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2024

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Articles 61 - 90 of 626

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

Assessing The Bioactivity Of Salvia Phytochemicals Against Breast Cancers, Allison C. Portaro, Jared L. Scott, David J. Schultz Nov 2024

Assessing The Bioactivity Of Salvia Phytochemicals Against Breast Cancers, Allison C. Portaro, Jared L. Scott, David J. Schultz

The Cardinal Edge

Breast cancer is one of the most common cancers diagnosed in adults, with 2.3 million new cases worldwide in 2020. Plants have been used in traditional medicine and are a potential source of pharmaceuticals. One example is the large Lamiaceae (mint) family. The Salvia genus, commonly known as the sages, is the largest genus in Lamiaceae with almost 900 known species. Different species of salvia are found in parts of the US, and some have a history in traditional medicine to treat cancers and other ailments. Preliminary research on three salvia species (S. lyrata, S. lyrata var. Purple …


Dysfunction Of Polyamine Metabolism In Down Syndrome Related To Cellular Senescence And Β-Amyloid Production, Andres D. Sola Nov 2024

Dysfunction Of Polyamine Metabolism In Down Syndrome Related To Cellular Senescence And Β-Amyloid Production, Andres D. Sola

Electronic Theses and Dissertations

Polyamines (PA) are ubiquitous in cells and highly involved in several important cellular functions and thus the dysregulation of their biosynthetic pathway is potentially associated with the progression of age-related diseases like Alzheimer’s’ disease (AD). Though there is research describing how PA content changes in organisms as they age or in those experiencing rapid aging from increased rates of senescence, as in Down syndrome (DS), it is not clear how this connection occurs and whether modulating this pathway may reveal downstream effects on related disease progression. This study examines how the modulation of the PA biosynthetic pathway by inhibition of …


Investigating The Role Of Tetherin Protein In Multivesicular Bodies Fusions In Lung Cancer Cells, Md. Rakib Miah Nov 2024

Investigating The Role Of Tetherin Protein In Multivesicular Bodies Fusions In Lung Cancer Cells, Md. Rakib Miah

Electronic Theses and Dissertations

Cells rely on the secretion of exosomes to communicate with one another and this process is potentially mediated by a protein called tetherin, which anchors exosomes to the cell surface to limit their spread. Tetherin protein has attracted a lot of attention because of its capacity to hinder the propagation of viruses by attaching virions to the surface of host cells. Treatment with interferon-alpha (IFNα) increases the production of tetherin, although it is not known how this affects tetherin localization and exosome-mediated communication. This thesis looks at how the expression of tetherin, which IFNα boosts, affects the dynamics of intercellular …


Effects Of Low Dose Exposure To Radiation And Sleep Fragmentation On Discrimination In String-Pulling Behavior With Female Rats, Jonathan F. Cortez, Diana Lloyd, T. L. Garcia, A. Adhikari, N. M. Attallah, N. Moges, D. H. Rodgers, K. S. Dhede, K. D. Omengan, A. A. Blackwell Nov 2024

Effects Of Low Dose Exposure To Radiation And Sleep Fragmentation On Discrimination In String-Pulling Behavior With Female Rats, Jonathan F. Cortez, Diana Lloyd, T. L. Garcia, A. Adhikari, N. M. Attallah, N. Moges, D. H. Rodgers, K. S. Dhede, K. D. Omengan, A. A. Blackwell

Undergraduate Research Symposium Posters

Astronauts will face harmful stressors, such as galactic cosmic radiation (GCR) and sleep fragmentation (SF), on a three-year space flight mission to Mars and back. Astronauts perform skilled reach-to-grasp behaviors on these missions, including interacting with controls to navigate the spacecraft. Recent work has shown that GCR and SF disrupt skilled reach-to-grasp behavior in rodent models; however, the underlying nature of these deficits is unknown. To determine if tactile sensation and proprioceptive feedback contribute to these impairments, this study evaluated the effects of radiation and SF exposure on memory and sensorimotor discrimination in a rodent model. Twenty-one outbred Wistar, retired …


