Perfluorinated alkyl substances (PFASs) in northern Spain municipal solid waste landfill leachates

Landfill leachates have been recognized as significant secondary sources of poly- and perfluoroalkyl substances (PFASs). This study presents data on the occurrence and concentration of 11 perfluoroalkyl carboxylates (PFCAs) and 5 perfluoroalkyl sulfonates (PFSAs) in leachates from 4 municipal solid waste landfill sites located across northern Spain. To the best of our knowledge, this is the first report of the presence of PFASs in Spanish landfill leachates. Two of the landfill sites applied on-site treatment using membrane bioreactors (MBR), and its effect on PFASs occurrence is also reported. Total PFASs (∑PFASs) in raw leachates reached 1378.9 ng/L, while in treated samples ∑PFASs was approximately two-fold (3162.3 ng/L). PFCAs accounted for the majority of the detected PFASs and perfluorooctanoic acid (PFOA) was the dominant compound in raw leachates (42.6%), followed by shorter chain PFHxA (30.1%), PFPeA and PFBA. The age of the sites might explain the PFASs pattern found in raw leachates as all of them were stabilized leachates. However, PFASs profile was different in treated samples where the most abundant compound was PFHxA (26.5%), followed by linear perfluorobutane sulfonate (L-PFBS) (18.7%) and PFOA (17.7%). The overall increase of the PFASs content as well as the change in the PFASs profile after the MBR treatment, could be explained by the possible degradation of PFASs precursors such as fluorotelomer alcohols or fluorotelomer sulfonates. Using the volume of leachates generated in the landfill sites, that served 1.8 million people, the discharge of 16 ∑PFASs contained in the landfill leachates was estimated as 1209 g/year.The authors thank financial support from the Spanish Ministry of Economy and Competitiveness (Project CTM2013-44081-R)

Gene and protein expression of glucose transporter 1 and glucose transporter 3 in human laryngeal cancer—the relationship with regulatory hypoxia-inducible factor-1α expression, tumor invasiveness, and patient prognosis

Increased glucose uptake mediated by glucose transporters and reliance on glycolysis are common features of malignant cells. Hypoxia-inducible factor-1α supports the adaptation of hypoxic cells by inducing genes related to glucose metabolism. The contribution of glucose transporter (GLUT) and hypoxia-inducible factor-1α (HIF-1α) activity to tumor behavior and their prognostic value in head and neck cancers remains unclear. The aim of this study was to examine the predictive value of GLUT1, GLUT3, and HIF-1α messenger RNA (mRNA)/protein expression as markers of tumor aggressiveness and prognosis in laryngeal cancer. The level of hypoxia/metabolic marker genes was determined in 106 squamous cell laryngeal cancer (SCC) and 73 noncancerous matched mucosa (NCM) controls using quantitative realtime PCR. The related protein levels were analyzed by Western blot. Positive expression of SLC2A1, SLC2A3, and HIF-1α genes was noted in 83.9, 82.1, and 71.7 % of SCC specimens and in 34.4, 59.4, and 62.5 % of laryngeal cancer samples. Higher levels of mRNA/protein for GLUT1 and HIF-1α were noted in SCC compared to NCM (p<0.05). SLC2A1 was found to have a positive relationship with grade, tumor front grading (TFG) score, and depth and mode of invasion (p<0.05). SLC2A3 was related to grade and invasion type (p<0.05). There were also relationships of HIF-1α with pTNM, TFG scale, invasion depth and mode, tumor recurrences, and overall survival (p<0.05). In addition, more advanced tumors were found to be more likely to demonstrate positive expression of these proteins. In conclusion, the hypoxia/metabolic markers studied could be used as molecular markers of tumor invasiveness in laryngeal cancer.This work was supported, in part, by the statutory fund of the Department of Cytobiochemistry, University of Łódź, Poland (506/811), and by grant fromtheNational Science Council, Poland (N403 043 32/2326)

Brahma Is Required for Proper Expression of the Floral Repressor FLC in Arabidopsis

