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- All Subjects: Civil Engineering
- Creators: Arizona State University
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Description
Intermittent social defeat stress induces cross-sensitization to psychostimulants and escalation of drug self-administration. These behaviors could result from the stress-induced neuroadaptation in the mesocorticolimbic dopamine circuit. Brain-derived neurotrophic factor (BDNF) in the ventral tegmental area (VTA) is persistently elevated after social defeat stress, and may contribute to the stress-induced neuroadaptation in the mesocorticolimbic dopamine circuit. BDNF modulates synaptic plasticity, and facilitates stress- and drug-induced neuroadaptations in the mesocorticolimbic system. The present research examined the role of mesolimbic BDNF signaling in social defeat stress-induced cross-sensitization to psychostimulants and the escalation of cocaine self-administration in rats. We measured drug taking behavior with the acquisition, progressive ratio, and binge paradigms during self-administration. With BDNF overexpression in the ventral tegmental area (VTA), single social defeat stress-induced cross-sensitization to amphetamine (AMPH) was significantly potentiated. VTA-BDNF overexpression also facilitates acquisition of cocaine self-administration, and a positive correlation between the level of VTA BDNF and drug intake during 12 hour binge was observed. We also found significant increase of DeltaFosB expression in the nucleus accumbens (NAc), the projection area of the VTA, in rats received intra-VTA BDNF overexpression. We therefore examined whether BDNF signaling in the NAc is important for social defeat stress-induced cross-sensitization by knockdown of the receptor of BDNF (neurotrophin tyrosine kinase receptor type 2, TrkB) there. NAc TrkB knockdown prevented social defeat stress-induced cross-sensitization to psychostimulant. Also social defeat stress-induced increase of DeltaFosB in the NAc was prevented by TrkB knockdown. Several other factors up-regulated by stress, such as the GluA1 subunit of Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and BDNF in the VTA were also prevented. We conclude that BDNF signaling in the VTA increases social defeat stress-induced vulnerability to psychostimulants, manifested as potentiated cross-sensitization/sensitization to AMPH and escalation of cocaine self-administration. Also BDNF signaling in the NAc is necessary for the stress-induced neuroadaptation and behavioral sensitization to psychostimulants. Therefore, TrkB in the NAc could be a therapeutic target to prevent stress-induced vulnerability to drugs of abuse in the future. DeltaFosB in the NAc shell could be a neural substrate underlying persistent cross-sensitization and augmented cocaine self-administration induced by social defeat stress.
ContributorsWang, Junshi (Author) / Hammer, Ronald (Thesis advisor) / Feuerstein, Burt (Committee member) / Nikulina, Ella (Committee member) / Neisewander, Janet (Committee member) / Arizona State University (Publisher)
Created2013
Description
Induced pluripotent stem cells (iPSCs) are an intriguing approach for neurological disease modeling, because neural lineage-specific cell types that retain the donors' complex genetics can be established in vitro. The statistical power of these iPSC-based models, however, is dependent on accurate diagnoses of the somatic cell donors; unfortunately, many neurodegenerative diseases are commonly misdiagnosed in live human subjects. Postmortem histopathological examination of a donor's brain, combined with premortem clinical criteria, is often the most robust approach to correctly classify an individual as a disease-specific case or unaffected control. We describe the establishment of primary dermal fibroblasts cells lines from 28 autopsy donors. These fibroblasts were used to examine the proliferative effects of establishment protocol, tissue amount, biopsy site, and donor age. As proof-of-principle, iPSCs were generated from fibroblasts from a 75-year-old male, whole body donor, defined as an unaffected neurological control by both clinical and histopathological criteria. To our knowledge, this is the first study describing autopsy donor-derived somatic cells being used for iPSC generation and subsequent neural differentiation. This unique approach also enables us to compare iPSC-derived cell cultures to endogenous tissues from the same donor. We utilized RNA sequencing (RNA-Seq) to evaluate the transcriptional progression of in vitro-differentiated neural cells (over a timecourse of 0, 35, 70, 105 and 140 days), and compared this with donor-identical temporal lobe tissue. We observed in vitro progression towards the reference brain tissue, supported by (i) a significant increasing monotonic correlation between the days of our timecourse and the number of actively transcribed protein-coding genes and long intergenic non-coding RNAs (lincRNAs) (P < 0.05), consistent with the transcriptional complexity of the brain, (ii) an increase in CpG methylation after neural differentiation that resembled the epigenomic signature of the endogenous tissue, and (iii) a significant decreasing monotonic correlation between the days of our timecourse and the percent of in vitro to brain-tissue differences (P < 0.05) for tissue-specific protein-coding genes and all putative lincRNAs. These studies support the utility of autopsy donors' somatic cells for iPSC-based neurological disease models, and provide evidence that in vitro neural differentiation can result in physiologically progression.
