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Influence of bacterial metabolism on bacteriophage and bacterial population dynamics
No full textDue to their considerable positive and negative influences on society, bacteria have been the subject of intense research since their discovery. Despite the wealth of knowledge on bacteria, their most voracious predator - the bacteriophage - remains relatively unknown. The bacteriophage offers a form of defence against the growing threat of multi drug resistant bacterial infections, but also is a threat to the vast industry based on utilising bacteria in the production of medication or the processing of materials. During a bacteriophage infection, the infecting virus must utilise the machinery and molecules present in the bacterium to shut down host processes and produce new bacteriophage progeny. By using a combined invitro and in-silico approach, I explore the influence of the bacterial metabolism on the progression of a bacteriophage infection at a population level. The ribosome content of a bacterium responds to the quality of carbon source available to the cell; higher quality carbon sources result in faster growth rates and more ribosomes in the bacterium. These ribosomes are then used by the phage to produce progeny. In this thesis I demonstrate that the fitness of a bacteriophage population (defined to be the exponential growth rate) is able to remain constant despite changes to the ribosome content of the host cell, even when these changes have been shown to affect the individual infection. A number of methods (of varying complexity) to probe these dynamics have been utilised and compared, with a simple model proving to be quite effective. Additionally, the influence of these metabolic changes on the bacterial response to infection has been studied, with the carbon source metabolised by a bacterium determining the likelihood of their resistant progeny to cluster after infection, and potentially the route taken by the bacteria through the resistance landscape
The SUPER-P approach: design, development, and evaluation of an education program for sport parents
No full textAfter-school sport involvement is progressively becoming an integral part of childhood and sport specialisation, high level competitions, pressure and intense involvement are increasingly becoming part of the landscape of childhood. The optimal approach to supporting a child athlete is characterised by a balanced partnership between the coach and parent, both playing equally important roles in the athlete's development. It is widely established that the role that parents play can have a profound influence on their child’s experience of sport, influencing both enjoyment and chances of success. However, in terms of knowledge and development more emphasis has been placed on coach education and to date there is no widely available sport parent education program designed through sport psychology research. Thus, the purpose of this study was to review the role of sport parents, explore the needs of child athletes, build a sport parent education program using recommendations from literature and assess the program in terms of both athlete and parent experience. Reviewing the literature in terms of high-level child athlete sport involvement it became clear that there was a need to gain insights from the children themselves. Therefore, an initial study was conducted to assess the experiences, views and needs of children involved in high level sport. This mixed methods study demonstrated the importance of passion as well as giving insights into the challenges faced by the children and what they most needed from their parents. The results were integral to the construction of the education program. Termed the SUPER-P Approach, the sport parent education program was designed using learnings from previous programs. The content was developed using three role categories, provider, interpreter and role model (Fredricks & Eccles, 2004) with the additional category of protector. The SUPER-P Approach was tested in two stages. Firstly, an initial in-depth qualitative study was conducted aimed to both evaluate the content of the program and test suitability for parents with children involved in high level competitive sports. Both parents and children were interviewed; firstly, separately and then together (once the parent undertook the sixty-minute, online pre-recorded workshop). The results were analysed using Interpretative Phenomenological Analysis and helped to enhance the program's structure as well as analyse initial feedback which indicated a positive reception from both parents and children. A second larger online, mixed methods study was conducted with 107 parent/child dyads. The dyads were asked to fill out an initial online questionnaire, parents were then invited to watch the online workshop and where possible after the child had attended a competition, feedback was obtained using a second online questionnaire. Child anxiety (including worry, somatic and focus) levels were tested before and after and feedback regarding the workshop was obtained. The analysis demonstrated that the SUPER-P Approach both supported positive parenting and mitigated negative practice. Parents reported feeling more confident, relaxed, and reassured following the program and the online delivery style was viewed as successful. The children reported a reduction in anxiety with a significant reduction in worry levels as well as a general positive view of their parents’ changed behaviour. Child sport is on the increase and there are concerning messages from the media regarding the state of youth sport. It is hoped that the introduction of the SUPER-P Approach will work to strengthen the coach/athlete/child triangle and thereby improve children’s experience of sport
Climate-induced scarcity or governance failure? Denaturalizing drought in Balochistan
No full textBalochistan, Pakistan’s largest and most arid province, faces severe environmental challenges, including persistent droughts, groundwater depletion, and periodic flash floods, which exacerbate socio-economic vulnerabilities and inequalities in resource access. In this context, Pishin district, a predominantly agricultural region in northern Balochistan, experiences significant environmental pressures that have critically undermined its primary livelihood, agriculture. This thesis critically explores the socio-political and environmental dimensions of drought vulnerability in Pishin, employing a framework that integrates an adapted Pressure and Release (PAR) model and the Theory of Access to examine the interconnected dynamics of structural marginalization, dynamic pressures, and access to resources, to advance the
discourse on critical disaster research.
