Relaxin stimulates leukocyte adhesion and migration through a relaxin receptor LGR7-dependent mechanism

Leukocytes are critical effectors of inflammation and tumor biology. Chemokine-like factors produced by such inflammatory sites are key mediators of tumor growth that activate leukocytic recruitment and tumor infiltration and suppress immune surveillance. Here we report that the endocrine peptide hormone, relaxin, is a regulator of leukocyte biology with properties important in recruitment to sites of inflammation. This study uses the human monocytic cell line THP-1 and normal human peripheral blood mononuclear cells to define a novel role for relaxin in regulation of leukocyte adhesion and migration. Our studies indicate that relaxin promotes adenylate cyclase activation, substrate adhesion, and migratory capacity of mononuclear leukocytes through a relaxin receptor LGR7-dependent mechanism. Relaxin-stimulated cAMP accumulation was observed to occur primarily in non-adherent cells. Relaxin stimulation results in increased substrate adhesion and increased migratory activity of leukocytes. In addition, relaxin-stimulated substrate adhesion resulted in enhanced chemotaxis to monocyte chemoattractant protein-1. These responses in THP-1 and peripheral blood mononuclear cells are relaxin dose-dependent and proportional to cAMP accumulation. We further demonstrate that LGR7 is critical for mediating these biological responses by use of RNA interference lentiviral short hairpin constructs. In summary, we provide evidence that relaxin is a novel leukocyte stimulatory agent with properties affecting adhesion and chemomigration

Adherence to fish oil intervention in patients with chronic kidney disease

Objective: With growing recognition of the role of inflammation in the development of chronic and acute disease, fish oil is increasingly used as a therapeutic agent, but the nature of the intervention may pose barriers to adherence in clinical populations. Our objective was to investigate the feasibility of using a fish oil supplement in hemodialysis patients. ---------- Design: This was a nonrandomized intervention study.---------- Setting: Eligible patients were recruited at the Hemodialysis Unit of Wesley Hospital, Brisbane, Queensland, Australia. Patients The sample included 28 maintenance hemodialysis patients out of 43 eligible patients in the unit. Exclusion criteria included patients regularly taking a fish oil supplement at baseline, receiving hemodialysis for less than 3 months, or being unable to give informed consent.---------- Intervention: Eicosapentaenoic acid (EPA) was administered at 2000 mg/day (4 capsules) for 12 weeks. Adherence was measured at baseline and weekly throughout the study according to changes in plasma EPA, and was further measured subjectively by self-report.---------- Results: Twenty patients (74%) adhered to the prescription based on changes in plasma EPA, whereas an additional two patients self-reported good adherence. There was a positive relationship between fish oil intake and change in plasma EPA. Most patients did not report problems with taking the fish oil. Using the baseline data, it was not possible to characterize adherent patients.---------- Conclusions: Despite potential barriers, including the need to take a large number of prescribed medications already, 74% of hemodialysis patients adhered to the intervention. This study demonstrated the feasibility of using fish oil in a clinical population.

Settlement geography of African refugee communities in Southeast Queensland : an analysis of residential distribution and secondary migration

Before 2001, most Africans immigrating to Australia were white South Africans and Zimbabweans who arrived as economic and family-reunion migrants (Cox, Cooper & Adepoju, 1999). Black African communities are a more recent addition to the Australian landscape, with most entering Australia as refugees after 2001. African refugees are a particularly disadvantaged immigrant group, which the Department of Immigration and Multicultural Affairs (in the Community Relations Commission of New South Wales, 2006) suggests require high levels of settlement support (p.23). Decision makers and settlement service providers need to have settlement data on the communities so that they can be effective in planning, budgeting and delivering support where it is most needed. Settlement data are also useful for determining the challenges that these communities face in trying to establish themselves in resettlement. There has been no verification of existing secondary data sources, however, or previous formal study of African refugee settlement geography in Southeast Queensland. This research addresses the knowledge gap by using a mixed-method approach to identify and describe the distribution and population size of eight African communities in Southeast Queensland, examine secondary migration patterns in these communities and assess the relationship between these geographic features and housing, a critical factor in successful settlement. Significant discrepancies exist between the primary data gathered in the study and existing secondary data relating to population size and distribution of the communities. Results also reveal a tension between the socio-cultural forces and the housing and economic imperatives driving secondary migration in the communities, and a general lack of engagement by African refugees with structured support networks. These findings have a wide range of implications for policy and for groups that provide settlement support to these communities.

Migration of breast cancer cells : understanding the roles of volume exclusion and cell-to-cell adhesion

We study MCF-7 breast cancer cell movement in a transwell apparatus. Various experimental conditions lead to a variety of monotone and nonmonotone responses which are difficult to interpret. We anticipate that the experimental results could be caused by cell-to-cell adhesion or volume exclusion. Without any modeling, it is impossible to understand the relative roles played by these two mechanisms. A lattice-based exclusion process random-walk model incorporating agent-to-agent adhesion is applied to the experimental system. Our combined experimental and modeling approach shows that a low value of cell-to-cell adhesion strength provides the best explanation of the experimental data suggesting that volume exclusion plays a more important role than cell-to-cell adhesion. This combined experimental and modeling study gives insight into the cell-level details and design of transwell assays.

Mechanistic investigations into interactions between IGF-I and IGFBPs and their impact on facilitating cell migration on vitronectin

Numerous studies have reported links between insulin-like growth factors (IGFs) and the extra-cellular matrix protein vitronectin (VN). We ourselves have reported that IGF-I binds to VN via IGF-binding proteins (IGFBPs) to stimulate HaCaT and MCF-7 cell migration. Here, we detail the functional evaluation of IGFBP-1, -2, -3, -4 and -6 in the presence and absence of IGF-I and VN. The data presented here, combined with our prior data on IGFBP-5, suggest that IGFBP-3, -4 and -5 are the most effective at stimulating cell migration in combination with IGF-I and VN. In addition, we demonstrate that different regions within IGFBP-3 and -4 are critical for complex formation. Furthermore, we examine whether multi-protein complexes of IGF-I and IGFBPs associated with fibronectin and collagen IV are also able to enhance functional biological responses.

