Tau is known for its pathological role in neurodegenerative diseases, including Alzheimer’s disease (AD) and other tauopathies. Tau is found in many subcellular compartments such as the cytosol and the nucleus. Although its normal role in microtubule binding is well established, its nuclear role is still unclear. Here, we reveal that tau localises to the nucleolus in undifferentiated and differentiated neuroblastoma cells (SHSY5Y), where it associates with TIP5, a key player in heterochromatin stability and ribosomal DNA (rDNA) transcriptional repression. Immunogold labelling on human brain sample confirms the physiological relevance of this finding by showing tau within the nucleolus colocalises with TIP5. Depletion of tau results in an increase in rDNA transcription with an associated decrease in heterochromatin and DNA methylation, suggesting that under normal conditions tau is involved in silencing of the rDNA. Cellular stress induced by glutamate causes nucleolar stress associated with the redistribution of nucleolar non-phosphorylated tau, in a similar manner to fibrillarin, and nuclear upsurge of phosphorylated tau (Thr231) which doesn’t colocalise with fibrillarin or nucleolar tau. This suggests that stress may impact on different nuclear tau species. In addition to involvement in rDNA transcription, nucleolar non-phosphorylated tau also undergoes stress-induced redistribution similar to many nucleolar proteins.Electronic supplementary materialThe online version of this article (10.1186/s40478-018-0565-6) contains supplementary material, which is available to authorized users.

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Conclusion:The successful complete ablation rate after a second ablation dose of is higher than first ablation dose of 100 mCi 1131. No significant difference between completely and non-completely ablated patients after the second ablation dose (30 mCi) as regards age, gender and histopathological details.The overall complete ablation rate after 130 mCi is 90%, this figure is significantly higher than the same figure post either first or second ablation dose separately.

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Well differentiated thyroid cancer is one of the least morbid solid malignancies, with favorable long term survival. However, presence of distant metastases at time of initial evaluation (synchronous metastases, SM) is a strong predictor of poor outcome, as 43-90% of those patients die from their thyroid malignancy. The aim of the current study is to detect significant prognostic factors that can affect patient outcome and disease specific survival in patients with well differentiated thyroid cancer associated with SM. Patients and methods: retrospective analysis of data from patients with pathologically proven well differentiated thyroid cancer having established SM was done. All patients were presented to three oncology centers in the period from Jan. 1992 to Jan 2007. 101 patients were included in the current study, they were followed up for a mean period of 60months, evaluating the effects of different factors on patient outcome and survival. Results: It was found that age, size and extent of metastases and their ability to accumulate I131 had positive impact on patient outcome and survival .Young patients with few small metastatic lesions that have the ability to accumulate radioactive iodine (I131) have significantly better outcome and survival compared to those older than 45 years, with multiple big metastases that do not accumulate I131.On the other hand, gender, type of histopathology, local recurrence, the site of metastases and serum thyroglobulin(Tg) level have no statistical significant difference on patient outcome and survival. Conclusion:In patients with well differentiated thyroid cancer associated with SM the most important factors that have significant impact on patient outcome and do affect survival are age, size, extent of metastatic lesions, as well as, their ability to accumulate I131. The most favorable outcome is for patients younger than 45 years with few small SM that accumulate I131.