Using a qualitative, case study-based methodology, this research draws on in-depth interviews with government officials, key experts, and local farming communities, supplemented by participant observation and oral histories. The findings reveal that entrenched governance inefficiencies, militarized control over resources, and socio-political exclusion have intensified environmental vulnerabilities, constraining the adaptive capacity of marginalized communities. These vulnerabilities are shaped by historical marginalization, bureaucratic ineffectiveness, and inequitable resource distribution. While local communities have adopted several adaptive strategies to mitigate their vulnerabilities, these efforts are undermined by systemic governance failures, socio-economic inequalities, and unsustainable water management practices. The decline of traditional, sustainable
irrigation systems such as karezes and the proliferation of tube-wells have further exacerbated groundwater depletion and environmental degradation.
This thesis deconstructs the concept of disasters by critically examining how socio-political structures transform environmental hazards into disasters. It offers a localized, evidence-based contribution to the field of political ecology, emphasizing the role of governance in shaping environmental outcomes. By highlighting the critical need for governance reforms, inclusive decision-making, and sustainable water management, this study aims to advance resilience in marginalized communities and address the root causes of environmental injustice in drought-affected regions of Balochistan
Automated construction of realistic clay models for molecular dynamics simulations: towards an accurate description of adsorption behaviours for biosignature identification on Mars
No full textClay minerals are characterised by their distinctive properties and have a wide range of applications, spanning from environmental to pharmaceutical and radioactive waste disposal. Their structures are highly diverse, and it is often impossible to experimentally elucidate the relationship between structural features and macroscopic material properties. Additionally, under extreme or extraterrestrial conditions, experimental analyses are either limited or impossible to conduct. In both cases, classical molecular dynamics simulations can provide essential information by elucidating the clay structure and interactions at an atomistic scale.
However, clay simulations are a relatively new field, and limited tools are available for automating a molecular dynamics simulation workflow. To address this gap, we present ClayCode, a Python package to automate the construction of realistic clay models and to generate simulation input files for the GROMACS simulation engine.
We used ClayCode in two adsorption studies, which demonstrate the importance of realistic clay models for accurately describing adsorption behaviours.
We first compare the competitive adsorption of toxic Ba²⁺ ions in the presence of Na⁺, a process relevant to radioactive wastewater remediation. Our results demonstrate that only realistic SWy-1 montmorillonite, KGa-1 kaolinite, and IMt-1 illite models reproduce experimentally observed selectivity for Ba²⁺ over Na⁺, whereas a commonly used simplified SWy-1 model does not.
In the second study, we apply ClayCode in a large-scale screening of astrobiological relevance. Here, we assess the adsorption mechanisms and affinities of 20 proteinogenic amino acids on the two Martian analogue NAu-1 and NAu-2 nontronite clays in the presence of Na⁺, K⁺, Ca2+ and Mg²⁺ cations. Our findings reveal that adsorption affinities depend on sidechain structure, cation species and clay structure and composition.
Our results emphasise the need for accurate clay models to reproduce realistic adsorption behaviours using classical molecular dynamics simulations, and show that ClayCode can be used to produce a wide variety of different atomistic clay models, which can be used to assess the adsorption behaviours of environmental and astrobiological relevance
Investigating pathological mechanisms in the Thy1-hTDP43 ALS mouse model
Get PDFAmyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease caused by the
death of both upper and lower motor neuron populations, which are responsible for
initiating and controlling movement. ALS is a complex and heterogeneous disease, with
only 10% of cases arising from an inherited genetic mutation. Although over 40 genes
have been linked to ALS pathology, the cause of disease is still unknown for the vast
majority of patients, and treatment options remain limited.
