Theoretical study of the interaction of agonists with the 5-HT2A receptor

The 5-HT2A receptor (5-HT2AR) is a biogenic amine receptor that belongs to the class A of G protein coupled receptors. It is characterized by a low affinity for serotonin (5-HT) and for other primary amines. Introduction of an ortho-methoxybenzyl substituent at the amine nitrogen increases the partial agonistic activity by a factor of 40 to 1400 compared with 5-HT. The present study was to analyse the QSAR of a series of 51 5-HT2AR partial agonistic arylethylamines, tested in vascular in-vitro assays on rats, at a structure-based level and to suggest ligand binding sites. The compounds belong to three different structural classes, (1) indoles, (2) methoxybenzenes and (3) quinazolinediones. Following a hierarchical strategy, different methods have been applied which all contribute to the investigation of ligand-receptor interactions: fragment regression analysis (FRA), receptor modeling, docking studies and 3D QSAR approaches (comparative molecular field analysis, CoMFA, and comparative molecular similarity index analysis, CoMSIA). An initial FRA indicated that methoxy substituents at indole and phenyl derivatives increase the activity and may be involved in polar interactions with the 5-HT2AR. The large contribution of lipophilic substituents in p position of phenethylamines suggests fit to a specific hydrophobic pocket. Secondary benzylamines are more than one order of magnitude more active than their NH2 analogs. An ortho-OH or -OMe substituent at the benzyl moiety further increases activity. Homology models of the human and rat 5-HT2AR were generated using the crystal structure of bovine rhodopsin and of the beta2-adrenoceptor as templates. The derivation of the putative binding sites for the arylethylamines was based on the results from FRA and on mutagenesis data. Both templates led to 5-HT2AR models with similar topology of the binding pocket within the transmembrane domains TM3, TM5, TM6 and TM7. Docking studies with representative members of the three structural classes suggested that the aryl moieties and particularly para-substituents in phenyl derivatives fit into a hydrophobic pocket formed by Phe2435.47, Phe2445.48 and Phe3406.52. The 5-methoxy substituents in indole and phenyl compounds form H bonds with Ser2395.43. In each case, an additional H bond with Ser1593.36 may be assumed. The cationic amine interacts with the conserved Asp1553.32. The benzyl group of secondary arylethylamines is inserted into another hydrophobic pocket formed by Phe3396.51, Trp3677.40 and Tyr3707.43. In this region, the docking poses depend on the template used for model generation, leading to different interactions especially of ortho- substituents. The docking studies with the beta2-adrenoceptor based rat 5-HT2AR model provided templates for a structure-based alignment of the whole series which was used in 3D QSAR analyses of the partial agonistic activity. Both approaches, CoMFA and CoMSIA, led to highly predictive models with low complexity (cross-validated q2 of 0.72 and 0.81 at 4 and 3 components, respectively). The results were largely compatible with the binding site and confirm the docking studies and the suggested ligand-receptor interactions. Steric and hydrophobic field effects on the potency indicate a hydrophobic pocket around the aryl moiety and near the para position of phenyl derivatives and account for the increased activity of secondary benzylamines. The effects of electrostatic and H-bond acceptor fields suggest a favourable influence of negative charges around the aryl moiety, corresponding to the increase in potency caused by methoxy substituents in 2-, 4-, 5- and 6-position of phenethylamines and by the quinazolinedione oxygens. This is in accord with the role of Ser1593.36 and Ser2395.43 as H bond donors. At the benzyl moiety, the negative charge and the acceptor potential of 2-hydroxy and -methoxy substituents is of advantage. Agonists stabilize or induce active receptor states not reflected by the existing crystal structures. Based on models of different rhodopsin states, a homology modeling and ligand docking study on corresponding 5-HT2AR states suggested to be specific to agonist and partial agonist binding, respectively, was performed. The models indicate collective conformational changes of TM domains during activation. The different 5-HT2AR states are similar with respect to the amino acids interacting with the arylethylamines, but show individual topologies of the binding sites. The interconversion of states by TM movements may be accompanied by co-translations and rotations of the ligands. In the case of the secondary amines considered, the tight fit of the benzyl substituent into a hydrophobic pocket containing key residues in TM6 probably impedes the complete receptor activation due to inhibiting the rotation of this helix. High affinity of a partial agonist is therefore often at the expense of its ability to fully activate a receptor

