Transferable denitrification capability of thermus thermophilus

Laboratory-adapted strains of Thermus spp. have been shown to require oxygen for growth, including the model strains T. thermophilus HB27 and HB8. In contrast, many isolates of this species that have not been intensively grown under laboratory conditions keep the capability to grow anaerobically with one or more electron acceptors. The use of nitrogen oxides, especially nitrate, as electron acceptors is one of the most widespread capabilities among these facultative strains. In this process, nitrate is reduced to nitrite by a reductase (Nar) that also functions as electron transporter toward nitrite and nitric oxide reductases when nitrate is scarce, effectively replacing respiratory complex III. In many T. thermophilus denitrificant strains, most electrons for Nar are provided by a new class of NADH dehydrogenase (Nrc). The ability to reduce nitrite to NO and subsequently to N2O by the corresponding Nir and Nor reductases is also strain specific. The genes encoding the capabilities for nitrate (nar) and nitrite (nir and nor) respiration are easily transferred between T. thermophilus strains by natural competence or by a conjugation-like process and may be easily lost upon continuous growth under aerobic conditions. The reason for this instability is apparently related to the fact that these metabolic capabilities are encoded in gene cluster islands, which are delimited by insertion sequences and integrated within highly variable regions of easily transferable extrachromosomal elements. Together with the chromosomal genes, these plasmid-associated genetic islands constitute the extended pangenome of T. thermophilus that provides this species with an enhanced capability to adapt to changing environments. © 2014, American Society for Microbiology.Spanish Ministry of Science. An institutional grant from Fundación Ramón ArecesPeer Reviewe

Guidelines for Accessibility to Microblogging: an Integral Approach

Microblogging is one of the most popular user-generated media, hence its accessibility has a large impact for users. However, the accessibility of this medium is poor in practice, due to the combination of bad practices by different agents ranging from the providers that host microblogging services to prosumers that post contents to them. Here we present an accessibility-oriented model of microblogging services, analyze the impact of its components, and propose guidelines for each of them to meet accessibility requirements. In particular, we base on an study we have performed on Twitter, one of the most-relevant microblogging platform, to identify good and bad practices in microblogging content generation regarding accessibility in microblogging content generation

Secretion into Milk of the Main Metabolites of the Anthelmintic Albendazole Is Mediated by the ABCG2/BCRP Transporter

Albendazole (ABZ) is an anthelmintic with a broad-spectrum activity, widely used in human and veterinary medicine. ABZ is metabolized in all mammalian species to albendazole sulfoxide (ABZSO), albendazole sulfone (ABZSO2) and albendazole 2-aminosulphone (ABZSO2-NH2). ABZSO and ABZSO2 are the main metabolites detected in plasma and all three are detected in milk. The ATP-binding cassette transporter G2 (ABCG2) is an efflux transporter that is involved in the active secretion of several compounds into milk. Previous studies have reported that ABZSO was in vitro transported by ABCG2. The aim of this work is to correlate the in vitro interaction between ABCG2 and the other ABZ metabolites with their secretion into milk by this transporter. Using in vitro transepithelial assays with cells transduced with murine Abcg2 and human ABCG2, we show that ABZSO2 and ABZSO2-NH2 are in vitro substrates of both. In vivo assays carried out with wild-type and Abcg2−/− lactating female mice demonstrated that secretion into milk of these ABZ metabolites was mediated by Abcg2. Milk concentrations and milk-to-plasma ratio were higher in wild-type compared to Abcg2−/− mice for all the metabolites tested. We conclude that ABZ metabolites are undoubtedly in vitro substrates of ABCG2 and actively secreted into milk by ABCG2.S

Ivermectin reduces secretion of meloxicam into milk by inhibition of ABCG2 transporter in sheep

[EN] The ATP-binding cassette transporter G2 (ABCG2) is an efflux protein involved in the bioavailability and secretion into milk of several compounds including anti- inflammatory drugs. The aim of this work was to determine the effect in sheep of an ABCG2 inhibitor, such as the macrocyclic lactone ivermectin, on the secretion into milk of meloxicam, a non-steroidal anti-inflammatory drug widely used in veterinary medicine, and recently reported as an ABCG2 substrate in mice. In vitro meloxicam transport assays in ovine ABCG2-transduced cells have shown that meloxicam is a substrate of ovine ABCG2 and that ivermectin is an efficient inhibitor of in vitro transport of meloxicam mediated by ovine ABCG2. In addition, the role of ovine ABCG2 in secretion into milk of meloxicam was corroborated using Assaf lactating sheep coadministered with ivermectin. Animals were administered subcutaneously with meloxicam (0.5 mg/kg) with or without ivermectin (0.2 mg/kg). A significantly lower concentration of meloxicam in milk was detected when ivermectin was coadministered, revealing a major role of ABCG2 in the secretion into milk of meloxicam and a relevant drug-drug interaction affecting this process. These results will contribute to the understanding of the potential factors that modulate the transfer of anti-inflammatory drugs into milk, opening their potential use in lactating ruminants, and the effect of drug coadministration on the presence of milk residues of these compounds.S

Pyridine Based Antitumour Compounds Acting at the Colchicine Site

[EN]Antimitotics binding at the colchicine site of tubulin are important antitumour and vascular disrupting agents. Pyridines and azines are privileged scaffolds in medicinal chemistry and in recent years many colchicine site ligands (CSL) have incorporated them into their structures with the aim of improving their pharmacokinetic and pharmacodynamics properties. CSL have been classified according to their chemical structures and the chemical structures of the pyridine and azine containing antimitotic compounds are described. The design principles behind the structural modifications and the achieved effect on the biological activity upon inclusion of these heterocycles are also discussed. Lessons from the achievements and failures have been extracted and future perspectives delineated

