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2023

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Articles 331 - 360 of 857

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

Protein Folding Kinetics Analysis Using Fluorescence Spectroscopy, Dhanya Dhananjayan Jun 2023

Protein Folding Kinetics Analysis Using Fluorescence Spectroscopy, Dhanya Dhananjayan

USF Tampa Graduate Theses and Dissertations

The conformational changes that occur during the folding of a protein is an intensely researched area because of the impact that it has on human health and cellular functions. Protein stability is crucial in the context of protein misfolding and aggregation due to its implications on misfolding diseases such as amyloid fibril degenerative diseases (Alzheimer’s, Parkinson’s). By examining the kinetics of protein folding, we can gain valuable information about the folding mechanism and help us identify potential targets for many of the protein misfolding diseases.

In this study, we present the folding and unfolding kinetics of TEM-1 β-lactamase from Escherichia …


A Novel Role For Enos In Regulating Lymphatic Valve Development During Embryogenesis, Drishya Iyer Jun 2023

A Novel Role For Enos In Regulating Lymphatic Valve Development During Embryogenesis, Drishya Iyer

USF Tampa Graduate Theses and Dissertations

Lymphedema is a disease that occurs when lymph flow is impaired, resulting in tissue swelling, fibrosis, chronic inflammation and recurrent secondary infections. Lymphatic valves play a critical role in maintaining unidirectional lymph flow and evidence for valve defects have been reported in lymphedema patients. The lack of drugs that can correct lymphatic valve defects warrants a better understanding of the molecular regulators of lymphatic valve development and maintenance. Lymphatic valves first develop during embryogenesis in response to mechanotransduction signaling pathways triggered by oscillatory lymph flow. Since eNOS (gene name: Nos3) is a well characterized mechanotransduction signaling molecule in blood vessels, …


Hematopoietic Stem Cells And Betaherpesvirus Latency, Lindsey B. Crawford Jun 2023

Hematopoietic Stem Cells And Betaherpesvirus Latency, Lindsey B. Crawford

Department of Biochemistry: Faculty Publications

The human betaherpesviruses including human cytomegalovirus (HCMV), human herpesvirus (HHV)-6a and HHV-6b, and HHV-7 infect and establish latency in CD34+ hematopoietic stem and progenitor cells (HPCs). The diverse repertoire of HPCs in humans and the complex interactions between these viruses and host HPCs regulate the viral lifecycle, including latency. Precise manipulation of host and viral factors contribute to preferential maintenance of the viral genome, increased host cell survival, and specific manipulation of the cellular environment including suppression of neighboring cells and immune control. The dynamic control of these processes by the virus regulate inter- and intra-host signals critical to the …


Obstructive Sleep Apnea-Induced Hypertension Is Associated With Increased Gut And Neuroinflammation, Sriram Ayyaswamy, Huanan Shi, Bojun Zhang, Robert M Bryan, David J Durgan Jun 2023

Obstructive Sleep Apnea-Induced Hypertension Is Associated With Increased Gut And Neuroinflammation, Sriram Ayyaswamy, Huanan Shi, Bojun Zhang, Robert M Bryan, David J Durgan

Faculty, Staff and Students Publications

Background

Obstructive sleep apnea (OSA) is an independent risk factor for the development of hypertension. We have demonstrated that OSA induces gut dysbiosis, and this dysbiotic microbiota contributes to hypertension. However, the mechanisms linking gut dysbiosis to blood pressure regulation remain unclear. Recent studies demonstrate that gut dysbiosis can induce a proinflammatory response of the host resulting in peripheral and neuroinflammation, key factors in the development of hypertension. We hypothesized that OSA induces inflammation in the gut that contributes to neuroinflammation and hypertension.

