Post-transcriptional regulation of the cystic fibrosis gene in cardiac development and hypertrophy

Eukaryotic gene expression, reflected in the amount of steady-state mRNA, is regulated at the post-transcriptional level. The 5'-untranslated regions (5'-UTRs) of some transcripts contain cis-acting elements, including upstream open reading frames (uORFs), that have been identified as being fundamental in modulating translation efficiency and mRNA stability. Previously, we demonstrated that uORFs present in the 5'-UTR of cystic fibrosis transmembrane conductance regular (CFTR) transcripts expressed in the heart were able to modulate translation efficiency of the main CFTR ORF. Here, we show that the same 5'-UTR elements are associated with the differential stability of the 5'-UTR compared to the main coding region of CFTR transcripts. Furthermore, these post-transcriptional mechanisms are important factors governing regulated CFTR expression in the heart, in response to developmental and pathophysiological stimuli. (C) 2004 Elsevier Inc. All rights reserved.

Origin of the Archean Sask craton and its extent within the Trans-Hudson orogen: evidence from Pb and Nd isotopic compositions of basement rocks and post-orogenic intrusions

U-Pb zircon ages from the exposed Sask craton are 2450-3100 Ma, from the Peter Lake Domain 2575-2640 Ma, and from rocks of the Trans-Hudson orogen 1840-1880 Ma. U-Pb monazite and zircon ages of post-orogenic pegmatites and aplites are 1770-1800 Ma. Common Pb and Sm-Nd isotopic compositions of post-orogenic intrusions, as probes of crust beneath the orogen, were compared to Sask craton rocks and ca. 1850 Ma orogenic rocks to infer the origin and subsurface distribution of the Sask craton within the internides of the Trans-Hudson orogen. Results show that post-orogenic intrusions within most of the Glennie Domain and Hanson Lake block were derived, at least in part, from Archean source materials, demonstrating that the Sask craton lies beneath Paleoproterozoic orogenic rocks present at the surface. In contrast, common Pb and Sm-Nd isotopic compositions from pegmatites and aplites of the La Ronge Domain are essentially identical with those of the Paleoproterozoic orogenic rocks into which they are intruded, indicating derivation by partial melting of similar rocks. Thus, if the Sask craton extended to the west beneath the La Ronge Domain, it was beneath the zone of melting that produced the post-orogenic intrusions, making it unlikely that the Sask craton is a detached part of the Hearne craton. Many samples from the Sask craton have elevated Pb-208/Pb-204 ratios, unlike Superior craton or Hearne craton rocks, suggesting that the Sask craton was derived from an exotic source, such as the Wyoming craton, which shares similar elevated Pb-208/Pb-204 ratios.

Post-Fordism, the welfare state and the personal social services: A comparison of Australia and Britain

The Post-Fordist welfare state thesis locates contemporary social welfare change within a wider analysis of the transformation of capitalist accumulation regimes. Whilst this analysis is useful in directing attention to macro socio-economic change, it has for the most part contained three shortcomings. First, the Post-Fordist thesis has overemphasized the role of historical 'breaks' in the development of social welfare as it purportedly passes from Fordism to Post-Fordism. Second, the thesis has assumed a degree of convergence between welfare states as a result of global economic forces. In doing so, it has underemphasized the mediating impact of existing institutional arrangements within nations. Third, the thesis has assumed, rather than demonstrated, the specific changes which are alleged to be taking place in various fields of social welfare. As a consequence, aspects of continuity in social welfare have been neglected. These three lacunae are addressed through a comparative analysis of developments in the personal social services in Australia and Britain. Services to older people are employed as the specific context of comparison in relation to three dimensions of measuring transformation along a Post-Fordist trajectory: a shift from a unitary economy to a mixed economy of service provision; changes in the model of service delivery and consumption; and strengthening the governance function of the central state. This comparative analysis suggests the need for refinement of the Post-Fordist welfare state thesis concerning the restructuring of social welfare and its impact on the personal social services.

