Murine model of autosomal dominant retinitis pigmentosa generated by targeted deletion at codon 307 of the rds-peripherin gene

We introduced a targeted single base deletion at codon 307 of the rds-peripherin gene in mice, similar mutations being known to cause autosomal dominant retinitis pigmentosa (RP) in man. Histopathological and electroretinographic analysis indicate that the retinopathy in mice homozygous for the codon 307 mutation appears more rapid than that in the naturally occurring null mutant, the rds(-/-) mouse, suggesting that the rds-307 mutation displays a dominant negative phenotype in combination with that due to haplosufficiency. RP is the most prevalent cause of registered visual handicap in those of working age in developed countries, the 50 or so mutations so far identified within the RDS-peripherin gene accounting for up to 10% of dominant cases of the disease. Given the sequence homologies that exist between the murine rds-peripherin and the human RDS-peripherin gene, this disease model, the first to be generated for peripherin-based RP using gene targeting techniques, should in principle be of value in the work-up in mice of therapeutics capable of targeting transcripts derived from the human gene.

An Irish three-generation family of Cornelia de Lange syndrome displaying autosomal dominant inheritance

The existence of familial de Lange syndrome has been documented in sibs and in parent-child families, but the inheritance pattern continues to be the cause of much debate. We describe a classically affected neonate with de Lange syndrome, an affected mother and probably affected maternal grandmother. These cases show evidence for a dominantly inherited syndrome with a de Lange phenotype.

Le 'bon Allemand' dans le roman français de l'immédiat après-Seconde Guerre mondiale: une erreur de casting?

The end of the Occupation, which was much more violent than its beginning, dramatically affected the overall perception of Germans and Germany for many years in post-WWII France. This vision is of course reflected to a large extent in French literature. Yet, paradoxically, many novels—including the ‘best-sellers’ E ´ ducation europe´enne (1945) by Romain Gary, Mon Village a` l’heure allemande (1945) by Jean-Louis Bory or Les Foreˆts de la nuit (1947) by Jean-Louis Curtis—contain a ‘good German’ character. Firstly, this article will give an overview of the dominant representations of Germans in post-WWII France, before suggesting that the ‘good German’ character follows both a literary tradition and the humanist values of the French Resistance, to which these writers claim to subscribe. Finally, it will show how this character, far from blurring the Manichean ideology of the novel in which he appears, actually reinforces it.

The Type Ic SN 2007gr: a census of the ejecta from late-time optical-infrared spectra

Nebular spectra of supernovae (SNe) offer an unimpeded view of the inner region of the ejecta, where most nucleosynthesis takes place. Optical spectra cover most, but not all, of the emitting elements and therefore offer only a partial view of the products of the explosion. Simultaneous optical-infrared spectra, on the other hand, contain emission lines of all important elements, from C and O through to the intermediate mass elements (IME) Mg, Si, S, Ca and to Fe and Ni. In particular, Si and S are best seen in the IR. The availability of IR data makes it possible to explore in greater detail the results of the explosion. SN 2007gr is the first Type Ic SN for which such data are available. Modelling the spectra with a non-local thermodynamic equilibrium (NLTE) code reveals that the inner ejecta contain similar to 1M(circle dot) of material within a velocity of approximate to 4500 km s(-1). The same mass of Ni-56 derived from the light-curve peak (0.076M(circle dot)) was used to power the spectrum, yielding consistent results. Oxygen is the dominant element, contributing similar to 0.8M(circle dot). The C/O ratio is

Local Area Plans: Best Practice Manual

This Manual has been prepared as a companion document for the Planning Guidelines, Local Area Plans: Creating Sustainable Communities - Guidelines for Planning Authorities (Hereafter referred to as ‘The Planning Guidelines’).

The aim of the Manual is to reinforce the key aspects of the Planning Guidelines by emphasising better and more consistent processes and highlighting examples of good practice.

Evidential Holism and Indispensability Arguments

The indispensability argument is a method for showing that abstract mathematical objects exist (call this mathematical Platonism). Various versions of this argument have been proposed (§1). Lately, commentators seem to have agreed that a holistic indispensability argument (§2) will not work, and that an explanatory indispensability argument is the best candidate. In this paper I argue that the dominant reasons for rejecting the holistic indispensability argument are mistaken. This is largely due to an overestimation of the consequences that follow from evidential holism. Nevertheless, the holistic indispensability argument should be rejected, but for a different reason (§3)—in order that an indispensability argument relying on holism can work, it must invoke an unmotivated version of evidential holism. Such an argument will be unsound. Correcting the argument with a proper construal of evidential holism means that it can no longer deliver mathematical Platonism as a conclusion: such an argument for Platonism will be invalid. I then show how the reasons for rejecting the holistic indispensability argument importantly constrain what kind of account of explanation will be permissible in explanatory versions (§4).