Ligand-Dependent Conformations and Dynamics of the Serotonin 5-HT2A Receptor Determine Its Activation and Membrane-Driven Oligomerization Properties

From computational simulations of a serotonin 2A receptor (5-HT2AR) model complexed with pharmacologically and structurally diverse ligands we identify different conformational states and dynamics adopted by the receptor bound to the full agonist 5-HT, the partial agonist LSD, and the inverse agonist Ketanserin. The results from the unbiased all-atom molecular dynamics (MD) simulations show that the three ligands affect differently the known GPCR activation elements including the toggle switch at W6.48, the changes in the ionic lock between E6.30 and R3.50 of the DRY motif in TM3, and the dynamics of the NPxxY motif in TM7. The computational results uncover a sequence of steps connecting these experimentally-identified elements of GPCR activation. The differences among the properties of the receptor molecule interacting with the ligands correlate with their distinct pharmacological properties. Combining these results with quantitative analysis of membrane deformation obtained with our new method (Mondal et al, Biophysical Journal 2011), we show that distinct conformational rearrangements produced by the three ligands also elicit different responses in the surrounding membrane. The differential reorganization of the receptor environment is reflected in (i)-the involvement of cholesterol in the activation of the 5-HT2AR, and (ii)-different extents and patterns of membrane deformations. These findings are discussed in the context of their likely functional consequences and a predicted mechanism of ligand-specific GPCR oligomerization

Preservice Elementary Science Teachers' Argumentation Competence: Impact of a Training Programme

The recent literature has shown the importance of Preservice Elementary Science Teachers (PESTs) having a deep understanding of argumentation, as this factor may affect the nature of the class activities that are taught and what students learn. A lack of understanding of this factor may represent an obstacle in the development of science education programmes in line with the development of scientific competences. This paper presents the results of the design and implementation of a training programme of 6 sessions (12 hours of class participation plus 8 hours of personal homework) on argumentation. The programme was carried out by 57 Spanish PESTs from Malaga, Spain. The training programme incorporates the innovative use of certain strategies to improve competence in argumentation, such as teaching PESTs to identify the elements of arguments in order to design assessment rubrics or by including peer assessment during evaluation with and without rubrics. The results obtained on implementing the training programme were evaluated based on the development of PESTs’ argumentation competence using Toulmin’s argumentative model. Data collection methods involved two tasks carried out at the beginning and the end of the programme, i.e., pre-test and post-test, respectively. The conclusion of the study is that students made significant progress in their argumentation competence on completing the course. In addition, PESTs who followed the training programme achieved statistically better results at the end than those in the control group (n = 41), who followed a traditional teaching programme. A 6-month transfer task showed a slight improvement for the PESTs of the experimental group in relation to the control group in their ability to transfer argumentation to practice, especially to the extent to which they mentioned argumentation in their practice portfolios.This work is part of the “I+D Excelencia” project “Development and evaluation of scientific competences through context based and modelling teaching approaches” case studies (EDU2013-41952-P), funded by the Spanish Ministry of Economy and Finance through its 2013 research call

'Dotcom' Women Entrepreneurs in the UK

Drawing on two areas of academic interest, i.e. female entrepreneurship and the Internet sector, this paper provides an overview of female entrepreneurship in the web-based business sector in the UK. Based on a field study of 20 web-based small Internet-based companies owned by women, the paper explores why women start up DotCom businesses and presents a typology of DotCom women entrepreneurs. Although the sample size of the project is limited, yet the findings provide interesting and indicative insights into patterns of female entrepreneurship in this growth sector

'Them and us': 'Black neighbourhoods' as a social capital resource among black youths living in inner-city London

This paper will examine the views and experiences of Black youths living in socially deprived areas of London in order to examine the way in which they recognise the term ‘Black neighbourhood’ as a resource for ethnic identity formation and collective mobilisation. Despite the apparent problems that are typically associated with ‘Black neighbourhoods’ for many Black youths, these neighbourhoods also represent urban spaces through which a range of bonding social capital resources are generated including ties of reciprocal trust, solidarity and civic participation. These spaces hold intrinsic value for these young people providing them with a sense of wellbeing and belonging. However, the analysis will also show that the young people’s experiences of the neighbourhood are not always positive ones, and such spaces create negative outcomes for Black youths residing there. In particular, the data will highlight the restrictive capacity of ‘Black neighbourhoods’ and the various ways in which they limit Black youths’ opportunities to ‘get on’ in terms of social mobility and their ability to move beyond neighbourhood boundaries