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2012

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Full-Text Articles in Physiology

(R)-Β-Lysine Modified Elongation Factor P Functions In Translation Elongation, Tammy J. Bullwinkle, S. Betty Zou, Andrei Rajkovic, Steven J. Hersch, Sara Elgamal, Nathaniel Robinson, David Smil, Yuri Bolshan, William Wiley Navarre, Michael Ibba Dec 2012

(R)-Β-Lysine Modified Elongation Factor P Functions In Translation Elongation, Tammy J. Bullwinkle, S. Betty Zou, Andrei Rajkovic, Steven J. Hersch, Sara Elgamal, Nathaniel Robinson, David Smil, Yuri Bolshan, William Wiley Navarre, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Post-translational modification of bacterial elongation factor P (EF-P) with (R)-β-lysine at a conserved lysine residue activates the protein in vivo and increases puromycin reactivity of the ribosome in vitro. The additional hydroxylation of EF-P at the same lysine residue by the YfcM protein has also recently been described. The roles of modified and unmodified EF-P during different steps in translation, and how this correlates to its physiological role in the cell, have recently been linked to the synthesis of polyproline stretches in proteins. Polysome analysis indicated that EF-P functions in translation elongation, rather than initiation as proposed previously. This was …


Effect Of Muscle Length On Cross-Bridge Kinetics In Intact Cardiac Trabeculae At Body Temperature, Nima Milani-Nejad, Ying Xu, Jonathan P. Davis, Kenneth S. Campbell, Paul M. L. Janssen Dec 2012

Effect Of Muscle Length On Cross-Bridge Kinetics In Intact Cardiac Trabeculae At Body Temperature, Nima Milani-Nejad, Ying Xu, Jonathan P. Davis, Kenneth S. Campbell, Paul M. L. Janssen

Physiology Faculty Publications

Dynamic force generation in cardiac muscle, which determines cardiac pumping activity, depends on both the number of sarcomeric cross-bridges and on their cycling kinetics. The Frank–Starling mechanism dictates that cardiac force development increases with increasing cardiac muscle length (corresponding to increased ventricular volume). It is, however, unclear to what extent this increase in cardiac muscle length affects the rate of cross-bridge cycling. Previous studies using permeabilized cardiac preparations, sub-physiological temperatures, or both have obtained conflicting results. Here, we developed a protocol that allowed us to reliably and reproducibly measure the rate of tension redevelopment (ktr; which depends …


Orofacial Neuropathic Pain Mouse Model Induced By Trigeminal Inflammatory Compression (Tic) Of The Infraorbital Nerve, Fei Ma, Liping Zhang, Danielle Lyons, Karin N. Westlund Dec 2012

Orofacial Neuropathic Pain Mouse Model Induced By Trigeminal Inflammatory Compression (Tic) Of The Infraorbital Nerve, Fei Ma, Liping Zhang, Danielle Lyons, Karin N. Westlund

Physiology Faculty Publications

BACKGROUND: Trigeminal neuropathic pain attacks can be excruciating for patients, even after being lightly touched. Although there are rodent trigeminal nerve research models to study orofacial pain, few models have been applied to studies in mice. A mouse trigeminal inflammatory compression (TIC) model is introduced here which successfully and reliably promotes vibrissal whisker pad hypersensitivity.

RESULTS: The chronic orofacial neuropathic pain model is induced after surgical placement of chromic gut suture in the infraorbital nerve fissure in the maxillary bone. Slight compression and chemical effects of the chromic gut suture on the portion of the infraorbital nerve contacted cause mild …


Selection Of Trna Charging Quality Control Mechanisms That Increase Mistranslation Of The Genetic Code, Srujana S. Yadavalli, Michael Ibba Dec 2012

Selection Of Trna Charging Quality Control Mechanisms That Increase Mistranslation Of The Genetic Code, Srujana S. Yadavalli, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Mistranslation can follow two events during protein synthesis: production of non-cognate amino acid:transfer RNA (tRNA) pairs by aminoacyl-tRNA synthetases (aaRSs) and inaccurate selection of aminoacyl-tRNAs by the ribosome. Many aaRSs actively edit non-cognate amino acids, but editing mechanisms are not evolutionarily conserved, and their physiological significance remains unclear. To address the connection between aaRSs and mistranslation, the evolutionary divergence of tyrosine editing by phenylalanyl-tRNA synthetase (PheRS) was used as a model. Certain PheRSs are naturally error prone, most notably a Mycoplasma example that displayed a low level of specificity consistent with elevated mistranslation of the proteome. Mycoplasma PheRS was found …