Methods and Results

OSA was induced in 8‐week‐old male rats. After 2 weeks of apneas, lymphocytes were …


Role Of Chronic Stress-Induced Neuroinflammation In Rodent Locus Coeruleus Physiology And Anxiety-Like Behaviors, Arthur Anthony Alfonso Reyes Jun 2023

Role Of Chronic Stress-Induced Neuroinflammation In Rodent Locus Coeruleus Physiology And Anxiety-Like Behaviors, Arthur Anthony Alfonso Reyes

Graduate School of Biomedical Sciences Theses and Dissertations

The locus coeruleus (LC), the primary site of brain norepinephrine (NE), is a key anatomical brain region implicated in the stress response. Stress is a neuroendocrine physiologic response to a stressor that promotes organism survival through adaptive change and restoration of homeostasis. The central stress response, which drives behavioral and physiological change, is primarily mediated by activating the hypothalamic-pituitary-adrenal (HPA) axis. While advantageous in the short term, chronic stress exposure can lead to HPA axis and LC dysregulation, which are thought to contribute to the etiology of anxiety disorders. Previous studies demonstrate the effects of acute stress in increasing LC …


Anti-Pancreatic Cancer Activity Of Rhus Coriaria (Sumac), Yassine Elmahi Jun 2023

Anti-Pancreatic Cancer Activity Of Rhus Coriaria (Sumac), Yassine Elmahi

Theses

Cancer is a major health problem and is considered a chronic disease globally. Pancreatic cancer is one of the deadliest types of cancer. That is because symptoms increase until the cancer is spread to other parts of the body in late stages. Among the many different therapeutic approaches to treat cancer, it appears that many plants have promising treatment effects, and one of these plants is Rhus coriaria, commonly known as Sumac. Previous studies have indicated that the Sumac plant, which is used in cooking, possesses various therapeutic values, including antioxidant and antibiotic activities. This study investigates the effect …


Molecular Mechanisms Of Natural And Synthetic Compounds Against Breast And Colon Cancer, Aysha Hamad Alneyadi Jun 2023

Molecular Mechanisms Of Natural And Synthetic Compounds Against Breast And Colon Cancer, Aysha Hamad Alneyadi

Dissertations

Cancer is a complex disease with various causes, including genetic mutations, viruses, chemical agents, and lifestyle factors. Although numerous studies have been conducted to develop a cure or novel medications for cancer, no standout treatment has been found. In this project, the use of various natural and synthetic compounds as potential cancer treatments was investigated using triple-negative breast cancer (TNBC) and colon cancer cells. The cancer therapy strategies investigated were based on plant-derived therapuetic approaches including an essential oil (Origanum majorana essential oil), a pure phytochemical (Carnosol), and newly developed synthetic drugs (Chromenes drevatives; C1 and C2). This study …


Understanding The Intracellular Positive Regulatory Interactions In The Metabolic Network, Sultana Mohammed Al Zubaidi Jun 2023

Understanding The Intracellular Positive Regulatory Interactions In The Metabolic Network, Sultana Mohammed Al Zubaidi

Theses

Metabolism is an essential cellular process that produces essential components such as energy molecules and cellular building blocks. It is regulated by intracellular metabolite-enzyme interactions, which can increase or decrease enzyme efficiency. Each metabolic process is not evolved in nature and may not contribute to the optimal efficiency of the organism's metabolism. However, this study aims to clarify the relationship between cellular positive regulatory interactions and the cell's metabolic network, especially how these relationships regulate metabolism and how it evolved in nature. To obtain that, for each enzyme, the activation molecules from the BRENDA database were downloaded, mapped data to …


Control Of The Electroporation Efficiency Of Nanosecond Pulses By Swinging The Electric Field Vector Direction, Vitalii Kim, Iurii Semenov, Allen S. Kiester, Mark A. Keppler, Bennett L. Ibey, Joel N. Bixler, Ruben M. L. Colunga Biancatelli, Andrei G. Pakhomov Jun 2023

Control Of The Electroporation Efficiency Of Nanosecond Pulses By Swinging The Electric Field Vector Direction, Vitalii Kim, Iurii Semenov, Allen S. Kiester, Mark A. Keppler, Bennett L. Ibey, Joel N. Bixler, Ruben M. L. Colunga Biancatelli, Andrei G. Pakhomov