Multiple pathological mechanisms are subsequentially activated in ALS, making the
development of therapeutic options diAicult. The activation of these pathways does
seem to have a common link, causing the generation of cellular stress. The generation of
cellular stress induces the activation of many protective mechanisms, such as the
formation of stress granules (SGs). SGs are typically transient structures that sequester
translationally-stalled mRNA, RNA-binding proteins, ribosomal components, and
translation initiation factors to promote cell survival upon stress induction. In ALS and
other neurodegenerative diseases, SGs are, however, hypothesised to play pathological
roles, with changes in SG composition and morphology observed in ALS models. SGs in
ALS are further seen to colocalise with ALS-associated proteins in patient tissues, hinting
at a causative role in disease pathogenesis.
SGs have only been investigated in ALS using an external stressor. As SGs are dynamic
structures, their composition and morphology have been seen to change depending on
the external stressor. Therefore, we sought to investigate the role of SG formation and
related mechanisms for the first time in vivo without the use of an external stressor using
the Thy1-hTDP-43 mouse model. At the late symptomatic disease stage, we found a
significant upregulation of SG formation in spinal motor neurons, significant upregulation
of SG formation markers in both brain and spinal cord tissue at both the protein level and
the transcription level in Tg/Tg mice. These SGs were seen to colocalise with an ALSassociated
protein, TDP43, in spinal motor neurons, implying a pathological role for their
formation. Additionally, key factors suppressed by protective SG formation were
upregulated ROS and NLRP3, indicating altered SG function in ALS. Pathological stress
granules are typically broken down by autophagy degradation. Autophagy degradation
was unchanged at the time of SG upregulation and significantly decreased at later time
points, implying a defective clearance of SGs in the hTDP43 mouse model. As SG
formation can occur from several diAerent cellular stress response pathways, we next
wanted to explore potential upstream causes of SG formation in ALS. We saw a
significant upregulation of inflammation and oxidative stress at the late symptomatic
stage, implicating these as possible SG-activating mechanisms. This work identifies a
novel pathway that is dysfunctional during ALS disease progression that could present a
possible target for future therapeutic options
Impact of sensory cortex dysfunction on sensory perception
Get PDFTactile sensitivities are a core feature of autism, which often manifest in early childhood as
aversions to non-harmful touch, such as food or clothing textures. These sensitivities are
reported in up to 70% of individuals with autism and are thought to perpetuate aversions,
anxiety and maladaptive behaviours including self-harm. Current therapies for autism are
limited and fail to address sensory impairments, making the understanding of sensory
function imperative for discovery of new treatments targets. Fragile X Syndrome (FXS) is the
leading monogenic cause of intellectual disability, with 30-60% of individuals also diagnosed
with autism. FXS is caused by the transcriptional silencing of the FMR1 gene, leading to a
deficiency in Fragile X Messenger Ribonucleoprotein (FMRP), which has crucial roles at both
synaptic and circuit levels. It is becoming increasingly apparent that synaptic plasticity, which
is the change in the synaptic strength and thus the connections between neurons, underpins
sensory experience and perceptual learning.
The mouse whisker system serves as a powerful tool for studying sensory processing as
whiskers are a major processing hub of tactile information in rodents. Tactile information is
encoded in the primary somatosensory cortex (S1), with whisker input being somatotopically
represented across the barrel cortex (BC). In typically developing mice, rhythmic paired
stimulation (RPS) of lower- and higher-order thalamocortical projections, carrying
respectively sensory and contextual information, triggers a form of synaptic plasticity termed
long-term potentiation (LTP) in cortical layer 2/3 (L2/3) pyramidal neurons (PNs) in S1 ex vivo.
This LTP is suggested to share mechanisms with potentiation driven by rhythmic whisker
stimulation (RWS), which is a passive repetitive whisker stimulation paradigm, in vivo.
