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Articles 121 - 150 of 902

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

Genome-Wide Investigation Of Snrk2 Gene Family In Two Jute Species: Corchorus Olitorius And Corchorus Capsularis, Borhan Ahmed, Fakhrul Hasan, Anika Tabassum, Rasel Ahmed, Rajnee Hassan, Ruhul Amin, Mobashwer Alam Jan 2023

Genome-Wide Investigation Of Snrk2 Gene Family In Two Jute Species: Corchorus Olitorius And Corchorus Capsularis, Borhan Ahmed, Fakhrul Hasan, Anika Tabassum, Rasel Ahmed, Rajnee Hassan, Ruhul Amin, Mobashwer Alam

Department of Biochemistry: Faculty Publications

Background Sucrose non-fermenting-1 (SNF1)-related protein kinase 2 (SnRK2), a plant-specifc serine/threonine kinase family, is associated with metabolic responses, including abscisic acid signaling under biotic and abiotic stresses. So far, no information on a genome-wide investigation and stress-mediated expression profling of jute SnRK2 is available. Recent whole-genome sequencing of two Corchorus species prompted to identify and characterize this SnRK2 gene family.

Result We identifed seven SnRK2 genes of each of Corchorus olitorius (Co) and C. capsularis (Cc) genomes, with similar physico-molecular properties and sub-group patterns of other models and related crops. In both species, the SnRK2 gene …


Oligogalactolipid Production During Cold Challenge Is Conserved In Early Diverging Lineages, Allison C. Barnes, Jennifer L. Myers, Samantha M. Surber, Zhikai Liang, Jeffrey P. Mower, James Schnable, Rebecca Roston Jan 2023

Oligogalactolipid Production During Cold Challenge Is Conserved In Early Diverging Lineages, Allison C. Barnes, Jennifer L. Myers, Samantha M. Surber, Zhikai Liang, Jeffrey P. Mower, James Schnable, Rebecca Roston

Department of Biochemistry: Faculty Publications

Oligogalactolipid production is a response to severe cold in many land plant lineages. It occurs during times of membrane damage and can be reproduced in multiple species by cytosolic acidification.

Severe cold, defined as a damaging cold beyond acclimation temperatures, has unique responses, but the signaling and evolution of these responses are not well understood. Production of oligogalactolipids, which is triggered by cytosolic acidification in Arabidopsis (Arabidopsis thaliana), contributes to survival in severe cold. Here, we investigated oligogalactolipid production in species from bryophytes to angiosperms. Production of oligogalactolipids differed within each clade, suggesting multiple evolutionary origins of severe …


A Facile Strategy For The Fabrication Of Cell-Laden Porous Alginate Hydrogels Based On Two-Phase Aqueous Emulsions, Wen Xue, Donghee Lee, Yunfan Kong, Mitchell Kuss, Ying Huang, Taesung Kim, Soonkyu Chung, Andrew T. Dudley, Seung-Hyun Ro, Bin Duan Jan 2023

A Facile Strategy For The Fabrication Of Cell-Laden Porous Alginate Hydrogels Based On Two-Phase Aqueous Emulsions, Wen Xue, Donghee Lee, Yunfan Kong, Mitchell Kuss, Ying Huang, Taesung Kim, Soonkyu Chung, Andrew T. Dudley, Seung-Hyun Ro, Bin Duan

Department of Biochemistry: Faculty Publications

Porous alginate (Alg) hydrogels possess many advantages as cell carriers. However, current pore generation methods require either complex or harsh fabrication processes, toxic components, or extra purification steps, limiting the feasibility and affecting the cellular survival and function. In this study, a simple and cell-friendly approach to generate highly porous cell-laden Alg hydrogels based on two-phase aqueous emulsions is reported. The pre-gel solutions, which contain two immiscible aqueous phases of Alg and caseinate (Cas), are cross-linked by calcium ions. The porous structure of the hydrogel construct is formed by subsequently removing the Cas phase from the ion-cross-linked Alg hydrogel. Those …


Structural Basis Of Dna Binding By The Whib-Like Transcription Factor Whib3 In Mycobacterium Tuberculosis, Tao Wan, Magdaléna Horová, Vimmy Khetrapal, Shanren Li, Camden Jones, Andrew Schacht, Xinghui Sun, Limei Zhang Jan 2023

