Biochemistry Commons^™

Likely Community Transmission Of Covid-19 Infections Between Neighboring, Persistent Hotspots In Ontario, Canada, Ben C. Shirley, Eliseos J. Mucaki, Peter Rogan

Biochemistry Publications

Introduction: This study aimed to produce community-level geo-spatial mapping of confirmed COVID-19 cases in Ontario Canada in near real-time to support decision-making. This was accomplished by area-to-area geostatistical analysis, space-time integration, and spatial interpolation of COVID-19 positive individuals.
Methods: COVID-19 cases and locations were curated for geostatistical analyses from March 2020 through June 2021, corresponding to the first, second, and third waves of infections. Daily cases were aggregated according to designated forward sortation area (FSA), and postal codes (PC) in municipal regions Hamilton, Kitchener/Waterloo, London, Ottawa, Toronto, and Windsor/Essex county. Hotspots were identified with area-to-area tests including Getis-Ord Gi*, Global …

Impact Of Pank1 Deletion On Mitochondrial Acetylation And Cardiac Function During Pressure Overload., Timothy N. Audam

Electronic Theses and Dissertations

Recent studies have associated elevated protein acetylation levels with heart failure in humans. Although mechanisms promoting elevated acetylation levels are not fully known, excess acetyl-CoA may drive enzyme-independent acetylation of cardiac proteins. Accumulation of acetyl-CoA depends on the availability of sufficient CoA, whose production is regulated by pantothenate kinases in the CoA biosynthetic pathway. We show that cardiac proteins are hyperacetylated during heart failure in humans and tested in mice whether limiting CoA abundance would improve ventricular remodeling during pressure overload-induced hypertrophy. We limited cardiac CoA levels by deleting the rate-limiting enzyme in CoA biosynthesis, Pank1 (one of three PANK-encoding …

Deciphering The Role Of Hsp110 Chaperones In Diseases Of Protein Misfolding, Unekwu M. Yakubu

Dissertations & Theses (Open Access)

Molecular chaperones maintain protein homeostasis (proteostasis) by ensuring the proper folding of polypeptides. Loss of proteostasis has been linked to the onset of numerous neurodegenerative disorders including Alzheimer’s, Parkinson’s, and Huntington’s disease. Hsp110 is a member of the Hsp70 class of molecular chaperones and acts as a nucleotide exchange factor (NEF) for Hsp70, the preeminent Hsp70-family protein folding chaperone. Hsp110 promotes rapid cycling of ADP for ATP, allowing Hsp70 to properly fold nascent or unfolded polypeptides in iterative cycles. In addition to its NEF activity, Hsp110 possesses an Hsp70-like substrate binding domain (SBD) whose biological roles are undefined. Previous work …

Hiv-1 Transcription Elongation By Tat-Mediated Recruitment Of P-Tefb, Elizabeth Griggs

Honors Theses

Over 38.0 million people live with the human immunodeficiency virus (HIV) as of 462019. HIV hijacks the host's cellular machinery to replicate its viral DNA and transcribe the corresponding RNA. HIV-1 transcription relies on both cellular and viral transcription factors for proper regulation. The viral transcriptional activator Tat is a primary regulator. Transcription activation and elongation is controlled through the interaction of Tat with Positive Transcription Elongation Factor b (P-TEFb), a cellular transcriptional activator. The focus of this paper is 1) an in-depth understanding of the interaction between P-TEFb and Tat in HIV transcription, and 2) a review of recent …

The Regulation Of Pannexin1 And Pannexin2 In The Skin In Health And Disease, Rafael E. Sanchez Pupo

Electronic Thesis and Dissertation Repository

Pannexins (PANX1, 2, 3) are a family of channel-forming glycoproteins that mediate intracellular and paracrine signaling. In contrast to PANX2, PANX1 has been extensively investigated in the skin, modulating cell differentiation, wound healing, and melanoma development. PANX1 and PANX2 can co-exist in the same cell and form mixed channels where their glycosylation seems to regulate their intermixing. N-glycosylation and caspase cleavage have been proposed as modulators of the function of PANX1, but their effects on PANX2 are unknown. We explored the PANX2 expression in mouse skin and showed that a Panx2 splice variant (PANX2-202) is continuously expressed throughout aging skin. …

Modulation Of Glucose Homeostasis By Nucleotide P2y2 Receptor And Biological Sex, Hailee Anne Marino

MSU Graduate Theses

Recent insights into the pathological role of Nucleotide P2Y₂ receptor suggest P2Y₂R involvement in high fat diet-induced obesity and potentiates insulin resistance. However, these recent insights do not demonstrate how P2Y₂R modulates glucose homeostasis under physiological conditions. Further, it remains unknown how sex biological factors influence P2Y₂R receptor signaling in the regulation of glucose homeostasis. The research objective for the present study is to elucidate the novel roles of P2Y₂ in fasting blood glucose and glucose tolerance (basal insulin sensitivity) under resting conditions in males and females. We expected that under physiological …

Type I Topoisomerases As Potential Targets For Therapeutics, Ahmed Seddek

FIU Electronic Theses and Dissertations

DNA topoisomerases are universal enzymes that control the topological features of DNA in all forms of life. This study aims to find potential inhibitors of some of the DNA topoisomerases in bacteria and humans that can be developed into potential therapeutics.

