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Articles 931 - 960 of 1227

Full-Text Articles in Biochemistry

Biomimetic Precipitation Of Uniaxially Grown Calcium Phosphate Crystals From Full-Length Human Amelogenin Sols, Vuk Uskoković, Wu Li, Stefan Habelitz Jan 2011

Biomimetic Precipitation Of Uniaxially Grown Calcium Phosphate Crystals From Full-Length Human Amelogenin Sols, Vuk Uskoković, Wu Li, Stefan Habelitz

Pharmacy Faculty Articles and Research

Human dental enamel forms over a period of 2 – 4 years by substituting the enamel matrix, a protein gel mostly composed of a single protein, amelogenin with fibrous apatite nanocrystals. Self-assembly of a dense amelogenin matrix is presumed to direct the growth of apatite fibers and their organization into bundles that eventually comprise the mature enamel, the hardest tissue in the mammalian body. This work aims to establish the physicochemical and biochemical conditions for the synthesis of fibrous apatite crystals under the control of a recombinant fulllength human amelogenin matrix in combination with a programmable titration system. The growth …


Lysophosphatidic Acid Production And Signaling In Platelets, Zachary Bennett Fulkerson Jan 2011

Lysophosphatidic Acid Production And Signaling In Platelets, Zachary Bennett Fulkerson

Theses and Dissertations--Physiology

Lysophosphatidic acid (LPA) belongs to a class of extracellular lipid signaling molecules. In the vasculature, LPA may regulate platelet activation and modulate endothelial and smooth muscle cell function. LPA has therefore been proposed as a mediator of cardiovascular disease.

The bulk of circulating LPA is produced from plasma lysophosphatidylcholine (LPC) by autotaxin (ATX), a secreted lysophospholipase D (lysoPLD). Early studies suggest that some of the production of circulating LPA is platelet-dependent. ATX possesses an N-terminal somatomedin B-like domain suggesting the hypothesis that ATX interacts with platelet integrins which may localize ATX to substrate in the membrane and/or alter the catalytic …


Carbon Monoxide And Nitric Oxide Induced-Heme-Based Modification Of Alpha-2-Antiplasmin And Plasmin Activity, Matthew R. Arkebauer Jan 2011

Carbon Monoxide And Nitric Oxide Induced-Heme-Based Modification Of Alpha-2-Antiplasmin And Plasmin Activity, Matthew R. Arkebauer

PCOM Biomedical Studies Student Scholarship

Objectives: Carbon monoxide (CO) derived from cigarette smoke or released from carbon monoxide releasing-molecule 2 (CORM-2), diminishes fibrinolysis. The primary purpose of this study was to determine if CO diminished fibrinolysis by means of enhancing α2-antiplasmin via an alleged heme group. Methods: Plasma, isolated α2-antiplasmin and isolated plasmin were exposed to CO released from CORM-2 (tricarbonyldichlororuthenium (II) dimer) and nitric oxide (NO) via a NO donor to induce carboxyheme and metheme states. Exposed, isolated enzymes were placed in either α2-antiplasmin deficient or normal plasma. Effects of CO and NO on tissue-type plasminogen activator initiated fibrinolysis were determined by thrombelastography. Liquid …


The Role Of Endothelial Nitric Oxide Synthase (Enos) Uncoupling On Leukocyte-Endothelial Interactions In Rat Mesenteric Postcapillary Venules, Maria Kern Jan 2011

The Role Of Endothelial Nitric Oxide Synthase (Enos) Uncoupling On Leukocyte-Endothelial Interactions In Rat Mesenteric Postcapillary Venules, Maria Kern

PCOM Biomedical Studies Student Scholarship

Endothelial derived nitric oxide (NO) is essential in the regulation of blood pressure and attenuates leukocyte-endothelial interactions associated with vascular injury. However, when endothelial-derived NO is decreased, endothelial dysfunction results and promotes inflammation characterized by increased leukocyte-endothelial interactions. Under normal conditions, eNOS produces NO in the presence of an essential cofactor, tetrahydrobiopetrin (BH4) by facilitating the reduction of molecular oxygen to L-arginine oxidation and generation of L-citrulline. Whereas uncoupled eNOS refers to the electron transfer that becomes uncoupled to L-arginine oxidation and therefore superoxide (SO) is generated when the dihydrobiopetrin (BH2) to BH4 ratio is increased. SO is subsequently converted …


