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Full-Text Articles in Biochemistry

Decreasing The Antibiotic Survival Of Multi-Drug Resistant Gram-Positive Organisms, Areej Malik Apr 2024

Decreasing The Antibiotic Survival Of Multi-Drug Resistant Gram-Positive Organisms, Areej Malik

Biomedical Sciences Theses & Dissertations

Biofilm production plays a crucial role in bacterial antibiotic tolerance and novel approaches are needed to combat it. The stringent response (SR), activated by nucleotide alarmones (pp)pGpp, is crucial for bacterial transcriptional reprogramming. In Clostridioides difficile, the SR is implicated in antibiotic survival, contributing to infection recurrence. Despite its known roles in sporulation and biofilm production in other bacterial species, the broader influence of the SR on C. difficile physiology remains undiscovered. This study deletes the C. difficile SR gene relQ, revealing the pivotal role of RelQ in regulating SR-dependent phenotypes in this organism. The absence of RelQ …


Exploring Cation Exchange: Unveiling Its Significance In Biochar And Bioenergetics Applications, Gyanendra Kharel Apr 2024

Exploring Cation Exchange: Unveiling Its Significance In Biochar And Bioenergetics Applications, Gyanendra Kharel

Chemistry & Biochemistry Theses & Dissertations

Cation exchange, a cornerstone of soil chemistry and nutrient cycling, is a fundamental chemical process that occurs in soils, sediments, membranes, and other solid materials. It involves the interchange of positively charged ions, or cations, between a solid matrix and a surrounding solution. This process is crucial in various natural and engineered systems, leading to a range of applications across different fields.

This dissertation presents an extensive investigation into the applications of cation exchange in the fields of biochar and bioenergetics, encompassing three distinct aims. The first aim concentrates on the surface oxygenation of biochar through ozonization, aiming to achieve …


A Comparison Of In Vitro Studies Between Cobalt(Iii) And Copper(Ii) Complexes With Thiosemicarbazone Ligands To Treat Triple Negative Breast Cancer, Duaa R. Alajroush, Chloe B. Smith, Brittney F. Anderson, Ifeoluwa T. Oyeyemi, Stephen J. Beebe, Alvin A. Holder Mar 2024

A Comparison Of In Vitro Studies Between Cobalt(Iii) And Copper(Ii) Complexes With Thiosemicarbazone Ligands To Treat Triple Negative Breast Cancer, Duaa R. Alajroush, Chloe B. Smith, Brittney F. Anderson, Ifeoluwa T. Oyeyemi, Stephen J. Beebe, Alvin A. Holder

Undergraduate Research Symposium

Triple negative breast cancer (TNBC) is one of the most aggressive forms of breast cancer, and disproportionately affects African American women. TNBC cells lack the common hormone receptors that many pre-existing cancer treatments target. Fortunately, metal-based complexes with thiosemicarbazone ligands have gained significant attention for their potential as anti-cancer agents. Cobalt(III) complex ([Co(phen)2(MeATSC)](NO3)3•1.5H2O•C2H5OH]) and Copper(II) complex ([Cu(acetylethTSC)Cl]Cl•0.25C2H5OH) specifically have properties of high toxicity, which can contribute to decreased cancer cell activity. The effects of these complexes are currently being investigated on cancerous and non-cancerous breast cell lines. The cytotoxic effect of the cobalt(lll) complex and the copper(ll) complex was analyzed …


Structural Insights Into The Cl-Par-4 Protein: Ionic Requirements, Conformational Transitions, And Interaction With Cisplatin, Krishna Kumar Raut Oct 2023

Structural Insights Into The Cl-Par-4 Protein: Ionic Requirements, Conformational Transitions, And Interaction With Cisplatin, Krishna Kumar Raut

Chemistry & Biochemistry Theses & Dissertations

Cancer continues to be the leading global cause of death, with challenges in early diagnosis, drug resistance, non-specific drug targeting, and cancer recurrence and metastasis posing formidable obstacles in cancer therapy. In this context, Prostate Apoptosis Response-4 (Par-4), a pro-apoptotic tumor suppressor protein, emerged as a promising therapeutic target due to its ability to selectively induce apoptosis in cancer cells, thereby minimizing the drug-associated adverse effects. However, a comprehensive understanding of the structural features of Par-4, specifically the caspase-cleaved fragment (cl-Par-4), is crucial for therapeutic advancements.