Bioelectrics Publications

Reversing the pulse polarity, i.e., changing the electric field direction by 180°, inhibits electroporation and electrostimulation by nanosecond electric pulses (nsEPs). This feature, known as “bipolar cancellation,” enables selective remote targeting with nsEPs and reduces the neuromuscular side effects of ablation therapies. We analyzed the biophysical mechanisms and measured how cancellation weakens and is replaced by facilitation when nsEPs are applied from different directions at angles from 0 to 180°. Monolayers of endothelial cells were electroporated by a train of five pulses (600 ns) or five paired pulses (600 + 600 ns) applied at 1 Hz or 833 kHz. Reversing …


Fate And Distribution Of Orally-Ingested Ceo2-Nanoparticles Based On A Mouse Model: Implication For Human Health, Xingmao Ma, Xiaoxuan Wang, Lei Xu, Honglan Shi, Hu Yang, Kerstin K. Landrock, Virender K. Sharma, Robert S. Chapkin Jun 2023

Fate And Distribution Of Orally-Ingested Ceo2-Nanoparticles Based On A Mouse Model: Implication For Human Health, Xingmao Ma, Xiaoxuan Wang, Lei Xu, Honglan Shi, Hu Yang, Kerstin K. Landrock, Virender K. Sharma, Robert S. Chapkin

Chemistry Faculty Research & Creative Works

The use of nanoparticles in agrichemical formula and food products as additives has increased their chances of accumulation in humans via oral intake. Due to their potential toxicity, it is critical to understand their fate and distribution following oral intake. Cerium oxide nanoparticle (CeO2NP) is commonly used in agriculture and is highly stable in the environment. as such, it has been used as a model chemical to investigate nanoparticle's distribution and clearance. based on their estimated human exposure levels, 0.15–0.75 mg/kg body weight/day of CeO2NPs with different sizes and surface charges (30–50 nm with negative charge and <25 >nm with positive …


Solving The Cable Equation, A Second-Order Time Dependent Pde For Non-Ideal Cables With Action Potentials In The Mammalian Brain Using Kss Methods, Nirmohi Charbe Jun 2023

Solving The Cable Equation, A Second-Order Time Dependent Pde For Non-Ideal Cables With Action Potentials In The Mammalian Brain Using Kss Methods, Nirmohi Charbe

Master's Theses

In this thesis we shall perform the comparisons of a Krylov Subspace Spectral method with Forward Euler, Backward Euler and Crank-Nicolson to solve the Cable Equation. The Cable Equation measures action potentials in axons in a mammalian brain treated as an ideal cable in the first part of the study. We shall subject this problem to the further assumption of a non-ideal cable. Assume a non-uniform cross section area along the longitudinal axis. At the present time, the effects of torsion, curvature and material capacitance are ignored. There is particular interest to generalize the application of the PDEs including and …


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 …


Synthesis And Study Of High-Spin Stable Organic Radicals For Electrical Conductors And Mannosamine Nitroxide For Mri Contrast Agents, Shuyang Zhang Jun 2023

Synthesis And Study Of High-Spin Stable Organic Radicals For Electrical Conductors And Mannosamine Nitroxide For Mri Contrast Agents, Shuyang Zhang

Department of Chemistry: Dissertations, Theses, and Student Research

In the first project, we describe the synthesis of an ambient stable high spin organic diradical 4 based on the Blatter moiety. The high-spin (S = 1) organic diradical 4, which consists of two Blatter radical moieties in a conjugated structure, exhibits a nearly exclusive population (88%) on triplet ground state at room temperature as a consequence of a large single-triplet energy gap (ΔEST = 0.5 kcal/mol). The target diradical molecule is synthesized over five steps with structural confirmation by single-crystal X-ray diffraction. The thermogravimetric analysis (TGA) shows the onset of decomposition at ~264 oC, indicating the diradical molecule has …


Extraction Of Challenging Forensic Samples Using The Microgem Dna Extraction Kit, Falyn R. Vega Jun 2023

Extraction Of Challenging Forensic Samples Using The Microgem Dna Extraction Kit, Falyn R. Vega

Student Theses

In forensic science, DNA extraction can be a tedious and resource-intensive process. Extraction with Proteinase K is an industry standard but has its drawbacks, such as requiring multiple ionic detergents and washing steps. MicroGEM has developed a new enzyme called forensicGEM that is temperature-dependent and compatible with mesophilic enzymes, offering complete DNA extraction in about 20 minutes in a single tube, limiting contamination, loss of sample, and working time. ForensicGEM can extract DNA from highly degraded samples, potentially leading to more complete STR profiles. Highly degraded tissue and bone samples were collected and extracted with the forensicGEM …


