Mutations in a gene encoding a novel protein tyrosine phosphatase cause progressive myoclonus epilepsy

Lafora's disease (LD; OMIM 254780) is an autosomal recessive form of progressive myoclonus epilepsy characterized by seizures and cumulative neurological deterioration. Onset occurs during late childhood and usually results in death within ten years of the first symptoms1,2. With few exceptions, patients follow a homogeneous clinical course despite the existence of genetic heterogeneity3. Biopsy of various tissues, including brain, revealed characteristic polyglucosan inclusions called Lafora bodies4-8, which suggested LD might be a generalized storage disease6,9. Using a positional cloning approach, we have identified at chromosome 6q24 a novel gene, EPM2A, that encodes a protein with consensus amino acid sequence indicative of a protein tyrosine phosphatase (PTP). mRNA transcripts representing alternatively spliced forms of EPM2A were found in every tissue examined, including brain. Six distinct DNA sequence variations in EPM2A in nine families, and one homozygous microdeletion in another family, have been found to cosegregate with LD. These mutations are predicted to cause deleterious effects in the putative protein product, named laforin, resulting in LD.link_to_subscribed_fulltex

Achieving Selective Targeting Using Engineered Nanomaterials

The development of Drug Delivery Systems (DDS) able to selectively deliver a controlled amount of a drug only to diseased cells would represent a dramatic development in nanomedicine. One of the multiple challenges still paving the way towards this goal is the elaboration of strategies that would allow targeting with extreme accuracy specific cells, as cancerous cells, among a large variety of closely related ones. In this work, we review the most recent nanotechnology applications aiming at controlling the selectivity of the interaction of delivery nanosystems with cells, with a focus on multivalent targeting. We briefly review thermodynamic models of multivalent interactions and highlight the challenges that still need to be addressed to transfer theoretical design principles into practical applications. In particular, suitable experimental systems based on multivalent models often require the control of the nanocarrier characteristics at the molecular level. Traditional delivery methods, however, fail to provide such degree of control. DNA nanotechnology is a growing field of nanoscience that has witnessed impressive developments in the past decades and has led to major advances in the fabrication of nanostructures and self-assembled systems. Relying on the possibility of controlling their molecular interactions by sequence design, nucleic acids can serve the drug delivery program by providing desired nanostructures with nearly atomic precision. In combination with the recent achievements in the research on DNA aptamers, short nucleic acid sequences isolated to interact selectively with a specific target, DNA nanotechnology is undoubtedly one of the most promising tools for the development of selective DDS.info:eu-repo/semantics/publishe