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Rat Brain Pro-Oxidant Effects Of Peripherally Administered 5 Nm Ceria 30 Days After Exposure, Sarita S. Hardas, Rukhsana Sultana, Govind Warrier, Mo Dan, Rebecca L. Florence, Peng Wu, Eric A. Grulke, Michael T. Tseng, Jason M. Unrine, Uschi M. Graham, Robert A. Yokel, D. Allan Butterfield Oct 2012

Rat Brain Pro-Oxidant Effects Of Peripherally Administered 5 Nm Ceria 30 Days After Exposure, Sarita S. Hardas, Rukhsana Sultana, Govind Warrier, Mo Dan, Rebecca L. Florence, Peng Wu, Eric A. Grulke, Michael T. Tseng, Jason M. Unrine, Uschi M. Graham, Robert A. Yokel, D. Allan Butterfield

Chemistry Faculty Publications

The objective of this study was to determine the residual pro-or anti-oxidant effects in rat brain 30 days after systemic administration of a 5 nm citrate-stabilized ceria dispersion. A ∼4% aqueous ceria dispersion was iv-infused (0 or 85 mg/kg) into rats which were terminated 30 days later. Ceria concentration, localization, and chemical speciation in the brain was assessed by inductively coupled plasma mass spectrometry (ICP-MS), light and electron microscopy (EM), and electron energy loss spectroscopy (EELS), respectively. Pro- or anti-oxidant effects were evaluated by measuring levels of protein carbonyls (PC), 3-nitrotyrosine (3NT), and protein-bound-4-hydroxy-2-trans-nonenal (HNE) in the hippocampus, cortex, and …


Myxobacteria Versus Sponge-Derived Alkaloids: The Bengamide Family Identified As Potent Immune Modulating Agents By Scrutiny Of Lc-Ms/Elsd Libraries., Tyler A. Johnson, Johann Sohn, Yvette M. Vaske, Kimberly N. White, Tanya L. Cohen, Helene C. Vervoort, Karen Tenney, Frederick A. Valeriote, Leonard F. Bjeldanes, Phillip Crews Jul 2012

Myxobacteria Versus Sponge-Derived Alkaloids: The Bengamide Family Identified As Potent Immune Modulating Agents By Scrutiny Of Lc-Ms/Elsd Libraries., Tyler A. Johnson, Johann Sohn, Yvette M. Vaske, Kimberly N. White, Tanya L. Cohen, Helene C. Vervoort, Karen Tenney, Frederick A. Valeriote, Leonard F. Bjeldanes, Phillip Crews

Natural Sciences and Mathematics | Faculty Scholarship

A nuclear factor-κB (NF-κB) luciferase assay has been employed to identify the bengamides, previously known for their anti-tumor activity, as a new class of immune modulators. A unique element of this study was that the bengamide analogs were isolated from two disparate sources, Myxococcus virescens (bacterium) and Jaspis coriacea (sponge). Comparative LC-MS/ELSD and NMR analysis facilitated the isolation of M. viriscens derived samples of bengamide E (8) and two congeners, bengamide E' (13) and F' (14) each isolated as an insperable mixture of diastereomers. Additional compounds drawn from the UC, Santa Cruz repository allowed expansion of the structure activity relationship …


Resting-State Connectivity Identifies Distinct Functional Networks In Macaque Cingulate Cortex., R Matthew Hutchison, Thilo Womelsdorf, Joseph S Gati, L Stan Leung, Ravi S Menon, Stefan Everling Jun 2012

Resting-State Connectivity Identifies Distinct Functional Networks In Macaque Cingulate Cortex., R Matthew Hutchison, Thilo Womelsdorf, Joseph S Gati, L Stan Leung, Ravi S Menon, Stefan Everling

Physiology and Pharmacology Publications

Subregions of the cingulate cortex represent prominent intersections in the structural networks of the primate brain. The relevance of the cingulate to the structure and dynamics of large-scale networks ultimately requires a link to functional connectivity. Here, we map fine-grained functional connectivity across the complete extent of the macaque (Macaca fascicularis) cingulate cortex and delineate subdivisions pertaining to distinct identifiable networks. In particular, we identified 4 primary networks representing the functional spectrum of the cingulate: somatomotor, attention-orienting, executive, and limbic. The cingulate nodes of these networks originated from separable subfields along the rostral-to-caudal axis and were characterized by positive and …