Multi-Target Ligand-Guided Selection (Ligs) Against B-Cell Specific Antigens Expressed In A Single Lymphoma Cell Population, Nicole B. Williams Jun 2023

Multi-Target Ligand-Guided Selection (Ligs) Against B-Cell Specific Antigens Expressed In A Single Lymphoma Cell Population, Nicole B. Williams

Dissertations, Theses, and Capstone Projects

Nucleic acid ligands called aptamers are single-stranded DNA or RNA molecules which fold into functional three-dimensional structures to facilitate their target binding with high affinity and specificity. The method used to generate aptamers is an in vitro process called Systematic Evolution of Ligands by Exponential enrichment (SELEX). A variant of SELEX, cell-SELEX has been used to select aptamers against cell-surface proteins in their native state. We recently introduced a novel method called Ligand-Guided Selection (LIGS) to identify aptamers against cell-surface markers. Herein, we expanded LIGS method into a multiplexing platform to partition multiple aptamers against B-cell-specific antigens, CD19 and CD20, …


Metabolic Reprogramming In Kras-Driven Cancer Cells, Ahmet Hatipoglu Jun 2023

Metabolic Reprogramming In Kras-Driven Cancer Cells, Ahmet Hatipoglu

Dissertations, Theses, and Capstone Projects

Cancer cells require nutrient uptake for anabolic reactions needed for cellular growth and proliferation. The mammalian target of rapamycin (mTOR) is a key regulator of cellular growth that links nutrient availability and growth factor signals. mTOR mediated signaling pathways are often dysregulated in a wide range of cancers. We previously reported that KRas-driven cancer cells sense exogenous lipids via de novo production of phosphatidic acid, which ultimately activates both mTOR complexes – mTORC1 and mTORC2. Activated mTORC2 phosphorylates the survival kinase Akt at Ser 473 which is required for full Akt activation. A direct substrate of Akt and a major …


Targeting Hif/Coregulator Complexes In Cancer: Characterizing Fragile Fold And Inhibitor Binding Sites Of Arnt, Xingjian Xu Jun 2023

Targeting Hif/Coregulator Complexes In Cancer: Characterizing Fragile Fold And Inhibitor Binding Sites Of Arnt, Xingjian Xu

Dissertations, Theses, and Capstone Projects

Hypoxia-inducible factors (HIFs) are transcription factors that play crucial roles in regulating adaptive cellular responses to low oxygen concentrations (hypoxia). Structurally, HIFs are heterodimers composed of one of three α-subunits (HIF-1α, -2α, and -3α) and a β subunit (HIF-β, also known as ARNT), with the heterodimerization mediated by the tandem PAS domains (PAS-A and PAS-B) found within both proteins. Dysregulation of the HIF pathway has been implicated in various types of cancers, contributing to cancer cell survival, tumor growth and progression, and resistance to therapies, resulting in poor treatment outcomes. As such, HIF-specific inhibitors have been extensively investigated as novel …


Leveraging Local Perturbations To Map Allosteric Networks Of Phosphatases, Tamar (Skaist) Mehlman Jun 2023

Leveraging Local Perturbations To Map Allosteric Networks Of Phosphatases, Tamar (Skaist) Mehlman

Dissertations, Theses, and Capstone Projects

Allostery is central to regulation of protein function, but our mechanistic understanding remains incomplete. A deeper understanding of how redistributions of conformational states drive allostery in proteins could allow us to better grasp natural regulatory principles in cells and open new doors to therapeutic development. Conformationally dynamic human Protein Tyrosine Phosphatases (PTPs) exemplify the challenges and opportunities associated with allostery. The archetypal PTP, PTP1B, has been highly validated as a therapeutic target but no allosteric inhibitors have been approved for clinical use. This is largely because our understanding of the mechanisms underlying allostery in PTP1B remains limited, despite the discovery …


