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Articles 871 - 900 of 1318

Full-Text Articles in Medical Biochemistry

Development Of Affinity Microcolumns For Drug–Protein Binding Studies In Personalized Medicine: Interactions Of Sulfonylurea Drugs With In Vivo Glycated Human Serum Albumin, Jeanethe Anguizola, K. S. Joseph, Omar S. Barnaby, Ryan Matsuda, Guadalupe Alvarado, William Clarke, Ronald Cerny, David S. Hage Jan 2013

Development Of Affinity Microcolumns For Drug–Protein Binding Studies In Personalized Medicine: Interactions Of Sulfonylurea Drugs With In Vivo Glycated Human Serum Albumin, Jeanethe Anguizola, K. S. Joseph, Omar S. Barnaby, Ryan Matsuda, Guadalupe Alvarado, William Clarke, Ronald Cerny, David S. Hage

David Hage Publications

This report used high-performance affinity microcolumns to examine the changes in binding by sulfonylurea drugs to in vivo glycated HSA that had been isolated from individual patients with diabetes. An immunoextraction approach was developed to isolate HSA and glycated HSA from clinical samples, using only 20 μL of plasma or serum and 6–12 nmol of protein to prepare each affinity microcolumn. It was found that the affinity microcolumns could be used in either frontal analysis or zonal elution studies, which typically required only 4–8 min per run. The microcolumns had good stability and allowed data to be obtained for multiple …


Hypoxia-Inducing Factors As Master Regulators Of Stemness Properties And Altered Metabolism Of Cancer- And Metastasis-Initiating Cells., Murielle Mimeault, Surinder K. Batra Jan 2013

Hypoxia-Inducing Factors As Master Regulators Of Stemness Properties And Altered Metabolism Of Cancer- And Metastasis-Initiating Cells., Murielle Mimeault, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Accumulating lines of experimental evidence have revealed that hypoxia-inducible factors, HIF-1α and HIF-2α, are key regulators of the adaptation of cancer- and metastasis-initiating cells and their differentiated progenies to oxygen and nutrient deprivation during cancer progression under normoxic and hypoxic conditions. Particularly, the sustained stimulation of epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF-1R), stem cell factor (SCF) receptor KIT, transforming growth factor-β receptors (TGF-βRs) and Notch and their downstream signalling elements such as phosphatidylinositol 3'-kinase (PI3K)/Akt/molecular target of rapamycin (mTOR) may lead to an enhanced activity of HIFs. Moreover, the up-regulation of HIFs in cancer cells may …


Dynein And Dynactin Leverage Their Bivalent Character To Form A High-Affinity Interaction., Amanda E Siglin, Shangjin Sun, Jeffrey K Moore, Sarah Tan, Martin Poenie, James D Lear, Tatyana Polenova, John A Cooper, John C Williams Jan 2013

Dynein And Dynactin Leverage Their Bivalent Character To Form A High-Affinity Interaction., Amanda E Siglin, Shangjin Sun, Jeffrey K Moore, Sarah Tan, Martin Poenie, James D Lear, Tatyana Polenova, John A Cooper, John C Williams

Department of Biochemistry and Molecular Biology Faculty Papers

Cytoplasmic dynein and dynactin participate in retrograde transport of organelles, checkpoint signaling and cell division. The principal subunits that mediate this interaction are the dynein intermediate chain (IC) and the dynactin p150(Glued); however, the interface and mechanism that regulates this interaction remains poorly defined. Herein, we use multiple methods to show the N-terminus of mammalian dynein IC, residues 10-44, is sufficient for binding p150(Glued). Consistent with this mapping, monoclonal antibodies that antagonize the dynein-dynactin interaction also bind to this region of the IC. Furthermore, double and triple alanine point mutations spanning residues 6 to 19 in the yeast IC homolog, …


Molecular Determinants Of Epidermal Growth Factor Binding: A Molecular Dynamics Study., Jeffrey M Sanders, Matthew E Wampole, Mathew L. Thakur, Eric Wickstrom Jan 2013

Molecular Determinants Of Epidermal Growth Factor Binding: A Molecular Dynamics Study., Jeffrey M Sanders, Matthew E Wampole, Mathew L. Thakur, Eric Wickstrom

