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Department of Biochemistry: Faculty Publications

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Articles 91 - 120 of 489

Full-Text Articles in Biochemistry

Vascular Endothelial Senescence: Pathobiological Insights, Emerging Long Noncoding Rna Targets, Challenges And Therapeutic Opportunities, Xinghui Sun, Mark W. Feinberg Jun 2021

Vascular Endothelial Senescence: Pathobiological Insights, Emerging Long Noncoding Rna Targets, Challenges And Therapeutic Opportunities, Xinghui Sun, Mark W. Feinberg

Department of Biochemistry: Faculty Publications

Cellular senescence is a stable form of cell cycle arrest in response to various stressors. While it serves as an endogenous pro-resolving mechanism, detrimental effects ensue when it is dysregulated. In this review, we introduce recent advances for cellular senescence and inflammaging, the underlying mechanisms for the reduction of nicotinamide adenine dinucleotide in tissues during aging, new knowledge learned from p16 reporter mice, and the development of machine learning algorithms in cellular senescence. We focus on pathobiological insights underlying cellular senescence of the vascular endothelium, a critical interface between blood and all tissues. Common causes and hallmarks of endothelial senescence …


Genetic Engineering Of Lesquerella With Increased Ricinoleic Acid Content In Seed Oil, Grace Q. Chen, Kumiko Johnson, Tara J. Nazarenus, Grisel Ponciano, Eva Morales, Edgar B. Cahoon May 2021

Genetic Engineering Of Lesquerella With Increased Ricinoleic Acid Content In Seed Oil, Grace Q. Chen, Kumiko Johnson, Tara J. Nazarenus, Grisel Ponciano, Eva Morales, Edgar B. Cahoon

Department of Biochemistry: Faculty Publications

Seeds of castor (Ricinus communis) are enriched in oil with high levels of the industrially valuable fatty acid ricinoleic acid (18:1OH), but production of this plant is limited because of the cooccurrence of the ricin toxin in its seeds. Lesquerella (Physaria fendleri) is being developed as an alternative industrial oilseed because its seeds accumulate lesquerolic acid (20:1OH), an elongated form of 18:1OH in seed oil which lacks toxins. Synthesis of 20:1OH is through elongation of 18:1OH by a lesquerella elongase, PfKCS18. Oleic acid (18:1) is the substrate for 18:1OH synthesis, but it is also used by fatty acid desaturase 2 …


Multi-Strategy Engineering Greatly Enhances Provitamin A Carotenoid Accumulation And Stability In Arabidopsis Seeds, Tianhu Sun, Qinlong Zhu, Ziqing Wei, Lauren A. Owens, Tara Fish, Hyojin Kim, Theodore W. Thannhauser, Edgar B. Cahoon, Li Li May 2021

Multi-Strategy Engineering Greatly Enhances Provitamin A Carotenoid Accumulation And Stability In Arabidopsis Seeds, Tianhu Sun, Qinlong Zhu, Ziqing Wei, Lauren A. Owens, Tara Fish, Hyojin Kim, Theodore W. Thannhauser, Edgar B. Cahoon, Li Li

Department of Biochemistry: Faculty Publications

Staple grains with low levels of provitamin A carotenoids contribute to the global prevalence of vitamin A deficiency and therefore are the main targets for provitamin A biofortification. However, carotenoid stability during both seed maturation and postharvest storage is a serious concern for the full benefits of carotenoid biofortified grains. In this study, we utilized Arabidopsis as a model to establish carotenoid biofortification strategies in seeds. We discovered that manipulation of carotenoid biosynthetic activity by seed-specific expression of Phytoene synthase (PSY) increases both provitamin A and total carotenoid levels but the increased carotenoids are prone to degradation during …


Integrative Computational Approach Identifies Drug Targets In Cd4+ T-Cell-Mediated Immune Disorders, Bhanwar L. Puniya, Rada Amin, Bailee Lichter, Robert Moore, Alex Ciurej, Sydney J. Bennett, Ab Rauf Shah, Matteo Barberis, Tomáš Helikar May 2021

Integrative Computational Approach Identifies Drug Targets In Cd4+ T-Cell-Mediated Immune Disorders, Bhanwar L. Puniya, Rada Amin, Bailee Lichter, Robert Moore, Alex Ciurej, Sydney J. Bennett, Ab Rauf Shah, Matteo Barberis, Tomáš Helikar

Department of Biochemistry: Faculty Publications

CD4+ T cells provide adaptive immunity against pathogens and abnormal cells, and they are also associated with various immunerelated diseases. CD4+ T cells’ metabolism is dysregulated in these pathologies and represents an opportunity for drug discovery and development. Genome-scale metabolic modeling offers an opportunity to accelerate drug discovery by providing high-quality information about possible target space in the context of a modeled disease. Here, we develop genome-scale models of naïve, Th1, Th2, and Th17 CD4+ T-cell subtypes to map metabolic perturbations in rheumatoid arthritis, multiple sclerosis, and primary biliary cholangitis. We subjected these models to in silico …