The first aim of this study is to find potential inhibitors of bacterial topoisomerase I that can be developed into antibiotics. There is an urgent need to develop novel antibiotics to overcome the world-wide health crisis of antimicrobial resistance. Virtual screening and biochemical assays were combined to screen thousands of compounds for potential inhibitors of bacterial topoisomerase I. NSC76027 …

Mucin And Splice Variant Profiles Of Pancreatic Adenocarcinoma Predict Patient Survival And Subtyping, Christopher M. Thompson

Theses & Dissertations

PDAC is a pancreatic epithelial malignancy and demonstrates aggressive progression and bleak patient prognosis. Despite decades of research, the evolution of novel diagnostics and intervention modalities for PDAC is stagnant. This dissertation explores the characteristic aberrant and elevated expression of mucins in PDAC. Beginning with the hypothesis that mucins are associated with disease aggressiveness, analysis of PDAC patient survival in TCGA revealed no associations between single mucin expression and patient survival. This led to the underlying issue of PDAC tumor cellularity since this disease demonstrates variability in the proportion of cancer cells within the tumor. Tumor purity assessed with the …

Finding The Balance​ The Effects Of Α-Cyclodextrin, 2-Hydroxypropyl-Β-Cyclodextrin, And Cholesterol Bacteroides Vulgatus And Clostridium Bolteae​, Bethany Weaver

Honors Program Projects

Atherosclerosis is a cardiovascular disease that is characterized by the hardening of arteries through the formation of cholesterol plaques. Cyclodextrins could potentially treat atherosclerosis by shrinking plaques. These cyclic oligosaccharides can make complexes with cholesterol but have also shown toxic side effects. This study looked for potential negative effects of cyclodextrins and cholesterol on gut bacteria. It was hypothesized that Bacteroides vulgatus will have decreased growth when grown in broth with cholesterol. In contrast, Clostridium bolteae will have decreased growth when grown in broth with cyclodextrins. Due to the fact that these bacteria are anaerobic, Clostridium bolteae and Bacteroides vulgatus, …

Purification And Functional Characterization Of The Iron-Responsive Transcription Factor Aft1 From C. Glabrata, Jade Ikahihifo-Bender

Senior Theses

Due to its unique ability to serve as both an electron donor and acceptor, iron is utilized as a co-factor for many biological processes, including electron transfer, oxygen binding, and vitamin synthesis. Iron is also a key factor during fungal infections as the human host and invading pathogens battle over limited iron pools. The primary iron-responsive transcription factor Aft1 in the opportunistic pathogenic yeast Candida glabrata responds to iron deficiency by activating expression of iron acquisition genes. However, the mechanisms for sensing intracellular iron levels and regulating Aft1 activity in response to iron are unknown. The C. glabrata iron regulation …

Development Of Light Actuated Chemical Delivery Platform On A 2-D Array Of Micropore Structure, Hojjat Rostami Azmand, Hojjat Rostami Azmand

Dissertations and Theses

Localized chemical delivery plays an essential role in the fundamental information transfers within biological systems. Thus, the ability to mimic the natural chemical signal modulation would provide significant contributions to understand the functional signaling pathway of biological cells and develop new prosthetic devices for neurological disorders. In this paper, we demonstrate a light-controlled hydrogel platform that can be used for localized chemical delivery in a high spatial resolution. By utilizing the photothermal behavior of graphene-hydrogel composites confined within micron-sized fluidic channels, patterned light illumination creates the parallel and independent actuation of chemical release in a group of fluidic ports. The …

From Inner Segment To Outer Segment: Palmitoylation Of Photoreceptor Na+, K+-Atpase And The Importance Of Prcd In Photoreceptor Outer Segment Morphogenesis, Emily R. Sechrest

Graduate Theses, Dissertations, and Problem Reports

Photoreceptors are specialized neuroepithelial cells which are optimized for efficient capture of light and initiation of visual transduction. These cells have several compartments which are very important for proper visual function and segregation of cellular processes, including the outer segment (OS), inner segment (IS), nucleus, and synapse. The IS houses all of the cellular organelles and biosynthetic molecular machinery the cell requires and is the site of protein synthesis. The light-sensing OS is a highly modified, primary cilium, which contains many stacks of double membranous discs which house proteins required for formation and maintenance of OS structure, as well as …

Use Of Small Molecule Fanconi Anemia Pathway Inhibitors As Sensitizing Agents To Laromustine., Sam W. Marchant

Honors Theses

Laromustine is an experimental chemotherapeutic sulfonyl hydrazine prodrug shown in clinical trials to be effective against acute myeloid leukemia. The mechanism of action of laromustine involves interstrand crosslinking, via chloroethylation, and enzyme inhibition, caused by carbamoylation. The work described herein aims to investigate whether inhibition of the replication-dependent interstrand crosslink repair Fanconi Anemia pathway further sensitizes cells to laromustine. By measuring metabolic activity immediately after drug exposure, we find laromustine to be equally as cytotoxic towards Fanconi Anemia deficient and wild type cells. However, through clonogenic assays we show Fanconi Anemia mutations sensitize cells to laromustine’s anti-proliferative effect. Furthermore, we …

Sars-Cov-2: An Investigation On Mutagenicity And Its Effects On Infectivity And Mortality, Tyler Elliott Silverwood

Honors Theses and Capstones

SARS-CoV-2, the etiological agent of the COVID-19 pandemic, has rapidly become a worldwide public health concern. Classified as a betacoronavirus, it is the third human coronavirus (HCoV) to emerge in the 21st century that causes severe disease, alongside SARS-CoV and MERS-CoV. The genome consists of open reading frames encoding accessory proteins and four structural proteins, including the spike protein which is a key determinant of host cell tropism. Mutations within the genome, particularly the spike gene, have been linked in-vitro to increased binding affinity to the human receptor angiotensin-converting enzyme 2 (hACE2), increased fitness in human hosts, and immune evasion. …