Gene conversion limits divergence of mammalian TLR1 and TLR6

<p>Abstract</p> <p>Background</p> <p>Toll-like receptors (TLR) recognize pathogen-associated molecular patterns and are important mediators of the innate immune system. TLR1 and TLR6 are paralogs and located in tandem on the same chromosome in mammals. They form heterodimers with TLR2 and bind lipopeptide components of gram-positive and gram-negative bacterial cell walls. To identify conserved stretches in TLR1 and TLR6, that may be important for their function, we compared their protein sequences in nine mammalian species(<it>Homo sapiens</it>, <it>Pan troglodytes</it>, <it>Macaca mulatta</it>, <it>Mus musculus</it>, <it>Rattus norvegicus</it>; <it>Erinaceus europaeus</it>, <it>Bos Taurus</it>, <it>Sus scrofa </it>and <it>Canis familiaris</it>).</p> <p>Results</p> <p>The N-terminal sequences of the orthologous proteins showed greater similarity than corresponding paralog sequences. However, we identified a region of 300 amino acids towards the C-terminus of TLR1 and TLR6, where paralogs had a greater degree of sequence identity than orthologs. Preservation of DNA sequence identity of paralogs in this region was observed in all nine mammalian species investigated, and is due to independent gene conversion events. The regions having undergone gene conversion in each species are almost identical and encode the leucine-rich repeat motifs 16 to 19, the C-terminal cap motif, the transmembrane domain and most of the intracellular Toll/interleukin-1 receptor (TIR) domain.</p> <p>Conclusion</p> <p>Our results show that, for a specific conserved region, divergence of TLR1 and TLR6 is limited by gene conversion, most likely because of the need for co-evolution with multiple intracellular and extracellular binding partners. Thus, gene conversion provides a mechanism for limiting the divergence of functional regions of protein paralogs, while allowing other domains to evolve diversified functions.</p

Anti-ApoA-1 IgGs in Familial Hypercholesterolemia Display Paradoxical Associations with Lipid Profile and Promote Foam Cell Formation

Anti-Apolipoprotein A-1 autoantibodies (anti-ApoA-1 IgG) promote atherogenesis via innate immune receptors, and may impair cellular cholesterol homeostasis (CH). We explored the presence of anti-ApoA-1 IgG in children (5-15 years old) with or without familial hypercholesterolemia (FH), analyzing their association with lipid profiles, and studied their in vitro effects on foam cell formation, gene regulation, and their functional impact on cholesterol passive diffusion (PD)

Observation of the B0 → ρ0ρ0 decay from an amplitude analysis of B0 → (π+π−)(π+π−) decays

Proton–proton collision data recorded in 2011 and 2012 by the LHCb experiment, corresponding to an integrated luminosity of 3.0 fb−1 , are analysed to search for the charmless B0→ρ0ρ0 decay. More than 600 B0→(π+π−)(π+π−) signal decays are selected and used to perform an amplitude analysis, under the assumption of no CP violation in the decay, from which the B0→ρ0ρ0 decay is observed for the first time with 7.1 standard deviations significance. The fraction of B0→ρ0ρ0 decays yielding a longitudinally polarised final state is measured to be fL=0.745−0.058+0.048(stat)±0.034(syst) . The B0→ρ0ρ0 branching fraction, using the B0→ϕK⁎(892)0 decay as reference, is also reported as B(B0→ρ0ρ0)=(0.94±0.17(stat)±0.09(syst)±0.06(BF))×10−6

Measurement of the (eta c)(1S) production cross-section in proton-proton collisions via the decay (eta c)(1S) -&gt; p(p)over-bar

