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Full-Text Articles in Medicine and Health Sciences
Motor And Sensory Characterization Of A Mouse Model Of Charcot-Marie-Tooth Type 2o Disease, Swaran Nandini
Motor And Sensory Characterization Of A Mouse Model Of Charcot-Marie-Tooth Type 2o Disease, Swaran Nandini
Electronic Theses and Dissertations
Dynein is an essential motor protein required for the maintenance and survival of cells. Dynein forms a motor complex to carry intracellular cargoes like organelles, growth factors, peptides, and hormones along the microtubules inside the cells. In neurons, the dynein is the retrograde motor protein that moves cargoes from the neuronal tip to the neuronal soma along the length of an axon. Dynein has an established role in neuronal nuclear migration, transport of neuronal survival signals and growth factors, organelle positioning inside neurons etc. Hence, it is not very surprising that numerous mutations in dynein have been reported in association …
Ab Toxins: Recovery From Intoxication And Relative Potencies, Patrick Cherubin
Ab Toxins: Recovery From Intoxication And Relative Potencies, Patrick Cherubin
Electronic Theses and Dissertations
AB-type protein toxins have a catalytic A subunit attached to a cell-binding B subunit. Ricin, Shiga toxin (Stx), exotoxin A, and diphtheria toxin are AB toxins that act within the host cytosol and kill the host cell through pathways involving the inhibition of protein synthesis. Our overall goal is to help elucidate the cellular basis of intoxication for therapeutic development. According to the current model of intoxication, the effect of AB toxins is irreversible. To test this model, we developed a system that uses flow cytometry and a fluorescent reporter to examine the cellular potency of toxins that inhibit protein …
Unraveling Pdi And Its Interaction With Ab Toxins, Jessica Guyette
Unraveling Pdi And Its Interaction With Ab Toxins, Jessica Guyette
Electronic Theses and Dissertations
Protein disulfide isomerase (PDI) is an essential endoplasmic reticulum (ER) protein that acts as both an oxidoreductase and chaperone. It exhibits substantial flexibility and undergoes cycles of unfolding and refolding in its interaction with cholera toxin (Ctx), which is a unique property of PDI. This unfolding allows PDI to disassemble the Ctx holotoxin, which is required for Ctx activity. Here, we investigated the unfolding and refolding property of PDI and how this affects its interaction with bacterial toxins. PDI showed remarkable redox-linked conformational resilience that allows it to refold after being thermally stressed. Deletion constructs of PDI showed that both …
It Takes Two To Tango: The Toxin-Chaperone Relationship, Alisha Kellner
It Takes Two To Tango: The Toxin-Chaperone Relationship, Alisha Kellner
Electronic Theses and Dissertations
Cholera toxin (CT) enters the cell via receptor-mediated endocytosis and travels in a retrograde fashion to the endoplasmic reticulum (ER). The catalytic A1 subunit (CTA1) is then displaced from the rest of the holotoxin, unfolds, and is exported to the cytosol where it regains an active conformation for the ADP-ribosylation of its G-protein target. We have shown that the cytosolic chaperones Hsp90 and Hsc70 are required for CTA1 translocation to the cytosol. We have also shown that both are able to independently bind and refold CTA1. Using libraries of CTA1-derived peptides, we have identified a single Hsc70 binding site, YYIYVI …
Development Of A Functional Testing Platform For The Sensory Segment Of The Neuromuscular Reflex Arc, Alisha Colon
Development Of A Functional Testing Platform For The Sensory Segment Of The Neuromuscular Reflex Arc, Alisha Colon
Electronic Theses and Dissertations
Investigations of human biology and disease have been hindered by the use of animal models. The information obtained from such studies often results in clinically irrelevant results and drug trial failures. Additionally, several governing bodies have been formulating legislation to move away from animal models and toward more ethical and efficient testing platforms for drug discovery and cosmetic research. As an answer to these issues, "body-on-a-chip" systems have been a rapidly developing field which easily recapitulates in vivo functionality, providing a more relevant, repeatable, and ethical testing platform to better predict biology. These systems can be used as human-based testing …
Synthesis And Bioevaluation Of Methionine Depletion Agents, Houssine Ikhlef
Synthesis And Bioevaluation Of Methionine Depletion Agents, Houssine Ikhlef
Electronic Theses and Dissertations
The native polyamines (putrescine, spermidine, and spermine) are low molecular weight amines that exist as polycations at physiological pH. These polycations interact with DNA, RNA, and influence many cellular processes. Intracellular polyamine levels are maintained via a balance of polyamine biosynthesis, catabolism, and transport. Ornithine, an amino acid obtained from L-arginine, is decarboxylated by ornithine decarboxylase (ODC) to form putrescine. The biosynthesis of the higher polyamines, spermidine and spermine, requires the addition of an amino-propyl group donated by decarboxylated S-adenosylmethionine (dc-SAM), which itself is derived from the amino acid L-methionine (Met). Tumor cells are heavily reliant on methionine because it …
Mechanism Of Nanogp8 In Glioblastoma Multiforme, Jonhoi Smith
Mechanism Of Nanogp8 In Glioblastoma Multiforme, Jonhoi Smith
Electronic Theses and Dissertations
Glioblastoma multiforme (GBM) is an incurable brain tumor, with patients only expecting to live 15 to 16 months post-diagnosis with the most current treatments options including surgery, chemotherapy, and radiation. How GBM resist treatment is still not very well known. However, cancer stem cells (CSCs), a subset of cells in GBM tissue considered responsible for therapeutic resistance and the poor patient prognosis. NANOG, a homeobox gene, is responsible for maintaining pluripotency of embryonic stem cells and is observed in CSCs. NANOGP8, a retrogene in the NANOG family is expressed in CSCs and provides cells with stem-like characteristics previously observed in …