groups. Bax expression was greater in preantral and AFs from PCOS ovarian sections than in the controls. In contrast, intense Bcl-2 immunostaining was observed in the control AFs, while Bcl-2 protein was either absent in PFs (preantral follicles) or weakly expressed in AFs from PCOS rats. These results were partially confirmed by Western studies. Data revealed that the ovarian level of Bcl-2 protein was lower in PCOS than in the control and that there were no differences in Bax ovarian levels between groups. However, Bax/Bcl-2 ratio was significantly higher in PCOS group than in the control group. In conclusion, an increase in ovarian apoptosis through an imbalance among the Bcl-2 family members may be involved in the transformation of growing follicles in cystic follicles in the ovaries from DHEA-induced PCOS rats.