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int64
2
DISCUSSION
1
35
[ "b35", "b69", "b70", "b30", "b32", "b56", "b71" ]
17,135,188
pmid-9111037|pmid-15907190|pmid-12134943|pmid-16377019|pmid-12771197|pmid-16321967|pmid-15907190|pmid-9438412|pmid-16516138|pmid-12621426|pmid-15687999|pmid-15640444|pmid-15203910|pmid-15935328|pmid-15035618|pmid-15859953|pmid-11856307|pmid-15687490|pmid-12411431|pmid-15653149|pmid-3035599|pmid-11711547|pmid-15628847|p...
Such extracellularly attached carrier/cargo complexes are an important source of overestimation of cargo internalised (35).
[ "35", "69", "70", "30", "32", "56", "71" ]
123
3,500
1
false
Such extracellularly attached carrier/cargo complexes are an important source of overestimation of cargo internalised.
[ "35" ]
Such extracellularly attached carrier/cargo complexes are an important source of overestimation of cargo internalised.
true
true
true
true
true
593
2
DISCUSSION
1
35
[ "b35", "b69", "b70", "b30", "b32", "b56", "b71" ]
17,135,188
pmid-9111037|pmid-15907190|pmid-12134943|pmid-16377019|pmid-12771197|pmid-16321967|pmid-15907190|pmid-9438412|pmid-16516138|pmid-12621426|pmid-15687999|pmid-15640444|pmid-15203910|pmid-15935328|pmid-15035618|pmid-15859953|pmid-11856307|pmid-15687490|pmid-12411431|pmid-15653149|pmid-3035599|pmid-11711547|pmid-15628847|p...
As opposed to the commonly used trypsin treatment, a heparin wash was much more effective in our hands (Supplementary Figure 2A and B).
[ "35", "69", "70", "30", "32", "56", "71" ]
135
3,501
0
false
As opposed to the commonly used trypsin treatment, a heparin wash was much more effective in our hands (Supplementary Figure 2A and B).
[]
As opposed to the commonly used trypsin treatment, a heparin wash was much more effective in our hands (Supplementary Figure 2A and B).
true
true
true
true
true
593
2
DISCUSSION
1
35
[ "b35", "b69", "b70", "b30", "b32", "b56", "b71" ]
17,135,188
pmid-9111037|pmid-15907190|pmid-12134943|pmid-16377019|pmid-12771197|pmid-16321967|pmid-15907190|pmid-9438412|pmid-16516138|pmid-12621426|pmid-15687999|pmid-15640444|pmid-15203910|pmid-15935328|pmid-15035618|pmid-15859953|pmid-11856307|pmid-15687490|pmid-12411431|pmid-15653149|pmid-3035599|pmid-11711547|pmid-15628847|p...
Similar results were reported by Kaplan et al.
[ "35", "69", "70", "30", "32", "56", "71" ]
46
3,502
0
false
Similar results were reported by Kaplan et al.
[]
Similar results were reported by Kaplan et al.
true
true
true
true
true
593
2
DISCUSSION
1
69
[ "b35", "b69", "b70", "b30", "b32", "b56", "b71" ]
17,135,188
pmid-9111037|pmid-15907190|pmid-12134943|pmid-16377019|pmid-12771197|pmid-16321967|pmid-15907190|pmid-9438412|pmid-16516138|pmid-12621426|pmid-15687999|pmid-15640444|pmid-15203910|pmid-15935328|pmid-15035618|pmid-15859953|pmid-11856307|pmid-15687490|pmid-12411431|pmid-15653149|pmid-3035599|pmid-11711547|pmid-15628847|p...
(69) for the cellular uptake of Tat peptide in the absence of cargo.
[ "35", "69", "70", "30", "32", "56", "71" ]
68
3,503
1
false
for the cellular uptake of Tat peptide in the absence of cargo.
[ "69" ]
for the cellular uptake of Tat peptide in the absence of cargo.
false
true
true
true
false
593
2
DISCUSSION
1
35
[ "b35", "b69", "b70", "b30", "b32", "b56", "b71" ]
17,135,188
pmid-9111037|pmid-15907190|pmid-12134943|pmid-16377019|pmid-12771197|pmid-16321967|pmid-15907190|pmid-9438412|pmid-16516138|pmid-12621426|pmid-15687999|pmid-15640444|pmid-15203910|pmid-15935328|pmid-15035618|pmid-15859953|pmid-11856307|pmid-15687490|pmid-12411431|pmid-15653149|pmid-3035599|pmid-11711547|pmid-15628847|p...
The negatively charged heparin molecules, with a molecular weight of 4–6 kDa, are much smaller than trypsin and thus might be able to infiltrate the extracellular matrix more effectively and both detach and, more importantly, dissociate MPGα/siRNA complexes bound there.
[ "35", "69", "70", "30", "32", "56", "71" ]
270
3,504
0
false
The negatively charged heparin molecules, with a molecular weight of 4–6 kDa, are much smaller than trypsin and thus might be able to infiltrate the extracellular matrix more effectively and both detach and, more importantly, dissociate MPGα/siRNA complexes bound there.
[]
The negatively charged heparin molecules, with a molecular weight of 4–6 kDa, are much smaller than trypsin and thus might be able to infiltrate the extracellular matrix more effectively and both detach and, more importantly, dissociate MPGα/siRNA complexes bound there.
true
true
true
true
true
593
2
DISCUSSION
1
35
[ "b35", "b69", "b70", "b30", "b32", "b56", "b71" ]
17,135,188
pmid-9111037|pmid-15907190|pmid-12134943|pmid-16377019|pmid-12771197|pmid-16321967|pmid-15907190|pmid-9438412|pmid-16516138|pmid-12621426|pmid-15687999|pmid-15640444|pmid-15203910|pmid-15935328|pmid-15035618|pmid-15859953|pmid-11856307|pmid-15687490|pmid-12411431|pmid-15653149|pmid-3035599|pmid-11711547|pmid-15628847|p...
In contrast to this, trypsin considerably increased the apparent uptake of the complexes (Supplementary Figure 2B).
[ "35", "69", "70", "30", "32", "56", "71" ]
115
3,505
0
false
In contrast to this, trypsin considerably increased the apparent uptake of the complexes (Supplementary Figure 2B).
[]
In contrast to this, trypsin considerably increased the apparent uptake of the complexes (Supplementary Figure 2B).
true
true
true
true
true
593
2
DISCUSSION
1
70
[ "b35", "b69", "b70", "b30", "b32", "b56", "b71" ]
17,135,188
pmid-9111037|pmid-15907190|pmid-12134943|pmid-16377019|pmid-12771197|pmid-16321967|pmid-15907190|pmid-9438412|pmid-16516138|pmid-12621426|pmid-15687999|pmid-15640444|pmid-15203910|pmid-15935328|pmid-15035618|pmid-15859953|pmid-11856307|pmid-15687490|pmid-12411431|pmid-15653149|pmid-3035599|pmid-11711547|pmid-15628847|p...
This might be due to a membrane destabilising effect of this enzyme which has been shown to enhance the uptake of small molecules or oligonucleotides (70).
[ "35", "69", "70", "30", "32", "56", "71" ]
155
3,506
1
false
This might be due to a membrane destabilising effect of this enzyme which has been shown to enhance the uptake of small molecules or oligonucleotides.
[ "70" ]
This might be due to a membrane destabilising effect of this enzyme which has been shown to enhance the uptake of small molecules or oligonucleotides.
true
true
true
true
true
593
2
DISCUSSION
1
35
[ "b35", "b69", "b70", "b30", "b32", "b56", "b71" ]
17,135,188
pmid-9111037|pmid-15907190|pmid-12134943|pmid-16377019|pmid-12771197|pmid-16321967|pmid-15907190|pmid-9438412|pmid-16516138|pmid-12621426|pmid-15687999|pmid-15640444|pmid-15203910|pmid-15935328|pmid-15035618|pmid-15859953|pmid-11856307|pmid-15687490|pmid-12411431|pmid-15653149|pmid-3035599|pmid-11711547|pmid-15628847|p...
For several CPPs without a cargo it has previously been shown that the cellular penetration is inhibited by certain GAGs suggesting that uptake is mediated by GAG receptors on the cell surface (30,32,56,71).
[ "35", "69", "70", "30", "32", "56", "71" ]
207
3,507
0
false
For several CPPs without a cargo it has previously been shown that the cellular penetration is inhibited by certain GAGs suggesting that uptake is mediated by GAG receptors on the cell surface.
[ "30,32,56,71" ]
For several CPPs without a cargo it has previously been shown that the cellular penetration is inhibited by certain GAGs suggesting that uptake is mediated by GAG receptors on the cell surface.
true
true
true
true
true
593
2
DISCUSSION
1
35
[ "b35", "b69", "b70", "b30", "b32", "b56", "b71" ]
17,135,188
pmid-9111037|pmid-15907190|pmid-12134943|pmid-16377019|pmid-12771197|pmid-16321967|pmid-15907190|pmid-9438412|pmid-16516138|pmid-12621426|pmid-15687999|pmid-15640444|pmid-15203910|pmid-15935328|pmid-15035618|pmid-15859953|pmid-11856307|pmid-15687490|pmid-12411431|pmid-15653149|pmid-3035599|pmid-11711547|pmid-15628847|p...
To what extent these receptors are equally involved in the uptake of MPGα/siRNA complexes cannot be answered with certainty as heparin has a very strong destabilising effect on the peptide/nucleic acid complexes (A.T., unpublished data).
[ "35", "69", "70", "30", "32", "56", "71" ]
237
3,508
0
false
To what extent these receptors are equally involved in the uptake of MPGα/siRNA complexes cannot be answered with certainty as heparin has a very strong destabilising effect on the peptide/nucleic acid complexes (A.T., unpublished data).
[]
To what extent these receptors are equally involved in the uptake of MPGα/siRNA complexes cannot be answered with certainty as heparin has a very strong destabilising effect on the peptide/nucleic acid complexes (A.T., unpublished data).
true
true
true
true
true
593
3
DISCUSSION
1
72
[ "b72", "b73", "b74" ]
17,135,188
pmid-9207018|pmid-15196012|pmid-10751399|pmid-12746500|pmid-16682561
With a reliable washing procedure to remove extracellular complexes in place we were able to accurately quantify the intracellular amounts of cargo after carrier-mediated delivery (Figure 3 and Table 2).
[ "72", "73", "74" ]
203
3,509
0
false
With a reliable washing procedure to remove extracellular complexes in place we were able to accurately quantify the intracellular amounts of cargo after carrier-mediated delivery (Figure 3 and Table 2).
[]
With a reliable washing procedure to remove extracellular complexes in place we were able to accurately quantify the intracellular amounts of cargo after carrier-mediated delivery.
true
true
true
true
true
594
3
DISCUSSION
1
72
[ "b72", "b73", "b74" ]
17,135,188
pmid-9207018|pmid-15196012|pmid-10751399|pmid-12746500|pmid-16682561
The amount of siRNA internalised, increased as expected with the incubation time of transfection showing a maximum at ∼4 h (Supplementary Figure 3B and C).
