Intracellular trafficking and secretion of inflammatory cytokines

The secretion of cytokines by immune cells plays a significant role in determining the course of an inflammatory response. The levels and timing of each cytokine released are critical for mounting an effective but confined response, whereas excessive or dysregulated inflammation contributes to many diseases. Cytokines are both culprits and targets for effective treatments in some diseases. The multiple points and mechanisms that have evolved for cellular control of cytokine secretion highlight the potency of these mediators and the fine tuning required to manage inflammation. Cytokine production in cells is regulated by cell signaling, and at mRNA and protein synthesis levels. Thereafter, the intracellular transport pathways and molecular trafficking machinery have intricate and essential roles in dictating the release and activity of cytokines. The trafficking machinery and secretory (exocytic) pathways are complex and highly regulated in many cells, involving specialized membranes, molecules and organelles that enable these cells to deliver cytokines to often-distinct areas of the cell surface, in a timely manner. This review provides an overview of secretory pathways - both conventional and unconventional - and key families of trafficking machinery. The prevailing knowledge about the trafficking and secretion of a number of individual cytokines is also summarized. In conclusion, we present emerging concepts about the functional plasticity of secretory pathways and their modulation for controlling cytokines and inflammation.

Understanding the operational structure of Southeast Asian drug trafficking groups in Australia

This thesis examined the operational structure of Southeast Asian drug trafficking groups operating on the eastern seaboard of Australia by testing the validity and application of organised crime and drug trafficking typologies using data obtained from 159 drug trafficking cases in three Australian states: New South Wales; Queensland; and Victoria. Key findings indicated that the usefulness of typologies is limited when classifying and analysing organised crime groups. In particular, Southeast Asian drug trafficking groups operated largely in small, informal, family-based hierarchies or groups that were better conceptualised using theoretical perspectives from network and cultural studies. The study recommended that replicating previous empirical research in the field is an effective approach that will contribute towards building a cumulative body of knowledge on organised crime structures.

The Politics of Sex Trafficking : a Moral Geography

This book offers a unique insight into the moral politics behind the making of human trafficking policy in Australia and the United States of America. As governments around the world rush to meet their international obligations to combat human trafficking, a heated debate has emerged over the rights, wrongs, and harms of prostitution, and its relationship to sex trafficking. The Politics of Sex Trafficking identifies and challenges intrinsic notions of moral harm that have pervaded trafficking discourse and resulted in a distinctly anti-prostitution agenda in trafficking policy in recent decades. Including rare interviews with key political actors, this book charts the competing perspectives of feminist, faith-based, and sex-worker activists, and their efforts to influence policy-makers. This critical account of the creation of anti-trafficking policy challenges the sex trafficking narrative dominant in US Congressional and Australian Parliamentary hearings, and demonstrates the power of a moral politics in shaping policy. This book will appeal to academics across the fields of criminology, criminal justice, law, human rights and gender studies, as well as policy-makers.

Help-seeking strategies of victim/survivors of human trafficking involving partner migration

Victim/survivors of human trafficking involving partner migration employ diverse help-seeking strategies, both formal and informal, to exit their exploitative situations. Drawing on primary research conducted by Lyneham and Richards (forthcoming), the authors highlight the importance of educating the community and professionals from a wide range of sectors—including health, mental health, child protection, social welfare, social work, domestic violence, migration, legal and law enforcement services—about human trafficking and the help-seeking strategies of victims/survivors in order to support them to leave exploitative situations. Enhancing Australia’s knowledge of victim/survivors’ help-seeking strategies will better inform government and community responses to this crime, improve detection and identification of human trafficking matters and subsequent referral to appropriate victim services.

Human trafficking involving marriage and partner migration to Australia

In this report, what is known about human trafficking involving marriage and partner migration to Australia is described, drawing on primary information obtained from victim/survivor testimonies, stakeholder knowledge and expertise, and reported cases that progressed through the Australian justice system. It confirms what some stakeholders in the human trafficking area have long suspected—that marriage and partner migration have been used to facilitate the trafficking of people into Australia.

Cholesterol regulates Syntaxin 6 trafficking at trans-Golgi network endosomal boundaries.

Inhibition of cholesterol export from late endosomes causes cellular cholesterol imbalance, including cholesterol depletion in the trans-Golgi network (TGN). Here, using Chinese hamster ovary (CHO) Niemann-Pick type C1 (NPC1) mutant cell lines and human NPC1 mutant fibroblasts, we show that altered cholesterol levels at the TGN/endosome boundaries trigger Syntaxin 6 (Stx6) accumulation into VAMP3, transferrin, and Rab11-positive recycling endosomes (REs). This increases Stx6/VAMP3 interaction and interferes with the recycling of αVβ3 and α5β1 integrins and cell migration, possibly in a Stx6-dependent manner. In NPC1 mutant cells, restoration of cholesterol levels in the TGN, but not inhibition of VAMP3, restores the steady-state localization of Stx6 in the TGN. Furthermore, elevation of RE cholesterol is associated with increased amounts of Stx6 in RE. Hence, the fine-tuning of cholesterol levels at the TGN-RE boundaries together with a subset of cholesterol-sensitive SNARE proteins may play a regulatory role in cell migration and invasion.