Europium Sulfide Nanoprobes Predict Antiretroviral Drug Delivery Into Hiv-1 Cell And Tissue Reservoirs, Jonathan Herskovitz, Mahmudul Hasan, Jatin Machhi, Insiya Mukadam, Brendan M. Ottemann, James R. Hilaire, Christopher Woldstad, Joellyn Mcmillan, Yutong Liu, Javier Seravalli, Anandakumar Sarella, Howard E. Gendelman, Bhavesh D. Kevadiya Apr 2021

Europium Sulfide Nanoprobes Predict Antiretroviral Drug Delivery Into Hiv-1 Cell And Tissue Reservoirs, Jonathan Herskovitz, Mahmudul Hasan, Jatin Machhi, Insiya Mukadam, Brendan M. Ottemann, James R. Hilaire, Christopher Woldstad, Joellyn Mcmillan, Yutong Liu, Javier Seravalli, Anandakumar Sarella, Howard E. Gendelman, Bhavesh D. Kevadiya

Department of Biochemistry: Faculty Publications

Background: Delivery of long-acting nanoformulated antiretroviral drugs (ARVs) to human immunodeficiency virus type one cell and tissue reservoirs underlies next generation antiretroviral therapeutics. Nanotheranostics, comprised of trackable nanoparticle adjuncts, can facilitate ARV delivery through real-time drug tracking made possible through bioimaging platforms. Methods: To model HIV-1 therapeutic delivery, europium sulfide (EuS) nanoprobes were developed, characterized and then deployed to cells, tissues, and rodents. Tests were performed with nanoformulated rilpivirine (NRPV), a non-nucleoside reverse transcriptase inhibitor (NNRTI) used clinically to suppress or prevent HIV-1 infection. First, CD4+ T cells and monocyte-derived macrophages were EuS-treated with and without endocytic blockers to identify …


Crispr/Cas9-Induced Fad2 And Rod1 Mutations Stacked With Fae1 Confer High Oleic Acid Seed Oil In Pennycress (Thlaspi Arvense L.), Brice A. Jarvis, Trevor B. Romsdahl, Michaela G. Mcginn, Tara J. Nazarenus, Edgar B. Cahoon, Kent D. Chapman, John C. Sedbrook Apr 2021

Crispr/Cas9-Induced Fad2 And Rod1 Mutations Stacked With Fae1 Confer High Oleic Acid Seed Oil In Pennycress (Thlaspi Arvense L.), Brice A. Jarvis, Trevor B. Romsdahl, Michaela G. Mcginn, Tara J. Nazarenus, Edgar B. Cahoon, Kent D. Chapman, John C. Sedbrook

Department of Biochemistry: Faculty Publications

Pennycress (Thlaspi arvense L.) is being domesticated as an oilseed cash cover crop to be grown in the off-season throughout temperate regions of the world. With its diploid genome and ease of directed mutagenesis using molecular approaches, pennycress seed oil composition can be rapidly tailored for a plethora of food, feed, oleochemical and fuel uses. Here, we utilized Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 technology to produce knockout mutations in the FATTY ACID DESATURASE2 (FAD2) and REDUCED OLEATE DESATURATION1 (ROD1) genes to increase oleic acid content. High oleic acid (18:1) oil is valued for its oxidative stability that is …


Isoprene Production From Municipal Wastewater Biosolids By Engineered Archaeon Methanosarcina Acetivorans, Sean Carr, Jared Aldridge, Nicole R. Buan Apr 2021

Isoprene Production From Municipal Wastewater Biosolids By Engineered Archaeon Methanosarcina Acetivorans, Sean Carr, Jared Aldridge, Nicole R. Buan

Department of Biochemistry: Faculty Publications

Wastewater biosolids are a promising feedstock for production of value-added renewable chemicals. Methane-producing archaea (methanogens) are already used to produce renewable biogas via the anaerobic treatment of wastewater. The ability of methanogens to efficiently convert dissolved organic carbon into methane makes them an appealing potential platform for biorefining using metabolic engineering. We have engineered a strain of the methanogen Methanosarcina acetivorans to produce the volatile hemiterpene isoprene in addition to methane. The engineered strain was adapted to grow in municipal wastewater through cultivation in a synthetic wastewater medium. When introduced to municipal wastewater the engineered methanogens were able to compete …