Distribution, Elimination, And Biopersistence To 90 Days Of A Systemically Introduced 30 Nm Ceria-Engineered Nanomaterial In Rats, Robert A. Yokel, Tu C. Au, Robert Macphail, Sarita S. Hardas, D. Allan Butterfield, Rukhsana Sultana, Michael Goodman, Michael T. Tseng, Mo Dan, Hamed Haghnazar, Jason M. Unrine, Uschi M. Graham, Peng Wu, Eric A. Grulke May 2012

Distribution, Elimination, And Biopersistence To 90 Days Of A Systemically Introduced 30 Nm Ceria-Engineered Nanomaterial In Rats, Robert A. Yokel, Tu C. Au, Robert Macphail, Sarita S. Hardas, D. Allan Butterfield, Rukhsana Sultana, Michael Goodman, Michael T. Tseng, Mo Dan, Hamed Haghnazar, Jason M. Unrine, Uschi M. Graham, Peng Wu, Eric A. Grulke

Pharmaceutical Sciences Faculty Publications

Nanoceria is used as a catalyst in diesel fuel, as an abrasive in printed circuit manufacture, and is being pursued as an antioxidant therapeutic. Our objective is to extend previous findings showing that there were no reductions of cerium in organs of the mononuclear phagocyte (reticuloendothelial) system up to 30 days after a single nanoscale ceria administration. An ~5% aqueous dispersion of citrate-stabilized 30 nm ceria, synthesized and characterized in-house, or vehicle, was iv infused into rats terminated 1, 7, 30, or 90 days later. Cageside observations were obtained daily, body weight weekly. Daily urinary and fecal cerium outputs were …


A Model Of Intracellular Θ Phase Precession Dependent On Intrinsic Subthreshold Membrane Currents., L Stan Leung Aug 2011

A Model Of Intracellular Θ Phase Precession Dependent On Intrinsic Subthreshold Membrane Currents., L Stan Leung

Physiology and Pharmacology Publications

A hippocampal place cell fires at an increasingly earlier phase in relation to the extracellular theta rhythm as a rodent moves through the place field. The present report presents a compartment model of a CA1 pyramidal cell that explains the increase in amplitude and the phase precession of intracellular theta oscillations, with the assumption that the cell receives an asymmetric ramp depolarization (<10 >mV) in the place field and rhythmic inhibitory and/or excitatory synaptic driving. Intracellular subthreshold membrane potential oscillations (MPOs) increase in amplitude and frequency, and show phase precession within the place field. Theta phase precession and MPO power …


Controlling The Activity Of A Phosphatase And Tensin Homolog (Pten) By Membrane Potential, Jérôme J. Lacroix, Christian R. Halaszovich, Daniela N. Schreiber, Michael G. Leitner, Francisco Bezanilla, Dominik Oliver, Carlos A. Villalba-Galea May 2011

Controlling The Activity Of A Phosphatase And Tensin Homolog (Pten) By Membrane Potential, Jérôme J. Lacroix, Christian R. Halaszovich, Daniela N. Schreiber, Michael G. Leitner, Francisco Bezanilla, Dominik Oliver, Carlos A. Villalba-Galea

School of Pharmacy Faculty Articles

The recently discovered voltage-sensitive phosphatases (VSPs) hydrolyze phosphoinositides upon depolarization of the membrane potential, thus representing a novel principle for the transduction of electrical activity into biochemical signals. Here, we demonstrate the possibility to confer voltage sensitivity to cytosolic enzymes. By fusing the tumor suppressor PTEN to the voltage sensor of the prototypic VSP from Ciona intestinalis, Ci-VSP, we generated chimeric proteins that are voltage-sensitive and display PTEN-like enzymatic activity in a strictly depolarization-dependent manner in vivo. Functional coupling of the exogenous enzymatic activity to the voltage sensor is mediated by a phospholipid-binding motif at the interface between voltage sensor …


Plant Phenolics: Extraction, Analysis And Their Antioxidant And Anticancer Properties, Jin Dai, Russell J. Mumper Oct 2010

Plant Phenolics: Extraction, Analysis And Their Antioxidant And Anticancer Properties, Jin Dai, Russell J. Mumper

Pharmaceutical Sciences Faculty Publications

Phenolics are broadly distributed in the plant kingdom and are the most abundant secondary metabolites of plants. Plant polyphenols have drawn increasing attention due to their potent antioxidant properties and their marked effects in the prevention of various oxidative stress associated diseases such as cancer. In the last few years, the identification and development of phenolic compounds or extracts from different plants has become a major area of health- and medical-related research. This review provides an updated and comprehensive overview on phenolic extraction, purification, analysis and quantification as well as their antioxidant properties. Furthermore, the anticancer effects of phenolics in-vitro …


