Bioanalytical and chemical evaluation of disinfection by-products in swimming pool water

Pool water disinfection is vital to prevent microbial pathogens. However, potentially hazardous disinfection by-products (DBP) are formed from the reaction between disinfectants and organic/inorganic precursors. The aim of this study was to evaluate the presence of DBPs in various swimming pool types in Brisbane, Australia, including outdoor, indoor and baby pools, and the dynamics after a complete water renewal. Chemical analysis of 36 regulated and commonly found DBPs and total adsorbable organic halogens as well as invitro bioassays targeting cytotoxicity, oxidative stress and genotoxicity were used to evaluate swimming pool water quality. Dichloroacetic acid and trichloroacetic acid dominated in the pool water samples with higher levels (up to 2600μg/L) than the health guideline values set by the Australian Drinking Water Guidelines (100μg/L). Chlorinated DBPs occurred at higher concentrations compared to tap water, while brominated DBPs decreased gradually with increasing pool water age. Biological effects were expressed as chloroacetic acid equivalent concentrations and compared to predicted effects from chemical analysis and biological characterisation of haloacetic acids. The quantified haloacetic acids explained 35-118% of the absorbable organic halogens but less than 4% of the observed non-specific toxicity (cytotoxicity), and less than 1% of the observed oxidative stress response and genotoxicity. While the DBP concentrations in Australian pools found in this study are not likely to cause any adverse health effect, they are higher than in other countries and could be reduced by better hygiene of pool users, such as thorough showering prior to entering the pool and avoiding urination during swimming

Hydrogen peroxide is not the cause of fish kills associated with Chattonella marina : cytological and physiological evidence

Author Posting. © The Authors, 2005. This is the author's version of the work. It is posted here by permission of Elsevier B. V. for personal use, not for redistribution. The definitive version was published in Aquatic Toxicology 72 (2005): 351-360, doi:10.1016/j.aquatox.2005.01.007.Chattonella marina, a harmful algal bloom (HAB) causative species, was used to study the mortality, physiology, and pathology of a marine stenohaline fish, goldlined seabream exposed to the toxic alga. The median lethal time (LT50) was 3 h upon exposure to 8000 cells/ml of C. marina. Significant induction of filamental chloride cells (CCs) [i.e. increases in CC fractional area and in the volume density of CCs], concomitant with significant reduction of blood osmolality, were found in C. marina treated fish. To verify whether the toxicity of C. marina was mediated through oxidative stress, a hydrogen peroxide exposure experiment was carried out and the toxicity as well as cytological and physiological changes were compared with the C. marina treatment. Hydrogen peroxide at a concentration of 500 μM H2O2, (i.e. 25 times higher than that produced by 8000 cells/ml of C. marina (20 μM H2O2)) was unable to induce similar CC alterations and osmoregulatory impairment in fish as observed in the C. marina treatment. Non-specific membrane damage such as severe loss of microvilli projections on the CC apical opening and rupture of epithelial membranes in the lamellae were observed. The LT50 was 6 h, two times longer than that with 8000 cells/ml of C. marina. Based on the cytological and physiological evidence and toxicity data, the mechanism by which C. marina kills fish appears to be very different from that caused by H2O2/ROS. Osmoregulatory distress is the major cause of fish death upon exposure to C. marina.The work described in this paper was supported by a grant from the Research Grants Council (Project No. 9040547 CityU 1105/00M) and a grant from the University Grants Committee (Project No. AoE/P-04/04) of the Hong Kong Special Administrative Region, China. Support for D. Anderson was also provided by the US National Science Foundation through grant no. OCE-0136861

Evaluation of Physicochemical and Antioxidant Properties of Peanut Protein Hydrolysate