[ "72", "73", "74" ]
155
3,510
0
false
The amount of siRNA internalised, increased as expected with the incubation time of transfection showing a maximum at ∼4 h (Supplementary Figure 3B and C).
[]
The amount of siRNA internalised, increased as expected with the incubation time of transfection showing a maximum at ∼4 h (Supplementary Figure 3B and C).
true
true
true
true
true
594
3
DISCUSSION
1
72
[ "b72", "b73", "b74" ]
17,135,188
pmid-9207018|pmid-15196012|pmid-10751399|pmid-12746500|pmid-16682561
Similar results were observed with a RNA aptamer [(72), S.L., unpublished data].
[ "72", "73", "74" ]
80
3,511
0
false
Similar results were observed with a RNA aptamer.
[ "(72), S.L., unpublished data" ]
Similar results were observed with a RNA aptamer.
true
true
true
true
true
594
3
DISCUSSION
1
72
[ "b72", "b73", "b74" ]
17,135,188
pmid-9207018|pmid-15196012|pmid-10751399|pmid-12746500|pmid-16682561
Accordingly, unless otherwise indicated, all transfections were performed for a period of 4 h before cells were either subjected to quantification (after an additional 1 h heparin wash) or further incubated in the absence of carrier/cargo complexes for later analyses.
[ "72", "73", "74" ]
268
3,512
0
false
Accordingly, unless otherwise indicated, all transfections were performed for a period of 4 h before cells were either subjected to quantification (after an additional 1 h heparin wash) or further incubated in the absence of carrier/cargo complexes for later analyses.
[]
Accordingly, unless otherwise indicated, all transfections were performed for a period of 4 h before cells were either subjected to quantification (after an additional 1 h heparin wash) or further incubated in the absence of carrier/cargo complexes for later analyses.
true
true
true
true
true
594
3
DISCUSSION
1
72
[ "b72", "b73", "b74" ]
17,135,188
pmid-9207018|pmid-15196012|pmid-10751399|pmid-12746500|pmid-16682561
After 24 h approximately half of the maximal amount of siRNA internalised was still detectable.
[ "72", "73", "74" ]
95
3,513
0
false
After 24 h approximately half of the maximal amount of siRNA internalised was still detectable.
[]
After 24 h approximately half of the maximal amount of siRNA internalised was still detectable.
true
true
true
true
true
594
3
DISCUSSION
1
72
[ "b72", "b73", "b74" ]
17,135,188
pmid-9207018|pmid-15196012|pmid-10751399|pmid-12746500|pmid-16682561
All in all <5% of the siRNA present in the initial transfection mixture was internalised into the cells regardless of the delivery agent.
[ "72", "73", "74" ]
137
3,514
0
false
All in all <5% of the siRNA present in the initial transfection mixture was internalised into the cells regardless of the delivery agent.
[]
All in all <5% of the siRNA present in the initial transfection mixture was internalised into the cells regardless of the delivery agent.
true
true
true
true
true
594
3
DISCUSSION
1
72
[ "b72", "b73", "b74" ]
17,135,188
pmid-9207018|pmid-15196012|pmid-10751399|pmid-12746500|pmid-16682561
After 4 h, twice as much siRNA was detected inside the cells after transfection with LF2000 when compared to MPGα-mediated delivery.
[ "72", "73", "74" ]
132
3,515
0
false
After 4 h, twice as much siRNA was detected inside the cells after transfection with LF2000 when compared to MPGα-mediated delivery.
[]
After 4 h, twice as much siRNA was detected inside the cells after transfection with LF2000 when compared to MPGα-mediated delivery.
true
true
true
true
true
594
3
DISCUSSION
1
72
[ "b72", "b73", "b74" ]
17,135,188
pmid-9207018|pmid-15196012|pmid-10751399|pmid-12746500|pmid-16682561
Surprisingly, 24 h after transfection this difference rose to a factor of 4–6.
[ "72", "73", "74" ]
78
3,516
0
false
Surprisingly, 24 h after transfection this difference rose to a factor of 4–6.
[]
Surprisingly, 24 h after transfection this difference rose to a factor of 4–6.
true
true
true
true
true
594
3
DISCUSSION
1
72
[ "b72", "b73", "b74" ]
17,135,188
pmid-9207018|pmid-15196012|pmid-10751399|pmid-12746500|pmid-16682561
In vitro experiments, on the other hand, show that siRNA complexed with the carrier peptide is strongly protected from degradation (data not shown).
[ "72", "73", "74" ]
148
3,517
0
false
In vitro experiments, on the other hand, show that siRNA complexed with the carrier peptide is strongly protected from degradation (data not shown).
[]
In vitro experiments, on the other hand, show that siRNA complexed with the carrier peptide is strongly protected from degradation (data not shown).
true
true
true
true
true
594
3
DISCUSSION
1
72
[ "b72", "b73", "b74" ]
17,135,188
pmid-9207018|pmid-15196012|pmid-10751399|pmid-12746500|pmid-16682561
The observed uptake of siRNA was linear over a tested range of 0.1–100 nM of siRNA.
[ "72", "73", "74" ]
83
3,518
0
false
The observed uptake of siRNA was linear over a tested range of 0.1–100 nM of siRNA.
[]
The observed uptake of siRNA was linear over a tested range of 0.1–100 nM of siRNA.
true
true
true
true
true
594
3
DISCUSSION
1
72
[ "b72", "b73", "b74" ]
17,135,188
pmid-9207018|pmid-15196012|pmid-10751399|pmid-12746500|pmid-16682561
We deliberately did not apply concentrations >100 nM siRNA to examine if the process would eventually be saturable, since too high concentrations of siRNA lead to off-target effects (73,74).
[ "72", "73", "74" ]
190
3,519
0
false
We deliberately did not apply concentrations >100 nM siRNA to examine if the process would eventually be saturable, since too high concentrations of siRNA lead to off-target effects.
[ "73,74" ]
We deliberately did not apply concentrations >100 nM siRNA to examine if the process would eventually be saturable, since too high concentrations of siRNA lead to off-target effects.
true
true
true
true
true
594
3
DISCUSSION
1
72
[ "b72", "b73", "b74" ]
17,135,188
pmid-9207018|pmid-15196012|pmid-10751399|pmid-12746500|pmid-16682561
Taken together, the difference in uptake between the peptide and the cationic lipid was much smaller than anticipated from the above described IC50 values with a factor of about 2–6 in favor of LF2000.
[ "72", "73", "74" ]
201
3,520
0
false
Taken together, the difference in uptake between the peptide and the cationic lipid was much smaller than anticipated from the above described IC50 values with a factor of about 2–6 in favor of LF2000.
[]
Taken together, the difference in uptake between the peptide and the cationic lipid was much smaller than anticipated from the above described IC50 values with a factor of about 2–6 in favor of LF2000.
true
true
true
true
true
594
3
DISCUSSION
1
72
[ "b72", "b73", "b74" ]
17,135,188
pmid-9207018|pmid-15196012|pmid-10751399|pmid-12746500|pmid-16682561
These findings clearly indicate that uptake per se was not the limiting factor of the peptide approach.
[ "72", "73", "74" ]
103
3,521
0
false
These findings clearly indicate that uptake per se was not the limiting factor of the peptide approach.
[]
These findings clearly indicate that uptake per se was not the limiting factor of the peptide approach.
true
true
true
true
true
594
3
DISCUSSION
1
72
[ "b72", "b73", "b74" ]
17,135,188
pmid-9207018|pmid-15196012|pmid-10751399|pmid-12746500|pmid-16682561
Combining both techniques, the analysis of uptake and RNAi effect, it became apparent that for a half maximal inhibition of reporter gene activity, ∼10 000 siRNA molecules were necessary in case of MPGα-mediated delivery, whereas in case of LF2000 only ∼300 molecules were required.
[ "72", "73", "74" ]
282
3,522
0
false
Combining both techniques, the analysis of uptake and RNAi effect, it became apparent that for a half maximal inhibition of reporter gene activity, ∼10 000 siRNA molecules were necessary in case of MPGα-mediated delivery, whereas in case of LF2000 only ∼300 molecules were required.
[]
Combining both techniques, the analysis of uptake and RNAi effect, it became apparent that for a half maximal inhibition of reporter gene activity, ∼10 000 siRNA molecules were necessary in case of MPGα-mediated delivery, whereas in case of LF2000 only ∼300 molecules were required.
true
true
true
true
true
594
3
DISCUSSION
1
72
[ "b72", "b73", "b74" ]
17,135,188
pmid-9207018|pmid-15196012|pmid-10751399|pmid-12746500|pmid-16682561
Thus, the amount of bio-available siRNA molecules inside the cells was about 30-fold lower for peptide-mediated delivery as compared to cationic lipid-mediated delivery.
[ "72", "73", "74" ]
169
3,523
0
false
Thus, the amount of bio-available siRNA molecules inside the cells was about 30-fold lower for peptide-mediated delivery as compared to cationic lipid-mediated delivery.
[]
Thus, the amount of bio-available siRNA molecules inside the cells was about 30-fold lower for peptide-mediated delivery as compared to cationic lipid-mediated delivery.
true
true
true
true
true
594
3
DISCUSSION
1
72
[ "b72", "b73", "b74" ]
17,135,188
pmid-9207018|pmid-15196012|pmid-10751399|pmid-12746500|pmid-16682561
To the best of our knowledge, this is the first time the number of siRNA molecules per cell has been determined for half maximal inhibition of the target for peptide- versus cationic lipid-mediated delivery.
[ "72", "73", "74" ]
207
3,524
0
false
To the best of our knowledge, this is the first time the number of siRNA molecules per cell has been determined for half maximal inhibition of the target for peptide- versus cationic lipid-mediated delivery.
[]
To the best of our knowledge, this is the first time the number of siRNA molecules per cell has been determined for half maximal inhibition of the target for peptide- versus cationic lipid-mediated delivery.
true
true
true
true
true
594
3
DISCUSSION
1
72
[ "b72", "b73", "b74" ]
17,135,188
pmid-9207018|pmid-15196012|pmid-10751399|pmid-12746500|pmid-16682561
At this point the question arose, what the cause of this observed discrepancy was.
[ "72", "73", "74" ]
82
3,525
0
false
At this point the question arose, what the cause of this observed discrepancy was.
[]
At this point the question arose, what the cause of this observed discrepancy was.
true
true
true
true
true
594
3
DISCUSSION
1
72
[ "b72", "b73", "b74" ]
17,135,188
pmid-9207018|pmid-15196012|pmid-10751399|pmid-12746500|pmid-16682561
An obvious reason for these findings would be a difference in the mechanism of uptake.
[ "72", "73", "74" ]
86
3,526
0
false
An obvious reason for these findings would be a difference in the mechanism of uptake.
[]
An obvious reason for these findings would be a difference in the mechanism of uptake.
true
true
true
true
true
594
3
DISCUSSION
1
72
[ "b72", "b73", "b74" ]
17,135,188
pmid-9207018|pmid-15196012|pmid-10751399|pmid-12746500|pmid-16682561
As outlined above, the mechanisms underlying the cellular translocation of CPPs are poorly understood and remain hotly debated.
