The effect of ageing and hypertension on the proton-coupled transporters PEPT1 and PEPT2 located in the apical membrane of the renal proximal tubule, and on PEPT2 in cardiac sarcolemmal membrane Background: A number of studies have shown the critical importance of the integral membrane cotransporters PEPT1 and PEPT2 in physiology, pathophysiology, pharmacology, and nutrition. This significance lies in the dynamic role of these cotransporters in the uptake of more than 8000 different di-and tripeptide combinations and a wide range of peptidomimetic drugs with clinical and pharmacological relevance. This body of work seeks, for the first time, to systematically investigate prospective changes of PEPT1 and PEPT2 cotransporters in the kidneys and hearts with ageing and/or hypertension at the gene, protein expression, localisation and functional levels.

The aim of this research is to elucidate the function of BMPR-IB using passive neutralization of BMPR-IB in vivo and in vitro placing specific attention to its role in the male reproductive system, given the importance of BMPR-IB in females and the lack of publications available for its function in males. BMP and BMP receptor mRNA expression was also screened in male reproductive tissues to establish the presence and relative quantitation of these genes. We hypothesize that BMPR-IB has important roles in male reproduction based on a limited amount research investigating BMPs and their receptors in this area and the fact that the receptor has crucial roles in females. The significance of any findings could be translated in numerous fields and includes a greater understanding of normal male reproductive physiology, a better understanding of abnormalities present in male infertility and cancer of male reproductive organs as well as the identification of possible future therapeutic targets.

Equine chorionic gonadotrophin (eCG) is a placental hormone produced during the first third of gestation in mares, and exists in a range of isoforms. At approximately 30 days of gestation, eCG becomes detectable in circulation and peaks around 60 days, thereafter declining to undetectable concentrations by around 120 days. The functions of eCG include revival of the ovarian corpus luteum which sustains progesterone production supporting the pregnancy until placentally-derived steroid production is sufficient. One unusual characteristic of eCG is the dual LH and FSH activity it possesses. For this reason, eCG is harvested from pregnant mare plasma, isolated, and concentrated to formulate commercial gonadotrophin products which are used extensively in assisted reproductive technologies in agricultural livestock. A large proportion of the eCG product market comprises the sheep industry. A major complication with the use of commercial eCG is the considerable variation in bioactivity between batches as well as in individual animal responses to treatment which may lead to insufficient stimulation or superovulation with negative consequences on embryo survival. It was therefore a prerogative to investigate the isoform composition of eCG and how this impacted on the bioactive properties both in vivo and in vitro. The research findings in this thesis show an expansive range of very acidic to very basic eCG isoforms circulating in mare plasma. When eCG isoforms were collectively analysed in three groups (acidic, intermediate, and basic), isoforms had greater acidity prior to and during the eCG peak, but thereafter experience a substantial drop in hormone concentration and acidity, with significantly increased intermediate isoforms. Within the acidic group, the most acidic fraction showed greatest percentage composition prior to the eCG peak. The differences in isoform composition may be indicative of altered function and numerous studies have shown that pituitary gonadotrophin isoform composition has a major impact on bioactivity.

Lateralization, referring to differential processing of information by the left and right sides of the brain and to side biases in behaviour, has been reported in domestic horses. To determine whether lateralization is characteristic of the horse ('Equus caballus') as a species and not simply a result of training or domestication, field studies were carried out observing Przewalski horses ('Equus ferus przewalski') and two groups of feral horses that differed in number of generations removed from domestication. Przewalski horses are the closest wild relative of domestic horses. Left-side biases of approximately 57–68% were found in agonistic interactions, 63–73% in high alert and 53–54% in vigilance. As in other vertebrates, the right hemisphere of the horse is specialised to control agonistic interactions and responses to potential threats. Also consistent with previous research, showing right-hemisphere control of the expression of strong emotion, leftwards bias was stronger in measures of behaviour involving higher aggression and reactivity. Domestic riding horses were also studied using the same methodology and found to display left-side biases for the above measures, with the exception of vigilance, but the strength was weaker than in feral and Przewalski horses. This suggests (a) ancestral horses were more strongly lateralized for attack, vigilance and reactivity than are present-day domestic horses, and/or (b) lateralization is stronger in horses living in natural habitats. Limb preference, measured as the forelimb placed in front of the other during grazing, was investigated because previous research has shown limb preference in some breeds of domestic horse.

Food detection and predator recognition are crucial for survival in the wild and this thesis asks how animals respond if one or several signals are provided. Are responses to multimodal signals different than to unimodal ones and is the modality of the signal of vital importance? Marmosets ('Callithrix jacchus') are an ideal species in which to test the relative importance of interactions of several senses and the processing of signals because we know that their hearing, vision and sense of smell are excellent. I presented predator- and food-based stimuli in these three modalities, first individually and then in various combinations (related and conflicting). Results of individual stimuli showed responses that might be expected in wild populations but not necessarily in captive-born animals: the marmosets mobbed a taxidermic specimen of a quoll, avoided the odour of cat faeces, and froze, hid and fell silent in response to leopard growls. In contrast, marshmallow and its odour elicited highly positive responses and playback of marmoset food-related calls increased activity levels. Interaction of modalities manifested not necessarily as sensory hierarchies but as sensory input of equal weight repudiating the concept of visual dominance in primates. In some cases, olfactory and auditory stimuli actually shaped the responses to the visual stimuli. By and large, my results supported the threat-sensitivity hypothesis in that more than one predator-based stimulus reduced response time, indicating a perception of greater risk. Presentation of conflicting stimuli showed high-risk behaviour and uncertainty. In a separate experiment, testing responses to sounds alone, of snake, red-shouldered hawk and leopard, results showed strong fear responses to each vocalisation but the marmosets looked up more often (whilst indoors) when hearing the hawk calls. The discovery of new facial expressions in response to olfactory and auditory cues is also reported. Two facial expressions, one negative, one positive, were then tested by playback on a screen; results indicating responsiveness to the positive expression by staying in the vicinity of the screen and by leaving when a negative expression was shown. Hence, this demonstrates that marmosets may be sensitive to displays of emotions by conspecifics.