Digital Commons Network^™

Genetic Analysis Of A Novel Ftsk Homolog, Hfka, In Streptomyces Coelicolor Development-Associated Chromosome Segregation, Sumedha Sethi

Electronic Theses and Dissertations

A quintessential phenomenon occurring during prokaryotic development is accurate segregation of the replicated genomes into the daughter cells. Key energy-dependent processes like chromosome condensation and subcellular partitioning of the genomes are driven by conserved proteins like SMC, ParB, FtsK. During its complex developmental cycle, Streptomyces coelicolor segregates its genomes into chains of unicellular spores when its multigenomic syncytial aerial hyphae undergo division.

A novel ftsK-like gene, hfkA (Homolog of FtsK protein A), was examined for function and localization during development-associated chromosome segregation. Individual deletions did not affect segregation, but a ΔhfkA ΔftsK mutant exhibited 8% anucleate …

Transcription Regulation Of Human Il1b Gene In Monocytes And Lymphoid Cd4 T Cells, Sree H. Pulugulla

Electronic Theses and Dissertations

Cytokines are key regulators of the inflammatory response and play an important role in facilitating intercellular communication between various immune cell types. Interleukin‑1β (IL‑1β) is a potent pro-inflammatory cytokine that is required for robust initiation of innate immune response and subsequent development of adaptive immunity. IL-1β is first synthesized as an inactive cytoplasmic, non‑glycosylated, precursor molecule (proIL‑1β) by monocytes and macrophages in response to invading pathogenic microbes. The activation of caspase‑1 by inflammasomes cleaves proIL-1β into mature biologically active IL-1β that is released from cells via a non-classical, endoplasmic reticulum‑independent secretory pathway directly from the cytoplasm via Gasdermin D membrane …

State-Dependent Mapping Of Glyr-Cholesterol Interactions By Coupling Crosslinking With Mass Spectrometry, Nicholas Ferraro

Electronic Theses and Dissertations

The glycine receptor (GlyR) belongs to a superfamily of pentameric ligand-gated ion channels (pLGICs) that mediate fast neurotransmission. GlyR typically modulates inhibitory transmission by antagonizing membrane depolarization through anion influx. Allosteric interactions between the receptor and its lipid surroundings affect receptor function, and cholesterol is essential for pLGIC activity. Human α1 GlyR was purified from baculovirus infected insect cells and reconstituted in unilamellar vesicles at cholesterol: lipid ratios below and above the cholesterol activity threshold with aliquots of azi-cholesterol. State-dependent crosslinking studies of receptors primarily in its resting (no glycine), desensitized (10mM glycine) and open (F207A/A288G, 30nM ivermectin) states were …

Genetic And Biochemical Analysis Of A Conserved, Multi-Gene System Regulation Spore-Associated Proteins In Streptomyces Coelicolor, Joseph Sallmen

Electronic Theses and Dissertations

Streptomyces coelicolor is a Gram positive, filamentous soil dwelling bacterium that exhibits a complex life cycle including the transition from a vegetative mycelium to a sporulating, aerial mycelium. Early genetic studies identified two classes of genes that resulted in developmental blocks, bald and white. The bald (bld) phenotype occurs when colonies cannot produce aerial hyphae. White (whi) colonies exhibit incomplete sporulation and/or loss of production of the concurrently produced grey pigment. While some of the original mutants have been explored, the developmental functions of many of the identified genes are not well understood. Of particular interest …

Nanomedicine-Driven Neuropathic Pain Relief In Rat Model Is Associated With Macrophage Polarity And Mast Cell Activation, Muzamil Saleem

Electronic Theses and Dissertations

We explored the immune neuropathology underlying multi-day relief from neuropathic pain in a rat model initiated at the sciatic nerve by using a nanoemulsion-based nanomedicine as a biological probe. The nanomedicine is theranostic: both therapeutic (containing celecoxib drug) and diagnostic (containing near-infrared fluorescent (NIRF) dye) and is small enough to be phagocytosed by circulating monocytes. A model of neuropathic pain is initiated by tying four 1mm spaced knots around the sciatic nerve with chromic gut suture, which results in neuroinflammation, and a resultant pain-like behavior manifests. We show that pain-like behavior reaches a plateau of maximum hypersensitivity 8 days post-surgery, …

