13506 research outputs found
Sort by
Demonstrating the Role of Histidine as a Cytosolic Buffer of Ni(II) Ions in Escherichia coli
Get PDFTransition metals are cofactors in many essential proteins. The correct function of these proteins hinges on metalation by their cognate metal ion, regardless of its ranking in the Irving-Williams series of metal-complex affinities. In the bacterial cytosol, evidence suggests that buffer molecules compete with proteins for metal ions, which will partition according to their relative affinities for various possible binding sites. Controlling metal availability in this manner prevents mismetallation by more competitive metals. This thesis seeks to test the buffer model using a genetic approach to alter cytosolic buffer molecule levels. A key test of the hypothesis will be changes in the cellular metalation of a metal-responsive transcription factor (RcnR), as proteins responsible for regulating metal homeostasis have affinities finely poised to sense the level of buffered metal, altering gene expression to match metal supply with demand.
L-histidine (His) is a candidate buffer of Ni(II) in E. coli. His levels were altered by mutating hisG, which encodes the feedback-inhibited first enzyme in the His biosynthetic pathway. A small library of mutant strains with altered levels of cytosolic His was generated. These strains were tested for growth sensitivity to Ni(II), and changes in Ni(II) and Co(II) responsive gene regulation by the RcnR sensor. Strains that produce more His, as assessed by qualitative bioassay for His excretion, were more resistant to the effects of Ni(II) on cell growth and showed a diminished transcriptional response to Ni(II). Strains that produced less His showed increased sensitivity to Ni(II) in a growth assay. In contrast, increased cytosolic His levels did not affect the Co(II)-responsiveness of RcnR compared to the parent strain. Thus, this work shows that His is a cytosolic buffer of Ni(II) in E. coli but is not a universal metal buffer
Sleep, Circadian Behaviour, Physical Activity, Social Networks and Psychological Health: Factors Helping to Preserve Healthy Memory Performance in Normal Ageing
Get PDFIntroduction: Although dementia today blights the lives of nearly 1 million people in the UK, the majority of older people will never have to live with it; but they are likely nevertheless to suffer the unwelcome loss of memory function that accompanies normal ageing. Maximising the cognitive health span of an ageing population is critically important to the efficient use of increasingly limited public health resources. In examining those factors that may preserve healthy memory performance in normal ageing, this study is not directly concerned with developing strategies to prevent or forestall dementia. However, it is likely that any memory-protective factors which help to preserve good cognitive health in normal ageing may well extend also to clinical-level memory impairment.
Methods: A large sample of cognitively normal subjects (N=145, M=55 years) underwent two separate phases of neuropsychological testing in different memory domains, including a new two-week delayed recall test of verbal episodic memory. Actigraphy was used to measure subjects’ sleep, Circadian behaviour patterns and physical activity levels over two weeks. In addition, subjects completed a range of psychological health and other questionnaires, including the Pittsburgh Sleep Questionnaire (PSQ). Factor analysis was used to reduce tested memory domains into four discrete domains: (1) short-term verbal episodic memory (2) long-term forgetting in verbal episodic memory (3) face memory and perception and (4) working memory. The same factor analysis process was used to reduce psychological health measures into three main constructs; (1) social experience (positive and negative), (2) social confidence and fearfulness, and (3) social connectedness. Comparison groups were established for age (younger, M=36 years, older, M=66 years), sleep quality (PSQ good and poor sleepers), and Circadian behaviour (owls and larks).
Results: Younger subjects outperformed older subjects in all memory domains except long-term forgetting (p=.16). Good sleepers outperformed poor sleepers in long-term forgetting (p=.0001), but not in any other memory domain. Older subjects had lower levels of Circadian dysfunctional behaviours, such as Sleep Debt and Social Jet Lag, than younger persons (p=.002 and p<.0001 respectively). However, neither Sleep Debt nor Social Jet Lag had any bearing on sleep quality (or on long term memory consolidation) and they did not differ between owls and larks (p=.18 and p=.67 respectively). Owls though tended to have larger social networks than larks (p=.007). Being more active (and less sedentary) protected working memory, and the levels of beneficial activity were different for older subjects (more light to moderate activity) than they were for younger subjects (more sustained and vigorous activity). Older subjects had better psychological health than younger subjects (p<.0001) but had no difference in social networks (p=.9). Poor sleepers had lower psychological mood than good sleepers (p=.001) but did not differ in sociability. Importantly, better psychological mood contributes to better long-term forgetting alongside good sleep.
