Does the antibiotic amoxicillin affect haemocyte parameters in non-target aquatic invertebrates? The clam Ruditapes philippinarum and the mussel Mytilus galloprovincialis as model organisms

Amoxicillin (AMX) is one of the most widely used antibiotics worldwide, and its levels in aquatic ecosystems are expected to be detectable. At present, information concerning the toxic effects of AMX on non-target aquatic organisms, such as bivalves, is scarce. Consequently, in this study, we investigated for the first time the effects of AMX on the haemocyte parameters of two bivalve species, the clam Ruditapes philippinarum and the mussel Mytilus galloprovincialis, which share the same habitat in the Lagoon of Venice, in order to compare the relative sensitivity of the two species. The bivalves were exposed to 100, 200 and 400 mg AMX/L for 1, 3 and 7 days, and the effects on the total haemocyte count (THC), the diameter and volume of the haemocytes, haemocyte proliferation, lactate dehydrogenase (LDH) activity in cell-free haemolymph, the haemolymph pH, and the formation of micronuclei were evaluated. The actual concentrations of AMX in the seawater samples from the experimental tanks were also measured. Overall, the obtained results demonstrated that AMX affected slightly the haemocyte parameters of bivalves. In addition, no clear differences in terms of sensitivity to AMX exposure were recorded between the two bivalve species

Biocontrol traits of Bacillus licheniformis GL174, a culturable endophyte of Vitis vinifera cv. Glera 06 Biological Sciences 0604 Genetics 06 Biological Sciences 0607 Plant Biology 06 Biological Sciences 0605 Microbiology

Abstract Background Bacillus licheniformis GL174 is a culturable endophytic strain isolated from Vitis vinifera cultivar Glera, the grapevine mainly cultivated for the Prosecco wine production. This strain was previously demonstrated to possess some specific plant growth promoting traits but its endophytic attitude and its role in biocontrol was only partially explored. In this study, the potential biocontrol action of the strain was investigated in vitro and in vivo and, by genome sequence analyses, putative functions involved in biocontrol and plant-bacteria interaction were assessed. Results Firstly, to confirm the endophytic behavior of the strain, its ability to colonize grapevine tissues was demonstrated and its biocontrol properties were analyzed. Antagonism test results showed that the strain could reduce and inhibit the mycelium growth of diverse plant pathogens in vitro and in vivo. The strain was demonstrated to produce different molecules of the lipopeptide class; moreover, its genome was sequenced, and analysis of the sequences revealed the presence of many protein-coding genes involved in the biocontrol process, such as transporters, plant-cell lytic enzymes, siderophores and other secondary metabolites. Conclusions This step-by-step analysis shows that Bacillus licheniformis GL174 may be a good biocontrol agent candidate, and describes some distinguished traits and possible key elements involved in this process. The use of this strain could potentially help grapevine plants to cope with pathogen attacks and reduce the amount of chemicals used in the vineyard

Synthesis, antimitotic and antivascular activity of 1-(3\ue2\u80\ub2,4\ue2\u80\ub2, 5\ue2\u80\ub2-trimethoxybenzoyl)-3-arylamino-5-amino-1,2,4-triazoles

A new class of compounds that incorporated the structural motif of the 1-(3′,4′,5′-trimethoxtbenzoyl)-3-arylamino-5-amino-1,2,4-triazole molecular skeleton was synthesized and evaluated for their antiproliferative activity in vitro, interactions with tubulin, and cell cycle effects. The most active agent, 3c, was evaluated for antitumor activity in vivo. Structure–activity relationships were elucidated with various substituents on the phenyl ring of the anilino moiety at the C-3 position of the 1,2,4-triazole ring. The best results for inhibition of cancer cell growth were obtained with the p-Me, m,p-diMe, and p-Et phenyl derivatives 3c, 3e, and 3f, respectively, and overall, these compounds were more or less as active as CA-4. Their vascular disrupting activity was evaluated in HUVEC cells, with compound 3c showing activity comparable with that of CA-4. Compound 3c almost eliminated the growth of syngeneic hepatocellular carcinoma in Balb/c mice, suggesting that 3c could be a new antimitotic agent with clinical potential

Possible new targets for GPCR modulation: allosteric interactions, plasma membrane domains, intercellular transfer and epigenetic mechanisms.

It has been estimated that at least 50% of the drugs available on the market act on G-protein coupled receptors (GPCRs) and most of these are basically or agonists or antagonists of this type of receptors. Herein, we propose new putative targets for drug development based on recent data on GPCR allosterism and on the existence of receptor mosaics (RMs). The main target for drug development is still GPCRs, but the focus is not the orthosteric binding pocket. According to the mosaic model of the plasma membrane, we mainly discuss the possibility of indirect modulatory pharmacological actions on expression/function of GPCRs. In particular, the following two new targets will be analyzed: a) The possibility of pharmacological interventions on the roamer-type of volume transmission (VT), which allow the intercellular transfer of set of signal molecules such as GPCRs, tetraspanins and ribonucleic acids. Thus, there is the possibility of pharmacological interventions on the decoding capabilities of neurons and/or glial cells by means of an action on composition and release of micro-vesicles. b) The possibility of pharmacological interventions on epigenetic mechanisms by taking into account their inter-relationships with GPCRs. As a matter of fact, there are epigenetic changes that are characteristic of periods of developmental plasticity that could provide a target for therapeutic intervention in the event of brain damage. We believe that almost all the biochemical knowledge presently available on GPCRs can be used in the development of these new pharmacological approaches