Voluntary exercise in the C57B1/6J mouse: phenotypic effects of varying dietary fat levels and hippocampal gene expression differences between high-level and low-level exercisers

The drive to exercise voluntarily likely results from complex interactions between genes in many organ systems and various psychological parameters, such as motivation and the perception of fatigue. Reproducible variations in exercise intensity and duration are well established in laboratory rodents, but the genes responsible remain largely unknown. Also, to date, studies addressing the adaptive changes to exercise that might prevent dietary-induced obesity have focused primarily on energy intake and nutrient oxidation/partitioning, as opposed to genetics. We hypothesize that increased voluntary physical activity may be a normal mechanism in certain rodent strains to deter dietary-induced obesity and that in an inbred strain of mice, environmentally sensitive genes must be responsible for observed differences in individual voluntary exercise performance. To study this theory, we have designed a set of experiments that establish an animal model to address whether different gene expression profiles can be detected using microarrays and confirmed with quantitative real-time PCR (qRT-PCR) in distinct exercise phenotypes. We also used the model to address whether dietary manipulations affect voluntary exercise performance in a single strain of inbred mice susceptible to dietary-induced obesity. We determined that animals weaned onto high fat diet exercise at levels significantly higher than those weaned onto low fat diet. These animals were able to maintain body weight and decrease body fat after three weeks of exercise. We also report the results and validation of three microarray comparisons using pooled RNA from the hippocampi of exercising animals. These data suggest that several genes from the HSP 70 family, specifically several molecular chaperones localized to the endoplasmic reticulum, are differentially regulated in running versus sedentary animals at several exercise time points. We suggest that increased voluntary physical activity may be an adaptive response in male C57Bl/6J mice that prevents dietary-induced obesity on high fat diets, and we demonstrate that differential gene expression profiles related to exercise could be identified in the brain using microarrays and qRT-PCR. We conclude that genes from the molecular chaperone family, a well-described environmentally sensitive gene family, are differentially regulated in response to voluntary exercise in an inbred mouse strain

An Investigation of Host Variation In the Host-Parasite Interaction of Sciurus carolinensis and Cuterebra emasculator

Within a population, susceptibility to parasitism may vary. Individuals possessing certain intrinsic or extrinsic traits are often more likely to be parasitized than individuals within that population that do not possess those certain traits. As a result, parasites can have profound effects of the population dynamics of theirs hosts. Much research has been done on the host-parasite interaction of the eastern grey squirrel {Sciurus caroUnensis) and the tree squirrel hot fly {Cuterebra emasculator). However, relatively little research has been done on host susceptibility to this parasite. Knowing that bot flies can lower reproductive success, reduce fitness, and cause death of their hosts, it is important to determine whether or not a certain characteristic may increase a squirrel’s likelihood of becoming infested by bot flies. Along with number of bot flies larvae and bot fly scars present on the host, physical characteristics were measured from 35 squirrels including sex, second to fourth digit ratio, testes mass, body surface area, and spleen mass. There was a statistically significant relationship between the number of bots present and the sex of the host (unpaired t-test, t = -2.528, DF = 33, P = 0.0164). Males were more heavily parasitized than females. All other results were not statistically significant. Based on these findings, bot fly parasitism may affect the dynamics of squirrel populations by decreasing the fitness and reproductive success of males. Future research should focus on determining what trait makes individual males more susceptible than other males

The Effects of Temperate Phage on Streptococcus Pneumoniae During Colonization

The first step in the pathogenesis of bacterial pathogens is colonization of the host. During colonization, bacteria encounter host defenses, other commensal flora and selective pressures from lytic and temperate bacteriophage. Phages and bacteria have a long history of co-evolution, which has led to bacterial resistance mechanisms and phage counter-resistance mechanisms. One mechanism that phage have adapted is to provide a fitness advantage to the host during colonization and disease, thereby promoting survival of both bacteria and phages. Herein I examine how temperate phages affect streptococcal fitness while colonizing the host, specifically looking at the interactions between Streptococcus pneumoniae, phage element Spn1 and colonization of a murine nasopharynx. Temperate phages have been identified in the genomes of up to 70% of clinical isolates of Streptococcus pneumoniae. How these phages affect the bacterial host during colonization has not been previously demonstrated. To ask this question, we used a clinical isolate, which carries a novel prophage Spn1. Spn1 was detected as integrated and episomal forms both in vitro and in vivo. Surprisingly, Spn1 also expresses both lytic and lysogenic genes during normal growth conditions. Since Spn1 could not be spontaneously cured, a clean deletion was made to create the Spn1- strain. We used a competitive colonization assay in a murine model to test the fitness of the Spn1+ vs. the Spn1- strain. The Spn1- strain outcompeted the Spn1+ strain seventy-fold after seven days of colonization. To determine if Spn1 is causing a fitness defect by a trans-acting factor, we made an Spn1+ mutant that does not become an episome or express any phage genes. This mutant competed equally with the Spn1- strain, indicating that the fitness defect required expression of phage genes. Further experiments interrogating autolysis, chain length and resistance to lysis by penicillin indicated differences in the cell wall physiology associated with the presence of Spn1. This change in cell wall physiology may be responsible for the fitness defect of Spn1+ strain during colonization. This study provides new insight into how bacteria and prophages can interact and how these interactions may impact the relationship between bacteria and the host

FINJ: A Fault Injection Tool for HPC Systems

We present FINJ, a high-level fault injection tool for High-Performance Computing (HPC) systems, with a focus on the management of complex experiments. FINJ provides support for custom workloads and allows generation of anomalous conditions through the use of fault-triggering executable programs. FINJ can also be integrated seamlessly with most other lower-level fault injection tools, allowing users to create and monitor a variety of highly-complex and diverse fault conditions in HPC systems that would be difficult to recreate in practice. FINJ is suitable for experiments involving many, potentially interacting nodes, making it a very versatile design and evaluation tool.Comment: To be presented at the 11th Resilience Workshop in the 2018 Euro-Par conferenc