Evaluating Human Plasma Biomakers For Alzheimer's Disease; Phosphorylated-Tau 217, Phosphorylated-Tau 181, And Glial Fibrillary Acidic Protein, Mason Jonah, Mayarae N. Mugosa, Bella Hou, Emma-Nikole Krilchev, Zhengshi Yang, Dietmar Cordes, Aaron Ritter, Jefferson W. Kinney Nov 2024

Evaluating Human Plasma Biomakers For Alzheimer's Disease; Phosphorylated-Tau 217, Phosphorylated-Tau 181, And Glial Fibrillary Acidic Protein, Mason Jonah, Mayarae N. Mugosa, Bella Hou, Emma-Nikole Krilchev, Zhengshi Yang, Dietmar Cordes, Aaron Ritter, Jefferson W. Kinney

Undergraduate Research Symposium Posters

Alzheimer’s Disease (AD) is a progressive neurodegenerative disease that is primarily identifiable by amyloid-beta (Aβ) neuronal plaques, neurofibrillary tangles (NFT) that form as aggregates of hyperphosphorylated tau (ptau) proteins clump together, and the presence of neuroinflammation; all of which are otherwise known as the hallmarks of AD pathology. Recent emerging research has discovered striking similarities between AD and diabetes mellitus pathology, illustrating how insulin deficiency and insulin resistance–both of which result in the chronic hyperglycemic state seen in the diabetic–are involved in an increase in the phosphorylation of tau. This leads to and intensifies the formation of intracellular NFTs serving …


Phagolysosomes Break Down The Membrane Of A Non-Apoptotic Corpse Independent Of Macroautophagy, Shruti Kolli, Cassidy J. Kline, Kimya M. Rad, Ann M. Wehman Nov 2024

Phagolysosomes Break Down The Membrane Of A Non-Apoptotic Corpse Independent Of Macroautophagy, Shruti Kolli, Cassidy J. Kline, Kimya M. Rad, Ann M. Wehman

Biological Sciences: Faculty Scholarship

Cell corpses must be cleared in an efficient manner to maintain tissue homeostasis and regulate immune responses. Ubiquitin-like Atg8/LC3 family proteins promote the degradation of membranes and internal cargo during both macroautophagy and corpse clearance, raising the question how macroautophagy contributes to corpse clearance. Studying the clearance of non-apoptotic dying polar bodies in Caenorhabditis elegans embryos, we show that the LC3 ortholog LGG-2 is enriched inside the polar body phagolysosome independent of autophagosome formation. We demonstrate that ATG-16.1 and ATG-16.2, which promote membrane association of lipidated Atg8/LC3 proteins, redundantly promote polar body membrane breakdown in phagolysosomes independent of their role …


Therapeutic Potential Of Astrocyte-Derived Extracellular Vesicles In Mitigating Cytotoxicity And Transcriptome Changes In Human Brain Endothelial Cells, Ruth Juliana Stewart Nov 2024

Therapeutic Potential Of Astrocyte-Derived Extracellular Vesicles In Mitigating Cytotoxicity And Transcriptome Changes In Human Brain Endothelial Cells, Ruth Juliana Stewart

Doctoral Dissertations

Extracellular vesicles (EVs) play a major role in cell-to-cell communication via the horizontal transfer of RNA, DNA, proteins, and lipids that affect the physiological response of the recipient cells. Astrocytes are a type of glial cell that exerts a protective effect on neurons and brain endothelial cells. The astrocytes and the endothelial cells form the blood-brain barrier. Due to their nano-size and non-complex structure, EVs can efficiently cross the blood-brain barrier. This study investigated and assessed the impact of EVs on reducing oxidative DNA damage in human brain endothelial cells (HBECs). The protective potential of astrocyte-derived EVs was determined by …


Reduced K+ Build-Up In T-Tubules Contributes To Resistance Of The Diaphragm To Myotonia, Jessica H. Myers, Kirsten Denman, Chris Dupont, Brent D. Foy, Mark M. Rich Nov 2024

Reduced K+ Build-Up In T-Tubules Contributes To Resistance Of The Diaphragm To Myotonia, Jessica H. Myers, Kirsten Denman, Chris Dupont, Brent D. Foy, Mark M. Rich

