Search

Objective Small molecule inhibitors able to bind to gp120 and prevent CD4-induced HIV-1 envelope conformational change provide an important class of inhibitors. Currently, only Fostemsavir is approved for HAART, which makes this class of inhibitors attractive candidates for prevention. We assessed the activity of DS003 (BMS-599793), an analogue of BMS-378806, in different mucosal tissues and elucidated its mechanism of action. Design Pre-clinical analysis was performed with human mucosal tissue models as surrogates of in vivo activity. Methods Antiviral efficacy of DS003 was assessed in mucosal tissue explants (ecto-cervical, penile and colorectal) and in trans-infection models (co-cultures of dendritic or mucosal migratory cells with CD4+T cells) with several dosing times (2 h, 24 h and sustained) and in combination with a fusion inhibitor. Binding of DS003 to gp120 was assessed by flow cytometry and bio-layer interferometry and further probed in competitive studies using soluble CD4 (sCD4) and an anti-CD4 induced antibody, 17b. Results In all models, the inhibitory activity of DS003 was increased with longer periods of exposure and by combination with a fusion inhibitor. Pre-exposure to sCD4 impeded DS003 binding to viral envelope (Env). In contrast, DS003 did not impact subsequent binding of sCD4. Furthermore, sCD4-induced epitope exposure as assessed by 17b binding was significantly reduced in the presence of DS003. Conclusion DS003 inhibits HIV-1 infection by binding to or near the CD4 binding site of gp120, preventing CD4-induced conformational change essential for viral fusion. These data highlight the potential of DS003 for development as a pre-exposure prophylaxis candidate.

The River Thames and 15 of its major tributaries have been monitored at weekly intervals since March 2009. Monitored determinands include major nutrient fractions, anions, cations, metals, pH, alkalinity, and chlorophyll a and are linked to mean daily river flows at each site. This catchment-wide biogeochemical monitoring platform captures changes in the water quality of the Thames basin during a period of rapid change, related to increasing pressures (due to a rapidly growing human population, increasing water demand and climate change) and improvements in sewage treatment processes and agricultural practices. The platform provides the research community with a valuable data and modelling resource for furthering our understanding of pollution sources and dynamics, as well as interactions between water quality and aquatic ecology. Combining Thames Initiative data with previous (non-continuous) monitoring data sets from many common study sites, dating back to 1997, has shown that there have been major reductions in phosphorus concentrations at most sites, occurring at low river flow, and these are principally due to reduced loadings from sewage treatment works (STWs). This ongoing monitoring programme will provide the vital underpinning environmental data required to best manage this vital drinking water resource, which is key for the sustainability of the city of London and the wider UK economy. The Thames Initiative data set is freely available from the Centre for Ecology and Hydrology's (CEH) Environmental Information Data Centre at https://doi.org/10.5285/e4c300b1-8bc3-4df2-b23a-e72e67eef2fd.

Bromine in rainfall, cloud water, stream water and groundwater were measured in the upper River Severn catchments at Plynlimon in mid-Wales using two analytical procedures for bromide determination: a colorimetric method and, later, ion chromatography. Discrepancies between the methods indicated that the colorimetric method was measuring more than just bromide so it was "dissolved labile bromine" (DLBr) (Neal et al., 2007). This paper reports the variation in DLBr and bromide across the Plynlimon region and assesses the differences between these two measures. The average DLBr concentration in the streams ranges between 18.3 and 27.8 µg l−1 compared with a rainfall average concentration of 15.6 µg l−1. The corresponding bromide concentrations in the streams are 13.8–18.6 µg l−1 and 13.2 µg l−1 in rainfall. For cloud water, throughfall and stemflow, DLBr concentrations are an order of magnitude higher than in rainfall and the concentrations are strongly correlated with chloride. Average values of bromide in rainfall and cloud water are similar to those of DLBr and are strongly correlated with chloride: unfortunately, no bromide measurements were taken in throughfall and stemflow. These results indicate that marine aerosol inputs are high and that the DLBr in these inputs is dominated by bromide. For cloud water, DLBr was correlated with dissolved organic carbon (DOC) as well as with chloride; hence, there may well be an organic-associated component. Within the streams draining the forested areas, DLBr increases with time as DOC increases. DLBr concentrations in the streams are correlated with DOC in most cases and, to a lesser degree, with chloride. However, for bromide there is no correlation with DOC, but a weak correlation with chloride remains and the gradient is higher than for the DLBr case. Increasing concentrations of both DLBr and DOC may well reflect the wetting up of the catchments as transpiration diminshes as the trees age as well as through felling. In groundwater, only DLBr has been measured, and its concentration is similar to that for the streams. However, in the groundwater zone, DLBr is poorly correlated with DOC concentrations, in which DOC is largely converted to CO2. Atmospheric input–stream output flux estimates indicate a net uptake of bromide by the catchment of around 30%, matched by a corresponding release of DOC-associated bromine.

