Therapeutic Efficacy of Stable Analogues of Vasoactive Intestinal Peptide against Pathogens

Vasoactive intestinal peptide (VIP) is an anti-inflammatory neuropeptide recently identified as a potential antimicrobial peptide. To overcome the metabolic limitations of VIP, we modified the native peptide sequence and generated two stable synthetic analogues (VIP51 and VIP51(6–30)) with better antimicrobial profiles. Herein we investigate the effects of both VIP analogues on cell viability, membrane integrity, and ultrastructure of various bacterial strains and Leishmania species. We found that the two VIP derivatives kill various non-pathogenic and pathogenic Gram-positive and Gram-negative bacteria as well as the parasite Leishmania major through a mechanism that depends on the interaction with certain components of the microbial surface, the formation of pores, and the disruption of the surface membrane. The cytotoxicity of the VIP derivatives is specific for pathogens, because they do not affect the viability of mammalian cells. Docking simulations indicate that the chemical changes made in the analogues are critical to increase their antimicrobial activities. Consequently, we found that the native VIP is less potent as an antibacterial and fails as a leishmanicidal. Noteworthy from a therapeutic point of view is that treatment with both derivatives increases the survival and reduces bacterial load and inflammation in mice with polymicrobial sepsis. Moreover, treatment with VIP51(6–30) is very effective at reducing lesion size and parasite burden in a model of cutaneous leishmaniasis. These results indicate that the VIP analogues emerge as attractive alternatives for treating drug-resistant infectious diseases and provide key insights into a rational design of novel agents against these pathogens.This work was supported, in whole or in part, by National Institutes of Health Grant RO1 AI031078 (to S. M. B.). This work was also supported by Excellence Grants from Junta de Andalucia (P09/CTS-4705) (to E. G.-R.) and European Cost Action (BM0802) (to E. G.-R.).Peer reviewe

Transverse-target-spin asymmetry in exclusive ω\omega-meson electroproduction

Hard exclusive electroproduction of $\omega$ mesons is studied with the HERMES spectrometer at the DESY laboratory by scattering 27.6 GeV positron and electron beams off a transversely polarized hydrogen target. The amplitudes of five azimuthal modulations of the single-spin asymmetry of the cross section with respect to the transverse proton polarization are measured. They are determined in the entire kinematic region as well as for two bins in photon virtuality and momentum transfer to the nucleon. Also, a separation of asymmetry amplitudes into longitudinal and transverse components is done. These results are compared to a phenomenological model that includes the pion pole contribution. Within this model, the data favor a positive $\pi\omega$ transition form factor.Comment: DESY Report 15-14

Longitudinal double-spin asymmetries in semi-inclusive deep-inelastic scattering of electrons and positrons by protons and deuterons

A comprehensive collection of results on longitudinal double-spin asymmetries is presented for charged pions and kaons produced in semi-inclusive deep-inelastic scattering of electrons and positrons on the proton and deuteron, based on the full HERMES data set. The dependence of the asymmetries on hadron transverse momentum and azimuthal angle extends the sensitivity to the flavor structure of the nucleon beyond the distribution functions accessible in the collinear framework. No strong dependence on those variables is observed. In addition, the hadron charge-difference asymmetry is presented, which under certain model assumptions provides access to the helicity distributions of valence quarks

Measurement of single-spin azimuthal asymmetries in semi-inclusive electroproduction of pions and kaons on a longitudinally polarised deuterium target

Single-spin asymmetries have been measured for semi-inclusive electroproduction of $\pi^+$, $\pi^-$, $\pi^0$ and $K^+$ mesons in deep-inelastic scattering off a longitudinally polarised deuterium target. The asymmetries appear in the distribution of the hadrons in the azimuthal angle $\phi$ around the virtual photon direction, relative to the lepton scattering plane. The corresponding analysing powers in the $\sin \phi$ moment of the cross section are $0.012 \pm 0.002 {(stat.)} \pm 0.002 {(syst.)}$ for $\pi^+$, $0.006 \pm 0.003 {(stat.)} \pm 0.002 {(syst.)}$ for $\pi^-$, $0.021 \pm 0.005 {(stat.)} \pm 0.003 {(syst.)}$ for $\pi^0$ and $0.013 \pm 0.006 {(stat.)} \pm 0.003 {(syst.)}$ for $K^+$. The $\sin 2\phi$ moments are compatible with zero for all particles.Comment: Revised version shortened 9 pages, 3 tables, 7 figure

