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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Soil Organic Matter Processes From The Treetops To The Clay Particle: The Role Of Climate, Minerals, And Organic Matter Chemistry In Soil Carbon Accumulation And Stability, Jessica G. Murray Dec 2024

Soil Organic Matter Processes From The Treetops To The Clay Particle: The Role Of Climate, Minerals, And Organic Matter Chemistry In Soil Carbon Accumulation And Stability, Jessica G. Murray

All Graduate Theses and Dissertations, Fall 2023 to Present

Soils store more carbon than plants and the atmosphere, yet release ten times more carbon dioxide (CO2) to the atmosphere than human activities each year. Small shifts in the balance of soil carbon storage and soil carbon emissions could make climate change less severe, by acting as a sink for the carbon plants pull from the atmosphere, or make climate change worse, by releasing even more planet-warming greenhouse gases. The processes governing whether soils store or release carbon depend on tiny soil microorganisms which convert plant carbon to soil organic matter, releasing CO2 in the process. In …


The Auxotrophic Formate (For) Mutant Of Neurospora Crassa Has Significantly Delayed Growth But A Normal Circadian Clock, Ziyan Wang, Kristin M. Lindgren, Jennifer J. Loros, Jay C. Dunlap Oct 2024

The Auxotrophic Formate (For) Mutant Of Neurospora Crassa Has Significantly Delayed Growth But A Normal Circadian Clock, Ziyan Wang, Kristin M. Lindgren, Jennifer J. Loros, Jay C. Dunlap

Fungal Genetics Reports

Some cell biological studies of Neurospora crassa have been limited by the rapid rates of hyphal growth and fusion. In this study, we investigated the causative mutation in the standard C24 allele of for (FGSC #9) and assayed the growth and circadian phenotype of the for strain under different nutritional conditions. We show that the for strain can be maintained as metabolically active single cells for 2 days before its growth advances into branched mycelia. This culturing system offers the potential to advance subcellular dynamic research and to facilitate greater understanding of N. crassa in the early developmental stages.


Ferroptotic Cardiomyocytes Regulate Angiogenesis In The Regenerative Mouse Heart After Myocardial Infarction Through Direct And Indirect Mechanisms, Rebecca Stairey Oct 2024

Ferroptotic Cardiomyocytes Regulate Angiogenesis In The Regenerative Mouse Heart After Myocardial Infarction Through Direct And Indirect Mechanisms, Rebecca Stairey

MUSC Theses and Dissertations

Cardiovascular diseases (CVDs) are the leading cause of death in the United States, and heart attack occurs every 40 seconds in the US. A myocardial infarction (MI), or heart attack, results in ischemic injury and cardiomyocyte (CM) death. Mature mammalian CM renewal in the heart is insufficient to repopulate the lost tissue. However, the neonatal mouse heart retains its regenerative capacity through the first week of life, providing a valuable model to identifying regenerative factors.

Recent work by our lab revealed that the main mechanism of CM death in the heart post-MI is ferroptosis. In this study, we investigate the …


Electric Potential Energy Optimized 3d Radial Sampling Trajectories For Mri, Christopher Huynh, Datta Singh Goolaub, Christopher K Macgowan Oct 2024

Electric Potential Energy Optimized 3d Radial Sampling Trajectories For Mri, Christopher Huynh, Datta Singh Goolaub, Christopher K Macgowan

Faculty and Staff Publications

A novel method for creating “golden” 3D center-out radial MRI sampling trajectories was developed and analyzed. This method, called ELECTRO (ELECTRic potential energy Optimized), uses repulsive forces to minimize electric potential energy. An objective function , the electric potential energies of all subsets of consecutive readouts in a 3D radial trajectory, and its reduced form were minimized using a multi-stage optimization strategy. A metric called normalized mean nearest neighbor angular distance (NMNA) was proposed for describing distributions of points on a sphere. ELECTRO and other relevant golden trajectories were compared in silico using NMNA and point spread function analysis. Consecutive …