The Effects Of Protein Kinase C Inhibitors On Blood Nitric Oxide And Hydrogen Peroxide Release In Ischemia And Reperfusion Injury, Kyle D. Bartol Jan 2011

The Effects Of Protein Kinase C Inhibitors On Blood Nitric Oxide And Hydrogen Peroxide Release In Ischemia And Reperfusion Injury, Kyle D. Bartol

PCOM Biomedical Studies Student Scholarship

Vascular endothelial dysfunction is a key component initiating oxidative stress in ischemia/reperfusion (I/R). Endothelial dysfunction is characterized by an increase in hydrogen peroxide (H2O2) and a decrease in the bioavailability of nitric oxide (NO). Previous studies using protein kinase C (PKC) inhibitor Gö 6983 or PKC Beta (β) II inhibitor improved cardiac function in myocardial I/R, decreased leukocyte-endothelial interactions and leukocyte superoxide (SO) release and increased endothelial-derived NO release in vitro. This study examined the effects of Gö 6983 or PKC β II inhibitor on realtime H2O2 and NO release in femoral vein I/R in vivo. NO or H2O2 microsensors …


Mechanisms Of Decreased Cholesterol Absorption Mediated By Phytosterols In The Intestinal Lumen, Andrew W. Brown Jan 2011

Mechanisms Of Decreased Cholesterol Absorption Mediated By Phytosterols In The Intestinal Lumen, Andrew W. Brown

Department of Nutrition and Health Sciences: Dissertations, Theses, and Student Research

Phytosterols and their fatty acyl esters have been known for decades to lower LDL cholesterol, making them powerful nutraceuticals in lowering cardiovascular disease risk. The mechanisms by which phytosterols lower cholesterol, though, have been incompletely characterized. Three studies were executed to examine three aspects of cholesterol and phytosterol interactions in the intestinal lumen. In the first study, the ability of pancreatic cholesterol esterase to hydrolyze phytosterol esters was examined. Pancreatic cholesterol esterase hydrolyzed phytosterol esters, but the rate of hydrolysis proved sensitive to the structures of both the sterol and ester components. In the second study, cholesterol micellarization was challenged …


Infection With Chlamydia Pneumoniae In Neuronal Cells Alters The Expression Of Genes Involved In Apoptosis And Autophagy Pathways, Annette K. Slutter Jan 2011

Infection With Chlamydia Pneumoniae In Neuronal Cells Alters The Expression Of Genes Involved In Apoptosis And Autophagy Pathways, Annette K. Slutter

PCOM Biomedical Studies Student Scholarship

Dysfunctions in cellular mechanisms such as apoptosis and autophagy have been implicated in the neurodegeneration associated with Alzheimer’s disease (AD). Autophagy in AD pathogenesis has been linked to the endosomal-lysosomal system, which has been shown to play a role in amyloid processing. Studies have suggested that apoptosis may contribute to the neuronal cell loss observed in AD; however, there is no evidence of the apoptotic process leading to terminal completion. Aβ1-42 has been shown to induce apoptosis in neurons and may be an initiating factor in AD. Our previous studies demonstrated that neurons infected with C. pneumoniae are resistant to …


Synthesis, Biochemical And Molecular Modelling Studies Of Antiproliferative Azetidinones Causing Microtubule Disruption And Mitotic Catastrophe, Niamh O'Boyle, Miriam Carr, Lisa M. Greene, Niall O. Keely, Andrew Js Knox, Thomas Mccabe, David G. Lloyd, Daniela M. Zisterer, Mary J. Meegan Jan 2011

Synthesis, Biochemical And Molecular Modelling Studies Of Antiproliferative Azetidinones Causing Microtubule Disruption And Mitotic Catastrophe, Niamh O'Boyle, Miriam Carr, Lisa M. Greene, Niall O. Keely, Andrew Js Knox, Thomas Mccabe, David G. Lloyd, Daniela M. Zisterer, Mary J. Meegan

