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Postprandial Glucose Responses to a High Glycemic Meal with Raw or Cooked Vegetables

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Early humans adapted to eating cooked food with increased energy density and absorption of macronutrients. However, in modern times many suffer from diseases like obesity and type 2 diabetes which can result from too much energy being absorbed from food.

Early humans adapted to eating cooked food with increased energy density and absorption of macronutrients. However, in modern times many suffer from diseases like obesity and type 2 diabetes which can result from too much energy being absorbed from food. This study measures glucose responses to a high glycemic meal with a side dish of raw or cooked vegetables. There was a slight trend for raw vegetables to have decreased postprandial blood glucose responses when compared to cooked vegetables.

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2014-05

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The evolution of addiction: a case study of nicotine dependence

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A variety of studies have shown that the tendency toward nicotine dependence has a genetic component. The work described in this thesis addresses three separate questions: i) are there unidentified SNPs in the nicotinic receptors or other genes that contribute

A variety of studies have shown that the tendency toward nicotine dependence has a genetic component. The work described in this thesis addresses three separate questions: i) are there unidentified SNPs in the nicotinic receptors or other genes that contribute to the risk for nicotine dependence; ii) is there evidence of ongoing selection at nicotinic receptor loci; and, iii) since nicotine dependence is unlikely to be the phenotype undergoing selection, is a positive effect on memory or cognition the selected phenotype. I first undertook a genome –wide association scan of imputed data using samples from the Collaborative Study of the Genetics of Nicotine Dependence (COGEND). A novel association was found between nicotine dependence and SNPs at 13q31. The genes at this newly associated locus on chromosome 13 encode a group of micro-RNAs and a member of the glypican gene family. These are among the first findings to implicate a non-candidate gene in risk for nicotine dependence. I applied several complimentary methods to sequence data from the 1000 Genomes Project to test for evidence of selection at the nicotinic receptor loci. I found strong evidence for selection for alleles in the nicotinic receptor cluster on chromosome 8 that confer risk of nicotine dependence. I then used the dataset from the Collaborative Studies on the Genetics of Alcoholism (COGA) and looked for an association between neuropsychological phenotypes and SNPs conferring risk of nicotine dependence. One SNP passed multiple test correction for association with WAIS digit symbol score. This SNP is not itself associated with nicotine dependence but is in reasonable (r 2 = 0.75) LD with SNPs that are associated with nicotine dependence. These data suggest at best, a weak correlation between nicotine dependence and any of the tested cognitive phenotypes. Given the reproducible finding of an inverse relationship between SNPs associated with risk for nicotine dependence and cocaine dependence, I hypothesize that the apparently detrimental phenotype of nicotine dependence may confer decreased risk for cocaine dependence. As cocaine use impairs the positive rewards associated with social interactions, reducing the risk of cocaine addiction may be beneficial to both the individual and the group.

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2014

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Metabolic engineering for the biosynthesis of styrene and its derivatives

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Metabolic engineering is an extremely useful tool enabling the biosynthetic production of commodity chemicals (typically derived from petroleum) from renewable resources. In this work, a pathway for the biosynthesis of styrene (a plastics monomer) has been engineered in Escherichia coli

Metabolic engineering is an extremely useful tool enabling the biosynthetic production of commodity chemicals (typically derived from petroleum) from renewable resources. In this work, a pathway for the biosynthesis of styrene (a plastics monomer) has been engineered in Escherichia coli from glucose by utilizing the pathway for the naturally occurring amino acid phenylalanine, the precursor to styrene. Styrene production was accomplished using an E. coli phenylalanine overproducer, E. coli NST74, and over-expression of PAL2 from Arabidopsis thaliana and FDC1 from Saccharomyces cerevisiae. The styrene pathway was then extended by just one enzyme to either (S)-styrene oxide (StyAB from Pseudomonas putida S12) or (R)-1,2-phenylethanediol (NahAaAbAcAd from Pseudomonas sp. NCIB 9816-4) which are both used in pharmaceutical production. Overall, these pathways suffered from limitations due to product toxicity as well as limited precursor availability. In an effort to overcome the toxicity threshold, the styrene pathway was transferred to a yeast host with a higher toxicity limit. First, Saccharomyces cerevisiae BY4741 was engineered to overproduce phenylalanine. Next, PAL2 (the only enzyme needed to complete the styrene pathway) was then expressed in the BY4741 phenylalanine overproducer. Further strain improvements included the deletion of the phenylpyruvate decarboxylase (ARO10) and expression of a feedback-resistant choristmate mutase (ARO4K229L). These works have successfully demonstrated the possibility of utilizing microorganisms as cellular factories for the production styrene, (S)-styrene oxide, and (R)-1,2-phenylethanediol.