The results of determination of bromide, chloride, fluoride, nitrate and sulphate using ion chromatography (IC) are compared with those obtained by colorimetric and inductively coupled plasma optical emission spectroscopy (ICPOES) for rainfall, cloud water and stream waters in the Plynlimon experimental catchments of mid-Wales. For bromide, the concentrations determined by IC are lower than those for the colorimetric method used; the colorimetric method probably determined bromide plus organo-bromine compounds. It is suggested that the values determined by the colorimetric method be termed dissolved labile bromine (DLBr). The study shows that sulphate is the overriding form of sulphur in the waters. For chloride and nitrate, measurements by both methods approach a 1:1 relationship that is barely statistically significantly different from unity. For fluoride, the IC method gives lower values than the colorimetric, especially for the stream waters. However, the colorimetric method determines total fluorine so that a difference is to be expected (for example, fluoride strongly complexes with aluminium that is present, especially in the streamwater).

Early work in fan studies examined fan activities as forms of resistance, enabling fans to reclaim ownership of popular culture. Jonathan Gray (2003) and Cornel Sandvoss (2005) , however, argue that to fully understand what it means to interact with texts we must also examine anti-fans. This article builds on Gray and Sandvoss’s work by expanding on Francesca Haig’s (2013) discussion of ‘snark’ fandom. We suggest that the Fifty Shades of Grey trilogy (2012) has generated an ironic, even guilty fandom, in which readers and viewers bemoan the series’ flaws, while enjoying (sometimes furtively) the texts. We structure this as an analysis of the anti-fandom’s denigration of Fifty Shades as ‘bad literature’ and ‘bad eroticism’ to be consumed by an imagined female reader. We argue that this cultural disavowal of Fifty Shades is based upon cultural distinctions of taste (Bourdieu, 1984) and suggest that the BDSM community’s rejection of the books’ sexual politics is founded upon its own distinction of taste.

This scientific briefing announces the availability of a new multi-element high-frequency water quality data set that is openly accessible to the research community. The data set comprises up to 2 years of 7-hourly water quality data for two streams and one rainfall site in the Upper Severn catchment at Plynlimon in Mid-Wales. The measurements cover 50 analytes ranging from H+ to U and spanning six orders of magnitude in concentration, including major, minor and trace elements as well as nutrients, and they complement decades of weekly measurements of the same analytes at the Upper Severn. Together, the weekly and 7-hourly time series provide a unique data set for studying both long-term trends and short-term dynamics. The data show complex behaviour over a wide range of timescales, challenging our understanding of catchment processes and informing future modelling efforts. Copyright © 2013 John Wiley & Sons, Ltd.

River phytoplankton blooms can pose a serious risk to water quality and the structure and function of aquatic ecosystems. Developing a greater understanding of the physical and chemical controls on the timing, magnitude and duration of blooms is essential for the effective management of phytoplankton development. Five years of weekly water quality monitoring data along the River Thames, southern England were combined with hourly chlorophyll concentration (a proxy for phytoplankton biomass), flow, temperature and daily sunlight data from the mid-Thames. Weekly chlorophyll data was of insufficient temporal resolution to identify the causes of short term variations in phytoplankton biomass. However, hourly chlorophyll data enabled identification of thresholds in water temperature (between 9 and 19 °C) and flow (

Chlorophyll-a and nutrient concentrations were monitored at weekly intervals across 21 river sites throughout the River Thames basin, southern England, between 2009 and 2011. Despite a 90% decrease in soluble reactive phosphorus (SRP) concentration of the lower River Thames since the 19905, very large phytoplankton blooms still occur. Chlorophyll concentrations were highest in the mid and lower River Thames and the larger tributaries. Lowest chlorophyll concentrations were observed in the smaller tributaries, despite some having very high phosphorus concentrations of over 300 mu g l(-1). There was a strong positive correlation between river length and mean chlorophyll concentration (R-2=0.82), and rivers connected to canals had ca. six times greater chlorophyll concentration than 'natural' rivers with similar phosphorus concentrations, indicating the importance that residence time has on determining phytoplankton biomass. Phosphorus concentration did have some influence, with phosphorus-enriched rivers having much larger phytoplankton blooms than nutrient-poor rivers of a similar length. Water quality improvements may now be capping chlorophyll peaks in the Rivers Thames and Kennet, due to SRP depletion during the spring/early summer phytoplankton bloom period. Dissolved reactive silicon was also depleted to potentially-limiting concentrations for diatom growth in the River Thames during these phytoplankton blooms, but nitrate remained in excess for all rivers throughout the study period. Other potential mitigation measures, such as increasing riparian shading and reducing residence times by removing impoundments may be needed, alongside phosphorus mitigation, to reduce the magnitude of phytoplankton blooms in the future.