Altering the ribosomal subunit ratio in yeast maximizes recombinant protein yield

Background The production of high yields of recombinant proteins is an enduring bottleneck in the post-genomic sciences that has yet to be addressed in a truly rational manner. Typically eukaryotic protein production experiments have relied on varying expression construct cassettes such as promoters and tags, or culture process parameters such as pH, temperature and aeration to enhance yields. These approaches require repeated rounds of trial-and-error optimization and cannot provide a mechanistic insight into the biology of recombinant protein production. We published an early transcriptome analysis that identified genes implicated in successful membrane protein production experiments in yeast. While there has been a subsequent explosion in such analyses in a range of production organisms, no one has yet exploited the genes identified. The aim of this study was to use the results of our previous comparative transcriptome analysis to engineer improved yeast strains and thereby gain an understanding of the mechanisms involved in high-yielding protein production hosts. Results We show that tuning BMS1 transcript levels in a doxycycline-dependent manner resulted in optimized yields of functional membrane and soluble protein targets. Online flow microcalorimetry demonstrated that there had been a substantial metabolic change to cells cultured under high-yielding conditions, and in particular that high yielding cells were more metabolically efficient. Polysome profiling showed that the key molecular event contributing to this metabolically efficient, high-yielding phenotype is a perturbation of the ratio of 60S to 40S ribosomal subunits from approximately 1:1 to 2:1, and correspondingly of 25S:18S ratios from 2:1 to 3:1. This result is consistent with the role of the gene product of BMS1 in ribosome biogenesis. Conclusion This work demonstrates the power of a rational approach to recombinant protein production by using the results of transcriptome analysis to engineer improved strains, thereby revealing the underlying biological events involved.

Comparing German and British political culture through values : and analysis of the values of health care reform

This research sets out to compare the values in British and German political discourse, especially the discourse of social policy, and to analyse their relationship to political culture through an analysis of the values of health care reform. The work proceeds from the hypothesis that the known differences in political culture between the two countries will be reflected in the values of political discourse, and takes a comparison of two major recent legislative debates on health care reform as a case study. The starting point in the first chapter is a brief comparative survey of the post-war political cultures of the two countries, including a brief account of the historical background to their development and an overview of explanatory theoretical models. From this are developed the expected contrasts in values in accordance with the hypothesis. The second chapter explains the basis for selecting the corpus texts and the contextual information which needs to be recorded to make a comparative analysis, including the context and content of the reform proposals which comprise the case study. It examines any contextual factors which may need to be taken into account in the analysis. The third and fourth chapters explain the analytical method, which is centred on the use of definition-based taxonomies of value items and value appeal methods to identify, on a sentence-by-sentence basis, the value items in the corpus texts and the methods used to make appeals to those value items. The third chapter is concerned with the classification and analysis of values, the fourth with the classification and analysis of value appeal methods. The fifth chapter will present and explain the results of the analysis, and the sixth will summarize the conclusions and make suggestions for further research.

Did mass privatisation really increase post-communist male mortality?

A recent article in the Lancet, by David Stuckler, Larry King and Martin McKee, investigated anew the fluctuations in adult male mortality rates that have come to characterise the so-called post-communist mortality crisis. Adopting a cross-country, time-series perspective the authors examined how the economic policy strategies of the 1990s impacted upon observed fluctuations in mortality. They conclude that the adoption of a strategy of rapid (mass) privatisation contributed to the adverse mortality trends. We subject that finding to closer scrutiny using the same data from which the Stuckler et al claim stems. We find that their claim that mass privatisation adversely affected male mortality trends in the post-Communist world does not stand up to closer examination. It is not supported empirically and is at odds with what we know about both transition in the post-communist world and about health trends over time in this region.