Peanut protein and its hydrolysate were compared with a view to their use as food additives. The effects of pH, temperature and protein concentration on some of their key physicochemical properties were investigated. Compared with peanut protein, peanut peptides exhibited a significantly higher solubility and significantly lower turbidity at pH values 2–12 and temperature between 30 and 80°C. Peanut peptide showed better emulsifying capacity, foam capacity and foam stability, but had lower water holding and fat adsorption capacities over a wide range of protein concentrations (2–5 g/100 ml) than peanut protein isolate. In addition, peanut peptide exhibited in vitro antioxidant properties measured in terms of reducing power, scavenging of hydroxyl radical, and scavenging of DPPH radical. These results suggest that peanut peptide appeared to have better functional and antioxidant properties and hence has a good potential as a food additive

Caveolae-dependent and -independent uptake of albumin in cultured rodent pulmonary endothelial cells

Although a critical role for caveolae-mediated albumin transcytosis in pulmonary endothelium is well established, considerably less is known about caveolae-independent pathways. In this current study, we confirmed that cultured rat pulmonary microvascular (RPMEC) and pulmonary artery (RPAEC) endothelium endocytosed Alexa488-labeled albumin in a saturable, temperature-sensitive mode and internalization resulted in co-localization by fluorescence microscopy with cholera B toxin and caveolin-1. Although siRNA to caveolin-1 (cav-1) in RPAEC significantly inhibited albumin uptake, a remnant portion of albumin uptake was cav-1-independent, suggesting alternative pathways for albumin uptake. Thus, we isolated and cultured mouse lung endothelial cells (MLEC) from wild type and cav-1-/- mice and noted that ∼ 65% of albumin uptake, as determined by confocal imaging or live cell total internal reflectance fluorescence microscopy (TIRF), persisted in total absence of cav-1. Uptake of colloidal gold labeled albumin was evaluated by electron microscopy and demonstrated that albumin uptake in MLEC from cav-1-/- mice was through caveolae-independent pathway(s) including clathrin-coated pits that resulted in endosomal accumulation of albumin. Finally, we noted that albumin uptake in RPMEC was in part sensitive to pharmacological agents (amiloride [sodium transport inhibitor], Gö6976 [protein kinase C inhibitor], and cytochalasin D [inhibitor of actin polymerization]) consistent with a macropinocytosis-like process. The amiloride sensitivity accounting for macropinocytosis also exists in albumin uptake by both wild type and cav-1 -/- MLEC. We conclude from these studies that in addition to the well described caveolar-dependent pulmonary endothelial cell endocytosis of albumin, a portion of overall uptake in pulmonary endothelial cells is cav-1 insensitive and appears to involve clathrin-mediated endocytosis and macropinocytosis-like process. © 2013 Li et al

Prime–boost vaccination with plasmid and adenovirus gene vaccines control HER2/neu(+ )metastatic breast cancer in mice

INTRODUCTION: Once metastasis has occurred, the possibility of completely curing breast cancer is unlikely, particularly for the 30 to 40% of cancers overexpressing the gene for HER2/neu. A vaccine targeting p185, the protein product of the HER2/neu gene, could have therapeutic application by controlling the growth and metastasis of highly aggressive HER2/neu(+ )cells. The purpose of this study was to determine the effectiveness of two gene vaccines targeting HER2/neu in preventive and therapeutic tumor models. METHODS: The mouse breast cancer cell line A2L2, which expresses the gene for rat HER2/neu and hence p185, was injected into the mammary fat pad of mice as a model of solid tumor growth or was injected intravenously as a model of lung metastasis. SINCP-neu, a plasmid containing Sindbis virus genes and the gene for rat HER2/neu, and Adeno-neu, an E1,E2a-deleted adenovirus also containing the gene for rat HER2/neu, were tested as preventive and therapeutic vaccines. RESULTS: Vaccination with SINCP-neu or Adeno-neu before tumor challenge with A2L2 cells significantly inhibited the growth of the cells injected into the mammary fat or intravenously. Vaccination 2 days after tumor challenge with either vaccine was ineffective in both tumor models. However, therapeutic vaccination in a prime–boost protocol with SINCP-neu followed by Adeno-neu significantly prolonged the overall survival rate of mice injected intravenously with the tumor cells. Naive mice vaccinated using the same prime–boost protocol demonstrated a strong serum immunoglobulin G response and p185-specific cellular immunity, as shown by the results of ELISPOT (enzyme-linked immunospot) analysis for IFNγ. CONCLUSION: We report herein that vaccination of mice with a plasmid gene vaccine and an adenovirus gene vaccine, each containing the gene for HER2/neu, prevented growth of a HER2/neu-expressing breast cancer cell line injected into the mammary fat pad or intravenously. Sequential administration of the vaccines in a prime–boost protocol was therapeutically effective when tumor cells were injected intravenously before the vaccination. The vaccines induced high levels of both cellular and humoral immunity as determined by in vitro assessment. These findings indicate that clinical evaluation of these vaccines, particularly when used sequentially in a prime–boost protocol, is justified

