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1
INTRODUCTION
1
8
[ "B8", "B9", "B10" ]
17,586,814
pmid-16170216|pmid-9235897|pmid-12718851|pmid-11236674|pmid-8231883|pmid-12536207|pmid-15987787|pmid-12459495|pmid-15240889|pmid-12679785|pmid-12679785|pmid-15987787
Mitogen activated protein kinases (MAPKs), also called extracellular signal-regulated kinases (ERKs), are a group of serine/threonine terminal protein kinases evolutionarily conserved from yeast to human.
[ "8", "9", "10" ]
204
1,300
0
false
Mitogen activated protein kinases (MAPKs), also called extracellular signal-regulated kinases (ERKs), are a group of serine/threonine terminal protein kinases evolutionarily conserved from yeast to human.
[]
Mitogen activated protein kinases (MAPKs), also called extracellular signal-regulated kinases (ERKs), are a group of serine/threonine terminal protein kinases evolutionarily conserved from yeast to human.
true
true
true
true
true
227
1
INTRODUCTION
1
8
[ "B8", "B9", "B10" ]
17,586,814
pmid-16170216|pmid-9235897|pmid-12718851|pmid-11236674|pmid-8231883|pmid-12536207|pmid-15987787|pmid-12459495|pmid-15240889|pmid-12679785|pmid-12679785|pmid-15987787
They form an intracellular signaling cascade regulating fundamental cellular functions including proliferation, cell survival and differentiation (8).
[ "8", "9", "10" ]
150
1,301
1
false
They form an intracellular signaling cascade regulating fundamental cellular functions including proliferation, cell survival and differentiation.
[ "8" ]
They form an intracellular signaling cascade regulating fundamental cellular functions including proliferation, cell survival and differentiation.
true
true
true
true
true
227
1
INTRODUCTION
1
9
[ "B8", "B9", "B10" ]
17,586,814
pmid-16170216|pmid-9235897|pmid-12718851|pmid-11236674|pmid-8231883|pmid-12536207|pmid-15987787|pmid-12459495|pmid-15240889|pmid-12679785|pmid-12679785|pmid-15987787
The MAPK pathway plays also an important role in neurons as it is involved in synaptic plasticity, neuronal survival and regeneration (9).
[ "8", "9", "10" ]
138
1,302
1
false
The MAPK pathway plays also an important role in neurons as it is involved in synaptic plasticity, neuronal survival and regeneration.
[ "9" ]
The MAPK pathway plays also an important role in neurons as it is involved in synaptic plasticity, neuronal survival and regeneration.
true
true
true
true
true
227
1
INTRODUCTION
1
10
[ "B8", "B9", "B10" ]
17,586,814
pmid-16170216|pmid-9235897|pmid-12718851|pmid-11236674|pmid-8231883|pmid-12536207|pmid-15987787|pmid-12459495|pmid-15240889|pmid-12679785|pmid-12679785|pmid-15987787
A regulatory function of MAPK signaling for anxiety and depression-like behavior of adult mice has been proposed (10) but not tested with genetic models in vivo.
[ "8", "9", "10" ]
161
1,303
1
false
A regulatory function of MAPK signaling for anxiety and depression-like behavior of adult mice has been proposed but not tested with genetic models in vivo.
[ "10" ]
A regulatory function of MAPK signaling for anxiety and depression-like behavior of adult mice has been proposed but not tested with genetic models in vivo.
true
true
true
true
true
227
1
INTRODUCTION
1
8
[ "B8", "B9", "B10" ]
17,586,814
pmid-16170216|pmid-9235897|pmid-12718851|pmid-11236674|pmid-8231883|pmid-12536207|pmid-15987787|pmid-12459495|pmid-15240889|pmid-12679785|pmid-12679785|pmid-15987787
Here, we show that a conditional knockdown of Braf and Mek1 and Mek2 in the adult murine brain is possible with our RNAi approach, which gives the possibility to test the role of these genes in anxiety and depression-like behavior in vivo.
[ "8", "9", "10" ]
239
1,304
0
false
Here, we show that a conditional knockdown of Braf and Mek1 and Mek2 in the adult murine brain is possible with our RNAi approach, which gives the possibility to test the role of these genes in anxiety and depression-like behavior in vivo.
[]
Here, we show that a conditional knockdown of Braf and Mek1 and Mek2 in the adult murine brain is possible with our RNAi approach, which gives the possibility to test the role of these genes in anxiety and depression-like behavior in vivo.
true
true
true
true
true
227
0
DISCUSSION
1
24
[ "B24" ]
17,586,814
pmid-13129706|pmid-12778125|pmid-12679785|pmid-12941798|pmid-15107481|pmid-15123829|pmid-11236674|pmid-11910072
Here, we describe a novel technique to inactivate one or two related genes in the adult murine brain with RNA interference in a tissue-specific manner.
