Fifty Million Elvis Fans Can’t be Wrong

This essay revisits some classic problems in the philosophy of space and time concerning the counting of possibilities. I argue that we should think that two Newtonian worlds can differ only as to when or where things happen and that general relativistic worlds can differ in something like the same way—the first of these theses being quaintly heterodox, the second baldly heretical, according to the mores of contemporary philosophy of physics

Intergenerational justice of what: welfare, resources or capabilities?

An important aspect of intergenerational justice concerns the specification of a 'currency of advantage' that can be used to evaluate distributive outcomes across time. Environmental theorists have introduced several innovative currencies of justice in recent years, such as ecological space and critical natural capital. However they have often downplayed the application of established currencies (such as welfare, resources or capabilities) to issues of futurity. After exploring the merits of a number of rival currencies, it is argued that the currency of 'capabilities to function' provides a promising basis for a theory of justice that takes seriously the rights and duties of intergenerational justice

To what extent is behaviour a problem in English schools?:Exploring the scale and prevalence of deficits in classroom climate

The working atmosphere in the classroom is an important variable in the process of education in schools, with several studies suggesting that classroom climate is an important influence on pupil attainment. There are wide differences in the extent to which classroom climate is considered to be a problem in English schools. Some ‘official’ reports suggest that behaviour in schools is ‘satisfactory or better’ in the vast majority of schools; other sources have pointed to behaviour being a serious and widespread problem. The paper details four studies conducted over the past decade which aimed to explore these disparities. The aim of the research was to gain a more accurate insight into the extent to which deficits in classroom climate limit educational attainment and equality of educational opportunity in English schools. The findings question the suggestion that behaviour is satisfactory or better in 99.7% of English schools and the concluding section suggests ways in which deficits in classroom climate might be addressed. Although the study is limited to classrooms in England, OECD studies suggest that deficits in the working atmosphere in classrooms occur in many countries. The study therefore has potential relevance for education systems in other countries

Educating for Autonomy: Liberalism and Autonomy in the Capabilities Approach

Martha Nussbaum grounds her version of the capabilities approach in political liberalism. In this paper, we argue that the capabilities approach, insofar as it genuinely values the things that persons can actually do and be, must be grounded in a hybrid account of liberalism: in order to show respect for adults, its justification must be political; in order to show respect for children, however, its implementation must include a commitment to comprehensive autonomy, one that ensures that children develop the skills necessary to make meaningful choices about whether or not to exercise their basic capabilities. Importantly, in order to show respect for parents who do not necessarily recognize autonomy as a value, we argue that the liberal state, via its system of public education, should take on the role of ensuring that all children within the state develop a sufficient degree of autonomy

Comparative genomics of proteins involved in RNA nucleocytoplasmic export

Background: The establishment of the nuclear membrane resulted in the physical separation of transcription and translation, and presented early eukaryotes with a formidable challenge: how to shuttle RNA from the nucleus to the locus of protein synthesis. In prokaryotes, mRNA is translated as it is being synthesized, whereas in eukaryotes mRNA is synthesized and processed in the nucleus, and it is then exported to the cytoplasm. In metazoa and fungi, the different RNA species are exported from the nucleus by specialized pathways. For example, tRNA is exported by exportin-t in a RanGTP-dependent fashion. By contrast, mRNAs are associated to ribonucleoproteins (RNPs) and exported by an essential shuttling complex (TAP-p15 in human, Mex67-mtr2 in yeast) that transports them through the nuclear pore. The different RNA export pathways appear to be well conserved among members of Opisthokonta, the eukaryotic supergroup that includes Fungi and Metazoa. However, it is not known whether RNA export in the other eukaryotic supergroups follows the same export routes as in opisthokonts. Methods: Our objective was to reconstruct the evolutionary history of the different RNA export pathways across eukaryotes. To do so, we screened an array of eukaryotic genomes for the presence of homologs of the proteins involved in RNA export in Metazoa and Fungi, using human and yeast proteins as queries. Results: Our genomic comparisons indicate that the basic components of the RanGTP-dependent RNA pathways are conserved across eukaryotes, and thus we infer that these are traceable to the last eukaryotic common ancestor (LECA). On the other hand, several of the proteins involved in RanGTP-independent mRNA export pathways are less conserved, which would suggest that they represent innovations that appeared later in the evolution of eukaryotes. Conclusions: Our analyses suggest that the LECA possessed the basic components of the different RNA export mechanisms found today in opisthokonts, and that these mechanisms became more specialized throughout eukaryotic evolution

