AimsOption to attenuate atherosclerosis by depleting B2 cells is currently limited to anti-CD20 antibodies which deplete all B-cell subtypes. In the present study we evaluated the capacity of a monoclonal antibody to B cell activating factor-receptor (BAFFR) to selectively deplete atherogenic B2 cells to prevent both development and progression of atherosclerosis in the ApoE−/− mouse.Methods and ResultsTo determine whether the BAFFR antibody prevents atherosclerosis development, we treated ApoE−/− mice with the antibody while feeding them a high fat diet (HFD) for 8 weeks. Mature CD93− CD19+ B2 cells were reduced by treatment, spleen B-cell zones disrupted and spleen CD20 mRNA expression decreased while B1a cells and non-B cells were spared. Atherosclerosis was ameliorated in the hyperlipidemic mice and CD19+ B cells, CD4+ and CD8+ T cells were reduced in atherosclerotic lesions. Expressions of proinflammatory cytokines, IL1β, TNFα, and IFNγ in the lesions were also reduced, while MCP1, MIF and VCAM-1 expressions were unaffected. Plasma immunoglobulins were reduced, but MDA-oxLDL specific antibodies were unaffected. To determine whether anti-BAFFR antibody ameliorates progression of atherosclerosis, we first fed ApoE−/− mice a HFD for 6 weeks, and then instigated anti-BAFFR antibody treatment for a further 6 week-HFD. CD93− CD19+ B2 cells were selectively decreased and atherosclerotic lesions were reduced by this treatment.ConclusionAnti-BAFFR monoclonal antibody selectively depletes mature B2 cells while sparing B1a cells, disrupts spleen B-cell zones and ameliorates atherosclerosis development and progression in hyperlipidemic ApoE−/− mice. Our findings have potential for clinical translation to manage atherosclerosis-based cardiovascular diseases.
iii AHURI AHURI is a national independent research network with an expert not-for-profit research management company, AHURI Limited, at its centre.AHURI's mission is to deliver high quality research that influences policy development and practice change to improve the housing and urban environments of all Australians.Using high quality, independent evidence and through active, managed engagement, AHURI works to inform the policies and practices of governments and the housing and urban development industries, and stimulate debate in the broader Australian community.AHURI undertakes evidence-based policy development on a range of priority policy topics that are of interest to our audience groups, including housing and labour markets, urban growth and renewal, planning and infrastructure development, housing supply and affordability, homelessness, economic productivity, and social cohesion and wellbeing. AcknowledgementsThis material was produced with funding from the Australian Government and state and territory governments. AHURI Limited gratefully acknowledges the financial and other support it has received from these governments, without which this work would not have been possible.AHURI Limited also gratefully acknowledges the contributions, both financial and in-kind, of its university research partners who have helped make the completion of this material possible.We are indebted to each of the individuals who generously shared their experiences of renting, as well as their insights into how the sector can be improved from a consumer perspective. We thank the community providers and tenancy managers who provided an in-depth understanding of the practice and policy issues faced by low-income renters for sharing their practice innovation and also for assisting with the recruitment of renters for the research. The responses from investors/landlords to our survey is greatly appreciated and has provided much needed background on the motivations for investing and receptiveness to different policy scenarios in providing more affordable rentals.Sincere thanks is also extended to Dr Farnaz Zirakbash for providing invaluable research assistance with entering interviews into NVivo. Finally, we would like to thank Professor Terry Burke, who graciously shared his wisdom on earlier drafts of the introductory and future directions policy chapters, as well as providing advice on the landlord survey.
The importance of property ownership for feelings of control and ontological security has received significant academic attention. Yet tenure may not be the only indicator of control over one's dwelling. This paper considers the importance of control within the household in relation to household members' feelings of home and highlights the importance of one's relationship with other household members and their relative control over decisionmaking and the use of space. It draws upon research on multigenerational households in Australian cities, including a survey (n = 392), diaries (n = 21) and interviews (n = 21). Individuals' feelings of home were influenced by their sense of control over their dwellings, which varied for different household members. This has significant implications for research on the meaning of home, and suggests that important synergies are possible between researchers concerned with the form and nature of social interactions within the family and housing researchers concerned with the meaning of home.
The predominant Fascilin 1 (FAS1)-containing proteins in plants belong to the Fasciclin-Like Arabinogalactan-protein (FLA) family of extracellular glycoproteins. In addition to FAS1 domains, these multi-domain FLA proteins contain glycomotif regions predicted to direct addition of large arabinogalactan (AG) glycans and many contain signal sequences for addition of a glycosylphosphatidylinositol (GPI)-anchor to tether them to the plasma membrane. FLAs are proposed to play both structural and signaling functions by forming a range of interactions in the plant extracellular matrix, similar to FAS1-containing proteins in animals. FLA group B members contain two FAS1 domains and are not predicted to be GPI-anchored. None of the group B members have been functionally characterized or their sub-cellular location resolved, limiting understanding of their function. We investigated the group B FLA16 in Arabidopsis that is predominantly expressed in inflorescence tissues. FLA16 is the most highly expressed FLA in the stem after Group A members FLA11 and FLA12 that are stem specific. A FLA16-YFP fusion protein driven by the endogenous putative FLA16 promoter in wild type background showed expression in cells with secondary cell walls, and FLA16 displayed characteristics of cell wall glycoproteins with moderate glycosylation. Investigation of a fla16 mutant showed loss of FLA16 leads to reduced stem length and altered biomechanical properties, likely as a result of reduced levels of cellulose. Immuno-labeling indicated support for FLA16 location to the plasma-membrane and (apoplastic) cell wall of interfascicular stem fiber cells. Together these results indicate FLA16, a two-FAS1 domain FLAs, plays a role in plant secondary cell wall synthesis and function.
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