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Articles 661 - 690 of 13689

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

Dnajb6: A Potent Dnajb Chaperone In Regulating Tau Proteostasis, Abigail R. Esquivel Mar 2025

Dnajb6: A Potent Dnajb Chaperone In Regulating Tau Proteostasis, Abigail R. Esquivel

USF Tampa Graduate Theses and Dissertations

Neurodegenerative diseases often feature the pathological buildup of misfolded proteins, and tau is a principal culprit in multiple tauopathies. One chaperone of emerging interest is DnaJB6b, a member of the Hsp40/DnaJ family, which exhibits potent anti-aggregation activity against several disease-related proteins. Recent investigations highlight its unique capacity to recognize and neutralize aggregation-prone forms of tau. DnaJB6b appears potent against multiple variants of tau and may be acting against tau, in part, by directing misfolded tau toward proteasomal clearance. The first lines of evidence come from systematic chaperone screens, where DnaJB6b repeatedly emerged as a strong suppressor of tau seeding. Further …


Functional Connectivity Of Red Chlorophylls In Cyanobacterial Photosystem I Revealed By Fluence-Dependent Transient Absorption, Sara Sohail, S. Sohoni, P.-C. Ting, L. R. Fantz, S. M. Abdulhadi, C. Macgregor-Chatwin, A. Hitchcock, C. N. Hunter, G. S. Engel, S. C. Massey Mar 2025

Functional Connectivity Of Red Chlorophylls In Cyanobacterial Photosystem I Revealed By Fluence-Dependent Transient Absorption, Sara Sohail, S. Sohoni, P.-C. Ting, L. R. Fantz, S. M. Abdulhadi, C. Macgregor-Chatwin, A. Hitchcock, C. N. Hunter, G. S. Engel, S. C. Massey

Chemistry & Biochemistry Faculty Works

External stressors modulate the oligomerization state of photosystem I (PSI) in cyanobacteria. The number of red chlorophylls (Chls), pigments lower in energy than the P₇₀₀ reaction center, depends on the oligomerization state of PSI. Here, we use ultrafast transient absorption spectroscopy to interrogate the effective connectivity of the red Chls in excitonic energy pathways in trimeric PSI in native thylakoid membranes of the model cyanobacterium Synechocystis sp. PCC 6803, including emergent dynamics, as red Chls increase in number and proximity. Fluence-dependent dynamics indicate singlet–singlet annihilation within energetically connected red Chl sites in the PSI antenna but not within bulk Chl …


College Of Natural Sciences 2024 Year-End Publication, College Of Natural Sciences Mar 2025

College Of Natural Sciences 2024 Year-End Publication, College Of Natural Sciences

College of Natural Sciences Newsletters and Reports

Page 2 Dean's Message
Page 3 Department Highlights
Page 4 One Day for State
Page 5 New Students in Wecota
Page 6-8 Faculty Excellence
Page 9 SDSU Physics Students Recognized
Page 9 Prairie Doc Watch Party
Page 10-11 Student Excellence
Page 11 Connections Abroad
Page 12-13 CNS’s Research Centers
Page 14 Connections Abroad
Page 14 Dean Wolf-Hall Retired
Page 15 Outreach Program
Page 15 Events and Traditions
Page 16 Student Spotlight
Page 17 Alumni Spotlight
Page 18-19 SDSU Alum at Paris Paralympics
Page 20 Work Anniversaries & Programs


Induced Mutagenesis In West Nile Virus Non-Structural Protein 3 With A Discussion Of The Mutation's Effects On Viral Properties, Caden Connealy Mar 2025

Induced Mutagenesis In West Nile Virus Non-Structural Protein 3 With A Discussion Of The Mutation's Effects On Viral Properties, Caden Connealy

Honors Program: Senior Projects (Public)

West Nile Virus (WNV), a member of the Flaviviridae family and introduced to the Western hemisphere in 1999, presents a unique and emerging threat to human health. Infection in humans is often mild but can occasionally result in severe neurological impairment and even death. West Nile Virus non-structural protein 3 (NS3) plays an important role in the process of viral genome amplification. More specifically, the C-terminal domain of the protein folds into a helicase enzyme, which is responsible for the “unwinding” of double-stranded RNA intermediates and RNA secondary structure on the WNV genome. This is a vitally important step in …


