London mutation

Several authors have successfully demonstrated the feasibility of targeting AD genes (e.g., APP-London mutation, APP-Swedish mutation, PSl, APLPl, APLP2, PEN-2, APH-la, Nicastrin, BACE, MAPP-V337M) with RNAi (418-423). Some authors have speculated about the possibility that ABP overproduction might be caused by the loss of epigenetic control in the expression of the genes involved in... 

Feng, X., Zhao, P., He, Y., Zuo, Z. (2006) AUele-specific silencing of Alzheimer s disease genes the amyloid precursor protein genes with Swedish or London mutations. Gene, 371, 68-74. 

Auerbach, C. Mutation Research Problems, Results and Perspectives. London Chapman and Hall New York Wiley. 1976. 504 p. 

Nusslein-Volhard, C. Wieschaus, E. (1980). Mutations affecting segment number and polarity in Drosophila. Nature (London) 287,795-801. 

Improvements in medication by use of acetyl cholinesterase inhibitors and general therapy significantly reduce symptoms at the onset of the disease [3, 4] but do not address the severe mortality in the final stages. A causal therapy is, therefore, still very much in demand, because no existing therapy effectively stops or even cures the disease. Identification of gene mutations linked to Alzheimer s disease-afflicted families in London and Sweden and additional polymorphisms that either cause or promote Alzheimer s disease have provided some insight into the biological pathways and the involvement of the amyloid precursor protein (APP) [5-8],... 

Heinemann, S.H., Terlau, H., Stuhmer, W., Imoto, K Numa, S. (1992). Calcium channel characteristics conferred on the sodium channel by single mutations. Nature (London) 356,441-443. 

Mutation Research Problems, Results, and Perspectives. London Chapman... 

Lindberg, R. L. P., and Negishi, M., 1989, Alteration of mouse cytochrome P450 jj substrate specificity by mutation of a single amino acid residue. Nature (London) 339 6326634. 

Figure 43-3 Thiopurine S-methyltransferase (TPMT) allele variants. Gray boxes represent mutations that result in amino acid changes.TPMT 4 is a 5 splice site mutation for exon 10 that does not alter an amino acid. White boxes represent untranslated regions. Black boxes represent exons in the open reading frame.The dashed box represents exon 2, which was detected in 6.25% of human liver cDNAs during initial evaluation. (From McLeod HL, Siva C. The thiopurine S-mefhy/transferose gene locus—implications for clinical pharmacogenomics. Pharmacogenomics 2002 3 89-98. Reproduced by permission from future Medicine Ltd [London].)...

In 2005, a case report was published of two patients with early onset of AD (one with the London APT mutation) who received treatment with CQ 250 mg bid for 9 and 14 months [ 191 ]. Both cases exhibited Locally augmented cerebral glucose metaboHsm with arrested clinical deterioration over this period and neither developed signs of neurotoxicity, hi the famihal AD case (the only one who consented to liunbar puncture) CSF-tau levels rose at 4 months and fell to below baseline at 9 months of treatment, and the AP42/40 ratio also rose at 4 months and fell to below baseline at 9 months of treatment [191]. 

BMC Molecular Biology. London BioMed Central Ltd. Electronic. ISSN 1471-2164. URL http //www.biomedcentral. com/bmcmolbiol/. DNA and RNA in a cellular context, transcription, mRNA processing, translation, replication, recombination, mutation, and repair are within scope. 

Alber, T. A. (1989). Mutational effects on protein stability. Ann. Rev. Biochem. 58, 765-798. Branden, C., Tooze, J. (1991). Introduction to Protein Stiucture, Garland Publishing, New York and London. 

A very interesting series of studies of the influence of end effects in the rotating concentric cylinder problem has been published by Mullin and co-workers T. Mullin, Mutations of steady cellular flows in the Taylor experiment,J. Fluid Mech. 121, 207-18 (1982) T. B. Benjamin and T. Mullin, Notes on the multiplicity of flows in the Taylor experiment, J. Fluid Mech. 121, 219-30 (1982) K. A. Cliff and T. Mullin, A numerical and expwerimental study of anomalous modes in the Taylor experiment, J. Fluid Mech. 153, 243-58 (1985) G. Pfister, H. Schmidt, K. A. Cliffe and T. Mullin, Bifurcation phenomena in Taylor-Couette flow in a very short annulus, J. Fluid Mech. 191, 1-18 (1988) K. A. Cliffe, 1.1. Kobine, and T. Mullin, The role of anomalous modes in Taylor-Couette flow, Proc. R. Soc. London Ser. A 439, 341-57 (1992) T. Mullin, Y. Toya, and S. I. Tavener, Symmetry breaking and multiplicity of states in small aspect ratio Taylor-Couette flow, Phys. Fluids 14, 2778-87 (2002). 

A nicotinic acetylcholine receptor point mutation (Y151S) conferring insecticide resistance causes reduced agonist potency to a range of neonicotinoids (N. S. Millar, Univ. College London, UK)... 

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