Late Embryogenesis Abundant Proteins Protect Human Hepatoma Cells During Acute Desiccation, Shumin Li, Nilay Chakraborty, Apurva Borcar, Michael A. Menze, Mehmet Toner, Steven C. Hand Nov 2012

Late Embryogenesis Abundant Proteins Protect Human Hepatoma Cells During Acute Desiccation, Shumin Li, Nilay Chakraborty, Apurva Borcar, Michael A. Menze, Mehmet Toner, Steven C. Hand

Faculty Research & Creative Activity

Expression of late embryogenesis abundant (LEA) proteins is highly correlated with desiccation tolerance in anhydrobiotic animals, selected land plants, and bacteria. Genes encoding two LEA proteins, one localized to the cytoplasm/nucleus (AfrLEA2) and one targeted to mitochondria (AfrLEA3m), were stably transfected into human HepG2 cells. A trehalose transporterwas used for intracellular loading of this disaccharide. Cellswere rapidly and uniformly desiccated to low water content (<0.12 g H2O/g dry weight) with a recently developed spin-drying technique. Immediately on rehydration, control cells without LEA proteins or trehalose exhibited 0% membrane integrity, comparedwith 98% in cells loaded with trehalose and expressing AfrLEA2 or AfrLEA3m; surprisingly, AfrLEA3m without trehalose conferred 94% protection. Cell proliferation across 7 d showed an 18-fold increase for cells dried with AfrLEA3m and trehalose, compared with 27-fold for nondried controls. LEA proteins dramatically enhance desiccation tolerance in mammalian cells and offer the opportunity for engineering biostability in the dried state.


Late Embryogenesis Abundant Proteins Protect Human Hepatoma Cells During Acute Desiccation., Shumin Li, Nilay Chakraborty, Apurva Borcar, Michael Menze, Mehmet Toner, Steven Hand Nov 2012

Late Embryogenesis Abundant Proteins Protect Human Hepatoma Cells During Acute Desiccation., Shumin Li, Nilay Chakraborty, Apurva Borcar, Michael Menze, Mehmet Toner, Steven Hand

Faculty Scholarship

Expression of late embryogenesis abundant (LEA) proteins is highly correlated with desiccation tolerance in anhydrobiotic animals, selected land plants, and bacteria. Genes encoding two LEA proteins, one localized to the cytoplasm/nucleus (AfrLEA2) and one targeted to mitochondria (AfrLEA3m), were stably transfected into human HepG2 cells. A trehalose transporterwas used for intracellular loading of this disaccharide. Cellswere rapidly and uniformly desiccated to low water content (< 0.12 g H2O/g dry weight) with a recently developed spin-drying technique. Immediately on rehydration, control cells without LEA proteins or trehalose exhibited 0% membrane integrity, comparedwith 98% in cells loaded with trehalose and expressing AfrLEA2 or AfrLEA3m; surprisingly, AfrLEA3m without trehalose conferred 94% protection. Cell proliferation across 7 d showed an 18-fold increase for cells dried with AfrLEA3m and trehalose, compared with 27-fold for nondried controls. LEA proteins dramatically enhance desiccation tolerance in mammalian cells and offer the opportunity for engineering biostability in the dried state.


A Novel Method For Comparative Analysis Of Retinal Specialization Traits From Topographic Maps, Bret A. Moore, Jason M. Kamilar, Shaun P. Collin, Olaf R. P. Bininda-Emonds, Nathaniel J. Dominy, Margaret I. Hall, Christopher P. Hessy, Sonke Johnsen, Thomas J. Lisney, Ellis R. Loew, Gillian Moritz Nov 2012

A Novel Method For Comparative Analysis Of Retinal Specialization Traits From Topographic Maps, Bret A. Moore, Jason M. Kamilar, Shaun P. Collin, Olaf R. P. Bininda-Emonds, Nathaniel J. Dominy, Margaret I. Hall, Christopher P. Hessy, Sonke Johnsen, Thomas J. Lisney, Ellis R. Loew, Gillian Moritz