The production of the $\eta_c (1S)$ state in proton-proton collisions is probed via its decay to the $p \bar{p}$ final state with the LHCb detector, in the rapidity range $2.0 6.5$ GeV/c. The cross-section for prompt production of $\eta_c (1S)$ mesons relative to the prompt $J/\psi$ cross-section is measured, for the first time, to be $\sigma_{\eta_c (1S)}/\sigma_{J/\psi} = 1.74 \pm 0.29 \pm 0.28 \pm 0.18 _{B}$ at a centre-of-mass energy $\sqrt{s} = 7$ TeV using data corresponding to an integrated luminosity of 0.7 fb$^{-1}$, and $\sigma_{\eta_c (1S)}/\sigma_{J/\psi} = 1.60 \pm 0.29 \pm 0.25 \pm 0.17 _{B}$ at $\sqrt{s} = 8$ TeV using 2.0 fb$^{-1}$. The uncertainties quoted are, in order, statistical, systematic, and that on the ratio of branching fractions of the $\eta_c (1S)$ and $J/\psi$ decays to the $p \bar{p}$ final state. In addition, the inclusive branching fraction of $b$-hadron decays into $\eta_c (1S)$ mesons is measured, for the first time, to be $B ( b \rightarrow \eta_c X ) = (4.88 \pm 0.64 \pm 0.25 \pm 0.67 _{B}) \times 10^{-3}$, where the third uncertainty includes also the uncertainty on the $J/\psi$ inclusive branching fraction from $b$-hadron decays. The difference between the $J/\psi$ and $\eta_c (1S)$ meson masses is determined to be $114.7 \pm 1.5 \pm 0.1$ MeV/c$^2$.The production of the $\eta _c (1S)$ state in proton-proton collisions is probed via its decay to the $p\overline{p}$ final state with the LHCb detector, in the rapidity range $2.0 6.5 \mathrm{{\,GeV/}{ c}}$ . The cross-section for prompt production of $\eta _c (1S)$ mesons relative to the prompt ${{ J}}/{\psi }$ cross-section is measured, for the first time, to be $\sigma _{\eta _c (1S)}/\sigma _{{{{ J}}/{\psi }}} = 1.74\, \pm \,0.29\, \pm \, 0.28\, \pm \,0.18 _{{\mathcal{B}}}$ at a centre-of-mass energy ${\sqrt{s}} = 7 {~\mathrm{TeV}}$ using data corresponding to an integrated luminosity of 0.7 fb$^{-1}$ , and $\sigma _{\eta _c (1S)}/\sigma _{{{{ J}}/{\psi }}} = 1.60 \pm 0.29 \pm 0.25 \pm 0.17 _{{\mathcal{B}}}$ at ${\sqrt{s}} = 8 {~\mathrm{TeV}}$ using 2.0 fb$^{-1}$ . The uncertainties quoted are, in order, statistical, systematic, and that on the ratio of branching fractions of the $\eta _c (1S)$ and ${{ J}}/{\psi }$ decays to the $p\overline{p}$ final state. In addition, the inclusive branching fraction of ${b}$ -hadron decays into $\eta _c (1S)$ mesons is measured, for the first time, to be ${\mathcal{B}}( b {\rightarrow } \eta _c X ) = (4.88\, \pm \,0.64\, \pm \,0.29\, \pm \, 0.67 _{{\mathcal{B}}}) \times 10^{-3}$ , where the third uncertainty includes also the uncertainty on the ${{ J}}/{\psi }$ inclusive branching fraction from ${b}$ -hadron decays. The difference between the ${{ J}}/{\psi }$ and $\eta _c (1S)$ meson masses is determined to be $114.7 \pm 1.5 \pm 0.1 {\mathrm {\,MeV\!/}c^2}$ .The production of the $\eta_c (1S)$ state in proton-proton collisions is probed via its decay to the $p \bar{p}$ final state with the LHCb detector, in the rapidity range $2.0 6.5$ GeV/c. The cross-section for prompt production of $\eta_c (1S)$ mesons relative to the prompt $J/\psi$ cross-section is measured, for the first time, to be $\sigma_{\eta_c (1S)}/\sigma_{J/\psi} = 1.74 \pm 0.29 \pm 0.28 \pm 0.18 _{B}$ at a centre-of-mass energy $\sqrt{s} = 7$ TeV using data corresponding to an integrated luminosity of 0.7 fb$^{-1}$, and $\sigma_{\eta_c (1S)}/\sigma_{J/\psi} = 1.60 \pm 0.29 \pm 0.25 \pm 0.17 _{B}$ at $\sqrt{s} = 8$ TeV using 2.0 fb$^{-1}$. The uncertainties quoted are, in order, statistical, systematic, and that on the ratio of branching fractions of the $\eta_c (1S)$ and $J/\psi$ decays to the $p \bar{p}$ final state. In addition, the inclusive branching fraction of $b$-hadron decays into $\eta_c (1S)$ mesons is measured, for the first time, to be $B ( b \rightarrow \eta_c X ) = (4.88 \pm 0.64 \pm 0.29 \pm 0.67 _{B}) \times 10^{-3}$, where the third uncertainty includes also the uncertainty on the $J/\psi$ inclusive branching fraction from $b$-hadron decays. The difference between the $J/\psi$ and $\eta_c (1S)$ meson masses is determined to be $114.7 \pm 1.5 \pm 0.1$ MeV/c$^2$

