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Social psychology suggests that racism, as captured by explicit prejudice and racial discrimination, is perceived negatively in the United States. However, considering the hierarchy-enhancing nature of racism, it may be that negative perceptions of racism are attenuated among perceivers high in anti-egalitarian sentiment. The reported studies support this, suggesting that racist candidates were tolerated more and had relatively greater hireability ratings as a function of perceivers' social dominance orientation (SDO; Studies 1-4). Candidate race did not impact these evaluations-only the hierarchy relevance of their actions did (i.e., whether the candidate's behavior was hierarchy enhancing or had no clear implication for the hierarchy; Study 2). Furthermore, anti-racist candidates (e.g., those displaying hierarchy-attenuating behavior) were tolerated less and had lower hireability ratings as a function of perceivers' SDO (Study 3). Finally, the perceived intentionality of the candidate's actions affected tolerance toward them as a function of SDO. This suggests hierarchy relevance impacts evaluative outcomes.

The increase of mental illness cases around the world can be described as an urgent and serious global health threat. Around 500 million people suffer from mental disorders, among which depression, schizophrenia, and dementia are the most prevalent. Revolutionary technological paradigms such as the Internet of Things (IoT) provide us with new capabilities to detect, assess, and care for patients early. This paper comprehensively survey works done at the intersection between IoT and mental health disorders. We evaluate multiple computational platforms, methods and devices, as well as study results and potential open issues for the effective use of IoT systems in mental health. We particularly elaborate on relevant open challenges in the use of existing IoT solutions for mental health care, which can be relevant given the potential impairments in some mental health patients such as data acquisition issues, lack of self-organization of devices and service level agreement, and security, privacy and consent issues, among others. We aim at opening the conversation for future research in this rather emerging area by outlining possible new paths based on the results and conclusions of this work.

Neurodegenerative diseases in which the decrease of the acetylcholine is observed are growing worldwide. In the present study, a series of new arylaminopropanone derivatives with N -phenylcarbamate moiety ( 1-16 ) were prepared as potential acetylcholinesterase and butyrylcholinesterase inhibitors. In vitro enzyme assays were performed; the results are expressed as a percentage of inhibition and the IC 50 values. The inhibitory activities were compared with reference drugs galantamine and rivastigmine showing piperidine derivatives ( 1-3 ) as the most potent. A possible mechanism of action for these compounds was determined from a molecular modelling study by using combined techniques of docking, molecular dynamics simulations and quantum mechanics calculations.

Aim: DNA gyrase and topoisomerase IV are essential bacterial enzymes, and in the fight against bacterial resistance, they are important targets for the development of novel antibacterial drugs. Results: Building from our first generation of 4,5,6,7-tetrahydrobenzo[ d ]thiazole-based DNA gyrase inhibitors, we designed and prepared an optimized series of analogs that show improved inhibition of DNA gyrase and topoisomerase IV from Staphylococcus aureus and Escherichia coli , with IC 50 values in the nanomolar range. Importantly, these inhibitors also show improved antibacterial activity against Gram-positive strains. Conclusion: The most promising inhibitor, 29 , is active against Enterococcus faecalis , Enterococcus faecium and S. aureus wild-type and resistant strains, with minimum inhibitory concentrations between 4 and 8 μg/ml, which represents good starting point for development of novel antibacterials.