Department of Biochemistry and Molecular Biology Faculty Papers

The epidermal growth factor receptor (EGFR) is a member of the receptor tyrosine kinase family that plays a role in multiple cellular processes. Activation of EGFR requires binding of a ligand on the extracellular domain to promote conformational changes leading to dimerization and transphosphorylation of intracellular kinase domains. Seven ligands are known to bind EGFR with affinities ranging from sub-nanomolar to near micromolar dissociation constants. In the case of EGFR, distinct conformational states assumed upon binding a ligand is thought to be a determining factor in activation of a downstream signaling network. Previous biochemical studies suggest the existence of both …


The Tip Of The Tail Needle Affects The Rate Of Dna Delivery By Bacteriophage P22., Justin C Leavitt, Lasha Gogokhia, Eddie B Gilcrease, Anshul Bhardwaj, Gino Cingolani, Sherwood R Casjens Jan 2013

The Tip Of The Tail Needle Affects The Rate Of Dna Delivery By Bacteriophage P22., Justin C Leavitt, Lasha Gogokhia, Eddie B Gilcrease, Anshul Bhardwaj, Gino Cingolani, Sherwood R Casjens

Department of Biochemistry and Molecular Biology Faculty Papers

The P22-like bacteriophages have short tails. Their virions bind to their polysaccharide receptors through six trimeric tailspike proteins that surround the tail tip. These short tails also have a trimeric needle protein that extends beyond the tailspikes from the center of the tail tip, in a position that suggests that it should make first contact with the host's outer membrane during the infection process. The base of the needle serves as a plug that keeps the DNA in the virion, but role of the needle during adsorption and DNA injection is not well understood. Among the P22-like phages are needle …


Structural Implications For Selective Targeting Of Parps., Jamin D Steffen, Md, Jonathan Brody, Md, Roger S Armen, Md, John M Pascal, Md Jan 2013

Structural Implications For Selective Targeting Of Parps., Jamin D Steffen, Md, Jonathan Brody, Md, Roger S Armen, Md, John M Pascal, Md

Department of Biochemistry and Molecular Biology Faculty Papers

Poly(ADP-ribose) polymerases (PARPs) are a family of enzymes that use NAD(+) as a substrate to synthesize polymers of ADP-ribose (PAR) as post-translational modifications of proteins. PARPs have important cellular roles that include preserving genomic integrity, telomere maintenance, transcriptional regulation, and cell fate determination. The diverse biological roles of PARPs have made them attractive therapeutic targets, which have fueled the pursuit of small molecule PARP inhibitors. The design of PARP inhibitors has matured over the past several years resulting in several lead candidates in clinical trials. PARP inhibitors are mainly used in clinical trials to treat cancer, particularly as sensitizing agents …


Biomarkers Of Disease : Concentrations In The Serum Of Women During Natural And Stimulated Ovarian Cycles And During Early Pregnancy, Melissa Stemp Jan 2013

Biomarkers Of Disease : Concentrations In The Serum Of Women During Natural And Stimulated Ovarian Cycles And During Early Pregnancy, Melissa Stemp

Theses: Doctorates and Masters

Molecular biomarkers are chemical signatures that all cell types possess. They are used in medicine to evaluate both normal biological events and pathogenic processes. A series of biomarkers associated with cancer of the breast, ovaries and other parts of the female reproductive tract and the monitoring of pregnancy were measured in disease‐free women. The biomarkers measured were prostate specific antigen (PSA), CA125, CA15‐3, CA72‐4, and pregnancy associated plasma protein‐a (PAPP‐A). The patterns of change during natural and stimulated ovarian cycles and early pregnancy were investigated to determine if these biomarkers could reflect normal events relating to ovulation and implantation/placentation. In …


Hydrodynamic Modeling Of Ns-Laser Ablation, David Autrique, Vasilios Alexiades, Harihar Khanal Jan 2013

Hydrodynamic Modeling Of Ns-Laser Ablation, David Autrique, Vasilios Alexiades, Harihar Khanal

Publications

Laser ablation is a versatile and widespread technique, applied in an increasing number of medical, industrial and analytical applications. A hydrodynamic multiphase model describing nanosecond-laser ablation (ns- LA) is outlined. The model accounts for target heating and mass removal mechanisms as well as plume expansion and plasma formation. A copper target is placed in an ambient environment consisting of helium and irradiated by a nanosecond-laser pulse. The effect of variable laser settings on the ablation process is explored in 1-D numerical simulations.


