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

Centrifuge Modelling With Transparent Soil and Laser Aided Imaging

Transparent synthetic soils have been developed as a soil surrogate to enable internal visualization of geotechnical processes in physical models. While significant developments have been made to enhance the methodology and capabilities of transparent soil modelling, the technique is not yet exploited to its fullest potential. Tests are typically conducted at 1 g in small bench size models, which invokes concerns about the impact of scale and stress level observed in previously reported work. This paper recognized this limitation and outlines the development of improved testing methodology whereby the transparent soil and laser aided imaging technique are translated to the centrifuge environment. This has a considerable benefit such that increased stresses are provided, which better reflect the prototype condition. The paper describes the technical challenges associated with implementing this revised experimental methodology, summarizes the test equipment/systems developed, and presents initial experimental results to validate and confirm the successful implementation and scaling of transparent soil testing to the high gravity centrifuge test environment. A 0.6 m wide prototype strip foundation was tested at two scales using the principle of “modelling of models,” in which similar performance was observed. The scientific developments discussed have the potential to provide a step change in transparent soil modelling methodology, crucially providing more representative stress conditions that reflect prototype conditions, while making a broader positive contribution to physical modelling capabilities to assess complex soil–structure boundary problems

Investigating the effects of particle shape on normal compression and overconsolidation using DEM

Discrete element modelling of normal compression has been simulated on a sample of breakable two-ball clumps and compared to that of spheres. In both cases the size effect on strength is assumed to be that of real silica sand. The slopes of the normal compression lines are compared and found to be consistent with the proposed equation of the normal compression line. The values of the coefficient of earth pressure at rest K0,nc are also compared and related to the critical state fiction angles for the two materials. The breakable samples have then been unloaded to establish the stress ratios on unloading. At low overconsolidation ratios the values of K0 follow a well-established empirical relationship and realistic Poisson ratios are observed. On progressive unloading both samples head towards passive failure, and the values of the critical state lines in extension in q–p' space are found to be consistent with the critical state angles deduced from the values of K0 during normal compression. The paper highlights the important role of particle shape in governing the stress ratio during both normal compression and subsequent overconsolidation

Insights into the Binding of Phenyltiocarbamide (PTC) Agonist to Its Target Human TAS2R38 Bitter Receptor

Humans' bitter taste perception is mediated by the hTAS2R subfamily of the G protein-coupled membrane receptors (GPCRs). Structural information on these receptors is currently limited. Here we identify residues involved in the binding of phenylthiocarbamide (PTC) and in receptor activation in one of the most widely studied hTAS2Rs (hTAS2R38) by means of structural bioinformatics and molecular docking. The predictions are validated by site-directed mutagenesis experiments that involve specific residues located in the putative binding site and trans-membrane (TM) helices 6 and 7 putatively involved in receptor activation. Based on our measurements, we suggest that (i) residue N103 participates actively in PTC binding, in line with previous computational studies. (ii) W99, M100 and S259 contribute to define the size and shape of the binding cavity. (iii) W99 and M100, along with F255 and V296, play a key role for receptor activation, providing insights on bitter taste receptor activation not emerging from the previously reported computational models

Does the Potential for Chaos Constrain the Embryonic Cell-Cycle Oscillator?

Although many of the core components of the embryonic cell-cycle network have been elucidated, the question of how embryos achieve robust, synchronous cellular divisions post-fertilization remains unexplored. What are the different schemes that could be implemented by the embryo to achieve synchronization? By extending a cell-cycle model previously developed for embryos of the frog Xenopus laevis to include the spatial dimensions of the embryo, we establish a novel role for the rapid, fertilization-initiated calcium wave that triggers cell-cycle oscillations. Specifically, in our simulations a fast calcium wave results in synchronized cell cycles, while a slow wave results in full-blown spatio-temporal chaos. We show that such chaos would ultimately lead to an unpredictable patchwork of cell divisions across the embryo. Given this potential for chaos, our results indicate a novel design principle whereby the fast calcium-wave trigger following embryo fertilization synchronizes cell divisions