MS

thesisComparatively few investigations concerning the metabolic behavior of virus had been reported before 1942. Since that time, there has been appearing a steady increase in the number of publications. Most of the studies have been concerned with isolated phases of this large problem. However, a widely accepted theory attempting to explain viral metabolism has been proposed. Upon entrance into a susceptible host cell, the virus particle shifts the normal metabolic activities of the host cell in such a manner as to result in the synthesis of more virus particles. The mechanism by which the virus particle accomplishes this is unknown. The above theory in itself suggests a need for more extensive metabolic studies of viruses; for, if we are to know how the virus particle duplicates itself within its host, we must first gain a clearer and broader knowledge of virus metabolism. Also, the planning of a logical approach to a chemotherapeutic attack on virus diseases necessitates a better understanding of the biochemistry of virus infections. This study was suggested by the work of Bauer (1947). Mouse brains infected with either of the viruses of yellow fever, lymphocytic choriomeningitis or lymphogranuloma inguinale were studied. The virus-infected brains showed a significant increase in dehydrogenase activity when compared with that in normal brains. This, increase was due, in part at least, to an increase in xamthine oxidase and pryuvic dehydrogenase activities. Bauer suggested that these to enzymes were in all probability essential for virus multiplication. In the present investigation an attempt has been made to determine whether or not there is an increase dehydrogenase activity of chorioallantoic fluid of 13 day-old embryonated chicken eggs previously infected with influenza A virus (PRS)

An Empirical Model of Demand for Future Health States when Valuing Risk-Mitigating Programs

51 p.We develop a structural option price model in which individuals choose among competing risk-mitigating programs to alter their probability of experiencing future years in various degraded health states. The novel aspects of this model include separate estimates of the marginal utilities of avoiding years of morbidity and lost life-years. With these marginal utilities, we may evaluate a broad spectrum of probabilistic health outcomes over any period of an individual’s future life. The model also reduces potential biases associated with singleperiod, single-risk models typically used to produce estimates of the Value of a Statistical Life (VSL) by allowing individuals to substitute risk mitigation across competing sources of risk and across future years of their lives. We evaluate this model using data from a national survey that contains a choice experiment on demand for the mitigation of illness-specific risks.US Environmental Protection Agency (R829485) and Health Canada (Contract H5431-010041/001/SS

Comparative growth and static allometry in the genus Chlorocebus

Characterizing variation in growth across populations is critical to understanding multiple aspects of development in primates, including within-taxon developmental plasticity and the evolution of life history patterns. Growth in wild primates has often been reported and directly compared across larger taxonomic groups and within social groups, but comparisons are rarely investigated across widely dispersed populations of a single taxon. With the Vervet Phenome-Genome Project and the International Vervet Research Consortium, we trapped 936 vervet monkeys of all ages representing three populations (Kenyan pygerythrus, South African pygerythrus, and sabaeus from St. Kitts & Nevis). We gathered 10 different body measurements from each including mass, body breadth and length, segmental limb lengths, and chest circumference. To gain a better understanding of how ontogenetic patterns vary in these populations, we calculated bivariate allometry coefficients, derived using PCA on log-transformed and z-standardized trait values, and compared them to isometric vector coefficients. Within all population samples, around weaning age most traits showed a negative allometric relationship to body length. As each population ages, however, distinct patterns emerge, showing population differences in onset and intensity of growth among traits. In concordance with other analyses on growth in these populations, our results suggest that there exist relative differences in patterns of growth between Chlorocebus populations, further suggesting selection for unique developmental pathways in each

The importance of RSV F protein conformation in VLPs in stimulation of neutralizing antibody titers in mice previously infected with RSV

Respiratory syncytial virus (RSV) is a significant respiratory pathogen but no vaccine is available. RSV infections present 2 major, unique problems. First, humans can experience repeated infections caused by the same virus sero-group indicating that protective memory responses to RSV infection are defective. Second, most people have been infected with RSV by age 5. Immune responses to these infections, while poorly protective, could impact the effectiveness of a vaccine. The goal of this study was to assess the generation of protective immune responses in mice previously infected with RSV by virus-like particle (VLP) vaccine candidates containing a stabilized pre-fusion form of the RSV F protein or a stabilized post-fusion F protein. We report that a single immunization of RSV-experienced animals with a stabilized pre-fusion F protein VLP stimulated high titers of neutralizing antibody while a single injection of a post-fusion F protein VLP or a second RSV infection only weakly stimulated neutralizing antibody titers. These results suggest that prior RSV infection can induce neutralizing antibody memory responses, which can be activated by pre-F protein VLPs but not by post-F protein VLPs or a subsequent infection. Thus the F protein conformation has a major impact on enhancing production of neutralizing antibodies in RSV-experienced animals. Furthermore, although both VLPs contained the same RSV G protein, the pre-F VLP stimulated significantly higher titers of total anti-G protein IgG than the post-F VLP in both naive and RSV-experienced animals. Thus the F protein conformation also influences anti-G protein responses