A study of CP violation in B-+/- -&gt; DK +/- and B-+/- -&gt; D pi(+/-) decays with D -&gt; (KSK +/-)-K-0 pi(-/+) final states

A first study of CP violation in the decay modes $B^\pm\to [K^0_{\rm S} K^\pm \pi^\mp]_D h^\pm$ and $B^\pm\to [K^0_{\rm S} K^\mp \pi^\pm]_D h^\pm$, where $h$ labels a $K$ or $\pi$ meson and $D$ labels a $D^0$ or $\overline{D}^0$ meson, is performed. The analysis uses the LHCb data set collected in $pp$ collisions, corresponding to an integrated luminosity of 3 fb$^{-1}$. The analysis is sensitive to the CP-violating CKM phase $\gamma$ through seven observables: one charge asymmetry in each of the four modes and three ratios of the charge-integrated yields. The results are consistent with measurements of $\gamma$ using other decay modes

Study of the rare B-s(0) and B-0 decays into the pi(+) pi(-) mu(+) mu(-) final state

A search for the rare decays $B_s^0 \to \pi^+\pi^-\mu^+\mu^-$ and $B^0 \to \pi^+\pi^-\mu^+\mu^-$ is performed in a data set corresponding to an integrated luminosity of 3.0 fb$^{-1}$ collected by the LHCb detector in proton-proton collisions at centre-of-mass energies of 7 and 8 TeV. Decay candidates with pion pairs that have invariant mass in the range 0.5-1.3 GeV/$c^2$ and with muon pairs that do not originate from a resonance are considered. The first observation of the decay $B_s^0 \to \pi^+\pi^-\mu^+\mu^-$ and the first evidence of the decay $B^0 \to \pi^+\pi^-\mu^+\mu^-$ are obtained and the branching fractions are measured to be $\mathcal{B}(B_s^0 \to \pi^+\pi^-\mu^+\mu^-)=(8.6\pm 1.5\,({\rm stat}) \pm 0.7\,({\rm syst})\pm 0.7\,({\rm norm}))\times 10^{-8}$ and $\mathcal{B}(B^0 \to \pi^+\pi^-\mu^+\mu^-)=(2.11\pm 0.51\,({\rm stat}) \pm 0.15\,({\rm syst})\pm 0.16\,({\rm norm}) )\times 10^{-8}$, where the third uncertainty is due to the branching fraction of the decay $B^0\to J/\psi(\to \mu^+\mu^-)K^*(890)^0(\to K^+\pi^-)$, used as a normalisation.A search for the rare decays Bs0→π+π−μ+μ− and B0→π+π−μ+μ− is performed in a data set corresponding to an integrated luminosity of 3.0 fb−1 collected by the LHCb detector in proton–proton collisions at centre-of-mass energies of 7 and 8 TeV . Decay candidates with pion pairs that have invariant mass in the range 0.5–1.3 GeV/c2 and with muon pairs that do not originate from a resonance are considered. The first observation of the decay Bs0→π+π−μ+μ− and the first evidence of the decay B0→π+π−μ+μ− are obtained and the branching fractions, restricted to the dipion-mass range considered, are measured to be B(Bs0→π+π−μ+μ−)=(8.6±1.5 (stat)±0.7 (syst)±0.7(norm))×10−8 and B(B0→π+π−μ+μ−)=(2.11±0.51(stat)±0.15(syst)±0.16(norm))×10−8 , where the third uncertainty is due to the branching fraction of the decay B0→J/ψ(→μ+μ−)K⁎(892)0(→K+π−) , used as a normalisation.A search for the rare decays Bs0→π+π−μ+μ− and B0→π+π−μ+μ− is performed in a data set corresponding to an integrated luminosity of 3.0 fb−1 collected by the LHCb detector in proton–proton collisions at centre-of-mass energies of 7 and 8 TeV . Decay candidates with pion pairs that have invariant mass in the range 0.5–1.3 GeV/c2 and with muon pairs that do not originate from a resonance are considered. The first observation of the decay Bs0→π+π−μ+μ− and the first evidence of the decay B0→π+π−μ+μ− are obtained and the branching fractions, restricted to the dipion-mass range considered, are measured to be B(Bs0→π+π−μ+μ−)=(8.6±1.5 (stat)±0.7 (syst)±0.7(norm))×10−8 and B(B0→π+π−μ+μ−)=(2.11±0.51(stat)±0.15(syst)±0.16(norm))×10−8 , where the third uncertainty is due to the branching fraction of the decay B0→J/ψ(→μ+μ−)K⁎(892)0(→K+π−) , used as a normalisation.A search for the rare decays $B_s^0 \to \pi^+\pi^-\mu^+\mu^-$ and $B^0 \to \pi^+\pi^-\mu^+\mu^-$ is performed in a data set corresponding to an integrated luminosity of 3.0 fb$^{-1}$ collected by the LHCb detector in proton-proton collisions at centre-of-mass energies of 7 and 8 TeV. Decay candidates with pion pairs that have invariant mass in the range 0.5-1.3 GeV/$c^2$ and with muon pairs that do not originate from a resonance are considered. The first observation of the decay $B_s^0 \to \pi^+\pi^-\mu^+\mu^-$ and the first evidence of the decay $B^0 \to \pi^+\pi^-\mu^+\mu^-$ are obtained and the branching fractions, restricted to the dipion-mass range considered, are measured to be $\mathcal{B}(B_s^0 \to \pi^+\pi^-\mu^+\mu^-)=(8.6\pm 1.5\,({\rm stat}) \pm 0.7\,({\rm syst})\pm 0.7\,({\rm norm}))\times 10^{-8}$ and $\mathcal{B}(B^0 \to \pi^+\pi^-\mu^+\mu^-)=(2.11\pm 0.51\,({\rm stat}) \pm 0.15\,({\rm syst})\pm 0.16\,({\rm norm}) )\times 10^{-8}$, where the third uncertainty is due to the branching fraction of the decay $B^0\to J/\psi(\to \mu^+\mu^-)K^*(890)^0(\to K^+\pi^-)$, used as a normalisation

