103 research outputs found

    Direct observation of DNA threading in flap endonuclease complexes

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    Maintenance of genome integrity requires that branched nucleic acid molecules are accurately processed to produce double-helical DNA. Flap endonucleases are essential enzymes that trim such branched molecules generated by Okazaki fragment synthesis during replication. Here, we report crystal structures of bacteriophage T5 flap endonuclease in complexes with intact DNA substrates, and products, at resolutions of 1.9–2.2 Å. They reveal single-stranded DNA threading through a hole in the enzyme enclosed by an inverted Vshaped helical arch straddling the active site. Residues lining the hole induce an unusual barb-like conformation in the DNA substrate juxtaposing the scissile phosphate and essential catalytic metal ions. A series of complexes and biochemical analyses show how the substrate’s single-stranded branch approaches, threads through, and finally emerges on the far side of the enzyme. Our studies suggest that substrate recognition involves an unusual “flycasting, thread, bend and barb” mechanis

    Hyperon polarization along the beam direction relative to the second and third harmonic event planes in isobar collisions at sNN\sqrt{s_{NN}} = 200 GeV

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    The polarization of Λ\Lambda and Λˉ\bar{\Lambda} hyperons along the beam direction has been measured relative to the second and third harmonic event planes in isobar Ru+Ru and Zr+Zr collisions at sNN\sqrt{s_{NN}} = 200 GeV. This is the first experimental evidence of the hyperon polarization by the triangular flow originating from the initial density fluctuations. The amplitudes of the sine modulation for the second and third harmonic results are comparable in magnitude, increase from central to peripheral collisions, and show a mild pTp_T dependence. The azimuthal angle dependence of the polarization follows the vorticity pattern expected due to elliptic and triangular anisotropic flow, and qualitatively disagree with most hydrodynamic model calculations based on thermal vorticity and shear induced contributions. The model results based on one of existing implementations of the shear contribution lead to a correct azimuthal angle dependence, but predict centrality and pTp_T dependence that still disagree with experimental measurements. Thus, our results provide stringent constraints on the thermal vorticity and shear-induced contributions to hyperon polarization. Comparison to previous measurements at RHIC and the LHC for the second-order harmonic results shows little dependence on the collision system size and collision energy.Comment: 6 pages, 5 figures, Published in Physical Review Letter

    Event-by-event correlations between Λ\Lambda (Λˉ\bar{\Lambda}) hyperon global polarization and handedness with charged hadron azimuthal separation in Au+Au collisions at sNN=27 GeV\sqrt{s_{\text{NN}}} = 27 \text{ GeV} from STAR

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    Global polarizations (PP) of Λ\Lambda (Λˉ\bar{\Lambda}) hyperons have been observed in non-central heavy-ion collisions. The strong magnetic field primarily created by the spectator protons in such collisions would split the Λ\Lambda and Λˉ\bar{\Lambda} global polarizations (ΔP=PΛPΛˉ<0\Delta P = P_{\Lambda} - P_{\bar{\Lambda}} < 0). Additionally, quantum chromodynamics (QCD) predicts topological charge fluctuations in vacuum, resulting in a chirality imbalance or parity violation in a local domain. This would give rise to an imbalance (Δn=NLNRNL+NR0\Delta n = \frac{N_{\text{L}} - N_{\text{R}}}{\langle N_{\text{L}} + N_{\text{R}} \rangle} \neq 0) between left- and right-handed Λ\Lambda (Λˉ\bar{\Lambda}) as well as a charge separation along the magnetic field, referred to as the chiral magnetic effect (CME). This charge separation can be characterized by the parity-even azimuthal correlator (Δγ\Delta\gamma) and parity-odd azimuthal harmonic observable (Δa1\Delta a_{1}). Measurements of ΔP\Delta P, Δγ\Delta\gamma, and Δa1\Delta a_{1} have not led to definitive conclusions concerning the CME or the magnetic field, and Δn\Delta n has not been measured previously. Correlations among these observables may reveal new insights. This paper reports measurements of correlation between Δn\Delta n and Δa1\Delta a_{1}, which is sensitive to chirality fluctuations, and correlation between ΔP\Delta P and Δγ\Delta\gamma sensitive to magnetic field in Au+Au collisions at 27 GeV. For both measurements, no correlations have been observed beyond statistical fluctuations.Comment: 10 pages, 10 figures; paper from the STAR Collaboratio

