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Molecular basis of ataxia telangiectasia and related diseases

Acta Pharmacologica Sinica 2005年第8期26卷 897-907页

作者： lindsay g ball Department of Microbiotogy and Lmmunology University of Saskatchewan S7n 5E5 SK Canada Saskatoon

Ataxia telangiectasia (AT) is a rare human disease characterized by extreme cellular sensitivity to radiation and a predisposition to cancer, with a hallmark of onset in early childhood. Several human diseases also share similar symptoms with AT albeit with different degrees of severity and different associated disorders. While all AT patients contain mutations in the AT-mutated gene (ATM), most other AT-like disorders are defective in genes encoding an MRN protein complex consisting of Mre11, Rad50 and Nbs1. Both ATM and MRN function as cellular sensors to DNA double-strand breaks, which lead to the recruitment and phosphorylation of an array of substrate proteins involved in DNA repair, apoptosis and cell-cycle cbeckpoints, as well as gene regulation, translation initiation and telomere maintenance. ATM is a member of the family of phosphatidylinositol 3-kinase-like protein kinases (PIKK), and the discovery of many ATM substrates provides the underlying mechanisms of heterologous symptoms among AT patients. This review article focuses on recent findings related to the initial recognition of double-strand breaks by ATM and MRN, as well as a DNA-dependent protein kinase complex consisting of the heterodimer Ku70/Ku80 and its catalytic subunit DNA-PKcs, another member of PIKK. This possible interaction suggests that a much greater complex is involved in sensing, transducing and co-ordinating cellular events in response to genome instability.

关键词： ataxia telangiectasia DNA damage DNA repair cdc genes phosphotransferases

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Pragmatic language production deficits in Parkinson’s disease

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Advances in Parkinson's Disease 2013年第1期2卷 31-36页

作者： Thomas Holtgraves Kelly Fogle lindsay Marsh Department of Psychological Science Ball State University Muncie USA

This study examines pragmatic language production deficits in people with Parkinson’s disease (PD). Participants (PD and non-PD) were interviewed and their responses coded for degree of informativeness. PD participants weremore under-informative than non-PD participants. Response underinformativeness was associated with decreased executive control, mental status, and speech act comprehension measures. However, both speech act priming and utterance informativeness were strongly related to a measure of executive control, and when this variable (i.e., Stroop performance) was controlled, the correlation between speech act priming and utterance underinformativeness was no longer significant. It appears, then, that executive control deficits are related to the ability to comprehend and produce conversational utterances.

关键词： Pragmatic Deficits Parkinson’s Disease Conversation Maxims

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