MacIntyre, Weber and institutional logics.

This paper explores "what more and what else" MacIntyre's concepts can contribute, specifically as applied to neoinstitutional theory and especially institutional logics. Drawing on the common influence of Max Weber's work as further developed by Friedland, MacIntyre's concept of eudaimonia being furthered by the pursuit of internal goods supported by external goods is used to develop a typology of goods. This typology is then deployed to show how the differing institutional logics of, for example, the market and the family have differing rationalities with differing emphases on internal and external goods, and consequently differing moral content. A simple picture of the market economy is then developed to show how such MacIntyrean concepts can be used to address the critique of a lack of morality in neoinstitutional theory. Conversely, the analytical framework provided by the institutional logics perspective is used to show how MacIntyrean concepts can be applied practically in a way that provides an interesting perspective on the current world.

Functional Characterization of TMEM127 Variants Reveals Novel Insights into Its Membrane Topology and Trafficking.

CONTEXT: TMEM127 is a poorly known tumor suppressor gene associated with pheochromocytomas, paragangliomas, and renal carcinomas. Our incomplete understanding of TMEM127 function has limited our ability to predict variant pathogenicity. PURPOSE: To better understand the function of the transmembrane protein TMEM127 we undertook cellular and molecular evaluation of patient-derived germline variants. DESIGN: Subcellular localization and steady-state levels of tumor-associated, transiently expressed TMEM127 variants were compared to the wild-type protein using immunofluorescence and immunoblot analysis, respectively, in cells genetically modified to lack endogenous TMEM127. Membrane topology and endocytic mechanisms were also assessed. RESULTS: We identified 3 subgroups of mutations and determined that 71% of the variants studied are pathogenic or likely pathogenic through loss of membrane-binding ability, stability, and/or internalization capability. Investigation into an N-terminal cluster of missense variants uncovered a previously unrecognized transmembrane domain, indicating that TMEM127 is a 4- transmembrane, not a 3-transmembrane domain-containing protein. Additionally, a C-terminal variant with predominant plasma membrane localization revealed an atypical, extended acidic, dileucine-based motif required for TMEM127 internalization through clathrin-mediated endocytosis. CONCLUSION: We characterized the functional deficits of several germline TMEM127 variants and identified novel structure-function features of TMEM127. These findings will assist in determining pathogenicity of TMEM127 variants and will help guide future studies investigating the cellular role of TMEM127.