56 research outputs found
Investigating the foot-and-mouth disease virus 3A protein
Foot-and-Mouth Disease Virus (FMDV) is a globally important pathogen responsible for causing Foot-and-Mouth Disease (FMD) in wildlife and domestic livestock species and has significant economic impacts. FMD is difficult to control due to its highly infectious nature, wide diversity of host species and the existence of multiple serotypes; therefore, understanding the processes of FMDV infection and viral RNA replication are key to the development of improved diagnostics and vaccines. This thesis investigates the potential roles of the FMDV 3A non-structural protein using a combination of sub-genomic replicons, recombinant viruses and proteomics techniques. The picornavirus 3A protein has previously been linked with roles in replication complex formation, virulence and determining viral host range.
This thesis presents findings showing that a naturally occurring deletion in 3A had differing effects on replication in cells lines derived from different natural hosts thereby supporting the conclusion that 3A has an important role in viral host range.
Proteomic (immunoprecipitation and mass spectroscopy) investigations were carried out to identify potential cellular interaction partners of FMDV 3A, and the impact on infection and replication of reducing expression of two selected cellular proteins Rab7L1 and TBC1D20 was investigated. The 3A protein of FMDV was shown to include a conserved FFAT motif (which bind the ER resident protein VAP) in its N terminal domain. A role for this motif was also investigated with the results suggesting that the 3A FFAT motif is important for efficient viral replication.
Finally, the potential role of 3A to act as the donor of 3B during replication was investigated. Key findings from experiments using FMDV replicons and recombinant viruses showed that full-length P3 and the processing intermediate 3ABBB are not required for viral RNA replication suggesting that the preferred donor of 3B for uridylation is likely a 3BC containing precursor protein
The Oldest Stars in the Galaxy – Searching for Metal-Poor Stars in the Galactic Bulge
The nature of the first generations of stars that formed after
the Big Bang is one of the major topics in contemporary
astrophysics and cosmology. Such stars formed out of gas that was
relatively free of elements heavier than helium, during a time
before generations of supernovae had polluted the environment.
Previous hunts have found many of these ‘old’ stars in the
Galactic halo. However, not all parts of the Milky Way evolved at
the same rate. Cosmological models of galaxy formation have drawn
the conclusion that, due to the "inside-out" formation of
galaxies like the Milky Way, the oldest stars should today
preferentially reside close to the centre of the Galaxy – in or
near the Galactic bulge.
This thesis documents the initial results of the EMBLA Survey,
the first successful search for ancient and metal-poor stars in
the bulge of the Milky Way. By utilising the metallicity
indicator provided by SkyMapper photometry, we were able to
search through more than five million bulge stars, looking for
those rare objects with extremely low iron abundances. The
AAOmega spectrograph on the AAT gave us the opportunity to obtain
intermediate- spectroscopy of approximately 350 stars
simultaneously; during 24 nights of observing spread over three
years, we observed more than 14,000 candidate metal-poor stars to
spectroscopically confirm the photometric metallicity estimates.
We found that 49% of the stars observed with the AAT had
metallicities below [Fe/H]= 1.0, and around 1,000 stars with
[Fe/H]< 2.0. This is a remarkable achievement given that
previous searches had only found a total of 21 stars with
metallicities that low.
Thirty-seven of the most metal-poor stars were then observed with
high-resolution spectro- scopy using 8 m telescopes like Magellan
and the Very Large Telescope (VLT), to determine their detailed
chemical compositions. As part of the Gaia-ESO Survey, four stars
were observed in 2012 on the VLT, with metallicities of
2.72[Fe/H] 2.48. We then observed a further ten stars with
the MIKE spectrograph at Magellan in 2012, and in 2014 we
observed a final 23 targets.
