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Full-Text Articles in Life Sciences

Endocannabinoid-Mediated Synaptic Plasticity In The Ventral Tegmental Area And Hippocampus, Lindsey Nicole Friend Dec 2016

Endocannabinoid-Mediated Synaptic Plasticity In The Ventral Tegmental Area And Hippocampus, Lindsey Nicole Friend

Theses and Dissertations

Synaptic plasticity is the process whereby connections between neurons can be altered in an experience dependent manner. For example, drugs of abuse alter plasticity in the ventral tegmental area (VTA) of the midbrain. A large amount of research has been applied to uncovering the mechanism whereby synapses on the reward signaling dopamine cells is altered, however, less is known regarding the VTA inhibitory GABA neurons. Our objective was to examine the ability of GABA neurons to exhibit plasticity, and determine how drugs of abuse could influence it. Here we report a novel type of plasticity of excitatory neurotransmission onto VTA …


The Effects Of L-Cysteine On Alzheimer's Disease Pathology In Apoe2, Apoe3, And Apoe4 Homozygous Mice, Stephen Gerard Cieslak Dec 2016

The Effects Of L-Cysteine On Alzheimer's Disease Pathology In Apoe2, Apoe3, And Apoe4 Homozygous Mice, Stephen Gerard Cieslak

Theses and Dissertations

The APOE gene is of profound importance regarding the onset of Alzheimer's disease (AD). From the small physical differences among the protein products of the isoforms of this gene arises a profound difference in their physiologies. For example, the APOE2 isoform confers resistance to AD, the APOE3 isoform confers neutral susceptibility to AD, and the APOE4 isoform confers proneness to AD. L-cysteine is an amino acid that has several anti-AD properties, among which are its ability to sequester iron and form glutathione – a powerful antioxidant – and therefore may be a promising potential dietary supplement for ameliorating AD …


A Semi-Automated Algorithm For Segmenting The Hippocampus In Patient And Control Populations, Nathan Mckay Muncy Jun 2016

A Semi-Automated Algorithm For Segmenting The Hippocampus In Patient And Control Populations, Nathan Mckay Muncy

Theses and Dissertations

Calculating hippocampal volume from Magnetic Resonance (MR) images is an essential task in many studies of neurocognition in healthy and diseased populations. The `gold standard' method involves hand tracing, which is accurate but laborious, requiring expertly trained researchers and significant amounts of time. As such, segmenting large datasets with the standard method is impractical. Current automated pipelines are inaccurate at hippocampal demarcation and volumetry. We developed a semi-automated hippocampal segmentation pipeline based on the Advanced Normalization Tools (ANTs) suite of programs to segment the hippocampus. We applied the semi-automated segmentation pipeline to 70 participant scans (26 female) from groups that …


Glutamate And Gaba Receptor-Mediated Plasticity In The Mesolimbic Dopamine System By Alcohol, Ashley Cerise Nelson Jun 2016

Glutamate And Gaba Receptor-Mediated Plasticity In The Mesolimbic Dopamine System By Alcohol, Ashley Cerise Nelson

Theses and Dissertations

Alcoholism is a devastating chronic relapsing disorder with significant costs to individuals and society. The mesolimbic dopamine (DA) system plays an important role in regulating reward and addiction. GABA neurons located in the ventral tegmental area (VTA) regulate VTA DA neuron activity, and are a relevant target for alcohol in the brain. VTA GABA neurons exhibit marked hyperexcitability during withdrawal from ethanol. Past research has demonstrated that the motivational effects of opiates cause a change in VTA GABA(A) receptors in opiate-dependent animals, which switch from a GABA-induced hyperpolarization of GABA neurons to a GABA-induced depolarization. The focus of this study …


An Evaluation Of The Influences Of Extra-Hippocampal Processes On Pattern Separation, Malia L. Anderson Apr 2016

An Evaluation Of The Influences Of Extra-Hippocampal Processes On Pattern Separation, Malia L. Anderson

Theses and Dissertations

Long-term declarative memory depends on pattern separation, which reduces the degree of overlap between similar representations, to maintain memory specificity, and on pattern completion, which occurs when a degraded cue is used to retrieve a previously stored memory. Previous studies aimed at evaluating the underlying neuronal substrates of these computational processes have used a mnemonic discrimination paradigm and fMRI to focus on the hippocampus, to the exclusion of cortical processing. We aim to investigate the influences extra-hippocampal processes have on pattern separation in the following two studies. Study 1. Computational models of pattern completion suggest it occurs cortically and results …


Identification And Characterization Of Serum Biomarkers Associated With Breast Cancer Progression, Adhari Abdullah Alzaabi Mar 2016