Technological characterization of vaginal probiotic lactobacilli: resistance to osmotic stress and strains compatibility

Aims: The aim was to evaluate the osmotic stress resistance of vaginal beneficial probiotic strains, their growth kinetics and parameters when growing in salt-added culture media, and their compatibility to go further in the design of a probiotic formula for reconstitution of vaginal microbiome in women. Methods and Results: The resistance to osmotic stress of the lactobacilli was evaluated by determining their growth in MRS (as control) added with NaCl (2–8%). The most resistant strains were Lactobacillus gasseri CRL1509, L. rhamnosus CRL1332 and L. reuteri CRL1327 selected by statistical approaches and growth parameters. Electron microscopy was applied to determine changes. They maintain probiotic properties and viability. Some strains showed incompatibility, then they cannot be included in multistrain formulas. Conclusions: The resistance to different salt concentrations in vaginal lactobacilli is strain-specific, because the behaviour is different in strains identified into the same species. The resistance is not related to the metabolic groups. Significance and Impact of the Study: The resistance and survival to extreme osmotic resistance is one of the specific requirements of beneficial bacteria after the technological processes for their inclusion in probiotic formulas, in a way to express their beneficial characteristics and exert the effect on the host.Fil: Silva, Jessica Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Marchesi, Antonella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Birgitt, Wiese. Hannover Medical School; AlemaniaFil: Nader, Maria Elena Fatima. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentin

"In vitro" evaluation of some properties in spore former bacteria isolated from calves faeces

Aims: To isolate and evaluate spore-former bacteria for being used as probiotic additives in animal nutrition by their technological features. Study Design: The study was experimental, by using calves’ faeces for spore-forming identification and further evaluation of their “in vitro” probiotic-related properties. Place and Duration of Study: Laboratory of Preventive Microbiology, Centro de Referencia para Lactobacilos (CERELA-CONICET), between June 2013 and November 2013. Methodology: In this work, some Bacillus strains were isolated from calves’ faeces and evaluated for their “in vitro” beneficial characteristics: Surface properties, biosurfactant and emulsification production, and inhibition of pathogens. The antibiotic sensibility was also assayed. Results: Two Bacillus strains were selected, identified by phenotypic and molecular techniques as Bacillus subtilis strains M14 and M12. Spores resulted to be more hydrophobic than vegetative cells. The M14 strain showed biosurfactant and emulsifying properties. Inhibition assays against pathogenic bacteria indicated they inhibit gram-positive microorganisms. The antibiotic susceptibility showed that the two strains were sensitive to the antibiotics assayed, except Bacillus M12 that was resistant to Kanamycin. Conclusion: The results indicate these strains can be further studied for their inclusion in the design of a probiotic product for newborn calves.Fil: Maldonado, Natalia Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Silva de Ruíz, Clara. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; ArgentinaFil: Nader, Maria Elena Fatima. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentin

Assessment process in the technical education: how teenager’s students show their emotions in challenging situations

This article aims to analyze how students' emotions appear in challenging pedagogical situations, more specific periods of evaluations in regular face-to-face classes. The research is characterized as qualitative phenomenological. The data were collected through a semi-structured questionnaire, analyzed according to the Discursive Textual Analysis methodology. The context in which the investigation was carried out is the integrated technical education of a campus of the Federal Farroupilha Institute, a technical education institution in the south of Brazil. The analysis of the data collected showed that in assessment situations, negative emotions such as anxiety, fear, and insecurity predominate. On the other hand, negative emotions may vary, depending on the assessment instrument used, but they are predominantly associated with the evidence. The analysis showed that it is necessary to look for alternatives to minimize the effects of negative emotions on the teaching-learning process, especially about the evaluation process, and to find ways to improve these practices so that they contribute to learning with more quality

Editorial: The Vascular Niche in Tissue Repair: A Therapeutic Target for Regeneration.

