N-(Anilinoethyl)amide Melatonergic Ligands with Improved Water Solubility and Metabolic Stability

The MT₂-selective melatonin receptor ligand UCM765 (N-(2-((3-methoxyphenyl)(phenyl)amino)ethyl)acetamide), showed interesting sleep inducing, analgesic and anxiolytic properties in rodents, but suffers from low water solubility and modest metabolic stability. To overcome these limitations, different strategies were investigated, including modification of metabolically liable sites, introduction of hydrophilic substituents and design of more basic derivatives. Thermodynamic solubility, microsomal stability and lipophilicity of new compounds were experimentally evaluated, together with their MT₁ and MT₂ binding affinities. Introduction of a m-hydroxymethyl substituent on the phenyl ring of UCM765 and replacement of the replacement of the N,N-diphenyl-amino scaffold with a N-methyl-N-phenyl-amino one led to highly soluble compounds with good microsomal stability and receptor binding affinity. Docking studies into the receptor crystal structure provided a rationale for their binding affinity. Pharmacokinetic characterization in rats highlighted higher plasma concentrations for the N-methyl-N-phenyl-amino derivative, consistent with its improved microsomal stability and makes this compound worthy of consideration for further pharmacological investigation.     

Optical properties of hybrid T3Pyr/SiO2/3C-SiC nanowires

A new class of nanostructured hybrid materials is developed by direct grafting of a model thiophene-based organic dye on the surface of 3C-SiC/SiO₂ core/shell nanowires. TEM-EDX analysis reveals that the carbon distribution is more spread than it would be, considering only the SiC core size, suggesting a main contribution from C of the oligothiophene framework. Further, the sulfur signal found along the treated wires is not detected in the as-grown samples. In addition, the fluorescent spectra are similar for the functionalized nanostructures and T3Pyr in solution, confirming homogeneous molecule grafting on the nanowire surface. Chemical and luminescence characterizations confirm a homogeneous functionalization of the nanowires. In particular, the fluorophore retains its optical properties after functionalization.     

Zinc supplementation of Friesian cows: Effect on chemical-nutritional composition and aromatic profile of dairy products

Zinc represents an essential microelement for several biochemical mechanisms. The body's inability to store zinc necessarily requires a constant dietary supply to avoid alteration of physiological functions. The aim of the present study was to investigate the effect of dietary enrichment with zinc on chemical-nutritional and aromatic properties of milk and cheese. Thirty commercial dairy cows, balanced for parity, milk production, and days in milk, were randomly assigned to 2 groups. The control group was fed with a conventional complete diet (22 kg of dry matter/animal per day), whereas the experimental group received a daily zinc supplementation of 60 mg per kg of dry complete feed. During the experimental period, the milk yield was monitored and samples of milk and caciotta cheese were collected to obtain information about the chemical-nutritional composition and aromatic profile. Dietary zinc integration did not influence milk yield and composition, but induced a marked reduction of somatic cell count and improved the oxidative stability of ripened caciotta cheese. In both milk and cheese, the experimental group samples were characterized by a lower concentration of saturated fatty acids and an increase in oleic acid, vaccenic acid, and rumenic acid. The aromatic profile of dairy products was also positively affected by dietary zinc intake, with an increase in concentration of carboxylic acids, aldehydes, and esters. The present results suggest a positive role of zinc in improving animal health and nutraceutical properties of milk and corresponding cheese. Taking into account the analysis of volatile compounds, zinc dietary supplementation of dairy cows should contribute to the production of cheeses with interesting organoleptic properties, although more studies are necessary to confirm the consumer acceptability of these changes.     

Double Mutant Cycles as a Tool to Address Folding,Binding, and Allostery

Quantitative measurement of intramolecular and intermolecular interactions in protein structure is an elusive task, not easy to address experimentally. The phenomenon denoted ‘energetic coupling’ describes short- and long-range interactions between two residues in a protein system. A powerful method to identify and quantitatively characterize long-range interactions and allosteric networks in proteins or protein–ligand complexes is called double-mutant cycles analysis. In this review we describe the thermodynamic principles and basic equations that underlie the double mutant cycle methodology, its fields of application and latest employments, and caveats and pitfalls that the experimentalists must consider. In particular, we show how double mutant cycles can be a powerful tool to investigate allosteric mechanisms in protein binding reactions as well as elusive states in protein folding pathways.     

GutSelf: Interindividual Variability in the Processing of Dietary Compounds by the Human Gastrointestinal Tract

Nutritional research is currently entering the field of personalized nutrition, to a large extent driven by major technological breakthroughs in analytical sciences and biocomputing. An efficient launching of the personalized approach depends on the ability of researchers to comprehensively monitor and characterize interindividual variability in the activity of the human gastrointestinal tract. This information is currently not available in such a form. This review therefore aims at identifying and discussing published data, providing evidence on interindividual variability in the processing of the major nutrients, i.e., protein, fat, carbohydrates, vitamins, and minerals, along the gastrointestinal tract, including oral processing, intestinal digestion, and absorption. Although interindividual variability is not a primary endpoint of most studies identified, a significant number of publications provides a wealth of information on this topic for each category of nutrients. This knowledge remains fragmented, however, and understanding the clinical relevance of most of the interindividual responses to food ingestion described in this review remains unclear. In that regard, this review has identified a gap and sets the base for future research addressing the issue of the interindividual variability in the response of the human organism to the ingestion of foods.     

Weissella cibaria short-fermented liquid sourdoughs based on quinoa or amaranth flours as fat replacer in focaccia bread formulation

Production of the traditional Italian Focaccia bread (FcBread) requires reformulation to meet the new rules for healthier foods. We tested the applicability of a short-fermented (15 h) liquid sourdough (LS) (dough yield, DY, 250), obtained using quinoa (Q) or amaranth (Am) flour fermented with a Weissella cibaria strain (C43-11) producing exopolysaccharides (EPS) as fat replacer in yeast-leavened FcBread. The LSs were applied during the FcBread-making process at industrial pilot plant, reducing the added fat amount by 20% (FcBread-QLS and FcBread-AmLS) and products were compared with reference samples not containing EPS. All the products were analysed for physico-chemical properties (pH, TTA, organic acids, protein content and profile, instrumental colour), textural properties, sensory quality and glycemic index. The application of both pseudo-cereal-based W. cibaria LSs in FcBread allowed obtaining products with a reduced amount of fat, increased protein amount, mainly due to the albumin and glutenin/glutelin fractions, reduced glycemic index, improved texture and preserved in the traditional sensory profile of ‘focaccia’.     

Some recent advances in polyolefin functionalization

Polyolefin‐based materials are increasingly being used in many industrial applications for packaging, automotive and construction materials. The recent developments of research have been aimed at making these materials, often complex, being mixtures, block copolymers, micro‐ and nanocomposites with inorganic and organic fillers, more efficient and environmentally friendly (through recycling processes, and the use of bio‐polyolefins). In this context, functionalized polyolefins, on the one hand, play a fundamental role in improving the morphology and thus the thermal and mechanical properties of heterophase systems, and, on the other hand, provide new materials difficult to obtain by conventional synthesis in connection with the type of inserted functionality. Therefore it appears to be of interest to report and discuss here the recent results concerning the radical grafting in the melt of different functionalities onto polyolefins as well as the capability reached of modulating ad hoc the degree of grafting and the final structure/architecture of functionalized polyolefins. © 2013 Society of Chemical Industry