Conformation and dynamics of human urotensin II and urotensin related peptide in aqueous solution

Conformation and dynamics of the vasoconstrictive peptides human urotensin II (UII) and urotensin related peptide (URP) have been investigated by both unrestrained and enhanced-sampling molecular-dynamics (MD) simulations and NMR spectroscopy. These peptides are natural ligands of the G-protein coupled urotensin II receptor (UTR) and have been linked to mammalian pathophysiology. UII and URP cannot be characterized by a single structure but exist as an equilibrium of two main classes of ring conformations, <i>open</i> and <i>folded</i>, with rapidly interchanging subtypes. The <i>open</i> states are characterized by turns of various types centered at K⁸Y⁹ or F⁶W⁷ predominantly with no or only sparsely populated transannular hydrogen bonds. The <i>folded</i> conformations show multiple turns stabilized by highly populated transannular hydrogen bonds comprising centers F⁶W⁷K⁸ or W⁷K⁸Y⁹. Some of these conformations have not been characterized previously. The equilibrium populations that are experimentally difficult to access were estimated by replica-exchange MD simulations and validated by comparison of experimental NMR data with chemical shifts calculated with density-functional theory. UII exhibits approximately 72% <i>open</i>:28% <i>folded</i> conformations in aqueous solution. URP shows very similar ring conformations as UII but differs in an <i>open:folded</i> equilibrium shifted further toward <i>open</i> conformations (86:14) possibly arising from the absence of folded N-terminal tail-ring interaction. The results suggest that the different biological effects of UII and URP are not caused by differences in ring conformations but rather by different interactions with UTR

Federalism and decentralization: Impact on International and Brazilian Health Policies

This article discusses the implications of decentralization in the light of international and Brazilian federalism, and its effects on public health policy. In a comparative analysis among countries, the authors find there is no single model; rather, each country has a unique structure of institutions and norms that have important implications for the operation of its health system. Brazil shares some similarities with other countries that have adopted a decentralized system and is assuming features ever closer to U.S. federalism, with a complex web of relationships. The degree of inequality among Brazilian municipalities and states, along with the budgetary imbalances caused by the minimal levels of resource utilization, undermines Brazil's constitutional principles and, consequently, its federalism. To ensure the constitutional mandate in Brazil, it is essential, as in other countries, to create a stable source of funds and increase the volume and efficiency of spending. Also important are investing in the training of managers, improving information systems, strengthening the principles of autonomy and interdependence, and defining patterns of cooperation within the federation

Caribou, Petroleum, and the Limits of Locality in the Canada–US Borderlands

his article discusses Karsten Heuer’s 2006 book Being Caribou in light of debates in ecocriticism and border studies about how to define the local in the context of environmental problems of vast range and uncertain temporality. It explores how Heuer’s book about following the Porcupine Caribou herd’s migration engages in multiple forms of boundary crossing—between countries, between hemispheric locations, and between species—and shows how insights from Indigenous storytelling complicate the book’s appeal to environmentalist readers by asserting a prior, transnational Indigenous presence in the transboundary landscapes of present-day Alaska and the Yukon

What is the 'dominant model' of British policymaking? Comparing majoritarian and policy community ideas

The aim of this article is to help identify the fundamental characteristics of the British policymaking system. It highlights an enduring conflict of interpretation within the literature. On the one hand, most contemporary analysts argue that the ‘Westminster model' is outmoded and that it has been replaced by modern understandings based on ‘governance'. On the other, key ideas associated with the Westminster model, regarding majoritarian government and policy imposition, are still in good currency in the academic literature, which holds firm to Lijphart's description of the United Kingdom as a majoritarian democracy. These very different understandings of British government are both commonly cited, but without much recognition that their conclusions may be mutually incompatible. To address this lack of comparison of competing narratives, the article outlines two main approaches to describe and explain the ‘characteristic and durable' ways of doing things in Britain: the ‘policy styles' literature initiated by Richardson in Policy Styles in Western Europe and the Lijphart account found in Democracies and revised in 1999 as Patterns of Democracy. The article encourages scholars to reject an appealing compromise between majoritarian and governance accounts