Articles

The structure-activity relationships of antiproliferative β-lactams, focusing on modifications at the 4-position of the β-lactam ring, is described. Synthesis of this series of compounds was achieved utilizing the Staudinger and Reformatsky reactions. The antiproliferative activity was assessed in MCF-7 cells, where the 4-(4-ethoxy)phenyl substituted compound 26 displayed the most potent activity with an IC50 value of 0.22 μM. The mechanism of action was demonstrated to be by inhibition of tubulin. Cell exposure to combretastatin A-4 and 26 led to arrest of MCF-7 cells in the G2/M phase of the cell cycle and induction of apoptosis. Additionally, mitotic catastrophe for …


Lead Identification Of Β-Lactam And Related Imine Inhibitors Of The Molecular Caperone Heat Shock Protein 90, Niamh O'Boyle, Andrew Js Knox, Trevor P. Price, D. Clive Williams, Daniela M. Zisterer, David G. Lloyd, Mary J. Meegan Jan 2011

Lead Identification Of Β-Lactam And Related Imine Inhibitors Of The Molecular Caperone Heat Shock Protein 90, Niamh O'Boyle, Andrew Js Knox, Trevor P. Price, D. Clive Williams, Daniela M. Zisterer, David G. Lloyd, Mary J. Meegan

Articles

Heat shock protein 90 is an emerging target for oncology therapeutics. Inhibitors of this molecular chaperone, which is responsible for the maintenance of a number of oncogenic proteins, have shown promise in clinical trials and represent a new and exciting area in the treatment of cancer. Heat shock protein 90 inhibitors have huge structural diversity, and here we present the identification of inhibitors based on β-lactam and imine templates. β-Lactam 5 and imines 12 and 18 exhibit binding to heat shock protein 90-α with IC50 values of 5.6 μM, 14.5 μM and 22.1 μM respectively. The binding affinity displayed …


Enhancement Of Reactive Oxygen Species Production And Chlamydial Infection By The Mitochondrial Nod-Like Family Member Nlrx1, Ali A. Abdul-Sater, Najwene Saïd-Sadier, Verissa M. Lam, Bhavni Singh, Matthew A. Pettengill, Fraser Soares, Ivan Tattoli, Simone Lipinski, Stephen E. Girardin, Philip Rosenstiel, David M. Ojcius Dec 2010

Enhancement Of Reactive Oxygen Species Production And Chlamydial Infection By The Mitochondrial Nod-Like Family Member Nlrx1, Ali A. Abdul-Sater, Najwene Saïd-Sadier, Verissa M. Lam, Bhavni Singh, Matthew A. Pettengill, Fraser Soares, Ivan Tattoli, Simone Lipinski, Stephen E. Girardin, Philip Rosenstiel, David M. Ojcius

All Dugoni School of Dentistry Faculty Articles

Chlamydia trachomatis infections cause severe and irreversible damage that can lead to infertility and blindness in both males and females. Following infection of epithelial cells, Chlamydia induces production of reactive oxygen species (ROS). Unconventionally, Chlamydiae use ROS to their advantage by activating caspase-1, which contributes to chlamydial growth. NLRX1, a member of the Nod-like receptor family that translocates to the mitochondria, can augment ROS production from the mitochondria following Shigella flexneri infections. However, in general, ROS can also be produced by membrane-bound NADPH oxidases. Given the importance of ROS-induced caspase-1 activation in growth of the chlamydial vacuole, we investigated the …


Mechanism Of N-Methylation By The Trna M1g37 Methyltransferase Trm5., Thomas Christian, Georges Lahoud, Cuiping Liu, Katherine Hoffmann, John J Perona, Ya-Ming Hou Dec 2010

Mechanism Of N-Methylation By The Trna M1g37 Methyltransferase Trm5., Thomas Christian, Georges Lahoud, Cuiping Liu, Katherine Hoffmann, John J Perona, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

Trm5 is a eukaryal and archaeal tRNA methyltransferase that catalyzes methyl transfer from S-adenosylmethionine (AdoMet) to the N(1) position of G37 directly 3' to the anticodon. While the biological role of m(1)G37 in enhancing translational fidelity is well established, the catalytic mechanism of Trm5 has remained obscure. To address the mechanism of Trm5 and more broadly the mechanism of N-methylation to nucleobases, we examined the pH-activity profile of an archaeal Trm5 enzyme, and performed structure-guided mutational analysis. The data reveal a marked dependence of enzyme-catalyzed methyl transfer on hydrogen ion equilibria: the single-turnover rate constant for methylation increases by one …


