Transmembrane helix dynamics of bacterial chemoreceptors supports a piston model of signalling.

Transmembrane α-helices play a key role in many receptors, transmitting a signal from one side to the other of the lipid bilayer membrane. Bacterial chemoreceptors are one of the best studied such systems, with a wealth of biophysical and mutational data indicating a key role for the TM2 helix in signalling. In particular, aromatic (Trp and Tyr) and basic (Arg) residues help to lock α-helices into a membrane. Mutants in TM2 of E. coli Tar and related chemoreceptors involving these residues implicate changes in helix location and/or orientation in signalling. We have investigated the detailed structural basis of this via high throughput coarse-grained molecular dynamics (CG-MD) of Tar TM2 and its mutants in lipid bilayers. We focus on the position (shift) and orientation (tilt, rotation) of TM2 relative to the bilayer and how these are perturbed in mutants relative to the wildtype. The simulations reveal a clear correlation between small (ca. 1.5 Å) shift in position of TM2 along the bilayer normal and downstream changes in signalling activity. Weaker correlations are seen with helix tilt, and little/none between signalling and helix twist. This analysis of relatively subtle changes was only possible because the high throughput simulation method allowed us to run large (n = 100) ensembles for substantial numbers of different helix sequences, amounting to ca. 2000 simulations in total. Overall, this analysis supports a swinging-piston model of transmembrane signalling by Tar and related chemoreceptors

Association of a functional microsatellite within intron 1 of the BMP5 gene with susceptibility to osteoarthritis

<p>Abstract</p> <p>Background</p> <p>In a previous study carried out by our group, the genotyping of 36 microsatellite markers from within a narrow interval of chromosome 6p12.3-q13 generated evidence for linkage and for association to female hip osteoarthritis (OA), with the most compelling association found for a marker within intron 1 of the bone morphogenetic protein 5 gene (<it>BMP5</it>). In this study, we aimed to further categorize the association of variants within intron 1 of <it>BMP5 </it>with OA through an expanded genetic association study of the intron and subsequent functional analysis of associated polymorphisms.</p> <p>Methods</p> <p>We genotyped 18 common polymorphisms including 8 microsatellites and 9 single nucleotide polymorphisms (SNPs) and 1 insertion/deletion (INDEL) from within highly conserved regions between human and mouse within intron 1 of <it>BMP5</it>. These markers were then tested for association to OA by a two-stage approach in which the polymorphisms were initially genotyped in a case-control cohort comprising 361 individuals with associated polymorphisms (<it>P </it>≤ 0.05) then genotyped in a second case-control cohort comprising 1185 individuals.</p> <p>Results</p> <p>Two <it>BMP5 </it>intron 1 polymorphisms demonstrated association in the combined case-control cohort of 1546 individuals (765 cases and 781 controls): microsatellite D6S1276 (<it>P </it>= 0.018) and SNP rs921126 (<it>P </it>= 0.013). Functional analyses in osteoblastic, chondrocytic, and adipocytic cell lines indicated that allelic variants of D6S1276 have significant effects on the transcriptional activity of the <it>BMP5 </it>promoter <it>in vitro</it>.</p> <p>Conclusion</p> <p>Variability in gene expression of <it>BMP5 </it>may be an important contributor to OA genetic susceptibility.</p

Search for R-Parity Breaking Sneutrino Exchange at LEP

We report on a search for R--parity breaking effects due to supersymmetric tau--sneutrino exchange in the reactions e+e- to e+e- and e+e- to mu+mu- at centre--of--mass energies from 91~{\GeV} to 172~{\GeV}, using the L3 detector at LEP. No evidence for deviations from the Standard Model expectations of the measured cross sections and forward--backward asymmetries for these reactions is found. Upper limits for the couplings $\lambda_{131}$ and $\lambda_{232}$ for sneutrino masses up to m_{\SNT} \leq 190~\GeV are determined from an analysis of the expected effects due to tau sneutrino exchange

Inclusive Charm Production in Two-Photon Collisions at LEP

The cross section of charm production in $\mathrm{\gamma \gamma}$ collisions $\mathrm{\sigma (e^+e^- \rightarrow e^+e^-c\bar{c} X)}$ is measured at LEP with the L3 detector at centre of mass energies from 91 GeV to 183 GeV. Charmed hadrons are identified by electrons and muons from semi-leptonic decays. The direct process $\mathrm{\gamma \gamma \rightarrow c \bar{c}}$ is found to be insufficient to describe the data. The measured cross section values and event distributions require contributions from resolved processes, which are sensitive to the gluon density in the photon