Experimental Models to Study Autism Spectrum Disorders: hiPSCs, Rodents and Zebrafish

Autism Spectrum Disorders (ASD) affect around 1.5% of the global population, which manifest alterations in communication and socialization, as well as repetitive behaviors or restricted interests. ASD is a complex disorder with known environmental and genetic contributors; however, ASD etiology is far from being clear. In the past decades, many efforts have been put into developing new models to study ASD, both in vitro and in vivo. These models have a lot of potential to help to validate some of the previously associated risk factors to the development of the disorder, and to test new potential therapies that help to alleviate ASD symptoms. The present review is focused on the recent advances towards the generation of models for the study of ASD, which would be a useful tool to decipher the bases of the disorder, as well as to conduct drug screenings that hopefully lead to the identification of useful compounds to help patients deal with the symptoms of ASDConsellería de Educación, Universidade e Formación Profesional (ED431C 2018/28)//FIS PI19/00809 ISCIII//Xunta de Galicia (Centro singular de investigación de Galicia acreditación 2019–2022) and the European Union (European Regional Development Fund - ERDF) (ED431G 2019/02)S

ABCG2 transporter plays a key role in the biodistribution of melatonin and its main metabolites

[EN] The ATP-binding cassette G2 (ABCG2) is an efflux transporter expressed in the apical membrane of cells from a large number of tissues, directly affecting bioavailability, tissue accumulation, and secretion into milk of both xenobiotics and endogenous compounds. The aim of this work was to characterize the role of ABCG2 in the systemic distribution and secretion into milk of melatonin and its main metabolites, 6-hydroxymelatonin, and 6-sulfatoxymelatonin. For this purpose, we first showed that these three molecules are transported by this transporter using in vitro transepithelial assays with MDCK-II polarized cells transduced with different species variants of ABCG2. Second, we tested the in vivo effect of murine Abcg2 in the systemic distribution of melatonin and its metabolites using wild-type and Abcg2−/− mice. Our results show that after oral administration of melatonin, the plasma concentration of melatonin metabolites in Abcg2−/− mice was between 1.5 and 6-fold higher compared to the wild-type mice. We also evaluated in these animals differences in tissue accumulation of melatonin metabolites. The most relevant differences between both types of mice were found for small intestine and kidney (>sixfold increase for 6-sulfatoxymelatonin in Abcg2−/− mice). Finally, melatonin secretion into milk was also affected by the murine Abcg2 transporter, with a twofold higher milk concentration in wild-type compared with Abcg2−/− lactating female mice. In addition, melatonin metabolites showed a higher milk-to-plasma ratio in wild-type mice. Overall, our results show that the ABCG2 transporter plays a critical role in the biodistribution of melatonin and its main metabolites, thereby potentially affecting their biological and therapeutic activity.SIPublicación en abierto financiada por el Consorcio de Bibliotecas Universitarias de Castilla y León (BUCLE), con cargo al Programa Operativo 2014ES16RFOP009 FEDER 2014-2020 DE CASTILLA Y LEÓN, Actuación:20007-CL - Apoyo Consorcio BUCL

Abcg2 transporter affects plasma, milk and tissue levels of meloxicam

https://doi.org/10.1016/j.bcp.2020.113924ATP-binding cassette (ABCG2) is an efflux transporter that extrudes xenotoxins from cells in liver, intestine, mammary gland, brain and other organs, affecting the pharmacokinetics, brain accumulation and secretion into milk of several compounds, including antitumoral, antimicrobial and anti-inflammatory drugs. The aim of this study was to investigate whether the widely used anti-inflammatory drug meloxicam is an Abcg2 sustrate, and how this transporter affects its systemic distribution. Using polarized ABCG2-transduced cell lines, we found that meloxicam is efficiently transported by murine Abcg2 and human ABCG2. After oral administration of meloxicam, the area under the plasma concentration-time curve in Abcg2-/- mice was 2-fold higher than in wild type mice (146.06 ± 10.57 μg·h/ml versus 73.80 ± 10.00 μg·h/ml). Differences in meloxicam distribution were reported for several tissues after oral and intravenous administration, with a 20-fold higher concentration in the brain of Abcg2-/- after oral administration. Meloxicam secretion into milk was also affected by the transporter, with a 2-fold higher milk-to-plasma ratio in wild-type compared with Abcg2-/- lactating female mice after oral and intravenous administration. We conclude that Abcg2 is an important determinant of the plasma and brain distribution of meloxicam and is clearly involved in its secretion into milk.S

Lead Me, Lord (3): Two-Part Voices

4 pages

Teaching to Promote Entrepreneurship in the Degree in Advertising and Public Relations. Analysis Methodologies and Content

El trabajo parte de la reflexión sobre las oportunidades laborales de los egresados en publicidad y relaciones públicas, con una hipótesis inicial sobre las posibilidades de desarrollo de una carrera profesional autónoma a partir de la formación en competencias para el emprendimiento. La investigación contempla el análisis de contenido de guías docentes de diferentes asignaturas y universidades. Además se cuenta con dos doctorandas docentes y emprendedoras. Los resultados obtenidos revelan puntos fuertes y áreas de mejora que conviene atender si se pretende fomentar el emprendimiento en Publicidad y Relaciones Públicas, y abre una agenda de investigación específica sobre el tema.This paper reflects about employment opportunities of Advertising and Public Relations’ graduates and it suggests an initial assumption about possibilities for development of a self-sufficient professional career from skills training for entrepreneurship. This research includes content analysis of several teaching guides. In addition, it counts with the collaboration of two PhD students and entrepreneurs. The results show strength points and improvement areas that should be considerate to encourage entrepreneurship within the Degree of Advertising and Public Relation and it allows the beginning of a specific research roadmap on this issue