Editorial on the Research Topic The Vascular Niche in Tissue Repair: A Therapeutic Target for Regeneration In mammals, although regeneration is quite restricted to a number of tissues and organs, this particular healing process is possible through the existence of tissue-resident stem/progenitor cells. Upon injury, these cells are activated, they proliferate, migrate, and differentiate into tissue-specific cells and functionally replace the damaged or lost cells. Besides this, angiogenesis and neovascularization play crucial roles in tissue repair. Blood vessels (BV) together with the resident surrounding cells create a vascular niche which is central to local and distant signaling thereby shaping the regenerative response. The Frontiers Research Topic “The Vascular Niche in Tissue Repair: A Therapeutic Target for Regeneration” encompasses 14 articles highlighting various aspects of the vascular niche (VN) in health and disease. This research topic first describes ex vivo methodological aspects to study the role of the VN in regeneration, second addresses the VN cellular composition and roles during regeneration, third described local as well as distant signaling mechanisms regulating the VN in regeneration and, finally addresses the VN responses in pathology

La producción de discurso narrativo en jóvenes y adultos letrados e iletrados

En este trabajo se presentan los resultados de una investigación que exploró y comparó el desempeño en la producción de discurso narrativo de un grupo de jóvenes y adultos iletrados con el de otro grupo de adultos letrados. Se seleccionaron dos tipos de tareas: relato de experiencia personal y relato a partir de una secuencia de imágenes; pues se consideró que cada tarea planteaba diferentes demandas cognitivas y lingüísticas que podían favorecer, u obstaculizar, el uso de recursos. Se consideró: extensión del relato, largo promedio de la emisión y uso cohesivo de formas anafóricas. Los resultados mostraron tendencias distintas en los dos grupos según la tarea. Mientras que los adultos letrados tuvieron, en general, un buen desempeño discursivo en ambas tareas; el grupo de adultos iletrados tuvo dificultades para producir un relato a partir de imágenes pero mostró un uso adecuado y variado de recursos lingüísticos al relatar experiencias personales.The present work explores and compares the performance of two groups of literate and illiterate people (between 25 and 58 years old the former, and 14 to 65 the latter) in narrative’s production. To this end two different narrative tasks were selected: the production of a personal experience narrative and a narrative based on a sequence of images. It was assumed that each task would present different cognitive and linguistic demands which might support or obstruct subjects’ performance. The analysis of narratives extension, mlu and use of anaphoric expression was undertaken. Results showed a different performance trend between illiterate and literate groups depending on the task. While the literate group had a good performance in the production of both narratives, the illiterate group had difficulties to produce a narrative based on a sequence of images but showed an adequate use of varied linguistic resources when producing personal experiences.Fil: Borzone, Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Centro Interdisciplinario de Investigaciones En Psicología Matemática y Experimental Dr. Horacio J.a Rimoldi; ArgentinaFil: Silva, María Luisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Centro Interdisciplinario de Investigaciones En Psicología Matemática y Experimental Dr. Horacio J.a Rimoldi; ArgentinaFil: Benítez, María Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Centro Interdisciplinario de Investigaciones En Psicología Matemática y Experimental Dr. Horacio J.a Rimoldi; Argentin

Integración del personal y el clima organizacional en los trabajadores de la municipalidad de San Martín de Pangoa - Satipo, 2020

La investigación: Integración del personal y el clima organizacional en los trabajadores de la municipalidad San Martín de Pangoa - Satipo, 2020, formuló su objetivo como sigue: establecer la relación entre la integración del personal y el clima organizacional en los trabajadores de la municipalidad San Martín de Pangoa - Satipo, 2020. La metodología utilizada para realizar la investigación fue un enfoque cuantitativo. La investigación fue de tipo aplicada, puesto que pone a prueba la aplicación de las teorías y por ende sus resultados serán útiles para ser implementados. El diseño utilizado fue no experimental, transversal correlacional. La muestra conformada por 32 trabajadores de la municipalidad San Martín de Pangoa - Satipo. Se utilizó la encuesta y se aplicó como instrumento un cuestionario en escala de Likert. Como resultado se obtuvo que existe una relación moderada estadísticamente significativa en la población entre integración del personal y clima organizacional en los trabajadores de la municipalidad San Martín de Pangoa - Satipo. Su conclusión fue que existe una correlación moderada y positiva entre la integración del personal y el clima organizacional en los trabajadores de la municipalidad San Martín de Pangoa – Satipo, 2020

