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No description available.

Intraspecific phenotype diversity allows for local adaption and the ability for species to respond to changing environmental conditions, enhancing survivability. Phenotypic variation could be stochastic, genetically based, and/or the result of different environmental conditions. Mojave Rattlesnakes, Crotalus scutulatus, are known to have high intraspecific venom variation, but the geographic extent of the variation and factors influencing venom evolution are poorly understood. Three primary venom types have been described in this species based on the presence (Type A) or absence (Type B) of a neurotoxic phospholipase A2 called Mojave toxin and an inverse relationship with the presence of snake venom metalloproteinases (SVMPs). Individuals that contain both Mojave toxin and SVMPs, although rare, are the third, and designated Type A + B. I sought to describe the proteomic and transcriptomic venom diversity of C. scutulatus across its range and test whether diversity was correlated with genetic or environmental differences. This study includes the highest geographic sampling of Mojave Rattlesnakes and includes the most venom-gland transcriptomes known for one species. Of the four mitochondrial lineages known, only one was monophyletic for venom type. Environmental variables poorly correlated with the phenotypes. Variability in toxin and toxin family composition of venom transcriptomes was largely due to differences in transcript expression. Four of 19 toxin families identified in C. scutulatus account for the majority of differences in toxin number and expression variation. I was able to determine that the toxins primarily responsible for venom types are inherited in a Mendelian fashion and that toxin expression is additive when comparing heterozygotes and homozygotes. Using the genetics to define venom type is more informative and the Type A + B phenotype is not unique, but rather heterozygous for the PLA2 and/or SVMP alleles. Intraspecific venom variation in C. scutulatus highlights the need for fine scale ecological and natural history information to understand how phenotypic diversity is generated and maintained geographically through time.

Biological organisms have evolved complex epigenetic mechanisms to tailor their gene expression programs to specific needs. These adaptations allow cells, that otherwise have identical genomes, to carry out specialized functions. In this work I develop and use data-integrative techniques to examine the mechanisms and consequences of epigenetic processes. To better understand the changes in DNA methylation landscape that accompany breast cancer molecular subtypes, I integrated DNA methylation and gene expression data from 208 breast cancer samples obtained from a Polish population-based case-control study. Using a weighted correlation network approach, I identified gene co-methylation modules and asked if the genes in these modules are preferentially methylated and silenced in a breast cancer subtype-specific manner. This approach identified two non-overlapping gene co-methylation modules. The first module is silenced in Basal breast cancers, while the second is silenced in Luminal B breast cancers. Gene-set enrichment analysis suggests that epigenetic silencing of these modules interferes with processes that maintain cellular differentiation, and that the methylation status of the Luminal B module is associated with disease prognosis. To uncover the determinants of the temporal order of metazoan genome replication, I used a reductionist model of DNA replication to test the ability of hundreds of epigenetic marks to predict replication timing. My work showed that DNA replication timing can be completely predicted from locations of DNase I hypersensitive sites. I further demonstrated the robust emergent character of DNA replication that could be understood without invoking a complex regulatory mechanism. To determine the underlying cause of cell de-differentiation in osteosarcoma, I examined the relationship between microRNA expression and the bone-cell differentiation program. Focusing on the inhibitory role of miR-23a in bone differentiation, I analyzed the effect of its over-expression in osteosarcoma cells. Extensive computational analysis led me to propose that a major mechanism by which miR-23a exerts its effect is by interfering with expression of GJA1, which encodes a gap junction channel essential for intercellular communication and external stimuli sensing in bone cells. Follow-up experiments indicate that GJA1 is sharply up-regulated during bone cell differentiation and that GJA1 inhibition significantly delays the onset of differentiation. Together, this work uses data integrative techniques to provide new insights into the decisive role of epigenetic processes in cellular differentiation. / 2019-04-01T00:00:00Z

