Identification and Characterization of the Host Protein DNAJC14 as a Broadly Active Flavivirus Replication Modulator

Viruses in the Flavivirus genus of the Flaviviridae family are arthropod-transmitted and contribute to staggering numbers of human infections and significant deaths annually across the globe. To identify cellular factors with antiviral activity against flaviviruses, we screened a cDNA library using an iterative approach. We identified a mammalian Hsp40 chaperone protein (DNAJC14) that when overexpressed was able to mediate protection from yellow fever virus (YFV)-induced cell death. Further studies revealed that DNAJC14 inhibits YFV at the step of viral RNA replication. Since replication of bovine viral diarrhea virus (BVDV), a member of the related Pestivirus genus, is also known to be modulated by DNAJC14, we tested the effect of this host factor on diverse Flaviviridae family members. Flaviviruses, including the pathogenic Asibi strain of YFV, Kunjin, and tick-borne Langat virus, as well as a Hepacivirus, hepatitis C virus (HCV), all were inhibited by overexpression of DNAJC14. Mutagenesis showed that both the J-domain and the C-terminal domain, which mediates self-interaction, are required for anti-YFV activity. We found that DNAJC14 does not block YFV nor HCV NS2-3 cleavage, and using non-inhibitory mutants demonstrate that DNAJC14 is recruited to YFV replication complexes. Immunofluorescence analysis demonstrated that endogenous DNAJC14 rearranges during infection and is found in replication complexes identified by dsRNA staining. Interestingly, silencing of endogenous DNAJC14 results in impaired YFV replication suggesting a requirement for DNAJC14 in YFV replication complex assembly. Finally, the antiviral activity of overexpressed DNAJC14 occurs in a time- and dose-dependent manner. DNAJC14 overexpression may disrupt the proper stoichiometry resulting in inhibition, which can be overcome upon restoration of the optimal ratios due to the accumulation of viral nonstructural proteins. Our findings, together with previously published work, suggest that the members of the Flaviviridae family have evolved in unique and important ways to interact with this host Hsp40 chaperone molecule

Observation of Two New Excited Ξb0 States Decaying to Λb0 K-π+

Two narrow resonant states are observed in the Λb0K-π+ mass spectrum using a data sample of proton-proton collisions at a center-of-mass energy of 13 TeV, collected by the LHCb experiment and corresponding to an integrated luminosity of 6 fb-1. The minimal quark content of the Λb0K-π+ system indicates that these are excited Ξb0 baryons. The masses of the Ξb(6327)0 and Ξb(6333)0 states are m[Ξb(6327)0]=6327.28-0.21+0.23±0.12±0.24 and m[Ξb(6333)0]=6332.69-0.18+0.17±0.03±0.22 MeV, respectively, with a mass splitting of Δm=5.41-0.27+0.26±0.12 MeV, where the uncertainties are statistical, systematic, and due to the Λb0 mass measurement. The measured natural widths of these states are consistent with zero, with upper limits of Γ[Ξb(6327)0]<2.20(2.56) and Γ[Ξb(6333)0]<1.60(1.92) MeV at a 90% (95%) credibility level. The significance of the two-peak hypothesis is larger than nine (five) Gaussian standard deviations compared to the no-peak (one-peak) hypothesis. The masses, widths, and resonant structure of the new states are in good agreement with the expectations for a doublet of 1D Ξb0 resonances

Measurement of D s ^± production asymmetry in pp collisions at √s=7 and 8 TeV

The inclusive $D_s^{\pm}$ production asymmetry is measured in $pp$ collisions collected by the LHCb experiment at centre-of-mass energies of $\sqrt{s} =7$ and 8 TeV. Promptly produced $D_s^{\pm}$ mesons are used, which decay as $D_s^{\pm}\to\phi\pi^{\pm}$, with $\phi\to K^+K^-$. The measurement is performed in bins of transverse momentum, $p_{\rm T}$, and rapidity, $y$, covering the range $2.5<p_{\rm T}<25.0$ GeV$/c$ and $2.0<y<4.5$. No kinematic dependence is observed. Evidence of nonzero $D_s^{\pm}$ production asymmetry is found with a significance of 3.3 standard deviations.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2018-010.htm

Search for CP violation in Λb0→pK− and Λb0→pπ− decays

A search for CP violation in Λb0→pK− and Λb0→pπ− decays is presented using a sample of pp collisions collected with the LHCb detector and corresponding to an integrated luminosity of 3.0fb−1. The CP -violating asymmetries are measured to be ACPpK−=−0.020±0.013±0.019 and ACPpπ−=−0.035±0.017±0.020, and their difference ACPpK−−ACPpπ−=0.014±0.022±0.010, where the first uncertainties are statistical and the second systematic. These are the most precise measurements of such asymmetries to date

Precision measurement of CP\it{CP} violation in the penguin-mediated decay Bs0→ϕϕB_s^{0}\rightarrow\phi\phi