The nitrone spin trap 5,5‑dimethyl‑1‑pyrroline N‑oxide (DMPO) dampens endotoxin-induced and TLR4-driven priming of macrophages, but the mechanism remains unknown. The available information suggests a direct binding of DMPO to the TIR domain, which is shared between TLRs. However, TLR2-TIR domain is the only TLR that have been crystallized. Our in silico data show that DMPO binds to four specific residues in the BB-loop within the TLR2-TIR domain. Our functional analysis using hTLR2.6-expressing HEKs cells showed that DMPO can block zymosan-triggered-TLR2-mediated NF-κB activation. However, DMPO did not affect the overall TLR2-MyD88 protein-protein interaction. DMPO binds to the BB-loop in the TIR-domain and dampens downstream signaling without affecting the overall TIR-MyD88 interaction. These data encourage the use of DMPO-derivatives as potential mechanism-based inhibitors of TLR-triggered inflammation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A series of tetrahydroisoquinolines functionalized with carbamates is reported here as highly selective ligands on the dopamine D2 receptor. These compounds were selected by means of a molecular modeling study. The studies were carried out in three stages: first an exploratory study was carried out using combined docking techniques and molecular dynamics simulations. According to these results, the bioassays were performed; these experimental studies corroborated the results obtained by molecular modeling. In the last stage of our study, a QTAIM analysis was performed in order to determine the main molecular interactions that stabilize the different ligand-receptor complexes. Our results show that the adequate use of combined simple techniques is a very useful tool to predict the potential affinity of new ligands at dopamine D1 and D2 receptors. In turn the QTAIM studies show that they are very useful to evaluate in detail the molecular interactions that stabilize the different ligand-receptor complexes; such information is crucial for the design of new ligands.

We report here two new small-size peptides acting as modulators of the β-site APP cleaving enzyme 1 (BACE1) exosite. Ac-YPYFDPL-NH2 and Ac-YPYDIPL-NH2 displayed a moderate but significant inhibitory effect on BACE1. These peptides were obtained from a molecular modeling study. By combining MD simulations with ab initio and DFT calculations, a simple and generally applicable procedure to evaluate the binding energies of small-size peptides interacting with the exosite of the BACE1 is reported here. The structural aspects obtained for the different complexes were analyzed providing a clear picture about the binding interactions of these peptides. These interactions have been investigated within the framework of the density functional theory and the quantum theory of atoms in molecules using a reduced model. Although the approach used here was traditionally applied to the study of noncovalent interactions in small molecules complexes in gas phase, we show, through in this work, that this methodology is also a very powerful tool for the study of biomolecular complexes, providing a very detailed description of the binding event of peptides modulators at the exosite of BACE1.

Dopamine receptors (DR) ligands are potential drug candidates for treating neurological disorders including schizophrenia or Parkinson's disease. Three series of isoquinolines: (E)-1-styryl-1,2,3,4-tetrahydroisoquinolines (series 1), 7-phenyl-1,2,3,7,8,8a-hexahydrocyclopenta[ij]-IQs (HCPIQs) (series 2) and (E)-1-(prop-1-en-1-yl)-1,2,3,4- tetrahydroisoquinolines (series 3), were prepared to determine their affinity for both D1 and D2-like DR. The effect of different substituents on the nitrogen atom (methyl or allyl), the dioxygenated function (methoxyl or catechol), the substituent at the β-position of the THIQ skeleton, and the presence or absence of the cyclopentane motif, were studied. We observed that the most active compounds in the three series (2c, 2e, 3a, 3c, 3e, 5c and 5e) possessed a high affinity for D2-like DR and these remarkable features: a catechol group in the IQ-ring and the N-substitution (methyl or allyl). The series showed the following trend to D2-RD affinity: HCPIQs > 1-styryl > 1-propenyl. Therefore, the substituent at the β-position of the THIQ and the cyclopentane ring also modulated this affinity. Among these dopaminergic isoquinolines, HCPIQs stood out for unexpected selectivity to D2-DR since the Ki D1/D2 ratio reached values of 2465, 1010 and 382 for compounds 3a, 3c and 3e, respectively. None of the most active THIQs in D2 DR displayed relevant cytotoxicity in human neutrophils and HUVEC. Finally, and in agreement with the experimental data, molecular modeling studies on DRs of the most characteristic ligands of the three series revealed stronger molecular interactions with D2 DR than with D1 DR, which further supports to the encountered enhanced selectivity to D2 DR., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

The structure-based drug design has been an extremely useful technique used for searching and developing of new therapeutic agents in various biological systems. In the case of AD, this approach has been difficult to implement. Among other several causes, the main problem might be the lack of a specific stable and reliable molecular target. In this paper the results obtained using a pentameric amyloid beta (Aβ) model as a molecular target are discussed. Our MD simulations have shown that this system is relatively structured and stable, displaying a lightly conformational flexibility during 2.0 μs of simulation time. This study allowed us to distinguish characteristic structural features in specific regions of the pentamer which should be taken into account when choosing this model as a molecular target. This represents a clear advantage compared to the monomer or dimer models which are highly flexible structures with large numbers of possible conformers. Using this pentameric model we performed two types of studies usually carried out on a molecular target: a virtual screening and the design on structural basis of new mimetic peptides with antiaggregant properties. Our results indicate that this pentameric model might be a good molecular target for these particular studies of molecular modeling. Details about the predictive power of our virtual screening as well as about the molecular interactions that stabilize the mimetic peptide-pentamer Aβ complexes are discussed in this paper.

