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Jet-hadron correlations with respect to the event plane in √sNN = 200 GeV Au+Au collisions in STAR
(2024)
Angular distributions of charged particles relative to jet axes are studied in sNN−−−√ = 200 GeV Au+Au collisions as a function of the jet orientation with respect to the event plane. This differential study tests the expected path-length dependence of energy loss experienced by a hard-scattered parton as it traverses the hot and dense medium formed in heavy-ion collisions. A second-order event plane is used in the analysis as an experimental estimate of the reaction plane formed by the collision impact parameter and the beam direction. Charged-particle jets with 15<pT,jet< 20 and 20<pT,jet< 40 GeV/c were reconstructed with the anti-kT algorithm with radius parameter setting of (R=0.4) in the 20-50\% centrality bin to maximize the initial-state eccentricity of the interaction region. The reaction plane fit method is implemented to remove the flow-modulated background with better precision than prior methods. Yields and widths of jet-associated charged-hadron distributions are extracted in three angular bins between the jet axis and the event plane. The event-plane (EP) dependence is further quantified by ratios of the associated yields in different EP bins. No dependence on orientation of the jet axis with respect to the event plane is seen within the uncertainties in the kinematic regime studied. This finding is consistent with a similar experimental observation by ALICE in sNN−−−√ = 2.76 TeV Pb+Pb collision data.
In high-energy heavy-ion collisions, partonic collectivity is evidenced by the constituent quark number scaling of elliptic flow anisotropy for identified hadrons. A breaking of this scaling and dominance of baryonic interactions is found for identified hadron collective flow measurements in sNN−−−√ = 3 GeV Au+Au collisions. In this paper, we report measurements of the first- and second-order azimuthal anisotropic parameters, v1 and v2, of light nuclei (d, t, 3He, 4He) produced in sNN−−−√ = 3 GeV Au+Au collisions at the STAR experiment. An atomic mass number scaling is found in the measured v1 slopes of light nuclei at mid-rapidity. For the measured v2 magnitude, a strong rapidity dependence is observed. Unlike v2 at higher collision energies, the v2 values at mid-rapidity for all light nuclei are negative and no scaling is observed with the atomic mass number. Calculations by the Jet AA Microscopic Transport Model (JAM), with baryonic mean-field plus nucleon coalescence, are in good agreement with our observations, implying baryonic interactions dominate the collective dynamics in 3 GeV Au+Au collisions at RHIC.
In high-energy heavy-ion collisions, partonic collectivity is evidenced by the constituent quark number scaling of elliptic flow anisotropy for identified hadrons. A breaking of this scaling and dominance of baryonic interactions is found for identified hadron collective flow measurements in sNN−−−√ = 3 GeV Au+Au collisions. In this paper, we report measurements of the first-order and second-order azimuthal anisotropic parameters, v1 and v2, of light nuclei (d, t, 3He, 4He) produced in sNN−−−√ = 3 GeV Au+Au collisions at the STAR experiment. An atomic mass number scaling is found in the measured v1 slopes of light nuclei at mid-rapidity. For the measured v2 magnitude, a strong rapidity dependence is observed. Unlike v2 at higher collision energies, the v2 values at mid-rapidity for all light nuclei are negative and no scaling is observed with the atomic mass number. Calculations by the Jet AA Microscopic Transport Model (JAM), with baryonic mean-field plus nucleon coalescence, are in good agreement with our observations, implying baryonic interactions dominate the collective dynamics in 3 GeV Au+Au collisions at RHIC.
We report precision measurements of hypernuclei 3ΛH and 4ΛH lifetimes obtained from Au+Au collisions at \snn = 3.0\,GeV and 7.2\,GeV collected by the STAR experiment at RHIC, and the first measurement of 3ΛH and 4ΛH mid-rapidity yields in Au+Au collisions at \snn = 3.0\,GeV. 3ΛH and 4ΛH, being the two simplest bound states composed of hyperons and nucleons, are cornerstones in the field of hypernuclear physics. Their lifetimes are measured to be 221±15(stat.)±19(syst.)\,ps for 3ΛH and 218±6(stat.)±13(syst.)\,ps for 4ΛH. The pT-integrated yields of 3ΛH and 4ΛH are presented in different centrality and rapidity intervals. It is observed that the shape of the rapidity distribution of 4ΛH is different for 0--10\% and 10--50\% centrality collisions. Thermal model calculations, using the canonical ensemble for strangeness, describes the 3ΛH yield well, while underestimating the 4ΛH yield. Transport models, combining baryonic mean-field and coalescence (JAM) or utilizing dynamical cluster formation via baryonic interactions (PHQMD) for light nuclei and hypernuclei production, approximately describe the measured 3ΛH and 4ΛH yields. Our measurements provide means to precisely assess our understanding of the fundamental baryonic interactions with strange quarks, which can impact our understanding of more complicated systems involving hyperons, such as the interior of neutron stars or exotic hypernuclei.
The process 𝑒+𝑒−→Σ+¯Σ− is studied from threshold up to 3.04 GeV/𝑐2 via the initial-state radiation technique using data with an integrated luminosity of 12.0 fb−1, collected at center-of-mass energies between 3.773 and 4.258 GeV with the BESIII detector at the BEPCII collider. The pair production cross sections and the effective form factors of Σ are measured in eleven Σ+¯Σ− invariant mass intervals from threshold to 3.04 GeV/𝑐2. The results are consistent with the previous results from Belle and BESIII. Furthermore, the branching fractions of the decays 𝐽/𝜓→Σ+¯Σ− and 𝜓(3686)→Σ+¯Σ− are determined and the obtained results are consistent with the previous results of BESIII.
We report precision measurements of hypernuclei 3ΛH and 4ΛH lifetimes obtained from Au+Au collisions at \snn = 3.0\,GeV and 7.2\,GeV collected by the STAR experiment at RHIC, and the first measurement of 3ΛH and 4ΛH mid-rapidity yields in Au+Au collisions at \snn = 3.0\,GeV. 3ΛH and 4ΛH, being the two simplest bound states composed of hyperons and nucleons, are cornerstones in the field of hypernuclear physics. Their lifetimes are measured to be 221±15(stat.)±19(syst.)\,ps for 3ΛH and 218±6(stat.)±13(syst.)\,ps for 4ΛH. The pT-integrated yields of 3ΛH and 4ΛH are presented in different centrality and rapidity intervals. It is observed that the shape of the rapidity distribution of 4ΛH is different for 0--10\% and 10--50\% centrality collisions. Thermal model calculations, using the canonical ensemble for strangeness, describes the 3ΛH yield well, while underestimating the 4ΛH yield. Transport models, combining baryonic mean-field and coalescence (JAM) or utilizing dynamical cluster formation via baryonic interactions (PHQMD) for light nuclei and hypernuclei production, approximately describe the measured 3ΛH and 4ΛH yields. Our measurements provide means to precisely assess our understanding of the fundamental baryonic interactions with strange quarks, which can impact our understanding of more complicated systems involving hyperons, such as the interior of neutron stars or exotic hypernuclei.
We report measurements of the longitudinal double-spin asymmetry, ALL, for inclusive jet and dijet production in polarized proton-proton collisions at midrapidity and center-of-mass energy s√ = 510 GeV, using the high luminosity data sample collected by the STAR experiment in 2013. These measurements complement and improve the precision of previous STAR measurements at the same center-of-mass energy that probe the polarized gluon distribution function at partonic momentum fraction 0.015 ≲x≲ 0.25. The dijet asymmetries are separated into four jet-pair topologies, which provide further constraints on the x dependence of the polarized gluon distribution function. These measurements are in agreement with previous STAR measurements and with predictions from current next-to-leading order global analyses. They provide more precise data at low dijet invariant mass that will better constraint the shape of the polarized gluon distribution function of the proton.
We report precision measurements of hypernuclei 3ΛH and 4ΛH lifetimes obtained from Au+Au collisions at \snn = 3.0\,GeV and 7.2\,GeV collected by the STAR experiment at RHIC, and the first measurement of 3ΛH and 4ΛH mid-rapidity yields in Au+Au collisions at \snn = 3.0\,GeV. The lifetimes are measured to be 221±15(stat.)±19(syst.)\,ps for 3ΛH and 218±6(stat.)±13(syst.)\,ps for 4ΛH. The pT-integrated yields of 3ΛH and 4ΛH are presented in different centrality and rapidity intervals. It is observed that the shape of the rapidity distribution of 4ΛH is different for 0--10\% and 10--50\% centrality collisions. Thermal model calculations, using the canonical ensemble for strangeness, describes the 3ΛH yield well, while underestimating the 4ΛH yield. Transport models, combining baryonic mean-field and coalescence (JAM) or utilizing dynamical cluster formation via baryonic interactions (PHQMD) for light nuclei and hypernuclei production, approximately describe the measured 3ΛH and 4ΛH yields.
We measure triangular flow relative to the reaction plane at 3 GeV center-of-mass energy in Au+Au collisions at the BNL Relativistic Heavy Ion Collider. A significant v3 signal for protons is observed, which increases for higher rapidity, higher transverse momentum, and more peripheral collisions. The triangular flow is essentially rapidity-odd with a slope at mid-rapidity, dv3/dy|(y=0), opposite in sign compared to the slope for directed flow. No significant v3 signal is observed for charged pions and kaons. Comparisons with models suggest that a mean field potential is required to describe these results, and that the triangular shape of the participant nucleons is the result of stopping and nuclear geometry.
Density fluctuations near the QCD critical point can be probed via an intermittency analysis in relativistic heavy-ion collisions. We report the first measurement of intermittency in Au+Au collisions at √sNN = 7.7-200 GeV measured by the STAR experiment at the Relativistic Heavy Ion Collider (RHIC). The scaled factorial moments of identified charged hadrons are analyzed at mid-rapidity and within the transverse momentum phase space. We observe a power-law behavior of scaled factorial moments in Au+Au collisions and a decrease in the extracted scaling exponent (ν) from peripheral to central collisions. The ν is consistent with a constant for different collisions energies in the mid-central (10-40%) collisions. Moreover, the ν in the 0-5% most central Au+Au collisions exhibits a non-monotonic energy dependence that reaches a minimum around √sNN = 27 GeV. The physics implications on the QCD phase structure are discussed.
Using a data sample of 448.1×106 ψ(3686) events collected at s√= 3.686 GeV with the BESIII detector at the BEPCII, we search for the rare decay J/ψ→ϕe+e− via ψ(3686)→π+π−J/ψ. No signal events are observed and the upper limit on the branching fraction is set to be B(J/ψ→ϕe+e−)<1.2×10−7 at the 90\% confidence level, which is still about one order of magnitude higher than the Standard Model prediction.
Measurement of inclusive charged-particle jet production in Au+Au collisions at √sNN = 200 GeV
(2021)
The STAR Collaboration at the Relativistic Heavy Ion Collider reports the first measurement of inclusive jet production in peripheral and central Au+Au collisions at sNN−−−−√=200 GeV. Jets are reconstructed with the anti-kT algorithm using charged tracks with pseudorapidity |η|<1.0 and transverse momentum 0.2<pchT,jet<30 GeV/c, with jet resolution parameter R=0.2, 0.3, and 0.4. The large background yield uncorrelated with the jet signal is observed to be dominated by statistical phase space, consistent with a previous coincidence measurement. This background is suppressed by requiring a high-transverse-momentum (high-pT) leading hadron in accepted jet candidates. The bias imposed by this requirement is assessed, and the pT region in which the bias is small is identified. Inclusive charged-particle jet distributions are reported in peripheral and central Au+Au collisions for 5<pchT,jet<25 GeV/c and 5<pchT,jet<30 GeV/c, respectively. The charged-particle jet inclusive yield is suppressed for central Au+Au collisions, compared to both the peripheral Au+Au yield from this measurement and to the pp yield calculated using the PYTHIA event generator. The magnitude of the suppression is consistent with that of inclusive hadron production at high pT, and that of semi-inclusive recoil jet yield when expressed in terms of energy loss due to medium-induced energy transport. Comparison of inclusive charged-particle jet yields for different values of R exhibits no significant evidence for medium-induced broadening of the transverse jet profile for R<0.4 in central Au+Au collisions. The measured distributions are consistent with theoretical model calculations that incorporate jet quenching.
We report measurements of the longitudinal double-spin asymmetry, ALL, for inclusive jet and dijet production in polarized proton-proton collisions at midrapidity and center-of-mass energy s√ = 510 GeV, using the high luminosity data sample collected by the STAR experiment in 2013. These measurements complement and improve the precision of previous STAR measurements at the same center-of-mass energy that probe the polarized gluon distribution function at partonic momentum fraction 0.015 ≲x≲ 0.25. The dijet asymmetries are separated into four jet-pair topologies, which provide further constraints on the x dependence of the polarized gluon distribution function. These measurements are in agreement with previous STAR measurements and with predictions from current next-to-leading order global analyses. They provide more precise data at low dijet invariant mass that will better constraint the shape of the polarized gluon distribution function of the proton.