Dartmouth Scholarship

Abstract Vertebrates possess different types of retinal specializations that vary in number, size, shape, and position in the retina. This diversity in retinal configuration has been revealed through topographic maps, which show variations in neuron density across the retina. Although topographic maps of about 300 vertebrates are available, there is no method for characterizing retinal traits quantitatively. Our goal is to present a novel method to standardize information on the position of the retinal specializations and changes in retinal ganglion cell (RGC) density across the retina from published topographic maps. We measured the position of the retinal specialization using two …


Metabolic Preconditioning Of Mammalian Cells: Mimetic Agents For Hypoxia Lack Fidelity In Promoting Phosphorylation Of Pyruvate Dehydrogenase, Apurva Borcar, Michael A. Menze, Mehmet Toner, Steven C. Hand Nov 2012

Metabolic Preconditioning Of Mammalian Cells: Mimetic Agents For Hypoxia Lack Fidelity In Promoting Phosphorylation Of Pyruvate Dehydrogenase, Apurva Borcar, Michael A. Menze, Mehmet Toner, Steven C. Hand

Faculty Research & Creative Activity

Induction of HIF-1α by oxygen limitation promotes increased phosphorylation and catalytic depression of mitochondrial pyruvate dehydrogenase (PDH) and an enhanced glycolytic poise in cells. Cobalt chloride and desferrioxamine are widely used as mimics for hypoxia because they increase the levels of HIF-1α. We evaluated the ability of these agents to elicit selected physiological responses to hypoxia as a means to metabolically precondition mammalian cells, but without the detrimental effects of hypoxia. We show that, while CoCl2 does increase HIF-1α in a dose-dependent manner, it unexpectedly and strikingly decreases PDH phosphorylation at E1α sites 1, 2, and 3 (Ser293, Ser300, and …


Metabolic Preconditioning Of Mammalian Cells : Mimetic Agents For Hypoxia Lack Fidelity In Promoting Phosphorylation Of Pyruvate Dehydrogenase., Apurva Borcar, Michael Menze, Mehmet Toner, Steven Hand Nov 2012

Metabolic Preconditioning Of Mammalian Cells : Mimetic Agents For Hypoxia Lack Fidelity In Promoting Phosphorylation Of Pyruvate Dehydrogenase., Apurva Borcar, Michael Menze, Mehmet Toner, Steven Hand

Faculty Scholarship

Induction of HIF-1α by oxygen limitation promotes increased phosphorylation and catalytic depression of mitochondrial pyruvate dehydrogenase (PDH) and an enhanced glycolytic poise in cells. Cobalt chloride and desferrioxamine are widely used as mimics for hypoxia because they increase the levels of HIF-1α. We evaluated the ability of these agents to elicit selected physiological responses to hypoxia as a means to metabolically precondition mammalian cells, but without the detrimental effects of hypoxia. We show that, while CoCl2 does increase HIF-1α in a dose-dependent manner, it unexpectedly and strikingly decreases PDH phosphorylation at E1α sites 1, 2, and 3 (Ser293, Ser300, and …


Characterization Of Secretory Sphingomyelinase Activity, Lipoprotein Sphingolipid Content And Ldl Aggregation In Ldlr-/- Mice Fed On A High-Fat Diet, Gergana M. Deevska, Manjula Sunkara, Andrew J. Morris, Mariana N. Nikolova‑Karakashian Oct 2012

Characterization Of Secretory Sphingomyelinase Activity, Lipoprotein Sphingolipid Content And Ldl Aggregation In Ldlr-/- Mice Fed On A High-Fat Diet, Gergana M. Deevska, Manjula Sunkara, Andrew J. Morris, Mariana N. Nikolova‑Karakashian

Physiology Faculty Publications

The propensity of LDLs (low-density lipoproteins) for aggregation and/or oxidation has been linked to their sphingolipid content, specifically the levels of SM (sphingomyelin) and ceramide. To investigate this association in vivo, ldlr (LDL receptor)-null mice (ldlr-/-) were fed on a modified (atherogenic) diet containing saturated fats and cholesterol. The diet led to significantly elevated SM content in all serum lipoproteins. In contrast, ceramide increased only in the LDL particles. MS-based analyses of the lipid acyl chain composition revealed a marked elevation in C16:0 fatty acid in SM and ceramide, consistent with the prevalence of palmitic acid in the modified diet. …