Some members of a series of cinnamic acid derivatives possess promising inhibitory activities in cellular assays against fungi of the Aspergillus genus. In order to search for a possible molecular target of such compounds, their role as Taq polymerase I inhibitors was studied. Four of the compounds studied displayed IC50 values within the range of those considered active as DNA polymerase inhibitors when searching for new cytotoxic molecules. The results obtained in our molecular modeling study appear to show that the inhibitory activity depends on the presence of a stabilizing interaction between the phenylpropanoid derivatives and the residues Asp610, Thr664, Phe667, Tyr671, and Asp785 located in the active site of Taq polymerase I. Also, it is possible to assert that the polymerization of DNA would be the molecular target of cinnamic acid derivatives with antifungal activity, which correlates with the inhibition of Taq polymerase I and the quantitative descriptor for the lipophilia (ClogP).

We report a molecular modeling study aimed to locate and provide the full structural characteristics of the exosite binding site of the BACE1. A three-step procedure was followed. In the first stage, we performed blind docking studies on the whole target surface. In a second stage, the mode of binding was further refined by molecular dynamics (MD) simulation. Finally, binding free energy calculations, through the MM-PBSA protocol, were carried out to gain insight into the stability and thermodynamics of the inhibitor located at the selected binding pockets. Twelve binding pockets were identified on the surface of BACE1 by blind docking studies. The calculations of binding free energies for the 12 complexes show that van der Waals interactions dominate the mode of binding of these complexes. The best ranked complex shows that residues Glu255-Pro258, Phe261, Gly264-Ala272, Asp311-Ala313, Ser315, and Asp317-Tyr320 are located within 6 Å from the INH located at the exosite. The hydrogen bonds formed between the INH peptide, residues Tyr1, Tyr3, and Leu7 with the BACE1 residues Leu267, Cys269, Trp270, Asp311, and Asp 317 can strengthen the binding of the BACE1−INH complex.

ABSTRACT The abundance and diversity of phlD(+) Pseudomonas spp. colonizing the rhizospheres of young, field-grown corn and soybean plants were assayed over a 3-year period. Populations of these bacteria were detected on the large majority of plants sampled in the state of Ohio, but colonization was greater on corn. Although significant variation in the incidence of rhizosphere colonization was observed from site to site and year to year on both crops, the magnitude of the variation was greatest for soybean. The D genotype was detected on plants collected from all 15 counties examined, and it represented the most abundant subpopulation on both crops. Additionally, six other genotypes (A, C, F, I, R, and S) were found to predominate in the rhizosphere of some plants. The most frequently observed of these were the A genotype and a newly discovered S genotype, both of which were found on corn and soybean roots obtained from multiple locations. Multiple isolates of the most abundant genotypes were recovered and characterized. The S genotype was found to be phylogenetically and phenotypically similar to the D genotype. In addition, the novel R genotype was found to be most similar to the A genotype. All of the isolates displayed significant capacities to inhibit the growth of an oomycete pathogen in vitro, but such phenotypes were highly dependent on media used. When tested against multiple oomycete pathogens isolated from soybean, the A genotype was significantly more inhibitory than the D genotype when incubated on 1/10x tryptic soy agar and 1/5x corn meal agar. Seed inoculation with different isolates of the A, D, and S genotypes indicated that significant root colonization, generally in excess of log 5 cells per gram of root, could be attained on both crops. Field trials of the A genotype isolate Wayne1R indicated the capacity of inoculant populations to supplement the activities of native populations so as to increase soybean stands and yields. The relevance of these findings to natural and augmentative biocontrol of root pathogens by these bacteria is discussed.