Fragmenting the S100B–p53 Interaction: Combined Virtual/Biophysical Screening Approaches to Identify Ligands

S100B contributes to cell proliferation by binding the C terminus of p53 and inhibiting its tumor suppressor function. The use of multiple computational approaches to screen fragment libraries targeting the human S100B–p53 interaction site is reported. This in silico screening led to the identification of 280 novel prospective ligands. NMR spectroscopic experiments revealed specific binding at the p53 interaction site for a set of these compounds and confirmed their potential for further rational optimization. The X‐ray crystal structure determined for one of the binders revealed key intermolecular interactions, thus paving the way for structure‐based ligand optimization.     

Active packaging material based on buriti oil – Mauritia flexuosa L.f. (Arecaceae) incorporated into chitosan films

Active and biodegradable materials have great potential in food packaging applications, improving the safety and quality of products. The objective of this study was to develop a new material based on buriti oil incorporated into a chitosan film. Different concentrations of buriti oil in dried films (2.1 g/m², 10.4 g/m², 20.8 g/m², and 31.3 g/m²) were added into a chitosan matrix (41.7 g/m²). The chitosan/buriti oil films were characterized by water‐vapor barrier properties, total water‐soluble matter (TSM), tensile properties, thermogravimetric analysis, microstructure, microbial permeation properties, and biodegradation estimation. The higher oil concentration improved the water‐vapor barrier and the buriti oil acted largely as a plasticizer and increased the elongation at break, and decreased the tensile strength (TS) of chitosan films. The total water‐soluble matter of chitosan films decreased in function of the buriti oil concentration, but the biodegradation and thermal stability increased. The chitosan films presented a microbial barrier against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43210.     

Electrospun polyamide‐6 membranes containing titanium dioxide as photocatalyst

Electrospun polyamide‐6 membranes containing titanium dioxide (TiO₂) photocatalyst were prepared and characterized. By tailoring the electrospinning parameters it was possible to obtain membranes having two different thicknesses, namely 5 and 20 µm, in which TiO₂ particles were homogeneously dispersed. As a comparison, hybrid films made with polyamide‐6 matrix and TiO₂ filler were successfully produced, with inorganic/organic ratios of 10 and 20 wt%. The photocatalytic activity of both hybrid systems was evaluated by following the degradation of methylene blue as a target molecule as a function of UV irradiation time. A smoother degradation was recorded for the electrospun membranes with respect to the hybrid films probably due to a less exposed surface because of the highly porous structure. Even if a longer photodegradation time was necessary, the degradation of the dye was successfully achieved. Copyright © 2010 Society of Chemical Industry     

Inhibition of Leishmania infantum Trypanothione Reductase by Azole‐Based Compounds: a Comparative Analysis with Its Physiological Substrate by X‐ray Crystallography

Herein we report a study aimed at discovering a new class of compounds that are able to inhibit Leishmania donovani cell growth. Evaluation of an in‐house library of compounds in a whole‐cell screening assay highlighted 4‐((1‐(4‐ethylphenyl)‐2‐methyl‐5‐(4‐(methylthio)phenyl)‐1H‐pyrrol‐3‐yl)methyl)thiomorpholine (compound 1 ) as the most active. Enzymatic assays on Leishmania infantum trypanothione reductase (LiTR, belonging to the Leishmania donovani complex) shed light on both the interaction with, and the nature of inhibition by, compound 1 . A molecular modeling approach based on docking studies and on the estimation of the binding free energy aided our rationalization of the biological data. Moreover, X‐ray crystal structure determination of LiTR in complex with compound 1 confirmed all our results: compound 1 binds to the T(SH)₂ binding site, lined by hydrophobic residues such as Trp21 and Met113, as well as residues Glu18 and Tyr110. Analysis of the structure of LiTR in complex with trypanothione shows that Glu18 and Tyr110 are also involved in substrate binding, according to a competitive inhibition mechanism.     

Epoxy/BaTiO3 Light‐Cured Composites as Organic Capacitors

Epoxy/BaTiO₃ hybrid materials are prepared as good candidates for organic capacitors. The hybrid system is cured by using camphorquinone and a iodonium salt through a free‐radical promoted cationic polymerization using a long‐wavelength tungsten halogen lamp. The cured films are fully characterized. Morphological characterization shows a well‐dispersed inorganic phase within the organic matrix. Electrical characterization demonstrates a linear increase of the dielectric constant with increasing filler content, while low dielectric loss values are obtained.