Time-Stepping For Laser Ablation, Harihar Khanal, David Autrique, Vasilios Alexiades Jan 2013

Time-Stepping For Laser Ablation, Harihar Khanal, David Autrique, Vasilios Alexiades

Publications

Nanosecond laser ablation is a popular technique, applied in many areas of science and technology such as medicine, archaeology, chemistry, environmental and materials sciences. We outline a computational model for radiative and collisional processes occurring during ns-laser ablation, and compare the performance of various low and high order time-stepping algorithms.


Targeting Astrocytes Ameliorates Neurologic Changes In A Mouse Model Of Alzheimer's Disease, Jennifer L. Furman, Diana M. Sama, John C. Gant, Tina L. Beckett, M. Paul Murphy, Adam D. Bachstetter, Linda J. Van Eldik, Christopher M. Norris Nov 2012

Targeting Astrocytes Ameliorates Neurologic Changes In A Mouse Model Of Alzheimer's Disease, Jennifer L. Furman, Diana M. Sama, John C. Gant, Tina L. Beckett, M. Paul Murphy, Adam D. Bachstetter, Linda J. Van Eldik, Christopher M. Norris

Pharmacology and Nutritional Sciences Faculty Publications

Astrocytes are the most abundant cell type in the brain and play a critical role in maintaining healthy nervous tissue. In Alzheimer's disease (AD) and most other neurodegenerative disorders, many astrocytes convert to a chronically "activated" phenotype characterized by morphologic and biochemical changes that appear to compromise protective properties and/or promote harmful neuroinflammatory processes. Activated astrocytes emerge early in the course of AD and become increasingly prominent as clinical and pathological symptoms progress, but few studies have tested the potential of astrocyte-targeted therapeutics in an intact animal model of AD. Here, we used adeno-associated virus (AAV) vectors containing the astrocyte-specific …


Muc4 And Muc1 Expression In Adenocarcinoma Of The Stomach Correlates With Vessel Invasion And Lymph Node Metastasis: An Immunohistochemical Study Of Early Gastric Cancer., Yukihiro Tamura, Michiyo Higashi, Sho Kitamoto, Seiya Yokoyama, Masahiko Osako, Michiko Horinouchi, Takeshi Shimizu, Mineo Tabata, Surinder K. Batra, Masamichi Goto, Suguru Yonezawa Nov 2012

Muc4 And Muc1 Expression In Adenocarcinoma Of The Stomach Correlates With Vessel Invasion And Lymph Node Metastasis: An Immunohistochemical Study Of Early Gastric Cancer., Yukihiro Tamura, Michiyo Higashi, Sho Kitamoto, Seiya Yokoyama, Masahiko Osako, Michiko Horinouchi, Takeshi Shimizu, Mineo Tabata, Surinder K. Batra, Masamichi Goto, Suguru Yonezawa

Journal Articles: Biochemistry & Molecular Biology

We have previously reported that MUC4 expression is a poor prognostic factor in various carcinomas. Our previous study also showed that MUC1 expression in gastric cancers, including the early and advanced stages is a poor prognostic factor. In the present study, the expression profiles of MUC4 and MUC1 were examined by immunohistochemistry (IHC) using two anti-MUC4 monoclonal antibodies (MAbs), 8G7 and 1G8, and anti-MUC1 MAb DF3 in 104 gastrectomy specimens of early gastric adenocarcinoma with submucosal invasion (pT1b2), including 197 histological subtype lesions. Before the IHC study of the human specimens, we evaluated the specificity of the two MAbs by …


Stem Cell Transplantation Increases Antioxidant Effects In Diabetic Mice, Ming Li, Luca Vanella, Yuming Zhang, Ming Shi, Takashi Takaki, Joseph I. Shapiro M.D., Susuma Ikehera Oct 2012

Stem Cell Transplantation Increases Antioxidant Effects In Diabetic Mice, Ming Li, Luca Vanella, Yuming Zhang, Ming Shi, Takashi Takaki, Joseph I. Shapiro M.D., Susuma Ikehera