Using (10087±44)×106 J/ψ events collected with the BESIII detector, numerous Ξ− and Λ decay asymmetry parameters are simultaneously determined from the process J/ψ→Ξ−Ξ¯+→Λ(pπ−)π−Λ¯(n¯π0)π+ and its charge-conjugate channel. The precisions of α0 for Λ→nπ0 and α¯0 for Λ¯→n¯π0 compared to world averages are improved by factors of 4 and 1.7, respectively. The ratio of decay asymmetry parameters of Λ→nπ0 to that of Λ→pπ−, ⟨α0⟩/⟨αΛ−⟩, is determined to be 0.873±0.012+0.011−0.010, where the first and the second uncertainties are statistical and systematic, respectively. The ratio is smaller than unity more than 5σ, which signifies the existence of the ΔI=3/2 transition in Λ for the first time. Beside, we test for CP violation in Ξ−→Λπ− and in Λ→nπ0 with the best precision to date.
Measurement of inclusive charged-particle jet production in Au + Au collisions at √sNN=200 GeV
(2020)
The STAR Collaboration at the Relativistic Heavy Ion Collider reports the first measurement of inclusive jet production in peripheral and central Au+Au collisions at √𝑠𝑁𝑁=200 GeV. Jets are reconstructed with the anti-𝑘𝑇 algorithm using charged tracks with pseudorapidity |𝜂|<1.0 and transverse momentum 0.2<𝑝ch
𝑇,jet<30 GeV/𝑐, with jet resolution parameter 𝑅=0.2, 0.3, and 0.4. The large background yield uncorrelated with the jet signal is observed to be dominated by statistical phase space, consistent with a previous coincidence measurement. This background is suppressed by requiring a high-transverse-momentum (high-𝑝𝑇) leading hadron in accepted jet candidates. The bias imposed by this requirement is assessed, and the 𝑝𝑇 region in which the bias is small is identified. Inclusive charged-particle jet distributions are reported in peripheral and central Au+Au collisions for 5<𝑝ch
𝑇,jet<25 GeV/𝑐 and 5<𝑝ch
𝑇,jet<30 GeV/𝑐, respectively. The charged-particle jet inclusive yield is suppressed for central Au+Au collisions, compared to both the peripheral Au+Au yield from this measurement and to the 𝑝𝑝 yield calculated using the PYTHIA event generator. The magnitude of the suppression is consistent with that of inclusive hadron production at high 𝑝𝑇 and that of semi-inclusive recoil jet yield when expressed in terms of energy loss due to medium-induced energy transport. Comparison of inclusive charged-particle jet yields for different values of 𝑅 exhibits no significant evidence for medium-induced broadening of the transverse jet profile for 𝑅 <0.4 in central Au+Au collisions. The measured distributions are consistent with theoretical model calculations that incorporate jet quenching.
Using e+e− collision data, corresponding to an integrated luminosity of 892pb−1 collected at center-of-mass energies from 4.84 to 4.95\,GeV with the BESIII detector, we search for the process e+e−→K+K−ψ(3770) by reconstructing two charged kaons and one D meson from ψ(3770). No significant signal of e+e−→K+K−ψ(3770) is found and the upper limits of the Born cross sections are reported at 90\% confidence level.
We report on new measurements of Cabibbo-suppressed semileptonic D+s decays using 3.19 fb−1 of e+e− annihilation data sample collected at a center-of-mass energy of 4.178~GeV with the BESIII detector at the BEPCII collider. Our results include branching fractions B(D+s→K0e+νe)=(3.25±0.38(stat.)±0.16(syst.))×10−3 and B(D+s→K∗0e+νe)=(2.37±0.26(stat.)±0.20(syst.))×10−3 which are much improved relative to previous measurements, and the first measurements of the hadronic form-factor parameters for these decays. For D+s→K0e+νe, we obtain f+(0)=0.720±0.084(stat.)±0.013(syst.), and for D+s→K∗0e+νe, we find form-factor ratios rV=V(0)/A1(0)=1.67±0.34(stat.)±0.16(syst.) and r2=A2(0)/A1(0)=0.77±0.28(stat.)±0.07(syst.).
Using a data sample with an integrated luminosity of 2.93 fb−1 taken at the center-of-mass energy of 3.773 GeV, we search for the Majorana neutrino (𝜈𝑚) in the lepton number violating decays 𝐷→𝐾𝜋𝑒+𝑒+. No significant signal is observed, and the upper limits on the branching fraction at the 90% confidence level are set to be ℬ(𝐷0→𝐾−𝜋−𝑒+𝑒+)<2.8×10−6, ℬ(𝐷+→𝐾0𝑆𝜋−𝑒+𝑒+)<3.3×10−6 and ℬ(𝐷+→𝐾−𝜋0𝑒+𝑒+)<8.5×10−6. The Majorana neutrino is searched for with different mass assumptions ranging from 0.25 to 1.0 GeV/𝑐2 in the decays 𝐷0→𝐾−𝑒+𝜈𝑚,𝜈𝑚→𝜋−𝑒+ and 𝐷+→𝐾0𝑆𝑒+𝜈𝑚,𝜈𝑚→𝜋−𝑒+, and the upper limits on the branching fraction at the 90% confidence level are at the level of 10−7∼10−6, depending on the mass of the Majorana neutrino. The constraints on the mixing matrix element |𝑉𝑒𝜈𝑚|2 are also evaluated.
Using a sample of 448.1×106 ψ(2S) events collected with the BESIII detector, we perform a study of the decay J/ψ→K+K− via ψ(2S)→π+π−J/ψ.
The branching fraction of J/ψ→K+K− is determined to be BK+K−=(3.072±0.023(stat.)±0.050(syst.))×10−4, which is consistent with previous measurements but with significantly improved precision.
We study the hadronic decays of Λ+c to the final states Σ+η and Σ+η′, using an e+e− annihilation data sample of 567 pb−1 taken at a center-of-mass energy of 4.6 GeV with the BESIII detector at the BEPCII collider. We find evidence for the decays Λ+c→Σ+η and Σ+η′ with statistical significance of 2.5σ and 3.2σ, respectively. Normalizing to the reference decays Λ+c→Σ+π0 and Σ+ω, we obtain the ratios of the branching fractions B(Λ+c→Σ+η)B(Λ+c→Σ+π0) and B(Λ+c→Σ+η′)B(Λ+c→Σ+ω) to be 0.35±0.16±0.03 and 0.86±0.34±0.07, respectively. The upper limits at the 90\% confidence level are set to be B(Λ+c→Σ+η)B(Λ+c→Σ+π0)<0.58 and B(Λ+c→Σ+η′)B(Λ+c→Σ+ω)<1.2. Using BESIII measurements of the branching fractions of the reference decays, we determine B(Λ+c→Σ+η)=(0.41±0.19±0.05)% (<0.68%) and B(Λ+c→Σ+η′)=(1.34±0.53±0.21)% (<1.9%). Here, the first uncertainties are statistical and the second systematic. The obtained branching fraction of Λ+c→Σ+η is consistent with the previous measurement, and the branching fraction of Λ+c→Σ+η′ is measured for the first time.
We study the electromagnetic Dalitz decay 𝐽/𝜓→𝑒+𝑒−𝜂 and search for dielectron decays of a dark gauge boson (𝛾′) in 𝐽/𝜓→𝛾′𝜂 with the two 𝜂 decay modes 𝜂→𝛾𝛾 and 𝜂→𝜋+𝜋−𝜋0 using (1310.6±7.0)×106 𝐽/𝜓 events collected with the BESIII detector. The branching fraction of 𝐽/𝜓→𝑒+𝑒−𝜂 is measured to be (1.43±0.04(stat)±0.06(syst))×10−5, with a precision that is improved by a factor of 1.5 over the previous BESIII measurement. The corresponding dielectron invariant mass dependent modulus square of the transition form factor is explored for the first time, and the pole mass is determined to be Λ=2.84±0.11(stat)±0.08(syst) GeV/𝑐2. We find no evidence of 𝛾′ production and set 90% confidence level upper limits on the product branching fraction ℬ(𝐽/𝜓→𝛾′𝜂)×ℬ(𝛾′→𝑒+𝑒−) as well as the kinetic mixing strength between the standard model photon and 𝛾′ in the mass range of 0.01≤𝑚𝛾′≤2.4 GeV/𝑐2.
Measurement of inclusive J/ψ polarization in p + p collisions at √s=200 GeV by the STAR experiment
(2020)
We report on new measurements of inclusive 𝐽/𝜓 polarization at midrapidity in 𝑝+𝑝 collisions at √𝑠=200 GeV by the STAR experiment at the Relativistic Heavy Ion Collider. The polarization parameters, 𝜆𝜃, 𝜆𝜙, and 𝜆𝜃𝜙, are measured as a function of transverse momentum (𝑝T) in both the helicity and Collins-Soper (CS) reference frames within 𝑝T<10 GeV/𝑐. Except for 𝜆𝜃 in the CS frame at the highest measured 𝑝T, all three polarization parameters are consistent with 0 in both reference frames without any strong 𝑝T dependence. Several model calculations are compared with data, and the one using the Color Glass Condensate effective field theory coupled with nonrelativistic QCD gives the best overall description of the experimental results, even though other models cannot be ruled out due to experimental uncertainties.
We report results on an elastic cross section measurement in proton-proton collisions at a center-of-mass energy s√=510 GeV, obtained with the Roman Pot setup of the STAR experiment at the Relativistic Heavy Ion Collider (RHIC). The elastic differential cross section is measured in the four-momentum transfer squared range 0.23≤−t≤0.67 GeV2. We find that a constant slope B does not fit the data in the aforementioned t range, and we obtain a much better fit using a second-order polynomial for B(t). The t dependence of B is determined using six subintervals of t in the STAR measured t range, and is in good agreement with the phenomenological models. The measured elastic differential cross section dσ/dt agrees well with the results obtained at s√=546 GeV for proton--antiproton collisions by the UA4 experiment. We also determine that the integrated elastic cross section within the STAR t-range is σfidel=462.1±0.9(stat.)±1.1(syst.)±11.6(scale) μb.
We report results on an elastic cross section measurement in proton-proton collisions at a center-of-mass energy s√=510 GeV, obtained with the Roman Pot setup of the STAR experiment at the Relativistic Heavy Ion Collider (RHIC). The elastic differential cross section is measured in the four-momentum transfer squared range 0.23≤−t≤0.67 GeV2. We find that a constant slope B does not fit the data in the aforementioned t range, and we obtain a much better fit using a second-order polynomial for B(t). The t dependence of B is determined using six subintervals of t in the STAR measured t range, and is in good agreement with the phenomenological models. The measured elastic differential cross section dσ/dt agrees well with the results obtained at s√=546 GeV for proton--antiproton collisions by the UA4 experiment. We also determine that the integrated elastic cross section within the STAR t-range is σfidel=462.1±0.9(stat.)±1.1(syst.)±11.6(scale) μb.
We report new measurements of the cross sections for the production of Dbar D final states at the ψ(3770) resonance. Our data sample consists of an integrated luminosity of 2.93 fb−1 of e+e− annihilation data produced by the BEPCII collider and collected and analyzed with the BESIII detector. We exclusively reconstruct three D0 and six D+ hadronic decay modes and use the ratio of the yield of fully reconstructed Dbar D events ("double tags") to the yield of all reconstructed D or bar D mesons ("single tags") to determine the number of D0bar D0 and D+D− events, benefiting from the cancellation of many systematic uncertainties. Combining these yields with an independent determination of the integrated luminosity of the data sample, we find the cross sections to be σ(e+e− → D0bar D0) nb and σ(e+e− → D+D−) = (2.830 ± 0.011 ± 0.026) nb, where the uncertainties are statistical and systematic, respectively.
Measurements of mass and Λ binding energy of 4ΛH and 4ΛHe in Au+Au collisions at sNN−−−√=3 GeV are presented, with an aim to address the charge symmetry breaking (CSB) problem in hypernuclei systems with atomic number A = 4. The Λ binding energies are measured to be 2.22±0.06(stat.)±0.14(syst.) MeV and 2.38±0.13(stat.)±0.12(syst.) MeV for 4ΛH and 4ΛHe, respectively. The measured Λ binding-energy difference is 0.16±0.14(stat.)±0.10(syst.) MeV for ground states. Combined with the γ-ray transition energies, the binding-energy difference for excited states is −0.16±0.14(stat.)±0.10(syst.) MeV, which is negative and comparable to the value of the ground states within uncertainties. These new measurements on the Λ binding-energy difference in A = 4 hypernuclei systems are consistent with the theoretical calculations that result in ΔB4Λ(1+exc)≈−ΔB4Λ(0+g.s.)<0 and present a new method for the study of CSB effect using relativistic heavy-ion collisions.
This report explores the question of compatibility between annotation projects including translating annotation formalisms to each other or to common forms. Compatibility issues are crucial for systems that use the results of multiple annotation projects. We hope that this report will begin a concerted effort in the field to track the compatibility of annotation schemes for part of speech tagging, time annotation, treebanking, role labeling and other phenomena.
Central counterparties (CCPs) have increasingly become a cornerstone of financial markets infrastructure. We present a model where trades are time-critical, liquidity is limited and there is limited enforcement of trades. We show a CCP novating trades implements efficient trading behaviour. It is optimal for the CCP to face default losses to achieve the efficient level of trade. To cover these losses, the CCP optimally uses margin calls, and, as the default problem becomes more severe, also requires default funds and then imposes position limits.