Structural Basis Of Dna Binding By The Whib-Like Transcription Factor Whib3 In Mycobacterium Tuberculosis, Tao Wan, Magdaléna Horová, Vimmy Khetrapal, Shanren Li, Camden Jones, Andrew Schacht, Xinghui Sun, Limei Zhang

Department of Biochemistry: Faculty Publications

Mycobacterium tuberculosis (Mtb) WhiB3 is an iron–sulfur cluster-containing transcription factor belonging to a subclass of the WhiB-Like (Wbl) family that is widely distributed in the phylum Actinobacteria. WhiB3 plays a crucial role in the survival and pathogenesis of Mtb. It binds to the conserved region 4 of the principal sigma factor (σA4) in the RNA polymerase holoenzyme to regulate gene expression like other known Wbl proteins in Mtb. However, the structural basis of how WhiB3 coordinates with σA4 to bind DNA and regulate transcription is unclear. Here we determined crystal structures …


Akkermansia Muciniphila And Its Membrane Protein Ameliorates Intestinal Inflammatory Stress And Promotes Epithelial Wound Healing Via Crebh And Mir‑143/145, Henry Wade, Kaichao Pan, Qihua Duan, Szczepan Kaluzny, Ekta Pandey, Linda Fatumoju, Viswanathan Saraswathi, Rongxue Wu, Edward N. Harris, Qiaozhu Su Jan 2023

Akkermansia Muciniphila And Its Membrane Protein Ameliorates Intestinal Inflammatory Stress And Promotes Epithelial Wound Healing Via Crebh And Mir‑143/145, Henry Wade, Kaichao Pan, Qihua Duan, Szczepan Kaluzny, Ekta Pandey, Linda Fatumoju, Viswanathan Saraswathi, Rongxue Wu, Edward N. Harris, Qiaozhu Su

Department of Biochemistry: Faculty Publications

Background The intestinal epithelial barrier is the interface for interaction between gut microbiota and host metabolic systems. Akkermansia muciniphila (A. muciniphila) is a key player in the colonic microbiota that resides in the mucus layer, whose abundance is selectively decreased in the faecal microbiota of inflammatory bowel disease (IBD) patients. This study aims to investigate the regulatory mechanism among A. muciniphila, a transcription factor cAMPresponsive element-binding protein H (CREBH), and microRNA-143/145 (miR-143/145) in intestinal inflammatory stress, gut barrier integrity and epithelial regeneration.

Methods A novel mouse model with increased colonization of A muciniphila in the intestine of CREBH knockout …


Factors Influencing Instructors’ Adoption And Continued Use Of Computing Science Technologies: A Case Study In The Context Of Cell Collective, Changsoo Song, Resa M. Helikar, Wendy M. Smith, Tomáš Helikar Jan 2023

Factors Influencing Instructors’ Adoption And Continued Use Of Computing Science Technologies: A Case Study In The Context Of Cell Collective, Changsoo Song, Resa M. Helikar, Wendy M. Smith, Tomáš Helikar

Department of Biochemistry: Faculty Publications

Acquiring computational modeling and simulation skills has become ever more critical for students in life sciences courses at the secondary and tertiary levels. Many modeling and simulation tools have been created to help instructors nurture those skills in their classrooms. Understanding the factors that may motivate instructors to use such tools is crucial to improve students’ learning, especially for having authentic modeling and simulation learning experiences. This study designed and tested a decomposed technology acceptance model in which the perceived usefulness and perceived ease of use constructs are split between the teaching and learning sides of the technology to examine …


Conformal Electrodeposition Of Antimicrobial Hydrogels Formed By Self-Assembled Peptide Amphiphiles, Gervasio Zaldivar, Jiachen Feng, Leonardo Lizarraga, Yafan Yu, Luana De Campos, Kelly Mari Pires De Oliveira, Kurt Piepenbrink, Martin Conda-Sheridan, Mario Tagliazucchi Jan 2023

