Diphenyl-Methane Based Thyromimetic Inhibitors for Transthyretin Amyloidosis

Thyromimetics, whose physicochemical characteristics are analog to thyroid hormones (THs) and their derivatives, are promising candidates as novel therapeutics for neurodegenerative and metabolic pathologies. In particular, sobetirome (GC-1), one of the initial halogen-free thyromimetics, and newly synthesized IS25 and TG68, with optimized ADME-Tox profile, have recently attracted attention owing to their superior therapeutic benefits, selectivity, and enhanced permeability. Here, we further explored the functional capabilities of these thyromimetics to inhibit transthyretin (TTR) amyloidosis. TTR is a homotetrameric transporter protein for THs, yet it is also responsible for severe amyloid fibril formation, which is facilitated by tetramer dissociation into non-native monomers. By combining nuclear magnetic resonance (NMR) spectroscopy, computational simulation, and biochemical assays, we found that GC-1 and newly designed diphenyl-methane-based thyromimetics, namely IS25 and TG68, are TTR stabilizers and efficient suppressors of TTR aggregation. Based on these observations, we propose the novel potential of thyromimetics as a multi-functional therapeutic molecule for TTR-related pathologies, including neurodegenerative diseases.     

The Role of microRNAs in Development of Colitis-Associated Colorectal Cancer

Colorectal cancer (CRC) is the third most deadly cancer worldwide, and inflammatory bowel disease (IBD) is one of the critical factors in CRC carcinogenesis. IBD is responsible for an unphysiological and sustained chronic inflammation environment favoring the transformation. MicroRNAs (miRNAs) belong to a class of highly conserved short single-stranded segments (18–25 nucleotides) non-coding RNA and have been extensively discussed in both CRC and IBD. However, the role of miRNAs in the development of colitis-associated CRC (CAC) is less clear. The aim of this review is to summarize the major upregulated (miR-18a, miR-19a, miR-21, miR-31, miR-155 and miR-214) and downregulated (miR-124, miR-193a-3p and miR-139-5p) miRNAs in CAC, and their roles in genes’ expression modulation in chronic colonic-inflammation-induced carcinogenesis, including programmed cell-death pathways. These miRNAs dysregulation could be applied for early CAC diagnosis, to predict therapy efficacy and for precision treatment.     

Model-driven engineering for mobile robotic systems: a systematic mapping study

Software and Systems Modeling - Mobile robots operate in various environments (e.g. aquatic, aerial, or terrestrial), they come in many diverse shapes and they are increasingly becoming parts of...     

Application of the novel Droplet digital PCR technology for identification of meat species

The authenticity and traceability of meat products are issues of primary importance to ensure food safety. Unfortunately, food adulteration (e.g. the addition of inexpensive cuts to minced meat products) and mislabelling (e.g. the inclusion of meat from species other than those declared) happens frequently worldwide. The aim of this study was to apply a droplet digital PCR assay for the detection and quantification (copies μL⁻¹) of the beef, pork, horse, sheep, chicken and turkey in meat products. The analysis conducted on commercial meat showed the presence of traces of DNA from other animal species than those declared. We show that the method is highly sensitive, specific and accurate (accuracy = 100%). This method could be adopted by competent food safety authorities to verify compliance with the labelling of meat products and to ensure quality and safety throughout the meat supply chain, from primary production to consumption.     

Metabolism of phospholipids in the yeast Schizosaccharomyces pombe

The fission yeast Schizosaccharomyces pombe is an important model organism for the study of fundamental questions in eukaryotic cell and molecular biology. A plethora of cellular processes are membrane associated and/or dependent on the proper functioning of cellular membranes. Phospholipids are not only the basic building blocks of cellular membranes; they also serve as precursors to numerous signaling molecules. In this review, we describe the biosynthetic pathways leading to major S. pombe phospholipids, how these pathways are regulated, and what is known about degradation and turnover of fission yeast phospholipids. This review also addresses the synthesis, regulation and the role of water-soluble phospholipid precursors. The last chapter of the review is devoted to the use of S. pombe for the biotechnological production of value-added lipid molecules.     

Biodegradable hollow microfibres to produce bioactive scaffolds

Biodegradable hollow microfibres containing particles loaded with specific active agents can be potentially employed to produce a special kind of substrate for tissue engineering, able to function as a scaffold and at the same time to act as a drug‐releasing system. Biodegradable hollow microfibres based on poly(lactic acid) were produced by a dry–wet spinning procedure. Drug‐loaded microparticles were prepared by a simple oil‐in‐water emulsion and entrapped inside the fibres. The morphology of both fibres and particles was investigated by scanning electron microscopy. The mechanical and thermal properties of the fibres were investigated by tensile tests and differential scanning calorimetry. In vitro tests were performed to evaluate the release of the drug from the fibres loaded with the particles Copyright © 2004 Society of Chemical Industry     

Non-pinched, minimum energy distillation designs

Non-pinched, minimum energy solutions are important class of distillation designs that offer the potential advantage of a better trade-off between capital investment and operating costs. In this paper, two important tasks associated with non-pinched distillation designs are studied. Thus the novel contributions of this work to the literature are

(1) A comprehensive methodology for finding non-pinched minimum energy designs.

(2) Understanding of the reasons for the existence of non-pinched distillation designs.

It is shown that the recent shortest stripping line distance approach of Lucia et al. [Lucia, A., Amale, A. and Taylor, R., 2007, Distillation pinch points and more. Comput Chem Eng, available on-line] is capable of systematically and reliably finding non-pinched, minimum energy distillation designs. In addition, we provide an understanding of the reasons behind the existence of non-pinched designs, which include trajectories that follow unstable branches of a pinch point curve in azeotropic systems, the inherent looping structure of trajectories in hydrocarbon separations, and the presence of ancillary constraints in multi-unit processes like extraction/distillation. Several distillation examples are studied and many numerical results and geometric illustrations are presented that show the shortest stripping line distance methodology is indeed a powerful and systematic tool for computing non-pinched, minimum energy designs and that support the underlying reason we provide for the existence of non-pinched designs.     

Direct Methods Optimised for Solving Crystal Structure by Powder Diffraction Data: Limits,Strategies, and Prospects

The ab-initio crystal structure solution by powder diffraction data requires great efforts because of the collapse of the experimental information onto the one dimensional 2θ axis of the pattern. Different strategies will be described aiming at improving the process of extraction of the integrated intensities from the experimental pattern in order to make more straightforward the structure solution process by direct methods. Particular attention will be devoted to the EXPO program. Some of its performance will be analysed and results will be shown.