Domain Communication In Bifunctional Proline Utilization A From Sinorhizobium Meliloti, Emma Bitterman Mar 2025

Domain Communication In Bifunctional Proline Utilization A From Sinorhizobium Meliloti, Emma Bitterman

Honors Program: Senior Projects (Public)

The reduction potential of flavin bound to Sinorhizobium meliloti proline utilization A (SmPutA) is beneficial in providing vital information on enzyme activity and the active site environment. Flavin is crucial in biological metabolism such as aerobic respiration and other important processes like oxygen activation that are catalyzed by flavin-dependent enzymes. (4). In this study, we seek to determine whether the redox potential of SmPutA-bound flavin can be used to characterize potential long-distance communication and analyze the possibilities of inactivation reversibility. SmPutA is a large bifunctional enzyme that catalyzes the overall oxidation of proline to glutamate via two catalytic domains (1). …


Development, Optimization, And Validation Of A High-Sensitivity Capillary Zone Electrophoresis System For Bioanalytical Applications, Aaron I. Mena Mar 2025

Development, Optimization, And Validation Of A High-Sensitivity Capillary Zone Electrophoresis System For Bioanalytical Applications, Aaron I. Mena

Electronic Theses and Dissertations

Capillary zone electrophoresis (CZE) is a powerful analytical technique widely used for biomolecular separation due to its high resolution, efficiency, and sensitivity. This report presents the development and validation of a novel CZE system designed to improve modularity, reproducibility, and operational efficiency. The system integrates a laser-induced fluorescence (LIF) detection method with a 488 nm laser, enhanced fluid control through a negative pressure system, and a user-friendly GUI for automated operation and data acquisition. Performance verification included pressure stability tests, fluorescence accuracy assessments, and electrophoretic reproducibility studies. Comparative analysis with a previous CZE iteration confirmed improved baseline stability, peak resolution, …


Synthetic Protein Mimetic Based Therapies For Neurodegeneration, Nicholas H. Stillman Mar 2025

Synthetic Protein Mimetic Based Therapies For Neurodegeneration, Nicholas H. Stillman

Electronic Theses and Dissertations

Protein-protein interactions (PPIs) are crucial for the regulation of a majority of, if not every fundamental cellular process. Despite their role in regular biological processes, dysregulated and/or aberrant protein-protein interactions (aPPIs) are often related to the onset of disease including cancer, viral infection, and amyloid diseases. aPPIs have historically been deemed ‘undruggable’ due to their large surface area and lack of a binding cavity; however, today, more than 40 disease-related aPPIs have been targeted with small molecules and several of those have reached clinical trials.

A class of synthetic protein mimetics called oligopyridylamides (OPs) has been shown to inhibit disease-related …


The Guanine Nucleotide Exchange Factor Ric-8a Regulates The Sensitivity Of Constitutively Active Gαq To The Inhibitor Ym-254890, Morgan Dwyer, Jiansong Luo, Tyson Todd, Kendall Blumer, Gregory Tall, Philip Wedegaertner Mar 2025

The Guanine Nucleotide Exchange Factor Ric-8a Regulates The Sensitivity Of Constitutively Active Gαq To The Inhibitor Ym-254890, Morgan Dwyer, Jiansong Luo, Tyson Todd, Kendall Blumer, Gregory Tall, Philip Wedegaertner

Department of Biochemistry and Molecular Biology Faculty Papers

Heterotrimeric G proteins are stimulated under normal circumstances by G protein-coupled receptors to promote downstream intracellular signaling. Mutations can occur in αq at glutamine 209 (Q209) that cause constitutive, G protein-coupled receptor independent signaling due to disruption of GTPase activity. Specifically, Q209L/P mutations are oncogenic drivers of uveal melanoma. YM-254890 (YM) has been shown to selectively inhibit both WT and constitutively active (CA) αqQ209L/P by preventing the release of GDP and exchange for GTP, thereby halting downstream signaling. Because αqQL/P are thought to be primarily GTP-bound and GTPase deficient, the current mechanistic understanding of YM inhibition needs further investigation to …


