Bamford Action Plan 2009-2011 Easy Read Version (PDF 905KB)

Making life better for people with a learning disability and people with menal health prblems who live in Northern ireland

Bamford Action Plan 2009-11 (PDF 635KB)

THE RESPONSE OF NORTHERN IRELAND EXECUTIVE TO THE BAMFORD REVIEW OF MENTAL HEALTH AND LEARNING DISABILITY åÊ

Tackling Violence at Home 09-10 Action Plan

Tackling Violence at Home

Tackling Sexual Violence and Abuse 09-10 Action Plan

Tackling Sexual Violence and Abuse

Addressing Young People's Drinking in Northern Ireland: Action to Support the New Strategic Direction for Alcohol and Drugs

This action plan focuses on three main areas: • reducing young people’s demand for alcohol by providing information, education and training to young people and their parents; •restricting the supply of alcohol via measures to reduce accessibility to alcohol (including how alcohol is priced, marketed, and promoted); and • providing treatment and support for those who require additional help. While the emphasis of this action plan is on young people, it recognises that their drinking patterns are very much influenced by modelling the drinking patterns of adults in our society, and it therefore contains actions that will impact on the entire population. Alcohol misuse - however you measure the cost, whether to the individual, the family, the community, the health service, or society as a whole - is one of the biggest public health issues facing Northern Ireland.

Regional Hidden Harm Action Plan (PDF 2.21MB)

Regional Hidden Harm Action Plan

Functional analysis and structural modeling of human APOBEC3G reveal the role of evolutionarily conserved elements in the inhibition of human immunodeficiency virus type 1 infection and Alu transposition.

Retroelements are important evolutionary forces but can be deleterious if left uncontrolled. Members of the human APOBEC3 family of cytidine deaminases can inhibit a wide range of endogenous, as well as exogenous, retroelements. These enzymes are structurally organized in one or two domains comprising a zinc-coordinating motif. APOBEC3G contains two such domains, only the C terminal of which is endowed with editing activity, while its N-terminal counterpart binds RNA, promotes homo-oligomerization, and is necessary for packaging into human immunodeficiency virus type 1 (HIV-1) virions. Here, we performed a large-scale mutagenesis-based analysis of the APOBEC3G N terminus, testing mutants for (i) inhibition of vif-defective HIV-1 infection and Alu retrotransposition, (ii) RNA binding, and (iii) oligomerization. Furthermore, in the absence of structural information on this domain, we used homology modeling to examine the positions of functionally important residues and of residues found to be under positive selection by phylogenetic analyses of primate APOBEC3G genes. Our results reveal the importance of a predicted RNA binding dimerization interface both for packaging into HIV-1 virions and inhibition of both HIV-1 infection and Alu transposition. We further found that the HIV-1-blocking activity of APOBEC3G N-terminal mutants defective for packaging can be almost entirely rescued if their virion incorporation is forced by fusion with Vpr, indicating that the corresponding region of APOBEC3G plays little role in other aspects of its action against this pathogen. Interestingly, residues forming the APOBEC3G dimer interface are highly conserved, contrasting with the rapid evolution of two neighboring surface-exposed amino acid patches, one targeted by the Vif protein of primate lentiviruses and the other of yet-undefined function.

Priorities for Action 2008-09 (PDF 146 KB)

Priorities for Action 2008/09

Macrophage migration inhibitory factor: a counter-regulator of glucocorticoid action and critical mediator of septic shock.

Recent studies have led to the discovery of a mediator that acts as an endogenous counter-regulator of glucocorticoid action within the immune system. Isolated as a product of anterior pituitary cells, this protein was found to have the sequence of macrophage migration inhibitory factor (MIF), one of the first cytokine activities to be described. Macrophages and T cells release MIF in response both to various inflammatory stimuli and upon incubation with low concentrations of glucocorticoids. The glucocorticoid-induced secretion of MIF is tightly regulated and decreases at high, anti-inflammatory steroid concentrations. Once secreted, MIF "overrides" the anti-inflammatory and immunosuppressive effects of steroids on macrophage and T-cell cytokine production. The physiological role of MIF thus appears to be to counter-balance steroid inhibition of the inflammatory response. Anti-MIF antibodies fully protect animals from experimentally induced gram-negative or gram-positive septic shock, an effect that may be the result of the increased anti-inflammatory effects of glucocorticoids after neutralization of endogenous MIF. Anti-MIF therapeutic strategies are presently under development and may prove to be a means to modulate cytokine production in septic shock as well as in other inflammatory disease states.