ContributorsHjelm, Brooke E (Author) / Craig, David W. (Thesis advisor) / Wilson-Rawls, Norma J. (Thesis advisor) / Huentelman, Matthew J. (Committee member) / Mason, Hugh S. (Committee member) / Kusumi, Kenro (Committee member) / Arizona State University (Publisher)
Created2013
Description
Alzheimer's Disease (AD) is a progressive neurodegenerative disease accounting for 50-80% of dementia cases in the country. This disease is characterized by the deposition of extracellular plaques occurring in regions of the brain important for cognitive function. A primary component of these plaques is the amyloid-beta protein. While a natively unfolded protein, amyloid-beta can misfold and aggregate generating a variety of different species including numerous different soluble oligomeric species some of which are precursors to the neurofibrillary plaques. Various of the soluble amyloid-beta oligomeric species have been shown to be toxic to cells and their presence may correlate with progression of AD. Current treatment options target the dementia symptoms, but there is no effective cure or alternative to delay the progression of the disease once it occurs. Amyloid-beta aggregates show up many years before symptoms develop, so detection of various amyloid-beta aggregate species has great promise as an early biomarker for AD. Therefore reagents that can selectively identify key early oligomeric amyloid-beta species have value both as potential diagnostics for early detection of AD and as well as therapeutics that selectively target only the toxic amyloid-beta aggregate species. Earlier work in the lab includes development of several different single chain antibody fragments (scFvs) against different oligomeric amyloid-beta species. This includes isolation of C6 scFv against human AD brain derived oligomeric amyloid-beta (Kasturirangan et al., 2013). This thesis furthers research in this direction by improving the yields and investigating the specificity of modified C6 scFv as a diagnostic for AD. It is motivated by experiments reporting low yields of the C6 scFv. We also used the C6T scFv to characterize the variation in concentration of this particular oligomeric amyloid-beta species with age in a triple transgenic AD mouse model. We also show that C6T can be used to differentiate between post-mortem human AD, Parkinson's disease (PD) and healthy human brain samples. These results indicate that C6T has potential value as a diagnostic tool for early detection of AD.
ContributorsVenkataraman, Lalitha (Author) / Sierks, Michael (Thesis advisor) / Rege, Kaushal (Committee member) / Pauken, Christine (Committee member) / Arizona State University (Publisher)
Created2013
Description
It is commonly known that the left hemisphere of the brain is more efficient in the processing of verbal information, compared to the right hemisphere. One proposal suggests that hemispheric asymmetries in verbal processing are due in part to the efficient use of top-down mechanisms by the left hemisphere. Most evidence for this comes from hemispheric semantic priming, though fewer studies have investigated verbal memory in the cerebral hemispheres. The goal of the current investigations is to examine how top-down mechanisms influence hemispheric asymmetries in verbal memory, and determine the specific nature of hypothesized top-down mechanisms. Five experiments were conducted to explore the influence of top-down mechanisms on hemispheric asymmetries in verbal memory. Experiments 1 and 2 used item-method directed forgetting to examine maintenance and inhibition mechanisms. In Experiment 1, participants were cued to remember or forget certain words, and cues were presented simultaneously or after the presentation of target words. In Experiment 2, participants were cued again to remember or forget words, but each word was repeated once or four times. Experiments 3 and 4 examined the influence of cognitive load on hemispheric asymmetries in true and false memory. In Experiment 3, cognitive load was imposed during memory encoding, while in Experiment 4, cognitive load was imposed during memory retrieval. Finally, Experiment 5 investigated the association between controlled processing in hemispheric semantic priming, and top-down mechanisms used for hemispheric verbal memory. Across all experiments, divided visual field presentation was used to probe verbal memory in the cerebral hemispheres. Results from all experiments revealed several important findings. First, top-down mechanisms used by the LH primarily used to facilitate verbal processing, but also operate in a domain general manner in the face of increasing processing demands. Second, evidence indicates that the RH uses top-down mechanisms minimally, and processes verbal information in a more bottom-up manner. These data help clarify the nature of top-down mechanisms used in hemispheric memory and language processing, and build upon current theories that attempt to explain hemispheric asymmetries in language processing.