[ "72", "73", "74" ]
127
3,527
0
false
As outlined above, the mechanisms underlying the cellular translocation of CPPs are poorly understood and remain hotly debated.
[]
As outlined above, the mechanisms underlying the cellular translocation of CPPs are poorly understood and remain hotly debated.
true
true
true
true
true
594
3
DISCUSSION
1
72
[ "b72", "b73", "b74" ]
17,135,188
pmid-9207018|pmid-15196012|pmid-10751399|pmid-12746500|pmid-16682561
Nonetheless, there is considerable evidence that endocytosis is a major route of the internalisation of many CPPs.
[ "72", "73", "74" ]
114
3,528
0
false
Nonetheless, there is considerable evidence that endocytosis is a major route of the internalisation of many CPPs.
[]
Nonetheless, there is considerable evidence that endocytosis is a major route of the internalisation of many CPPs.
true
true
true
true
true
594
3
DISCUSSION
1
72
[ "b72", "b73", "b74" ]
17,135,188
pmid-9207018|pmid-15196012|pmid-10751399|pmid-12746500|pmid-16682561
In an attempt to address this question we performed fluorescence microscopy studies and analysed the influence of specific inhibitors/effectors of different endocytotic pathways on the delivery of siRNA and the inhibition of reporter gene activity simultaneously.
[ "72", "73", "74" ]
263
3,529
0
false
In an attempt to address this question we performed fluorescence microscopy studies and analysed the influence of specific inhibitors/effectors of different endocytotic pathways on the delivery of siRNA and the inhibition of reporter gene activity simultaneously.
[]
In an attempt to address this question we performed fluorescence microscopy studies and analysed the influence of specific inhibitors/effectors of different endocytotic pathways on the delivery of siRNA and the inhibition of reporter gene activity simultaneously.
true
true
true
true
true
594
4
DISCUSSION
1
32
[ "b32", "b75", "b76", "b77", "b80" ]
17,135,188
pmid-15628847|pmid-10401530|pmid-16684885|pmid-6159360|pmid-15643423
A first clear hint for an endocytotic pathway involved in the uptake of MPGα/siRNA complexes arose from microscopy studies (Figure 4).
[ "32", "75", "76", "77", "80" ]
134
3,530
0
false
A first clear hint for an endocytotic pathway involved in the uptake of MPGα/siRNA complexes arose from microscopy studies (Figure 4).
[]
A first clear hint for an endocytotic pathway involved in the uptake of MPGα/siRNA complexes arose from microscopy studies (Figure 4).
true
true
true
true
true
595
4
DISCUSSION
1
32
[ "b32", "b75", "b76", "b77", "b80" ]
17,135,188
pmid-15628847|pmid-10401530|pmid-16684885|pmid-6159360|pmid-15643423
Consistent with the assumption of an endocytotic pathway, a typical vesicular distribution pattern in the cytoplasm could be observed by fluorescence microscopy.
[ "32", "75", "76", "77", "80" ]
161
3,531
0
false
Consistent with the assumption of an endocytotic pathway, a typical vesicular distribution pattern in the cytoplasm could be observed by fluorescence microscopy.
[]
Consistent with the assumption of an endocytotic pathway, a typical vesicular distribution pattern in the cytoplasm could be observed by fluorescence microscopy.
true
true
true
true
true
595
4
DISCUSSION
1
32
[ "b32", "b75", "b76", "b77", "b80" ]
17,135,188
pmid-15628847|pmid-10401530|pmid-16684885|pmid-6159360|pmid-15643423
Moreover, the siRNA internalised was observed to partially co-localise with endosomal/lysosomal compartments (data not shown).
[ "32", "75", "76", "77", "80" ]
126
3,532
0
false
Moreover, the siRNA internalised was observed to partially co-localise with endosomal/lysosomal compartments (data not shown).
[]
Moreover, the siRNA internalised was observed to partially co-localise with endosomal/lysosomal compartments (data not shown).
true
true
true
true
true
595
4
DISCUSSION
1
32
[ "b32", "b75", "b76", "b77", "b80" ]
17,135,188
pmid-15628847|pmid-10401530|pmid-16684885|pmid-6159360|pmid-15643423
The results were very similar for LF2000-mediated transfection though here a slight diffuse distribution of fluorescence throughout the cytoplasm was recognisable but hard to document.
[ "32", "75", "76", "77", "80" ]
184
3,533
0
false
The results were very similar for LF2000-mediated transfection though here a slight diffuse distribution of fluorescence throughout the cytoplasm was recognisable but hard to document.
[]
The results were very similar for LF2000-mediated transfection though here a slight diffuse distribution of fluorescence throughout the cytoplasm was recognisable but hard to document.
true
true
true
true
true
595
4
DISCUSSION
1
32
[ "b32", "b75", "b76", "b77", "b80" ]
17,135,188
pmid-15628847|pmid-10401530|pmid-16684885|pmid-6159360|pmid-15643423
To avoid any artefacts due to cell fixation, all fluorescence microscopy experiments were performed with living cells.
[ "32", "75", "76", "77", "80" ]
118
3,534
0
false
To avoid any artefacts due to cell fixation, all fluorescence microscopy experiments were performed with living cells.
[]
To avoid any artefacts due to cell fixation, all fluorescence microscopy experiments were performed with living cells.
true
true
true
true
true
595
4
DISCUSSION
1
32
[ "b32", "b75", "b76", "b77", "b80" ]
17,135,188
pmid-15628847|pmid-10401530|pmid-16684885|pmid-6159360|pmid-15643423
The heparin wash described above proved to be essential as images of cells not treated with heparin showed large aggregates on the cell surface impairing the view on complexes internalised (as clearly seen in Supplementary Figure 2A).
[ "32", "75", "76", "77", "80" ]
234
3,535
0
false
The heparin wash described above proved to be essential as images of cells not treated with heparin showed large aggregates on the cell surface impairing the view on complexes internalised (as clearly seen in Supplementary Figure 2A).
[]
The heparin wash described above proved to be essential as images of cells not treated with heparin showed large aggregates on the cell surface impairing the view on complexes internalised.
true
true
true
true
true
595
4
DISCUSSION
1
32
[ "b32", "b75", "b76", "b77", "b80" ]
17,135,188
pmid-15628847|pmid-10401530|pmid-16684885|pmid-6159360|pmid-15643423
Addition of trypan blue to quench external fluorescence (32,75) was only suitable for smaller complexes but larger ones remained visible.
[ "32", "75", "76", "77", "80" ]
137
3,536
0
false
Addition of trypan blue to quench external fluorescence was only suitable for smaller complexes but larger ones remained visible.
[ "32,75" ]
Addition of trypan blue to quench external fluorescence was only suitable for smaller complexes but larger ones remained visible.
true
true
true
true
true
595
4
DISCUSSION
1
32
[ "b32", "b75", "b76", "b77", "b80" ]
17,135,188
pmid-15628847|pmid-10401530|pmid-16684885|pmid-6159360|pmid-15643423
Carboxyfluorescein in the medium turned out to be very useful to distinguish between the inside and the outside of the cell and was used to clearly discriminate between intra- and extracellular complexes.
[ "32", "75", "76", "77", "80" ]
204
3,537
0
false
Carboxyfluorescein in the medium turned out to be very useful to distinguish between the inside and the outside of the cell and was used to clearly discriminate between intra- and extracellular complexes.
[]
Carboxyfluorescein in the medium turned out to be very useful to distinguish between the inside and the outside of the cell and was used to clearly discriminate between intra- and extracellular complexes.
true
true
true
true
true
595
4
DISCUSSION
1
32
[ "b32", "b75", "b76", "b77", "b80" ]
17,135,188
pmid-15628847|pmid-10401530|pmid-16684885|pmid-6159360|pmid-15643423
Although MPGα harbors an NLS sequence, no nuclear localisation could be observed nor was there any change in the apparent RNAi effect when the NLS sequence was mutated (data not shown).
[ "32", "75", "76", "77", "80" ]
185
3,538
0
false
Although MPGα harbors an NLS sequence, no nuclear localisation could be observed nor was there any change in the apparent RNAi effect when the NLS sequence was mutated (data not shown).
[]
Although MPGα harbors an NLS sequence, no nuclear localisation could be observed nor was there any change in the apparent RNAi effect when the NLS sequence was mutated (data not shown).
true
true
true
true
true
595
4
DISCUSSION
1
32
[ "b32", "b75", "b76", "b77", "b80" ]
17,135,188
pmid-15628847|pmid-10401530|pmid-16684885|pmid-6159360|pmid-15643423
On the other hand, it cannot be ruled out that the amount of cargo localised in the nucleus was below the detection limit.
[ "32", "75", "76", "77", "80" ]
122
3,539
0
false
On the other hand, it cannot be ruled out that the amount of cargo localised in the nucleus was below the detection limit.
[]
On the other hand, it cannot be ruled out that the amount of cargo localised in the nucleus was below the detection limit.
true
true
true
true
true
595
4
DISCUSSION
1
32
[ "b32", "b75", "b76", "b77", "b80" ]
17,135,188
pmid-15628847|pmid-10401530|pmid-16684885|pmid-6159360|pmid-15643423
According to a recent study of Berezhna et al.
[ "32", "75", "76", "77", "80" ]
46
3,540
0
false
According to a recent study of Berezhna et al.
[]
According to a recent study of Berezhna et al.
true
true
true
true
true
595
4
DISCUSSION
1
76
[ "b32", "b75", "b76", "b77", "b80" ]
17,135,188
pmid-15628847|pmid-10401530|pmid-16684885|pmid-6159360|pmid-15643423
(76) the intracellular localisation of siRNA is suggested to depend on the localisation of the target.
[ "32", "75", "76", "77", "80" ]
102
3,541
1
false
the intracellular localisation of siRNA is suggested to depend on the localisation of the target.
[ "76" ]
the intracellular localisation of siRNA is suggested to depend on the localisation of the target.
false
true
true
true
false
595
4
DISCUSSION
1
32
[ "b32", "b75", "b76", "b77", "b80" ]
17,135,188
pmid-15628847|pmid-10401530|pmid-16684885|pmid-6159360|pmid-15643423
Nonetheless, applying a fluorescently labeled siRNA against the 7SK RNA, which was shown to strictly localise in the nucleus (77–80), we did not observe any fluorescence there (data not shown).
[ "32", "75", "76", "77", "80" ]
193
3,542
0
false
Nonetheless, applying a fluorescently labeled siRNA against the 7SK RNA, which was shown to strictly localise in the nucleus, we did not observe any fluorescence there (data not shown).
[ "77–80" ]
Nonetheless, applying a fluorescently labeled siRNA against the 7SK RNA, which was shown to strictly localise in the nucleus, we did not observe any fluorescence there (data not shown).
true
true
true
true
true
595
5
DISCUSSION
1
81
[ "b81", "b82", "b31", "b83", "b84", "b85", "b86", "b87", "b88", "b89", "b90", "b89", "b91", "b93", "b94", "b96", "b97", "b98", "b99" ]
17,135,188
pmid-2022649|pmid-6155379|pmid-12837762|pmid-12783857|pmid-16287236|pmid-8797088|pmid-8947549|pmid-596521|pmid-10637311|pmid-6322305|pmid-16344372|pmid-6322305|pmid-9177342|pmid-12075072|pmid-2158158|pmid-11809836|pmid-6183281|pmid-6298741|pmid-11337152
Lowering of the temperature markedly reduces flexibility and fluidity of the plasma membrane, thereby also slowing membrane traffic (81) and blocking all endocytotic processes (82).
