Hydrogeomorphic stressing and the response of endangered freshwater pearl mussels, Margaritifera margaritifera: a trait-based approach to inform conservation management

The freshwater pearl mussel, Margaritifera margaritifera, is considered vital to conserving the ecological integrity of freshwater systems, fulfilling the criteria of a keystone, flagship, indicator and umbrella species. Yet populations of this rare, long lived freshwater bivalve have witnessed substantial declines across the species’ Holarctic range. River systems in the Scottish Highlands continue to support large reproductively viable populations; many of which inhabit regulated rivers, managed for hydroelectric energy production. However, there has been limited study concerning the response of M. margaritifera to alterations in habitat characteristics resulting from dam operation. Utilising a combination of field and laboratory experiments, this study aimed to address knowledge gaps regarding interactions between M. margaritifera and the hydrogeomorphological processes occurring within their habitat, providing urgently needed empirical evidence to drive future conservation strategies implemented by government (NatureScot, SEPA) and utilised by the hydroelectric industry (SSE). Initial lab-based work sought to derive methods to non-invasively quantify mussel stress. Here, variation in the expression of particular behavioural metrics was examined in accordance with measurements of oxygen consumption, across environmental stressors, and between two freshwater mussel species. Results from this study revealed an increase in the presence of behavioural traits associated with valve activity in response to stress exposure, in accordance with substantial deviations in metabolic functioning of corresponding individuals. This study corroborates previous work highlighting the potential of bivalve filter feeding organisms as indicator species for alterations in habitat conditions. Furthermore, results exhibit the applicability of these techniques to non-invasively quantify physiological stress in Unionid mussels, towards understanding thresholds in response to environmental stressors across individuals, populations and species. To understand the response of M. margaritifera to alterations in flow regime, resulting from drought conditions and dam operation, flume experiments examined the responses M.margaritifera from two different populations, to three different rates of drawdown, using two different spatial arrangements. Results demonstrated a propensity of M. margaritifera to detect alterations in flow depth, utilising vertical and horizontal movements to avoid prolonged aerial exposure. Data from this study foregrounded intraspecific variation between populations, indicating potential variation in behavioural phenotypic traits. Results from a field trial in a regulated system, using a subset of the corresponding M. margaritifera population, endorsed findings from the flume study. Evidence presented in this study advocates forcontrolled drawdowns in regulated rivers to assist in reducing mortalities associated with receding water levels, during periods of drought. Finally, this study developed and tested novel smart-sensors housed within mussel shells to provide an affordable, accurate and accessible tool to record near-bed flow dynamics in aquatic systems. The resulting instrumented shells were found to accurately detect, and potentially predict entrainment events in M. margaritifera. Entrainment risk was dependent on the flowrate, shell orientation and size; consequently, highlighting the importance of vertical movements in mitigating flow forcing, and the vulnerability of smaller mussels to high flow events. This tool could assist in identifying suitable habitat for M. margaritifera, guiding reintroduction and translocation efforts, and identifying at risk populations to surges in flow discharge. Recommendations are made towards future conservation management of M. margaritifera in Scotland, with a focus on adopting a context-driven approach at the population level. Work in this thesis has provided a foundation for the development of future monitoring techniques to improve understanding of M. margaritifera habitat requirements, in consideration of hydrogeomorphological processes

Downpayments on the American Dream Policy Demonstration

This report presents findings from the first annual evaluation of the American Dream Demonstration, a multiyear, nationwide test of Individual Development Accounts. Covering the period from the demonstration’s start-up through June 30, 1998, the report details insights from an implementation assessment and from preliminary analyses of monitoring data

Cultivating Accessible Learning Communities: The Role of GTAs and Small Group Teaching

As highlighted by Muzaka (2009), the flexible approach of GTAs to delivering course material has great strengths in the small group setting, providing collaborative, adaptive and student-centred environments. The diversity of our GTA cohort in Geographical and Earth Sciences (GES) compliments this flexibility and is key in constructing and maintaining effective learning spaces. The GTA support and progression structure in GES is key to developing the confidence and independence that underpins our model for iterative teaching development which empowers student and GTA voices within the community of practice. We reflect on a positively-received year of online tutorial and lab-teaching, foregrounding the value of GTAs in achieving this. Utilising local examples from SGT contexts, we offer a framework to increase opportunities for student and GTA involvement in curriculum co-design, working towards an inclusive learning environment

