Digital Commons Network^™

Plasma Tnf-Α And Soluble Tnf Receptor Levels After Doxorubicin With Or Without Co-Administration Of Mesna-A Randomized, Cross-Over Clinical Study, John Hayslip, Emily Van Meter Dressler, Heidi L. Weiss, Tammy J. Taylor, Mara D. Chambers, Teresa Noel, Sumitra Miriyala, Jeriel T. R. Keeney, Xiaojia Ren, Rukhsana Sultana, Mary Vore, D. Allan Butterfield, Daret St. Clair, Jeffrey A. Moscow

Markey Cancer Center Faculty Publications

PURPOSE: Chemotherapy-induced cognitive impairment (CICI) is a common sequelae of cancer therapy. Recent preclinical observations have suggested that CICI can be mediated by chemotherapy-induced plasma protein oxidation, which triggers TNF-α mediated CNS damage. This study evaluated sodium-2-mercaptoethane sulfonate (Mesna) co-administration with doxorubicin to reduce doxorubicin-induced plasma protein oxidation and resultant cascade of TNF-α, soluble TNF receptor levels and related cytokines.

METHODS: Thirty-two evaluable patients were randomized using a crossover design to receive mesna or saline in either the first or second cycle of doxorubicin in the context of a standard chemotherapy regimen for either non-Hodgkin lymphoma or breast …

Closed Head Injury In An Age-Related Alzheimer Mouse Model Leads To An Altered Neuroinflammatory Response And Persistent Cognitive Impairment, Scott J. Webster, Linda J. Van Eldik, D. Martin Watterson, Adam D. Bachstetter

Sanders-Brown Center on Aging Faculty Publications

Epidemiological studies have associated increased risk of Alzheimer's disease (AD)-related clinical symptoms with a medical history of head injury. Currently, little is known about pathophysiology mechanisms linked to this association. Persistent neuroinflammation is one outcome observed in patients after a single head injury. Neuroinflammation is also present early in relevant brain regions during AD pathology progression. In addition, previous mechanistic studies in animal models link neuroinflammation as a contributor to neuropathology and cognitive impairment in traumatic brain injury (TBI) or AD-related models. Therefore, we explored the potential interplay of neuroinflammatory responses in TBI and AD by analysis of the temporal …

What Did We Learn About Vads In 2014?, Maya Guglin

The VAD Journal

No abstract provided.

Targeting Human Central Nervous System Protein Kinases: An Isoform Selective P38Αmapk Inhibitor That Attenuates Disease Progression In Alzheimer's Disease Mouse Models, Saktimayee M. Roy, Valerie L. Grum-Tokars, James P. Schavocky, Faisal Saeed, Agnieszka Staniszewski, Andrew F. Teich, Ottavio Arancio, Adam D. Bachstetter, Scott J. Webster, Linda J. Van Eldik, George Minasov, Wayne F. Anderson, Jeffrey C. Pelletier, D. Martin Watterson

Spinal Cord and Brain Injury Research Center Faculty Publications

The first kinase inhibitor drug approval in 2001 initiated a remarkable decade of tyrosine kinase inhibitor drugs for oncology indications, but a void exists for serine/threonine protein kinase inhibitor drugs and central nervous system indications. Stress kinases are of special interest in neurological and neuropsychiatric disorders due to their involvement in synaptic dysfunction and complex disease susceptibility. Clinical and preclinical evidence implicates the stress related kinase p38αMAPK as a potential neurotherapeutic target, but isoform selective p38αMAPK inhibitor candidates are lacking and the mixed kinase inhibitor drugs that are promising in peripheral tissue disease indications have limitations for neurologic indications. Therefore, …

Chaperone Hsp47 Drives Malignant Growth And Invasion By Modulating An Ecm Gene Network, Jieqing Zhu, Gaofeng Xiong, Hanjiang Fu, B. Mark Evers, Binhua P. Zhou, Ren Xu

Markey Cancer Center Faculty Publications

The extracellular matrix (ECM) is a determining factor in the tumor microenvironment that restrains or promotes malignant growth. In this report, we show how the molecular chaperone protein Hsp47 functions as a nodal hub in regulating an ECM gene transcription network. A transcription network analysis showed that Hsp47 expression was activated during breast cancer development and progression. Hsp47 silencing reprogrammed human breast cancer cells to form growth-arrested and/or noninvasive structures in 3D cultures, and to limit tumor growth in xenograft assays by reducing deposition of collagen and fibronectin. Coexpression network analysis also showed that levels of microRNA(miR)-29b and -29c were …

Microcystins As Agents For Treatment Of Cancer, Noel R. Monks, Shuqian Liu, Jeffrey A. Moscow

Pharmaceutical Sciences Faculty Patents

This invention relates to the use of microcystins as agents for treatment of cancer. Also provided are methods of screening for microcystins with improved cytotoxicity.

