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.

Digital intermediary: Korean transnational cinema

Since censorship was lifted in Korea in 1996, collaboration between Korean and foreign filmmakers has grown in both extent and visibility. Korean films have been shot in Australia, New Zealand and mainland China, while the Korean digital post-production and visual effects firms behind blockbusters infused with local effects have gone on to work with filmmakers from greater China and Hollywood Korean cinema has become known for its universal storylines, genre experimentation and high production values. The number of exported Korean films has increased, as has the number of Korean actors starring in films made in other countries. Korea has hosted major international industry events. These milestones have facilitated an unprecedented international expansion of the Korean film industry. With the advent of the 'digital wave in Korea the film industry's transition to digital production practices this expansion has accelerated Korean film agencies the pillars of the national cinema have played important parts in this internationalisation, particularly in promoting Korean films and filmmakers outside Korea and in facilitating international events in Korea itself Yet, for the most part, projects involving Korean filmmakers working in partnership with filmmakers from other countries are the products of individuals and businesses working outside official channels. That is, they are often better understood as 'transnational rather than 'national' or 'international' projects. In this article, we focus on a range of collaborations involving Korean, Australian, New Zealand and Chinese filmmakers and firms. These collaborations highlight some of the forces that have shaped the digital wave in the Korean film industry, and illustrate the increasingly influential role that the 'digital expertise of Korean filmmakers is playing in film industries, both regionally and around the world.

The role of strategic intelligence in anticipating transnational organised crime: A literary review

Transnational Organised Crime (TOC) has become a focal point for a range of private and public stakeholders. While not a new phenomenon, the rapid expansion of TOC activities and interests, its increasingly complex structures and ability to maximise opportunity by employing new technologies at a rate impossible for law enforcement to match complicates law enforcement’s ability to develop strategies to detect, disrupt, prevent and investigate them. In an age where the role of police has morphed from simplistic response and enforcement activities to one of managing human security risk, it is argued that intelligence can be used to reduce the impact of strategic surprise from evolving criminal threats and environmental change. This review specifically focuses on research that has implications for strategic intelligence and strategy setting in a TOC context. The review findings suggest that current law enforcement intelligence literature focuses narrowly on the management concept of intelligence-led policing in a tactical, operational setting. As such the review identifies central issues surrounding strategic intelligence and highlights key questions that future research agendas must address to improve strategic intelligence outcomes, particularly in the fight against TOC.

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.

Producing solidarity : a settlement strategy of the Karen refugee community in Brisbane, Australia

This paper explores the link between experience and context. It places the lived experiences of Karen refugees during settlement in Brisbane, Australia within the socio-political context of Burma, or particularly the historical context of persecution. Two key events – the Wrist-tying Ceremony and the Karen New Year – provide a link between experience and context. The findings of this study show a community strategically at work in a new and ongoing settlement process. This process pays respect to the complexities of cultural integrity whilst also engaging with the challenges of integration. The complexities are local (in terms of cultural, linguistic and religious diversity), national (maintaining a broader sense of community that includes linkages across Australia, as well as an engagement with the Australian socio-political context), and transnational (participating in a global Karen community). This transnational community encompasses Karen settling elsewhere in the world, Karen in refugee camps neighbouring Burma, and Karen living inside Burma. This paper argues that substantial “identity work” is involved in Karen settlement. The two key community events are useful vignettes of this identity work. Both events demonstrate how Karen cultural practices can meaningfully negotiate deeply historical ideas of Karen identity with contemporary challenges of settlement. In addition, they set out a version of settlement that departs from traditional settlement constructs; they show how the lived experience of settlement is messy, complex and dynamic, and not reflective of the neat, idealistic models that immigration policy and settlement theory project.

Stratum basale keratinocyte expression of the cell surface glycoprotein CDCP1 during epidermogenesis and its role in keratinocyte migration

Background: Epidermogenesis and epidermal wound healing are tightly regulated processes during which keratinocytes must migrate, proliferate and differentiate. Cell to cell adhesion is crucial to the initiation and regulation of these processes. CUB domain containing protein 1 (CDCP1) is a transmembrane glycoprotein that is differentially tyrosine phosphorylated during changes in cell adhesion and survival signalling and is expressed by keratinocytes in native human skin, as well as in primary cultures. Objectives: To investigate the expression of CDCP1 during epidermogenesis and its role in keratinocyte migration. Methods: We examined both human skin tissue and an in vitro three-dimensional human skin equivalent model to examine the expression of CDCP1 during epidermogenesis. To examine the role of CDCP1 in keratinocyte migration we used a function blocking anti-CDCP1 antibody and a real-time Transwell™ cell migration assay. Results: Immunohistochemical analysis indicated that in native human skin CDCP1 is expressed in the stratum basale and stratum spinosum. In contrast, during epidermogenesis in a 3-dimensional human skin equivalent model CDCP1 was expressed only in the stratum basale, with localization restricted to the cell-cell membrane. No expression was detected in basal keratinocytes that were in contact with the basement membrane. Further, an anti-CDCP1 function blocking antibody was shown to disrupt keratinocyte chemotactic migration in vitro. Conclusions: These findings delineate the expression of CDCP1 in human epidermal keratinocytes during epidermogenesis and demonstrate that CDCP1 is involved in keratinocyte migration.

