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Search Results: 1 - 10 of 169961 matches for " Robert F Margolskee "
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Transsynaptic transport of wheat germ agglutinin expressed in a subset of type II taste cells of transgenic mice
Sami Damak, Bedrich Mosinger, Robert F Margolskee
BMC Neuroscience , 2008, DOI: 10.1186/1471-2202-9-96
Abstract: Immunohistochemistry showed co-expression of WGA, GFP and endogenous T1r3 in the taste bud cells of transgenic mice: the only taste cells immunoreactive for WGA were the T1r3-expressing cells. The WGA antibody also stained intragemmal nerves. WGA, but not GFP immunoreactivity was found in the geniculate and petrosal ganglia of transgenic mice, indicating that WGA was transported across synapses. WGA immunoreactivity was also found in the trigeminal ganglion, suggesting that T1r3-expressing cells make synapses with trigeminal neurons. In the medulla, WGA was detected in the nucleus of the solitary tract but also in the nucleus ambiguus, the vestibular nucleus, the trigeminal nucleus and in the gigantocellular reticular nucleus. WGA was not detected in the parabrachial nucleus, or the gustatory cortex.These results show the usefulness of genetically encoded WGA as a tracer for the first and second order neurons that innervate a subset of taste cells, but not for higher order neurons, and demonstrate that the main route of output from type II taste cells is the gustatory neuron, not the type III cells.In the past few years, there have been tremendous advances in our understanding of the mechanisms of taste signal transduction. Many components of the mammalian taste signal transduction cascade have been identified, including the sweet and umami responsive T1r receptors, the bitter responsive T2r receptors, α-gustducin, Gγ13, PDE1A, PLCβ2, Trpm5, and PKDs (for reviews see [1-3]). Despite these advances at the molecular level, the mechanisms of taste coding remain unclear: how does depolarization of a subset of taste receptor cells lead to discrimination between tastants of different quality? There has been an on-going debate for several decades as to how taste qualities are coded. One view, the across fiber pattern model, maintains that taste qualities are represented by patterns of activity across afferent nerve populations. In another view, the labeled-line model, tast
Mouse taste cells with G protein-coupled taste receptors lack voltage-gated calcium channels and SNAP-25
Tod R Clapp, Kathryn F Medler, Sami Damak, Robert F Margolskee, Sue C Kinnamon
BMC Biology , 2006, DOI: 10.1186/1741-7007-4-7
Abstract: Depolarization with high K+ resulted in an increase in intracellular Ca2+ in a small subset of non-GFP labeled cells of both transgenic mouse lines. In contrast, no depolarization-evoked Ca2+ responses were observed in GFP-expressing taste cells of either genotype, but GFP-labeled cells responded to the PLC activator m-3M3FBS, suggesting that these cells were viable. Whole cell recording indicated that the GFP-labeled cells of both genotypes had small voltage-dependent Na+ and K+ currents, but no evidence of Ca2+ currents. A subset of non-GFP labeled taste cells exhibited large voltage-dependent Na+ and K+ currents and a high threshold voltage-gated Ca2+ current. Immunocytochemistry indicated that SNAP-25 was expressed in a separate population of taste cells from those expressing T1R3 or TRPM5. These data indicate that G protein-coupled taste receptors and conventional synaptic signaling mechanisms are expressed in separate populations of taste cells.The taste receptor cells responsible for the transduction of bitter, sweet, and umami stimuli are unlikely to communicate with nerve fibers by using conventional chemical synapses.Taste buds, the transducing elements of gustatory sensation, contain a heterogeneous population of 50 to 100 elongate taste receptor cells, which extend from the basal lamina to the surface of the epithelium. Taste stimuli interact with receptors on the apical membrane, while the basolateral membranes of some taste cells associate with gustatory nerve fibers to transmit taste information to the brain.Several types of taste cells have been identified morphologically. Type I cells, also known as "dark" cells, generally comprise about half of the taste bud. These cells are not believed to have a receptive function, but to play a more glial-like role in the taste bud [1,2]. About 35% of the cells are Type II cells, which are also known as "light" cells due to the electron lucent nature of their cytoplasm. Type II cells express T1R and T2R taste re