Managing the threat of terrorism in British travel and leisure organizations

Purpose - To study how the threats of terrorism are being handled by a variety of UK companies in the travel and leisure sector in the UK in the post 9/11 era. Design/methodology/approach - A review of the literature of risk management in a world that is perceived to be more risky as a result of the terrorist attacks on the US on 11 September 2001 (9/11) is presented. Describes the application of theories of organizational resilience and institutions to frame an understanding of how managers make sense of terrorism risk and comprehend uncertainty. Reports a qualitative analysis of themes in interviews conducted with 25 managers from 6 unnamed organizations in the aviation industry (3 organizations) and the UK travel and leisure industry (3 organizations), representing a catering supplier, an airport, an airline, a tour company, a convention centre, and an arts and entertainment centre. Findings - The results indicated that the three organizations in the aviation industry prioritize threats from terrorism, whilst the three organizations in the leisure and travel sector do not, suggesting that the managers in the travel and leisure industry apply a probabilistic type of thinking and believe the likelihood of terrorism to be low. Reports that they give precedence to economic concerns and numerous other threats to the industry. Concludes that managers fall prey to the 'ludic fallacy', which conceives all odds as being calculable and hence managers conceive the terrorism risk as low while also expecting institutional factors to pre-empt and control terrorism threats, a reaction which the authors believe to be rather complacent and dangerous. Originality/value - Contributes to the research literature on risk management by revealing the gap in the ability of existing management tools and methodologies to deal with current and uncertain threats facing organizations due to terrorism.

Reinstatement of flood affected properties:experiences of SMEs affected by the 2009 Cockermouth flood event

Recent policy changes in the UK encourage at-risk communities to learn to live with and adapt to flooding. Adaptation of individual properties by embracing resilient and resistant measures is an important aspect endorsed therein. Uptake of such protection measures by property owners, including that of Small and Medium-sized Enterprises (SMEs), has traditionally been low. A post-flood situation offers an opportunity to reinstate / reconstruct by integrating flood protection measures, in such a way that reduce damage and enhance the ability to recover in the event of a future flood incidence. In order to investigate the reinstatement / reconstruction experiences of flood affected SMEs, those affected by the 2009 Cockermouth flood event were studied. The results of a questionnaire survey revealed that many SMEs have opted for traditional reinstatement rather than resilient reinstatement. A detailed case study revealed requirements of getting the business back and running as soon as possible, a lack of guidance and advice from professionals and financial concerns as some of the barriers faced by SMEs. It is important that SMEs are provided with necessary guidance during the post-flood reinstatement stage, in order to make sure that the opportunity to build back better, integrating flood-protection measures is grasped by the SME owners. Stakeholders related to the construction industry, who are actively involved with post-flood reinstatement work, have an important role to play in this regard, providing necessary guidance and expertise to flooded SMEs.

Post-revolutionary post-modernism: Central American detective fiction by the turn of the 21st century

Contemporary Central American fiction has become a vital project of revision of the tragic events and the social conditions in the recent history of the countries from which they emerge. The literary projects of Sergio Ramirez (Nicaragua), Dante Liano (Guatemala), Horacio Castellanos Moya (El Salvador), and Ramon Fonseca Mora (Panama), are representative of the latest trends in Central American narrative. These trends conform to a new literary paradigm that consists of an amalgam of styles and discourses, which combine the testimonial, the historical, and the political with the mystery and suspense of noir thrillers. Contemporary Central American noir narrative depicts the persistent war against social injustice, violence, criminal activities, as well as the new technological advances and economic challenges of the post-war neo-liberal order that still prevails throughout the region. ^ Drawing on postmodernism theory proposed by Ihab Hassan, Linda Hutcheon and Brian MacHale, I argued that the new Central American literary paradigm exemplified by Sergio Ramirez's El cielo llora por mí, Dante Liano's El hombre de Montserrat, Horacio Castellanos Moya's El arma en el hombre and La diabla en el espejo , and Ramon Fonseca Mora's El desenterrador, are highly structured novels that display the characteristic marks of postmodern cultural expression through their ambivalence, which results from the coexistence of multiple styles and conflicting ideologies and narrative trends. The novels analyzed in this dissertation make use of a noir sensitivity in which corruption, decay and disillusionment are at their core to portray the events that shaped the modern history of the countries from which they emerge. The revolutionary armed struggle, the state of terror imposed by military regimes and the fight against drug trafficking and organized crime, are among the major themes of these contemporary works of fiction, which I have categorized as perfect examples of the post-revolutionary post-modernism Central American detective fiction at the turn of the 21st century.^