Conformal Electrodeposition Of Antimicrobial Hydrogels Formed By Self-Assembled Peptide Amphiphiles, Gervasio Zaldivar, Jiachen Feng, Leonardo Lizarraga, Yafan Yu, Luana De Campos, Kelly Mari Pires De Oliveira, Kurt Piepenbrink, Martin Conda-Sheridan, Mario Tagliazucchi

Department of Biochemistry: Faculty Publications

The colonization of biomedical surfaces by bacterial biofilms is concerning because these microorganisms display higher antimicrobial resistance in biofilms than in liquid cultures. Developing antimicrobial coatings that can be easily applied to medically-relevant complex-shaped objects, such as implants and surgical instruments, is an important and challenging research direction. This work reports the preparation of antibacterial surfaces via the electrodeposition of a conformal hydrogel of self-assembling cationic peptide-amphiphiles (PAs). Hydrogels of three PAs are electrodeposited: C16K2, C16K3, and C18K2, where Cn is an alkyl chain of n methylene …


Genetic Control Of Photoprotection And Photosystem Ii Operating Efficiency In Plants, Seema Sahay, Marcin Grzybowski, James Schnable, Katarzyna Głowacka Jan 2023

Genetic Control Of Photoprotection And Photosystem Ii Operating Efficiency In Plants, Seema Sahay, Marcin Grzybowski, James Schnable, Katarzyna Głowacka

Department of Biochemistry: Faculty Publications

• Photoprotection against excess light via nonphotochemical quenching (NPQ) is indispensable for plant survival. However, slow NPQ relaxation under low light conditions can decrease yield of field-grown crops up to 40%.

• Using semi-high-throughput assay, we quantified the kinetics of NPQ and photosystem II operating efficiency (ΦPSII) in a replicated field trial of more than 700 maize (Zea mays) genotypes across 2 yr. Parametrized kinetics data were used to conduct genome-wide association studies.

• For six candidate genes involved in NPQ and ΦPSII kinetics in maize the loss of function alleles of orthologous genes in Arabidopsis (Arabidopsis thaliana) …


Advancements In Computational Modelling Of Biological Systems: Seventh Annual Sysmod Meeting, Bhanwar Lal Puniya, Andreas Dräger Jan 2023

Advancements In Computational Modelling Of Biological Systems: Seventh Annual Sysmod Meeting, Bhanwar Lal Puniya, Andreas Dräger

Department of Biochemistry: Faculty Publications

The Computational Modelling of Systems Biology (SysMod) Community of Special Interest (COSI) convenes annually at the Intelligent Systems for Molecular Biology (ISMB) conference to facilitate knowledge dissemination and exchange of research findings on systems modelling from interdisciplinary domains. The SysMod meeting 2022 was held in a hybrid mode in Madison, Wisconsin, spanning a 1-day duration centred on modelling techniques, applications, and single-cell technology implementations. The meeting showcased innovative approaches to modelling biological systems using cell-specific and multiscale modelling, multiomics data integration, and novel tools to develop systems models using single-cell and multiomics technology. The meeting also recognized outstanding research by …


Heat Shock Protein 90 (Hsp90) System In Health And Disease., Daniella Munezero Jan 2023

Heat Shock Protein 90 (Hsp90) System In Health And Disease., Daniella Munezero

Graduate Theses, Dissertations, and Problem Reports (ETD)

Cells rely on heat shock proteins (HSP) to facilitate and regulate the folding of the substrate proteins into their native state, and degradation if misfolding cannot be prevented. HSP90, a member of the HSP family, is a potential target for treatment of cancer and neurodegenerative diseases. Unfortunately, several clinical trials for cancer treatment have been discontinued due to cell toxicity accompanying HSP90 inhibition. HSP90 has four distinct but structurally similar paralogs. HSP90 inhibitors target all the paralogs despite increasing proof of functional differences among the paralogs. Understanding the in vivo function of HSP90 and the role played by each paralog …


Development Of A Chemical Biology Approach To Uncover The Influence Of Sequence Variations On Ces1 Activity In Live Cells, Samuel James Knebel Jan 2023

Development Of A Chemical Biology Approach To Uncover The Influence Of Sequence Variations On Ces1 Activity In Live Cells, Samuel James Knebel

