Marco
Alarcon
Sponsor: Weici Zhang, Ph.D. MED: Int Med Rheumatology Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by the immune-mediated inflammatory destruction of small bile ducts. However, the mechanisms of PBC remain unknown. Since the presence of anti-mitochondrial antibodies (AMAs) is one of the biomarkers of PBC, we aim to investigate whether AMAs exerts a pathogenic role in PBC. To do so, we took advantage of an ARE-Del murine model to study the effects of injecting mice with the recombinant hPDC-E2 protein in order to activate an immune response. In doing so, we induced the mice to develop AMAs and harvested serum samples at week 0 (pre-immunization), 2 (two weeks post-immunization), and 4 (two weeks post-secondary immunization). We measured the relative auto-antibody titer of each set of serum samples by running ELISA experiments on heart and liver lysates. Furthermore, we harvested and stained the liver to visualize the extent of immune cell infiltrations as a proxy for AMA induced damage. Our results showed that there was a significant increase in auto-antibodies against the heart and liver lysates as well as increased liver infiltration of immune cells compared to the controls. Based on these findings, we can now further investigate the pathogenesis of AMAs in relation to PBC. Mutagenesis of PSD-95 To Identify Residues Important for Regulating Synaptic Plasticity
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Authors:
Marco Alarcon
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Dendritic spines are dynamic neuronal structures that play an integral role in the synaptic plasticity vital for learning and memory. Previous experiments demonstrate that the expression level of PSD-95, a synaptic scaffolding protein present in dendritic spines, regulates their ability to undergo long-term changes in size that are associated with learning. However, which domains of PSD-95 play important roles in this effect remains unknown. In order to identify the domains that are vital for this function of PSD-95 in synaptic plasticity, I am cloning mutant forms of PSD-95 which contain mutations in the PDZ binding domains of the protein, thus inhibiting the ability of PSD-95 to bind to other proteins in dendritic spines. Initial attempts at mutagenesis have focused on the PDZ1-2 domains of PSD-95, which inhibit binding to transmembrane receptors, such as glutamate receptors, in dendritic spines. These mutations have strong potential to shed light on the mechanisms of spaced learning, a learning strategy which has been shown to improve learning in animal models that display learning deficiencies, such as fragile X and down syndrome models. Morphology of Lower and Middle Cambrian Oncoids from the Carrara Formation at Emigrant Pass Eduardo Alatorre Acevedo
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UC Davis / Neuro Physio & Behavior / 2024
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Marco Alarcon