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Isobel J. Whitehouse J. Scott Miners Elizabeth B. C. Glennon Patrick G. Kehoe Seth Love Katherine A. B. Kellett Nigel M. Hooper 《PloS one》2013,8(4)
The cellular prion protein (PrPC) has been implicated in the development of Alzheimer''s disease (AD). PrPC decreases amyloid-β (Aβ) production, which is involved in AD pathogenesis, by inhibiting β-secretase (BACE1) activity. Contactin 5 (CNTN5) has also been implicated in the development of AD by a genome-wide association study. Here we measured PrPC and CNTN5 in frontal cortex samples from 24 sporadic AD and 24 age-matched control brains and correlated the expression of these proteins with markers of AD. PrPC was decreased in sporadic AD compared to controls (by 49%, p = 0.014) but there was no difference in CNTN5 between sporadic AD and controls (p = 0.217). PrPC significantly inversely correlated with BACE1 activity (rs = −0.358, p = 0.006), Aβ load (rs = −0.456, p = 0.001), soluble Aβ (rs = −0.283, p = 0.026) and insoluble Aβ (rs = −0.353, p = 0.007) and PrPC also significantly inversely correlated with the stage of disease, as indicated by Braak tangle stage (rs = −0.377, p = 0.007). CNTN5 did not correlate with Aβ load (rs = 0.040, p = 0.393), soluble Aβ (rs = 0.113, p = 0.223) or insoluble Aβ (rs = 0.169, p = 0.125). PrPC was also measured in frontal cortex samples from 9 Down''s syndrome (DS) and 8 age-matched control brains. In contrast to sporadic AD, there was no difference in PrPC in the DS brains compared to controls (p = 0.625). These data are consistent with a role for PrPC in regulating Aβ production and indicate that brain PrPC level may be important in influencing the onset and progression of sporadic AD. 相似文献
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Katherine E. Sloan Sandy Mattijssen Simon Lebaron David Tollervey Ger J.M. Pruijn Nicholas J. Watkins 《The Journal of cell biology》2013,200(5):577-588
Human ribosome production is up-regulated during tumorogenesis and is defective in many genetic diseases (ribosomopathies). We have undertaken a detailed analysis of human precursor ribosomal RNA (pre-rRNA) processing because surprisingly little is known about this important pathway. Processing in internal transcribed spacer 1 (ITS1) is a key step that separates the rRNA components of the large and small ribosomal subunits. We report that this was initiated by endonuclease cleavage, which required large subunit biogenesis factors. This was followed by 3′ to 5′ exonucleolytic processing by RRP6 and the exosome, an enzyme complex not previously linked to ITS1 removal. In contrast, RNA interference–mediated knockdown of the endoribonuclease MRP did not result in a clear defect in ITS1 processing. Despite the apparently high evolutionary conservation of the pre-rRNA processing pathway and ribosome synthesis factors, each of these features of human ITS1 processing is distinct from those in budding yeast. These results also provide significant insight into the links between ribosomopathies and ribosome production in human cells. 相似文献
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Joost Willemse Beata Ruban-O?mialowska David Widdick Katherine Celler Matthew I. Hutchings Gilles P. van Wezel Tracy Palmer 《Journal of bacteriology》2012,194(22):6272-6281
The Tat pathway transports folded proteins across the bacterial cytoplasmic membrane and is a major route of protein export in the Streptomyces genus of bacteria. In this study, we have examined the localization of Tat components in the model organism Streptomyces coelicolor by constructing enhanced green fluorescent protein (eGFP) and mCherry fusions with the TatA, TatB, and TatC proteins. All three components colocalized dynamically in the vegetative hyphae, with foci of each tagged protein being prominent at the tips of emerging germ tubes and of the vegetative hyphae, suggesting that this may be a primary site of Tat secretion. Time-lapse imaging revealed that localization of the Tat components was highly dynamic during tip growth and again demonstrated a strong preference for apical sites in growing hyphae. During aerial hypha formation, TatA-eGFP and TatB-eGFP fusions relocalized to prespore compartments, indicating repositioning of Tat components during the Streptomyces life cycle. 相似文献
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Leonard Machlis Gerry G. C. Hill Katherine E. Steinback Walfred Reed 《Journal of phycology》1974,10(2):199-204
A bioassay for the sperm attractant from Oedogonium cardiacum was developed. The attractant was confirmed to be highly water soluble, destroyed by heating to 100 C and by dilute acid or alkali. It was fractionated by gel filtration with the attractant accompanied by yellow pigments. It has it molecular weight between 500 and about 1500, based on gel filtration, ultrafiltration, and dialysis. Freezing changes this to both larger and smaller molecules. It appears to have cationic groups. A paper chromatographic separation was found that divided the pigment into at least 3 major bands, one of which was closely associated with the attractant. An absorption spectrum of this pigment showed 1 peak in the visible spectrum at 417 mμ and 3 well-defined peaks in the ultraviolet region. The lack of a peak at 280 mμ indicates the attractant is not a polypeptide. 相似文献
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