Biochemistry and Microbiology

Intra bone marrow-bone marrow transplantation (IBM- BMT) + thymus transplantation (TT) has been shown to reduce the incidence of graft versus host disease (GVHD) and restore donor-derived T cell function. In addition, an increase in insulin sensitivity occurred in db/db mice after IBM-BMT+TT treatment. Heme oxygenase (HO)-1 is a stress inducible enzyme which exert antioxidant, antiapoptotic, and immune-modulating properties. We examined whether IBM-BMT+TT could modulate the expression of HO-1 in the kidneys of db/db mice. Six-week-old db/db mice with blood glucose levels higher than 250 mg/dl were treated with IBM-BMT+TT. Six weeks later, the db/db mice showed decreased body weight, …


Mucin (Muc) Expression During Pancreatic Cancer Progression In Spontaneous Mouse Model: Potential Implications For Diagnosis And Therapy., Satyanarayana Rachagani, María P Torres, Sushil Kumar, Dhanya Haridas, Michael J. Baine, Muzafar A. Macha, Sukhwinder Kaur, Moorthy P. Ponnusamy, Parama Dey, Parthasarathy Seshacharyulu, Sonny L. Johansson, Maneesh Jain, Kay-Uwe Wagner, Surinder K. Batra Oct 2012

Mucin (Muc) Expression During Pancreatic Cancer Progression In Spontaneous Mouse Model: Potential Implications For Diagnosis And Therapy., Satyanarayana Rachagani, María P Torres, Sushil Kumar, Dhanya Haridas, Michael J. Baine, Muzafar A. Macha, Sukhwinder Kaur, Moorthy P. Ponnusamy, Parama Dey, Parthasarathy Seshacharyulu, Sonny L. Johansson, Maneesh Jain, Kay-Uwe Wagner, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Pancreatic cancer (PC) is a lethal malignancy primarily driven by activated Kras mutations and characterized by the deregulation of several genes including mucins. Previous studies on mucins have identified their significant role in both benign and malignant human diseases including PC progression and metastasis. However, the initiation of MUC expression during PC remains unknown because of lack of early stage tumor tissues from PC patients.

METHODS: In the present study, we have evaluated stage specific expression patterns of mucins during mouse PC progression in (Kras(G12D);Pdx1-Cre (KC)) murine PC model from pancreatic intraepithelial neoplasia (PanIN) to pancreatic ductal adenocarcinoma (PDAC) …


Possible Steps Of Complete Disassembly Of Post-Termination Complex By Yeast Eef3 Deduced From Inhibition By Translocation Inhibitors., Shinya Kurata, Ben Shen, Jun O Liu, Nono Takeuchi, Akira Kaji, Hideko Kaji Oct 2012

Possible Steps Of Complete Disassembly Of Post-Termination Complex By Yeast Eef3 Deduced From Inhibition By Translocation Inhibitors., Shinya Kurata, Ben Shen, Jun O Liu, Nono Takeuchi, Akira Kaji, Hideko Kaji

Department of Biochemistry and Molecular Biology Faculty Papers

Ribosomes, after one round of translation, must be recycled so that the next round of translation can occur. Complete disassembly of post-termination ribosomal complex (PoTC) in yeast for the recycling consists of three reactions: release of tRNA, release of mRNA and splitting of ribosomes, catalyzed by eukaryotic elongation factor 3 (eEF3) and ATP. Here, we show that translocation inhibitors cycloheximide and lactimidomycin inhibited all three reactions. Cycloheximide is a non-competitive inhibitor of both eEF3 and ATP. The inhibition was observed regardless of the way PoTC was prepared with either release factors or puromycin. Paromomycin not only inhibited all three reactions …


Expression Of Muc17 Is Regulated By Hif1Α-Mediated Hypoxic Responses And Requires A Methylation-Free Hypoxia Responsible Element In Pancreatic Cancer., Sho Kitamoto, Seiya Yokoyama, Michiyo Higashi, Norishige Yamada, Shyuichiro Matsubara, Sonshin Takao, Surinder K. Batra, Suguru Yonezawa Sep 2012

Expression Of Muc17 Is Regulated By Hif1Α-Mediated Hypoxic Responses And Requires A Methylation-Free Hypoxia Responsible Element In Pancreatic Cancer., Sho Kitamoto, Seiya Yokoyama, Michiyo Higashi, Norishige Yamada, Shyuichiro Matsubara, Sonshin Takao, Surinder K. Batra, Suguru Yonezawa