Development Of Novel Biomarkers In Cancer: Detection Of Circulating Mir-141 As A Potential Prognostic Marker For Prostate Cancer, Jason Cadaoas Gonzales Dec 2010

Development Of Novel Biomarkers In Cancer: Detection Of Circulating Mir-141 As A Potential Prognostic Marker For Prostate Cancer, Jason Cadaoas Gonzales

UNLV Theses, Dissertations, Professional Papers, and Capstones

Prostate cancer (CAP) is the most common epithelial malignancy and the second leading cause of cancer deaths in American men. The identification of predictive and prognostic biomarkers in CAP patients is critical for improving clinical outcomes. Although the measurement of prostate-specific antigen (PSA) and radiographic studies are clinically approved to predict response to therapy, these tests can oftentimes prove to be inadequate in certain patients. Thus, it is important to discover new biomarkers to improve chances of survivability. We and others have shown that longitudinal measurements of circulating tumor cells (CTC) and lactate dehydrogenase (LDH) may aid in predicting response …


An Archaeal Trna-Synthetase Complex That Enhances Aminoacylation Under Extreme Conditions, Vlatka Godinic-Mikulcic, Jelena Jaric, Corinne D. Hausmann, Michael Ibba, Ivana Weygand-Durasevic Nov 2010

An Archaeal Trna-Synthetase Complex That Enhances Aminoacylation Under Extreme Conditions, Vlatka Godinic-Mikulcic, Jelena Jaric, Corinne D. Hausmann, Michael Ibba, Ivana Weygand-Durasevic

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Aminoacyl-tRNA synthetases (aaRSs) play an integral role in protein synthesis, functioning to attach the correct amino acid with its cognate tRNA molecule. AaRSs are known to associate into higher-order multi-aminoacyl-tRNA synthetase complexes (MSC) involved in archaeal and eukaryotic translation, although the precise biological role remains largely unknown. To gain further insights into archaeal MSCs, possible protein-protein interactions with the atypical Methanothermobacter thermautotrophicus seryl-tRNA synthetase (MtSerRS) were investigated. Yeast two-hybrid analysis revealed arginyl-tRNA synthetase (MtArgRS) as an interacting partner of MtSerRS. Surface plasmon resonance confirmed stable complex formation, with a dissociation constant (KD) of 250 nm. Formation of the MtSerRS·MtArgRS complex …


Studies On Antidyslipidemic Effects Of Morinda Citrifolia (Noni) Fruit, Leaves And Root Extracts., Saf-Ur Rehman Mandukhail, Nauman Aziz, Anwar Gilani Aug 2010

Studies On Antidyslipidemic Effects Of Morinda Citrifolia (Noni) Fruit, Leaves And Root Extracts., Saf-Ur Rehman Mandukhail, Nauman Aziz, Anwar Gilani

Department of Biological & Biomedical Sciences

Background: The objective of present study was to provide the pharmacological basis for the medicinal use of Morinda citrifolia Linn in dyslipidemia using the aqueous-ethanolic extracts of its fruits (Mc.Cr.F), leaves (Mc.Cr.L) and roots (Mc.Cr.R). Results: Mc.Cr.F, Mc.Cr.L and Mc.Cr.R showed antidyslipidemic effects in both triton (WR-1339) and high fat diet-induced dyslipidemic rat models to variable extents. All three extracts caused reduction in total cholesterol and triglyceride levels in triton-induced dyslipidemia. In high fat diet-induced dyslipidemia all these extracts caused significant reduction in total cholesterol, triglyceride, low density lipoprotein-cholesterol (LDL-C), atherogenic index and TC/HDL ratio. Mc.Cr.R extract also caused increase …


Mechanisms Of Oxidant Generation By Catalase, Diane E. Heck, Michael Shakarjian, Hong-Duck Kim, Jeffrey Laskin, Anna M. Vetrano Aug 2010

Mechanisms Of Oxidant Generation By Catalase, Diane E. Heck, Michael Shakarjian, Hong-Duck Kim, Jeffrey Laskin, Anna M. Vetrano

