THE ELECTRONIC BRIEFCASE AND WORK-FAMILY CONFLICT: AN ANALYSIS BY GENDER

Individuals who have personal computers or terminals at home which they use for job-related purposes outside of regular office hours are said to use an electronic bn\u27efcase. This study uses Profile Analysis to examine how selection of an electronic briefcase workstyle affects employee work-family conflict. Data was collected from 359 dual-career couples with children. Seventy-three percent of the men in the sample and forty-nine percent of the women used an electronic briefcase workstyle. The rest of the sample choose not to use this work arrangement. Men and women with computers at home work significantly more hours per week and a significantly greater number of hours of overtime than do men and women who do not use an electronic briefcase. Based upon the profile analysis, a genderelectronic briefcase interaction effect appears to exist. Men and women who do not use an electronic briefcase experience essentially the same levels of work-family conflict as do men who work at home on a computer outside of office hours. However, women who use this work arrangement show a considerably different profile. Using an electronic briefcase seems to enable men to work longer hours without increasing their work-family conflict. A computer at home does not help women cope with conflict caused by dual role expectations. Women who use an electronic briefcase experience significantly more work-family conflict than do women who do not use such a work arrangement and men who do

Chemokine Signalling in Malignant Cell Migration

Communication within and between cells is called signalling; elucidation of cell signalling in diseases, especially metastatic cancers, creates opportunities for developing therapeutic interventions. Signalling initiation occurs when a cell surface receptor binds a ligand; the signal then transmits via phosphorylation events through cytosolic signalling proteins to nuclear or effector proteins that orchestrate a cellular response. G-protein coupled receptors (GPCRs) are one type of receptor; a sub-family of GPCRs are chemokine receptors, their ligands, chemokines, can trigger directional migration. Homeostatic chemokine-triggered migration can be hijacked by cancer cells to facilitate metastasis. This study explored various poorly understood aspects of chemokine signalling that may support metastasis with the aim of identifying therapeutic targets. Methodology employed THP-1, Jurkat and MCF7 cell-lines, the manipulation of signalling by antagonists, siRNA knockdown or plasmid modification, followed by calcium and chemotaxis assays, protein visualisation using immunofluorescence, flow cytometry and western blot. Investigations found that in THP-1 cofilin phosphorylation temporally relates to CXCL12-stimulation and to chemotactic migration. In THP-1, but not Jurkat, JAK2 and STAT3 signalling support chemotaxis to CXCL12 and CCL2. Various NSAIDs, Aspirin and Paracetamol drug-specifically influenced chemokine-induced migration and cofilin activity. Rac1, FAK/Pyk2 and Pi3K were found important for chemotaxis to CXC- but not CC-chemokines and to modulate cofilin phosphorylation. Rac1 inhibitor NSC23766 was found to compete with CXCR4 ligands. Many signalling proteins involved in cancer, including GRKs, Src, Raf, MEK, ERK, Cdc42, ROCK, β-catenin and p38MAPK were shown to positively influence chemotactic migration, also Arrestin-2 to support chemotaxis to CXCL12, and Arrestin-3 chemotaxis to CCL3. Dynamin inhibitors and siRNA knockdown produced chemokine, cell type, and dynamin domain-specific responses, Dynamin’s G-domain being important for CXCL12- and PH domain for CCL3-induced migration. PKC’s role in malignancies was found contradictory and isoform specific; PKCε and PKCδ supporting chemotaxis to CXCL12 but not CCL3, whereas PKCα and PKCζ influenced migration to both CXCL12 and CCL3. This thesis offers novel insights into the complexities of chemokine-induced migration. It examines many key signalling proteins implicated in cancer; reports that NSC23766 offers promise as a lead compound for developing CXCR4 biased antagonists; and offers possible mechanisms, through cofilin phosphorylation and effects on cell migration, for the mixed epidemiology reported for different NSAID’s with respect to their influences on cancer incidence and progression, and suggests Ibuprofen may offer anti-metastatic efficacy