[ "24" ]
151
1,305
0
false
Here, we describe a novel technique to inactivate one or two related genes in the adult murine brain with RNA interference in a tissue-specific manner.
[]
Here, we describe a novel technique to inactivate one or two related genes in the adult murine brain with RNA interference in a tissue-specific manner.
true
true
true
true
true
228
0
DISCUSSION
1
24
[ "B24" ]
17,586,814
pmid-13129706|pmid-12778125|pmid-12679785|pmid-12941798|pmid-15107481|pmid-15123829|pmid-11236674|pmid-11910072
We developed conditional shRNA expression vectors that can be activated upon Cre mediated recombination.
[ "24" ]
104
1,306
0
false
We developed conditional shRNA expression vectors that can be activated upon Cre mediated recombination.
[]
We developed conditional shRNA expression vectors that can be activated upon Cre mediated recombination.
true
true
true
true
true
228
0
DISCUSSION
1
24
[ "B24" ]
17,586,814
pmid-13129706|pmid-12778125|pmid-12679785|pmid-12941798|pmid-15107481|pmid-15123829|pmid-11236674|pmid-11910072
After testing various configurations for the positional effect of a transcriptional stop cassette within H1 or U6 promoter driven shRNA vectors, we selected one construct with high knockdown efficiency after Cre recombination.
[ "24" ]
226
1,307
0
false
After testing various configurations for the positional effect of a transcriptional stop cassette within H1 or U6 promoter driven shRNA vectors, we selected one construct with high knockdown efficiency after Cre recombination.
[]
After testing various configurations for the positional effect of a transcriptional stop cassette within H1 or U6 promoter driven shRNA vectors, we selected one construct with high knockdown efficiency after Cre recombination.
true
true
true
true
true
228
0
DISCUSSION
1
24
[ "B24" ]
17,586,814
pmid-13129706|pmid-12778125|pmid-12679785|pmid-12941798|pmid-15107481|pmid-15123829|pmid-11236674|pmid-11910072
Due to the position of the stop cassette, the loop region of the shRNA transcribed from this expression construct is elongated by 34 nt.
[ "24" ]
136
1,308
0
false
Due to the position of the stop cassette, the loop region of the shRNA transcribed from this expression construct is elongated by 34 nt.
[]
Due to the position of the stop cassette, the loop region of the shRNA transcribed from this expression construct is elongated by 34 nt.
true
true
true
true
true
228
0
DISCUSSION
1
24
[ "B24" ]
17,586,814
pmid-13129706|pmid-12778125|pmid-12679785|pmid-12941798|pmid-15107481|pmid-15123829|pmid-11236674|pmid-11910072
In contrast to former studies asserting a 9 nt loop sequence being the most efficient configuration (24), our elongated loop sequence does not interfere with shRNA efficiency.
[ "24" ]
175
1,309
1
false
In contrast to former studies asserting a 9 nt loop sequence being the most efficient configuration, our elongated loop sequence does not interfere with shRNA efficiency.
[ "24" ]
In contrast to former studies asserting a 9 nt loop sequence being the most efficient configuration, our elongated loop sequence does not interfere with shRNA efficiency.
true
true
true
true
true
228
0
DISCUSSION
1
24
[ "B24" ]
17,586,814
pmid-13129706|pmid-12778125|pmid-12679785|pmid-12941798|pmid-15107481|pmid-15123829|pmid-11236674|pmid-11910072
Essential for this technique, we could show that the insertion of a loxP flanked stop segment into the loop region of shRNA vectors disrupts RNAi induction and that such vectors can be activated through Cre mediated recombination.
[ "24" ]
230
1,310
0
false
Essential for this technique, we could show that the insertion of a loxP flanked stop segment into the loop region of shRNA vectors disrupts RNAi induction and that such vectors can be activated through Cre mediated recombination.
[]
Essential for this technique, we could show that the insertion of a loxP flanked stop segment into the loop region of shRNA vectors disrupts RNAi induction and that such vectors can be activated through Cre mediated recombination.
true
true
true
true
true
228
1
DISCUSSION
1
7
[ "B7", "B25", "B26 B27 B28", "B29", "B3", "B3", "B27" ]
17,586,814
pmid-16170216|pmid-9235897|pmid-12718851|pmid-11236674|pmid-8231883|pmid-12536207|pmid-15987787|pmid-12459495|pmid-15240889|pmid-12679785|pmid-12679785|pmid-15987787
An obvious application for conditional RNAi are shRNA vector transgenic mice since a large collection of mouse strains that express Cre recombinase in specific cell types is available and can be used to activate conditional shRNA in different developmental stages and cell types (7).
[ "7", "25", "26–28", "29", "3", "3", "27" ]
283
1,311
1
false
An obvious application for conditional RNAi are shRNA vector transgenic mice since a large collection of mouse strains that express Cre recombinase in specific cell types is available and can be used to activate conditional shRNA in different developmental stages and cell types.
