Contiguous ∼16 Mb 1p36 deletion: Dominant features of classical distal 1p36 monosomy with haplo-lethality

Monosomy 1p36 results from heterozygous deletions of the terminal short chromosome 1 arm, the most common terminal deletion in humans. The microdeletion is split in two usually non-overlapping and clinically distinct classical distal and proximal 1p36 monosomy syndromes. Using comparative genome hybridization, MLPA and qPCR we identified the largest contiguous ∼16 Mb terminal 1p36 deletion reported to date. It covers both distal and proximal regions, causes a neonatally lethal variant with virtually exclusive features of distal 1p36 monosomy, highlighting the key importance of the gene-rich distal region for the "compound" 1p36 phenotype and a threshold deletion-size effect for haplo-lethality.

Distinct proteinase K-resistant prion protein fragment in goats with no signs of disease in a classical scrapie outbreak

Considerable efforts have been directed toward the identification of small-ruminant prion diseases, i.e., classical and atypical scrapie as well as bovine spongiform encephalopathy (BSE). Here we report the in-depth molecular analysis of the proteinase K-resistant prion protein core fragment (PrP(res)) in a highly scrapie-affected goat flock in Greece. The PrP(res) profile by Western immunoblotting in most animals was that of classical scrapie in sheep. However, in a series of clinically healthy goats we identified a unique C- and N-terminally truncated PrP(res) fragment, which is akin but not identical to that observed for atypical scrapie. These findings reveal novel aspects of the nature and diversity of the molecular PrP(res) phenotypes in goats and suggest that these animals display a previously unrecognized prion protein disorder.

Caprine PRNP polymorphisms at codons 171, 211, 222 and 240 in a Greek herd and their association with classical scrapie

The association between PRNP variation and scrapie incidence was investigated in a highly affected Greek goat herd. Four mutations were identified at codons 171Q/R, 211R/Q, 222Q/K and 240P/S. Lysine at codon 222 was found to be associated with the protection from natural scrapie (P=0.0111). Glutamine at codon 211 was observed in eight animals, all of them being scrapie-negative, indicating a possible protective role of this polymorphism although statistical analysis failed to support it (P=0.1074). A positive association (P=0.0457) between scrapie-affected goats and the wild-type Q(171)R(211)Q(222)S(240) allele is presented for the first time. In addition, a novel R(171)RQS allele, which is identical to the A(136)R(154)R(171) allele that has been associated with resistance to classical scrapie in sheep, was observed in low frequency. Resistant alleles that include K(222) and Q(211) are absent or rare in sheep and can provide the basis for the development of a feasible breeding programme for scrapie eradication in goats.

Exploring Magic Realism in Salman Rushdie's Fiction

Kluwick breaks new ground in this book, moving away from Rushdie studies that focus on his status as postcolonial or postmodern, and instead considering the significance of magic realism in his fiction. Rushdie’s magic realism, in fact, lies at the heart of his engagement with the post/colonial. In a departure from conventional descriptions of magic realism—based primarily on the Latin-American tradition—Kluwick here proposes an alternative definition, allowing for a more accurate description of the form. She argues that it is disharmony, rather than harmony, that is decisive: that the incompatibility of the realist and the supernatural needs to be recognized as a driving force in Rushdie’s fiction. In its rigorous analysis of this Rushdian magic realism, this book considers the entire corpus—Midnight’s Children, Shame, The Satanic Verses, The Moor’s Last Sigh, The Ground Beneath Her Feet, Shalimar the Clown, and The Enchantress of Florence. This study is the first of its kind to do so.

Verifying Harder's Conjecture for Classical and Siegel Modular Forms

A conjecture by Harder shows a surprising congruence between the coefficients of “classical” modular forms and the Hecke eigenvalues of corresponding Siegel modular forms, contigent upon “large primes” dividing the critical values of the given classical modular form. Harder’s Conjecture has already been verified for one-dimensional spaces of classical and Siegel modular forms (along with some two-dimensional cases), and for primes p 37. We verify the conjecture for higher-dimensional spaces, and up to a comparable prime p.

