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Articles 1 - 11 of 11
Full-Text Articles in Molecular and Cellular Neuroscience
Visualization And Characterization Of The Immunological Synapse Between Chlorotoxin Chimeric Antigen (Cltx-Car) Redirected T Cells And Targeted Glioblastoma Tumors, Arianna Livi
CMC Senior Theses
Chimeric Antigen Receptor T (CAR-T) cells have demonstrated anti-tumor activity against aggressive and invasive cancers such as glioblastoma (GBM); however, clinical response rates remain low in clinical trial studies. Tumor heterogeneity and tumor microenvironment conditions pose significant challenges for treatment of GBM, thus continuous optimization of CAR-T cell therapies and identification of novel, widely expressed, and highly specific GBM antigens are vital to better patient outcomes. A newly developed CAR-T cell construct incorporating chlorotoxin (CLTX) as the targeting domain exhibited broad GBM-targeting capabilities and elicited potent cytotoxic effects during preclinical studies and is currently being tested in a phase I …
Expression Of Htyr In Drosophila As A Novel Model Of Parkinson’S Disease, Madeleine Callan
Expression Of Htyr In Drosophila As A Novel Model Of Parkinson’S Disease, Madeleine Callan
Scripps Senior Theses
Parkinson’s disease is a debilitating and often deadly neurodegenerative disease affecting a growing and large population. Its etiology has long remained elusive, and because no other organisms have Parkinsonian-like diseases, it is difficult to study PD using model organisms. Neuromelanin (NM), an insoluble melanin synthesized in the dopaminergic synthesis pathway in DA neurons, has recently been implicated in PD as a major causal factor. At high levels in DA lysosomes, it functions as a proteostatic pathway inhibitor–blocking dopaminergic neurons from breaking down harmful molecules until the lysosomes eventually degenerate as well as triggering autophagy, inflammation, and total neurodegeneration. Recently, neuromelanin …
Biomechanics And Neural Control Of Movement: Cmi's Effects On Downstream Motor Processing And Gait In Forwards And Backwards Walking, Christopher Choi
Biomechanics And Neural Control Of Movement: Cmi's Effects On Downstream Motor Processing And Gait In Forwards And Backwards Walking, Christopher Choi
CMC Senior Theses
Analyzing the effects of cognitive motor interferences (CMI) on walking is usually done in patients with neurological comorbidity or during forward walking (FW). However, there are few studies that examine gait differences between FW and backward walking (BW) under the presence of CMI when speed is kept constant on a treadmill. In this study we examined how CMI would disrupt sensory feedback and affect the descending motor pathway. We hypothesized that subjects that walked backwards and were given a cognitive task would show the greatest differences in gait due to a lack of visual input and the presence of CMI. …
Targeted Genome-Scale Gene Activation And Gene Editing In Human Cells To Understand Disease Models, Michael De La Cruz
Targeted Genome-Scale Gene Activation And Gene Editing In Human Cells To Understand Disease Models, Michael De La Cruz
KGI Theses and Dissertations
Since the discovery of sequence directed DNA editing reagents such as CRISPR-Cas9 RNA-guided and TALEN DNA endonucleases, there has been a snowball of advances in the life sciences due to the ability to efficiently edit and control genomes within living cells. CRISPR-Cas9 based genomic tools, which facilitate the high-throughput precise manipulation of genes, allow for unbiased functional genomic screens. We used a human CRISPR-Cas9 Synergistic Activation Mediator pooled library which utilizes an engineered protein complex for transcriptional activation of 23,430 endogenous genes to investigate the development of novel resistance mechanisms to lung cancer targeted therapy, Erlotinib. We set out to …
A Composite Review Of The Proposed Molecular Mechanisms And Genetic Components Underlying Parkinson’S Disease, Paige Brodrick
A Composite Review Of The Proposed Molecular Mechanisms And Genetic Components Underlying Parkinson’S Disease, Paige Brodrick
Scripps Senior Theses
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the progressive death of dopaminergic neurons present in the substantia nigra. The clinical presentation of PD includes tremors, slowed movement (bradykinesia), muscle and limb rigidity, and difficulty with walking and balancing. While many environmental factors can affect the onset and progression of the disease, genetic mutations have a large influence. Of the identified PD-linked genetic mutations, mutations in the leucine-rich repeat kinase 2 (LRRK2) are one of the most common genetic causes of PD. Located in endosomes, LRRK2 has been shown to play a role in the sorting and endocytosis …
Investigating Neurogenesis As A Veritable Epigenetic Endophenotype For Alzheimer's Disease, Layne Wells
Investigating Neurogenesis As A Veritable Epigenetic Endophenotype For Alzheimer's Disease, Layne Wells
Scripps Senior Theses
