Structural investigation of nucleophosmin interaction with the tumor suppressor Fbw7γ

Nucleophosmin (NPM1) is a multifunctional nucleolar protein implicated in ribogenesis, centrosome duplication, cell cycle control, regulation of DNA repair and apoptotic response to stress stimuli. The majority of these functions are played through the interactions with a variety of protein partners. NPM1 is frequently overexpressed in solid tumors of different histological origin. Furthermore NPM1 is the most frequently mutated protein in acute myeloid leukemia (AML) patients. Mutations map to the C-terminal domain and lead to the aberrant and stable localization of the protein in the cytoplasm of leukemic blasts. Among NPM1 protein partners, a pivotal role is played by the tumor suppressor Fbw7γ, an E3-ubiquitin ligase that degrades oncoproteins like c-MYC, cyclin E, Notch and c-jun. In AML with NPM1 mutations, Fbw7γ is degraded following its abnormal cytosolic delocalization by mutated NPM1. This mechanism also applies to other tumor suppressors and it has been suggested that it may play a key role in leukemogenesis. Here we analyse the interaction between NPM1 and Fbw7γ, by identifying the protein surfaces implicated in recognition and key aminoacids involved. Based on the results of computational methods, we propose a structural model for the interaction, which is substantiated by experimental findings on several site-directed mutants. We also extend the analysis to two other NPM1 partners (HIV Tat and CENP-W) and conclude that NPM1 uses the same molecular surface as a platform for recognizing different protein partners. We suggest that this region of NPM1 may be targeted for cancer treatment

The long-lasting story of one sensor development: from novel ionophore design toward the sensor selectivity modeling and lifetime improvement

The metalloporphyrin ligand bearing incorporated anion-exchanger fragment, 5-[4-(3-trimethylammonium)propyloxyphenyl]-10,15,20-triphenylporphyrinate of Co(II) chloride, CoTPP-N, has been tested as anion-selective ionophore in PVC-based solvent polymeric membrane sensors. A plausible sensor working mechanism includes the axial coordination of the target anion on ionophore metal center followed by the formed complex aggregation with the second ionophore molecule through positively charged anion-exchanger fragment. The UV-visible spectroscopic studies in solution have revealed that the analyte concentration increase induces the J-type porphyrin aggregation. Polymeric membranes doped with CoTPP-N showed close to the theoretical Nernstian response toward nitrite ion, preferably coordinated by the ionophore, and were dependent on the presence of additional membrane-active components (lipophilic ionic sites and ionophore) in the membrane phase. The resulting selectivity was a subject of specific interaction and/or steric factors. Moreover, it was demonstrated theoretically and confirmed experimentally that the selection of a proper ratio of ionophore and anionic additive can optimize the sensor selectivity and lifetime

3D mosaic documentation using close range photogrammetry

The paper describes the close range photogrammetric survey of a roman mosaic stored at Regional Archaeological Museum “Antonino Salinas” in Palermo (Italy). The aim of the work is the production of a full-scale representation (scale 1:1) of the mosaic useful for documentation and restoration processes. The research has allowed evaluating limit and potentiality of image-based approach using photogrammetric and computer vision (Structure for Motion) techniques in a context where the metric point of view is a very important factor

Sensor-embedded face masks for detection of volatiles in breath: a proof of concept study

The correlation between breath volatilome and health is prompting a growing interest in the development of sensors optimized for breath analysis. On the other hand, the outbreak of COVID-19 evidenced that breath is a vehicle of infection; thus, the introduction of low-cost and disposable devices is becoming urgent for a clinical implementation of breath analysis. In this paper, a proof of concept about the functionalization of face masks is provided. Porphyrin-based sensors are among the most performant devices for breath analysis, but since porphyrins are scarcely conductive, they make use of costly and bulky mass or optical transducers. To overcome this drawback, we introduce here a hybrid material made of conducting polymer and porphyrins. The resulting material can be easily deposited on the internal surface of standard FFP face masks producing resistive sensors that retain the chemical sensitivity of porphyrins implementing their combinatorial selectivity for the identification of volatile compounds and the classification of complex samples. The sensitivity of sensors has been tested with respect to a set of seven volatile compounds representative of diverse chemical families. Sensors react to all compounds but with a different sensitivity pattern. Functionalized face masks have been tested in a proof-of-concept test aimed at identifying changes of breath due to the ingestion of beverages (coffee and wine) and solid food (banana- and mint-flavored candies). Results indicate that sensors can detect volatile compounds against the background of normal breath VOCs, suggesting the possibility to embed sensors in face masks for extensive breath analysis