Immunocytochemical evidence for co-expression of Type III IP3 receptor with signaling components of bitter taste transduction
Tod R Clapp, Leslie M Stone, Robert F Margolskee, Sue C Kinnamon
BMC Neuroscience , 2001, DOI: 10.1186/1471-2202-2-6
Abstract: Antibodies against Type I, II, and III IP3 receptors were tested on sections of rat and mouse circumvallate papillae. Robust cytoplasmic labeling for the Type III IP3 receptor (IP3R3) was found in a large subset of taste cells in both species. In contrast, little or no immunoreactivity was seen with antibodies against the Type I or Type II IP3 receptors. To investigate the potential role of IP3R3 in bitter taste transduction, we used double-label immunocytochemistry to determine whether IP3R3 is expressed in the same subset of cells expressing other bitter signaling components. IP3R3 immunoreactive taste cells were also immunoreactive for PLCβ2 and γ13. Alpha-gustducin immunoreactivity was present in a subset of IP3R3, PLCβ2, and γ13 positive cells.IP3R3 is the dominant form of the IP3 receptor expressed in taste cells and our data suggest it plays an important role in bitter taste transduction.Taste receptor cells are specialized epithelial cells, which are organized into discrete endorgans called taste buds. Typical taste buds contain 50-100 polarized taste cells, which extend from the basal lamina to the taste pore, where apical microvilli protrude into the oral cavity. The basolateral membrane forms chemical synapses with primary gustatory neurons (Fig. 1A). In mammals, lingual taste buds are housed in connective tissue structures called papillae. Fungiform papillae are located on the anterior two-thirds of the tongue and typically contain 1-2 taste buds each. Vallate and foliate papillae are found on the posterior tongue and house several hundred taste buds each. Taste transduction begins when sapid stimuli interact with the apical membrane of taste cells, usually resulting in taste cell depolarization, calcium influx, and transmitter release onto gustatory afferent neurons. Simple stimuli, such as salts and acids depolarize taste cells by direct interaction with apical ion channels. In contrast, complex stimuli, such as sugars, amino acids, and most bitter com
The Bamboo-Eating Giant Panda (Ailuropoda melanoleuca) Has a Sweet Tooth: Behavioral and Molecular Responses to Compounds That Taste Sweet to Humans
Peihua Jiang, Jesusa Josue-Almqvist, Xuelin Jin, Xia Li, Joseph G. Brand, Robert F. Margolskee, Danielle R. Reed, Gary K. Beauchamp
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0093043
Abstract: A growing body of behavioral and genetic information indicates that taste perception and food sources are highly coordinated across many animal species. For example, sweet taste perception is thought to serve to detect and motivate consumption of simple sugars in plants that provide calories. Supporting this is the observation that most plant-eating mammals examined exhibit functional sweet perception, whereas many obligate carnivores have independently lost function of their sweet taste receptors and exhibit no avidity for simple sugars that humans describe as tasting sweet. As part of a larger effort to compare taste structure/function among species, we examined both the behavioral and the molecular nature of sweet taste in a plant-eating animal that does not consume plants with abundant simple sugars, the giant panda (Ailuropoda melanoleuca). We evaluated two competing hypotheses: as plant-eating mammals, they should have a well-developed sweet taste system; however, as animals that do not normally consume plants with simple sugars, they may have lost sweet taste function, as has occurred in strict carnivores. In behavioral tests, giant pandas avidly consumed most natural sugars and some but not all artificial sweeteners. Cell-based assays revealed similar patterns of sweet receptor responses toward many of the sweeteners. Using mixed pairs of human and giant panda sweet taste receptor units (hT1R2+gpT1R3 and gpT1R2+hT1R3) we identified regions of the sweet receptor that may account for behavioral differences in giant pandas versus humans toward various sugars and artificial sweeteners. Thus, despite the fact that the giant panda's main food, bamboo, is very low in simple sugars, the species has a marked preference for several compounds that taste sweet to humans. We consider possible explanations for retained sweet perception in this species, including the potential extra-oral functions of sweet taste receptors that may be required for animals that consume plants.