Masters Theses

Drug metabolism is the biochemical process of modifying drugs to detoxify and remove them through enzymatic transformations. These biotransformation’s occur primarily in the liver and are critical to understanding how pharmaceutical compounds are chemically altered inside the human body. Human carboxylesterases (CESs) catalyze the hydrolysis of esters, amides, thioesters, and carbamates. CES-mediated hydrolysis plays an important role in the metabolism of many drugs including the first FDA approved antiviral treatment for COVID-19, remdesivir (Veklury), the seizure control medication rufinamide (Banzel), and the flu antiviral drug oseltamivir (Tamiflu). CES activity is known to be influenced by a variety of factors including …


Assessing The Biocatalytic Promiscuity Of Pep- Transformations For Geminal-Difluorination, Eloy Jose Torres Garcia Jan 2023

Assessing The Biocatalytic Promiscuity Of Pep- Transformations For Geminal-Difluorination, Eloy Jose Torres Garcia

Theses and Dissertations (Comprehensive)

Fluorine is the most electronegative chemical element and can drastically change molecular properties, such as drug pharmacokinetics and agrochemical half-life. Although a great deal of progress is occurring in synthetic methods to access various organofluorines, these methods struggle with harsh conditions and limited substrate scope. Biocatalytic approaches offer the potential to access organofluorines that are difficult or impossible with the current methodology. Phosphoenolpyruvate (PEP) is a central metabolite and biosynthetic precursor for diverse molecules. Phosphoenol pyruvate mutase (Ppm) catalyses the interconversion of Phosphonopyruvate (PnPy) to Phosphoenolpyruvate (PEP). This research successfully expressed and …


Hiv-Tat Exacerbates The Actions Of Atazanavir, Efavirenz, And Ritonavir On Cardiac Ryanodine Receptor (Ryr2), Imam Abdulrahman Bin Faisal University, Chengju Tian, Sean R. Bidasee, Zachary L. Venn, Evan Schroder, Nick Y. Palermo, Mohammad Alshabeeb, Benson J. Edagwa, Jason J. Payne, Keshoer R. Bidasee Dec 2022

Hiv-Tat Exacerbates The Actions Of Atazanavir, Efavirenz, And Ritonavir On Cardiac Ryanodine Receptor (Ryr2), Imam Abdulrahman Bin Faisal University, Chengju Tian, Sean R. Bidasee, Zachary L. Venn, Evan Schroder, Nick Y. Palermo, Mohammad Alshabeeb, Benson J. Edagwa, Jason J. Payne, Keshoer R. Bidasee

Department of Biochemistry: Faculty Publications

The incidence of sudden cardiac death (SCD) in people living with HIV infection (PLWH), especially those with inadequate viral suppression, is high and the reasons for this remain incompletely characterized. The timely opening and closing of type 2 ryanodine receptor (RyR2) is critical for ensuring rhythmic cardiac contraction–relaxation cycles, and the disruption of these processes can elicit Ca2+ waves, ventricular arrhythmias, and SCD. Herein, we show that the HIV protein Tat (HIVTat: 0–52 ng/mL) and therapeutic levels of the antiretroviral drugs atazanavir (ATV: 0–25,344 ng/mL), efavirenz (EFV: 0–11,376 ng/mL), and ritonavir (RTV: 0–25,956 ng/mL) bind to and modulate the …


Therapies For Mitochondrial Disorders, Kayli Sousa Smyth, Anne Mulvihill Dec 2022

Therapies For Mitochondrial Disorders, Kayli Sousa Smyth, Anne Mulvihill

SURE Journal: Science Undergraduate Research Experience Journal

Mitochondria are cytoplasmic, double-membrane organelles that synthesise adenosine triphosphate (ATP). Mitochondria contain their own genome, mitochondrial DNA (mtDNA), which is maternally inherited from the oocyte. Mitochondrial proteins are encoded by either nuclear DNA (nDNA) or mtDNA, and both code for proteins forming the mitochondrial oxidative phosphorylation (OXPHOS) complexes of the respiratory chain. These complexes form a chain that allows the passage of electrons down the electron transport chain (ETC) through a proton motive force, creating ATP from adenosine diphosphate (ADP). This study aims to explore current and prospective therapies for mitochondrial disorders (MTDS). MTDS are clinical syndromes coupled with abnormalities …


