Correction of a mouse model of Menkes disease by the human Menkes gene

The brindled mouse is an accurate model of the fatal human X-linked copper deficiency disorder, Menkes disease. Males carrying the mutant allele of the Menkes gene orthologue Atp7a die in the second week of life. To determine whether the genetic defect in the brindled mice could be corrected by expression of the human Menkes gene, male transgenic mice expressing ATP7A from the chicken β-actin composite promoter (CAG) were mated with female carriers of the brindled mutation (Atp7aMo-br). Mutant males carrying the transgene survived and were fertile but the copper defect was not completely corrected. Unexpectedly males corrected with one transgenic line (T25#5) were mottled and resembled carrier females, this effect appeared to be caused by mosaic expression of the transgene. In contrast, males corrected with another line (T22#2) had agouti coats. Copper concentrations in tissues of the rescued mutants also resembled those of the heterozygous females, with high levels in kidney (84.6 ± 4.9 μg/g in corrected males vs. 137.0 ± 44.3 μg/g in heterozygotes) and small intestine (15.6 ± 2.5 μg/g in corrected males vs. 15.7 ± 2.8 μg/g in heterozygotes). The results show that the Menkes defect in mice is corrected by the human Menkes gene and that adequate correction is obtained even when the transgene expression does not match that of the endogenous gene.

Une methode graphique pour interpreter et representer des classes

Dans ce papier, une technique simple pour représenter et interpréter des classes est proposée. La méthode comprends deux phases et s’appuie sur un centrage-réduction des variables initiales et sur une analyse factorielle d’un tableau croisé qui contient les sommes des variables initiales par classe. Il en résulte un graphique qui met en évidence les différences entre les classes.

Arts governance - marching Western models to Asia

Corporate failures and fraud have turned attention to company governance. While much of the literature is on for-profit governance, there is a steadily increasing non-profit literature arguing for industry specific governance studies, such as this one. Researching arts organisation governance in Asia, where profitability or sustainability are not the only measures for performance, provides a better understanding of theses cultures and economies. Here, a comparative review of arts governance is undertaken in order to inform debate in a discipline and in countries less frequently included in analysis. The Hong Kong Special Administrative Region (SAR) and Singapore are included in this brief review of Asian governance. What constitutes good governance and the unique cultural variables in each region are considered.

Toward a new understanding of the social impact of the arts

Australia was pivotal in placing empirical study of the social impact of the arts on the map, and yet, a lack of continued robust research has meant that it no longer holds this place. Despite a general acceptance within the arts and health industries that the arts can have positive social impacts, there is little robust evidence to prove this. This paper reviews existing research, finding three primary debates around meaning, methodology, and mastery. This paper recommends a holistic approach to arts impact studies that juxtapose the social and intrinsic impacts. This paper is part of a larger research project into the impact of the arts that will redeem Australia’s place as leaders in social impact of the arts studies.

On the margins : a study of the representation of the arts in the news pages of the newspaper

The principal objective of this paper is to investigate how the arts are represented in the Australian print media. The research is conducted by means of textual analysis focusing on a number of case studies where arts stories appeared in the news pages of an Australian daily broadsheet newspaper. This paper argues that in these case studies the arts are represented in terms of a limited range of rhetorical frameworks. These frameworks help constitute public knowledge about the arts and their marginalised status in Australia. This paper offers a critique of current arts policy which fails to recognise the role of the media in reinforcing the marginalisation of the arts.

The impact of under-estimated length of jobs on EASY-backfill scheduling

The issue of under-estimated length of jobs (parallel applications) on backfill-based scheduling is ignored in the current literature because users want to avoid their jobs to be killed when the requested time expires. Therefore, users prefer to over-estimate the length of their jobs. This paper shows the impact of underestimated length of jobs on their execution performance in an EASY-backfill scheduling-based system. We have developed a batch job scheduler for Linux clusters that implements an enhanced EASY- backfilling algorithm in such a way that a job with an under-estimated execution time would not be killed unless it would delay other jobs. We have carried out performance evaluation by scheduling static workloads of well known MPI parallel applications on a real cluster. Our results show that most of the jobs do not have to be aborted even though their job lengths are under-estimated whereas the slowdown of jobs and the throughput of the system are only slightly degraded.

COPD results in a reduction in UCP3 long mRNA and UCP3 protein content in types I and IIa skeletal muscle fibers.

Purpose: Findings recently have shown coupling protein-3 (UCP3) content to be decreased in the skeletal muscle of patients with chronic obstructive pulmonary disease (COPD). Uncoupling protein-3 mRNA exists as two isoforms: long (UCP3L) and short (UCP3S). The UCP3 protein is expressed the least in oxidative and the most in glycolytic muscle fibers. Levels of UCP3 have been associated positively with intramyocellular triglyceride (IMTG) contents in conditions of altered fatty acid metabolism. As a source for muscle free fatty acid metabolism, IMTG is decreased in COPD. The current study completely characterized all the parameters of UCP3 expression (ie, UCP3L and UCP3S mRNA expression in whole muscle samples) and UCP3 protein content as well as IMTG content in the different fiber types in patients with COPD and healthy control subjects.

