New polycyclic dual inhibitors of the wild type and the V27A mutant M2 channel of the influenza A virus with unexpected binding mode

Two new polycyclic scaffolds were synthesized and evaluated as anti-influenza A compounds. The 5-azapentacyclo[6.4.0.02,10.03,7.09,11]dodecane derivatives were only active against the wild-type M2 channel in the low-micromolar range. However, some of the 14-azaheptacyclo[8.6.1.02,5.03,11.04,9.06,17.012,16]heptadecane derivatives were dual inhibitors of the wild-type and the V27A mutant M2 channels. The antiviral activity of these molecules was confirmed by cell culture assays. Their binding mode was analysed through molecular dynamics simulations, which showed the existence of distinct binding modes in the wild type M2 channel and its V27A variant

Histological and ultrastructural comparison of cauterization and thrombosis stroke models in immune-deficient mice

<p>Abstract</p> <p>Background</p> <p>Stroke models are essential tools in experimental stroke. Although several models of stroke have been developed in a variety of animals, with the development of transgenic mice there is the need to develop a reliable and reproducible stroke model in mice, which mimics as close as possible human stroke.</p> <p>Methods</p> <p>BALB/Ca-RAG2^-/-γc^-/-mice were subjected to cauterization or thrombosis stroke model and sacrificed at different time points (48hr, 1wk, 2wk and 4wk) after stroke. Mice received BrdU to estimate activation of cell proliferation in the SVZ. Brains were processed for immunohistochemical and EM.</p> <p>Results</p> <p>In both stroke models, after inflammation the same glial scar formation process and damage evolution takes place. After stroke, necrotic tissue is progressively removed, and healthy tissue is preserved from injury through the glial scar formation. Cauterization stroke model produced unspecific damage, was less efficient and the infarct was less homogeneous compared to thrombosis infarct. Finally, thrombosis stroke model produces activation of SVZ proliferation.</p> <p>Conclusions</p> <p>Our results provide an exhaustive analysis of the histopathological changes (inflammation, necrosis, tissue remodeling, scarring...) that occur after stroke in the ischemic boundary zone, which are of key importance for the final stroke outcome. This analysis would allow evaluating how different therapies would affect wound and regeneration. Moreover, this stroke model in RAG 2^-/-γC ^-/-allows cell transplant from different species, even human, to be analyzed.</p

Competency training of students of the Faculty of Chemistry of the University of Barcelona by conducting internal audits

This work deals with the competences and skills training of the students of the Faculty of Chemistry of the University of Barcelona (UB) through participation in internal audits at different laboratories in which different experimental subjects are taught. Students have been able to work cross competences related to ethics, the ability on oral and written expression, the ability to dialogue, the ability to leadership, the teamwork, the analysis and the data interpretation, among others

Formación competencial de los estudiantes de la Facultad de Química de la Universidad de Barcelona mediante la realización de auditorías internas

Se ha trabajado la formación competencial de los estudiantes de la Facultad de Química de la Universidad de Barcelona (UB) mediante su participación en auditorías a diferentes laboratorios de prácticas y diferentes tipos de asignaturas prácticas. Los estudiantes han podido trabajar competencias transversales relacionadas con la ética, la capacidad de expresión oral y escrita, la capacidad de diálogo, la capacidad de liderazgo, el trabajo en equipo, el análisis y la interpretación de datos, etc

A mobile ELF4 delivers circadian temperature information from shoots to roots

Extended Data and Source Data can be found at https://doi.org/10.1038/s41477-020-0634-2Ajuts: the Mas laboratory is funded by the FEDER/Spanish Ministry of Economy and Competitiveness, the Ramon Areces Foundation and the Generalitat de Catalunya (AGAUR). The P.M. laboratory also acknowledges financial support from the CERCA Program, Generalitat de Catalunya and by the Spanish Ministry of Economy and Competitiveness through the Severo Ochoa Program for Centers of Excellence in R&D 2016-2019 (SEV-2015-0533).The circadian clock is synchronized by environmental cues, mostly by light and temperature. Explaining how the plant circadian clock responds to temperature oscillations is crucial to understanding plant responsiveness to the environment. Here, we found a prevalent temperature-dependent function of the Arabidopsis clock component EARLY FLOWERING 4 (ELF4) in the root clock. Although the clocks in roots are able to run in the absence of shoots, micrografting assays and mathematical analyses show that ELF4 moves from shoots to regulate rhythms in roots. ELF4 movement does not convey photoperiodic information, but trafficking is essential for controlling the period of the root clock in a temperature-dependent manner. Low temperatures favour ELF4 mobility, resulting in a slow-paced root clock, whereas high temperatures decrease movement, leading to a faster clock. Hence, the mobile ELF4 delivers temperature information and establishes a shoot-to-root dialogue that sets the pace of the clock in root

Study of TLR3, TLR4 and TLR9 in breast carcinomas and their association with metastasis

<p>Abstract</p> <p>Background</p> <p>Toll-like receptors (TLRs) have garnered an extraordinary amount of interest in cancer research due to their role in tumor progression. By activating the production of several biological factors, TLRs induce type I interferons and other cytokines, which drive an inflammatory response and activate the adaptive immune system. The aim of this study was to investigate the expression and clinical relevance of TLR3, 4 and 9 in breast cancer.</p> <p>Methods</p> <p>The expression levels of TLR3, TLR4 and TLR9 were analyzed on tumors from 74 patients with breast cancer. The analysis was performed by immunohistochemistry.</p> <p>Results</p> <p>Samples of carcinomas with recurrence exhibited a significant increase in the mRNA levels of TLR3, TLR4 and TLR9. Tumors showed high expression of TLRs expression levels by cancer cells, especially TLR4 and 9. Nevertheless, a significant percentage of tumors also showed TLR4 expression by mononuclear inflammatory cells (21.6%) and TLR9 expression by fibroblast-like cells (57.5%). Tumors with high TLR3 expression by tumor cell or with high TLR4 expression by mononuclear inflammatory cells were significantly associated with higher probability of metastasis. However, tumours with high TLR9 expression by fibroblast-like cells were associated with low probability of metastasis.</p> <p>Conclusions</p> <p>The expression levels of TLR3, TLR4 and TLR9 have clinical interest as indicators of tumor aggressiveness in breast cancer. TLRs may represent therapeutic targets in breast cancer.</p

Decadal soil carbon accumulation across Tibetan permafrost regions

Acknowledgements We thank the members of Peking University Sampling Teams (2001–2004) and IBCAS Sampling Teams (2013–2014) for assistance in field data collection. We also thank the Forestry Bureau of Qinghai Province and the Forestry Bureau of Tibet Autonomous Region for their permission and assistance during the sampling process. This study was financially supported by the National Natural Science Foundation of China (31670482 and 31322011), National Basic Research Program of China on Global Change (2014CB954001 and 2015CB954201), Chinese Academy of Sciences-Peking University Pioneer Cooperation Team, and the Thousand Young Talents Program.Peer reviewedPostprintPostprin