    Observation of the electromagnetic field effect via charge-dependent directed flow in heavy-ion collisions at the Relativistic Heavy Ion Collider

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    The deconfined quark-gluon plasma (QGP) created in relativistic heavy-ion collisions enables the exploration of the fundamental properties of matter under extreme conditions. Non-central collisions can produce strong magnetic fields on the order of 101810^{18} Gauss, which offers a probe into the electrical conductivity of the QGP. In particular, quarks and anti-quarks carry opposite charges and receive contrary electromagnetic forces that alter their momenta. This phenomenon can be manifested in the collective motion of final-state particles, specifically in the rapidity-odd directed flow, denoted as v1(y)v_1(\mathsf{y}). Here we present the charge-dependent measurements of dv1/dydv_1/d\mathsf{y} near midrapidities for π±\pi^{\pm}, K±K^{\pm}, and p(pˉ)p(\bar{p}) in Au+Au and isobar (4496_{44}^{96}Ru+4496_{44}^{96}Ru and 4096_{40}^{96}Zr+4096_{40}^{96}Zr) collisions at sNN=\sqrt{s_{\rm NN}}= 200 GeV, and in Au+Au collisions at 27 GeV, recorded by the STAR detector at the Relativistic Heavy Ion Collider. The combined dependence of the v1v_1 signal on collision system, particle species, and collision centrality can be qualitatively and semi-quantitatively understood as several effects on constituent quarks. While the results in central events can be explained by the uu and dd quarks transported from initial-state nuclei, those in peripheral events reveal the impacts of the electromagnetic field on the QGP. Our data put valuable constraints on the electrical conductivity of the QGP in theoretical calculations

    Efficacy and safety of alirocumab in reducing lipids and cardiovascular events.

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    The wonders of flap endonucleases: structure, function, mechanism and regulation.

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    Processing of Okazaki fragments to complete lagging strand DNA synthesis requires coordination among several proteins. RNA primers and DNA synthesised by DNA polymerase α are displaced by DNA polymerase δ to create bifurcated nucleic acid structures known as 5'-flaps. These 5'-flaps are removed by Flap Endonuclease 1 (FEN), a structure-specific nuclease whose divalent metal ion-dependent phosphodiesterase activity cleaves 5'-flaps with exquisite specificity. FENs are paradigms for the 5' nuclease superfamily, whose members perform a wide variety of roles in nucleic acid metabolism using a similar nuclease core domain that displays common biochemical properties and structural features. A detailed review of FEN structure is undertaken to show how DNA substrate recognition occurs and how FEN achieves cleavage at a single phosphate diester. A proposed double nucleotide unpairing trap (DoNUT) is discussed with regards to FEN and has relevance to the wider 5' nuclease superfamily. The homotrimeric proliferating cell nuclear antigen protein (PCNA) coordinates the actions of DNA polymerase, FEN and DNA ligase by facilitating the hand-off intermediates between each protein during Okazaki fragment maturation to maximise through-put and minimise consequences of intermediates being released into the wider cellular environment. FEN has numerous partner proteins that modulate and control its action during DNA replication and is also controlled by several post-translational modification events, all acting in concert to maintain precise and appropriate cleavage of Okazaki fragment intermediates during DNA replication

    Measurement of electrons from open heavy-flavor hadron decays in Au+Au collisions at sNN=200\sqrt{s_{\rm NN}}=200 GeV with the STAR detector