The pseudorapidity asymmetry and centrality dependence of charged hadron spectra in d+Au collisions at sqrt[sNN ]=200 GeV are presented. The charged particle density at midrapidity, its pseudorapidity asymmetry, and centrality dependence are reasonably reproduced by a multiphase transport model, by HIJING, and by the latest calculations in a saturation model. Ratios of transverse momentum spectra between backward and forward pseudorapidity are above unity for pT below 5 GeV/c . The ratio of central to peripheral spectra in d+Au collisions shows enhancement at 2< pT <6 GeV/c , with a larger effect at backward rapidity than forward rapidity. Our measurements are in qualitative agreement with gluon saturation and in contrast to calculations based on incoherent multiple partonic scatterings.
The short-lived K(892)* resonance provides an efficient tool to probe properties of the hot and dense medium produced in relativistic heavy-ion collisions. We report measurements of K* in sqrt[sNN]=200GeV Au+Au and p+p collisions reconstructed via its hadronic decay channels K(892)*0-->K pi and K(892)*±-->K0S pi ± using the STAR detector at the Relativistic Heavy Ion Collider at Brookhaven National Laboratory. The K*0 mass has been studied as a function of pT in minimum bias p+p and central Au+Au collisions. The K*pT spectra for minimum bias p+p interactions and for Au+Au collisions in different centralities are presented. The K*/K yield ratios for all centralities in Au+Au collisions are found to be significantly lower than the ratio in minimum bias p+p collisions, indicating the importance of hadronic interactions between chemical and kinetic freeze-outs. A significant nonzero K*0 elliptic flow (v2) is observed in Au+Au collisions and is compared to the K0S and Lambda v2. The nuclear modification factor of K* at intermediate pT is similar to that of K0S but different from Lambda . This establishes a baryon-meson effect over a mass effect in the particle production at intermediate pT (2<pT <= 4GeV/c).
Midrapidity open charm spectra from direct reconstruction of D0(D0-bar)-->K± pi ± in d+Au collisions and indirect electron-positron measurements via charm semileptonic decays in p+p and d+Au collisions at sqrt[sNN]=200 GeV are reported. The D0(D0-bar) spectrum covers a transverse momentum (pT) range of 0.1<pT<3 GeV/c, whereas the electron spectra cover a range of 1<pT<4 GeV/c. The electron spectra show approximate binary collision scaling between p+p and d+Au collisions. From these two independent analyses, the differential cross section per nucleon-nucleon binary interaction at midrapidity for open charm production from d+Au collisions at BNL RHIC is d sigma NNcc-bar/dy=0.30±0.04(stat)±0.09(syst) mb. The results are compared to theoretical calculations. Implications for charmonium results in A+A collisions are discussed.
Correlations in the hadron distributions produced in relativistic Au+Au collisions are studied in the discrete wavelet expansion method. The analysis is performed in the space of pseudorapidity (| eta | <= 1) and azimuth(full 2 pi ) in bins of transverse momentum (pt) from 0.14 <= pt <= 2.1GeV/c. In peripheral Au+Au collisions a correlation structure ascribed to minijet fragmentation is observed. It evolves with collision centrality and pt in a way not seen before, which suggests strong dissipation of minijet fragmentation in the longitudinally expanding medium.
The 70 Frullania species (+ 1 subspecies, 9 varieties, and 3 formae) belonging to 9 subgenera are confirmed in China, among which 1 subgenus and 4 species are new to science, and 12 species are newly reported from China. A new name (nom. nov.) and 12 combinations are proposed and several species are reduced to synonyms of other species. This study reveals the Frullania flora of China, particularly Yunnan and the neighboring provinces, to be most highly differentiated, containing many phytogeographic ally interesting taxa, and may be regarded as a center of the Paleotropic Frullania flora.
Two new species of the genus Eponisiella Emeljanov, 1984 are described and illustrated from China (Guizhou and Shandong Provinces). These are E. dafangensis sp. nov. and E. shandongensis sp. nov., giving the genus eight species in total. A key to the species of Eponisiella is provided as well as a map of their geographic distribution, which is briefly discussed.
Elliptic flow from nuclear collisions is a hadronic observable sensitive to the early stages of system evolution. We report first results on elliptic flow of charged particles at midrapidity in Au+Au collisions at sqrt[sNN] = 130 GeV using the STAR Time Projection Chamber at the Relativistic Heavy Ion Collider. The elliptic flow signal, v2, averaged over transverse momentum, reaches values of about 6% for relatively peripheral collisions and decreases for the more central collisions. This can be interpreted as the observation of a higher degree of thermalization than at lower collision energies. Pseudorapidity and transverse momentum dependence of elliptic flow are also presented.
Damage control resuscitation may lead to postoperative intra-abdominal hypertension or abdominal compartment syndrome. These conditions may result in a vicious, self-perpetuating cycle leading to severe physiologic derangements and multiorgan failure unless interrupted by abdominal (surgical or other) decompression. Further, in some clinical situations, the abdomen cannot be closed due to the visceral edema, the inability to control the compelling source of infection or the necessity to re-explore (as a “planned second-look” laparotomy) or complete previously initiated damage control procedures or in cases of abdominal wall disruption. The open abdomen in trauma and non-trauma patients has been proposed to be effective in preventing or treating deranged physiology in patients with severe injuries or critical illness when no other perceived options exist. Its use, however, remains controversial as it is resource consuming and represents a non-anatomic situation with the potential for severe adverse effects. Its use, therefore, should only be considered in patients who would most benefit from it. Abdominal fascia-to-fascia closure should be done as soon as the patient can physiologically tolerate it. All precautions to minimize complications should be implemented.
Spirochetes belonging to the Borrelia (B.) burgdorferi sensu lato (s.l.) complex differ in their ability to establish infection and to survive in diverse vertebrate hosts. Association with and adaption to various hosts most likely correlates with the spirochetes' ability to acquire complement regulator factor H (FH) to overcome the host's innate immune response. Here we assessed binding of serum FH from human and various animals including bovine, cat, chicken, dog, horse, mouse, rabbit, and rat to viable B. burgdorferi sensu stricto (s.s.), B. afzelii, B. garinii, B. spielmanii, B. valaisiana, and B. lusitaniae. Spirochetes ectopically producing CspA orthologs of B. burgdorferi s.s., B. afzelii, and B. spielmanii, CspZ, ErpC, and ErpP, respectively, were also investigated. Our comparative analysis using viable bacterial cells revealed a striking heterogeneity among Lyme disease spirochetes regarding their FH-binding patterns that almost mirrors the serum susceptibility of the respective borrelial genospecies. Moreover, native CspA from B. burgdorferi s.s., B. afzelii, and B. spielmanii as well as CspZ were identified as key ligands of FH from human, horse, and rat origin while ErpP appears to bind dog and mouse FH and to a lesser extent human FH. By contrast, ErpC did not bind FH from human as well as from animal origin. These findings indicate a strong restriction of distinct borrelial proteins toward binding of polymorphic FH of various vertebrate hosts.
Lyme disease (LD), which is caused by genospecies of the Borrelia burgdorferi sensu lato complex, is the most common vector-borne disease in the Northern hemisphere. Spirochetes are transmitted by Ixodes ticks and maintained in diverse vertebrate animal hosts. Following tick bite, spirochetes initially establish a localized infection in the skin. However, they may also disseminate hematogenously to several distal sites, including heart, joints, or the CNS. Because they need to survive in diverse microenvironments, from tick vector to mammalian hosts, spirochetes have developed multiple strategies to combat the numerous host defense mechanisms. One of these strategies includes the production of a number of complement-regulator acquiring surface proteins (CRASPs) which encompass CspA, CspZ, and OspE paralogs to blunt the complement pathway. These proteins are capable of preventing complement activation on the spirochete surface by binding to complement regulator Factor H. The genes encoding these CRASPs differ in their expression patterns during the tick-to-host infection cycle, implying that these proteins may exhibit different functions during infection. This review summarizes the recent published reports which investigated the roles that each of these molecules plays in conferring tick-borne transmission and dissemination in vertebrate hosts. These findings offer novel mechanistic insights into LD pathobiology and may facilitate the identification of new targets for preventive strategies against Lyme borreliosis.
In this short note, we investigate simultaneous recovery inverse problems for semilinear elliptic equations with partial data. The main technique is based on higher order linearization and monotonicity approaches. With these methods at hand, we can determine the diffusion, cavity and coefficients simultaneously by knowing the corresponding localized Dirichlet-Neumann operators.
Distichophyllum meizhii Tan & Lin and D. wanianum Tan & Lin (Hookeriaceae) collected from southwestern region of China are described as new to science. Also, Horikawaea redfearnii Tan & Lin is described as a new species based on collections from Hainan Island of China and Palawan Island of the Philippines. The sporophytic specimen of Horikawaea Nog. was collected for the first time and support a family placement in Pterobryaceae.
A new species complex, the eparmata complex, is established within the subgenus Phortica s. str., based on eight known and five new species, all of which are endemic to the Oriental Region: P. bipartita (Toda & Peng, 1992), P. eparmata (Okada, 1977), P. lanuginosa Chen & Toda, 2007, P. latipenis Chen & Gao, 2005, P. pangi Chen & Wen, 2005, P. setitabula Chen & Gao, 2005, P. unipetala Chen & Wen, 2005 and P. zeta Chen & Toda, 2007; P. jadete sp. nov., P. kava sp. nov., P. mengda sp. nov., P. wongding sp. nov. and P. yena sp. nov. A key to all species of this complex is provided. Barcoding sequences (mitochondrial COI gene) were obtained for 22 specimens of five known and the five abovementioned new species. The intra- and inter-specific pairwise K-2P (Kimura’s two-parameter) distances of COI were determined. Phylogenetic analysis was performed using Bayesian inference based on COI sequences, confirming the monophyletic status of the eparmata complex, which is distinct from the species complexes of magna, omega, variegata and another two ungrouped species.
Autophagy is a physiological process for the recycling and degradation of cellular materials. Forming the autophagosome from the phagophore, a cup-shaped double-membrane vesicle, is a critical step in autophagy. The origin of the cup shape of the phagophore is poorly understood. In yeast, fusion of a small number of Atg9-containing vesicles is considered a key step in autophagosome biogenesis, aided by Atg1 complexes (ULK1 in mammals) localized at the preautophagosomal structure (PAS). In particular, the S-shaped Atg17-Atg31-Atg29 subcomplex of Atg1 is critical for phagophore nucleation at the PAS. To study this process, we simulated membrane remodeling processes in the presence and absence of membrane associated Atg17. We show that at least three vesicles need to fuse to induce the phagophore shape, consistent with experimental observations. However, fusion alone is not sufficient. Interactions with 34-nm long, S-shaped Atg17 complexes are required to overcome a substantial kinetic barrier in the transition to the cup-shaped phagophore. Our finding rationalizes the recruitment of Atg17 complexes to the yeast PAS, and their unusual shape. In control simulations without Atg17, with weakly binding Atg17, or with straight instead of S-shaped Atg17, the membrane shape transition did not occur. We confirm the critical role of Atg17-membrane interactions experimentally by showing that mutations of putative membrane interaction sites result in reduction or loss of autophagic activity in yeast. Fusion of a small number of vesicles followed by Atg17-guided membrane shape-remodeling thus emerges as a viable route to phagophore formation.
The Asplenium coenobiale complex is distributed in Eastern Asia and Southeast Asia with its distribution center in southwestern China. In this study, we carried out a detailed morphological, cytological, and phylogenetic study by adding two samples from Danxia landform in Guangdong. The sequences of five chloroplast markers and one nuclear marker of the A. coenobiale complex were analyzed with maximum likelihood and Bayesian inference, respectively. The morphological and phylogenetic analyses support the recognition of a new species (A. danxiaense K.W.Xu sp. nov.) of the A. coenobiale complex from a cave of Danxia mountain, Guangdong province, southern China. This new species can be distinguished from A. coenobiale and A. pulcherrimum by having scales narrowly triangular to lanceolate, apex ending in a short apical tail, basal basiscopic pinnule usually largest, fertile segment scarce, and exospore length usually more than 50 μm and shows significant molecular differences from other species in this complex. A detailed description and illustrations are presented.
Background: Denosumab treatment for up to 8 years in the FREEDOM study and Extension was associated with low fracture incidence. It was not clear whether subjects who discontinued during the study conduct had a higher risk of fracture than those who remained enrolled, thereby underestimating the true fracture risk for the entire trial cohort. Thus, we explored the influence of early withdrawals on nonvertebral fracture incidence during the Extension study.
Methods: To understand the potential effect of depletion of susceptible subjects on fracture incidence, we first evaluated subject characteristics in patients who were enrolled in the Extension vs those who were not. We subsequently employed a Kaplan-Meier multiple imputation (KMMI) approach to consider subjects who discontinued as if they remained enrolled with a 0%, 20%, 50%, and 100% increase in fracture risk compared with participants remaining on study.
Results: Extension enrollees were generally similar to nonparticipants in median age (71.9 and 73.1 years, respectively), mean total hip bone mineral density T-score (–1.9 and –2.0, respectively), and probability of fracture risk by Fracture Risk Assessment Tool (FRAX®) at FREEDOM baseline (16.9% and 17.7% for major osteoporotic fracture and 6.7% and 7.4% for hip fracture, respectively). When we assumed a doubled fracture risk (100% increase) after discontinuation in KMMI analyses, nonvertebral fracture rate estimates were only marginally higher than the observed rates for both the crossover group (10.32% vs 9.16%, respectively) and the long-term group (7.63% vs 6.63%, respectively).
