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Search Results: 1 - 10 of 213313 matches for " Douglas L. Bayley "
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Biochemical enrichment and biophysical characterization of a taste receptor for L-arginine from the catfish, Ictalurus puntatus
William Grosvenor, Yuri Kaulin, Andrew I Spielman, Douglas L Bayley, D Lynn Kalinoski, John H Teeter, Joseph G Brand
BMC Neuroscience , 2004, DOI: 10.1186/1471-2202-5-25
Abstract: Both PHA-E and RCA-I almost exclusively labeled an 82–84 kDa protein band of an SDS-PAGE of solubilized barbel taste epithelial membranes. Further, both rhodamine-conjugated RCA-I and polyclonal antibodies raised to the 82–84 kDa electroeluted peptides labeled the apical region of catfish taste buds. Because of the specificity shown by RCA-I, lectin affinity was chosen as the first of a three-step procedure designed to enrich the presumed LGICR for L-Arg. Purified and CHAPS-solubilized taste epithelial membrane proteins were subjected successively to (1), lectin (RCA-I) affinity; (2), gel filtration (Sephacryl S-300HR); and (3), ion exchange chromatography. All fractions from each chromatography step were evaluated for L-Arg-induced ion channel activity by reconstituting each fraction into a lipid bilayer. Active fractions demonstrated L-Arg-induced channel activity that was inhibited by D-arginine (D-Arg) with kinetics nearly identical to those reported earlier for L-Arg-stimulated ion channels of native barbel membranes reconstituted into lipid bilayers. After the final enrichment step, SDS-PAGE of the active ion channel protein fraction revealed a single band at 82–84 kDa which may be interpreted as a component of a multimeric receptor/channel complex.The data are consistent with the supposition that the L-Arg receptor is a LGICR. This taste receptor remains active during biochemical enrichment procedures. This is the first report of enrichment of an active LGICR from the taste system of vertebrata.The initial event in taste transduction involves recognition of taste stimuli by plasma membrane-associated receptor proteins. These proteins are concentrated at the apical end of specialized neuro-epithelial cells (taste cells) found within multicellular end-organs known as taste buds [1,2]. The recognition binding sites for most taste stimuli face the exterior environment. The interaction of a taste stimulus with this recognition site triggers a chain of metabolic an
Sour Ageusia in Two Individuals Implicates Ion Channels of the ASIC and PKD Families in Human Sour Taste Perception at the Anterior Tongue
Taufiqul Huque, Beverly J. Cowart, Luba Dankulich-Nagrudny, Edmund A. Pribitkin, Douglas L. Bayley, Andrew I. Spielman, Roy S. Feldman, Scott A. Mackler, Joseph G. Brand
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0007347
Abstract: Background The perception of sour taste in humans is incompletely understood at the receptor cell level. We report here on two patients with an acquired sour ageusia. Each patient was unresponsive to sour stimuli, but both showed normal responses to bitter, sweet, and salty stimuli. Methods and Findings Lingual fungiform papillae, containing taste cells, were obtained by biopsy from the two patients, and from three sour-normal individuals, and analyzed by RT-PCR. The following transcripts were undetectable in the patients, even after 50 cycles of amplification, but readily detectable in the sour-normal subjects: acid sensing ion channels (ASICs) 1a, 1β, 2a, 2b, and 3; and polycystic kidney disease (PKD) channels PKD1L3 and PKD2L1. Patients and sour-normals expressed the taste-related phospholipase C-β2, the δ-subunit of epithelial sodium channel (ENaC) and the bitter receptor T2R14, as well as β-actin. Genomic analysis of one patient, using buccal tissue, did not show absence of the genes for ASIC1a and PKD2L1. Immunohistochemistry of fungiform papillae from sour-normal subjects revealed labeling of taste bud cells by antibodies to ASICs 1a and 1β, PKD2L1, phospholipase C-β2, and δ-ENaC. An antibody to PKD1L3 labeled tissue outside taste bud cells. Conclusions These data suggest a role for ASICs and PKDs in human sour perception. This is the first report of sour ageusia in humans, and the very existence of such individuals (“natural knockouts”) suggests a cell lineage for sour that is independent of the other taste modalities.
