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Description
Asperger's syndrome is a high-functioning subset of Autism Spectrum Disorders (ASD). Diagnosed patients often lack refined social skills but possess a normal level of cognitive skills without delay in language development. These deficient social skills can impact the ability to find and maintain a job, which can be burdensome for all individuals involved in the patient's life. Although the causes of this condition are largely unknown, a wide variety of social and cognitive therapies have been used to reduce symptom severity, one of which is Mindfulness-Based Stress Reduction (MBSR). Mindfulness is the act of being aware on purpose to whatever is being experienced in the present moment with non-judgment and receptivity. MBSR has been used to bring greater awareness to sensations, thoughts and emotions with the result being reduced reactivity and increased purposeful responsiveness. It is therefore the aim of this study to address the use of an 8-week Mindfulness-Based Stress Reduction in adolescents with clinical Asperger's Syndrome to reduce reactive tendencies. This study will utilize a randomized control group of waitlisted participants given MBSR informational material and a practicing MBSR group. Post-MBSR Parent Global Impressions-III (PGI-III) and Social Responsiveness Scale scores are hypothesized to be improved in MBSR group and unaffected in the control for behavioral markers with no change in core autistic symptoms. Daily average cortisol response is also expected to decrease in the experimental group with unaffected levels in the control.
ContributorsBrzezinski, Molly Alexandra (Author) / Smith, Brian (Thesis director) / Sebren, Ann (Committee member) / School of Music (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
The mammalian olfactory system is commonly studied by using the mouse as a model system. Odor habituation is used to investigate odor perception and learning processes. Most previous experimental preparations have been tedious, requiring a researcher to manually change odorants, record investigation time and duration at each odorant, or physical alteration on the mice to enable video tracking. These limitations were overcame by creating an odorized hole-board to allow for systematic and automatic recording of olfactory behavior in mice. A cohort of five male mice were utilized in these experiments and the responses to the odor of strawberries, a diet staple of wile mice, were examined. Experiment 1 showed that free-feeding mice exhibit a preference to locations with strawberry (over control locations), even when these locations can only be identified using olfaction. This preference habituates within a trial but not across days. Experiment 2 showed that strawberry odor without reward causes habituation or extinction to the odor both within trials and across days. From these experiments, it can be concluded that mice innately explore strawberry odor and this can be exploited to the study odor habituation using an odorized hole-board.
ContributorsMa, Jason (Author) / Smith, Brian (Thesis director) / Gerkin, Richard (Committee member) / Oddo, Salvatore (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Animals must learn to ignore stimuli that are irrelevant to survival, a process referred to as latent inhibition. The Amtyr1 gene has been shown through quantitative trait loci mapping to be linked to strong latent inhibition in honey bees. Here we implicate this G-protein coupled receptor for the biogenic amine tyramine as an important factor underlying this form of learning in honey bees. We show that dsRNA targeted to disrupt the tyramine receptors, specifically affects latent inhibition but not excitatory associative conditioning. Our results therefore identify a distinct reinforcement pathway for latent inhibition in insects.
ContributorsPetersen, Mary Margaret (Author) / Smith, Brian (Thesis director) / Wang, Ying (Committee member) / Sinakevitch, Irina (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
In Apis mellifera, gustatory responsiveness to sucrose is a good indicator of learning ability \u2014 in that individuals with high sucrose responsiveness will typically form faster, longer-lasting associations with conditioned stimulus than individuals with a low sucrose responsiveness. The purpose of this study was to determine whether experience with olfactory conditioning had lasting effects on gustatory responsiveness. Groups were placed in an environment that would facilitate association of an odor to a sucrose reward, tested for retention, then tested for gustatory responsiveness. Control groups underwent the same testing schedule, but were not exposed to odor in the first environment. There was no significant difference in gustatory responsiveness between the two groups. Mann-Whitney tests were used to analyze the results, and though the mean GRS score was lower among the treatment group there was no significant trend, possibly due to small sample sizes.
