The effect of sediment characteristics and a fine sediment pulse on invertebrate distributional patterns

The amount of fine sediment entering river systems has increased dramatically in the last century and this has been recognised as a leading cause of ecological degradation and water quality impairment. In order to monitor and manage this problem more effectively further research is needed in to the quantitative, mechanistic relationships between the amount of fine sediment delivery in to river systems and the response of the lotic freshwater community. At present, this lack of information is problematic for environmental managers and regulators as they attempt to meet the challenges posed by this issue. This thesis aimed to address this research gap by using stream mesocosms to investigate the response of invertebrates to a fine sediment pulse. It was unique in considering the effect of prior exposure to increased fine sediment deposition, whilst examining the response of benthic, hyporheic and drifting invertebrates concurrently. The research also set out to assess the effectiveness of fine sediment biomonitoring approaches, comparing them with more traditional metrics, it also investigated the power of a functional trait approach to discriminate fine sediment stress. The results detailed in this thesis demonstrate that biomonitoring approaches have the ability to identify fine sediment stress more effectively than traditional taxonomic metrics (e.g. abundance and taxonomic richness), particularly when applied to invertebrate communities which are relatively tolerant of fine sediment stress. This was one of the first studies to identify the effects of prior fine sediment deposition on the response of invertebrates to a fine sediment pulse, finding that this factor plays an important role in their response, providing important evidence which may be used to better tailor our fine sediment management strategies. Examining, in tandem, the effects of a fine sediment pulse on invertebrate drifting behavior and their use of the hyporheic zone identified taxa-specific responses to fine sediment which will be useful to further refine our understanding of the mechanistic relationship between increased amounts of fine sediment and invertebrate communities. This information will help to inform the refinement of functional trait databases, which has been identified by the work in this thesis as one of the major factors limiting their effective use

Do legacy effects of deposited fine sediment influence the ecological response of drifting invertebrates to a fine sediment pulse?

The deposition of excess fine sediment and clogging of benthic substrates is recognised as a global threat to ecosystem functioning and community dynamics. Legacy effects of previous sedimentation create a habitat template on which subsequent ecological responses occur, and therefore, may have a long-lasting influence on community structure. Our experimental study examined the effects of streambed colmation (representing a legacy effect of fine sediment deposition) and a suspended fine sediment pulse on macroinvertebrate drift and community dynamics. We used 12 outdoor stream mesocosms that were split into two sections of 6.2 m in length (24 mesocosm sections in total). Each mesocosm section contained a coarse bed substrate with clear bed interstices or a fine bed substrate representing a colmated streambed. After 69 days, a fine sediment pulse with three differing fine sediment treatments was applied to the stream mesocosms. Added fine sediment influenced macroinvertebrate movements by lowering benthic density and taxonomic richness and increasing drift density, taxonomic richness, and altering drift assemblages. Our study found the highest dose of sediment addition (an estimated suspended sediment concentration of 1112 mg l caused significant differences in benthic and drift community metrics and drift assemblages compared with the control treatment (30 l of water, no added sediment). Our results indicate a rapid response in drifting macroinvertebrates after stressor application, where ecological impairment varies with the concentration of suspended sediment. Contrary to expectations, bed substrate characteristics had no effect on macroinvertebrate behavioural responses to the fine sediment pulse

Cardiovascular disease in a cohort exposed to the 1940-45 Channel Islands occupation