Hepatic Targets To Control Blood Glucose And Potentially Aid In The Treatment Of Diabetes, Rena A. Velissarios Oct 2024

Hepatic Targets To Control Blood Glucose And Potentially Aid In The Treatment Of Diabetes, Rena A. Velissarios

PANDION: The Osprey Journal of Research and Ideas

Maintaining glucose homeostasis is extremely important to remain in good health and prevent disease. This homeostasis is achieved via the regulation of hepatic metabolic pathways like gluconeogenesis and glycogenesis by insulin, which is expressed during high blood glucose. Insulin is responsible for facilitating the uptake of glucose into other tissues from the blood, as well as signaling whether to stimulate or slow glucose metabolism in the liver. Hyperglycemia is one of the main effects of diabetes, a disease characterized by the body’s inability to produce or respond to insulin. Without insulin, hepatic glucose output continues and blood glucose accumulates, causing …


Cryo-Em Analysis Of Pseudomonas Phage Pa193 Structural Components, Stephano M. Iglesias, Chun-Feng Hou, Johnny Reid, Evan Schauer, Renae Geier, Angela Soriaga, Lucy Sim, Lucy Gao, Julian Whitelegge, Pierre Kyme, Deborah Birx, Sebastien Lemire, Gino Cingolani Oct 2024

Cryo-Em Analysis Of Pseudomonas Phage Pa193 Structural Components, Stephano M. Iglesias, Chun-Feng Hou, Johnny Reid, Evan Schauer, Renae Geier, Angela Soriaga, Lucy Sim, Lucy Gao, Julian Whitelegge, Pierre Kyme, Deborah Birx, Sebastien Lemire, Gino Cingolani

Department of Biochemistry and Molecular Biology Faculty Papers

The World Health Organization has designated Pseudomonas aeruginosa as a critical pathogen for the development of new antimicrobials. Bacterial viruses, or bacteriophages, have been used in various clinical settings, commonly called phage therapy, to address this growing public health crisis. Here, we describe a high-resolution structural atlas of a therapeutic, contractile-tailed Pseudomonas phage, Pa193. We used bioinformatics, proteomics, and cryogenic electron microscopy single particle analysis to identify, annotate, and build atomic models for 21 distinct structural polypeptide chains forming the icosahedral capsid, neck, contractile tail, and baseplate. We identified a putative scaffolding protein stabilizing the interior of the capsid 5-fold …


Enzyme Encapsulation Within The Hk97 Virus-Like Particle: An Investigation Of Substrate Inhibition Kinetics Within A Confined And Crowded Environment, Joseph B. Lively Oct 2024

Enzyme Encapsulation Within The Hk97 Virus-Like Particle: An Investigation Of Substrate Inhibition Kinetics Within A Confined And Crowded Environment, Joseph B. Lively

Chemistry Theses

Substrate inhibition is a paradoxical phenomenon observed in enzyme kinetics where increasing substrate concentrations lead to a marked decrease in the rates of enzyme-catalyzed reactions. Affecting an estimated 20% of studied enzymes, substrate inhibition poses significant challenges to the understanding of their function in essential biological processes and to their exploitation in industrial and therapeutic contexts. Studies show substrate inhibition to be a real limitation in vitro and rational conclusions have been drawn to explain the relevance of substrate inhibition in the self-regulation of biological pathways. However, there is currently no consensus on what role substrate inhibition plays in vivo …


Crystal Archer: Profile Of The Newest Chbc Faculty Member, Danna Jaimes-Fajardo, Jeremy J. Smith, Lutishoor Salisbury Oct 2024

Crystal Archer: Profile Of The Newest Chbc Faculty Member, Danna Jaimes-Fajardo, Jeremy J. Smith, Lutishoor Salisbury

University Libraries Faculty Publications and Presentations

Presents the research profile of Crystal Archer, Assistant Professor, Chemistry and Biochemistry department. It highlights her research interests, education, and impact of her research.