This dissertation investigated the effects of various ions, both monovalent and divalent, on the …


Metals And Metal Complexes In Diseases With A Focus On Covid-19: Facts And Opinions, Agnieszka Ścibior, Manuel Aureliano, Alvin A. Holder, Juan Llopis Jun 2023

Metals And Metal Complexes In Diseases With A Focus On Covid-19: Facts And Opinions, Agnieszka Ścibior, Manuel Aureliano, Alvin A. Holder, Juan Llopis

Chemistry & Biochemistry Faculty Publications

In the present Special Issue on “Metals and Metal Complexes in Diseases with a Focus on COVID-19: Facts and Opinions”, an attempt has been made to include reports updating our knowledge of elements considered to be potential candidates for therapeutic applications and certain metal-containing species, which are extensively being examined towards their potential biomedical use due to their specific physicochemical properties. The Special Issue compiles data on the role of metals in COVID-19 and focuses on other illnesses and biological processes that affect metal metabolism. It consists of eight manuscripts, including five review articles and three original research papers (Figure …


Nanosecond Pulsed Electric Field Modulates Electron Transport And Mitochondrial Structure And Function, Lucas Nelson Potter May 2023

Nanosecond Pulsed Electric Field Modulates Electron Transport And Mitochondrial Structure And Function, Lucas Nelson Potter

Biomedical Engineering Theses & Dissertations

Pulsed power treatment has been used to induce regulated cell death (RCD) in cells or ablate tumors in animals. A subset of pulsed power as electroporation with high voltage and pulse duration of milliseconds is used for biomedical treatment to induce pores in the plasma membrane of cells. Nanosecond Pulsed Electric Fields (nsPEFs)– an extension of electroporation, uses waveforms with pulse durations on the order of 10-900 nanoseconds. nsPEF treatment has demonstrated intracellular effects for potential biomedical applications. In this work, nsPEF treatment is used to demonstrate changes that affect viability, plasma membrane permeability ROS (Reactive Oxygen Species) in the …


Characterization Of Cl-Par-4: Wt Vs. Mutant, Samjhana Pandey, Krishna K. Raut, Andrea M. Clark, Antoine Baudin, Lamya Djemri, David S. Libich, Steven M. Pascal Jan 2023

Characterization Of Cl-Par-4: Wt Vs. Mutant, Samjhana Pandey, Krishna K. Raut, Andrea M. Clark, Antoine Baudin, Lamya Djemri, David S. Libich, Steven M. Pascal

The Graduate School Posters

Intrinsically disordered proteins (IDPs) play important roles in regulation of cell signaling pathways as well as cellular processes. Dysregulation of these proteins is associated with several human diseases. Prostate apoptosis response-4 (Par-4), a proapoptotic tumor suppressor protein, is categorized as an intrinsically disordered protein and downregulation of this protein has been reported in myriad of cancers including glioma, breast cancers, and prostate cancers. The caspase-cleaved fragment of Par-4 (cl-Par-4) plays an active role in tumor suppression by inhibiting several cell survival pathways.

Here, we employed site-directed mutagenesis to introduce a point mutation in the cl-Par-4 wildtype (WT) to generate the …


Using Nspefs To Sensitize Mrsa To Vancomycin Treatment, Areej Malik, Alexandra E. Chittams-Miles, Claudia Muratori, Erin B. Purcell Jan 2023

Using Nspefs To Sensitize Mrsa To Vancomycin Treatment, Areej Malik, Alexandra E. Chittams-Miles, Claudia Muratori, Erin B. Purcell