Discussion: This study revealed a number of new findings that are important to the preservation of healthy memory performance in normal ageing. First, the double dissociation between age groups and good/poor sleep quality groups in long-term forgetting provides good evidence for the benefit of sleep to long-term memory consolidation, regardless of age. Second, while Sleep Debt and Social Jet Lag are dysfunctional behaviours, they are not necessarily embedded within ordinary chronotype differences between owls and larks, and they appear to have no relationship to sleep quality. As such, they have no overt bearing on long-term forgetting or sleep-based memory consolidation. Third, good and poor sleepers differ extensively in measures of psychological mood but do not differ in sociability, even though many of the measures of psychological mood and sociability are themselves strongly correlated. For example, poor sleepers are lonelier than good sleepers but do not have smaller social networks, although higher loneliness is strongly correlated with having smaller social networks. Also, being an owl appears to confer advantages in terms of size of friendship networks. Most importantly, good sleep and better psychological mood together predict better (lower) long-term forgetting. Finally, it is not necessary for physical activity in older age to be at similar intensity levels to that achieved by younger persons in order to secure comparable benefits to working memory. It is clear from these results that older subjects find it easier to maintain lighter levels of physical activity with increasing age, and the cognitive benefits of doing so are not to be under-estimated
Bakhtin, Shakespeare, and Theatre
Get PDFThis thesis makes a case for Mikhail Bakhtin (1895-1975) as a critic of drama. It uses
Bakhtin’s notes for revision of Rabelais and His World, written in 1942, as a catalyst for
exploration of Shakespeare and of drama more generally. In the Rabelais revision notes,
Bakhtin comments on Shakespeare’s major tragedies, identifying patterns in them that
expand on, complicate, and darken the festive, utopian themes found in the main text of
Rabelais and His World. He also discusses drama as a genre, in particular the ways that
meaning is made in theatrical spaces by bodies onstage. Bakhtin is at times openly dismissive
of drama elsewhere in his work but the Rabelais revision notes demonstrate an unprecedented
engagement with theatre. This thesis close reads these notes, exploring them play by play and
concept by concept, then constructs a Bakhtinian aesthetics of drama, split into sections titled
‘Dialogism’, ‘Embodiment’, and ‘Eventness’. The second half of the thesis takes this
aesthetics forward to consider twenty-first-century Shakespeare performance, investigating
each section of its theoretical chapter via different productions. These productions encompass
work by Ivo van Hove, Ian Rickson, Thomas Ostermeier, Punchdrunk Theatre, Robert
Lepage, the National Theatre of Scotland, Caroline Byrne at Shakespeare’s Globe, the RSC,
and the Wooster Group. The thesis concludes with a consideration of broadcast and streaming
theatre and looks at the current moment of recovery from the COVID-19 pandemic, as well
as projecting forward to think about uses of technology in performance in the future. The
analysis conducted stands as a reappraisal of Bakhtin as a critic of drama, and as an example
of the ways in which his work can be used to explore theatre throughout time
Mechanisms of Nanoparticle Synthesis for the Production of Well-Defined Models of Heterogeneous Catalysts
Get PDFThe synthesis of metal nanoparticles (NPs) by hot-injection/heating-up chemical reduction methods is a widely used method for generating size-controlled nanoparticles with narrow dispersity. These are important in a number of fields, for instance, their use in studies to understand structure-activity relationships in catalysis (the focus of our research group). These methods generate capping agent-controlled metal NPs. This thesis focuses mainly on methods using an organic solvent with long-chain amines and acids, along with a reducing agent, to carry out nanoparticle synthesis by chemical reduction.