[ "81", "82", "31", "83", "84", "85", "86", "87", "88", "89", "90", "89", "91", "93", "94", "96", "97", "98", "99" ]
181
3,543
1
false
Lowering of the temperature markedly reduces flexibility and fluidity of the plasma membrane, thereby also slowing membrane traffic and blocking all endocytotic processes.
[ "81", "82" ]
Lowering of the temperature markedly reduces flexibility and fluidity of the plasma membrane, thereby also slowing membrane traffic and blocking all endocytotic processes.
true
true
true
true
true
596
5
DISCUSSION
1
81
[ "b81", "b82", "b31", "b83", "b84", "b85", "b86", "b87", "b88", "b89", "b90", "b89", "b91", "b93", "b94", "b96", "b97", "b98", "b99" ]
17,135,188
pmid-2022649|pmid-6155379|pmid-12837762|pmid-12783857|pmid-16287236|pmid-8797088|pmid-8947549|pmid-596521|pmid-10637311|pmid-6322305|pmid-16344372|pmid-6322305|pmid-9177342|pmid-12075072|pmid-2158158|pmid-11809836|pmid-6183281|pmid-6298741|pmid-11337152
Consistent with this concept, we could neither detect MPGα-mediated siRNA delivery at 4°C as shown by liquid hybridisation analyses as well as by fluorescence microscopy (Supplementary Figure 3), nor did we observe any RNAi effect (Figure 5).
[ "81", "82", "31", "83", "84", "85", "86", "87", "88", "89", "90", "89", "91", "93", "94", "96", "97", "98", "99" ]
242
3,544
0
false
Consistent with this concept, we could neither detect MPGα-mediated siRNA delivery at 4°C as shown by liquid hybridisation analyses as well as by fluorescence microscopy (Supplementary Figure 3), nor did we observe any RNAi effect (Figure 5).
[]
Consistent with this concept, we could neither detect MPGα-mediated siRNA delivery at 4°C as shown by liquid hybridisation analyses as well as by fluorescence microscopy (Supplementary Figure 3), nor did we observe any RNAi effect (Figure 5).
true
true
true
true
true
596
5
DISCUSSION
1
81
[ "b81", "b82", "b31", "b83", "b84", "b85", "b86", "b87", "b88", "b89", "b90", "b89", "b91", "b93", "b94", "b96", "b97", "b98", "b99" ]
17,135,188
pmid-2022649|pmid-6155379|pmid-12837762|pmid-12783857|pmid-16287236|pmid-8797088|pmid-8947549|pmid-596521|pmid-10637311|pmid-6322305|pmid-16344372|pmid-6322305|pmid-9177342|pmid-12075072|pmid-2158158|pmid-11809836|pmid-6183281|pmid-6298741|pmid-11337152
In accordance with our findings, other authors also suggested an energy-dependent uptake process for CPP-mediated delivery based on the observation that uptake was strongly decreased at low temperatures (31,83,84).
[ "81", "82", "31", "83", "84", "85", "86", "87", "88", "89", "90", "89", "91", "93", "94", "96", "97", "98", "99" ]
214
3,545
0
false
In accordance with our findings, other authors also suggested an energy-dependent uptake process for CPP-mediated delivery based on the observation that uptake was strongly decreased at low temperatures.
[ "31,83,84" ]
In accordance with our findings, other authors also suggested an energy-dependent uptake process for CPP-mediated delivery based on the observation that uptake was strongly decreased at low temperatures.
true
true
true
true
true
596
5
DISCUSSION
1
81
[ "b81", "b82", "b31", "b83", "b84", "b85", "b86", "b87", "b88", "b89", "b90", "b89", "b91", "b93", "b94", "b96", "b97", "b98", "b99" ]
17,135,188
pmid-2022649|pmid-6155379|pmid-12837762|pmid-12783857|pmid-16287236|pmid-8797088|pmid-8947549|pmid-596521|pmid-10637311|pmid-6322305|pmid-16344372|pmid-6322305|pmid-9177342|pmid-12075072|pmid-2158158|pmid-11809836|pmid-6183281|pmid-6298741|pmid-11337152
In order to address this issue in more detail, we performed studies on MPGα with different modulators of endocytosis (Figure 5).
[ "81", "82", "31", "83", "84", "85", "86", "87", "88", "89", "90", "89", "91", "93", "94", "96", "97", "98", "99" ]
128
3,546
0
false
In order to address this issue in more detail, we performed studies on MPGα with different modulators of endocytosis (Figure 5).
[]
In order to address this issue in more detail, we performed studies on MPGα with different modulators of endocytosis (Figure 5).
true
true
true
true
true
596
5
DISCUSSION
1
85
[ "b81", "b82", "b31", "b83", "b84", "b85", "b86", "b87", "b88", "b89", "b90", "b89", "b91", "b93", "b94", "b96", "b97", "b98", "b99" ]
17,135,188
pmid-2022649|pmid-6155379|pmid-12837762|pmid-12783857|pmid-16287236|pmid-8797088|pmid-8947549|pmid-596521|pmid-10637311|pmid-6322305|pmid-16344372|pmid-6322305|pmid-9177342|pmid-12075072|pmid-2158158|pmid-11809836|pmid-6183281|pmid-6298741|pmid-11337152
First we analysed the effect of wortmannin, a compound, which is supposed to affect clathrin-dependent endocytosis (85) and macropinocytosis (86).
[ "81", "82", "31", "83", "84", "85", "86", "87", "88", "89", "90", "89", "91", "93", "94", "96", "97", "98", "99" ]
146
3,547
1
false
First we analysed the effect of wortmannin, a compound, which is supposed to affect clathrin-dependent endocytosis and macropinocytosis.
[ "85", "86" ]
First we analysed the effect of wortmannin, a compound, which is supposed to affect clathrin-dependent endocytosis and macropinocytosis.
true
true
true
true
true
596
5
DISCUSSION
1
81
[ "b81", "b82", "b31", "b83", "b84", "b85", "b86", "b87", "b88", "b89", "b90", "b89", "b91", "b93", "b94", "b96", "b97", "b98", "b99" ]
17,135,188
pmid-2022649|pmid-6155379|pmid-12837762|pmid-12783857|pmid-16287236|pmid-8797088|pmid-8947549|pmid-596521|pmid-10637311|pmid-6322305|pmid-16344372|pmid-6322305|pmid-9177342|pmid-12075072|pmid-2158158|pmid-11809836|pmid-6183281|pmid-6298741|pmid-11337152
Wortmannin led to a strong reduction in the uptake of MPGα/siRNA complexes.
[ "81", "82", "31", "83", "84", "85", "86", "87", "88", "89", "90", "89", "91", "93", "94", "96", "97", "98", "99" ]
75
3,548
0
false
Wortmannin led to a strong reduction in the uptake of MPGα/siRNA complexes.
[]
Wortmannin led to a strong reduction in the uptake of MPGα/siRNA complexes.
true
true
true
true
true
596
5
DISCUSSION
1
81
[ "b81", "b82", "b31", "b83", "b84", "b85", "b86", "b87", "b88", "b89", "b90", "b89", "b91", "b93", "b94", "b96", "b97", "b98", "b99" ]
17,135,188
pmid-2022649|pmid-6155379|pmid-12837762|pmid-12783857|pmid-16287236|pmid-8797088|pmid-8947549|pmid-596521|pmid-10637311|pmid-6322305|pmid-16344372|pmid-6322305|pmid-9177342|pmid-12075072|pmid-2158158|pmid-11809836|pmid-6183281|pmid-6298741|pmid-11337152
Like with sucrose, which also blocks clathrin-dependent endocytosis unselectively, the RNAi effect was reduced significantly.
[ "81", "82", "31", "83", "84", "85", "86", "87", "88", "89", "90", "89", "91", "93", "94", "96", "97", "98", "99" ]
125
3,549
0
false
Like with sucrose, which also blocks clathrin-dependent endocytosis unselectively, the RNAi effect was reduced significantly.
[]
Like with sucrose, which also blocks clathrin-dependent endocytosis unselectively, the RNAi effect was reduced significantly.
true
true
true
true
true
596
5
DISCUSSION
1
81
[ "b81", "b82", "b31", "b83", "b84", "b85", "b86", "b87", "b88", "b89", "b90", "b89", "b91", "b93", "b94", "b96", "b97", "b98", "b99" ]
17,135,188
pmid-2022649|pmid-6155379|pmid-12837762|pmid-12783857|pmid-16287236|pmid-8797088|pmid-8947549|pmid-596521|pmid-10637311|pmid-6322305|pmid-16344372|pmid-6322305|pmid-9177342|pmid-12075072|pmid-2158158|pmid-11809836|pmid-6183281|pmid-6298741|pmid-11337152
On the other hand, no clear-cut influence on uptake of siRNA could be seen applying cytochalasin B, which is supposed to affect the assembly of actin microfilaments (87,88), whereas the RNAi effect was strongly diminished in the presence of this compound.
[ "81", "82", "31", "83", "84", "85", "86", "87", "88", "89", "90", "89", "91", "93", "94", "96", "97", "98", "99" ]
255
3,550
0
false
On the other hand, no clear-cut influence on uptake of siRNA could be seen applying cytochalasin B, which is supposed to affect the assembly of actin microfilaments, whereas the RNAi effect was strongly diminished in the presence of this compound.
[ "87,88" ]
On the other hand, no clear-cut influence on uptake of siRNA could be seen applying cytochalasin B, which is supposed to affect the assembly of actin microfilaments, whereas the RNAi effect was strongly diminished in the presence of this compound.
true
true
true
true
true
596
5
DISCUSSION
1
81
[ "b81", "b82", "b31", "b83", "b84", "b85", "b86", "b87", "b88", "b89", "b90", "b89", "b91", "b93", "b94", "b96", "b97", "b98", "b99" ]
17,135,188
pmid-2022649|pmid-6155379|pmid-12837762|pmid-12783857|pmid-16287236|pmid-8797088|pmid-8947549|pmid-596521|pmid-10637311|pmid-6322305|pmid-16344372|pmid-6322305|pmid-9177342|pmid-12075072|pmid-2158158|pmid-11809836|pmid-6183281|pmid-6298741|pmid-11337152
Hence, we could not distinguish, whether this was due to a blockage of macropinocytosis or what appears more realistic was caused by a block of intracellular vesicle transport.
[ "81", "82", "31", "83", "84", "85", "86", "87", "88", "89", "90", "89", "91", "93", "94", "96", "97", "98", "99" ]
176
3,551
0
false
Hence, we could not distinguish, whether this was due to a blockage of macropinocytosis or what appears more realistic was caused by a block of intracellular vesicle transport.
