A different monoaminergic system (MS) of fundamental importance in invertebrates compared with mammals is the octopaminergic system, which exerts and regulates different central and peripheral processes by specific receptors and transporters. Despite the abundant information available on the functions of octopamine and their receptors in insect physiology, differences associated at octopamine re-uptake process in this neural system remain unexplored. Using AutoDock 4.0 (1) dopamine (DA) and octopamine (OA) were evaluated in the crystal structure of Drosophila melanogaster DAT (PDBid: 4XP1). The complex DAT/ligand was inserted into a POPC membrane, solvating with water model TIP3. The PBC and NPT ensemble was used to perform MD calculations for 20 ns using NAMD 2.6 (2). Finally steered molecular dynamics simulations fixed the center of mass of the ligands and a constant velocity protocol was employed, with a pulling velocity of 0.0001 Å/timestep, for 40 ns and SMD spring constant to each system was 4 Kcal/mol/Å2. Thus, force profile determination to DA and OA crossing DAT were obtained using steered molecular dynamics simulations. Our computational results show a similar profile to both substrates in DAT.

References.

(1) Autodock: G. Morris, R. Huey, A. Olson, Using AutoDock for ligand-receptor docking. Current Protocols in Bioinformatics, (2008) chapter 8 Unit 8.14.

(2) NAMD: J. Phillips, R. Braun, W. Wang, J. Gumbart, E. Tajkhorshid, E. Villa, C. Chipot, R. Skeel, L. Kalé, K. Schulten, Scalable molecular dynamics with NAMD. Journal of Computational Chemestry, (2005) 26 1781–1802.

The antibacterial activity of a bisacodyl and its deacetylated metabolite, DDPM was investigated against Gram-positive pathogens including Staphylococcus aureus (ATCC 9144), Micrococcus luteus (LB14110), Salmonella enterica (NCTC 6017) with minimum inhibitory concentration (MIC) ranging from 12.5 to 25 µg/mL, 6.25 to 12.5 µg/mL and 25 to 50 µg/mL respectively. The results of antibacterial activity against Gram-negative foodborne Pseudomonas aeruginosa (ATCC 9027), Escherichia coli (ATCC 8739), show MIC values between 12.5 -25 μg/mL and 25-50 μg/mL. The antifungal activity was also evaluated against the opportunistic pathogenic yeast Candida albicans (ATCC 2091) with MIC ranging from 12.5 to 25 µg/mL. Furthermore, the anticancer activity was evaluated against epithelial cervical cancer cell line (ATCC, Manassas,VA, USA). The results obtained indicated that bisacodyl and its deacetylated metabolite, DDPM have a cytotoxic activity at 63.69 µg/mL and 16.7 µg/mL respectively.

Legal norms, generally, go very far behind social relations. By the time a norm comes to see the light, it is quite possible that the situation that it intends to regulate has changed and this - the norm - is outdated and ineffective from its very birth. Well, let us think the more difficult is the relationship between Law and emerging technologies; since, in order for them to be effectively regulated, it is necessary that there is a noticeable degree of anticipation on the part of the legislator. The task seems unfeasible, however, we believe that it is possible and essential to find, among the international legal acquis, a minimum standard establish the margins of action of scientific work, without suppose a brake for progress.

Currently, pain is closely linked to pathologies of high incidence worldwide. The in silico methods encompass all computer-aided techniques used in the design of compounds with desired properties, avoiding the high costs for the current tasks of synthesis and bioassays. In this sense, the fundamental objective of the present work is the identification of new analgesic candidates through virtual in silico screening using classification trees. For this purpose, a database of the literature is initially collected and analgesic activity has been reported experimentally. Through the DRAGON software, a series of molecular descriptors were calculated and a Hierarchical Conglomerate Analysis (CAs) was performed in the STATISTICA software, allowing the separation of the initial database in training series and prediction series. Then we proceeded to obtain and validate the model used (Tree J48) through the WEKA software. Finally, eight isolated compounds of Boldoa purpurascens and 12 products of the hydrolysis of these were screened for a total of 20 compounds. Of these three compounds were evaluated experimentally in vivo with excellent results as analgesic drugs. In general, we can conclude that the use of these computational tools generates a great saving of resources with respect to traditional methods of analysis and also allows a rapid identification of compounds with a high probability that they are potential analgesics.

