Behavioral Spillover Across Health and Environmental Domains

Existing research on behavioral spillover reveals that an intervention targeting one behavior has the potential to increase or decrease the motivation to engage in other related behaviors. Given the focus of prior spillover research is largely within one domain (e.g., environmental behaviors), it is not known if behavioral spillover occurs between health behaviors and environmental behaviors. Our research focuses on documenting positive spillover between these two domains, - which will open up an opportunity to promote environmental behaviors through health-based interventions (or vice versa). In an attempt to mend this gap in existing behavioral research, a Qualtrics survey has been developed and administered to Ohio State Undergraduate students to study the relationship between environmental and health behaviors and the existence of shared motivations that may lead to positive spillover. Specifically, we proposed that positive spillover between the two behavioral domains would occur for easy behaviors when the individual has strong and positive attitudes toward both the environment and personal health behaviors. Data collection and analysis presented correlations between these domains but not in a Mediation, Moderator model used to interpret causal pathways. This research has significant implications for society at large because individual health frames resonate for most people as a reason to act to address environmental issues. If we can document ways to establish positive spillover between health and environmental behaviors, this would help us understand how to better promote change in the environmental domain. Specifically, we could then increase pro-environmental behaviors by promoting healthy behaviors more generally, increasing- positive, collective environmental outcomes in addition to personal health outcomes.No embargoAcademic Major: Political Scienc

HIV-1 Inhibits Phagocytosis and Inflammatory Cytokine Responses of Human Monocyte-Derived Macrophages to P. falciparum Infected Erythrocytes

HIV-1 infection increases the risk and severity of malaria by poorly defined mechanisms. We investigated the effect of HIV-1Ba-L infection of monocyte-derived macrophages (MDM) on phagocytosis of opsonised P. falciparum infected erythrocytes (IE) and subsequent proinflammatory cytokine secretion. Compared to mock-infected MDM, HIV-1 infection significantly inhibited phagocytosis of IE (median (IQR) (10 (0–28) versus (34 (27–108); IE internalised/100 MDM; p = 0.001) and decreased secretion of IL-6 (1,116 (352–3,387) versus 1,552 (889–6,331); pg/mL; p = 0.0078) and IL-1β (16 (7–21) versus 33 (27–65); pg/mL; p = 0.0078). Thus inadequate phagocytosis and cytokine production may contribute to impaired control of malaria in HIV-1 infected individuals

Differential Expression of CD163 on Monocyte Subsets in Healthy and HIV-1 Infected Individuals

CD163, a haptoglobin-hemoglobin (Hp-Hb) scavenger receptor, expressed by monocytes and macrophages, is important in resolution of inflammation. Age-related non-AIDS co-morbidities in HIV-infected individuals, particularly dementia and cardiovascular disease, result in part from effects of HIV-1 infection on monocyte and macrophage biology. CD163 co-expression on CD14+CD16++ monocytes has been proposed as a useful biomarker for HIV-1 disease progression and the presence of HIV associated dementia. Here we investigated CD163 expression on monocyte subsets ex vivo, on cultured macrophages, and soluble in plasma, in the setting of HIV-1 infection. Whole blood immunophenotyping revealed CD163 expression on CD14++CD16- monocytes but not on CD14+CD16++ monocytes (P = 0.004), supported by CD163 mRNA levels. Incubation with M-CSF induced CD163 protein expression on CD14+CD16++ monocytes to the same extent as CD14++CD16− monocytes. CD163 expression on CD14++CD16+ monocytes from HIV-infected subjects was significantly higher than from uninfected individuals, with a trend towards increased expression on CD14++CD16− monocytes (P = 0.019 and 0.069 respectively), which is accounted for by HIV-1 therapy including protease inhibitors. Shedding of CD163 was shown to predominantly occur from the CD14++CD16− subset after Ficoll isolation and LPS stimulation. Soluble CD163 concentration in plasma from HIV-1 infected donors was similar to HIV-1 uninfected donors. Monocyte CD163 expression in HIV-1 infected patients showed a complicated relationship with classical measures of disease progression. Our findings clarify technical issues regarding CD163 expression on monocyte subsets and further elucidates its role in HIV-associated inflammation by demonstrating that CD163 is readily lost from CD14++CD16− monocytes and induced in pro-inflammatory CD14+CD16++ monocytes by M-CSF. Our data show that all monocyte subsets are potentially capable of differentiating into CD163-expressing anti-inflammatory macrophages given appropriate stimuli. Levels of CD163 expression on monocytes may be a potential biomarker reflecting efforts by the immune system to resolve immune activation and inflammation in HIV-infected individuals