Physics Faculty Publications

Patients with myotonia congenita suffer from slowed muscle relaxation caused by hyperexcitability. The diaphragm is only mildly affected in myotonia congenita; discovery of the mechanism underlying its resistance to myotonia could identify novel therapeutic targets. Intracellular recordings from two mouse models of myotonia congenita revealed the diaphragm had less myotonia than either the extensor digitorum longus (EDL) or the soleus muscles. A mechanism contributing to resistance of the diaphragm to myotonia was reduced depolarization of the interspike membrane potential during repetitive firing of action potentials, a process driven by build-up of K+ in small invaginations of muscle membrane known as …


Impact Of Chytrid Fungal Infection On Muscle Structure In Amphibians, Esther Hassan, Chisom Ukachukwu Nov 2024

Impact Of Chytrid Fungal Infection On Muscle Structure In Amphibians, Esther Hassan, Chisom Ukachukwu

Science University Research Symposium (SURS)

Many fungal infections affect a wide variety of ecosystems. They cause numerous negative consequences, one in particular being the disruption of biodiversity. disrupting biodiversity and leading to numerous negative consequences. A previous study in the Kinsey lab focused on a chytrid fungal disease, Batrachochytrium dendrobatidis (Bd), a species of chytrid fungus. This disease poses a major threat to amphibian populations worldwide. The Bd zoospores infect the epidermis impacting essential systems. This leads to electrolyte transport that is conducted through the epidermis from the environment has now become disrupted and the ions required for daily functions are diminished. Eventually, these lack …


Genome-Guided Isolation Of The Hyperthermophilic Aerobe Fervidibacter Sacchari Reveals Conserved Polysaccharide Metabolism In The Armatimonadota, Nancy O. Nou, Jonathan K. Covington, Dengxun Lai, Xavier Mayali, Cale O. Seymour, Juliet Johnston, Jian-Yu Jiao, Steffen Buessecker, Damon Mosier, Alise R. Muok, Nicole Torosian, Allison M. Cook, Ariane Briegel, Tanja Woyke, Emiley Eloe-Fadrosh, Nicole Shapiro, Scott G. Bryan, Savannah Sleezer, Joshua Dimapilis, Cristina Gonzalez, Lizett Gonzalez, Marlene Noriega, Matthias Hess, Ross P. Carlson, Lan Liu, Meng-Meng Li, Zheng-Han Lian, Siqii Zhu, Fan Liu, Xian Sun, Beile Gao, Ritesh Mewalal, Miranda Harmon-Smith, Ian K. Blaby, Jan-Fang Cheng, Peter K. Weber, Gabriela Grigorean, Wen-Jun Li, Anne E. Dekas, Jennifer E. Pett-Ridge, Jeremy A. Dodsworth, Marike Palmer, Brian P. Hedlund Nov 2024

Genome-Guided Isolation Of The Hyperthermophilic Aerobe Fervidibacter Sacchari Reveals Conserved Polysaccharide Metabolism In The Armatimonadota, Nancy O. Nou, Jonathan K. Covington, Dengxun Lai, Xavier Mayali, Cale O. Seymour, Juliet Johnston, Jian-Yu Jiao, Steffen Buessecker, Damon Mosier, Alise R. Muok, Nicole Torosian, Allison M. Cook, Ariane Briegel, Tanja Woyke, Emiley Eloe-Fadrosh, Nicole Shapiro, Scott G. Bryan, Savannah Sleezer, Joshua Dimapilis, Cristina Gonzalez, Lizett Gonzalez, Marlene Noriega, Matthias Hess, Ross P. Carlson, Lan Liu, Meng-Meng Li, Zheng-Han Lian, Siqii Zhu, Fan Liu, Xian Sun, Beile Gao, Ritesh Mewalal, Miranda Harmon-Smith, Ian K. Blaby, Jan-Fang Cheng, Peter K. Weber, Gabriela Grigorean, Wen-Jun Li, Anne E. Dekas, Jennifer E. Pett-Ridge, Jeremy A. Dodsworth, Marike Palmer, Brian P. Hedlund