Synthesis Of A Series Of Rare-Earth-Based Multi-Anion Chalcogenide Iodides Re3Si2SeXS8-XI (Re = La, Ce, Pr, And Nd) Using The Flux-Assisted Boron-Chalcogen Mixture Method, Gopabandhu Panigrahi, Habiba Binte Kashem, Gregory Morrison, Hans Conrad Zur Loye Mar 2025

Synthesis Of A Series Of Rare-Earth-Based Multi-Anion Chalcogenide Iodides Re3Si2SeXS8-XI (Re = La, Ce, Pr, And Nd) Using The Flux-Assisted Boron-Chalcogen Mixture Method, Gopabandhu Panigrahi, Habiba Binte Kashem, Gregory Morrison, Hans Conrad Zur Loye

Faculty Publications

Single crystals and polycrystalline powders of rare earth mixed chalcogenide iodides La3Si2Se1.21S6.79I, Ce3Si2Se1.39S6.61I, Pr3Si2Se1.22S6.78I, and Nd3Si2Se1.18S6.82I were prepared using the reactive flux-assisted boron-chalcogen mixture (BCM) method at 850 °C. All compounds crystallized in the monoclinic crystal system, space group C2/c (space group number 15). The series adopts the La3Si2O8Cl structure type, containing isolated SiQ4 tetrahedra connected by REQ8 (RE = La, Ce, Pr and Nd) polyhedra; this arrangement creates tunnels that are filled by I atoms. The partial substitution of S by Se was carried out to modulate the optical properties. Phase pure samples and uniform solid solutions were obtained …


The Expression Profile Of The Rank/Rankl/Opg Pathway In Breast Cancer Stem Cells Isolated From Breast Cancer Cell Lines, Mohamed M. Kamal, Hassnaa H. Elgohary, Sherine Maher Rizk, Nadine H. Maurice Mar 2025

The Expression Profile Of The Rank/Rankl/Opg Pathway In Breast Cancer Stem Cells Isolated From Breast Cancer Cell Lines, Mohamed M. Kamal, Hassnaa H. Elgohary, Sherine Maher Rizk, Nadine H. Maurice

Pharmacy

The RANK/RANKL/OPG signaling pathway plays a crucial role in breast cancer progression and metastasis. However, its expression patterns and potential implications in breast cancer stem cells remain poorly understood. This study aimed to characterize the expression profile of this pathway in breast cancer stem cells isolated from two distinct breast cancer cell lines: MDA‐MB‐231 and MCF‐7. Mammospheres (MS), representing breast cancer stem cells, were generated using agar‐coated 6 well tissue culture plates in suitable mammospheres culture conditions. Flow cytometric analysis showed enrichment of the CD44+/ CD24− subpopulations in the mammospheres cultures, with MDA‐MB‐231 exhibiting a higher percentage compared to MCF‐7. …


Inter-Simple Sequence Repeats Application On The Identification Of Genetic Variation Of A New Indonesian Melon Cultivar “Melona”, Tantri Ajeng Salma Salsabila, Adib Fakhruddin Yusuf, Wiko Arif Wibowo, Prima Sekti Kusnanda, Budi Setiadi Daryono Mar 2025

Inter-Simple Sequence Repeats Application On The Identification Of Genetic Variation Of A New Indonesian Melon Cultivar “Melona”, Tantri Ajeng Salma Salsabila, Adib Fakhruddin Yusuf, Wiko Arif Wibowo, Prima Sekti Kusnanda, Budi Setiadi Daryono

Makara Journal of Science

The field of identification of molecular markers has seen significant advancements, with the Inter-Simple Sequence Repeat (ISSR) emerging as a prominent tool for characterizing genetic variation within species. This study focuses on the new Indonesian melon cultivar “Melona,” developed through selective breeding of commercial melons. This study aimed to assess the utility of ISSR markers in evaluating the genetic variation and stability of the “Melona” cultivar. Comparisons were made with established cultivars—‘Inthanon,” “Rich Sweetness,” “Chamoe,” and “Hikapel”—using five ISSR primers: UBC 807, UBC 808, UBC 810, UBC 812, and UBC 826. A total of 70 DNA fragments with a high …