Endogenous Inhibitor Proteins That Connect Ser/Thr Kinases And Phosphatases In Cell Signaling., Masumi Eto, David L Brautigan Sep 2012

Endogenous Inhibitor Proteins That Connect Ser/Thr Kinases And Phosphatases In Cell Signaling., Masumi Eto, David L Brautigan

Department of Molecular Physiology and Biophysics Faculty Papers

Protein phosphatase activity acts as a primary determinant of the extent and duration of phosphorylation of cellular proteins in response to physiological stimuli. Ser/Thr protein phosphatase-1 (PP1) belongs to the PPP superfamily, and is associated with regulatory subunits that confer substrate specificity, allosteric regulation, and subcellular compartmentalization. In addition, all eukaryotic cells contain multiple heat-stable proteins that originally were thought to inhibit phosphatase catalytic subunits released from the regulatory subunits, as a fail-safe mechanism. However, discovery of C-kinase-activated PP1 inhibitor, Mr of 17 kDa (CPI-17) required fresh thinking about the endogenous inhibitors as specific regulators of particular phosphatase complexes, acting …


Atovaquone Ameliorate Gastrointestinal Toxoplasmosis Complications In A Pregnancy Model, Helieh S. Oz, Thomas Tobin Sep 2012

Atovaquone Ameliorate Gastrointestinal Toxoplasmosis Complications In A Pregnancy Model, Helieh S. Oz, Thomas Tobin

Physiology Faculty Publications

Background: Toxoplasma is an important source of foodborne hospitalization with no safe and effective therapy against chronic or congenital Toxopalsmosis. Atovaquone is a drug of choice but not approved for use in congenital Toxoplasmosis. We hypothesized atovaquone to be safe and effective against feto-maternal Toxoplasmosis.

Material/Methods: Programmed pregnant mice were i.p. infected with 50–2400 Tachyzoites from Type II strain (clone PTG). Dams were treated daily with atovaquone or sham and monitored for pain, and complications.

Results: Dams developed pain related abdominal hypersensitivity (allodynia) to mechanical stimuli in a Tachyzoites dose dependent manner. Infected dams were anemic and exhibited ascities and …


Mutations In Dmrt3 Affect Locomotion In Horses And Spinal Circuit Function In Mice, Lisa S. Andersson, Martin Larhammar, Fatima Memic, Hanna Wootz, Doreen Schwochow, Carl-Johan Rubin, Kalicharan Patra, Thorvaldur Arnason, Lisbeth Wellbring, Göran Hjälm, Freyja Imsland, Jessica Lynn Petersen, Molly E. Mccue, James R. Mickelson, Gus Cothran, Nadav Ahituv, Lars Roepstorff, Sofia Mikko, Anna Vallstedt, Gabriella Lindgren, Leif Andersson, Klas Kullander Aug 2012

Mutations In Dmrt3 Affect Locomotion In Horses And Spinal Circuit Function In Mice, Lisa S. Andersson, Martin Larhammar, Fatima Memic, Hanna Wootz, Doreen Schwochow, Carl-Johan Rubin, Kalicharan Patra, Thorvaldur Arnason, Lisbeth Wellbring, Göran Hjälm, Freyja Imsland, Jessica Lynn Petersen, Molly E. Mccue, James R. Mickelson, Gus Cothran, Nadav Ahituv, Lars Roepstorff, Sofia Mikko, Anna Vallstedt, Gabriella Lindgren, Leif Andersson, Klas Kullander

Department of Animal Science: Faculty Publications

Locomotion in mammals relies on a central pattern-generating circuitry of spinal interneurons established during development that coordinates limb movement. These networks produce left–right alternation of limbs as well as coordinated activation of flexor and extensor muscles. Here we show that a premature stop codon in the DMRT3 gene has a major effect on the pattern of locomotion in horses. The mutation is permissive for the ability to perform alternate gaits and has a favorable effect on harness racing performance. Examination of wild-type and Dmrt3-null mice demonstrates that Dmrt3 is expressed in the dI6 subdivision of spinal cord neurons, takes …


Taking Aim At The Start Of Translation, Medha Raina, Michael Ibba Aug 2012

Taking Aim At The Start Of Translation, Medha Raina, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

No abstract provided.