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2014

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A comparative study of dragonfly flight in variable oxygen atmospheres

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One hypothesis for the small size of insects relative to vertebrates, and the existence of giant fossil insects, is that atmospheric oxygen levels have constrained body sizes because oxygen delivery would be unable to match the needs of metabolically active

One hypothesis for the small size of insects relative to vertebrates, and the existence of giant fossil insects, is that atmospheric oxygen levels have constrained body sizes because oxygen delivery would be unable to match the needs of metabolically active tissues in larger insects. This study tested whether oxygen delivery becomes more challenging for larger insects by measuring the oxygen-sensitivity of flight metabolic rates and behavior during hovering for 11 different species of dragonflies that range in mass by an order of magnitude. Animals were flown in 7 different oxygen concentrations ranging from 30% to 2.5% to assess the sensitivity of their behavior and flight metabolic rates to oxygen. I also assessed the oxygen-sensitivity of flight in low-density air (nitrogen replaced with helium), to increase the metabolic demands of hovering flight. Lowered atmosphere densities did induce higher metabolic rates. Flight behaviors but not flight metabolic rates were highly oxygen-sensitive. A significant interaction between oxygen and mass was found for total flight time, with larger dragonflies varying flight time more in response to atmospheric oxygen. This study provides some support for the hypothesis that larger insects are more challenged in oxygen delivery, as predicted by the oxygen limitation hypothesis for insect gigantism in the Paleozoic.

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2011

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Enhancement, commodification, and human flourishing, or, The reason why human enhancement is wrong is because it leads to people being treated like pots

Description

At present, the ideological bias in the human enhancement debate holds that opponents to human enhancement are primarily techno-conservatives who, lacking any reasonable, systematic account of why we ought to be so opposed, simply resort to a sort of fear-mongering

At present, the ideological bias in the human enhancement debate holds that opponents to human enhancement are primarily techno-conservatives who, lacking any reasonable, systematic account of why we ought to be so opposed, simply resort to a sort of fear-mongering and anti-meliorism. This dissertation means to counteract said bias by offering just such an account. Offered herein is a heuristic explanation of how, given a thorough understanding of enhancement both as a technology and as an attitude, we can predict a likely future of rampant commodification and dehumanization of man, and a veritable assault on human flourishing.

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2012

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The ketogenic diet in the treatment of malignant glioma: mechanistic effects on hypoxia and angiogenesis

Description

Patients with malignant brain tumors have a median survival of approximately 15 months following diagnosis, regardless of currently available treatments which include surgery followed by radiation and chemotherapy. Improvement in the survival of brain cancer patients requires the design of

Patients with malignant brain tumors have a median survival of approximately 15 months following diagnosis, regardless of currently available treatments which include surgery followed by radiation and chemotherapy. Improvement in the survival of brain cancer patients requires the design of new therapeutic modalities that take advantage of common phenotypes. One such phenotype is the metabolic dysregulation that is a hallmark of cancer cells. It has therefore been postulated that one approach to treating brain tumors may be by metabolic alteration such as that which occurs through the use of the ketogenic diet (KD). The KD is high-fat, low-carbohydrate diet that induces ketosis and has been utilized for the non-pharmacologic treatment of refractory epilepsy. It has been shown that this metabolic therapy enhances survival and potentiates standard therapy in mouse models of malignant gliomas, yet the anti-tumor mechanisms are not fully understood.