Conclusion: The observation of continued denosumab efficacy over 8 years of treatment was robust and does not seem to be explained by depletion of susceptible subjects.
Trial registration: ClincalTrials.gov registration number NCT00523341; registered August 30, 2007
The genus Zingiber contains about 180 species distributed mainly in tropical regions. Several species of Zingiber are cultivated globally for their medicinal and culinary value, such as true gingers (Z. officinale), bitter gingers (Z. zerumbet), and Z. purpureum. In Taiwan, two endemic species and one incompletely known taxon were recorded in the last edition of Flora of Taiwan, and several taxonomic issues still remain unresolved. Therefore, we revised the Taiwanese Zingiber based on morphological, palynological, anatomical, and molecular evidence, as well as their distribution. The results showed that floral characters such as labellum, fertile bracts, and corolla tubes are of great taxonomic value in distinguishing taxa of Zingiber of Taiwan. Accordingly, five species are treated in the present study, namely Z. chengii Y.H.Tseng, C.M.Wang & Y.C.Lin, Z. mioga Thunb., Z. oligophyllum K.Schum., Z. pleiostachyum K.Schum., and Z. shuanglongense C.L.Yeh & S.W.Chung. Zingiber mioga might be a newly naturalized species to Taiwan. Zingiber kawagoii Hayata and Z. koshunense C.T.Moo are treated as synonyms of Z. pleiostachyum.
Consistent individual differences in behavioral tendencies (animal personality) can affect individual mate choice decisions. We asked whether personality traits affect male and female mate choice decisions similarly and whether potential personality effects are consistent across different mate choice situations. Using western mosquitofish (Gambusia affinis) as our study organism, we characterized focal individuals (males and females) twice for boldness, activity, and sociability/shoaling and found high and significant behavioral repeatability. Additionally, each focal individual was tested in two different dichotomous mate choice tests in which it could choose between computer-animated stimulus fish of the opposite sex that differed in body size and activity levels, respectively. Personality had different effects on female and male mate choice: females that were larger than average showed stronger preferences for large-bodied males with increasing levels of boldness/activity (i.e., towards more proactive personality types). Males that were larger than average and had higher shoaling tendencies showed stronger preferences for actively swimming females. Size-dependent effects of personality on the strength of preferences for distinct phenotypes of potential mating partners may reflect effects of age/experience (especially in females) and social dominance (especially in males). Previous studies found evidence for assortative mate choice based on personality types or hypothesized the existence of behavioral syndromes of individuals’ choosiness across mate choice criteria, possibly including other personality traits. Our present study exemplifies that far more complex patterns of personality-dependent mate choice can emerge in natural systems.
Baupläne des späten 19. und frühen 20. Jahrhunderts zeigen in den britischen Kolonialstadtgründungen Penang (Malaysia) und Singapur, dass genderdifferenzierte Raumkonzepte das Wohnen geprägt haben. In diesem Artikel werden die Formen des Wohnens sowie der Wandel der Raum- und Stadtstrukturen im kolonialstädtischen Südostasien beschrieben, die zur Herausbildung dieser binären Raumstrukturen geführt haben. Neben den sozioökonomischen Veränderungsprozessen verdienen Aspekte wie Geschlechterbeziehungen, Familien- und Haushaltsformen sowie vorbildprägende Wohnformen der Oberschichten besondere Aufmerksamkeit. Der Wandel der Wohnformen und -verhältnisse wird am Beispiel des innerstädtischen Shophouses konkretisiert. Das Shophouse hatte sich von einem teilgewerblich genutzten Stadthaus, das nach dem chinesischen Hofhaus angelegt war, zu einem Wohnreihenhaus nach Vorbildern viktorianischer Vorstadthäuser in Großbritannien entwickelt und diente schließlich als suburbanes Wohnhaus.
Gene targeting in embryonic stem (ES) cells remains best practice for introducing complex mutations into the mouse germline. One aspect in this multistep process that has not been streamlined with regard to the logistics and ethics of mouse breeding is the efficiency of germline transmission: the transmission of the ES cell-derived genome through the germline of chimeras to their offspring. A method whereby male chimeras transmit exclusively the genome of the injected ES cells to their offspring has been developed. The new technology, referred to as goGermline, entails injecting ES cells into blastocysts produced by superovulated homozygous Tsc22d3 floxed females mated with homozygous ROSA26-Cre males. This cross produces males that are sterile due to a complete cell-autonomous defect in spermatogenesis. The resulting male chimeras can be sterile but when fertile, they transmit the ES cell-derived genome to 100% of their offspring. The method was validated extensively and in two laboratories for gene-targeted ES clones that were derived from the commonly used parental ES cell lines Bruce4, E14, and JM8A3. The complete elimination of the collateral birth of undesired, non-ES cell-derived offspring in goGermline technology fulfills the reduction imperative of the 3R principle of humane experimental technique with animals. genesis 54:326-333, 2016. © 2016 The Authors. Genesis Published by Wiley Periodicals, Inc.
In the mouse, most mature olfactory sensory neurons (OSNs) express one allele of one gene from the repertoire of ~1100 odorant receptor (OR) genes, which encode G-protein coupled receptors (GPCRs). Axons of OSNs that express a given OR coalesce into homogeneous glomeruli, which reside at conserved positions in the olfactory bulb. ORs are intimately involved in ensuring the expression of one OR per OSN and the coalescence of OSN axons into glomeruli. But the mechanisms whereby ORs accomplish these diverse functions remain poorly understood. An experimental approach that has been informative is to substitute an OR genetically with another GPCR that is normally not expressed in OSNs, in order to determine in which aspects this GPCR can serve as surrogate OR in mouse OSNs. Thus far only the β2-adrenergic receptor (β2AR, Ardb2) has been shown to be able to serve as surrogate OR in OSNs; the β2AR could substitute for the M71 OR in all aspects examined. Can other non-olfactory GPCRs function equally well as surrogate ORs in OSNs? Here, we have generated and characterized two novel gene-targeted mouse strains in which the mouse melanocortin 4 receptor (Mc4r) or the mouse dopamine receptor D1 (Drd1a) is coexpressed with tauGFP in OSNs that express the OR locus M71. These alleles and strains are abbreviated as Mc4r→M71-GFP and Drd1a→M71-GFP. We detected strong Mc4r or Drd1a immunoreactivity in axons and dendritic knobs and cilia of OSNs that express Mc4r or Drd1a from the M71 locus. These OSNs responded physiologically to cognate agonists for Mc4r (Ro27-3225) or Drd1a (SKF81297), and not to the M71 ligand acetophenone. Axons of OSNs expressing Mc4r→M71-GFP coalesced into glomeruli. Axons of OSNs expressing Drd1a→M71-GFP converged onto restricted areas of the olfactory bulb but did not coalesce into glomeruli. Thus, OR functions in OSNs can be substituted by Mc4r or Drd1a, but not as well as by β2AR. We attribute the weak performance of Drd1a as surrogate OR to poor OSN maturation.
The current knowledge of the scorpionfly genus Dicerapanorpa Zhong & Hua, 2013 is taxonomically reviewed. Two new species of Dicerapanorpa are described and illustrated, increasing the species number of this genus to 20. Dicerapanorpa bifurcata sp. nov. from the Minshan Mountains, Sichuan Province, is characterized by the absence of the paramere basal branch and the elongated mesal branch in males, and the medigynium having a short basal stalk in females. Dicerapanorpa zhengkuni sp. nov. from the Wuling and Miaoling Mountains, Guizhou Province, is distinguishable by the greatly elongated hypovalves, the very short basal branch of the paramere, and the dorsomedially curved lateral branch in males, and the rounded main plate of the medigynium in females. An updated key to species of Dicerapanorpa is presented.
Die Analyse früher Entwicklungsstadien von Säugetierembryonen und daraus gewonnener Stammzelllinien kann entscheidende Erkenntnisse im Bereich der Reproduktionsbiologie und der regenerativen Medizin hervorbringen. Dabei spielt die Maus, als geeignetes Modellsystem für die Übertragbarkeit auf den Menschen eine wichtige Rolle, in erster Linie weil die Blastozysten der Maus verglichen mit menschliche Blastozysten eine morphologische Ähnlichkeit aufweisen. Humane embryonale Stammzelllinien haben großes Potential für die Anwendung in der regenerativen Medizin und vergleichend dazu wurde Gen-Targeting in embryonalen Stammzellen verwendet, um tausende neuer Mausstämme zu generieren. Die Gewinnung embryonaler Stammzellen erfolgt im Blastozystenstadium, diese können dann nach Injektion in eine andere Blastozyste zur Entwicklung aller Gewebearten, einschließlich der Keimbahngewebe, beitragen (Martin, 1981; Evans and Kaufman 1981).
Ursache einer Fehlgeburt können vor allem Defekte in der Entwicklung des Trophoblasten und des primitive Entoderms (PrE) sein, dabei sind ca. 5 % der Paare betroffen die versuchen ein Kind zu bekommen (Stephenson and Kutteh, 2007). Eine Untersuchung dieser Zelllinien im Mausmodell könnte weitere Erkenntnisse für die Gründe einer Fehlentwicklung liefern. Trophoblasten Stammzelllinien können aus den Blastozysten der Maus und dem extraembryonalen Ektoderm von bereits implantieren Embryonen gewonnen werden (Tanaka et al., 1998). Diese Zelllinien geben Aufschluss über die Entwicklung des Trophoblasten, fördern die Entwicklung der Plazenta und sind gleichzeitig ein gutes Modellsystem um die Implantation des Embryos im Uterus näher zu untersuchen. Zellen des primitive Entoderms (PrE) beeinflussen das im Dottersack vorhandene extraembryonale Entoderm, welches dort als “frühe Plazenta” fungiert und für die Versorgung des Embryos mit Nährstoffen zuständig ist (Cross et al., 1994). Des Weiteren besitzt das Entoderm einen induktiven Einfluss auf die Bildung von anterioren Strukturen und die Bildung von Endothelzellen sowie Blutinseln (Byrd et al., 2002).
Extraembryonale Endodermstammzellen (XEN Zellen) können aus Blastozysten gewonnen und in embryonale Stammzellen (ES-Zellen) umgewandelt werden (Fujikura et al., 2002; Kunath et al., 2005). Es war jedoch nicht bekannt, ob XEN-Zellen auch aus Postimplantations-Embryonen gewonnen werden können. XEN-Zellen tragen in vivo zur Entwicklung des Darmendoderms bei (Kwon et al., 2008; Viotti et al., 2014) und könnten als alternative, selbsterneuernde Quelle für extraembryonale Endoderm-abgeleitete Zellen dienen, die zur Herstellung von Geweben für die regenerative Medizin verwendet werden könnten (Niakan et al., 2013).
In der Embryogenese der Maus zeigt sich an Tag E3.0 eine kompakte Morula die sich allmählich in das Trophektoderm (TE) differenziert, welches wiederum den Embryonalknoten (“innere Zellmasse”) umschließt (Johnson and Ziomek, 1981). Ein wichtiger Schritt im Rahmen der Entwicklung findet an Tag E3.5 statt, in diesem Zeitraum gehen aus dem Embryonalknoten der pluripotente Epiblast und das primitive Entoderm hervor. Im späten Blastozystenstadium an Tag E4.5 liegt das PrE als Zellschicht entlang der Oberfläche der Blastocoel-Höhle. Aus dem Epiblast entwickeln sich im weiteren Verlauf der Embryo, das Amnion und das extraembryonale Mesoderm des Dottersacks. Die Zellen des Trophektoderm führen zur Entwicklung der Plazenta. Das PrE differenziert sich im Zuge der Weiterentwicklung in das viszerale Entoderm (VE) und das parietale Entoderm (PE) des Dottersacks (Chazaud et al., 2006; Gardner and Rossant, 1979; Plusa et al., 2008). VE umgibt den Epiblast und extraembryonisches Ektoderm (ExE). PE-Zellen wandern entlang der inneren Oberfläche von TE und sezernieren zusammen mit Trophoblasten-Riesenzellen Basalmembranproteine, um die Reichert-Membran zu bilden (Hogan et al., 1980). Die Reichert-Membran besteht aus Basalmembranproteinen, einschließlich Kollagenen und Lamininen, die zwischen den parietalen Endoderm- und Trophoblastzellen liegen. Diese Membran wirkt als ein Filter, der dem Embryo den Zugang zu Nährstoffen ermöglicht, während er eine Barriere zu den Zellen der Mutter bildet (Gardner, 1983).
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A wealth of data has elucidated the mechanisms by which sensory inputs are encoded in the neocortex, but how these processes are regulated by the behavioral relevance of sensory information is less understood. Here, we focus on neocortical layer 1 (L1), a key location for processing of such top-down information. Using Neuron-Derived Neurotrophic Factor (NDNF) as a selective marker of L1 interneurons (INs) and in vivo 2-photon calcium imaging, electrophysiology, viral tracing, optogenetics, and associative memory, we find that L1 NDNF-INs mediate a prolonged form of inhibition in distal pyramidal neuron dendrites that correlates with the strength of the memory trace. Conversely, inhibition from Martinotti cells remains unchanged after conditioning but in turn tightly controls sensory responses in NDNF-INs. These results define a genetically addressable form of dendritic inhibition that is highly experience dependent and indicate that in addition to disinhibition, salient stimuli are encoded at elevated levels of distal dendritic inhibition.
