Teacher agency and professional learning communities; what can Learning Rounds in Scotland teach us?

Recently there has been growth in researching teacher agency. Some research has considered the relationship between teacher agency and professional learning. Similarly, there has been growing interest in professional learning communities as resources for professional learning. Connections have been made between professional learning communities and teacher agency, with professional learning communities seen as an affordance for the exercise of teacher agency. However, it has also been argued that there is little detailed evidence of what happens inside professional learning communities or of teacher agency in action. The research reported here focuses on a form of professional learning community from Scotland: Learning Rounds. It uses data from transcripts of post classroom observation conversations to consider the extent to which Learning Rounds provide an affordance for teacher agency and the extent to which that affordance is utilised. This research makes a contribution in three ways: adding to an empirical understanding of what happens in professional learning communities; understanding how teacher agency is (or is not) exercised in practice; considering what factors might affect the utilisation (or otherwise) of affordances for teacher agency. The paper concludes with several recommendations for developing effective professional learning communities as an affordance for teacher agency

The pattern-recognition molecule Nod1 is localized at the plasma membrane at sites of bacterial interaction.

The pattern-recognition molecule Nod1 is a critical sensor for bacterial derived diaminopimelic acid-containing peptidoglycan fragments which induces innate immune responses in epithelial cells. Here we report the subcellular localization of this protein in human epithelial cells. Nod1 is localized in the cytosol and at the plasma membrane in human cells. This membrane association is dependent on the integrity of the protein, on its signalling capacity and on an intact actin cytoskeleton. Signalling-inactive mutants of Nod1 or disruption of the actin cytoskeleton interferes with this localization pattern and impacts on downstream NF-kappaB activation. Moreover, the invasive bacterium Shigella flexneri was used as a model for physiological activation of Nod1. Imaging revealed that Nod1 is recruited to the site of bacterial entry, where it colocalizes with NEMO. Our data provide evidence that membrane association is linked to Nod1 function and, in view of recent findings on Nod2, that this may be a common feature of NLR family members

Crohn's disease-associated ATG16L1 polymorphism modulates pro-inflammatory cytokine responses selectively upon activation of NOD2

Contains fulltext : 96772.pdf (publisher's version ) (Closed access)OBJECTIVE: Autophagy has recently been shown to modulate the production of pro-inflammatory cytokine production and to contribute to antigen processing and presentation through the major histocompatibility complex. Genetic variation in the autophagy gene ATG16L1 has been recently implicated in Crohn's disease pathogenesis. The mechanisms underlying this association are not yet known, although experimental models suggest an inhibitory effect of autophagy on interleukin 1beta (IL-1beta) responses. Here, the effect of ATG16L1 genetic variation on cytokine responses has been assessed in humans. DESIGN AND SETTING: Peripheral blood mononuclear cells from healthy individuals and patients with Crohn's disease with different ATG16L1 genotypes were stimulated with ligands for Toll-like receptor 2 (TLR2), TLR4 and nucleotide-binding oligomerisation domain 2 (NOD2), with or without the autophagy inhibitor 3-methyladenine. Induction of cytokine production and related factors were measured at the mRNA and protein level. Furthermore, protein levels of ATG16L1 were assessed by western blot. RESULTS: The present study demonstrates that cells isolated from individuals bearing the ATG16L1 Thr300Ala risk variant, which is shown to affect ATG16L1 protein expression upon NOD2 stimulation, display increased production of the pro-inflammatory cytokines IL-1beta and IL-6, specifically after stimulation with NOD2 ligands. In contrast, no differences were found when cells were stimulated with TLR2 or TLR4 agonists. These findings were confirmed in two independent cohorts of volunteers and in a group of patients with Crohn's disease. The increased production could be ascribed to increased mRNA expression, while processing of pro-IL-1beta by caspase-1 activation was not affected. The effect of the ATG16L1 polymorphism was abrogated when autophagy was blocked. CONCLUSIONS: The present study is the first to link the ATG16L1 polymorphism with an excessive production of IL-1beta and IL-6 in humans, which may explain the effects of this polymorphism on the inflammatory process in Crohn's disease

The frameshift mutation in Nod2 results in unresponsiveness not only to Nod2- but also Nod1-activating peptidoglycan agonists.

Contains fulltext : 48380.pdf (Publisher’s version ) (Open Access)NOD2/CARD15 is the first characterized susceptibility gene in Crohn disease. The Nod2 1007fs (Nod2fs) frameshift mutation is the most prevalent in Crohn disease patients. Muramyl dipeptide from bacterial peptidoglycan is the minimal motif detected by Nod2 but not by Nod2fs. Here we investigated the response of human peripheral blood mononuclear cells (PBMCs) from Crohn disease patients not only to muramyl dipeptide but also to several other muramyl peptides. Most unexpectedly, we observed that patients homozygous for the Nod2fs mutation were totally unresponsive to MurNAc-L-Ala-D-Glu-meso-diaminopimelic acid (DAP) (M-Tri(DAP)), the specific agonist of Nod1, and to Gram-negative bacterial peptidoglycan. In contrast, PBMCs from a patient homozygous for the Nod2 R702W mutation, also associated with Crohn disease, displayed normal response to Gram-negative bacterial peptidoglycan. In addition, the blockage of the Nod1/M-Tri(DAP) pathway could be partially overcome by co-stimulation with the Toll-like receptors agonists lipoteichoic acid or lipopolysaccharide. Investigation into the mechanism of this finding revealed that Nod2fs did not act as a dominant-negative molecule for the Nod1/M-Tri(DAP) pathway, implying that the blockage is dependent upon the expression or activity of other factors. We demonstrated that PBMCs from Nod2fs patients express high levels of the peptidoglycan recognition protein S, a secreted protein known to interact with muramyl peptides. We proposed that through a scavenger function, peptidoglycan recognition protein S may dampen M-Tri(DAP)-dependent responses in Nod2fs patients. Together, our results identified a cross-talk between the Nod1 and Nod2 pathways and suggested that down-regulation of Nod1/M-Tri(DAP) pathway may be associated with Crohn disease

In vivo imaging of NF-kappa B activity during Escherichia coli-induced mammary gland infection

In mammary gland infections, the contribution of NF-kappa B is not well defined, and was therefore investigated following intramammary inoculation of Escherichia coli. Non-invasive real-time in vivo imaging of the transcription factor activation was performed in mammary glands of transgenic mice expressing luciferase under the control of NF-kappa B. Bacterial inoculation resulted in a major increase in luminescence as compared with control glands. This activation was confirmed by immunohistochemical nuclear staining of the NF-kappa B p65 subunit in mammary epithelium of infected glands, while nuclear p50 was not detected. The systemic response to the intramammary inoculation of Escherichia coli was also studied. NF-kappa B activation in the liver increased over time, and a relatively mild but longer-lasting response was observed as compared with the acute hepatic response of mice receiving lipopolysaccharide. This systemic reaction was confirmed by increased circulating levels of the acute phase protein serum amyloid A, tumour necrosis factor-alpha and interleukin-6. In addition, high concentrations of both cytokines in the mammary gland inoculated with bacteria showed that the infection was also well established at the local level. These results indicate that in vivo monitoring of NF-kappa B activation is an attractive novel approach to study mammary gland inflammation, and that this transcription factor is imperative in the early stages of the host immune response towards coliform intramammary infections, both at the local and systemic level