[]
Hence, we could not distinguish, whether this was due to a blockage of macropinocytosis or what appears more realistic was caused by a block of intracellular vesicle transport.
true
true
true
true
true
596
5
DISCUSSION
1
81
[ "b81", "b82", "b31", "b83", "b84", "b85", "b86", "b87", "b88", "b89", "b90", "b89", "b91", "b93", "b94", "b96", "b97", "b98", "b99" ]
17,135,188
pmid-2022649|pmid-6155379|pmid-12837762|pmid-12783857|pmid-16287236|pmid-8797088|pmid-8947549|pmid-596521|pmid-10637311|pmid-6322305|pmid-16344372|pmid-6322305|pmid-9177342|pmid-12075072|pmid-2158158|pmid-11809836|pmid-6183281|pmid-6298741|pmid-11337152
In the presence of nystatin, which is supposed to inhibit caveolin-dependent lipid-raft-mediated endocytosis (89,90), the RNAi effect was clearly reduced and could neither be rescued by combining nystatin with okadaic acid, chloroquine nor filipin complex (Figure 5A).
[ "81", "82", "31", "83", "84", "85", "86", "87", "88", "89", "90", "89", "91", "93", "94", "96", "97", "98", "99" ]
268
3,552
0
false
In the presence of nystatin, which is supposed to inhibit caveolin-dependent lipid-raft-mediated endocytosis, the RNAi effect was clearly reduced and could neither be rescued by combining nystatin with okadaic acid, chloroquine nor filipin complex (Figure 5A).
[ "89,90" ]
In the presence of nystatin, which is supposed to inhibit caveolin-dependent lipid-raft-mediated endocytosis, the RNAi effect was clearly reduced and could neither be rescued by combining nystatin with okadaic acid, chloroquine nor filipin complex (Figure 5A).
true
true
true
true
true
596
5
DISCUSSION
1
81
[ "b81", "b82", "b31", "b83", "b84", "b85", "b86", "b87", "b88", "b89", "b90", "b89", "b91", "b93", "b94", "b96", "b97", "b98", "b99" ]
17,135,188
pmid-2022649|pmid-6155379|pmid-12837762|pmid-12783857|pmid-16287236|pmid-8797088|pmid-8947549|pmid-596521|pmid-10637311|pmid-6322305|pmid-16344372|pmid-6322305|pmid-9177342|pmid-12075072|pmid-2158158|pmid-11809836|pmid-6183281|pmid-6298741|pmid-11337152
Pre-incubation of the cells with nystatin led to an increase in uptake during the first 4 h, which was even more pronounced when the quantification was performed after 24 h (Figure 5B).
[ "81", "82", "31", "83", "84", "85", "86", "87", "88", "89", "90", "89", "91", "93", "94", "96", "97", "98", "99" ]
185
3,553
0
false
Pre-incubation of the cells with nystatin led to an increase in uptake during the first 4 h, which was even more pronounced when the quantification was performed after 24 h (Figure 5B).
[]
Pre-incubation of the cells with nystatin led to an increase in uptake during the first 4 h, which was even more pronounced when the quantification was performed after 24 h (Figure 5B).
true
true
true
true
true
596
5
DISCUSSION
1
89
[ "b81", "b82", "b31", "b83", "b84", "b85", "b86", "b87", "b88", "b89", "b90", "b89", "b91", "b93", "b94", "b96", "b97", "b98", "b99" ]
17,135,188
pmid-2022649|pmid-6155379|pmid-12837762|pmid-12783857|pmid-16287236|pmid-8797088|pmid-8947549|pmid-596521|pmid-10637311|pmid-6322305|pmid-16344372|pmid-6322305|pmid-9177342|pmid-12075072|pmid-2158158|pmid-11809836|pmid-6183281|pmid-6298741|pmid-11337152
An additional effect of nystatin is supposed to be an increase in cell membrane permeability (89).
[ "81", "82", "31", "83", "84", "85", "86", "87", "88", "89", "90", "89", "91", "93", "94", "96", "97", "98", "99" ]
98
3,554
1
false
An additional effect of nystatin is supposed to be an increase in cell membrane permeability.
[ "89" ]
An additional effect of nystatin is supposed to be an increase in cell membrane permeability.
true
true
true
true
true
596
5
DISCUSSION
1
81
[ "b81", "b82", "b31", "b83", "b84", "b85", "b86", "b87", "b88", "b89", "b90", "b89", "b91", "b93", "b94", "b96", "b97", "b98", "b99" ]
17,135,188
pmid-2022649|pmid-6155379|pmid-12837762|pmid-12783857|pmid-16287236|pmid-8797088|pmid-8947549|pmid-596521|pmid-10637311|pmid-6322305|pmid-16344372|pmid-6322305|pmid-9177342|pmid-12075072|pmid-2158158|pmid-11809836|pmid-6183281|pmid-6298741|pmid-11337152
This property of nystatin could account for the high amount of siRNA taken up.
[ "81", "82", "31", "83", "84", "85", "86", "87", "88", "89", "90", "89", "91", "93", "94", "96", "97", "98", "99" ]
78
3,555
0
false
This property of nystatin could account for the high amount of siRNA taken up.
[]
This property of nystatin could account for the high amount of siRNA taken up.
true
true
true
true
true
596
5
DISCUSSION
1
81
[ "b81", "b82", "b31", "b83", "b84", "b85", "b86", "b87", "b88", "b89", "b90", "b89", "b91", "b93", "b94", "b96", "b97", "b98", "b99" ]
17,135,188
pmid-2022649|pmid-6155379|pmid-12837762|pmid-12783857|pmid-16287236|pmid-8797088|pmid-8947549|pmid-596521|pmid-10637311|pmid-6322305|pmid-16344372|pmid-6322305|pmid-9177342|pmid-12075072|pmid-2158158|pmid-11809836|pmid-6183281|pmid-6298741|pmid-11337152
Together with the reduced RNAi effect observed, this would mean that nucleic acids internalised this way, are not available for the RNAi machinery.
[ "81", "82", "31", "83", "84", "85", "86", "87", "88", "89", "90", "89", "91", "93", "94", "96", "97", "98", "99" ]
147
3,556
0
false
Together with the reduced RNAi effect observed, this would mean that nucleic acids internalised this way, are not available for the RNAi machinery.
[]
Together with the reduced RNAi effect observed, this would mean that nucleic acids internalised this way, are not available for the RNAi machinery.
true
true
true
true
true
596
5
DISCUSSION
1
81
[ "b81", "b82", "b31", "b83", "b84", "b85", "b86", "b87", "b88", "b89", "b90", "b89", "b91", "b93", "b94", "b96", "b97", "b98", "b99" ]
17,135,188
pmid-2022649|pmid-6155379|pmid-12837762|pmid-12783857|pmid-16287236|pmid-8797088|pmid-8947549|pmid-596521|pmid-10637311|pmid-6322305|pmid-16344372|pmid-6322305|pmid-9177342|pmid-12075072|pmid-2158158|pmid-11809836|pmid-6183281|pmid-6298741|pmid-11337152
Then again, taking the results of experiments into account in which different inhibitors were combined to counteract nystatin, it could be concluded that nystatin itself had a severe negative effect on the RNAi machinery.
[ "81", "82", "31", "83", "84", "85", "86", "87", "88", "89", "90", "89", "91", "93", "94", "96", "97", "98", "99" ]
221
3,557
0
false
Then again, taking the results of experiments into account in which different inhibitors were combined to counteract nystatin, it could be concluded that nystatin itself had a severe negative effect on the RNAi machinery.
[]
Then again, taking the results of experiments into account in which different inhibitors were combined to counteract nystatin, it could be concluded that nystatin itself had a severe negative effect on the RNAi machinery.
true
true
true
true
true
596
5
DISCUSSION
1
81
[ "b81", "b82", "b31", "b83", "b84", "b85", "b86", "b87", "b88", "b89", "b90", "b89", "b91", "b93", "b94", "b96", "b97", "b98", "b99" ]
17,135,188
pmid-2022649|pmid-6155379|pmid-12837762|pmid-12783857|pmid-16287236|pmid-8797088|pmid-8947549|pmid-596521|pmid-10637311|pmid-6322305|pmid-16344372|pmid-6322305|pmid-9177342|pmid-12075072|pmid-2158158|pmid-11809836|pmid-6183281|pmid-6298741|pmid-11337152
Filipin complex like nystatin shows sterol-binding properties (91–93).
[ "81", "82", "31", "83", "84", "85", "86", "87", "88", "89", "90", "89", "91", "93", "94", "96", "97", "98", "99" ]
70
3,558
0
false
Filipin complex like nystatin shows sterol-binding properties.
[ "91–93" ]
Filipin complex like nystatin shows sterol-binding properties.
true
true
true
true
true
596
5
DISCUSSION
1
81
[ "b81", "b82", "b31", "b83", "b84", "b85", "b86", "b87", "b88", "b89", "b90", "b89", "b91", "b93", "b94", "b96", "b97", "b98", "b99" ]
17,135,188
pmid-2022649|pmid-6155379|pmid-12837762|pmid-12783857|pmid-16287236|pmid-8797088|pmid-8947549|pmid-596521|pmid-10637311|pmid-6322305|pmid-16344372|pmid-6322305|pmid-9177342|pmid-12075072|pmid-2158158|pmid-11809836|pmid-6183281|pmid-6298741|pmid-11337152
However, in contrast to nystatin almost no change in siRNA uptake was detected after MPGα-mediated delivery, whereas the RNAi effect was slightly increased.
[ "81", "82", "31", "83", "84", "85", "86", "87", "88", "89", "90", "89", "91", "93", "94", "96", "97", "98", "99" ]
156
3,559
0
false
However, in contrast to nystatin almost no change in siRNA uptake was detected after MPGα-mediated delivery, whereas the RNAi effect was slightly increased.
[]
However, in contrast to nystatin almost no change in siRNA uptake was detected after MPGα-mediated delivery, whereas the RNAi effect was slightly increased.
true
true
true
true
true
596
5
DISCUSSION
1
81
[ "b81", "b82", "b31", "b83", "b84", "b85", "b86", "b87", "b88", "b89", "b90", "b89", "b91", "b93", "b94", "b96", "b97", "b98", "b99" ]
17,135,188
pmid-2022649|pmid-6155379|pmid-12837762|pmid-12783857|pmid-16287236|pmid-8797088|pmid-8947549|pmid-596521|pmid-10637311|pmid-6322305|pmid-16344372|pmid-6322305|pmid-9177342|pmid-12075072|pmid-2158158|pmid-11809836|pmid-6183281|pmid-6298741|pmid-11337152
This may be due to a selective inhibition of caveolin-mediated endocytosis, which in turn might shift the balance towards clathrin-mediated endocytosis.
[ "81", "82", "31", "83", "84", "85", "86", "87", "88", "89", "90", "89", "91", "93", "94", "96", "97", "98", "99" ]
152
3,560
0
false
This may be due to a selective inhibition of caveolin-mediated endocytosis, which in turn might shift the balance towards clathrin-mediated endocytosis.