Journal Articles: Biochemistry & Molecular Biology

MUC17 is a type 1 membrane-bound glycoprotein that is mainly expressed in the digestive tract. Recent studies have demonstrated that the aberrant overexpression of MUC17 is correlated with the malignant potential of pancreatic ductal adenocarcinomas (PDACs); however, the exact regulatory mechanism of MUC17 expression has yet to be identified. Here, we provide the first report of the MUC17 regulatory mechanism under hypoxia, an essential feature of the tumor microenvironment and a driving force of cancer progression. Our data revealed that MUC17 was significantly induced by hypoxic stimulation through a hypoxia-inducible factor 1α (HIF1α)-dependent pathway in some pancreatic cancer cells (e.g., …


Global Cellular Regulation Including Cardiac Function By Post-Translational Protein Arginylation., Hideko Kaji, Akira Kaji Sep 2012

Global Cellular Regulation Including Cardiac Function By Post-Translational Protein Arginylation., Hideko Kaji, Akira Kaji

Department of Biochemistry and Molecular Biology Faculty Papers

In this issue a very significant contribution to cardiology describing critical roles of ATE1 appears by Kurosaka et al. [1]. In view of this paper, as the discoverers of ATE1, we have been asked to contribute an article (editorial) regarding ATE1 (enzyme which transfers arginine from arginyl tRNA to protein acceptors). This short article consists of three sections: 1) a historical anecdote describing how ATE1 was discovered; 2) its possible role in aging and cellular transformation, and most importantly; 3) its role in the development and maintenance of cardiac activity. The last section has direct bearing to the Kurosaka …


Reactions Of Methyl Perfluoroalkyl Ethers With Isopropyl Alcohol: Experimental And Theoretical Studies, Howard Knachel, Vladimir Benin, Chadwick Barklay, Janine C. Birkbeck, Billy D. Faubion, William E. Moddeman Aug 2012

Reactions Of Methyl Perfluoroalkyl Ethers With Isopropyl Alcohol: Experimental And Theoretical Studies, Howard Knachel, Vladimir Benin, Chadwick Barklay, Janine C. Birkbeck, Billy D. Faubion, William E. Moddeman

Chemistry Faculty Publications

The reaction of an isomeric mixture of the methyl perfluoroalkyl ether, C4F9OCH3 (Novec-7100), in the presence of isopropyl alcohol (IPA) and/or water has been studied by measuring the rate of product formation using an ion-selective electrode (ISE) for fluoride ion, Karl Fisher coulometric titrations for water, and 1H and 19F NMR spectroscopy for product identification and rate studies. The results showed the methyl perfluoroalkyl ether to be very stable with products forming at the rate of ∼1 ppm per year at a laboratory temperature of 20 °C. Measurements over the temperature range of 6° to 100 °C were made on …


The New Role Of Proprotein Convertase Subtilisin/Kexin Type 9: A Connection Of Proprotein Convertase Subtilisin/Kexin Type 9, Apolipoprotein B, And Autophagy, Hua Sun Aug 2012

The New Role Of Proprotein Convertase Subtilisin/Kexin Type 9: A Connection Of Proprotein Convertase Subtilisin/Kexin Type 9, Apolipoprotein B, And Autophagy, Hua Sun

Dissertations and Theses (Open Access)

Plasma low-density lipoprotein (LDL) levels are positively correlated with the incidence of coronary artery disease. In the circulation, the plasma LDL clearance is mainly achieved by the uptake via LDL receptor (LDLR). Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a newly discovered gene, playing an important role in LDL metabolism. Gain-of-function mutations of PCSK9 lead to hypercholesterolemia and loss-of-function mutations of PCSK9 are associated with decrease of LDL cholesterol. The effects of PCSK9 on cholesterol levels are the consequence of a strong interaction between the catalytic domain of PCSK9 and epidermal growth factor-like repeat A (EGF-A) domain of …


Peptoid Based Slide Coatings For Disease Detection Via Elisa Microarray Analysis, Melissa Lea Hebert Aug 2012

Peptoid Based Slide Coatings For Disease Detection Via Elisa Microarray Analysis, Melissa Lea Hebert

Graduate Theses and Dissertations

Poly-N-substituted glycines (peptoids) are a very versatile family of synthetic molecules that can be customized for any number of applications. In this study, we chose to use peptoids as a foundation for sandwich ELISA microarray analysis with a long term goal of creating an early detection device for complex diseases such as cancer. The peptoids were designed to self-assemble into microspheres to be used in coatings on the surface of the microarray substrates to increase the surface area available for antibody attachment. This increased antibody density would lead to an increase in the microarray analysis sensitivity and dynamic range. Studies …


