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1.
Dr. Francesca Ferlenghi Dr. Michele Mari Prof. Gabriella Gobbi Dr. Gian Marco Elisi Prof. Marco Mor Prof. Silvia Rivara Prof. Federica Vacondio Dr. Silvia Bartolucci Prof. Annalida Bedini Dr. Fabiola Fanini Prof. Gilberto Spadoni 《ChemMedChem》2021,16(19):3071-3082
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. 相似文献
2.
Variations in yield and gluten proteins in durum wheat varieties under late‐season foliar versus soil application of nitrogen fertilizer in a northern Mediterranean environment 下载免费PDF全文
3.
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. 相似文献
4.
Lopez Daniel Andres Sanchez Chagas Luciana Gomes Batista Aline Domingues Guaita Maria Gabriella Detone Amorin Luís Henrique Cardozo da Silva Paulo Rogério Catarini Yamanishi Gustavo Zaia Dimas Augusto Morozin de Santana Henrique Urbano Alexandre 《Journal of Materials Science: Materials in Electronics》2021,32(13):17462-17472
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... 相似文献
5.
Bokyung Kim Young Ho Ko Massimiliano Runfola Simona Rapposelli Gabriella Ortore Grazia Chiellini Jin Hae Kim 《International journal of molecular sciences》2021,22(7)
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. 相似文献
6.
Gökelma Mertol Einarsrud Kristian Etienne Tranell Gabriella Friedrich Bernd 《Metallurgical and Materials Transactions B》2020,51(2):850-860
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... 相似文献
7.
Gabriella Di Lena Irene Casini Roberto Caproni Elena Orban 《Food Additives and Contaminants: Part B: Surveillance Communications》2018,11(3):175-182
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. 相似文献
8.
9.
Project success is a widely studied and discussed phenomenon of project management. Whilst certain success criteria and success factors are common across different project types, there are unique criteria and factors that apply only to specific projects. This paper presents the development and investigation of the attributes of the success criteria and factors of organisational event projects, as well as an analysis of the relationship between the criteria and factor areas. The study is based on a questionnaire survey of world and European championships. The findings of the study are of interest because they distinguish the success factors that represent relationship orientation and task focus. An analysis of the correlations suggests that relationship-oriented success factors, such as communication, co-operation and project leadership, play a crucial role in carrying out successful organisational event projects. 相似文献
10.
Gian-Pietro Di Sansebastiano Silvia Fornaciari Fabrizio Barozzi Gabriella Piro Laura Arru 《International journal of molecular sciences》2014,15(3):4565-4582
We investigated the effect of auxin and acetylcholine on the expression of the tomato expansin gene LeEXPA2, a specific expansin gene expressed in elongating tomato hypocotyl segments. Since auxin interferes with clathrin-mediated endocytosis, in order to regulate cellular and developmental responses we produced protoplasts from tomato elongating hypocotyls and followed the endocytotic marker, FM4-64, internalization in response to treatments. Tomato protoplasts were observed during auxin and acetylcholine treatments after transient expression of chimerical markers of volume-control related compartments such as vacuoles. Here we describe the contribution of auxin and acetylcholine to LeEXPA2 expression regulation and we support the hypothesis that a possible subcellular target of acetylcholine signal is the vesicular transport, shedding some light on the characterization of this small molecule as local mediator in the plant physiological response. 相似文献