Structural remodeling and oligomerization of human cathelicidin on membranes suggest fibril-like structures as active species

Antimicrobial peptides as part of the mammalian innate immune system target and remove major bacterial pathogens, often through irreversible damage of their cellular membranes. To explore the mechanism by which the important cathelicidin peptide LL-37 of the human innate immune system interacts with membranes, we performed biochemical, biophysical and structural studies. The crystal structure of LL-37 displays dimers of anti-parallel helices and the formation of amphipathic surfaces. Peptide-detergent interactions introduce remodeling of this structure after occupation of defined hydrophobic sites at the dimer interface. Furthermore, hydrophobic nests are shaped between dimer structures providing another scaffold enclosing detergents. Both scaffolds underline the potential of LL-37 to form defined peptide-lipid complexes in vivo. After adopting the activated peptide conformation LL-37 can polymerize and selectively extract bacterial lipids whereby the membrane is destabilized. The supramolecular fibril-like architectures formed in crystals can be reproduced in a peptide-lipid system after nanogold-labelled LL-37 interacted with lipid vesicles as followed by electron microscopy. We suggest that these supramolecular structures represent the LL-37-membrane active state. Collectively, our study provides new insights into the fascinating plasticity of LL-37 demonstrated at atomic resolution and opens the venue for LL-37-based molecules as novel antibiotics.We would like to thank Sandra Delgado for the technical help in the preparation of the cryoEM vitrified grids and Dr. Isabel Uson and Dr. Ivan De Marino for the Arcimboldo software and valuable help. Funding was provided by the Unidad de Biofisica and the IKERBASQUE and MINECO science foundations

First Direct Measurement of the Absolute Branching Fraction of Σ+→Λe+νe\Sigma^+ \to \Lambda e^+ \nu_{e}

The first direct measurement of the absolute branching fraction of $\Sigma^+ \to \Lambda e^+ \nu_{e}$ is reported based on an $e^+e^-$ annihilation sample of $(10087\pm44) \times 10^6$ $J/\psi$ events collected with the BESIII detector at $\sqrt{s}=3.097$ GeV. The branching fraction is determined to be ${\mathcal B}(\Sigma^+ \to \Lambda e^+ \nu_{e}) = [2.93\pm0.74(\rm stat) \pm 0.13(\rm syst)]\times 10^{-5}$, which is the most precise measurement obtained in a single experiment to date and also the first result obtained at a collider experiment. Combining this result with the world average of ${\mathcal B}(\Sigma^- \to \Lambda e^- \bar{\nu}_{e})$ and the lifetimes of $\Sigma^{\pm}$, the ratio, $\frac{\Gamma(\Sigma^- \to \Lambda e^- \bar{\nu}_{e})}{\Gamma(\Sigma^+ \to \Lambda e^+ \nu_{e})}$, is determined to be $1.06 \pm 0.28$, which is within 1.8 standard deviations of the value expected in the absence of second-class currents that are forbidden in the Standard Model.Comment: 8 pages, 3 figure

Observation of the Y(4220)Y(4220) and Y(4360)Y(4360) in the process e+e−→ηJ/ψe^{+}e^{-} \to \eta J/\psi

The cross sections of the process $e^{+}e^{-} \to \eta J/\psi$ at center-of-mass energies ($\sqrt{s}$) between 3.81 and 4.60 GeV are measured with high precision by using data samples collected with the BESIII detector operating at the BEPCII storage ring. Three structures are observed by analyzing the lineshape of the measured cross sections, and a maximum-likelihood fit including three resonances is performed by assuming the lowest lying structure is the $\psi(4040)$. For the other resonances, we obtain masses of $(4218.7 \pm 4.0 \pm 2.5)$ and $(4380.4 \pm 14.2 \pm 1.8)$ MeV/c$^{2}$ with corresponding widths of $(82.5 \pm 5.9 \pm 0.5)$ and $(147.0 \pm 63.0 \pm 25.8)$ MeV, respectively, where the first uncertainties are statistical and the second ones systematic. The measured resonant parameters are consistent with those of the $Y(4220)$ and $Y(4360)$ from pr evious measurements of different final states. For the first time, we observe the decays of the $Y(4220)$ and $Y(4360)$ into $\eta J/\psi$ final states

Measurement of the absolute branching fraction of the inclusive semileptonic Λc+\Lambda_c^+ decay

Using a data sample corresponding to an integrated luminosity of 567 pb$^{-1}$ collected at a center-of-mass energy of $\sqrt{s}=4.6$ GeV with the BESIII detector, we measure the absolute branching fraction of the inclusive semileptonic $\Lambda_c^+$ decay with a double-tag method. We obtain $\mathcal{B}(\Lambda_c^+ \rightarrow X e^+ \nu_e) = (3.95\pm0.34\pm0.09)\%$, where the first uncertainty is statistical and the second systematic. Using the known $\Lambda_c^+$ lifetime and the charge-averaged semileptonic decay width of nonstrange charmed measons ($D^0$ and $D^+$), we obtain the ratio of the inclusive semileptonic decay widths $\Gamma(\Lambda_c^+ \rightarrow X e^+ \nu_e)/\bar{\Gamma}(D\rightarrow X e^+ \nu_e)= 1.26\pm0.12$.Comment: 7 pages, 3 figure

Axisymmetric slow viscous flow due to the motion of two equal coaxial disks

11Nsciescopu

Measurement of the Branching Fraction for the Semileptonic Decay D0 (+) →π- (0)μ+νμ and Test of Lepton Flavor Universality

Using a data sample corresponding to an integrated luminosity of 2.93 fb-1 taken at a center-of-mass energy of 3.773 GeV with the BESIII detector operated at the BEPCII collider, we perform an analysis of the semileptonic decays D0(+)→π-(0)μ+νμ. The branching fractions of D0→π-μ+νμ and D+→π0μ+νμ are measured to be (0.272±0.008stat±0.006syst)% and (0.350±0.011stat±0.010syst)%, respectively, where the former is of much improved precision compared to previous results and the latter is determined for the first time. Using these results along with previous BESIII measurements of D0(+)→π-(0)e+νe, we calculate the branching fraction ratios to be R0≡BD0→π-μ+νμ/BD0→π-e+νe=0.922±0.030stat±0.022syst and R+≡BD+→π0μ+νμ/BD+→π0e+νe=0.964±0.037stat±0.026syst, which are compatible with the theoretical expectation of lepton flavor universality within 1.7σ and 0.5σ, respectively. We also examine the branching fraction ratios in different four-momentum transfer square regions, and find no significant deviations from the standard model predictions