Cancer: Tumor Iron Metabolism, Mitochondrial Dysfunction and Tumor Immunosuppression; “A Tight Partnership—Was Warburg Correct?”  [PDF]
Robert L. Elliott, Jonathan F. Head
Journal of Cancer Therapy (JCT) , 2012, DOI: 10.4236/jct.2012.34039
Abstract: Over the last 30 years there have been numerous worldwide investigators involved in cancer research. Billions of dollars have been spent on drug development and cancer research; however, with all of the new agents and modalities of treatment, we have honestly not significantly improved the overall survival of the Stage IV cancer patient. There is and will not be a magic bullet treatment, thus the extensive title of this paper. We are convinced that unless we use multiple innovative therapies in combination with conventional treatment, we will never truly defeat this disease. We have attempted to address this problem by presenting in detail some of these complex mechanisms involved in tumorigenesis, progression, escape, and metastasis. Most investigators have their own special area of interest, but if we are to conquer this scourge, we must develop an extensive, multifaceted, comprehensive approach. Hopefully this article will contribute to awareness and further insight into this very serious and complicated problem, so we can improve quality of life and improve the survival of the Stage IV cancer patient.
Hydrodynamical Accretion Onto Sgr A* From Distributed Point Sources
Robert F. Coker,F. Melia
Physics , 1997, DOI: 10.1086/310925
Abstract: Spectral and kinematic studies suggest that the nonthermal radio source Sgr A*, located at the center of the Milky Way, is a supermassive compact object with a mass 2-3 million solar masses. Winds from nearby stars, located approximately 0.06 pc to the east of Sgr A*, should, in the absence of any outflow from the putative black hole itself, be accreting onto this object. We report the results of the first 3D Bondi-Hoyle hydrodynamical numerical simulations of this process under the assumption that the Galactic center wind is generated by several different point sources (here assumed to be 10 pseudo-randomly placed stars). Our results show that the accretion rate onto the central object can be higher than in the case of a uniform flow since wind-wind shocks dissipate some of the bulk kinetic energy and lead to a higher capture rate for the gas. However, even for this highly non-uniform medium, most of the accreting gas carries with it a relatively low level of specific angular momentum, though large transient fluctuations can occur. Additionally, the post-bow-shock focusing of the gas can be substantially different than that for a uniform flow, but it depends strongly on the stellar spatial distribution. We discuss how this affects the morphology of the gas in the inner 0.15 pc of the Galaxy and the consequences for accretion disk models of Sgr A*.
Thermodynamic Origin of the Vitreous Transition
Robert Tournier F.
Materials , 2011, DOI: 10.3390/ma4050869
Abstract: The vitreous transition is characterized by a freezing of atomic degrees of freedom at a temperature T g depending on the heating and cooling rates. A kinetic origin is generally attributed to this phenomenon instead of a thermodynamic one which we develop here. Completed homogeneous nucleation laws reflecting the energy saving due to Fermi energy equalization of nascent crystals and their melt are used. They are applied to bulk metallic glasses and extended to inorganic glasses and polymers. A transition T* g among various T g corresponds to a crystal homogeneous nucleation temperature, leading to a preliminary formation of a cluster distribution during the relaxation time preceding the long steady-state nucleation time of crystals in small samples. The thermally-activated energy barrier ΔG* 2ls/k BT at T* g for homogeneous nucleation is nearly the same in all glass-forming melts and determined by similar values of viscosity and a thermally-activated diffusion barrier from melt to cluster. The glass transition T* g is a material constant and a linear function of the energy saving associated with charge transfers from nascent clusters to the melt. The vitreous transition and the melting temperatures alone are used to predict the free-volume disappearance temperature equal to the Vogel-Fulcher-Tammann temperature of fragile glass-forming melts, in agreement with many viscosity measurements. The reversible thermodynamic vitreous transition is determined by the disappearance temperature T* g of the fully-relaxed enthalpy H r that is not time dependent; the observed specific heat jump at T* g is equal to the proportionality coefficient of H r with (T* g ? T a) for T ≤ T* g as expected from the enthalpy excess stored by a quenched undercooled melt at the annealing temperature T a and relaxed towards an equilibrium vitreous state. However, the heat flux measurements found in literature over the last 50 years only gave an out-of-equilibrium T g since the enthalpy is continuous at T* g without visible heat jump.