Differential Inhibition Of Anaplerotic Pyruvate Carboxylation And Glutaminolysis-Fueled Anabolism Underlies Distinct Toxicity Of Selenium Agents In Human Lung Cancer, Teresa W-M Fan, Jason Winnike, Ahmad Al-Attar, Alex C. Belshoff, Pawel Lorkiewicz, Jin Lian Tan, Min Wu, Richard M. Higashi, Andrew N. Lane Jun 2023

Differential Inhibition Of Anaplerotic Pyruvate Carboxylation And Glutaminolysis-Fueled Anabolism Underlies Distinct Toxicity Of Selenium Agents In Human Lung Cancer, Teresa W-M Fan, Jason Winnike, Ahmad Al-Attar, Alex C. Belshoff, Pawel Lorkiewicz, Jin Lian Tan, Min Wu, Richard M. Higashi, Andrew N. Lane

Markey Cancer Center Faculty Publications

Past chemopreventive human trials on dietary selenium supplements produced controversial outcomes. They largely employed selenomethionine (SeM)-based diets. SeM was less toxic than selenite or methylseleninic acid (MSeA) to lung cancer cells. We thus investigated the toxic action of these Se agents in two non-small cell lung cancer (NSCLC) cell lines and ex vivo organotypic cultures (OTC) of NSCLC patient lung tissues. Stable isotope-resolved metabolomics (SIRM) using 13C6-glucose and 13C5,15N2-glutamine tracers with gene knockdowns were employed to examine metabolic dysregulations associated with cell type- and treatment-dependent phenotypic changes. Inhibition of key anaplerotic processes, pyruvate carboxylation (PyC) and glutaminolysis were elicited by …


Noncovalent Interactions That Tune The Reactivities Of The Flavins In Bifurcating Electron Transferring Flavoprotein, María González-Viegas, Rajiv K. Kar, Anne-Frances Miller, Maria-Andrea Mroginski Jun 2023

Noncovalent Interactions That Tune The Reactivities Of The Flavins In Bifurcating Electron Transferring Flavoprotein, María González-Viegas, Rajiv K. Kar, Anne-Frances Miller, Maria-Andrea Mroginski

Markey Cancer Center Faculty Publications

Bifurcating electron transferring flavoproteins (Bf-ETFs) tune chemically identical flavins to two contrasting roles. To understand how, we used hybrid quantum mechanical molecular mechanical calculations to characterize noncovalent interactions applied to each flavin by the protein. Our computations replicated the differences between the reactivities of the flavins: the electron transferring flavin ( ETflavin) was calculated to stabilize anionic semiquinone (ASQ) as needed to execute its single-electron transfers, whereas the Bf flavin (Bfflavin) was found to disfavor the ASQ state more than does free flavin and to be less susceptible to reduction. The stability of ETflavin ASQ was attributed in part to …


Novel Isolation Method Reveals Sex-Specific Composition And Neurotoxicity Of Small Extracellular Vesicles In A Mouse Model Of Alzheimer’S Disease, Ahmed Elsherbini, Zhihui Zhu, Zainuddin Quadri, Simone M. Crivelli, Xiaojia Ren, Hemendra J. Vekaria, Priyanka Tripathi, Liping Zhang, Wenbo Zhi, Erhard Bieberich Jun 2023

Novel Isolation Method Reveals Sex-Specific Composition And Neurotoxicity Of Small Extracellular Vesicles In A Mouse Model Of Alzheimer’S Disease, Ahmed Elsherbini, Zhihui Zhu, Zainuddin Quadri, Simone M. Crivelli, Xiaojia Ren, Hemendra J. Vekaria, Priyanka Tripathi, Liping Zhang, Wenbo Zhi, Erhard Bieberich

Markey Cancer Center Faculty Publications

We developed a new method to isolate small extracellular vesicles (sEVs) from male and female wild-type and 5xFAD mouse brains to investigate the sex-specific functions of sEVs in Alzheimer’s disease (AD). A mass spectrometric analysis revealed that sEVs contained proteins critical for EV formation and Aβ. ExoView analysis showed that female mice contained more GFAP and Aβ-labeled sEVs, suggesting that a larger proportion of sEVs from the female brain is derived from astrocytes and/or more likely to bind to Aβ. Moreover, sEVs from female brains had more acid sphingomyelinase (ASM) and ceramide, an enzyme and its sphingolipid product important for …


