An investigation of the changes of species richness and distribution of the unionidae (Bivalvia: Molusca) within the Pamunkey Watershed

A survey of the Unionidae within the Pamunkey Watershed was conducted to investigate changes in distribution and species richness compared to a previous survey (Riddick, 1973) conducted over 30 years ago. Species richness decreased from 10 species in the previous survey to four species in the present survey. Notable increases of species richness were found in the upper South Anna and the lower North Anna regions, while sizable decreases were found in the lower South Anna and the upper and middle regions of the Pamunkey River. Regression analyses and t-tests comparing mussel survey data with habitat parameters were conducted to investigate the habitat characteristics most linked to unionid populations. The results indicated that greater composition of larger substrates and lower levels of silt deposition were significantly correlated to mussel presence. Crop land was the only quantified land use to correlate significantly (negatively) with changes in species richness and regional abundance parameters

The antigenic evolution of human influenza A haemagglutinin

A detailed understanding of the B-cell response to influenza A haemagglutinin is key to the accurate matching of vaccines to seasonal strains, and may inform the development of broader spectrum vaccines. In this study, I develop techniques for predicting the location of the epitopes of protective antibodies by observing the physical locations of amino acid substitutions in human wild-type strains. By linking the understanding gained from this analysis with a large body of assay data, I present a model which can predict antigenic distance from HA1 amino acid sequences and which meets or exceeds the predictive power of previously developed models while retaining generality. An interesting conclusion from the epitope analysis discussed above is that antibodies to the HA head bind in two regions. The antigenic evolution of influenza H3N2 is more punctuated than its genetic evolution. I propose that the dual regions might contribute to the punctuated nature of antigenic evolution, and explore this through the use of a simple simulation. Stalk-binding antibodies to HA have attracted much interest in recent years: a number of broad-binding examples have been isolated, and the slower evolution of the stalk gives hope that these may provide broad protection against future strains. Stalk-binding neutralising antibodies to H3 are known to bind in two regions, and I use data from crystal studies to identify the constituent residues of these regions, which I term antigenic sites F and G, in a manner that is consistent with previous analyses of the constituent residues of HA1 antigenic sites A-E. I analyse the degree of conservation of residues in sites F and G, and conclude that there have been episodes of change in the H3 stalk which are consistent with antigenic evolution

Utilities for high-throughput analysis of B-cell clonal lineages

There are at present few tools available to assist with the determination and analysis of B-cell lineage trees from next-generation sequencing data. Here we present two utilities that support automated large-scale analysis and the creation of publication-quality results. The tools are available on the web, and are also available for download so that they can be integrated into an automated pipeline. Critically, and in contrast to previously published tools, these utilities can be used with any suitable phylogenetic inference method and with any antibody germline library, and hence are species-independent

Reconnaissance Survey of the Proposed Berkeley County Wastewater System Plant Site, Robert E. Lee Tract, Berkeley County, South Carolina

https://scholarcommons.sc.edu/archanth_books/1115/thumbnail.jp

An Archeological Reconnaissance Survey and Evaluation of Cultural Resources of the Cane Creek 10-D Reservoir, Lancaster County, South Carolina

https://scholarcommons.sc.edu/archanth_books/1118/thumbnail.jp

Proposed policy guidelines for managing heritage at risk based on public engagement and communicating climate change

The deterioration and loss of our historic environment due to natural erosive processes, exacerbated by climate change, already outpaces available resources for preservation and will accelerate over the coming century. While this process is divisive and destructive, it is also bringing together international collaborators who are developing more holistic approaches to addressing heritage at risk. In 2018, an intensive fieldtrip and series of workshops as part of the Learning from Loss project brought researchers and practitioners from both sides of the Atlantic together with community stakeholders. Over twelve days, the delegates considered alternative futures for heritage at risk, exploring diverse perspectives and observing action previously taken at threatened sites by both heritage professionals and local communities, often working in collaboration. Recognising that not everything can be saved, the structured discussions and site visits revealed a number of insights into ways that action could be planned in the future. The suggestions also highlighted differences in the way that heritage is managed in the UK and the US. This paper summarises the findings of the field trip and discusses how there may need to be a sea-change in thinking in the United Sates in order to prepare for the growing disaster facing an increasing number of archaeological monuments.Publisher PDFPeer reviewe