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 …


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 …


Coupling Between The Voltage-Sensing And Phosphatase Domains Of Ci-Vsp, Carlos A. Villalba-Galea, Francesco Miceli, Maurizio Taglialatela, Francisco Bezanilla Jul 2009

Coupling Between The Voltage-Sensing And Phosphatase Domains Of Ci-Vsp, Carlos A. Villalba-Galea, Francesco Miceli, Maurizio Taglialatela, Francisco Bezanilla

School of Pharmacy Faculty Articles

The Ciona intestinalis voltage sensor-containing phosphatase (Ci-VSP) shares high homology with the phosphatidylinositol phosphatase enzyme known as PTEN (phosphatase and tensin homologue deleted on chromosome 10). We have taken advantage of the similarity between these proteins to inquire about the coupling between the voltage sensing and the phosphatase domains in Ci-VSP. Recently, it was shown that four basic residues (R11, K13, R14, and R15) in PTEN are critical for its binding onto the membrane, required for its catalytic activity. Ci-VSP has three of the basic residues of PTEN. Here, we show that when R253 and R254 (which are the homologues …


Mass Stranding Of Marine Birds Caused By A Surfactant-Producing Red Tide., David A. Jessup, Melissa A. Miller, John P. Ryan, Hannah M. Nevins, Heather A. Kerkering, Abdou Mekebri, David B. Crane, Tyler A. Johnson, Raphael M. Kudela Jan 2009

Mass Stranding Of Marine Birds Caused By A Surfactant-Producing Red Tide., David A. Jessup, Melissa A. Miller, John P. Ryan, Hannah M. Nevins, Heather A. Kerkering, Abdou Mekebri, David B. Crane, Tyler A. Johnson, Raphael M. Kudela

Natural Sciences and Mathematics | Faculty Scholarship

In November-December 2007 a widespread seabird mortality event occurred in Monterey Bay, California, USA, coincident with a massive red tide caused by the dinoflagellate Akashiwo sanguinea. Affected birds had a slimy yellow-green material on their feathers, which were saturated with water, and they were severely hypothermic. We determined that foam containing surfactant-like proteins, derived from organic matter of the red tide, coated their feathers and neutralized natural water repellency and insulation. No evidence of exposure to petroleum or other oils or biotoxins were found. This is the first documented case of its kind, but previous similar events may have gone …


Manganese Distribution Across The Blood-Brain Barrier. Iv. Evidence For Brain Influx Through Store-Operated Calcium Channels, Janelle S. Crossgrove, Robert A. Yokel Jun 2005

Manganese Distribution Across The Blood-Brain Barrier. Iv. Evidence For Brain Influx Through Store-Operated Calcium Channels, Janelle S. Crossgrove, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Manganese (Mn) is a required co-factor for many ubiquitous enzymes; however, chronic Mn overexposure can cause manganism, a parkinsonian-like syndrome. Previous studies showed Mn influx into brain is carrier-mediated, though the putative carrier(s) were not established. Studies conducted with cultured bovine brain microvascular endothelial cells (bBMECs), which comprise the blood–brain barrier, revealed 54Mn (II) uptake positively correlated with pH, was temperature-dependent, and was sodium- and energy-independent. Brain 54Mn uptake correlated inversely with calcium (Ca) concentration, but 45Ca uptake was unaltered by high Mn concentration. Lanthanum (La), a non-selective inhibitor of several Ca channel types, as well as …


Manganese Distribution Across The Blood-Brain Barrier. I. Evidence For Carrier-Mediated Influx Of Managanese Citrate As Well As Manganese And Manganese Transferrin, Janelle S. Crossgrove, David D. Allen, Bonny L. Bukaveckas, Susan S. Rhineheimer, Robert A. Yokel Jan 2003