Isoprene Production From Municipal Wastewater Biosolids By Engineered Archaeon Methanosarcina Acetivorans, Sean Carr, Jared Aldridge, Nicole R. Buan Apr 2021

Isoprene Production From Municipal Wastewater Biosolids By Engineered Archaeon Methanosarcina Acetivorans, Sean Carr, Jared Aldridge, Nicole R. Buan

Department of Biochemistry: Faculty Publications

Wastewater biosolids are a promising feedstock for production of value-added renewable chemicals. Methane-producing archaea (methanogens) are already used to produce renewable biogas via the anaerobic treatment of wastewater. The ability of methanogens to efficiently convert dissolved organic carbon into methane makes them an appealing potential platform for biorefining using metabolic engineering. We have engineered a strain of the methanogen Methanosarcina acetivorans to produce the volatile hemiterpene isoprene in addition to methane. The engineered strain was adapted to grow in municipal wastewater through cultivation in a synthetic wastewater medium. When introduced to municipal wastewater the engineered methanogens were able to compete …


Structural Basis For Clostridium Perfringens Enterotoxin Targeting Of Claudins At Tight Junctions In Mammalian Gut, Alex J. Vecchio, Sewwandi S. Rathnayake, Robert M. Stroud Apr 2021

Structural Basis For Clostridium Perfringens Enterotoxin Targeting Of Claudins At Tight Junctions In Mammalian Gut, Alex J. Vecchio, Sewwandi S. Rathnayake, Robert M. Stroud

Department of Biochemistry: Faculty Publications

The bacterium Clostridium perfringens causes severe, sometimes lethal gastrointestinal disorders in humans, including enteritis and enterotoxemia. Type F strains produce an enterotoxin (CpE) that causes the third most common foodborne illness in the United States. CpE induces gut breakdown by disrupting barriers at cell–cell contacts called tight junctions (TJs), which are formed and maintained by claudins. Targeted binding of CpE to specific claudins, encoded by its C-terminal domain (cCpE), loosens TJ barriers to trigger molecular leaks between cells. Cytotoxicity results from claudin-bound CpE complexes forming pores in cell membranes. In mammalian tissues, ∼24 claudins govern TJ barriers—but the basis for …


Highlighting Membrane Protein Structure And Function: A Celebration Of The Protein Data Bank, Fei Li, Pascal F. Egea, Alex J. Vecchio, Ignacio Asial, Meghna Gupta, Joana Paulino, Ruchika Bajaj, Miles Sasha Dickinson, Shelagh Fergunson-Miller, Brian C. Monk, Robert M. Stroud Mar 2021

Highlighting Membrane Protein Structure And Function: A Celebration Of The Protein Data Bank, Fei Li, Pascal F. Egea, Alex J. Vecchio, Ignacio Asial, Meghna Gupta, Joana Paulino, Ruchika Bajaj, Miles Sasha Dickinson, Shelagh Fergunson-Miller, Brian C. Monk, Robert M. Stroud

Department of Biochemistry: Faculty Publications

Biological membranes define the boundaries of cells and compartmentalize the chemical and physical processes required for life. Many biological processes are carried out by proteins embedded in or associated with such membranes. Determination of membrane protein (MP) structures at atomic or near-atomic resolution plays a vital role in elucidating their structural and functional impact in biology. This endeavor has determined 1198 unique MP structures as of early 2021. The value of these structures is expanded greatly by deposition of their three-dimensional (3D) coordinates into the Protein Data Bank (PDB) after the first atomic MP structure was elucidated in 1985. Since …


A Co-Opted Steroid Synthesis Gene, Maintained In Sorghum But Not Maize, Is Associated With A Divergence In Leaf Wax Chemistry, Lucas Busta, Elizabeth Schmitz, Dylan K. Kosma, James Schnable, Edgar B. Cahoon Mar 2021

A Co-Opted Steroid Synthesis Gene, Maintained In Sorghum But Not Maize, Is Associated With A Divergence In Leaf Wax Chemistry, Lucas Busta, Elizabeth Schmitz, Dylan K. Kosma, James Schnable, Edgar B. Cahoon

Department of Biochemistry: Faculty Publications

Virtually all land plants are coated in a cuticle, a waxy polyester that prevents nonstomatal water loss and is important for heat and drought tolerance. Here, we describe a likely genetic basis for a divergence in cuticular wax chemistry between Sorghum bicolor, a drought tolerant crop widely cultivated in hot climates, and its close relative Zea mays (maize). Combining chemical analyses, heterologous expression, and comparative genomics, we reveal that: 1) sorghum and maize leaf waxes are similar at the juvenile stage but, after the juvenile-to-adult transition, sorghum leaf waxes are rich in triterpenoids that are absent from maize; 2) …