Mapk Signaling Pathway Alters Expression Of Midgut Alp And Abcc Genes And Causes Resistance To Bacillus Thuringiensis Cry1ac Toxin In Diamondback Moth, Zhaojiang Guo, Shi Kang, Defeng Chen, Qingjun Wu, Shaoli Wang, Wen Xie, Xun Zhu, Simon W. Baxter, Xuguo Zhou, Juan Luis Jurat-Fuentes, Youjun Zhang

Entomology Faculty Publications

Insecticidal crystal toxins derived from the soil bacterium Bacillus thuringiensis (Bt) are widely used as biopesticide sprays or expressed in transgenic crops to control insect pests. However, large-scale use of Bt has led to field-evolved resistance in several lepidopteran pests. Resistance to Bt Cry1Ac toxin in the diamondback moth, Plutella xylostella (L.), was previously mapped to a multigenic resistance locus (BtR-1). Here, we assembled the 3.15 Mb BtR-1 locus and found high-level resistance to Cry1Ac and Bt biopesticide in four independent P. xylostella strains were all associated with differential expression of a midgut membrane-bound alkaline phosphatase (ALP …

Attenuation Of Traumatic Brain Injury-Induced Cognitive Impairment In Mice By Targeting Increased Cytokine Levels With A Small Molecule Experimental Therapeutic, Adam D. Bachstetter, Scott J. Webster, Danielle S. Goulding, Jonathan E. Morton, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Evidence from clinical studies and preclinical animal models suggests that proinflammatory cytokine overproduction is a potential driving force for pathology progression in traumatic brain injury (TBI). This raises the possibility that selective targeting of the overactive cytokine response, a component of the neuroinflammation that contributes to neuronal dysfunction, may be a useful therapeutic approach. MW151 is a CNS-penetrant, small molecule experimental therapeutic that selectively restores injury- or disease-induced overproduction of proinflammatory cytokines towards homeostasis. We previously reported that MW151 administered post-injury (p.i.) is efficacious in a closed head injury (CHI) model of diffuse TBI in mice. Here we test …

Transcriptional Activity Of The Islet Β Cell Factor Pdx1 Is Augmented By Lysine Methylation Catalyzed By The Methyltransferase Set7/9, Aarthi V. Maganti, Bernhard Maier, Sarah A. Tersey, Megan L. Sampley, Amber L. Mosley, Sabire Özcan, Boobalan Pachaiyappan, Patrick M. Woster, Chad S. Hunter, Roland Stein, Raghavendra G. Mirmira

Molecular and Cellular Biochemistry Faculty Publications

The transcription factor Pdx1 is crucial to islet β cell function and regulates target genes in part through interaction with coregulatory factors. Set7/9 is a Lys methyltransferase that interacts with Pdx1. Here we tested the hypothesis that Lys methylation of Pdx1 by Set7/9 augments Pdx1 transcriptional activity. Using mass spectrometry and mutational analysis of purified proteins, we found that Set7/9 methylates the N-terminal residues Lys-123 and Lys-131 of Pdx1. Methylation of these residues occurred only in the context of intact, full-length Pdx1, suggesting a specific requirement of secondary and/or tertiary structural elements for catalysis by Set7/9. Immunoprecipitation assays and mass …

Tall Fescue Cultivar And Fungal Endophyte Combinations Influence Plant Growth And Root Exudate Composition, Jingqi Guo, Rebecca L. Mcculley, David H. Mcnear Jr.