Mouse Models Of Spontaneous Atrial Fibrillation, Joshua A Keefe, Mohit M Hulsurkar, Svetlana Reilly, Xander H T Wehrens Jun 2023

Mouse Models Of Spontaneous Atrial Fibrillation, Joshua A Keefe, Mohit M Hulsurkar, Svetlana Reilly, Xander H T Wehrens

Faculty, Staff and Students Publications

Atrial fibrillation (AF) is the most common arrhythmia in adults, with a prevalence increasing with age. Current clinical management of AF is focused on tertiary prevention (i.e., treating the symptoms and sequelae) rather than addressing the underlying molecular pathophysiology. Robust animal models of AF, particularly those that do not require supraphysiologic stimuli to induce AF (i.e., showing spontaneous AF), enable studies that can uncover the underlying mechanisms of AF. Several mouse models of AF have been described to exhibit spontaneous AF, but pathophysiologic drivers of AF differ among models. Here, we describe relevant AF mechanisms and provide an overview of …


Comprehensive Ecg Reference Intervals In C57bl/6n Substrains Provide A Generalizable Guide For Cardiac Electrophysiology Studies In Mice, Manuela A Oestereicher, Janine M Wotton, Shinya Ayabe, Ghina Bou About, Tsz Kwan Cheng, Jae-Hoon Choi, Dave Clary, Emily M Dew, Lahcen Elfertak, Alain Guimond, Hamed Haseli Mashhadi, Jason D Heaney, Lois Kelsey, Piia Keskivali-Bond, Federico Lopez Gomez, Susan Marschall, Michael Mcfarland, Hamid Meziane, Violeta Munoz Fuentes, Ki-Hoan Nam, Zuzana Nichtová, Dale Pimm, Lynette Bower, Jan Prochazka, Jan Rozman, Luis Santos, Michelle Stewart, Nobuhiko Tanaka, Christopher S Ward, Amelia M E Willett, Robert Wilson, Robert E Braun, Mary E Dickinson, Ann M Flenniken, Yann Herault, K C Kent Lloyd, Ann-Marie Mallon, Colin Mckerlie, Stephen A Murray, Lauryl M J Nutter, Radislav Sedlacek, Je Kyung Seong, Tania Sorg, Masaru Tamura, Sara Wells, Elida Schneltzer, Helmut Fuchs, Valerie Gailus-Durner, Martin Hrabe De Angelis, Jacqueline K White, Nadine Spielmann Jun 2023

Comprehensive Ecg Reference Intervals In C57bl/6n Substrains Provide A Generalizable Guide For Cardiac Electrophysiology Studies In Mice, Manuela A Oestereicher, Janine M Wotton, Shinya Ayabe, Ghina Bou About, Tsz Kwan Cheng, Jae-Hoon Choi, Dave Clary, Emily M Dew, Lahcen Elfertak, Alain Guimond, Hamed Haseli Mashhadi, Jason D Heaney, Lois Kelsey, Piia Keskivali-Bond, Federico Lopez Gomez, Susan Marschall, Michael Mcfarland, Hamid Meziane, Violeta Munoz Fuentes, Ki-Hoan Nam, Zuzana Nichtová, Dale Pimm, Lynette Bower, Jan Prochazka, Jan Rozman, Luis Santos, Michelle Stewart, Nobuhiko Tanaka, Christopher S Ward, Amelia M E Willett, Robert Wilson, Robert E Braun, Mary E Dickinson, Ann M Flenniken, Yann Herault, K C Kent Lloyd, Ann-Marie Mallon, Colin Mckerlie, Stephen A Murray, Lauryl M J Nutter, Radislav Sedlacek, Je Kyung Seong, Tania Sorg, Masaru Tamura, Sara Wells, Elida Schneltzer, Helmut Fuchs, Valerie Gailus-Durner, Martin Hrabe De Angelis, Jacqueline K White, Nadine Spielmann

