Intrinsic Fluorescence of the Active and the Inactive Functional Forms of Human Thymidylate Synthase

The observables associated with protein intrinsic fluorescence – spectra, time decays, anisotropies – offer opportunities to monitor in real time and non-invasively a protein‘s functional form and its interchange with other forms with different functions. We employed these observables to sketch the fluorometric profiles of two functional forms of human thymidylate synthase (hTS), a homodimeric enzyme crucial for cell proliferation and thus targeted by anticancer drugs. The protein takes an active and an inactive form. Stabilization of the latter by peptides that, unlike classical hTS inhibitors, bind it at the monomer/monomer interface offers an alternative inhibition mechanism that promises to avoid the onset of drug resistance in anticancer therapy. The fluorescence features depicted herein can be used as tools to identify and quantify each of the two protein forms in solution, thus making it possible to investigate the kinetic and thermodynamic aspects of the active/inactive conformational interchange. Two examples of fluorometrically monitored interconversion kinetics are provided.     

Postharvest performance of fresh‐cut ‘Big Top’ nectarine as affected by dipping in chemical preservatives and packaging in modified atmosphere

Fresh‐cut ‘Big Top’ nectarines were dipped in 2% (w/v) ascorbic acid–1% (w/v) calcium lactate and stored at 4 °C for up to 12 days in 10 kPa O₂‐ and 10 kPa CO₂‐modified atmosphere packaging (MAP). The used microperforated plastic film allowed O₂ and CO₂ concentrations to reach steady values from the fifth day in storage onwards. Samples stored in MAP after chemical dipping showed the highest visual quality score, slight browning symptoms, increment in firmness and very low ethanol and acetaldehyde content. The chemical dipping also increased antioxidant capacity, probably due to the effect of ascorbic acid. The results suggested that the control of yeasts was mainly exerted by MAP, whereas only a slight effect was achieved by the chemical dipping. Therefore, MAP plus ascorbic acid/calcium lactate dipping was the best combination to preserve phytochemical content, antioxidant capacity and microbiological safety of fresh‐cut nectarines during storage.     

Perception of Host Plant Volatiles in Hyalesthes obsoletus: Behavior, Morphology, and Electrophysiology

The Palearctic planthopper Hyalesthes obsoletus is the natural vector of the grapevine yellow disease Bois noir. Grapevine is an occasional host plant of this polyphagous planthopper. To deepen our knowledge of the role of plant volatile organic compounds for H. obsoletus host plant searching, we carried out behavioral, morphological, and electrophysiological studies. We tested the attraction of H. obsoletus to nettle, field bindweed, hedge bindweed, chaste tree, and grapevine by using a Y-shaped olfactometer. The results showed a significant attraction of male H. obsoletus to chaste tree, and of the females to nettle. Male H. obsoletus were repelled by odor from hedge bindweed. Ultrastructural studies of the antennae showed at least two types of olfactory sensilla at the antennal pedicel: plaque organs and trichoid sensilla. Volatile organic compounds from nettle and chaste tree were collected, and the extracts were analyzed by coupling gas-chromatography to both mass-spectrometry and electroantennography. The volatile organic compounds that elicited electrophysiological responses in male and female antennae were identified. These findings are discussed with respect to behavior of H. obsoletus males and females in the field.     

Evaluation of 4-(4-Fluorobenzyl)piperazin-1-yl]-Based Compounds as Competitive Tyrosinase Inhibitors Endowed with Antimelanogenic Effects

There is a considerable attention for the development of inhibitors of tyrosinase (TYR) as therapeutic strategy for the treatment of hyperpigmentation disorders in humans. Continuing in our efforts to identify TYR inhibitors, we describe the design, synthesis and pharmacophore exploration of new small molecules structurally characterized by the presence of the 4-fluorobenzylpiperazine moiety as key pharmacophoric feature for the inhibition of TYR from Agaricus bisporus (AbTYR). Our investigations resulted in the discovery of the competitive inhibitor [4-(4-fluorobenzyl)piperazin-1-yl]-(3-chloro-2-nitro-phenyl)methanone 26 (IC₅₀=0.18 μM) that proved to be ∼100-fold more active than reference compound kojic acid (IC₅₀=17.76 μM). Notably, compound 26 exerted antimelanogenic effect on B16F10 cells in absence of cytotoxicity. Docking analysis suggested its binding mode into AbTYR and into modelled human TYR.     

Astringency sub-qualities of red wines and the influence of wine–saliva aggregates

Astringency is a sensory attribute, related to the quality and mouthfeel of red wines. However, the origin of astringency sub-qualities, such as the typical drying astringency found in immature grapes, is still unknown. Astringency of red wines with similar tannin content but different astringency sub-qualities, from different harvest dates, is studied. Astringency was characterised in terms of friction coefficient, polyphenol content, sensory analysis and tannin/salivary–proteins aggregates characterisation. A different evolution during ripening was found for both Cabernet Sauvignon and Carménère, and tannin–protein aggregates showed differences in size, shape and surface. The velvety sub-quality appears to be related to aggregates with low precipitation, and with specific surface characteristics as roundness and Feret diameter. Results from this work propose an effect of aggregates on sensory perception and opens the possibility to explore their effect on oral lubrication.     

Optimal buffer inventory and preventive maintenance for an imperfect production process

In this paper we present a model to determine the optimal length of continuous production periods between maintenance actions and the optimal buffer inventory to satisfy demand during preventive maintenance or repair of a manufacturing facility. We include in the model the possibility of imperfect production. We consider that the duration and cost of the maintenance action depend on the state of the production facility.     

Mimetic Discretizations of Elliptic Control Problems

We investigate the performance of the Mimetic Finite Difference (MFD) method for the approximation of a constraint optimal control problem governed by an elliptic operator. Low-order and high-order mimetic discretizations are considered and a priori error estimates are derived, in a suitable discrete norm, for both the control and the state variables. A wide class of numerical experiments performed on a set of examples selected from the literature assesses the robustness of the MFD method and confirms the convergence analysis.     

VFC-SMOTE: very fast continuous synthetic minority oversampling for evolving data streams

Data Mining and Knowledge Discovery - The world is constantly changing, and so are the massive amount of data produced. However, only a few studies deal with online class imbalance learning that...