ContributorsTat, Michael J (Author) / Azuma, Tamiko (Thesis advisor) / Goldinger, Stephen D (Committee member) / Liss, Julie M (Committee member) / Arizona State University (Publisher)
Created2013
Description
In recent years, an increase of environmental temperature in urban areas has raised many concerns. These areas are subjected to higher temperature compared to the rural surrounding areas. Modification of land surface and the use of materials such as concrete and/or asphalt are the main factors influencing the surface energy balance and therefore the environmental temperature in the urban areas. Engineered materials have relatively higher solar energy absorption and tend to trap a relatively higher incoming solar radiation. They also possess a higher heat storage capacity that allows them to retain heat during the day and then slowly release it back into the atmosphere as the sun goes down. This phenomenon is known as the Urban Heat Island (UHI) effect and causes an increase in the urban air temperature. Many researchers believe that albedo is the key pavement affecting the urban heat island. However, this research has shown that the problem is more complex and that solar reflectivity may not be the only important factor to evaluate the ability of a pavement to mitigate UHI. The main objective of this study was to analyze and research the influence of pavement materials on the near surface air temperature. In order to accomplish this effort, test sections consisting of Hot Mix Asphalt (HMA), Porous Hot Mix asphalt (PHMA), Portland Cement Concrete (PCC), Pervious Portland Cement Concrete (PPCC), artificial turf, and landscape gravels were constructed in the Phoenix, Arizona area. Air temperature, albedo, wind speed, solar radiation, and wind direction were recorded, analyzed and compared above each pavement material type. The results showed that there was no significant difference in the air temperature at 3-feet and above, regardless of the type of the pavement. Near surface pavement temperatures were also measured and modeled. The results indicated that for the UHI analysis, it is important to consider the interaction between pavement structure, material properties, and environmental factors. Overall, this study demonstrated the complexity of evaluating pavement structures for UHI mitigation; it provided great insight on the effects of material types and properties on surface temperatures and near surface air temperature.
ContributorsPourshams-Manzouri, Tina (Author) / Kaloush, Kamil (Thesis advisor) / Wang, Zhihua (Thesis advisor) / Zapata, Claudia E. (Committee member) / Mamlouk, Michael (Committee member) / Arizona State University (Publisher)
Created2013
Description
Perceptual learning by means of coherent motion training paradigms has been shown to produce plasticity in lower and higher-level visual systems within the human occipital lobe both supra- and subliminally. However, efficiency of training methods that produce consolidation in the visual system via coherent motion has yet to be experimentally determined. Furthermore, the effects of coherent motion training on reading comprehension, in clinical and normal populations, are still nascent. In the present study, 20 participants were randomly assigned to one of four experimental conditions. Two conditions had a participation requirement of four days while two conditions required eight days of participation. These conditions were further divided into 500 or 1000 trials per day (4 x 500, 4 x 1000, 8 x 500, 8 x 1000). Additional pre-test and post-test days were used to attain timed pre- and post-tests on the Wide Range Achievement Test IV (WRAT IV) reading comprehension battery. Furthermore, a critical flicker fusion threshold (CFFT) score was taken on a macular pigment densitometer on the pre-test and post-test day. Participants showed significant improvement in CFFT levels, WRAT IV reading comprehension, and speed of completion between pre-test and post-test; however, degree of improvement did not vary as a function of training condition. An interaction between training condition and degree of improvement was evident in coherent dot motion contrast scores, with significant training plasticity occurring in the 4 x 1000 and 8 x 500 conditions.
