APOE genotype influences the gut microbiome structure and function in humans and mice: relevance for Alzheimer’s disease pathophysiology

Apolipoprotein E (APOE) genotype is the strongest prevalent genetic risk factor for Alzheimer’s disease (AD). Numerous studies have provided insights into the pathologic mechanisms. However, a comprehensive understanding of the impact ofAPOEgenotype onmicroflora speciation and metabolismis completely lacking. In this study,we investigated the association between APOE genotype and the gut microbiome composition in human and APOE–targeted replacement (TR) transgenic mice. Fecal microbiota amplicon sequencing from matched individuals with different APOE genotypes revealed no significant differences in overall microbiota diversity in group aggregated human APOE genotypes. However, several bacterial taxa showed significantly different relative abundance between APOE genotypes. Notably, we detected an association of Prevotellaceae and Ruminococcaceae and several butyrate-producing genera abundances with APOE genotypes. These findings were confirmed by comparing the gutmicrobiota ofAPOE-TRmice. Furthermore, metabolomic analysis of murine fecalwater detected significant differences in microbe-associated amino acids and short-chain fatty acids between APOE genotypes. Together, these findings indicate that APOE genotype is associated with specific gut microbiome profiles in both humans and APOE-TR mice. This suggests that the gut microbiome is worth further investigation as a potential target to mitigate the deleterious impact of the APOE4 allele on cognitive decline and the prevention of A

Tickets for the Afterlife

Sound Design for Website / App Platform Tickets for the Afterlife aims to introduce people to planning end of life wishes. Through visual communication, interaction and personal decision making. It uses artistic research methods that position diverse rituals and potential futures as options to be chosen within the digital experience/ website. It also uses the library's collections of books as a way of giving people personalised recommendations for further inquiry. The Tickets for the Afterlife website was creatively directed by Dr Stacey Pitsillides with graphic designer Elena Demireva, web developer’s Parvin Asadzadeh Birjandi & Tom Hegarty and sound designer Emma Margetson. Content research and co-design with Dr Claire Nally and the Death Positive Library team. Together this team have investigated the role of Death Positive Libraries during the pandemic through author/Filmmaker Q&A’s, death cafes and A Grief Spoon Room with the Loss Project. This project has been funded by the Wellcome Trust, Carnegie UK, and The Wolfson Foundation and has recently been awarded the Health and Wellbeing Award from Libraries Connected, an organisation which promotes and represents libraries as important resources at the heart of communities. Presented online and at Redbridge Central Library, Newcastle City Library and Kirklees Libraries between 27th October - 19th November 2021

Exploiting a fast neutron mutant genetic resource in Pisum sativum (pea) for functional genomics

A fast neutron mutagenised population was generated in Pisum sativum L. (pea) to enable the identification and isolation of genes underlying traits and processes. Studies of a number of phenotypic traits have clearly demonstrated the utility of the resource by associating gene deletions with phenotype followed by functional tests exploiting additional mutant sources, from both induced and natural variant germplasm. For forward genetic screens next generation sequencing methodologies provide an opportunity for identifying genes associated with deletions rapidly and systematically. The application of rapid reverse genetic screens of the fast neutron mutant pea population supports conclusions on the frequency of deletions based on phenotype alone. These studies further suggest that large deletions affecting one or more loci can be non-deleterious to the pea genome, yielding mutants that could not be obtained by other means. Deletion mutants affecting genes associated with seed metabolism and storage are providing unique opportunities to identify the products of complex and related gene families, and to study the downstream consequences of such deletion

The effects of inhibitory control training on alcohol consumption, implicit alcohol-related cognitions and brain electrical activity

This study aimed to replicate findings that alcohol consumption and positive implicit beer-related cognitions can be reduced using inhibitory control (IC) training, with the addition of an active training control. Frontal EEG asymmetry, an objective psychophysiological index of approach motivation, was used as a dependent measure to examine training outcomes. Participants were randomly assigned to one of two IC training conditions (Beer NoGo or Beer Go) or a Brief Alcohol Intervention (BAI) (i.e. the active training control). The IC training tasks consistently paired a stimulus that required a response with images of water (Beer NoGo) or images of beer (Beer Go). Alcohol consumption and implicit beer-related cognitions were measured at pre-training, post-training and at one week follow-up. Frontal EEG asymmetry was recorded during a passive image viewing task that presented neutral, healthy, and beer stimuli - at pre-training, post-training and follow-up. Participants in the Beer NoGo and BAI conditions consumed less beer in a taste test immediately after training than Beer Go participants, suggesting that IC training may be as effective as the already established BAI. The taste test findings were in line with the frontal EEG asymmetry data, which indicated that approach motivation for beer stimuli was altered in the expected directions. However, the positive correlation between post-training frontal EEG asymmetry data and taste test consumption was not significant. While there were no significant changes in implicit beer-related cognitions following training, a trending positive relationship between implicit beer-related cognitions at post-training and taste test consumption was reported. Further exploration addressing the limitations of the current study is required in order to clarify the implications of these findings