Colin Neal, Michael Bowes,* Helen P. Jarvie, Paul Scholefield, Graham Leeks, Margaret Neal, Philip Rowland, Heather Wickham, Sarah Harman, Linda Armstrong, Darren Sleep, Alan Lawlor and Cynthia E Davies 1 Centre for Ecology and Hydrology, Crowmarsh Gifford, Wallingford, Oxfordshire, OX10 8BB, UK 2 Centre for Ecology and Hydrology, Lancaster Environment Centre, Library Avenue, Bailrigg, Lancaster LA1 4AP, UK

The water quality of the River Frome, Dorset, southern England, was monitored at weekly intervals from 1965 until 2009. Determinands included phosphorus, nitrogen, silicon, potassium, calcium, sodium, magnesium, pH, alkalinity and temperature. Nitrate-N concentrations increased from an annual average of 2.4 mg l⁻¹ in the mid to late 1960s to 6.0 mg l⁻¹ in 2008-2009, but the rate of increase was beginning to slow. Annual soluble reactive phosphorus (SRP) concentrations increased from 101 μg l⁻¹ in the mid 1960s to a maximum of 190 μg l⁻¹ in 1989. In 2002, there was a step reduction in SRP concentration (average=88 μg l⁻¹ in 2002-2005), with further improvement in 2007-2009 (average=49 μg l⁻¹), due to the introduction of phosphorus stripping at sewage treatment works. Phosphorus and nitrate concentrations showed clear annual cycles, related to the timing of inputs from the catchment, and within-stream bioaccumulation and release. Annual depressions in silicon concentration each spring (due to diatom proliferation) reached a maximum between 1980 and 1991, (the period of maximum SRP concentration) indicating that algal biomass had increased within the river. The timing of these silicon depressions was closely related to temperature. Excess carbon dioxide partial pressures (EpCO₂) of 60 times atmospheric CO₂ were also observed through the winter periods from 1980 to 1992, when phosphorus concentration was greatest, indicating very high respiration rates due to microbial decomposition of this enhanced biomass. Declining phosphorus concentrations since 2002 reduced productivity and algal biomass in the summer, and EpCO₂ through the winter, indicating that sewage treatment improvements had improved riverine ecology. Algal blooms were limited by phosphorus, rather than silicon concentration. The value of long-term water quality data sets is discussed. The data from this monitoring programme are made freely available to the wider science community through the CEH data portal (http://gateway.ceh.ac.uk/).

This paper provides an overview of the impacts of rural land use on lowland streamwater phosphorus (P) and nitrogen (N) concentrations and P loads and sources in lowland streams. Based on weekly water quality monitoring, the impacts of agriculture on streamwater P and N hydrochemistry were examined along a gradient of rural–agricultural land use, by monitoring three sets of ‘paired’ (near-adjacent) rural headwater streams, draining catchments which are representative of the major geology, soil types and rural/agricultural land use types of large areas of lowland Britain. The magnitude and timing of P and N inputs were assessed and the load apportionment model (LAM) was applied to quantify ‘continuous’ (point) source and ‘flow-dependent’ (diffuse) source contributions of P to these headwater streams. The results show that intensive arable farming had only a comparatively small impact on streamwater total phosphorus (TP loads), with highly consistent stream diffuse-source TP yields of ca. 0.5 kg-P ha −1 year −1 for the predominantly arable catchments with both clay and loam soils, compared with 0.4 kg-P ha −1 year −1 for low agricultural intensity grassland/woodland on similar soil types. In contrast, intensive livestock farming on heavy clay soils resulted in dramatically higher stream diffuse-source TP yields of 2 kg-P ha −1 year −1 . The streamwater hydrochemistry of the livestock-dominated catchment was characterised by high concentrations of organic P, C and N fractions, associated with manure and slurry sources. Across the study sites, the impacts of human settlement were clearly identifiable with effluent inputs from septic tanks and sewage treatment works resulting in large-scale increases in soluble reactive phosphorus (SRP) loads and concentrations. At sites heavily impacted by rural settlements, SRP concentrations under baseflow conditions reached several hundred μg-P L −1 . Load apportionment modelling demonstrated significant ‘point-source’ P inputs to the streams even where there were no sewage treatment works within the upstream catchment. This indicates that, even in sparsely populated rural headwater catchments, small settlements and even isolated groups of houses are sufficient to cause significant nutrient pollution and that septic tank systems serving these rural communities are actually operating as multiple point sources, rather than a diffuse input.

The changing patterns of riverine boron concentration are examined for the Thames catchment in southern/southeastern England using data from 1997 to 2007. Boron concentrations are related to an independent marker for sewage effluent, sodium. The results show that boron concentrations in the main river channels have declined with time especially under baseflow conditions when sewage effluent dilution potential is at its lowest. While boron concentrations have reduced, especially under low-flow conditions, this does not fully translate to a corresponding reduction in boron flux and it seems that the “within-catchment” supplies of boron to the river are contaminated by urban sources. The estimated boron reduction in the effluent input to the river based on the changes in river chemistry is typically around 60% and this figure matches with an initial survey of more limited data for the industrial north of England. Data for effluent concentrations at eight sewage treatment works within the Kennet also indicate substantial reductions in boron concentrations: 80% reduction occurred between 2001 and 2008. For the more contaminated rivers there are issues of localised rather than catchment-wide sources and uncertainties over the extent and nature of water/boron stores. Atmospheric sources average around 32 to 61% for the cleaner and 4 to 14% for the more polluted parts. The substantial decreases in the boron concentrations correspond extremely well with the timing and extent of European wide trends for reductions in the industrial and domestic usage of boron-bearing compounds. It clearly indicates that such reductions have translated into lower average and peak concentrations of boron in the river although the full extent of these reductions has probably not yet occurred due to localised stores that are still to deplete.