ContributorsSeemann, J. H. (Author) / Amdam, Gro (Thesis director) / Smith, Brian (Committee member) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Virus-Like Particles (VLPs) are self-assembling structures that lack the viral genetic material. Therefore they are safer and more immunogenic than other forms of vaccines. The Hepatitis B core (HBc) VLPs are a novel mechanism through which delivery of DNA-based human vaccines are plausible. Production of VLPs require recombinant, rapidly replicating, plant-based systems such as the geminiviral replicon system. This project entails the cloning process of HBc-DIII fusion protein, a VLP that should form Domain III of the Envelope protein on West Nile Virus, into deconstructed geminiviral vector. The cloning process includes the HBc-DIII fusion protein DNA isolation, restriction enzyme digestion with NcoI and SacI, PCR changing the NcoI site on the HBc-DIII insert to XbaI, sequencing, ligation into geminiviral vector and transformation into an agrobacterium strain. The major impediment to the cloning process was the presence of multiple bands instead of the expected two bands while doing restriction enzyme digests. The troubleshooting process enabled speculating that due to the excess of restriction enzymes in the digestion volume, some of the DNA was not digested completely. Hence, multiple bands were observed. However, sequencing analysis and further cloning process ensured the presence of HBc-DIII insert band (approximately 800bp) in the Gemini vector. Lastly, the construct HBc-DIII in Gemini vector was ensured to be in agrobacterium for further experiments such as agro-infiltration.
ContributorsSuresh Kumar, Reshma (Author) / Chen, Qiang (Thesis director) / Zhang, Peiming (Committee member) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Vaccines are one of the most effective ways of combating infectious diseases and developing vaccine platforms that can be used to produce vaccines can greatly assist in combating global public health threats. This dissertation focuses on the development and pre-clinical testing of vaccine platforms that are highly immunogenic, easily modifiable, economically viable to produce, and stable. These criteria are met by the recombinant immune complex (RIC) universal vaccine platform when produced in plants. The RIC platform is modeled after naturally occurring immune complexes that form when an antibody, a component of the immune system that recognizes protein structures or sequences, binds to its specific antigen, a molecule that causes an immune response. In the RIC platform, a well-characterized antibody is linked via its heavy chain, to an antigen tagged with the antibody-specific epitope. The RIC antibody binds to the epitope tags on other RIC molecules and forms highly immunogenic complexes. My research has primarily focused on the optimization of the RIC platform. First, I altered the RIC platform to enable an N-terminal antigenic fusion instead of the previous C-terminal fusion strategy. This allowed the platform to be used with antigens that require an accessible N-terminus. A mouse immunization study with a model antigen showed that the fusion location, either N-terminal or C-terminal, did not impact the immune response. Next, I studied a synergistic response that was seen upon co-delivery of RIC with virus-like particles (VLP) and showed that the synergistic response could be produced with either N-terminal or C-terminal RIC co-delivered with VLP. Since RICs are inherently insoluble due to their ability to form complexes, I also examined ways to increase RIC solubility by characterizing a panel of modified RICs and antibody-fusions. The outcome was the identification of a modified RIC that had increased solubility while retaining high immunogenicity. Finally, I modified the RIC platform to contain multiple antigenic insertion sites and explored the use of bioinformatic tools to guide the design of a broadly protective vaccine.