Structural Basis For Intrinsic Strand Displacement Activity Of Mitochondrial Dna Polymerase, Ashok Nayak, Viktoriia Sokolova, Sirelin Sillamaa, Karl Herbine, Juhan Sedman, Dmitry Temiakov Mar 2025

Structural Basis For Intrinsic Strand Displacement Activity Of Mitochondrial Dna Polymerase, Ashok Nayak, Viktoriia Sokolova, Sirelin Sillamaa, Karl Herbine, Juhan Sedman, Dmitry Temiakov

Department of Biochemistry and Molecular Biology Faculty Papers

Members of the Pol A family of DNA polymerases, found across all domains of life, utilize various strategies for DNA strand separation during replication. In higher eukaryotes, mitochondrial DNA polymerase γ relies on the replicative helicase TWINKLE, whereas the yeast ortholog, Mip1, can unwind DNA independently. Using Mip1 as a model, we present a series of high-resolution cryo-EM structures that capture the process of DNA strand displacement. Our data reveal previously unidentified structural elements that facilitate the unwinding of the downstream DNA duplex. Yeast cells harboring Mip1 variants defective in strand displacement exhibit impaired oxidative phosphorylation and loss of mtDNA, …


Molecular Interaction Of Purple Rice Ferulic Acid And Skin Aging-Related Enzymes, Ernanin Dyah Wijayanti, Fatchiyah Fatchiyah, Anna Safitri, Dian Siswanto Mar 2025

Molecular Interaction Of Purple Rice Ferulic Acid And Skin Aging-Related Enzymes, Ernanin Dyah Wijayanti, Fatchiyah Fatchiyah, Anna Safitri, Dian Siswanto

Makara Journal of Science

Purple rice is rich in ferulic acid, a phenolic acid abundant in rice. Ferulic acid (FA) has long been recognized for its anti-oxidant properties, which are linked to its skin anti-aging activity owing to its ability to scavenge free radicals and pro-tect cells from damage. Skin anti-aging activity could be assessed by inhibiting skin aging enzymes. However, there was limited information on the mechanism of FA inhibition of these enzymes. This study focused on the molecular interac-tion between purple rice FA and collagenase or tyrosinase, both with and without their substrates. The interaction be-tween FA (CID 445858), collagenase (2Y6I), tyrosinase …


Investigating The Ability Of Foxo1 To Maintain Stem Cells, Stella A. Rios, Megan E. Keniry Mar 2025

Investigating The Ability Of Foxo1 To Maintain Stem Cells, Stella A. Rios, Megan E. Keniry

Research Symposium

Background: Our group discovered that FOXO transcription factors drive stem gene expression in cancer to promote aggressiveness. Work by our group and others demonstrated that FOXO factors universally maintain stem cells including in cancer, embryonic, hematogenic and neuronal contents. Our current efforts are delineating the molecular underpinnings by which FOXO factors halt differentiation to maintain stem cells.

In this project, we are employing myoblasts as a valuable model to examine how Foxo1 maintains stem cells. Foxo1-regulated genes in myoblasts closely parallel its targets in glioblastoma and basal breast cancer stem cells, including targets such as Leukemia Inhibitory Factor, …


Uca1 As A Key Regulator Of The Warburg Effect During Anoikis Resistance In Colorectal Cancer Metastasis, Ricardo Pequeno Bracho, Salique Hassan Shaham, Yamile Abuchard Anaya, Sophia Leslie, Kyle Doxtater, Subhash Chauhan, Bilal Hafeez, Tamer Oraby, Manish K. Tripathi Mar 2025

Uca1 As A Key Regulator Of The Warburg Effect During Anoikis Resistance In Colorectal Cancer Metastasis, Ricardo Pequeno Bracho, Salique Hassan Shaham, Yamile Abuchard Anaya, Sophia Leslie, Kyle Doxtater, Subhash Chauhan, Bilal Hafeez, Tamer Oraby, Manish K. Tripathi

Research Symposium

Colorectal carcinoma (CRC) is the second leading cause of cancer-related mortality in the United States. While localized CRC has a 90% five-year survival rate, this drops sharply to 14% upon metastasis. Metastasis occurs in approximately 40–50% of CRC cases and requires cancer cells to acquire anoikis resistance—a critical adaptation allowing survival after detachment from the extracellular matrix, enabling migration and colonization of secondary sites. Understanding the molecular mechanisms driving anoikis resistance, particularly those linked to altered glucose metabolism, is essential for developing targeted therapies for metastatic CRC.

