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Search Results: 1 - 10 of 318805 matches for " Robert J. French "
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Inorganic Polyphosphate Modulates TRPM8 Channels
Eleonora Zakharian, Baskaran Thyagarajan, Robert J. French, Evgeny Pavlov, Tibor Rohacs
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0005404
Abstract: Polyphosphate (polyP) is an inorganic polymer built of tens to hundreds of phosphates, linked by high-energy phosphoanhydride bonds. PolyP forms complexes and modulates activities of many proteins including ion channels. Here we investigated the role of polyP in the function of the transient receptor potential melastatin 8 (TRPM8) channel. Using whole-cell patch-clamp and fluorescent calcium measurements we demonstrate that enzymatic breakdown of polyP by exopolyphosphatase (scPPX1) inhibits channel activity in human embryonic kidney and F-11 neuronal cells expressing TRPM8. We demonstrate that the TRPM8 channel protein is associated with polyP. Furthermore, addition of scPPX1 altered the voltage-dependence and blocked the activity of the purified TRPM8 channels reconstituted into planar lipid bilayers, where the activity of the channel was initiated by cold and menthol in the presence of phosphatidylinositol 4,5-biphosphate (PtdIns(4,5)P2). The biochemical analysis of the TRPM8 protein also uncovered the presence of poly-(R)-3-hydroxybutyrate (PHB), which is frequently associated with polyP. We conclude that the TRPM8 protein forms a stable complex with polyP and its presence is essential for normal channel activity.
Marine Toxins That Target Voltage-gated Sodium Channels
Ahmed Al-Sabi,Jeff McArthur,Vitaly Ostroumov,Robert J. French
Marine Drugs , 2006, DOI: 10.3390/md403157
Abstract: Eukaryotic, voltage-gated sodium (NaV) channels are large membrane proteins which underlie generation and propagation of rapid electrical signals in nerve, muscle and heart. Nine different NaV receptor sites, for natural ligands and/or drugs, have been identified, based on functional analyses and site-directed mutagenesis. In the marine ecosystem, numerous toxins have evolved to disrupt NaV channel function, either by inhibition of current flow through the channels, or by modifying the activation and inactivation gating processes by which the channels open and close. These toxins function in their native environment as offensive or defensive weapons in prey capture or deterrence of predators. In composition, they range from organic molecules of varying size and complexity to peptides consisting of ~10-70 amino acids. We review the variety of known NaV-targeted marine toxins, outlining, where known, their sites of interaction with the channel protein and their functional effects. In a number of cases, these natural ligands have the potential applications as drugs in clinical settings, or as models for drug development.
The Tetrodotoxin Receptor of Voltage-Gated Sodium Channels—Perspectives from Interactions with μ-Conotoxins
Robert J. French,Doju Yoshikami,Michael F. Sheets,Baldomero M. Olivera
Marine Drugs , 2010, DOI: 10.3390/md8072153
Abstract: Neurotoxin receptor site 1, in the outer vestibule of the conducting pore of voltage-gated sodium channels (VGSCs), was first functionally defined by its ability to bind the guanidinium-containing agents, tetrodotoxin (TTX) and saxitoxin (STX). Subsequent studies showed that peptide μ-conotoxins competed for binding at site 1. All of these natural inhibitors block single sodium channels in an all-or-none manner on binding. With the discovery of an increasing variety of μ-conotoxins, and the synthesis of numerous derivatives, observed interactions between the channel and these different ligands have become more complex. Certain μ-conotoxin derivatives block single-channel currents partially, rather than completely, thus enabling the demonstration of interactions between the bound toxin and the channel’s voltage sensor. Most recently, the relatively small μ-conotoxin KIIIA (16 amino acids) and its variants have been shown to bind simultaneously with TTX and exhibit both synergistic and antagonistic interactions with TTX. These interactions raise new pharmacological possibilities and place new constraints on the possible structures of the bound complexes of VGSCs with these toxins.
