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Alterations in Brain Metabolism in Pilocarpine-Induced Epilepsy and Potential Treatment Modalities.
No full textAbstract: Epilepsy is one of the most common chronic neurological disorders and is manifested by abnormal hypersynchronized neuronal discharge. A cascade of molecular, neuronal and metabolic alterations are involved in the process of developing epilepsy (epileptogenesis). The exact mechanisms underlying epileptogenesis are still unclear. In order to expand our knowledge and improve our understanding of epilepsy, we have investigated two main objectives. The first objective is identifying the role of HBP1 in epilepsy. HBP1 acts as Wnt repressor, and epileptogenesis occurs when Wnt signaling is up-regulated in an HBP1 knockout mouse. Importantly, deletion of 9 genes in the HBP1 chromosomal region in human populations (7q22.3) is associated with seizure or abnormal EEG, indicating the mouse model may recapitulate human disease. Utilizing 1H and 13C NMR spectroscopy, the metabolic profile of HBP1 knock out and wild type has been quantified in hippocampus, but no significant differences were detected. The second objective in this project was testing the efficacy of the EGCG/DAC combination (a HBP1 inducer) and observing its effect on the metabolism of normal and epileptogenic brain. The EGCG/DAC is proposed to be protective against the development of epilepsy. Using NMR the metabolite concentrations were obtained. A comparison between pilocarpine induced status epilepticus and control mice revealed a series of significant metabolite alterations. In hippocampus, GABA, AMP, NAD+, were significantly decreased in the pilocarpine group compared to control mice. In contrast, concentrations of IMP, lactate, UMP and myo-inositol were significantly increased in hippocampus. Glutamate and NAA were significantly decreased in pilocarpine group. On the other hand, glutamine was significantly up regulated in pilocarpine mice in both brain regions. Also, comparisons between pilocarpine and control in the background of being treated with the drugs versus pilocarpine and control groups respectively, showed significant increase of fumarate and UDP-glucuronate in treated control and no significant change was detected in the treated pilocarpine mice. Additionally, a comparison between treated pilocarpine and treated control groups displayed no significant difference, except for the significant increase of the O-phosphoethanolamine in treated control in contrast to ethanolamine which increased significantly in treated pilocarpine group. In conclusion, besides investigating the essential signaling pathway Wnt/𝛽-catenin and HBP1, we have examined the effect of EGCG/DAC in epilepsy in order to develop a paradigm shift in treating and preventing epilepsy disorders.Thesis (M.S.)--Tufts University, 2018.Submitted to the Dept. of Pharmacology and Drug Development.Advisor: James Baleja.Keyword: Pharmacology
The Placebo Effect in a Dish: Implications for Underlying Subcellular Mechanisms
No full textAbstract: The placebo effect is well known as one of the founding premises for FDA-sanctioned clinical trials of new medications, yet there is very little scientific understanding of the cellular substrates of the phenomenon and lack of predictive biomarkers for the strength of the placebo response. Few prior correlative studies on the neurobiology of the placebo effect suggests the activation of central dopamine neurotransmission during a placebo response. The present project intends to identify the cellular and molecular mechanisms that are linked to the placebo effect in peripheral paracrine and central monoamine-secreting cells. We follow an innovative and unconventional approach in trying to induce neurotransmitter release as a response to an inert stimulus in primary dissociated cells in culture. At this first stage of our studies, we chose to conduct our experiments in rat adrenal chromaffin cells which are considered an excellent model of exocytosis for catecholamine-releasing neurons and at the same time are crucially involved at the systems level in setting the sympathetic tone and in disorders like the Cushing syndrome and hyperprolactinemia. We use the cutting-edge method of carbon fiber amperometry to assess catecholamine quantal release in real time in response to a high potassium stimulating solution in physiological temperature (37oC). Following two stimulations within 10 minutes, we expose each chromaffin cell to only a physiological temperature saline and assess release of catecholamine quanta by cells based on the prior association between the active secretagogue and physiological temperature. Cells are otherwise bathing in room temperature aCSF media. We predict that the cells predisposed to a placebo response will release catecholamine quanta when exposed to physiological temperature saline without the active secretagogue. We then proceed to identify differences in catecholamine kinetics and vesicular stores involved in the release of quanta from placebo prone cells versus non-responding cells. The above study represents the first effort to describe the molecular signature of the placebo effect in an animal and cellular model. The end overall objective of such an effort would be the development of a screening assay for human patients identifying biomarkers for the potential of a placebo therapy in advance.Thesis (M.S.)--Tufts University, 2018.Submitted to the Dept. of Pharmacology and Drug Development.Advisor: Emmanuel Pothos.Keywords: Pharmacology, and Neurosciences
Epstein Barr Virus Encoded MicroRNAs Impact Proliferation and Autophagy in Transfected Cells in vitro