"Deep Learning For Microscope Image Denoising", Nasreen Buhn, Sriya Adunur, Guy Hagen, Jonathan Ventura Oct 2024

"Deep Learning For Microscope Image Denoising", Nasreen Buhn, Sriya Adunur, Guy Hagen, Jonathan Ventura

College of Engineering Summer Undergraduate Research Program

In order to avoid damaging live cells, optical microscope imaging must be conducted under low-excitation light intensity and/or short exposure times, resulting in low signal-to-noise ratios (SNR). Deep learning methods offer an effective solution for removing microscope noise, utilizing algorithms that are able to reconstruct finer features in low SNR images. This research explores the denoising capability of several deep learning methods based on PSNR and SSIM. Tested methods include traditional approaches (BMED), supervised learning (CARE and Restormer), and unsupervised methods (Noise2Fast, N2V, SSD-Unsupervised, and SASSID). The Restormer model, which employs an encoder-decoder transformer architecture and progressive learning, stood out …


Investigating Neurite Outgrowth Influenced By Breast Cancer Progression Using In Vitro Models Of Collagen I Hydrogels, Emma Waskom '27, Nikolas Ala-Kokko, Younghye Song Oct 2024

Investigating Neurite Outgrowth Influenced By Breast Cancer Progression Using In Vitro Models Of Collagen I Hydrogels, Emma Waskom '27, Nikolas Ala-Kokko, Younghye Song

Annual Student Research Poster Session

Through the use of vitro modeling of tumor progression, using collagen I hydrogels and progressing cell lines, a demonstration of the interactions between breast cancer cells and nerve cells can be investigated. With these models, our goal is to compare the measurement of outgrowth of nerve cells through the use of supplemented NGF and co cultures of breast cancer cells. Human MCF-CA1a.cl1, -AneoT, and -10A, adipose-derived stem cells (ASCs), and rat PC-12 cells, were all passaged from 2D cultures and cultured in a collagen I hydrogen at a cell density of 250,000 cells/ml of media. Collagen hydrogels were then made …


A Comparative Analysis Of Urea Vs. Acetamide In Aot Reverse Micelles, Kate Walsh '26, Bridget Gourley, Nancy E. Levinger Oct 2024

A Comparative Analysis Of Urea Vs. Acetamide In Aot Reverse Micelles, Kate Walsh '26, Bridget Gourley, Nancy E. Levinger

Annual Student Research Poster Session

In our exploration of the interactions between water and amide osmolytes, we focused on the effects of urea and acetamide on the stability of reverse micelles (RMs) formed with Sodium Bis(2-ethylhexyl)sulfosuccinate (AOT) in isooctane. Water, with its unique polarity and its ability to facilitate hydrogen and proton transfer, played a crucial role in our study, as we aimed to uncover how these amides would influence micellar behaviour. Our results revealed a compelling contrast between urea and acetamide. Acetamide, with its lower polarity due to a methyl group substitution, demonstrated superior solubility and significantly reduced precipitate formation compared to urea. This …


E-Textbook For Better Learning In Chemistry 120, Anh Vu '27, Jeffery A. Hansen Oct 2024

E-Textbook For Better Learning In Chemistry 120, Anh Vu '27, Jeffery A. Hansen

Annual Student Research Poster Session

Organic chemistry is a highly visual subject since organic compounds are 3D objects. For this reason, in order to fully understand the composition, properties, and chemistry of these compounds, it is essential to understand and visualize their 3D structures. Nevertheless, there is a frequent necessity to depict organic substances on 2D surfaces, such as paper, a computer screen, or a whiteboard. As a result, one of the biggest obstacles we will face is learning these molecules in a 2D format while maintaining an accurate understanding of 3D nature. The purpose of this e-textbook is to fully utilize the digital medium …


Comparison Of Two Disaccharides And Their Saccharide Components In Aot Reverse Micelles: Impacts Of D-Trehalose And D-Sucrose, Delaney Collier '25, Bridget L. Gourley, Nancy E. Levinger Oct 2024