     

A Presurgical Study of Curcumin Combined with Anthocyanin Supplements in Patients with Colorectal Adenomatous Polyps

Adenomatous polyps are precancerous lesions associated with a higher risk of colorectal cancer (CRC). Curcumin and anthocyanins have shown promising CRC-preventive activity in preclinical and epidemiological studies. The objective of this window-of-opportunity, proof-of principle trial was to evaluate the effect of curcumin combined with anthocyanin supplements on tissue biomarkers of colorectal adenomatous polyps. Eligible patients received either anthocyanin and curcumin supplementation or related matching placebo for 4–6 weeks before polyp removal. Adenomatous polyps and adjacent tissue biopsies were collected at baseline and after supplementation for immunohistochemical assessment of β-catenin, NF-kappa B (NF-κB), Ki-67, P53, and dysplasia. No differences were observed in baseline biomarker expression between normal and dysplastic tissues. The combination of anthocyanins and curcumin resulted in a significant borderline reduction of NF-κB immunohistochemistry (IHC) expression in adenoma tissue (geometric mean ratio (GMR): 0.72; 95% confidence interval (CI): 0.51–1.00; p-value: 0.05) and a trend to a reduction of Ki-67 (GMR: 0.73; 95% CI: 0.50–1.08; p-value: 0.11). No significant modulation of biomarkers in normal adjacent mucosa was observed. We concluded that the combined supplementation of anthocyanins and curcumin seems to lead to a potentially favorable modulation of tissue biomarkers of inflammation and proliferation in colon adenomas.     

Market research for requirements analysis using linguistic tools

Numerous studies in recent months have proposed the use of linguistic instruments to support requirements analysis. There are two main reasons for this: (i) the progress made in natural language processing and (ii) the need to provide the developers of software systems with support in the early phases of requirements definition and conceptual modelling. This paper presents the results of an online market research intended (a) to assess the economic advantages of developing a CASE (computer-aided software engineering) tool that integrates linguistic analysis techniques for documents written in natural language, and (b) to verify the existence of the potential demand for such a tool. The research included a study of the language – ranging from completely natural to highly restricted – used in documents available for requirements analysis, an important factor given that on a technological level there is a trade-off between the language used and the performance of the linguistic instruments. To determine the potential demand for such tool, some of the survey questions dealt with the adoption of development methodologies and consequently with models and support tools; other questions referred to activities deemed critical by the companies involved. Through statistical correspondence analysis of the responses, we were able to outline two profiles of companies that correspond to two potential market niches, which are characterised by their very different approach to software development.

Cancer-Homing CAR-T Cells and Endogenous Immune Population Dynamics

Chimeric antigen receptor (CAR) therapy is based on patient blood-derived T cells and natural killer cells, which are engineered in vitro to recognize a target antigen in cancer cells. Most CAR-T recognize target antigens through immunoglobulin antigen-binding regions. Hence, CAR-T cells do not require the major histocompatibility complex presentation of a target peptide. CAR-T therapy has been tremendously successful in the treatment of leukemias. On the other hand, the clinical efficacy of CAR-T cells is rarely detected against solid tumors. CAR-T-cell therapy of cancer faces many hurdles, starting from the administration of engineered cells, wherein CAR-T cells must encounter the correct chemotactic signals to traffic to the tumor in sufficient numbers. Additional obstacles arise from the hostile environment that cancers provide to CAR-T cells. Intense efforts have gone into tackling these pitfalls. However, we argue that some CAR-engineering strategies may risk missing the bigger picture, i.e., that a successful CAR-T-cell therapy must efficiently intertwine with the complex and heterogeneous responses that the body has already mounted against the tumor. Recent findings lend support to this model.     

Agronomic performance of experimental fertilizers on spinach (<Emphasis Type="Italic">Spinacia oleracea</Emphasis> L.) in organic farming

In organic farming, soil application of processed agro-industrial by-products could sustain soil fertility for vegetables, which have short cropping cycles. Therefore, the objectives of this 2-year research on organic spinach crop were to assess the productive performance of different experimental fertilizers, the effects on soil fertility, and investigate the dynamics of some soil properties and the N balance. Two types of olive pomace mixtures, with a different initial C/N ratio, were composted and both stopped at the active phase (A1 and B1) and processed until maturation (A2 and B2). Also an anaerobic digestate (DA), and the B2 applied as amendment (B2A) were studied. The four composts, DA, and B2A were compared with a commercial organic fertilizer (Org), and a control (N0). The Org resulted as not sustainable in maintaining soil fertility in the long-term, mainly due to reduction in the soil of total organic carbon by 32 %, compared to the average of the other treatments. Conversely, choosing stage of maturity and adequate C/N of starting mixtures was among the best practices for compost use in spinach crop. The great content of nutrients (N and K higher by 102 and 86 % than Org, respectively), and N surplus (1431 kg ha^?1) in the B2A plots would suggest that they could accumulate after subsequent soil applications, with the risk of losses in the environment. The DA appeared to be the most suitable fertilizer to get a favorable trade-off among yield, quality and N-use efficiency, when applied according to best agronomic practices.