"Ypt/Rab GTPases form the largest branch of the Ras-related small GTPase superfamily and regulate intracellular membrane trafficking in all eukaryotes. Since their discovery over two decades ago, a wealth of information has accumulated about the roles that"

Rab GTPases are master regulators of membrane trafficking in eukaryotic cells. With GTP bound, they regulate trafficking by recruiting effectors to specific membrane-bound compartments. GTPase-activating proteins (GAPs) stimulate a Rab's intrinsic rate of GTP hydrolysis, thus inactivating the Rab by converting bound GTP to GDP. Regulation of Rab proteins links the formation and breakdown of sequential, Rab-regulated membrane domains in the secretory and endocytic pathways. This thesis presents the characterization of a novel RabGAP, RUTBC1. RUTBC1 binds Rab9 in vitro and in cells through interactions with its N-terminus. Overexpression of RUTBC1 only slightly disrupts MPR trafficking and RUTBC1 does not function as a GAP for Rab9. In vitro biochemical screening of Rab proteins revealed that RUTBC1 has GAP activity toward Rab33b and Rab32. These data suggest that RUTBC1 might function to link inactivation of these Rabs in relation to a Rab9 microdomain, in support of the existence of a Rab cascade at the interface between the Golgi apparatus and endosomes. Depletion of RUTBC1 unexpectedly led to concomitant depletion of Atg16L1. Atg16L1 has an established and essential role in macroautophagy, a highly conserved cellular recycling process. Overexpression of Atg16L1 caused the formation of large puncta in the cytoplasm, which are also labeled by endogenous RUTBC1 and may represent autophagosomes. Atg16L1 is a known Rab33b effector, suggesting that Rab33b, RUTBC1 and Atg16L1 function together to regulate autophagosome formation. Finally, RUTBC2, which is highly related to RUTBC1, also binds specifically to Rab9. In vitro biochemical screening for RUTBC2's Rab substrates showed that RUTBC2 had highest GAP activity toward Rab34 and Rab36, two very similar Rabs thought to play a role in secretion. The difference in substrate specificity between RUTBC1 and RUTBC2 further exemplifies the highly complex integration of diverse membrane trafficking pathways in mammalian cells.

Richard Austin Butler remains the great enigma of post-war British politics. Independent, indiscreet and never anything but irreverent, Butler commanded the respect of both sides of the Commons and would have been, on several occasions, the people's choice for premier. From his entry into politics in 1929 to his retirement from that arena in 1965, Butler's story is also that of British political life through almost four decades. Scarred by his association with the appeasers of Munich, he won the respect of the nation as the architect of the 1944 Education Act. From the viewpoint of these times of Tory wets and dries, Butler appears the victim of the age that divided gentlemen from players. In these pages, one of our most distinguished political journalists offers a revealing portrait of 'the best Prime Minister we never had'.

Isaac Rab (1893 - 1986) was a well-known agitator for Socialism in the Boston area, as a soap-box orator, a lecturer and a teacher, for most of the Twentieth Century. He was among the founding members of the World Socialist Party and organized a Boston Local in 1932, in which he was a central figure for many years. Today the WSP(US) remains a companion party of the World Socialist Movement.