An Analysis on the Decline in the Authoritative Powers of the Papacy and its Application to Challenges to Authoritative Powers Faced By the Permanent Membership of the UN Security Council

The organizational authority of the Papacy in the Roman Catholic Church and the permanent membership of the UN Security Council are unique from institutions that are commonly compared with the UN, like the Concert of Europe and the League of Nations, in that these institutional organs possessed strong authoritative and veto powers. Both organs also owe their strong authority during their founding to a need for stability: The Papacy after the crippling of Western Roman Empire and the P-5 to deal with the insecurities of the post-WWII world. While the P-5 still possesses similar authoritative powers within the Council as it did after WWII, the historical authoritative powers of the Papacy within the Church was debilitated to such a degree that by the time of the Reformation in Europe, condemnations of practices within the Church itself were not effective. This paper will analyze major challenges to the authoritative powers of the Papacy, from the crowning of Charlemagne to the beginning of the Reformation, and compare the analysis to challenges affecting the authoritative powers of the P-5 since its creation. From research conducted thus far, I hypothesize that common themes affecting the authoritative powers of the P-5 and the Papacy would include: major changes in the institutions organization (i.e. the Avignon Papacy and Japan’s bid to become a permanent member); the decline in power of actors supporting the institutional organ (i.e. the Holy Roman Empire and the P-5 members); and ideological clashes affecting the institution’s normative power (i.e. the Great Western Schism and Cold War politics).

An Analysis on the Decline in the Authoritative Powers of the Papacy and its Application to Challenges to Authoritative Powers Faced By the Permanent Membership of the UN Security Council

The organizational authority of the Papacy in the Roman Catholic Church and the permanent membership of the UN Security Council are unique from institutions that are commonly compared with the UN, like the Concert of Europe and the League of Nations, in that these institutional organs possessed strong authoritative and veto powers. Both organs also owe their strong authority during their founding to a need for stability: The Papacy after the crippling of Western Roman Empire and the P-5 to deal with the insecurities of the post-WWII world. While the P-5 still possesses similar authoritative powers within the Council as it did after WWII, the historical authoritative powers of the Papacy within the Church was debilitated to such a degree that by the time of the Reformation in Europe, condemnations of practices within the Church itself were not effective. This paper will analyze major challenges to the authoritative powers of the Papacy, from the crowning of Charlemagne to the beginning of the Reformation, and compare the analysis to challenges affecting the authoritative powers of the P-5 since its creation. From research conducted thus far, I hypothesize that common themes affecting the authoritative powers of the P-5 and the Papacy would include: major changes in the institutions organization (i.e. the Avignon Papacy and Japan’s bid to become a permanent member); the decline in power of actors supporting the institutional organ (i.e. the Holy Roman Empire and the P-5 members); and ideological clashes affecting the institution’s normative power (i.e. the Great Western Schism and Cold War politics).

Assessing the legacy of the pine point mine: post-industrial land cover and land use

While mining is a major component of the northern Canadian economy, including the contemporary mixed economy of Aboriginal communities, it often leaves legacies of environmental and economic transformation that persist after closure. The legacies of historical mines in northern Canada challenge industry claims of sustainability. This thesis addresses how industrial mineral development and closure continue to affect local environments and economies after abandonment. The abandoned Pine Point mine in the Northwest Territories provides a case study for explaining the ongoing relationships among land cover, land use, and the post-industrial landscape. Drawing from landscape ecology and micropolitical ecology, I adopt an interdisciplinary approach to examine environmental and socioeconomic changes in the wake of industrial development and closure at Pine Point. The results show that passive reclamation is not sufficient for restoring ecological function in a subarctic environment. Land use, however, persists as land users adapt to the post-industrial landscape despite grave concern about its environmental condition. If mining is to be considered sustainable, decommissioning and reclamation must explicitly account for long-term environmental transformation as well as ongoing post-industrial land use, particularly in Aboriginal contexts.

