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Item The role of expectation in the determination of proprietary estoppel remedies(Hart Publishing, 2009-11-03) Mee, John; Dixon, MartinThis paper analyses the various roles which expectation could play in relation to the determination of proprietary estoppel remedies. It argues, by a process of eliminating the various alternatives, that the only appropriate role for expectation is as a cap on a remedy determined on the basis of other factors. The first possible approach to be analysed is that the remedy would invariably be determined by reference to the expectation. It is pointed out that this runs into difficulties in the context of countervailing benefits and also requires a willingness, in certain cases, to grant a remedy which is disproportionate to the detriment suffered by the claimant. The second approach, supported by Jennings v Rice [2002] EWCA Civ 159, is that the fulfillment of the expectation should be the prima facie remedy, to be granted unless such a remedy would be disproportionate to the detriment suffered by C. The paper argues that such an approach does not stand up to close scrutiny and leads to demonstrably illogical results. It then looks at the possibility of treating the expectation as one factor in the determination of the remedy, as appears to be advocated by Gardner; the possibility of regarding the fulfilment of the expectation as a proxy for erasing the detriment, as argued by Robertson; and the possibility of linking the expectation and the detriment by reference to a bargain, as suggested by Robert Walker LJ in Jennings v Rice. By way of conclusion, some observations are offered in respect of the possible future development of equity's approach to proprietary estoppel remedies.Item Envisioning emerging frontiers on human gut microbiota and its applications(Wiley, 2020-09) Ventura, Marco; Milani, Christian; Turroni, Francesca; van Sinderen, Douwe; European Commission; Fondazione Cariparma; Science Foundation Ireland; GenProbioThe human gut microbiota is involved in multiple health-influencing host interactions during the host's entire life span. Microbes colonize the infant gut instantaneously after birth and subsequently the founding and interactive progress of this early gut microbiota is considered to be driven and modulated by different host- and microbe-associated forces. A rising number of studies propose that the composition of the human gut microbiota in the early stages of life impact on the human health conditions at later stages of life. This notion has powered research aimed at detailed investigations of the infant gut microbiota composition. Nevertheless, the molecular mechanisms supporting the gut microbiome functionality and the interaction of the early gut microbes with the human host remain largely unknown.Item Bifidobacterium breve UCC2003 induces a distinct global transcriptomic program in neonatal murine intestinal epithelial cells(Elsevier, 2020-07) Kiu, Raymond; Treveil, Agatha; Harnisch, Lukas C.; Caim, Shabhonam; Leclaire, Charlotte; van Sinderen, Douwe; Korcsmaros, Tamas; Hall, Lindsay J.; Norwich Bioscience Institutes (NBI) Computing infrastructure for Science (CiS) group; Wellcome Trust; Gut Microbes and Health; Genomics for Food security; Norwich Research Park Biosciences; Science Foundation IrelandThe underlying health-driving mechanisms of Bifidobacterium during early life are not well understood, particularly how this microbiota member may modulate the intestinal barrier via programming of intestinal epithelial cells (IECs). We investigated the impact of Bifidobacterium breve UCC2003 on the transcriptome of neonatal murine IECs. Small IECs from two-week-old neonatal mice administered B. breve UCC2003 or PBS (control) were subjected to global RNA sequencing, and differentially expressed genes, pathways, and affected cell types were determined. We observed extensive regulation of the IEC transcriptome with ∼4,000 genes significantly up-regulated, including key genes linked with epithelial barrier function. Enrichment of cell differentiation pathways was observed, along with an overrepresentation of stem cell marker genes, indicating an increase in the regenerative potential of the epithelial layer. In conclusion, B. breve UCC2003 plays a central role in driving intestinal epithelium homeostatic development during early life and suggests future avenues for next-stage clinical studies.Item Human milk oligosaccharides: shaping the infant gut microbiota and supporting health(Elsevier, 2020-09) Walsh, Clodagh; Lane, Jonathan A.; van Sinderen, Douwe; Hickey, Rita M.; H and H Group; Science Foundation IrelandHuman milk oligosaccharides (HMO) are complex sugars which are found in breast milk at significant concentrations and with unique structural diversity. These sugars are the fourth most abundant component of human milk after water, lipids, and lactose and yet provide no direct nutritional value to the infant. Recent research has highlighted that HMOs have various functional roles to play in infant development. These sugars act as prebiotics by promoting growth of beneficial intestinal bacteria thereby generating short-chain fatty acids which are critical for gut health. HMOs also directly modulate host-epithelial immune responses and can selectively reduce binding of pathogenic bacteria and viruses to the gut epithelium preventing the emergence of a disease. This review covers current knowledge related to the functional biology of HMOs and their associated impact on infant gut health.Item From lab bench to formulated ingredient: characterization, production, and commercialization of human milk oligosaccharides(Elsevier, 2020-09) Walsh, Clodagh; Lane, Jonathan A.; van Sinderen, Douwe; Hickey, Rita M.; H & H Group; Science Foundation IrelandHuman milk oligosaccharides (HMOs) are known to positively influence infant health. Extensive variation exists in the levels, diversity, and complexity of oligosaccharides in the milk of a lactating mother. Until recently, limited availability of HMOs hampered their use in clinical applications. Most HMOs are unique to human milk, and have proven difficult and expensive to isolate and synthesize. Added to that, analysis of these complex glycans in milk samples requires state-of-the-art analytical instruments and associated technologies. The current review provides a critical overview of methods used in HMO analysis, and highlights the importance of understanding the factors which influence their composition and structural diversity. We also discuss recently employed strategies to overcome the availability of HMOs at industrial scale including microbial metabolic engineering and chemoenzymatic techniques. Finally, we examine how these recent advancements have opened up new avenues for future research and nutraceutical applications.