Gestión financiera y su incidencia en la liquidez de la empresa Renz S.A.C. La Victoria 2020

La presente investigación se enfoca en la gestión financiera y la liquidez para determinar y descubrir métodos ayuden a mejorar la liquidez de las empresas, el cual tiene como objetivo determinar de qué manera la gestión financiera incide en la liquidez de la Empresa Renz SAC, La Victoria 2020. La metodología que se aplicó fue de tipo básica de nivel descriptivo-correlacional, de enfoque cuantitativo, y de diseño no experimental de corte transversal, la técnica que se utilizó para recolectar información y datos fue mediante un cuestionario que consta de una encuesta de 23 preguntas que fueron encuestados a 20 trabajadores de la empresa Renz SAC, luego de obtener la información se realiza el procesamiento de resultados mediante el programa estadístico SPSS versión 26 y se analizan cada resultado con frecuencias y porcentajes de manera descriptiva, luego se comprueban las hipótesis planteadas, se concluye que la gestión financiera incide significativamente en la liquidez de la Empresa Renz SAC, La Victoria 2020, el valor (sig.) fue 0.006, el cual es menor a 0.05, resultado que se acepta la hipótesis planteada, dado que una gestión financiera eficiente es una función vital y utilizando las herramientas adecuadas permitirá a los gerentes a tomar decisiones oportunas y hacer uso de los recursos de forma eficiente, el cual se reflejará con una buena liquidez y se cumplirán con las obligaciones en los plazos determinados.This research focuses on financial management and liquidity to determine and discover methods to help improve the liquidity of companies, which aims to determine how financial management affects the liquidity of the Company Renz SAC, La Victoria. 2020. The methodology that was applied was basic type of descriptive level, quantitative approach, and non-experimental design, the technique that was obtained to collect information and data was through a questionnaire that consists of a survey of 23 questions that were surveyed to 20 workers of the company Renz SAC, after obtaining the information, the processing of results is carried out using the statistical program SPSS version 26 and each result is analyzed with frequencies and percentages in a descriptive manner, then the hypotheses proposed are verified, it is concluded that the management financial has a significant impact on the liquidity of the Renz SAC Company, La Victoria 2020, the value (sig.) was 0.006, which is less than 0.05, a result that the proposed hypothesis is accepted, since efficient financial management is a vital function and using the right tools will allow managers to make timely decisions and make use of resources efficiently, which will be reflected with a good liquidity and the obligations will be fulfilled in the determined terms

Técnicas de teledetección para identificar el impacto de la perdida de la cobertura vegetal sobre la calidad del aire - Chiclayo

La pérdida de la cobertura vegetal y su relación con la calidad del aire se determinan a partir de la aplicación de técnicas de teledetección con el uso de imágenes satelitales, información a partir de la cual se define el área de estudio con un análisis multicriterio, a su vez que se estima el índice de la pérdida de la cobertura vegetal aplicando tres índices de vegetación SAVI, EVI y ARVI; en una línea temporal que abarca los años 2014, 2017 y 2021. Los resultados más cercanos a lo esperado se dan con el índice de vegetación (IV) EVI, con una disminución de cobertura vegetal a medida que persiste la contaminación y un ligero aumento de la cobertura vegetal cuando cesan sus emisiones las fuentes contaminantes (periodo de pandemia), existen aspectos externos al estudio como las características propias del suelo y otros relacionados a la atmósfera que deben analizarse minuciosamente para evitar errores o sesgos al obtener resultados

Powder Technology

Combining two or more granular or powder ingredients requires a suitable mixing process, which can be either free or random flow with no attraction forces between the particles or interactive or orderly with the presence of large active particles that attract others forming stable clumps. Food systems have very complex properties that make it difficult to standardize the mixing process. In order to achieve an efficient mixture, diffusive and convective mechanisms must be combined, and its success is achieved with a predominance of homogenization over segregation. Powder products are typically used in industry as dispersion in a liquid and should have some properties such as good wettability, water incorporation, flowability, and instantization. To work with powder products, it is necessary to make determinations such as density, particle size, texture, and compaction force, among others. All these physical properties affect and determine the behavior of powdered products during storage, handling, and processing