Cancer cells frequently exhibit the Warburg Effect, a metabolic adaptation favoring glycolysis over …


Biochemical, Structural, And Conformational Characterization Of A Fungal Ethylene-Forming Enzyme, Shramana Chatterjee, Joel A. Rankin, Mark A. Farrugia, Simahudeen Bathir J S Rifayee, Christo Z. Christov, Jian Hu, Et. Al. Mar 2025

Biochemical, Structural, And Conformational Characterization Of A Fungal Ethylene-Forming Enzyme, Shramana Chatterjee, Joel A. Rankin, Mark A. Farrugia, Simahudeen Bathir J S Rifayee, Christo Z. Christov, Jian Hu, Et. Al.

Michigan Tech Publications

The ethylene-forming enzyme (EFE) from the fungus Penicillium digitatum strain Pd1 was heterologously produced in Escherichia coli and its properties were compared to the extensively characterized bacterial enzyme from Pseudomonas savastanoi strain PK2. Both enzymes catalyze four reactions: the conversion of 2-oxoglutarate (2OG) to ethylene and CO2, oxidative decarboxylation of 2OG coupled to L-arginine (L-Arg) hydroxylation, uncoupled oxidative decarboxylation of 2OG, and the production of 3-hydroxypropionate (3-HP) from 2OG. The strain Pd1 enzyme exhibited a greater ratio of ethylene production over L-Arg hydroxylation than the PK2 strain EFE. The uncoupled decarboxylation of 2OG and …


Mechanisms Of Macrophage Metabolic Activation And Paracrine Wnt Signaling In The Pathogenesis Of Systemic Sclerosis, Emily Ann Morris Mar 2025

Mechanisms Of Macrophage Metabolic Activation And Paracrine Wnt Signaling In The Pathogenesis Of Systemic Sclerosis, Emily Ann Morris

Dartmouth College Ph.D Dissertations

Systemic sclerosis (SSc) is a chronic autoimmune disease of unknown etiology. We have previously shown that macrophages (MØs) play a critical role in its pathogenesis; however, the mechanisms driving MØ activation in SSc remain poorly understood. This dissertation investigates the molecular signaling pathways and biochemical mechanisms underlying profibrotic MØ activity in SSc.

First, I identify a novel MØ-specific effect of mycophenolate mofetil (MMF), the standard-of-care treatment for SSc. While MMF is a well characterized lymphostatic, my findings demonstrate that its active metabolite, mycophenolic acid (MPA), is also capable of directly inhibiting myeloid viability and profibrotic MØ activation by suppressing de …


Proteomics Of Extracellular Vesicles: Recent Updates, Challenges And Limitations, Mohini Singh, Prashant Kumar Tiwari, Vivek Kumar Kashyap, Sanjay Kumar Mar 2025

Proteomics Of Extracellular Vesicles: Recent Updates, Challenges And Limitations, Mohini Singh, Prashant Kumar Tiwari, Vivek Kumar Kashyap, Sanjay Kumar

School of Medicine Publications

Extracellular vesicles (EVs) are lipid-bound vesicles secreted by cells, including exosomes, microvesicles, and apoptotic bodies. Proteomic analyses of EVs, particularly in relation to cancer, reveal specific biomarkers crucial for diagnosis and therapy. However, isolation techniques such as ultracentrifugation, size-exclusion chromatography, and ultrafiltration face challenges regarding purity, contamination, and yield. Contamination from other proteins complicates downstream processing, leading to difficulties in identifying biomarkers and interpreting results. Future research will focus on refining EV characterization for diagnostic and therapeutic applications, improving proteomics tools for greater accuracy, and exploring the use of EVs in drug delivery and regenerative medicine. In this review, we …


First-In-Class Peptide Molecules Targeting The Mien1 Cancer Signaling Pathway, For Which No Inhibitors Have Been Identified To Date., Amit Tripathi, Jamboor K. Vishwanatha Mar 2025

