Gonadotropin-induced ovarian cancer cell migration and proliferation require extracellular signal-regulated kinase 1/2 activation regulated by calcium and protein kinase Cδ

The gonadotropin hypothesis proposes that elevated serum gonadotropin levels may increase the risk of epithelial ovarian cancer (EOC). We have studied the effect of treating EOC cell lines (OV207 and OVCAR-3) with FSH or LH. Both gonadotropins activated the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1/2 (ERK1/2) pathway and increased cell migration that was inhibited by the MAPK 1 inhibitor PD98059. Both extra- and intracellular calcium ion signalling were implicated in gonadotropin-induced ERK1/2 activation as treatment with either the calcium chelator EGTA or an inhibitor of intracellular calcium release, dantrolene, inhibited gonadotropin-induced ERK1/2 activation. Verapamil was also inhibitory, indicating that gonadotropins activate calcium influx via L-type voltage-dependent calcium channels. The cAMP/protein kinase A (PKA) pathway was not involved in the mediation of gonadotropin action in these cells as gonadotropins did not increase intracellular cAMP formation and inhibition of PKA did not affect gonadotropin-induced phosphorylation of ERK1/2. Activation of ERK1/2 was inhibited by the protein kinase C (PKC) inhibitor GF 109203X as well as by the PKCδ inhibitor rottlerin, and downregulation of PKCδ was inhibited by small interfering RNA (siRNA), highlighting the importance of PKCδ in the gonadotropin signalling cascade. Furthermore, in addition to inhibition by PD98059, gonadotropin-induced ovarian cancer cell migration was also inhibited by verapamil, GF 109203X and rottlerin. Similarly, gonadotropin-induced proliferation was inhibited by PD98059, verapamil, GF 109203X and PKCδ siRNA. Taken together, these results demonstrate that gonadotropins induce both ovarian cancer cell migration and proliferation by activation of ERK1/2 signalling in a calcium- and PKCδ-dependent manner.

Why do nurses migrate? – a review of recent literature

Aim  To identify the reasons why nurses continue migrating across international borders. Background  International nurse recruitment and migration have been increasing in the last decade and recent trends show an increase in the movement of nurses between developing and developed countries, resulting in a worldwide shortage of nurses. Methods  A manual and electronic database literature search was conducted from January 2004 to May 2010. Qualitative content analysis was completed for the final 17 articles that satisfied the inclusion criteria. Results  Motivators to nurse migration were linked to financial, professional, political, social and personal factors. Although economic factors were the most commonly reported, they were not the only reason for migration. This was especially evident among nurses migrating between developed countries. Conclusion  Nurses migrate for a wide variety of reasons as they respond to push and pull factors. Implications for nursing management  It is important for nurse managers in the source countries to advocate incentives to retain nurses. In the recipient countries the number of international nurses continues to increase implying the need for more innovative ways to mentor and orientate these nurses.

Are alphabetic language-derived models of L2 reading relevant to L1 logographic background readers?

In this paper, we argue that second language (L2) reading research, which has been informed by studies involving first language (L1) alphabetic English reading, may be less relevant to L2 readers with non-alphabetic reading backgrounds, such as Chinese readers with an L1 logographic (Chinese character) learning history. We provide both neuroanatomical and behavioural evidence from Chinese language reading studies to support our claims. The paper concludes with an argument outlining the need for a universal L2 reading model which can adequately account for readers with diverse L1 orthographic language learning histories.

VAMP3 regulates podosome organisation in macrophages and together with Stx4/SNAP23 mediates adhesion, cell spreading and persistent migration

The ability of cells to adhere, spread and migrate is essential to many physiological processes, particularly in the immune system where cells must traffic to sites of inflammation and injury. By altering the levels of individual components of the VAMP3/Stx4/SNAP23 complex we show here that this SNARE complex regulates efficient macrophage adhesion, spreading and migration on fibronectin. During cell spreading this complex mediates the polarised exocytosis of VAMP3- positive recycling endosome membrane into areas of membrane expansion, where VAMP3's surface partner Q-SNARE complex Stx4/SNAP23 was found to accumulate. Lowering the levels of VAMP3 in spreading cells resulted in a more rounded cell morphology and most cells were found to be devoid of the typical ring-like podosome superstructures seen normally in spreading cells. In migrating cells lowering VAMP3 levels disrupted the polarised localisation of podosome clusters. The reduced trafficking of recycling endosome membrane to sites of cell spreading and the disorganised podosome localisation in migrating macrophages greatly reduced their ability to persistently migrate on fibronectin. Thus, this important SNARE complex facilitates macrophage adhesion, spreading, and persistent macrophage migration on fibronectin through the delivery of VAMP3-positive membrane with its cargo to expand the plasma membrane and to participate in organising adhesive podosome structures.