Faculty, Staff and Students Publications

Reference ranges provide a powerful tool for diagnostic decision-making in clinical medicine and are enormously valuable for understanding normality in pre-clinical scientific research that uses in vivo models. As yet, there are no published reference ranges for electrocardiography (ECG) in the laboratory mouse. The first mouse-specific reference ranges for the assessment of electrical conduction are reported herein generated from an ECG dataset of unprecedented scale. International Mouse Phenotyping Consortium data from over 26,000 conscious or anesthetized C57BL/6N wildtype control mice were stratified by sex and age to develop robust ECG reference ranges. Interesting findings include that heart rate and key …


Magnesium Increases Numbers Of Foxp3+ Treg Cells And Reduces Arthritis Severity And Joint Damage In An Il-10-Dependent Manner Mediated By The Intestinal Microbiome, Teresina Laragione, Carolyn Harris, Nasim Azizgolshani, Christine Beeton, Gerold Bongers, Percio S Gulko Jun 2023

Magnesium Increases Numbers Of Foxp3+ Treg Cells And Reduces Arthritis Severity And Joint Damage In An Il-10-Dependent Manner Mediated By The Intestinal Microbiome, Teresina Laragione, Carolyn Harris, Nasim Azizgolshani, Christine Beeton, Gerold Bongers, Percio S Gulko

Faculty, Staff and Students Publications

BACKGROUND: Rheumatoid arthritis (RA) is a common autoimmune disease with emerging environmental and microbiome risk factors. The western diet is typically deficient in magnesium (Mg), and there is some evidence suggesting that Mg may have anti-inflammatory properties. But the actual role of Mg supplementation in arthritis or in T cell subsets has not been explored.

METHODS: We investigated the role of a high Mg diet in two different mouse models of RA induced with the KRN serum, and collagen-induced arthritis. We also characterized the phenotypes of splenocytes, gene expression, and an extensive intestinal microbiome analyses including fecal material transplantation (FMT). …


Three-Dimensional Microct Imaging Of Mouse Heart Development From Early Post-Implantation To Late Fetal Stages, Nanbing Li-Villarreal, Tara L Rasmussen, Audrey E Christiansen, Mary E Dickinson, Chih-Wei Hsu Jun 2023

Three-Dimensional Microct Imaging Of Mouse Heart Development From Early Post-Implantation To Late Fetal Stages, Nanbing Li-Villarreal, Tara L Rasmussen, Audrey E Christiansen, Mary E Dickinson, Chih-Wei Hsu

Faculty, Staff and Students Publications

Comprehensive detailed characterization of new mouse models can be challenging due to the individual focus involved in developing these models. Often models are engineered to test a specific hypothesis in a limited number of tissues, stages, and/or other contexts. Whether or not the model produces the desired phenotypes, phenotyping beyond the desired context can be extremely work intensive and these studies are often not undertaken. However, the general information resulting from broader phenotyping can be invaluable to the wider scientific community. The International Mouse Phenotyping Consortium (IMPC) and its subsidiaries, like the Knockout Mouse Project (KOMP), has made great strides …


The Alternating Access Mechanism In Mammalian Multidrug Resistance Transporters And Their Bacterial Homologs, Shadi A. Badiee, Ugochi H. Isu, Ehsaneh Khodadadi, Mahmoud Moradi Jun 2023

The Alternating Access Mechanism In Mammalian Multidrug Resistance Transporters And Their Bacterial Homologs, Shadi A. Badiee, Ugochi H. Isu, Ehsaneh Khodadadi, Mahmoud Moradi

Chemistry & Biochemistry Faculty Publications and Presentations

Multidrug resistance (MDR) proteins belonging to the ATP-Binding Cassette (ABC) transporter group play a crucial role in the export of cytotoxic drugs across cell membranes. These proteins are particularly fascinating due to their ability to confer drug resistance, which subsequently leads to the failure of therapeutic interventions and hinders successful treatments. One key mechanism by which multidrug resistance (MDR) proteins carry out their transport function is through alternating access. This mechanism involves intricate conformational changes that enable the binding and transport of substrates across cellular membranes. In this extensive review, we provide an overview of ABC transporters, including their classifications …


First Course Portfolio For Bioc205: Scientific Analysis And Technical Writing, Lindsey B. Crawford Jun 2023