Methods: Using real-time polymerase chain reaction, UCP3 gene expression was quantified. Skeletal muscle fiber type and UCP3 protein and IMTG content were measured using immunofluorescence and Oil red oil staining, respectively.

Results: The findings showed that UCP3L mRNA expression was 44% lower (P < .005) in the patients with COPD than in the control subjects, whereas the UCP3S mRNA content was similar in the two groups. As compared with control subjects, UCP3 protein content was decreased by 89% and 83% and the IMTG content by 64% and 54%, respectively, in types I and IIa fibers (P < .0167) of patients with COPD, whereas they were unchanged in IIx fibers.

Conclusions: The reduced UCP3 and IMTG content in the more oxidative fibers may be linked to the altered muscle fatty acid metabolism associated with COPD. Further studies are required to determine the exact role and clinical relevance of the reduced UCP3 content in patients with COPD.

The role of copper transport proteins in the small intestines

Physiological copper homeostasis involves striking a balance between absorption and secretion. ATP7A was identified at the trans-Golgi network but relocalized to vesicles under copper exposure in the intestine. This suggests that ATP7A may be a rate limiting step in intestinal uptake of copper.

Diversity and clonotypic composition of influenza-specific CD8+ TCR repertoires remain unaltered in the absence of Aire

TCR repertoire diversity is important for the protective efficacy of CD8⁺ T cells, limiting viral escape and cross-reactivity between unrelated epitopes. The exact mechanism for selection of restricted versus diverse TCR repertoires is far from clear, although one thought is that the epitopes resembling self-peptides might select a limited array of TCR due to the deletion of autoreactive TCR. The molecule Aire promotes the expression of tissue-specific Ag on thymic medullary epithelial cells and the deletion of autoreactive cells, and in the absence of Aire autoreactive cells persist. However, the contribution of Aire-dependent peptides to the selection of the Ag-specific TCR repertoire remains unknown. In this study, we dissect restricted (D^bNP₃₆₆%⁺CD8⁺) and diverse (D^bPA₂₂₄%⁺CD8⁺, K^dNP₁₄₇%⁺CD8⁺) TCR repertoires responding to three influenza-derived peptides in Aire-deficient mice on both B6 and BALB/c backgrounds. Our study shows that the number, qualitative characteristics and TCR repertoires of all influenza-specific, D^bNP₃₆₆%⁺CD8⁺, D^bPA₂₂₄%⁺CD8⁺ and K^dNP₁₄₇%⁺CD8⁺ T cells are not significantly altered in the absence of Aire. This provides the first demonstration that the selection of an Ag-specific T-cell repertoire is not significantly perturbed in the absence of Aire.

The Sophists (Ancient Greek)

The sophists were itinerant professional teachers and intellectuals who frequented Athens and other Greek cities in the second half of the fifth century B.C.E. In return for a fee, the sophists offered young wealthy Greek men an education in aretē (virtue or excellence), thereby attaining wealth and fame while also arousing significant antipathy. Prior to the fifth century B.C.E., aretē was predominately associated with aristocratic warrior virtues such as courage and physical strength. In democratic Athens of the latter fifth century B.C.E., however, aretē was increasingly understood in terms of the ability to influence one’s fellow citizens in political gatherings through rhetorical persuasion; the sophistic education both grew out of and exploited this shift. The most famous representatives of the sophistic movement are Protagoras, Gorgias, Antiphon, Hippias, Prodicus and Thrasymachus.

The historical and philological difficulties confronting an interpretation of the sophists are significant. Only a handful of sophistic texts have survived and most of what we know of the sophists is drawn from second-hand testimony, fragments and the generally hostile depiction of them in Plato’s dialogues.

The philosophical problem of the nature of sophistry is arguably even more formidable. Due in large part to the influence of Plato and Aristotle, the term sophistry has come to signify the deliberate use of fallacious reasoning, intellectual charlatanism and moral unscrupulousness. It is, as the article explains, an oversimplification to think of the historical sophists in these terms because they made genuine and original contributions to Western thought. Plato and Aristotle nonetheless established their view of what constitutes legitimate philosophy in part by distinguishing their own activity – and that of Socrates – from the sophists. If one is so inclined, sophistry can thus be regarded, in a conceptual as well as historical sense, as the ‘other’ of philosophy.

Perhaps because of the interpretative difficulties mentioned above, the sophists have been many things to many people. For Hegel (1995/1840) the sophists were subjectivists whose sceptical reaction to the objective dogmatism of the presocratics was synthesised in the work of Plato and Aristotle. For the utilitarian English classicist George Grote (1904), the sophists were progressive thinkers who placed in question the prevailing morality of their time. More recent work by French theorists such as Jacques Derrida (1981) and Jean Francois-Lyotard (1985) suggests affinities between the sophists and postmodernism.

This article provides a broad overview of the sophists, and indicates some of the central philosophical issues raised by their work. Section 1 discusses the meaning of the term sophist. Section 2 surveys the individual contributions of the most famous sophists. Section 3 examines three themes that have often been taken as characteristic of sophistic thought: the distinction between nature and convention, relativism about knowledge and truth and the power of speech. Finally, section 4 analyses attempts by Plato and others to establish a clear demarcation between philosophy and sophistry.