The antibacterial activity of a series of functionalized arybenzothiazoles was investigated against Gram-positive pathogens including Staphylococcus aureus (ATCC 9144), Micrococcus luteus (LB14110), Salmonella enterica (NCTC 6017) and Gram-negative foodborne Pseudomonas aeruginosa (ATCC 9027), Escherichia coli (ATCC 8739). The antifungal activity was also evaluated against the opportunistic pathogenic yeast Candida albicans (ATCC 2091). The results displayed that these compounds exhibit a good antimicrobial activity compared with fusidic acid. The structure-antimicrobial activity relationships are also discussed

Diarylmethanes (DAMs) and triarylmethanes (TAMs) are molecules with two or three aryl groups (phenyls or heterocycles) bonded to a central carbon atom and they have numerous applications. The biological and therapeutic relevancy of this class of molecules have been demonstrated in diverse areas such as antimicrobials, infectious, cardiovascular and nervous system disorders, genital tract diseases, estrogen related disorders and bone remodeling is quite well known. These interesting compounds have also been used as starting materials for the development of high value added molecules. Several synthetic approaches towards bioactive diarylmethanes and triarylmethanes have been published in the literature. This article reviews some approaches followed for the synthesis of diarylmethanes and triarylmethanes as well their biological applications. We will also illustrate the synthesis and antibacterial evaluation of a new triarylmethane series developed in our laboratory using McMurry coupling reaction.

In this study, we were interested in the characterization of Conyza canadensis essential oil composition and evaluation of the antiviral activity from Conyza’s plant extracts. Terpenoids, phenols, sesquiterpenoids and triterpenoids were the major compounds identified from plant essential oil analyzed by gas-chromatography coupled to mass spectrometry.
The test of activities of the extracts from different parts (leave, flower and stalk) of Conyza canadensis revealed that this plant has a remarkable antiviral activity. This activity was evaluated for inhibition of Dengue virus (DV), West Nile virus (WNV), Hepatitis C virus (HCV) and Human Immunodeficiency virus (HIV) polymerases.
Due to his important antiviral activity, the crude methanolic stalk extract (89% of inhibition) was subjected to silica gel column chromatography to obtain eleven fractions (A-K). None of those fractions, tested at 50 μg/ml, was active against HCV and HIV polymerases but six fractions (B, C, D, E, I and J) were active against DEN and WN polymerases. These results were confirmed at lower concentration (10 μg/ml).

In the real world there are many problems which involve the optimization of multiple objective functions at the same time. These are known as Multi-objective Optimization Problems (MOPs). Solving this kind of problems implies generating a set of good solutions, commonly known as Pareto-optimal solutions. The Multi-Objective Evolutionary Algorithms (MOEAs) have been extensively used to address this type of problems, since it allowing to get a set of the Pareto solutions in a particular run. Nevertheless, finding this solution set does not resolve the problem since the Decision-Maker (DM) still must select from that set the solution that matches more with his/her preferences. Determine the Region of Interest (RoI), in accordance with the DM’s preferences, is an option that would make easy the selection process. The RoI has been defined as the region on the Pareto frontier which suits better to the DM's preferences. In order to help the DM in the selection process, different approaches in literature have added preferential information into the optimization process to lead the search towards the RoI.

Such is the case of the approach presented by (Cruz-Reyes et al., 2017) called Hybrid Multi-Criteria Sorting Genetic Algorithm (H-MCSGA). This method addresses the preferences incorporation a priori into a MOEA to characterize the RoI by a multicriteria sorting method called THESEUS (Fernandez et al., 2011). H-MCSGA consists by two phases. First, a metaheuristic is used to create a set of solutions (reference set) that are assigned to ordered classes by the DM. The objective of this process is that the DM's preferences are indirectly reflected in this set. In the second phase, THESEUS is incorporated into an evolutionary algorithm to sort the new solutions created during optimization process. For this, THESEUS uses the reference set, generating selective pressure in the direction of the RoI. The performance of H-MCSGA was verified using nine instances of a public project portfolio problem. The achieve results show that H-MCSGA reach a good definition of the RoI and outperforms the well-known NSGA-II (Deb et al., 2002). A first interactive version of the H-MCSGA is presented in (Cruz-Reyes et al., 2014), where the reference set is updated, only once, while exploration process. Consequently, the DM’s preferences are updated. In examples on the portfolio problem, this proposal maintains its superiority over the NSGAII.

