The Lymnaea Cardioexcitatory Peptide (LyCEP) Receptor: A G-Protein–Coupled Receptor for a Novel Member of the RFamide Neuropeptide Family

A novel G-protein–coupled receptor (GRL106) resembling neuropeptide Y and tachykinin receptors was cloned from the molluscLymnaea stagnalis. Application of a peptide extract from the Lymnaea brain to Xenopus oocytes expressing GRL106 activated a calcium-dependent chloride channel. Using this response as a bioassay, we purified the ligand for GRL106,Lymnaea cardioexcitatory peptide (LyCEP), an RFamide-type decapeptide (TPHWRPQGRF-NH2) displaying significant similarity to the Achatina cardioexcitatory peptide (ACEP-1) as well as to the recently identified family of mammalian prolactin-releasing peptides. In the Lymnaeabrain, the cells that produce egg-laying hormone are the predominant site of GRL106 gene expression and appear to be innervated by LyCEP-containing fibers. Indeed, LyCEP application transiently hyperpolarizes isolated egg-laying hormone cells. In theLymnaea pericardium, LyCEP-containing fibers end blindly at the pericardial lumen, and the heart is stimulated by LyCEPin vitro. These data confirm that LyCEP is an RFamide ligand for GRL10

Two-body Photodisintegration of 4^{4}He with Full Final State Interaction

The cross sections of the processes $^4$He($\gamma,p$)$^3$H and $^4$He($\gamma,n$)$^3$He are calculated taking into account the full final state interaction via the Lorentz integral transform (LIT) method. This is the first consistent microscopic calculation beyond the three--body breakup threshold. The results are obtained with a semirealistic central NN potential including also the Coulomb force. The cross sections show a pronounced dipole peak at 27 MeV which lies within the rather broad experimental band. At higher energies, where experimental uncertainties are considerably smaller, one finds a good agreement between theory and experiment. The calculated sum of three-- and four--body photodisintegration cross sections is also listed and is in fair agreement with the data.Comment: 18 pages, 6 figure

Characterization of the Modes of Binding between Human Sweet Taste Receptor and Low-Molecular-Weight Sweet Compounds

One of the most distinctive features of human sweet taste perception is its broad tuning to chemically diverse compounds ranging from low-molecular-weight sweeteners to sweet-tasting proteins. Many reports suggest that the human sweet taste receptor (hT1R2–hT1R3), a heteromeric complex composed of T1R2 and T1R3 subunits belonging to the class C G protein–coupled receptor family, has multiple binding sites for these sweeteners. However, it remains unclear how the same receptor recognizes such diverse structures. Here we aim to characterize the modes of binding between hT1R2–hT1R3 and low-molecular-weight sweet compounds by functional analysis of a series of site-directed mutants and by molecular modeling–based docking simulation at the binding pocket formed on the large extracellular amino-terminal domain (ATD) of hT1R2. We successfully determined the amino acid residues responsible for binding to sweeteners in the cleft of hT1R2 ATD. Our results suggest that individual ligands have sets of specific residues for binding in correspondence with the chemical structures and other residues responsible for interacting with multiple ligands

The perception of quinine taste intensity is associated with common genetic variants in a bitter receptor cluster on chromosome 12

The perceived taste intensities of quinine HCl, caffeine, sucrose octaacetate (SOA) and propylthiouracil (PROP) solutions were examined in 1457 twins and their siblings. Previous heritability modeling of these bitter stimuli indicated a common genetic factor for quinine, caffeine and SOA (22–28%), as well as separate specific genetic factors for PROP (72%) and quinine (15%). To identify the genes involved, we performed a genome-wide association study with the same sample as the modeling analysis, genotyped for approximately 610 000 single-nucleotide polymorphisms (SNPs). For caffeine and SOA, no SNP association reached a genome-wide statistical criterion. For PROP, the peak association was within TAS2R38 (rs713598, A49P, P = 1.6 × 10−104), which accounted for 45.9% of the trait variance. For quinine, the peak association was centered in a region that contains bitter receptor as well as salivary protein genes and explained 5.8% of the trait variance (TAS2R19, rs10772420, R299C, P = 1.8 × 10−15). We confirmed this association in a replication sample of twins of similar ancestry (P = 0.00001). The specific genetic factor for the perceived intensity of PROP was identified as the gene previously implicated in this trait (TAS2R38). For quinine, one or more bitter receptor or salivary proline-rich protein genes on chromosome 12 have alleles which affect its perception but tight linkage among very similar genes precludes the identification of a single causal genetic variant

