Community challenges when using large plastic bottles for Solar Energy Disinfection of Water (SODIS).

BACKGROUND: Communities living in developing countries as well as populations affected by natural or man-made disasters can be left at great risk from water related diseases, especially those spread through the faecal-oral route. Conventional water treatments such as boiling and chlorination can be effective but may prove costly for impoverished communities. Solar water disinfection (SODIS) has been shown to be a cheap and effective way for communities to treat their water. The exposure to sunlight is typically carried out in small volume plastic beverage bottles (up to 2 l). Given the water requirements of consumption and basic personal hygiene, this may not always meet the needs of communities. Recent work has shown 19-L plastic water dispenser containers to be effective SODIS reactors, comparable in efficacy to PET bottles. In this paper we outline the need for studying SODIS in large volumes and discuss 4 main associated challenges. DISCUSSION: Apart from clean water needed for consumption, access to adequate water is essential for sanitation and hygiene. Contamination of treated water through unwashed hands or vessels contributes heavily to the spread of water borne pathogens in communities. Traditional water treatments such as boiling and chlorination can be effective but may prove financially burdensome for low income communities. SODIS in large vessels could be used as a simple method to meet water requirements in low income and disaster affected populations. However, there have been some concerns associated with the conventional SODIS method; we identify the main ones to be: (1) cold or cloudy weather; (2) the fear of leaching in plastic bottles; (3) water turbidity, and; (4) community acceptance. The application of SODIS in large bottles like WDCs has the potential to be an efficient and cost effective method of disinfecting water, either for consumption until more rigorous water treatments can be put in place, or for sanitation and hygiene to curb the spread of fecal contamination. Further research is needed that can address some of the limitations and challenges associated with the use of large bottles for SODIS.

An investigation of Sigma-1 receptor expression and ligand-induced endoplasmic reticulum stress in breast cancer.

Targeted therapeutic options and prognostic biomarkers for hormone receptor- or Her2 receptor-negative breast cancers are severely limited. The sigma-1 receptor, a stress-activated chaperone, is frequently dysregulated in disease. However, its significance in breast cancer (BCa) has not been adequately explored. Here, we report that the sigma-1 receptor gene (SIGMAR1) is elevated in BCa, particularly in the aggressive triple-negative (TNBC) subtype. By examining several patient datasets, we found that high expression at both the gene (SIGMAR1) and protein (Sig1R) levels associated with poor survival outcomes, specifically in ER-Her2- groups. Our data further show that high SIGMAR1 was predictive of shorter survival times in patients treated with adjuvant chemotherapy (ChT). Interestingly, in a separate cohort who received neoadjuvant taxane + anthracycline treatment, elevated SIGMAR1 associated with higher rates of pathologic complete response (pCR). Treatment with a Sig1R antagonist, 1-(4-iodophenyl)-3-(2-adamantyl)guanidine (IPAG), activated the unfolded protein response (UPR) in TNBC (high-Sig1R expressing) and ER + (low-Sig1R expressing) BCa cell lines. In tamoxifen-resistant LY2 cells, IPAG caused Sig1R to aggregate and co-localise with the stress marker BiP. These findings showcase the potential of Sig1R as a novel biomarker in TNBC as well as highlight its ligand-induced interference with the stress-coping mechanisms of BCa cells.

Hazards of Using Masking Protocols When Performing Ligand Binding Assays: Lessons From the Sigma-1 and Sigma-2 Receptors.

Sigma-1 and sigma-2 receptors are emerging therapeutic targets. Although the molecular identity of the sigma-2 receptor has recently been determined, receptor quantitation has used, and continues to use, the sigma-1 selective agents (+) pentazocine or dextrallorphan to mask the sigma-1 receptor in radioligand binding assays. Here, we have assessed the suitability of currently established saturation and competition binding isotherm assays that are used to quantify parameters of the sigma-2 receptor. We show that whilst the sigma-1 receptor mask (+) pentazocine has low affinity for the sigma-2 receptor (Ki 406 nM), it can effectively compete at this site with [³H] di-O-tolyl guanidine (DTG) at the concentrations frequently used to mask the sigma-1 receptor (100 nM and 1 µM). This competition influences the apparent affinity of DTG and other ligands tested in this system. A more troublesome issue is that DTG can displace (+) pentazocine from the sigma-1 receptor, rendering it partly unmasked. Indeed, commonly used concentrations of (+) pentazocine, 100 nM and 1 µM, allowed 37 and 11% respectively of sigma-1 receptors to be bound by DTG (300 nM), which could result in an overestimation of sigma-2 receptor numbers in assays where sigma-1 receptors are also present. Similarly, modelled data for 1 µM dextrallorphan show that only 71-86% of sigma-1 receptors would be masked in the presence of 300 nM DTG. Therefore, the use of dextrallorphan as a masking agent would also lead to the overestimation of sigma-2 receptors in systems where sigma-1 receptors are present. These data highlight the dangers of using masking agents in radioligand binding studies and we strongly recommend that currently used masking protocols are not used in the study of sigma-2 receptors. In order to overcome these problems, we recommend the use of a cell line apparently devoid of sigma-1 receptors [e.g., MCF7 (ATCC HTB-22)] in the absence of any masking agent when determining the affinity of agents for the sigma-2 receptor. In addition, assessing the relative levels of sigma-1 and sigma-2 receptors can be achieved using [³H] DTG saturation binding followed by two-site analysis of (+) pentazocine competition binding with [³H] DTG.