Finally, an interactive method more robust is proposed in (Cruz-Reyes et al., 2016) called the Interactive Multi-Criteria Sorting Genetic Algorithm (I-MCSGA). This method allows the DM to assimilate progressively respecting the problem and to clarify his/her preferences. I-MCSGA was assessed on project portfolio optimization problems. This algorithm was measure against with NSGA-II in three and four objectives problems and in nine and sixteen objectives problems with A2-NSGA-III (Jain, Deb, 2013). I-MCSGA presented better outcomes than these algorithms in regard to Pareto-dominance and to its ability to accomplish the RoI. The automatic-enhancement procedure results efficient to include new solutions into the reference set, aiding THESEUS to propose more suitable assignments. Moreover, the proposed procedure to update preferences interactively is efficient to validate the enhanced reference set, still when the real DM was supplanted by the preference model proposed by (Fernandez et al., 2011). Therefore, I-MCSGA shown its capacity to identify the RoI and, to address optimization problems with a few and many numbers of objectives, effectively.

Future research directions should be leads towards extend the experimentation to problems where the true Pareto frontier is known, the use of others multicriteria sorting methods and the comparing with others most recent MOEAs. This with the aim of validating the outcomes of these approach with greater certainty.

Ethyl acetate and methanol crude extracts from various parts of eighteen Tunisian plant extracts were screened for antibacterial and antioxidant activities. Evaluations of antioxidant activity include 1, 1-diphenyl-2-picrylhydrazyl free radical- scavenging ability and β- carotene bleaching activity. Total phenolic content and total flavonoid content were determined spectrometrically according to the Folin-Ciocalteu procedure and a colorimetric method respectively.
The Results showed that total phonolic and flavonoid contents of the samples as well as antioxidant activities varied greatly among different plant parts and suggest that many plants are rich in antioxidant coumpounds. Interest will be taken to promising active plants particularly those which combine antioxidant properties with antimicrobial activities.

Halophilic organisms have evolved to live in environments of high salinity, therefore their
molecular machinery has adapted to carry out its functions in presence of molar concentrations of
salt. Most of the work aimed to understand the structural adaptations of these proteins has been
done using proteins from the archeon class Halobacteria. Proteins from these organisms are
characterized by a low abundance of basic residues and a high amount of acidic residues, which
accumulate on the protein surface, coupled with a reduction of bulky hydrophobic residues in its
core [1]. Nevertheless, halophilic organisms have been reported in a wide variety of taxa, including
other archaea orders, which their adaptation mechanisms have not been explored. To evaluate the
ubiquity of the protein structural adaptations found in Halobacteria, we built homology models
of ADP-dependent kinases from halophilic and non-halophilic organisms of the archaeal order
Methanosarcinales and compared them to models from Halobacterial and Eucariotic proteins.
Our results show that proteins from halophilic organisms of the Methanosarcinales order do not
show the classical bias in amino acid composition observed in Halobacteria, like the reduction of
the hydrophobic core and negative surface charge. However, experimental characterization of the
ADP-dependent phosphofructokinase of the halophilic organism Methanohalobium evestigatum
(from Methanosarcinales order) confirmed that the protein is indeed halotolerant, and this
character can be further exacerbated in presence of osmolytes commonly found on halophilic
archaea, like betaine [2]. These results suggest that the adaptations required to maintain the
structure and function of a protein in extreme salt concentrations can vary widely between
different organisms. These adaptations do not rely exclusively on the amino acidic composition,
being instead a product of the coevolutionary process between the protein and its intracellular
environment. Fondecyt 1150460

References

[1] Graziano, G., & Merlino, A. (2014). Molecular bases of protein halotolerance. Biochimica et Biophysica Acta
(BBA) - Proteins and Proteomics, 1844(4), 850–858
[2] Sowers, K. R., & Gunsalus, R. P. (1995). Halotolerance in Methanosarcina spp.: Role of N (sup (epsilon))-
Acetyl-(beta)-Lysine,(alpha)-Glutamate, Glycine Betaine, and K (sup+) as Compatible Solutes for Osmotic
Adaptation. Applied and environmental microbiology, 61(12), 4382-4388.