The current study reports that KetoCal® (KC; 4:1 fat:protein/carbohydrates), fed ad libitum, alters hypoxia, angiogenic, and inflammatory pathways in a mouse model of glioma. Tumors from animals maintained on KC showed reduced expression of the hypoxia marker carbonic anhydrase 9 (CA IX), a reduction in hypoxia inducible factor 1-alpha (HIF-1α) and decreased activation of nuclear factor kappa B (NF-κB). Animals maintained on KC also showed a reduction in expression of vascular endothelial growth factor receptor 2 (VEGFR2) and decreased microvasculature in their tumors. Further, peritumoral edema was significantly reduced in animals fed the KC and protein analysis showed significantly altered expression of the tight junction protein zona occludens-1 (ZO-1) and the water channeling protein aquaporin-4 (AQP4), both of which have been implicated in malignant processes in glioma, including the formation of peritumoral edema in patients. Taken together the data suggests that KC alters multiple processes involved in malignant progression of gliomas. A greater understanding of the effects of the ketogenic diet as an adjuvant therapy will allow for a more rational approach to its clinical use.

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Date Created
2014

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Can a vegetarian diet affect resting metabolic rate or satiety: a pilot study utilizing a metabolic cart and the SenseWear armband

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Dietary protein is known to increase postprandial thermogenesis more so than carbohydrates or fats, probably related to the fact that amino acids have no immediate form of storage in the body and can become toxic if not readily incorporated into

Dietary protein is known to increase postprandial thermogenesis more so than carbohydrates or fats, probably related to the fact that amino acids have no immediate form of storage in the body and can become toxic if not readily incorporated into body tissues or excreted. It is also well documented that subjects report greater satiety on high- versus low-protein diets and that subject compliance tends to be greater on high-protein diets, thus contributing to their popularity. What is not as well known is how a high-protein diet affects resting metabolic rate over time, and what is even less well known is if resting metabolic rate changes significantly when a person consuming an omnivorous diet suddenly adopts a vegetarian one. This pilot study sought to determine whether subjects adopting a vegetarian diet would report decreased satiety or demonstrate a decreased metabolic rate due to a change in protein intake and possible increase in carbohydrates. Further, this study sought to validate a new device called the SenseWear Armband (SWA) to determine if it might be sensitive enough to detect subtle changes in metabolic rate related to diet. Subjects were tested twice on all variables, at baseline and post-test. Independent and related samples tests revealed no significant differences between or within groups for any variable at any time point in the study. The SWA had a strong positive correlation to the Oxycon Mobile metabolic cart but due to a lack of change in metabolic rate, its sensitivity was undetermined. These data do not support the theory that adopting a vegetarian diet results in a long-term change in metabolic rate.

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2012

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Where did you come from? Where will you go?: human evolutionary biology education and American students' academic interests and achievements, professional goals, and socioscientific decision-making

Description

In the United States, there is a national agenda to increase the number of qualified science, technology, engineering, and maths (STEM) professionals and a movement to promote science literacy among the general public. This project explores the association between formal

In the United States, there is a national agenda to increase the number of qualified science, technology, engineering, and maths (STEM) professionals and a movement to promote science literacy among the general public. This project explores the association between formal human evolutionary biology education (HEB) and high school science class enrollment, academic achievement, interest in a STEM degree program, motivation to pursue a STEM career, and socioscientific decision–making for a sample of students enrolled full–time at Arizona State University. Given a lack of a priori knowledge of these relationships, the Grounded Theory Method was used and was the foundation for a mixed–methods analysis involving qualitative and quantitative data from one–on–one interviews, focus groups, questionnaires, and an online survey. Theory development and hypothesis generation were based on data from 44 students. The survey instrument, developed to test the hypotheses, was completed by 486 undergraduates, age 18–22, who graduated from U.S. public high schools. The results showed that higher exposure to HEB was correlated with greater high school science class enrollment, particularly for advanced biological science classes, and that, for some students, HEB exposure may have influenced their enrollment, because the students found the content interesting and relevant. The results also suggested that students with higher K–12 HEB exposure felt more prepared for undergraduate science coursework. There was a positive correlation between HEB exposure and interest in a STEM degree and an indirect relationship between higher HEB exposure and motivation to pursue a STEM career. Regarding a number of socioscientific issues, including but not limited to climate change, homosexuality, and stem cell research, students' behaviors and decision–making more closely reflected a scientific viewpoint—or less–closely aligned to a religion–based perspective—when students had greater HEB exposure, but this was sometimes contingent on students' lifetime exposure to religious doctrine and acceptance of general evolution or human evolution. This study has implications for K–12 and higher education and justifies a paradigm shift in evolution education research, such that more emphasis is placed on students' interests, perceived preparation for continued learning, professional goals and potential contributions to society rather than just their knowledge and acceptance.

