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991.
Huntington’s disease: from huntingtin function and dysfunction to therapeutic strategies 总被引:3,自引:0,他引:3
Borrell-Pagès M Zala D Humbert S Saudou F 《Cellular and molecular life sciences : CMLS》2006,63(22):2642-2660
Huntington’s disease (HD) is a neurodegenerative disorder that usually starts in middle age and is characterized by involuntary
movements (chorea), personality changes and dementia, leading to death within 10–20 years. The defective gene in HD contains
a trinucleotide CAG repeat expansion within its coding region that expresses a polyglutamine repeat in the protein huntingtin.
Together with the characteristic formation of aggregates in HD, aberrant protein interactions and several post-translational
modifications affect huntingtin during disease progression and lead to the dysfunction and death of selective neurons in the
brains of patients. The exact molecular mechanisms by which mutant huntingtin induces cell death are not completely understood
but may involve the gain of new toxic functions and the loss of the beneficial properties of huntingtin. This review focuses
on the cellular functions in which huntingtin is involved and how a better understanding of pathogenic pathways can lead to
new therapeutic approaches.
Received 24 May 2006; received after revision 5 July 2006; accepted 23 August 2006 相似文献
992.
Glycogen synthase kinase 3β and Alzheimer’s disease: pathophysiological and therapeutic significance 总被引:3,自引:0,他引:3
Balaraman Y Limaye AR Levey AI Srinivasan S 《Cellular and molecular life sciences : CMLS》2006,63(11):1226-1235
Alzheimer’s disease (AD) is a neurodegenerative disorder associated with cognitive and behavioral dysfunction and is the leading
cause of dementia in the elderly. Several studies have implicated molecular and cellular signaling cascades involving the
serine-threonine kinase, glycogen synthase kinase β(GSK-3β) in the pathogenesis of AD. GSK-3β may play an important role in
the formation of neurofibrillary tangles and senile plaques, the two classical pathological hallmarks of AD. In this review,
we discuss the interaction between GSK-3β and several key molecules involved in AD, including the presenilins, amyloid precursor
protein, tau, and β-amyloid. We identify the signal transduction pathways involved in the pathogenesis of AD, including Wnt,
Notch, and the PI3 kinase/Akt pathway. These may be potential therapeutic targets in AD.
Received 19 December 2005; received after revision 24 January 2006; accepted 6 February 2006 相似文献
993.
994.
New Giemsa method for the differential staining of sister chromatids 总被引:127,自引:0,他引:127
995.
996.
Mark C. Hove Bernard E. Sietman Matthew S. Berg Erika C. Frost Kiru Wolf Tony R. Brady 《Journal of Natural History》2016,50(9-10):523-542
Managing a rare species can be improved with knowledge of its natural history. The sheepnose (Plethobasus cyphyus) is a freshwater mussel recently listed by the US as federally endangered. We used standard methods to study P. cyphyus brooding behaviour, host fishes in the laboratory and under natural conditions, and glochidial morphology. We monitored a population of P. cyphyus in the Chippewa River, WI during spring and summer 2007–2009 and 2011 and found brooding animals between mid-May and early August. Gravid individuals ranged between 5 and 27 yr (mean age ± 1 s.d. = 13 ± 4 yr). Plethobasus cyphyus brooded glochidia in outer gills, which varied in colour from red, orange, pink, cream, or white. We observed mature glochidia more commonly in individuals with cream or white gills and these glochidia were released in a clear, adhesive, mucus matrix. In laboratory trials we found several minnow and topminnow species (29 spp.) served as productive suitable native hosts. The mean number of juvenile mussels released per cyprinid per day was significantly higher for trials conducted at 22–25°C compared with those at 18–20°C, and 83% of trials conducted at 18–20°C using suitable host species produced no juveniles. Glochidia had a unique outline and shell morphometrics that distinguished P. cyphyus from seven other Chippewa River mussel species that produce similar sized glochidia. Using morphometrics we determined that mimic shiners (Notropis volucellus) were natural hosts for P. cyphyus, round pigtoe (Pleurobema sintoxia), and Wabash pigtoe (Fusconaia flava). Releasing mucus-bound glochidia has evolved in a variety of mussel species and may be more common than is currently realized. Our data show that P. cyphyus is a cyprinid host specialist, and propagation efforts for this species can be strengthened through improved access to mature glochidia by using females with cream-coloured gills and increased juvenile production through warmer fish holding temperatures. 相似文献
997.
<正>Dedication.This Special Issue on Parameterized Complexity of Tsinghua Science and Technology is a tribute to the influential contributions of Jianer Chen to parameterized complexity algorithmics.It is an occasion to celebrate the many important contributions to this new and prospering branch of theoretical computer science made by Jianer Chen,as he reaches the ripe young age of 60.Happy birthday,Jianer,from 相似文献
998.
999.
桥梁结构在各种荷载作用下产生的内力和弯矩影响着桥梁的性能.桥梁弯曲、扭转和挠度等过大时会导致结构的破坏,这在结构设计阶段就应加以分析.本文提出一种有限条简化分析方法,可以较好地分析桥梁的挠度、弯曲和扭转变形.通过对一座简支板梁桥模型的分析,与现行有限元方法的分析结果进行了比较.结果表明,本方法能够较好地处理边界条件,只需要很少的输入工作就可以得到正确的分析结果,从而为结构工程师提供了一种用于分析板梁桥在交通荷载作用下行为的有效工具. 相似文献
1000.
Transthyretin (formerly called prealbumin) plays important physiological roles as a transporter of thyroxine and retinol-binding
protein. X-ray structural studies have provided information on the active conformation of the protein and the site of binding
of both ligands. Transthyretin is also one of the precursor proteins commonly found in amyloid deposits. Both wild-type and
single-amino-acid-substituted variants have been identified in amyloid deposits, the variants being more amyloidogenic. Sequencing
of the gene and the resulting production of a transgenic mouse model have resulted in progress toward solving the mechanism
of amyloid formation and detecting the variant gene in individuals at risk.
Received 23 January 2001; received after revision 4 April 2001; accepted 30 April 2001 相似文献