NYMC Faculty Publications

The enzyme catalase converts solar radiation into reactive oxidant species (ROS). In this study, we report that several bacterial catalases (hydroperoxidases, HP), including Escherichia coli HP-I and HP-II also generate reactive oxidants in response to ultraviolet B light (UVB). HP-I and HP-II are identical except for the presence of NADPH. We found that only one of the catalases, HPI, produces oxidants in response to UVB light, indicating a potential role for the nucleotide in ROS production. This prompts us to speculate that NADPH may act as a cofactor regulating ROS generation by mammalian catalases. Structural analysis of the NADPH domains …


The Marine Sponge Metabolite Mycothiazole: A Novel Prototype Mitochondrial Complex I Inhibitor., J Brian Morgan, Fakhri Mahdi, Yang Liu, Veena Coothankandaswamy, Mika B. Jekabsons, Tyler A. Johnson, Koneni V. Sashidhara, Phillip Crews, Dale G. Nagle, Yu-Dong Zhou Aug 2010

The Marine Sponge Metabolite Mycothiazole: A Novel Prototype Mitochondrial Complex I Inhibitor., J Brian Morgan, Fakhri Mahdi, Yang Liu, Veena Coothankandaswamy, Mika B. Jekabsons, Tyler A. Johnson, Koneni V. Sashidhara, Phillip Crews, Dale G. Nagle, Yu-Dong Zhou

Natural Sciences and Mathematics | Faculty Scholarship

A natural product chemistry-based approach was applied to discover small-molecule inhibitors of hypoxia-inducible factor-1 (HIF-1). A Petrosaspongia mycofijiensis marine sponge extract yielded mycothiazole (1), a solid tumor selective compound with no known mechanism for its cell line-dependent cytotoxic activity. Compound 1 inhibited hypoxic HIF-1 signaling in tumor cells (IC(50) 1nM) that correlated with the suppression of hypoxia-stimulated tumor angiogenesis in vitro. However, 1 exhibited pronounced neurotoxicity in vitro. Mechanistic studies revealed that 1 selectively suppresses mitochondrial respiration at complex I (NADH-ubiquinone oxidoreductase). Unlike rotenone, MPP(+), annonaceous acetogenins, piericidin A, and other complex I inhibitors, mycothiazole is a mixed polyketide/peptide-derived compound …


Poxa, Yjek And Elongation Factor P Coordinately Modulate Virulence And Drug Resistance In Salmonella Enterica, William Wiley Navarre, Shicong Zou, Hervé Roy, Jinglin Lucy Xie, Alexei Savchenko, Alexander Singer, Elena Edvokimova, Lynne R. Prost, Runjun Kumar, Michael Ibba, Ferric C. Fang Jul 2010

Poxa, Yjek And Elongation Factor P Coordinately Modulate Virulence And Drug Resistance In Salmonella Enterica, William Wiley Navarre, Shicong Zou, Hervé Roy, Jinglin Lucy Xie, Alexei Savchenko, Alexander Singer, Elena Edvokimova, Lynne R. Prost, Runjun Kumar, Michael Ibba, Ferric C. Fang

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

We report an interaction between poxA, encoding a paralog of lysyl tRNA-synthetase, and the closely linked yjeK gene, encoding a putative 2,3-β-lysine aminomutase, that is critical for virulence and stress resistance in Salmonella enterica. Salmonella poxA and yjeK mutants share extensive phenotypic pleiotropy, including attenuated virulence in mice, an increased ability to respire under nutrient-limiting conditions, hypersusceptibility to a variety of diverse growth inhibitors, and altered expression of multiple proteins, including several encoded on the SPI-1 pathogenicity island. PoxA mediates posttranslational modification of bacterial elongation factor P (EF-P), analogous to the modification of the eukaryotic EF-P homolog, eIF5A, with …


2,4,6-Triphenyl­Aniline, Onome Ugono, Stephanie Cowin, Alicia Beatty Jul 2010

2,4,6-Triphenyl­Aniline, Onome Ugono, Stephanie Cowin, Alicia Beatty

Chemistry & Biochemistry Faculty Works

Individual mol­ecules of the title compound, C24H19N, do not participate in hydrogen-bonding inter­actions due to the steric bulk of the phenyl rings ortho to the amine. The dihedral angles between the central ring and the pendant rings are 68.26 (10), 55.28 (10) and 30.61 (11)°.


