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This investigation aimed to evaluate the preferences of sheep for a range of pasture species using species choice trials of living swards, rate of intake experiments with cut fresh herbage and observations of grazing in the field. Sheep exhibited no specific preference for pure species grown in pots in a very high fertility soil. Sheep were fed fresh cut herbage to examine the rate of intake of 11 pasture species. Leaf was consumed at faster rates (6.9-10.2g DM/min) than pseudostem (4.1-6.3g DM/min) except for cocksfoot leaf which was eaten at a significantly lower rate (4.8g DM/min) than the leaf of all other species. Timothy leaf was consumed at a significantly faster rate (10.2g DM/min) than all other herbage followed by Hakari mountain brome leaf (8.2g DM/min). Chicory and white lover were consumed at significantly higher rates than all other species on a fresh matter basis however the low DM% of these two species resulted in reduced dry matter intake rates of 6.8 and 8.1g DM/min respectively. Field grazing trials showed dicotyledon species to be preferred over grasses. Preference was measured via the rate of decline in height of five grass species. Roa tall fescue and Maru phalaris were reduced in height at the fastest rate and were preferred over Matua prairie grass which was of intermediate preference. Yatsyn ryegrass and Wana cocksfoot were species of low preference as they were only grazed when preferred species had been reduced to low levels. Sheep showed strong preference for herbage of high nitrogen content by grazing sites where 300kg N/ha had earlier been applied. This preference for high nitrogen herbage overcame any preference differences between species with all species on high nitrogen sites being grazed to low levels on day one of the seven day grazing duration. Rate of intake trials showed close correlation with preferences observed in the field and it is strongly suggested that sheep grazing preferred species will have higher intakes and superior liveweight gains than those grazing lower preference species.

Preterm labour is the most important cause of perinatal mortality. Our ability to prevent preterm labour has been hindered by poor understanding of the factors that initiate human parturition. cAMP is a second messenger which plays significant role in respiratory, cardiovascular, and reproductive systems. The role of cAMP-signalling pathway in the maintenance of pregnancy has been investigated. My results suggest that during pregnancy, high cAMP levels repress OTR via PKA-dependent pathway and this repression may contribute to myometrial quiescence. My results also suggest that as pregnancy advances, the activity of cAMP/PKA pathway declines and, in contrast, the levels of Epac1, rise. This pattern may be associated with an increase in OTR expression, which may contribute to uterine contractions. The ability of cAMP to repress inflammation in human myometrial cells was explored. My results show that cAMP repress the expression of inflammation related genes and pro-inflammatory cytokines. These results suggest that high cAMP/PKA tone in pregnancy may exert an anti-inflammatory effect and a reduction of cAMP/PKA tone may contribute to the pro-inflammatory effects of labour. AKIP1 has been identified to act as a molecular switch, determining cAMP/PKA action towards NFκB activity in various cell types. To date, no study was done to investigate the role played by AKIP1 in myometrial cells. My results suggest that in myometrial cells, low AKIP1 levels, helps to promote the anti-inflammatory effects of cAMP/PKA. The ability of cAMP in enhancing myometrial response to progesterone was tested. The results suggest that cAMP enhanced progesterone responsive genes via PKA. Furthermore, the ability of progesterone to repress IL-1β-induced inflammation may be enhanced by cAMP. Knockdown studies using siRNA, suggest that cAMP acts via PKA to enhance the anti-inflammatory action of progesterone. Overall, these data support a novel role for cAMP which may help in the prevention of preterm labour.

A novel technology for the generation of light emitting somatic transgenic animals has been developed using lentiviral vectors where luciferase expression is transcriptionally regulated by tandem, synthetic, transcription factor binding elements. This allows signalling pathways in diseased organs to be monitored continually and consciously and in a non-invasive manner. I was able to confirm my hypothesis that long term somatic transgenesis could be achieved within the CNS after a single neonatal intracranial injection of the biosensors. No signs of activated microglia or astrogliosis from the injection or the vector expression was observed. I generated several lentiviral biosensors and this included an astrocyte specific biosensor GFAP. I established and validated a Hypoxic Ischemic Encephalopathy mouse model in outbred CD1 mice. I applied somatic transgenic technology to the HIE mouse model to investigate whether it was possible to predict the severity of the disease in live mice. Unexpectedly, the luciferase expression from the four biosensors failed to correlate with the extent of brain infarct or the weight of the mice. To investigate this surprising results, I challenged the underlying assumption that GP64 enveloped lentiviral vectors target GFAP positive astrocytes. Interestingly very few astrocyte positive cells were being targeted by the GP64 pseudotyped lentiviral vectors. As GFP expression from lentiviral vectors was limited and mainly situated around the injection site, I investigated the use of AAV delivery to the CNS. AAV8 vector generated strong and homogenous GFP expression. An AAV8 NFκB biosensor was made and injected intracranially to new-born mice. This showed substantially more stable luciferase expression compared with lentivirus vectors.