Structural Basis For Clostridium Perfringens Enterotoxin Targeting Of Claudins At Tight Junctions In Mammalian Gut, Alex J. Vecchio, Sewwandi S. Rathnayake, Robert M. Stroud Feb 2021

Structural Basis For Clostridium Perfringens Enterotoxin Targeting Of Claudins At Tight Junctions In Mammalian Gut, Alex J. Vecchio, Sewwandi S. Rathnayake, Robert M. Stroud

Department of Biochemistry: Faculty Publications

The bacterium Clostridium perfringens causes severe, sometimes lethal gastrointestinal disorders in humans, including enteritis and enterotoxemia. Type F strains produce an enterotoxin (CpE) that causes the third most common foodborne illness in the United States. CpE induces gut breakdown by disrupting barriers at cell–cell contacts called tight junctions (TJs), which are formed and maintained by claudins. Targeted binding of CpE to specific claudins, encoded by its C-terminal domain (cCpE), loosens TJ barriers to trigger molecular leaks between cells. Cytotoxicity results from claudin-bound CpE complexes forming pores in cell membranes. In mammalian tissues, 24 claudins govern TJ barriers—but the basis for …


Protease Oma1 Modulates Mitochondrial Bioenergetics And Ultrastructure Through Dynamic Association With Micos Complex, Martonio Ponte Viana, Roman M. Levytskyy, Ruchika Anand, Andreas S. Reichert, Oleh Khalimonchuk Feb 2021

Protease Oma1 Modulates Mitochondrial Bioenergetics And Ultrastructure Through Dynamic Association With Micos Complex, Martonio Ponte Viana, Roman M. Levytskyy, Ruchika Anand, Andreas S. Reichert, Oleh Khalimonchuk

Department of Biochemistry: Faculty Publications

Remodeling of mitochondrial ultrastructure is a process that is critical for organelle physiology and apoptosis. Although the key players in this process—mitochondrial contact site and cristae junction organizing system (MICOS) and Optic Atrophy 1 (OPA1)—have been characterized, the mechanisms behind its regulation remain incompletely defined. Here, we found that in addition to its role in mitochondrial division, metallopeptidase OMA1 is required for the maintenance of intermembrane connectivity through dynamic association with MICOS. This association is independent of OPA1, mediated via the MICOS subunit MIC60, and is important for stability of MICOS and the intermembrane contacts. The OMA1-MICOS relay is required …


Generating Pennycress (Thlaspi Arvense) Seed Triacylglycerols And Acetyl-Triacylglycerols Containing Medium-Chain Fatty Acids, Maliheh Esfahanian, Tara J. Nazarenus, Meghan M. Freund, Gary Mcintosh, Winthrop B. Phippen, Mary E. Phippen, Timothy P. Durrett, Edgar B. Cahoon, John C. Sedbrook Jan 2021

Generating Pennycress (Thlaspi Arvense) Seed Triacylglycerols And Acetyl-Triacylglycerols Containing Medium-Chain Fatty Acids, Maliheh Esfahanian, Tara J. Nazarenus, Meghan M. Freund, Gary Mcintosh, Winthrop B. Phippen, Mary E. Phippen, Timothy P. Durrett, Edgar B. Cahoon, John C. Sedbrook

Department of Biochemistry: Faculty Publications

Thlaspi arvense L. (pennycress) is a cold-tolerant Brassicaceae that produces large amounts of seeds rich in triacylglycerols and protein, making it an attractive target for domestication into an offseason oilseed cash cover crop. Pennycress is easily genetically transformed, enabling synthetic biology approaches to tailor oil properties for specific biofuel and industrial applications. To test the feasibility in pennycress of producing TAGs and acetyl-TAGs rich in medium-chain fatty acids (MCFAs; C6–C14) for industrial, biojet fuel and improved biodiesel applications, we generated transgenic lines with seed-specific expression of unique acyltransferase (LPAT and diacylglycerol acyltransferase) genes and thioesterase (FatB) genes isolated from Cuphea …


Genetic Engineering Of Lesquerella With Increased Ricinoleic Acid Content In Seed Oil, Grace Q. Chen, Kumiko Johnson, Tara J. Nazarenus, Grisel Ponciano, Eva Morales, Edgar B. Cahoon Jan 2021

Genetic Engineering Of Lesquerella With Increased Ricinoleic Acid Content In Seed Oil, Grace Q. Chen, Kumiko Johnson, Tara J. Nazarenus, Grisel Ponciano, Eva Morales, Edgar B. Cahoon

