Tuning the relative affinities for activating and repressing operators of a temporally regulated restriction-modification system

Most type II restriction-modification (R-M) systems produce separate endonuclease (REase) and methyltransferase (MTase) proteins. After R-M genes enter a new cell, MTase activity must appear before REase or the host chromosome will be cleaved. Temporal control of these genes thus has life-or-death consequences. PvuII and some other R-M systems delay endonuclease expression by cotranscribing the REase gene with the upstream gene for an autogenous activator/repressor (C protein). C.PvuII was previously shown to have low levels early, but positive feedback later boosts transcription of the C and REase genes. The MTase is expressed without delay, and protects the host DNA. C.PvuII binds to two sites upstream of its gene: OL, associated with activation, and OR, associated with repression. Even when symmetry elements of each operator are made identical, C.PvuII binds preferentially to OL. In this study, the intra-operator spacers are shown to modulate relative C.PvuII affinity. In light of a recently reported C.Esp1396I-DNA co-crystal structure, in vitro and in vivo effects of altering OL and OR spacers were determined. The results suggest that the GACTnnnAGTC consensus is the primary determinant of C.PvuII binding affinity, with intra-operator spacers playing a fine-tuning role that affects mobility of this R-M system

Natural Law in Islam

This chapter will introduce the basic, theoretical architecture of com- peting Islamic natural law theories from the pre-modern period (ninth to fourteenth centuries). Specifically, it will outline juristic debates in the usul al-fiqh genre on reason as a source of law, where revelation is silent. Thereafter it will reflect on a range of doctrinal debates in which many of those same pre-modern jurists came to a legal determination without reference to scriptural (or any other) texts. Drawing on a curious heur- istic they labelled huquq Allah and huquq al-ʿibad (the claims of God and the claims of individuals), I will show that despite not invoking (expressly or otherwise) any natural law account of Islamic law, jurists nonetheless developed law based on a mode of rationality that could be called anything from ‘rational’ to ‘common-sense’ to ‘pragmatic’. Whether or not the huquq Allah/huquq al-ʿibad heuristic is proof posi- tive of natural law in Islam is less important than recognising the scope of questions that have yet to be examined. But as I will suggest in the third and concluding part, there are political reasons (some of which enjoy disciplinary cover) that help explain why some questions are not asked, and why some answers are deemed naïve, if not impolitic