Alzheimer's disease (AD) is the most common neurodegenerative disease, characterized by progressive amyloid plaque aggregation, neurofibrillary tangles, and cortical tissue death. As the prevalence of AD is projected to climb in coming years, there is a vested interest in identifying endophenotypes by which to improve diagnostics and direct clinical interventions. The risk for complex disorders, such as AD, is influenced by multiple genetic, environmental, and lifestyle factors. Significant strides have been made in identifying genetic variants linked to AD through the genome-wide association study (GWAS). It has been estimated in more recent years, however, that GWAS-identified variants account for limited …
Evidence-Based Probiotic Intervention For Behavioral And Social Deficits In Autism Spectrum Disorder, Allisen To
Evidence-Based Probiotic Intervention For Behavioral And Social Deficits In Autism Spectrum Disorder, Allisen To
Scripps Senior Theses
Autism Spectrum Disorder (ASD) refers to a heterogeneous neurological condition characterized by repetitive and restrictive behaviors and social communication deficits. ASD diagnoses are at a record high, at approximately 1 in 59 children according to the US Center for Disease Control. Currently, there are no available interventions that effectively treat the core symptoms of ASD. All pharmaceutical options address comorbid side effects of ASD but not core deficits and are particularly associated with negative side effects. Additionally, there are economic and geographic barriers that can prevent families of individuals with ASD from seeking or receiving effective interventions. Many of the …
Understanding Huntington's Disease Using Machine Learning Approaches, Sonali Lokhande
Understanding Huntington's Disease Using Machine Learning Approaches, Sonali Lokhande
KGI Theses and Dissertations
Huntington’s disease (HD) is a debilitating neurodegenerative disorder with a complex pathophysiology. Despite extensive studies to study the disease, the sequence of events through which mutant Huntingtin (mHtt) protein executes its action still remains elusive. The phenotype of HD is an outcome of numerous processes initiated by the mHtt protein along with other proteins that act as either suppressors or enhancers of the effects of mHtt protein and PolyQ aggregates. Utilizing an integrative systems biology approach, I construct and analyze a Huntington’s disease integrome using human orthologs of protein interactors of wild type and mHtt protein. Analysis of this integrome …
Characterizing A Novel Monoclonal Ampa Receptor 1/2/3 Antibody In The Hippocampus And Prefrontal Cortex Of Rat, Monkey, And Human, Sebastian Aguiar
Characterizing A Novel Monoclonal Ampa Receptor 1/2/3 Antibody In The Hippocampus And Prefrontal Cortex Of Rat, Monkey, And Human, Sebastian Aguiar
Pitzer Senior Theses
The excitatory, ionotropic glutamatergic AMPA receptor is the most common membrane-bound receptor in the central nervous system. AMPARs and the NMDA receptors are central to synaptic plasticity, memory, and mechanisms of neurodegeneration. The AMPAR is an obligate heterotetramer, composed of subunits GluA1-4. Subunit permutation determines ion conductance, trafficking and other functional characteristics. Few available antibodies are subunit-specific, disabling researchers from accurately visualizing differential AMPAR subunit distribution in the nervous system. This study sought to visualize a novel monoclonal GluA1/2/3 antibody with functional avidity for three of four receptor subunits and to characterize the ultrastructural localization of these receptors using confocal …
A Dna Computer For Glioblastoma Multiforme Diagnosis And Drug Delivery, Sumaiya F. Hashmi
A Dna Computer For Glioblastoma Multiforme Diagnosis And Drug Delivery, Sumaiya F. Hashmi
CMC Senior Theses
Glioblastoma multiforme (GBM) is a debilitating malignant brain tumor with expected patient survival of less than a year and limited responsiveness to most treatments, often requiring biopsy for diagnosis and invasive surgery for treatment. We propose a DNA computer system, consisting of input, computation, and output components, for diagnosis and treatment. The input component will detect the presence of three GBM biomarkers: vascular endothelial growth factor (VEGF), caveolin-1α (CAV), and B2 receptors. The computation component will include indicator segments for each of these genes, and ensure that output is only released if all the biomarkers are present. The output component …
A Proposal To Test The Effects Of Factor Ecat1 On Pluripotency, From Reprogramming To Differentiation Of Human Somatic Cells, Vritti R. Goel
A Proposal To Test The Effects Of Factor Ecat1 On Pluripotency, From Reprogramming To Differentiation Of Human Somatic Cells, Vritti R. Goel
CMC Senior Theses
The field of stem cell research has been growing more because of the interest in using stem cells to cure diseases and heal injuries. Human embryonic stem cells, because of the controversy surrounding them—and subsequently the difficulties in acquiring samples of the existing aging cell lines—can only be used in limited capacities. While the development of induced pluripotent stem cells in the last decade has allowed the field to progress closer to medical treatments, the low efficiency of reprogramming a somatic cell to a pluripotent state, and the vast molecular and genomic differences between human embryonic stem cells and human …