First Course Portfolio For Bioc205: Scientific Analysis And Technical Writing, Lindsey B. Crawford

UNL Faculty Course Portfolios

BIOC205: Scientific Analysis and Technical Writing is a core course for the Department of Biochemistry at the University of Nebraska-Lincoln. This course is geared for second year (sophomore students) with minimal prerequisites and as a foundation for future classes. Challenges include 1) teaching the needed scientific background and elements of scientific analysis and writing to a broad cohort of students with diverse backgrounds and interests, 2) building student skills towards analysis of primary peer-reviewed scientific literature, 3) developing students as writers of scientific information for different audiences. This course used Genetic Engineering as a broad topic choice to capture students …


Molecular Mechanisms Protecting Centromeres From Self-Sabotage And Implications For Cancer Therapy, Rim Nassar, Lily Thompson, Elise Fouquerel Jun 2023

Molecular Mechanisms Protecting Centromeres From Self-Sabotage And Implications For Cancer Therapy, Rim Nassar, Lily Thompson, Elise Fouquerel

Student Papers, Posters & Projects

Centromeres play a crucial role in DNA segregation by mediating the cohesion and separation of sister chromatids during cell division. Centromere dysfunction, breakage or compromised centromeric integrity can generate aneuploidies and chromosomal instability, which are cellular features associated with cancer initiation and progression. Maintaining centromere integrity is thus essential for genome stability. However, the centromere itself is prone to DNA breaks, likely due to its intrinsically fragile nature. Centromeres are complex genomic loci that are composed of highly repetitive DNA sequences and secondary structures and require the recruitment and homeostasis of a centromere-associated protein network. The molecular mechanisms engaged to …


The Development Of Novel Radioimmunoconjugates For The Pet Imaging And Radioimmunotherapy Of Cancer, Samantha M. Sarrett Jun 2023

The Development Of Novel Radioimmunoconjugates For The Pet Imaging And Radioimmunotherapy Of Cancer, Samantha M. Sarrett

Dissertations, Theses, and Capstone Projects

Antibodies have long played a vital role in nuclear medicine for both the diagnosis and therapy of various malignancies. The role and development of antibodies in nuclear medicine can be broadly separated into three different categories: 1) bioconjugation strategies, 2) immunoPET imaging, and 3) radioimmunotherapy. This dissertation will attempt to comprehensively cover each of these categories through a series of studies, protocols, and reviews. For the bioconjugation strategies, we will describe the development of a novel site-selective bioconjugation strategy using an innovative lysine-targeting reagent, PFP-bisN3, to prepare [89Zr]Zr-SSKDFO-pertuzumab for visualizing HER2+ breast cancer. Further, …


A Short-Term Method To Evaluate Anti-Leishmania Drugs By Inhibition Of Stage Differentiation In Leishmania Mexicana Using Flow Cytometry, Christian Florian Teh-Poot, Victor Manuel Dzul-Huchim, Jonathan M Mercado, Liliana Estefanía Villanueva-Lizama, Maria Elena Bottazzi, Kathryn M Jones, Francis T F Tsai, Julio Vladimir Cruz-Chan Jun 2023

A Short-Term Method To Evaluate Anti-Leishmania Drugs By Inhibition Of Stage Differentiation In Leishmania Mexicana Using Flow Cytometry, Christian Florian Teh-Poot, Victor Manuel Dzul-Huchim, Jonathan M Mercado, Liliana Estefanía Villanueva-Lizama, Maria Elena Bottazzi, Kathryn M Jones, Francis T F Tsai, Julio Vladimir Cruz-Chan

Faculty, Staff and Students Publications

Leishmaniasis is a vector-borne neglected tropical disease caused by the Leishmania spp. Parasite. The disease is transmitted to humans and animals by the bite of infected female sandflies during the ingestion of bloodmeal. Because current drug treatments induce toxicity and parasite resistance, there is an urgent need to evaluate new drugs. Most therapeutics target the differentiation of promastigotes to amastigotes, which is necessary to maintain Leishmania infection. However, in vitro assays are laborious, time-consuming, and depend on the experience of the technician. In this study, we aimed to establish a short-term method to assess the differentiation status of Leishmania mexicana …