ContributorsGroth, Anthony (Author) / Náñez, José E. (Thesis advisor) / Hall, Deborah (Committee member) / Risko, Evan F. (Committee member) / Arizona State University (Publisher)
Created2013
Description
Vehicle type choice is a significant determinant of fuel consumption and energy sustainability; larger, heavier vehicles consume more fuel, and expel twice as many pollutants, than their smaller, lighter counterparts. Over the course of the past few decades, vehicle type choice has seen a vast shift, due to many households making more trips in larger vehicles with lower fuel economy. During the 1990s, SUVs were the fastest growing segment of the automotive industry, comprising 7% of the total light vehicle market in 1990, and 25% in 2005. More recently, due to rising oil prices, greater awareness to environmental sensitivity, the desire to reduce dependence on foreign oil, and the availability of new vehicle technologies, many households are considering the use of newer vehicles with better fuel economy, such as hybrids and electric vehicles, over the use of the SUV or low fuel economy vehicles they may already own. The goal of this research is to examine how vehicle miles traveled, fuel consumption and emissions may be reduced through shifts in vehicle type choice behavior. Using the 2009 National Household Travel Survey data it is possible to develop a model to estimate household travel demand and total fuel consumption. If given a vehicle choice shift scenario, using the model it would be possible to calculate the potential fuel consumption savings that would result from such a shift. In this way, it is possible to estimate fuel consumption reductions that would take place under a wide variety of scenarios.
ContributorsChristian, Keith (Author) / Pendyala, Ram M. (Thesis advisor) / Chester, Mikhail (Committee member) / Kaloush, Kamil (Committee member) / Ahn, Soyoung (Committee member) / Arizona State University (Publisher)
Created2013
Description
Manufacture of building materials requires significant energy, and as demand for these materials continues to increase, the energy requirement will as well. Offsetting this energy use will require increased focus on sustainable building materials. Further, the energy used in building, particularly in heating and air conditioning, accounts for 40 percent of a buildings energy use. Increasing the efficiency of building materials will reduce energy usage over the life time of the building. Current methods for maintaining the interior environment can be highly inefficient depending on the building materials selected. Materials such as concrete have low thermal efficiency and have a low heat capacity meaning it provides little insulation. Use of phase change materials (PCM) provides the opportunity to increase environmental efficiency of buildings by using the inherent latent heat storage as well as the increased heat capacity. Incorporating PCM into concrete via lightweight aggregates (LWA) by direct addition is seen as a viable option for increasing the thermal storage capabilities of concrete, thereby increasing building energy efficiency. As PCM change phase from solid to liquid, heat is absorbed from the surroundings, decreasing the demand on the air conditioning systems on a hot day or vice versa on a cold day. Further these materials provide an additional insulating capacity above the value of plain concrete. When the temperature drops outside the PCM turns back into a solid and releases the energy stored from the day. PCM is a hydrophobic material and causes reductions in compressive strength when incorporated directly into concrete, as shown in previous studies. A proposed method for mitigating this detrimental effect, while still incorporating PCM into concrete is to encapsulate the PCM in aggregate. This technique would, in theory, allow for the use of phase change materials directly in concrete, increasing the thermal efficiency of buildings, while negating the negative effect on compressive strength of the material.