No full textAbstract: Epstein Barr Virus infects greater than 95% of the adult population and remains latent in memory B cells for the life of the host. EBV is associated with a number of cancers including Burkitt's lymphoma (BL), nasopharyngeal carcinoma (NPC), gastric carcinoma (GC), Hodgkin Lymphoma (HL) and others. Investigations into the causes of this association are necessary to improve outcomes for patients. The EBV viral genome encodes a number of genes that are transcribed during the course on infection, including proteins and microRNAs. Each transcription program is associated with a different stage in B cell differentiation, for example Latency III during the activated lymphoblast stage, Latency II during germinal center differentiation, and Latency I/0 during memory. EBV associated cancers can be characterized based on the infection stage of the cells they arose from. For example, NPC is Latency II, while BL is Latency I. Of the EBV encoded microRNAs, a subset of BARTs are only expressed during the proliferative Latency III phase, and are also found to be expressed in EBV associated cancers that otherwise characterized as EBV Latency II or I/0 cancers. Therefore, these microRNAs are expressed during rapid proliferation and are dysregulated in tumor samples, suggesting there may be a link between tumorigenesis and expression of this subset of microRNAs due to their common expression during period of cell cycle disregulation. Thus, I aimed to further elucidate the role of one or more BART microRNAs that are highly expressed during Latency III as well as in a number of EBV associated tumor samples. I sought to characterize the impact on host cell processes, including proliferation, growth, and survival. I was able to identify and validate a target for miR-BART10, ATP6V0e, which encodes a subunit of a V-Type ATPase that is involved in pH maintenance and autophagy. I also observed an increase in proliferation of relevant cell lines in vitro when transfected with miR-BART10, as well as miR-BART 14* and 18-5p.Thesis (M.S.)--Tufts University, 2018.Submitted to the Dept. of Immunology.Advisor: David Thorley Lawson.Committee: Alexander Poltorak, Linden Hu, and Marta Gaglia.Keyword: Immunology
An Uphill Battle: Nashville's Fight for Affordable Housing
No full textAbstract: Nashville, Tennessee adopted an inclusionary zoning ordinance in September 2016 that aims to incentivize affordable housing creation by requesting that new developments that contain five or more units or use public resources or property shall set aside a percentage of their units for affordable housing, so long as adequate financial incentives are available from the City to subsidize these units. The ordinance was created as a direct result of the rapid gentrification and displacement that long-term residents have been experiencing since development skyrocketed in Nashville after 2010. In April 2017, The Beacon Center of Tennessee filed a suit on behalf of the Homebuilders Association of Middle Tennessee against the City of Nashville, claiming that Nashville's inclusionary zoning ordinance is illegal and unconstitutional because it violates state law and the Fifth Amendment's Takings Clause. Although Nashville was able to get the Beacon Center of Tennessee's suit against it dismissed, the state of Tennessee stepped in and passed bill SB 0363, in March 2018, that nullified Nashville's inclusionary zoning ordinance. This thesis gives an overview of inclusionary zoning jurisprudence and assesses the legality of Nashville's policy through inclusionary zoning as a valid land use regulation adopted to ensure a proper balance of housing within a community and inclusionary zoning as an exaction. It also highlights the state government versus local government political barriers that Nashville's ordinance faced during its short-lived existence.Thesis (M.A.)--Tufts University, 2018.Submitted to the Dept. of Urban and Environmental Policy and Planning.Advisor: Jonathan Witten.Committee: Barbara Parmenter.Keyword: Urban planning
Land Use Change Patterns In Massachusetts 2001-2011: A Case Study using NLCD land cover data
No full textAbstract: This thesis will explore the utility of publicly available datasets specifically the National Land Cover Database (NLCD), Smart Location Database and MassGIS data to show ways in which urban planners and policy-makers in Massachusetts could better understand spatial land use change patterns and the correlation between land use change and built environment characteristics. In addition, the literature review provides an assessment of the use of NLCD data and a survey of existing research on how land use change is related to the built environment. The results suggest that a significantly large area changed to lower intensity developed urban area from forest in Massachusetts between 2001 and 2011. Land use change patterns were also significantly affected by the built environment of the location. Specifically, the regression models suggest that proximity to transit and transit-based accessibility to jobs were significant in making low-intensity land use change less likely and automobile-based access to jobs led to significantly higher low-intensity land use change. This thesis finds that NLCD, Smart Location and local GIS data like the data obtained from MassGIS, could be used to better understand the land use change patterns. Finally, it concludes with some limitations in data and methodology and suggestions for future research as well as some recommendations for planners and policy makers.Thesis (M.A.)--Tufts University, 2018.Submitted to the Dept. of Urban and Environmental Policy and Planning.Advisor: Sumeeta Srinivasan.Committee: Barbara Parmenter.Keywords: Land use planning, Geographic information science and geodesy, and Transportation
