Antimicrobial resistance genotypes and phenotypes of Campylobacter jejuni isolated in Italy from humans, birds from wild and urban habitats, and poultry

Campylobacter jejuni, a common foodborne zoonotic pathogen, causes gastroenteritis worldwide and is increasingly resistant to antibiotics. We aimed to investigate the antimicrobial resistance (AMR) genotypes of C. jejuni isolated from humans, poultry and birds from wild and urban Italian habitats to identify correlations between phenotypic and genotypic AMR in the isolates. Altogether, 644 C. jejuni isolates from humans (51), poultry (526) and wild- and urban-habitat birds (67) were analysed. The resistance phenotypes of the isolates were determined using the microdilution method with EUCAST breakpoints, and AMR-associated genes and single nucleotide polymorphisms were obtained from a publicly available database. Antimicrobial susceptibility testing showed that C. jejuni isolates from poultry and humans were highly resistant to ciprofloxacin (85.55% and 76.47%, respectively), nalidixic acid (75.48% and 74.51%, respectively) and tetracycline (67.87% and 49.02%, respectively). Fewer isolates from the wild- and urban-habitat birds were resistant to tetracycline (19.40%), fluoroquinolones (13.43%), and quinolone and streptomycin (10.45%). We retrieved seven AMR genes (tet (O), cmeA, cmeB, cmeC, cmeR, blaOXA-61 and blaOXA- 184) and gyrA-associated point mutations. Two major B-lactam genes called blaOXA-61 and blaOXA-184 were prevalent at 62.93% and 82.08% in the poultry and the other bird groups, respectively. Strong correlations between genotypic and phenotypic resistance were found for fluoroquinolones and tetracycline. Compared with the farmed chickens, the incidence of AMR in the C. jejuni isolates from the other bird groups was low, confirming that the food-production birds are much more exposed to antimicrobials. The improper and overuse of antibiotics in the human population and in animal husbandry has resulted in an increase in antibiotic-resistant infections, particularly fluoroquinolone resistant ones. Better understanding of the AMR mechanisms in C. jejuni is necessary to develop new strategies for improving AMR programs and provide the most appropriate therapies to human and veterinary populations

PKCε-dependent signalling in cardiac differentiation

The Protein kinase C (PKC) family, composed by 12 different isoforms, plays a pivotal role in many biological contexts such as cell differentiation, proliferation and survival. PKCe has been demonstrated to be relevant for cardio-protection as well as in ischemia-reperfusion injury (Budas et al. 2010). Transgenic mice over-expressing a constitutively active PKCε show concentric hypertrophy (Takeishi et al. 2000) suggesting negative effects of a permanently active PKCε in cardiac cells. Although the effects of PKCε over-expression have been analyzed both from the physiological and morphological points of view, molecular studies of its consequences on early cardiac marker gene expression are still lacking. On the other side Bone Marrow Mesenchymal Stem Cells (BMMSCs) can be induced to acquire a cardiac fate by treatment with 5-azacytidine (5-AZ) (Wakitani et al. 1995), representing a good in vitro model for cardiac differentiation studies. We addressed the role of in vivo PKCε over-expression on early cardiac genes (namely, nkx2.5 and gata4) regulation. Our results suggest a negative role of PKCε, mediated by ERK1/2, on expression of these two genes both in vivo and in ex-vivo rat BMMSCs, showing that this protein is a fine tuner of precursor cardiac cells

Synthesis and evaluation of thymol-based synthetic derivatives as dual-action inhibitors against different strains of h. pylori and AGS cell line

Following a similar approach on carvacrol-based derivatives, we investigated the synthesis and the microbiological screening against eight strains of H. pylori, and the cytotoxic activity against human gastric adenocarcinoma (AGS) cells of a new series of ether compounds based on the structure of thymol. Structural analysis comprehended elemental analysis and 1H/13C/19F NMR spectra. The analysis of structure-activity relationships within this molecular library of 38 structurally-related compounds reported that some chemical modifications of the OH group of thymol led to broad-spectrum growth inhibition on all isolates. Preferred substitutions were benzyl groups compared to alkyl chains, and the specific presence of functional groups at para position of the benzyl moiety such as 4-CN and 4-Ph endowed the most anti-H. pylori activity toward all the strains with minimum inhibitory concentration (MIC) values up to 4 µg/mL. Poly-substitution on the benzyl ring was not essential. Moreover, several compounds characterized by the lowest minimum inhibitory concentration/minimum bactericidal concentration (MIC/MBC) values against H. pylori were also tested in order to verify a cytotoxic effect against AGS cells with respect to 5-fluorouracil and carvacrol. Three derivatives can be considered as new lead compounds alternative to current therapy to manage H. pylori infection, preventing the occurrence of severe gastric diseases. The present work confirms the possibility to use natural compounds as templates for the medicinal semi-synthesis