Comparison Of Two Disaccharides And Their Saccharide Components In Aot Reverse Micelles: Impacts Of D-Trehalose And D-Sucrose, Delaney Collier '25, Bridget L. Gourley, Nancy E. Levinger

Annual Student Research Poster Session

Reverse micelles, featuring an AOT surfactant with a polar head group and nonpolar tail, encapsulate a polar phase at the nanoscale. With water as the polar phase, the nanoconfined water pool interactions and water-interface interactions mimic biological nanoconfinement. Thus, we investigated the impact of osmolytes on AOT reverse micelles to explore the role they play in biological systems. We investigated two disaccharides, D-trehalose and D-sucrose, and their monosaccharide components, glucose+glucose and glucose+fructose. We chose these molecules for their biological significance and to allow us to investigate whether subtle structural changes in the osmolyte impacts the intermolecular interactions in confinement as …


Designing An Attachment Assay For Epidermal Cell-To-Cell Attachment, Tiala Ortega '26, Colleen L. Doçi Oct 2024

Designing An Attachment Assay For Epidermal Cell-To-Cell Attachment, Tiala Ortega '26, Colleen L. Doçi

Annual Student Research Poster Session

Cell adhesion includes various processes and is essential in cell communication and regulation. The mechanical interactions between a cell and its extracellular matrix control the behavior and function of a cell. In this project, we are studying cell attachment in different ways. The epidermal monostrato layer is a vertical and horizontal interaction and is not accounted for in usual assay protocols so I wanted to investigate this by creating an assay including multiple cell layers, a monolayer and an attached layer, to further develop a protocol for optimal cell-to-cell attachment. I hypothesized that the number of cell attachments to the …


Inhibition Of Integrin Binding: Exploring Its Impact On Epidermal Cell Attachment, Erin R. Johnson '25, Colleen L. Doçi Oct 2024

Inhibition Of Integrin Binding: Exploring Its Impact On Epidermal Cell Attachment, Erin R. Johnson '25, Colleen L. Doçi

Annual Student Research Poster Session

I worked with HaCaT cells, human epidermal cells that are sticky and like to attach to their surroundings in the skin. They have a surface protein called integrin, which interacts directly with collagen to induce cell attachment. I was particularly interested in interrupting this connection between integrin and collagen. I achieved this by using an inhibitory peptide that bound to the active site of integrin. This would allow me to calculate the cell attachment of HaCaT cells while in the presence of collagen. If we were able to target this treatment to tumor cells, we could help to stop them …


Nanopore Signal Deviations From Pseudouridine Modifications In Rna Are Sequence-Specific: Quantification Requires Dedicated Synthetic Controls, Amr Makhamreh, Sepideh Tavakoli, Ali Fallahi, Xinqi Kang, Howard Gamper, Mohammad Nabizadehmashhadtoroghi, Miten Jain, Ya-Ming Hou, Sara H Rouhanifard, Meni Wanunu Sep 2024

Nanopore Signal Deviations From Pseudouridine Modifications In Rna Are Sequence-Specific: Quantification Requires Dedicated Synthetic Controls, Amr Makhamreh, Sepideh Tavakoli, Ali Fallahi, Xinqi Kang, Howard Gamper, Mohammad Nabizadehmashhadtoroghi, Miten Jain, Ya-Ming Hou, Sara H Rouhanifard, Meni Wanunu

Department of Biochemistry and Molecular Biology Faculty Papers

Chemical modifications to mRNA respond dynamically to environmental cues and are important modulators of gene expression. Nanopore direct RNA sequencing has been applied for assessing the presence of pseudouridine (ψ) modifications through basecalling errors and signal analysis. These approaches strongly depend on the sequence context around the modification, and the occupancies derived from these measurements are not quantitative. In this work, we combine direct RNA sequencing of synthetic RNAs bearing site-specific modifications and supervised machine learning models (ModQuant) to achieve near-analytical, site-specific ψ quantification. Our models demonstrate that the ionic current signal features important for accurate ψ classification are sequence …