The static allometry of sexual and non-sexual traits in vervet monkeys

Sexual traits vary tremendously in static allometry. This variation may be explained in part by body size-related differences in the strength of selection. We tested this hypothesis in two populations of vervet monkeys, using estimates of the level of condition dependence for different morphological traits as a proxy for body size-related variation in the strength of selection. In support of the hypothesis, we found that the steepness of allometric slopes increased with the level of condition dependence. One trait of particular interest, the penis, had shallow allometric slopes and low levels of condition dependence, in agreement with one of the most consistent patterns yet detected in the study of allometry, namely that of genitalia exhibiting shallow allometries.This research was supported by NIH grant R01RR0163009

Effects of Fluorescein Staining on Laser In Vivo Confocal Microscopy Images of the Cornea

This study was designed to identify whether topical fluorescein, a common ophthalmic tool, affects laser in vivo confocal microscopy of the cornea, a tool with growing applications. Twenty-five eye care specialists were asked to identify presence or absence of fluorescein in 99 confocal micrographs of healthy corneas. Responses were statistically similar to guessing for the epithelium (48% ± 14% of respondents correct per image) and the subbasal nerve plexus (49% ± 11% correct), but results were less clear for the stroma. Dendritic immune cells were quantified in bilateral images from subjects who had been unilaterally stained with fluorescein. Density of dendritic immune cells was statistically similar between the unstained and contralateral stained eyes of 24 contact lens wearers (P = .72) and of 10 nonwearers (P = .53). Overall, the results indicated that fluorescein staining did not interfere with laser confocal microscopy of corneal epithelium, subbasal nerves, or dendritic immune cells

Integrating Geographic Information into the Analysis of the Genetic Distribution of South African Vervet Monkeys

This project uses the program Geneland to reanalyze McAuliffe’s (2008) thesis data on genetic variability in three South African vervet monkey populations (Polokwane, Oribi and Blyde). Using information on the geographic location and genetic variability of these populations, the spatially explicit Geneland program shows that the three populations are weakly differentiated. These findings oppose the results of previous genetic studies of South African vervet monkeys as well as the results obtained by McAuliffe with the spatially implicit Structure program, which found that the 34 individuals all come from one population. Based on this historic data and the fact that other studies have found the same number of subpopulations with both Structure and Geneland, I conclude that Polokwane, Oribi and Blyde are slightly differentiated, though not distinct enough to be considered separate populations (Latch et al. 2008). These results need to be supported by an analysis of the entire sample of South African vervet monkey genetic data from up to 200 animals prior to suggesting policy changes regarding genetic structuring in South African vervet monkeys

Variable responses of human and non-human primate gut microbiomes to a Western diet

BACKGROUND: The human gut microbiota interacts closely with human diet and physiology. To better understand the mechanisms behind this relationship, gut microbiome research relies on complementing human studies with manipulations of animal models, including non-human primates. However, due to unique aspects of human diet and physiology, it is likely that host-gut microbe interactions operate differently in humans and non-human primates. RESULTS: Here, we show that the human microbiome reacts differently to a high-protein, high-fat Western diet than that of a model primate, the African green monkey, or vervet (Chlorocebus aethiops sabaeus). Specifically, humans exhibit increased relative abundance of Firmicutes and reduced relative abundance of Prevotella on a Western diet while vervets show the opposite pattern. Predictive metagenomics demonstrate an increased relative abundance of genes associated with carbohydrate metabolism in the microbiome of only humans consuming a Western diet. CONCLUSIONS: These results suggest that the human gut microbiota has unique properties that are a result of changes in human diet and physiology across evolution or that may have contributed to the evolution of human physiology. Therefore, the role of animal models for understanding the relationship between the human gut microbiota and host metabolism must be re-focused.P40 OD010965 - NIH HHS; P40 RR019963 - NCRR NIH HHS; P51 OD011132 - NIH HHS; R01 RR016300 - NCRR NIH HHS; 5R01RR016300 - NCRR NIH HH

Two-Stage Two-Locus Models in Genome-Wide Association

Studies in model organisms suggest that epistasis may play an important role in the etiology of complex diseases and traits in humans. With the era of large-scale genome-wide association studies fast approaching, it is important to quantify whether it will be possible to detect interacting loci using realistic sample sizes in humans and to what extent undetected epistasis will adversely affect power to detect association when single-locus approaches are employed. We therefore investigated the power to detect association for an extensive range of two-locus quantitative trait models that incorporated varying degrees of epistasis. We compared the power to detect association using a single-locus model that ignored interaction effects, a full two-locus model that allowed for interactions, and, most important, two two-stage strategies whereby a subset of loci initially identified using single-locus tests were analyzed using the full two-locus model. Despite the penalty introduced by multiple testing, fitting the full two-locus model performed better than single-locus tests for many of the situations considered, particularly when compared with attempts to detect both individual loci. Using a two-stage strategy reduced the computational burden associated with performing an exhaustive two-locus search across the genome but was not as powerful as the exhaustive search when loci interacted. Two-stage approaches also increased the risk of missing interacting loci that contributed little effect at the margins. Based on our extensive simulations, our results suggest that an exhaustive search involving all pairwise combinations of markers across the genome might provide a useful complement to single-locus scans in identifying interacting loci that contribute to moderate proportions of the phenotypic variance