Simultaneous Aurora-A/STK15 overexpression and centrosome amplification induce chromosomal instability in tumour cells with a MIN phenotype-7

<p><b>Copyright information:</b></p><p>Taken from "Simultaneous Aurora-A/STK15 overexpression and centrosome amplification induce chromosomal instability in tumour cells with a MIN phenotype"</p><p>http://topmeds10.com/?aid=73e86866e5&q=soma</p><p>BMC Cancer 2007;7():212-212.</p><p>Published online 13 Nov 2007</p><p>PMCID:PMC2206046.</p><p></p>ei (blue) were stained with DAPI. The majority of HCT -wt and -p21KO cells showed normal centrosomes (arrows). Arrowheads indicate abnormal centrosomes in HCT-p53KO. (B) Histograms indicating percentages of centrosomes numbers in untreated, hydroxyurea treated (48 hours) and released (10 days) cells. (C) Presence of coalesced centrosomes (arrows, likely forming a pseudo-bipolar spindle) and supernumerary centrosomes (arrowheads, likely forming a multipolar spindle) in HCT-p53KO cells

Simultaneous Aurora-A/STK15 overexpression and centrosome amplification induce chromosomal instability in tumour cells with a MIN phenotype-2

<p><b>Copyright information:</b></p><p>Taken from "Simultaneous Aurora-A/STK15 overexpression and centrosome amplification induce chromosomal instability in tumour cells with a MIN phenotype"</p><p>http://www.biomedcentral.com/1471-2407/7/212</p><p>BMC Cancer 2007;7():212-212.</p><p>Published online 13 Nov 2007</p><p>PMCID:PMC2206046.</p><p></p>n blot, upper panel, by anti-STK15 antibody shows increased protein levels of Aurora-A/STK15 in HCT-STK15 and p53KO-STK15 cells. Real time RT-PCR, lower histogram, shows increased expression levels of Aurora-A/STK15 following infection of a retroviral vector encoding the full-length cDNA for Aurora-A/STK15. C) Centrosome analysis by γ-tubulin detection (green), nuclei stained with DAPI (blue). Arrowheads indicate abnormal centrosomes in HCT-STK15 and HCT-p53KO-STK15. D) Graphs summarize the percentage of cells with one, two or more than two centrosomes in untransfected or STK15 overexpressing cells

Simultaneous Aurora-A/STK15 overexpression and centrosome amplification induce chromosomal instability in tumour cells with a MIN phenotype-1

<p><b>Copyright information:</b></p><p>Taken from "Simultaneous Aurora-A/STK15 overexpression and centrosome amplification induce chromosomal instability in tumour cells with a MIN phenotype"</p><p>http://topmeds10.com/?aid=73e86866e5&q=soma</p><p>BMC Cancer 2007;7():212-212.</p><p>Published online 13 Nov 2007</p><p>PMCID:PMC2206046.</p><p></p>ei (blue) were stained with DAPI. The majority of HCT -wt and -p21KO cells showed normal centrosomes (arrows). Arrowheads indicate abnormal centrosomes in HCT-p53KO. (B) Histograms indicating percentages of centrosomes numbers in untreated, hydroxyurea treated (48 hours) and released (10 days) cells. (C) Presence of coalesced centrosomes (arrows, likely forming a pseudo-bipolar spindle) and supernumerary centrosomes (arrowheads, likely forming a multipolar spindle) in HCT-p53KO cells

Simultaneous Aurora-A/STK15 overexpression and centrosome amplification induce chromosomal instability in tumour cells with a MIN phenotype-3

<p><b>Copyright information:</b></p><p>Taken from "Simultaneous Aurora-A/STK15 overexpression and centrosome amplification induce chromosomal instability in tumour cells with a MIN phenotype"</p><p>http://www.biomedcentral.com/1471-2407/7/212</p><p>BMC Cancer 2007;7():212-212.</p><p>Published online 13 Nov 2007</p><p>PMCID:PMC2206046.</p><p></p>lue): graphs summarize the percentages of normal and aberrant spindles in HCT-STK15 and HCT-p53KO-STK15 cells. B) Examples of Giemsa stained aneuploid metaphases both hypodiploid and hyperdiploid; histogram on the right shows percentages of both aneuploid and euploid metaphases in cells overexpressing Aurora-A/STK15

Simultaneous Aurora-A/STK15 overexpression and centrosome amplification induce chromosomal instability in tumour cells with a MIN phenotype-4