Inorganic Pyrophosphate Plasma Levels In Patients With Ggcx-Associated Pxe-Like Phenotypes, Qiaoli Li, Catherine Troutman, Mary Peckiconis, Tamara Wurst, Sharon Terry Sep 2024

Inorganic Pyrophosphate Plasma Levels In Patients With Ggcx-Associated Pxe-Like Phenotypes, Qiaoli Li, Catherine Troutman, Mary Peckiconis, Tamara Wurst, Sharon Terry

Department of Biochemistry and Molecular Biology Faculty Papers

ntroduction: Pseudoxanthoma elasticum (PXE) is an autosomal recessive ectopic calcification disorder clinically affecting the skin, eyes, and vascular system. Most cases of PXE are caused by inactivating pathogenic variants in the ABCC6 gene encoding a hepatic transmembrane efflux transporter, which facilitates the extracellular release of ATP, the precursor of inorganic pyrophosphate (PPi), a potent endogenous inhibitor of calcification. Pathogenic variants in GGCX, encoding γ-glutamyl carboxylase required for activation of vitamin K-dependent coagulation factors as well as matrix Gla protein (MGP) and Gla-rich protein (GRP), two inhibitors of ectopic calcification, have also been reported to cause cutaneous changes like those seen …


The C-Terminal 4cxxc-Type Zinc Finger Domain Of Cdca7 Recognizes Hemimethylated Dna And Modulates Activities Of Chromatin Remodeling Enzyme Hells, Akeo Shinkai, Hideharu Hashimoto, Chikako Shimura, Hiroaki Fujimoto, Kei Fukuda, Naoki Horikoshi, Masaki Okano, Hitoshi Niwa, Erik W Debler, Hitoshi Kurumizaka, Yoichi Shinkai Sep 2024

The C-Terminal 4cxxc-Type Zinc Finger Domain Of Cdca7 Recognizes Hemimethylated Dna And Modulates Activities Of Chromatin Remodeling Enzyme Hells, Akeo Shinkai, Hideharu Hashimoto, Chikako Shimura, Hiroaki Fujimoto, Kei Fukuda, Naoki Horikoshi, Masaki Okano, Hitoshi Niwa, Erik W Debler, Hitoshi Kurumizaka, Yoichi Shinkai

Department of Biochemistry and Molecular Biology Faculty Papers

The chromatin-remodeling enzyme helicase lymphoid-specific (HELLS) interacts with cell division cycle-associated 7 (CDCA7) on nucleosomes and is involved in the regulation of DNA methylation in higher organisms. Mutations in these genes cause immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome, which also results in DNA hypomethylation of satellite repeat regions. We investigated the functional domains of human CDCA7 in HELLS using several mutant CDCA7 proteins. The central region is critical for binding to HELLS, activation of ATPase, and nucleosome sliding activities of HELLS-CDCA7. The N-terminal region tends to inhibit ATPase activity. The C-terminal 4CXXC-type zinc finger domain contributes to CpG …


Effects Of Microplastic Biofilms On An Anthropogenically Impacted Suburban Lake, Paris M. Velsaquez Sep 2024

Effects Of Microplastic Biofilms On An Anthropogenically Impacted Suburban Lake, Paris M. Velsaquez

Masters Theses

Plastics have been observed in every location on the planet, and their prevalence in the environment is due in part to their strong resistance to degradation. Inland lakes are susceptible to plastic pollution by highway runoff, which contains plastic fragments of brake pads, car tires, litter, and road paint. These plastics eventually enter freshwater environments and degrade into microplastics (


Predicting Mutation-Induced Allosteric Changes In Structures And Conformational Ensembles Of The Abl Kinase Using Alphafold2 Adaptations With Alanine Sequence Scanning, Nishank Raisinghani, Mohammed Alshahrani, Grace Gupta, Gennady M. Verkhivker Sep 2024