First-In-Class Peptide Molecules Targeting The Mien1 Cancer Signaling Pathway, For Which No Inhibitors Have Been Identified To Date., Amit Tripathi, Jamboor K. Vishwanatha

Research Symposium

Background: Migration and Invasion Enhancer 1 (MIEN1) is a critical oncogene that drives cancer cell migration, invasion, and epithelial-to-mesenchymal transition (EMT) in various cancers. MIEN1 overexpression is linked to aggressive tumor progression and poor prognosis. Despite its established role in cancer biology, targeted therapeutic options remain unexplored. This study aimed to identify and characterize first-in-class therapeutic molecules targeting the MIEN1 signaling pathway to inhibit cancer progression.

Methods: To develop novel bio-active peptides, we leveraged conserved immunoreceptor tyrosine-based activation motif (ITAM) and prenylation motifs within the MIEN1 protein sequence. Using rational peptide design, we identified and synthesized bioactive peptides, namely LA3IK …


Nanostructure Retention To 1100 °C In Soft-Templated Niobium Tungstates Using Dual-Carbon Strategy, Sean C. Wechsler, Alexander Gregg, Coby S. Collins, Santosh Kiran Balijepalli, Morgan Stefik Mar 2025

Nanostructure Retention To 1100 °C In Soft-Templated Niobium Tungstates Using Dual-Carbon Strategy, Sean C. Wechsler, Alexander Gregg, Coby S. Collins, Santosh Kiran Balijepalli, Morgan Stefik

Faculty Publications

Mesoporous metal oxides (MMOs) have diverse applications including energy storage, catalysis, and separation membranes. Block polymer structure directing agents enable the control of morphology and pore size, however preservation of the nanostructure is often limited to a narrow range of heat treatment temperatures which constrains the tailoring of defect chemistries. High temperature treatments typically lead to collapse of the porous structure as surface area is reduced during crystal growth. Here, using a mesoporous niobium tungstate it is shown that neither in situ carbon generation nor ex situ carbon infiltration alone enable preservation of the ordered mesostructure at temperatures high enough …


Cargo Hitchhiking Autophagy - A Hybrid Autophagy Pathway Utilized In Yeast, Katrina F Cooper Mar 2025

Cargo Hitchhiking Autophagy - A Hybrid Autophagy Pathway Utilized In Yeast, Katrina F Cooper

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Macroautophagy is a catabolic process that maintains cellular homeostasis by recycling intracellular material through the use of double-membrane vesicles called autophagosomes. In turn, autophagosomes fuse with vacuoles (in yeast and plants) or lysosomes (in metazoans), where resident hydrolases degrade the cargo. Given the conservation of autophagy,


Cryptosporidium Virus Integration Into The Host Cells, Alyssa Genaro Mar 2025

Cryptosporidium Virus Integration Into The Host Cells, Alyssa Genaro

Biochemistry and Molecular Biology

Cryptosporidiosis is a disease that affects a large amount of people and having a high mortality rate for those that are immunocompromised such as the elderly and infants. The disease is linked to a parasite called Cryptosporidium parvum, which is mostly known to infect cattle and other mammals such as mice and humans. The parasite contains a double stranded RNA virus, the Cryspovirus (CSpV1) that has a non-enveloped icosahedral capsid, with a T=2* icosahedral symmetry. Little is known is known about the contribution of CSpV1 to the disease; In this study we show that infection of an immunocompromised mouse model …


Applications Of Archaeal Antioxidant Coenzyme M As An Agricultural Biostimulant, Jeremy Hunter Brown Mar 2025

Applications Of Archaeal Antioxidant Coenzyme M As An Agricultural Biostimulant, Jeremy Hunter Brown

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

As the demand to meet global food security goals continue to increase, the need to increase efficiency and productivity of agricultural output also rises. This calls for innovative and cost-effective methods for improving plant growth and yield. Here we explore how antioxidants, molecules that inhibit oxidation and are necessary for redox based signaling and redox homeostasis, can be utilized as chemical biostimulants. Specifically, we investigated Coenzyme M, an antioxidant from archaea that holds potential economic advantages over other antioxidants. Chapter 1 provides a comprehensive review of antioxidants and how exogenously application of them affects plant growth and biology, highlighting the …