Heterosexual transmission of human immunodeficiency virus (HIV) remains the major route of infection worldwide; thus, there is an urgent need for additional prevention strategies, particularly strategies that could be controlled by women, such as topical microbicides. Potential microbicide candidates must be both safe and effective. Using cellular and tissue explant models, we have evaluated the activity of the nonnucleoside reverse transcriptase inhibitor (NNRTI) dapivirine as a vaginal microbicide. In tissue compatibility studies, dapivirine was well tolerated by epithelial cells, T cells, macrophages, and cervical tissue explants. Dapivirine demonstrated potent dose-dependent inhibitory effects against a broad panel of HIV type 1 isolates from different clades. Furthermore, dapivirine demonstrated potent activity against a wide range of NNRTI-resistant isolates. In human cervical explant cultures, dapivirine was able not only to inhibit direct infection of mucosal tissue but also to prevent the dissemination of the virus by migratory cells. Activity was retained in the presence of semen or a cervical mucus simulant. Furthermore, dapivirine demonstrated prolonged inhibitory effects: it was able to prevent both localized and disseminated infection for as long as 6 days posttreatment. The prolonged protection observed following pretreatment of genital tissue and the lack of observable toxicity suggest that dapivirine has considerable promise as a potential microbicide candidate.

Summary The water quality along the River Kennet, in the Thames basin of southern England, was examined in terms of the influence of point- and diffuse-nutrient inputs. The river is supplied mainly from a Cretaceous Chalk aquifer and hence the waters are of a calcium bicarbonate type. The nitrate largely comes from agricultural sources, with concentrations decreasing downstream due to plant uptake and probable denitrification. In contrast, soluble reactive phosphorus (SRP) is largely associated with sewage inputs and concentrations increase downstream in line with effluents from major towns such as Newbury and Reading. Adjacent to the river in the lower half of the catchment is the Kennet and Avon Canal and the two are in places hydrologically connected. The canal inputs may influence calcium carbonate (calcite) precipitation and increase suspended sediment and particulate phosphorus concentrations in the river. Monitoring upstream and downstream of Marlborough sewage treatment works (STW) showed that SRP concentrations in the effluent were highly variable due to variable efficiency of P stripping and still sufficiently concentrated to dominate downstream river SRP with potential impacts on stream ecology. Biological recovery in this river following P stripping at STWs is complex and controlling those spikes in SRP that are above a threshold of 100 μg l −1 may be a critical requirement. More stringent effluent targets than are currently recommended may be needed (less than 800 μg RP l −1 ) to achieve good ecological status in this river depending on SRP concentrations upstream.

DET (diffusive equilibrium in thin films) gel probes were used for sampling river-bed sediment porewaters, to characterise in situ soluble reactive phosphorus (SRP) concentration profiles and fluxes. DET probes were deployed in three contrasting rural streams: (1) a headwater ‘pristine’ stream, with minimal P inputs from low intensity grassland and no point sources, (2) an intensively cultivated arable catchment, and (3) a stream subject to high P loadings from sewage effluent and intensive arable farming. The DET results showed highly enriched porewater SRP concentrations of between ca. 400 and 5000 ug-P/1 in the sewage-impacted stream. In contrast, the arable and pristine streams had porewater SRP concentrations

Summary This study examined stream water quality across a range of catchments which are representative of the key environments and land uses of rural south-west England. These catchments included: (a) an acidic upland headwater catchment, rising on the moorlands of Dartmoor, with low-intensity sheep rearing; (b) a headwater catchment rising on the weathered granite lower slopes of Dartmoor, with cattle farming; (c) a lowland headwater clay catchment with sub-surface drainage and high intensity livestock farming, fodder crop cultivation, and hard-standing/slurry storage; and (d) the main River Taw, a lowland river system receiving drainage from a range of tributaries, exemplified by the above catchment types. Variations in water chemistry and quality were observed along an upland–lowland transition, from headwater streams to the main river channel. Within the livestock-dominated headwater streams, total phosphorus (TP) was dominated by particulate phosphorus (PP). These PP concentrations appeared to be mainly linked to two sets of processes: (1) in-stream sediment precipitation with sorption/co-precipitation of phosphate and/or localised in-channel mobilisation of sediment (by cattle or channel-clearing operations) under low flow conditions, and (2) sediment erosion and transportation associated with near-surface runoff during storm events. Under baseflow conditions, in-stream and/or riparian processes played a significant role in controlling general nutrient chemistry, particularly in the headwater streams which were heavily impacted by livestock.

Summary Concentrations and loads of N and P fractions were examined for lowland rivers, the Wye and Avon, draining a range of representative agricultural land-use types in two major UK river basins. Data collected over a 2-year period demonstrated important diffuse agricultural source contributions to N and P loads in these rivers. Ground water provided a major source of total dissolved nitrogen (TDN) loads, whereas near-surface sources provided a major contribution to total phosphorus (TP) loads. In terms of aquatic ecology, concentrations of nutrients, at times of eutrophication risk (spring and summer low flows) were of key environmental and management significance. Agricultural diffuse sources provided the major source of long-term P loads across the two basins. However, the results demonstrated the dominance of point-source contributions to TP and SRP concentrations at times of ecological risk. Point sources typically ‘tip the balance’ of dissolved inorganic P (soluble reactive P, SRP) above the 100 μg l−1 guideline value indicative of eutrophication risk. The significance of point sources for TP and SRP concentrations was shown by (a) the strong correlations between TP, SRP and B concentrations, using B as a tracer of sewage effluent, (b) the dominant contribution of SRP to TP concentrations and (c) the predominant pattern of dilution of SRP and B with flow. The clean Chalk streams draining low intensity grassland in areas of the Avon with sparse human settlement were oligotrophic and P limited with low SRP concentrations under spring and summer baseflows attributable to groundwater sources. The data provide important insights into the ecological functioning of different lowland stream systems. There was evidence of greater SRP losses and N-limitation in a stream which drains a pond system, demonstrating the importance of longer water residence times for biological nutrient uptake.