Inflammation in sputum relates to progression of disease in subjects with COPD: a prospective descriptive study
David G Parr, Andrew J White, Darren L Bayley, Peter J Guest, Robert A Stockley
Respiratory Research , 2006, DOI: 10.1186/1465-9921-7-136
Abstract: A cohort of 56 patients with chronic bronchitis was characterized in the stable state at baseline and after an interval of four years, using physiological measures and CT densitometry. Sputum markers of airway inflammation were quantified at baseline from spontaneously produced sputum in a sub-group (n = 38), and inflammation severity was related to subsequent disease progression.Physiological and CT measures indicated disease progression in the whole group. In the sub-group, sputum myeloperoxidase correlated with decline in FEV1 (rs = -0.344, p = 0.019, n = 37). LTB4 and albumin leakage correlated with TLCO decline (rs = -0.310, p = 0.033, rs = -0.401, p = 0.008, respectively, n = 35) and IL-8 correlated with progression of lung densitometric indices (rs = -0.464, p = 0.005, n = 38).The data support a principal causative role for neutrophilic inflammation in the pathogenesis of COPD and suggest that the measurement of sputum inflammatory markers may have a predictive role in clinical practice.Chronic obstructive pulmonary disease (COPD) is a slowly progressive condition characterised by airflow obstruction that is 'not fully reversible' [1]. The main aetiological factor is cigarette smoking and it is generally accepted that the pathogenic mechanism is the development of an abnormal inflammatory response to inhaled particles and gases in the lung. Exposure to tobacco smoke appears to be universally associated with lung inflammation, but only a proportion of smokers develop COPD. Nevertheless, an enhanced inflammatory response has been demonstrated in the lungs of susceptible individuals that is more marked with continuing exposure to tobacco smoke [2] and the level of inflammation has been shown to relate to disease severity [3-6]. In addition, sputum neutrophilia has been related to FEV1 decline over the preceding 15 years [7]. Consequently, lung inflammation is likely to play a primary pathogenic role and offers a common unifying theme to the varied clinical pheno
The TNFalpha gene relates to clinical phenotype in alpha-1-antitrypsin deficiency
Alice M Wood, Matthew J Simmonds, Darren L Bayley, Paul R Newby, Stephen C Gough, Robert A Stockley
Respiratory Research , 2008, DOI: 10.1186/1465-9921-9-52
Abstract: 424 unrelated subjects of the PiZZ genotype were assessed for history of chronic bronchitis, impairment of lung function and radiological presence of emphysema and bronchiectasis. A subset of subjects with 3 years consecutive lung function data was assessed for decline of lung function. Four single nucleotide polymorphisms (SNPs) tagging TNFα were genotyped using TaqMan? genotyping technologies and compared between subjects affected by each phenotype and those unaffected. Plasma TNFα levels were measured in all PiZZ subjects.All SNPs were in Hardy-Weinberg equilibrium. A significant difference in rs361525 genotype (p = 0.01) and allele (p = 0.01) frequency was seen between subjects with and without chronic bronchitis, independent of the presence of other phenotypes. TNFα plasma level showed no phenotypic or genotypic associations.Variation in TNFα is associated with chronic bronchitis in AATD.Chronic obstructive pulmonary disease (COPD) is thought to be the result of environmental triggers in genetically susceptible individuals. Although cigarette smoking is the main environmental risk factor, only about 15% of smokers develop clinically significant disease[1], suggesting other influences on disease expression. This is supported by family studies showing ancestral aggregation of spirometric abnormalities both in the general population [2] and in relatives of patients with COPD [3]. Moreover, differences in rate of decline of lung function between smokers[4] suggests a gene-environment interaction.COPD is associated with an abnormal inflammatory response in which proteases[5] and oxidants[6] play a significant pathogenic role. Inflammation is particularly important in systemic disease and associated co-morbidities[7]. Tumour necrosis factor alpha (TNFα) is an inflammatory cytokine which is elevated in the sputum[8], bronchial biopsies[9] and circulation [10] of COPD patients. The TNFα gene (TNFα) has been investigated in several COPD phenotypes [11-14] but in general
The evolution of nonlinear dynamics in political science and public administration: Methods, modeling and momentum
L. Douglas Kiel
Discrete Dynamics in Nature and Society , 2000, DOI: 10.1155/s1026022600000571
Abstract: This paper examines the evolution of the application of nonlinear dynamics and related methods to the study of political science and public administration throughout the 20th century. Some analysts understood the importance of nonlinearity to political and administrative studies in the early part of the century. More recently, a growing number of scholars understand that the political and administrative worlds are ripe with nonlinearity and thus amenable to nonlinear dynamical techniques and models. The current state of the application of both discrete and continuous time models in political science and public administration are presented. There is growing momentum in political and public administration studies that may serve to enhance the realism and applicability of these sciences to a nonlinear world.