Epoxide-Mediated Cifr Repression Of Cif Gene Expression Utilizes Two Binding Sites In Pseudomonas Aeruginosa, Alicia E. Ballok, Christopher D. Bahl, Emily L. Dolben, Allia K. Lindsay, Jessica D. St. Laurent, Deborah Hogan, Dean Madden, George A. O'Toole Jul 2012

Epoxide-Mediated Cifr Repression Of Cif Gene Expression Utilizes Two Binding Sites In Pseudomonas Aeruginosa, Alicia E. Ballok, Christopher D. Bahl, Emily L. Dolben, Allia K. Lindsay, Jessica D. St. Laurent, Deborah Hogan, Dean Madden, George A. O'Toole

Dartmouth Scholarship

Pseudomonas aeruginosa secretes an epoxide hydrolase virulence factor that reduces the apical membrane expression of ABC transporters such as the cystic fibrosis transmembrane conductance regulator (CFTR). This virulence factor, named CFTR inhibitory factor (Cif), is regulated by a TetR-family, epoxide-responsive repressor known as CifR via direct binding and repression. We identified two sites of CifR binding in the intergenic space between cifR and morB, the first gene in the operon containing the cif gene. We have mapped these binding sites and found they are 27 bp in length, and they overlap the -10 and +1 sites of both the cifR …


Secreted Semaphorin 5a Suppressed Pancreatic Tumour Burden But Increased Metastasis And Endothelial Cell Proliferation., A Sadanandam, S S. Sidhu, S Wullschleger, S Singh, M L. Varney, C-S Yang, A E. Ashour, Surinder K. Batra, Rakesh Singh Jul 2012

Secreted Semaphorin 5a Suppressed Pancreatic Tumour Burden But Increased Metastasis And Endothelial Cell Proliferation., A Sadanandam, S S. Sidhu, S Wullschleger, S Singh, M L. Varney, C-S Yang, A E. Ashour, Surinder K. Batra, Rakesh Singh

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Our earlier reports demonstrated that membrane-bound semaphorin 5A (SEMA5A) is expressed in aggressive pancreatic cancer cells and tumours, and promotes tumour growth and metastasis. In this study, we examine whether (1) pancreatic cancer cells secrete SEMA5A and (2) that secreted SEMA5A modulates certain phenotypes associated with tumour progression, angiogenesis and metastasis through various other molecular factors and signalling proteins.

METHODS AND RESULTS: In this study, we show that human pancreatic cancer cell lines secrete the extracellular domain (ECD) of SEMA5A (SEMA5A-ECD) and overexpression of mouse Sema5A-ECD in Panc1 cells (not expressing SEMA5A; Panc1-Sema5A-ECD; control cells - Panc1-control) significantly increases …


Cofactor Molecules Maintain Infectious Conformation And Restrict Strain Properties In Purified Prions, Nathan R. Deleault, Daniel J. Walsh, Justin R. Piro, Fei Wang, Xinhe Wang, Jiyan Ma, Judy R. Rees, Surachai Supattapone Jun 2012

Cofactor Molecules Maintain Infectious Conformation And Restrict Strain Properties In Purified Prions, Nathan R. Deleault, Daniel J. Walsh, Justin R. Piro, Fei Wang, Xinhe Wang, Jiyan Ma, Judy R. Rees, Surachai Supattapone

Dartmouth Scholarship

No abstract provided.


Engrailed Cooperates Directly With Extradenticle And Homothorax On A Distinct Class Of Homeodomain Binding Sites To Repress Sloppy Paired., Miki Fujioka, Brian Gebelein, Zenobia C Cofer, Richard S Mann, James B Jaynes Jun 2012

Engrailed Cooperates Directly With Extradenticle And Homothorax On A Distinct Class Of Homeodomain Binding Sites To Repress Sloppy Paired., Miki Fujioka, Brian Gebelein, Zenobia C Cofer, Richard S Mann, James B Jaynes