Data Analysis for Precision Spectroscopy: the ESPRESSO Case

Astronomical Spectroscopy is rapidly evolving into a precision science, with several science cases increasingly relying on long-term instrumental stability and centimeter-per-second accuracy in wavelength calibration. These requirements strongly call for integrated software tools to manage not only the reduction of data, but also the scientific analysis. The ultra-stable, high-resolution echelle spectrograph ESPRESSO, currently under integration for the ESO Very Large Telescope (first light: 2017) is the first instrument of its kind to include a dedicated Data Analysis Software among its deliverables, to process both stellar and quasar spectra. This software will extract physical information from the reduced data on the fly (e.g., stellar radial velocities, or characterisation of the absorption systems along the sightline to quasars) and will allow interaction through a configurable graphical user interface. In this article we present the features of the ESPRESSO Data Analysis Software and its development status at the first complete internal release. A particular attention is devoted to the algorithms developed for quasar spectral analysis (continuum determination and interpretation of the absorption systems)

Data treatment towards the ELT age. The ESPRESSO case

Several ambitious scientific projects are currently pushing the limits of astrophysical spectroscopy, in terms of wavelength accuracy and long-term stability. These objectives put strong constraints also on the treatment of observational data, requiring dedicated software to be developed as an integral part of the instrument. In this context, a key role will be played by ESPRESSO, an ultra-stable, high-resolution spectrograph for the VLT. ESPRESSO will be the first ESO instrument to be delivered with a dedicated tool for data analysis, in addition to data reduction. New solutions to treat ESPRESSO data have been developed in view of their application to the the next-generation spectrographs. <P /

ESPRESSO: The next European exoplanet hunter

The acronym ESPRESSO stems for Echelle SPectrograph for Rocky Exoplanets and Stable Spectroscopic Observations; this instrument will be the next VLT high resolution spectrograph. The spectrograph will be installed at the Combined-Coud\'e Laboratory of the VLT and linked to the four 8.2 m Unit Telescopes (UT) through four optical Coud\'e trains. ESPRESSO will combine efficiency and extreme spectroscopic precision. ESPRESSO is foreseen to achieve a gain of two magnitudes with respect to its predecessor HARPS, and to improve the instrumental radial-velocity precision to reach the 10 cm/s level. It can be operated either with a single UT or with up to four UTs, enabling an additional gain in the latter mode. The incoherent combination of four telescopes and the extreme precision requirements called for many innovative design solutions while ensuring the technical heritage of the successful HARPS experience. ESPRESSO will allow to explore new frontiers in most domains of astrophysics that require precision and sensitivity. The main scientific drivers are the search and characterization of rocky exoplanets in the habitable zone of quiet, nearby G to M-dwarfs and the analysis of the variability of fundamental physical constants. The project passed the final design review in May 2013 and entered the manufacturing phase. ESPRESSO will be installed at the Paranal Observatory in 2016 and its operation is planned to start by the end of the same year.Comment: 12 pages, figures included, accepted for publication in Astron. Nach

Automatic model-based telluric correction for the ESPRESSO data reduction software. Model description and application to radial velocity computation

Ground-based high-resolution spectrographs are key instruments for several astrophysical domains. Unfortunately, the observed spectra are contaminated by the Earth's atmosphere. While different techniques exist to correct for telluric lines in exoplanet atmospheric studies, in radial velocity (RV) studies, telluric lines with an absorption depth of >2% are generally masked, which poses a problem for faint targets and M dwarfs as most of their RV content is present where telluric contamination is important. We propose a simple telluric model to be embedded in the ESPRESSO DRS. The goal is to provide telluric-free spectra and enable RV measurements, including spectral ranges where telluric lines fall. The model is a line-by-line radiative transfer code that assumes a single atmospheric layer. We use the sky conditions and the physical properties of the lines from HITRAN to create the telluric spectrum. A subset of selected telluric lines is used to robustly fit the spectrum through a Levenberg-Marquardt minimization algorithm. When applied to stellar spectra from A0- to M5-type stars, the residuals of the strongest H2O lines are below 2% for all spectral types, with the exception of M dwarfs, which are within the pseudo-continuum. We then determined the RVs from the telluric-corrected ESPRESSO spectra of Tau Ceti and Proxima. We created telluric-free masks and compared the obtained RVs with the DRS RVs. In the case of Tau Ceti, we identified that micro-telluric lines introduce systematics up to an amplitude of 58 cm/s and with a period of one year. For Proxima, the gain in spectral content at redder wavelengths is equivalent to a gain of 25% in photon noise. This leads to better constraints on the semi-amplitude and eccentricity of Proxima d. We showcase that our model can be applied to other molecules, and thus to other wavelength regions observed by other spectrographs, such as NIRPS.Comment: 18 pages, 18 figures, accepted to A&