The Predicted Binding Site and Dynamics of Peptide Inhibitors to the Methuselah GPCR from Drosophila melanogaster

Peptide inhibitors of Methuselah (Mth), a G protein-coupled receptor (GPCR), were reported that can extend the life span of Drosophila melanogaster. Mth is a class B GPCR, which is characterized by a large, N-terminal ectodomain that is often involved with ligand recognition. The crystal structure of the Mth ectodomain, which binds to the peptide inhibitors with high affinity, was previously determined. Here we report the predicted structures for RWR motif peptides in complex with the Mth ectodomain. We studied representatives of both Pro-class and Arg-class RWR motif peptides and identified ectodomain residues Asp139, Phe130, Asp127, and Asp78 as critical in ligand binding. To validate these structures, we predicted the effects of various ligand mutations on the structure and binding to Mth. The binding of five mutant peptides to Mth was characterized experimentally by surface plasmon resonance, revealing measured affinities that are consistent with predictions. The electron density map calculated from our MD structure compares well with the experimental map of a previously determined peptide/Mth crystal structure and could be useful in refining the current low-resolution data. The elucidation of the ligand binding site may be useful in analyzing likely binding sites in other class B GPCRs

Predicted Structures and Dynamics for Agonists and Antagonists Bound to Serotonin 5-HT2B and 5-HT2C Receptors

Subtype 2 serotonin (5-hydroxytryptamine, 5-HT) receptors are major drug targets for schizophrenia, feeding disorders, perception, depression, migraines, hypertension, anxiety, hallucinogens, and gastrointestinal dysfunctions.' We report here the predicted structure of 5-HT2B and 5-HT2C receptors bound to highly potent and selective 5-HT2B antagonist PRX-08066 3, (pKi: 30 nM), including the key binding residues [V103 (2.53), L132 (3.29), V190 (4.60), and L347 (6.58)] determining the selectivity of binding to 5-HT2B over 5-HT2A. We also report structures of the endogenous agonist (5 HT) and a HT2B selective antagonist 2 (1-methyl-1-1,6,7,8-tetrahydro-pyrrolo [2,3-g]quinoline-5-carboxylic acid pyridine-3-ylamide). We examine the dynamics for the agonist-and antagonist-bound HT2B receptors in explicit membrane and water finding dramatically different patterns of water migration into the NPxxY motif and the binding site that correlates with the stability of ionic locks in the D(E)RY region

A cohort study of the associations between udder conformation, milk somatic cell count, and lamb weight in suckler ewes

A cohort study of 67 suckler ewes from 1 farm was carried out from January to May 2010 to investigate associations between udder conformation, udder half milk somatic cell count (SCC), and lamb weight. Ewes and lambs were observed at lambing. Ewe health and teat condition and lamb health and weight were recorded on 4 to 5 further occasions at 14-d intervals. At each observation, a milk sample was collected from each udder half for somatic cell counting. Two weeks after lambing, ewe udder conformation and teat placement were scored. Low lamb weight was associated with ewe SCC >400,000 cells/mL (−0.73kg), a new teat lesion 14 d previously (−0.91kg), suboptimal teat position (−1.38kg), rearing in a multiple litter (−1.45kg), presence of diarrhea at the examination (−1.19kg), and rearing by a 9-yr-old ewe compared with a 6-yr-old ewe (−2.36kg). High lamb weight was associated with increasing lamb age (0.21kg/d), increasing birth weight (1.65kg/kg at birth), and increasing number of days the ewe was given supplementary feed before lambing (0.06kg/d). High udder half SCC was associated with pendulous udders (9.6% increase in SCC/cm of drop) and greater total cross-sectional area of the teats (7.2% increase of SCC/cm2). Low SCC were associated with a heavier mean litter weight (6.7% decrease in SCC/kg). Linear, quadratic, and cubic terms for days in lactation were also significant. We conclude that poor udder and teat conformation are associated with high levels of intramammary infection, as indicated by increased SCC and that both physical attributes of the udder and SCC are linked to lamb growth, suggesting that selection of suckler ewes with better udder and teat conformation would reduce intramammary infection and increase lamb growth rate