Identification And Characterization Of Serum Biomarkers Associated With Breast Cancer Progression, Adhari Abdullah Alzaabi

Theses and Dissertations

Despite the recognized advances in the treatment of breast cancer, it still accounts for 15% of all cancer-related deaths. 90% of breast cancer deaths are due to unpredicted metastasis. There is neither successful treatment for metastatic patients nor a specific test to predict or detect secondary lesions. Patients with primary tumor will be either over-treated with cytotoxic side effects or under-treated and risk recurrence. This necessitates the need for personalized treatment, which is hard to offer for such heterogeneous disease. Obstacles in treating breast cancer metastasis are mainly due to the gaps exist in the understanding of the molecular mechanism …


Forward Chemical Genetics Drug Screen Yields Novel Proteases And Proteolytic Inhibitors Of Hgf–Induced Epithelial–Mesenchymal Transition, Jeffrey Thomas Schuler Mar 2016

Forward Chemical Genetics Drug Screen Yields Novel Proteases And Proteolytic Inhibitors Of Hgf–Induced Epithelial–Mesenchymal Transition, Jeffrey Thomas Schuler

Theses and Dissertations

Hepatocyte Growth Factor (HGF)–induced Epithelial–Mesenchymal Transition (EMT) is a complex cellular pathway that causes epithelial cell scattering by breaking cell–cell contacts, eliminating apical–basal polarity, and replacing epithelial markers and characteristics with mesenchymal markers. Early EMT events include a brief period of cell spreading, followed by cell compaction and cell–cell contact breaks. A forward chemical genetics drug screen of 50,000 unique compounds measuring HGF–induced cell scattering identified 26 novel EMT inhibitors, including 2 proteolytic inhibitors. Here, we show that B5500–4, one of the EMT inhibitors from the screen, blocks HGF–induced EMT by a predicted blocking of the protease furin, in addition …


A Neuroimaging Investigation Of The Effects Of Age And Sleep On Pattern Separation, Christopher Robert Doxey Mar 2016

A Neuroimaging Investigation Of The Effects Of Age And Sleep On Pattern Separation, Christopher Robert Doxey

Theses and Dissertations

Effective memory representations must be specific to prevent interference between episodes that may overlap in terms of place, time, or items present. Pattern separation, a computational process performed by the hippocampus overcomes this interference by establishing non-overlapping memory representations. This project explores pattern separation and how it is impacted by age and sleep. Experiment 1. Structures of the medial temporal lobe (MTL) are known to be involved in declarative memory processes. However, little is known about how age-related changes in MTL structures, white matter integrity, and functional connectivity affect pattern separation processes in the MTL. In the present study, we …


Rab8 Mediates Trpv4 Vesicle Trafficking To The Plasma Membrane In Hgf-Stimulated Mdck Cells, Hillary Jean Haws Mar 2016

Rab8 Mediates Trpv4 Vesicle Trafficking To The Plasma Membrane In Hgf-Stimulated Mdck Cells, Hillary Jean Haws

Theses and Dissertations

Epithelial to mesenchymal transition (EMT) is a process whereby epithelial cells, which act collectively through robust cell–cell interactions, take on mesenchymal characteristics, breaking cell–cell junctions to become solitary, invasive and motile. Our previous results show that a transient increase in calcium influxes through TRP channels at the plasma membrane is required for hepatocyte growth factor (HGF)– stimulated EMT. Since this transient increase requires an intact microtubule cytoskeleton, we propose that HGF stimulation results in the mobilization of calcium channels to the plasma membrane from an intracellular compartment via microtubule–dependent vesicle trafficking. Through immunofluorescence, we show that prior to HGF treatment, …


The Role Of Hypoxia On Pyruvate Kinase M2, Mammalian Target Of Rapamycin, Mitochondrial Function, And Cell Invasion In The Trophoblast, Rebecca Lutz Kimball Mar 2016

The Role Of Hypoxia On Pyruvate Kinase M2, Mammalian Target Of Rapamycin, Mitochondrial Function, And Cell Invasion In The Trophoblast, Rebecca Lutz Kimball

Theses and Dissertations

This thesis will be organized into two chapters discussing the role of hypoxia in the human placenta. The goal of this thesis is to characterize pyruvate kinase M2, mammalian target of rapamycin, mitochondrial function, and cell invasion in hypoxic conditions in the trophoblast. Understanding the mechanisms of placental metabolism can lead to further treatments for placental diseases. Chapter one covers the background of intrauterine growth restriction, hypoxia, placental metabolism, and pyruvate kinase M2 (PKM2). Little is currently understood about the role of the mitochondria in placental diseases. Expression of PKM2, trophoblast cell invasion, and mitochondrial function is shown to be …