The Graduate School Posters

Staphylococcus aureus (S. aureus) is a biofilm-forming pathogen. S. aureus treatment is marked by the development of antibiotic resistance. The public health impact has increased since the emergence of methicillin-resistant S. aureus (MRSA), which has started to show intermediate resistance to vancomycin in MRSA. Nano-second pulse electric fields (nsPEFs) are low-energy and high-power electric pulses, which have been suggested to sensitize pathogens to antibiotics by creating transient pores in the cell membrane. Our combinatorial treatment includes nsPEF pre-treatment and vancomycin post-treatment of MRSA cells. Our results show that MRSA log phase cells had the highest susceptibility to vancomycin. …


Par-4: An Attractive Target For Cancer Therapy, Krishna K. Raut, Antoine Baudin, David S. Libich, Lijun Liu, Scott Lovell, Steven M. Pascal Jan 2023

Par-4: An Attractive Target For Cancer Therapy, Krishna K. Raut, Antoine Baudin, David S. Libich, Lijun Liu, Scott Lovell, Steven M. Pascal

College of Sciences Posters

Lack of early diagnosis, cancer recurrence, metastasis, and adverse side effects are some of the major problems in the treatment of cancers. Par-4, a tumor suppressor protein, is an attractive target for cancer therapy as it selectively kills cancer cells. Cl-Par-4 is the active fragment of Par-4 that enters the nucleus and selectively induces apoptosis in cancer cells. It has also been reported that Par-4 increases the susceptibility of cancer cells to chemotherapy and reverses cancer recurrence. Further, Par-4 has been shown to play a dual role: inhibition of EMT (Epithelial-mesenchymal transition) as well as assistance in the reverse process, …


Isotopic Evidence For Sources Of Dissolved Carbon And The Role Of Organic Matter Respiration In The Fraser River Basin, Canada, Britta M. Voss, Timothy I. Eglinton, Bernhard Peucker-Ehrenbrink, Valier Galy, Susan Q. Lang, Cameron Mcintyre, Robert G.M. Spencer, Ekaterina Bulygina, Zhaohui Aleck Wang, Katherine A. Guay Jan 2023

Isotopic Evidence For Sources Of Dissolved Carbon And The Role Of Organic Matter Respiration In The Fraser River Basin, Canada, Britta M. Voss, Timothy I. Eglinton, Bernhard Peucker-Ehrenbrink, Valier Galy, Susan Q. Lang, Cameron Mcintyre, Robert G.M. Spencer, Ekaterina Bulygina, Zhaohui Aleck Wang, Katherine A. Guay

OES Faculty Publications

Sources of dissolved and particulate carbon to the Fraser River system vary significantly in space and time. Tributaries in the northern interior of the basin consistently deliver higher concentrations of dissolved organic carbon (DOC) to the main stem than other tributaries. Based on samples collected near the Fraser River mouth throughout 2013, the radiocarbon age of DOC exported from the Fraser River does not change significantly across seasons despite a spike in DOC concentration during the freshet, suggesting modulation of heterogeneous upstream chemical and isotopic signals during transit through the river basin. Dissolved inorganic carbon (DIC) concentrations are highest in …


Investigating The Biorisk Of Genetically Engineered Thermosynechococcus Elongatus Bp1, Cherrelle Leah Barnes Aug 2022

Investigating The Biorisk Of Genetically Engineered Thermosynechococcus Elongatus Bp1, Cherrelle Leah Barnes

Chemistry & Biochemistry Theses & Dissertations

Cyanobacteria, also known as blue-green algae, are an ancient group of microorganisms that use simple materials, such as sunlight, carbon dioxide and water, to produce energy while providing oxygen to the atmosphere by performing photosynthesis. Synthetic biology approaches have been employed with cyanobacteria as a platform to produce a range of products, such as biofuels, by inserting a series of genes into the cyanobacterial genome that will allow the conversion of metabolic intermediates to such desired products. Although these methods are promising, it is important to understand any potential bio-risk they pose. This research evaluates the potential bio-risk of genetically …


Clostridioides Difficile Biofilm And Spore Production In Response To Antibiotics And Immune Stress, Adenrele M. Oludiran Aug 2022

Clostridioides Difficile Biofilm And Spore Production In Response To Antibiotics And Immune Stress, Adenrele M. Oludiran

