Phylogenetic lineage and pilus protein Spb1/SAN1518 affect opsonin-independent phagocytosis and intracellular survival of Group B Streptococcus

Opsonin-independent phagocytosis of Group B Streptococcus (GBS) is important in defense against neonatal GBS infections. A recent study indicated a role for GBS pilus in macrophage phagocytosis (Maisey et al Faseb J 22 2008 1715-24). We studied 163 isolates from different phylogenetic backgrounds and those possessing or lacking the gene encoding the pilus backbone protein, Spb1 (SAN1518, PI-2b) and spb1-deficient mutants of wild-type (WT) serotype III-3 GBS 874391 in non-opsonic phagocytosis assays using J774A.1 macrophages. Numbers of GBS phagocytosed differed up to 23-fold depending on phylogenetic background; isolates possessing spb1 were phagocytosed more than isolates lacking spb1. Comparing WT GBS and isogenic spb1-deficient mutants showed WT was phagocytosed better compared to mutants; Spb1 also enhanced intracellular survival as mutants were killed more efficiently. Complementation of mutants restored phagocytosis and resistance to killing in J774A.1 macrophages. Spb1 antiserum revealed surface expression in WT GBS and spatial distribution relative to capsular polysaccharide. spb1 did not affect macrophage nitric oxide and TNF-alpha responses; differences in phagocytosis did not correlate with N-acetyl d-glucosamine (from GBS cell-wall) according to enzyme-linked lectin-sorbent assay. Together, these findings support a role for phylogenetic lineage and Spb1 in opsonin-independent phagocytosis and intracellular survival of GBS in J774A.1 macrophages.

Relations between chronic regulatory focus and future time perspective: Results of a cross-lagged structural equation model

Future time perspective - the way individuals perceive their remaining time in life - importantly influences socio-emotional goals and motivational outcomes. Recently, researchers have called for studies that investigate relationships between personality and future time perspective. Using a cross-lagged panel design, this study investigated effects of chronic regulatory focus dimensions (promotion and prevention orientation) on future time perspective dimensions (focus on opportunities and limitations). Survey data were collected two times, separated by a 3. month time lag, from 85 participants. Results of structural equation modeling showed that promotion orientation had a positive lagged effect on focus on opportunities, and prevention orientation had a positive lagged effect on focus on limitations.

The doctrinal method: Incorporating interdisciplinary methods in reforming the law

The doctrinal methodology is in a period of change and transition. Realising that the scope of the doctrinal method is too constricting, academic lawyers are becoming eclectic in their use of research method. In this transitional time, legal scholars are increasingly infusing evidence (and methods) from other disciplines into their reasoning to bolster their reform recommendations. This article considers three examples of the interplay of the discipline of law with other disciplines in the pursuit of law reform. Firstly the article reviews studies on the extent of methodologies and reformist frameworks in PhD research in Australia. Secondly it analyses a ‘snapshot’ of recently published Australian journal articles on criminal law reform. Thirdly, it focuses on the law reform commissions, those independent government committees that play such an important role in law reform in common law jurisdictions. This examination demonstrates that while the doctrinal core of legal scholarship remains intact, legal scholars are endeavouring to accommodate statistics, comparative perspectives, social science evidence and methods, and theoretical analysis, within the legal research framework, in order to provide additional ballast to the recommendations for reform.

A promoter-level mammalian expression atlas

Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly 'housekeeping', whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.

A preliminary analysis of the impact of UN MDGs and RIO+20 on corporate social accountability practices

This chapter explores the impact of UN Millennium Development Goals (MDGs) and Rio + 20 in improving Corporate Social Responsibility (CSR) practices. While MDGs and Rio + 20 have suggested additive guidelines for improving CSR practices, they do not provide a strong legislative mandate. We find both MDGs and Rio + 20 have had limited cumulative effect on CSR practices and discourses within the corporate reports. UN bodies should bring a new policy and regulatory framework that addresses limitations in the principles espoused in the MDGs and Rio + 20. An independent monitoring system (a social compliance audit mechanism) can be mandated in an attempt to make incremental substantive change.

Health complaints and regulatory reform: Implications for vulnerable populations?

Complaints and disciplinary processes play a significant role in health professional regulation. Many countries are transitioning from models of self-regulation to greater external oversight through systems including meta regulation, responsive (risk–based) regulation, and “networked governance”. Such systems harness, in differing ways, public, private, professional and non-governmental bodies to exert influence over the conduct of health professionals and services. Interesting literature is emerging regarding complainants’ motivations and experiences, the impact of complaints processes on health professionals and identification of features such as complainant and health professional profiles, types of complaints and outcomes. This paper concentrates on studies identifying vulnerable groups and their participation in health care regulatory systems.

Clathrin-independent carriers form a high capacity endocytic sorting system at the leading edge of migrating cells

Although the importance of clathrin- and caveolin-independent endocytic pathways has recently emerged, key aspects of these routes remain unknown. Using quantitative ultrastructural approaches, we show that clathrin-independent carriers (CLICs) account for approximately three times the volume internalized by the clathrin-mediated endocytic pathway, forming the major pathway involved in uptake of fluid and bulk membrane in fibroblasts. Electron tomographic analysis of the 3D morphology of the earliest carriers shows that they are multidomain organelles that form a complex sorting station as they mature. Proteomic analysis provides direct links between CLICs, cellular adhesion turnover, and migration. Consistent with this, CLIC-mediated endocytosis of key cargo proteins, CD44 and Thy-1, is polarized at the leading edge of migrating fibroblasts, while transient ablation of CLICs impairs their ability to migrate. These studies provide the first quantitative ultrastructural analysis and molecular characterization of the major endocytic pathway in fibroblasts, a pathway that provides rapid membrane turnover at the leading edge of migrating cells.