Elucidating the aryl hydrocarbon receptor antagonism from a chemical-structural perspective

The aryl hydrocarbon receptor (AhR) plays an important role in several biological processes such as reproduction, immunity and homoeostasis. However, little is known on the chemical-structural and physicochemical features that influence the activity of AhR antagonistic modulators. In the present report, in vitro AhR antagonistic activity evaluations, based on a chemical-activated luciferase gene expression (AhR-CALUX) bioassay, and an extensive literature review were performed with the aim of constructing a structurally diverse database of contaminants and potentially toxic chemicals. Subsequently, QSAR models based on Linear Discriminant Analysis and Logistic Regression, as well as two toxicophoric hypotheses were proposed to model the AhR antagonistic activity of the built dataset. The QSAR models were rigorously validated yielding satisfactory performance for all classification parameters. Likewise, the toxicophoric hypotheses were validated using a diverse set of 350 decoys, demonstrating adequate robustness and predictive power. Chemical interpretations of both the QSAR and toxicophoric models suggested that hydrophobic constraints, the presence of aromatic rings and electron-acceptor moieties are critical for the AhR antagonism. Therefore, it is hoped that the deductions obtained in the present study will contribute to elucidate further on the structural and physicochemical factors influencing the AhR antagonistic activity of chemical compounds

Capturado y registrado: potencial de las redes de varamientos para el estudio de las capturas accidentales de cetáceos

XII Congreso de la Sociedad Española de Cetáceos, 4 al 7 de octubre de 2021, onlineN

Structure-Based Virtual Screening for Drug Discovery: a Problem-Centric Review

Structure-based virtual screening (SBVS) has been widely applied in early-stage drug discovery. From a problem-centric perspective, we reviewed the recent advances and applications in SBVS with a special focus on docking-based virtual screening. We emphasized the researchers’ practical efforts in real projects by understanding the ligand-target binding interactions as a premise. We also highlighted the recent progress in developing target-biased scoring functions by optimizing current generic scoring functions toward certain target classes, as well as in developing novel ones by means of machine learning techniques

Long term survival of cryopreserved mussel larvae (Mytilus galloprovinciallis)

Due to the economic importance of the mussel Mytilus galloprovincialis in the Spanish aquaculture, there is a growing interest in developing alternative methods to ensure the supply of good-quality biological material and to minimize the uncertainty and variability that might be a source of economic risk for this sector. The aim of this work was to develop a successful cryopreservation protocol for Mytilus galloprovincialis larvae and study long-term effects by assessing survival and development post cryobanking. We evaluated the effect of previously studied cryoprotecting agent, Ethylene glycol (EG) for cryopreservation of trochophore larvae and D-veliger larvae 48 h and 72 h old, following an existing preliminary protocol for M. galloprovincialis mussel trochophores. The protocol selected for cryopreservation consisted on holding at 4 °C for 2 min, then cooling at 1 °C/min to −12 °C, holding for 5 min, then cooling at −35 °C with a rate of 1 °C/min, then plunging into liquid nitrogen for storage. Thawing took place by immersion in 35 °C water bath. With this protocol the initial percentage of short-term developed a D-larvae (48 h incubation post-thaw) was 48.9 ± 7.6% with 10% EG + 0.2 M Trehalose (TRE). This initial test only studied the trochophore larvae until they reached the D-stage (48 h old); in the present experiment experiments, we replicated this study but also carried out a long-term larval rearing with cryopreserved trochophore larvae in comparison to fresh larvae. This experiment allowed a comparative post-freezing analysis of both larval development and survival. Larval settlement was also characterized after 13 days. The data revealed that until settling, the survival of the cryopreserved larvae was slightly lower than the 2.8% reported in the larval rearing for Greenshell™ mussel. Over time, there was an initial difference in size of cryopreserved larvae when compared to controls, but from day 17 onwards the size between both types of larvae began to stabilize. Attending to settlement, we obtained a 64% of success of cryopreserved larvae respect to the control

Application de la topologie moléculaire à la prédiction de la viscosité liquide des composés organiques

Nous avons appliqué la topologie moléculaire à la recherche d'un modèle mathématique capable de prédire la viscosité liquide d'un large groupe de composés organiques contenant C, H, O, N, S et des halogènes. Les descripteurs topologiques utilisés pour cette étude des relations quantitatives structure-propiété, R.Q.S.P., sont les indices de connectivité de Kier et Hall -jusqu'à l'ordre quatre- ainsi que les indices atomiques électrotopologiques. La qualité de l'équation de régression multilinéaire obtenue (aussi dite “fonction de connectivité") a été évaluée par une étude de validation croisée. Tous les composés excepté le 1,1,2-trichlorotrifluoréthane s'ajustent au modèle proposé

Computational evaluation and in Vitro validation of new epidermal growth Factor receptor inhibitors

Computational Evaluation and In Vitro Validation of New Epidermal Growth Factor Receptor Inhibitor

Conii e scene di coniazione

A survey and catalogue of existing dies from antiquity and early modern Europe is here provided, including also a survey of existing mint-scenes. The contributions here collected are a useful tool to the study of technology, but also of the role of coins and the entire mint process for the imagery of the Stat