Angular analysis of the B-0 -&gt; K*(0) e(+) e(-) decay in the low-q(2) region

An angular analysis of the $B^0 \rightarrow K^{*0} e^+ e^-$ decay is performed using a data sample, corresponding to an integrated luminosity of 3.0 {\mbox{fb}^{-1}}, collected by the LHCb experiment in $pp$ collisions at centre-of-mass energies of 7 and 8 TeV during 2011 and 2012. For the first time several observables are measured in the dielectron mass squared ($q^2$) interval between 0.002 and 1.120${\mathrm{\,Ge\kern -0.1em V^2\!/}c^4}$. The angular observables $F_{\mathrm{L}}$ and $A_{\mathrm{T}}^{\mathrm{Re}}$ which are related to the $K^{*0}$ polarisation and to the lepton forward-backward asymmetry, are measured to be $F_{\mathrm{L}}= 0.16 \pm 0.06 \pm0.03$ and $A_{\mathrm{T}}^{\mathrm{Re}} = 0.10 \pm 0.18 \pm 0.05$, where the first uncertainty is statistical and the second systematic. The angular observables $A_{\mathrm{T}}^{(2)}$ and $A_{\mathrm{T}}^{\mathrm{Im}}$ which are sensitive to the photon polarisation in this $q^2$ range, are found to be $A_{\mathrm{T}}^{(2)} = -0.23 \pm 0.23 \pm 0.05$ and $A_{\mathrm{T}}^{\mathrm{Im}} =0.14 \pm 0.22 \pm 0.05$. The results are consistent with Standard Model predictions.An angular analysis of the B$^{0}$ → K^{*}^{0} e$^{+}$ e$^{−}$ decay is performed using a data sample, corresponding to an integrated luminosity of 3.0 fb$^{−1}$, collected by the LHCb experiment in pp collisions at centre-of-mass energies of 7 and 8 TeV during 2011 and 2012. For the first time several observables are measured in the dielectron mass squared (q$^{2}$) interval between 0.002 and 1.120 GeV$^{2}$ /c$^{4}$. The angular observables F$_{L}$ and A$_{T}^{Re}$ which are related to the K^{*}^{0} polarisation and to the lepton forward-backward asymmetry, are measured to be F$_{L}$ = 0.16 ± 0.06 ± 0.03 and A$_{T}^{Re}$  = 0.10 ± 0.18 ± 0.05, where the first uncertainty is statistical and the second systematic. The angular observables A$_{T}^{(2)}$ and A$_{T}^{Im}$ which are sensitive to the photon polarisation in this q$^{2}$ range, are found to be A$_{T}^{(2)}$  = − 0.23 ± 0.23 ± 0.05 and A$_{T}^{Im}$  = 0.14 ± 0.22 ± 0.05. The results are consistent with Standard Model predictions.An angular analysis of the $B^0 \rightarrow K^{*0} e^+ e^-$ decay is performed using a data sample, corresponding to an integrated luminosity of 3.0 {\mbox{fb}^{-1}}, collected by the LHCb experiment in $pp$ collisions at centre-of-mass energies of 7 and 8 TeV during 2011 and 2012. For the first time several observables are measured in the dielectron mass squared ($q^2$) interval between 0.002 and 1.120${\mathrm{\,Ge\kern -0.1em V^2\!