Chemistry & Biochemistry Theses & Dissertations

The development of new therapeutic options against Clostridioides difficile (C. difficile) infection is a critical public health concern, as the causative bacterium is highly resistant to multiple classes of antibiotics. C. difficile, an anaerobic spore-forming Gram-positive pathogenic bacterium, is a major cause of hospital-acquired infections. C. difficile persists in the environment and spreads the infection to new hosts in the form of dormant spores and can persist within hosts as surface-attached biofilms. These studies investigate bacterial vegetative cell survival, biofilm formation, and sporulation in response to stress. Antimicrobial host-defense peptides (HDPs) are highly effective at simultaneously modulating …


A Pathway To Solving The Structure Of Cl-Par-4 Tumor Suppressor Protein: Challenges & Findings, Krishna Raut, Samjhana Pandey, Andrea M. Clark, Komala Ponniah, Steven M. Pascal Apr 2022

A Pathway To Solving The Structure Of Cl-Par-4 Tumor Suppressor Protein: Challenges & Findings, Krishna Raut, Samjhana Pandey, Andrea M. Clark, Komala Ponniah, Steven M. Pascal

College of Sciences Posters

Prostate apoptosis response-4 (Par-4) is a pro-apoptotic tumor suppressor protein. Down-regulation of this protein has been reported in a myriad of cancers. Conversely, up-regulation of Par-4 is found to be associated with several neurodegenerative disorders. Par-4 is unique in the sense it can selectively induce apoptosis in cancer cells. For this, caspase-dependent intracellular cleavage of Par-4 is essential to produce the functionally active fragment, cl-Par-4 (caspase-cleaved Par-4). The cl-Par-4 protein inhibits the NF-κB-mediated cell survival pathway and causes selective apoptosis in various tumor cells.

Our laboratory is interested in determining the structure of cl-Par-4 and understanding it’s interaction with various …


Investigation Of Magnesium Cation-Proton Exchange With Transmembrane Electrostatically Localized Protons (Telp) At A Liquid-Membrane Interface: Fundamental To Bioenergetics, Gyanendra Kharel, Andrew J. Evans, Christopher M. Russo, Michael Eason, James W. Lee Apr 2022

Investigation Of Magnesium Cation-Proton Exchange With Transmembrane Electrostatically Localized Protons (Telp) At A Liquid-Membrane Interface: Fundamental To Bioenergetics, Gyanendra Kharel, Andrew J. Evans, Christopher M. Russo, Michael Eason, James W. Lee

College of Sciences Posters

The Lee transmembrane electrostatic proton localization (TELP) theory is a revolutionary scientific theory that has successfully explained decades long-standing quandary in the field of bioenergetics in regards to ATP synthesis in biological systems, specifically alkalophilic bacteria. This study provides experimental support for the TELP theory by further demonstrating evidence of a localized proton layer existing at the liquid-membrane interface in a simulated biological membrane apparatus. Whilst monovalent cations have been studied extensively, divalent cation exchange has not been studied experimentally.

A previous study determined equilibrium constant for Na+ and K+ to exchange with localized H+ layer to …


Natural Phaeosphaeride A Derivatives Overcome Drug Resistance Of Tumor Cells And Modulate Signaling Pathways, Victoria Abzianidze, Natalia Moiseeva, Diana Suponina, Sofya Zakharenkova, Nadezhda Rogovskaya, Lidia Laletina, Alvin A. Holder, Denis Krivorotov, Alexander Bogachenkov, Alexander Garabadzhiu, Anton Ukolov, Vyacheslav Kosorukov Mar 2022

Natural Phaeosphaeride A Derivatives Overcome Drug Resistance Of Tumor Cells And Modulate Signaling Pathways, Victoria Abzianidze, Natalia Moiseeva, Diana Suponina, Sofya Zakharenkova, Nadezhda Rogovskaya, Lidia Laletina, Alvin A. Holder, Denis Krivorotov, Alexander Bogachenkov, Alexander Garabadzhiu, Anton Ukolov, Vyacheslav Kosorukov