Differential Expression of CD163 on Monocyte Subsets in Healthy and HIV-1 Infected Individuals

CD163, a haptoglobin-hemoglobin (Hp-Hb) scavenger receptor, expressed by monocytes and macrophages, is important in resolution of inflammation. Age-related non-AIDS co-morbidities in HIV-infected individuals, particularly dementia and cardiovascular disease, result in part from effects of HIV-1 infection on monocyte and macrophage biology. CD163 co-expression on CD14+CD16++ monocytes has been proposed as a useful biomarker for HIV-1 disease progression and the presence of HIV associated dementia. Here we investigated CD163 expression on monocyte subsets ex vivo, on cultured macrophages, and soluble in plasma, in the setting of HIV-1 infection. Whole blood immunophenotyping revealed CD163 expression on CD14++CD16- monocytes but not on CD14+CD16++ monocytes (P = 0.004), supported by CD163 mRNA levels. Incubation with M-CSF induced CD163 protein expression on CD14+CD16++ monocytes to the same extent as CD14++CD16− monocytes. CD163 expression on CD14++CD16+ monocytes from HIV-infected subjects was significantly higher than from uninfected individuals, with a trend towards increased expression on CD14++CD16− monocytes (P = 0.019 and 0.069 respectively), which is accounted for by HIV-1 therapy including protease inhibitors. Shedding of CD163 was shown to predominantly occur from the CD14++CD16− subset after Ficoll isolation and LPS stimulation. Soluble CD163 concentration in plasma from HIV-1 infected donors was similar to HIV-1 uninfected donors. Monocyte CD163 expression in HIV-1 infected patients showed a complicated relationship with classical measures of disease progression. Our findings clarify technical issues regarding CD163 expression on monocyte subsets and further elucidates its role in HIV-associated inflammation by demonstrating that CD163 is readily lost from CD14++CD16− monocytes and induced in pro-inflammatory CD14+CD16++ monocytes by M-CSF. Our data show that all monocyte subsets are potentially capable of differentiating into CD163-expressing anti-inflammatory macrophages given appropriate stimuli. Levels of CD163 expression on monocytes may be a potential biomarker reflecting efforts by the immune system to resolve immune activation and inflammation in HIV-infected individuals

The role of monocyte subsets in HIV-1 pathogenesis and their contribution to the viral reservoir.

Cells of macrophage lineage have long been known to be a target for HIV-1 infection. Given their potential ability to live for extensive periods of time, to constitutively produce low levels of virus with minimal cytopathic effects and to migrate into tissues and establish local infection, HIV-1 infected macrophages significantly contribute to the viral reservoir and are a major hurdle to clearance of HIV-1 infection. Understanding the origin of infected macrophages and the mechanisms of infection is important in targeting infection in this compartment. Circulating blood monocytes are generally considered to be resistant to HIV-1 infection. However, we have previously shown that a subset of monocytes (CD16+ monocytes which, unless otherwise specified in this thesis, include both CD14++CD16+ and CD14+CD16++ monocytes) are more susceptible to HIV-1 infection than the majority of monocytes (CD14++CD16-). To investigate the role of the CD16+ monocyte subset in HIV-1 pathogenesis and its contribution to the viral reservoir we have investigated HIV-1 infection of CD16+ monocytes, the potential of a monocyte scavenger protein CD163 for clinical application and the cell biology of family of proteins called tetraspanins and their role in HIV-1 infection of monocytes and macrophages. Chapter 2 -HIV-1 infection of CD16+ monocytes Overview: Our laboratory has previously shown the CD16+ monocyte subset is preferentially infected in HIV-1 infected individuals and so may be a major component of the viral reservoir. To investigate this we have measured the contribution of HIV-1 infected CD16+ monocytes to the viral reservoir in comparison to the major monocyte subset and to the known reservoir of resting memory T cells. We have then examined the mechanisms that account for increased susceptibility to HIV-1 infection that is demonstrated by CD16+ monocytes when compared to CD14++CD16-monocytes. Results: This chapter quantifies HIV-1 DNA in monocyte subsets from HIV-1 infected donors compared to resting memory T cells and shows CD16+ monocytes contain more HIV-1 DNA than CD14++CD16-monocytes and comparable levels to resting memory T cells. We have confirmed that CD16+ monocytes can produce infectious virus through experiments using monocyte subsets isolated from the blood of HIV-1 infected donors co-cultured with activated uninfected donor PBMC. Our investigations of the mechanisms which account for increased infection in this subset show that despite increased CCR5 expression, CD16+ monocytes do not bind more HIV-1, nor does HIV-1 entry occur in higher levels than in CD14++CD16-monocytes. Finally, we show that CD16+ monocytes express the HIV-1 resistance host factor APOBEC3G (apolipoprotein B mRNA editing enzyme, catalytic polypeptide like) mainly in an inactive high molecular weight form which may account for their increased susceptibility to infection. Tippett E*, Ellery PJ*, Chui YL, Paukovics G, Cameron PU, Solomon A, Lewin SR, Gorry PR, Jaworowski A, Greene W, Sonza S, Crowe SM. The CD16+ monocyte subset is more permissive to infection and preferentially harbours HIV in vivo. J Immuno/2007; 178(10):6581¬9 (*authors contributed equally) Chapter 3 -Examination of the scavenger receptor CD163 in HIV-1 infection Overview: CD163 has been suggested play an important role in immune resolution, however, relatively little is known about its function. It is expressed on monocytes and shown to be increased in brain tissue from people with HIV-1 associated dementia as well as in simian immunodeficiency virus (SIV) macaque models. We have examined the regulation of CD163 in health and in HIV-1 infection and have investigated the potential of soluble CD163 as a prognostic marker of disease. Results: We show CD163 is differentially expressed on monocyte subsets, with highest levels of expression on CD14++CD16-monocytes. Culture in the presence of M-CSF can stimulate CD163 expression to comparable levels in all subsets. We show CD163 is readily shed from the cell surface during blood processing and that following LPS stimulation shedding predominantly occurs from the CD14++CD16-subset. CD163 expression is increased on CD14++CD16-monocytes in HIV-1 infected patients receiving protease inhibitors as part of their drug regimen compared to uninfected donors. CD163 is also increased on CD14++CD16+ monocytes from HIV-1 positive donors by an undetermined mechanism. Plasma levels of soluble CD163 are not affected by HIV-1 infection in this cohort. Correlation analyses of soluble CD163 with clinical parameters suggests multifactorial regulation of CD163 in the setting of HIV-1 infection. Tippett E, Cheng W, Westhorpe C, Cameron PU, Brew B, Lewin S, Jaworowski A, Crowe S. Differential expression of CD163 on monocyte subsets in healthy and HIV-1 infected individuals PLOS One 2011; 6(5):e19968 Chapter 4 -The role of tetraspanins in HIV-1 infection Overview: There is some evidence that tetraspanins are involved in HIV-1 infection of macrophages, however, their role in the infection of monocytes and the potential that they may contribute to the increased susceptibility to infection shown by CD16+ monocytes has not been investigated. Results: Little is known regarding tetraspanin regulation. Our investigation of tetraspanin expression on monocyte subsets from healthy and HIV-1 infected donors revealed differential expression on monocyte subsets without being significantly altered by HIV-1 infection. We found tetraspanin expression by macrophages was modulated by cytokine exposure and that CD9 is a marker of anti-inflammatory macrophages and CD53 of pro-inflammatory macrophages. Our investigation of the early events in HIV-1 infection has shown that tetraspanins can be found in association with the HIV-1 co-receptor CCR5 in macrophages, and in monocytes tetraspanins are concentrated with virions during HIV-1 entry. However, depletion of tetraspanins with siRNA did not impair HIV-1 entry. Using reporter virus and molecular techniques to investigate HIV-1 reverse transcription and gene expression we demonstrated that CD81, CD63 and to a lesser extent CD53 are required for HIV-1 infection of monocytes and macrophages at a post entry stage; CD81 is required for a stage in the viral replication cycle between early and late reverse transcription and CD63 and CD53 at a point after late reverse transcription but before nuclear importation. Tippett E, Jones KL, Hawkes D, Pereira C, Roche M, Gorry P. Lewin SL, Cameron PU, Marsh M, Crowe SM. Tetraspanins are required for HIV-1 infection of monocytes and macrophaqes Submitted Journal of Immunology

The role of monocyte subsets in HIV-1 pathogenesis and their contribution to the viral reservoir.

Cells of macrophage lineage have long been known to be a target for HIV-1 infection. Given their potential ability to live for extensive periods of time, to constitutively produce low levels of virus with minimal cytopathic effects and to migrate into tissues and establish local infection, HIV-1 infected macrophages significantly contribute to the viral reservoir and are a major hurdle to clearance of HIV-1 infection. Understanding the origin of infected macrophages and the mechanisms of infection is important in targeting infection in this compartment. Circulating blood monocytes are generally considered to be resistant to HIV-1 infection. However, we have previously shown that a subset of monocytes (CD16+ monocytes which, unless otherwise specified in this thesis, include both CD14++CD16+ and CD14+CD16++ monocytes) are more susceptible to HIV-1 infection than the majority of monocytes (CD14++CD16-). To investigate the role of the CD16+ monocyte subset in HIV-1 pathogenesis and its contribution to the viral reservoir we have investigated HIV-1 infection of CD16+ monocytes, the potential of a monocyte scavenger protein CD163 for clinical application and the cell biology of family of proteins called tetraspanins and their role in HIV-1 infection of monocytes and macrophages. Chapter 2 -HIV-1 infection of CD16+ monocytes Overview: Our laboratory has previously shown the CD16+ monocyte subset is preferentially infected in HIV-1 infected individuals and so may be a major component of the viral reservoir. To investigate this we have measured the contribution of HIV-1 infected CD16+ monocytes to the viral reservoir in comparison to the major monocyte subset and to the known reservoir of resting memory T cells. We have then examined the mechanisms that account for increased susceptibility to HIV-1 infection that is demonstrated by CD16+ monocytes when compared to CD14++CD16-monocytes. Results: This chapter quantifies HIV-1 DNA in monocyte subsets from HIV-1 infected donors compared to resting memory T cells and shows CD16+ monocytes contain more HIV-1 DNA than CD14++CD16-monocytes and comparable levels to resting memory T cells. We have confirmed that CD16+ monocytes can produce infectious virus through experiments using monocyte subsets isolated from the blood of HIV-1 infected donors co-cultured with activated uninfected donor PBMC. Our investigations of the mechanisms which account for increased infection in this subset show that despite increased CCR5 expression, CD16+ monocytes do not bind more HIV-1, nor does HIV-1 entry occur in higher levels than in CD14++CD16-monocytes. Finally, we show that CD16+ monocytes express the HIV-1 resistance host factor APOBEC3G (apolipoprotein B mRNA editing enzyme, catalytic polypeptide like) mainly in an inactive high molecular weight form which may account for their increased susceptibility to infection. Tippett E*, Ellery PJ*, Chui YL, Paukovics G, Cameron PU, Solomon A, Lewin SR, Gorry PR, Jaworowski A, Greene W, Sonza S, Crowe SM. The CD16+ monocyte subset is more permissive to infection and preferentially harbours HIV in vivo. J Immuno/2007; 178(10):6581¬9 (*authors contributed equally) Chapter 3 -Examination of the scavenger receptor CD163 in HIV-1 infection Overview: CD163 has been suggested play an important role in immune resolution, however, relatively little is known about its function. It is expressed on monocytes and shown to be increased in brain tissue from people with HIV-1 associated dementia as well as in simian immunodeficiency virus (SIV) macaque models. We have examined the regulation of CD163 in health and in HIV-1 infection and have investigated the potential of soluble CD163 as a prognostic marker of disease. Results: We show CD163 is differentially expressed on monocyte subsets, with highest levels of expression on CD14++CD16-monocytes. Culture in the presence of M-CSF can stimulate CD163 expression to comparable levels in all subsets. We show CD163 is readily shed from the cell surface during blood processing and that following LPS stimulation shedding predominantly occurs from the CD14++CD16-subset. CD163 expression is increased on CD14++CD16-monocytes in HIV-1 infected patients receiving protease inhibitors as part of their drug regimen compared to uninfected donors. CD163 is also increased on CD14++CD16+ monocytes from HIV-1 positive donors by an undetermined mechanism. Plasma levels of soluble CD163 are not affected by HIV-1 infection in this cohort. Correlation analyses of soluble CD163 with clinical parameters suggests multifactorial regulation of CD163 in the setting of HIV-1 infection. Tippett E, Cheng W, Westhorpe C, Cameron PU, Brew B, Lewin S, Jaworowski A, Crowe S. Differential expression of CD163 on monocyte subsets in healthy and HIV-1 infected individuals PLOS One 2011; 6(5):e19968 Chapter 4 -The role of tetraspanins in HIV-1 infection Overview: There is some evidence that tetraspanins are involved in HIV-1 infection of macrophages, however, their role in the infection of monocytes and the potential that they may contribute to the increased susceptibility to infection shown by CD16+ monocytes has not been investigated. Results: Little is known regarding tetraspanin regulation. Our investigation of tetraspanin expression on monocyte subsets from healthy and HIV-1 infected donors revealed differential expression on monocyte subsets without being significantly altered by HIV-1 infection. We found tetraspanin expression by macrophages was modulated by cytokine exposure and that CD9 is a marker of anti-inflammatory macrophages and CD53 of pro-inflammatory macrophages. Our investigation of the early events in HIV-1 infection has shown that tetraspanins can be found in association with the HIV-1 co-receptor CCR5 in macrophages, and in monocytes tetraspanins are concentrated with virions during HIV-1 entry. However, depletion of tetraspanins with siRNA did not impair HIV-1 entry. Using reporter virus and molecular techniques to investigate HIV-1 reverse transcription and gene expression we demonstrated that CD81, CD63 and to a lesser extent CD53 are required for HIV-1 infection of monocytes and macrophages at a post entry stage; CD81 is required for a stage in the viral replication cycle between early and late reverse transcription and CD63 and CD53 at a point after late reverse transcription but before nuclear importation. Tippett E, Jones KL, Hawkes D, Pereira C, Roche M, Gorry P. Lewin SL, Cameron PU, Marsh M, Crowe SM. Tetraspanins are required for HIV-1 infection of monocytes and macrophaqes Submitted Journal of Immunology

Applying Systems to Capacity-Building in Participatory, Ecologically Informed Planning

Environmental legislation such as the European Union Water Framework Directive calls for more effective stakeholder and public participation in planning. Achieving the ambitious objectives of such legislation will require changes in behavior from a wide range of people. This adds impetus to call for more effective participation in planning, as people’s motivation to change is linked to their understanding. Recent policy reviews have identified a lack of skilled practitioners able to engage stakeholders in such planning as a major barrier to sustainable development in the UK. Developing effective training in facilitation and a supporting learning resource would help address this lack. This research in the NorthWest of England aims to develop a participatory process for ecological planning, which is based on a systems thinking framework, into a transferable methodology available to a range of practitioners. This will be approached through action research in 2006, and is supported by the Environment Agency and Manchester City Council. A literature review will examine best practices. The researchers will work with trainee facilitators to engage stakeholder and community participation in planning projects. Training techniques, to enable the facilitators to learn how best to use the process, will be developed and evaluated. Sources of data will include: • In-depth, semi-structured ‘before and after’ interviews with trainee facilitators; • Analysis of data collected during the action research from participant observation; and • In-depth workshops with stakeholders to test and develop the training approaches. The application of systems thinking principles to capacity building in participatory, ecological design will be explored in this research. In this paper a conceptual model based on systems thinking principles is developed for analysis of results from the ongoing empirical research. This builds on work to explore the teaching of ecological principles in design education, the development of living systems thinking in relationship to ecological design and eco-literacy, and recent applications of complexity theory principles to learning and innovation in organizations. This conceptual framework is developed within the contexts of shifts of the roles of practitioners in spatial planning