Robust Multi-Image HDR Reconstruction for the Modulo Camera

Photographing scenes with high dynamic range (HDR) poses great challenges to consumer cameras with their limited sensor bit depth. To address this, Zhao et al. recently proposed a novel sensor concept - the modulo camera - which captures the least significant bits of the recorded scene instead of going into saturation. Similar to conventional pipelines, HDR images can be reconstructed from multiple exposures, but significantly fewer images are needed than with a typical saturating sensor. While the concept is appealing, we show that the original reconstruction approach assumes noise-free measurements and quickly breaks down otherwise. To address this, we propose a novel reconstruction algorithm that is robust to image noise and produces significantly fewer artifacts. We theoretically analyze correctness as well as limitations, and show that our approach significantly outperforms the baseline on real data.Comment: to appear at the 39th German Conference on Pattern Recognition (GCPR) 201

Entanglement-assisted codeword stabilized quantum codes

Entangled qubit can increase the capacity of quantum error correcting codes based on stabilizer codes. In addition, by using entanglement quantum stabilizer codes can be construct from classical linear codes that do not satisfy the dual-containing constraint. We show that it is possible to construct both additive and non-additive quantum codes using the codeword stabilized quantum code framework. Nonadditive codes may offer improved performance over the more common sta- bilizer codes. Like other entanglement-assisted codes, the encoding procedure acts only the qubits on Alice's side, and only these qubits are assumed to pass through the channel. However, errors the codeword stabilized quantum code framework gives rise to effective Z errors on Bob side. We use this scheme to construct new entanglement-assisted non-additive quantum codes, in particular, ((5,16,2;1)) and ((7,4,5;4)) codes

Magnetic interactions in transition metal doped ZnO : An abinitio study

We calculate the nature of magnetic interactions in transition-metal doped ZnO using the local spin density approximation and LSDA+\textit{U} method of density functional theory. We investigate the following four cases: (i) single transition metal ion types (Cr, Mn, Fe, Co, Ni and Cu) substituted at Zn sites, (ii) substitutional magnetic transition metal ions combined with additional Cu and Li dopants, (iii) substitutional magnetic transition metal ions combined with oxygen vacancies and (iv) pairs of magnetic ion types (Co and Fe, Co and Mn, etc.). Extensive convergence tests indicate that the calculated magnetic ground state is unusually sensitive to the k-point mesh and energy cut-off, the details of the geometry optimizations and the choice of the exchange-correlation functional. We find that ferromagnetic coupling is sometimes favorable for single type substitutional transition metal ions within the local spin density approximation. However, the nature of magnetic interactions changes when correlations on the transition-metal ion are treated within the more realistic LSDA + \textit{U} method, often disfavoring the ferromagnetic state. The magnetic configuration is sensitive to the detailed arrangement of the ions and the amount of lattice relaxation, except in the case of oxygen vacancies when an antiferromagnetic state is always favored.Comment: 11 pages, 17 figure

Z_3 Strings and their Interactions

We construct Z_3 vortex solutions in a model in which SU(3) is spontaneously broken to Z_3. The model is truncated to one in which there are only two dimensionless free parameters and the interaction of vortices within this restricted set of models is studied numerically. We find that there is a curve in the two dimensional space of parameters for which the energy of two asymptotically separated vortices equals the energy of the vortices at vanishing separation. This suggests that the inter-vortex potential for Z_3 strings might be flat for these couplings, much like the case of U(1) strings in the Bogomolnyi limit. However, we argue that the intervortex potential is attractive at short distances and repulsive at large separations leading to the possibility of unstable bound states of Z_3 vortices.Comment: 8 pages; mainly corrected typos in table