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Image Search Results
Journal: Scientific Data
Article Title: High content organelle trafficking enables disease state profiling as powerful tool for disease modelling
doi: 10.1038/sdata.2018.241
Figure Lengend Snippet: (a) Schematic live set up of MNs in Zona MFCs. The central microgroove of channels formed a physical barrier between the distal (left) and proximal (right) site where the somas were seeded. Only axons could penetrate the microchannels. The tightness of the microgroove barrier enabled site–specific drug application: oligomycin A (pink) and nocodazole (black) were added exclusively to the distal MFC site to locally disrupt distal organelle trafficking, whereas a mixture of M1 & Mdivi-1 (green) was applied to either site to promote fusion and elongation of mitochondria. (b) Maximum intensity projections of movie raw data acquired live with mitotracker (left) and lysotracker (right) at the distal (left) versus the proximal (right) microchannel readout position . Note how distal application of oligomycin a (pink) or nocodazole (black) disrupted distal organelle motility whereas proximal motility remained unaltered, indicating local action of both drugs exclusively at the distal MFC site.. As for M1 & Mdivi-1 mix, note how application to either MFC site led to extended elongation of mitochondria (only first movie frame shown here). Scale bar = 10 μm. (c) Multiparametric HC Z-score signatures obtained on Ctrl MNs after treatment with oligmycin A (pink), nocodazole (black) or a M1 & Mdivi-1 mix. Site – specific drug application was as indicated in the header and (a). Z-scores show deviations from proximal Ctrl Mock (blue baseline), Z-score above 5 and below -5 (grey lines) were considered as clearly significant deviations from Ctrl Mock (blue). (d) Hierarchical cluster dendrogram of entire signatures shown in (c). The hierarchical Z-score (ordinate) indicates the deviation of entire signatures from each other and is not to be mistaken with the individual parameter Z-scores in (c). (e) Hierarchical cluster dendogram of partial signatures comprising either only all distal or proximal parameters (Mitotracker and Lysotracker, respectively) to compare site – specific phenotypes.
Article Snippet: We generated a
Techniques:
Journal: Scientific Data
Article Title: High content organelle trafficking enables disease state profiling as powerful tool for disease modelling
doi: 10.1038/sdata.2018.241
Figure Lengend Snippet: (a) Maximum intensity projections of movie raw data acquired live with mitotracker (left) and lysotracker (right) at the distal (left) versus the proximal (right) microchannel readout position . Note the virtual organelle arrest in the FUS (red) and TDP43 (green) mutants at the distal MFC readout site (loss of straight trajectories compared to Ctrl Mock above) whereas proximal motility remained unaltered. Scale bar = 10 μm. (b) Multiparametric HC signatures corresponding to (a). Note the nearly unaltered trafficking of both mutants at the proximal MFC readout site as compared to Ctrl Mock (blue) as opposed to strong negative parameter deviations at the distal site in FUS (red) distinct from the more modest phenotype of TDP43 (green). (c) Hierarchical cluster dendrogram of entire signatures in (b). Note how the modest TDP43 mutant (green) clustered with Ctrl Mock (blue) against the phenotypically more distinct FUS mutant (red). (d) Hierarchical cluster dendrogram of partial signatures comprising either only all distal or proximal parameters to compare site – specific phenotypes. Note how both physiological Ctrl Mock parts (blue, distal and proximal) clustered closely with the proximal FUS Mock part (red) on the right due to the close physiological trafficking state whereas the drastic organelle arrest in the distal FUS Mock part on the far left (red) was highly distinct to the physiological parts at the proximal site. TDP43 showed some moderate deviation in its proximal part (green) from the physiological clusters (Ctrl Mock, blue, and FUS Mock proximal, red) and a clear deviation in its distal part (green), albeit less drastic than FUS Mock (red).
Article Snippet: We generated a
Techniques: Mutagenesis
Journal: Scientific Data
Article Title: High content organelle trafficking enables disease state profiling as powerful tool for disease modelling
doi: 10.1038/sdata.2018.241
Figure Lengend Snippet: (a) Schematic live set up of MNs in Zona MFCs. PARP1i was added to Ctrl MNs exclusively either to the distal (pink) or proximal (orange) MFC site while PARGi was added to FUS MNs exclusively either to the distal (pale blue) or proximal (green) MFC site to discriminate between local and remote action. (b) Maximum intensity projections of movie raw data acquired live with mitotracker (left) and lysotracker (right) at the distal (left) versus the proximal (right) microchannel readout position . Note how proximal application of PARP1i (orange) on Ctrl MNs (mid gallery) led to virtual distal organelle arrest whereas proximal trafficking remained unaltered (loss of distal straight trajectories compared to Ctrl Mock in top gallery). Conversely, distal application of PARP1i (pink) on Ctrl MNs (mid gallery) had no impact on trafficking on either MFC site, arguing against a local mode of PARPi action. Proximal application of PARGi (green) on FUS MNs (bottom gallery) rescued distal organelle motility (restauration of distal straight trajectories compared to Ctrl Mock in top gallery). Conversely, distal application of PARGi (pale blue) on FUS MNs (bottom gallery) had no beneficial impact on trafficking on either MFC site (unaltered loss of distal straight trajectories compared to FUS Mock in top gallery), arguing against a local mode of PARGi action. Scale bar = 10 μm. (c) Multiparametric HC Z-score signatures corresponding to site – specific PARP1i/PARGi treatments in (a) and (b). Site – specific drug application was as indicated in the header. (d) Hierarchical cluster dendrogram of entire signatures shown in (c). (e) Hierarchical cluster dendrogram of partial signatures comprising either only all distal or proximal parameters (Mitotracker and Lysotracker, respectively) to compare site – specific phenotypes.
Article Snippet: We generated a
Techniques: