Online fluorescence spectroscopy for the real-time evaluation of the microbial quality of drinking water

We assessed the utility of online fluorescence spectroscopy for the real-time evaluation of the microbial quality of untreated drinking water. Online fluorimeters were installed on the raw water intake at four groundwater -derived UK public water supplies alongside existing turbidity sensors that are used to forewarn of the presence of microbial contamination in the water industry. The fluorimeters targeted fluorescent dissolved organic matter (DOM) peaks at excitation/emission wavelengths of 280/365 nm (tryptophan-like fluorescence, TLF) and 280/450 nm (humic-like fluorescence, HLF). Discrete samples were collected for Escherichia coli, total bacterial cell counts by flow cytometry, and laboratory-based fluorescence and absorbance. Both TLF and HLF were strongly correlated with E. coli (r ¼ 0.71e0.77)and total bacterial cell concentrations (r ¼ 0.73e0.76), whereas the correlations between turbidity and E. coli (r ¼ 0.48) and total bacterial cell counts (r ¼ 0.40) were much weaker. No clear TLF peak was observed at the sites and all apparent TLF was considered to be optical bleed-through from the neighbouring HLF peak. Therefore, a HLF fluorimeter alone would be sufficient to evaluate the microbial water quality at these sources. Fluorescent DOM was also influenced by site operations such as pump start-up and the precipitation of cations on the sensor windows. Online fluorescent DOM sensors are a better indicator of the microbial quality of untreated drinking water than turbidity and they have wide-ranging potential applications within the water industry

SARS-CoV-2 Spike triggers barrier dysfunction and vascular leak via integrins and TGF-β signaling

Severe COVID-19 is associated with epithelial and endothelial barrier dysfunction within the lung as well as in distal organs. While it is appreciated that an exaggerated inflammatory response is associated with barrier dysfunction, the triggers of vascular leak are unclear. Here, we report that cell-intrinsic interactions between the Spike (S) glycoprotein of SARS-CoV-2 and epithelial/endothelial cells are sufficient to induce barrier dysfunction in vitro and vascular leak in vivo, independently of viral replication and the ACE2 receptor. We identify an S-triggered transcriptional response associated with extracellular matrix reorganization and TGF-β signaling. Using genetic knockouts and specific inhibitors, we demonstrate that glycosaminoglycans, integrins, and the TGF-β signaling axis are required for S-mediated barrier dysfunction. Notably, we show that SARS-CoV-2 infection caused leak in vivo, which was reduced by inhibiting integrins. Our findings offer mechanistic insight into SARS-CoV-2-triggered vascular leak, providing a starting point for development of therapies targeting COVID-19

2-Aminophenoxazine-3-one and 2-amino-4,4α-dihydro-4α,7-dimethyl-3H-phenoxazine-3-one cause cellular apoptosis by reducing higher intracellular pH in cancer cells

We examined intracellular pH (pHi) of ten cancer cell lines derived from different organs and two normal cell lines including human embryonic lung fibroblast cells (HEL) and human umbilical vein endothelial cells (HUVEC) in vitro, and found that pHi of most of these cancer cells was evidently higher (pH 7.5 to 7.7) than that of normal cells (7.32 and 7.44 for HEL and HUVEC, respectively) and that of primary leukemic cells and erythrocytes hitherto reported (≤7.2). Higher pHi in these cancer cells could be related to the Warburg effect in cancer cells with enhanced glycolytic metabolism. Since reversal of the Warburg effect may perturb intracellular homeostasis in cancer cells, we looked for compounds that cause extensive reduction of pHi, a major regulator of the glycolytic pathway and its associated metabolic pathway. We found that phenoxazine compounds, 2-aminophenoxazine-3-one (Phx-3) and 2-amino-4,4α-dihydro-4α,7-dimethyl-3H-phenoxazine-3-one (Phx-1) caused a rapid and drastic dose-dependent decrease of pHi in ten different cancer cells within 30 min, though the extent of the decrease of pHi was significantly larger for Phx-3 (ΔpHi = 0.6 pH units or more for 100 µM Phx-3) than for Phx-1 (ΔpHi = 0.1 pH units or more for 100 µM Phx-1). This rapid and drastic decrease of pHi in a variety of cancer cells caused by Phx-3 and Phx-1 possibly perturbed their intracellular homeostasis, and extensively affected the subsequent cell death, because these phenoxazines exerted dose-dependent proapoptotic and cytotoxic effects on these cells during 72 h incubation, confirming a causal relationship between ΔpHi and cytotoxic effects due to Phx-3 and Phx-1. Phx-3 and Phx-1 also reduced pHi of normal cells including HEL and HUVEC, although they exerted less proapoptotic and cytotoxic effects on these cells than on cancer cells. Drugs such as Phx-3 and Phx-1 that reduce pHi and thereby induce cellular apoptosis might serve as benevolent anticancer drugs