Transposons that clean up after themselves
Douglas L Chalker
Genome Biology , 2009, DOI: 10.1186/gb-2009-10-6-224
Abstract: The genomes of eukaryotes are littered with transposon-derived sequences. As much as 45% of the human genome is composed of various types of mobile DNA elements or their remnants [1], and in plants such as maize, more than 60% of the genome consists of such repetitive sequences [2]. The ability of transposons to take over large chunks of genomes has given them the reputation of being selfish elements only interested in their own propagation. The fact that movement of these sequences into genes can inactivate genes and cause disease [3] is further evidence that they are up to no good. But can sequences that make up such a large fraction of genomes be all bad?It is quite possible that mobile DNAs have positive influences on genomes that outweigh their deleterious effects [4]. Transposons do provide novel sequences that can be exploited by their host cells. Several examples are known of transposon functions that have been 'domesticated'; that is, a once-foreign sequence has been co-opted to carry out a host process (reviewed in [5]). For example, what was once probably some element's transposase, the enzyme that mediates the movement into and out of DNA, is now the mammalian Rag1/2 recombinase. This domestication event spurred the innovation of immunoglobulin gene rearrangement and the advent of the vertebrate adaptive immune system. The Rag1/2 proteins recognize recombination signal sequences (RSS), probably also derived from the transposon, that border hundreds of variable exons. Excision of the intervening sequences between selected exons leads to the assembly of a unique immunoglobulin gene from a non-expressible precursor locus [6]. This recombinase can be made to perform the reverse reaction and insert RSS-bound DNA into a target sequence, thereby acting as a transposase and supporting its likely transposon origin [7,8]. In a paper published recently in Science, Laura Landweber and colleagues (Nowacki et al. [9]) investigate another instance of the domestication
Functional genomics does not have to be limited to a few select organisms
Douglas L Crawford
Genome Biology , 2001, DOI: 10.1186/gb-2001-2-1-interactions1001
Abstract: In response to Andrew Murray's article 'Whither Genomics' (Genome Biology 2000, 1:comment003), I would like to take issue with the assertion that "genomics will accelerate the migration of biologists to...humans, mice, fruit-flies, worms, yeast and Arabidopsis". Functional genomic studies attempt to relate genome sequences to functional changes in an organism. If we are seeking to understand the functional importance of DNA sequences and how patterns of mRNA expression affect the biology of organisms, one of the more productive approaches is to follow August Krogh's principle [1]: for many problems there will be an animal in which it can be most conveniently studied. Thus, functional genomics will be enhanced by a comparative approach: studying a diversity of organisms, in which physiological, developmental or biochemical traits are more readily determined. Unfortunately, many believe that functional genomics is only suited for 'model species' or, more accurately, species that are well defined genetically.The strength of the comparative approach lies in the use of species or groups of species best suited to address specific physiological or biochemical processes. For example, Hans Krebs's research depended on muscle tissue from the common dove to elucidate the 'Krebs' cycle [2]. Krebs's Nobel Prize winning (1953) research used this non-model species because the breast muscle was rich in mitochondria and these organelles were 'tough' [3]. Warburg (Nobel Prize, 1931) used a wide range of species in his elucidation of metabolic principles [4,5]. The Nobel Prize for the fundamental work on neural conduction by Hodgkin and Huxley depended on the use of the giant nerve fiber of the squid Loligo [6,7]. The basic research on sodium transport was done using toad bladder [8]. The elucidation of acetylcholine esterase's role in neural impulses used the electric organ of the fish Electrophorns electricus [9]. Isolation of influenza virus used the ferret [10]. Studies of nuclear
On universal common ancestry, sequence similarity, and phylogenetic structure: the sins of P-values and the virtues of Bayesian evidence
Douglas L Theobald
Biology Direct , 2011, DOI: 10.1186/1745-6150-6-60