Preliminary data indicate that L2/3 LTP is impaired ex vivo in Fmr1-KO mice, a genetic rodent
model of FXS that also exhibits tactile impairments. I therefore hypothesised that RWSevoked
plasticity will also be impaired in vivo at L2/3 of S1 in Fmr1-KO mice. To test this, I
assessed the tactile-driven plasticity using 2-photon calcium imaging in head-fixed
anaesthetised or awake Fmr1-KO mice after undergoing the RWS paradigm. L2/3 neuronal
responses in S1 were monitored via calcium (Ca²⁺) levels, which serve as a proxy for neuronal
activity, using a fluorescent calcium indicator GCaMP6s. I successfully established and
standardised a 2-photon calcium imaging data acquisition and analysis pipeline, recording
neuronal activity in 6 wildtype (358 neurons) and 7 Fmr1-KO (347 neurons) anaesthetised
mice, as well as 2 wildtype (137 neurons) and 6 Fmr1-KO (317 neurons) awake mice.
Potentiation of neuronal responses following RWS was evident in Fmr1-KO mice under
anaesthesia, however, it was less robust than in wildtype mice. Under awake conditions, there
was no potentiation of neuronal responses in Fmr1-KO mice, but due to limited sample size
of awake wildtype mice no comparison between the two genotypes could be made.
Moreover, this impaired experience-dependent plasticity of L2/3 neurons in S1 seemed to be
associated with an altered distribution of neuronal responsivity types between Fmr1-KO and
wildtype mice, with Fmr1-KO mice exhibiting more neurons not responding to whisker
stimulation.
Lastly, I investigated whether the synaptic plasticity impairments observed in Fmr1-KO mice
ex vivo are due to structural changes in key postsynaptic proteins. Immunohistochemical
analysis of glutamate AMPA receptor (AMPAR) and postsynaptic density protein-95 (PSD95)
synaptic puncta abundance in L2/3 neurons of S1 revealed no differences between wildtype
and Fmr1-KO mice. This implies that AMPAR and PSD95 alterations do not underlie the
disruption of synaptic plasticity observed in Fmr1-KO mice
Conflict in a Warming World: How Climate Shocks Impact Rebel Demands and Peace Agreement Outcomes
Get PDFAs climate change becomes more severe and its effects more frequently observed, its impact on global conflict is increasingly important. Climate shocks, acting as threat multipliers, worsen vulnerabilities in conflict areas, increasing demands for scarce resources like water and land. This report explores how climate shocks influence rebel demands and violence, and whether these changes are reflected in peace agreements.
Not only are the demands for redistribution or influence on management of resources increasing, but the salience of these demands grows for all sides in the conflict, making these topics more likely to be added to the core topics of peace talks.
Using geospatial climatological and conflict data, this study tests two main hypotheses: 1) climate shocks will increase rebel demands for climate-related resources, and 2) these increased demands will lead to more provisions for water, land, and resources in peace agreements. The research employs difference-in-differences and panel linear regression methods that allow us to isolate the effects of climate shocks on rebel activity and assess whether these demands are addressed in peace agreements.
The findings provide key insights into how climate pressures shape conflict and how we can expect conflicts to evolve in a future of worsening climatic conditions. It is reasonable to assume that any effects found now will be smaller than what we can expect under unmitigated global warming. Therefore, the effects observed with existing data are substantively significant, as they likely represent a conservative estimate of future impacts. These insights are crucial for understanding the dynamics of conflict and for informing conflict resolution strategies in a warming world
Conservation genetics for Britain’s rarest fern: Woodsia ilvensis (L.) R.Br.
