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Articles 1 - 7 of 7
Full-Text Articles in Life Sciences
Antibiotic Drug Discovery Targeting Bacterial Metabolism, Miranda J. Wallace
Antibiotic Drug Discovery Targeting Bacterial Metabolism, Miranda J. Wallace
Theses and Dissertations (ETD)
Over the last century, the use of antibiotics has enabled many advances in modern medicine, making life as we know it possible. In recent years, however, emerging bacterial resistance to virtually all major antibiotic classes has resulted in a worldwide increase in morbidity, mortality, and financial burden associated with drug resistant infections. The antimicrobial resistance crisis presents an urgent need for new antimicrobials with distinct mechanisms of action from existing drugs. The current pharmaceutical pipeline of new antibiotics is limited due to three obstacles: a lack of understanding of resistance mechanisms, a dearth of novel mechanisms of action among new …
Investigation Of Riluzole’S Synaptic Protection Mechanism Through Hsf1-Bdnf Axis, Yi Zhang
Investigation Of Riluzole’S Synaptic Protection Mechanism Through Hsf1-Bdnf Axis, Yi Zhang
Theses and Dissertations (ETD)
The FDA-approved amyotrophic lateral sclerosis (ALS) drug Riluzole has great potential in treating Alzheimer’s disease (AD) based on promising animal data as well as its known action on modulating synaptic transmission. However, its detailed mechanism of action is not fully understood. Here, we proposed work aiming to address this aspect via focus- ing on the Heat Shock Factor 1 (HSF1)-dependent mechanisms. We found that Riluzole could increase HSF1 and BDNF (Brain-Derived Neurotrophic Factor) expression both at transcriptional and translational levels. CA1 (Cornu Ammonia, the first region in the hip- pocampal circuit), is its main target. We also demonstrated a protective …
The Role Of Secretory Phospholipase A2 Group Iia In Obesity And Metabolism, Michael S. Kuefner
The Role Of Secretory Phospholipase A2 Group Iia In Obesity And Metabolism, Michael S. Kuefner
Theses and Dissertations (ETD)
Secretory phospholipase A2 group IIA (PLA2G2A) is a member of a family of secretory phospholipases previously implicated in inflammation, atherogenesis, and antibacterial actions. These enzymes hydrolyze glycerophospholipids at the sn-2 position releasing lysophospholipids and fatty acids. Though studies have shown PLA2G2A is pro-inflammatory and promotes atherosclerosis, no research has analyzed the role of this enzyme in obesity and metabolism. Studies in the past 5-10 years utilizing various knock- out or over-expression mouse models have analyzed the role of different secretory phospholipase A2s (sPLA2) in metabolic diseases. From these studies, it is known that at least seven of the 11 sPLA2 …
Regulation Of Cyp3a5 In Pancreatic Ductal Adenocarcinoma, Jessica D. Hoyer
Regulation Of Cyp3a5 In Pancreatic Ductal Adenocarcinoma, Jessica D. Hoyer
Theses and Dissertations (ETD)
CYP3A5 is a drug metabolism enzyme that is polymorphically expressed in normal tissues and expressed in high amounts in some cancers, including pancreatic ductal adenocarcinoma (PDAC). There have been several published studies regarding CYP3A5 regulators, but there is still much to be discovered concerning CYP3A5 regulation in cancer. To further understand the regulation of CYP3A5, a high-throughput screen was performed in the AsPC-1 PDAC cell line. This screen employed small interfering RNA (siRNA) targeting transcription factors and chromatin-associated proteins. We identified siRNA that decreased CYP3A5 mRNA and protein levels in AsPC-1 cells and probed into the potential mechanisms. Taken together, …
Challenging The Paradigm Of Clinical Triazole Resistance In Aspergillus Fumigatus, Jeffrey Michael Rybak
Challenging The Paradigm Of Clinical Triazole Resistance In Aspergillus Fumigatus, Jeffrey Michael Rybak
Theses and Dissertations (ETD)
Invasive aspergillosis is a leading cause of morbidity and mortality among immunocompromised populations and is predicted to cause more than 200,000 life- threatening infections each year. Aspergillus fumigatus is the most prevalent pathogen isolated from patients with invasive aspergillosis, accounting for more than 60% of all cases. Currently, the only antifungal agents available with consistent activity against A. fumigatus are the mold-active triazoles and amphotericin B, of which the triazoles commonly represent both front-line and salvage therapeutic options. Unfortunately, the treatment of infections caused by A. fumigatus has recently been further complicated by the global emergence of triazole resistance among …
An Investigation Into Clinically Relevant Determinants Of Azole Resistance In Candida Albicans, Andrew T. Nishimoto
An Investigation Into Clinically Relevant Determinants Of Azole Resistance In Candida Albicans, Andrew T. Nishimoto
Theses and Dissertations (ETD)
"Candida albicans is a commensal organism commonly colonizing the human gut and skin. As an opportunistic pathogen, it can cause persistent and serious infections in individuals with compromised immune systems, including the very young and elderly. Moreover, C. albicans can cause a wide spectrum of diseases ranging from superficial mucosal infections to life-threatening invasions of the organs and bloodstream. Candida species are the most common cause of invasive fungal disease, which is associated with high mortality and imposes a heavy toll on the healthcare system. Over the last 30 years, the azole antifungals have been a mainstay of antifungal therapy, …
Using Genetic Diversity To Understand Susceptibility To Cognitive Decline In Aging And Alzheimer’S Disease, Sarah M. Neuner
Using Genetic Diversity To Understand Susceptibility To Cognitive Decline In Aging And Alzheimer’S Disease, Sarah M. Neuner
Theses and Dissertations (ETD)
An individual's genetic makeup plays an important role in determining susceptibility to cognitive aging and transition to dementia such as Alzheimer's disease (AD). Identifying the specific genetic variants that contribute to cognitive aging and AD may aid in early diagnosis of at-risk patients, as well as identify novel therapeutics targets to treat or prevent development of symptoms. Challenges to identifying these specific genes in human studies include complex genetics, difficulty in controlling environmental factors, and limited access to human brain tissue. Here, we turned to genetically diverse mice from the BXD genetic reference panel (GRP) to overcome some of the …