In silico Investigations of the Mode of Action of Novel Colchicine Derivatives Targeting β-Tubulin Isotypes: A Search for a Selective and Specific β-III Tubulin Ligand

The cardinal role of microtubules in cell mitosis makes them interesting drug targets for many pharmacological treatments, including those against cancer. Moreover, different expression patterns between cell types for several tubulin isotypes represent a great opportunity to improve the selectivity and specificity of the employed drugs and to design novel compounds with higher activity only on cells of interest. In this context, tubulin isotype βIII represents an excellent target for anti-tumoral therapies since it is overexpressed in most cancer cells and correlated with drug resistance. Colchicine is a well-known antimitotic agent, which is able to bind the tubulin dimer and to halt the mitotic process. However, it shows high toxicity also on normal cells and it is not specific for isotype βIII. In this context, the search for colchicine derivatives is a matter of great importance in cancer research. In this study, homology modeling techniques, molecular docking, and molecular dynamics simulations have been employed to characterize the interaction between 55 new promising colchicine derivatives and tubulin isotype βIII. These compounds were screened and ranked based on their binding affinity and conformational stability in the colchicine binding site of tubulin βIII. Results from this study point the attention on an amide of 4-chlorine thiocolchicine. This colchicine-derivative is characterized by a unique mode of interaction with tubulin, compared to all other compounds considered, which is primarily characterized by the involvement of the α-T5 loop, a key player in the colchicine binding site. Information provided by the present study may be particularly important in the rational design of colchicine-derivatives targeting drug resistant cancer phenotypes

Horses for courses: exploring the limits of leadership development through equine-assisted learning

YesThis essay draws on insights taken from Lacanian psychoanalysis to rethink and resituate notions of the self and subjectivity within the theory and practice of experiential leadership development. Adopting an auto-ethnographic approach, it describes the author’s own experience as a participant in a programme of equine assisted learning or ‘horse whispering’ and considers the consequences of human-animal interactions as a tool for self-development and improvement. Through an analysis of this human/animal interaction, the essay presents and applies three Lacanian concepts of subjectivity, desire and fantasy and considers their form and function in determining the often fractured relationship between self and other that characterises leader-follower relations

A quest for patient-safe culture : contextual influences on patient safety performance

Peer reviewedPostprin

Films and critical pedagogy in management education: A tourism studies context

This article examines and critically assesses the role of films in the practice of critical pedagogy in undergraduate management education, using tourism studies as a context. Utilising online focus groups, it aims to gain an in-depth knowledge and understanding of the role of films as an effective pedagogical medium in enhancing experiential approaches to learning. It argues that films play an important role in facilitating critical analyses of the studied phenomenon, illustrating and problematising abstract concepts and ideas, as well as in facilitating students’ ability to discern multiple and alternative discourses about management. The findings highlight the role of films in context-specific critical engagement with the studied content and in stimulating emotionality in learning development, thereby enhancing deep approaches to learning. Emotional responses, even negative ones, prove to be critical in engaging with intellectual and critical reflection after watching films. The findings yield new and empirical insights into the pedagogic use of films in management education, thereby contributing to some of the goals of critical management studies

“It’s Like Hating Puppies!” Employee Disengagement and Corporate Social Responsibility

Corporate social responsibility (CSR) has been linked with numerous organizational advantages, including recruitment, retention, productivity, and morale, which relate specifically to employees. However, despite specific benefits of CSR relating to employees and their importance as a stakeholder group, it is noteworthy that a lack of attention has been paid to the individual level of analysis with CSR primarily being studied at the organizational level. Both research and practice of CSR have largely treated the individual organization as a “black box,” failing to account for individual differences amongst employees and the resulting variations in antecedents to CSR engagement or disengagement. This is further exacerbated by the tendency in stakeholder theory to homogenize priorities within a single stakeholder group. In response, utilizing case study data drawn from three multinational tourism and hospitality organizations, combined with extensive interview data collected from CSR leaders, industry professionals, engaged, and disengaged employees, this exploratory research produces a finer-grained understanding of employees as a stakeholder group, identifying a number of opportunities and barriers for individual employee engagement in CSR interventions. This research proposes that employees are situated along a spectrum of engagement from actively engaged to actively disengaged. While there are some common drivers of engagement across the entire spectrum of employees, differences also exist depending on the degree to which employees, rather than senior management, support corporate responsibility within their organizations. Key antecedents to CSR engagement that vary depending on employees’ existing level of broader engagement include organizational culture, CSR intervention design, employee CSR perceptions, and the observed benefits of participation