Predicting Mutation-Induced Allosteric Changes In Structures And Conformational Ensembles Of The Abl Kinase Using Alphafold2 Adaptations With Alanine Sequence Scanning, Nishank Raisinghani, Mohammed Alshahrani, Grace Gupta, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Despite the success of AlphaFold2 approaches in predicting single protein structures, these methods showed intrinsic limitations in predicting multiple functional conformations of allosteric proteins and have been challenged to accurately capture the effects of single point mutations that induced significant structural changes. We examined several implementations of AlphaFold2 methods to predict conformational ensembles for state-switching mutants of the ABL kinase. The results revealed that a combination of randomized alanine sequence masking with shallow multiple sequence alignment subsampling can significantly expand the conformational diversity of the predicted structural ensembles and capture shifts in populations of the active and inactive ABL states. …


Economic Impacts Of Establishing A Neutron Source Facility In Windsor, Abdur Rahman Sep 2024

Economic Impacts Of Establishing A Neutron Source Facility In Windsor, Abdur Rahman

Major Papers

Cancer poses a significant health challenge in Canada, with two in five individuals likely to develop the disease. This paper explores the economic impacts of establishing a prototype compact accelerator-based neutron source (PC-CANS) facility in Windsor that will produce medical isotopes locally in Windsor, Ontario, rather than relying on centralized production and transportation from London, Ontario. Fluorine-18 medical isotopes, crucial for positron emission tomography (PET) scans, experience significant decay losses during transportation due to their short half-life of 109.8 minutes, increasing costs and restricting availability. Using a differential analysis approach, the study quantifies economic benefits, focusing on three main impacts: …


A Preliminary Fuzzy Inference System For Predicting Atmospheric Ozone In An Intermountain Basin, John R. Lawson, Seth N. Lyman Sep 2024

A Preliminary Fuzzy Inference System For Predicting Atmospheric Ozone In An Intermountain Basin, John R. Lawson, Seth N. Lyman

Mathematics and Statistics Faculty Publications

High concentrations of ozone in the Uinta Basin, Utah, can occur after sufficient snowfall and a strong atmospheric anticyclone creates a persistent cold pool that traps emissions from oil and gas operations, where sustained photolysis of the precursors builds ozone to unhealthy concentrations. The basin's winter-ozone system is well understood by domain experts and supported by archives of atmospheric observations. Rules of the system can be formulated in natural language ("sufficient snowfall and high pressure leads to high ozone"), lending itself to analysis with a fuzzy-logic inference system. This method encodes human expertise as machine intelligence in a more prescribed …


Exploring Biosignatures And Biogeochemical Processes In Lanzarote Lava Tubes: Implications For Martian Analog Research, Vera Palma, Ana Z. Miller, Francesco Sauro, Bogdan P. Onac, José M. De La Rosa, Sara Gutiérrez-Patricio, Beatriz Cubero, José A. Gonzalez-Perez, Jesus Martínez-Frías, A Teresa Caldeira Sep 2024

Exploring Biosignatures And Biogeochemical Processes In Lanzarote Lava Tubes: Implications For Martian Analog Research, Vera Palma, Ana Z. Miller, Francesco Sauro, Bogdan P. Onac, José M. De La Rosa, Sara Gutiérrez-Patricio, Beatriz Cubero, José A. Gonzalez-Perez, Jesus Martínez-Frías, A Teresa Caldeira

FRONTIERS UNBOUND: Exploring Extreme Environments

No abstract provided.


Exploring Pristine Microbial Ecosystems From The Uninhabited Volcanic Selvagens Islands, Pedro N. Jiménez-Morillo, Sara Gutiérrez-Patricio, Vera Palma, Ana Teresa Caldeira, Nicasio Tomás Jiménez-Morillo, Ana Z. Miller Sep 2024

Exploring Pristine Microbial Ecosystems From The Uninhabited Volcanic Selvagens Islands, Pedro N. Jiménez-Morillo, Sara Gutiérrez-Patricio, Vera Palma, Ana Teresa Caldeira, Nicasio Tomás Jiménez-Morillo, Ana Z. Miller

FRONTIERS UNBOUND: Exploring Extreme Environments

No abstract provided.