[]
This may be due to a selective inhibition of caveolin-mediated endocytosis, which in turn might shift the balance towards clathrin-mediated endocytosis.
true
true
true
true
true
596
5
DISCUSSION
1
81
[ "b81", "b82", "b31", "b83", "b84", "b85", "b86", "b87", "b88", "b89", "b90", "b89", "b91", "b93", "b94", "b96", "b97", "b98", "b99" ]
17,135,188
pmid-2022649|pmid-6155379|pmid-12837762|pmid-12783857|pmid-16287236|pmid-8797088|pmid-8947549|pmid-596521|pmid-10637311|pmid-6322305|pmid-16344372|pmid-6322305|pmid-9177342|pmid-12075072|pmid-2158158|pmid-11809836|pmid-6183281|pmid-6298741|pmid-11337152
This interpretation would be consistent with our idea that clathrin-mediated endocytosis yields more bio-available cargo and is further supported by the observation that the RNAi effect is increased even more by combining filipin complex with chloroquine (Figure 5A).
[ "81", "82", "31", "83", "84", "85", "86", "87", "88", "89", "90", "89", "91", "93", "94", "96", "97", "98", "99" ]
267
3,561
0
false
This interpretation would be consistent with our idea that clathrin-mediated endocytosis yields more bio-available cargo and is further supported by the observation that the RNAi effect is increased even more by combining filipin complex with chloroquine (Figure 5A).
[]
This interpretation would be consistent with our idea that clathrin-mediated endocytosis yields more bio-available cargo and is further supported by the observation that the RNAi effect is increased even more by combining filipin complex with chloroquine (Figure 5A).
true
true
true
true
true
596
5
DISCUSSION
1
81
[ "b81", "b82", "b31", "b83", "b84", "b85", "b86", "b87", "b88", "b89", "b90", "b89", "b91", "b93", "b94", "b96", "b97", "b98", "b99" ]
17,135,188
pmid-2022649|pmid-6155379|pmid-12837762|pmid-12783857|pmid-16287236|pmid-8797088|pmid-8947549|pmid-596521|pmid-10637311|pmid-6322305|pmid-16344372|pmid-6322305|pmid-9177342|pmid-12075072|pmid-2158158|pmid-11809836|pmid-6183281|pmid-6298741|pmid-11337152
Okadaic acid, a specific phosphatase inhibitor, is supposed to stimulate mobility and internalization of caveolae (94–96).
[ "81", "82", "31", "83", "84", "85", "86", "87", "88", "89", "90", "89", "91", "93", "94", "96", "97", "98", "99" ]
122
3,562
0
false
Okadaic acid, a specific phosphatase inhibitor, is supposed to stimulate mobility and internalization of caveolae.
[ "94–96" ]
Okadaic acid, a specific phosphatase inhibitor, is supposed to stimulate mobility and internalization of caveolae.
true
true
true
true
true
596
5
DISCUSSION
1
81
[ "b81", "b82", "b31", "b83", "b84", "b85", "b86", "b87", "b88", "b89", "b90", "b89", "b91", "b93", "b94", "b96", "b97", "b98", "b99" ]
17,135,188
pmid-2022649|pmid-6155379|pmid-12837762|pmid-12783857|pmid-16287236|pmid-8797088|pmid-8947549|pmid-596521|pmid-10637311|pmid-6322305|pmid-16344372|pmid-6322305|pmid-9177342|pmid-12075072|pmid-2158158|pmid-11809836|pmid-6183281|pmid-6298741|pmid-11337152
In the presence of okadaic acid no RNAi effect could be detected.
[ "81", "82", "31", "83", "84", "85", "86", "87", "88", "89", "90", "89", "91", "93", "94", "96", "97", "98", "99" ]
65
3,563
0
false
In the presence of okadaic acid no RNAi effect could be detected.
[]
In the presence of okadaic acid no RNAi effect could be detected.
true
true
true
true
true
596
5
DISCUSSION
1
81
[ "b81", "b82", "b31", "b83", "b84", "b85", "b86", "b87", "b88", "b89", "b90", "b89", "b91", "b93", "b94", "b96", "b97", "b98", "b99" ]
17,135,188
pmid-2022649|pmid-6155379|pmid-12837762|pmid-12783857|pmid-16287236|pmid-8797088|pmid-8947549|pmid-596521|pmid-10637311|pmid-6322305|pmid-16344372|pmid-6322305|pmid-9177342|pmid-12075072|pmid-2158158|pmid-11809836|pmid-6183281|pmid-6298741|pmid-11337152
Uptake of siRNA, on the other hand, was not affected.
[ "81", "82", "31", "83", "84", "85", "86", "87", "88", "89", "90", "89", "91", "93", "94", "96", "97", "98", "99" ]
53
3,564
0
false
Uptake of siRNA, on the other hand, was not affected.
[]
Uptake of siRNA, on the other hand, was not affected.
true
true
true
true
true
596
5
DISCUSSION
1
81
[ "b81", "b82", "b31", "b83", "b84", "b85", "b86", "b87", "b88", "b89", "b90", "b89", "b91", "b93", "b94", "b96", "b97", "b98", "b99" ]
17,135,188
pmid-2022649|pmid-6155379|pmid-12837762|pmid-12783857|pmid-16287236|pmid-8797088|pmid-8947549|pmid-596521|pmid-10637311|pmid-6322305|pmid-16344372|pmid-6322305|pmid-9177342|pmid-12075072|pmid-2158158|pmid-11809836|pmid-6183281|pmid-6298741|pmid-11337152
This could be interpreted as an increase of caveolin-dependent endocytosis accompanied by a reduction of clathrin-dependent uptake leading to an unchanged net amount of intracellular siRNA.
[ "81", "82", "31", "83", "84", "85", "86", "87", "88", "89", "90", "89", "91", "93", "94", "96", "97", "98", "99" ]
189
3,565
0
false
This could be interpreted as an increase of caveolin-dependent endocytosis accompanied by a reduction of clathrin-dependent uptake leading to an unchanged net amount of intracellular siRNA.
[]
This could be interpreted as an increase of caveolin-dependent endocytosis accompanied by a reduction of clathrin-dependent uptake leading to an unchanged net amount of intracellular siRNA.
true
true
true
true
true
596
5
DISCUSSION
1
81
[ "b81", "b82", "b31", "b83", "b84", "b85", "b86", "b87", "b88", "b89", "b90", "b89", "b91", "b93", "b94", "b96", "b97", "b98", "b99" ]
17,135,188
pmid-2022649|pmid-6155379|pmid-12837762|pmid-12783857|pmid-16287236|pmid-8797088|pmid-8947549|pmid-596521|pmid-10637311|pmid-6322305|pmid-16344372|pmid-6322305|pmid-9177342|pmid-12075072|pmid-2158158|pmid-11809836|pmid-6183281|pmid-6298741|pmid-11337152
Caveolae direct most of their cargo via caveosomes to the Golgi apparatus where they are probably beyond reach of the RNAi machinery.
[ "81", "82", "31", "83", "84", "85", "86", "87", "88", "89", "90", "89", "91", "93", "94", "96", "97", "98", "99" ]
133
3,566
0
false
Caveolae direct most of their cargo via caveosomes to the Golgi apparatus where they are probably beyond reach of the RNAi machinery.
[]
Caveolae direct most of their cargo via caveosomes to the Golgi apparatus where they are probably beyond reach of the RNAi machinery.
true
true
true
true
true
596
5
DISCUSSION
1
81
[ "b81", "b82", "b31", "b83", "b84", "b85", "b86", "b87", "b88", "b89", "b90", "b89", "b91", "b93", "b94", "b96", "b97", "b98", "b99" ]
17,135,188
pmid-2022649|pmid-6155379|pmid-12837762|pmid-12783857|pmid-16287236|pmid-8797088|pmid-8947549|pmid-596521|pmid-10637311|pmid-6322305|pmid-16344372|pmid-6322305|pmid-9177342|pmid-12075072|pmid-2158158|pmid-11809836|pmid-6183281|pmid-6298741|pmid-11337152
In addition, combining filipin complex and okadaic acid resulted in levels of luciferase activity equal to those measured with siRNA alone.
[ "81", "82", "31", "83", "84", "85", "86", "87", "88", "89", "90", "89", "91", "93", "94", "96", "97", "98", "99" ]
139
3,567
0
false
In addition, combining filipin complex and okadaic acid resulted in levels of luciferase activity equal to those measured with siRNA alone.
[]
In addition, combining filipin complex and okadaic acid resulted in levels of luciferase activity equal to those measured with siRNA alone.
true
true
true
true
true
596
5
DISCUSSION
1
81
[ "b81", "b82", "b31", "b83", "b84", "b85", "b86", "b87", "b88", "b89", "b90", "b89", "b91", "b93", "b94", "b96", "b97", "b98", "b99" ]
17,135,188
pmid-2022649|pmid-6155379|pmid-12837762|pmid-12783857|pmid-16287236|pmid-8797088|pmid-8947549|pmid-596521|pmid-10637311|pmid-6322305|pmid-16344372|pmid-6322305|pmid-9177342|pmid-12075072|pmid-2158158|pmid-11809836|pmid-6183281|pmid-6298741|pmid-11337152
Here, induction of caveolin-mediated endocytosis by okadaic acid was possibly compensated by the inhibitory effect of filipin complex.
[ "81", "82", "31", "83", "84", "85", "86", "87", "88", "89", "90", "89", "91", "93", "94", "96", "97", "98", "99" ]
134
3,568
0
false
Here, induction of caveolin-mediated endocytosis by okadaic acid was possibly compensated by the inhibitory effect of filipin complex.
[]
Here, induction of caveolin-mediated endocytosis by okadaic acid was possibly compensated by the inhibitory effect of filipin complex.
true
true
true
true
true
596
5
DISCUSSION
1
81
[ "b81", "b82", "b31", "b83", "b84", "b85", "b86", "b87", "b88", "b89", "b90", "b89", "b91", "b93", "b94", "b96", "b97", "b98", "b99" ]
17,135,188
pmid-2022649|pmid-6155379|pmid-12837762|pmid-12783857|pmid-16287236|pmid-8797088|pmid-8947549|pmid-596521|pmid-10637311|pmid-6322305|pmid-16344372|pmid-6322305|pmid-9177342|pmid-12075072|pmid-2158158|pmid-11809836|pmid-6183281|pmid-6298741|pmid-11337152
Chloroquine, a weak base, is supposed to prevent lysosomal degradation by inhibiting the acidification of endosomes (97,98).
[ "81", "82", "31", "83", "84", "85", "86", "87", "88", "89", "90", "89", "91", "93", "94", "96", "97", "98", "99" ]
124
3,569
0
false
Chloroquine, a weak base, is supposed to prevent lysosomal degradation by inhibiting the acidification of endosomes.
[ "97,98" ]
Chloroquine, a weak base, is supposed to prevent lysosomal degradation by inhibiting the acidification of endosomes.
true
true
true
true
true
596
5
DISCUSSION
1
99
[ "b81", "b82", "b31", "b83", "b84", "b85", "b86", "b87", "b88", "b89", "b90", "b89", "b91", "b93", "b94", "b96", "b97", "b98", "b99" ]
17,135,188
pmid-2022649|pmid-6155379|pmid-12837762|pmid-12783857|pmid-16287236|pmid-8797088|pmid-8947549|pmid-596521|pmid-10637311|pmid-6322305|pmid-16344372|pmid-6322305|pmid-9177342|pmid-12075072|pmid-2158158|pmid-11809836|pmid-6183281|pmid-6298741|pmid-11337152
This eventually leads to the disruption of a large portion of the endosomes which then release their content into the cytoplasm (99).