Characterization Of The Effect Of Exercise Dose And Integrative Nonpharmacological Therapies In The Treatment Of Chronic Pain, Anna M. Polaski

Electronic Theses and Dissertations

Chronic pain includes debilitating conditions affecting large populations of people throughout the world. These diseases are further complicated by comorbid psychological disorders which make chronic pain conditions difficult to treat. Nonpharmacological treatment options have more recently become an important mainstay of effective therapies and are currently being used to supplement or replace traditional pharmacological treatment methods. Exercise-based therapies in particular are of interest due to their demonstrated success in reducing pain symptoms as well as improving psychological outcomes. Dose is an important factor in being able to effectively prescribe treatments in the context of specific exercise interventions and specific pain …

Dual Inhibition Of The Pi3k/Akt And Mek5/Erk5 Pathways For The Treatment Of Breast Cancer, Thomas Douglas Wright

Electronic Theses and Dissertations

Breast cancer is a heterogeneous disease state with several challenging frontiers. In particular, aberrations in the Phosphoinositide-3-kinase (PI3K) and Mitogen Activated Protein Kinase (MAPK) pathways have been linked to increased breast cancer proliferation and survival. It has been proposed that these survival characteristics are enhanced through compensatory signaling and crosstalk mechanisms. New evidence suggests that MEK5/ERK5, a member of the MAPK family, is a crucial component in the proliferation and survival of several aggressive cancers. We hypothesize that inhibiting both PI3K/Akt and MEK5/ERK5 pathways will decrease cell viability while maintaining limited collateral toxicity. In this study, we examined the effects …

Genetic Diversity Of White-Tailed Deer Populations In Southwestern Pennsylvania And The Development Of A Forensics Panel, Melanie Quain

Electronic Theses and Dissertations

During the 20^thcentury, white-tailed deer (Odocoileus virginianus) became scarce, prompting conservation efforts by hunters and wildlife managers with the goal to recover this species. Various strategies were implemented including reintroductions from areas that still had large deer populations, developing bag limits, seasonal restrictions, and habitat management. These efforts were highly successful across the United States.

Today, white-tailed deer are one of the most abundant and widely-distributed large-bodied mammals in North America. However, there are several important management concerns. In numerous states, including Pennsylvania, CWD negatively impacts deer populations and has become a major health concern. When …

The Effects Of Constructed Wetlands On Metal Solubilization And Bioavailability In Passive Mine Remediation, Elizabeth Cochran

Electronic Theses and Dissertations

The legacy of coal mining in Appalachia has left many watersheds impacted by abandoned mine drainage. The drainage degrades streams, groundwater and habitats with acidity and toxic heavy metals. The Lowber Passive Remediation System has been in operation since 2004 to remediate high amounts of dissolved Fe, SO₄, Al, and Mn. The site consists of six settling ponds and an extensive wetlands at the finish. This study investigated the resolubilization of Fe and Mn in the wetlands and the role of bacteria in resolubilization. During three seasons, field measurements of water quality and lab analysis of Fe, Mn, …

Role Of The Glycerophosphocholine Acyltransferase, Gpc1, In Phosphatidylcholine (Pc) Biosynthesis And Remodeling In Saccharomyces Cerevisiae, Sanket Anaokar

Electronic Theses and Dissertations

Biomembranes are permeable barriers that enclose the cell and the intracellular organelles in a cell. The selective nature of these robust barriers acts as the first line of defense towards the harsh factors that can compromise cell survival. Biomembranes primarily consist of membrane lipids that are organized into layers to form a dynamic bilayer structure. The dynamic nature of the membrane requires the synchronized modulation of lipid composition through de novo synthesis, degradation, intracellular movement, and remodeling. Phospholipids are the major membrane lipid class, and phosphatidylcholine (PC) is the most abundant phospholipid in most eukaryotic biomembranes.

PC is primarily produced …