Parliamentary sovereignty, popular sovereignty, and Henry Parker's adjudicative standpoint

Discussions of popular sovereignty in early modern England have usually been premised upon a sharp distinction between ‘legal/constitutional’ forms of discourse (which merely interpret the law) and ‘political’ ones (which focus upon the right to make it). In such readings of the period, Henry Parker has a pivotal position as a writer who abandoned merely legalistic thinking. This chapter takes a different view. It argues that Parker’s major intellectual achievement was not so much to abandon legal/constitutional discourse as to offer a theorisation of its most distinctive features: he offered an account of a new kind of politics in which concern for ‘interests’ in property and in self-preservation replaced humanist concern with promotion of virtue. Parker drew upon ideas about representation best expressed by Sir Thomas Smith and ideas about law best expressed by Oliver St John. The theory he developed was not intended as a justification of legislative sovereignty, but of adjudicative supremacy. His picture of the two Houses as supreme adjudicators was meant to block the path to direct democracy. But the adjudicative standpoint they came to occupy presupposed that freeborn adults had ‘interests’ in life, liberty, and possessions. This had democratising implications.

Intracellular trafficking, localization, and mobilization of platelet-borne thiol isomerases

OBJECTIVE: Thiol isomerases facilitate protein folding in the endoplasmic reticulum, and several of these enzymes, including protein disulfide isomerase and ERp57, are mobilized to the surface of activated platelets, where they influence platelet aggregation, blood coagulation, and thrombus formation. In this study, we examined the synthesis and trafficking of thiol isomerases in megakaryocytes, determined their subcellular localization in platelets, and identified the cellular events responsible for their movement to the platelet surface on activation. APPROACH AND RESULTS: Immunofluorescence microscopy imaging was used to localize protein disulfide isomerase and ERp57 in murine and human megakaryocytes at various developmental stages. Immunofluorescence microscopy and subcellular fractionation analysis were used to localize these proteins in platelets to a compartment distinct from known secretory vesicles that overlaps with an inner cell-surface membrane region defined by the endoplasmic/sarcoplasmic reticulum proteins calnexin and sarco/endoplasmic reticulum calcium ATPase 3. Immunofluorescence microscopy and flow cytometry were used to monitor thiol isomerase mobilization in activated platelets in the presence and absence of actin polymerization (inhibited by latrunculin) and in the presence or absence of membrane fusion mediated by Munc13-4 (absent in platelets from Unc13dJinx mice). CONCLUSIONS: Platelet-borne thiol isomerases are trafficked independently of secretory granule contents in megakaryocytes and become concentrated in a subcellular compartment near the inner surface of the platelet outer membrane corresponding to the sarco/endoplasmic reticulum of these cells. Thiol isomerases are mobilized to the surface of activated platelets via a process that requires actin polymerization but not soluble N-ethylmaleimide-sensitive fusion protein attachment receptor/Munc13-4-dependent vesicular-plasma membrane fusion.