Chemistry & Biochemistry Faculty Publications

n the present study, natural phaeosphaeride A (PPA) derivatives are synthesized. Anti-tumor studies are carried out on the PC3, K562, HCT-116, THP-1, MCF-7, A549, NCI-H929, Jurkat, and RPMI8226 tumor cell lines, and on the human embryonic kidney (HEK293) cell line. All the compounds synthesized turned out to have better efficacy than PPA towards the tumor cell lines listed. Among them, three compounds exhibited an ability to overcome the drug resistance of tumor cells associated with the overexpression of the P-glycoprotein by modulating the work of this transporter. Luminex xMAP technology was used to assess the effect of five synthesized compounds …


Coastal Upwelling Enhances Abundance Of A Symbiotic Diazotroph (Ucyn-A) And Its Haptophyte Host In The Arctic Ocean, Corday R. Selden, Sveinn V. Einarsson, Kate E. Lowry, Katherine E. Crider, Robert S. Pickart, Peigen Lin, Carin J. Ashjian, P. Dreux Chappell Jan 2022

Coastal Upwelling Enhances Abundance Of A Symbiotic Diazotroph (Ucyn-A) And Its Haptophyte Host In The Arctic Ocean, Corday R. Selden, Sveinn V. Einarsson, Kate E. Lowry, Katherine E. Crider, Robert S. Pickart, Peigen Lin, Carin J. Ashjian, P. Dreux Chappell

OES Faculty Publications

The apparently obligate symbiosis between the diazotroph Candidatus Atelocyanobacterium thalassa (UCYN-A) and its haptophyte host, Braarudosphaera bigelowii, has recently been found to fix dinitrogen (N2) in polar waters at rates (per cell) comparable to those observed in the tropical/subtropical oligotrophic ocean basins. This study presents the novel observation that this symbiosis increased in abundance during a wind-driven upwelling event along the Alaskan Beaufort shelfbreak. As upwelling relaxed, the relative abundance of B. bigelowii among eukaryotic phytoplankton increased most significantly in waters over the upper slope. As the host’s nitrogen demands are believed to be supplied primarily by UCYN-A, …


Microbial Labilization And Diversification Of Pyrogenic Dissolved Organic Matter, Aleksandar I. Goranov, Andrew S. Wozniak, Kyle W. Bostick, Andrew R. Zimmerman, Siddhartha Mitra, Patrick G. Hatcher Jan 2022

Microbial Labilization And Diversification Of Pyrogenic Dissolved Organic Matter, Aleksandar I. Goranov, Andrew S. Wozniak, Kyle W. Bostick, Andrew R. Zimmerman, Siddhartha Mitra, Patrick G. Hatcher

Chemistry & Biochemistry Faculty Publications

With the increased occurrence of wildfires around the world, interest in the chemistry of pyrogenic organic matter (pyOM) and its fate in the environment has increased. Upon leaching from soils by rain events, significant amounts of dissolved pyOM (pyDOM) enter the aquatic environment and interact with microbial communities that are essential for cycling organic matter within the different biogeochemical cycles. To evaluate the biodegradability of pyDOM, aqueous extracts of laboratory-produced biochars were incubated with soil microbes, and the molecular changes to the composition of pyDOM were probed using ultrahigh-resolution mass spectrometry (Fourier transform–ion cyclotron resonance–mass spectrometry). Given that solar irradiation …


Mechanisms Of Stress Survival In Gram Positive Bacterial Pathogens, Asia Poudel Dec 2021

Mechanisms Of Stress Survival In Gram Positive Bacterial Pathogens, Asia Poudel

Chemistry & Biochemistry Theses & Dissertations

Anaerobic Gram-positive bacteria are not a well-characterized group but include many human pathogens that are resilient against stresses caused by the human immune system or by antibiotic treatment. This dissertation investigated the survival mechanisms of two clinically relevant Gram-positive organisms, Clostridioides difficile and Cutibacterium acnes under extracellular stresses. The response of the opportunistic skin pathogen Cutibacterium acnes to nanosecond electric pulses is characterized and found that growth in a biofilm, which usually protects bacteria from stress, renders this species more killable by this treatment. In addition, the stringent response (SR), a conserved bacterial stress survival mechanism, is studied in the …


