No description available.

No description available.

This thesis documents the contribution of my bioinformatics research activities, including novel software development, to a range of research projects aimed at investigating the interactions between bacterial and viral pathogens and their hosts. The focus is largely on farm animal species and their pathogens, although some of the research has a wider scientific impact. RNA interference (RNAi) refers to a variety of related regulatory pathways present in animals, plants and insects. The major pathways are microRNAs (miRNAs), small-interfering RNAs (siRNAs) and PIWI-interacting RNAs (piRNAs). Marek’s disease virus is an important pathogen of poultry, causing T-cell lymphoma. We identified the presence and expression patterns of several MDV-encoded microRNAs, including the identification of 5 novel microRNAs. We also showed that not only do virus-encoded microRNAs dominate the mirNome within chicken cells, but also that specific host-microRNAs are down-regulated. We also identify novel virus-encoded microRNAs in other Herpesviridae and provide the first evidence of miRNA evolution by duplication in viruses. In related work, we present a novel microRNA generated by the canonical miRNA biogenesis pathway in Avian Leukosis Virus, another avian oncogenic virus, and publish data showing the expression pattern of known chicken microRNAs across a range of important avian cells. Two of the other RNAi pathways (siRNA and piRNA) form an important part of the antiviral response in arthropods. We have published work demonstrating an siRNA antiviral response to bluetongue virus and Schmallenberg virus in cells from the Culicoides midge, an important insect vector, as well as work demonstrating the importance of the piRNA pathway in the antiviral response to Semliki forest virus (SFV). Further work on flaviviruses in ticks demonstrates the active suppression of the siRNA response by Langat Virus, as well as a key difference between the siRNA responses in Mosquitos compared to ticks. Salmonella is one of the most important zoonoses, with an estimated 1.4 million cases of human salmonellosis per annum in the USA alone. Salmonella infections of farm animals are an important route into the human food chain. This thesis presents work on the comparative structure and function of 13 fimbrial operons within Salmonella enterica serovar Enteritidis as well as a genomic comparison of that serovar with Salmonella enterica serovar Gallinarum, a chicken-specific serovar. We characterised the global expression profile of Salmonella enterica serovar Typhimurium during colonization of the chicken intestine, and we have published the genomes of four strains of Salmonella eneterica serovars of well-defined virulence in food-producing animals. Our work in this area led to us publishing an important and comprehensive review of the automatic annotation of bacterial genomes. Finally, I present work on novel software development. ProGenExpress, a software tool that allows the easy and accurate integration and visualisation of quantitative data with the genome annotation of bacteria; Meta4 is a web application that allows data sharing of bacterial genome annotations from metagenomes; CORNA, a software tool that allows scientists to link together microRNA targets, gene expression and functional annotation; viRome, a software tool for the analysis of siRNA and piRNA responses in virus-infection studies; DetectiV, a software tool for the analysis of pathogen-detection microarray data; and poRe, a software tool that enables users to organise and analyse nanopore sequencing data.