Study of slab on grade thickness for racking throughout Finite Element Method

[EN] In the current paper, comparative analyses between three procedures of calculation have been developed, in order to obtain slab on grade thicknesses when the slabs are loaded with racking posts. For this case, the classical expression of Westergaard cannot be applied directly because of the influence of the remainder posts and their proximity. Firstly, the comparative analysis has been done by means of bibliographical design abacus; in the second place, the slab is discretized with finite elements resting above the soil modelled with soil reaction springs; and in third place, a three dimensional solid finite element model represents the base and subgrade set. In the paper some innovative issues regarding the thickness performance and the grade slab interaction are developed. Finally, a series of graphical results are obtained allowing for the pre-design.[ES] En el presente artículo se realiza un estudio comparativo entre tres procedimientos de cálculo para obtener espesores en soleras de hormigón ligeramente armadas por retracción, con cargas debidas a estanterías. Las fórmulas para cargas aisladas de Westergaard no tienen para este caso una aplicación directa debido a la influencia del resto de soportes y su cercanía. El estudio comparativo se realiza en primer lugar mediante nomogramas de cálculo de la bibliografía; en segundo lugar, la solera se discretiza con elementos finitos y apoya sobre el terreno modelizado con coeficiente de balasto, y en tercer lugar, mediante elementos finitos tridimensionales sólidos que representan la base y la explanada, desarrollándose aspectos novedosos en el tratamiento del conjunto solera-terreno tanto en sus expresiones como en su interacción. Asimismo, se obtienen una serie de gráficas que permiten realizar predimensionados.Ferrer Gisbert, CM.; Ferran Gozalvez, JJ.; Torregrosa Soler, JB.; Sánchez Romero, FJ.; Redón Santafé, M.; Pérez Sánchez, M. (2016). Contribución al estudio de espesores de soleras de hormigón para cargas de estanterías mediante elementos finitos. Informes de la Construcción. 68(543):1-10. doi:10.3989/ic.15.093S11068543(1) Mecalux, S. A. (2011). Manual técnico del almacenaje. Mecalux, p. 155. Mecalux, S. A.(3) Westergaard, H.M. (1926). Stresses in Concrete Pavements Computed by Theoretical Analysis. Public Roads, 7(2): 25.(4) Pickett, G., Ray, G.K. (1951). Influence Charts for Concrete Pavements. Trans. ASCE, 116: 49.(5) Meyerhof, G.G. (1962). Load carrying capacity of concrete pavements. Journal of the Soil Mechanics and Foundations Division, Proceedings of the American Society of Civil Engineers.Shentu, L., Jiang, D., & Hsu, C.-T. T. (1997). Load-Carrying Capacity for Concrete Slabs on Grade. Journal of Structural Engineering, 123(1), 95-103. doi:10.1061/(asce)0733-9445(1997)123:1(95)(12) Fwa, T.F. (2006). The Handbook of Highway Engineering, p. 9-53. Taylor & Francis.(14) Ferrer Gisbert, C. (1998). Contribución al estudio de soleras de hormigón de industrias agroalimentarias mediante la técnica de los elementos finitos. Tesis Doctoral. Universidad Politécnica de Valencia, pp. 164-166.Look, B. G. (2007). Handbook of Geotechnical Investigation and Design Tables. doi:10.1201/9780203946602(17) Ministerio de Vivienda. (2006). CTE-DB-SE-C. Cimientos, p. 123.(18) PG3. (2007). Pliego de prescripciones técnicas generales para obras de carreteras y puentes, pp. 229-238. Liteam Ediciones.(20) Winterkorn, H.F., Fang H. (1975). Foundation Engineering Handbook, p. 519. Van Nostrand Reinhold Company.(21) PCA. (1966). Thickness Design for concrete Pavements. Portland Cement Association.(23) Escario, J.L., Escario, V., Balaguer, E. (1973). Caminos (Tomo II) Firmes de carreteras y aeropuertos, p. 982. ETSI, Caminos, Canales y Puertos, Universidad Politécnica de Madrid.(25) Australia T34. (1985). Concrete Industrial Floor and Pavement Design. Cement and Concrete Association of Australia.(26) Jofré, C., Vaquero, J.J. (2000). Manual de pavimentos industriales, pp. 60-63. IECA.(27) Wilson, E.L. (1999). Three Dimensional Static and Dynamic Analysis of Structures. Berkeley, California (USA): Computers & Structures, Inc.(28) Ferrer, C.M., Vallés, J.J. (1992). Apuntes de Construcción II. Universidad Politécnica de Valencia