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Acid mine drainage (AMD), a result of oxidation of minerals containing reduced forms of sulfur (pyrites, sulfides) upon exposure to water and oxygen, is an environmental problem associated with abandoned mined lands (AML). Numerous studies have documented the impacts of AMD upon aquatic communities within acidified stream reaches; these impacts include reduced taxonomic richness and abundance, and/or a shift from pollution sensitive to pollution tolerant species. This dissertation comprises a number of integrative assessments and experiments conducted to investigate the nature of AMD ecotoxicity in the upper Powell River watershed. Emphasis was placed upon bioassessment methodologies and AMD impacts beyond the zone of pH depression. Major findings and processes developed included: 1) an Ecotoxicological Rating (ETR) system was developed that integrates chemical, toxicological, and ecological data into a single value depicting the relative environmental integrity of a given station within a watershed; 2) water column chemistry rather than sediment toxicity was the major factor causing acute toxicity to aquatic biota in close proximity to AMD discharges; 3) solid ferric hydroxide can cause acute toxicity to standard test organisms in the absence of dissolved iron; 4) Asian clams (Corbicula fluminea) can be used to detect both acutely toxic AMD inputs and nutrient loading in low order streams, and clam responses of survival and growth reflect those of indigenous communities to the two contaminant types; 5) aluminum (Al) in transition from acidic to neutral pH waters can cause acute toxicity to aquatic invertebrates, and may be the cause of impaired benthic macroinvertebrate communities in neutral pH (>7.0) waters downstream of an acidic tributary; 6) in the larger river system (North Fork Powell and Powell mainstem), urban inputs appear to have a greater influence upon aquatic communities than metal loading from AMD impacted tributaries; 7) the use of individual level assessment endpoints, such as Asian clam growth in in situ toxicity tests, eliminates variables that may confound attribution of community level impacts to contaminants; and 8) the near elimination of predatory stoneflies (Plecoptera) downstream of the Stone/Straight Creek tributary to the North Fork Powell River was associated with water column Al concentrations. This research was funded by the Virginia Department of Mines, Minerals, and Energy, Division of Mined Land Reclamation, and by the Powell River Project. / Ph. D.

The field of mindfulness research is rapidly growing as mindfulness is being utilized as a tool to improve mental and cognitive health. Mindfulness is paying attention in the present moment with non-judgmental awareness. As the research body increases, weaknesses in mindfulness research have surfaced. There is a need for improved measurement tools, an increased understanding of, meditation techniques used, the dose of meditation, and the population samples being studied. Meditation and movement are both tools that can improve an individual's mindfulness. The proposed dissertation will investigate mindfulness through three studies. Study 1 was completed in a population of individual members of the International Quit and Recovery Registry and met the Diagnostic and Statistical Manual, 5th edition criteria for substance use disorder. It was found that individuals with higher mindfulness and engagement with Integrative Health Practices demonstrate success in recovery, measured by the World-Health Organization Quality of Life Scale, craving, and Days in Recovery and are more likely to have reached remission. Engagement with meditation showed more and higher correlations with success in recovery than other Integrative Health Practices measured. Study 2 investigated how mindfulness is taught. Participants were divided into two groups, comparing traditional cueing to compassion cueing. Participants received neuroscience education paired with weekly meditation techniques. There were no group differences; however, all participants expressed improvements in mindfulness, self-compassion, decreased depression symptoms, and gains in neuroscience knowledge. The impact of mindfulness curriculum development can be seen through differences in daily outcomes assessing participants' thoughts, emotions, and body on a 10-point Likert scale from settled to active. Study 3 validated a new tool to measure the multidimensional impacts of movement based on a traditional yogic framework and validated with neuroscience tools. The Multidimensional Impacts of Movement Scale (MIMS) is a valid and reliable tool showing stability over time (r = 0.737, p<0.001) and strong Cronbach's Alpha for each scale ranging from α = 0.775 to α = 0.840. These three studies combine as a body of work supporting continued research in the field of mindfulness by adding new knowledge about teaching mindfulness, measuring mindfulness, and how mindfulness can be applied to improve quality of recovery for individuals with substance use disorder. / Doctor of Philosophy / The field of mindfulness research is rapidly growing as mindfulness is being utilized as a tool to improve mental and cognitive health. Mindfulness is paying attention in the present moment with non-judgmental awareness. As the research body increases, weaknesses in mindfulness research have surfaced. There is a need for improved measurement tools, an increased understanding of, meditation techniques used, the dose of meditation, and the population samples being studied. Meditation and movement are both tools that can improve an individual's mindfulness. The proposed dissertation will investigate mindfulness through three studies. Study 1 was completed in a population of individual members of the International Quit and Recovery Registry and met the Diagnostic and Statistical Manual, 5th edition criteria for substance use disorder. It was found that individuals with higher mindfulness and engagement with Integrative Health Practices demonstrate success in recovery, measured by the World-Health Organization Quality of Life Scale, craving, and Days in Recovery and are more likely to have reached remission. Engagement with meditation showed more and higher correlations with success in recovery than other Integrative Health Practices measured. Study 2 investigated how mindfulness is taught. Participants were divided into two groups, comparing traditional cueing to compassion cueing. Participants received neuroscience education paired with weekly meditation techniques. There were no group differences; however, all participants expressed improvements in mindfulness, self-compassion, decreased depression symptoms, and gains in neuroscience knowledge. The impact of mindfulness curriculum development can be seen through differences in daily outcomes assessing participants' thoughts, emotions, and body on a 10-point Likert scale from settled to active. Study 3 validated a new tool to measure the multidimensional impacts of movement based on a traditional yogic framework and validated with neuroscience tools. The Multidimensional Impacts of Movement Scale (MIMS) is a valid and reliable tool showing stability over time (r = 0.737, p<0.001) and strong Cronbach's Alpha for each scale ranging from α = 0.775 to α = 0.840. These three studies combine as a body of work supporting continued research in the field of mindfulness by adding new knowledge about teaching mindfulness, measuring mindfulness, and how mindfulness can be applied to improve quality of recovery for individuals with substance use disorder.

