Addiction in the Light of African Values: Undermining Vitality and Community

In this article I address the question of what makes addiction morally problematic, and seek to answer it by drawing on values salient in the sub-Saharan African philosophical tradition. Specifically, I appeal to life-force and communal relationship, each of which African philosophers have at times advanced as a foundational value, and spell out how addiction, or at least salient instances of it, could be viewed as unethical for flouting them. I do not seek to defend either vitality or community as the best explanation of when and why addiction is immoral, instead arguing that each of these characteristically African values grounds an independent and plausible account of that. I conclude that both vitalism and communalism merit consideration as rivals to accounts that Western ethicists would typically make, according to which addiction is immoral insofar as it degrades rationality or autonomy, as per Kantianism, or causes pain or dissatisfaction, à la utilitarianism

A common SNP risk variant MT1-MMP causative for Dupuytren’s Disease has a specific defect in collagenolytic activity

Dupuytren's Disease (DD) is a common fibroproliferative disease of the palmar fascia. We previously identified a causal association with a non-synonymous variant (rs1042704, p.D273N) in MMP14 (encoding MT1-MMP). In this study, we investigated the functional consequences of this variant, and demonstrated that the variant MT1-MMP (MT1-N273) exhibits only 17% of cell surface collagenolytic activity compared to the ancestral enzyme (MT1-D273). Cells expressing both MT1-D273 and MT1-N273 in a 1:1 ratio, mimicking the heterozygous state, possess 38% of the collagenolytic activity compared to the cells expressing MT1-D273, suggesting that MT1-N273 acts in a dominant negative manner. Consistent with the above observation, patient-derived DD myofibroblasts with the alternate allele demonstrated around 30% of full collagenolytic activity detected in ancestral G/G genotype cells, regardless of the heterozygous (G/A) or homozygous (A/A) state. Small angle X-ray scattering analysis of purified soluble Fc-fusion enzymes allowed us to construct a 3D-molecular envelope of MT1-D273 and MT1-N273, and demonstrate altered flexibility and conformation of the ectodomains due to D273 to N substitution. Taking together, rs1042704 significantly reduces collagen catabolism in tissue, which tips the balance of homeostasis of collagen in tissue, contributing to the fibrotic phenotype of DD. Since around 30% of the worldwide population have at least one copy of the low collagenolytic alternate allele, further investigation of rs1042704 across multiple pathologies is needed