Thousands of Rab GTPases for the Cell Biologist

Rab proteins are small GTPases that act as essential regulators of vesicular trafficking. 44 subfamilies are known in humans, performing specific sets of functions at distinct subcellular localisations and tissues. Rab function is conserved even amongst distant orthologs. Hence, the annotation of Rabs yields functional predictions about the cell biology of trafficking. So far, annotating Rabs has been a laborious manual task not feasible for current and future genomic output of deep sequencing technologies. We developed, validated and benchmarked the Rabifier, an automated bioinformatic pipeline for the identification and classification of Rabs, which achieves up to 90% classification accuracy. We cataloged roughly 8.000 Rabs from 247 genomes covering the entire eukaryotic tree. The full Rab database and a web tool implementing the pipeline are publicly available at www.RabDB.org. For the first time, we describe and analyse the evolution of Rabs in a dataset covering the whole eukaryotic phylogeny. We found a highly dynamic family undergoing frequent taxon-specific expansions and losses. We dated the origin of human subfamilies using phylogenetic profiling, which enlarged the Rab repertoire of the Last Eukaryotic Common Ancestor with Rab14, 32 and RabL4. Furthermore, a detailed analysis of the Choanoflagellate Monosiga brevicollis Rab family pinpointed the changes that accompanied the emergence of Metazoan multicellularity, mainly an important expansion and specialisation of the secretory pathway. Lastly, we experimentally establish tissue specificity in expression of mouse Rabs and show that neo-functionalisation best explains the emergence of new human Rab subfamilies. With the Rabifier and RabDB, we provide tools that easily allows non-bioinformaticians to integrate thousands of Rabs in their analyses. RabDB is designed to enable the cell biology community to keep pace with the increasing number of fully-sequenced genomes and change the scale at which we perform comparative analysis in cell biology

Rab protein evolution and the history of the eukaryotic endomembrane system

Spectacular increases in the quantity of sequence data genome have facilitated major advances in eukaryotic comparative genomics. By exploiting homology with classical model organisms, this makes possible predictions of pathways and cellular functions currently impossible to address in intractable organisms. Echoing realization that core metabolic processes were established very early following evolution of life on earth, it is now emerging that many eukaryotic cellular features, including the endomembrane system, are ancient and organized around near-universal principles. Rab proteins are key mediators of vesicle transport and specificity, and via the presence of multiple paralogues, alterations in interaction specificity and modification of pathways, contribute greatly to the evolution of complexity of membrane transport. Understanding system-level contributions of Rab proteins to evolutionary history provides insight into the multiple processes sculpting cellular transport pathways and the exciting challenges that we face in delving further into the origins of membrane trafficking specificity

Liberal Neutrality and Charitable Purposes

Under UK charity law, organisations seeking charitable status must demonstrate, inter alia, that they will pursue a purpose the state deems ‘charitable’. Such purposes inevitably reflect conceptions of the good, thus it is argued here that the state, in granting charitable status, affirms the value of ideas about the good; it indicates that a set of conceptions of the good are worthy of special advantages that are not provided for the pursuit of other conceptions. The designation of charitable status appears to be at odds with liberal neutrality, which argues that the state should not pursue, promote or pass judgement on particular conceptions of the good. In short, there is a prima facie tension between the general liberal neutrality doctrine and charity law. Yet liberal neutralists have not addressed this policy area. This article surveys the grounds for reconciliation between some conceptions of liberal neutrality and the present charity law. ‘Neutrality of effect’ addresses some concerns but its implications for charity law are not in accord with the general practice and principles regarding charities. Barry's process of abstraction is argued to be untenable as a policy option for charities. The article concludes that in so far as one is neutralist, ‘neutrality of justification’ in the form of neutral goods provides the most plausible account of charity law. However, such an account entails alterations to the existing legislation that one may view as a failure to account for well-established, legitimate principles and traditions in charity law. </jats:p