Genomics Of Mature And Immature Olfactory Sensory Neurons, Melissa D. Nickell, Patrick Breheny, Arnold J. Stromberg, Timothy S. Mcclintock Aug 2012

Genomics Of Mature And Immature Olfactory Sensory Neurons, Melissa D. Nickell, Patrick Breheny, Arnold J. Stromberg, Timothy S. Mcclintock

Physiology Faculty Publications

The continuous replacement of neurons in the olfactory epithelium provides an advantageous model for investigating neuronal differentiation and maturation. By calculating the relative enrichment of every mRNA detected in samples of mature mouse olfactory sensory neurons (OSNs), immature OSNs, and the residual population of neighboring cell types, and then comparing these ratios against the known expression patterns of >300 genes, enrichment criteria that accurately predicted the OSN expression patterns of nearly all genes were determined. We identified 847 immature OSN-specific and 691 mature OSN-specific genes. The control of gene expression by chromatin modification and transcription factors, and neurite growth, protein …


Physiologically-Based Pharmacokinetic Modeling Of Acetaminophen Metabolism And Toxicity, David M. Ng, Ali Navid Aug 2012

Physiologically-Based Pharmacokinetic Modeling Of Acetaminophen Metabolism And Toxicity, David M. Ng, Ali Navid

STAR Program Research Presentations

Acetaminophen is a common analgesic and antipyretic. Metabolism of acetaminophen and acetaminophen-induced liver necrosis are predicted using physiologically-based pharmacokinetic (PBPK) modeling. Pharmacokinetic means the model determines where the drug is distributed in the body over time. Physiologically-based means the anatomy and physiology of the human body is reflected in the structure and functioning of the model. Acetaminophen is usually safe and effective when taken as recommended, but consumption at higher levels may lead to liver damage. Additionally, other factors such as alcoholic liver disease, smoking, and malnutrition affect the maximum safe dose of acetaminophen.


Long-Term Survival Of Anoxia Despite Rapid Atp Decline In Embryos Of The Annual Killifish Austrofundulus Limnaeus, Jason E. Podrabsky, Michael A. Menze, Steven C. Hand Aug 2012

Long-Term Survival Of Anoxia Despite Rapid Atp Decline In Embryos Of The Annual Killifish Austrofundulus Limnaeus, Jason E. Podrabsky, Michael A. Menze, Steven C. Hand

Faculty Research & Creative Activity

Embryos of the annual killifish Austrofundulus limnaeus can survive for months in the complete absence of oxygen. Survival of anoxia is associated with entry into a state of metabolic dormancy known as diapause. However, extreme tolerance of anoxia is retained for several days of post-diapause development. Rates of heat dissipation in diapause II and 4 days post-diapause II embryos were measured under aerobic conditions and during the transition into anoxia. Phosphorylated adenylate compounds were quantified in embryos during entry into anoxia and after 12 hr of aerobic recovery. Rates of heat dissipation were not affected by exposure to anoxia in …


Long-Term Survival Of Anoxia Despite Rapid Atp Decline In Embryos Of The Annual Killifish Austrofundulus Limnaeus., Jason Podrabsky, Michael Menze, Steven Hand Aug 2012

Long-Term Survival Of Anoxia Despite Rapid Atp Decline In Embryos Of The Annual Killifish Austrofundulus Limnaeus., Jason Podrabsky, Michael Menze, Steven Hand

Faculty Scholarship

Embryos of the annual killifish Austrofundulus limnaeus can survive for months in the complete absence of oxygen. Survival of anoxia is associated with entry into a state of metabolic dormancy known as diapause. However, extreme tolerance of anoxia is retained for several days of post-diapause development. Rates of heat dissipation in diapause II and 4 days post-diapause II embryos were measured under aerobic conditions and during the transition into anoxia. Phosphorylated adenylate compounds were quantified in embryos during entry into anoxia and after 12 hr of aerobic recovery. Rates of heat dissipation were not affected by exposure to anoxia in …