ContributorsSharma, Breeann (Author) / Neithalath, Narayanan (Thesis advisor) / Mobasher, Barzin (Committee member) / Rajan, Subramaniam D. (Committee member) / Arizona State University (Publisher)
Created2013
Description
Specific dendritic morphologies are a hallmark of neuronal identity, circuit assembly, and behaviorally relevant function. Despite the importance of dendrites in brain health and disease, the functional consequences of dendritic shape remain largely unknown. This dissertation addresses two fundamental and interrelated aspects of dendrite neurobiology. First, by utilizing the genetic power of Drosophila melanogaster, these studies assess the developmental mechanisms underlying single neuron morphology, and subsequently investigate the functional and behavioral consequences resulting from developmental irregularity. Significant insights into the molecular mechanisms that contribute to dendrite development come from studies of Down syndrome cell adhesion molecule (Dscam). While these findings have been garnered primarily from sensory neurons whose arbors innervate a two-dimensional plane, it is likely that the principles apply in three-dimensional central neurons that provide the structural substrate for synaptic input and neural circuit formation. As such, this dissertation supports the hypothesis that neuron type impacts the realization of Dscam function. In fact, in Drosophila motoneurons, Dscam serves a previously unknown cell-autonomous function in dendrite growth. Dscam manipulations produced a range of dendritic phenotypes with alteration in branch number and length. Subsequent experiments exploited the dendritic alterations produced by Dscam manipulations in order to correlate dendritic structure with the suggested function of these neurons. These data indicate that basic motoneuron function and behavior are maintained even in the absence of all adult dendrites within the same neuron. By contrast, dendrites are required for adjusting motoneuron responses to specific challenging behavioral requirements. Here, I establish a direct link between dendritic structure and neuronal function at the level of the single cell, thus defining the structural substrates necessary for conferring various aspects of functional motor output. Taken together, information gathered from these studies can inform the quest in deciphering how complex cell morphologies and networks form and are precisely linked to their function.
ContributorsHutchinson, Katie Marie (Author) / Duch, Carsten (Thesis advisor) / Neisewander, Janet (Thesis advisor) / Newfeld, Stuart (Committee member) / Smith, Brian (Committee member) / Orchinik, Miles (Committee member) / Arizona State University (Publisher)
Created2013
Description
The history of outdoor water use in the Phoenix, Arizona metropolitan area has given rise to a general landscape aesthetic and pattern of residential irrigation that seem in discord with the natural desert environment. While xeric landscaping that incorporates native desert ecology has potential for reducing urban irrigation demand, there are societal and environmental factors that make mesic landscaping, including shade trees and grass lawns, a common choice for residential yards. In either case, there is potential for water savings through irrigation schedules based on fluxes affecting soil moisture in the active plant rooting zone. In this thesis, a point-scale model of soil moisture dynamics was applied to two urban sites in the Phoenix area: one with xeric landscaping, and one with mesic. The model was calibrated to observed soil moisture data from irrigated and non-irrigated sensors, with local daily precipitation and potential evapotranspiration records as model forcing. Simulations were then conducted to investigate effects of irrigation scheduling, plant stress parameters, and precipitation variability on soil moisture dynamics, water balance partitioning, and plant water stress. Results indicated a substantial difference in soil water storage capacity at the two sites, which affected sensitivity to irrigation scenarios. Seasonal variation was critical in avoiding unproductive water losses at the xeric site, and allowed for small water savings at the mesic site by maintaining mild levels of plant stress. The model was also used to determine minimum annual irrigation required to achieve specified levels of plant stress at each site using long-term meteorological records. While the xeric site showed greater potential for water savings, a bimodal schedule consisting of low winter and summer irrigation was identified as a means to conserve water at both sites, with moderate levels of plant water stress. For lower stress levels, potential water savings were found by fixing irrigation depth and seasonally varying the irrigation interval, consistent with municipal recommendations in the Phoenix metropolitan area. These results provide a deeper understanding of the ecohydrologic differences between the two types of landscape treatments, and can assist water and landscape managers in identifying opportunities for water savings in desert urban areas.
ContributorsVolo, Thomas J (Author) / Vivoni, Enrique R (Thesis advisor) / Ruddell, Benjamin L (Committee member) / Wang, Zhihua (Committee member) / Arizona State University (Publisher)
Created2013