MTSEA prevents ligand binding to the human melanocortin-4 receptor by modification of cysteine 130 in transmembrane helix 3

AbstractWe have investigated the effect of the sulfhydryl-reactive reagent, methyl thiosulfonate ethylammonium (MTSEA), on ligand binding to the human melanocortin-4 (MC4) receptor stably expressed in HEK-293 cells. MTSEA inhibited binding of the agonist, 125I-NDPα-MSH, and the antagonist, 125I-SHU9119, in a concentration-dependent manner. Pre-incubation of cells with either the agonist or antagonist protected from subsequent MTSEA inhibition of radioligand binding. Mutation of Cys130 in transmembrane helix 3 to alanine, whilst not affecting ligand binding, led to a complete loss of the inhibitory effect of MTSEA. Since other types of sulfhydryl-reactive reagents had no effect on ligand binding, we conclude that covalent modification of Cys130 by MTSEA disrupts ligand binding by neutralising a close-by negative charge, most likely on Asp126

Understanding engagement and disengagement from pro-environmental behaviour: The role of neutralization and affirmation techniques in maintaining persistence in and desistance from car use

Despite mounting evidence that car use is a prime culprit of global warming, our love affair with the car persists. General awareness of the environmental consequences of car usage is high but fails to correspond to moderated car use. This paper contributes to an understanding of how university students’ environmental beliefs affect decisions to engage in continued car use (persistence) and/or to discontinue or reduce car use (desistance). The aim of the research presented here was to explore the range of neutralizations and counterneutralizations (affirmations) employed by students and to examine the ways in which they are used to justify and maintain either persistence or desistance in car use. The research consisted of six focus group sessions with thirty-four UK-based Higher Education students. Analysis of the study’s data highlights the range of neutralizations and counter-neutralizations employed by students in social settings. The article discusses the usefulness of neutralization theory in accounting for actual and/or intended nonenvironmentally friendly behaviour such as car use. In addition, the study’s findings are discussed in relation to prior research and to potential implications for public policy interventions which favour moderating car usage

ABSTRACT SYSTEMS THINKING- A STUDIE OF ALTERNATIVES OF

The call for papers for this special issue under the heading "Critical Systems Thinking " (Jackson, Flood, Midgley, Mingers, Ulrich) aroused my interest because my approach to systems thinking differs from theirs- and raised questions which I welcome the opportunity to respond to. For the purposes of this paper, in the following I will select and discuss some implications of certain of the terms and concepts used in the systems thinking of the above-mentioned authors, such as metaphor, critical system, systems approaches. The wide range of literature available means that, to a great degree, the decision as to the questions one wishes to highlight is dependent on what one's aims and purposes are; the questions chosen cannot be seen as providing a representative account of the respective authors ' wide-ranging systems thinking. I have attempted to point out differences and similarities in various kinds of systems thinking, especially in relation to how I myself interpret and apply systems thinking. The following is necessarily restricted to presenting just a few of the subjects which over a number of years I have found it interesting and relevant to discuss. I am aware that readers may raise any number of legitimate objections, and claim that it is not possible to deal with such a voluminous body of material in this way, or that there is every reason to spotlight other questions than those I have selected for consideration. My article can and does not claim to do anything other than aim at best to serve as a platform for discussion

Towards technology and entrepreneurship: a perspective with cyclic conditions

In this paper aspects of technology and entrepreneurship interaction are considered. Firstly some dynamic aspects of technology are presented from a brief literature perspective. This is then contrasted to and integrated with some elements of entrepreneurship where cyclic aspects are influenced by unemployment in the business and possibly technology environment. This work is built on some views presented by previous authors such as Faria and others. Their work is extended to a conceptual systems thinking model representing cyclic factors in entrepreneurship using a causal loop diagram (CLD) approach. Some business statistics from databases are gathered and analysed for entrepreneurship to show and support some arguments of Faria and others about cyclic nature of entrepreneurship. A conceptual system dynamics approach for the entrepreneurship dynamics is presente