Extraembryonic endoderm stem (XEN) cell lines can be derived and maintained in vitro and reflect the primitive endoderm lineage. Platelet-derived growth factor receptor alpha (PDGFRA) is thought to be essential for the derivation and maintenance of mouse XEN cell lines. Here, we have re-evaluated this requirement for PDGFRA. We derived multiple PDGFRA-deficient XEN cell lines from postimplantation and preimplantation embryos of a PDGFRA-GFP knockout strain. We also converted PDGFRA-deficient embryonic stem cell lines into XEN cell lines chemically by transient culturing with retinoic acid and Activin A. We confirmed the XEN profile of our 12 PDGFRA-deficient cell lines by immunofluorescence with various markers, by NanoString gene expression analyses, and by their contribution to the extraembryonic endoderm of chimeric embryos produced by injecting these cells into blastocysts. Thus, PDGFRA is not essential for the derivation and maintenance of XEN cell lines.
Transcatheter left atrial appendage occlusion (LAAO) is non-inferior to vitamin K antagonists (VKAs) in preventing thromboembolic events in atrial fibrillation (AF). Non-vitamin K antagonists (NOACs) have an improved safety profile over VKAs; however, evidence regarding their effect on cardiovascular and neurological outcomes relative to LAAO is limited. Up-to-date randomized trials or propensity-score-matched data comparing LAAO vs. NOACs in high-risk patients with AF were pooled in our study. A total of 2849 AF patients (LAAO: 1368, NOACs: 1481, mean age: 75 ± 7.5 yrs, 63.5% male) were enrolled. The mean CHA2DS2-VASc score was 4.3 ± 1.7, and the mean HAS-BLED score was 3.4 ± 1.2. The baseline characteristics were comparable between the two groups. In the LAAO group, the success rate of device implantation was 98.8%. During a mean follow-up of 2 years, as compared with NOACs, LAAO was associated with a significant reduction of ISTH major bleeding (p = 0.0002). There were no significant differences in terms of ischemic stroke (p = 0.61), ischemic stroke/thromboembolism (p = 0.63), ISTH major and clinically relevant minor bleeding (p = 0.73), cardiovascular death (p = 0.63), and all-cause mortality (p = 0.71). There was a trend toward reduction of combined major cardiovascular and neurological endpoints in the LAAO group (OR: 0.84, 95% CI: 0.64–1.11, p = 0.12). In conclusion, for high-risk AF patients, LAAO is associated with a significant reduction of ISTH major bleeding without increased ischemic events, as compared to “contemporary NOACs”. The present data show the superior role of LAAO over NOACs among high-risk AF patients in terms of reduction of major bleeding; however, more randomized controlled trials are warranted.
Background: Macrophage Migration Inhibitory Factor (MIF) is highly elevated after cardiac surgery and impacts the postoperative inflammation. The aim of this study was to analyze whether the polymorphisms CATT5–7 (rs5844572/rs3063368,“-794”) and G>C single-nucleotide polymorphism (rs755622,-173) in the MIF gene promoter are related to postoperative outcome. Methods: In 1116 patients undergoing cardiac surgery, the MIF gene polymorphisms were analyzed and serum MIF was measured by ELISA in 100 patients. Results: Patients with at least one extended repeat allele (CATT7) had a significantly higher risk of acute kidney injury (AKI) compared to others (23% vs. 13%; OR 2.01 (1.40–2.88), p = 0.0001). Carriers of CATT7 were also at higher risk of death (1.8% vs. 0.4%; OR 5.12 (0.99–33.14), p = 0.026). The GC genotype was associated with AKI (20% vs. GG/CC:13%, OR 1.71 (1.20–2.43), p = 0.003). Multivariate analyses identified CATT7 predictive for AKI (OR 2.13 (1.46–3.09), p < 0.001) and death (OR 5.58 (1.29–24.04), p = 0.021). CATT7 was associated with higher serum MIF before surgery (79.2 vs. 50.4 ng/mL, p = 0.008). Conclusion: The CATT7 allele associates with a higher risk of AKI and death after cardiac surgery, which might be related to chronically elevated serum MIF. Polymorphisms in the MIF gene may constitute a predisposition for postoperative complications and the assessment may improve risk stratification and therapeutic guidance.
Variants resistant to compounds specifically targeting HCV are observed in clinical trials. A multi-variant viral dynamic model was developed to quantify the evolution and in vivo fitness of variants in subjects dosed with monotherapy of an HCV protease inhibitor, telaprevir. Variant fitness was estimated using a model in which variants were selected by competition for shared limited replication space. Fitness was represented in the absence of telaprevir by different variant production rate constants and in the presence of telaprevir by additional antiviral blockage by telaprevir. Model parameters, including rate constants for viral production, clearance, and effective telaprevir concentration, were estimated from 1) plasma HCV RNA levels of subjects before, during, and after dosing, 2) post-dosing prevalence of plasma variants from subjects, and 3) sensitivity of variants to telaprevir in the HCV replicon. The model provided a good fit to plasma HCV RNA levels observed both during and after telaprevir dosing, as well as to variant prevalence observed after telaprevir dosing. After an initial sharp decline in HCV RNA levels during dosing with telaprevir, HCV RNA levels increased in some subjects. The model predicted this increase to be caused by pre-existing variants with sufficient fitness to expand once available replication space increased due to rapid clearance of wild-type (WT) virus. The average replicative fitness estimates in the absence of telaprevir ranged from 1% to 68% of WT fitness. Compared to the relative fitness method, the in vivo estimates from the viral dynamic model corresponded more closely to in vitro replicon data, as well as to qualitative behaviors observed in both on-dosing and long-term post-dosing clinical data. The modeling fitness estimates were robust in sensitivity analyses in which the restoration dynamics of replication space and assumptions of HCV mutation rates were varied.
Using 10.1 × 109 J/ψ events produced by the Beijing Electron Positron Collider (BEPCII) at a center-of-mass energy √s = 3.097 GeV and collected with the BESIII detector, we present a search for the rare semi-leptonic decay J/ψ → D−e+νe + c.c. No excess of signal above background is observed, and an upper limit on the branching fraction ℬ(J/ψ → D−e+νe + c. c.) < 7.1 × 10−8 is obtained at 90% confidence level. This is an improvement of more than two orders of magnitude over the previous best limit.
The process e+e−→ϕη is studied at 22 center-of-mass energy points (√s) between 2.00 and 3.08 GeV using 715 pb−1 of data collected with the BESIII detector. The measured Born cross section of e+e−→ϕη is found to be consistent with BABAR measurements, but with improved precision. A resonant structure around 2.175 GeV is observed with a significance of 6.9σ with mass (2163.5±6.2±3.0) MeV/c2 and width (31.1+21.1−11.6±1.1) MeV, where the first uncertainties are statistical and the second are systematic.
A new planthopper genus, Aodingus Chen & Li gen. nov. and three new species (A. hainanensis Chen & Li gen. et sp. nov., A. obscurus Chen & Li gen. et sp. nov. and A. cuongi Chen & Li gen. et sp. nov.) are described from China and Vietnam. The new genus is superficially similar to Procidelphax Bartlett, 2009 in general appearance in that the body is strongly dorsoventrally flattened. Distinctive features of the new taxon include broadly compressed body with vertex broad, apical margin broadly rounded, middle part concave, median and submedian carinae absent, frons broad and large, wider at base than at apex, forewing broad and long, aedeagus tubular, curved ventrally. A diagnosis for all species, illustrations and an identification key of new genus are provided. A key to the Chinese genera of Tropidocephalini is also provided.
Unique features of a global human ectoparasite identified through sequencing of the bed bug genome
(2016)
The bed bug, Cimex lectularius, has re-established itself as a ubiquitous human ectoparasite throughout much of the world during the past two decades. This global resurgence is likely linked to increased international travel and commerce in addition to widespread insecticide resistance. Analyses of the C. lectularius sequenced genome (650 Mb) and 14,220 predicted protein-coding genes provide a comprehensive representation of genes that are linked to traumatic insemination, a reduced chemosensory repertoire of genes related to obligate hematophagy, host–symbiont interactions, and several mechanisms of insecticide resistance. In addition, we document the presence of multiple putative lateral gene transfer events. Genome sequencing and annotation establish a solid foundation for future research on mechanisms of insecticide resistance, human–bed bug and symbiont–bed bug associations, and unique features of bed bug biology that contribute to the unprecedented success of C. lectularius as a human ectoparasite.
Periplasmic Sud protein encoded by the Wolinella succinogenes catalyses the transfer of bound polysulfide-sulfur to the active site of the membrane bound polysulfide reductase. The homodimeric protein consists of 131 residues per monomer, each with one cysteine residue in the active site. Polysulfide-sulfur is covalently bound to the catalytic Cys residues of the Sud protein. In order to understand the structure-function relationship of this protein, the features of its solution structure determined by heteronuclear multidimensional NMR techniques are reported here. The first step of structure determination leads to resonance assignments using 15N/13C/2H- and 15N/13C-labeled protein. The sequential backbone and side chain resonance assignments have been successfully completed. Structure calculations were carried out using the ARIA program package. The structure is based on 2688 NOE-derived distance restraints, 68 backbone hydrogen bond restraints derived from 34 slow-exchanging backbone amide protons and 334 torsion angle restraints obtained from the TALOS program as well as 158 residual dipolar coupling restraints for the refinement of relative vector orientations. The three-dimensional structure of the Sud protein was determined with an averaged rootmean- square deviation of 0.72 Å and 1.28 Å for the backbone and heavy atoms, respectively, excluding the terminal residues. Without the poorly defined segment between residues 90-94 the average r.m.s.d. value drops down to 0.6 Å and 1.14 Å. The ensemble refined with residual dipolar coupling (rdc) restraints shows good convergence. The r.m.s.d. value for the backbone heavy atoms, excluding residues 90- 94, drops down from 0.97 to 0.66 for the rdc-refined ensemble. The relative orientation of the two monomers in the protein structures refined with residual dipolar coupling restraints are also different from those without residual dipolar coupling restraints. The structure determination of the dimeric protein has been hampered by the high molecular mass (30 kDa), severe peak degeneracy, and by the small number of experimental intermonomer NOEs (relative orientation problem of two monomers). For the resonance assignments of aliphatic side chain, many resonances were ambiguously assigned because of severe overlap of signals. The Sud dimer protein contains 17 Lys, 14 Leu and one His tag for each monomer. It complicated the resonance assignments. The conventional 3D 15N-separated TOCSY HSQC experiment failed because of the large molecular weight which results in line broadening and hence made the resonance assignments of side chains more difficult. The determined structure contains a five-stranded parallel ß-sheet enclosing a hydrophobic core, a two-stranded anti-parallel ß-sheet and seven a-helices. The dimer structure is stabilized predominantly by hydrophobic residues. Sud catalyses the transfer of the polysulfide-sulfur to cyanide, similar to rhodanese encoded by Azotobacter vinelandii (Bordo et al., 2000). The two proteins are similar in the active site environment primarily owing to the main-chain conformation of the active-site loop with the cysteine residue and with respect to the surrounding positively charged residues. The active-site loop (residues 89-95) in the Sud protein appears to be flexible, reflected by few assigned proton resonances of residues 90-94 in the active site. Despite their similarity in function and their similar structure in active site, the amino acid sequences and the folds of the two proteins are remarkably different. The negatively charged polysulfide interacts with positively charged R46, R67, and R94 and hence may be stabilized in structure. The mutation of one of the three arginines that are also conserved in rhodanese from A. vinelandii leads to a loss of sulfur-transfer activity. The polysulfide chain extends from inside of Sud protein to outside, where Sud may form contacts with polysulfide reductase. These contacts provide the possible polysulfide-sulfur transfer from Sud protein to the active site of polysulfide reductase.
The genus Parandes Muir, 1925 (Cixiinae, Andini) is recorded from China for the first time with two new species, Parandes circinatus Wang & Chen sp. nov. and Parandes fuscus Wang & Chen sp. nov. Color images for the adults of the two new species and line drawings for the genitalia are provided. A key is presented to separate all species within the genus.
Background Although current molecular clock methods offer greater flexibility in modelling historical evolutionary events, calibration of the clock with dates from the fossil record is still problematic for many groups. Here we implement several new approaches in molecular dating to estimate evolutionary ages of Lacertidae, an Old World family of lizards with a poor fossil record and uncertain phylogeny. Four different models of rate variation are tested in a new program for Bayesian phylogenetic analysis called TreeTime, based on a combination of mitochondrial and nuclear gene sequences. We incorporate paleontological uncertainty into divergence estimates by expressing multiple calibration dates as a range of probabilistic distributions. We also test the reliability of our proposed calibrations by exploring effects of individual priors on posterior estimates. Results According to the most reliable model, as indicated by Bayes factor comparison, modern lacertids arose shortly after the K/T transition and entered Africa about 45 million years ago, with the majority of their African radiation occurring in the Eocene and Oligocene. Our findings indicate much earlier origins for these clades than previously reported, and we discuss our results in light of paleogeographic trends during the Cenozoic. Conclusions This study represents the first attempt to estimate evolutionary ages of a specific group of reptiles exhibiting uncertain phylogenetic relationships, molecular rate variation and a poor fossil record. Our results emphasize the sensitivity of molecular divergence dates to fossil calibrations, and support the use of combined molecular data sets and multiple, well-spaced dates from the fossil record as minimum node constraints. The bioinformatics program used here, TreeTime, is publicly available, and we recommend its use for molecular dating of taxa faced with similar challenges.