Abstract: For the real universal protein sequences, hierarchical phylogenetic structure (induced by genealogical history) is the overriding reason for why the tests choose UCA; sequence similarity is a relatively minor factor. First, for cases of conflicting phylogenetic structure, the tests choose independent ancestry even with highly similar sequences. Second, certain models, like star trees and K&W's profile model (corresponding to their simulation), readily explain sequence similarity yet lack phylogenetic structure. However, these are extremely poor models for the real proteins, even worse than independent ancestry models, though they explain K&W's artificial data well. Finally, K&W's simulation is an implementation of a well-known phylogenetic model, and it produces sequences that mimic homologous proteins. Therefore the model selection tests work appropriately with the artificial data.For K&W's artificial protein data, sequence similarity is the predominant factor influencing the preference for common ancestry. In contrast, for the real proteins, model selection tests show that phylogenetic structure is much more important than sequence similarity. Hence, the model selection tests demonstrate that real universally conserved proteins are homologous, a conclusion based primarily on the specific nested patterns of correlations induced in genetically related protein sequences.This article was reviewed by Rob Knight, Robert Beiko (nominated by Peter Gogarten), and Michael Gilchrist.In a recent study, I applied model selection theory to a data set of universally conserved protein sequences, in an attempt to formally quantify the phylogenetic evidence for and against the theory of universal common ancestry (UCA) [1]. For the conserved protein data, this study demonstrated that UCA is a much more probable model than competing independent ancestry models. One of the notable strengths of this study is that it provides evidence for common ancestry without recourse to the common a
Aprender Uma Nova Língua : D. Carlos e a Arte da Biografia Histórica
Douglas L. Wheeler
Rela??es Internacionais (R:I) , 2008,
Effect of C–O Bonding on the Stability and Energetics of High-Energy Nitrogen-Carbon Molecules N10C2 and N16C2
Douglas L. Strout
Advances in Chemistry , 2014, DOI: 10.1155/2014/175384
Abstract: Molecules consisting of nitrogen have been the subject of much attention due to their potential as high-energy materials. Complex molecules consisting entirely of nitrogen can be subject to rapid decomposition, and therefore other atoms are incorporated into the structure to enhance stability. Previous studies have explored the incorporation of carbon atoms into otherwise all-nitrogen cages molecules. The current study involves two such cages, N10C2 and N16C2, whose structures are derived from N12 and N18, respectively. The N10C2 and N16C2 cages in this study are modified by bonding groups O3 and CO3 to determine the effect on the relative energies between the isomers and on the thermodynamic energy release properties. Energetic trends for N10C2 and N16C2 are calculated and discussed. 1. Introduction Molecules consisting entirely or predominantly of nitrogen have been the subject of much research because of their potential as high-energy materials. Decomposition reactions of the type can be exothermic by up to 50?kcal/mol per nitrogen atom (approximately 3.5 kilocalories per gram of material). Experimental synthetic successes in high-energy nitrogen materials include the and ions [1–4] as well as various azido compounds [5–9] and even a network polymer of nitrogen [10]. Additionally, nitrogen-rich salts [11] and the N7O+ ion [12] have been achieved experimentally. The production of such a diverse group of nitrogen systems demonstrates the potential for such materials as novel high-energy molecules. Nitrogen-based energetic systems have also been the subject of much theoretical research. Theoretical studies of high-energy nitrogen include cyclic and acyclic compounds [13–20], as well as nitrogen cages [21–27]. Structures and thermodynamics of energetic nitrogen systems have been calculated for both small molecules and larger structures with up to seventy-two atoms. Theoretical studies [28] of cage isomers of N24, N30, and N36 showed that the most stable isomers are narrow cylindrical structures consisting of bands of hexagons capped by triangle-pentagon endcaps in either or point group symmetry. A previous study [29] of molecules of N22C2 showed that the most stable isomer has a C2 parallel to the long axis of the molecule, which allows the C2 unit and its C=C double bond the most planar, ethylene-like environment. The least stable isomers have the C2 unit in proximity to the triangular endcaps, where angle strain around the C=C double bond becomes a destabilizing factor. In the current study, the smaller analogues N10C2 and N16C2 are considered, with
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