[ "81", "82", "31", "83", "84", "85", "86", "87", "88", "89", "90", "89", "91", "93", "94", "96", "97", "98", "99" ]
133
3,570
1
false
This eventually leads to the disruption of a large portion of the endosomes which then release their content into the cytoplasm.
[ "99" ]
This eventually leads to the disruption of a large portion of the endosomes which then release their content into the cytoplasm.
true
true
true
true
true
596
5
DISCUSSION
1
81
[ "b81", "b82", "b31", "b83", "b84", "b85", "b86", "b87", "b88", "b89", "b90", "b89", "b91", "b93", "b94", "b96", "b97", "b98", "b99" ]
17,135,188
pmid-2022649|pmid-6155379|pmid-12837762|pmid-12783857|pmid-16287236|pmid-8797088|pmid-8947549|pmid-596521|pmid-10637311|pmid-6322305|pmid-16344372|pmid-6322305|pmid-9177342|pmid-12075072|pmid-2158158|pmid-11809836|pmid-6183281|pmid-6298741|pmid-11337152
In our hands, chloroquine caused a slightly enhanced RNAi effect leading to the conclusion that an increased number of siRNA molecules have become bio-available by endosomal release.
[ "81", "82", "31", "83", "84", "85", "86", "87", "88", "89", "90", "89", "91", "93", "94", "96", "97", "98", "99" ]
182
3,571
0
false
In our hands, chloroquine caused a slightly enhanced RNAi effect leading to the conclusion that an increased number of siRNA molecules have become bio-available by endosomal release.
[]
In our hands, chloroquine caused a slightly enhanced RNAi effect leading to the conclusion that an increased number of siRNA molecules have become bio-available by endosomal release.
true
true
true
true
true
596
6
DISCUSSION
1
100
[ "b100", "b102" ]
17,135,188
pmid-12573284|pmid-16507881
Equivalent experiments with LF2000 as transfection reagent yielded a slightly different pattern, for example regarding uptake in the presence of nystatin or chloroquine, nevertheless strongly indicating uptake via endocytosis (Supplementary Figure 4).
[ "100", "102" ]
251
3,572
0
false
Equivalent experiments with LF2000 as transfection reagent yielded a slightly different pattern, for example regarding uptake in the presence of nystatin or chloroquine, nevertheless strongly indicating uptake via endocytosis (Supplementary Figure 4).
[]
Equivalent experiments with LF2000 as transfection reagent yielded a slightly different pattern, for example regarding uptake in the presence of nystatin or chloroquine, nevertheless strongly indicating uptake via endocytosis (Supplementary Figure 4).
true
true
true
true
true
597
6
DISCUSSION
1
100
[ "b100", "b102" ]
17,135,188
pmid-12573284|pmid-16507881
This observation is consistent with the findings of others concerning the uptake mechanism of several cationic lipids (100–102).
[ "100", "102" ]
128
3,573
0
false
This observation is consistent with the findings of others concerning the uptake mechanism of several cationic lipids.
[ "100–102" ]
This observation is consistent with the findings of others concerning the uptake mechanism of several cationic lipids.
true
true
true
true
true
597
7
DISCUSSION
1
103
[ "b103", "b50", "b104", "b105", "b39", "b40", "b42" ]
17,135,188
pmid-15546190|pmid-12621426|pmid-14732047|pmid-14505488|pmid-12771197|pmid-15581849|pmid-16042396
Overall, our data, especially those addressing the temperature-dependency of the uptake, strongly indicate that both MPGα and LF2000/siRNA complexes are taken up by endocytotic processes.
[ "103", "50", "104", "105", "39", "40", "42" ]
187
3,574
0
false
Overall, our data, especially those addressing the temperature-dependency of the uptake, strongly indicate that both MPGα and LF2000/siRNA complexes are taken up by endocytotic processes.
[]
Overall, our data, especially those addressing the temperature-dependency of the uptake, strongly indicate that both MPGα and LF2000/siRNA complexes are taken up by endocytotic processes.
true
true
true
true
true
598
7
DISCUSSION
1
103
[ "b103", "b50", "b104", "b105", "b39", "b40", "b42" ]
17,135,188
pmid-15546190|pmid-12621426|pmid-14732047|pmid-14505488|pmid-12771197|pmid-15581849|pmid-16042396
The differences between transfections with MPGα and LF2000 concerning the IC50 values of siRNA could be explained by the property of LF2000 to promote endosomal escape at least partially, which is consistent with the microscopic observations described above.
[ "103", "50", "104", "105", "39", "40", "42" ]
258
3,575
0
false
The differences between transfections with MPGα and LF2000 concerning the IC50 values of siRNA could be explained by the property of LF2000 to promote endosomal escape at least partially, which is consistent with the microscopic observations described above.
[]
The differences between transfections with MPGα and LF2000 concerning the IC50 values of siRNA could be explained by the property of LF2000 to promote endosomal escape at least partially, which is consistent with the microscopic observations described above.
true
true
true
true
true
598
7
DISCUSSION
1
103
[ "b103", "b50", "b104", "b105", "b39", "b40", "b42" ]
17,135,188
pmid-15546190|pmid-12621426|pmid-14732047|pmid-14505488|pmid-12771197|pmid-15581849|pmid-16042396
The somewhat controversial results concerning different inhibitors of endocytosis described above support the notion that not one single pathway is responsible for the uptake of the complexes but rather several pathways are involved.
[ "103", "50", "104", "105", "39", "40", "42" ]
233
3,576
0
false
The somewhat controversial results concerning different inhibitors of endocytosis described above support the notion that not one single pathway is responsible for the uptake of the complexes but rather several pathways are involved.
[]
The somewhat controversial results concerning different inhibitors of endocytosis described above support the notion that not one single pathway is responsible for the uptake of the complexes but rather several pathways are involved.
true
true
true
true
true
598
7
DISCUSSION
1
103
[ "b103", "b50", "b104", "b105", "b39", "b40", "b42" ]
17,135,188
pmid-15546190|pmid-12621426|pmid-14732047|pmid-14505488|pmid-12771197|pmid-15581849|pmid-16042396
This may be due to a relatively unspecific interaction of the complexes with numerous negatively charged molecules on the cell surface.
[ "103", "50", "104", "105", "39", "40", "42" ]
135
3,577
0
false
This may be due to a relatively unspecific interaction of the complexes with numerous negatively charged molecules on the cell surface.
[]
This may be due to a relatively unspecific interaction of the complexes with numerous negatively charged molecules on the cell surface.
true
true
true
true
true
598
7
DISCUSSION
1
103
[ "b103", "b50", "b104", "b105", "b39", "b40", "b42" ]
17,135,188
pmid-15546190|pmid-12621426|pmid-14732047|pmid-14505488|pmid-12771197|pmid-15581849|pmid-16042396
As a result, various pathways of endocytosis might be triggered.
[ "103", "50", "104", "105", "39", "40", "42" ]
64
3,578
0
false
As a result, various pathways of endocytosis might be triggered.
[]
As a result, various pathways of endocytosis might be triggered.
true
true
true
true
true
598
7
DISCUSSION
1
103
[ "b103", "b50", "b104", "b105", "b39", "b40", "b42" ]
17,135,188
pmid-15546190|pmid-12621426|pmid-14732047|pmid-14505488|pmid-12771197|pmid-15581849|pmid-16042396
Accordingly, individual inhibitors used in this study might show just moderate effects by shifting the balance in favour of a particular endocytotic pathway.
[ "103", "50", "104", "105", "39", "40", "42" ]
157
3,579
0
false
Accordingly, individual inhibitors used in this study might show just moderate effects by shifting the balance in favour of a particular endocytotic pathway.
[]
Accordingly, individual inhibitors used in this study might show just moderate effects by shifting the balance in favour of a particular endocytotic pathway.
true
true
true
true
true
598
7
DISCUSSION
1
103
[ "b103", "b50", "b104", "b105", "b39", "b40", "b42" ]
17,135,188
pmid-15546190|pmid-12621426|pmid-14732047|pmid-14505488|pmid-12771197|pmid-15581849|pmid-16042396
Analogous results were reported by Säälik et al.
[ "103", "50", "104", "105", "39", "40", "42" ]
48
3,580
0
false
Analogous results were reported by Säälik et al.
[]
Analogous results were reported by Säälik et al.
true
true
true
true
true
598
7
DISCUSSION
1
103
[ "b103", "b50", "b104", "b105", "b39", "b40", "b42" ]
17,135,188
pmid-15546190|pmid-12621426|pmid-14732047|pmid-14505488|pmid-12771197|pmid-15581849|pmid-16042396
for CPP/avidin complexes (103).
[ "103", "50", "104", "105", "39", "40", "42" ]
31
3,581
1
false
for CPP/avidin complexes.
[ "103" ]
for CPP/avidin complexes.
false
true
true
true
false
598
7
DISCUSSION
1
103
[ "b103", "b50", "b104", "b105", "b39", "b40", "b42" ]
17,135,188
pmid-15546190|pmid-12621426|pmid-14732047|pmid-14505488|pmid-12771197|pmid-15581849|pmid-16042396
However, it should be kept in mind, that the interpretation of these particular experimental data is problematic, as many aspects of endocytosis are still poorly understood to date.
[ "103", "50", "104", "105", "39", "40", "42" ]
181
3,582
0
false
However, it should be kept in mind, that the interpretation of these particular experimental data is problematic, as many aspects of endocytosis are still poorly understood to date.
[]
However, it should be kept in mind, that the interpretation of these particular experimental data is problematic, as many aspects of endocytosis are still poorly understood to date.
true
true
true
true
true
598
7
DISCUSSION
1
103
[ "b103", "b50", "b104", "b105", "b39", "b40", "b42" ]
17,135,188
pmid-15546190|pmid-12621426|pmid-14732047|pmid-14505488|pmid-12771197|pmid-15581849|pmid-16042396
Even more important, the compounds may have additional unknown effects, which could lead to unexpected changes in reporter gene activity and/or affect the RNAi machinery.
[ "103", "50", "104", "105", "39", "40", "42" ]
170
3,583
0
false
Even more important, the compounds may have additional unknown effects, which could lead to unexpected changes in reporter gene activity and/or affect the RNAi machinery.
[]
Even more important, the compounds may have additional unknown effects, which could lead to unexpected changes in reporter gene activity and/or affect the RNAi machinery.
true
true
true
true
true
598
7
DISCUSSION
1
103
[ "b103", "b50", "b104", "b105", "b39", "b40", "b42" ]
17,135,188
pmid-15546190|pmid-12621426|pmid-14732047|pmid-14505488|pmid-12771197|pmid-15581849|pmid-16042396
Besides, the involvement of several pathways of endocytosis could also be a direct result of an inhomogeneous size distribution of the MPGα/siRNA complexes (S.V.