Department of Biochemistry: Faculty Publications

Seeds of castor (Ricinus communis) are enriched in oil with high levels of the industrially valuable fatty acid ricinoleic acid (18:1OH), but production of this plant is limited because of the cooccurrence of the ricin toxin in its seeds. Lesquerella (Physaria fendleri) is being developed as an alternative industrial oilseed because its seeds accumulate lesquerolic acid (20:1OH), an elongated form of 18:1OH in seed oil which lacks toxins. Synthesis of 20:1OH is through elongation of 18:1OH by a lesquerella elongase, PfKCS18. Oleic acid (18:1) is the substrate for 18:1OH synthesis, but it is also used by fatty acid desaturase 2 …


Long Non-Coding Rna Meg3 Deficiency Impairs Glucose Homeostasis And Insulin Signaling By Inducing Cellular Senescence Of Hepatic Endothelium In Obesity, Xiao Cheng, Mohamed Sham Shihabudeen Haider Ali, Matthew Moran, Martonio Ponte Viana, Sarah L. Schlichte, Matthew C. Zimmerman, Oleh Khalimonchuk, Mark W. Feinberg, Xinghui Sun Jan 2021

Long Non-Coding Rna Meg3 Deficiency Impairs Glucose Homeostasis And Insulin Signaling By Inducing Cellular Senescence Of Hepatic Endothelium In Obesity, Xiao Cheng, Mohamed Sham Shihabudeen Haider Ali, Matthew Moran, Martonio Ponte Viana, Sarah L. Schlichte, Matthew C. Zimmerman, Oleh Khalimonchuk, Mark W. Feinberg, Xinghui Sun

Department of Biochemistry: Faculty Publications

Obesity-induced insulin resistance is a risk factor for diabetes and cardiovascular disease. However, the mechanisms underlying endothelial senescence in obesity, and how it impacts obesity-induced insulin resistance remain incompletely understood. In this study, transcriptome analysis revealed that the long non-coding RNA (lncRNA) Maternally expressed gene 3 (Meg3) is one of the top differentially expressed lncRNAs in the vascular endothelium in diet-induced obese mice. Meg3 knockdown induces cellular senescence of endothelial cells characterized by increased senescence-associated β–galactosidase activity, increased levels of endogenous superoxide, impaired mitochondrial structure and function, and impaired autophagy. Moreover, Meg3 knockdown causes cellular senescence of hepatic endothelium in …


Root Nrt, Nir, Amt, Gs, Gogat And Gdh Expression Levels Reveal No Andaba Mediated Drought Tolerance In Brassica Juncea L., Seema Sahay, Luis Robledo-Arratia, Katarzyna Glowacka, Meetu Gupta Jan 2021

Root Nrt, Nir, Amt, Gs, Gogat And Gdh Expression Levels Reveal No Andaba Mediated Drought Tolerance In Brassica Juncea L., Seema Sahay, Luis Robledo-Arratia, Katarzyna Glowacka, Meetu Gupta

Department of Biochemistry: Faculty Publications

Little is known about the interactive effects of exogenous nitric oxide (NO) and abscisic acid (ABA) on nitrogen (N) metabolism and related changes at molecular and biochemical levels under drought stress. The present study highlights the independent and combined effect of NO and ABA (grouped as “nitrate agonists”) on expression profiles of representative key genes known to be involved in N-uptake and assimilation, together with proline metabolism, N–NO metabolism enzyme’s activity and nutrient content in polyethylene glycol (PEG) treated roots of Indian mustard (B. juncea cv. Varuna). Here we report that PEG mediated drought stress negatively inhibited growth performance, as …


Integrative Network Analyses Of Transcriptomics Data Reveal Potential Drug Targets For Acute Radiation Syndrome, Robert Moore, Bhanwar Lal Puniya, Robert Powers, Chittibabu Guda, Kenneth W. Bayles, David Berkowitz, Tomas Helikar Jan 2021

Integrative Network Analyses Of Transcriptomics Data Reveal Potential Drug Targets For Acute Radiation Syndrome, Robert Moore, Bhanwar Lal Puniya, Robert Powers, Chittibabu Guda, Kenneth W. Bayles, David Berkowitz, Tomas Helikar

Department of Biochemistry: Faculty Publications

Recent political unrest has highlighted the importance of understanding the short- and long-term effects of gamma-radiation exposure on human health and survivability. In this regard, effective treatment for acute radiation syndrome (ARS) is a necessity in cases of nuclear disasters. Here, we propose 20 therapeutic targets for ARS identified using a systematic approach that integrates gene co-expression networks obtained under radiation treatment in humans and mice, drug databases, disease-gene association, radiation-induced differential gene expression, and literature mining. By selecting gene targets with existing drugs, we identified potential candidates for drug repurposing. Eight of these genes (BRD4, NFKBIA, CDKN1A, TFPI, MMP9, …