Investigating Therapeutic Activity Of Br-Ormeloxifene (Br-Orm) Against Cervical Cancer, Mohammed Sikander, Shabnam Malik, John Apraku, Sonam Kumari, Parvez Khan, Daniel Zubieta, Hassan Mandil, Aditya Ganju, Bhavin Chauhan, Maria C. Bell, Man Mohan Singh, Sheema Khan, Murali Yallapu, Fathi T. Halaweish, Meena Jaggi, Subhash Chauhan Sep 2024

Investigating Therapeutic Activity Of Br-Ormeloxifene (Br-Orm) Against Cervical Cancer, Mohammed Sikander, Shabnam Malik, John Apraku, Sonam Kumari, Parvez Khan, Daniel Zubieta, Hassan Mandil, Aditya Ganju, Bhavin Chauhan, Maria C. Bell, Man Mohan Singh, Sheema Khan, Murali Yallapu, Fathi T. Halaweish, Meena Jaggi, Subhash Chauhan

Research Colloquium

Aberrant activation of β-catenin signaling is strongly associated with cancer proliferation, invasion, migration, and metastasis, thus small molecules that can inhibit this pathway might have great clinical significance. Our molecular modeling studies suggest that Ormeloxifene (ORM), a triphenylethylene molecule docks with β-catenin, and its brominated analogue (Br-ORM) bind more effectively with relatively less energy (-7.6 kcal/mol) to the active site of β-catenin as compared to parent ORM. Herein, we report the synthesis and characterization of a Br-ORM by NMR and FTIR, as well as its anti-cancer potential in cervical cancer models in vitro and in vivo. Br-ORM treatment effectively …


Engineered Nls-Chimera Downregulates Expression Of Aggregation-Prone Endogenous Fus, Miyuki Hayashi, Amandeep Girdhar, Ying-Hui Ko, Kevin Kim, Jacquelyn Depierro, Joseph R. Buchler, Nikhita Arunprakash, Aditya Bajaj, Gino Cingolani, Lin Guo Sep 2024

Engineered Nls-Chimera Downregulates Expression Of Aggregation-Prone Endogenous Fus, Miyuki Hayashi, Amandeep Girdhar, Ying-Hui Ko, Kevin Kim, Jacquelyn Depierro, Joseph R. Buchler, Nikhita Arunprakash, Aditya Bajaj, Gino Cingolani, Lin Guo

Department of Biochemistry and Molecular Biology Faculty Papers

Importin β-superfamily nuclear import receptors (NIRs) mitigate mislocalization and aggregation of RNA-binding proteins (RBPs), like FUS and TDP-43, which are implicated in neurodegenerative diseases. NIRs potently disaggregate RBPs by recognizing their nuclear localization signal (NLS). However, disease-causing mutations in NLS compromise NIR binding and activity. Here, we define features that characterize the anti-aggregation activity of NIR and NLS. We find that high binding affinity between NIR and NLS, and optimal NLS location relative to the aggregating domain plays a role in determining NIR disaggregation activity. A designed FUS chimera (FUSIBB), carrying the importin β binding (IBB) domain, is …


Dissecting The Interplay Of Protein Synthesis And Degradation Pathways In Cellular Adaptation To Stress, Brittany Friedson Sep 2024

Dissecting The Interplay Of Protein Synthesis And Degradation Pathways In Cellular Adaptation To Stress, Brittany Friedson

Theses and Dissertations

Adaptation to stress requires cells to reprogram transcription, translation, and proteolytic pathways. Although much is known about the response of each program, it remains unclear how they coordinate following stress. My studies in S. cerevisiae identified the Cdk8 kinase module (CKM) of the Mediator complex as a new player in coordinating these processes. It is well established that the CKM consists of four highly conserved proteins (cyclin C, its cognate kinase Cdk8, and two structural proteins Med12 and Med13) and predominantly represses a subset of stress responsive genes in yeast. We demonstrated for the first time that the CKM also …