Behavioural and metabolic responses of unionida mussels to stress

The aim of this study was to assess the extent to which the behavioural traits of freshwater mussels provide suitable indicators of stress in individuals, towards the advancement of non-invasive, remote monitoring techniques to examine population condition. Variation in the expression of particular behavioural metrics was examined in accordance with measurements of oxygen consumption, across environmental stressors (aerial exposure and high concentrations of total suspended solids), and between two freshwater mussel species (Margaritifera margaritifera and Anodonta anatina) Aerobic metabolic rate was quantified using intermittent respirometry, and behaviour was observed using time-lapse footage. Comparisons of metabolic response and the occurrence of behavioural traits, across the two stressors, focused on differences between the 24 h pre-exposure period (pre-exposure), the first 3 h of post-exposure (immediate post-exposure), and the time following the initial 3 h of post-exposure until the end of the experimental run (extended post-exposure). The results of this study demonstrated a relationship between the frequency of occurrence of behavioural responses to stress exposure, associated with valve activity, and significant changes in the metabolic functioning of A. anatina and M. margaritifera mussels. The findings from the study also highlighted substantial intraspecific variation across species and stressors. Data from this research could assist in the development of novel biosensors that track mussel valve activity remotely in their natural environment. When coupled with real-time data examining alterations in environmental metrics, this technology could assist in the monitoring of population condition and aid conservation management

Germline MBD4 deficiency causes a multi-tumor predisposition syndrome

We report an autosomal recessive, multi-organ tumor predisposition syndrome, caused by bi-allelic loss-of-function germline variants in the base excision repair (BER) gene MBD4. We identified five individuals with bi-allelic MBD4 variants within four families and these individuals had a personal and/or family history of adenomatous colorectal polyposis, acute myeloid leukemia, and uveal melanoma. MBD4 encodes a glycosylase involved in repair of G:T mismatches resulting from deamination of 5′-methylcytosine. The colorectal adenomas from MBD4-deficient individuals showed a mutator phenotype attributable to mutational signature SBS1, consistent with the function of MBD4. MBD4-deficient polyps harbored somatic mutations in similar driver genes to sporadic colorectal tumors, although AMER1 mutations were more common and KRAS mutations less frequent. Our findings expand the role of BER deficiencies in tumor predisposition. Inclusion of MBD4 in genetic testing for polyposis and multi-tumor phenotypes is warranted to improve disease management

Preclinical Evaluation of Long-Acting Emtricitabine Semi-Solid Prodrug Nanoparticle Formulations.

Long-acting injectable (LAI) formulations promise to deliver patient benefits by overcoming issues associated with non-adherence. A preclinical assessment of semi-solid prodrug nanoparticle (SSPN) LAI formulations of emtricitabine (FTC) is reported here. Pharmacokinetics over 28 days were assessed in Wistar rats, New Zealand white rabbits, and Balb/C mice following intramuscular injection. Two lead formulations were assessed for the prevention of an HIV infection in NSG-cmah-/- humanised mice to ensure antiviral activities were as anticipated according to the pharmacokinetics. Cmax was reached by 12, 48, and 24 h in rats, rabbits, and mice, respectively. Plasma concentrations were below the limit of detection (2 ng/mL) by 21 days in rats and rabbits, and 28 days in mice. Mice treated with SSPN formulations demonstrated undetectable viral loads (700 copies/mL detection limit), and HIV RNA remained undetectable 28 days post-infection in plasma, spleen, lung, and liver. The in vivo data presented here demonstrate that the combined prodrug/SSPN approach can provide a dramatically extended pharmacokinetic half-life across multiple preclinical species. Species differences in renal clearance of FTC mean that longer exposures are likely to be achievable in humans than in preclinical models

Germline MBD4-deficiency causes a multi-tumor predisposition syndrome

We report an autosomal recessive, multi-organ tumor predisposition syndrome, caused by bi-allelic loss-of-function germline variants in the base excision repair (BER) gene MBD4. We identified five individuals with bi-allelic MBD4 variants within four families and these individuals had a personal and/or family history of adenomatous colorectal polyposis, acute myeloid leukemia, and uveal melanoma. MBD4 encodes a glycosylase involved in repair of G:T mismatches resulting from deamination of 5′-methylcytosine. The colorectal adenomas from MBD4-deficient individuals showed a mutator phenotype attributable to mutational signature SBS1, consistent with the function of MBD4. MBD4-deficient polyps harbored somatic mutations in similar driver genes to sporadic colorectal tumors, although AMER1 mutations were more common and KRAS mutations less frequent. Our findings expand the role of BER deficiencies in tumor predisposition. Inclusion of MBD4 in genetic testing for polyposis and multi-tumor phenotypes is warranted to improve disease management