Effects of calorie labeling and value size pricing on fast food meal choices: Results from an experimental trial
Lisa J Harnack, Simone A French, J Michael Oakes, Mary T Story, Robert W Jeffery, Sarah A Rydell
International Journal of Behavioral Nutrition and Physical Activity , 2008, DOI: 10.1186/1479-5868-5-63
Abstract: To examine the effect of point-of-purchase calorie information and value size pricing on fast food meal choices a randomized 2 × 2 factorial experiment was conducted in which participants ordered a fast food meal from one of four menus that varied with respect to whether calorie information was provided and whether value size pricing was used. Study participants included 594 adolescents and adults who regularly ate at fast food restaurants. Study staff recorded the foods ordered and consumed by each participant. Participants also completed surveys to assess attitudes, beliefs and practices related to fast food and nutrition.No significant differences in the energy composition of meals ordered or eaten were found between menu conditions. The average energy content of meals ordered by those randomized to a menu that included calorie information and did not include value size pricing was 842 kcals compared with 827 kcals for those who ordered their meal from a menu that did not include calorie information but had value size pricing (control menu). Results were similar in most analyses conducted stratified by factors such as age, race and education level.Additional research is needed to better evaluate the effects of calorie labeling and value size pricing on fast food meal choices. Studies in which participants are repeatedly exposed to these factors are needed since long term exposure may be required for behavior change.The prevalence of overweight and obesity in the United States has increased dramatically [1]. One factor that many believe to be an important contributor to this increase is the number of meals and snacks eaten away from home. Over the past several decades the proportion of total food expenditures spent on food away from home has increased from 34% in 1974 to about half in 2004 [2]. Foods available at restaurants and other away from home eating locations tend to be higher in calories and fat [3-6] and often larger in portion size [7,8] compared to food
Continuous Renal Replacement Therapy Clearance Rate for Salicylate Toxicity in Multi-System Trauma  [PDF]
Daniel Silverman, L. Keith French, Robert G. Hendrickson
International Journal of Clinical Medicine (IJCM) , 2012, DOI: 10.4236/ijcm.2012.36099
Abstract: The management of patients with concomitant xenobiotic toxicity and multisystem trauma can be complex. While hemodialysis is generally the modality of choice for extracorporeal elimination of salicylates, the potential for large volume shifts and hypotension may pose a risk in patients with traumatic brain injury. An alternative therapy to hemodialysis is continuous renal replacement therapy, which has slower clearance rates than hemodialysis, but has decreased adverse effects in cases of traumatic brain injury. However, there are few published reports of clearance rates of salicylates using continuous renal replacement therapy. We report a case of multisystem trauma with concomitant intentional salicylate overdose in which continuous renal replacement therapy was employed. The salicylate clearance rate that was obtained in this case was 7.5 mL/minute using continuous veno-venous hemodiafiltration, a form of continuous renal replacement therapy.
Visualising a Fuse
M M J French
Physics , 2010,
Abstract: In this brief article I describe an experiment to illustrate how a fuse works. I have used this as part of lessons for my year 11 classes to demonstrate how an electrical fuse 'blows' when too high a current passes through it.
The Wonders of Levitation
M M J French
Physics , 2010, DOI: 10.1088/0031-9120/45/1/003
Abstract: I discuss some interesting classroom demonstrations of diamagnetism and how this effect can produce levitation. The possibilities for hands-on demonstrations of diamagnetic and superconducting levitation are discussed. To conclude I discuss some practical uses for levitation in daily life.
Mobile Phone Faraday Cage
M M J French
Physics , 2011, DOI: 10.1088/0031-9120/46/3/005
Abstract: A Faraday cage is an interesting physics phenomena where an electromagnetic wave can be excluded from a volume of space by enclosure with an electrically conducting material. The practical application of this in the classroom is to block the signal to a mobile phone by enclosing it in a metal can! The background of the physics behind this is described in some detail followed by a explanation of some demonstrations and experiments which I have used.
Ten Years of Surveillance for Invasive Streptococcus pneumoniae during the Era of Antiretroviral Scale-Up and Cotrimoxazole Prophylaxis in Malawi
Dean B. Everett,Mavuto Mukaka,Brigitte Denis,Stephen B. Gordon,Enitan D. Carrol,Joep J. van Oosterhout,Elizabeth M. Molyneux,Malcolm Molyneux,Neil French,Robert S. Heyderman
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0017765
Abstract: To document trends in invasive pneumococcal disease (IPD) in a central hospital in Malawi during the period of national scale-up of antiretroviral therapy (ART) and cotrimoxazole prophylaxis.
A Low Metallicity Molecular Cloud In The Lower Galactic Halo
Audra K. Hernandez,Bart P. Wakker,Robert A. Benjamin,David French,Juergen Kerp,Felix J. Lockman,Simon O'Toole,Benjamin Winkel
Physics , 2013, DOI: 10.1088/0004-637X/777/1/19
Abstract: We find evidence for the impact of infalling, low-metallicity gas on the Galactic disk. This is based on FUV absorption line spectra, 21-cm emission line spectra, and FIR mapping to estimate the abundance and physical properties of IV21 (IVC135+54-45), a galactic intermediate-velocity molecular cloud (IVMC) that lies ~300 pc above the disk. The metallicity of IV21 was estimated using observations toward the sdB star PG1144+615, located at a projected distance of 16 pc from the cloud's densest core, by measuring ion and HI column densities for comparison with known solar abundances. Despite the cloud's bright FIR emission and large column densities of molecular gas as traced by CO, we find that it has a sub-solar metallicity of log(Z/Z_Sun)=-0.43 +/- 0.12dex. IV21 is thus the first known sub-solar metallicity cloud in the solar neighborhood. In contrast, most intermediate-velocity clouds (IVC) have near-solar metallicities and are believed to originate in the Galactic Fountain. The cloud's low metallicity is also atypical for Galactic molecular clouds, especially in the light of the bright FIR emission which suggest a substantial dust content. The measured I_100mu/N(HI) ratio is a factor of three below the average found in high latitude \HI clouds within the solar neighborhood. We argue that IV21 represents the impact of an infalling, low-metallicity high-velocity cloud (HVC) that is mixing with disk gas in the lower Galactic halo.
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