The role of the recycling endosome in regulating lamellipodia formation and macrophage migration

Cell migration is a highly complex process that requires the extension of cell membrane in the direction of travel. This membrane is continuously remodeled to expand the leading edge and alter its membrane properties. For a long time it has been known that there is a continual flow of polarized membrane traffic towards the leading edge during migration and that this trafficking is essential for cell migration. However, there is little information on how the cell coordinates exocytosis at the leading edge. It is also unclear whether these internal membranes are incorporated into the leading edge or are just delivering the necessary proteins for migration to occur. We have shown that recycling endosome membrane is incorporated into the plasma membrane at the leading edge to expand the membrane and at the same time delivers receptors to the leading edge to mediate migration. In order for this to happen the surface Q-SNARE complex Stx4/SNAP23 translocates to the leading edge where it binds to the R-SNARE VAMP3 on the recycling endosome allowing incorporation into the plasma membrane. Loss of any one of the components of this complex reduces efficient lamellipodia formation and restrains cell migration.

Recycling endosome membrane incorporation into the leading edge regulates lamellipodia formation and macrophage migration

In comparison to our knowledge of the recycling of adhesion receptors and actin assembly, exactly how the cell controls its surface membrane to form a lamellipodium during migration is poorly understood. Here, we show the recycling endosome membrane is incorporated into the leading edge of a migrating cell to expand lamellipodia membrane. We have identified the SNARE complex that is necessary for fusion of the recycling endosome with the cell surface, as consisting of the R-SNARE VAMP3 on the recycling endosome partnering with the surface Q-SNARE Stx4/SNAP23, which was found to translocate and accumulate on the leading edge of migrating cells. Increasing VAMP3-mediated fusion of the recycling endosome with the surface increased membrane ruffling, while inhibition of VAMP3-mediated fusion showed that incorporation of the recycling endosome is necessary for efficient lamellipodia formation. At the same time, insertion of this recycling endosome membrane also delivers its cargo integrin α5β1 to the cell surface. The loss of this extra membrane for lamellipodia expansion and delivery of cargo in cells resulted in macrophages with a diminished capacity to effectively migrate. Thus, the recycling endosome membrane is incorporated into the leading edge and this aids expansion of the lamellipodia and simultaneously delivers integrins necessary for efficient cell migration.

Mean-field descriptions of collective migration with strong adhesion

Random walk models based on an exclusion process with contact effects are often used to represent collective migration where individual agents are affected by agent-to-agent adhesion. Traditional mean field representations of these processes take the form of a nonlinear diffusion equation which, for strong adhesion, does not predict the averaged discrete behavior. We propose an alternative suite of mean-field representations, showing that collective migration with strong adhesion can be accurately represented using a moment closure approach.

A case study examination of the influence of cultural diversity in the multicultural nursing workforce on the quality of care and patient safety in a Saudi Arabian hospital

The purpose of the study: The purpose of this study is to investigate the influence of cultural diversity, in a multicultural nursing workforce, on the quality and safety of patient care and the work environment at King Abdul-Aziz Medical City, Riyadh region. Study background: Due to global migration and workforce mobility, to varying degrees, cultural diversity exists in most health services around the world, particularly occurring where the health care workforce is multicultural or where the domestic population comprises minority groups from different cultures speaking different languages. Further complexities occur when countries have a multicultural workforce which is different from the population for whom they care, in addition to the workers being from culturally diverse countries and with different languages. In Saudi Arabia the health system is mainly staffed by expatriate nurses who comprise 67.7% of the total number of nurses. Study design: This research utilised a case study design which incorporated multiple methods including survey, qualitative interviews and document review. Methods: The participant nurses were selected for the survey via a population sampling strategy; 319 nurses returned their completed Safety Climate Survey questionnaires. Descriptive and inferential statistics (Kruskal–Wallis test) were used to analyse survey data. For the qualitative component of the study, a purposive sampling strategy was used; 24 nurses were interviewed using a semi-structured interview technique. The documentary review included KAMC-R policy documents that met the inclusion criteria using a predetermined data abstraction instrument. Content analysis was used to analyse the policy documents data. Results: The data revealed the nurses‘ perceptions of the clinical climate in this multicultural environment is that it was unsafe, with a mean score of 3.9 out of 5. No significant difference was detected between the age groups or years of experience of the nurses and the perception of safety climate in this context; the study did reveal a statistically significant difference between the cultural background categories and the perception of safety climate. The qualitative phase indicated that the nurses within this environment were struggling to achieve cultural competence; consequently, they were having difficulties in meeting the patients‘ cultural and spiritual needs as well as maintaining a high standard of care. The results also indicated that nurses were disempowered in this context. Importantly, there was inadequate support by the organisation to manage the cultural diversity issue and to protect patients from any associated risks, as demonstrated by the policy documents and supported by the nurses‘ experiences. The study also illustrated the limitations of the conceptual framework of cultural competence when tested in this multicultural workforce context. Therefore, this study generated amendments to the model that is suitable to be used in the context of a multicultural nursing workforce. Conclusion: The multicultural nature of this nursing work environment is inherently risky due to the conflicts that arise from the different cultural norms, beliefs, behaviours and languages. Further, there was uncertainty within the multicultural nursing workforce about the clinical and cultural safety of the patient care environment and about the cultural safety of the nursing workforce. The findings of the study contribute important new knowledge to the area of patient and nurse safety in a multicultural environment and contribute theoretical development to the field of cultural competence. Specifically, the findings will inform policy and practice related to patient care in the context of cultural diversity.