Department of Biochemistry and Molecular Biology Faculty Papers

Even skipped (Eve) and Engrailed (En) are homeodomain-containing transcriptional repressors with similar DNA binding specificities that are sequentially expressed in Drosophila embryos. The sloppy-paired (slp) locus is a target of repression by both Eve and En. At blastoderm, Eve is expressed in 7 stripes that restrict the posterior border of slp stripes, allowing engrailed (en) gene expression to be initiated in odd-numbered parasegments. En, in turn, prevents expansion of slp stripes after Eve is turned off. Prior studies showed that the two tandem slp transcription units are regulated by cis-regulatory modules (CRMs) with activities that overlap in space and time. …


Med5(Nut1) And Med17(Srb4) Are Direct Targets Of Mediator Histone H4 Tail Interactions, Zhongle Liu, Lawrence C. Myers Jun 2012

Med5(Nut1) And Med17(Srb4) Are Direct Targets Of Mediator Histone H4 Tail Interactions, Zhongle Liu, Lawrence C. Myers

Dartmouth Scholarship

The Mediator complex transmits activation signals from DNA bound transcription factors to the core transcription machinery. In addition to its canonical role in transcriptional activation, recent studies have demonstrated that S. cerevisiae Mediator can interact directly with nucleosomes, and their histone tails. Mutations in Mediator subunits have shown that Mediator and certain chromatin structures mutually impact each other structurally and functionally in vivo. We have taken a UV photo cross-linking approach to further delineate the molecular basis of Mediator chromatin interactions and help determine whether the impact of certain Mediator mutants on chromatin is direct. Specifically, by using histone …


Perk-Dependent Repression Of Mir-106b-25 Cluster Is Required For Er Stress-Induced Apoptosis., S. Gupta, D. E. Read, A. Deepti, K. Cawley, A. Gupta, D. Oommen, T. Verfaillie, S. Matus, Mary A. Smith, Justin L. Mott, P. Agostinis, C. Hetz, A. Samali Jun 2012

Perk-Dependent Repression Of Mir-106b-25 Cluster Is Required For Er Stress-Induced Apoptosis., S. Gupta, D. E. Read, A. Deepti, K. Cawley, A. Gupta, D. Oommen, T. Verfaillie, S. Matus, Mary A. Smith, Justin L. Mott, P. Agostinis, C. Hetz, A. Samali

Journal Articles: Biochemistry & Molecular Biology

Activation of the unfolded protein response sensor PKR-like endoplasmic reticulum kinase (Perk) attenuates endoplasmic reticulum (ER) stress levels. Conversantly, if the damage is too severe and ER function cannot be restored, this signaling branch triggers apoptosis. Bcl-2 homology 3-only family member Bim is essential for ER stress-induced apoptosis. However, the regulatory mechanisms controlling Bim activation under ER stress conditions are not well understood. Here, we show that downregulation of the miR-106b-25 cluster contributes to ER stress-induced apoptosis and the upregulation of Bim. Hypericin-mediated photo-oxidative ER damage induced Perk-dependent cell death and led to a significant decrease in the levels of …


Kinetically Controlled Synthesis Of Triblock Copolymer Stabilized Gold Nanoparticles, Theodore Saleem Sabir Jun 2012

Kinetically Controlled Synthesis Of Triblock Copolymer Stabilized Gold Nanoparticles, Theodore Saleem Sabir

Loma Linda University Electronic Theses, Dissertations & Projects

Concerns for the environmental and economic impact of organic solvents in gold nanoparticle synthesis have motivated the search for more environmentally benign alternatives. One viable approach is the synthesis of AuNPs from tetrachloroauric(III) acid (HAuCl4) using triblock copolymers (TBPs). However, a major challenge of using TBPs is the heterogeneous nature of the formed nanocrystals. Establishing control over AuNP size and shape requires a detailed mechanistic understanding of precursor reduction and nanoparticle growth. By using mixtures of TBPs (L31 and F68), a more flexible method to tune AuNP size and shape is demonstrated. This is achieved by adjusting the TBP/Au(III) ratio …


Isolation Of Phosphatidylethanolamine As A Solitary Cofactor For Prion Formation In The Absence Of Nucleic Acids, Nathan R. Deleault, Justin R. Piro, Daniel J. Walsh, Fei Wang, Jiyan Ma, James C. Geoghegan, Surachai Supattapone May 2012