Post-Political Ontologies and the Problems of Anti-Anthropocentrism: Reply to Tsouvalis

Judith Tsouvalis mounts a lively and interesting critique of the post-foundational Left’s theorisations through the marshalling of Latourian insights into the possibilities for a more grounded, pragmatic and concrete approach to political action. Tsouvalis takes Latour’s appropriation of John Dewey’s philosophical pragmatism (classically stated in the 1927 [1954] work, The Public and Its Problems) to argue that problems enable Dingpolitik – object or problem-orientated politics – through assembling concrete plural publics around matters of shared concern and contestation. She counter positions this pragmatic politics of concern, through which new communities of understanding are formed, to the abstract and ‘anthropomorphic’ critiques of the ‘post-political condition’ which offer little in the way of a constructive engagement in the collective making of a better world.

The magical transformation contest in the ancient storytelling tradition

El concurso de transformación mágica, esquema narrativo difundido en la tradición popular, se presenta en dos variantes principales: los hechiceros que compiten pueden metamorfosearse en varios seres o crear esos seres por medios mágicos. En cualquier caso el concursante ganador da a luz criaturas más fuertes que superan las de su oponente. La segunda variante fue preferida en el antiguo Cercano Oriente (Sumeria, Egipto, Israel). La primera se puede encontrar en algunos mitos griegos sobre cambiadores de forma (por ejemplo, Zeus y Némesis). El mismo esquema narrativo puede haber influido en un episodio de la Novela de Alejandro (1.36-38), en el que Darío envía regalos simbólicos a Alejandro y los dos monarcas enemigos ofrecen contrastantes explicaciones de ellos. Esta historia griega racionaliza el concurso de cuento de hadas, transfiriendo las fantásticas hazañas de creaciones milagrosas a un plano secundario pero realista de metáfora lingüística.

Through Class Darkly: Class in the British TV Noir

Class has always been at the heart of the television crime drama. Whether it is the post-war paternalism of Dixon of Dock Green (1955 – 1976), the harsh social realism of The Sweeney (1975-1978), or the almost mythical evocations of Britain in Heartbeat (1992 – 2010) and Midsomer Murders (1997- present), class and crime have always been seen as being inextricably linked. Since the 1990s, the British crime drama has been influenced by successive waves of cultural imports from, firstly, the US and then from Scandinavia. There is now a recognisable ‘genre’ for what we might think of as British TV Noir. Beginning with shows such as Cracker (1993 – 2006), Prime Suspect (1991 – 2006) and Messiah (2001) and continuing with dramas like Red Riding (2008), Southcliffe (2013) and Hinterland (2013 – present), the British TV Noir employs narratives and stylistic tropes that might usually be associated with the cinema of the 1940s. Although drawing influence from high profile shows such as Twin Peaks (1990 – 1991), Millennium (1996) and (latterly) The Wire (2002 – 2008), CSI (2000 – present) and The Killing (2007) these British Noir shows also articulate the nation’s shifting class system. As Susan Sydney-Smith has ably demonstrated, the crime drama is “historically contingent” (Sydney-Smith, 2002, p. 5) and shaped by the surrounding socio-political, as well aesthetic, context. To this end, this chapter traces the depiction of class in three key crime series – Prime Suspect, Red Riding and Southcliffe - and explores how social class, and more importantly, its changing face provides a constant background to the narratives and characterisations. These three texts were each produced at pivotal moments in Britain’s relationship to class – Prime Suspect was shown 6 months after Margaret Thatcher vacated office; Red Riding was produced in the midst of the global recession in 2008 and Southcliffe was made in the shadows of stringing welfare and immigration reforms. These texts span three successive political administrations and over two decades of social and political change. Understanding the relationship between criminal activity and class in these dramas however is far more complicated than simply reading the historical context through the text. Commensurate with its cinematic incarnation, TV Noir is both reflective and productive, employing visual and narrative tropes to manipulate, as well reflect, its audience’s moral and social positioning. The picture that emerges from an examination of class and the British TV Noir is one of suspicion and discontent. As Andrew Spicer suggests (with reference to British cinema) the Noir sensibility both depicts and critiques a society that it sees as being “class-ridden, racist and misogynist” (Spicer, 2002, p.202). This is certainly the case with the texts that are being examined here, as social positions and taxonomies are constantly being redefined and renegotiated.