THM and HAA formation from NOM in raw and treated surface waters

The disinfection by-product (DBP) formation potential (FP) of natural organic matter (NOM) in surface water sources has been studied with reference to the key water quality determinants (WQDs) of UV absorption (UV254), colour, and dissolved organic carbon (DOC) concentration. The data set used encompassed raw and treated water sampled over a 30-month period from 30 water treatment works (WTWs) across Scotland, all employing conventional clarification. Both trihalomethane (THM) and haloacetic acid (HAA) FPs were considered. In addition to the standard bulk WQDs, the DOC content was fractionated and analysed for the hydrophobic (HPO) and hydrophilic (HPI) fractions. Results were quantified in terms of the yield (dDBPFP/dWQD) and the linear regression coefficient R2 of the yield trend. The NOM in the raw waters was found to comprise 30–84% (average 66%) of the more reactive HPO material, with this proportion falling to 18–63% (average 50%) in the treated water. Results suggested UV254 to be as good an indicator of DBPFP as DOC or HPO for the raw waters, with R2 values ranging from 0.79 to 0.82 for THMs and from 0.71 to 0.73 for HAAs for these three determinants. For treated waters the corresponding values were significantly lower at 0.52–0.67 and 0.46–0.47 respectively, reflecting the lower HPO concentration and thus UV254 absorption and commensurately reduced precision due to the limit of detection of the analytical instrument. It is concluded that fractionation offers little benefit in attempting to discern or predict chlorinated carbonaceous DBP yield for the waters across the geographical region studied. UV254 offered an adequate estimate of DBPFP based on a mean yield of ∼2600 and ∼2800 μg per cm−1 absorbance for THMFP for the raw and treated waters respectively and ∼3800 and2900 μg cm−1 for HAAFP, albeit with reduced precision for the treated waters

Spectroscopy of z ~ 7 candidate galaxies: using Lyman α to constrain the neutral fraction of hydrogen in the high-redshift universe

Following our previous spectroscopic observations of z > 7 galaxies with Gemini/Gemini Near Infra-Red Spectrograph (GNIRS) and Very Large Telescope (VLT)/XSHOOTER, which targeted a total of eight objects, we present here our results from a deeper and larger VLT/FOcal Reducer and Spectrograph (FORS2) spectroscopic sample of Wide Field Camera 3 selected z > 7 candidate galaxies. With our FORS2 setup we cover the 737–1070 nm wavelength range, enabling a search for Lyman α in the redshift range spanning 5.06–7.80. We target 22 z-band dropouts and find no evidence of Lyman α emission, with the exception of a tentative detection (<5σ, which is our adopted criterion for a secure detection) for one object. The upper limits on Lyman α flux and the broad-band magnitudes are used to constrain the rest-frame equivalent widths for this line emission. We analyse our FORS2 observations in combination with our previous GNIRS and XSHOOTER observations, and suggest that a simple model where the fraction of high rest-frame equivalent width emitters follows the trend seen at z = 3-6.5 is inconsistent with our non-detections at z ∼ 7.8 at the 96 per cent confidence level. This may indicate that a significant neutral H I fraction in the intergalactic medium suppresses Lyman α, with an estimated neutral fraction χHI∼0.5, in agreement with other estimates

Noncompetitive Inhibition of 5-HT3 Receptors by Citral, Linalool, and Eucalyptol Revealed by Nonlinear Mixed-Effects Modeling.