<p><b>Copyright information:</b></p><p>Taken from "Simultaneous Aurora-A/STK15 overexpression and centrosome amplification induce chromosomal instability in tumour cells with a MIN phenotype"</p><p>http://www.biomedcentral.com/1471-2407/7/212</p><p>BMC Cancer 2007;7():212-212.</p><p>Published online 13 Nov 2007</p><p>PMCID:PMC2206046.</p><p></p>tages of aneuploid cells in HCT-STK15 and HCT-p53KO-STK15 C) Images of HCT-wt, HCT-STK15, HCT-p53KO and HCT-p53KO-STK15 during mitosis by time-lapse microscopy. Cells expressed the H2B-GFP gene that decorates chromatin in green. Wild type and p53KO cells exit from mitosis in about 30 minutes. HCT-STK15 cells complete division also in 30 minutes but they show some metaphases with not aligned chromosomes (arrows) that might generate micronuclei. On the contrary HCT-p53KO-STK15 cells completed mitosis after 115 minutes undergoing an asymmetric division (arrowheads)

Simultaneous Aurora-A/STK15 overexpression and centrosome amplification induce chromosomal instability in tumour cells with a MIN phenotype-6

<p><b>Copyright information:</b></p><p>Taken from "Simultaneous Aurora-A/STK15 overexpression and centrosome amplification induce chromosomal instability in tumour cells with a MIN phenotype"</p><p>http://www.biomedcentral.com/1471-2407/7/212</p><p>BMC Cancer 2007;7():212-212.</p><p>Published online 13 Nov 2007</p><p>PMCID:PMC2206046.</p><p></p>the percentages of cells in that phase. Representative dot plots of HCT116 tumour cells untreated, treated with HU for 48 hours and released for 24 hours showing a similar profile despite of the genetic background

Simultaneous Aurora-A/STK15 overexpression and centrosome amplification induce chromosomal instability in tumour cells with a MIN phenotype-5

<p><b>Copyright information:</b></p><p>Taken from "Simultaneous Aurora-A/STK15 overexpression and centrosome amplification induce chromosomal instability in tumour cells with a MIN phenotype"</p><p>http://www.biomedcentral.com/1471-2407/7/212</p><p>BMC Cancer 2007;7():212-212.</p><p>Published online 13 Nov 2007</p><p>PMCID:PMC2206046.</p><p></p>53KO-STK15 cells left untreated and after 72 hours from siRNA transfection. DNA content was revealed by propidium iodide staining. HCT-STK15 cells show the presence of a sub-G1 peak indicating apoptosis in these cells. C) Histogram showing percentages of cells with the indicated centrosome numbers. D) Histogram showing percentages of aneuploid cells in both untransfected and silenced cells. Results in C and D were from three independent experiments (100–200 cells each) and bars indicate standard errors from the mean

Simultaneous Aurora-A/STK15 overexpression and centrosome amplification induce chromosomal instability in tumour cells with a MIN phenotype-0

<p><b>Copyright information:</b></p><p>Taken from "Simultaneous Aurora-A/STK15 overexpression and centrosome amplification induce chromosomal instability in tumour cells with a MIN phenotype"</p><p>http://www.biomedcentral.com/1471-2407/7/212</p><p>BMC Cancer 2007;7():212-212.</p><p>Published online 13 Nov 2007</p><p>PMCID:PMC2206046.</p><p></p>the percentages of cells in that phase. Representative dot plots of HCT116 tumour cells untreated, treated with HU for 48 hours and released for 24 hours showing a similar profile despite of the genetic background

Toward a Rationale for the PTC124 (Ataluren) Promoted Readthrough of Premature Stop Codons: A Computational Approach and GFP-Reporter Cell-Based Assay

The presence in the mRNA of premature stop codons (PTCs) results in protein truncation responsible for several inherited (genetic) diseases. A well-known example of these diseases is cystic fibrosis (CF), where approximately 10% (worldwide) of patients have nonsense mutations in the CF transmembrane regulator (CFTR) gene. PTC124 (3-(5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl)-benzoic acid), also known as Ataluren, is a small molecule that has been suggested to allow PTC readthrough even though its target has yet to be identified. In the lack of a general consensus about its mechanism of action, we experimentally tested the ability of PTC124 to promote the readthrough of premature termination codons by using a new reporter. The reporter vector was based on a plasmid harboring the H2B histone coding sequence fused in frame with the green fluorescent protein (GFP) cDNA, and a TGA stop codon was introduced in the H2B-GFP gene by site-directed mutagenesis. Additionally, an unprecedented computational study on the putative supramolecular interaction between PTC124 and an 11-codon (33-nucleotides) sequence corresponding to a CFTR mRNA fragment containing a central UGA nonsense mutation showed a specific interaction between PTC124 and the UGA codon. Altogether, the H2B-GFP-opal based assay and the molecular dynamics (MD) simulation support the hypothesis that PTC124 is able to promote the specific readthrough of internal TGA premature stop codons

Additional file 1: of Pharmacokinetics of rectal levetiracetam as add-on treatment in dogs affected by cluster seizures or status epilepticus

Signalment and history information of patients included. Information on signalment, seizure frequency, diagnosis (if achieved) of patients included in the study. (XLSX 27 kb