Redox Status Affects The Catalytic Activity Of Glutamyl-Trna Synthetase, Assaf Katz, Ranat Banerjee, Merly De Armas, Michael Ibba, Omar Orellana Jun 2010

Redox Status Affects The Catalytic Activity Of Glutamyl-Trna Synthetase, Assaf Katz, Ranat Banerjee, Merly De Armas, Michael Ibba, Omar Orellana

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Glutamyl-tRNA synthetases (GluRS) provide Glu-tRNA for different processes including protein synthesis, glutamine transamidation and tetrapyrrole biosynthesis. Many organisms contain multiple GluRSs, but whether these duplications solely broaden tRNA specificity or also play additional roles in tetrapyrrole biosynthesis is not known. Previous studies have shown that GluRS1, one of two GluRSs from the extremophile Acidithiobacillus ferrooxidans, is inactivated when intracellular heme is elevated suggesting a specific role for GluRS1 in the regulation of tetrapyrrole biosynthesis. We now show that, in vitro, GluRS1 activity is reversibly inactivated upon oxidation by hemin and hydrogen peroxide. The targets for oxidation-based inhibition were …


Ricin B Chain-Insulin Fusion Protein Immunomodulation Of Type 1 Diabetes, James Edward Carter Iii Jun 2010

Ricin B Chain-Insulin Fusion Protein Immunomodulation Of Type 1 Diabetes, James Edward Carter Iii

Loma Linda University Electronic Theses, Dissertations & Projects

Type 1 diabetes mellitus (T1D) is a debilitating chronic inflammatory disease of the insulin-producing pancreatic islet β-cells that results from a combination of genetic and environmental factors. Attempts to suppress Th1-mediated autoimmune diseases such as T1D by mucosal delivery of autoantigens for immunotolerization have yielded only partial success. Attainment of satisfactory levels of sustained immunological tolerance remains to be accomplished. To restore self-tolerance requires delivery of sufficient amounts of autoantigen to stimulate regulatory T helper cells that function to survey the gut and induce tolerance to consumed antigens such as food. Oral delivery of autoantigens has previously been shown to …


Protein Evolution Via Amino Acid And Codon Elimination, Lise Goltermann, Marie Sofie Yoo Larsen, Ranat Banerjee, Andreas C. Joerger, Michael Ibba, Thomas Bentin Apr 2010

Protein Evolution Via Amino Acid And Codon Elimination, Lise Goltermann, Marie Sofie Yoo Larsen, Ranat Banerjee, Andreas C. Joerger, Michael Ibba, Thomas Bentin

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Background
Global residue-specific amino acid mutagenesis can provide important biological insight and generate proteins with altered properties, but at the risk of protein misfolding. Further, targeted libraries are usually restricted to a handful of amino acids because there is an exponential correlation between the number of residues randomized and the size of the resulting ensemble. Using GFP as the model protein, we present a strategy, termed protein evolution via amino acid and codon elimination, through which simplified, native-like polypeptides encoded by a reduced genetic code were obtained via screening of reduced-size ensembles.

Methodology/Principal Findings
The strategy involves combining a sequential …


How The Sequence Of A Gene Can Tune Its Translation, Kurt Fredrick, Michael Ibba Apr 2010

How The Sequence Of A Gene Can Tune Its Translation, Kurt Fredrick, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Sixty-one codons specify 20 amino acids, offering cells many options for encoding a polypeptide sequence. Two new studies (Cannarrozzi et al., 2010, Tuller et al., 2010) now foster the idea that patterns of codon usage can control ribosome speed, fine-tuning translation to increase the efficiency of protein synthesis.