Root Nrt, Nir, Amt, Gs, Gogat And Gdh Expression Levels Reveal No Andaba Mediated Drought Tolerance In Brassica Juncea L., Seema Sahay, Luis Robledo-Arratia, Katarzyna Glowacka, Meetu Gupta Jan 2021

Root Nrt, Nir, Amt, Gs, Gogat And Gdh Expression Levels Reveal No Andaba Mediated Drought Tolerance In Brassica Juncea L., Seema Sahay, Luis Robledo-Arratia, Katarzyna Glowacka, Meetu Gupta

Department of Biochemistry: Faculty Publications

Little is known about the interactive effects of exogenous nitric oxide (NO) and abscisic acid (ABA) on nitrogen (N) metabolism and related changes at molecular and biochemical levels under drought stress. The present study highlights the independent and combined effect of NO and ABA (grouped as “nitrate agonists”) on expression profiles of representative key genes known to be involved in N-uptake and assimilation, together with proline metabolism, N–NO metabolism enzyme’s activity and nutrient content in polyethylene glycol (PEG) treated roots of Indian mustard (B. juncea cv. Varuna). Here we report that PEG mediated drought stress negatively inhibited growth performance, as …


Lysosomal Slc46a3 Modulates Hepatic Cytosolic Copper Homeostasis, Jung-Hwan Kim, Tsutomu Matsubara, Jaekwom Lee, Cristina Fenollar-Ferrer, Kyungreem Han, Donghwan Kim, Shang Jia, Christopher J. Chang, Heejung Yang, Tomokazu Nagano, Kristopher W. Krausz, Sun Hee Yim, Frank J. Gonzalez Jan 2021

Lysosomal Slc46a3 Modulates Hepatic Cytosolic Copper Homeostasis, Jung-Hwan Kim, Tsutomu Matsubara, Jaekwom Lee, Cristina Fenollar-Ferrer, Kyungreem Han, Donghwan Kim, Shang Jia, Christopher J. Chang, Heejung Yang, Tomokazu Nagano, Kristopher W. Krausz, Sun Hee Yim, Frank J. Gonzalez

Department of Biochemistry: Faculty Publications

The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes hepatic toxicity associated with prominent lipid accumulation in humans. Here, the authors report that the lysosomal copper transporter SLC46A3 is induced by TCDD and underlies the hepatic lipid accumulation in mice, potentially via effects on mitochondrial function. SLC46A3 was localized to the lysosome where it modulated intracellular copper levels. Forced expression of hepatic SLC46A3 resulted in decreased mitochondrial membrane potential and abnormal mitochondria morphology consistent with lower copper levels. SLC46A3 expression increased hepatic lipid accumulation similar to the known effects of TCDD exposure in mice and humans. The TCDD-induced hepatic triglyceride accumulation was significantly …


Long Non-Coding Rna Meg3 Deficiency Impairs Glucose Homeostasis And Insulin Signaling By Inducing Cellular Senescence Of Hepatic Endothelium In Obesity, Xiao Cheng, Mohamed Sham Shihabudeen Haider Ali, Matthew Moran, Martonio Ponte Viana, Sarah L. Schlichte, Matthew C. Zimmerman, Oleh Khalimonchuk, Mark W. Feinberg, Xinghui Sun Jan 2021

Long Non-Coding Rna Meg3 Deficiency Impairs Glucose Homeostasis And Insulin Signaling By Inducing Cellular Senescence Of Hepatic Endothelium In Obesity, Xiao Cheng, Mohamed Sham Shihabudeen Haider Ali, Matthew Moran, Martonio Ponte Viana, Sarah L. Schlichte, Matthew C. Zimmerman, Oleh Khalimonchuk, Mark W. Feinberg, Xinghui Sun

Department of Biochemistry: Faculty Publications

Obesity-induced insulin resistance is a risk factor for diabetes and cardiovascular disease. However, the mechanisms underlying endothelial senescence in obesity, and how it impacts obesity-induced insulin resistance remain incompletely understood. In this study, transcriptome analysis revealed that the long non-coding RNA (lncRNA) Maternally expressed gene 3 (Meg3) is one of the top differentially expressed lncRNAs in the vascular endothelium in diet-induced obese mice. Meg3 knockdown induces cellular senescence of endothelial cells characterized by increased senescence-associated β–galactosidase activity, increased levels of endogenous superoxide, impaired mitochondrial structure and function, and impaired autophagy. Moreover, Meg3 knockdown causes cellular senescence of hepatic endothelium in …


Teaching Metabolism In Upper-Division Undergraduate Biochemistry Courses Using Online Computational Systems And Dynamical Models Improves Student Performance, Christine S. Booth, Changsoo Song, Michelle E. Howell, Achilles Rasquinha, Aleš Saska, Resa M. Helikar, Sharmin M. Sikich, Brain A. Couch, Karin Van Dijk, Rebecca Roston, Tomáš Helikar Jan 2021