Iodine concentrations in rainfall, cloud water, throughfall, stemflow, stream water and groundwater are described for the upper River Severn Plynlimon catchments in mid-Wales. Iodine concentrations average 1.55 µg l−1 in rainfall while the corresponding averages of iodine concentrations in cloud water, throughfall and stemflow iodine concentrations are three to eight times higher. For the atmospheric inputs, there are both marine and anthropogenic sources while, for stemflow and throughfall, humic substances may be a dominant component. The average concentrations in the streams and groundwaters vary between 1.00 to 4.22 µg l−1 and 0.57 to 8.51 µg l−1, respectively. The higher averages are for waters associated with gley soils that are high in dissolved organic carbon (DOC). For the streams draining forested catchments, iodine concentrations have increased over time, probably due to wetting up of the soils because of reduction in transpiration as the trees are maturing and felling activities. The increases vary between 0.025±0.003 and 0.044±0.010 µg l−1 per year and are associated partly with an increase in DOC concentration: adjusted for the effect of DOC, the increases range between 0.013±0.003 and 0.023±0.009 µg l−1 per year. For the moorland areas, no such trend is observed but the value is lower. For most of the Plynlimon catchments, a net uptake of iodine of around 40% is lower for streams draining gley soils with even a net export for the smaller streams. Within the streams, iodine concentrations are highly correlated with DOC and there is an annual cycle of iodine and DOC concentration change, with maxima between July and November. For the groundwaters, a loss of iodine and DOC relative to the streams probably reflects within catchment losses in the lower inorganic soils and bedrock areas. However, in one case, groundwater iodine concentrations were relatively high and this coincided with high DOC concentrations.

This work examines baseflow nutrient concentrations and loads along two rural Chalk streams, the Pang and Lambourn. Soluble reactive phosphorus (SRP) and boron (B) concentrations in these streams were heavily influenced by point-source inputs and the effects of downstream flow accretion and dilution. Unlike B (which is chemically conservative), SRP loads were also strongly influenced by in-stream processing resulting in uptake of SRP, particularly immediately downstream of sewage effluent discharges, where rates of SRP uptake were highest. For the upper River Pang, up to 80% of SRP loads were lost within 4 km downstream of Compton sewage treatment works (STW) and on the River Lambourn up to 55% of SRP loads were lost within 1.6 km downstream of East Shefford STW. In contrast, nitrate (NO3) concentrations at sites along the Pang and Lambourn were largely controlled by groundwater inputs and plant uptake during periods of high photosynthetic activity in spring and summer and silicon (Si) by diatom uptake in April/May. There were net gains in NO3 loads along the river reaches, as a result of volumetric increases in groundwater discharge, and, compared with SRP, the role of in-stream processing of NO3 appeared low. Examination of SRP exchange by bed sediment and uptake of SRP into algal biofilms indicated that biofilms accounted for only a very small percentage of in-stream P-uptake, but that bed sediment SRP-exchanges had a more important control on baseflow SRP concentrations and loads. Point source P remediation at East Shefford STW, by removal of P from final effluent (P-stripping), resulted in 70–90% reductions in river-water SRP loads. After introduction of P-stripping at East Shefford STW, bed sediments immediately downstream of the STW switched from being net sinks to net sources of SRP. Our results show that, in the immediate aftermath of P-stripping, bed sediment SRP-release was responsible for a 30 μg-P l−1 rise in river-water SRP along this reach. While this increase in SRP concentration, as a result of bed sediment SRP release, is potentially ecologically significant, it is small in relation to the increase in SRP concentrations from effluent prior to P-stripping, which resulted in increases in SRP concentration of up to 500 μg-P l−1. There was a six-month lag between the introduction of P-stripping at East Shefford STW and bed sediment EPC0 recovering to equilibrium levels with the overlying river water (and thus negligible SRP release). Recovery of bed sediments to equilibrium levels is likely to have occurred as a result of winnowing and removal of high-EPC0 sediment and delivery of lower EPC0 sediment from upstream. Under higher/more variable flow conditions and greater rates of in-channel sediment erosion/delivery, more rapid recovery of bed sediment EPC0 levels following P-stripping might be expected.