Isolation Of Phosphatidylethanolamine As A Solitary Cofactor For Prion Formation In The Absence Of Nucleic Acids, Nathan R. Deleault, Justin R. Piro, Daniel J. Walsh, Fei Wang, Jiyan Ma, James C. Geoghegan, Surachai Supattapone

Dartmouth Scholarship

Infectious prions containing the pathogenic conformer of the mammalian prion protein (PrP(Sc)) can be produced de novo from a mixture of the normal conformer (PrP(C)) with RNA and lipid molecules. Recent reconstitution studies indicate that nucleic acids are not required for the propagation of mouse prions in vitro, suggesting the existence of an alternative prion propagation cofactor in brain tissue. However, the identity and functional properties of this unique cofactor are unknown. Here, we show by purification and reconstitution that the molecule responsible for the nuclease-resistant cofactor activity in brain is endogenous phosphatidylethanolamine (PE). Synthetic PE alone facilitates conversion of …


Scavenger Receptor Cd36 Expression Contributes To Adipose Tissue Inflammation And Cell Death In Diet-Induced Obesity, Lei Cai, Zhen Wang, Ailing Ji, Jason M. Meyer, Deneys R. Van Der Westhuyzen May 2012

Scavenger Receptor Cd36 Expression Contributes To Adipose Tissue Inflammation And Cell Death In Diet-Induced Obesity, Lei Cai, Zhen Wang, Ailing Ji, Jason M. Meyer, Deneys R. Van Der Westhuyzen

Internal Medicine Faculty Publications

OBJECTIVE: The enlarged adipose tissue in obesity is characterized by inflammation, including the recruitment and infiltration of macrophages and lymphocytes. The objective of this study was to investigate the role of the scavenger receptor CD36 in high fat diet-induced obesity and adipose tissue inflammation and cell death.

EXPERIMENTAL APPROACH: Obesity and adipose tissue inflammation was compared in CD36 deficient (CD36 KO) mice and wild type (WT) mice fed a high fat diet (60% kcal fat) for 16 weeks and the inflammatory response was studied in primary adipocytes and macrophages isolated from CD36 KO and WT mice.

RESULTS: Compared to WT …


Reduction Of Na/K-Atpase Potentiates Marinobufagenin-Induced Cardiac Dysfunction And Myocyte Apoptosis, Changxuan Liu, Yan Bai, Yiliang Chen, Yu Wang, Yoann Sottejeau, Lijun Liu, Xiaomei Li, Jerry B. Lingrel, Deepak Malhorta, Christopher Cooper, Joseph I. Shapiro M.D., Zi-Jian Xie, Jiang Tian May 2012

Reduction Of Na/K-Atpase Potentiates Marinobufagenin-Induced Cardiac Dysfunction And Myocyte Apoptosis, Changxuan Liu, Yan Bai, Yiliang Chen, Yu Wang, Yoann Sottejeau, Lijun Liu, Xiaomei Li, Jerry B. Lingrel, Deepak Malhorta, Christopher Cooper, Joseph I. Shapiro M.D., Zi-Jian Xie, Jiang Tian

Biochemistry and Microbiology

Background: Na/K-ATPase decrease has been reported in patients with heart failure and is related to cardiac dysfunction.

Results: Reducing Na/K-ATPase activates caspase 9 and induces cardiac dilation when treated with marinobufagenin.

Conclusion: Reduction of Na/K-ATPase potentiates marinobufagenin-induced cardiac myocyte apoptosis.

Significance: Decreased Na/K-ATPase content together with increased cardiotonic steroids levels is a novel mechanism that may account for cardiac dysfunction.


Effects Of Burn Injury On Biological Ethanol And Ethyl Glucuronide Concentrations, Trista Haupt Wright May 2012

Effects Of Burn Injury On Biological Ethanol And Ethyl Glucuronide Concentrations, Trista Haupt Wright

Electronic Theses and Dissertations

Alcohol is the most abused drug in the United States and most frequently performed assay in forensic laboratories. Alcohol is routinely present in biological specimens from fatal residential fires and forensic toxicologists must interpret if these individuals are impaired by determination of their blood alcohol concentrations on post-incineration blood collected at autopsy. There is no known data available to confirm or refute blood alcohol concentrations and impairment in fire-related deaths. Ethyl glucuronide (EtG), a non-volatile minor ethanol metabolite, may provide a better biomarker for ethanol consumption prior to burn injury. The literature does not address the possibility that ethanol or …