Chapter 4 starts to build on a procedure reported (but not thoroughly investigated) in the literature that has shown it was possible to synthesize 3.2 nm Ni NPs by using oleic acid (OA), oleylamine (Oly) and borane tributylamine (BTB). This chapter studies the changes in the colour of the solution over time before the reducing agent is added (including with UV-vis-NIR spectroscopy) and develops the method further to produce smaller 1.3 nm Ni NPs.
Chapter 5 continues the work done by previous group members to develop a method to synthesise size-controlled Cu NPs. This chapter shows the ability to manipulate the reaction temperature to yield a uniform size of 4.3 nm Cu NPs. Then, the study of the solvent system over time before the reduction reaction shows the ability to produce monodispersed 1.8 nm Cu NPs.
Chapter 6 reports studies to investigate the amine-borane type reducing agent used in the previous chapters. Amine-borane (AB) compounds are used without understanding how the reduction process is happening. This chapter uses several approaches to suggest that the amine-borane is releasing H2 that supersaturates the solution, and then the H2 reduces the M(acac)2 directly.
Finally, Chapter 7 presents a way to couple two metals NPs of different metals (i.e. unsymmetrical pairs) with covalent tethers. Cu, Pd, and Ni NPs were used with a series of more complex amide linkage coupling systems more commonly used in biological applications. While early attempts were unsuccessful when more complex combinations of coupling reagents were used, it was shown that it was possible to get around 60% of nanoparticles in pairs.
In summary, the thesis examines the synthesis of metal nanoparticles in detail, both the formation of in situ precursors and the impact of this on the resultant nanoparticles and the behaviour of the now widely used amine-borane class of reducing agents. It then goes on to demonstrate their use in developing nanostructures with the long-term goal of exploring mechanisms in catalysis using materials that cannot be prepared without recourse to nanoparticle synthesis
Primary teachers’ conceptions and approaches to using visual arts in writing in Saudi Arabia
Get PDFThis thesis investigates the use of visual arts (drawing and images) in teaching writing from the perspective of Saudi language teachers. The interviews were conducted with primary-school teachers and the data was interpreted through the lens of the phenomenographic paradigm. The analysis of the gathered data revealed three main conceptions that teachers have adopted regarding the use of visual arts in teaching writing: curriculum-focused, knowledge-transfer, and student-needs.
The curriculum-focused teachers relied predominantly on the textbook and curriculum requirements and used visual arts sparingly, leaving such activities to the student’s choice. Knowledge-transfer teachers focused on how visual arts could be used as an effective means to transfer knowledge. The teachers who applied the visual arts approach to meet students’ learning needs were those most in favour of visual arts and stress their benefit. The knowledge-transfer and student-needs categories were further subdivided into subcategories to reflect the original experience. Student perception and writing quality were the categories identified in the knowledge-transfer group, while the student need-focused experience was divided into beginner students and those with learning difficulties.
The data were further categorized according to three common dimensions that emerged from the analysis of the teachers’ conceptions: significance of visual arts, type of impact, and student learning level. The findings showed that the curriculum-focused category viewed the use of visual arts in teaching writing as a marginal and indirect approach for post-beginner students. The student needs-focused category viewed the use of visual arts as an essential and direct approach that perfectly matches the needs of first graders and students with learning difficulties. The knowledge-transfer category shared the view that this approach is essential, but at the same time, it considered the indirect impact on post-beginner students. The thesis concludes by recommending more research in this area in Saudi Arabia. The main implication for practice refers to the teachers’ opportunity to enhance students’ literacy learning and especially, writing by employing visual arts
Narrative Nefas and the Taboos of Incest and Bestiality in Ovid’s Metamorphoses
Get PDFThis thesis explores the taboos on incest and bestiality, as they are presented in Ovid’s Metamorphoses, from a psychoanalytic and narratological perspective, through the lens of nefas (‘unspeakability’). I argue that taboo has a destructively transformative effect on Ovid’s poetic language and that, in bringing incest and bestiality to the page, the fabric of the epic warps and ruptures.
