http://hdl.handle.net/10468/107 Sat, 28 Oct 2017 17:05:21 GMT 2017-10-28T17:05:21Z http://hdl.handle.net/10468/4846 Deletion of TLX and social isolation impairs exercise-induced neurogenesis in the adolescent hippocampus Kozareva, Danka A.; O'Leary, Olivia F.; Cryan, John F.; Nolan, Yvonne M. Adolescence is a sensitive period of neurodevelopment during which life experiences and the surrounding environment can have profound effects on the brain. Neurogenesis is a neurodevelopmental process of generating functional neurons from neural stem cells. Hippocampal neurogenesis occurs throughout the lifespan and has been shown to play a role in learning, memory and in mood regulation. In adulthood it is influenced by extrinsic environmental factors such as exercise and stress. Intrinsic factors that regulate hippocampal neurogenesis include the orphan nuclear receptor TLX (Nr2e1) which is primarily expressed in the neurogenic niches of the brain. While mechanisms regulating adult hippocampal neurogenesis have been widely studied, less is known on how hippocampal neurogenesis is affected during adolescence. Thus, the aim of this study was to investigate the influence of both TLX and isolation stress on exercise-induced increases in neurogenesis in running and sedentary conditions during adolescence. Single- (i.e. isolation stress) wild type and Nr2e1-/- or pair-housed wild type mice were housed in sedentary conditions or allowed free access to running wheels for 3 weeks during the adolescent period. A reduction of neuronal survival was evident in mice lacking TLX, and exercise did not increase hippocampal neurogenesis in these Nr2e1-/- mice. This suggests that TLX is necessary for the pro-neurogenic effects of exercise during adolescence. Interestingly, although social isolation during adolescence did not affect hippocampal neurogenesis, it prevented an exercise-induced increase in neurogenesis in the ventral hippocampus. Together these data demonstrate the importance of intrinsic and extrinsic factors in promoting an exercise-induced increase in neurogenesis at this key point in life. This article is protected by copyright. All rights reserved. Tue, 03 Oct 2017 00:00:00 GMT http://hdl.handle.net/10468/4846 2017-10-03T00:00:00Z http://hdl.handle.net/10468/4835 Designer bacteria as intratumoural enzyme biofactories Lehouritis, Panos; Hogan, Glenn; Tangney, Mark Bacterial-directed enzyme prodrug therapy (BDEPT) is an emerging form of treatment for cancer. It is a biphasic variant of gene therapy in which a bacterium, armed with an enzyme that can convert an inert prodrug into a cytotoxic compound, induces tumour cell death following tumour-specific prodrug activation. BDEPT combines the innate ability of bacteria to selectively proliferate in tumours, with the capacity of prodrugs to undergo contained, compartmentalised conversion into active metabolites in vivo. Although BDEPT has undergone clinical testing, it has received limited clinical exposure, and has yet to achieve regulatory approval. In this article, we review BDEPT from the system designer's perspective, and provide detailed commentary on how the designer should strategize its development de novo. We report on contemporary advancements in this field which aim to enhance BDEPT in terms of safety and efficacy. Finally, we discuss clinical and regulatory barriers facing BDEPT, and propose promising approaches through which these hurdles may best be tackled. Tue, 12 Sep 2017 00:00:00 GMT http://hdl.handle.net/10468/4835 2017-09-12T00:00:00Z http://hdl.handle.net/10468/4774 Simulated gastrointestinal digestion of nisin and interaction between nisin and bile Gough, Ronan; O'Connor, Paula M.; Rea, Mary C.; Gómez-Sala, Beatriz; Miao, Song; Hill, Colin; Brodkorb, André Nisin, an antimicrobial peptide showing activity against many Gram positive bacteria, is widely used as a food preservative. The simulated gastrointestinal digestion of nisin (variant A) was studied using the in vitro INFOGEST digestion method. Following oral, gastric and small intestinal digestion, there was no intact nisin in the system and the nisin was primarily digested by pancreatin. After digestion, six nisin fragments (1–11, 1–12, 1–20, 1–21, 1–29 and 1–32) were identified by reversed phase high performance liquid chromatography and mass spectroscopy and four of these nisin fragments (1–20, 1–21, 1–29 and 1–32) demonstrated low antibacterial activity against Lactococcus lactis HP in agar diffusion activity assays. Additionally, it was observed that bile salts form a complex with nisin. This was examined by atomic force microscopy, turbidity and dynamic light scattering, which showed that this interaction resulted in significantly larger bile salt micelles. The presence of bile salts at physiological levels significantly altered the relative amounts of the nisin fragments 1–12, 1–20 and 1–29 produced during an in vitro digestion. This study highlights the importance of including bile in simulated digestions of antimicrobial peptides in order to obtain a more accurate simulation of the in vivo digestion products and their activity. Mon, 14 Aug 2017 00:00:00 GMT http://hdl.handle.net/10468/4774 2017-08-14T00:00:00Z http://hdl.handle.net/10468/4768 Research gaps in diet and nutrition in inflammatory bowel disease. A topical review by D-ECCO Working Group (Dietitians of ECCO) Sigall-Boneh, Rotem; Levine, Arie; Lomer, Miranda; Wierdsma, Nicolette; Allan, Philip; Fiorino, Gionata; Gatti, Simona; Jonkers, Daisy; Kierkuś, Jarosław; Katsanos, Konstantinos H.; Melgar, Silvia; Yuksel, Elif Saritas; Whelan, Kevin; Wine, Eytan; Gerasimidis, Konstantinos Although the current doctrine of IBD pathogenesis proposes an interaction between environmental factors and gut microbiota in genetically susceptible individuals, dietary exposures have attracted recent interest and are, at least in part, likely to explain the rapid rise in disease incidence and prevalence. The D-ECCO working group along with other ECCO experts with expertise in nutrition, microbiology, physiology, and medicine reviewed the evidence investigating the role of diet and nutritional therapy in the onset, perpetuation, and management of IBD. A narrative topical review is presented where evidence pertinent to the topic is summarised collectively under three main thematic domains: i] the role of diet as an environmental factor in IBD aetiology; ii] the role of diet as induction and maintenance therapy in IBD; and iii] assessment of nutritional status and supportive nutritional therapy in IBD. A summary of research gaps for each of these thematic domains is proposed, which is anticipated to be agenda-setting for future research in the area of diet and nutrition in IBD. Thu, 10 Aug 2017 00:00:00 GMT http://hdl.handle.net/10468/4768 2017-08-10T00:00:00Z