Life Sciences Faculty Research

Few aerobic hyperthermophilic microorganisms degrade polysaccharides. Here, we describe the genome-enabled enrichment and optical tweezer-based isolation of an aerobic polysaccharide-degrading hyperthermophile, Fervidibacter sacchari, previously ascribed to candidate phylum Fervidibacteria. F. sacchari uses polysaccharides and monosaccharides for growth at 65–87.5 °C and expresses 191 carbohydrate-active enzymes (CAZymes) according to RNA-Seq and proteomics, including 31 with unusual glycoside hydrolase domains (GH109, GH177, GH179). Fluorescence in-situ hybridization and nanoscale secondary ion mass spectrometry confirmed rapid assimilation of 13C-starch in spring sediments. Purified GHs were optimally active at 80–100 °C on ten different polysaccharides. Finally, we propose reassigning Fervidibacteria as a class …


Viral Genome Delivery Across Bacterial Cell Surfaces, Stephano M. Iglesias, Fenglin Li, Federica Briani, Gino Cingolani Nov 2024

Viral Genome Delivery Across Bacterial Cell Surfaces, Stephano M. Iglesias, Fenglin Li, Federica Briani, Gino Cingolani

Department of Biochemistry and Molecular Biology Faculty Papers

In 1952, Hershey and Chase used bacteriophage T2 genome delivery inside Escherichia coli to demonstrate that DNA, not protein, is the genetic material. Over 70 years later, our understanding of bacteriophage structure has grown dramatically, mainly thanks to the cryogenic electron microscopy revolution. In stark contrast, phage genome delivery in prokaryotes remains poorly understood, mainly due to the inherent challenge of studying such a transient and complex process. Here, we review the current literature on viral genome delivery across bacterial cell surfaces. We focus on icosahedral bacterial viruses that we arbitrarily sort into three groups based on the presence and …


Diverse Pathways In Gpcr-Mediated Activation Of Ca2+ Mobilization In Hek293 Cells, Francesco De Pascali, Asuka Inoue, Jeffrey L. Benovic Nov 2024

Diverse Pathways In Gpcr-Mediated Activation Of Ca2+ Mobilization In Hek293 Cells, Francesco De Pascali, Asuka Inoue, Jeffrey L. Benovic

Department of Biochemistry and Molecular Biology Faculty Papers

G protein-coupled receptors transduce extracellular stimuli into intracellular signaling. Ca2+ is a well-known second messenger that can be induced by G protein-coupled receptor activation through the primary canonical pathways involving Gαq- and Gβγ-mediated activation of phospholipase C-β (PLCβ). While some Gs-coupled receptors are shown to trigger Ca2+ mobilization, underlying mechanisms remain elusive. Here, we evaluated whether Gs-coupled receptors including the β2-adrenergic receptor (β2AR) and the prostaglandin EP2 and EP4 receptors (EP2R and EP4R) that are endogenously expressed in human embryonic kidney 293 …


Engineering The Coherent Phonon Transport In Polar Ferromagnetic Oxide Superlattices, In Hyeok Choi, Seung Gyo Jeong, Do-Gyeom Jeong, Ambrose Seo, Woo Seok Choi, Jong Seok Lee Nov 2024

Engineering The Coherent Phonon Transport In Polar Ferromagnetic Oxide Superlattices, In Hyeok Choi, Seung Gyo Jeong, Do-Gyeom Jeong, Ambrose Seo, Woo Seok Choi, Jong Seok Lee

Chemical and Materials Engineering Faculty Publications

Artificial superlattices composed of perovskite oxides serves as an essential platform for engineering coherent phonon transport by redefining the lattice periodicity, which strongly influences the lattice-coupled phase transitions in charge and spin degrees of freedom. However, previous methods of manipulating phonons have been limited to controlling the periodicity of superlattice, rather than utilizing complex mutual interactions that are prominent in transition metal oxides. In this study on oxide superlattices composed of ferromagnetic metallic SrRuO3 and quantum paraelectric SrTiO3 , phonon modulation by controlling the geometry of superlattice in atomic-scale precision is realized, demonstrating the coherent phonon engineering using structural and …


