Antimicrobial Nanoplexes meet Model Bacterial Membranes: the key role of Cardiolipin

Antimicrobial resistance to traditional antibiotics is a crucial challenge of medical research. Oligonucleotide therapeutics, such as antisense or Transcription Factor Decoys (TFDs), have the potential to circumvent current resistance mechanisms by acting on novel targets. However, their full translation into clinical application requires efficient delivery strategies and fundamental comprehension of their interaction with target bacterial cells. To address these points, we employed a novel cationic bolaamphiphile that binds TFDs with high affinity to form self-assembled complexes (nanoplexes). Confocal microscopy revealed that nanoplexes efficiently transfect bacterial cells, consistently with biological efficacy on animal models. To understand the factors affecting the delivery process, liposomes with varying compositions, taken as model synthetic bilayers, were challenged with nanoplexes and investigated with Scattering and Fluorescence techniques. Thanks to the combination of results on bacteria and synthetic membrane models we demonstrate for the first time that the prokaryotic-enriched anionic lipid Cardiolipin (CL) plays a key-role in the TFDs delivery to bacteria. Moreover, we can hypothesize an overall TFD delivery mechanism, where bacterial membrane reorganization with permeability increase and release of the TFD from the nanoplexes are the main factors. These results will be of great benefit to boost the development of oligonucleotides-based antimicrobials of superior efficacy

Fragmentation functions at ZEUS

The scaled momentum spectra of final state charged hadrons produced in Deep Inelastic Scattering in the ranges 10 < Q(2) < 1280 GeV2 and 6 . 10(-4) < x(Bjorken) < 5 . 10(-2) have been measured in the current region of the Breit frame using the ZEUS detector. The evolution with Q(2) of the scaled momentum, x(p) = 2p(Breit)/Q, has been investigated and preliminary results are presented which show evidence for scaling violations and support for the universality of quark fragmentation

Jet shapes at HERA

The shape of jets produced in quasi-real photon-proton interactions and deep inelastic positron-proton scattering (DIS) at high Q(2) (Q(2) > 100 GeV2) has been measured with the ZEUS detector at HERA. Jets with transverse energies E-T(jet) > 14 GeV and pseudorapidities (eta(jet)) in the range -1 collisions, and are similar to those in e(+)e(-) interactions

D* and J/psi inelastic photoproduction at HERA

Cross sections of D* and J/Psi inelastic photoproduction were measured by the ZEUS detector at HERA collider. Comparisons of the data with calculations in NLO pQCD and SHA QCD approaches were made

Measurement of the proton structure function F-2 and the total gamma*p cross-section at low Q(2) and low x

The ZEUS-experiment at HERA has significantly enhanced the kinematic coverage for low Q(2) and low x inelastic e(+)p --> e(+) X scattering with an upgrade of the ZEUS-detector in 1995 which extends the acceptance for small positron scattering angles. The upgrade included the modification of the beam pipe with low mass exit windows and the installation of a small electromagnetic sampling calorimeter, the Beam Pipe Calorimeter (BPC), to explore the region in Q(2) of 0.11 less than or equal to Q(2) less than or equal to 0.65 GeV2. A shift of two rear uranium calorimeter (RCAL) modules and the small rear tracking detector (SRTD) closer to the beam together with a data sample taken with a shifted event vertex extended the Q(2) coverage of the main detector down to 0.6 GeV2. Both data sets have been used to measure the proton structure function F-2 and the total virtual photonproton gamma*p cross-section. Results are presented for 0.11 less than or equal to Q(2) less than or equal to 6.10 GeV2 and 2.10(-6) less than or equal to x less than or equal to 7.10(-4) along with a comparison to various models