Closing the loop Approaches to monitoring the state of the Arctic Mediterranean during the International Polar Year 20072008

During the 4th International Polar Year 2007–2009 (IPY), it has become increasingly obvious that we need to prepare for a new era in the Arctic. IPY occurred during the time of the largest retreat of Arctic sea ice since satellite observations started in 1979. This minimum in September sea ice coverage was accompanied by other signs of a changing Arctic, including the unexpectedly rapid transpolar drift of the Tara schooner, a general thinning of Arctic sea ice and a double-dip minimum of the Arctic Oscillation at the end of 2009. Thanks to the lucky timing of the IPY, those recent phenomena are well documented as they have been scrutinized by the international research community, taking advantage of the dedicated observing systems that were deployed during IPY. However, understanding changes in the Arctic System likely requires monitoring over decades, not years. Many IPY projects have contributed to the pilot phase of a future, sustained, observing system for the Arctic. We now know that many of the technical challenges can be overcome. The Norwegian projects iAOOS-Norway, POLEWARD and MEOP were significant ocean monitoring/research contributions during the IPY. A large variety of techniques were used in these programs, ranging from oceanographic cruises to animal-borne platforms, autonomous gliders, helicopter surveys, surface drifters and current meter arrays. Our research approach was interdisciplinary from the outset, merging ocean dynamics, hydrography, biology, sea ice studies, as well as forecasting. The datasets are tremendously rich, and they will surely yield numerous findings in the years to come. Here, we present a status report at the end of the official period for IPY. Highlights of the research include: a quantification of the Meridional Overturning Circulation in the Nordic Seas (“the loop”) in thermal space, based on a set of up to 15-year-long series of current measurements; a detailed map of the surface circulation as well as characterization of eddy dispersion based on drifter data; transport monitoring of Atlantic Water using gliders; a view of the water mass exchanges in the Norwegian Atlantic Current from both Eulerian and Lagrangian data; an integrated physical–biological view of the ice-influenced ecosystem in the East Greenland Current, showing for instance nutrient-limited primary production as a consequence of decreasing ice cover for larger regions of the Arctic Ocean. Our sea ice studies show that the albedo of snow on ice is lower when snow cover is thinner and suggest that reductions in sea ice thickness, without changes in sea ice extent, will have a significant impact on the arctic atmosphere. We present up-to-date freshwater transport numbers for the East Greenland Current in the Fram Strait, as well as the first map of the annual cycle of freshwater layer thickness in the East Greenland Current along the east coast of Greenland, from data obtained by CTDs mounted on seals that traveled back and forth across the Nordic Seas. We have taken advantage of the real-time transmission of some of these platforms and demonstrate the use of ice-tethered profilers in validating satellite products of sea ice motion, as well as the use of Seagliders in validating ocean forecasts, and we present a sea ice drift product – significantly improved both in space and time – for use in operational ice-forecasting applications. We consider real-time acquisition of data from the ocean interior to be a vital component of a sustained Arctic Ocean Observing System, and we conclude by presenting an outline for an observing system for the European sector of the Arctic Ocean