Peripheral Nerve Injury Increases Glutamate-Evoked Calcium Mobilization In Adult Spinal Cord Neurons, Suzanne Doolen, Camille B. Blake, Bret N. Smith, Bradley K. Taylor Jul 2012

Peripheral Nerve Injury Increases Glutamate-Evoked Calcium Mobilization In Adult Spinal Cord Neurons, Suzanne Doolen, Camille B. Blake, Bret N. Smith, Bradley K. Taylor

Physiology Faculty Publications

BACKGROUND: Central sensitization in the spinal cord requires glutamate receptor activation and intracellular Ca2+ mobilization. We used Fura-2 AM bulk loading of mouse slices together with wide-field Ca2+ imaging to measure glutamate-evoked increases in extracellular Ca2+ to test the hypotheses that: 1. Exogenous application of glutamate causes Ca2+ mobilization in a preponderance of dorsal horn neurons within spinal cord slices taken from adult mice; 2. Glutamate-evoked Ca2+ mobilization is associated with spontaneous and/or evoked action potentials; 3. Glutamate acts at glutamate receptor subtypes to evoked Ca2+ transients; and 4. The magnitude of glutamate-evoked Ca2+ responses increases in the setting of …


Robust Analysis Of Metabolic Pathways, Emily Gruber, Amy Ko, Michael Macgillvray, Miranda Sawyer Jul 2012

Robust Analysis Of Metabolic Pathways, Emily Gruber, Amy Ko, Michael Macgillvray, Miranda Sawyer

Mathematical Sciences Technical Reports (MSTR)

Flux Balance Analysis (FBA) is a widely used computational model for studying the metabolic pathways of cells and the role individual metabolites and reactions play in maintaining cell function. However, the successes of FBA have been limited by faulty biological assumptions and computational imperfections. We introduce Robust Analysis of Metabolic Pathways (RAMP) to provide a more theoretically sound and computationally accurate model of cellular metabolism. RAMP overcomes the faulty assumptions of traditional FBA by allowing deviation from steady-state and accounting for variability across a cellular culture. Computationally, RAMP more successfully predicts the lethality of gene knockouts and reduces degeneracy in …


Early Stage Drug Treatment That Normalizes Proinflammatory Cytokine Production Attenuates Synaptic Dysfunction In A Mouse Model That Exhibits Age-Dependent Progression Of Alzheimer's Disease-Related Pathology, Adam D. Bachstetter, Christopher M. Norris, Pradoldej Sompol, Donna M. Wilcock, Danielle Goulding, Janna H. Neltner, Daret St. Clair, D. Martin Watterson, Linda J. Van Eldik Jul 2012

Early Stage Drug Treatment That Normalizes Proinflammatory Cytokine Production Attenuates Synaptic Dysfunction In A Mouse Model That Exhibits Age-Dependent Progression Of Alzheimer's Disease-Related Pathology, Adam D. Bachstetter, Christopher M. Norris, Pradoldej Sompol, Donna M. Wilcock, Danielle Goulding, Janna H. Neltner, Daret St. Clair, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

Overproduction of proinflammatory cytokines in the CNS has been implicated as a key contributor to pathophysiology progression in Alzheimer's disease (AD), and extensive studies with animal models have shown that selective suppression of excessive glial proinflammatory cytokines can improve neurologic outcomes. The prior art, therefore, raises the logical postulation that intervention with drugs targeting dysregulated glial proinflammatory cytokine production might be effective disease-modifying therapeutics if used in the appropriate biological time window. To test the hypothesis that early stage intervention with such drugs might be therapeutically beneficial, we examined the impact of intervention with MW01-2-151SRM (MW-151), an experimental therapeutic that …


A Pseudo-Trna Modulates Antibiotic Resistance In Bacillus Cereus, Theresa E. Rogers, Sandro F. Ataide, Kiley Dare, Assaf Katz, Stephanie Seveau, Hervé Roy, Michael Ibba Jul 2012