Plant and Soil Sciences Faculty Publications

Tall fescue [Lolium arundinaceum (Schreb.)] is a cool-season perennial grass used in pastures throughout the Southeastern United States. The grass can harbor a shoot-specific fungal endophyte (Epichloë coenophiala) thought to provide the plant with enhanced resistance to biotic and abiotic stresses. Because alkaloids produced by the common variety of the endophyte cause severe animal health issues, focus has been on replacing the common-toxic strain with novel varieties that do not produce the mammal-toxic alkaloids but maintain abiotic and biotic stress tolerance benefits. Little attention has been given to the influence of the plant-fungal symbiosis on rhizosphere processes. …

Forage News [2015-04], Department Of Plant And Soil Sciences, University Of Kentucky

Forage News

• Farewell to Garry Lacefield
• Silvopasture
• High Traffic Area Pads
• What if you could watch plants grow in minutes?
• National Forage Spokesperson Winner Now Online
• Rotational Grazing
• Grazing News

Apparent Role For Borrelia Burgdorferi Luxs During Mammalian Infection, William K. Arnold, Christina R. Savage, Alyssa D. Antonicello, Brian Stevenson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The Lyme disease spirochete, Borrelia burgdorferi, controls protein expression patterns during its tick-mammal infection cycle. Earlier studies demonstrated that B. burgdorferi synthesizes 4,5-dihydroxy-2,3-pentanedione (autoinducer-2 [AI-2]) and responds to AI-2 by measurably changing production of several infection-associated proteins. luxS mutants, which are unable to produce AI-2, exhibit altered production of several proteins. B. burgdorferi cannot utilize the other product of LuxS, homocysteine, indicating that phenotypes of luxS mutants are not due to the absence of that molecule. Although a previous study found that a luxS mutant was capable of infecting mice, a critical caveat to those results is that bacterial …

Disparate Independent Genetic Events Disrupt The Secondary Metabolism Gene Pera In Certain Symbiotic Epichloë Species, Daniel Berry, Johanna E. Takach, Christopher L. Schardl, Nikki D. Charlton, Barry Scott, Carolyn A. Young

Plant Pathology Faculty Publications

Peramine is an insect-feeding deterrent produced by Epichloë species in symbiotic association with C₃ grasses. The perA gene responsible for peramine synthesis encodes a two-module nonribosomal peptide synthetase. Alleles of perA are found in most Epichloë species; however, peramine is not produced by many perA-containing Epichloë isolates. The genetic basis of these peramine-negative chemotypes is often unknown. Using PCR and DNA sequencing, we analyzed the perA genes from 72 Epichloë isolates and identified causative mutations of perA null alleles. We found nonfunctional perA-ΔR* alleles, which contain a transposon-associated deletion of the perA region encoding the C-terminal reductase …

Transylvania University And Its Hemp Connection, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

No abstract provided.

Detection Of Phlpp1Α/Β In Human And Mouse Brain By Different Anti-Phlpp1 Antibodies, Travis C. Jackson, Hülya Bayir, Milos D. Ikonomovic, Keri Janesko-Feldman, Zaichuan Mi, Tianyan Gao, Edwin K. Jackson, Patrick M. Kochanek

Markey Cancer Center Faculty Publications

Pleckstrin homology domain and leucine rich repeat protein phosphatase 1 (PHLPP1) is a member of the serine/threonine family of phosphatases. It has been studied in organs including brain, heart, pancreas, adipose, breast, and prostate. Human PHLPP1 encodes two splice variants - PHLPP1α (~140-150 kDa) and PHLPP1β (~180-190 kDa). Commercial antibodies are widely used to characterize PHLPP1 proteins in cells/tissues. Here we validate five different antibodies to detect PHLPP1α/β by Western blot using PHLPP1 WT/KO mice. All antibodies recognize PHLPP1β in brain. Only a single antibody (Cosmo Bio Co) detects PHLPP1α (~145-150 kDa). The other four antibodies detect a non-specific signal …

G9a Is Essential For Emt-Mediated Metastasis And Maintenance Of Cancer Stem Cell-Like Characters In Head And Neck Squamous Cell Carcinoma, Shuli Liu, Dongxia Ye, Wenzheng Guo, Wenwen Yu, Yue He, Jingzhou Hu, Yanan Wang, Ling Zhang, Yueling Liao, Hongyong Song, Shuangshuang Zhong, Dongliang Xu, Huijing Yin, Beibei Sun, Xiaofei Wang, Jingyi Liu, Yadi Wu, Binhua P. Zhou, Zhiyuan Zhang, Jiong Deng

Markey Cancer Center Faculty Publications

Head and neck squamous cell carcinoma (HNSCC) is a particularly aggressive cancer with poor prognosis, largely due to lymph node metastasis and local recurrence. Emerging evidence suggests that epithelial-to-mesenchymal transition (EMT) is important for cancer metastasis, and correlated with increased cancer stem cells (CSCs) characteristics. However, the mechanisms underlying metastasis to lymph nodes in HNSCC is poorly defined. In this study, we show that E-cadherin repression correlates with cancer metastasis and poor prognosis in HNSCC. We found that G9a, a histone methyltransferase, interacts with Snail and mediates Snail-induced transcriptional repression of E-cadherin and EMT, through methylation of histone H3 lysine-9 …