Overexpression And Biophysical And Functional Characterization Of A Recombinant Fgf21, Phuc Phan, Jason Hoang, Thallapuranam Krishnaswamy Suresh Kumar Mar 2025

Overexpression And Biophysical And Functional Characterization Of A Recombinant Fgf21, Phuc Phan, Jason Hoang, Thallapuranam Krishnaswamy Suresh Kumar

Chemistry & Biochemistry Faculty Publications and Presentations

Fibroblast growth factor 21 (FGF21) is an endocrine FGF that plays a vital role in regulating essential metabolic pathways. FGF21 increases glucose uptake by cells, promotes fatty acid oxidation, reduces blood glucose levels, and alleviates metabolic diseases. However, detailed studies on its stability and biophysical characteristics have not been reported. Herein, we present the overexpression, biophysical characterization, and metabolic activity of a soluble recombinant FGF21 (rFGF21). The far-UV circular dichroism spectra of rFGF21 show a negative trough at 215 nm, indicating that the protein’s backbone predominantly adopts a β sheet conformation. rFGF21 shows intrinsic tyrosine fluorescence at 305 nm. Thermal …


Insulin Receptor Responsiveness Governs Tgfβ-Induced Hepatic Stellate Cell Activation: Insulin Resistance Instigates Liver Fibrosis, Wang-Hsin Lee, Evelyn A. Bates, Zachary A. Kipp, Sally Pauss, Genesee J. Martinez, Cheavar A. Blair, Terry D. Hinds Jr. Mar 2025

Insulin Receptor Responsiveness Governs Tgfβ-Induced Hepatic Stellate Cell Activation: Insulin Resistance Instigates Liver Fibrosis, Wang-Hsin Lee, Evelyn A. Bates, Zachary A. Kipp, Sally Pauss, Genesee J. Martinez, Cheavar A. Blair, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

The insulin receptor (INSR) has been shown to be hyperactive in hepatic stellate cells (HSCs) in humans and rodents with liver fibrosis. To explore HSC cellular mechanisms that INSR regulates during pro-fibrotic stimulation, we used CRISPR-Cas9 technology. We knocked out a portion of the INSR gene in human LX2 HSC cells (INSRe5- 8 KO) that regulates insulin responsiveness but not the insulin-like growth factor (IGF) or transforming growth factor-β (TGFβ) signaling. The INSRe5- 8 KO HSCs had significantly higher cell growth, BrdU incorporation, and lower TP53 expression that suppresses growth, and they also exhibited increased migration compared to the Scramble …


Exploring Oxylipins In Host–Microbe Interactions And Their Impact On Infection And Immunity, Robert J. Neff, Christopher D. Radka Mar 2025

Exploring Oxylipins In Host–Microbe Interactions And Their Impact On Infection And Immunity, Robert J. Neff, Christopher D. Radka

Markey Cancer Center Faculty Publications

Plasma lipids are essential components of biological systems, transported through interactions with proteins to maintain cellular functions. These lipids exist in various forms, such as fatty acids, glycerolipids, glycerophospholipids, sphingolipids, sterols, and prenol lipids, derived from dietary intake, adipose tissue, and biosynthesis. While the association between certain fatty acids and cardiovascular diseases has been widely recognized, polyunsaturated fatty acids (PUFAs) exhibit cardioprotective effects, reducing risks of arrhythmias and heart-related mortality. This is due to their role in the production of eicosanoids, which modulate inflammation. Chronic inflammation, particularly in obesity, is significantly influenced by fatty acids, with saturated fatty acids promoting …


Predicting The Pathway Involvement Of Compounds Annotated In The Reactome Knowledgebase, Erik D. Huckvale, Hunter N. B. Moseley Mar 2025

Predicting The Pathway Involvement Of Compounds Annotated In The Reactome Knowledgebase, Erik D. Huckvale, Hunter N. B. Moseley

Markey Cancer Center Faculty Publications

Background/Objectives: Pathway annotations of non-macromolecular (relatively small) biomolecules facilitate biological and biomedical interpretation of metabolomics datasets. However, low pathway annotation levels of detected biomolecules hinder this type of interpretation. Thus, predicting the pathway involvement of detected but unannotated biomolecules has a high potential to improve metabolomics data analysis and omics integration. Past publications have only made use of the Kyoto Encyclopedia of Genes and Genomes-derived datasets to develop machine learning models to predict pathway involvement. However, to our knowledge, the Reactome knowledgebase has not been utilized to develop these types of predictive models.