Nanoparticle Conjugated Photosensitizer For Targeted Photodynamic Inactivation Of Cancer Cells, Symone D. Crowder Dec 2022

Nanoparticle Conjugated Photosensitizer For Targeted Photodynamic Inactivation Of Cancer Cells, Symone D. Crowder

Honors College Theses

Photodynamic therapy (PDT) is considered to be a potential replacement for traditional methods of chemotherapy. It includes the administration of photosensitizing agents (PS), which generate reactive oxygen species (ROS) upon excitation at a specific wavelength. With new outlooks and techniques, cancer research is advancing each day. It has allowed the progress of several theranostic drug delivery systems (DDS) exploring the area of nanomedicine.2 In the present work, a Rhodamine derivative, Rhodamine 6G (R6G) was used as the PS. In general, rhodamine compounds undergo cytotoxic reactions on photoexcitation by electron transfer reactions with folic acid within cells, making them a favorable …


Insights Into The Biotechnology Potential Of Methanosarcina, Sean Carr, Nicole R. Buan Dec 2022

Insights Into The Biotechnology Potential Of Methanosarcina, Sean Carr, Nicole R. Buan

Department of Biochemistry: Faculty Publications

Methanogens are anaerobic archaea which conserve energy by producing methane. Found in nearly every anaerobic environment on earth, methanogens serve important roles in ecology as key organisms of the global carbon cycle, and in industry as a source of renewable biofuels. Environmentally, methanogenic archaea play an essential role in the reintroducing unavailable carbon to the carbon cycle by anaerobically converting low-energy, terminal metabolic degradation products such as one and two-carbon molecules into methane which then returns to the aerobic portion of the carbon cycle. In industry, methanogens are commonly used as an inexpensive source of renewable biofuels as well as …


A Review Of Radiation-Induced Alterations Of Multi-Omic Profiles, Radiation Injury Biomarkers, And Countermeasures, Sushil K. Shakyawar, Nitish K. Mishra, Neetha N. Vellichirammal, Lynnette Cary, Tomáš Helikar, Robert Powers, Rebecca E. Oberley-Deegan, David B. Berkowitz, Kenneth W. Bayles, Vijay K. Singh, Chittibabu Guda Nov 2022

A Review Of Radiation-Induced Alterations Of Multi-Omic Profiles, Radiation Injury Biomarkers, And Countermeasures, Sushil K. Shakyawar, Nitish K. Mishra, Neetha N. Vellichirammal, Lynnette Cary, Tomáš Helikar, Robert Powers, Rebecca E. Oberley-Deegan, David B. Berkowitz, Kenneth W. Bayles, Vijay K. Singh, Chittibabu Guda

Department of Biochemistry: Faculty Publications

Increasing utilization of nuclear power enhances the risks associated with industrial accidents, occupational hazards, and the threat of nuclear terrorism. Exposure to ionizing radiation interferes with genomic stability and gene expression resulting in the disruption of normal metabolic processes in cells and organs by inducing complex biological responses. Exposure to high-dose radiation causes acute radiation syndrome, which leads to hematopoietic, gastrointestinal, cerebrovascular, and many other organ-specific injuries. Altered genomic variations, gene expression, metabolite concentrations, and microbiota profiles in blood plasma or tissue samples reflect the whole-body radiation injuries. Hence, multi-omic profiles obtained from high-resolution omics platforms offer a holistic approach …


Using The Embl-Ebi Clustal Omega Tool To Calculate Diversity Of Heavy Chain Phage-Display Libraries, Michael Bodri, Shane A. Webb Oct 2022

Using The Embl-Ebi Clustal Omega Tool To Calculate Diversity Of Heavy Chain Phage-Display Libraries, Michael Bodri, Shane A. Webb

Georgia Journal of Science

Here we show that traditional Sanger sequencing combined with analysis tools available from the European Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI), specifically EMBOSS Transeq and Clustal Omega, is extremely effective in the analysis of naïve phage display antibody libraries for the determination of library size and diversity. The free tools are easy to use and require little manipulation of reads by hand, allowing analysis to be performed on a standard personal computer. Utilization of this technique has applicability to researchers with limited access to deep sequencing. The primary drawback to this analysis methodology is that antibodies with particular molecular or …