Citral, eucalyptol, and linalool are widely used as flavorings, fragrances, and cosmetics. Here, we examined their effects on electrophysiological and binding properties of human 5-HT3 receptors expressed in Xenopus oocytes and human embryonic kidney 293 cells, respectively. Data were analyzed using nonlinear mixed-effects modeling to account for random variance in the peak current response between oocytes. The oils caused an insurmountable inhibition of 5-HT-evoked currents (citral IC50 = 120 µM; eucalyptol = 258 µM; linalool = 141 µM) and did not compete with fluorescently labeled granisetron, suggesting a noncompetitive mechanism of action. Inhibition was not use-dependent but required a 30-second preapplication. Compound washout caused a slow (∼180 seconds) but complete recovery. Coapplication of the oils with bilobalide or diltiazem indicated they did not bind at the same locations as these channel blockers. Homology modeling and ligand docking predicted binding to a transmembrane cavity at the interface of adjacent subunits. Liquid chromatography coupled to mass spectrometry showed that an essential oil extracted from Lippia alba contained 75.9% citral. This inhibited expressed 5-HT3 receptors (IC50 = 45 µg ml(-1)) and smooth muscle contractions in rat trachea (IC50 = 200 µg ml(-1)) and guinea pig ileum (IC50 = 20 µg ml(-1)), providing a possible mechanistic explanation for why this oil has been used to treat gastrointestinal and respiratory ailments. These results demonstrate that citral, eucalyptol, and linalool inhibit 5-HT3 receptors, and their binding to a conserved cavity suggests a valuable target for novel allosteric modulators.Our thanks are given to John Peters (University of Dundee) for the 5-HT3A subunit, to Martin Lochner (Bern University) for reviewing our chemical structures and providing G-FL, and to Ruth Murrell-Lagnado for hosting the experimental work. AJT was supported by the British Heart Foundation (PG/13/39/30293).This is the final version of the article. It first appeared from the American Society for Pharmacology and Experimental Therapeutics via https://doi.org/10.1124/jpet.115.230011

Evidence for an effect of receptor density on ligand occupancy and agonist EC 50

Abstract: Drug-receptor interaction theory predicts that proportional receptor occupancy is a function of ligand concentration as defined by a ligand-receptor affinity constant, and is independent of receptor density. However, we previously observed that the EC50 of 5-HT reduced as the density of 5-HT3 receptors increased, suggesting an effect of receptor density on occupancy. The current study was designed to maximise variability in experimentally observed currents and confirm this apparent contradiction prospectively. Xenopus oocytes were injected with RNA encoding 5-HT3A receptors under conditions designed to achieve varying receptor expression levels and 5-HT-evoked currents measured using two electrode voltage clamp. Results from 99 oocytes showed that as the maximal peak current increased from 0.05 µA to 12.1 µA there was a 3.7-fold reduction in EC50. Since occupancy and conductance are directly related in this system, this indicates that for a given concentration of 5-HT, proportional occupancy increases with increased receptor density. We conclude that normalising data masks this correlation, and can result in reduced accuracy of pharmacological measurements. We propose a mechanistic explanation for our observations

Co-evolution of network structure and consumer inequality in a spatially explicit model of energetic resource acquisition

Energetic resources in ecological and social–ecological systems are distributed through complex networks, which co-evolve with the system and consumers to move resources from points of origin to those of end use. Past research has focused on effects of spatiotemporal resource heterogeneity in ecosystems and society, or socioeconomic drivers of inequality, with less attention to interactions between resource network structure and population-level outcomes. Here, we develop a spatially explicit, stock-flow consistent agent-based model of generic consumers building and crossing links between resources, and we explore the co-evolution of the emergent network structure and inequality in consumers’ resource reserves across three distinct landscapes. We show that the consumer inequality initially decreased during network expansion, then increased rapidly as the network reached a more stable state. The spatial distribution of resources in each of the three landscapes constrained the structures that could emerge, and therefore the specific rates and timings of these dynamics. This work demonstrates the use of energetically consistent modelling to understand possible relationships among a spatially distributed set of resources, the network structure that connects them to a population, and inequality in that population. This can provide a theoretical underpinning informing further work to better understand causes of resource inequality and heterogeneity in observed systems