Methods: We created a dataset ready for …


Computational Design And In Vitro And In Vivo Characterization Of An Apoe-Based Synthetic High-Density Lipoprotein For Sepsis Therapy, Ling Guo, Yaxia Yuan, Fang Zhang, Chang-Guo Zhan, Xiangan Li Mar 2025

Computational Design And In Vitro And In Vivo Characterization Of An Apoe-Based Synthetic High-Density Lipoprotein For Sepsis Therapy, Ling Guo, Yaxia Yuan, Fang Zhang, Chang-Guo Zhan, Xiangan Li

Markey Cancer Center Faculty Publications

Introduction: Septic patients have low levels of high-density lipoproteins (HDLs), which is a risk factor. Replenishing HDLs with synthetic HDLs (sHDLs) has shown promise as a therapy for sepsis. This study aimed to develop a computational approach to design and test new types of sHDLs for sepsis treatment. Methods: We used a three-step computational approach to design sHDL nanoparticles based on the structure of HDLs and their binding to endotoxins. We tested the efficacy of these sHDLs in two sepsis mouse models—cecal ligation and puncture (CLP)-induced and P. aeruginosa-induced sepsis models—and assessed their impact on inflammatory signaling in cells. Results: …


Artesunate Enhances The Efficacy Of Enzalutamide In Advanced Prostate Cancer, Xinyi Wang, Jinghui Liu, Fengyi Mao, Yifan Kong, Qiongsi Zhang, Chaohao Li, Daheng He, Chi Wang, Yanquan Zhang, Ruixin Wang, Sally R. Ellingson, Qiou Wei, Zhiguo Li, Xiaoqi Liu Mar 2025

Artesunate Enhances The Efficacy Of Enzalutamide In Advanced Prostate Cancer, Xinyi Wang, Jinghui Liu, Fengyi Mao, Yifan Kong, Qiongsi Zhang, Chaohao Li, Daheng He, Chi Wang, Yanquan Zhang, Ruixin Wang, Sally R. Ellingson, Qiou Wei, Zhiguo Li, Xiaoqi Liu

Markey Cancer Center Faculty Publications

Prostate cancer (PCa) is one of the leading causes of death among men worldwide. Treatments targeting the androgen receptor pathway remain the standard therapy for PCa patients. Enzalutamide (ENZ), a second-generation androgen receptor inhibitor, was developed to treat castration-resistant prostate cancer. However, while patients initially respond to ENZ, drug resistance typically develops within a few months. Artesunate (ART), a semisynthetic derivative of the Artemisinin plant, is approved for antimalaria treatment. In this study, we conducted an FDA-approved drug screening and identified ART as a potential candidate for overcoming ENZ resistance in PCa. Mechanistically, ART induces the degradation of c-Myc, enhancing …


Assessment Of Physiological & Biochemical Changes In Tomato Plants Treated With Plant Growth Promoting Rhizobacteria (Pgpr) Under Salinity Stress Conditions, Mohammed Sharif Alhosani Mar 2025

Assessment Of Physiological & Biochemical Changes In Tomato Plants Treated With Plant Growth Promoting Rhizobacteria (Pgpr) Under Salinity Stress Conditions, Mohammed Sharif Alhosani

Theses

Plant growth-promoting rhizobacteria (PGPRs) can effectively mitigate the negative impacts of salt stress on plants. The present study reports the isolation of PGPRs from a high-saline mangrove ecosystem in Abu Dhabi, with isolates exhibiting ACC deaminase (ACCD) activity to reduce stress-induced ethylene, along with additional plant growth-promoting (PGP) characteristics, including phosphate solubilization (P+). A total of 57 salt-tolerant bacterial isolates from the mangrove rhizosphere were initially screened for ACCD and P+ activities. Of these, 24 isolates tested positive for PGP characteristics and were further evaluated for their ability to enhance salt stress tolerance in tomato seedlings. In addition, seedlings inoculated …