Reproducibility Of Protein X-Ray Diffuse Scattering And Potential Utility For Modeling Atomic Displacement Parameters, Zhen Su, Medhanjali Dasgupta, Frédéric Poitevin, Irimpan I. Mathews, Henry Van Den Bedem, Michael E. Wall, Chun Hong Yoon, Mark A. Wilson Sep 2022

Reproducibility Of Protein X-Ray Diffuse Scattering And Potential Utility For Modeling Atomic Displacement Parameters, Zhen Su, Medhanjali Dasgupta, Frédéric Poitevin, Irimpan I. Mathews, Henry Van Den Bedem, Michael E. Wall, Chun Hong Yoon, Mark A. Wilson

Department of Biochemistry: Faculty Publications

Protein structure and dynamics can be probed using x-ray crystallography. Whereas the Bragg peaks are only sensitive to the average unit-cell electron density, the signal between the Bragg peaks—diffuse scattering—is sensitive to spatial correlations in electron-density variations. Although diffuse scattering contains valuable information about protein dynamics, the diffuse signal is more difficult to isolate from the background compared to the Bragg signal, and the reproducibility of diffuse signal is not yet well understood. We present a systematic study of the reproducibility of diffuse scattering from isocyanide hydratase in three different protein forms. Both replicate diffuse datasets and datasets obtained from …


Editorial: Function And Formation Of Mitochondrial Metalloproteome, Michał Wasilewski, Vishal M. Gohil, Oleh Khalimonchuk Sep 2022

Editorial: Function And Formation Of Mitochondrial Metalloproteome, Michał Wasilewski, Vishal M. Gohil, Oleh Khalimonchuk

Department of Biochemistry: Faculty Publications

No abstract provided.


Loss Of Num1-Mediated Cortical Dynein Anchoring Negatively Impacts Respiratory Growth, Antoineen J. White, Clare S. Harper, Erica M. Rosario, Jonathan V. Dietz, Hannah G. Addis, Jennifer L. Fox, Oleh Khalimonchuk, Laura L. Lackner Sep 2022

Loss Of Num1-Mediated Cortical Dynein Anchoring Negatively Impacts Respiratory Growth, Antoineen J. White, Clare S. Harper, Erica M. Rosario, Jonathan V. Dietz, Hannah G. Addis, Jennifer L. Fox, Oleh Khalimonchuk, Laura L. Lackner

Department of Biochemistry: Faculty Publications

Num1 is a multifunctional protein that both tethers mitochondria to the plasma membrane and anchors dynein to the cell cortex during nuclear inheritance. Previous work has examined the impact loss of Num1-based mitochondrial tethering has on dynein function in Saccharomyces cerevisiae; here, we elucidate its impact on mitochondrial function. We find that like mitochondria, Num1 is regulated by changes in metabolic state, with the protein levels and cortical distribution of Num1 differing between fermentative and respiratory growth conditions. In cells lacking Num1, we observe a reproducible respiratory growth defect, suggesting a role for Num1 in not only maintaining mitochondrial …


Examination Of The Time Delayed Induction Between Prior Encapsulation Of Catalytic Enzymes In P22 Virus-Like Particles, Andrea Hernandez Irias Sep 2022

Examination Of The Time Delayed Induction Between Prior Encapsulation Of Catalytic Enzymes In P22 Virus-Like Particles, Andrea Hernandez Irias

Chemistry Theses

Protein cages found in nature have the ability to protect and develop new nanomaterials in order to enhance catalytic reactions. This is due to the ability of these organelle structures to mimic protein-based organelles such as Virus-Like Particles (VLPs). VLPs have the ability to not only resemble virus protein structures but to encapsulate enzymes while retaining their activity. This research examines the in vitro encapsulation withing the bacteriophage P22 derived VLP, and show that some enzymes may require a delay in encapsulation to allowed proper folding

and maturation before they can be encapsulated inside P22 as fully active enzymes. Exploring …


Ncoa4 Regulates Iron Recycling And Responds To Hepcidin Activity And Lipopolysaccharide In Macrophages, Cole A. Guggisberg, Juyoung Kim, Jaekwon Lee, Xiaoli Chen, Moon-Suhn Ryu Aug 2022

