Regional identity and the politics of belonging in the consumption of Zimbabwe's vernacular tabloid newspaper, uMthunywa in Bulawayo

This paper is a qualitative study of the consumption of uMthunywa, a Zimbabwean state-controlled tabloid newspaper. It focuses on its Bulawayo readers who constitute the bulk of the paper’s readership and particularly explores the meanings and relevance of its content to their everyday lives. The study establishes that the paper constitutes a forceful alternative mediated sphere that cements a regional identity and accommodates feelings of belonging among a readership that feels disenfranchised and neglected by the ‘power bloc’. The newspaper has (re)kindled a relationship with readers through its use of the vernacular language, isiNdebele and the coverage of community issues that resonate with the readers’ everyday lives

Engineering of Insulin Receptor Isoform-Selective Insulin Analogues

BACKGROUND: The insulin receptor (IR) exists in two isoforms, A and B, and the isoform expression pattern is tissue-specific. The C-terminus of the insulin B chain is important for receptor binding and has been shown to contact the IR just adjacent to the region where the A and B isoforms differ. The aim of this study was to investigate the importance of the C-terminus of the B chain in IR isoform binding in order to explore the possibility of engineering tissue-specific/liver-specific insulin analogues. METHODOLOGY/PRINCIPAL FINDINGS: Insulin analogue libraries were constructed by total amino acid scanning mutagenesis. The relative binding affinities for the A and B isoform of the IR were determined by competition assays using scintillation proximity assay technology. Structural information was obtained by X-ray crystallography. Introduction of B25A or B25N mutations resulted in analogues with a 2-fold preference for the B compared to the A isoform, whereas the opposite was observed with a B25Y substitution. An acidic amino acid residue at position B27 caused an additional 2-fold selective increase in affinity for the receptor B isoform for analogues bearing a B25N mutation. Furthermore, the combination of B25H with either B27D or B27E also resulted in B isoform-preferential analogues (2-fold preference) even though the corresponding single mutation analogues displayed no differences in relative isoform binding affinity. CONCLUSIONS/SIGNIFICANCE: We have discovered a new class of IR isoform-selective insulin analogues with 2-4-fold differences in relative binding affinities for either the A or the B isoform of the IR compared to human insulin. Our results demonstrate that a mutation at position B25 alone or in combination with a mutation at position B27 in the insulin molecule confers IR isoform selectivity. Isoform-preferential analogues may provide new opportunities for developing insulin analogues with improved clinical benefits

Popular Cultural Materials and Public Spheres: Perspectives from Africa, India and Europe

No Abstrac