Borrelia burgdorferi sensu lato (Bbsl), the causative agent of Lyme disease, establishes an initial infection in the host’s skin following a tick bite, and then disseminates to distant organs, leading to multisystem manifestations. Tick-to-vertebrate host transmission requires that Bbsl survives during blood feeding. Complement is an important innate host defense in blood and interstitial fluid. Bbsl produces a polymorphic surface protein, CspA, that binds to a complement regulator, Factor H (FH) to block complement activation in vitro. However, the role that CspA plays in the Bbsl enzootic cycle remains unclear. In this study, we demonstrated that different CspA variants promote spirochete binding to FH to inactivate complement and promote serum resistance in a host-specific manner. Utilizing a tick-to-mouse transmission model, we observed that a cspA-knockout B. burgdorferi is eliminated from nymphal ticks in the first 24 hours of feeding and is unable to be transmitted to naïve mice. Conversely, ectopically producing CspA derived from B. burgdorferi or B. afzelii, but not B. garinii in a cspA-knockout strain restored spirochete survival in fed nymphs and tick-to-mouse transmission. Furthermore, a CspA point mutant, CspA-L246D that was defective in FH-binding, failed to survive in fed nymphs and at the inoculation site or bloodstream in mice. We also allowed those spirochete-infected nymphs to feed on C3-/- mice that lacked functional complement. The cspA-knockout B. burgdorferi or this mutant strain complemented with cspA variants or cspA-L246D was found at similar levels as wild type B. burgdorferi in the fed nymphs and mouse tissues. These novel findings suggest that the FH-binding activity of CspA protects spirochetes from complement-mediated killing in fed nymphal ticks, which ultimately allows Bbsl transmission to mammalian hosts.
Global investment in biomedical research has grown significantly over the last decades, reaching approximately a quarter of a trillion US dollars in 2010. However, not all of this investment is distributed evenly by gender. It follows, arguably, that scarce research resources may not be optimally invested (by either not supporting the best science or by failing to investigate topics that benefit women and men equitably). Women across the world tend to be significantly underrepresented in research both as researchers and research participants, receive less research funding, and appear less frequently than men as authors on research publications. There is also some evidence that women are relatively disadvantaged as the beneficiaries of research, in terms of its health, societal and economic impacts. Historical gender biases may have created a path dependency that means that the research system and the impacts of research are biased towards male researchers and male beneficiaries, making it inherently difficult (though not impossible) to eliminate gender bias. In this commentary, we – a group of scholars and practitioners from Africa, America, Asia and Europe – argue that gender-sensitive research impact assessment could become a force for good in moving science policy and practice towards gender equity. Research impact assessment is the multidisciplinary field of scientific inquiry that examines the research process to maximise scientific, societal and economic returns on investment in research. It encompasses many theoretical and methodological approaches that can be used to investigate gender bias and recommend actions for change to maximise research impact. We offer a set of recommendations to research funders, research institutions and research evaluators who conduct impact assessment on how to include and strengthen analysis of gender equity in research impact assessment and issue a global call for action.
Bayessche Methoden zur Schätzung von Stammbäumen mit Verzweigungszeitpunkten aus molekularen Daten
(2009)
Ein großes Ziel der Evolutionsbiologie ist es, die Stammesgeschichte der Arten zu rekonstruieren. Historisch verwendeten Systematiker hierfür morphologische und anatomische Merkmale. Mit dem stetigen Zuwachs an verfügbaren Sequenzdaten werden heute verstärkt Methoden entwickelt und eingesetzt, welche die Rekonstruktion auf Basis von molekularen Daten ermöglichen. Im Fokus der aktuellen Forschung steht die Anwendung und Weiterentwicklung Bayesscher Methoden. Diese Methoden besitzen große Popularität, da sie in Verbindung mit Markov-Ketten-Monte-Carlo-Verfahren eingesetzt werden können, um einen Stammbaum zu vorgegebenen Spezies zu schätzen und dessen Variabilität zu bestimmen. Im Rahmen dieser Dissertation wurde die erweiterbare Software TreeTime entwickelt. TreeTime bietet Schnittstellen für die Einbindung von molekularen Evolutions- und Ratenänderungsmodellen und stellt neu entwickelte Methoden bereit, um Stammbäume mit Verzweigungszeitpunkten zu rekonstruieren. In TreeTime werden die molekularen Daten und die zeitlichen Informationen, wie z.B. Fossilfunde, in einem Bayes-Verfahren simultan berücksichtigt, um die Zeitpunkte der Artaufspaltungen genauer zu datieren. Für die Anwendung Bayesscher Methoden in der Rekonstruktion von Stammbäumen wird ein stochastisches Modell benötigt, das die Evolution der molekularen Sequenzen entlang den Kanten eines Stammbaums beschreibt. Der Mutationsprozess der Sequenzen wird durch ein molekulares Evolutionsmodell definiert. Die Verwendung der klassischen molekularen Evolutionsmodelle impliziert die Annahme einer konstanten Evolutionsgeschwindigkeit der Sequenzen im Stammbaum. Diese Annahme wird als Hypothese der molekularen Uhr bezeichnet und bildet die Grundlage zum Schätzen der Verzweigungszeiten des Stammbaums. Der Verzweigungszeitpunkt, an dem sich zwei Spezies im Stammbaum aufspalten, spiegelt sich in der Ähnlichkeit der zugehörigen molekularen Sequenzen. Je älter dieser Verzweigungszeitpunkt ist, desto größer ist die Anzahl der unterschiedlichen Positionen in den Sequenzen. Häufig ist jedoch die Annahme der molekularen Uhr verletzt, so dass in gewissen Teilbereichen eines Stammbaums eine erhöhte Evolutionsgeschwindigkeit nachweisbar ist. Falls die Verletzung konstanter Evolutionsgeschwindigkeiten nicht ausgeschlossen werden kann, sollten schwankende Mutationsraten in der Modellierung explizit berücksichtigt werden. Hierfür wurden verschiedene Ratenänderungsmodelle vorgeschlagen. Bisher sind nur wenige dieser Ratenänderungsmodelle in Softwarepaketen verfügbar und ihre Eigenschaften sind nicht ausreichend erforscht. Das Ziel dieser Arbeit ist die Entwicklung und Bereitstellung von Bayesschen Modellen und Methoden zum Schätzen von Stammbäumen mit Verzweigungszeitpunkten. Die Methoden sollten auch bei unterschiedlichen Evolutionsgeschwindigkeiten im Stammbaum anwendbar sein. Vorgestellt wird ein neues Ratenänderungsmodell, eine neue Möglichkeit der Angabe von flexiblen Beschränkungen für die Topologie des Stammbaums sowie die Nutzung dieser Beschränkungen für die zeitliche Kalibrierung. Das neue Raten Änderungsmodell sowie die topologischen und zeitlichen Beschränkungen werden in einen modularen Softwareentwurf eingebettet. Durch den erweiterbaren Entwurf können bestehende und zukünftige molekulare Evolutionsmodelle und Ratenänderungsmodelle in die Software eingebunden und verwendet werden. Die vorgestellten Modelle und Methoden werden gemäß dem Softwareentwurf in das neu entwickelte Programm TreeTime aufgenommen und effzient implementiert. Zusätzlich werden bereits vorhandene Modelle programmiert und eingebunden, die nicht in anderen Softwarepaketen verfügbar sind. Des Weiteren wird eine neue Methode entwickelt und angewendet, um die Passgenauigkeit eines Modells für die Apriori-Verteilung auf der Menge der Baumtopologien zu beurteilen. Diese Methode wird zur Auswahl geeigneter Modelle benutzt, indem eine Auswertung der beobachteten Baumtopologien der Datenbank TreeBASE durchgeführt wird. Anschließend wird die Software TreeTime in einer Simulationsstudie eingesetzt, um die Eigenschaften der implementierten Ratenänderungsmodelle zu vergleichen. Die Software wird für die Rekonstruktion des Stammbaums zu 38 Spezies aus der Familie der Eidechsen (Lacertidae) verwendet. Da die zugehörigen molekularen Daten von der Hypothese der molekularen Uhr abweichen, werden unterschiedliche Ratenänderungsmodelle bei der Rekonstruktion verwendet und abschließend bewertet. ........
BACKGROUND & AIMS: Proton pump inhibitors (PPIs) are commonly prescribed to treat acid-related disorders. Some direct-acting antiviral regimens for chronic hepatitis C virus (HCV) infection have reduced efficacy in patients taking concomitant acid-reducing agents, including PPIs, due to interactions between drugs. We analyzed data from 9 multicenter, phase 2 and 3 trials to determine the efficacy and pharmacokinetics of an HCV therapeutic regimen comprising glecaprevir and pibrentasvir (glecaprevir/pibrentasvir) in patients taking concomitant acid-reducing agents.
METHODS: We analyzed data from 2369 patients infected with HCV genotypes 1-6 and compensated liver disease treated with an all-oral regimen of glecaprevir/pibrentasvir for 8-16 weeks. We compared efficacy and pharmacokinetics among patients receiving at least 1 dose of an acid-reducing agent (a PPI, an H2 blocker, or antacid). High-dose PPI was defined as daily dose greater than 20 mg omeprazole dose equivalent. The objectives were to evaluate rate of sustained virologic response 12 weeks post-treatment (SVR12) and to assess steady-state glecaprevir and pibrentasvir exposures in patients on acid-reducing agents.
RESULTS: Of the 401 patients (17%) who reported use of acid-reducing agents, 263 took PPIs (11%; 109 patients took a high-dose PPI and 154 patients took a low-dose PPI). Rates of SVR12 were 97.0% among patients who used acid-reducing agents and 97.5% among those not using acid-reducing agents (P = .6). An SVR12 was achieved in 96.3% taking a high-dose PPI and 97.4% taking a low-dose PPI, with no virologic failures in those receiving a high-dose PPI (P = .7). Glecaprevir, but not pibrentasvir, bioavailability was affected; its exposure decreased by 41% in patients taking a high-dose PPI.
CONCLUSIONS: In an analysis of data from 9 clinical trials, we observed a high rate of SVR12 (approximately 97%) among patients treated with glecaprevir/pibrentasvir for HCV infection-even among patients taking concomitant ARA or high-dose PPI. This was despite decreased glecaprevir exposures in patients when on high-dose PPIs. ClinicalTrials.gov numbers, NCT02243280 (SURVEYOR-I), NCT02243293 (SURVEYOR-II), NCT02604017 (ENDURANCE-1), NCT02640482 (ENDURANCE-2), NCT02640157 (ENDURANCE-3), NCT02636595 (ENDURANCE-4), NCT02642432 (EXPEDITION-1), NCT02651194 (EXPEDITION-4), NCT02446717 (MAGELLAN-I).
Camellia sinensis is one of the major crops grown in Taiwan and has been widely cultivated around the island. Tea leaves are prone to various fungal infections, and leaf spot is considered one of the major diseases in Taiwan tea fields. As part of a survey on fungal species causing leaf spots on tea leaves in Taiwan, 19 fungal strains morphologically similar to the genus Diaporthe were collected. ITS (internal transcribed spacer), tef1-α (translation elongation factor 1-α), tub2 (beta-tubulin), and cal (calmodulin) gene regions were used to construct phylogenetic trees and determine the evolutionary relationships among the collected strains. In total, six Diaporthe species, including one new species, Diaporthe hsinchuensis, were identified as linked with leaf spot of C. sinensis in Taiwan based on both phenotypic characters and phylogeny. These species were further characterized in terms of their pathogenicity, temperature, and pH requirements under laboratory conditions. Diaporthe tulliensis, D. passiflorae, and D. perseae were isolated from C. sinensis for the first time. Furthermore, pathogenicity tests revealed that, with wound inoculation, only D. hongkongensis was pathogenic on tea leaves. This investigation delivers the first assessment of Diaporthe taxa related to leaf spots on tea in Taiwan.
Pathogens possess the ability to adapt and survive in some host species but not in others–an ecological trait known as host tropism. Transmitted through ticks and carried mainly by mammals and birds, the Lyme disease (LD) bacterium is a well-suited model to study such tropism. Three main causative agents of LD, Borrelia burgdorferi, B. afzelii, and B. garinii, vary in host ranges through mechanisms eluding characterization. By feeding ticks infected with different Borrelia species, utilizing feeding chambers and live mice and quail, we found species-level differences in bacterial transmission. These differences localize on the tick blood meal, and specifically complement, a defense in vertebrate blood, and a polymorphic bacterial protein, CspA, which inactivates complement by binding to a host complement inhibitor, Factor H (FH). CspA selectively confers bacterial transmission to vertebrates that produce FH capable of allele-specific recognition. CspA is the only member of the Pfam54 gene family to exhibit host-specific FH-binding. Phylogenetic analyses revealed convergent evolution as the driver of such uniqueness, and that FH-binding likely emerged during the last glacial maximum. Our results identify a determinant of host tropism in Lyme disease infection, thus defining an evolutionary mechanism that shapes host-pathogen associations.
