Human ß-defensin 3 affects the activity of pro-inflammatory pathways associated with MyD88 and TRIF.

ß-Defensins are cationic host defense peptides that form an amphipathic structure stabilized by three intramolecular disulfide bonds. They are key players in innate and adaptive immunity and have recently been shown to limit the production of pro-inflammatory cytokines in TLR4-stimulated macrophages. In the present study, we investigate the mechanism underlying the anti-inflammatory effect of human ß-defensin 3 (hBD3). We show that the canonical structure of hBD3 is required for this immunosuppressive effect and that hBD3 rapidly associates with and enters macrophages. Examination of the global effect of hBD3 on transcription in TLR4-stimulated macrophages shows that hBD3 inhibits the transcription of pro-inflammatory genes. Among the altered genes there is significant enrichment of groups involved in the positive regulation of NF-κB including components of Toll-like receptor signaling pathways. We confirm these observations by showing corresponding decreases in protein levels of pro-inflammatory cytokines and cell surface molecules. In addition, we show that hBD3 reduces NF-κB signaling in cells transfected with MyD88 or TRIF and that hBD3 inhibits the TLR4 response in both MyD88- and TRIF-deficient macrophages. Taken together these findings suggest that the mechanism of hBD3 anti-inflammatory activity involves specific targeting of TLR signaling pathways resulting in transcriptional repression of pro-inflammatory genes.

An anatomically based finite element model of the lower limbs in the seated posture.

In this study an anatomically accurate 3D Finite Element (FE) model of the lower limbs was developed from axial cryosection images of the Visible Man (VM). The relative position of the lower limbs of a subject in standing and sitting positions was acquired with a laser scanner. A subset of these data points were used as control points in a novel application of the Host Mesh Fitting (HMF) technique, where the generic model geometry was morphed to subject data in the standing position, and then this subject-specific model was articulated to the seated posture. The gluteus maximus muscle and a portion of the skin mesh of the customised model were selected to provide a framework with which to examine the mechanics of sitting. Passive material properties were taken from the literature and were implemented in two two-parameter Mooney-Rivlin models to assess the response of the anatomical models to applied forces and pressures. The average deformation of the skin mesh was 0.77+/-1.525 mm which resulted in a maximum von Mises stress of 3.98 kPa. The average deformation of the gluteus maximus mesh was 2.69+/-0.6 mm which produced a maximum von Mises stress of 43 kPa. The results of the von Mises stress distribution support the theory that the highest stress occurs in the region immediately beneath the ischial tuberosities. The results of this research confirm previous conclusions reached using geometrically less complex models and the application of customisation to nonlinear mechanics provides a novel avenue to quantitatively assess office chair design and to analyse the mechanics of sitting.

Threats to group value, domain-specific self-esteem and intergroup discrimination amongst minimal and national groups.

The research reported in this investigation sought to examine the self-esteem hypothesis (SEH) using measures of domain-specific and public collective self-esteem (CSE). Two studies were conducted. Each tested both propositions of the SEH. The first study revealed that minimal group members (a) experienced an increase in that domain of self-esteem judged to be relatively more important to the in-group, following the display of in-group favouritism and (b) that minimal group members with low public CSE (and who thus believed that the in-group was negatively evaluated by the out-group) showed enhanced levels of in-group favouritism. The second study, which utilized the members of real social categories (i.e. New Zealanders and Australians) and negative outcome allocations (i.e. white noise) revealed identical findings. The theoretical implications of these results are discussed.