OREXIN 1 AND 2 RECEPTOR INVOLVEMENT IN CO2 -INDUCED PANIC-ASSOCIATED BEHAVIOR AND AUTONOMIC RESPONSES

BACKGROUND: The neuropeptides orexin A and B play a role in reward and feeding and are critical for arousal. However, it was not initially appreciated that most prepro-orexin synthesizing neurons are almost exclusively concentrated in the perifornical hypothalamus, which when stimulated elicits panic-associated behavior and cardiovascular responses in rodents and self-reported "panic attacks" and "fear of dying" in humans. More recent studies support a role for the orexin system in coordinating an integrative stress response. For instance, orexin neurons are highly reactive to anxiogenic stimuli, are hyperactive in anxiety pathology, and have strong projections to anxiety and panic-associated circuitry. Although the two cognate orexin receptors are colocalized in many brain regions, the orexin 2 receptor (OX2R) most robustly maps to the histaminergic wake-promoting region, while the orexin 1 receptor (OX1R) distribution is more exclusive and dense in anxiety and panic circuitry regions, such as the locus ceruleus. Overall, this suggests that OX1Rs play a critical role in mobilizing anxiety and panic responses. METHODS: Here, we used a CO2 -panic provocation model to screen a dual OX1/2R antagonist (DORA-12) to globally inhibit orexin activity, then a highly selective OX1R antagonist (SORA1, Compound 56) or OX2R antagonist (SORA2, JnJ10397049) to assess OX1R and OX2R involvement. RESULTS: All compounds except the SORA2 attenuated CO2 -induced anxiety-like behaviors, and all but the SORA2 and DORA attenuated CO2 -induced cardiovascular responses. CONCLUSIONS: SORA1s may represent a novel method of treating anxiety disorders, with no apparent sedative effects that were present with a benzodiazepine

Problems and Prospects for the “Fourth Corridor”: The Position and Role of Turkey in Gas Transit to Europe

The Russian-Ukrainian gas crisis of January 2009, occurring three years after a similar dispute between Moscow and Kyiv had disrupted Russian natural gas supplies to Europe, led many European commentators to question the continued reliability of Russia as a supplier of natural gas. The role of Ukraine as an energy transit state was also put under the spotlight. The January 2009 crisis followed the conflict between Russia and Georgia in August 2008. This brief war had compelled governments in member states of the European Union (EU) to reconsider the wisdom of being dependent for over 40 percent of their gas imports from an increasingly emboldened and aggressive Russia. Attention has focussed more on developing projects which would supply natural gas to Europe from sources other than Russia along routes which would bypass Russian territory. The so-called “fourth” or “southern” gas corridor connecting the Caspian and Gulf regions and the Middle East to Europe (the other three corridors running to EU member states from Russia, Norway and north Africa), has been identified by the European Commission as Natural Gas (NG) Route Number 3 in the framework of the Trans-European energy networks (TEN-E)

Kinstate intervention in ethnic conflicts : Albania and Turkey compared

Albania and Turkey did not act in overtly irredentist ways towards their ethnic brethren in neighboring states after the end of communism. Why, nonetheless, did Albania facilitate the increase of ethnic conflict in Kosovo and Macedonia, while Turkey did not, with respect to the Turks of Bulgaria? I argue that kin-states undergoing transition are more prone to intervene in external conflicts than states that are not, regardless of the salience of minority demands in the host-state. The transition weakens the institutions of the kin-state. Experiencing limited institutional constraints, self-seeking state officials create alliances with secessionist and autonomist movements across borders alongside their own ideological, clan-based and particularistic interests. Such alliances are often utilized to advance radical domestic agendas. Unlike in Albania's transition environment, in Turkey there were no emerging elites that could potentially form alliances and use external movements to legitimize their own domestic existence or claims

