The impact of mutation and gene conversion on the local diversification of antigen genes in African trypanosomes

Patterns of genetic diversity in parasite antigen gene families hold important information about their potential to generate antigenic variation within and between hosts. The evolution of such gene families is typically driven by gene duplication, followed by point mutation and gene conversion. There is great interest in estimating the rates of these processes from molecular sequences for understanding the evolution of the pathogen and its significance for infection processes. In this study, a series of models are constructed to investigate hypotheses about the nucleotide diversity patterns between closely related gene sequences from the antigen gene archive of the African trypanosome, the protozoan parasite causative of human sleeping sickness in Equatorial Africa. We use a hidden Markov model approach to identify two scales of diversification: clustering of sequence mismatches, a putative indicator of gene conversion events with other lower-identity donor genes in the archive, and at a sparser scale, isolated mismatches, likely arising from independent point mutations. In addition to quantifying the respective probabilities of occurrence of these two processes, our approach yields estimates for the gene conversion tract length distribution and the average diversity contributed locally by conversion events. Model fitting is conducted using a Bayesian framework. We find that diversifying gene conversion events with lower-identity partners occur at least five times less frequently than point mutations on variant surface glycoprotein (VSG) pairs, and the average imported conversion tract is between 14 and 25 nucleotides long. However, because of the high diversity introduced by gene conversion, the two processes have almost equal impact on the per-nucleotide rate of sequence diversification between VSG subfamily members. We are able to disentangle the most likely locations of point mutations and conversions on each aligned gene pair

Isolation of 39 polymorphic microsatellite loci and the development of a fluorescently labelled marker set for the Eurasian badger

We have isolated 78 microsatellite loci from the Eurasian badger (Meles meles). Of the 52 loci characterized, 39 were found to be polymorphic. A fluorescently labelled primer set was developed to enable individual-specific 17-locus genotypes to be obtained efficiently

Adherence to medication in bipolar disorder: a qualitative study exploring the role of patients' beliefs about the condition and its treatment.

Patients' perceptions of illness and treatment have been found to predict adherence to medication in many chronic conditions. This has not yet been fully explored in bipolar disorder (BD). The aim was to use a qualitative methodology to explore in depth the beliefs about BD and its treatment that are associated with adherence to medication prescribed for BD

Patients' perceptions of information received about medication prescribed for bipolar disorder: Implications for informed choice

Background: Previous research suggests that patients are dissatisfied with information provided about medication prescribed for mental illness, but has not identified which aspects of information provision are unsatisfactory. Methods: 223 members of the Manic Depression Fellowship (MDF) completed the Satisfaction with Information about Medicines Scale (SIMS), a validated measure of patients' satisfaction with various aspects of information provision. Results Patients reported highest dissatisfaction with information about potential problems associated with medication; over 60% of participants reported dissatisfaction with information about the risks of side effects and whether the medication would affect their sex lives. Participants were significantly less satisfied with information about potential problems associated with their medication than people prescribed medication for HIV in a previously reported study (p < .01). Those reporting low adherence to medication had significantly lower satisfaction with information scores than those reporting high adherence (p < .05). Limitations: The sample could be prone to selection bias; participants were members of an organisation for people affected by bipolar disorder, whilst the comparator group was a NHS HIV clinic sample. Furthermore, the objective amount and type of information provided was not assessed, therefore the cause of patients' dissatisfaction is not known. Conclusions: Perceived satisfaction with information is low, particularly in relation to possible drug side-effects. Health practitioners need to elicit individuals' information requirements and tailor information to meet their needs, in order to facilitate informed choice and adherence to treatment. Moreover, they need to provide information in a manner appropriate for a patient's cognitive functioning at different illness phases

Feasibility study of the solar scientific instruments for Spacelab/Orbiter

The feasibility and economics of mounting and operating a set of solar scientific instruments in the backup Skylab Apollo Telescope Mount (ATM) hardware was evaluated. The instruments used as the study test payload and integrated into the ATM were: the Solar EUV Telescope/Spectrometer; the Solar Active Region Observing Telescope; and the Lyman Alpha White Light Coronagraph. The backup ATM hardware consists of a central cruciform structure, called the "SPAR', a "Sun End Canister' and a "Multiple Docking Adapter End Canister'. Basically, the ATM hardware and software provides a structural interface for the instruments; a closely controlled thermal environment; and a very accurate attitude and pointing control capability. The hardware is an identical set to the hardware that flow on Skylab

The Maritime Archaeology of Duplex Drive Tanks in the United Kingdom.

The catastrophe at Dieppe in 1942, where unsupported infantry attempted to capture a fortified beachhead, showed the allied forces how difficult such a venture was. As part of the invasion plan for what became Operation NEPTUNE or the Normandy landings, the allied staff saw the need for armoured support for the first waves of troops ashore. This need evolved into the concept of ‘swimming tanks’ that would land a few minutes ahead of the first infantry waves. The development of such a weapon was undertaken in conditions of absolute secrecy in the UK from late 1942 onwards. This secrecy led to the destruction of much of the historical records that relate to these armoured vehicles, leaving a confused and largely unknown record of what was an important aspect of WWII. This project sets out to record the known examples of such vehicles on the coast of the UK including a group lost as part of ‘Exercise SMASH’, the largest live ammunition exercise of the war, a full scale beach assault training exercise with all supporting arms including amphibious tanks. Though six tanks were lost during the exercise in conditions, which are not fully understood, the loss led to the changing of the operational plans for D-Day. Using archaeological and historic data, this project offers an alternative interpretation for these loses and provides a better understanding of their subsequent impact on Operation NEPTUNE

The TAO-Gen Algorithm for Identifying Gene Interaction Networks with Application to SOS Repair in E. coli

One major unresolved issue in the analysis of gene expression data is the identification and quantification of gene regulatory networks. Several methods have been proposed for identifying gene regulatory networks, but these methods predominantly focus on the use of multiple pairwise comparisons to identify the network structure. In this article, we describe a method for analyzing gene expression data to determine a regulatory structure consistent with an observed set of expression profiles. Unlike other methods this method goes beyond pairwise evaluations by using likelihood-based statistical methods to obtain the network that is most consistent with the complete data set. The proposed algorithm performs accurately for moderate-sized networks with most errors being minor additions of linkages. However, the analysis also indicates that sample sizes may need to be increased to uniquely identify even moderate-sized networks. The method is used to evaluate interactions between genes in the SOS signaling pathway in Escherichia coli using gene expression data where each gene in the network is over-expressed using plasmids inserts