This study focuses on the ability, or inability, to replicate or compare the design of text-related research from the perspective of the independent or dependent variables employed in such designs. Prior text-related research has used variables that were not clearly described or defined, could not be directly compared from one study or time period to the next, or were applied inappropriately. Measurements of typography-related and substrate-related variables may have absolute or relative values, and confusion can arise if the variables are not clearly identified and defined. The study is an integrative review with mixed methods research design investigating 44 books and two websites (part 1), and 83 journal articles and four theses/dissertations (part 2). The integrative review shows that the sources investigated present neither essential information on typographic and substrate characteristics nor consistent definitions of legibility and readability in order to allow comparable replication from one study to another. Findings are displayed in Chapter 4. Discussion and the related details are presented in Chapter 5. / PHD / This study focuses on the ability, or inability, to replicate or compare the design of text-related research from the perspective of the independent or dependent variables employed in such designs. Previous text-related research has used variables that were not clearly described or defined, could not be directly compared from one study or time period to the next, or were applied inappropriately. Measurements of typography-related and substrate-related variables may have absolute or relative values, and confusion can arise if the variables are not clearly identified and defined. The study is an integrative review with both qualitative and quantitative research design analyzing 44 books and two websites (part 1); and 83 journal articles, one thesis, and three dissertations (part 2). The integrative review shows that the sources investigated do not present essential information on typographic and substrate characteristics, and consistent definitions of legibility and readability to permit comparable replication from one study to another. Findings are displayed in Chapter 4. Discussion and the related details are presented in Chapter 5.

Vibratory communication has evolved in numerous animal groups, including insects, spiders, fishes, mammals, and was recently discovered in veiled chameleons (Chamaeleo calyptratus). I examined the mechanism by which C. calyptratus produce these biotremors. Muscle activity data were gathered during simulated anti-predator responses via electromyography (EMG) with simultaneous recordings of biotremor production using an accelerometer. I correlated EMG data with the accelerometer data to implicate the muscles responsible for the production of the biotremors. Mixed-effect linear regression models described the mechanism, and a model selection framework determined which model fit the data best. I then used an analysis of variance to partition the variance to each variable to determine which muscles were most important in the biotremor producing mechanism. The Mm. sternohyoideus superficialis et profundus, Mm. mandibulohyoideus, and M. levator scapulae were active during the production of biotremors. Mean latency calculations revealed that the M. levator scapulae and Mm. mandibulohyoideus activated prior to the vibration onset, and the Mm. sternohyoideus superficialis et profundus activated after the vibration onset. The M. sternohyoideus superficialis then ceased activity prior to vibration cessation, and the M. sternohyoideus profundus, Mm. mandibulohyoideus, and M. levator scapulae ceased activity after the vibration had ended. The description of the biotremor producing mechanism further supports that C. calyptratus can produce biotremors, possibly for communication.