Stably Expressed Housekeeping Genes Across Developmental Stages In The Two-Spotted Spider Mite, Tetranychus Urticae, Chunxiao Yang, Huipeng Pan, Yong Liu, Xuguo Zhou

Entomology Faculty Publications

Quantitative real-time PCR (qRT-PCR) is a reliable and reproducible technique for measuring mRNA expression. To facilitate gene expression studies and obtain more accurate qRT-PCR analysis, normalization relative to stable housekeeping genes is mandatory. In this study, ten housekeeping genes, including beta-actin (Actin), elongation factor 1 α (EF1A), glyceralde hyde-3-phosphate dehydrogenase (GAPDH), ribosomal protein L13 (RPL13), ribosomal protein 49 (RP49), α-tubulin (Tubulin), vacuolar-type H+-ATPase (v-ATPase), succinate dehydrogenase subunit A (SDHA) , 28S ribosomal RNA (28S), and 18S ribosomal RNA (18S) from …

Immune Function And Muscle Adaptations To Resistance Exercise In Older Adults: Study Protocol For A Randomized Controlled Trial Of A Nutritional Supplement, Richard A. Dennis, Usha Ponnappan, Ralph L. Kodell, Kimberly K. Garner, Christopher M. Parkes, Melinda M. Bopp, Kalpana P. Padala, Charlotte A. Peterson, Prasad R. Padala, Dennis H. Sullivan

Physical Therapy Faculty Publications

BACKGROUND: Immune function may influence the ability of older adults to maintain or improve muscle mass, strength, and function during aging. Thus, nutritional supplementation that supports the immune system could complement resistance exercise as an intervention for age-associated muscle loss. The current study will determine the relationship between immune function and exercise training outcomes for older adults who consume a nutritional supplement or placebo during resistance training and post-training follow-up. The supplement was chosen due to evidence suggesting its ingredients [arginine (Arg), glutamine (Gln), and β-hydroxy β-methylbutyrate (HMB)] can improve immune function, promote muscle growth, and counteract muscle loss. …

Ppm1a Regulates Antiviral Signaling By Antagonizing Tbk1-Mediated Sting Phosphorylation And Aggregation, Zexing Li, Ge Liu, Liwei Sun, Yan Teng, Xuejiang Guo, Jianhang Jia, Jiahao Sha, Xiao Yang, Dahua Chen, Qinmiao Sun

Markey Cancer Center Faculty Publications

Stimulator of interferon genes (STING, also known as MITA and ERIS) is critical in protecting the host against DNA pathogen invasion. However, the molecular mechanism underlying the regulation of STING remains unclear. Here, we show that PPM1A negatively regulates antiviral signaling by targeting STING in its phosphatase activity-dependent manner, and in a line with this, PPM1A catalytically dephosphorylates STING and TBK1 in vitro. Importantly, we provide evidence that whereas TBK1 promotes STING aggregation in a phosphorylation-dependent manner, PPM1A antagonizes STING aggregation by dephosphorylating both STING and TBK1, emphasizing that phosphorylation is crucial for the efficient activation of STING. Our …

Thrombospondin1 Deficiency Attenuates Obesity-Associated Microvascular Complications In Apoe-/- Mice, Hasiyeti Maimaitiyiming, Kate Clemons, Qi Zhou, Heather Norman, Shuxia Wang

Pharmacology and Nutritional Sciences Faculty Publications

Obesity is associated with insulin resistance and the increased development of vascular complications. Previously, we have demonstrated that thrombospondin1 (TSP1) regulates macrophage function and contributes to obesity associated inflammation and insulin resistance. However, the role of TSP1 in the development of obesity associated vascular complications is not clear. Therefore, in the current study, we investigated whether TSP1 deficiency protects mice from obesity associated micro as well as macro-vascular complications in ApoE-/- mice. In this study, male ApoE-/- mice and ApoE-/-TSP1-/- mice were fed with a low-fat (LF) or a high-fat (HF) diet for 16 weeks. We found that body weight …

