20 research outputs found
Past and future corollaries of theories on causes of metabolic syndrome and obesity related co-morbidities part 2: a composite unifying theory review of human-specific co-adaptations to brain energy consumption
Protein kinase C gamma mutations in spinocerebellar ataxia 14 increase kinase activity and alter membrane targeting
The protein kinase C gamma (PKCgamma) gene is mutated in spinocerebellar ataxia type 14 (SCA14). In this study, we investigated the effects of two SCA14 missense mutations, G118D and C150F, on PKCgamma function. We found that these mutations increase the intrinsic activity of PKCgamma. Direct visualization of labelled PKCgamma in living cells demonstrates that the mutant protein translocates more rapidly to selected regions of the plasma membrane in response to Ca2+ influx. These results point to specific alterations in mutant PKCgamma function that could lead to the selective neuronal degeneration of SCA14
Targeting the 5' untranslated region of SMN2 as a therapeutic strategy for spinal muscular atrophy
Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by mutations in the survival motor neuron 1 (SMN2) gene. All patients have at least one copy of a paralog, SMN2, but a C-to-T transition in this gene results in exon 7 skipping in a majority of transcripts. Approved treatment for SMA involves promoting exon 7 inclusion in the SMN2 transcript or increasing the amount of full-length SMN by gene replacement with a viral vector. Increasing the pool of SMN2 transcripts and increasing their translational efficiency can be used to enhance splice correction. We sought to determine whether the 5' untranslated region (5' UTR) of SMN2 contains a repressive feature that can be targeted to increase SMN levels. We found that antisense oligonucleotides (ASOs) complementary to the 5' end of SMN2 increase SMN mRNA and protein levels and that this effect is due to inhibition of SMN2 mRNA decay. Moreover, use of the 5' UTR ASO in combination with a splice-switching oligonucleotide (SSO) increases SMN levels above those attained with the SSO alone. Our results add to the current understanding of SMN regulation and point toward a new therapeutic target for SMA
Acceleration of the Reaction between, Thrombin and Antithrombin III by Non-stoichiometric Amounts of Heparin
Research Fundamentals
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71637/1/j.1553-2712.1999.tb00099.x.pd
Mutation in CPT1C Associated With Pure Autosomal Dominant Spastic Paraplegia
The family of genes implicated in hereditary spastic paraplegias (HSPs) is quickly expanding, mostly owing to the widespread availability of next-generation DNA sequencing methods. Nevertheless, a genetic diagnosis remains unavailable for many patients