A method to constrain the neutron star magnetic field in Low Mass X-ray Binaries

We describe here a method to put an upper limit to the strength of the magnetic field of neutron stars in low mass X‐ray binaries for which the spin period and the X‐ray luminosity during X‐ray quiescent periods are known. This is obtained using simple considerations about the position of the magnetospheric radius during quiescent periods. We applied this method to the accreting millisecond pulsar SAX J1808.4‐3658, which shows coherent X‐ray pulsations at a frequency of ∼ 400 Hz and a quiescent X‐ray luminosity of ∼ 5 × 1031 ergs/s, and found that B ⩽ 5 × 108 Gauss in this source. Combined with the lower limit inferred from the presence of X‐ray pulsations, this constrains the SAX J1808.4‐3658 neutron star magnetic field in the quite narrow range (1 – 5) × 108 Gauss. Similar considerations applied to the case of Aql X‐1 and KS 1731‐260 give neutron star magnetic fields lower than ∼ 109 Gauss

a mathematical description accounting for the superfluous hydrogen evolution and the inductive behaviour observed during electrochemical measurements on magnesium

Abstract When electrochemical techniques are used to probe the surface of corroding magnesium with the aim of obtaining quantitative information on the corrosion process, two peculiarities are generally observed: i) with anodic polarization, the rate of hydrogen evolution increases instead of decreasing and ii) during electrochemical impedance spectroscopy measurements, an inductive contribution is often observed at the low-frequency end of the spectra. The presence of these two phenomena clearly has an impact on the methodology that should be applied to correctly estimate corrosion rates from electrochemical data. The aim of this work is to provide a general mathematical description of the corroding magnesium surface that, under minimal a priori assumptions regarding the reaction kinetics, can account simultaneously for both superfluous hydrogen evolution and inductive response. The mathematical results are consistent with the suggestion that the superfluous hydrogen evolution is mainly related to the increase of the surface of the active corrosion front during anodic polarization. Further, the obtained results show that the inductive response is expected when, at the corrosion front, oxidation of magnesium proceeds faster than hydrogen evolution

Keeping track of phaeodactylum tricornutum (Bacillariophyta) culture contamination by potentiometric e-tongue

The large-scale cultivation of microalgae provides a wide spectrum of marketable bioproducts, profitably used in many fields, from the preparation of functional health products and feed supplement in aquaculture and animal husbandry to biofuels and green chemistry agents. The commercially successful algal biomass production requires effective strategies to maintain the process at desired productivity and stability levels. Hence, the development of effective early warning methods to timely indicate remedial actions and to undertake countermeasures is extremely important to avoid culture collapse and consequent economic losses. With the aim to develop an early warning method of algal contamination, the potentiometric E-tongue was applied to record the variations in the culture environments, over the whole growth process, of two unialgal cultures, Phaeodactylum tricornutum and a microalgal contaminant, along with those of their mixed culture. The E-tongue system ability to distinguish the cultures and to predict their growth stage, through the application of multivariate data analysis, was shown. A PLS regression method applied to the E-tongue output data allowed a good prediction of culture growth time, expressed as growth days, with R-2 values in a range from 0.913 to 0.960 and RMSEP of 1.97-2.38 days. Moreover, the SIMCA and PLS-DA techniques were useful for cultures contamination monitoring. The constructed PLS-DA model properly discriminated 67% of cultures through the analysis of their growth media, i.e., environments, thus proving the potential of the E-tongue system for a real time monitoring of contamination in microalgal intensive cultivation

General relativistic effects on the evolution of binary systems.

When a radio pulsar brakes down due to magnetodipole emission,its gravitational mass decreases accordingly. If the pulsar is hosted in a binary system, this mass loss will Increase the orbital period of the system. We show that this relativistic effect can be indeed observable if the neutron star is fast and magnetized enough and that, if observed, it will help to put tight constraints to the equation of state of ultradense matter. Moreover, in Low Mass X-ray Binaries that evolve towards short periods, the neutron star lights up as a radio pulsar during the "period gap". As the effect we consider contrasts the orbital period decay, the system spends a longer time in this phase. As a consequence, the neutron star can survive this phase only if it is non-supramassive, Since in such bianries similar to 0.84M(circle dot) can be accreted onto the neutron star, short period (P <= 2 h) millisecond Xray pulsars like SAX J1808.4-3658 can be formed only if either a large part of the accreting matter has been ejected from the system, or the equation of state of ultradense matter is very stiff

PROMON: a profile monitor of software applications

Software techniques can be efficiently used to increase the dependability of safety-critical applications. Many approaches are based on information redundancy to prevent data and code corruption during the software execution. This paper presents PROMON, a C++ library that exploits a new methodology based on the concept of “Programming by Contract” to detect system malfunctions. Resorting to assertions, pre- and post-conditions, and marginal programmer interventions, PROMON-based applications can reach high level of dependability