We have found the first EMP stars in the bulge; nine of our stars
have [Fe/H]< 3.0, and one has [Fe/H]= 4.0. We compared the
abundances found in our sample with stars of the same
metallicities found in the Galactic halo, and found in general
similar trends. Unexpectedly, however, we only found one
carbon-enhanced metal-poor (CEMP) star (3%) while 20% of halo
stars with [Fe/H]< 2.0 are CEMP stars. In order to verify the
predicted old ages of our stars, we also investigated their
kinematics. We found that half the stars examined have tightly
bound orbits; remaining within the inner Galaxy rather than being
merely halo stars passing through the bulge region. This is
crucial, as the oldest stars are predicted to have the lowest
binding energies. The two most metal-poor stars in our sample
have binding energies low enough that there is a 50% chance they
formed at redshifts of z > 12, which would make them the oldest
known objects in the Universe
Estimating stellar ages and metallicities from parallaxes and broadband photometry - successes and shortcomings
A deep understanding of the Milky Way galaxy, its formation and evolution
requires observations of huge numbers of stars. Stellar photometry, therefore,
provides an economical method to obtain intrinsic stellar parameters. With the
addition of distance information - deriving reliable ages from photometry is a
possibility. We have developed a Bayesian method that generates 2D probability
maps of a star's age and metallicity from photometry and parallax using
isochrones. Our synthetic tests show that including a near-UV passband enables
us to break the degeneracy between a star's age and metallicity for certain
evolutionary stages. It is possible to find well-constrained ages and
metallicities for turn-off and sub-giant stars with colours including a U band
and a parallax with uncertainty less than ~20%. Metallicities alone are
possible for the main sequence and giant branch. We find good agreement with
the literature when we apply our method to the Gaia benchmark stars,
particularly for turn-off and young stars. Further tests on the old open
cluster NGC 188, however, reveal significant limitations in the stellar
isochrones. The ages derived for the cluster stars vary with evolutionary
stage, such that turn-off ages disagree with those on the sub-giant branch, and
metallicities vary significantly throughout. Furthermore, the parameters vary
appreciably depending on which colour combinations are used in the derivation.
We identify the causes of these mismatches and show that improvements are
needed in the modelling of giant branch stars and in the creation and
calibration of synthetic near-UV photometry. Our results warn against applying
isochrone fitting indiscriminately. In particular, the uncertainty on the
stellar models should be quantitatively taken into account. Further efforts to
improve the models will result in significant advancements in our ability to
study the Galaxy.Comment: Accepted for publication in A&A. 22 pages, 19 figures (+ 6 pages of
appendix). Abstract abridged for the arXi
Dive tourism in Luganville, Vanuatu: shocks, stressors and vulnerability to climate change
Luganville is a developing dive tourism destination region (DTDR) in Vanuatu, which relies on tourism.
This article reports on the shocks and stressors faced by Luganville’s dive tourism sector and climate
change’s exacerbation of these. The study’s methodology was based on rapid rural appraisal and
case study principles, involving methods of semistructured interviews, group discussions, and personal
observations. Data were analyzed using a thematic analysis approach. Key shocks identified include
cyclones, earthquakes, effect on demand due to media footage, and changes to international flights.
Main stressors were starfish outbreaks and environmental degradation. Unlike the indigenous communities,
expatriates show little concern for the potential impact of climate change, presenting response
challenges that must incorporate different perspectives to develop effective adaptation options.