Bose-Einstein correlations in hadron-pairs from lepto-production on nuclei ranging from hydrogen to xenon

Bose-Einstein correlations of like-sign charged hadrons produced in deep-inelastic electron and positron scattering are studied in the HERMES experiment using nuclear targets of $^1$H, $^2$H, $^3$He, $^4$He, N, Ne, Kr, and Xe. A Gaussian approach is used to parametrize a two-particle correlation function determined from events with at least two charged hadrons of the same sign charge. This correlation function is compared to two different empirical distributions that do not include the Bose-Einstein correlations. One distribution is derived from unlike-sign hadron pairs, and the second is derived from mixing like-sign pairs from different events. The extraction procedure used simulations incorporating the experimental setup in order to correct the results for spectrometer acceptance effects, and was tested using the distribution of unlike-sign hadron pairs. Clear signals of Bose-Einstein correlations for all target nuclei without a significant variation with the nuclear target mass are found. Also, no evidence for a dependence on the invariant mass W of the photon-nucleon system is found when the results are compared to those of previous experiments

Subleading-twist effects in single-spin asymmetries in semi-inclusive deep-inelastic scattering on a longitudinally polarized hydrogen target

Single-spin asymmetries in the semi-inclusive production of charged pions in deep-inelastic scattering from transversely and longitudinally polarized proton targets are combined to evaluate the subleading-twist contribution to the longitudinal case. This contribution is significantly positive for (\pi^+) mesons and dominates the asymmetries on a longitudinally polarized target previously measured by \hermes. The subleading-twist contribution for (\pi^-) mesons is found to be small

Double hadron leptoproduction in the nuclear medium

First measurement of double-hadron production in deep-inelastic scattering has been measured with the HERMES spectrometer at HERA using a 27.6 GeV positron beam with deuterium, nitrogen, krypton and xenon targets. The influence of the nuclear medium on the ratio of double-hadron to single-hadron yields has been investigated. Nuclear effects are clearly observed but with substantially smaller magnitude and reduced $A$-dependence compared to previously measured single-hadron multiplicity ratios. The data are in fair agreement with models based on partonic or pre-hadronic energy loss, while they seem to rule out a pure absorptive treatment of the final state interactions. Thus, the double-hadron ratio provides an additional tool for studying modifications of hadronization in nuclear matter

Single-spin asymmetries in semi-inclusive deep-inelastic scattering on a transversely polarized hydrogen target

Single-spin asymmetries for semi-inclusive electroproduction of charged pions in deep-inelastic scattering of positrons are measured for the first time with transverse target polarization. The asymmetry depends on the azimuthal angles of both the pion ($\phi$) and the target spin axis ($\phi_S$) about the virtual photon direction and relative to the lepton scattering plane. The extracted Fourier component \cmpi is a signal of the previously unmeasured quark transversity distribution, in conjunction with the so-called Collins fragmentation function, also unknown. The Fourier component \smpi of the asymmetry arises from a correlation between the transverse polarization of the target nucleon and the intrinsic transverse momentum of quarks, as represented by the previously unmeasured Sivers distribution function. Evidence for both signals is observed, but the Sivers asymmetry may be affected by exclusive vector meson productio

First Measurement of the Tensor Structure Function b1b_1 of the Deuteron

The \Hermes experiment has investigated the tensor spin structure of the deuteron using the 27.6 GeV/c positron beam of \Hera. The use of a tensor polarized deuteron gas target with only a negligible residual vector polarization enabled the first measurement of the tensor asymmetry \At and the tensor structure function \bd for average values of the Bj{\o}rken variable $0.01<0.45$ and of the squared four-momentum transfer $0.5 {\rm GeV^2} <5 {\rm GeV^2}$. The quantities \At and \bd are found to be non-zero. The rise of \bd for decreasing values of $x$ can be interpreted to originate from the same mechanism that leads to nuclear shadowing in unpolarized scattering