A Pseudo-Trna Modulates Antibiotic Resistance In Bacillus Cereus, Theresa E. Rogers, Sandro F. Ataide, Kiley Dare, Assaf Katz, Stephanie Seveau, Hervé Roy, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Bacterial genomic islands are often flanked by tRNA genes, which act as sites for the integration of foreign DNA into the host chromosome. For example, Bacillus cereus ATCC14579 contains a pathogenicity island flanked by a predicted pseudo-tRNA, tRNAOther, which does not function in translation. Deletion of tRNAOther led to significant changes in cell wall morphology and antibiotic resistance and was accompanied by changes in the expression of numerous genes involved in oxidative stress responses, several of which contain significant complementarities to sequences surrounding tRNAOther. This suggested that tRNAOther might be expressed as part of a larger RNA, and RACE analysis …


Mice Deficient In Gem Gtpase Show Abnormal Glucose Homeostasis Due To Defects In Beta-Cell Calcium Handling, Jenny E. Gunton, Mary Sisavanh, Rebecca A. Stokes, Jon Satin, Leslie S. Satin, Min Zhang, Sue M. Liu, Weikang Cai, Kim Cheng, Gregory J. Cooney, D. Ross Laybutt, Trina So, Juan-Carlos Molero, Shane T. Grey, Douglas A. Andres, Michael S. Rolph, Charles R. Mackay Jun 2012

Mice Deficient In Gem Gtpase Show Abnormal Glucose Homeostasis Due To Defects In Beta-Cell Calcium Handling, Jenny E. Gunton, Mary Sisavanh, Rebecca A. Stokes, Jon Satin, Leslie S. Satin, Min Zhang, Sue M. Liu, Weikang Cai, Kim Cheng, Gregory J. Cooney, D. Ross Laybutt, Trina So, Juan-Carlos Molero, Shane T. Grey, Douglas A. Andres, Michael S. Rolph, Charles R. Mackay

Physiology Faculty Publications

AIMS AND HYPOTHESIS: Glucose-stimulated insulin secretion from beta-cells is a tightly regulated process that requires calcium flux to trigger exocytosis of insulin-containing vesicles. Regulation of calcium handling in beta-cells remains incompletely understood. Gem, a member of the RGK (Rad/Gem/Kir) family regulates calcium channel handling in other cell types, and Gem over-expression inhibits insulin release in insulin-secreting Min6 cells. The aim of this study was to explore the role of Gem in insulin secretion. We hypothesised that Gem may regulate insulin secretion and thus affect glucose tolerance in vivo.

METHODS: Gem-deficient mice were generated and their metabolic phenotype characterised by in …


Association Of A Multi-Synthetase Complex With Translating Ribosomes In The Archaeon Thermococcus Kodakarensis, Medha Raina, Sara Elgamal, Thomas J. Santangelo, Michael Ibba Jun 2012

Association Of A Multi-Synthetase Complex With Translating Ribosomes In The Archaeon Thermococcus Kodakarensis, Medha Raina, Sara Elgamal, Thomas J. Santangelo, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

In archaea and eukaryotes aminoacyl-tRNA synthetases (aaRSs) associate in multi-synthetase complexes (MSCs), however the role of such MSCs in translation is unknown. MSC function was investigated in vivo in the archaeon Thermococcus kodakarensis, wherein six aaRSs were affinity co-purified together with several other factors involved in protein synthesis, suggesting that MSCs may interact directly with translating ribosomes. In support of this hypothesis, the aminoacyltRNA synthetase (aaRS) activities of the MSC were enriched in isolated T. kodakarensis polysome fractions. These data indicate that components of the archaeal protein synthesis machinery associate into macromolecular assemblies in vivo and provide the potential …


Mechanism Of Inhibition Of Influenza A Virus M2 Proton Channel, Douglas Randall Bretzing, Victoria Man-Fung Burr May 2012

Mechanism Of Inhibition Of Influenza A Virus M2 Proton Channel, Douglas Randall Bretzing, Victoria Man-Fung Burr

Faculty Publications

The influenza A virus integral membrane protein, M2, is a proton-conducting channel. The ability of influenza A virus to unpack its genome, replicate, and infect its host is contingent upon the M2-mediated acidification of the viral interior. The antiviral drugs amantadine and rimantadine were previously effective in blocking proton influx through M2; however, mutations in the proton channel have rendered these drugs ineffective. Multiple models for the inhibiting mechanism of the adamantane drugs have been hypothesized. In an attempt to better understand the mechanism of M2 inhibition, and ultimately to assist in the development of a replacement M2-targeting antiviral drug, …


