Forward precision medicine: Micelles for active targeting driven by peptides

Precision medicine is based on innovative administration methods of active principles. Drug delivery on tissue of interest allows improving the therapeutic index and reducing the side effects. Active targeting by means of drug-encapsulated micelles decorated with targeting bioactive moieties represents a new frontier. Between the bioactive moieties, peptides, for their versatility, easy synthesis and immunogenicity, can be selected to direct a drug toward a considerable number of molecular targets overexpressed on both cancer vasculature and cancer cells. Moreover, short peptide sequences can facilitate cellular intake. This review focuses on micelles achieved by self-assembling or mixing peptide-grafted surfactants or peptide-decorated amphiphilic copolymers. Nanovectors loaded with hydrophobic or hydrophilic cytotoxic drugs or with gene silence sequences and externally functionalized with natural or synthetic peptides are described based on their formulation and in vitro and in vivo behaviors

New molecular tool for a quick and easy detection of apple scab in the field

Venturia inaequalis, an agent of apple scab, is the most important pathogen of Malus x domestica. Control measures against this pathogen rely on intensive phytosanitary programs based on predictive models to identify the meteorological conditions conducive to the primary infection. The detection of the pathogen in field, both in naturally infected symptomatic and asymptomatic leaves, is desirable. Loop-mediated isothermal amplification (LAMP) assays are profitable molecular diagnostic tools for the direct detection of pathogens in field. A LAMP assay for V. inaequalis has been designed on the elongation factor 1-alpha sequence. The validation of the LAMP assay was carried out following the international EPPO standard PM 7/98 in terms of specificity, sensitivity, repeatability and reproducibility. Specificity testing was performed using target and non-target species, such as phylogenetically related Venturia species and other pathogens commonly found in apple, resulting in positive amplification only for the target with a time to positive ranging from 20 to 30 min. Sensitivity testing was performed with serial dilutions of DNA of the target and by artificial inoculation of young apple leaves. The reliability of the LAMP assay as an early-detection tool and its user-friendly application make it suitable for the diagnosis of apple scab in the field

Toward an accurate ab initio estimation of compressibility and thermal expansion of diamond in the [0, 3000 K] temperature and [0, 30 GPa] pressures ranges, at the hybrid HF/DFT theoretical level

The isothermal bulk modulus, together with its temperature dependence, and the thermal expansion of diamond at various pressures were calculated from first principles in the [0, 30 GPa] and [0, 3000 K] pressure and temperature ranges, within the limits of the quasi-harmonic approximation (QHA). The hybrid HF/DFT functional employed (WC1LYP) proved to be particularly effective in providing a very close agreement between the calculated and the available experimental data. In particular, the bulk modulus at 300 K was estimated to be 444.6 GPa (K' = 3.60); at the same temperature, the (volume) thermal expansion coefficient was 3.19×10-6 K-1. To the authors’ knowledge, among the theoretical papers devoted to the subject, the present one provides the most accurate thermo-elastic data in high-pressure and temperature ranges. Such data can confidently be used in the determination of the pressure of formation using the “elastic method” for minerals found as inclusions in diamonds (recently applied on different minerals included in diamonds), thus shedding light upon the genesis of diamonds in the Earth’s upper mantle

The (100), (111) and (110) surfaces of diamond: an ab initio B3LYP study

We present an accurate ab initio study of the structure and surface energy of the low-index (100),(111) and (110) diamond faces, by using the hybrid Hartree-Fock/Density Functional B3LYPHamiltonian and a localized all-electron Gaussian-type basis set. A 2D periodic slab model has been adopted, for which convergence on both structural and energetic parameters has been thoroughly investigated. For all the three surfaces, possible relaxations and reconstructions have been considered; a detailed geometrical characterization is provided for the most stable structure of each orientation. Surface energy is discussed for all the investigated faces

Observation of the Decay B^-→D_s^((*)+)K^-ℓ^-ν̅ _ℓ

We report the observation of the decay B^- → D_s^((*)+)K^-ℓ^-ν̅ _ℓ based on 342  fb^(-1) of data collected at the Υ(4S) resonance with the BABAR detector at the PEP-II e^+e^- storage rings at SLAC. A simultaneous fit to three D_s^+ decay chains is performed to extract the signal yield from measurements of the squared missing mass in the B meson decay. We observe the decay B^- → D_s^((*)+)K^-ℓ^-ν̅ _ℓ with a significance greater than 5 standard deviations (including systematic uncertainties) and measure its branching fraction to be B(B^- → D_s^((*)+)K^-ℓ^-ν̅ _ℓ)=[6.13_(-1.03)^(+1.04)(stat)±0.43(syst)±0.51(B(D_s))]×10^(-4), where the last error reflects the limited knowledge of the D_s branching fractions