BACKGROUND To clarify the nature of the relationship between food deprivation/undernutrition during pre- and postnatal development and cardiovascular disease (CVD) in later life, this study examined the relationship between birth weight (as a marker of prenatal nutrition) and the incidence of hospital admissions for CVD from 1997–2005 amongst 873 Guernsey islanders (born in 1923–1937), 225 of whom had been exposed to food deprivation as children, adolescents or young adults (i.e. postnatal undernutrition) during the 1940–45 German occupation of the Channel Islands, and 648 of whom had left or been evacuated from the islands before the occupation began. METHODS Three sets of Cox regression models were used to investigate (A) the relationship between birth weight and CVD, (B) the relationship between postnatal exposure to the occupation and CVD and (C) any interaction between birth weight, postnatal exposure to the occupation and CVD. These models also tested for any interactions between birth weight and sex, and postnatal exposure to the occupation and parish of residence at birth (as a marker of parish residence during the occupation and related variation in the severity of food deprivation). RESULTS The first set of models (A) found no relationship between birth weight and CVD even after adjustment for potential confounders (hazard ratio (HR) per kg increase in birth weight: 1.12; 95% confidence intervals (CI): 0.70 – 1.78), and there was no significant interaction between birth weight and sex (p = 0.60). The second set of models (B) found a significant relationship between postnatal exposure to the occupation and CVD after adjustment for potential confounders (HR for exposed vs. unexposed group: 2.52; 95% CI: 1.54 – 4.13), as well as a significant interaction between postnatal exposure to the occupation and parish of residence at birth (p = 0.01), such that those born in urban parishes (where food deprivation was worst) had a greater HR for CVD than those born in rural parishes. The third model (C) found no interaction between birth weight and exposure to the occupation (p = 0.43). CONCLUSION These findings suggest that the levels of postnatal undernutrition experienced by children, adolescents and young adults exposed to food deprivation during the 1940–45 occupation of the Channel Islands were a more important determinant of CVD in later life than the levels of prenatal undernutrition experienced in utero prior to the occupatio

Regional versus local drivers of water quality in the Windermere catchment, Lake District, United Kingdom: the dominant influence of wastewater pollution over the past 200 years

Freshwater ecosystems are threatened by multiple anthropogenic stressors acting over different spatial and temporal scales, resulting in toxic algal blooms, reduced water quality and hypoxia. However, while catchment characteristics act as a ‘filter’ modifying lake response to disturbance, little is known of the relative importance of different drivers and possible differentiation in the response of upland remote lakes in comparison to lowland, impacted lakes. Moreover, many studies have focussed on single lakes rather than looking at responses across a set of individual, yet connected lake basins. Here we used sedimentary algal pigments as an index of changes in primary producer assemblages over the last~200 years in a northern temperate watershed consisting of 11 upland and lowland lakes within the Lake District, United Kingdom, to test our hypotheses about landscape drivers. Specifically, we expected that the magnitude of change in phototrophic assemblages would be greatest in lowland rather than upland lakes due to more intensive human activities in the watersheds of the former (agriculture, urbanization). Regional parameters, such as climate dynamics, would be the predominant factors regulating lake primary producers in remote upland lakes and thus, synchronize the dynamic of primary producer assemblages in these basins. We found broad support for the hypotheses pertaining to lowland sites as wastewater treatment was the main predictor of changes to primary producer assemblages in lowland lakes. In contrast, upland headwaters responded weakly to variation in atmospheric temperature, and dynamics in primary producers across upland lakes were asynchronous. Collectively, these findings show that nutrient inputs from point sources overwhelm climatic controls of algae and nuisance cyanobacteria, but highlights that large-scale stressors do not always initiate coherent regional lake response. Furthermore, a lake’s position in its landscape, its connectivity and proximity to point nutrients are important determinants of changes in production and composition of phototrophic assemblages

Governing the world at a distance : the practice of global benchmarking

Benchmarking practices have rapidly diffused throughout the globe in recent years. This can be traced to their popularity amongst non-state actors, such as civil society organisations and corporate actors, as well as states and international organisations (IOs). Benchmarks serve to both ‘neutralise’ and ‘universalise’ a range of overlapping normative values and agendas, including freedom of speech, democracy, human development, environmental protection, poverty alleviation, ‘modern’ statehood, and ‘free’ markets. The proliferation of global benchmarks in these key areas amounts to a comprehensive normative vision regarding what various types of transnational actors should look like, what they should value, and how they should behave. While individual benchmarks routinely differ in terms of scope and application, they all share a common foundation, with normative values and agendas being translated into numerical representations through simplification and extrapolation, commensuration, reification, and symbolic judgements. We argue that the power of benchmarks chiefly stems from their capacity to create the appearance of authoritative expertise on the basis of forms of quantification and numerical representation. This politics of numbers paves the way for the exercise of various forms of indirect power, or ‘governance at a distance’, for the purposes of either status quo legitimation or political reform

WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics

Prostate cancer cells with stem cell characteristics were identified in human prostate cancer cell lines by their ability to form from single cells self-renewing prostaspheres in non-adherent cultures. Prostaspheres exhibited heterogeneous expression of proliferation, differentiation and stem cell-associated makers CD44, ABCG2 and CD133. Treatment with WNT inhibitors reduced both prostasphere size and self-renewal. In contrast, addition of Wnt3a caused increased prostasphere size and self-renewal, which was associated with a significant increase in nuclear Β-catenin, keratin 18, CD133 and CD44 expression. As a high proportion of LNCaP and C4-2B cancer cells express androgen receptor we determined the effect of the androgen receptor antagonist bicalutamide. Androgen receptor inhibition reduced prostasphere size and expression of PSA, but did not inhibit prostasphere formation. These effects are consistent with the androgen-independent self-renewal of cells with stem cell characteristics and the androgen-dependent proliferation of transit amplifying cells. As the canonical WNT signaling effector Β-catenin can also associate with the androgen receptor, we propose a model for tumour propagation involving a balance between WNT and androgen receptor activity. That would affect the self-renewal of a cancer cell with stem cell characteristics and drive transit amplifying cell proliferation and differentiation. In conclusion, we provide evidence that WNT activity regulates the self-renewal of prostate cancer cells with stem cell characteristics independently of androgen receptor activity. Inhibition of WNT signaling therefore has the potential to reduce the self-renewal of prostate cancer cells with stem cell characteristics and improve the therapeutic outcome.Peer reviewe

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference

Combining RNA interference and kinase inhibitors against cell signalling components involved in cancer

BACKGROUND: The transcription factor activator protein-1 (AP-1) has been implicated in a large variety of biological processes including oncogenic transformation. The tyrosine kinases of the epidermal growth factor receptor (EGFR) constitute the beginning of one signal transduction cascade leading to AP-1 activation and are known to control cell proliferation and differentiation. Drug discovery efforts targeting this receptor and other pathway components have centred on monoclonal antibodies and small molecule inhibitors. Resistance to such inhibitors has already been observed, guiding the prediction of their use in combination therapies with other targeted agents such as RNA interference (RNAi). This study examines the use of RNAi and kinase inhibitors for qualification of components involved in the EGFR/AP-1 pathway of ME180 cells, and their inhibitory effects when evaluated individually or in tandem against multiple components of this important disease-related pathway. METHODS: AP-1 activation was assessed using an ME180 cell line stably transfected with a beta-lactamase reporter gene under the control of AP-1 response element following epidermal growth factor (EGF) stimulation. Immunocytochemistry allowed for further quantification of small molecule inhibition on a cellular protein level. RNAi and RT-qPCR experiments were performed to assess the amount of knockdown on an mRNA level, and immunocytochemistry was used to reveal cellular protein levels for the targeted pathway components. RESULTS: Increased potency of kinase inhibitors was shown by combining RNAi directed towards EGFR and small molecule inhibitors acting at proximal or distal points in the pathway. After cellular stimulation with EGF and analysis at the level of AP-1 activation using a β-lactamase reporter gene, a 10–12 fold shift or 2.5–3 fold shift toward greater potency in the IC(50 )was observed for EGFR and MEK-1 inhibitors, respectively, in the presence of RNAi targeting EGFR. CONCLUSION: EGFR pathway components were qualified as targets for inhibition of AP-1 activation using RNAi and small molecule inhibitors. The combination of these two targeted agents was shown to increase the efficacy of EGFR and MEK-1 kinase inhibitors, leading to possible implications for overcoming or preventing drug resistance, lowering effective drug doses, and providing new strategies for interrogating cellular signalling pathways