Bioinformatics for Membrane Lipid Simulations: Models, Computational Methods, and Web Server Tools

Biological membranes are complex environments consisting of different types of lipids and membrane proteins. The structure of a lipid bilayer is typically difficult to study because the membrane liquid crystalline state is made up of multiple disordered lipid molecules. This complicates the description of the lipid membrane properties by the conformation of any single lipid molecule. Molecular dynamics (MD) simulations have been used extensively to investigate properties of membrane lipids, lipid vesicles, and membrane protein systems. All-atom membrane models can elucidate detailed contacts between membrane proteins and its surrounding lipids, while united-atom and coarse-grained description have allowed larger models and longer timescales up to microsecond mark to be probed. Additionally, membrane models with mixed phospholipids and lipopolysaccharide content have made it possible to model improved views of biological membranes. Here, we present an overview of commonly used lipid force fields by the biosimulation community, useful tools for membrane MD simulations, and recent advances in membrane simulations

The Full Range of Predictions for B Physics From Iso-singlet Down Quark Mixing

We extend the range of predictions of the isosinglet (or vector) down quark model to the fully allowed physical ranges, and also update this with the effect of new physics constraints. We constrain the present allowed ranges of sin(2*beta) and sin(2*alpha), gamma, x_s, and A_{B_s}. In models allowing mixing to a new isosinglet down quark (as in E_6) flavor changing neutral currents are induced that allow a Z^0 mediated contribution to B-Bbar mixing and which bring in new phases. In (rho, eta), (x_s, sin(gamma)), and (x_s, A_{B_s}) plots for the extra isosinglet down quark model which are herein extended to the full physical range, we find new allowed regions that will require experiments on sin(gamma) and/or x_s to verify or to rule out an extra down quark contribution.Comment: 13 pages in RevTeX, 7 postscript figure

Sexual health and fertility in Duchenne muscular dystrophy—An exploratory study

Introduction/Aims Recent clinical guidelines recommend that adolescents with Duchenne muscular dystrophy (DMD) who are on daily glucocorticoid treatment should be offered pubertal induction in order to ensure adult levels of sex hormones as they reach adulthood. However, it remains unclear how gonadal status, including androgen concentrations, impacts physical function and future fertility. The aim of this study was to give a voice to adults with DMD, exploring their perspectives around sexual health, hormone treatment, and fertility. Methods Qualitative data was collected from six adults with DMD through two online focus groups. Participants were recruited through Pathfinders Neuromuscular Alliance and Duchenne UK and invited to take part if they had DMD and were 18 years of age or older. Conversations were transcribed verbatim and an interpretivist paradigm was used with thematic analysis. Results The main themes identified were (1) the need for communication and information about sexual health, (2) dealing with the potential fear of rejection, (3) physical barriers to relationships including sex, (4) testosterone supplementation in DMD, and (5) parenthood and fertility. Discussion We recommend that clinicians work with young people with DMD individually, to explore the benefits of testosterone treatment for them and their personal sexual health needs. If they are offered treatment, this should always be accompanied by the opportunity for psychological support. This work highlights the need for further research to establish the role of testosterone supplementation in adults with DMD and its effects on fertility and the value of specific emotional and practical support for sexual health

Fundamental thickness limit of itinerant ferromagnetic SrRuO3_3 thin films

We report on a fundamental thickness limit of the itinerant ferromagnetic oxide SrRuO$_3$ that might arise from the orbital-selective quantum confinement effects. Experimentally, SrRuO$_3$ films remain metallic even for a thickness of 2 unit cells (uc), but the Curie temperature, T$_C$, starts to decrease at 4 uc and becomes zero at 2 uc. Using the Stoner model, we attributed the T$_C$ decrease to a decrease in the density of states (N$_o$). Namely, in the thin film geometry, the hybridized Ru-d$_yz,zx$ orbitals are terminated by top and bottom interfaces, resulting in quantum confinement and reduction of N$_o$.Comment: 20 pages, 4 figure

Iso-singlet Down Quark Mixing And CP Violation Experiments

We confront the new physics models with extra iso-singlet down quarks in the new CP violation experimental era with $\sin{(2\beta)}$ and $\epsilon'/\epsilon$ measurements, $K^+ \to \pi^+ \nu \bar{\nu}$ events, and $x_s$ limits. The closeness of the new experimental results to the standard model theory requires us to include full SM amplitudes in the analysis. In models allowing mixing to a new isosinglet down quark, as in E$_6$, flavor changing neutral currents are induced that allow a $Z^0$ mediated contribution to $B-\bar B$ mixing and which bring in new phases. In $(\rho,\eta)$, $(x_s,\sin{(\gamma)})$, and $(x_s, \sin{(2\phi_s)})$ plots we still find much larger regions in the four down quark model than in the SM, reaching down to $\eta \approx 0$, $0 \leq \sin{(\gamma)} \leq 1$, $-.75 \leq \sin{(2\alpha)} \leq 0.15$, and $\sin{(2\phi_s)}$ down to zero, all at 1$\sigma$. We elucidate the nature of the cancellation in an order $\lambda^5$ four down quark mixing matrix element which satisfies the experiments and reduces the number of independent angles and phases. We also evaluate tests of unitarity for the $3\times3$ CKM submatrix.Comment: 14 pages, 16 figures, REVTeX

Properties of M31. II: A Cepheid disk sample derived from the first year of PS1 PAndromeda data

We present a sample of Cepheid variable stars towards M31 based on the first year of regular M31 observations of the PS1 survey in the r_P1 and i_P1 filters. We describe the selection procedure for Cepheid variable stars from the overall variable source sample and develop an automatic classification scheme using Fourier decomposition and the location of the instability strip. We find 1440 fundamental mode (classical \delta) Cep stars, 126 Cepheids in the first overtone mode, and 147 belonging to the Population II types. 296 Cepheids could not be assigned to one of these classes and 354 Cepheids were found in other surveys. These 2009 Cepheids constitute the largest Cepheid sample in M31 known so far and the full catalog is presented in this paper. We briefly describe the properties of our sample in its spatial distribution throughout the M31 galaxy, in its age properties, and we derive an apparent period-luminosity relation (PLR) in our two bands. The Population I Cepheids nicely follow the dust pattern of the M31 disk, whereas the 147 Type II Cepheids are distributed throughout the halo of M31. We outline the time evolution of the star formation in the major ring found previously and find an age gradient. A comparison of our PLR to previous results indicates a curvature term in the PLR

Androgen receptor genotyping in a large Australasian cohort with androgen insensitivity syndrome; identification of four novel mutations

We genotyped the androgen receptor (AR) gene in 31 Australasian patients with androgen insensitivity syndrome (AIS). The entire coding region of AR was examined including analysis of polymorphic CAG and GGN repeats in all patients. AR defects were found in 66.7% (6/9) of patients with complete AIS (CAIS) and 13.6% (3/22) of patients with partial AIS (PAIS). A novel deletion (N858delG) leading to a premature stop codon was found in CAIS patient P1. CAIS patient P2 has a novel deletion (N2676delGAGT) resulting in a stop at codon 787. These mutations would result in inactivation of AR protein. A novel insertion of a cysteine residue in the first zinc finger of the AR DNA-binding domain (N2045_2047dupCTG) was found in CAIS patient P3. PAIS patient P4 has a novel amino acid substitution (Arg760Ser) in the AR ligand binding domain, which may impair ligand binding. Five patients were found to have previously reported AR mutations and no mutations were identified in the remaining patients