Heart valve disease is a major clinical problem worldwide. Cardiac valve development and homeostasis need to be precisely controlled. Hippo signaling is essential for organ development and tissue homeostasis, while its role in valve formation and morphology maintenance remains unknown. VGLL4 is a transcription cofactor in vertebrates and we found it was mainly expressed in valve interstitial cells at the post-EMT stage and was maintained till the adult stage. Tissue specific knockout of VGLL4 in different cell lineages revealed that only loss of VGLL4 in endothelial cell lineage led to valve malformation with expanded expression of YAP targets. We further semi-knockout YAP in VGLL4 ablated hearts, and found hyper proliferation of arterial valve interstitial cells was significantly constrained. These findings suggest that VGLL4 is important for valve development and manipulation of Hippo components would be a potential therapy for preventing the progression of congenital valve disease.
Though immensely successful, the standard model of particle physics does not offer any explanation as to why our Universe contains so much more matter than antimatter. A key to a dynamically generated matter–antimatter asymmetry is the existence of processes that violate the combined charge conjugation and parity (CP) symmetry1. As such, precision tests of CP symmetry may be used to search for physics beyond the standard model. However, hadrons decay through an interplay of strong and weak processes, quantified in terms of relative phases between the amplitudes. Although previous experiments constructed CP observables that depend on both strong and weak phases, we present an approach where sequential two-body decays of entangled multi-strange baryon–antibaryon pairs provide a separation between these phases. Our method, exploiting spin entanglement between the double-strange Ξ− baryon and its antiparticle2 Ξ¯+
, has enabled a direct determination of the weak-phase difference, (ξP − ξS) = (1.2 ± 3.4 ± 0.8) × 10−2 rad. Furthermore, three independent CP observables can be constructed from our measured parameters. The precision in the estimated parameters for a given data sample size is several orders of magnitude greater than achieved with previous methods3. Finally, we provide an independent measurement of the recently debated Λ decay parameter αΛ (refs. 4,5). The ΛΛ¯
asymmetry is in agreement with and compatible in precision to the most precise previous measurement.
By analyzing 6.32 fb − 1 of e+ e− annihilation data collected at the center-of-mass energies between 4.178 and 4.226 GeV with the BESIII detector, we determine the branching fraction of the leptonic decay D + s → τ + ντ, with τ+ → π + π0¯ντ, to be B D + s → τ + ν τ = (5.29 ± 0.25 stat ± 0.20 syst) %. We estimate the product of the Cabibbo-Kobayashi-Maskawa matrix element |Vcs|and the D + s decay constant f D + s to be f D + s|Vcs| = (244.8 ± 5.8 stat ± 4.8syst) MeV, using the known values of the τ + and D + s masses as well as the D + s lifetime, together with our branching fraction measurement. Combining the value of |Vcs| obtained from a global fit in the standard model and f D + s from lattice quantum chromodynamics, we obtain f D + s = (251.6 ± 5.9 stat ± 4.9syst) MeV and |Vcs| = 0.980 ± 0.023 stat ± 0.019 syst. Using the branching fraction of B D + s → μ + νμ = (5.35±0.21)×10−3, we obtain the ratio of the branching fractions B D + s → τ + ντ/B D +s → μ+νμ = 9.89±0.71, which is consistent with the standard model prediction of lepton flavor universality.
We present the first measurement of the proton–Ω correlation function in heavy-ion collisions for the central (0–40%) and peripheral (40–80%) Au + Au collisions at √sNN = 200 GeV by the STAR experiment at the Relativistic Heavy-Ion Collider (RHIC). Predictions for the ratio of peripheral collisions to central collisions for the proton–Ω correlation function are sensitive to the presence of a nucleon– bound state. These predictions are based on the proton– interaction extracted from (2 + 1)-flavor lattice QCD calculations at the physical point. The measured ratio of the proton–Ω correlation function between the peripheral (small system) and central (large system) collisions is less than unity for relative momentum smaller than 40 MeV/c. Comparison of our measured correlation ratio with theoretical calculation slightly favors a proton– bound system with a binding energy of ∼ 27 MeV.
We report the direct virtual photon invariant yields in the transverse momentum ranges 1 < pT < 3 GeV/c and 5 < pT < 10 GeV/c at mid-rapidity derived from the dielectron invariant mass continuum region 0.10 < Mee < 0.28 GeV/c2 for 0–80% minimum-bias Au+Au collisions at √sN N = 200 GeV. A clear excess in the invariant yield compared to the nuclear overlap function T A A scaled p + p reference is observed in the pT range 1 < pT < 3 GeV/c. For pT > 6 GeV/c the production follows T A A scaling. Model calculations with contributions from thermal radiation and initial hard parton scattering are consistent ithin uncertainties with the direct virtual photon invariant yield.
While the liver, specifically hepatocytes, are widely accepted as the main source for hepatitis C virus (HCV) production, the role of the liver/hepatocytes in the clearance of circulating HCV remains largely unknown. Here we evaluated the function of the liver/hepatocytes in clearing virus from the circulation by investigating viral clearance during liver transplantation and from culture medium in vitro. Frequent HCV kinetic data during liver transplantation were recorded from 5 individuals throughout the anhepatic (AH) phase and for 4 hours after reperfusion (RP), along with recordings of fluid balances. Using mathematical modeling, the serum viral clearance rate, c, was estimated. Analogously, we monitored the clearance rate of HCV at 37°C from culture medium in vitro in the absence and presence of chronically infected Huh7 human hepatoma cells. During the AH phase, in 3 transplant cases viral levels remained at pre-AH levels, while in the other 2 cases HCV declined (half-life, t1/2~1h). Immediately post-RP, virus declined in a biphasic manner in Cases 1-4 consisting of an extremely rapid (median t1/2=5min) decline followed by a slower decline (HCV t1/2=67min). In Case 5, HCV remained at the same level post-RP as at the end of AH. Declines in virus level were not explained by adjusting for dilution from IV fluid and blood products. Consistent with what was observed in the majority of patients in the anhepatic phase, the t1/2 of HCV in cell culture was much longer in the absence of chronically HCV-infected Huh7 cells. Therefore, kinetic and modeling results from both in vivo liver transplantation cases and in vitro cell culture studies suggest that the liver plays a major role in clearing HCV from the circulation.
While the liver, specifically hepatocytes, are widely accepted as the main source of hepatitis C virus (HCV) production, the role of the liver/hepatocytes in clearance of circulating HCV remains unknown. Frequent HCV kinetic data were recorded and mathematically modeled from five liver transplant patients throughout the anhepatic (absence of liver) phase and for 4 hr post-reperfusion. During the anhepatic phase, HCV remained at pre-anhepatic levels (n = 3) or declined (n = 2) with t1/2~1 hr. Immediately post-reperfusion, virus declined in a biphasic manner in four patients consisting of a rapid decline (t1/2 = 5 min) followed by a slower decline (t1/2 = 67 min). Consistent with the majority of patients in the anhepatic phase, when we monitored HCV clearance at 37°C from culture medium in the absence/presence of chronically infected hepatoma cells that were inhibited from secreting HCV, the HCV t1/2 in cell culture was longer in the absence of chronically HCV-infected cells. The results suggest that the liver plays a major role in the clearance of circulating HCV and that hepatocytes may be involved.
Strong electron correlations can give rise to extraordinary properties of metals with renormalized Landau quasiparticles. Near a quantum critical point, these quasiparticles can be destroyed and non-Fermi liquid behavior ensues. YbRh2Si2 is a prototypical correlated metal exhibiting the formation of quasiparticle and Kondo lattice coherence, as well as quasiparticle destruction at a field-induced quantum critical point. Here we show how, upon lowering the temperature, Kondo lattice coherence develops at zero field and finally gives way to non-Fermi liquid electronic excitations. By measuring the single-particle excitations through scanning tunneling spectroscopy, we find the Kondo lattice peak displays a non-trivial temperature dependence with a strong increase around 3.3 K. At 0.3 K and with applied magnetic field, the width of this peak is minimized in the quantum critical regime. Our results demonstrate that the lattice Kondo correlations have to be sufficiently developed before quantum criticality can set in.
Efficient derivation of extraembryonic endoderm stem cell lines from mouse postimplantation embryos
(2016)
Various types of stem cell lines have been derived from preimplantation or postimplantation mouse embryos: embryonic stem cell lines, epiblast stem cell lines, and trophoblast stem cell lines. It is not known if extraembryonic endoderm stem (XEN) cell lines can be derived from postimplantation mouse embryos. Here, we report the derivation of 77 XEN cell lines from 85 postimplantation embryos at embryonic day E5.5 or E6.5, in parallel to the derivation of 41 XEN lines from 69 preimplantation embryos at the blastocyst stage. We attain a success rate of 100% of XEN cell line derivation with our E5.5 whole-embryo and E6.5 disaggregated-embryo methods. Immunofluorescence and NanoString gene expression analyses indicate that the XEN cell lines that we derived from postimplantation embryos (post-XEN) are very similar to the XEN cell lines that we derived from preimplantation embryos (pre-XEN) using a conventional method. After injection into blastocysts, post-XEN cells contribute to extraembryonic endoderm in chimeras at E6.5 and E7.5.
The spirochete Borrelia burgdorferi is the causative agent of Lyme disease, the most common tick-borne disease in the US and Europe. No potent human vaccine is currently available. The innate immune complement system is vital to host defense against pathogens, as complement activation on the surface of spirochetes results in bacterial killing. Complement system is inhibited by the complement regulator factor H (FH). To escape killing, B. burgdorferi produces an outer surface protein CspZ that binds FH to inhibit complement activation on the cell surface. Immunization with CspZ alone does not protect mice from infection, which we speculate is because FH-binding cloaks potentially protective epitopes. We modified CspZ by conjugating to virus-like particles (VLP-CspZ) and eliminating FH binding (modified VLP-CspZ) to increase immunogenicity. We observed greater bactericidal antibody titers in mice vaccinated with modified VLP-CspZ: A serum dilution of 1:395 (modified VLP-CspZ) vs 1:143 (VLP-CspZ) yielded 50% borreliacidal activity. Immunizing mice with modified VLP-CspZ cleared spirochete infection, as did passive transfer of elicited antibodies. This work developed a novel Lyme disease vaccine candidate by conjugating CspZ to VLP and eliminating FH-binding ability. Such a strategy of conjugating an antigen to a VLP and eliminating binding to the target ligand can serve as a general model for developing vaccines against other bacterial infectious agents.
Archaeological evidence indicates that pig domestication had begun by ∼10,500 y before the present (BP) in the Near East, and mitochondrial DNA (mtDNA) suggests that pigs arrived in Europe alongside farmers ∼8,500 y BP. A few thousand years after the introduction of Near Eastern pigs into Europe, however, their characteristic mtDNA signature disappeared and was replaced by haplotypes associated with European wild boars. This turnover could be accounted for by substantial gene flow from local European wild boars, although it is also possible that European wild boars were domesticated independently without any genetic contribution from the Near East. To test these hypotheses, we obtained mtDNA sequences from 2,099 modern and ancient pig samples and 63 nuclear ancient genomes from Near Eastern and European pigs. Our analyses revealed that European domestic pigs dating from 7,100 to 6,000 y BP possessed both Near Eastern and European nuclear ancestry, while later pigs possessed no more than 4% Near Eastern ancestry, indicating that gene flow from European wild boars resulted in a near-complete disappearance of Near East ancestry. In addition, we demonstrate that a variant at a locus encoding black coat color likely originated in the Near East and persisted in European pigs. Altogether, our results indicate that while pigs were not independently domesticated in Europe, the vast majority of human-mediated selection over the past 5,000 y focused on the genomic fraction derived from the European wild boars, and not on the fraction that was selected by early Neolithic farmers over the first 2,500 y of the domestication process.
Background. Intervertebral disc degeneration (IDD) at the cervicothoracic junction of spine is clinically relevant, however, little attention had been paid. T2 mapping and magnetic transfer ratio (MTR) are useful magnetic resonance imaging (MRI) techniques to quantitatively evaluate IDD, revealing the biochemical changes within the intervertebral disc. To compare T2 mapping with MTR imaging regarding their accuracy to quantitatively diagnose intervertebral disc degeneration at the cervicothoracic junction, influences of anatomical level, gender, age, and Pfrrmann grade of T2 relaxation time values and MTR values were evaluated.
Methods. Sixty-seven patients with neck and upper back pain were included and examined with both T2 mapping andMTR imaging. Te Pfrrmann grade, T2 relaxation time values, and MTR value of each disc between C7 and T3 were measured. Diferences were investigated among diferent segmental levels, genders, age ranges, and Pfrrmann grades. Te diagnostic accuracy of both MRI techniques was compared using the receiver operating characteristic (ROC) curves.
Results. No signifcant diference was detected comparing T2 relaxation time values or MTR values among diferent anatomical levels, genders, and segmental levels. And we generally found that T2 relaxation time values decreased, while MTR value increased with increasing age. Importantly, we demonstrated the signifcant correlation between either T2 relaxation time values or MTR value and Pfrrmann grade.
Conclusion. We proved the better accuracy of T2 mapping over MTR imaging to quantitatively evaluate the intervertebral disc degeneration of the cervicothoracic junction.