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    We report a new measurement of the production of electrons from open heavy-flavor hadron decays (HFEs) at mid-rapidity (y<|y|< 0.7) in Au+Au collisions at sNN=200\sqrt{s_{\rm NN}}=200 GeV. Invariant yields of HFEs are measured for the transverse momentum range of 3.5<pT<93.5 < p_{\rm T} < 9 GeV/cc in various configurations of the collision geometry. The HFE yields in head-on Au+Au collisions are suppressed by approximately a factor of 2 compared to that in pp+pp collisions scaled by the average number of binary collisions, indicating strong interactions between heavy quarks and the hot and dense medium created in heavy-ion collisions. Comparison of these results with models provides additional tests of theoretical calculations of heavy quark energy loss in the quark-gluon plasma

    Elliptic Flow of Heavy-Flavor Decay Electrons in Au+Au Collisions at sNN\sqrt{s_{_{\rm NN}}} = 27 and 54.4 GeV at RHIC

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    We report on new measurements of elliptic flow (v2v_2) of electrons from heavy-flavor hadron decays at mid-rapidity (y<0.8|y|<0.8) in Au+Au collisions at sNN\sqrt{s_{_{\rm NN}}} = 27 and 54.4 GeV from the STAR experiment. Heavy-flavor decay electrons (eHFe^{\rm HF}) in Au+Au collisions at sNN\sqrt{s_{_{\rm NN}}} = 54.4 GeV exhibit a non-zero v2v_2 in the transverse momentum (pTp_{\rm T}) region of pT<p_{\rm T}< 2 GeV/cc with the magnitude comparable to that at sNN=200\sqrt{s_{_{\rm NN}}}=200 GeV. The measured eHFe^{\rm HF} v2v_2 at 54.4 GeV is also consistent with the expectation of their parent charm hadron v2v_2 following number-of-constituent-quark scaling as other light and strange flavor hadrons at this energy. These suggest that charm quarks gain significant collectivity through the evolution of the QCD medium and may reach local thermal equilibrium in Au+Au collisions at sNN=54.4\sqrt{s_{_{\rm NN}}}=54.4 GeV. The measured eHFe^{\rm HF} v2v_2 in Au+Au collisions at sNN=\sqrt{s_{_{\rm NN}}}= 27 GeV is consistent with zero within large uncertainties. The energy dependence of v2v_2 for different flavor particles (π,ϕ,D0/eHF\pi,\phi,D^{0}/e^{\rm HF}) shows an indication of quark mass hierarchy in reaching thermalization in high-energy nuclear collisions.Comment: 12 pages, 7 figures, 1 tabl

    Search for the Chiral Magnetic Effect in Au+Au collisions at sNN=27\sqrt{s_{_{\rm{NN}}}}=27 GeV with the STAR forward Event Plane Detectors

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    A decisive experimental test of the Chiral Magnetic Effect (CME) is considered one of the major scientific goals at the Relativistic Heavy-Ion Collider (RHIC) towards understanding the nontrivial topological fluctuations of the Quantum Chromodynamics vacuum. In heavy-ion collisions, the CME is expected to result in a charge separation phenomenon across the reaction plane, whose strength could be strongly energy dependent. The previous CME searches have been focused on top RHIC energy collisions. In this Letter, we present a low energy search for the CME in Au+Au collisions at sNN=27\sqrt{s_{_{\rm{NN}}}}=27 GeV. We measure elliptic flow scaled charge-dependent correlators relative to the event planes that are defined at both mid-rapidity η<1.0|\eta|<1.0 and at forward rapidity 2.1<η<5.12.1 < |\eta|<5.1. We compare the results based on the directed flow plane (Ψ1\Psi_1) at forward rapidity and the elliptic flow plane (Ψ2\Psi_2) at both central and forward rapidity. The CME scenario is expected to result in a larger correlation relative to Ψ1\Psi_1 than to Ψ2\Psi_2, while a flow driven background scenario would lead to a consistent result for both event planes[1,2]. In 10-50\% centrality, results using three different event planes are found to be consistent within experimental uncertainties, suggesting a flow driven background scenario dominating the measurement. We obtain an upper limit on the deviation from a flow driven background scenario at the 95\% confidence level. This work opens up a possible road map towards future CME search with the high statistics data from the RHIC Beam Energy Scan Phase-II.Comment: main: 8 pages, 5 figures; supplementary material: 2 pages, 1 figur
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