The adhesion molecule L1 regulates transendothelial migration and trafficking of dendritic cells

The adhesion molecule L1, which is extensively characterized in the nervous system, is also expressed in dendritic cells (DCs), but its function there has remained elusive. To address this issue, we ablated L1 expression in DCs of conditional knockout mice. L1-deficient DCs were impaired in adhesion to and transmigration through monolayers of either lymphatic or blood vessel endothelial cells, implicating L1 in transendothelial migration of DCs. In agreement with these findings, L1 was expressed in cutaneous DCs that migrated to draining lymph nodes, and its ablation reduced DC trafficking in vivo. Within the skin, L1 was found in Langerhans cells but not in dermal DCs, and L1 deficiency impaired Langerhans cell migration. Under inflammatory conditions, L1 also became expressed in vascular endothelium and enhanced transmigration of DCs, likely through L1 homophilic interactions. Our results implicate L1 in the regulation of DC trafficking and shed light on novel mechanisms underlying transendothelial migration of DCs. These observations might offer novel therapeutic perspectives for the treatment of certain immunological disorders.

Global Human Trafficking : Critical Issues and Contexts

Human trafficking has moved from relative obscurity to a major area of research, policy and teaching over the past ten years. Research has sprung from criminology, public policy, women’s and gender studies, sociology, anthropology, and law, but has been somewhat hindered by the failure of scholars to engage beyond their own disciplines and favoured methodologies. Recent research has begun to improve efforts to understand the causes of the problem, the experiences of victims, policy efforts, and their consequences in specific cultural and historical contexts. Global Human Trafficking: Critical issues and contexts foregrounds recent empirical work on human trafficking from an interdisciplinary, critical perspective. The collection includes classroom-friendly features, such as introductory chapters that provide essential background for understanding the trafficking literature, textboxes explaining key concepts, discussion questions for each chapter, and lists of additional resources, including films, websites, and additional readings for each chapter. The authors include both eminent and emerging scholars from around the world, drawn from law, anthropology, criminology, sociology, cultural studies, and political science and the book will be useful for undergraduate and graduate courses in these areas, as well as for scholars interested in trafficking.

Cytokine secretion in macrophages : SNAREs, Rabs and membrane trafficking

Macrophages have the capacity to rapidly secrete a wide range of inflammatory mediators that influence the development and extent of an inflammatory response. Newly synthesized and/or preformed stored cytokines and other inflammatory mediators are released upon stimulation, the timing, and volume of which is highly regulated. To finely tune this process, secretion is regulated at many levels; at the level of transcription and translation and post-translationally at the endoplasmic reticulum (ER), Golgi, and at or near the cell surface. Here, we discuss recent advances in deciphering these cytokine pathways in macrophages, focusing on recent discoveries regarding the cellular machinery and mechanisms implicated in the synthesis, trafficking, and secretion of cytokines. The specific roles of trafficking machinery including chaperones, GTPases, cytoskeletal proteins, and SNARE membrane fusion proteins will be discussed.

Tropomyosin Tm5NM1 spatially restricts src kinase activity through perturbation of rab11 vesicle trafficking

In order for cells to stop moving, they must synchronously stabilize actin filaments and their associated focal adhesions. How these two structures are coordinated in time and space is not known. We show here that the actin association protein Tm5NM1, which induces stable actin filaments, concurrently suppresses the trafficking of focal-adhesion-regulatory molecules. Using combinations of fluorescent biosensors and fluorescence recovery after photobleaching (FRAP), we demonstrate that Tm5NM1 reduces the level of delivery of Src kinase to focal adhesions, resulting in reduced phosphorylation of adhesion-resident Src substrates. Live imaging of Rab11-positive recycling endosomes that carry Src to focal adhesions reveals disruption of this pathway. We propose that tropomyosin synchronizes adhesion dynamics with the cytoskeleton by regulating actin-dependent trafficking of essential focal-adhesion molecules.

Clinton, Bush, and Obama : changing policy and rhetoric in the United States Annual Trafficking in Persons Report

This chapter charts the political transitions in the anti-trafficking agenda and rhetoric of the U.S. Government across three Presidential administrations through a detailed examination of the annual Trafficking in Persons reports released by the Office to Monitor and Combat Trafficking in Persons between 2001 and 2012. We argue that the transitions in language and focus reflect key tensions that have dominated trafficking discourse throughout the Clinton, Bush and Obama Presidencies. These fissures include debate over law enforcement versus rights-based frameworks, competing approaches on victim protection and identification, and ongoing disputes about the relationship between prostitution and human trafficking.

Prostitution Ideology and Trafficking Policy: The Impact of Political Approaches to Domestic Sex Work on Human Trafficking Policy in Australia and the United States

Debates over the legitimacy and legality of prostitution have characterised human trafficking discourse for the last two decades. This article identifies the extent to which competing perspectives concerning the legitimacy of prostitution have influenced anti-trafficking policy in Australia and the United States, and argues that each nation-state’s approach to domestic sex work has influenced trafficking legislation. The legal status of prostitution in each country, and feminist influences on prostitution law reform, have had a significant impact on the nature of the legislation adopted.

Modulating power and 'new weapons': Taking aim at the education revolution

This paper looks at the emergent performative culture seducing education in the Australian context. It links this corporate discourse to Deleuzean theorising of control societies to postulate that what we are experiencing is a new form of power relations – that of the modulating mechanisms of power. These modulating mechanisms overlay disciplinary power such that the self is modulated through the amplification and frequencies of the instruments of modulation: the simulation, the categorical sorting and the sample. These instruments are increasingly utilised within the performative culture of the Australian Federal Government’s Education Revolution as examples of the performative ‘terror’ or the abstraction of the self from the terrain in which they move. Finally, some new weapons are suggested that may offer preliminary and tentative ‘movement’ in deterritorialising ways through the enclosed spaces of mass, compulsory school and the policy that shapes it.

Trafficking in Persons Report

Fifth annual Trafficking in Persons Report prepared by the Department of State and submitted to the U.S. Congress on foreign governments' efforts to eliminate severe forms of trafficking in persons.