I begin with a detailed study of nefas, its role in the Roman world generally and within the Ovidian corpus specifically; I then outline the taboos on incest and bestiality in the Augustan world and how their position as unlegislated crimes informs Ovid’s approach to them through the lens of nefas. In Chapter 2, I explore two ‘spectres’—Oedipus and Pasiphaë—who are absent from the text of the Metamorphoses, but who ‘haunt’ multiple figures in the poem and, so, make their absence present. My third chapter focuses on Byblis and her love for her twin brother, Caunus; in particular, I explore how unspeakable nefas runs up against the episode’s concern with speech, in the form of Byblis’ letter and monologues. Chapter 4 uses Kristevan notions of abjection to examine Myrrha, who sleeps with her father, Cinyras; I show that she is an ambiguous figure to whom polarities like ‘good’ and ‘bad’ do not apply. In Chapter 5, I analyse how Arachne’s tapestry—full of images of bestiality—interacts with the epic as a whole; Arachne becomes an avatar of Ovid’s super-ego, who critiques her creator for not telling the stories that she explosively creates. My final chapter groups three narratives which are concerned with aesthetics—Cyparissus, Io and Europa—in order to develop Chapter 3’s findings about the relationship between desire and aesthetics
THE DEVELOPMENT OF NOVEL FLUORESCENT PROBES FOR THE INVESTIGATION OF MELANOSOME TRAFFICKING
Get PDFMelanosomes are pigment cell-specific organelles in which melanin is produced and trafficked within the cell, before being transferred to neighbouring keratinocytes. Their production is essential for the protection of skin cells from UV radiation. Melanosomes are an ideal model for the study of vesicular transport, due to the ease with which they can be detected in darkly pigmented cells. Extensive research has identified the key proteins involved in melanogenesis, including Pmel17, TRP2 and Rab27A. However, melanosomal research thus far has been mostly static, using techniques such as electron microscopy. As a result, the dynamic movement of melanosomes both within melanocytes and during transfer to keratinocytes has not been observed.
Here, the three melanosome-related proteins Rab27A, TRP2 and Pmel17 are fluorescently tagged and examined in SKMEL28 cells for their use in the observation of melanosome dynamics. Rab27A is implicated in the transport of mature pigmented melanosomes to the cell periphery. TRP2 is associated with early stage melanosomes and mediates pigmentation, while Pmel17 initiates melanosome maturation, forming fibrils onto which melanin is deposited. Novel fluorescent probes tdTomato-TRP2 and mNG-Pmel17 were designed, and the latter was determined to be the most effective for the visualisation of melanosomes. The mNG-Pmel17 fluorescent probe produced punctate structures in live cells, of a size consistent with melansomes. The probe co-localised with the actin cytoskeleton and was shown to be distinct from lysosomal compartments. Finally, mNG-Pmel17 is reported as a valuable tool for the evaluation of the effects of bioactive compounds of interest.
The novel mNG-Pmel17 probe was shown to be a useful tool for dynamic melanosome observation, and may be used in further studies for the elucidation of the mechanism(s) of melanosome transfer to keratinocytes
The Glencoe caldera ring fault(s) as a detailed record of a magmatic sub-surface transport system and its collapse mechanics.
Get PDFSome of the largest and most hazardous natural events on Earth are silicic caldera-forming volcanic eruptions, where the eruption of vast volumes of magma results in the collapse of crustal material that forms the magma reservoir’s roof (Cole et al., 2005; Geyer and Martí, 2014; Sigurdsson et al., 2015; Kennedy et al., 2018; Geshi et al., 2021). Volcanic eruptions include 3 key regions of activity: magma storage, sub-surface magma transport, and surface magma eruption. The behaviour of the sub-surface transport system throughout a caldera-forming eruption is poorly constrained due to limitations in methods of study available, and because it suffers from being complicated by its interaction with the structural caldera collapse system (Wiebe et al., 2021). Along caldera ring fault surfaces the two separate movements occur (the upwards transport of magma, and the downwards collapse of the caldera block), so, it is difficult to unpick the relationship between these two processes and whether this interaction causes any changes to the mechanics of caldera-forming eruptions.
