Signaling Mediated by the Cytosolic Domain of Peptidylglycine α-Amidating Monooxygenase

The luminal domains of membrane peptidylglycine α-amidating monooxygenase (PAM) are essential for peptide α-amidation, and the cytosolic domain (CD) is essential for trafficking. Overexpression of membrane PAM in corticotrope tumor cells reorganizes the actin cytoskeleton, shifts endogenous adrenocorticotropic hormone (ACTH) from mature granules localized at the tips of processes to the TGN region, and blocks regulated secretion. PAM-CD interactor proteins include a protein kinase that phosphorylates PAM (P-CIP2) and Kalirin, a Rho family GDP/GTP exchange factor. We engineered a PAM protein unable to interact with either P-CIP2 or Kalirin (PAM-1/K919R), along with PAM proteins able to interact with Kalirin but not with P-CIP2. AtT-20 cells expressing PAM-1/K919R produce fully active membrane enzyme but still exhibit regulated secretion, with ACTH-containing granules localized to process tips. Immunoelectron microscopy demonstrates accumulation of PAM and ACTH in tubular structures at the trans side of the Golgi in AtT-20 cells expressing PAM-1 but not in AtT-20 cells expressing PAM-1/K919R. The ability of PAM to interact with P-CIP2 is critical to its ability to block exit from the Golgi and affect regulated secretion. Consistent with this, mutation of its P-CIP2 phosphorylation site alters the ability of PAM to affect regulated secretion.

Memoir of Maj.-Gen. George H. Thomas,

Mode of access: Internet.

Abundance, food habits, and life history aspects of Sacramento squawfish and striped bass at the Red Bluff diversion complex, including the Research Pumping Plant, Sacramento River, California, 1994-1996 : annual report /

"February 1998."

Lehrbuch der physiologischen chemie.

Mode of access: Internet.

The Adventurer.

Mode of access: Internet.

The travels of Peter Mundy in Europe and Asia, 1608-1667.

Vol. 5 "edited by the late Lt.-Col. Sir Richard Carnac Temple, bt. ... and Lavinia Mary Anstey."

Baptism, and the terms of communion; an argument,

On cover: Baptism and communion.

The Adventurer ...

Originally published in 140 numbers from November 7, 1752, to March 9, 1754, with John Hawkesworth, Samuel Johnson, Richard Bathurst and Joseph Warton as the principal contributors.

1879 University of Michigan Football Team

The UN Security Council and the question of humanitarian intervention in Darfur

This article explores the different moral and legal arguments used by protagonists in the debate about whether or not to conduct a humanitarian intervention in Darfur. The first section briefly outlines four moral and legal positions on whether there is (and should be) a right and/or duty of humanitarian intervention: communitarianism, restrictionist and counter-restrictionist legal positivism and liberal cosmopolitanism. The second section then provides an overview of the Security Council's debate about responding to Darfur's crisis, showing how its policy was influenced by both normative concerns and hard-nosed political calculations. The article concludes by asking what Darfur's case reveals about the legitimacy and likelihood of humanitarian intervention in such catastrophes and the role of the UN Security Council as the primary authorising body for the use of international force. The authors argue that this case demonstrates that for the cosmopolitan/counter-restrictionist case to prevail pivotal states need to put humanitarian emergencies on the global agenda and express a willingness to act without Council authorisation, though the question of how to proceed in cases where the Council is deadlocked remains vexed.

Late-career international migration and reproductive work. A comparison between Peruvian and Ukrainian women in the Southern Europe

Research on the relationship between reproductive work and women´s life trajectories including the experience of labour migration has mainly focused on the case of relatively young mothers who leave behind, or later re-join, their children. While it is true that most women migrate at a younger age, there are a significant number of cases of men and women who move abroad for labour purposes at a more advanced stage, undertaking a late-career migration. This is still an under-estimated and under-researched sub-field that uncovers a varied range of issues, including the global organization of reproductive work and the employment of migrant women as domestic workers late in their lives. By pooling the findings of two qualitative studies, this article focuses on Peruvian and Ukrainian women who seek employment in Spain and Italy when they are well into their forties, or older. A commonality the two groups of women share is that, independently of their level of education and professional experience, more often than not they end up as domestic and care workers. The article initially discusses the reasons for late-career female migration, taking into consideration the structural and personal determinants that have affected Peruvian and Ukrainian women’s careers in their countries of origin and settlement. After this, the focus is set on the characteristics of domestic employment at later life, on the impact on their current lives, including the transnational family organization, and on future labour and retirement prospects. Apart from an evaluation of objective working and living conditions, we discuss women’s personal impressions of being domestic workers in the context of their occupational experiences and family commitments. In this regard, women report varying levels of personal and professional satisfaction, as well as different patterns of continuity-discontinuity in their work and family lives, and of optimism towards the future. Divergences could be, to some extent, explained by the effect of migrants´ transnational social practices and policies of states.