The Twilight saga, a series of five films adapted from Stephanie Meyer's four vampire novels, has been a sensation, both at the box office and through the attention it has won from its predominantly teenaged fans. This series has also been the subject of criticism and sometimes derision - often from critics and on occasion even from fans. However, it also offers rich opportunities for analytic and critical attention, which the contributors to Screening Twilight demonstrate with energy and style. Through examining Twilight, the book unpacks how this popular group of films work as cinematic texts, what they have to say about cinema and culture today, and how fans may seek to re-read or subvert these messages. The chapters address Twilight in the context of the vampire and myth, in terms of genre and reception, identity, gender and sexuality, and through re-viewing the series fandom. Screening Twilight, edited by Wickham Clayton and Sarah Harman, is also a revelation of how a popular cinematic phenomenon like Twilight rewards close attention from contemporary critical scholars of cinema and culture.

The River Kennet in southern England has exhibited excessive benthic algal growth and associated ecological problems, such as loss of macrophytes and invertebrates, since the 1980s. These ecological problems were attributed to regular peaks in phosphorus concentration, which were widely attributed to intermittent failures of the Marlborough sewage treatment works (STW). This study deployed highfrequency phosphorus auto-analysers to monitor the total reactive phosphorus (TRP) concentrations of Marlborough STW final effluent and the downstream River Kennet at hourly and 30 minute resolution respectively, between 2008 and 2009. This monitoring confirmed that the Marlborough STW was operating well within its 1000 mg l-�1 annual mean total phosphorus consent limit, with mean total P and soluble reactive P concentrations of 675 and 345 mg l-�1 respectively. There were two occasions where effluent TRP concentration exceeded 1000 mg l-�1, and only one of these resulted in a peak in TRP concentration of over 100 mg l-�1 in the River Kennet at Mildenhall. The other nine peaks of over 100 mg l-�1 in the River Kennet during the monitoring period were associated with storm events, indicating that diffuse-source inputs and remobilisation of stored within-channel phosphorus were the cause of the peaks in river concentration, rather than Marlborough STW. The value of high-frequency environmental monitoring and the problems associated with using nutrient auto-analysers in the field are discussed. Seasonal phosphorus consents for STWs could provide a useful and cost effective means to improve both water quality and river ecology in the upper River Kennet.

Sulfate adsorption capacity of B-horizons of base-poor, predominantly stagnopodzol, soils from the Plynlimon catchments, mid-Wales was determined by combination of laboratory adsorption and desorption isotherms. Results show that sulfate adsorption capacity of a range of stagnopodzol (Histic-stagno-podzol (Leptic), WRB), brown podzolic soil (Histic-umbrisol (Leptic), WRB) and stagnohumic gley (Histic-stagno-gleysol, WRB) B-horizons was positively related to the amounts of extractable (pyrophosphate and oxalate) Fe + Al, with the stagnopodzol and brown podzolic soil Bs horizon having the largest adsorption capacity and stagnohumic gley Bg horizon the smallest adsorption capacity. Results show that dissolved organic carbon (DOC) has a negative but limited effect on sulfate adsorption in these soils. Results obtained from a set of historical soil samples revealed that the grassland brown podzolic soil Bs horizon and afforested stagnopodzol Bs horizon were highly saturated with sulfate in the 1980s, at 63% and 89% respectively, whereas data from some recently sampled soil from two sites revisited in 2010-11 indicates that percentage sulfate adsorption saturation has since fallen substantially, to 41% and 50% respectively. Between 1984 and 2009 the annual rainfall-weighted mean excess SO(4)-S concentration in bulk precipitation declined linearly from 0.37 mg S l(-1) to 0.17 mg S l(-1). Over the same period, flow weighted annual mean stream water SO(4)-S concentrations decreased approximately linearly from 1.47 mg S l(-1) to 0.97 mg S l(-1) in the plantation afforested Hafren catchment compared to a drop from 1.25 to 0.69 mg S l(-1) in the adjacent moorland catchment of the Afon Gwy. In flux terms, the mean decrease in annual stream water SO(4)-S flux has been approximately 0.4 kg S ha(-1) yr(-1), whilst the recovery in stream water quality in the Afon Cyff grassland catchment has been partly offset by loss of SO(4)-S by desorption from the soil sulfur pool of approximately 0.2 kg S ha(-1) yr(-1).

Topical blockade of the gp41 fusogenic protein of HIV-1 is one possible strategy by which microbicides could prevent HIV transmission, working early against infection, by inhibiting viral entry into host cells. In this study, we examined the potential of gp41 fusion inhibitors (FIs) as candidate anti-HIV microbicides. Preclinical evaluation of four FIs, C34, T20, T1249, and L'644, was performed using cellular and ex vivo genital and colorectal tissue explant models. Increased and sustained activity was detected for L'644, a cholesterol-derivatized version of C34, relative to the other FIs. The higher potency of L'644 was further increased with sustained exposure of cells or tissue to the compound. The activity of L'644 was not affected by biological fluids, and the compound was still active when tissue explants were treated after viral exposure. L'644 was also more active than other FIs against a viral escape mutant resistant to reverse transcriptase inhibitors (RTIs), demonstrating the potential of L'644 to be included as part of a multiactive antiretroviral (ARV) combination-based microbicide. These data support the further development of L'644 for microbicide application.