Modification and validation of a microwave-assisted digestion method for subsequent ICP-MS determination of selected heavy metals in sediment and fish samples in Agusan River, Philippines

This study investigated, validated, and applied the optimum conditions for a modified microwave assisted digestion method for subsequent ICP-MS determination of mercury, cadmium, and lead in two matrices relevant to water quality, that is, sediment and fish. Three different combinations of power, pressure, and time conditions for microwave-assisted digestion were tested, using two certified reference materials representing the two matrices, to determine the optimum set of conditions. Validation of the optimized method indicated better recovery of the studied metals compared to standard methods. The validated method was applied to sediment and fish samples collected from Agusan River and one of its tributaries, located in Eastern Mindanao, Philippines. The metal concentrations in sediment ranged from 2.85 to 341.06 mg/kg for Hg, 0.05 to 44.46 mg/kg for Cd and 2.20 to 1256.16 mg/kg for Pb. The results indicate that the concentrations of these metals in the sediments rapidly decrease with distance downstream from sites of contamination. In the selected fish species, the metals were detected but at levels that are considered safe for human consumption, with concentrations of 2.14 to 6.82 μg/kg for Hg, 0.035 to 0.068 μg/kg for Cd, and 0.019 to 0.529 μg/kg for Pb.

Insulin-like growth factor-i : vitronectin complex-induced changes in gene expression effect breast cell survival and migration

Recent studies have demonstrated that IGF-I associates with VN through IGF-binding proteins (IGFBP) which in turn modulate IGF-stimulated biological functions such as cell proliferation, attachment and migration. Since IGFs play important roles in transformation and progression of breast tumours, we aimed to describe the effects of IGF-I:IGFBP:VN complexes on breast cell function and to dissect mechanisms underlying these responses. In this study we demonstrate that substrate-bound IGF-I:IGFBP:VN complexes are potent stimulators of MCF-7 breast cell survival, which is mediated by a transient activation of ERK/MAPK and sustained activation of PI3-K/AKT pathways. Furthermore, use of pharmacological inhibitors of the MAPK and PI3-K pathways confirms that both pathways are involved in IGF-I:IGFBP:VN complex-mediated increased cell survival. Microarray analysis of cells stimulated to migrate in response to IGF-I:IGFBP:VN complexes identified differential expression of genes with previously reported roles in migration, invasion and survival (Ephrin-B2, Sharp-2, Tissue-factor, Stratifin, PAI-1, IRS-1). These changes were not detected when the IGF-I analogue (\[L24]\[A31]-IGF-I), which fails to bind to the IGF-I receptor, was substituted; confirming the IGF-I-dependent differential expression of genes associated with enhanced cell migration. Taken together, these studies have established that IGF-I:IGFBP:VN complexes enhance breast cell migration and survival, processes central to facilitating metastasis. This study highlights the interdependence of ECM and growth factor interactions in biological functions critical for metastasis and identifies potential novel therapeutic targets directed at preventing breast cancer progression.

Mental health of newly arrived Burmese refugees in Australia : contributions of pre-migration and post-migration experience

Objective: This study documents the mental health status of people from Burmese refugee backgrounds, recently arrived in Australia; then examines the contributions of gender, premigration and postmigration factors in predicting mental health. Method: Structured interviews, including a demographic questionnaire, the Harvard Trauma Questionnaire, Postmigration Living Difficulties Checklist and Hopkins Symptom Checklist assessed premigration trauma, postmigration living difficulties, depression, anxiety, somatisation and traumatisation symptoms in a sample of 70 adults across five Burmese ethnic groups. Results: Substantial proportions of participants reported psychological distress in symptomatic ranges including: posttraumatic stress disorder (9%); anxiety (20%), and; depression (36%), as well as significant symptoms of somatisation (37%). Participants reported multiple and severe premigration traumas. Postmigration living difficulties of greatest concern included communication problems and worry about family not in Australia. Gender did not predict mental health. Level of exposure to traumatic events and postmigration living difficulties each made unique and relatively equal contributions to traumatisation symptoms. Postmigration living difficulties made unique contributions to depression, anxiety and somatisation symptoms. Conclusions: While exposure to traumatic events impacted on participants’ mental wellbeing, postmigration living difficulties had greater salience in predicting mental health outcomes of people from Burmese refugee backgrounds. Reported rates of posttraumatic stress disorder symptoms were consistent with a large review of adults across seven western countries. High levels of somatisation pointed to a nuanced expression of distress. Findings have implications for service provision in terms of implementing appropriate interventions to effectively meet the needs of this newly arrived group in Australia.

A tale of six fish: achieving social presence through discussion forums in an offline learning environment

It is widely held, through the Socratic tradition, that discussion is at the heart of learning. Moderated discussion forums have been shown to replicate the debate, argument and verbal defence of viewpoints that we have come to expect in face-to-face learning environments and that we generally accept to underpin learning. While much has been written about discussion forums in educational settings, particularly in how to moderate and promote effective interaction with students at a distance, this paper takes a different approach. It looks at how forums may be used to support face-to-face learning in the contemporary context of the massification of on-campus classes. Further to this, it will argue for discussion forums as an indicator of social presence in the learning environment. It will cautiously conclude that, through purposeful design, this form of asynchronous communication has a valuable role to play in creating a positive and supportive environment for students entering university. Discussion forums are tools with a versatility yet to be fully exploited.