This is an open-access article distributed under the terms of the Creative Commons Attribution License.[Background]: BRAHMA (BRM) is a member of a family of ATPases of the SWI/SNF chromatin remodeling complexes from Arabidopsis. BRM has been previously shown to be crucial for vegetative and reproductive development. [Methodology/Principal Findings]: Here we carry out a detailed analysis of the flowering phenotype of brm mutant plants which reveals that, in addition to repressing the flowering promoting genes CONSTANS (CO), FLOWERING LOCUS T (FT) and SUPPRESSOR OF OVEREXPRESSION OF CO1 (SOC1), BRM also represses expression of the general flowering repressor FLOWERING LOCUS C (FLC). Thus, in brm mutant plants FLC expression is elevated, and FLC chromatin exhibits increased levels of histone H3 lysine 4 tri-methylation and decreased levels of H3 lysine 27 tri-methylation, indicating that BRM imposes a repressive chromatin configuration at the FLC locus. However, brm mutants display a normal vernalization response, indicating that BRM is not involved in vernalization-mediated FLC repression. Analysis of double mutants suggests that BRM is partially redundant with the autonomous pathway. Analysis of genetic interactions between BRM and the histone H2A.Z deposition machinery demonstrates that brm mutations overcome a requirement of H2A.Z for FLC activation suggesting that in the absence of BRM, a constitutively open chromatin conformation renders H2A.Z dispensable. [Conclusions/Significance]: BRM is critical for phase transition in Arabidopsis. Thus, BRM represses expression of the flowering promoting genes CO, FT and SOC1 and of the flowering repressor FLC. Our results indicate that BRM controls expression of FLC by creating a repressive chromatin configuration of the locus.This work was supported by Ministerio de Educacin y Ciencia (BFU2008-00238, CSD2006-00049), and by Junta de Andaluca (P06-CVI-01400) to J.C.R. and by the National Institutes of Health (grant no. 1R01GM079525), and the National Science Foundation (grant no. 0446440) to R.A. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe

Role of aberrant metalloproteinase activity in the pro-inflammatory phenotype of bronchial epithelium in COPD

<p>Abstract</p> <p>Background</p> <p>Cigarette smoke, the major risk factor for COPD, is known to activate matrix metalloproteinases in airway epithelium. We investigated whether metalloproteinases, particularly A Disintegrin and Metalloproteinase (ADAM)17, contribute to increased pro-inflammatory epithelial responses with respect to the release of IL-8 and TGF-α, cytokines implicated in COPD pathogenesis.</p> <p>Methods</p> <p>We studied the effects of cigarette smoke extract (CSE) and metalloproteinase inhibitors on TGF-α and IL-8 release in primary bronchial epithelial cells (PBECs) from COPD patients, healthy smokers and non-smokers.</p> <p>Results</p> <p>We observed that TGF-α was mainly shed by ADAM17 in PBECs from all groups. Interestingly, IL-8 production occurred independently from ADAM17 and TGF-α shedding, but was significantly inhibited by broad-spectrum metalloproteinase inhibitor TAPI-2. CSE did not induce ADAM17-dependent TGF-α shedding, while it slightly augmented the production of IL-8. This was accompanied by reduced endogenous inhibitor of metalloproteinase (TIMP)-3 levels, suggesting that CSE does not directly but rather indirectly alter activity of ADAM17 through the regulation of its endogenous inhibitor. Furthermore, whereas baseline TGF-α shedding was lower in COPD PBECs, the early release of IL-8 (likely due to its shedding) was higher in PBECs from COPD than healthy smokers. Importantly, this was accompanied by lower TIMP-2 levels in COPD PBECs, while baseline TIMP-3 levels were similar between groups.</p> <p>Conclusions</p> <p>Our data indicate that IL-8 secretion is regulated independently from ADAM17 activity and TGF-α shedding and that particularly its early release is differentially regulated in PBECs from COPD and healthy smokers. Since TIMP-2-sensitive metalloproteinases could potentially contribute to IL-8 release, these may be interesting targets to further investigate novel therapeutic strategies in COPD.</p

Are ethnic disparities in HbA1c levels explained by mental wellbeing? Analysis of population-based data from the Health Survey for England