Expression of taste receptors in Solitary Chemosensory Cells of rodent airways

<p>Abstract</p> <p>Background</p> <p>Chemical irritation of airway mucosa elicits a variety of reflex responses such as coughing, apnea, and laryngeal closure. Inhaled irritants can activate either chemosensitive free nerve endings, laryngeal taste buds or solitary chemosensory cells (SCCs). The SCC population lies in the nasal respiratory epithelium, vomeronasal organ, and larynx, as well as deeper in the airway. The objective of this study is to map the distribution of SCCs within the airways and to determine the elements of the chemosensory transduction cascade expressed in these SCCs.</p> <p>Methods</p> <p>We utilized a combination of immunohistochemistry and molecular techniques (rtPCR and in situ hybridization) on rats and transgenic mice where the Tas1R3 or TRPM5 promoter drives expression of green fluorescent protein (GFP).</p> <p>Results</p> <p>Epithelial SCCs specialized for chemoreception are distributed throughout much of the respiratory tree of rodents. These cells express elements of the taste transduction cascade, including Tas1R and Tas2R receptor molecules, α-gustducin, PLCβ2 and TrpM5. The Tas2R bitter taste receptors are present throughout the entire respiratory tract. In contrast, the Tas1R sweet/umami taste receptors are expressed by numerous SCCs in the nasal cavity, but decrease in prevalence in the trachea, and are absent in the lower airways.</p> <p>Conclusions</p> <p>Elements of the taste transduction cascade including taste receptors are expressed by SCCs distributed throughout the airways. In the nasal cavity, SCCs, expressing Tas1R and Tas2R taste receptors, mediate detection of irritants and foreign substances which trigger trigeminally-mediated protective airway reflexes. Lower in the respiratory tract, similar chemosensory cells are not related to the trigeminal nerve but may still trigger local epithelial responses to irritants. In total, SCCs should be considered chemoreceptor cells that help in preventing damage to the respiratory tract caused by inhaled irritants and pathogens.</p

Gustatory Imagery Reveals Functional Connectivity from the Prefrontal to Insular Cortices Traced with Magnetoencephalography

Our experience and prejudice concerning food play an important role in modulating gustatory information processing; gustatory memory stored in the central nervous system influences gustatory information arising from the peripheral nervous system. We have elucidated the mechanism of the 'top-down" modulation of taste perception in humans using functional magnetic resonance imaging (fMRI) and demonstrated that gustatory imagery is mediated by the prefrontal (PFC) and insular cortices (IC). However, the temporal order of activation of these brain regions during gustatory imagery is still an open issue. To explore the source of "top-down" signals during gustatory imagery tasks, we analyzed the temporal activation patterns of activated regions in the cerebral cortex using another non-invasive brain imaging technique, magnetoencephalography (MEG). Gustatory imagery tasks were presented by words (Letter G-V) or pictures (Picture G-V) of foods/beverages, and participants were requested to recall their taste. In the Letter G-V session, 7/9 (77.8%) participants showed activation in the IC with a latency of 401.7 +/- 34.7 ms (n = 7) from the onset of word exhibition. In 5/7 (71.4%) participants who exhibited IC activation, the PFC was activated prior to the IC at a latency of 315.2 +/- 56.5 ms (n = 5), which was significantly shorter than the latency to the IC activation. In the Picture G-V session, the IC was activated in 6/9 (66.7%) participants, and only 1/9 (11.1%) participants showed activation in the PFC. There was no significant dominance between the right and left IC or PFC during gustatory imagery. These results support those from our previous fMRI study in that the Letter G-V session rather than the Picture G-V session effectively activates the PFC and IC and strengthen the hypothesis that the PFC mediates "top-down" control of retrieving gustatory information from the storage of long-term memories and in turn activates the IC

Common Promoter Elements in Odorant and Vomeronasal Receptor Genes

In mammals, odorants and pheromones are detected by hundreds of odorant receptors (ORs) and vomeronasal receptors (V1Rs and V2Rs) expressed by sensory neurons that are respectively located in the main olfactory epithelium and in the vomeronasal organ. Even though these two olfactory systems are functionally and anatomically separate, their sensory neurons show a common mechanism of receptor gene regulation: each neuron expresses a single receptor gene from a single allele. The mechanisms underlying OR and VR gene expression remain unclear. Here we investigated if OR and V1R genes share common sequences in their promoter regions