Soluble reactive phosphorus (SRP) concentrations in the River Thames, south east England, have significantly decreased from an annual maximum of 2100 μg l − 1 in 1997 to 344 in 2010, primarily due to the introduction of phosphorus (P) removal at sewage treatment works within the catchment. However, despite this improvement in water quality, phytoplankton biomass in the River Thames has greatly increased in recent years, with peak chlorophyll concentrations increasing from 87 μg l − 1 in the period 1997 to 2002, to 328 μg l − 1 in 2009. A series of within-river flume mesocosm experiments were performed to determine the effect of changing nutrient concentrations and light levels on periphyton biomass accrual. Nutrient enrichment experiments showed that phosphorus, nitrogen and silicon were not limiting or co-limiting periphyton growth in the Thames at the time of the experiment (August–September 2010). Decreasing ambient SRP concentration from 225 μg l − 1 to 173 μg l − 1 had no effect on periphyton biomass accrual rate or diatom assemblage. Phosphorus limitation became apparent at 83 μg SRP l − 1 , at which point a 25% reduction in periphyton biomass was observed. Diatom assemblage significantly changed when the SRP concentration was reduced to 30 μg l − 1 . Such stringent phosphorus targets are costly and difficult to achieve for the River Thames, due to the high population density and intensive agriculture within the Thames basin. Reducing light levels by shading reduced the periphyton accrual rate by 50%. Providing shading along the River Thames by planting riparian tree cover could be an effective measure to reduce the risk of excessive algal growth. If the ecology of the Thames is to reach the WFD's “good ecological status”, then both SRP concentration reductions (probably to below 100 μg l − 1 ) and increased shading will be required.

Information is provided on phosphorus in the River Kennet and the adjacent Kennet and Avon Canal in southern England to assess their interactions and the changes following phosphorus reductions in sewage treatment work (STW) effluent inputs. A step reduction in soluble reactive phosphorus (SRP) concentration within the effluent (5 to 13 fold) was observed from several STWs discharging to the river in the mid-2000s. This translated to over halving of SRP concentrations within the lower Kennet. Lower Kennet SRP concentrations change from being highest under base-flow to highest under storm-flow conditions. This represented a major shift from direct effluent inputs to a within-catchment source dominated system characteristic of the upper part to the catchment. Average SRP concentrations in the lower Kennet reduced over time towards the target for good water quality. Critically, there was no corresponding reduction in chlorophyll-a concentration, the waters remaining eutrophic when set against standards for lakes. Following the up gradient input of the main water and SRP source (Wilton Water), SRP concentrations in the canal reduced down gradient to below detection limits at times near its junction with the Kennet downstream. However, chlorophyll concentrations in the canal were in an order of magnitude higher than in the river. This probably resulted from long water residence times and higher temperatures promoting progressive algal and suspended sediment generations that consumed SRP. The canal acted as a point source for sediment, algae and total phosphorus to the river especially during the summer months when boat traffic disturbed the canal's bottom sediments and the locks were being regularly opened. The short-term dynamics of this transfer was complex. For the canal and the supply source at Wilton Water, conditions remained hypertrophic when set against standards for lakes even when SRP concentrations were extremely low.

Phosphorus concentrations in the upper River Thames Basin (southeastern England) are described and linked to sewage effluent sources. Weekly surveys between 1997 and 2007 of the Thames and two of its major tributaries, the Thame and the Kennet indicated that phosphorus was mainly in soluble reactive (SRP) form. Baseflow concentrations in the Thames reduced from 1584microg/l in 1998 to 376microg/l in 2006 and from 2655 to 715microg/l for the Thame. Flow response, flux and endmember mixing analysis indicated that these declines resulted from SRP reductions in sewage treatment works (STW) effluent following phosphorus stripping for the major STWs in the region. This was confirmed by comparing our analysis with direct measurements of SRP in the effluents based on Environment Agency data. A within-river loss under baseflow of approximately 64% (range 56-78%) of the SRP-effluent input was estimated for the Thames, with a near balance for the Thame. SRP concentrations in the Kennet were an order of magnitude lower than the Thames/Thame: non-point sources dominated and were important for all the rivers at high flows. It was concluded that removal of SRP from effluents would be insufficient SRP in the Thames and Thame to meet annual average environmental targets of 50 to 120microg/l. The paper flags the value of combining hydrological/chemical tracing and concentration/flux approaches to data interrogation and the bonus of having actual measurements of the effluent. It highlights the need for fuller assessment of water storage/sediment/biota interactions for phosphorus and for caution in using boron as a long-term tracer for effluent inputs, its concentrations having declined markedly in response to reduced usage in washing powders: the value of using sodium as a tracer for examining SRP changes is shown.

Many promising microbicide candidates are proteins or peptides, including neutralizing monoclonal antibodies (mAbs). Here, the expression of the HIV-neutralizing mAb b12 in transgenic plants is described. The plant-derived mAb b12 was shown to have gp120 binding activity and HIV-neutralizing activity in vitro. However, it is likely that a protein-based microbicide will need to comprise a combination of two or more products, in order to provide long-lasting and cross-clade protection. Building on the expression of mAb b12 and to address the need for a combinational agent, the expression of a fusion protein of mAb b12 with cyanovirin-N, another protein microbicide, has been explored. This fusion protein molecule is predicted to have four binding sites for HIV gp120 with two different specificities. The fusion protein was assembled and expressed in planta, and functionality was confirmed by gp120 binding and HIV neutralization in vitro. Each moiety of the fusion protein retained its binding ability to gp120. In addition, this fusion protein demonstrated increased anti-HIV potency compared to b12 or CV-N alone. This fusion protein addresses the requirement to combine microbicide products, and the production in plants is a step toward resolving the issues of manufacturing scalability and cost for developing countries.

