Housing and neighbourhood development plans: an initial assessment of opportunities and impact of the Localism Act 2011 in England

The Localism Act 2011 created an opportunity for local communities to form Neighbourhood Forums and to prepare their own Neighbourhood Development Plans in urban and rural areas in England. Initial reactions suggested that, rather than leading to the development of more housing, these initiatives would confirm all the stereotypes of local residents blocking unwanted development in their defined neighbourhoods. However, neighbourhood plans need to be in general conformity with the Core Strategies of higher-tier plans and have to undergo an examination by an independent person appointed by government. This paper discusses the role and purpose of neighbourhood plans and the evidence base on which they are founded. It then reviews the ways in which housing strategies and evidence of need are reflected in a sample of plans which have been adopted to date. It concludes with an assessment of the broader impact of neighbourhood plans on the planning process.

Housing at the neighbourhood level: a review of the initial approaches to neighbourhood development plans under the Localism Act 2011 in England

The Localism Act 2011 created an opportunity for local communities to form neighbourhood forums and to prepare their own neighbourhood development plans in urban and rural areas in England. Initial reactions suggested that, rather than leading to the development of more housing, these initiatives would confirm all the stereotypes of local residents blocking unwanted development in their defined neighbourhoods. However, neighbourhood plans need to be in general conformity with the core strategies of higher-tier plans and often make provision for more new homes than planned before 2011. This article discusses the role and purpose of neighbourhood plans, the evidence base on which they are founded and some of the legal challenges which have helped clarify procedures. It then identifies two types of plan based on the ways housing strategies and evidence of need are reflected in a sample of 10 plans which have been made to date. It concludes that the voluntary nature of localism to date tends to favour more rural and affluent areas and ends with an assessment of the impact of neighbourhood plans on the planning process. It suggests that the implications for spatial planning may be far-reaching.

Protein deiminases: new players in the developmentally regulated loss of neural regenerative ability

Spinal cord regenerative ability is lost with development, but the mechanisms underlying this loss are still poorly understood. In chick embryos, effective regeneration does not occur after E13, when spinal cord injury induces extensive apoptotic response and tissue damage. As initial experiments showed that treatment with a calcium chelator after spinal cord injury reduced apoptosis and cavitation, we hypothesized that developmentally regulated mediators of calcium-dependent processes in secondary injury response may contribute to loss of regenerative ability. To this purpose we screened for such changes in chick spinal cords at stages of development permissive (E11) and non-permissive (E15) for regeneration. Among the developmentally regulated calcium-dependent proteins identified was PAD3, a member of the peptidylarginine deiminase (PAD) enzyme family that converts protein arginine residues to citrulline, a process known as deimination or citrullination. This post-translational modification has not been previously associated with response to injury. Following injury, PAD3 up-regulation was greater in spinal cords injured at E15 than at E11. Consistent with these differences in gene expression, deimination was more extensive at the non-regenerating stage, E15, both in the gray and white matter. As deimination paralleled the extent of apoptosis, we investigated the effect of blocking PAD activity on cell death and deiminated-histone 3, one of the PAD targets we identified by mass-spectrometry analysis of spinal cord deiminated proteins. Treatment with the PAD inhibitor, Cl-amidine, reduced the abundance of deiminated-histone 3, consistent with inhibition of PAD activity, and significantly reduced apoptosis and tissue loss following injury at E15. Altogether, our findings identify PADs and deimination as developmentally regulated modulators of secondary injury response, and suggest that PADs might be valuable therapeutic targets for spinal cord injury.

Platelets induce Pai-1 mRNA expression in monocytes through TGF-BETA

Introduction: Plasminogen activator inhibitor type-1 (PAI-1) is a physiological modulator of fibrinolysis. High plasma PAI-1 is associated with the 4G/5G promoter polymorphism and with increased cardiovascular risk. Here we explored the role of platelets in regulating expression of the PAI-1 gene in monocytes. Methods: Blood from PAI-1 4G/5G genotyped volunteers (n=6) was incubated with the platelet GPVI-specific agonist, cross-linked collagen related peptide (CRP-XL), in the presence or absence of Mab 9E1 that blocks the binding of P-selectin to PSGL1. Monocytes were isolated by +ve selection on CD14 beads and monocyte PAI-1 mRNA expression was measured by real-time PCR. Results: Activation of platelets with CRP-XL resulted in platelets binding to >70% of monocytes and was accompanied by >5000-fold induction of PAI-1 mRNA, peaking at 4hrs. PAI-1 expression was independent of the 4G/5G genotype. Blocking the binding of platelets to monocytes enhanced PAI-1 induction (p<0.05 at 4 hrs). Incubation of isolated monocytes with the releasate from CRP-XL stimulated platelets also led to PAI-1 mRNA expression. The platelet secretome contains >100 different proteins. To identify the soluble factor(s) responsible for induction of PAI-1, neutralizing antibodies to likely candidates were added to monocytes incubated with the platelet releasate. Anti- TGF-beta inhibited platelet releasate-mediated PAI-1 mRNA induction by >80%. Monocyte PAI-1 was also induced by stimulation of PSGL-1 with a P-selectin-Fc chimera, in the absence of platelets, which was also blocked by the TGF-beta antibody. Conclusions: These results suggest that platelets induce PAI-1 mRNA in monocytes predominantly via TGF-beta, released from both platelets, and monocytes via activation by PSGL-1 signalling.This stimulation is independent of 4G/5G genotype