Development of indole sulfonamides as cannabinoid receptor negative allosteric modulators

This Letter was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Scottish Universities Life Sciences Alliance (SULSA) in 2011Peer reviewedPostprin

Crystal structures of four indole derivatives as possible cannabinoid allosteric antagonists

Acknowledgements We thank the EPSRC National Crystallography Service (University of Southampton) for the data collections and the EPSRC National Mass Spectrometry Service (University of Swansea) for the HRMS data. We thank John Low for carrying out the Cambridge Database survey.Peer reviewedPublisher PD

Crystal structures of four indole derivatives with a phenyl substituent at the 2-position and a carbonyl group at the 3-position : the C(6) N-H⋯O chain remains the same, but the weak reinforcing inter-actions are different

Acknowledgements We thank the EPSRC National Crystallography Service (University of Southampton) for the data collections and the EPSRC National Mass Spectrometry Service (University of Swansea) for the HRMS data.Peer reviewedPublisher PD

Weak interactions in the crystal structures of two indole derivatives

Acknowledgements We thank the EPSRC National Crystallography Service (University of Southampton) for the data collections and the EPSRC National Mass Spectrometry Service (University of Swansea) for the HRMS data.Peer reviewedPublisher PD

Different N—H···π interactions in two indole derivatives

Acknowledgements We thank the EPSRC National Crystallography Service (University of Southampton) for the data collections and the EPSRC National Mass Spectrometry Service (University of Swansea) for the HRMS dataPeer reviewedPublisher PD

A Blind Test of Computational Technique for Predicting the Likelihood of Peptide Sequences to Cyclize

An in silico computational technique for predicting peptide sequences that can be cyclized by cyanobactin macrocyclases, e.g., PatGmac, is reported. We demonstrate that the propensity for PatGmac-mediated cyclization correlates strongly with the free energy of the so-called pre-cyclization conformation (PCC), which is a fold where the cyclizing sequence C and N termini are in close proximity. This conclusion is driven by comparison of the predictions of boxed molecular dynamics (BXD) with experimental data, which have achieved an accuracy of 84%. A true blind test rather than training of the model is reported here as the in silico tool was developed before any experimental data was given, and no parameters of computations were adjusted to fit the data. The success of the blind test provides fundamental understanding of the molecular mechanism of cyclization by cyanobactin macrocyclases, suggesting that formation of PCC is the rate-determining step. PCC formation might also play a part in other processes of cyclic peptides production and on the practical side the suggested tool might become useful for finding cyclizable peptide sequences in general

Особенности конструкции термической печи с барабанным механизмом перемещения заготовок

One of the most energy-intensive industries is ferrous metallurgy. The metallurgical sector in industrially developed countries is reducing its specific energy consumption per one ton of products by approximately 1.0 - 1.5 % per annum. In Russia, obsolete technology is the main reason for the high-energy intensity of industrial product. Energy saving in industrial production is associated with production technology and the scope of fuel and energy resources consumption. Therefore, ways to improve energy efficiency focus on reducing energy consumption of any kind during a specific process in a specific process or thermal unit. Ensuring the economical operation of furnace units requires detailed preliminary and verification analyses, upgrading and introduction of state-of-the-art equipment. The study presents a flow diagram and features of thermal operation of a new drum-type chamber furnace for heating metal products for quenching. The technical parameters of the furnace, the results of the thermo-technical analysis, the heat balance and the specific fuel consumption as applicable to the created design are also presented. The flow diagram of the furnace has significant advantages in terms of the energy efficiency of fuel as compared to the roller and conveyor methods of metal transportation. Placing blanks on the drum significantly reduces the complexity of their transportation. Thanks to its small length the proposed design is compact and easy to place in a workshop. The use of a recuperative fuel burning device allows the efficient use of the heat of waste gases in the heating process. The proposed design and method of products transportation in the furnace working space can be used for the heat treatment of bars, pipes, strips, as well as rolled steel of various shapes. © 2021 National University of Science and Technology MISIS. All rights reserved

IL-1β Promotes TGF-β1 and IL-2 Dependent Foxp3 Expression in Regulatory T Cells

Earlier, we have shown that GM-CSF-exposed CD8α− DCs that express low levels of pro-inflammatory cytokines IL-12 and IL-1β can induce Foxp3+ Tregs leading to suppression of autoimmunity. Here, we examined the differential effects of IL-12 and IL-1β on Foxp3 expression in T cells when activated in the presence and absence of DCs. Exogenous IL-12 abolished, but IL-1β enhanced, the ability of GM-CSF-exposed tolerogenic DCs to promote Foxp3 expression. Pre-exposure of DCs to IL-1β and IL-12 had only a modest effect on Foxp3− expressing T cells; however, T cells activated in the absence of DCs but in the presence of IL-1β or IL-12 showed highly significant increase and decrease in Foxp3+ T cell frequencies respectively suggesting direct effects of these cytokines on T cells and a role for IL-1β in promoting Foxp3 expression. Importantly, purified CD4+CD25+ cells showed a significantly higher ability to maintain Foxp3 expression when activated in the presence of IL-1β. Further analyses showed that the ability of IL-1β to maintain Foxp3 expression in CD25+ T cells was dependent on TGF-β1 and IL-2 expression in Foxp3+Tregs and CD25− effectors T cells respectively. Exposure of CD4+CD25+ T cells to IL-1β enhanced their ability to suppress effector T cell response in vitro and ongoing experimental autoimmune thyroidits in vivo. These results show that IL-1β can help enhance/maintain Tregs, which may play an important role in maintaining peripheral tolerance during inflammation to prevent and/or suppress autoimmunity

25th Annual Computational Neuroscience Meeting: CNS-2016

Abstracts of the 25th Annual Computational Neuroscience Meeting: CNS-2016 Seogwipo City, Jeju-do, South Korea. 2–7 July 201