Genetically Engineered Thermosynechococcus Elongatus Bp1: Assessment Of Potential Biorisks And Biofuel Production, Thu Ho Anh Nguyen-Jones Dec 2021

Genetically Engineered Thermosynechococcus Elongatus Bp1: Assessment Of Potential Biorisks And Biofuel Production, Thu Ho Anh Nguyen-Jones

Chemistry & Biochemistry Theses & Dissertations

According to the International Energy Outlook 2019, released by the U.S. Energy Information Administration, it is projected that the energy consumption will increase up to 50% between 2018 and 2050 worldwide. As fossil fuel being a finite source of energy with the risk of depletion, many countries are now facing an energy security crisis. Therefore, it is important to develop other renewable and sustainable energy sources that will allow countries to shift away from depending on fossil fuels. Among several types of renewable energy, biofuel production using genetically engineered cyanobacteria is capturing much interest due to its many advantages. Different …


Improvement Of Biochar Through Ozonization And Biosafety Of Genetically Engineered Cyanobacteria, Oumar Sacko Jul 2021

Improvement Of Biochar Through Ozonization And Biosafety Of Genetically Engineered Cyanobacteria, Oumar Sacko

Chemistry & Biochemistry Theses & Dissertations

Through the innovative technique of biochar post-production surface oxygenation by ozonization, we were able to improve certain properties of biochar. In project one, the incubation of an insoluble phosphate rock material (hydroxyapatite) with the wet ozonized pine 400 biochar and its filtrate resulted in a solubilization of 80 times more phosphate from hydroxyapatite (569.0 mg/L ± 6.4) compared to the pure water-hydroxyapatite control (7.2 mg/L ± 0.3). The ozonized biochar may provide a new possible way to unlock the phosphorus from insoluble phosphate mineral phases. The cation exchange capacity (CEC) is a key property of biochar when used as a …


Computational Analysis Of Type 3 Iodothyronine Deiodinase: Potential Inhibitors, Substrate Binding, And Dimer Structure, Eric Scott Marsan Jul 2021

Computational Analysis Of Type 3 Iodothyronine Deiodinase: Potential Inhibitors, Substrate Binding, And Dimer Structure, Eric Scott Marsan

Chemistry & Biochemistry Theses & Dissertations

Thyroid hormones (THs) in mammalian tissues are crucial for development and maintaining metabolic homeostasis. Iodothyronine deiodinases (Dios) remove iodines from THs by a selenocysteine (Sec) residue, which either activates or inactivates them. Halogen bonding (XB) has been proposed to describe the interaction between the Se and I atoms of the T4-Dio complex. Disruption of TH homeostasis by xenobiotics, such as polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) can cause deleterious effects on the endocrine system. Experimental studies have indicated that PBDEs and PCBs could disrupt TH homeostasis by inhibiting Dio through XB formation. However, no current quantitative study exists …


Computational And Experimental Investigation Into The Determinants Of Protein Structure, Folding, And Stability In The Β-Grasp Superfamily, John T. Bedford Ii Apr 2021

Computational And Experimental Investigation Into The Determinants Of Protein Structure, Folding, And Stability In The Β-Grasp Superfamily, John T. Bedford Ii

Chemistry & Biochemistry Theses & Dissertations

Elucidating the mechanisms of protein folding and unfolding is one of the greatest scientific challenges in basic science. The overarching goal is to predict three-dimensional structures from their amino acid sequences. Understanding the determinants of protein folding and stability can be facilitated through the study of evolutionarily related but diverse proteins. Insights can also be gained through the study of proteins from extremophiles that may more closely resemble the primordial proteins. In this doctoral research, three aims were accomplished to characterize the structure, folding and unfolding behavior within the β-grasp superfamily. We propose that the determinants of structure, stability, and …


Influence Of Monovalent And Divalent Ions In The Conformational Change Of Caspase-Cleaved Par-4 (Cl-Par-4) Tumor Suppressor Protein, Krishna K. Raut, Komala Ponniah, Steven M. Pascal Apr 2021