Characterization of Wave Actuation Methods in the Laboratory Environment for Use in Subsurface Investigation of Offshore Sites
No full textAbstract: There is a need for new technology to perform high resolution site characterization in subsea environments to support construction of offshore wind turbine foundations. The size and location of boulders across an offshore wind plot are crucial to the planning phase of these projects. Current site characterization techniques make use of high energy pressure waves in the water column, which are believed to harm the hearing of marine wildlife. In the Tufts Structures Lab an experimental setup has been built to test the use of localized waves with lower energies for conducting subsurface investigations. The electo-mechanical system consists of wave generation devices and transducers interfaced with sand. Two wave generation methods were developed, and responses were recorded by multiple subsurface transducers. Methods were compared based on wave velocities, polarization, and attenuation of energy through a 1-meter diameter tank filled with coarse sand.Thesis (M.S.)--Tufts University, 2018.Submitted to the Dept. of Mechanical Engineering.Advisor: Douglas Matson.Committee: John Germaine, and Laurie Baise.Keywords: Mechanical engineering, Civil engineering, and Geophysical engineering
Chalk talk & campus walks: Queer disruption and erasure on private, elite university campuses in the 80s and 90s
No full textAbstract: Chapter One of this thesis considers university belonging as it is formed, negotiated, and articulated around queer activism in three private, elite universities. It does so through building on Lauren Berlant and Michael Warner's (1998) classic polemic, "Sex in Public," and using a conceptual framework I call pure citizenship to explore the conditions of sanitization, erasure, and tenuous incorporation that often characterized universities' relationship to queer activism at the time. Specifically, I discuss four incidents in the late 1980s and early 1990s at Tufts University, Yale University, and Smith College when queer activist groups chalked "obscene" messages on the ground or postered "obscene" posters on walls, and the institutional and community response was to have them removed and erased. Using pure citizenship as a conceptual guide, this paper traces the complex institutional maneuvers through which the chalk and posters are removed—justifying the sanitization of "obscene" queer activism and incorporating more tenable forms of queerness within the fold of the university. Chapter Two is a methodological piece that introduces a way to examine archival photographs called foregrounding the background. Foregrounding the background is developed through critical pedagogical approaches to knowledge production. Specifically, foregrounding the background presents an optic switch, whereby the background of an archival photograph becomes the focal point of rigorous visual, analytical, and historical study. Foregrounding the background asks what an exploration of the background as critical subject might do to formulate a disruptive understanding of the photographed space and the actual, lived space. This paper explains this methodological approach using a 1981 photograph in the Tufts University yearbook.Thesis (M.A.)--Tufts University, 2018.Submitted to the Dept. of Education.Advisor: Sabina Vaught.Committee: Shameka Powell, and Nino Testa.Keywords: Education, and Education history
Development of a Three Dimensional Bioengineered hiPSC Derived Neural Network Model for the Study of Neurological Diseases
No full textAbstract: Three-dimensional (3D) in vitro cell culture models, particularly for the central nervous system, allow unparalleled exploration of human organ development, cellular interactions, and disease progression within defined environments. Here we describe the development and characterization of 3D tissue models that promote the differentiation and long-term survival of functional neural networks. These tissue models show diverse cell populations, including neurons and astroglial cells, interacting three-dimensionally with spontaneous neural activity. Electrophysiological recordings and calcium imaging performed over at least 14 months confirms this activity. This model allows for the direct integration of pluripotent stem cells into the 3D construct bypassing early neural differentiation steps (embryoid bodies and neural rosettes), which streamlines the process while also providing a system that can be manipulated to support a variety of experimental applications. We have tested this tissue model with stem cells derived from healthy individuals as well as from Alzheimer's and Parkinson's disease patients. Similar growth and gene expression indicate potential use in the modeling of disease states related to neurodegeneration.Thesis (Ph.D.)--Tufts University, 2018.Submitted to the Dept. of Cell, Molecular & Developmental Biology.Advisors: David Kaplan, and Yongie Yang.Committee: James Schwob, and Lauren Black.Keywords: Biomedical engineering, Cellular biology, and Neurosciences
Surface-initiated photopolymerization for cell immobilization and high-purity genome extraction.
No full textThis is the poster for the Summer Scholars conference (Oct 19th, 2018) on two projects I have been working on. Submitted in partial fulfillment of the grant requirement of the Tufts Summer Scholars Program
Making the Journey from Wild to Tame: What Makes Some Wild Horses More Adoptable.
No full textA summer scholars research project on American wild horses adopted in the Northeast and what factors contribute to their ease of integration into domestication. Submitted in partial fulfillment of the grant requirement of the Tufts Summer Scholars Program