Virology on the Internet: the time is right for a new journal
Robert F Garry
Virology Journal , 2004, DOI: 10.1186/1743-422x-1-1
Abstract: The outbreaks of SARS coronavirus and West Nile virus (WNV), and the troubling increase of poliovirus infections in Africa, are but a few recent examples of the unpredictable and ever-changing topography of the field of virology. Previously unknown viruses, such as the SARS coronavirus, may emerge at anytime, anywhere in the world. Viruses previously thought to be geographically restricted, such as WNV, may appear in new regions and spread rapidly. Poliovirus, once thought to be on the brink of elimination, has surged with a widespread distribution in nearly a dozen African nations that now poses a serious risk to the polio eradication initiative. Governments and individuals are increasingly aware of the threats posed by viruses, including established viruses, emerging viruses and the many viruses that are potential agents of bioterrorism. However, lack of information or misinformation regarding viruses can further exacerbate their impact on public health. There is an urgent need for a rapid forum for communications among virologists. Virology Journal will present high-quality original research concerning human, animal, plant, insect bacterial, and fungal viruses, while establishing a strategic alternative to the traditional virology communication process. Links to an extensive database of virology information on the Internet will be provided through our "All the Virology" (ATV) web site http://www.virology.net webcite.Virology Journal's Open Access policy changes the way in which articles in virology can be published [1]. First, all articles are freely and universally accessible online as soon as they are published, so an author's work can be read by anyone at no cost. Second, the authors hold copyright for their work and grant anyone the right to reproduce and disseminate the article, provided that it is correctly cited and no errors are introduced. Third, a copy of the full text of each Open Access article is permanently archived in an online repository separate
An invitation to recent graduates: publish your dissertation/thesis background section as a review in Virology Journal
Robert F Garry
Virology Journal , 2007, DOI: 10.1186/1743-422x-4-46
Abstract: May is graduation time. Over the years I have observed that a large amount of graduate student labor is spent on producing a comprehensive background section for dissertations or theses. Often, only the student and their committee (perhaps also some proud parents) are the only ones who ever read or benefit from this effort. Virology Journal will provide a mechanism for timely dissemination of this valuable information to the broader scientific community by publishing these background sections as Review Articles. Peer review will be expedited based on the notion that this background section will have already been stringently reviewed by a university committee. There are a few stipulations:1. The review should relate principally to viruses, prions or similar infectious agents.2. The dissertation/thesis has been approved by a Master's or Doctoral university committee, and all requirements for the degree have been met.3. The background section was written not more than two years ago. This requirement is in part to accommodate recent graduates, especially those of Katrina-affected institutions. In the future this requirement will be changed to not more than one year out-of-date.4. This review is a single-author publication. The author's mentor and dissertation/thesis advising committee must be listed by name in the acknowledgement section. Virology Journal considers multi-authored reviews, but these are subject to the normal course of external peer review.5. The penultimate section should be a brief summary of the experimental results obtained in the dissertation/thesis appropriately referenced.6. The final section should be a brief biographical summary of the author.7. Journal formatting must be followed, including references.8. As in all reviews, all permissions for figures published elsewhere must be obtained.9. Article fees will follow standard BMC policy. Fee waivers will be considered on a case-by-case basis.Please feel free to contact me directly, if you require a
First Encounters: Knowledge Interpretation on the Front-Lines of Cross-Cultural Encounters
Robert F. Barsky
Global Media Journal : Canadian Edition , 2012,
Abstract: The hypothesis that guides this work is that although it may be valuable to lobby for competent translators to help vulnerable foreigners in cross-cultural settings, such as the Canadian Convention refugee determination hearings or criminal trials, it is nevertheless too late to make much of a difference at that point, because most of the incriminating damage is done in the initial encounter between claimant/defendant and authority. Approaching a discussion about the relative merits of translation versus interpretation from this perspective, that emphasizes the time at which the conversation occurs, would suggest that linguistic accuracy is much more important in formal hearings, while interpretation is crucial during the initial encounter, because it is during this period of negotiation that a sensitive and qualified interpreter can keep a claimant from incriminating herself or mis-communicating the situation to authority.
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