A flavor-tagged time-dependent angular analysis of the decay $B_s^{0}\rightarrow\phi\phi$ is performed using $pp$ collision data collected by the LHCb experiment at % at $\sqrt{s}=13$ TeV, the center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 6 fb^{-1}. The $\it{CP}$-violating phase and direct $\it{CP}$-violation parameter are measured to be $\phi_{s\bar{s}s} = -0.042 \pm 0.075 \pm 0.009$ rad and $|\lambda|=1.004\pm 0.030 \pm 0.009$, respectively, assuming the same values for all polarization states of the $\phi\phi$ system. In these results, the first uncertainties are statistical and the second systematic. These parameters are also determined separately for each polarization state, showing no evidence for polarization dependence. The results are combined with previous LHCb measurements using $pp$ collisions at center-of-mass energies of 7 and 8 TeV, yielding $\phi_{s\bar{s}s} = -0.074 \pm 0.069$ rad and $|lambda|=1.009 \pm 0.030$. This is the most precise study of time-dependent $\it{CP}$ violation in a penguin-dominated $B$ meson decay. The results are consistent with $\it{CP}$ symmetry and with the Standard Model predictions.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-001.html (LHCb public pages

Measurement of the Λb0→Λ(1520)μ+μ−\Lambda_{b}^{0}\to \Lambda(1520) \mu^{+}\mu^{-} differential branching fraction

The branching fraction of the rare decay $\Lambda_{b}^{0}\to \Lambda(1520) \mu^{+}\mu^{-}$ is measured for the first time, in the squared dimuon mass intervals, $q^2$, excluding the $J/\psi$ and $\psi(2S)$ regions. The data sample analyzed was collected by the LHCb experiment at center-of-mass energies of 7, 8, and 13 TeV, corresponding to a total integrated luminosity of $9\ \mathrm{fb}^{-1}$. The result in the highest$q^{2}$interval,$q^{2} >15.0\ \mathrm{GeV}^2/c^4$, where theoretical predictions have the smallest model dependence, agrees with the predictions.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-050.html (LHCb public pages

Search for dark photons produced in 13 TeV pppp collisions

Searches are performed for both promptlike and long-lived dark photons, A 0 , produced in proton-proton collisions at a center-of-mass energy of 13 TeV, using A 0 → μ þ μ − decays and a data sample corresponding to an integrated luminosity of 1 . 6 fb − 1 collected with the LHCb detector. The promptlike A 0 search covers the mass range from near the dimuon threshold up to 70 GeV, while the long-lived A 0 search is restricted to the low-mass region 214 <m ð A 0 Þ < 350 MeV. No evidence for a signal is found, and 90% confidence level exclusion limits are placed on the γ – A 0 kinetic-mixing strength. The constraints placed on promptlike dark photons are the most stringent to date for the mass range 10 . 6 <m ð A 0 Þ < 70 GeV, and are comparable to the best existing limits for m ð A 0 Þ < 0 . 5 GeV. The search for long-lived dark photons is the first to achieve sensitivity using a displaced-vertex signature

Measurement of the CKM angle γ\gamma using B0→DK∗0B^0 \rightarrow D K^{*0} with D→KS0π+π−D \rightarrow K^0_S \pi^+ \pi^- decays

A model-dependent amplitude analysis of the decay $B^0\rightarrow D(K^0_S\pi^+\pi^-) K^{*0}$ is performed using proton-proton collision data corresponding to an integrated luminosity of 3.0fb$^{-1}$, recorded at $\sqrt{s}=7$ and $8 TeV$ by the LHCb experiment. The CP violation observables $x_{\pm}$ and $y_{\pm}$, sensitive to the CKM angle $\gamma$, are measured to be \begin{eqnarray*} x_- &=& -0.15 \pm 0.14 \pm 0.03 \pm 0.01, y_- &=& 0.25 \pm 0.15 \pm 0.06 \pm 0.01, x_+ &=& 0.05 \pm 0.24 \pm 0.04 \pm 0.01, y_+ &=& -0.65^{+0.24}_{-0.23} \pm 0.08 \pm 0.01, \end{eqnarray*} where the first uncertainties are statistical, the second systematic and the third arise from the uncertainty on the $D\rightarrow K^0_S \pi^+\pi^-$ amplitude model. These are the most precise measurements of these observables. They correspond to $\gamma=(80^{+21}_{-22})^{\circ}$ and $r_{B^0}=0.39\pm0.13$, where $r_{B^0}$ is the magnitude of the ratio of the suppressed and favoured $B^0\rightarrow D K^+ \pi^-$ decay amplitudes, in a $K\pi$ mass region of $\pm50 MeV$ around the $K^*(892)^0$ mass and for an absolute value of the cosine of the $K^{*0}$ decay angle larger than $0.4$.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-007.htm

Search for the Λb0→Λη′\Lambda^0_b \rightarrow \Lambda \eta^\prime and Λb0→Λη\Lambda^0_b \rightarrow \Lambda \eta decays with the LHCb detector

A search is performed for the as yet unobserved baryonic $\Lambda_b \rightarrow \Lambda \eta^\prime$ and $\Lambda_b \rightarrow \Lambda \eta$ decays with 3$fb^{-1}$ of proton-proton collision data recorded by the LHCb experiment. The $B^0 \rightarrow K_S^0 \eta^\prime$ decay is used as a normalisation channel. No significant signal is observed for the $\Lambda_b \rightarrow \Lambda \eta^\prime$ decay. An upper limit is found on the branching fraction of $\mathcal{B}(\Lambda_b \rightarrow \Lambda \eta^\prime)<3.1\times10^{-6}$} at 90\% confidence level. Evidence is seen for the presence of the $\Lambda_b \rightarrow \Lambda \eta$ decay at the level of $3\sigma$ significance, with a branching fraction $\mathcal{B}(\Lambda_b \rightarrow \Lambda \eta)=(9.3^{+7.3}_{-5.3})\times10^{-6}$}.Comment: 22 pages, 6 figures. v2 is published version (very minor revisions