Repeated Shifts In Sociality Are Associated With Fine-Tuning Of Highly Conserved And Lineage-Specific Enhancers In A Socially Flexible Bee, Beryl M. Jones, Andrew E. Webb, Scott M. Geib, Sheina Sim, Rena M. Schweizer, Michael G. Branstetter, Jay D. Evans, Sarah D. Kocher Nov 2024

Repeated Shifts In Sociality Are Associated With Fine-Tuning Of Highly Conserved And Lineage-Specific Enhancers In A Socially Flexible Bee, Beryl M. Jones, Andrew E. Webb, Scott M. Geib, Sheina Sim, Rena M. Schweizer, Michael G. Branstetter, Jay D. Evans, Sarah D. Kocher

Entomology Faculty Publications

Comparative genomic studies of social insects suggest that changes in gene regulation are associated with evolutionary transitions in social behavior, but the activity of predicted regulatory regions has not been tested empirically. We used self-transcribing active regulatory region sequencing, a high-throughput enhancer discovery tool, to identify and measure the activity of enhancers in the socially variable sweat bee, Lasioglossum albipes. We identified over 36,000 enhancers in the L. albipes genome from 3 social and 3 solitary populations. Many enhancers were identified in only a subset of L. albipes populations, revealing rapid divergence in regulatory regions within this species. Population-specific enhancers …


The Divergent Responses Of Salinity Generalists To Hyposaline Stress Provide Insights Into The Colonisation Of Freshwaters By Diatoms, Kathryn J. Judy, Eveline Pinseel, Kala M. Downey, Jeffrey A. Lewis, Andrew J. Alverson Nov 2024

The Divergent Responses Of Salinity Generalists To Hyposaline Stress Provide Insights Into The Colonisation Of Freshwaters By Diatoms, Kathryn J. Judy, Eveline Pinseel, Kala M. Downey, Jeffrey A. Lewis, Andrew J. Alverson

Biological Sciences Faculty Publications and Presentations

Environmental transitions, such as the salinity divide separating marine and fresh waters, shape biodiversity over both shallow and deep timescales, opening up new niches and creating opportunities for accelerated speciation and adaptive radiation. Understanding the genetics of environmental adaptation is central to understanding how organisms colonise and subsequently diversify in new habitats. We used time-resolved transcriptomics to contrast the hyposalinity stress responses of two diatoms. Skeletonema marinoi has deep marine ancestry but has recently invaded brackish waters. Cyclotella cryptica has deep freshwater ancestry and can withstand a much broader salinity range. Skeletonema marinoi is less adept at mitigating even mild …


The Effect Of Nerolidol On The Renal Dysfunction Following Bilateral Ureteral Obstruction In The Rat, Harun Rashed Toumi Nov 2024

The Effect Of Nerolidol On The Renal Dysfunction Following Bilateral Ureteral Obstruction In The Rat, Harun Rashed Toumi

Theses

This thesis addressed nerolidol’s potential therapeutic and protective effects on bilateral ureteral obstruction-induced uropathy in rats. Obstructive uropathy stands as a notable contributor to acute kidney injury (AKI), accounting for 5-10% of all AKI cases worldwide, with a particularly high prevalence among the elderly, constituting 22% of AKI cases in this age group. Urinary tract obstruction, often attributed to factors such as kidney stones, urinary tract deformities and benign/malignant growths such as benign prostatic hyperplasia (BPH) in older men can lead to detrimental outcomes if left untreated, potentially progressing to kidney failure and even mortality. The severity of the kidney …


Noncontact Diffuse Reflectance Spectroscopy Of Synovial Fluid Samples For Rapid Identification Of Infections, Erin E. Drewke, Robert L. Brand, Caroline G. Geels, Hanna K. Jensen, Kevin Wong, Jarret D. Sanders, Narasimhan Rajaram Nov 2024

Noncontact Diffuse Reflectance Spectroscopy Of Synovial Fluid Samples For Rapid Identification Of Infections, Erin E. Drewke, Robert L. Brand, Caroline G. Geels, Hanna K. Jensen, Kevin Wong, Jarret D. Sanders, Narasimhan Rajaram