Aspergillus Fumigatus Stimulates The Nlrp3 Inflammasome Through A Pathway Requiring Ros Production And The Syk Tyrosine Kinase, Najwane Saïd-Sadier, Eduardo V. Padilla, Gordon Langsley, David M. Ojcius Apr 2010

Aspergillus Fumigatus Stimulates The Nlrp3 Inflammasome Through A Pathway Requiring Ros Production And The Syk Tyrosine Kinase, Najwane Saïd-Sadier, Eduardo V. Padilla, Gordon Langsley, David M. Ojcius

All Dugoni School of Dentistry Faculty Articles

Invasive aspergillosis (IA) is a life-threatening disease that occurs in immunodepressed patients when infected with Aspergillus fumigatus. This fungus is the second most-common causative agent of fungal disease after Candida albicans. Nevertheless, much remains to be learned about the mechanisms by which A. fulmigatus activates the innate immune system. We investigated the inflammatory response to conidia and hyphae of A. fumigatus and specifically, their capacity to trigger activation of an inflammasome. Our results show that in contrast to conidia, hyphal fragments induce NLRP3 inflammasome assembly, caspase-1 activation and IL-1β release from a human monocyte cell line. The ability of Aspergillus …


Maternal Consumption Of Canola Oil Suppressed Mammary Gland Tumorigenesis In C3(1) Tag Mice Offspring, Gabriela Ion, Juliana A. Akinsete, W. Elaine Hardman Mar 2010

Maternal Consumption Of Canola Oil Suppressed Mammary Gland Tumorigenesis In C3(1) Tag Mice Offspring, Gabriela Ion, Juliana A. Akinsete, W. Elaine Hardman

Biochemistry and Microbiology

Background: Maternal consumption of a diet high in omega 6 polyunsaturated fats (n-6 PUFA) has been shown to increase risk whereas a diet high in omega 3 polyunsaturated fats (n-3 PUFA) from fish oil has been shown to decrease risk for mammary gland cancer in female offspring of rats. The aim of this study was to determine whether increasing n-3 PUFA and reducing n-6 PUFA by using canola oil instead of corn oil in the maternal diet might reduce the risk for breast cancer in female offspring.

Methods: Female SV 129 mice were divided into two groups and placed on …


Development And Validation Of A Rapid Method For The Detection Of Latrunculol A In Plasma., Jiajiu Shaw, Frederick A. Valeriote, Joseph Media, Tyler A. Johnson, Taro Amagata, Karen Tenney, Phillip Crews Mar 2010

Development And Validation Of A Rapid Method For The Detection Of Latrunculol A In Plasma., Jiajiu Shaw, Frederick A. Valeriote, Joseph Media, Tyler A. Johnson, Taro Amagata, Karen Tenney, Phillip Crews

Natural Sciences and Mathematics | Faculty Scholarship

Latrunculol A is a recently discovered 6,7-dihydroxy analog of the potent actin inhibitor latrunculin A. Latrunculol A has exhibited greater cytotoxicity than latrunculin A against both murine and human colon tumor cell lines in vitro. Currently, there are no reports regarding the bioavailability of latrunculol A in vivo. This study was undertaken as a prelude to pharmacokinetic assessments and it is the first work where bioavailability of latrunculol A was studied. In the present work, a simple plasma preparation and a rapid HPLC method have been developed. Mouse plasma containing latrunculol A was first treated by acetonitrile and then centrifuged …


Antispasmodic And Vasodilator Activities Of Morinda Citrifolia Root Extract Are Mediated Through Blockade Of Voltage Dependent Calcium Channels, Anwarul Hassan Gilani, Saf-Ur-Rehman Mandukhail, Javeid Iqbal, Masoom Yasinzai, Nauman Aziz, Aslam Khan, Najeeb-Ur-Rehman Jan 2010

Antispasmodic And Vasodilator Activities Of Morinda Citrifolia Root Extract Are Mediated Through Blockade Of Voltage Dependent Calcium Channels, Anwarul Hassan Gilani, Saf-Ur-Rehman Mandukhail, Javeid Iqbal, Masoom Yasinzai, Nauman Aziz, Aslam Khan, Najeeb-Ur-Rehman

Department of Biological & Biomedical Sciences

Background: Morinda citrifolia (Noni) is an edible plant with wide range of medicinal uses. It occurs exclusively in tropical climate zone from India through Southeast Asia and Australia to Eastern Polynesia and Hawaii. The objective of this study was to explore the possible mode(s) of action for its antispasmodic, vasodilator and cardio-suppressant effects to rationalize its medicinal use in gut and cardiovascular disorders. Methods: Isolated tissue preparations such as, rabbit jejunum, rat and rabbit aorta and guinea pig atria were used to test the antispasmodic and cardiovascular relaxant effects and the possible mode of action(s) of the 70% aqueous-ethanolic extract …