Non-Redundant Roles For The Human Mrna Decapping Cofactor Paralogs Dcp1a And Dcp1b, Ivana Vukovic, Samantha M. Barnada, Jonathan W. Ruffin, Jon Karlin, Ravi Kumar Lokareddy, Gino Cingolani, Steven B. Mcmahon Sep 2024

Non-Redundant Roles For The Human Mrna Decapping Cofactor Paralogs Dcp1a And Dcp1b, Ivana Vukovic, Samantha M. Barnada, Jonathan W. Ruffin, Jon Karlin, Ravi Kumar Lokareddy, Gino Cingolani, Steven B. Mcmahon

Department of Medicine Faculty Papers

Eukaryotic gene expression is regulated at the transcriptional and post-transcriptional levels, with disruption of regulation contributing significantly to human diseases. The 5' m7G mRNA cap is a central node in post-transcriptional regulation, participating in both mRNA stabilization and translation efficiency. In mammals, DCP1a and DCP1b are paralogous cofactor proteins of the mRNA cap hydrolase DCP2. As lower eukaryotes have a single DCP1 cofactor, the functional advantages gained by this evolutionary divergence remain unclear. We report the first functional dissection of DCP1a and DCP1b, demonstrating that they are non-redundant cofactors of DCP2 with unique roles in decapping complex integrity and specificity. …


Serum Proteomic Profile Of Subclinical Babesia Bovis Infection In Pcr-Positive Eld's Deer Using Serum Protein Electrophoresis Coupled With Lc-Ms/Ms, Vichayanee Pumpitakkul, Sittiruk Roytrakul, Narumon Phaonakrop, Gunnaporn Suriyaphol Assoc. Prof. Sep 2024

Serum Proteomic Profile Of Subclinical Babesia Bovis Infection In Pcr-Positive Eld's Deer Using Serum Protein Electrophoresis Coupled With Lc-Ms/Ms, Vichayanee Pumpitakkul, Sittiruk Roytrakul, Narumon Phaonakrop, Gunnaporn Suriyaphol Assoc. Prof.

The Thai Journal of Veterinary Medicine

Subclinical babesiosis observed in captive Eld’s deer, which act as reservoirs for ticks, poses a risk to healthy herds. However, the knowledge of biomarkers for subclinically infected Eld’s deer and host-parasite interactions is limited. This study aimed to investigate the serum proteomic profiles and protein interactions of Babesia bovis and subclinically infected Eld’s deer, PCR-positive for B. bovis, using automated serum protein electrophoresis and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The findings revealed albumin and four globulin fractions: alpha-1, alpha-2, beta, and gamma globulin. Albumin protein (ALB) was consistently detected across all fractions, highlighting its role in maintaining osmotic balance …


Application Of High-Resolution Nano-Scale Liquid Chromatography Tandem Mass Spectrometry To The Study Of S. Endobioticum-Induced Infection In Cultivated Potatoes, Daria Baskova Sep 2024

Application Of High-Resolution Nano-Scale Liquid Chromatography Tandem Mass Spectrometry To The Study Of S. Endobioticum-Induced Infection In Cultivated Potatoes, Daria Baskova

Electronic Thesis and Dissertation Repository

Potato wart is an infection of cultivated potato plants caused by the soil-borne biotrophic fungus Synchitrium endobioticum. The main symptoms of infection are formation of warts on the tuber tissue and the production of biflagellated mobile spores that undergo long-lasting dormancy periods. Genomic studies have significantly contributed to an overall understanding of the fungal life cycle, including the discovery of the first S. endobioticum avirulence genes, and the identification of multiple pathotypes. However, the molecular pathways involved in host-pathogen interactions during potato wart infection and the factors contributing to resistance in plants remain unknown. In this work, a combination …