An ARHGEF10 deletion is highly associated with a juvenile-onset inherited polyneuropathy in Leonberger and Saint Bernard dogs

An inherited polyneuropathy (PN) observed in Leonberger dogs has clinical similarities to a genetically heterogeneous group of peripheral neuropathies termed Charcot-Marie-Tooth (CMT) disease in humans. The Leonberger disorder is a severe, juvenile-onset, chronic, progressive, and mixed PN, characterized by exercise intolerance, gait abnormalities and muscle atrophy of the pelvic limbs, as well as inspiratory stridor and dyspnea. We mapped a PN locus in Leonbergers to a 250 kb region on canine chromosome 16 (Praw = 1.16×10-10, Pgenome, corrected = 0.006) utilizing a high-density SNP array. Within this interval is the ARHGEF10 gene, a member of the rho family of GTPases known to be involved in neuronal growth and axonal migration, and implicated in human hypomyelination. ARHGEF10 sequencing identified a 10 bp deletion in affected dogs that removes four nucleotides from the 3'-end of exon 17 and six nucleotides from the 5'-end of intron 17 (c.1955_1958+6delCACGGTGAGC). This eliminates the 3'-splice junction of exon 17, creates an alternate splice site immediately downstream in which the processed mRNA contains a frame shift, and generates a premature stop codon predicted to truncate approximately 50% of the protein. Homozygosity for the deletion was highly associated with the severe juvenile-onset PN phenotype in both Leonberger and Saint Bernard dogs. The overall clinical picture of PN in these breeds, and the effects of sex and heterozygosity of the ARHGEF10 deletion, are less clear due to the likely presence of other forms of PN with variable ages of onset and severity of clinical signs. This is the first documented severe polyneuropathy associated with a mutation in ARHGEF10 in any species.

Emergence of four cases of KPC-2 and KPC-3-carrying Klebsiella pneumoniae introduced to Switzerland, 2009-10

We report four epidemiologically unrelated cases of KPC-carrying Klebsiella pneumoniae identified in Switzerland between May 2009 and November 2010. Three cases were transferred from Italy (two KPC-3, one KPC-2) and one from Greece (KPC-2). Resistance to colistin and doxycycline emerged in one KPC-3-carrying K. pneumoniae strain during therapy. These results demonstrate ongoing dissemination of KPC throughout Europe. Rapid and reliable identification of KPC and implementation of control measures is essential to limit spread.

Saint Margaret's Tattoos: Empowering Marks on White Skin

Saint Margaret, as presented in the “Katherine Group” life of the virgin martyr, claims to have Christ’s “marks” and “seals” on her. Bringing together postmodern theories of body modification and Paul Zumthor’s concept of mouvance, this essay reads these marks as tattoos that consist of virtual (tattoo fantasies), oral (tattoo narratives), and written elements (the actual marks on skin). Margaret defends and empowers herself by claiming to possess Christ’s ownership tattoo. Her oppressor Olibrius, in turn, intends to overwrite that mark palimpsestically and hence to empower himself, not unlike slave-owners in antiquity. While the gruesome torture scenes suggest that Olibrius wins the upper hand in this contest, the outcome of the narrative instead proves that Margaret triumphs. She dies a virgin after defiantly appropriating, in her tattoo narrative, the torture marks as her own, divine tattoo.

Luxurious Merovingian Textiles Excavated from Burials in the Saint Denis Basilica, France, 6th-7th century

A new examination of the textile fragments found in the Merovingian burials in the basilica of Saint Denis, near Paris, has recently underscored the diversity of fabrics used to make garments in which members of the royal court were buried. Among them, some woolens of fine quality had been dyed with indigotin. The most astonishing fibre found belongs to a mixed textile (not skin) with beaver fibers and wool. Silks contained shellfish purple and in one case kermes? Two dyestuffs associated with royalty and privilege. Along with this was large number of gold threads, probably produced locally and that were used in tablet-woven borders or for embroideries. In addition, several figured silks, of oriental origin, testify to the importance of this "foreign" material and the taste for textiles woven with complex techniques and probably what had originally had beautiful designs. Although none of these designs have been preserved and many colors have been greatly damaged, the technical characteristics of the remnants indicate proveniences as far as Byzantium, Sassanid Persia and the Chinese court. Such precious textiles show the high social status and political power of the Merovingian court, a testament to their ability to access such luxurious and costly textiles through diplomacy and/or trade with other powerful empires. The examination of these rare textiles along with other fine silks and luxury objects from the same period found in France expand our view of the fundamental role of textiles in the political sphere of this early period of European history.

Scintillation crystal including a rare earth halide, and a radiation detection apparatus including the scintillation crystal.

A scintillation crystal can include Ln(1-y)REyX3, wherein Ln represents a rare earth element, RE represents a different rare earth element, y has a value at 0-1, and X represents a halogen. In an embodiment, the scintillation crystal is doped with a Group 1 element, a Group 2 element, or a mixt. thereof, and the scintillation crystal is formed from a melt having a concn. of such elements or mixt. thereof of at least ∼0.02%. In another embodiment, the scintillation crystal can have unexpectedly improved proportionality and unexpectedly improved energy resoln. properties. In a further embodiment, a radiation detection app. can include the scintillation crystal, a photosensor, and an electronics device. Such a radiation detection app. can be useful in a variety of applications.

Factors Associated with Durable Response to Infliximab in Crohnʼs Disease 5 Years and Beyond: A Multicenter International Cohort

BACKGROUND: Infliximab (IFX) has been used for over a decade worldwide. Less is known about the natural history of IFX use beyond a few years and which patients are more likely to sustain benefits. METHODS: Patients with Crohn's disease (CD) exposed to IFX from Massachusetts General Hospital, Boston, Saint-Antoine Hospital, Paris, and the Swiss IBD Cohort Study were identified through retrospective and prospective data collection, complemented by chart abstraction of electronic medical records. We compared long-term users of IFX (>5 yr of treatment, long-term users of infliximab [LTUI]), with non-LTUI patients to identify prognostic factors. RESULTS: We pooled data on 1014 patients with CD from 3 different databases, of whom 250 were defined as LTUI. The comparison group comprised 290 patients with CD who discontinued IFX: 48 primary nonresponses, 95 loss of responses, and 147 adverse events. Factors associated with LTUI were colonic involvements and an earlier age at the start of IFX. The prevalence of active smokers and obese patients differed markedly, but inversely, between American and European centers but did not impact outcome. The discontinuation rate was stable around 3% to 6%, each year from years 3 to 10. CONCLUSIONS: Young age at start of IFX and colonic CD are factors associated with a beneficial long-term use of IFX. After 5 years of IFX, there is still a 3% to 5% discontinuation rate annually. Several factors associated with a good initial response such as nonsmoker and shorter disease duration at IFX initiation do not seem associated with a longer term response.