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Literature review on the performance of diffusive samplers for the measurement of ammonia in ambient air and emissions to air

The information in this document has formed the basis from which a new standard on measurements employing ammonia diffusive samplers by CEN TC264 WG11 'Ambient air - Diffusive samplers' is being developed and provides an open reference document for the ammonia passive sampling techniques

Aberrant Expression of Oncogenic and Tumor-Suppressive MicroRNAs in Cervical Cancer Is Required for Cancer Cell Growth

MicroRNAs (miRNAs) play important roles in cancer development. By cloning and sequencing of a HPV16+ CaSki cell small RNA library, we isolated 174 miRNAs (including the novel miR-193c) which could be grouped into 46 different miRNA species, with miR-21, miR-24, miR-27a, and miR-205 being most abundant. We chose for further study 10 miRNAs according to their cloning frequency and associated their levels in 10 cervical cancer- or cervical intraepithelial neoplasia-derived cell lines. No correlation was observed between their expression with the presence or absence of an integrated or episomal HPV genome. All cell lines examined contained no detectable miR-143 and miR-145. HPV-infected cell lines expressed a different set of miRNAs when grown in organotypic raft cultured as compared to monolayer cell culture, including expression of miR-143 and miR-145. This suggests a correlation between miRNA expression and tissue differentiation. Using miRNA array analyses for age-matched normal cervix and cervical cancer tissues, in combination with northern blot verification, we identified significantly deregulated miRNAs in cervical cancer tissues, with miR-126, miR-143, and miR-145 downregulation and miR-15b, miR-16, miR-146a, and miR-155 upregulation. Functional studies showed that both miR-143 and miR-145 are suppressive to cell growth. When introduced into cell lines, miR-146a was found to promote cell proliferation. Collectively, our data indicate that downregulation of miR-143 and miR-145 and upregulation of miR-146a play a role in cervical carcinogenesis

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Structural similarity-based predictions of protein interactions between HIV-1 and Homo sapiens

Abstract Background In the course of infection, viruses such as HIV-1 must enter a cell, travel to sites where they can hijack host machinery to transcribe their genes and translate their proteins, assemble, and then leave the cell again, all while evading the host immune system. Thus, successful infection depends on the pathogen's ability to manipulate the biological pathways and processes of the organism it infects. Interactions between HIV-encoded and human proteins provide one means by which HIV-1 can connect into cellular pathways to carry out these survival processes. Results We developed and applied a computational approach to predict interactions between HIV and human proteins based on structural similarity of 9 HIV-1 proteins to human proteins having known interactions. Using functional data from RNAi studies as a filter, we generated over 2000 interaction predictions between HIV proteins and 406 unique human proteins. Additional filtering based on Gene Ontology cellular component annotation reduced the number of predictions to 502 interactions involving 137 human proteins. We find numerous known interactions as well as novel interactions showing significant functional relevance based on supporting Gene Ontology and literature evidence. Conclusions Understanding the interplay between HIV-1 and its human host will help in understanding the viral lifecycle and the ways in which this virus is able to manipulate its host. The results shown here provide a potential set of interactions that are amenable to further experimental manipulation as well as potential targets for therapeutic intervention