ContributorsPardhe, Mary (Author) / Mason, Hugh S (Thesis advisor) / Chen, Qiang (Committee member) / Mor, Tsafrir (Committee member) / Wilson, Melissa (Committee member) / Arizona State University (Publisher)
Created2021
Description
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19) that emerged from a zoonotic host at the end of 2019 and caused a public health crisis. In this collection of studies, Nicotiana benthamiana plants are used to set the foundation for producing monoclonal antibodies (mAbs) with homogeneous glycosylation to neutralize SARS-CoV-2 and potentially address the immunopathology often observed with severe COVID-19. Specifically, a mAb against the human interleukin (IL)-6 receptor (sarilumab) was generated and evaluated in vitro for its potential to reduce IL-6 signaling that has been shown to be associated with more severe cases of COVID-19. Furthermore, multiple mAbs that bind to the receptor-binding domain (RBD) of SARS-CoV-2 and efficiently neutralize the virus were developed using plant-based expression. Several of these mAbs are from different classes of RBD-binding mAbs that have distinct binding sites from one another. Several mAbs from different classes showed synergy in neutralizing the ancestral strain of SARS-CoV-2 and a smaller subset showed synergy when tested against the highly mutated Omicron (B.1.1.529) variant. Of interest, a novel RBD-binding mAb, termed 11D7, that was raised against the ancestral strain and derived from a hybridoma, appears to have an epitope on the RBD that contributes more synergy to a mAb combination that efficiently neutralizes the B.1.1.529 variant of SARS-CoV-2. This epitope was partially mapped by competitive binding and shows that it overlaps with another known antibody that binds a cryptic, distal epitope, away from the receptor binding site, giving insight into the potential mechanism by which 11D7 neutralizes SARS-CoV-2, as well as potentially allowing it to resist SARS-CoV-2 immune evasion more efficiently. Furthermore, this mAb carries a highly homogeneous glycan pattern when expressed in N. benthamiana, that may contribute to enhanced effector function and provides a tool to elucidate the precise role of crystallizable fragment (Fc)-mediated protection in SARS-CoV-2 infection. Ultimately, these studies provide evidence of the utility of plant-made mAbs to be used as cocktail members, giving clarity to the use of less potent mAbs as valuable cocktail components which will spur further investigations into how mAbs with unique epitopes work together to efficiently neutralize SARS-CoV-2.
ContributorsJugler, Collin (Author) / Chen, Qiang (Thesis advisor) / Lake, Douglas (Committee member) / Steele, Kelly (Committee member) / Mason, Hugh (Committee member) / Arizona State University (Publisher)
Created2022
Description
Scientists are entrusted with developing novel molecular strategies for effective prophylactic and therapeutic interventions. Antivirals are indispensable tools that can be targeted at viral domains directly or at cellular domains indirectly to obstruct viral infections and reduce pathogenicity. Despite their transformative potential in healthcare, to date, antivirals have been clinically approved to treat only 10 out of the greater than 200 known pathogenic human viruses. Additionally, as obligate intracellular parasites, many virus functions are intimately coupled with host cellular processes. As such, the development of a clinically relevant antiviral is challenged by the limited number of clear targets per virus and necessitates an extensive insight into these molecular processes. Compounding this challenge, many viral pathogens have evolved to evade effective antivirals. Therefore, a means to develop virus- or strain-specific antivirals without detailed insight into each idiosyncratic biochemical mechanism may aid in the development of antivirals against a larger swath of pathogens. Such an approach will tremendously benefit from having the specific molecular recognition of viral species as the lowest barrier. Here, I modify a nanobody (anti-green fluorescent protein) that specifically recognizes non-essential epitopes (glycoprotein M-pHluorin chimera) presented on the extra virion surface of a virus (Pseudorabies virus strain 486). The nanobody switches from having no inhibitory properties (tested up to 50 μM) to ∼3 nM IC50 in in vitro infectivity assays using porcine kidney (PK15) cells. The nanobody modifications use highly reliable bioconjugation to a three-dimensional wireframe deoxyribonucleic acid (DNA) origami scaffold. Mechanistic studies suggest that inhibition is mediated by the DNA origami scaffold bound to the virus particle, which obstructs the internalization of the viruses into cells, and that inhibition is enhanced by avidity resulting from multivalent virus and scaffold interactions. The assembled nanostructures demonstrate negligible cytotoxicity (<10 nM) and sufficient stability, further supporting their therapeutic potential. If translatable to other viral species and epitopes, this approach may open a new strategy that leverages existing infrastructures – monoclonal antibody development, phage display, and in vitro evolution - for rapidly developing novel antivirals in vivo.