Teaching Metabolism In Upper-Division Undergraduate Biochemistry Courses Using Online Computational Systems And Dynamical Models Improves Student Performance, Christine S. Booth, Changsoo Song, Michelle E. Howell, Achilles Rasquinha, Aleš Saska, Resa M. Helikar, Sharmin M. Sikich, Brain A. Couch, Karin Van Dijk, Rebecca Roston, Tomáš Helikar

Department of Biochemistry: Faculty Publications

Understanding metabolic function requires knowledge of the dynamics, interdependence, and regulation of metabolic networks. However, multiple professional societies have recognized that most undergraduate biochemistry students acquire only a surface-level understanding of metabolism. We hypothesized that guiding students through interactive computer simulations of metabolic systems would increase their ability to recognize how individual interactions between components affect the behavior of a system under different conditions. The computer simulations were designed with an interactive activity (i.e., module) that used the predict–observe–explain model of instruction to guide students through a process in which they iteratively predict outcomes, test their predictions, modify the interactions …


The Need For Research-Grade Systems Modeling Technologies For Life Science Education, Tomáš Helikar Jan 2021

The Need For Research-Grade Systems Modeling Technologies For Life Science Education, Tomáš Helikar

Department of Biochemistry: Faculty Publications

The coronavirus disease 2019 (COVID-19) pandemic not only challenged deeply-rooted daily patterns but also put a spotlight on the role of computational modeling in science and society. Amid the impromptu upheaval of in-person education across the world, this article aims to articulate the need to train students in computational and systems biology using research-grade technologies. ...

Life sciences education needs multiple technical infrastructures explicitly designed to support this field’s vast computational needs. Developing and sustaining effective, scientifically authentic educational technologies is not easy. It requires expertise in software development and the scientific domain as well as in education and education …


Covid19 Disease Map, A Computational Knowledge Repository Of Virus–Host Interaction Mechanisms, Marek Ostaszewski, Tomáš Helikar, Bhanwar Lal Puniya, A Host Of Co-Authors, Covid-19 Disease Map Community Jan 2021

Covid19 Disease Map, A Computational Knowledge Repository Of Virus–Host Interaction Mechanisms, Marek Ostaszewski, Tomáš Helikar, Bhanwar Lal Puniya, A Host Of Co-Authors, Covid-19 Disease Map Community

Department of Biochemistry: Faculty Publications

We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 molecular mechanisms. The COVID-19 Disease Map (C19DMap) is a graphical, interactive representation of disease-relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph-based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, …


Association Of The Malate Dehydrogenase‑Citrate Synthase Metabolon Is Modulated By Intermediates Of The Krebs Tricarboxylic Acid Cycle, Joy Omini, Izabela Wojciechowska, Aleksandra Skirycz, Hideaki Moriyama, Toshihiro Obata Jan 2021

Association Of The Malate Dehydrogenase‑Citrate Synthase Metabolon Is Modulated By Intermediates Of The Krebs Tricarboxylic Acid Cycle, Joy Omini, Izabela Wojciechowska, Aleksandra Skirycz, Hideaki Moriyama, Toshihiro Obata

Department of Biochemistry: Faculty Publications

Mitochondrial malate dehydrogenase (MDH)-citrate synthase (CS) multi-enzyme complex is a part of the Krebs tricarboxylic acid (TCA) cycle ‘metabolon’ which is enzyme machinery catalyzing sequential reactions without diffusion of reaction intermediates into a bulk matrix. This complex is assumed to be a dynamic structure involved in the regulation of the cycle by enhancing metabolic flux. Microscale Thermophoresis analysis of the porcine heart MDH-CS complex revealed that substrates of the MDH and CS reactions, NAD+ and acetyl-CoA, enhance complex association while products of the reactions, NADH and citrate, weaken the affinity of the complex. Oxaloacetate enhanced the interaction only when it …


Sestrins: Emerging Dynamic Stress-Sensors In Metabolic And Environmental Health, Seung Hyun Ro, Julianne Fay, Cesar I. Cyuzuzo, Yura Jang, Naeun Lee, Hyun Seob Song, Edward N. Harris Dec 2020

Sestrins: Emerging Dynamic Stress-Sensors In Metabolic And Environmental Health, Seung Hyun Ro, Julianne Fay, Cesar I. Cyuzuzo, Yura Jang, Naeun Lee, Hyun Seob Song, Edward N. Harris

