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.     

Effect of RF magnetron sputtering parameters on the optimization of the discharge capacity of ternary lithium oxide thin films

Journal of Materials Science: Materials in Electronics - The increasing demand for lithium-ion batteries has stimulated the investigation of new compounds in order to reduce the costs and the...     

Shape Factor Effect on Inclusion Sedimentation in Aluminum Melts

Metallurgical and Materials Transactions B - The quality requirements of aluminum products are steadily increasing, and the presence of non-metallic inclusions have a large impact on the quality of...     

Oxidative Stress in Obesity: A Critical Component in Human Diseases

Obesity, a social problem worldwide, is characterized by an increase in body weight that results in excessive fat accumulation. Obesity is a major cause of morbidity and mortality and leads to several diseases, including metabolic syndrome, diabetes mellitus, cardiovascular, fatty liver diseases, and cancer. Growing evidence allows us to understand the critical role of adipose tissue in controlling the physic-pathological mechanisms of obesity and related comorbidities. Recently, adipose tissue, especially in the visceral compartment, has been considered not only as a simple energy depository tissue, but also as an active endocrine organ releasing a variety of biologically active molecules known as adipocytokines or adipokines. Based on the complex interplay between adipokines, obesity is also characterized by chronic low grade inflammation with permanently increased oxidative stress (OS). Over-expression of oxidative stress damages cellular structures together with under-production of anti-oxidant mechanisms, leading to the development of obesity-related complications. The aim of this review is to summarize what is known in the relationship between OS in obesity and obesity-related diseases.     

Back to the Origins: Background and Perspectives of Grapevine Domestication

Domestication is a process of selection driven by humans, transforming wild progenitors into domesticated crops. The grapevine (Vitis vinifera L.), besides being one of the most extensively cultivated fruit trees in the world, is also a fascinating subject for evolutionary studies. The domestication process started in the Near East and the varieties obtained were successively spread and cultivated in different areas. Whether the domestication occurred only once, or whether successive domestication events occurred independently, is a highly debated mystery. Moreover, introgression events, breeding and intense trade in the Mediterranean basin have followed, in the last thousands of years, obfuscating the genetic relationships. Although a succession of studies has been carried out to explore grapevine origin and different evolution models are proposed, an overview of the topic remains pending. We review here the findings obtained in the main phylogenetic and genomic studies proposed in the last two decades, to clarify the fundamental questions regarding where, when and how many times grapevine domestication took place. Finally, we argue that the realization of the pan-genome of grapes could be a useful resource to discover and track the changes which have occurred in the genomes and to improve our understanding about the domestication.     

Total mercury levels in crustacean species from Italian fishery

This study investigated mercury contamination levels in eight commercially valuable crustacean species caught off the Central Adriatic and Tyrrhenian coasts of Italy. Total mercury levels were measured by Thermal Decomposition-Amalgamation-Atomic Absorption Spectrophotometry. Results showed a high variability among species with values ranging from 0.070 to 1.24 (mg kg^?1 wet weight). The lowest mercury levels were detected in caramote prawn (Penaeus kerathurus), warty crab (Eriphia verrucosa) and European spider crab (Maja squinado), decapods living in shallow waters. Levels exceeding the limits established by the European Commission were found in species living in close contact with bottom sediments: deepwater rose shrimp (Parapenaeus longirostris), blue and red shrimp (Aristeus antennatus) and Norway lobster (Nephrops norvegicus). For shrimps, the inter-individual variability observed was mostly related to the body size, indicating the accumulation of mercury with age. An estimation of the human intake of mercury associated to the consumption of the crustaceans sampled and its comparison with the Tolerable Weekly Intake are provided.