Biomedical Engineering Faculty Publications and Presentations

Severe joint infections, such as septic arthritis, require rapid diagnostic testing of the synovial fluid aspirated from joints level so that a surgical team can be assembled quickly. We present a diffuse reflectance spectroscopy (DRS) system for noncontact determination of infection. Using a light-tight syringe holder and fiber optic probe, diffusely reflected light from 475 to 655 nm was acquired from 18 patient samples through the wall of a syringe in a noncontact and sterile manner. We determined the reflectance ratios at two different wavelengths—R 490/R 600 and R 580/R 600 and found statistically significant …


A Phenotypic Characterization Of Staphylococcus Aureus Bacteremia Clinical Isolates, Sara Dj Daniels Oct 2024

A Phenotypic Characterization Of Staphylococcus Aureus Bacteremia Clinical Isolates, Sara Dj Daniels

USF Tampa Graduate Theses and Dissertations

Staphylococcus aureus is a human pathogen of serious concern because of its ability to cause serious and wide-ranging disease. Of particular concern is the ability of S. aureus to cause bacteremia (SAB), allowing the bacteria to disseminate and spread to various organs. This study addressed this issue through the phenotypic characterization of two methicillin-resistant S. aureus (MRSA) clinical isolates taken from patients with sustained complicated bacteremia at Tampa General Hospital, referred to as SA1097 and SA1098. A battery of phenotypic tests was conducted on these strains, including a growth curve, hemolysis and proteolysis screenings, cytotoxicity assays using human neutrophils, blood …


Rictor, A Mtorc2 Protein, Regulates Lymphatic Valve Formation And Maintenance Through The Akt-Foxo1 Signaling Axis, Richa Banerjee Oct 2024

Rictor, A Mtorc2 Protein, Regulates Lymphatic Valve Formation And Maintenance Through The Akt-Foxo1 Signaling Axis, Richa Banerjee

USF Tampa Graduate Theses and Dissertations

The lymphatic vasculature maintains tissue fluid homeostasis by absorbing interstitial fluid to form lymph and transporting it back to the bloodstream. Collecting lymphatic vessels have lymphatic valves (LVs) that prevent the retrograde flow of lymph generated by hydrostatic pressure from the blood vasculature. Backflow and accumulation of lymph leads to a lymphatic pathology called lymphedema. This implicates the involvement of defective LVs in the pathogenesis of lymphedema and warrants the study of lymphatic valve development and maintenance. The LVs are formed through a process called mechanotransduction which signals through the intracellular PI3K-AKT pathway in lymphatic endothelial cells. However, the activation …


Selective Pericyte Recruitment To Ec-Lined Tubes, Vessel Assembly Enhancement Through Pericyte Timp-3 Induction, And Pericyte Tbx2 In Capillary Formation And Maturation, Ksenia Marilyn Yrigoin Kaluguina Oct 2024

Selective Pericyte Recruitment To Ec-Lined Tubes, Vessel Assembly Enhancement Through Pericyte Timp-3 Induction, And Pericyte Tbx2 In Capillary Formation And Maturation, Ksenia Marilyn Yrigoin Kaluguina

USF Tampa Graduate Theses and Dissertations

Capillaries, the smallest blood vascular networks, are formed by narrow and elongated endothelial cell (EC)-lined tubes with associated pericytes anchored to the abluminal tube surface. Our laboratory demonstrated that dynamic interactions between ECs and pericytes during capillary tube network assembly are required for basement membrane matrix deposition and maturation. We have also shown that key EC-derived factors promote pericyte recruitment, proliferation, and pericyte-induced basement membrane formation during capillary assembly. In the first section, we aim to identify if vascular smooth muscle cells (VSMCs) respond to the same factors and have the same invasive ability as pericytes since they are both …


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

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

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 …


Conformational Cycle Of A Protease-Containing Abc Transporter In Lipid Nanodiscs Reveals The Mechanism Of Cargo-Protein Coupling, Ruojiing Zhang, Kevin L. Jagessar, University Of Arkansas, Fayetteville, Adithya Polasa, Richard A. Stein, Mahmoud Moradi, Erkan Karakas, Hassane S. Mchaourab Oct 2024