Spermine Oxidase (Smo) Activity In Breast Tumor Tissues And Biochemical Analysis Of The Anticancer Spermine Analogues Benspm And Cpenspm, Manuela Cervelli, Gabriella Bellavia, Emiliano Fratini, Roberto Amendola, Fabio Polticelli, Marco Barba, Rodolfo Federico, Fabrizio Signore, Giacomo Gucciardo, Rosalba Grillo, Patrick M. Woster, Robert A. Casero Jr, Paolo Mariottini Jan 2010

Spermine Oxidase (Smo) Activity In Breast Tumor Tissues And Biochemical Analysis Of The Anticancer Spermine Analogues Benspm And Cpenspm, Manuela Cervelli, Gabriella Bellavia, Emiliano Fratini, Roberto Amendola, Fabio Polticelli, Marco Barba, Rodolfo Federico, Fabrizio Signore, Giacomo Gucciardo, Rosalba Grillo, Patrick M. Woster, Robert A. Casero Jr, Paolo Mariottini

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Polyamine metabolism has a critical role in cell death and proliferation representing a potential target for intervention in breast cancer (BC). This study investigates the expression of spermine oxidase (SMO) and its prognostic significance in BC. Biochemical analysis of Spm analogues BENSpm and CPENSpm, utilized in anticancer therapy, was also carried out to test their property in silico and in vitro on the recombinant SMO enzyme.

Methods

BC tissue samples were analyzed for SMO transcript level and SMO activity. Student's t test was applied to evaluate the significance of the differences in value observed in T and NT …


Genetic Connections Between Neurological Disorders And Cholesterol Metabolism, Ingemar Bjorkhem, Valerio Leoni, Steve Meaney Jan 2010

Genetic Connections Between Neurological Disorders And Cholesterol Metabolism, Ingemar Bjorkhem, Valerio Leoni, Steve Meaney

Articles

Cholesterol is an essential component of both the peripheral and central nervous systems of mammals. Over the last decade, evidence has accumulated that disturbances in cholesterol metabolism are associated with the development of various neurological conditions. In addition to genetically defined defects in cholesterol synthesis, which will be covered in another review in this Thematic Series, defects in cholesterol metabolism (cerebrotendinous xanthomatosis) and intracellular transport (Niemann Pick Syndrome) lead to neurological disease. A subform of hereditary spastic paresis (type SPG5) and Huntington's disease are neurological diseases with mutations in genes that are of importance for cholesterol metabolism. Neurodegeneration is generally …


Prospects And Pits On The Path Of Biomimetics: The Case Of Tooth Enamel, Vuk Uskoković Jan 2010

Prospects And Pits On The Path Of Biomimetics: The Case Of Tooth Enamel, Vuk Uskoković

Pharmacy Faculty Articles and Research

This review presents a discourse on challenges in understanding and imitating the process of amelogenesis in vitro on the molecular scale. In light of the analysis of imitation of the growth of dental enamel, it also impends on the prospects and potential drawbacks of the biomimetic approach in general. As the formation of enamel proceeds with the protein matrix guiding the crystal growth, while at the same time conducting its own degradation and removal, it is argued that three aspects of amelogenesis need to be induced in parallel: a) crystal growth; b) protein assembly; c) proteolytic degradation. A particular emphasis …


Ligand-Protein Interactions Of Inhibitors With Dengue Virus Type 2 Serine Protease : A Structural Study., Rozana Othman Jan 2010

Ligand-Protein Interactions Of Inhibitors With Dengue Virus Type 2 Serine Protease : A Structural Study., Rozana Othman

Student Works (2010-2019)

Dengue is a serious infectious disease that is endemic in over 100 countries. There has been an estimate of 50 million infection per year globally, with more than 2.5 billion people are at risk for epidemic transmission. Two principal illnesses associated with dengue are Dengue Fever (DF) and Dengue Haemorrhagic Fever (DHF). To date, there is no licensed vaccine or therapeutic drug available for these illnesses, although there have been reports of some vaccine candidates in clinical trials. Treatments have only been supportive thus far. This thesis describes part of our ongoing effort to search for a lead therapeutic agent …