A review of Cambrian lingulate brachiopods of England and Wales

The taxonomy of Cambrian lingulate (phosphatic shelled) brachiopods from England and Wales are reviewed in detail for the first time in nearly a century. 37 linguliformean brachiopod species, assigned to 23 genera, are described; 19 taxa are recorded in open taxonomy. Giving provisional names, three new genera, Svenjaella, Alexellus and Kayleigha are erected and nine new species are described (Chapter 4). Detailed cladistic analysis supports previous reports that Acrotretidae is a paraphyletic grouping of brachiopods which gave rise to other families within the Acrotretoidea (Chapter 6). Curticiidae is identified as lying outside the Acrotretoidea. The remaining families are supported as valid taxonomic units, albeit with some potential minor revisions. A new Scaphelasmatidae-Ceratretidae clade is consistently recovered. Support for the previously proposed subfamilies Neotretinae and Linnarssoniinae is partially recovered. The preservation of polygonal imprints of epithelial cells in lingulate brachiopods is reviewed and supplemented by new data (Chapter 7). The imprints are confirmed as representing moulds of epithelial cells as they are best preserved in areas where the shell has been thickened, and are similar in size to cells recorded in Lingula, the closest living relative to the extinct acrotretoids. Analysis of the morphology and sizes of cell-moulds demonstrates that there is no consistent relationship between cell width and valve size, and that they are not a useful taxonomic character within this group. The distribution of lingulate brachiopods across the Iapetus region is analysed using a number of statistical measures (Chapter 8). Although lingulate brachiopods have traditionally been considered to be of little utility in assessing palaeobiogeography, this analysis shows a clear palaeobiogeographic signal where lingulate faunas are sufficiently diverse, reflecting the history of the Iapetus ocean and the relative separation of Laurentia and Baltica through the Cambrian and Ordovician and provides confirmatory evidence that Palaeozoic lingulates had long-lived planktotrophic larvae.Open Acces

Investigating the Relationship between Politics and Education

This paper looks into how politics plays a role in the public K-12 education system in the United States, specifically looking at the state of New Hampshire. Federal, state, and local governments provide important resources through funding to schools and create the laws that govern them. However, educational politics can be controversial at times. Within the past several years, there have been more tense school board meetings and divisive laws being passed or considered around the nation. Overall, the divisive political climate has influenced much of the discussion surrounding education and has created more stress for educators, administrators, school staff, and students. It is integral to be aware of proposed laws or changes to existing laws to better support educators and students as they navigate through these divisive times

Reconstituting sovereignty: the Young Turks’ efforts to secure external recognition and the transition from the Ottoman Empire to the Republic of Turkey, 1908 - 1923

This thesis addresses the question of how states, meaning organised political communities, were historically able to secure their sovereignty through gaining the recognition of other states. As sovereignty refers to the presence of a state’s authority, its existence is premised on states and other internal and external actors recognising claims to sovereignty. Therefore, states, such as the Ottoman Empire, which historically had a different understanding of legitimacy, faced challenges to their sovereignty following the emergence of new global understandings of sovereignty in the late nineteenth century. The Ottoman Empire was distinct in that it was the only Islamic state that was not subject to and was able to avoid completely falling under the influence of then-dominant European states. However, the Ottoman Empire still experienced European intervention and there was a desire to end forms of European extraterritorial jurisdiction. Ottoman elites, who were affiliated with the reformist Young Turks, sought to secure recognition of their state’s sovereignty by reconstituting it along novel international standards of legitimate statehood. These standards were based on the concepts of “civilised”, “militarist”, “popular” and “national” statehood, and were reinterpreted by the Young Turks in the course of their efforts to secure the recognition of European powers. These efforts included diplomacy with European powers, institutional reform and conceptual innovation. However, it also involved engaging in practices associated with sovereignty such as the control of territory. In all of these areas, the Young Turks reinterpreted aspects of the existing Ottoman legacy of statehood and international norms, to secure their claim to sovereignty. Therefore, the Ottoman state elites sought to convey an impression of governing a state that could be recognised as sovereign by other European powers. Ultimately, the remnants of the Young Turks, secured international recognition of their state, reconstituted as the nation-state of Turkey in 1923