Conformational Cycle Of A Protease-Containing Abc Transporter In Lipid Nanodiscs Reveals The Mechanism Of Cargo-Protein Coupling, Ruojiing Zhang, Kevin L. Jagessar, University Of Arkansas, Fayetteville, Adithya Polasa, Richard A. Stein, Mahmoud Moradi, Erkan Karakas, Hassane S. Mchaourab

Chemistry & Biochemistry Faculty Publications and Presentations

Protease-containing ABC transporters (PCATs) couple the energy of ATP hydrolysis to the processing and export of diverse cargo proteins across cell membranes to mediate antimicrobial resistance and quorum sensing. Here, we combine biochemical analysis, single particle cryoEM, and DEER spectroscopy in lipid bilayers along with computational analysis to illuminate the structural and energetic underpinnings of coupled cargo protein export. Our integrated investigation uncovers competitive interplay between nucleotides and cargo protein binding that ensures the latter’s orderly processing and subsequent transport. The energetics of cryoEM structures in lipid bilayers are congruent with the inferred mechanism from ATP turnover analysis and reveal …


Post-Transcriptional Methylation Of Mitochondrial-Trna Differentially Contributes To Mitochondrial Pathology, Sunita Maharjan, Howard Gamper, Yuka Yamaki, Thomas W. Christian, Robert Y. Henley, Nan-Sheng Li, Takeo Suzuki, Tsutomu Suzuki, Joseph A. Piccirilli, Meni Wanunu, Erin L. Seifert, Douglas C. Wallace, Ya-Ming Hou Oct 2024

Post-Transcriptional Methylation Of Mitochondrial-Trna Differentially Contributes To Mitochondrial Pathology, Sunita Maharjan, Howard Gamper, Yuka Yamaki, Thomas W. Christian, Robert Y. Henley, Nan-Sheng Li, Takeo Suzuki, Tsutomu Suzuki, Joseph A. Piccirilli, Meni Wanunu, Erin L. Seifert, Douglas C. Wallace, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

Human mitochondrial tRNAs (mt-tRNAs), critical for mitochondrial biogenesis, are frequently associated with pathogenic mutations. These mt-tRNAs have unusual sequence motifs and require post-transcriptional modifications to stabilize their fragile structures. However, whether a modification that stabilizes a wild-type (WT) mt-tRNA would also stabilize its pathogenic variants is unknown. Here we show that the N1-methylation of guanosine at position 9 (m1G9) of mt-Leu(UAA), while stabilizing the WT tRNA, has a destabilizing effect on variants associated with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes). This differential effect is further demonstrated, as removal of the m1G9 …


Effects Of Cadherin Mediated Contact Normalization On Oncogenic Src Kinase Mediated Gene Expression And Protein Phosphorylation, Rachel E Nicoletto, Cayla J Holdcraft, Ariel C Yin, Edward P Retzbach, Stephanie A Sheehan, Amanda A Greenspan, Christopher M Laugier, Jason Trama, Caifeng Zhao, Haiyan Zheng, Gary S Goldberg Oct 2024

Effects Of Cadherin Mediated Contact Normalization On Oncogenic Src Kinase Mediated Gene Expression And Protein Phosphorylation, Rachel E Nicoletto, Cayla J Holdcraft, Ariel C Yin, Edward P Retzbach, Stephanie A Sheehan, Amanda A Greenspan, Christopher M Laugier, Jason Trama, Caifeng Zhao, Haiyan Zheng, Gary S Goldberg

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Nontransformed cells form heterotypic cadherin junctions with adjacent transformed cells to inhibit tumor cell growth and motility. Transformed cells must override this form of growth control, called "contact normalization", to invade and metastasize during cancer progression. Heterocellular cadherin junctions between transformed and nontransformed cells are needed for this process. However, specific mechanisms downstream of cadherin signaling have not been clearly elucidated. Here, we utilized a β-catenin reporter construct to determine if contact normalization affects Wnt signaling in transformed cells. β-catenin driven GFP expression in Src transformed mouse embryonic cells was decreased when cultured with cadherin competent nontransformed cells compared to …


