Temporal Stability of the Location of the Esophagus in Patients Undergoing a Repeat Left Atrial Ablation Procedure for Atrial Fibrillation or Flutter

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71884/1/j.1540-8167.2007.01051.x.pd

DNM1 encephalopathy: A new disease of vesicle fission.

ObjectiveTo evaluate the phenotypic spectrum caused by mutations in dynamin 1 (DNM1), encoding the presynaptic protein DNM1, and to investigate possible genotype-phenotype correlations and predicted functional consequences based on structural modeling.MethodsWe reviewed phenotypic data of 21 patients (7 previously published) with DNM1 mutations. We compared mutation data to known functional data and undertook biomolecular modeling to assess the effect of the mutations on protein function.ResultsWe identified 19 patients with de novo mutations in DNM1 and a sibling pair who had an inherited mutation from a mosaic parent. Seven patients (33.3%) carried the recurrent p.Arg237Trp mutation. A common phenotype emerged that included severe to profound intellectual disability and muscular hypotonia in all patients and an epilepsy characterized by infantile spasms in 16 of 21 patients, frequently evolving into Lennox-Gastaut syndrome. Two patients had profound global developmental delay without seizures. In addition, we describe a single patient with normal development before the onset of a catastrophic epilepsy, consistent with febrile infection-related epilepsy syndrome at 4 years. All mutations cluster within the GTPase or middle domains, and structural modeling and existing functional data suggest a dominant-negative effect on DMN1 function.ConclusionsThe phenotypic spectrum of DNM1-related encephalopathy is relatively homogeneous, in contrast to many other genetic epilepsies. Up to one-third of patients carry the recurrent p.Arg237Trp variant, which is now one of the most common recurrent variants in epileptic encephalopathies identified to date. Given the predicted dominant-negative mechanism of this mutation, this variant presents a prime target for therapeutic intervention

A Recurrent Mutation in KCNA2 as a Novel Cause of Hereditary Spastic Paraplegia and Ataxia

The hereditary spastic paraplegias (HSPs) are heterogeneous neurodegenerative disorders with over 50 known causative genes. We identified a recurrent mutation in KCNA2 (c.881G>A, p.R294H), encoding the voltage-gated K+-channel, K(V)1.2, in two unrelated families with HSP, intellectual disability (ID), and ataxia. Follow-up analysis of >2,000 patients with various neurological phenotypes identified a de novo p.R294H mutation in a proband with ataxia and ID. Two-electrode voltage-clamp recordings of Xenopus laevis oocytes expressing mutant KV1.2 channels showed loss of function with a dominant-negative effect. Our findings highlight the phenotypic spectrum of a recurrent KCNA2 mutation, implicating ion channel dysfunction as a novel HSP disease mechanism.Peer reviewe

A holistic approach to use multi-scale fractions of dry carbon fibre production waste in filled Bulk Moulding Compounds (BMC)

The increasing demand for composites leads to a growing amount of end-of-life materialand production waste. The latter consists of a large fraction of unimpregnated fibre waste which is notsufficiently reprocessed using conventional textile processing procedures as they are either too expensiveor their mechanical performance is too low. Using pieces of dry non-crimp fabrics (patches) ina Bulk Moulding Compound process (BMC) displays a straightforward approach of fabric recycling.Adding fillers to the mixture not only offers the opportunity to modify mechanical and electrical propertiesas well as the costs but also a chance for a more holistic approach of dry fibre recycling, whenconventional fillers like chalk are replaced by ground recycled carbon fibres. In this way, all kindof dry fibre wastes can be reused in one process: Larger offcuts are chopped to smaller rectangularpatches whereas waste fractions of small offcuts are processed to carbon fibre powder as filler andprocessed together with resin to produce BMC materials. Mechanical investigations reveal that thepresented approach shows higher specific properties than the conventional filler without compromisingthe process and material quality.</jats:p

Survival analysis of infected mice reveals pathogenic variations in the genome of avian H1N1 viruses

Most influenza pandemics have been caused by H1N1 viruses of purely or partially avian origin. Here, using Cox proportional hazard model, we attempt to identify the genetic variations in the whole genome of wild-type North American avian H1N1 influenza A viruses that are associated with their virulence in mice by residue variations, host origins of virus (Anseriformes-ducks or Charadriiformes-shorebirds), and host-residue interactions. In addition, through structural modeling, we predicted that several polymorphic sites associated with pathogenicity were located in structurally important sites, especially in the polymerase complex and NS genes. Our study introduces a new approach to identify pathogenic variations in wild-type viruses circulating in the natural reservoirs and ultimately to understand their infectious risks to humans as part of risk assessment efforts towards the emergence of future pandemic strains

Damaging de novo missense variants in EEF1A2lead to a developmental and degenerative epileptic-dyskinetic encephalopathy

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