Evidence For Pit-Type (Slc20) And Napi-Ii-Type (Slc34) Transporters In The Rat Choroid Plexus, Hien M. Le May 2012

Evidence For Pit-Type (Slc20) And Napi-Ii-Type (Slc34) Transporters In The Rat Choroid Plexus, Hien M. Le

Honors Scholar Theses

: A major function of the brain choroid plexus (CP) is to regulate the exchange of solutes between the blood plasma and the cerebrospinal fluid (CSF) using selective transporters. CSF inorganic phosphate (Pi) concentration is maintained at about one-half that of plasma and is potentially important because of its regulatory, structural, and biochemical functions. Phosphate is critical for ATP and DNA formation, the linked regulation between phosphate and calcium, and as an intracellular buffer. The human body has two major Pi transporter gene families known as SLC34 (NaPi-II) and SLC20 (PiT), which have wide tissue distribution. Although …


The Effects Of Rectal Temperature And Hydration Status On Perceptual Ratings In Dehydrating Males, Ethan A. Talbot May 2012

The Effects Of Rectal Temperature And Hydration Status On Perceptual Ratings In Dehydrating Males, Ethan A. Talbot

Honors Scholar Theses

Athletes push the limits of what the human body can handle every day. When they exercise in the heat, they can attain dangerous levels of internal temperature and dehydration. Since athletes are sometimes not aware when they are experiencing severe hyperthermia or hypohydration, it is of interest to anyone who exercises in the heat to study whether athletes are consciously aware that they are approaching dangerous physiological limits. This study compares the perceptual values of athletes exercising in the heat to the changes in their internal temperature and hydration status, to see if athletes can reliably predict their heat and …


The Time-Course Of The Effects Of Growth Hormone During Zebrafish (Danio Rerio) Auditory Hair Cell Regeneration, Yajie Wang May 2012

The Time-Course Of The Effects Of Growth Hormone During Zebrafish (Danio Rerio) Auditory Hair Cell Regeneration, Yajie Wang

Masters Theses & Specialist Projects

Growth hormone (GH) was upregulated in the zebrafish inner ear following sound exposure in a previous study. To identify the specific role of GH in hair cell regeneration and the possible cellular mechanisms of this regeneration, groups of zebrafish were divided into baseline (no sound exposure, no injection), buffer-injected and GH-injected groups. Buffer- and GH-injected fish were exposed to a 150 Hz tone at a source level of 179 dB re 1 μPa root mean squared (RMS) for 36 h. Phalloidin-staining was used to assess the effects of GH on hair cell bundle density; BrdU-labeling was used to assess the …


Flowcell Systems For Single Molecule Detection, John G. K. Williams, Gregory R. Bashford, Jiyan Chen, Dan Draney, Nara Narayanan, Bambi L. Reynolds, Pamela Sheaff Apr 2012

Flowcell Systems For Single Molecule Detection, John G. K. Williams, Gregory R. Bashford, Jiyan Chen, Dan Draney, Nara Narayanan, Bambi L. Reynolds, Pamela Sheaff

Biomedical Imaging and Biosignal Analysis Laboratory

The present invention provides compounds, methods and systems for sequencing nucleic acid using single molecule detection. Using labeled NPs that exhibit charge-switching behavior, single-molecule DNA sequencing in a microchannel sorting system is realized. In operation, sequencing products are detected enabling real-time sequencing as successive detectable moieties flow through a detection channel. By electrically sorting charged molecules, the cleaved product molecules are detected in isolation without interference from unincorporated NPs and without illuminating the polymerase-DNA complex.


Integration Of Student Centered Physiology Learning Into Related High School Science Courses, Sowmya Anjur Apr 2012

Integration Of Student Centered Physiology Learning Into Related High School Science Courses, Sowmya Anjur

Faculty Publications & Research

Student centered teaching was previously found to enhance student understanding and even improve performance of students in other courses taken in the same semester in high school (6). In an effort to improve student performance in related science classes, the same student centered methods used in my Physiology and Disease (PAD) class were implemented in a Biophysics class this semester. Initial student surveys showed that students felt that integrating physiology concepts into Biophysics helped them understand the material from two very different perspectives, giving them a "more complete picture". Test scores from each of the four units were compared in …