Manganese Distribution Across The Blood-Brain Barrier. I. Evidence For Carrier-Mediated Influx Of Managanese Citrate As Well As Manganese And Manganese Transferrin, Janelle S. Crossgrove, David D. Allen, Bonny L. Bukaveckas, Susan S. Rhineheimer, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Manganese (Mn) is an essential element and a neurotoxicant. Regulation of Mn movement across the blood–brain barrier (BBB) contributes to whether the brain Mn concentration is functional or toxic. In plasma, Mn associates with water, small molecular weight ligands and proteins. Mn speciation may influence the kinetics of its movement through the BBB. In the present work, the brain influx rates of 54Mn2+, 54Mn citrate and 54Mn transferrin (54Mn Tf) were determined using the in situ brain perfusion technique. The influx rates were compared to their predicted diffusion rates, which were determined from …


Ryanodine Receptor Adaptation, Michael Fill, A. Zahradníková, Carlos A. Villalba-Galea, I. Zahradník, A. L. Escobar, S. Györke Dec 2000

Ryanodine Receptor Adaptation, Michael Fill, A. Zahradníková, Carlos A. Villalba-Galea, I. Zahradník, A. L. Escobar, S. Györke

School of Pharmacy Faculty Articles

In the heart, depolarization during the action potential activates voltage-dependent Ca2+ channels that mediate a small, localized Ca2+ influx (ICa). This small Ca2+ signal activates specialized Ca2+ release channels, the ryanodine receptors (RyRs), in the sarcoplasmic reticulum (SR). This process is called Ca2+-induced Ca2+ release (CICR). Intuitively, the CICR process should be self-regenerating because the Ca2+ released from the SR should feedback and activate further SR Ca2+ release. However, the CICR process is precisely controlled in the heart and, consequently, some sort of negative control mechanism(s) must exist to …


The Toxicology Of Aluminum In The Brain: A Review, Robert A. Yokel Oct 2000

The Toxicology Of Aluminum In The Brain: A Review, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Aluminum is environmentally ubiquitous, providing human exposure. Usual human exposure is primarily dietary. The potential for significant Al absorption from the nasal cavity and direct distribution into the brain should be further investigated. Decreased renal function increases human risk of Al-induced accumulation and toxicity. Brain Al entry from blood may involve transferrin-receptor mediated endocytosis and a more rapid process transporting small molecular weight Al species. There appears to be Al efflux from the brain, probably as Al citrate. There is prolonged retention of a fraction of Al that enters the brain, suggesting the potential for accumulation with repeated exposure. Al …


Effect Of Dietary Aluminum Sulfate On Calcium And Phosphorus Metabolism Of Broiler Chicks, Akmed S. Hussein, Austin H. Cantor, Thomas H. Johnson, Robert A. Yokel Jun 1990

Effect Of Dietary Aluminum Sulfate On Calcium And Phosphorus Metabolism Of Broiler Chicks, Akmed S. Hussein, Austin H. Cantor, Thomas H. Johnson, Robert A. Yokel

Animal and Food Sciences Faculty Publications

The effect of dietary aluminum sulfate on Ca and P metabolism was studied using 1-day-oldmale broiler chicks. In Experiment 1, practical diets providing .90% Ca plus .45% available P (Pav), .90% Ca plus .78% Pav, 1.80% Ca plus .45% Pav, or 1.80% Ca plus .90% Pav were fed with 0 or .392% Al as aluminum sulfate for 21 days. The control diet (.90% Caplus .45% Pav) without added A1 was fed to all chicks during Days 22 to 49. In general, Al significantly (Pi), tibia breaking strength, tibia weight, percentage of …


Relationship Of Dietary Aluminum, Phosphorus, And Calcium To Phosphorus And Calcium Metabolism And Growth Performance Of Broiler Chicks, Akmed S. Hussein, Austin H. Cantor, Thomas H. Johnson, Robert A. Yokel Jun 1990

Relationship Of Dietary Aluminum, Phosphorus, And Calcium To Phosphorus And Calcium Metabolism And Growth Performance Of Broiler Chicks, Akmed S. Hussein, Austin H. Cantor, Thomas H. Johnson, Robert A. Yokel

Animal and Food Sciences Faculty Publications

Dietary treatments providing three levels of added Al (0, .196, or .392%) as aluminum sulfate and of available phosphorus (Pav) (.45, .68, or .78%) in a factorial arrangement were administered to day-old chicks in Experiment 1. Plasma inorganic phosphorus (Pi) was significantly (P < .05) elevated by increasing Pav and was decreased by Al. Body weight gain, feed intake, and the gain:feed ratio at Day 21 were significantly decreased by increased concentrations of Al, but were unaffected by the Pav concentrations. Decreases of 39 and 73% in weight gain and of 34 and 66% in feed intake resulted from feeding …