Conventional treatments for mood disorders primarily focus on reducing negative affect, but little on enhancing positive affect. Loving-kindness meditation (LKM) is a traditional meditation practice directly oriented toward enhancing unconditional and positive emotional states of kindness towards oneself and others. We report here two independent and uncontrolled studies carried out at different centers, one in Boston, USA (n = 10), and one in Frankfurt, Germany (n = 8), to examine the potential therapeutic utility of a brief LKM group intervention for symptoms of dysthymia and depression. Results at both centers suggest that LKM was associated with large-sized effects on self-reported symptoms of depression (d = 3.33 and 1.90), negative affect (d = 1.98 and 0.92), and positive affect (d = 1.63 and 0.94). Large effects were also found for clinician-reported changes in depression, rumination and specific positive emotions, and moderate effects for changes in adaptive emotion regulation strategies. The qualitative data analyses provide additional support for the potential clinical utility of the intervention. This proof-of-concept evaluation of LKM as a clinical strategy warrants further investigation.
Background: While the efficacy of cognitive therapy (CT) has been well established for social anxiety disorder (SAD) in several randomized controlled trials, there are still large differences between trials with respect to effect sizes. The present study investigates the question of whether enhanced training and the use of behavioral experiments (BEs) increases the efficacy of traditional CT, based on verbal methods of cognitive restructuring. Methods/design: A mixed within/between conditions design will be applied, with therapists and patients being randomly allocated to one of two conditions: (1) training of CT plus BEs, (2) training of CT “as usual”. Sixty patients with the primary diagnosis of SAD will be recruited and treated in the outpatient clinic of the Department of Psychology, University of Frankfurt. To ensure adherence to therapist protocols, all therapists will be trained and supervised by the project coordinators. In addition, videotaped treatment sessions will be independently evaluated to guarantee both adherence to protocols and the quality of the intervention. Treatment effects will be assessed by independent SAD symptom ratings using the Liebowitz Social Anxiety Scale as the primary outcome measure and self-report measures as secondary outcome measures. Discussion: The present cognitive behavioral therapy (CBT) trial will be the first to clarify the contribution of BEs to the efficacy of CT in a randomized controlled design. Study results are relevant to clinical training and implementation of evidence-based treatments. Trial registration: German Clinical Trials Register International Clinical Trials Registry Platform (ICTRP) identifier: DRKS00014349. Trial status: recruiting.
The planthopper genus Arcofaciella Fennah, 1956 (Hemiptera: Fulgoromorpha: Delphacidae) is reviewed. Four species are recognized, of which A. obflexa Guo & Liang, 2005 and A. verrucosa Fennah, 1956 are redescribed, and one new species, A. indiana sp. nov., is described. Habitus photos for adults and illustrations of male genitalia (excluding A. penangensis (Muir, 1919)) are given. A key for identifying the species of Arcofaciella is also provided.
The planthopper genus Augilina Melichar, 1914, is recorded in China for the first time. Two new species of the genus Augilina, A. tetraina Chen & Gong sp. nov. and A. triaina Chen & Gong sp. nov., are described and illustrated from South China. The genus now has a total of four described species. New generic characteristics are proposed and photographs of the new species are provided. A checklist and a key to the species of Augilina are also included.
The Taiwan cobra (Naja naja atra) chymotrypsin inhibitor (NACI) consists of 57 amino acids and is related to other Kunitz-type inhibitors such as bovine pancreatic trypsin inhibitor (BPTI) and Bungarus fasciatus fraction IX (BF9), another chymotrypsin inhibitor. Here we present the solution structure of NACI. We determined the NMR structure of NACI with a root-mean-square deviation of 0.37 Å for the backbone atoms and 0.73 Å for the heavy atoms on the basis of 1,075 upper distance limits derived from NOE peaks measured in its NOESY spectra. To investigate the structural characteristics of NACI, we compared the three-dimensional structure of NACI with BPTI and BF9. The structure of the NACI protein comprises one 310-helix, one α-helix and one double-stranded antiparallel β-sheet, which is comparable with the secondary structures in BPTI and BF9. The RMSD value between the mean structures is 1.09 Å between NACI and BPTI and 1.27 Å between NACI and BF9. In addition to similar secondary and tertiary structure, NACI might possess similar types of protein conformational fluctuations as reported in BPTI, such as Cys14–Cys38 disulfide bond isomerization, based on line broadening of resonances from residues which are mainly confined to a region around the Cys14–Cys38 disulfide bond.
Three new species of the bamboo-feeding genus Bambusiphaga Huang & Ding, 1979, B. parvula sp. nov., B. angulosa sp. nov., and B. nigrigena sp. nov., are described and illustrated from China. A key to species of the genus is provided. Habitus photos for adults and illustrations of male genitalia are also given.
Elliptic flow from nuclear collisions is a hadronic observable sensitive to the early stages of system evolution. We report first results on elliptic flow of charged particles at midrapidity in Au+Au collisions at sqrt(s_NN)=130 GeV using the STAR TPC at RHIC. The elliptic flow signal, v_2, averaged over transverse momentum, reaches values of about 6% for relatively peripheral collisions and decreases for the more central collisions. This can be interpreted as the observation of a higher degree of thermalization than at lower collision energies. Pseudorapidity and transverse momentum dependence of elliptic flow are also presented.
Two new species, Russula pseudopunicea C.L.Hou, G.Q.Cheng & H.Zhou sp. nov. and R. wulingshanensis C.L.Hou, G.Q.Cheng & H.Zhou sp. nov., from Yanshan mountains in North China are described herein based on morphological and phylogenetic analyses of nrITS, and nrLSU-rpb2-mtSSU gene regions. Morphologically, R. pseudopunicea sp. nov. is characterised by a reddish brown, light brown to brownish orange pileus with a greyish yellow margin, subglobose to broadly ellipsoid basidiospores with warts forming a partial reticulum and pleurocystidia turning grey to purplish red in sulfovanillin. Russula wulingshanensis sp. nov. is characterised by a purple pinkish pileus with a grey-white to grey-purple margin, subglobose to broadly ellipsoid basidiospores with isolated warts, and pileocystidia turning black in sulfovanillin. Phylogenetic and morphological analyses resolved the two species in Russula subg. Heterophyllidia. Russula pseudopunicea sp. nov. and R. wulingshanensis sp. nov. were placed in the lineages of subsect. Virescentinae and subsect. Griseinae, respectively.
The emerging relapsing fever spirochete Borrelia (B.) miyamotoi is transmitted by ixodid ticks and causes the so-called hard tick-borne relapsing fever or B. miyamotoi disease (BMD). More recently, we identified a surface-exposed molecule, CbiA exhibiting complement binding and inhibitory capacity and rendering spirochetes resistant to complement-mediated lysis. To gain deeper insight into the molecular principles of B. miyamotoi-host interaction, we examined CbiA as a plasmin(ogen) receptor that enables B. miyamotoi to interact with the serine protease plasmin(ogen). Recombinant CbiA was able to bind plasminogen in a dose-dependent fashion. Moreover, lysine residues appear to play a crucial role in the protein-protein interaction as binding of plasminogen was inhibited by the lysine analog tranexamic acid as well as increasing ionic strength. Of relevance, plasminogen bound to CbiA can be converted by urokinase-type plasminogen activator (uPa) to active plasmin which cleaved both, the chromogenic substrate S-2251 and its physiologic substrate fibrinogen. Concerning the involvement of specific amino acids in the interaction with plasminogen, lysine residues located at the C-terminus are frequently involved in the binding as reported for various other plasminogen-interacting proteins of Lyme disease spirochetes. Lysine residues located within the C-terminal domain were substituted with alanine to generate single, double, triple, and quadruple point mutants. However, binding of plasminogen to the mutated CbiA proteins was not affected, suggesting that lysine residues distant from the C-terminus might be involved in the interaction.
The adaptor molecule stimulator of IFN genes (STING) is central to production of type I IFNs in response to infection with DNA viruses and to presence of host DNA in the cytosol. Excessive release of type I IFNs through STING-dependent mechanisms has emerged as a central driver of several interferonopathies, including systemic lupus erythematosus (SLE), Aicardi–Goutières syndrome (AGS), and stimulator of IFN genes-associated vasculopathy with onset in infancy (SAVI). The involvement of STING in these diseases points to an unmet need for the development of agents that inhibit STING signaling. Here, we report that endogenously formed nitro-fatty acids can covalently modify STING by nitro-alkylation. These nitro-alkylations inhibit STING palmitoylation, STING signaling, and subsequently, the release of type I IFN in both human and murine cells. Furthermore, treatment with nitro-fatty acids was sufficient to inhibit production of type I IFN in fibroblasts derived from SAVI patients with a gain-of-function mutation in STING. In conclusion, we have identified nitro-fatty acids as endogenously formed inhibitors of STING signaling and propose for these lipids to be considered in the treatment of STING-dependent inflammatory diseases.
Virus-infected cells are eliminated by cytotoxic T lymphocytes, which recognize viral epitopes displayed on major histocompatibility complex class I molecules at the cell surface. Herpesviruses have evolved sophisticated strategies to escape this immune surveillance. During the lytic phase of EBV infection, the viral factor BNLF2a interferes with antigen processing by preventing peptide loading of major histocompatibility complex class I molecules. Here we reveal details of the inhibition mechanism of this EBV protein. We demonstrate that BNLF2a acts as a tail-anchored protein, exploiting the mammalian Asna-1/WRB (Get3/Get1) machinery for posttranslational insertion into the endoplasmic reticulum membrane, where it subsequently blocks antigen translocation by the transporter associated with antigen processing (TAP). BNLF2a binds directly to the core TAP complex arresting the ATP-binding cassette transporter in a transport-incompetent conformation. The inhibition mechanism of EBV BNLF2a is distinct and mutually exclusive of other viral TAP inhibitors.
This paper provides new geochemical data focusing on valuable elements in the coal, parting, and floor samples in the No. 5 coal seam of the Taiyuan Formation from the Wujiawan mine, Datong coalfield, northern China. The minerals mainly consist of kaolinite, calcite, and pyrite, as well as trace amounts of quartz and illite. The No. 5 coal is enriched in Li, Ga, high field strength elements (HFSEs), and rare earth elements and yttrium (REY) when compared with world hard coals. Of particular interest is the high average concentration of Li (67.66 μg/g), which is around seven times higher than the value for world hard coals. Lithium, Ga, and HFSEs have strong inorganic affinities, whereas REY have organic affinities. The main carrier of Li, Ga, and HFSEs is aluminosilicate minerals, while REY appear to occur with organophosphorus. These HFSEs are enriched, both in the parting and in the adjacent coal samples. This suggests that these elements are likely to leach out during the diagenetic process. The distribution patterns of REY, along with the ratio of Al2O3/TiO2 and the figure of Zr/TiO2 vs. Nb/Y are suggestive of their derivation from felsic parent material. In the northern and eastern part of the Datong coalfield, there are several regions where the Li content is higher than the mineable grade, in particular in the northern Datong coalfield where there is a mine with an Li content of 294.6 μg/g. This is significantly higher than the mineable grade. Therefore, there is a potential for financially viable recovery of Li in these coals of the Datong coalfield.
Background: Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods: Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun’s electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results: This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p < 0.01. Conclusion: A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed.
Borrelia miyamotoi, a relapsing fever spirochete transmitted by Ixodid ticks causes B. miyamotoi disease (BMD). To evade the human host´s immune response, relapsing fever borreliae, including B. miyamotoi, produce distinct variable major proteins. Here, we investigated Vsp1, Vlp15/16, and Vlp18 all of which are currently being evaluated as antigens for the serodiagnosis of BMD. Comparative analyses identified Vlp15/16 but not Vsp1 and Vlp18 as a plasminogen-interacting protein of B. miyamotoi. Furthermore, Vlp15/16 bound plasminogen in a dose-dependent fashion with high affinity. Binding of plasminogen to Vlp15/16 was significantly inhibited by the lysine analog tranexamic acid suggesting that the protein–protein interaction is mediated by lysine residues. By contrast, ionic strength did not have an effect on binding of plasminogen to Vlp15/16. Of relevance, plasminogen bound to the borrelial protein cleaved the chromogenic substrate S-2251 upon conversion by urokinase-type plasminogen activator (uPa), demonstrating it retained its physiological activity. Interestingly, further analyses revealed a complement inhibitory activity of Vlp15/16 and Vlp18 on the alternative pathway by a Factor H-independent mechanism. More importantly, both borrelial proteins protect serum sensitive Borrelia garinii cells from complement-mediated lysis suggesting multiple roles of these two variable major proteins in immune evasion of B. miyamotoi.
Coevolution of viruses and their hosts represents a dynamic molecular battle between the immune system and viral factors that mediate immune evasion. After the abandonment of smallpox vaccination, cowpox virus infections are an emerging zoonotic health threat, especially for immunocompromised patients. Here we delineate the mechanistic basis of how cowpox viral CPXV012 interferes with MHC class I antigen processing. This type II membrane protein inhibits the coreTAP complex at the step after peptide binding and peptide-induced conformational change, in blocking ATP binding and hydrolysis. Distinct from other immune evasion mechanisms, TAP inhibition is mediated by a short ER-lumenal fragment of CPXV012, which results from a frameshift in the cowpox virus genome. Tethered to the ER membrane, this fragment mimics a high ER-lumenal peptide concentration, thus provoking a trans-inhibition of antigen translocation as supply for MHC I loading. These findings illuminate the evolution of viral immune modulators and the basis of a fine-balanced regulation of antigen processing.