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Date Created
2014

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Biosynthetic production of aromatic fine chemicals

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This dissertation focuses on the biosynthetic production of aromatic fine chemicals in engineered Escherichia coli from renewable resources. The discussed metabolic pathways take advantage of key metabolites in the shikimic acid pathway, which is responsible for the production of the

This dissertation focuses on the biosynthetic production of aromatic fine chemicals in engineered Escherichia coli from renewable resources. The discussed metabolic pathways take advantage of key metabolites in the shikimic acid pathway, which is responsible for the production of the aromatic amino acids phenylalanine, tyrosine, and tryptophan. For the first time, the renewable production of benzaldehyde and benzyl alcohol has been achieved in recombinant E. coli with a maximum titer of 114 mg/L of benzyl alcohol. Further strain development to knockout endogenous alcohol dehydrogenase has reduced the in vivo degradation of benzaldehyde by 9-fold, representing an improved host for the future production of benzaldehyde as a sole product. In addition, a novel alternative pathway for the production of protocatechuate (PCA) and catechol from the endogenous metabolite chorismate is demonstrated. Titers for PCA and catechol were achieved at 454 mg/L and 630 mg/L, respectively. To explore potential routes for improved aromatic product yields, an in silico model using elementary mode analysis was developed. From the model, stoichiometric optimums maximizing both product-to-substrate and biomass-to-substrate yields were discovered in a co-fed model using glycerol and D-xylose as the carbon substrates for the biosynthetic production of catechol. Overall, the work presented in this dissertation highlights contributions to the field of metabolic engineering through novel pathway design for the biosynthesis of industrially relevant aromatic fine chemicals and the use of in silico modelling to identify novel approaches to increasing aromatic product yields.

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2016

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Costly signaling and prey choice: the signaling value of hunted game

Description

For most of human history hunting has been the primary economic activity of men. Hunted animals are valued for their food energy and nutrients, however, hunting is associated with a high risk of failure. Additionally, large animals cannot be consumed

For most of human history hunting has been the primary economic activity of men. Hunted animals are valued for their food energy and nutrients, however, hunting is associated with a high risk of failure. Additionally, large animals cannot be consumed entirely by the nuclear family, so much of the harvest may be shared to others. This has led some researchers to ask why men hunt large and difficult game. The “costly signaling” and “show-off” hypotheses propose that large prey are hunted because the difficulty of finding and killing them is a reliable costly signal of the phenotypic quality of the hunter.

These hypotheses were tested using original interview data from Aché (hunter gatherer; n=52, age range 50-76, 46% female) and Tsimané (horticulturalist; n=40, age range 15-77, 45% female) informants. Ranking tasks and paired comparison tasks were used to determine the association between the costs of killing an animal and its value as a signal of hunter phenotypic quality for attracting mates and allies. Additional tasks compared individual large animals to groups of smaller animals to determine whether assessments of hunters’ phenotypes and preferred status were more impacted by the signal value of the species or by the weight and number of animals killed.

Aché informants perceived hunters who killed larger or harder to kill animals as having greater provisioning ability, strength, fighting ability, and disease susceptibility, and preferred them as mates and allies. Tsimané informants held a similar preference for hunters who killed large game, but not for hunters targeting hard to kill species. When total biomass harvested was controlled, both populations considered harvesting more animals in a given time period to be a better signal of preferred phenotypes than killing a single large and impressive species. Male and female informants both preferred hunters who consistently brought back small game over hunters who sometimes killed large animals and sometimes killed nothing. No evidence was found that hunters should forgo overall food return rates in order to signal phenotypic qualities by specializing on large game. Nutrient provisioning rather than costly phenotypic signaling was the strategy preferred by potential mates and allies.

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2019