Ncoa4 Regulates Iron Recycling And Responds To Hepcidin Activity And Lipopolysaccharide In Macrophages, Cole A. Guggisberg, Juyoung Kim, Jaekwon Lee, Xiaoli Chen, Moon-Suhn Ryu

Department of Biochemistry: Faculty Publications

Macrophages, via erythrophagocytosis, recycle iron from effete erythrocytes to newly developing red blood cells. Conversion of potentially cytotoxic levels of iron from its heme into nonheme form during iron recycling is safely accomplished via coordinated regulations of cellular iron transport and homeostasis. Herein, we demonstrate the roles and regulation of NCOA4 (nuclear receptor coactivator 4)-mediated ferritinophagy in macrophages after erythrophagocytosis using the mouse macrophage cell line J774 cells. Ferritin in J774 cells increased with the rise of nonheme iron by erythrocyte ingestion and declined when total cellular iron contents subsequently decreased. NCOA4, a selective autophagic cargo receptor for ferritin, was …


Editorial: Mitochondria, Metabolism And Cardiovascular Diseases, Jun-Ichiro Koga, Xinghui Sun, Masuko Ushio-Fukai Aug 2022

Editorial: Mitochondria, Metabolism And Cardiovascular Diseases, Jun-Ichiro Koga, Xinghui Sun, Masuko Ushio-Fukai

Department of Biochemistry: Faculty Publications

No abstract provided.


Perturbation Modeling For Molecular Design Of Protein Tyrosine Kinase Inhibitors Using Unsupervised Machine Learning, Keerthi Krishnan Aug 2022

Perturbation Modeling For Molecular Design Of Protein Tyrosine Kinase Inhibitors Using Unsupervised Machine Learning, Keerthi Krishnan

Computational and Data Sciences (MS) Theses

The field of computational drug discovery and development has grown, with the aid of new computational tools for novel molecule discovery. In specific, generative deep learning models have excelled as tools to aid in navigating the large space of known molecules and in the creation of new molecules. These models are fed various representations of molecules as inputs and learn to perform a variety of things, such as the optimization of these molecules towards a targeted property. Ultimately, these generative learning models allow us to build bridges between chemical and continuous spaces to understand the compromise between invoking small incremental …


Identifying A Glucocorticoid-Activated Gpcr That Rapidly And Non-Genomically Increases Camp Levels In Mammalian Cells, Francisco Nunez Aug 2022

Identifying A Glucocorticoid-Activated Gpcr That Rapidly And Non-Genomically Increases Camp Levels In Mammalian Cells, Francisco Nunez

Pharmaceutical Sciences (PhD) Dissertations

Glucocorticoids (GCs) are steroid hormones that regulate diverse physiological processes. Synthetic versions of GCs are commonly used to treat inflammatory diseases such as asthma by modulating gene expression to suppressing several inflammatory activities. However, it is estimated that 5-10% of asthmatics are unresponsive to GCs, which may be explained by receptor desensitization and/or the presence of a neutrophilic endotype. One understudied phenomenon of GCs is their ability to induce rapid, non-genomic actions. For example, GCs can acutely modulate calcium concentrations levels, induce smooth muscle relaxation and modulate nitric oxide synthase activity, within minutes and sometimes seconds, which is too rapid …


Metabolite Damage And Damage Control In A Minimal Genome, Drago Haas, Antje M. Thamm, Jiayi Sun, Lili Huang, Lijie Sun, Guillaume A.W. Beaudoin, Kim S. Wise, Claudia Lerma-Ortiz, Steven D. Bruner, Marian Breuer, Zaida Luthey-Schulten, Jiusheng Lin, Mark A. Wilson, Greg Brown, Alexander F. Yakunin, Inna Kurilyak, Jacob Folz, Oliver Fiehn, John I. Glass, Andrew D. Hanson, Christopher S. Henry, Valérie De Crécy-Lagard Aug 2022

Metabolite Damage And Damage Control In A Minimal Genome, Drago Haas, Antje M. Thamm, Jiayi Sun, Lili Huang, Lijie Sun, Guillaume A.W. Beaudoin, Kim S. Wise, Claudia Lerma-Ortiz, Steven D. Bruner, Marian Breuer, Zaida Luthey-Schulten, Jiusheng Lin, Mark A. Wilson, Greg Brown, Alexander F. Yakunin, Inna Kurilyak, Jacob Folz, Oliver Fiehn, John I. Glass, Andrew D. Hanson, Christopher S. Henry, Valérie De Crécy-Lagard