No Evidence for Lyman-alpha Emission in Spectroscopy of z > 7 Candidate Galaxies

We present Gemini/GNIRS spectroscopic observations of 4 z-band (z~7) dropout galaxies and VLT/XSHOOTER observations of one z-band dropout and 3 Y-band (z~8-9) dropout galaxies in the Hubble Ultra Deep Field, which were selected with Wide Field Camera 3 imaging on the Hubble Space Telescope. We find no evidence of Lyman-alpha emission with a typical 5-sigma sensitivity of 5X10^-18erg/cm^2/s, and we use the upper limits on Lyman-alpha flux and the broad-band magnitudes to constrain the rest-frame equivalent widths for this line emission. Accounting for incomplete spectral coverage, we survey 3.0 z-band dropouts and 2.9 Y-band dropouts to a Lyman-alpha rest-frame equivalent width limit > 120Ang (for an unresolved emission line); for an equivalent width limit of 50Ang the effective numbers of drop-outs surveyed fall to 1.2 z-band drop-outs and 1.5 Y-band drop-outs. A simple model where the fraction of high rest-frame equivalent width emitters follows the trend seen at z=3-6.5 is inconsistent with our non-detections at z=7-9 at the ~ 1-sigma level for spectrally unresolved lines, which may indicate that a significant neutral HI fraction in the intergalactic medium suppresses the Lyman-alpha line in z-drop and Y-drop galaxies at z > 7.Comment: Accepted for publication in MNRA

Probing ∼L* Lyman-break galaxies at z ≈ 7 in GOODS-South with WFC3 on Hubble Space Telescope

We analyse recently acquired near-infrared Hubble Space Telescope imaging of the Great Observatories Origins Deep Survey (GOODS)-South field to search for star-forming galaxies at z ≈ 7.0. By comparing Wide Field Camera 3 (WFC3) 0.98 μm Y-band images with Advanced Camera for Surveys (ACS) z-band (0.85 μm) images, we identify objects with colours consistent with Lyman-break galaxies at z ≃ 6.4–7.4. This new data cover an area five times larger than that previously reported in the WFC3 imaging of the Hubble Ultra Deep Field and affords a valuable constraint on the bright end of the luminosity function. Using additional imaging of the region in the ACS B, V and i bands from GOODS v2.0 and the WFC3J band, we attempt to remove any low-redshift interlopers. Our selection criteria yields six candidates brighter than Y_(AB) = 27.0, of which all except one are detected in the ACS z-band imaging and are thus unlikely to be transients. Assuming all six candidates are at z ≈ 7, this implies a surface density of objects brighter than Y_(AB) = 27.0 of 0.30 ± 0.12 arcmin⁻², a value significantly smaller than the prediction from z≈ 6 luminosity function. This suggests continued evolution of the bright end of the luminosity function between z= 6 and 7, with number densities lower at higher redshift

Probing Unexpected Reactivity in Radiometal Chemistry: Indium-111-Mediated Hydrolysis of Hybrid Cyclen-Hydroxypyridinone Ligands

Chelators based on hydroxypyridinones have utility in incorporating radioactive metal ions into diagnostic and therapeutic agents used in nuclear medicine. Over the course of our hydroxypyridinone studies, we have prepared two novel chelators, consisting of a cyclen (1,4,7,10-tetraazacyclododecane) ring bearing two pendant hydroxypyridinone groups, appended via methylene acetamide motifs at either the 1,4-positions (L1) or 1,7-positions (L2) of the cyclen ring. In radiolabeling reactions of L1 or L2 with the γ-emitting radioisotope, [111In]In3+, we have observed radiometal-mediated hydrolysis of a single amide group of either L1 or L2. The reaction of either [111In]In3+ or [natIn]In3+ with either L1 or L2, in aqueous alkaline solutions at 80 °C, initially results in formation of [In(L1)]+ or [In(L2)]+, respectively. Over time, each of these species undergoes In3+-mediated hydrolysis of a single amide group to yield species in which In3+ remains coordinated to the resultant chelator, which consists of a cyclen ring bearing a single hydroxypyridinone group and a single carboxylate group. The reactivity toward hydrolysis is higher for the L1 complex compared to that for the L2 complex. Density functional theory calculations corroborate these experimental findings and importantly indicate that the activation energy required for the hydrolysis of L1 is significantly lower than that required for L2. This is the first reported example of a chelator undergoing radiometal-mediated hydrolysis to form a radiometalated complex. It is possible that metal-mediated amide bond cleavage is a source of instability in other radiotracers, particularly those in which radiometal complexation occurs in aqueous, basic solutions at high temperatures. This study highlights the importance of appropriate characterization of radiolabeled products