The aim of this work was to study the interaction of melatonin and prolactin in the control of seasonal breeding and coat development in goats. British Saanen goats (n=5) were maintained for 8 weeks in long days (20L: 40) followed by 8 weeks exogenous melatonin. Group treatment was staggered over the year in an attempt to dissociate breeding season advance from advanced coat growth. To assess the effect of prolactin suppression, the 20L:4D treatment from January was repeated in consecutive years but followed in March by melatonin (Year 1) or bromocriptine (Year 2). To study further the interaction of melatonin and prolactin on coat development and reproductive advance, goats (n=5) were maintained as follows: 1) natural photoperiod and temperature, Jul-Juni 2) 16L: 8D, natural temperature, Jul-Deci 3) 16L:8D, 17°C, Jul-Decj 4) 8L:16D, 8°C, Dec-Jun. To study melatonin suppression of prolactin, the secretagogues arginine vasopressin, serotonin and thyrotropin releasing hormone were given to goats (n=6) maintained in sequence under 8L:16D, 20L:4D and simulated short days (20L:4D+melatonin). Depending on long-day Imelatonin treatment onset, the breeding season was advanced from November to May, August or September. With 20L:4D followed by melatonin or bromocriptine the spring prolactin rise was delayed. A corresponding delay in winter coat moulting was observed only under melatonin. However, a winter secondary to primary (SIP) follicle ratio was retained with both treatments. Prolactin may determine coat structure, whilst melatonin influences the duration of fibre retention. Under conditions of summer or winter solstice hold, the seasonal prolactin variation was inhibited and initial SIP follicle ratios were retained. A tendency for a spontaneous change in prolactin secretion suggested existence of an endogenous rhythm. Maintained seasonal temperature did not influence melatonin secretion. Dusk and dawn prolactin peaks corresponded with the rise and fall in nocturnal melatonin. Basal prolactin concentrations and peak responses to the secretagogues altered with photoperiod, being low under 8L:16D and increased under 20L:4D. Exogenous melatonin under 20L:4D did not suppress prolactin to short-day concentrations. Invol vement of another factor mediating photoperiodic changes in prolactin secretion is suggested.

No description available.

No description available.

No description available.

No description available.

Every year many thousands of newborn lambs die of cold exposure. This thesis is concerned with some of the physiological and genetic factors involved in the resistance of neonatal lambs of ten different breeds to hypothermia with particular reference to their heat production capabilities. The project was a development-of preliminary work carried out at the Animal Breeding Research Organisation, Edinburgh during the year immediately preceding this study. An attempt was made to reproduce in the laboratory, a standard cold stress comparable to that experienced by the newborn lamb born into cold, wet and windy conditions. A suitable test was evolved using water as the cooling medium to reduce body temperature and measuring heat production (in the form of oxygen consumption) using an indirect open-circuit calorimeter. 265 lambs of ten different breeds were tested. Significant breed differences were found for resistance to body cooling and base metabolic rate. Peak metabolic rate was significantly affected by weight. The results of the experimentation (1976-1979) give an insight and k4o into the variation existing, both within and between breeds, jit the traits likely to be useful in the selection of individuals and breeds most suited to survive severe environmental conditions during the neonatal period. An attempt was made to separate the effects of factors such as weight, skin thickness, age, sex and litter size. In particular, observations during cooling tests indicate the possible importance of tissue insulation, recorded in the form of skin thickness, in aiding the neonate to maintain body temperature in a cooling environment where fleece insulation is low. It was thought that the insulative properties of the birthcoat were unlikely to be expressed under waterbath conditions and no significant effects of birthcoat were found despite there being significant breed variation in this trait. To demonstrate birthcoat effects a wind tunnel procedure was used with artificial wind and rain providing a cold stress. Use of this equipment allowed separation of the effects of birthcoat extremes within the Welsh Mountain breed. The effect of fasting lambs from birth (4hrs) and pre-partum cold exposure of the dam were investigated for effects on the newborn's metabolic response to cold and cold resistance capabilities in the Scottish Blackface breed. The fasted lambs showed enhanced cold resistance possibly as a result of fat metabolism being initiated prior to the applied cold stress. Cold exposure of pre-partum ewes increased gestation length and the birth weight of their lambs. Base metabolic rate was lower for fasted lambs and peak metabolic rate enhanced in lambs from cold stressed ewes. The contribution of non-shivering thermogenesis was investigated and emphasis placed on fat metabolism in early post natal life when brown adipose tissue may be particularly relevant in cold thermogenesis. Metabolic responses to injected noradrenaline were investigated and a comparison made between maximum metabolic response to cold and catecholamine stimulation in the Cheviot breed. Some methods of rewarming were also studied with passive techniques showing possible field application. The possibilities for selection of more cold resistant types of sheep are discussed.

No description available.