eIF2α signaling regulates ischemic osteonecrosis through endoplasmic reticulum stress

Osteonecrosis of the femoral head (ONFH) primarily results from ischemia/hypoxia to the femoral head, and one of the cellular manifestations is the endoplasmic reticulum (ER) stress. To understand possible linkage of ischemic osteonecrosis to the ER stress, a surgery-induced animal model was employed and salubrinal was administered to evaluate the role of ER stress. Salubrinal is a synthetic chemical that inhibits de-phosphorylation of eIF2α, and it can suppress cell death from the ER stress at a proper dose. The results indicated that the ER stress was associated with ONFH and salubrinal significantly improved ONFH-induced symptoms such as osteonecrosis, bone loss, reduction in vessel perfusion, and excessive osteoclastogenesis in the femoral head. Salubrinal also protected osteoblast development by upregulating the levels of ATF4, ALP and RUNX2, and it stimulated angiogenesis of endothelial cells through elevating ATF4 and VEGF. Collectively, the results support the notion that the ER stress is an important pathological outcome in the surgery-induced ONFH model, and salubrinal improves ONFH symptoms by enhancing angiogenesis and bone healing via suppressing the ER stress

Introgression of an adult-plant powdery mildew resistance gene Pm4VL from Dasypyrum villosum chromosome 4V into bread wheat

Powdery mildew caused by Blumeria graminis f. sp. tritici (Bgt) seriously threatens wheat production worldwide. It is imperative to identify novel resistance genes from wheat and its wild relatives to control this disease by host resistance. Dasypyrum villosum (2n = 2x = 14, VV) is a relative of wheat and harbors novel genes for resistance against multi-fungal diseases. In the present study, we developed a complete set of new wheat-D. villosum disomic introgression lines through genomic in situ hybridization (GISH), fluorescence in situ hybridization (FISH) and molecular markers analysis, including four disomic substitution lines (2n=42) containing respectively chromosomes 1V#6, 2V#6, 3V#6, and 6V#6, and four disomic addition lines (2n=44) containing respectively chromosomes 4V#6, 5V#6, 6V#6 and 7V#6. These lines were subsequently evaluated for their responses to a mixture Bgt isolates at both seedling and adult-plant stages. Results showed that introgression lines containing chromosomes 3V#6, 5V#6, and 6V#6 exhibited resistance at both seedling and adult-plant stages, whereas the chromosome 4V#6 disomic addition line NAU4V#6-1 exhibited a high level of adult plant resistance to powdery mildew. Moreover, two translocation lines were further developed from the progenies of NAU4V#6-1 and the Ph1b mutation line NAU0686-ph1b. They were T4DL·4V#6S whole-arm translocation line NAU4V#6-2 and T7DL·7DS-4V#6L small-fragment translocation line NAU4V#6-3. Powdery mildew tests of the two lines confirmed the presence of an adult-plant powdery mildew resistance gene, Pm4VL, located on the terminal segment of chromosome arm 4V#6L (FL 0.6-1.00). In comparison with the recurrent parent NAU0686 plants, the T7DL·7DS-4V#6L translocation line NAU4V#6-3 showed no obvious negative effect on yield-related traits, providing a new germplasm in breeding for resistance

Origin and development of oligoadenylate synthetase immune system

Abstract Background Oligoadenylate synthetases (OASs) are widely distributed in Metazoa including sponges, fish, reptiles, birds and mammals and show large variation, with one to twelve members in any given species. Upon double-stranded RNA (dsRNA) binding, avian and mammalian OASs generate the second messenger 2'-5'-linked oligoadenylate (2-5A), which activates ribonuclease L (RNaseL) and blocks viral replication. However, how Metazoa shape their OAS repertoires to keep evolutionary balance to virus infection is largely unknown. We performed comprehensive phylogenetic and functional analyses of OAS genes from evolutionarily lower to higher Metazoa to demonstrate how the OAS repertoires have developed anti-viral activity and diversified their functions. Results Ancient Metazoa harbor OAS genes, but lack both upstream and downstream genes of the OAS-related pathways, indicating that ancient OASs are not interferon-induced genes involved in the innate immune system. Compared to OASs of ancient Metazoa (i.e. sponge), the corresponding ones of higher Metazoa present an increasing number of basic residues on the OAS/dsRNA interaction interface. Such an increase of basic residues might improve their binding affinity to dsRNA. Moreover, mutations of functional residues in the active pocket might lead to the fact that higher Metazoan OASs lose the ability to produce 3'-5'-linked oligoadenylate (3-5A) and turn into specific 2-5A synthetases. In addition, we found that multiple rounds of gene duplication and domain coupling events occurred in the OAS family and mutations at functionally critical sites were observed in most new OAS members. Conclusions We propose a model for the expansion of OAS members and provide comprehensive evidence of subsequent neo-functionalization and sub-functionalization. Our observations lay the foundation for interrogating the evolutionary transition of ancient OAS genes to host defense genes and provide important information for exploring the unknown function of the OAS gene family

Les droits disciplinaires des fonctions publiques : « unification », « harmonisation » ou « distanciation ». A propos de la loi du 26 avril 2016 relative à la déontologie et aux droits et obligations des fonctionnaires

The production of tt‾ , W+bb‾ and W+cc‾ is studied in the forward region of proton–proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98±0.02 fb−1 . The W bosons are reconstructed in the decays W→ℓν , where ℓ denotes muon or electron, while the b and c quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions.The production of $t\overline{t}$, $W+b\overline{b}$ and $W+c\overline{c}$ is studied in the forward region of proton-proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98 $\pm$ 0.02 \mbox{fb}^{-1}. The $W$ bosons are reconstructed in the decays $W\rightarrow\ell\nu$, where $\ell$ denotes muon or electron, while the $b$ and $c$ quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions

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

Measurement of the (eta c)(1S) production cross-section in proton-proton collisions via the decay (eta c)(1S) -> 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$^2$

Measurement of the Z plus b-jet cross-section in pp collisions at root s=7 TeV in the forward region

The associated production of a Z boson or an off-shell photon $\gamma^*$ with a bottom quark in the forward region is studied using proton-proton collisions at a centre-of-mass energy of $7{\mathrm{\,Te\kern -0.1em V}}$. The Z bosons are reconstructed in the ${\text{Z}/\gamma^*}\rightarrow{\mu^{+}\mu^{-}}$ final state from muons with a transverse momentum larger than $20{\mathrm{\,Ge\kern -0.1em V}}$, while two transverse momentum thresholds are considered for jets ($10{\mathrm{\,Ge\kern -0.1em V}}$ and $20{\mathrm{\,Ge\kern -0.1em V}}$). Both muons and jets are reconstructed in the pseudorapidity range $2.0 10{\mathrm{\,Ge\kern -0.1em V}}$, and \sigma(\text{\text{Z}/\gamma^*(\mu^{+}\mu^{-})+b-jet}) = 167 \pm 47 (\text{stat}) \pm 29 (\text{syst}) \pm 6 (\text{lumi}) {\,{fb}} for {p_{\rm T}}(jet)$>20{\mathrm{\,Ge\kern -0.1em V}}$

Angular analysis of the B-0 -> 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