Heavy Quarkonium Production in Z Decays

We report measurements of the inclusive production of heavy quarkonium states in $\mathrm {Z}$ decays based on the analysis of 3.6 million hadronic events collected by the L3 detector at LEP. The measurement of inclusive J production and an improved $95\%$ confidence level upper limit on $\Upsilon$ production are presented. In addition, two independent measurements of the ratio, $f_{\mathrm{p}}$, of prompt J mesons to those from B decay are made using two different isolation cuts to separate prompt J mesons from J mesons produced in the decays of b hadrons. The results are: % \begin{eqnarray} \mathrm{Br}(\mathrm{Z} \rightarrow \mathrm{J} + \mathrm{X}) & = & (3.21 \pm 0.21 \; \mathrm{(stat.)} \; ^{+ 0.19}_{- 0.28} \; \mathrm{(sys.)} ) \times 10^{-3} \; , \nonumber \\ \mathrm{Br}(\mathrm {Z} \rightarrow \Upsilon(\mathrm{1S} + X) & < & 4.4 \times 10^{-5} \; , \nonumber \\ %% f_{\mathrm{p}} & = & (7.1 \pm 2.1 \; \mathrm{(stat.)} \; \pm 1.2 \; \mathrm{(sys.)} \; ^{+1.5}_{-0.8} \;\mathrm{(theo.)} ) \times 10^{-2} \; . \nonumbe

Study of Neutral-Current Four-Fermion and ZZ Production in e+e−e^+ e^- Collisions at s\sqrt{s}= 183 GeV

Study of Neutral--Current Four--Fermion and ZZ \\ Production in $\rm e^+ e^-$ Collisions at $\rm \sqrt{s}=$ 183 GeV A study of neutral--current four--fermion processes is performed using a data sample corresponding to 55.3~pb$^{-1}$ of integrated luminosity collected by the L3 detector at LEP at an average centre--of--mass energy of 183~\GeV. The neutral--current four--fermion cross sections for final states with a pair of charged leptons plus jets and with four charged leptons are measured to be consistent with the Standard Model predictions. Events with fermion pair masses close to the Z boson mass are selected in all observable final states and the ZZ production cross section is measured to be %\begin{center} $\rm \sigma_{ZZ} = 0.30 ^{+0.22\,\,+0.07}_{-0.16\,\,-0.03}\,\mathrm{pb},$ %\end{center} in agreement with the Standard Model expectation. No evidence for the existence of anomalous triple gauge boson ZZZ and ZZ$\gamma$ couplings is found and limits on these couplings are set

Determination of the number of light neutrino species from single photon production at LEP

A determination of the number of light neutrino families performed by measuring the cross section of single photon production in \ee\ collision near the \Zo\ resonance is reported. From an integrated luminosity of $100~\mathrm{pb^{-1}}$, collected during the years 1991--94, we have observed 2091 single photon candidates with an energy above 1~\GeV\ in the polar angular region $45^\circ < \theta_\gamma < 135^\circ$. From a maximum likelihood fit to the single photon cross section, the \Zo\ decay width into invisible particles is measured to be \Ginv = 498 \pm 12 \mathrm{(stat)} \pm 12 \mathrm{(sys)~MeV}. Using the Standard Model couplings of neutrinos to the \Zo, the number of light neutrino species is determined to be $N_\nu = 2.98 \pm 0.07 (\mathrm{stat}) \pm 0.07 (\mathrm{sys}).

Search for new physics phenomena in fermion-pair production at LEP

The measurements of hadron and lepton--pair production cross sections and lepton--pair forward--backward asymmetries performed with the L3 detector at centre--of--mass energies between 130 GeV and 172 GeV are used to search for new physics phenomena. New physics effects involving four fermion vertices -- contact interactions -- are looked for in all channels. For hadron production the exchange of virtual leptoquarks and scalar quarks is studied. No evidence for deviations from the Standard Model expectations is found. Lower limits on the scale $\Lambda$ of contact interactions in the range 1.2 -- 7.1 TeV are obtained at the 95\% confidence level for various models. Upper limits on the coupling strengths of leptoquarks and scalar quarks are derived