Cross-sectional observational study of 208 patients with non-classical urea cycle disorders

Urea cycle disorders (UCDs) are inherited disorders of ammonia detoxification often regarded as mainly of relevance to pediatricians. Based on an increasing number of case studies it has become obvious that a significant number of UCD patients are affected by their disease in a non-classical way: presenting outside the newborn period, following a mild course, presenting with unusual clinical features, or asymptomatic patients with only biochemical signs of a UCD. These patients are surviving into adolescence and adulthood, rendering this group of diseases clinically relevant to adult physicians as well as pediatricians. In preparation for an international workshop we collected data on all patients with non-classical UCDs treated by the participants in 20 European metabolic centres. Information was collected on a cohort of 208 patients 50% of which were ≥ 16 years old. The largest subgroup (121 patients) had X-linked ornithine transcarbamylase deficiency (OTCD) of whom 83 were female and 29% of these were asymptomatic. In index patients, there was a mean delay from first symptoms to diagnosis of 1.6 years. Cognitive impairment was present in 36% of all patients including female OTCD patients (in 31%) and those 41 patients identified presymptomatically following positive newborn screening (in 12%). In conclusion, UCD patients with non-classical clinical presentations require the interest and care of adult physicians and have a high risk of neurological complications. To improve the outcome of UCDs, a greater awareness by health professionals of the importance of hyperammonemia and UCDs, and ultimately avoidance of the still long delay to correctly diagnose the patients, is crucial.

The Man-Made Environment in Post-Stalinist Europe 1953-1968

This project looked at the various responses, both political and aesthetic, to the end of socialist realism and the return of pre-war modernism as a desirable ideal. It considered both the built environment and objects of daily use (furniture, radios, TV sets, etc.) in several countries of the region, including Estonia, Hungary, Poland, Russia and Romania, also comparing developments there with corresponding ones in the west. Among particular aspects considered were the effects of Kruschev's speech in December 1954 to workers in construction, machine-building and design industries, in which he argued against monumentalism and criticised both "classical architecture" and socialist realism. The team see the real issue in interpreting Eastern European architecture as its lack of a critical edge, since official discourses took the place of any form of criticism and architects sought to implement the "official line". Megastructures became increasingly popular from the 1960s onwards and in Romania, for instance, came to dominate the city in the late 1980s. Such structures proved an efficient way to control the environment in countries plagued by prefabrication and social housing, and the group see the exhibition of inflated concrete grids as perhaps the most important feature of Eastern European architecture in the 1960s and 1970s. They also point out the rarity of glass and steel architecture in the east, where the preferred material was concrete, a material seen as "revolutionary" as it was the product of heavy industry and was grey, i.e. the workers' colour. Tactile elements were more important here than the visual elements favoured in the west, and a solidity more in line with the dominant ideology than the ephemeral qualities of glass.

Improved neo-endothelialization of small diameter ePTFEgrafts with titanium coating

BACKGROUND: Patency of small synthetic bypass grafts is inferior compared to autologous grafts for revascularization procedures. Titanium coating of foreign surfaces has shown to decrease thrombogenicity, enhance biocompatibility and promote adhesion of endothelial cells. The aim of this study was to test the effect of titanium coating of small diameter ePTFE grafts on short term patency, neo-endothelialization and neointimal proliferation. METHODS: Bilateral carotid graft interposition was performed in 5 pigs with uncoated (n=5) and titanium-coated (n=5) ePTFE grafts (internal diameter=4 mm, length=5 cm), thus each pig served as its own control. At the end of the study (30 +/- 3 days), patency and stenosis severity was assessed by carotid angiography. Animals were sacrificed and grafts were excised for histology and scanning electron microscopy. Morphometry of histologic sections was carried out to determine neointimal proliferation and percentage of neo-endothelial coverage. RESULTS: Patency rate was 80% for uncoated and titanium-coated grafts. Quantitative angiography did not show any significant difference in lumen size between two groups. Morphometry revealed a significantly higher cellular coverage with CD31 positive endothelial cells for titanium-coated (84 +/- 19%) than uncoated grafts (48 +/- 26%, p<0.001). There was a non significant trend (p=0.112) towards increased neointimal proliferation in titanium-coated (94 +/- 61 micron2/micron) compared to uncoated grafts (60 +/- 57 micron2/micron). CONCLUSIONS: Patency rate in uncoated and titanium-coated ePTFE grafts is similar at one month. However, titanium coated grafts show a significant improvement in neo-endothelialization compared to uncoated grafts.