ContributorsPradhan, Swechchha (Author) / Hariadi, Rizal (Thesis advisor) / Hogue, Ian (Committee member) / Varsani, Arvind (Committee member) / Chen, Qiang (Committee member) / Arizona State University (Publisher)
Created2022
Description
By increasing the mean and variance of environmental temperatures, climate change has caused local extinctions and range shifts of numerous species. However, biologists disagree on which populations and species are most vulnerable to future warming. This debate arises because biologists do not know which physiological processes are most vulnerable to temperature or how to model these processes in complex environments. Using the South American locust (Schistocerca cancellata) as a model system, my dissertation addressed this debate and explained how climate limits the persistence of locust populations. Locusts of S. cancellata are serious agricultural pests with occasional outbreaks covering up to 4 million km2 over six countries. Because outbreaks are largely driven by climate, understanding how climate limits the persistence of locusts may help predict crop losses in future climates. To achieve this aim, I integrated observational, experimental, and computational approaches. First, I tested a physiological model of heat stress. By measuring the heat tolerance of locusts under different oxygen concentrations, I demonstrated that heat tolerance depends on oxygen supply during the hatchling stage only. Second, I modeled the geographic distribution of locusts using physiological traits. I started by measuring thermal effects on consumption and defecation of field-captured locusts, and I then used these data to model energy gain in current and future climates. My results indicated that incorporating physiological mechanisms can improve the accuracy of models and alter predicted impacts of climate change. Finally, I explored the causes and consequences of intraspecific variation in heat tolerance. After measuring heat tolerance of locusts in different hydration states and developmental stages, I modeled survival in historical microclimates. My models indicated that recent climate change has amplified the risk of overheating for locusts, and this risk depended strongly on shade availability, hydration state, and developmental stage. Therefore, the survival of locusts in future climates will likely depend on their access to shade and water. Overall, my dissertation argues that modeling physiological mechanisms can improve the ability of biologists to predict the impacts of climate change.
ContributorsYoungblood, Jacob (Author) / Angilletta, Michael (Thesis advisor) / Buckley, Lauren (Committee member) / Cease, Arianne (Committee member) / Smith, Brian (Committee member) / Vanden Brooks, John (Committee member) / Arizona State University (Publisher)
Created2022
Description
Transorbital surgery has gained recent notoriety due to its incorporation into endoscopic skull base surgery. The body of published literature on the field is cadaveric and observation. The pre-clinical studies are focused on the use of the endoscope only. Furthermore the methodology utilised in the published literature is inconsistent and does not embody the optimal principles of scientific experimentation. This body of work evaluates a minimally invasive novel surgical corridor - the transorbital approach - its validity in neurosurgical practice, as well as both qualitatively and quantitatively assessing available technological advances in a robust experimental fashion. While the endoscope is an established means of visualisation used in clinical transorbital surgery, the microscope has never been assessed with respect to the transorbital approach. This question is investigated here and the anatomical and surgical benefits and limitations of microscopic visualisation demonstrated. The comparative studies provide increased knowledge on specifics pertinent to neurosurgeons and other skull base specialists when planning pre-operatively, such as pathology location, involved anatomical structures, instrument maneuvrability and the advantages and disadvantages of the distinct visualisation technologies. This is all with the intention of selecting the most suitable surgical approach and technology, specific to the patient, pathology and anatomy, so as to perform the best surgical procedure. The research findings illustrated in this body of work are diverse, reproducible and applicable. The transorbital surgical corridor has substantive potential for access to the anterior cranial fossa and specific surgical target structures. The neuroquantitative metrics investigated confirm the utility and benefits specific to the respective visualisation technologies i.e. the endoscope and microscope. The most appropriate setting wherein the approach should be used is also discussed. The transorbital corridor has impressive potential, can utilise all available technological advances, promotes multi-disciplinary co-operation and learning amongst clinicians and ultimately, is a means of improving operative patient care.
ContributorsHoulihan, Lena Mary (Author) / Preul, Mark C. (Thesis advisor) / Vernon, Brent (Thesis advisor) / O' Sullivan, Michael G.J. (Committee member) / Lawton, Michael T. (Committee member) / Santarelli, Griffin (Committee member) / Smith, Brian (Committee member) / Arizona State University (Publisher)
Created2021