Cyanovirin-N (CV-N) is a microbicide candidate that inactivates a wide range of HIV strains by binding to gp120. Production of CV-N, or any protein microbicide, needs to be at extremely high levels and low cost to have an impact on global health. Thus, it is unlikely that fermentor-based systems will be suitable, including recombinant E. coli, where CV-N aggregates and dimers have consistently been found. Transgenic plants may provide a suitable expression system for protein microbicides, as production can be easily and economically scaled up. Here, Nicotiana tabacum was transformed with a gene encoding CV-N to explore proof of concept for the production of CV-N in transgenic plants. Plant-derived rCV-N was recoverable at levels of 130 ng/mg of fresh leaf tissue, or at least 0.85% of total soluble plant protein. Western blot analysis demonstrated that virtually all of the rCV-N was expressed in the desired monomeric form. Functionality was demonstrated by specific binding to gp120 and protection of T-cells from in vitro HIV infection. Hydroponic culturing of transgenic plants demonstrated CV-N rhizosecretion at levels of 0.64 mug/ml hydroponic media after 24 days. Therefore, we suggest that transgenic plants have the potential to provide strategies for large-scale protein microbicide production.

Gornall is embarrassingly out of date in his detailed analysis of the B case (which was dealt with by the family courts nearly three years ago), and its relevance to proposed changes in the law to make the English family court system more transparent.1 Since then, notwithstanding the ever increasingly exaggerated claims from some quarters that opening the family courts would harm children and deter court experts, the …

Summary The introduction of tertiary treatment to many of the sewage treatment works (STW) across the Thames basin in southern England has resulted in major reductions in river phosphorus (P) concentrations. Despite this, excessive phytoplankton growth is still a problem in the River Thames and many of its tributaries. There is an urgent need to determine if future resources should focus on P removal from the remaining STW, or on reducing agricultural inputs, to improve ecological status. Nutrient concentration–flow relationships for monitoring sites along the River Thames and 15 of its major tributaries were used to estimate the relative inputs of phosphorus and nitrogen from continuous (sewage point sources) and rain-related (diffuse and within-channel) sources, using the Load Apportionment Model (LAM). The model showed that diffuse sources and remobilisation of within-channel phosphorus contributed the majority of the annual P load at all monitoring sites. However, the majority of rivers in the Thames basin are still dominated by STW P inputs during the ecologically-sensitive spring-autumn growing season. Therefore, further STW improvements would be the most effective way of improving water quality and ecological status along the length of the River Thames, and 12 of the 15 tributaries. The LAM outputs were in agreement with other indicators of sewage input, such as sewered population density, phosphorus speciation and boron concentration. The majority of N inputs were from diffuse sources, and LAM suggests that introducing mitigation measures to reduce inputs from agriculture and groundwater would be most appropriate for all but one monitoring site in this study. The utilisation of nutrient concentration–flow data and LAM provide a simple, rapid and effective screening tool for determining nutrient sources and most effective mitigation options.

Background The continued growth of the global HIV epidemic highlights the urgent need to develop novel prevention strategies to reduce HIV transmission. The development of topical microbicides is likely to take a number of years before such a product would be widely available. This has resulted in a call for the rapid introduction of simpler vaginal intervention strategies in the interim period. One suggested practice would be vaginal douching with natural products including lime or lemon juice. Here we present a comprehensive preclinical evaluation of lime juice (LiJ) as a potential intervention strategy against HIV. Results Pre-treatment of HIV with LiJ demonstrated direct virucidal activity, with 10% juice inactivating the virus within 5 minutes. However, this activity was significantly reduced in the presence of seminal plasma, where inactivation required maintaining a 1:1 mixture of neat LiJ and seminal plasma for more than 5 minutes. Additionally, LiJ demonstrated both time and dose-dependent toxicity towards cervicovaginal epithelium, where exposure to 50% juice caused 75–90% toxicity within 5 minutes increasing to 95% by 30 minutes. Cervicovaginal epithelial cell monolayers were more susceptible to the effects of LiJ with 8.8% juice causing 50% toxicity after 5 minutes. Reconstructed stratified cervicovaginal epithelium appeared more resilient to LiJ toxicity with 30 minutes exposure to 50% LiJ having little effect on viability. However viability was reduced by 75% and 90% following 60 and 120 minutes exposure. Furthermore, repeat application (several times daily) of 25% LiJ caused 80–90% reduction in viability. Conclusion These data demonstrate that the virucidal activity of LiJ is severely compromised in the presence of seminal plasma. Potentially, to be effective against HIV in vivo, women would need to apply a volume of neat LiJ equal to that of an ejaculate, and maintain this ratio vaginally for 5–30 minutes after ejaculation. Data presented here suggest that this would have significant adverse effects on the genital mucosa. These data raise serious questions about the plausibility and safety of such a prevention approach.