Aims: It is unclear how ethnic differences in HbA1c levels are affected by individual variations in mental wellbeing. Thus, the aim of this study was to assess the extent to which HbA1c disparities between Caucasian and South Asian adults are mediated by various aspects of positive psychological functioning. Methods: Data from the 2014 Health Survey for England was analysed using bootstrapping methods. A total of 3894 UK residents with HbA1c data were eligible to participate. Mental wellbeing was assessed using the Warwick-Edinburgh Mental Well-Being Scale. To reduce bias BMI, blood pressure, diabetes status, and other factors were treated as covariates. Results: Ethnicity directly predicted blood sugar control (unadjusted coefficient -2.15; 95% CI -3.64, -0.67), with Caucasians generating lower average HbA1c levels (37.68 mmol/mol (5.6%)) compared to South Asians (39.87 mmol/mol (5.8%)). This association was mediated by positive mental wellbeing, specifically concerning perceived vigour (unadjusted effect 0.30; 95% CI 0.13, 0.58): South Asians felt more energetic than Caucasians (unadjusted coefficient -0.32; 95% CI -0.49, -0.16), and greater perceived energy predicted lower HbA1c levels (unadjusted coefficient -0.92; 95% CI -1.29, -0.55). This mediator effect accounted for just over 14% of the HbA1c variance, and was negated after adjusting for BMI. Conclusions: Caucasian experience better HbA1c levels compared with their South Asian counterparts. However, this association is partly confounded by individual differences in perceived energy levels, which is implicated in better glycaemic control, and appears to serve a protective function in South Asians

Direct EPR Detection of Nitric Oxide in Mice Infected with the Pathogenic Mycobacterium Mycobacterium tuberculosis

It has been shown that treatment of mice preinfected with Mycobacterium tuberculosis with spin NO traps (iron complexes with diethyldithiocarbamate) enables detection of large amounts of NO in internal organs 2 and 4 weeks after infection (up to 55–57 μmol/kg of wet lung tissue accumulated with spin NO traps during 30 min). The animals were infected with the drug-sensitive laboratory strain H37Rv and a clinical isolate nonrespondent to antituberculous drugs (the multidrug-resistant strain of M. tuberculosis) obtained from a patient with an active form of tuberculosis. Two weeks after infection with the multidrug-resistant strain, the NO level in the lungs, spleen, liver and kidney increased sharply concurrently with slight lesions of lung tissue. A reverse correlation, i.e., low level of NO in the lungs and other internal organs and extensive injury of lung tissue, was established for H37Rv-infected mice. Four weeks after infection, NO production in the lungs increased dramatically for both M. tuberculosis strains resulting in 80–84% damage of lung tissue. The lesion is suggested to be due to the development of defense mechanisms in M. tuberculosis counteracting NO effects

The hTERT Promoter Enhances the Antitumor Activity of an Oncolytic Adenovirus under a Hypoxic Microenvironment

Hypoxia is a microenvironmental factor that contributes to the invasion, progression and metastasis of tumor cells. Hypoxic tumor cells often show more resistance to conventional chemoradiotherapy than normoxic tumor cells, suggesting the requirement of novel antitumor therapies to efficiently eliminate the hypoxic tumor cells. We previously generated a tumor-specific replication-competent oncolytic adenovirus (OBP-301: Telomelysin), in which the human telomerase reverse transcriptase (hTERT) promoter drives viral E1 expression. Since the promoter activity of the hTERT gene has been shown to be upregulated by hypoxia, we hypothesized that, under hypoxic conditions, the antitumor effect of OBP-301 with the hTERT promoter would be more efficient than that of the wild-type adenovirus 5 (Ad5). In this study, we investigated the antitumor effects of OBP-301 and Ad5 against human cancer cells under a normoxic (20% oxygen) or a hypoxic (1% oxygen) condition. Hypoxic condition induced nuclear accumulation of the hypoxia-inducible factor-1α and upregulation of hTERT promoter activity in human cancer cells. The cytopathic activity of OBP-301 was significantly higher than that of Ad5 under hypoxic condition. Consistent with their cytopathic activity, the replication of OBP-301 was significantly higher than that of Ad5 under the hypoxic condition. OBP-301-mediated E1A was expressed within hypoxic areas of human xenograft tumors in mice. These results suggest that the cytopathic activity of OBP-301 against hypoxic tumor cells is mediated through hypoxia-mediated activation of the hTERT promoter. Regulation of oncolytic adenoviruses by the hTERT promoter is a promising antitumor strategy, not only for induction of tumor-specific oncolysis, but also for efficient elimination of hypoxic tumor cells