Department of Biochemistry: Faculty Publications

Proper timely management of various external and internal stresses is critical for metabolic and redox homeostasis in mammals. In particular, dysregulation of mechanistic target of rapamycin complex (mTORC) triggered from metabolic stress and accumulation of reactive oxygen species (ROS) generated from environmental and genotoxic stress are well-known culprits leading to chronic metabolic disease conditions in humans. Sestrins are one of the metabolic and environmental stress-responsive groups of proteins, which solely have the ability to regulate both mTORC activity and ROS levels in cells, tissues and organs. While Sestrins are originally reported as one of several p53 target genes, recent studies …


Editorial: Structure And Function Of Chloroplasts - Volume Ii, Yan Lu, Lu Ning Liu, Rebecca L. Roston, Jurgen Soll, Hongbo Gao Nov 2020

Editorial: Structure And Function Of Chloroplasts - Volume Ii, Yan Lu, Lu Ning Liu, Rebecca L. Roston, Jurgen Soll, Hongbo Gao

Department of Biochemistry: Faculty Publications

No abstract provided.


A Co-Opted Steroid Synthesis Gene, Maintained In Sorghum But Not Maize, Is Associated With A Divergence In Leaf Wax Chemistry, Lucas Busta, Elizabeth Schmitz, Dylan K. Kosma, James C. Schnable, Edgar B. Cahoon Nov 2020

A Co-Opted Steroid Synthesis Gene, Maintained In Sorghum But Not Maize, Is Associated With A Divergence In Leaf Wax Chemistry, Lucas Busta, Elizabeth Schmitz, Dylan K. Kosma, James C. Schnable, Edgar B. Cahoon

Department of Biochemistry: Faculty Publications

Virtually all land plants are coated in a cuticle, a waxy polyester that prevents nonstomatal water loss and is important for heat and drought tolerance. Here, we describe a likely genetic basis for a divergence in cuticular wax chemistry between Sorghum bicolor, a drought tolerant crop widely cultivated in hot climates, and its close relative Zea mays (maize). Combining chemical analyses, heterologous expression, and comparative genomics, we reveal that: 1) sorghum and maize leaf waxes are similar at the juvenile stage but, after the juvenile-to-adult transition, sorghum leaf waxes are rich in triterpenoids that are absent from maize; 2) biosynthesis …


Curie Temperature Engineering In A Novel 2d Analog Of Iron Ore (Hematene) Via Strain, Renu Singla, Timothy A. Hackett, Sarvesh Kumar, Jyotsna Sharma, Manish K. Kashyap Oct 2020

Curie Temperature Engineering In A Novel 2d Analog Of Iron Ore (Hematene) Via Strain, Renu Singla, Timothy A. Hackett, Sarvesh Kumar, Jyotsna Sharma, Manish K. Kashyap

Department of Biochemistry: Faculty Publications

As a newly exfoliated magnetic 2D material from hematite, hematene is the most far-reaching ultrathin magnetic indirect bandgap semiconductor. We have carried out a detailed structural analysis of hematene via prefacing strain by means of first-principles calculations based on density functional theory (DFT). Hematene in the pristine form emerges out to be a magnetic semiconductor with a bandgap of 1.0/2.0 eV for the majority/minority spin channel. The dependence of magnetic anisotropy energy (MAE), TC, and the bandgap on compressive and tensile strains has been scanned exclusively. It is examined that TC depends firmly on the compressive strain …


Changes In Lipid Profiles Of Epileptic Mouse Mode, Alicia Johnson, Ryan A. Grove, Deepak Madhavan, Cory H.T. Boone, Camila Pereira Braga, Hannah Kyllo, Kaeli K. Samson, Kristina A. Simeone, Timothy A. Simeone, Tomáš Helikar, Corrine K. Hanson, Jiri Adamec Oct 2020

Changes In Lipid Profiles Of Epileptic Mouse Mode, Alicia Johnson, Ryan A. Grove, Deepak Madhavan, Cory H.T. Boone, Camila Pereira Braga, Hannah Kyllo, Kaeli K. Samson, Kristina A. Simeone, Timothy A. Simeone, Tomáš Helikar, Corrine K. Hanson, Jiri Adamec

Department of Biochemistry: Faculty Publications

Introduction Approximately 1% of the world’s population is impacted by epilepsy, a chronic neurological disorder characterized by seizures. One-third of epileptic patients are resistant to AEDs, or have medically refractory epilepsy (MRE). One non-invasive treatment that exists for MRE includes the ketogenic diet (KD), a high-fat, low-carbohydrate diet. Despite the KD’s success in seizure attenuation, it has a few risks and its mechanisms remain poorly understood. The KD has been shown to improve metabolism and mitochondrial function in epileptic phenotypes. Potassium channels have implications in epileptic conditions as they have dual roles as metabolic sensors and control neuronal excitation.

Objectives …