Department of Biochemistry: Faculty Publications

Analysis of the genes retained in the minimized Mycoplasma JCVI-Syn3A genome established that systems that repair or preempt metabolite damage are essential to life. Several genes known to have such functions were identified and experimentally validated, including 5-formyltetrahydrofolate cycloligase, coenzyme A (CoA) disulfide reductase, and certain hydrolases. Furthermore, we discovered that an enigmatic YqeK hydrolase domain fused to NadD has a novel proofreading function in NAD synthesis and could double as a MutT-like sanitizing enzyme for the nucleotide pool. Finally, we combined metabolomics and cheminformatics approaches to extend the core metabolic map of JCVI-Syn3A to include promiscuous enzymatic reactions and …


Cellular Mechanisms Underlying State-Dependent Neural Inhibition With Magnetic Stimulation, Hui Ye, Vincent Chiun-Fan Chen, Jenna Hendee Jul 2022

Cellular Mechanisms Underlying State-Dependent Neural Inhibition With Magnetic Stimulation, Hui Ye, Vincent Chiun-Fan Chen, Jenna Hendee

Engineering Science Faculty Publications

Novel stimulation protocols for neuromodulation with magnetic fields are explored in clinical and laboratory settings. Recent evidence suggests that the activation state of the nervous system plays a significant role in the outcome of magnetic stimulation, but the underlying cellular and molecular mechanisms of state-dependency have not been completely investigated. We recently reported that high frequency magnetic stimulation could inhibit neural activity when the neuron was in a low active state. In this paper, we investigate state-dependent neural modulation by applying a magnetic field to single neurons, using the novel micro-coil technology. High frequency magnetic stimulation suppressed single neuron activity …


Methanogen Metabolic Flexibility, Sean R. Carr Jul 2022

Methanogen Metabolic Flexibility, Sean R. Carr

School of Biological Sciences: Dissertations, Theses, and Student Research

Methanogens are obligately anaerobic archaea which produce methane as a byproduct of their respiration. They are found across a wide diversity of environments and play an important role in cycling carbon in anaerobic spaces and the removal of harmful fermentation byproducts which would otherwise inhibit other organisms. Methanogens subsist on low-energy substrates which requires them to utilize a highly efficient central metabolism which greatly favors respiratory byproducts over biomass. This metabolic strategy creates high substrate:product conversion ratios which is industrially relevant for the production of biomethane, but may also allow for the production of value-added commodities. Particularly of interest are …


Increasing The Resilience Of Plant Immunity To A Warming Climate, Jong Hum Kim, Christian Castroverde, Shuai Huang, Chao Li, Richard Hilleary, Adam Seroka, Reza Sohrabi, Diana Medina-Yerena, Bethany Huot, Jie Wang, Sharon Marr, Mary Wildermuth, Tao Chen, John Macmicking, Sheng Yang He Jun 2022

Increasing The Resilience Of Plant Immunity To A Warming Climate, Jong Hum Kim, Christian Castroverde, Shuai Huang, Chao Li, Richard Hilleary, Adam Seroka, Reza Sohrabi, Diana Medina-Yerena, Bethany Huot, Jie Wang, Sharon Marr, Mary Wildermuth, Tao Chen, John Macmicking, Sheng Yang He

Biology Faculty Publications

Extreme weather conditions associated with climate change affect many aspects of plant and animal life, including the response to infectious diseases. Production of salicylic acid (SA), a central plant defence hormone, is particularly vulnerable to suppression by short periods of hot weather above the normal plant growth temperature range via an unknown mechanism. Here we show that suppression of SA production in Arabidopsis thaliana at 28 °C is independent of PHYTOCHROME B (phyB) and EARLY FLOWERING 3 (ELF3), which regulate thermo-responsive plant growth and development. Instead, we found that formation of GUANYLATE BINDING PROTEIN-LIKE 3 (GBPL3) defence-activated biomolecular condensates (GDACs) …