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Bidirectional nucleolar dysfunction in C9orf72 frontotemporal lobar degeneration

Overview of attention for article published in Acta Neuropathologica Communications, April 2017
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (86th percentile)

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22 tweeters

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70 Mendeley
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Title
Bidirectional nucleolar dysfunction in C9orf72 frontotemporal lobar degeneration
Published in
Acta Neuropathologica Communications, April 2017
DOI 10.1186/s40478-017-0432-x
Pubmed ID
Authors

Sarah Mizielinska, Charlotte E. Ridler, Rubika Balendra, Annora Thoeng, Nathan S. Woodling, Friedrich A. Grässer, Vincent Plagnol, Tammaryn Lashley, Linda Partridge, Adrian M. Isaacs

Abstract

An intronic GGGGCC expansion in C9orf72 is the most common known cause of both frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). The repeat expansion leads to the generation of sense and antisense repeat RNA aggregates and dipeptide repeat (DPR) proteins, generated by repeat-associated non-ATG translation. The arginine-rich DPR proteins poly(glycine-arginine or GR) and poly(proline-arginine or PR) are potently neurotoxic and can localise to the nucleolus when expressed in cells, resulting in enlarged nucleoli with disrupted functionality. Furthermore, GGGGCC repeat RNA can bind nucleolar proteins in vitro. However, the relevance of nucleolar stress is unclear, as the arginine-rich DPR proteins do not localise to the nucleolus in C9orf72-associated FTLD/ALS (C9FTLD/ALS) patient brain. We measured nucleolar size in C9FTLD frontal cortex neurons using a three-dimensional, volumetric approach. Intriguingly, we found that C9FTLD brain exhibited bidirectional nucleolar stress. C9FTLD neuronal nucleoli were significantly smaller than control neuronal nucleoli. However, within C9FTLD brains, neurons containing poly(GR) inclusions had significantly larger nucleolar volumes than neurons without poly(GR) inclusions. In addition, expression of poly(GR) in adult Drosophila neurons led to significantly enlarged nucleoli. A small but significant increase in nucleolar volume was also observed in C9FTLD frontal cortex neurons containing GGGGCC repeat-containing RNA foci. These data show that nucleolar abnormalities are a consistent feature of C9FTLD brain, but that diverse pathomechanisms are at play, involving both DPR protein and repeat RNA toxicity.

Twitter Demographics

The data shown below were collected from the profiles of 22 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 70 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 70 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 22 31%
Student > Master 9 13%
Student > Bachelor 9 13%
Researcher 6 9%
Professor > Associate Professor 3 4%
Other 9 13%
Unknown 12 17%
Readers by discipline Count As %
Neuroscience 21 30%
Biochemistry, Genetics and Molecular Biology 14 20%
Agricultural and Biological Sciences 13 19%
Medicine and Dentistry 4 6%
Psychology 1 1%
Other 3 4%
Unknown 14 20%

Attention Score in Context

This research output has an Altmetric Attention Score of 15. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 28 May 2017.
All research outputs
#1,235,109
of 14,624,569 outputs
Outputs from Acta Neuropathologica Communications
#109
of 820 outputs
Outputs of similar age
#35,451
of 264,639 outputs
Outputs of similar age from Acta Neuropathologica Communications
#1
of 1 outputs
Altmetric has tracked 14,624,569 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 91st percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 820 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.7. This one has done well, scoring higher than 86% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 264,639 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 86% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them