Influence Of Monovalent And Divalent Ions In The Conformational Change Of Caspase-Cleaved Par-4 (Cl-Par-4) Tumor Suppressor Protein, Krishna K. Raut, Komala Ponniah, Steven M. Pascal

College of Sciences Posters

Prostate apoptosis response-4 (Par-4) is a pro-apoptotic tumor suppressor protein. We have shown that this 38 kDa full-length Par-4 (Fl-Par-4) protein is predominantly intrinsically disordered in vitro. In vivo, Par-4 is cleaved by caspase-3 at Asp-131 to generate a 24 kDa functionally active cleaved Par-4 (cl-Par-4) fragment. The cl-Par-4 protein inhibits the NF-κB-mediated cell survival pathway and causes selective apoptosis in various tumor cells. Our laboratory is interested in how the disorder-order balance within Fl-Par-4 and cl-Par-4 may be related to the balance between cell survival and cell death. Currently, we are using biophysical techniques such as circular …


Evaluating The Role Of The Stringent Response Mechanism In Clostridioides Difficile Survival And Pathogenesis, Astha Pokhrel Apr 2021

Evaluating The Role Of The Stringent Response Mechanism In Clostridioides Difficile Survival And Pathogenesis, Astha Pokhrel

Chemistry & Biochemistry Theses & Dissertations

The human pathogen Clostridioides difficile is increasingly tolerant of multiple antibiotics and causes infections with a high rate of recurrence, creating an urgent need for new preventive and therapeutic strategies. The stringent response, a universal bacterial response to extracellular stresses, governs antibiotic survival and pathogenesis in diverse organisms but has not previously been characterized in C. difficile. This dissertation explores the ability of C. difficile to mount the stringent response. The bacteria encode a full-length, canonical bifunctional Rel/Spo Homolog or RSH enzyme. C. difficile RSH is incapable of utilizing GTP as a substrate but readily synthesizes putative 5’-pGpp-3’ alarmones. …


Biophysical Characterization Of The Par-4 Tumor Suppressor: Evidence Of Structure Outside The Coiled Coil Domain And Interactions With Platinum Chemotherapeutics, Andrea Megan Clark Apr 2021

Biophysical Characterization Of The Par-4 Tumor Suppressor: Evidence Of Structure Outside The Coiled Coil Domain And Interactions With Platinum Chemotherapeutics, Andrea Megan Clark

Chemistry & Biochemistry Theses & Dissertations

Prostate apoptosis response-4 (Par-4) is an apoptosis-inducing tumor suppressor protein. Full-length Par-4 has previously been shown to be a predominantly intrinsically disordered protein (IDP) under neutral conditions, with significant regular secondary structure evident only within the C-terminal coiled coil domain. However, IDPs can gain ordered structure through the process of induced folding, which often occurs under non-neutral conditions. Previous work has shown that the Par-4 leucine zipper, which is a subset of the C-terminal coiled coil domain, is disordered under neutral conditions, but forms a dimeric coiled coil at acidic pH. Increase in ionic strength was also shown to increase …


Methylation Of The D2 Dopamine Receptor Affects Binding With The Human Regulatory Proteins Par-4 And Calmodulin, Alexander Bowitch, Ansuman Sahoo, Andrea M. Clark, Christiana Ntangka, Krishna K. Raut, Paul Gollnick, Michael C. Yu, Steven M. Pascal, Sarah E. Walker, Denise M. Ferkey Feb 2021

Methylation Of The D2 Dopamine Receptor Affects Binding With The Human Regulatory Proteins Par-4 And Calmodulin, Alexander Bowitch, Ansuman Sahoo, Andrea M. Clark, Christiana Ntangka, Krishna K. Raut, Paul Gollnick, Michael C. Yu, Steven M. Pascal, Sarah E. Walker, Denise M. Ferkey

Chemistry & Biochemistry Faculty Publications

No abstract provided.