The cell surface glycoprotein CUB domain-containing protein 1 (CDCP1) contributes to epidermal growth factor receptor-mediated cell migration

Epidermal growth factor (EGF) activation of the EGF receptor (EGFR) is an important mediator of cell migration, and aberrant signaling via this system promotes a number of malignancies including ovarian cancer. We have identified the cell surface glycoprotein CDCP1 as a key regulator of EGF/EGFR-induced cell migration. We show that signaling via EGF/EGFR induces migration of ovarian cancer Caov3 and OVCA420 cells with concomitant up-regulation of CDCP1 mRNA and protein. Consistent with a role in cell migration CDCP1 relocates from cell-cell junctions to punctate structures on filopodia after activation of EGFR. Significantly, disruption of CDCP1 either by silencing or the use of a function blocking antibody efficiently reduces EGF/EGFR-induced cell migration of Caov3 and OVCA420 cells. We also show that up-regulation of CDCP1 is inhibited by pharmacological agents blocking ERK but not Src signaling, indicating that the RAS/RAF/MEK/ERK pathway is required downstream of EGF/EGFR to induce increased expression of CDCP1. Our immunohistochemical analysis of benign, primary, and metastatic serous epithelial ovarian tumors demonstrates that CDCP1 is expressed during progression of this cancer. These data highlight a novel role for CDCP1 in EGF/EGFR-induced cell migration and indicate that targeting of CDCP1 may be a rational approach to inhibit progression of cancers driven by EGFR signaling including those resistant to anti-EGFR drugs because of activating mutations in the RAS/RAF/MEK/ERK pathway.

Investigating knowledge transfer through transnational programs between Indonesian and Australian universities : A conceptual framework

Globalization stimulated demand for transnational higher education. However, little is known about how transnational programs can facilitate knowledge transfer between the partner universities—something that is often implied in the partnership arrangement. For the purpose of this paper transnational programs will be limited to dual degree programs between Indonesian and Australian universities, which, in recent years have been rising. Nevertheless, the discussion and synthesis may have value to other transnational programs. Situating the knowledge transfer in the wider context of globalization of higher education and the current reforms in Indonesian education, the paper acknowledges the tension between the need to generate revenue and the ideals of facilitating knowledge transfer and capacity development for Indonesian universities. Drawing on a detailed review of research findings in the business and education sector literature, this paper presents a conceptual framework that may be used to analyze knowledge transfer between Indonesian and Australian universities. Such investigations delineate the significant drivers underlying transnational programs for supporting knowledge transfer. The proposed framework incorporates the types of knowledge, knowledge transfer mechanisms, and the processes. It also considers how the inter-university antecedents may affect the potential for knowledge transfer between the universities. A discussion of how the framework may be used to implemented knowledge transfer concludes this paper.

Dynamic optimization of migration topology in internet-based distributed genetic algorithms

Distributed Genetic Algorithms (DGAs) designed for the Internet have to take its high communication cost into consideration. For island model GAs, the migration topology has a major impact on DGA performance. This paper describes and evaluates an adaptive migration topology optimizer that keeps the communication load low while maintaining high solution quality. Experiments on benchmark problems show that the optimized topology outperforms static or random topologies of the same degree of connectivity. The applicability of the method on real-world problems is demonstrated on a hard optimization problem in VLSI design.

Transnational higher education programs for facilitating inter-university knowledge transfer : University of Indonesia’s experience

This paper explores the impacts and extent of knowledge transfer (KT) in an undergraduate engineering transnational program with an Australian university partner at the University of Indonesia (UI) using an inter-university KT conceptual framework (Sutrisno, Lisana, & Pillay 2012). For the purpose of this paper, the opportunity for KT in curriculum design is examined. Given the explicit nature of curriculum knowledge, assessing each partner’s curriculum was pivotal in allowing UI to enrich its own curriculum. The KT mechanism of face-to-face contact between Indonesian and Australian academics led to not only transfer of knowledge related to the curriculum of the undergraduate program but also to other cooperation beyond the transnational program in the form of joint research and joint supervision of post-graduate theses. Positive inter-university dynamics, such as trust and willingness to work together between the partners were underpinned by the presence of key actors from both sides at the earlier stages of the partnership. Retrospectively exploring the KT process in the UI’s transnational programs with its Australian partner suggests that there have been both structured and unstructured mechanisms, highlighting the ubiquitous and unbounded nature of KT between universities. While initially successful in facilitating KT, due to rapid succession of persons in charge of the program and the increasing focus on revenue generation, the useful lessons and practices unfortunately are being lost. Although the intention to use the transnational program for KT was always implied, it gradually was overlooked by newer staff members. Based on UI’s experience as the first provider of transnational program in Indonesia and other similar cases in China, seemingly transnational programs driven by short-term immediate financial return are unsuccessful in facilitating KT due to sensitivities to unfavourable economic situation. Those that remain operational and contribute to knowledge exchange between the partners apparently have genuine long-term engagement objective.

Higher education for capacity development or revenue maximisation? Lessons from transnational higher education programs at two Indonesian universities

HE has been changing rapidly due to globalisation that has increased the interconnectedness between nations and people throughout the world (Mok, 2012). As HE has manifested into different forms and governed by competing rationales in recent years, this paper focuses on transnational HE, which is an example of the interconnectedness of universities beyond the national borders. Indonesia is also influenced by the above changes. It took part in free-trade agreements that include HE as a sector to be liberated and accessed by international providers (Nizam, 2006). Indonesian universities found themselves bracing for the global competition for students and simultaneously having to improve their quality in order to survive amidst the growing competition. This competition gave birth to joint transnational HE programs with overseas partners among many Indonesian universities (Macaranas, 2010).