Get PDFThe thesis reports the findings of the investigation into the effects of habitat
fragmentation on the genetics and reproduction of Woodsia ilvensis (Woodsiaceae),
nationally an endangered fern native in the UK. Already rare in the UK, this fern was
heavily over-collected during the Victorian fern craze and populations never
recovered. This species now survives in small, isolated populations in five extant sites
across the UK with <300 plants/clumps which mainly fail to reproduce. In other
countries and areas such as Scandinavia or Eastern North America the species is
more widespread and found in stable, self-sustaining populations. The aim of this
research was to explore whether genetic constraints may limit natural recovery in the
UK and whether genetic rescue could help conservation efforts for this species. To
answer this question genetic analysis using 10 microsatellite loci has been conducted
for all UK populations and some plants in Canada and Norway. Furthermore, >1000
plants from the UK, Canada and Norway have been grown in a nursery environment
and fitness measurements (size and survival) have been recorded. Finally,
gametophyte crossing experiments have been attempted to explore whether spores
are likely to cross when given the opportunity. The results from this study indicate that
genetic diversity is very low in the UK (Hₑ ranging 0.08 - 0.31) but also in Norway (HE
= 0.21) and highest in Canada (Hₑ ranging 0.40 - 0.54), suggesting that W. ilvensis is
mainly selfing in the UK and Norway. Fitness measurements in the nursery showed
plant area cm² 67.66 (± 0.79 SE) and number of fronds 32.08 (± 0.79 SE) were
highest in the UK populations and may therefore not be a good proxy for population
fitness for this species. Efforts to improve the genetic diversity of this species may still
be an appropriate conservation strategy as a lack of diversity may affect the ability of
a species to adapt to environmental change such as climate change. More research
is required to fully understand reproductive constraints for this species in the UK
Neon dystopias, solar dreams: building climate centered game narratives with cyberpunk, steampunk, and solarpunk tropes
No full textAs the environment grows more unstable, the need to expand current methods of climate and activist communication grows more urgent. Storytelling has long been central to science communication, and climate stories have emerged in mainstream commercial movies and novels with increasing frequency, but even as video games grow more popular with each year, the medium has yet to fully step into the world of climate-centered narratives. This research aims to explore the potential of science fiction video games as climate activist media, specifically within three “punk” subgenres that have had historical ties to environmental messages in other media forms: cyberpunk, steampunk and solarpunk. It pursues questions of how genre reflects cultural relationships with nature, how genre influences tone and aesthetic, and further how the impacts of the genre influence what sort of climate stories can be effectively told without breaking genre. This research follows the process of creating the initial concept for a narrative video game, “Shatterpoint Reflections”—detailing character design, worldbuilding visuals, and narrative creation as all influenced by genre and centered around a message of individual and collective climate action. It was found that the studied subgenres of science fiction often already contain climate influence, which can be expanded on by pushing common background worldbuilding details to the center of the theoretical narrative—and that certain subgenres often as a result lend themselves to certain styles of climate story. Understanding how to craft worlds and narratives that stay true to what has allowed science fiction to enjoy its popularity without sacrificing the poignancy and directness of the climate activism message embedded within could help lead to the expansion of climate stories outside of certain game genres and into the mainstream world of Roleplay Games (RPGs)
Amine and amide containing novel polymers of intrinsic microporosity
Get PDFPolymers of Intrinsic Microporosity (PIMs) are a class of material that possess rigid and
contorted structures so that their lack of flexibility and rotational freedom reduces the
packing efficiency in the solid-state giving rise to microporosity and a large internal surface
area. A great many combinations of functional groups can be introduced to the
macromolecular structure of PIMs which helps to tune these polymers for application in
heterogenous catalysis, gas storage electrochemistry, as well as gas separation. Importantly,
owing to their solution processability, PIMs are suitable for membrane fabrication or
electrospinning of fibres.
Research reported in this thesis was focused on the incorporation of basic and nucleophilic
sites within PIMs by introducing amide and amine functional groups into novel spirocyclic and
propellane-based monomers that were suitable for polymerisation. In addition, these novel
PIMs were further functionalised by converting nitrile groups into amidoximes. By increasing
the basicity of the polymeric backbones of PIMs and introducing amidoxime groups, we aim
to explore new applications, such as the catalytic destruction of organophosphate-based
chemical warfare agents (CWAs) by amalgamating them into personal protective equipment
(PPE). The effect of increasing the overall basicity of PIMs on gas separation, particularly on
acidic gases such as carbon dioxide was investigated by analysing the gas permeability of the
novel PIMs. Although these objectives were unfulfilled, as the combination of high porosity,
super nucleophilic functionality and basis cut proved difficult to achieve, novel PIMs did have
potential as gas separation membranes due to a combination of high permeability and
moderate selectivity for a number of gas pairs
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