Special Issue : scuba diving touris
The detailed chemical composition of the terrestrial planet host Kepler-10
Chemical abundance studies of the Sun and solar twins have demonstrated that the solar composition of refractory elements is depleted when compared to volatile elements, which could be due to the formation of terrestrial planets. In order to further examine this scenario, we conducted a line-by-line differential chemical abundance analysis of the terrestrial planet host Kepler-10 and 14 of its stellar twins. Stellar parameters and elemental abundances of Kepler-10 and its stellar twins were obtained with very high precision using a strictly differential analysis of high quality Canada–France–Hawaii Telescope, Hobby–Eberly Telescope and Magellan spectra. When compared to the majority of thick disc twins, Kepler-10 shows a depletion in the refractory elements relative to the volatile elements, which could be due to the formation of terrestrial planets in the Kepler-10 system. The average abundance pattern corresponds to ∼13 Earth masses, while the two known planets in Kepler-10 system have a combined ∼20 Earth masses. For two of the eight thick disc twins, however, no depletion patterns are found. Although our results demonstrate that several factors [e.g. planet signature, stellar age, stellar birth location and Galactic chemical evolution (GCE)] could lead to or affect abundance trends with condensation temperature, we find that the trends give further support for the planetary signature hypothesis
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A cross-sectional MR study of body fat volumes and distribution in chronic schizophrenia
Funder: DH | National Institute for Health Research (NIHR); doi: https://doi.org/10.13039/501100000272Funder: RCUK | Medical Research Council (MRC); doi: https://doi.org/10.13039/501100000265AbstractPeople with schizophrenia show higher risk for abdominal obesity than the general population, which could contribute to excess mortality. However, it is unclear whether this is driven by alterations in abdominal fat partitioning. Here, we test the hypothesis that individuals with schizophrenia show a higher proportion of visceral to total body fat measured using magnetic resonance imaging (MRI). We recruited 38 participants with schizophrenia and 38 healthy controls matched on age, sex, ethnicity, and body mass index. We found no significant differences in body fat distribution between groups, suggesting that increased abdominal obesity in schizophrenia is not associated with altered fat distribution.</jats:p
HIP 10725: The first solar twin/analogue field blue straggler
Context. Blue stragglers are easy to identify in globular clusters, but are much harder to identify in the field. Here we present the serendipitous discovery of one field blue straggler, HIP 10725, that closely matches the Sun in mass and age, but with a metallicity slightly lower than solar.
Aims. We characterise the solar twin/analogue HIP 10725 to assess whether this star is a blue straggler.
Methods. We employed spectra with high resolution (R ~ 105) and high signal-to-noise ratio (330) obtained with UVES at the VLT to perform a differential abundance analysis of the solar analogue HIP 10725. Radial velocities obtained by other instruments were also used to check for binarity. We also studied its chromospheric activity, age, and rotational velocity.
Results. HIP 10725 is severely depleted in beryllium ([ Be/H ] ≤ −1.2 dex) for its stellar parameters and age. The abundances relative to solar of the elements with Z ≤ 30 show a correlation with condensation temperature, and the neutron capture elements produced by the s-process are greatly enhanced, while the r-process elements seem normal. We found its projected rotational velocity (vsini = 3.3 ± 0.1 km s-1) to be significantly higher than solar and incompatible with its isochrone-derived age. Radial velocity monitoring shows that the star has a binary companion.
Conclusions. Based on the high s-process element enhancements and low beryllium abundance, we suggest that HIP 10725 has been polluted by mass transfer from an AGB star that probably had an initial mass of about 2 M⊙. The radial velocity variations suggest the presence of an unseen binary companion, probably the remnant of a former AGB star. Isochrones predict a solar-age star, but this disagrees with the high projected rotational velocity and high chromospheric activity. We conclude that HIP 10725 is a field blue straggler, rejuvenated by the mass-transfer process of its former AGB companion
Abnormal P300 in people with high risk of developing psychosis
Background
Individuals with an “at-risk mental state” (or “prodromal” symptoms) have a 20–40% chance of developing psychosis; however it is difficult to predict which of them will become ill on the basis of their clinical symptoms alone. We examined whether neurophysiological markers could help to identify those who are particularly vulnerable.
Method
35 cases meeting PACE criteria for the at-risk mental state (ARMS) and 57 controls performed an auditory oddball task whilst their electroencephalogram was recorded. The latency and amplitude of the P300 and N100 waves were compared between groups using linear regression.
Results
The P300 amplitude was significantly reduced in the ARMS group [8.6 ± 6.4 microvolt] compared to controls [12.7 ± 5.8 microvolt] (p < 0.01). There were no group differences in P300 latency or in the amplitude and latency of the N100. Of the at-risk subjects that were followed up, seven (21%) developed psychosis.
Conclusion
Reduction in the amplitude of the P300 is associated with an increased vulnerability to psychosis. Neurophysiological and other biological markers may be of use to predict clinical outcomes in populations at high risk
Associations between personality disorder characteristics and treatment outcomes in people with co-occurring alcohol misuse and depression
The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study
Background:
Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy.
Methods:
Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored.
Results:
A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays.
Conclusions:
IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients
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