[ "103", "50", "104", "105", "39", "40", "42" ]
161
3,584
0
false
Besides, the involvement of several pathways of endocytosis could also be a direct result of an inhomogeneous size distribution of the MPGα/siRNA complexes (S.V.
[]
Besides, the involvement of several pathways of endocytosis could also be a direct result of an inhomogeneous size distribution of the MPGα/siRNA complexes (S.V.
true
true
true
true
true
598
7
DISCUSSION
1
103
[ "b103", "b50", "b104", "b105", "b39", "b40", "b42" ]
17,135,188
pmid-15546190|pmid-12621426|pmid-14732047|pmid-14505488|pmid-12771197|pmid-15581849|pmid-16042396
and A.T., unpublished data), since for each process only a certain range of particle sizes is believed to be predominantly taken up (50,104,105).
[ "103", "50", "104", "105", "39", "40", "42" ]
145
3,585
0
false
and A.T., unpublished data), since for each process only a certain range of particle sizes is believed to be predominantly taken up.
[ "50,104,105" ]
and A.T., unpublished data), since for each process only a certain range of particle sizes is believed to be predominantly taken up.
false
true
true
true
false
598
7
DISCUSSION
1
103
[ "b103", "b50", "b104", "b105", "b39", "b40", "b42" ]
17,135,188
pmid-15546190|pmid-12621426|pmid-14732047|pmid-14505488|pmid-12771197|pmid-15581849|pmid-16042396
Thus, the size of the complexes may determine their uptake route and consequently their fate.
[ "103", "50", "104", "105", "39", "40", "42" ]
93
3,586
0
false
Thus, the size of the complexes may determine their uptake route and consequently their fate.
[]
Thus, the size of the complexes may determine their uptake route and consequently their fate.
true
true
true
true
true
598
7
DISCUSSION
1
103
[ "b103", "b50", "b104", "b105", "b39", "b40", "b42" ]
17,135,188
pmid-15546190|pmid-12621426|pmid-14732047|pmid-14505488|pmid-12771197|pmid-15581849|pmid-16042396
Then again, we cannot entirely rule out that a certain percentage of complexes are taken up via a direct penetration of the plasma membrane as reported by others (39,40,42).
[ "103", "50", "104", "105", "39", "40", "42" ]
173
3,587
0
false
Then again, we cannot entirely rule out that a certain percentage of complexes are taken up via a direct penetration of the plasma membrane as reported by others.
[ "39,40,42" ]
Then again, we cannot entirely rule out that a certain percentage of complexes are taken up via a direct penetration of the plasma membrane as reported by others.
true
true
true
true
true
598
7
DISCUSSION
1
103
[ "b103", "b50", "b104", "b105", "b39", "b40", "b42" ]
17,135,188
pmid-15546190|pmid-12621426|pmid-14732047|pmid-14505488|pmid-12771197|pmid-15581849|pmid-16042396
In this context it would be very interesting to know the minimal number of siRNA molecules needed to trigger RNAi-mediated half maximal inhibition of luciferase activity.
[ "103", "50", "104", "105", "39", "40", "42" ]
170
3,588
0
false
In this context it would be very interesting to know the minimal number of siRNA molecules needed to trigger RNAi-mediated half maximal inhibition of luciferase activity.
[]
In this context it would be very interesting to know the minimal number of siRNA molecules needed to trigger RNAi-mediated half maximal inhibition of luciferase activity.
true
true
true
true
true
598
7
DISCUSSION
1
103
[ "b103", "b50", "b104", "b105", "b39", "b40", "b42" ]
17,135,188
pmid-15546190|pmid-12621426|pmid-14732047|pmid-14505488|pmid-12771197|pmid-15581849|pmid-16042396
In an attempt to answer this question, we performed technically challenging nuclear microinjection studies of a luciferase expression plasmid together with siR206 into HeLa and ECV304 cells, respectively (Figure 6).
[ "103", "50", "104", "105", "39", "40", "42" ]
215
3,589
0
false
In an attempt to answer this question, we performed technically challenging nuclear microinjection studies of a luciferase expression plasmid together with siR206 into HeLa and ECV304 cells, respectively (Figure 6).
[]
In an attempt to answer this question, we performed technically challenging nuclear microinjection studies of a luciferase expression plasmid together with siR206 into HeLa and ECV304 cells, respectively (Figure 6).
true
true
true
true
true
598
7
DISCUSSION
1
103
[ "b103", "b50", "b104", "b105", "b39", "b40", "b42" ]
17,135,188
pmid-15546190|pmid-12621426|pmid-14732047|pmid-14505488|pmid-12771197|pmid-15581849|pmid-16042396
From such experiments it could be calculated that ∼300 siRNA molecules per cell were necessary to observe a half maximal inhibition of luciferase activity.
[ "103", "50", "104", "105", "39", "40", "42" ]
155
3,590
0
false
From such experiments it could be calculated that ∼300 siRNA molecules per cell were necessary to observe a half maximal inhibition of luciferase activity.
[]
From such experiments it could be calculated that ∼300 siRNA molecules per cell were necessary to observe a half maximal inhibition of luciferase activity.
true
true
true
true
true
598
7
DISCUSSION
1
103
[ "b103", "b50", "b104", "b105", "b39", "b40", "b42" ]
17,135,188
pmid-15546190|pmid-12621426|pmid-14732047|pmid-14505488|pmid-12771197|pmid-15581849|pmid-16042396
Surprisingly, this number is very close to what was determined for LF2000-mediated delivery.
[ "103", "50", "104", "105", "39", "40", "42" ]
92
3,591
0
false
Surprisingly, this number is very close to what was determined for LF2000-mediated delivery.
[]
Surprisingly, this number is very close to what was determined for LF2000-mediated delivery.
true
true
true
true
true
598
7
DISCUSSION
1
103
[ "b103", "b50", "b104", "b105", "b39", "b40", "b42" ]
17,135,188
pmid-15546190|pmid-12621426|pmid-14732047|pmid-14505488|pmid-12771197|pmid-15581849|pmid-16042396
Microscopic studies of fluorescently labelled siRNA delivered with LF2000 on the other hand, showed a vesicular distribution similar to what has been observed with MPGα, indicative of the majority of siRNA molecules being not bio-available either (Supplementary Figure 5).
[ "103", "50", "104", "105", "39", "40", "42" ]
272
3,592
0
false
Microscopic studies of fluorescently labelled siRNA delivered with LF2000 on the other hand, showed a vesicular distribution similar to what has been observed with MPGα, indicative of the majority of siRNA molecules being not bio-available either (Supplementary Figure 5).
[]
Microscopic studies of fluorescently labelled siRNA delivered with LF2000 on the other hand, showed a vesicular distribution similar to what has been observed with MPGα, indicative of the majority of siRNA molecules being not bio-available either (Supplementary Figure 5).
true
true
true
true
true
598
7
DISCUSSION
1
103
[ "b103", "b50", "b104", "b105", "b39", "b40", "b42" ]
17,135,188
pmid-15546190|pmid-12621426|pmid-14732047|pmid-14505488|pmid-12771197|pmid-15581849|pmid-16042396
Thus, the microinjection approach, at least in our hands, turned out not to be practicable to answer this question.
[ "103", "50", "104", "105", "39", "40", "42" ]
115
3,593
0
false
Thus, the microinjection approach, at least in our hands, turned out not to be practicable to answer this question.
[]
Thus, the microinjection approach, at least in our hands, turned out not to be practicable to answer this question.
true
true
true
true
true
598
7
DISCUSSION
1
103
[ "b103", "b50", "b104", "b105", "b39", "b40", "b42" ]
17,135,188
pmid-15546190|pmid-12621426|pmid-14732047|pmid-14505488|pmid-12771197|pmid-15581849|pmid-16042396
A possible cause could simply be that the siRNA is retained inside the nucleus.
[ "103", "50", "104", "105", "39", "40", "42" ]
79
3,594
0
false
A possible cause could simply be that the siRNA is retained inside the nucleus.
[]
A possible cause could simply be that the siRNA is retained inside the nucleus.
true
true
true
true
true
598
7
DISCUSSION
1
103
[ "b103", "b50", "b104", "b105", "b39", "b40", "b42" ]
17,135,188
pmid-15546190|pmid-12621426|pmid-14732047|pmid-14505488|pmid-12771197|pmid-15581849|pmid-16042396
Then again, this could not be verified by microinjection of fluorescently labelled siRNA as initially strongly visible fluorescence in the nucleus completely disappeared within 30 min, probably either due to quenching effects or transport into cytoplasm.
[ "103", "50", "104", "105", "39", "40", "42" ]
254
3,595
0
false
Then again, this could not be verified by microinjection of fluorescently labelled siRNA as initially strongly visible fluorescence in the nucleus completely disappeared within 30 min, probably either due to quenching effects or transport into cytoplasm.
[]
Then again, this could not be verified by microinjection of fluorescently labelled siRNA as initially strongly visible fluorescence in the nucleus completely disappeared within 30 min, probably either due to quenching effects or transport into cytoplasm.
true
true
true
true
true
598
7
DISCUSSION
1
103
[ "b103", "b50", "b104", "b105", "b39", "b40", "b42" ]
17,135,188
pmid-15546190|pmid-12621426|pmid-14732047|pmid-14505488|pmid-12771197|pmid-15581849|pmid-16042396
In spite of this, transiently transfected cells might differ considerably from stably transfected ones.
[ "103", "50", "104", "105", "39", "40", "42" ]
103
3,596
0
false
In spite of this, transiently transfected cells might differ considerably from stably transfected ones.
[]
In spite of this, transiently transfected cells might differ considerably from stably transfected ones.
true
true
true
true
true
598
8
DISCUSSION
0
null
null
17,135,188
null
In conclusion, our data clearly show that a vesicular (presumably endosomal) accumulation of the cargo and not uptake per se is the bottleneck of MPGα-mediated RNA delivery rendering the vast majority of intracellular siRNA cargo molecules inactive.
null
249
3,597
0
false
null
null
In conclusion, our data clearly show that a vesicular (presumably endosomal) accumulation of the cargo and not uptake per se is the bottleneck of MPGα-mediated RNA delivery rendering the vast majority of intracellular siRNA cargo molecules inactive.
true
true
true
true
true
599
8
DISCUSSION
0
null
null
17,135,188
null
Thus, like for other non-viral delivery systems, solving the problem of vesicular escape remains the main challenge for this CPP approach.
null
138
3,598
0
false
null
null
Thus, like for other non-viral delivery systems, solving the problem of vesicular escape remains the main challenge for this CPP approach.
true
true
true
true
true
599
8
DISCUSSION
0
null
null
17,135,188
null
Nonetheless, this approach yields IC50 values for siRNA delivery in the sub-nanomolar range far superior to other CPP systems together with the advantage of non-covalent complex formation.
null
188
3,599
0
false
null
null
Nonetheless, this approach yields IC50 values for siRNA delivery in the sub-nanomolar range far superior to other CPP systems together with the advantage of non-covalent complex formation.
true
true
true
true
true
599