Dietary Uncoupling of Gut Microbiota and Energy Harvesting from Obesity and Glucose Tolerance in Mice

The authors gratefully acknowledge Doctoral Training Partnership funding from the BBSRC (M.J.D.) and funding from the Scottish Government (P.J.M., A.W.R., and A.W.W.). We also thank the Centre for Genome-Enabled Biology and Medicine for help with next-generation sequencing and Karen Garden and the Rowett’s Analytical Services for SCFA analysis. SUPPLEMENTAL INFORMATION Supplemental Information includes four figures and two tables and can be found with this article online at https://doi.org/10.1016/j.celrep.2017.10.056.Peer reviewedPublisher PD

High throughput genomic sequencing of bioaerosols in broiler chicken production facilities

Chronic inhalation exposure to agricultural dust promotes the development of chronic respiratory diseases among poultry workers. Poultry dust is composed of dander, chicken feed, litter bedding and microbes. However, the microbial composition and abundance has not been fully elucidated. Genomic DNA was extracted from settled dust and personal inhalable dust collected while performing litter sampling or mortality collection tasks. DNA libraries were sequenced using a paired-end sequencing-by-synthesis approach on an Illumina HiSeq 2500. Sequencing data showed that poultry dust is predominantly composed of bacteria (64–67%) with a small quantity of avian, human and feed DNA (\u3c 2% of total reads). Staphylococcus sp. AL1, Salinicoccus carnicancri and Lactobacillus crispatus were the most abundant bacterial species in personal exposure samples of inhalable dust. Settled dust had a moderate relative abundance of these species as well as Staphylococcus lentus and Lactobacillus salivarius. There was a statistical difference between the microbial composition of aerosolized and settled dust. Unlike settled dust composition, aerosolized dust composition had little variance between samples. These data provide an extensive analysis of the microbial composition and relative abundance in personal inhalable poultry dust and settled poultry dust

GAPS : a hybridised framework applied to vehicle routing problems

In this thesis we consider two combinatorial optimisation problems; the Capacitated Vehicle Routing Problem (CVRP) and the Capacitated Arc Routing Problem (CARP). In the CVRP, the objective is to find a set of routes for a homogenous fleet of vehicles, which must service a set of customers from a central depot. In contrast, the CARP requires a set of routes for a fleet of vehicles to service a set of customers at the street level of an intercity network. After a comprehensive discussion of the existing exact and heuristic algorithmic techniques presented in the literature for these problems, computational experiments to provide a benchmark comparison of a subset of algorithmic implementations for these methods are presented for both the CVRP and CARP, run against a series of dataset instances from the literature. All dataset instances are re-catalogued using a standard format to overcome the difficulties of the different naming schemes and duplication of instances that exist between different sources. We then present a framework, which we shall call Genetic Algorithm with Perturbation Scheme (GAPS), to solve a number of combinatorial optimisation problems. The idea is to use a genetic algorithm as a container framework in conjunction with a perturbation or weight coding scheme. These schemes make alterations to the underlying input data within a problem instance, after which the changed data is fed into a standard problem specific heuristic and the solution obtained decoded to give a true solution cost using the original unaltered instance data. We first present GAPS in a generic context, using the Travelling Salesman Problem (TSP) as an example and then provide details of the specific application of GAPS to both the CVRP and CARP. Computational experiments on a large set of problem instances from the literature are presented and comparisons with the results achieved by the current state of the art algorithmic approaches for both problems are given, highlighting the robustness and effectiveness of the GAPS framework.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

GAPS: a hybridised framework applied to vehicle routing problems

In this thesis we consider two combinatorial optimisation problems; the Capacitated Vehicle Routing Problem (CVRP) and the Capacitated Arc Routing Problem (CARP). In the CVRP, the objective is to find a set of routes for a homogenous fleet of vehicles, which must service a set of customers from a central depot. In contrast, the CARP requires a set of routes for a fleet of vehicles to service a set of customers at the street level of an intercity network. After a comprehensive discussion of the existing exact and heuristic algorithmic techniques presented in the literature for these problems, computational experiments to provide a benchmark comparison of a subset of algorithmic implementations for these methods are presented for both the CVRP and CARP, run against a series of dataset instances from the literature. All dataset instances are re-catalogued using a standard format to overcome the difficulties of the different naming schemes and duplication of instances that exist between different sources. We then present a framework, which we shall call Genetic Algorithm with Perturbation Scheme (GAPS), to solve a number of combinatorial optimisation problems. The idea is to use a genetic algorithm as a container framework in conjunction with a perturbation or weight coding scheme. These schemes make alterations to the underlying input data within a problem instance, after which the changed data is fed into a standard problem specific heuristic and the solution obtained decoded to give a true solution cost using the original unaltered instance data. We first present GAPS in a generic context, using the Travelling Salesman Problem (TSP) as an example and then provide details of the specific application of GAPS to both the CVRP and CARP. Computational experiments on a large set of problem instances from the literature are presented and comparisons with the results achieved by the current state of the art algorithmic approaches for both problems are given, highlighting the robustness and effectiveness of the GAPS framewor

A common cardiac sodium channel variant associated with sudden infant death in African Americans, SCN5A S1103Y.

Thousands die each year from sudden infant death syndrome (SIDS). Neither the cause nor basis for varied prevalence in different populations is understood. While 2 cases have been associated with mutations in type Valpha, cardiac voltage-gated sodium channels (SCN5A), the "Back to Sleep" campaign has decreased SIDS prevalence, consistent with a role for environmental influences in disease pathogenesis. Here we studied SCN5A in African Americans. Three of 133 SIDS cases were homozygous for the variant S1103Y. Among controls, 120 of 1,056 were carriers of the heterozygous genotype, which was previously associated with increased risk for arrhythmia in adults. This suggests that infants with 2 copies of S1103Y have a 24-fold increased risk for SIDS. Variant Y1103 channels were found to operate normally under baseline conditions in vitro. As risk factors for SIDS include apnea and respiratory acidosis, Y1103 and wild-type channels were subjected to lowered intracellular pH. Only Y1103 channels gained abnormal function, demonstrating late reopenings suppressible by the drug mexiletine. The variant appeared to confer susceptibility to acidosis-induced arrhythmia, a gene-environment interaction. Overall, homozygous and rare heterozygous SCN5A missense variants were found in approximately 5% of cases. If our findings are replicated, prospective genetic testing of SIDS cases and screening with counseling for at-risk families warrant consideration

Diet induced obesity is independent of metabolic endotoxemia and TLR4 signalling, but markedly increases hypothalamic expression of the acute phase protein, SerpinA3N

The authors gratefully acknowledge Doctoral Training Partnership funding from the BBSRC (M.J.D.), MRC (GA) and funding from the Scottish Government (P.J.M., A.W.R., A.W.W. and P.B.). The authors would like to acknowledge the support of the Maxwell compute cluster funded by the University of Aberdeen. We also thank the Centre for Genome-Enabled Biology and Medicine, University of Aberdeen for performing next-generation sequencing and RNAseq, Dr Sophie Shaw, for bioinformatic analysis of the RNAseq data, and Lynn Thomson for assistance with the TLR4−/− and CD14−/− mouse study, and Dr Richard Anderson and Dana Wilson for assistance with the long term high fat diet study. Supplementary information accompanies this paper at https://doi.org/10.1038/s41598-018-33928-4.Peer reviewedPublisher PD

Noninflammatory Changes of Microglia Are Sufficient to Cause Epilepsy.

Microglia are well known to play a critical role in maintaining brain homeostasis. However, their role in epileptogenesis has yet to be determined. Here, we demonstrate that elevated mTOR signaling in mouse microglia leads to phenotypic changes, including an amoeboid-like morphology, increased proliferation, and robust phagocytosis activity, but without a significant induction of pro-inflammatory cytokines. We further provide evidence that these noninflammatory changes in microglia disrupt homeostasis of the CNS, leading to reduced synapse density, marked microglial infiltration into hippocampal pyramidal layers, moderate neuronal degeneration, and massive proliferation of astrocytes. Moreover, the mice thus affected develop severe early-onset spontaneous recurrent seizures (SRSs). Therefore, we have revealed an epileptogenic mechanism that is independent of the microglial inflammatory response. Our data suggest that microglia could be an opportune target for epilepsy prevention