Role of the hedgehog signalling pathway in inflammatory bowel disease

Introduction. The inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC), are common in Western Europe (200-400 cases /100,000) and associated with substantial morbidity, although mortality is now low. There is presently a great unmet need for novel therapeutics in IBD as present agents are limited by lack of efficacy, toxicity and poor patient acceptance. Recent findings from genome-wide association studies (GWAS) have characterised the genetic architecture of CD and UC. Defects in innate and adaptive immunity have been clearly established, and substantial novel insights into disease pathogenesis have been gained. Over 30 genes / loci are now associated with CD; a number of these, along with a few specific loci, are also associated with UC. The hedgehog (HH) signalling pathway is critical to gastrointestinal development and plays key roles in intestinal and immune homeostasis. Furthermore, in addition to well described roles in tumorigenesis, it is evident that recapitulation of embryonic HH signals play critical roles in response to acute and chronic inflammatory challenge in diverse tissues. Aims. The main aims of the work presented in this thesis were to characterise the expression of key HH signalling components in the healthy and inflamed human intestine, establish whether germline variation in HH genes is associated with IBD and describe the in vitro responses of intestinal epithelial cells to pathogen associated molecular patterns. The WNT pathway, antagonised by HH in the intestine, and two HH target genes (NKX2.3 and CCL20) were also analysed for evidence of association with IBD. Methods. Expression of HH and WNT signalling components was described by immunohistochemistry and microarray analysis in healthy controls (HC), CD, UC, and non- IBD inflamed terminal ileal and colonic samples. Gene-wide haplotype-tagging studies were performed for GLI1 in Scottish, English and Swedish CD and UC, and Scottish early-onset colo-rectal cancer, IHH in Scottish IBD, NKX2.3 in Scottish and UK IBD, and CCL20 in Scottish, Swedish and Japanese IBD. Evidence for association of all HH (n=13) and WNT (n=27) signalling genes in CD was established by analysis of UK GWAS data and metaanalysis from UK, French/Belgium and N American studies. The effect of lipopolysaccharide (LPS) and muramyl dipeptide (MDP) on HH signalling was assessed in colonic epithelial cells (SW480). The effect of HH pathway agonists and antagonists on NFκB activity and cytokine expression was analysed in SW480 cells and peripheral blood mononuclear cells (HC and IBD patients) in vitro. Results. The expression of HH pathway ligand is present in the intestinal epithelium and the pathway response network in the lamina propria demonstrating the paracrine nature of HH signalling in the intestine. Immunohistochemical studies and microarray analysis demonstrates that HH pathway activity is decreased in all forms of colonic inflammation studied in man. Variation in Glioma-associated oncogene homolog 1 (GLI1), a key HH transcription factor located at 12q13 (IBD2), was associated with IBD (p<0.0001), UC (p<0.0001) and to a lesser extent CD (p=0.03) in Scotland, a finding replicated in English IBD and UC. This association was attributed to a non-synonymous SNP (rs2228226C→G) with pools odds ratio of 1.194 in meta-analysis of over 5000 individuals from Scotland, England and Sweden (p=0.0002). There was association of this SNP with early-onset colorectal cancer, but of borderline significance (p=0.05). The variant protein (Q1100E) is 50% less active than wild-type protein in vitro. IHH was not associated with CD or UC. Preliminary evidence was produced for association at SUFU (10q24; p=0.005), a GLI1- binding protein, and at the WNT3 / WNT9B locus (17q21; p=0.0005). MDP stimulation of colonic epithelial cells decreased HH pathway activity. Exogenous HH increased expression of CCL20. CCL20 promoter polymorphisms were associated with UC in Japanese patients (p=0.018) but not in Scotland or Sweden. NKX2.3 was associated with IBD in Scotland (UC>CD), but there was insufficient power for fine-mapping of causative variants. Conclusions. Multiple lines of evidence presented here demonstrate that the HH signalling pathway is involved in IBD pathogenesis. In key complementary in vivo studies (conceived by CWL; conducted in collaboration with the Gumucio lab in Ann Arbor) we have demonstrated that Gli1+/- mice develop early, severe colitis with high mortality in response to acute inflammatory challenge. Furthermore, lamina propria antigen presenting cells are identified as the key HH target cells. With HH agonists and antagonists in extensive preclinical and early clinical testing, these studies have real potential to translate into novel therapeutics for patients with IBD

Coastal heritage, global climate change, public engagement, and citizen science

Climate change is threatening an uncalculated number of archaeological sites globally, totalling perhaps hundreds of thousands of culturally and paleoenvironmentally significant resources. As with all archaeological sites, they provide evidence of humanity’s past and help us understand our place in the present world. Coastal sites, clustered at the water’s edge, are already experiencing some of the most dramatic damage due to anthropogenic climate change; and the situation is predicted to worsen in the future. In the face of catastrophic loss, organizations around the world are developing new ways of working with this threatened coastal resource. This paper uses three examples, from Scotland, Florida and Maine, to highlight how new partnerships and citizen science approaches are building communities of practice to better manage threatened coastal heritage. It compares methods on either side of the Atlantic and highlights challenges and solutions. The approaches are applicable to the increasing number of heritage sites everywhere at risk from climate change; the study of coastal sites thus helps society prepare for climate change impacts to heritage worldwide.PostprintPeer reviewe

The antigenic evolution of human influenza A haemagglutinin

A detailed understanding of the B-cell response to influenza A haemagglutinin is key to the accurate matching of vaccines to seasonal strains, and may inform the development of broader spectrum vaccines. In this study, I develop techniques for predicting the location of the epitopes of protective antibodies by observing the physical locations of amino acid substitutions in human wild-type strains. By linking the understanding gained from this analysis with a large body of assay data, I present a model which can predict antigenic distance from HA1 amino acid sequences and which meets or exceeds the predictive power of previously developed models while retaining generality. An interesting conclusion from the epitope analysis discussed above is that antibodies to the HA head bind in two regions. The antigenic evolution of influenza H3N2 is more punctuated than its genetic evolution. I propose that the dual regions might contribute to the punctuated nature of antigenic evolution, and explore this through the use of a simple simulation. Stalk-binding antibodies to HA have attracted much interest in recent years: a number of broad-binding examples have been isolated, and the slower evolution of the stalk gives hope that these may provide broad protection against future strains. Stalk-binding neutralising antibodies to H3 are known to bind in two regions, and I use data from crystal studies to identify the constituent residues of these regions, which I term antigenic sites F and G, in a manner that is consistent with previous analyses of the constituent residues of HA1 antigenic sites A-E. I analyse the degree of conservation of residues in sites F and G, and conclude that there have been episodes of change in the H3 stalk which are consistent with antigenic evolution