Scaling The Effects Of Ocean Acidification On Coral Growth And Coral-Coral Competition On Coral Community Recovery, Nicolas R. Evensen, Yves-Marie Bozec, Peter J. Edmunds, Peter J. Mumby Jan 2021

Scaling The Effects Of Ocean Acidification On Coral Growth And Coral-Coral Competition On Coral Community Recovery, Nicolas R. Evensen, Yves-Marie Bozec, Peter J. Edmunds, Peter J. Mumby

Biological Sciences Faculty Publications

Ocean acidification (OA) is negatively affecting calcification in a wide variety of marine organisms. These effects are acute for many tropical scleractinian corals under short-term experimental conditions, but it is unclear how these effects interact with ecological processes, such as competition for space, to impact coral communities over multiple years. This study sought to test the use of individual-based models (IBMs) as a tool to scale up the effects of OA recorded in short-term studies to community-scale impacts, combining data from field surveys and mesocosm experiments to parameterize an IBM of coral community recovery on the fore reef of Moorea, …


Detrital Neodymium And (Radio)Carbon As Complementary Sedimentary Bedfellows? The Western Arctic Ocean As A Testbed, Melissa S. Schwab, Jörg D. Rickli, Robie W. Macdonald, H. Rodger Harvey, Negar Haghipour, Timothy I. Eglinton Jan 2021

Detrital Neodymium And (Radio)Carbon As Complementary Sedimentary Bedfellows? The Western Arctic Ocean As A Testbed, Melissa S. Schwab, Jörg D. Rickli, Robie W. Macdonald, H. Rodger Harvey, Negar Haghipour, Timothy I. Eglinton

OES Faculty Publications

Interactions between organic and detrital mineral phases strongly influence both the dispersal and accumulation of terrestrial organic carbon (OC) in continental margin sediments. Yet the complex interplay among biological, chemical, and physical processes limits our understanding of how organo-mineral interactions evolve during sediment transfer and burial. In particular, diverse OC sources and complex hydrodynamic processes hinder the assessment of how the partnership of organic matter and its mineral host evolves during supply and dispersal over continental margins. In this study, we integrate new and compiled sedimentological (grain size, surface area), organic (%OC, OC-δ13C, OC-F14C), and inorganic …


Marine Phytoplankton Functional Types Exhibit Diverse Responses To Thermal Change, S. I. Anderson, A. D. Barton, Sophie Clayton, S. Dutkiewicz, T. A. Rynearson Jan 2021

Marine Phytoplankton Functional Types Exhibit Diverse Responses To Thermal Change, S. I. Anderson, A. D. Barton, Sophie Clayton, S. Dutkiewicz, T. A. Rynearson

OES Faculty Publications

Marine phytoplankton generate half of global primary production, making them essential to ecosystem functioning and biogeochemical cycling. Though phytoplankton are phylogenetically diverse, studies rarely designate unique thermal traits to different taxa, resulting in coarse representations of phytoplankton thermal responses. Here we assessed phytoplankton functional responses to temperature using empirically derived thermal growth rates from four principal contributors to marine productivity: diatoms, dinoflagellates, cyanobacteria, and coccolithophores. Using modeled sea surface temperatures for 1950-1970 and 2080-2100, we explored potential alterations to each group's growth rates and geographical distribution under a future climate change scenario. Contrary to the commonly applied Eppley formulation, our …


Structual Analysis Of The Cl-Par-4 Tumor Suppressor As A Function Of Ionic Environment, Krishna K. Raut, Komala Ponniah, Steven M. Pascal Jan 2021

Structual Analysis Of The Cl-Par-4 Tumor Suppressor As A Function Of Ionic Environment, Krishna K. Raut, Komala Ponniah, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

Prostate apoptosis response-4 (Par-4) is a proapoptotic tumor suppressor protein that has been linked to a large number of cancers. This 38 kilodalton (kDa) protein has been shown to be predominantly intrinsically disordered in vitro. In vivo, Par-4 is cleaved by caspase-3 at Asp-131 to generate the 25 kDa functionally active cleaved Par-4 protein (cl-Par-4) that inhibits NF-κB-mediated cell survival pathways and causes selective apoptosis in tumor cells. Here, we have employed circular dichroism (CD) spectroscopy and dynamic light scattering (DLS) to assess the effects of various monovalent and divalent salts upon the conformation of cl-Par-4 in vitro. We have …