Mapping the Active Site of CD59

CD59 is a widely distributed membrane-bound inhibitor of the cytolytic membrane attack complex (MAC) of complement. This small (77 amino acid) glycoprotein is a member of the Ly6 superfamily of proteins and is important in protecting host cells from the lytic and proinflammatory activity of the MAC. CD59 functions by binding to C8 and/or C9 in the nascent MAC and interfering with C9 membrane insertion and polymerization. We present data obtained from a combination of molecular modeling and mutagenesis techniques, which together indicate that the active site of CD59 is located in the vicinity of a hydrophobic groove on the face of the molecule opposite to a “hydrophobic strip” suggested earlier. In addition, removal of the single N-linked glycosylation site at Asn18 of CD59 resulted in an enhancement of complement inhibitory activity

Interplay between REST and nucleolin transcription factors: a key mechanism in the overexpression of genes upon increased phosphorylation

Non-malignant cells can be transformed via the activation of kinases that control degradation of neural-restrictive silencer factor (REST). Here, we identify a mechanism that contributes to the activation of genes, expression of which is controlled by responsive elements containing overlapping binding sites for REST and nucleolin. We demonstrate that both phosphorylated and non-phosphorylated nucleolin-bound DNA; however, only phosphorylated nucleolin successfully competed with either full-length REST or a REST-derived DNA-binding peptide, REST68, for binding to the overlapping binding sites. We show that this interplay between the two transcription factors regulates the activation of cell survival and immunomodulatory genes in tumors and non-malignant cells with activated protein kinase C, which is accompanied with alterations in cell proliferation and apoptosis. We propose a model for the regulation of these genes, which brings a new insight into the molecular mechanisms that control cellular transformation driven by activation of protein kinases

Androgen receptor-binding regions of androgen-responsive genes

SIGLEAvailable from British Library Document Supply Centre-DSC:DX192017 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Attention: mr J W Pienaar

Re: St Peter's Church site, South End. Application for the upliftment of the moratorium in relation to the St Peter's Church sit

‘Placing’ Caring Relationships in Education: Addressing Abstraction and Domination

The purpose of this paper is twofold: to underscore the possible dangers of abstraction, objectification and reification as roots of human domination over other human and non-human beings; and to suggest that, as one possibility, place-based education, can counter these dominating patterns by pulling up their roots through fostering relational ontologies based on care and emotional/sensuous experience. The author will foreground the work of Henri Lefebvre, Neil Evernden, and R. D. Laing in the abstraction discussion, while the discussion of place-based education will draw largely on the writings of David Gruenewald