Enhanced Nmda Receptor-Mediated Modulation Of Excitatory Neurotransmission In The Dorsal Vagal Complex Of Streptozotocin-Treated, Chronically Hyperglycemic Mice, Eva C. Bach, Katalin Cs. Halmos, Bret N. Smith

Physiology Faculty Publications

A variety of metabolic disorders, including complications experienced by diabetic patients, have been linked to altered neural activity in the dorsal vagal complex. This study tested the hypothesis that augmentation of N-Methyl-D-Aspartate (NMDA) receptor-mediated responses in the vagal complex contributes to increased glutamate release in the dorsal motor nucleus of the vagus nerve (DMV) in mice with streptozotocin-induced chronic hyperglycemia (i.e., hyperglycemic mice), a model of type 1 diabetes. Antagonism of NMDA receptors with AP-5 (100 μM) suppressed sEPSC frequency in vagal motor neurons recorded in vitro, confirming that constitutively active NMDA receptors regulate glutamate release in the DMV. There …

A Response Regulator From A Soil Metagenome Enhances Resistance To The Β-Lactam Antibiotic Carbenicillin In Escherichia Coli, Heather K. Allen, Ran An, Jo Handelsman, Luke A. Moe

Plant and Soil Sciences Faculty Publications

Functional metagenomic analysis of soil metagenomes is a method for uncovering as-yet unidentified mechanisms for antibiotic resistance. Here we report an unconventional mode by which a response regulator derived from a soil metagenome confers resistance to the β-lactam antibiotic carbenicillin in Escherichia coli. A recombinant clone (βlr16) harboring a 5,169 bp DNA insert was selected from a metagenomic library previously constructed from a remote Alaskan soil. The βlr16 clone conferred specific resistance to carbenicillin, with limited increases in resistance to other tested antibiotics, including other β-lactams (penicillins and cephalosporins), rifampin, ciprofloxacin, erythromycin, chloramphenicol, nalidixic acid, fusidic acid, and gentamicin. Resistance …

Methyl Farnesoate Plays A Dual Role In Regulating Drosophila Metamorphosis, Di Wen, Crisalejandra Rivera-Perez, Mohamed Abdou, Qiangqiang Jia, Qianyu He, Xi Liu, Ola Zyaan, Jingjing Xu, William G. Bendena, Stephen S. Tobe, Fernando G. Noriega, Subba R. Palli, Jian Wang, Sheng Li

Entomology Faculty Publications

Corpus allatum (CA) ablation results in juvenile hormone (JH) deficiency and pupal lethality in Drosophila. The fly CA produces and releases three sesquiterpenoid hormones: JH III bisepoxide (JHB3), JH III, and methyl farnesoate (MF). In the whole body extracts, MF is the most abundant sesquiterpenoid, followed by JHB3 and JH III. Knockout of JH acid methyl transferase (jhamt) did not result in lethality; it decreased biosynthesis of JHB3, but MF biosynthesis was not affected. RNAi-mediated reduction of 3-hydroxy-3-methylglutaryl CoA reductase (hmgcr) expression in the CA decreased biosynthesis and titers of the three sesquiterpenoids, resulting in …

Poster Session, Kentucky Water Resources Research Institute, University Of Kentucky

Kentucky Water Resources Annual Symposium

1. Quantification of Common Agricultural Herbicide Dispersal and Land Use in Selected Areas of the Kentucky River Watershed, Andrew Nagel and others, Northern Kentucky University, Highland Heights, KY
2. Exploring the Effects of Herbicides on Willow Seedlings, Sarah Stryffeler and others, Dept. of Biological Sciences, Northern Kentucky University, Highland Heights, KY
3. LiDAR Mapping Sinkholes in Cane Run Watershed, Fidele Tibouo and others, Dept. Earth and Environmental Sciences, University of Kentucky, Lexington, KY
4. Surface Enhanced Raman Spectroscopy to Study Photocatalytic Degradation of Organic Pollutants, Frankie Wallace and Matthew Nee, Dept. of Chemistry, Western Kentucky University, Bowling Green, KY
5. Test …

Session 2b, Kentucky Water Resources Research Institute, University Of Kentucky

Kentucky Water Resources Annual Symposium

• The Kentucky Nutrient Watershed Model, Ben Albritton and others, Kentucky Water Resources Research Institute, University of Kentucky, Lexington, KY
• Model Parameter Uncertainty Analysis for an Annual Field-Scale P Loss Model, Carl Bolster, Food Animal Environmental Systems Research Unit, USDA-ARS, Bowling Green, KY
• Flood Modeling Using a Virtual 3D Environment to Help Student Learning, C. V. Chandramouli and others, Mechanical Engineering Department, Purdue University Calumet, Hammond, IN
• Updating the Fresh-Saline Water Interface Map in Eastern Kentucky, Jerrad Grider and T. M. Parris, Kentucky Geological Survey, University of Kentucky, Lexington, KY