In order to address the poor understanding of caldera transport systems, this thesis addresses two questions. (1) How do the processes of caldera slip and magma transport initiate and interact with one another when both occurring along the common surface of the caldera ring fault? (2) In what state is magma transported through the crust? This study applies these questions to the ancient Glencoe caldera (Scotland) where erosion has allowed for exposure of the caldera on many levels including the ring fault/conduit fill (Kokelaar and Moore, 2006). Therefore, this study uses field, textural, petrological, geochemical, and theoretical evidence to discuss these key questions in order to build a model for the evolution of the sub-surface transport system throughout an eruption which is applicable to calderas worldwide where this exposure cannot be seen.
Here we show that friction along caldera ring faults is not high enough to produce frictional melts, as proposed by previous ‘superfault’ theories (Spray, 1997; Kokelaar, 2007; Han et al., 2019; Kim et al., 2019). Instead, we suggest that collapse is incremental, piecemeal, and dilational, and that ring faults are dominated by magma transport processes throughout an eruption. Hence, this provokes the idea that the naming of such ring faults may have a misleading emphasis. This work also shows that the subsurface transport of pyroclastic magma is deep, widespread and long-lived during caldera eruptions which progressively tap deeper magma chamber components. We anticipate this thesis will encourage future research to not focus on caldera models which rely on high friction along caldera ring faults, but instead understand that these systems are long lived and dominated by eruptions of pyroclastic material
How remembering predicts leadership outcomes through the use of a new events binding measure
Get PDFLearning is an important process we go through to accumulate knowledge. People can develop their skills and crystallise their identities around leadership through learning from related experiences. I propose that through a micro-level cognitive processing of binding together features of experienced events, contextual information can be stored in memory in a manner that facilitates skill development, allowing people to build knowledge structures that enhance/crystallise one’s leader identity as well as being a basis for developing context-specific leadership skills. This research extends existing leadership literature by focusing on how people process information to build leadership-specific knowledge structures by drawing on their binding capacity of encoding and retrieving associated information in memory to inform leadership related self-concepts. Four studies were conducted to test the proposed hypotheses. I developed the new event binding measure in Study 1 (N=74), investigated the effect of event binding capacity and leadership experience on leader identity, leadership self-efficacy, and affective-identity motivation to lead in Study 2 (N=128), and the interactive effect of event binding capacity with self- relevant/relational events on the leadership variables (Study 3, N=176; Study 4, N=173). Results suggested that individuals’ event binding capacity positively correlated with fluid intelligence. Individuals with higher event binding capacity and more leadership experience reported higher leader identity. A three-way interaction of event binding capacity, self- relevant events and relational events also predicted higher leader identity and leadership self-efficacy
The dynamics and ISM properties of high-redshift dusty star-forming galaxies
Get PDFIn this thesis we present a range of observations of submillimetre galaxies (SMGs), a subclass of dust-obscured star-forming galaxies (DSFGs) at redshifts of z~1-5. SMGs are among the most actively star forming sources ever observed, believed to contribute significantly to the star-formation rate density (SFRD) at its peak, so-called 'cosmic noon', at z~2. Given their extreme nature, SMGs provide a strong test of galaxy formation and evolution models. Advancements in instrumentation, in particular with the Submillimetre Common-User Bolometer Area 2 (SCUBA-2) and the Atacama Large (sub-)Millimeter Array (ALMA), have driven significant progress in SMGs studies over the last decade. We have now identified samples of hundreds of SMGs in survey fields with a plethora of photometric coverage, such as the Cosmic Evolution Survey (COSMOS), the UKIDSS Ultra Deep Survey (UDS) and the Extended Chandra Deep Field Survey (ECDFS). Indeed, the main motivation of this thesis is to exploit these samples of SMGs, with a particular focus on the molecular and ionised gas properties, using state-of-the-art instrumentation such as ALMA and the Northern Extended Millimeter Array (NOEMA) for the former, and the K-band Multi-Object Spectrograph (KMOS) mounted on the Very Large Telescope for the latter.