Characterizing The Influence Of Metabolism On Steady State Water Exchange In Yeast As A Potential Mri Diagnostic Biomarker, Samantha Mumford Oct 2024

Characterizing The Influence Of Metabolism On Steady State Water Exchange In Yeast As A Potential Mri Diagnostic Biomarker, Samantha Mumford

Dissertations and Theses

Under conditions of ionic equilibrium with the environment a cell maintains a constant volume yet rapidly exchanges water molecules with the extracellular space. The rate constant for steady state water efflux, kio, can be measured using contrast enhanced magnetic resonance (CE-MR). The active water cycling (AWC) hypothesis is puts forward that kio is primarily influenced by cellular ATP levels and H+ ATPase activity at the cell membrane. Due to the correlation between kio and ATP levels, kio is thought to be a probable MRI biomarker for metabolic diseases such as cancer. Yet, the molecular …


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 …


Examination Of Photoinduced Radicals In Two Crystal Forms Of Triphenylamine Bis-Urea Macrocycles, Md Faizul Islam, Gamage Isuri P. Wijesekera, Anmon J. Sindt, Mark D. Smith, Linda S. Shimizu Oct 2024

Examination Of Photoinduced Radicals In Two Crystal Forms Of Triphenylamine Bis-Urea Macrocycles, Md Faizul Islam, Gamage Isuri P. Wijesekera, Anmon J. Sindt, Mark D. Smith, Linda S. Shimizu

Faculty Publications

This study probes two solvates of triphenylamine (TPA) bis-urea macrocycle 1 and their activated structures to evaluate their maximum photoinduced radicals (PIRs), the subsequent decay of the radicals, and their regeneration. The hierarchical assembly of TPAs shows promise in stabilizing less substituted derivatives, potentially expanding the utility of TPAs that lack stabilizing para-substituents. Single crystal structure analysis reveals that host 1 adopts a planar conformation with the two ureas pointing in opposite directions when dimethoxyethane (DME) is encapsulated within the channel. Whereas previously, 1 adopted a bowl-shaped conformation with the two ureas pointing in the same direction (syn …


Examination Of Photoinduced Radicals In Two Crystal Forms Of Triphenylamine Bis-Urea Macrocycles, Md Faizul Islam, Gamage Isuri P. Wijesekera, Ammon J. Sindt, Mark D. Smith, Linda S. Shimizu Oct 2024

Examination Of Photoinduced Radicals In Two Crystal Forms Of Triphenylamine Bis-Urea Macrocycles, Md Faizul Islam, Gamage Isuri P. Wijesekera, Ammon J. Sindt, Mark D. Smith, Linda S. Shimizu

Faculty Publications

This study probes two solvates of triphenylamine (TPA) bis-urea macrocycle 1 and their activated structures to evaluate their maximum photoinduced radicals (PIRs), the subsequent decay of the radicals, and their regeneration. The hierarchical assembly of TPAs shows promise in stabilizing less substituted derivatives, potentially expanding the utility of TPAs that lack stabilizing para-substituents. Single crystal structure analysis reveals that host 1 adopts a planar conformation with the two ureas pointing in opposite directions when dimethoxyethane (DME) is encapsulated within the channel. Whereas previously, 1 adopted a bowl-shaped conformation with the two ureas pointing in the same direction (syn …


Water Quality Of Silver Creek, A Buried Urban Stream, Nick Bultje, Valerie Krause, Rebecca Nulty Oct 2024

Water Quality Of Silver Creek, A Buried Urban Stream, Nick Bultje, Valerie Krause, Rebecca Nulty

Student Papers and Reports

There are many sources of pollution that can affect a watershed. These pollutants can impact the water's pH, temperature, conductivity, and dissolved solids. Escherichia coli is a specific pollutant that comes from waste products of humans and animals. High levels of E. coli cause serious health problems. This study examines Silver Creek, a tributary within the Plaster Creek watershed. Silver Creek runs mostly underground and has storm drainage systems that flow into the creek. The goal was to explore the effects of the underground section of Silver Creek on water quality and E. coli levels. The water quality and levels …