/}c^4}$. The angular observables $F_{\mathrm{L}}$ and $A_{\mathrm{T}}^{\mathrm{Re}}$ which are related to the $K^{*0}$ polarisation and to the lepton forward-backward asymmetry, are measured to be $F_{\mathrm{L}}= 0.16 \pm 0.06 \pm0.03$ and $A_{\mathrm{T}}^{\mathrm{Re}} = 0.10 \pm 0.18 \pm 0.05$, where the first uncertainty is statistical and the second systematic. The angular observables $A_{\mathrm{T}}^{(2)}$ and $A_{\mathrm{T}}^{\mathrm{Im}}$ which are sensitive to the photon polarisation in this $q^2$ range, are found to be $A_{\mathrm{T}}^{(2)} = -0.23 \pm 0.23 \pm 0.05$ and $A_{\mathrm{T}}^{\mathrm{Im}} =0.14 \pm 0.22 \pm 0.05$. The results are consistent with Standard Model predictions

Search for the lepton flavour violating decay tau(-) -&gt; mu(-)mu(+)mu(-)

A search for the lepton flavour violating decay $\tau^-\rightarrow\mu^-\mu^+\mu^-$ is performed with the LHCb experiment. The data sample corresponds to an integrated luminosity of 1.0 fb$^{−1}$ of proton-proton collisions at a centre-of-mass energy of 7 TeV and 2.0 fb$^{−1}$ at 8 TeV. No evidence is found for a signal, and a limit is set at 90% confidence level on the branching fraction, $\mathcal{B}(\tau^-\rightarrow\mu^-\mu^+\mu^-)<4.6\times10^{−8}$.A search for the lepton flavour violating decay τ$^{−}$ → μ$^{−}$ μ$^{+}$ μ$^{−}$ is performed with the LHCb experiment. The data sample corresponds to an integrated luminosity of 1.0 fb$^{−1}$ of proton-proton collisions at a centre-of-mass energy of 7 TeV and 2.0 fb$^{−1}$ at 8 TeV. No evidence is found for a signal, and a limit is set at 90% confidence level on the branching fraction, $\mathrm{\mathcal{B}}\left({\tau}^{-}\to {\mu}^{-}{\mu}^{+}{\mu}^{-}\right)<4.6\times {10}^{-8}$ .A search for the lepton flavour violating decay $\tau^-\to \mu^-\mu^+\mu^-$ is performed with the LHCb experiment. The data sample corresponds to an integrated luminosity of $1.0\mathrm{\,fb}^{-1}$ of proton-proton collisions at a centre-of-mass energy of $7\mathrm{\,Te\kern -0.1em V}$ and $2.0\mathrm{\,fb}^{-1}$ at $8\mathrm{\,Te\kern -0.1em V}$. No evidence is found for a signal, and a limit is set at $90\%$ confidence level on the branching fraction, $\mathcal{B}(\tau^-\to \mu^-\mu^+\mu^-) < 4.6 \times 10^{-8}$