Firstly, in Chapter 2 we present CO observations of 47 SMGs, providing one of the largest and highest quality samples of its kind. With this study we demonstrate the capability of ALMA and NOEMA to undertake blind redshift scans in the 3mm waveband, and in doing so add significantly to the number of SMGs with spectroscopic redshifts, which prior to the work presented in this thesis was small. We also exploit the multi-wavelength coverage of the samples, together with the robust new spectroscopic redshifts, to model their spectral energy distributions (SEDs) with the MAGPHYS code and subsequently estimate key physical properties such as stellar masses and star-formation rates.
Perhaps more importantly, this survey has allowed us to characterise the molecular gas content in the SMG population, along with its excitation properties, results from which we present in Chapter 3. We also show that the gas depletion timescale in SMGs remains constant, and given that SMGs are significant contributors to the star-formation rate density (SFRD) at z~2, the global evolution of star-formation in SMGs appears to coincide with the evolution of the molecular gas content, as opposed to any variation in star-formation efficiency. We provide a new test of the SMG population as descendants of massive local early-type galaxies, using the derived CO linewidths and baryonic masses.
In Chapter 4 we present our Large Programme with KMOS which, when completed, will have observed ~400 SMGs in the COSMOS, UDS and ECDFS fields. Expanding on the work of Chapters 2 and 3 this is designed to further add to the catalog of SMGs with spectroscopic redshifts by detecting the H_alpha and/or [OIII] emission, which probes ionised gas and can also be used to estimate star-formation rates. We detail the target selection and observing strategy of this survey, before presenting early results for 43 emission line-detected sources, including the H_alpha-derived star-formation rates, the mass-metallicity relation and BPT diagram. We also compare the H_alpha, rest-frame optical/near-infrared and dust sizes where available, finding median radii of R_e = 3.6+/-0.3 kpc, R_Halpha = 4.2+/-0.4 kpc and R_dust = 1.2+/-0.3 kpc. Additionally, the sample are consistent with a median Sersic index of n=1, i.e. with an exponential disc-like light profile.
The integral field spectrograph (IFS) capabilities of KMOS allow us to spatially resolve the H_alpha/[OIII] emission when it is sufficiently bright and extended, and this provides valuable diagnostics of the galaxy kinematics. Therefore, in Chapter 5 we present resolved H_alpha/[OIII] velocity and velocity dispersion maps for 36 SMGs, from which we derive rotation curves and dispersion profiles. We compare the derived kinematics of our SMGs with less active galaxies at lower redshifts, and divide the sample into 28 'ordered' sources with clear velocity gradients, and rotation curves which can be modelled as Freeman disks, and eight 'disordered' sources with much more messy velocity maps, from which little reliable kinematic information can be obtained. We measure a median rotational velocity of v_rot = 190+/-20 km/s and a median intrinsic velocity dispersion of sigma_0 = 87+/-5 km/s from the 'ordered' subset, both of which are significantly higher than the less actively star-forming galaxies to which we compare. The median ratio of rotational velocity to intrinsic velocity dispersion in the 'ordered' sample is v_rot/sigma_0 = 2.2+/-0.5, indicating that our sources are somewhat rotationally supported, and we therefore suggest that our SMG sample likely represents 'scaled-up' versions of more 'normal' star-forming galaxies, rather than merger-dominated systems
Data sources:
Access Repository Dashboard
Do you manage Open Research Online? Become a CORE Member to access insider analytics, issue reports and manage access to outputs from your repository in the CORE Repository Dashboard! 👇