Proceedings Of 2015 Kentucky Water Resources Annual Symposium, Kentucky Water Resources Research Institute, University Of Kentucky

Kentucky Water Resources Annual Symposium

This symposium was planned and conducted as a part of the state water resources research institute annual program that is supported by Grant/Cooperative Agreement Number G11AP20081 from the United States Geological Survey. The contents of this proceedings document and the views and conclusions presented at the symposium are solely the responsibility of the individual authors and presenters and do not necessarily represent the official views of the USGS or of the symposium organizers and sponsors. This publication is produced with the understanding that the United States Government is authorized to reproduce and distribute reprints for government purposes.

Cd47 Deficiency Protects Mice From Diet-Induced Obesity And Improves Whole Body Glucose Tolerance And Insulin Sensitivity, Hasiyeti Maimaitiyiming, Heather Norman, Qi Zhou, Shuxia Wang

Pharmacology and Nutritional Sciences Faculty Publications

CD47 is a transmembrane protein with several functions including self-recognition, immune cell communication, and cell signaling. Although it has been extensively studied in cancer and ischemia, CD47 function in obesity has never been explored. In this study, we utilized CD47 deficient mice in a high-fat diet induced obesity model to study for the first time whether CD47 plays a role in the development of obesity and metabolic complications. Male CD47 deficient and wild type (WT) control mice were fed with either low fat (LF) or high fat (HF) diets for 16 weeks. Interestingly, we found that CD47 deficient mice were …

Determining The Role Of Il-4 Induced Neuroinflammation In Microglial Activity And Amyloid-Ss Using Bv2 Microglial Cells And App/Ps1 Transgenic Mice, Clare H. Latta, Tiffany L. Sudduth, Erica M. Weekman, Holly M. Brothers, Erin L. Abner, Gabriel J. Popa, Michael D. Mendenhall, Floracita Gonzalez-Oregon, Kaitlyn Braun, Donna M. Wilcock

Physiology Faculty Publications

Background

Microglia are considered the resident immune cells of the central nervous system (CNS). In response to harmful stimuli, an inflammatory reaction ensues in which microglia are activated in a sequenced spectrum of pro- and antiinflammatory phenotypes that are akin to the well-characterized polarization states of peripheral macrophages. A “classically” activated M1 phenotype is known to eradicate toxicity. The transition to an “alternatively” activated M2 phenotype encompasses neuroprotection and repair. In recent years, inflammation has been considered an accompanying pathology in response to the accumulation of extracellular amyloid-β (Aβ) in Alzheimer’s disease (AD). This study aimed to drive an M2a-biased …

Metabolic Reprogramming Of Cancer-Associated Fibroblasts By Idh3Α Downregulation, Daoxiang Zhang, Yongbin Wang, Zhimin Shi, Jingyi Liu, Pan Sun, Xiaodan Hou, Jian Zhang, Shimin Zhao, Binhua P. Zhou, Jun Mi

Markey Cancer Center Faculty Publications

Cancer-associated fibroblasts (CAFs) provide critical metabolites for tumor growth and undergo metabolic reprogramming to support glycolysis. However, the molecular mechanisms responsible for this change remain unclear. Here, we report that TGF-β1- or PDGF-induced CAFs switch from oxidative phosphorylation to aerobic glycolysis. We identify downregulation of isocitrate dehydrogenase 3α (IDH3α) as a marker for this switch. Furthermore, miR-424 downregulates IDH3α during CAF formation. Downregulation of IDH3α decreases the effective level of α-ketoglutarate (α-KG) by reducing the ratio of α-KG to fumarate and succinate, resulting in PHD2 inhibition and HIF-1α protein stabilization. The accumulation of HIF-1α, in turn, promotes glycolysis by increasing …

Fundamental Principles Of Plant Pathology For Agricultural Producers [2015], Paul C. Vincelli

Agriculture and Natural Resources Publications

All crop plants produced in Kentucky have the potential to become diseased under certain conditions. Diseases of crops can affect yield and/or quality of the harvested commodity, which can impact profitability and increase the risks of farming.