[ "7" ]
An obvious application for conditional RNAi are shRNA vector transgenic mice since a large collection of mouse strains that express Cre recombinase in specific cell types is available and can be used to activate conditional shRNA in different developmental stages and cell types.
true
true
true
true
true
229
1
DISCUSSION
1
25
[ "B7", "B25", "B26 B27 B28", "B29", "B3", "B3", "B27" ]
17,586,814
pmid-16170216|pmid-9235897|pmid-12718851|pmid-11236674|pmid-8231883|pmid-12536207|pmid-15987787|pmid-12459495|pmid-15240889|pmid-12679785|pmid-12679785|pmid-15987787
For the genomic integration of such expression vectors, different approaches are available (25).
[ "7", "25", "26–28", "29", "3", "3", "27" ]
96
1,312
1
false
For the genomic integration of such expression vectors, different approaches are available.
[ "25" ]
For the genomic integration of such expression vectors, different approaches are available.
true
true
true
true
true
229
1
DISCUSSION
1
26–28
[ "B7", "B25", "B26 B27 B28", "B29", "B3", "B3", "B27" ]
17,586,814
pmid-16170216|pmid-9235897|pmid-12718851|pmid-11236674|pmid-8231883|pmid-12536207|pmid-15987787|pmid-12459495|pmid-15240889|pmid-12679785|pmid-12679785|pmid-15987787
Transgenic RNAi mice have been generated by pronuclear injection (26–28), by lentiviral infection (29) or electroporation of ES cells (3).
[ "7", "25", "26–28", "29", "3", "3", "27" ]
138
1,313
1
false
Transgenic RNAi mice have been generated by pronuclear injection, by lentiviral infection or electroporation of ES cells.
[ "26–28", "29", "3" ]
Transgenic RNAi mice have been generated by pronuclear injection, by lentiviral infection or electroporation of ES cells.
true
true
true
true
true
229
1
DISCUSSION
1
7
[ "B7", "B25", "B26 B27 B28", "B29", "B3", "B3", "B27" ]
17,586,814
pmid-16170216|pmid-9235897|pmid-12718851|pmid-11236674|pmid-8231883|pmid-12536207|pmid-15987787|pmid-12459495|pmid-15240889|pmid-12679785|pmid-12679785|pmid-15987787
All these approaches result in random, multicopy integrants of the shRNA vector and therefore require a laborious analysis of multiple lines due to the influence of the genomic environment and the vector copy number on transgene expression (3,27).
[ "7", "25", "26–28", "29", "3", "3", "27" ]
247
1,314
0
false
All these approaches result in random, multicopy integrants of the shRNA vector and therefore require a laborious analysis of multiple lines due to the influence of the genomic environment and the vector copy number on transgene expression.
[ "3,27" ]
All these approaches result in random, multicopy integrants of the shRNA vector and therefore require a laborious analysis of multiple lines due to the influence of the genomic environment and the vector copy number on transgene expression.
true
true
true
true
true
229
1
DISCUSSION
1
7
[ "B7", "B25", "B26 B27 B28", "B29", "B3", "B3", "B27" ]
17,586,814
pmid-16170216|pmid-9235897|pmid-12718851|pmid-11236674|pmid-8231883|pmid-12536207|pmid-15987787|pmid-12459495|pmid-15240889|pmid-12679785|pmid-12679785|pmid-15987787
Apart from the time and resources needed for this initial screening of mouse lines, it is not applicable to conditional shRNA vectors since multicopy integrations could undergo unpredictable and non-functional rearrangements through Cre mediated recombination.
[ "7", "25", "26–28", "29", "3", "3", "27" ]
260
1,315
0
false
Apart from the time and resources needed for this initial screening of mouse lines, it is not applicable to conditional shRNA vectors since multicopy integrations could undergo unpredictable and non-functional rearrangements through Cre mediated recombination.
[]
Apart from the time and resources needed for this initial screening of mouse lines, it is not applicable to conditional shRNA vectors since multicopy integrations could undergo unpredictable and non-functional rearrangements through Cre mediated recombination.
true
true
true
true
true
229
1
DISCUSSION
1
7
[ "B7", "B25", "B26 B27 B28", "B29", "B3", "B3", "B27" ]
17,586,814
pmid-16170216|pmid-9235897|pmid-12718851|pmid-11236674|pmid-8231883|pmid-12536207|pmid-15987787|pmid-12459495|pmid-15240889|pmid-12679785|pmid-12679785|pmid-15987787
Hence, a single-copy approach using a defined and well-characterized genomic locus is preferable.
[ "7", "25", "26–28", "29", "3", "3", "27" ]
97
1,316
0
false
Hence, a single-copy approach using a defined and well-characterized genomic locus is preferable.
[]
Hence, a single-copy approach using a defined and well-characterized genomic locus is preferable.
true
true
true
true
true
229
2
DISCUSSION
1
30–32
[ "B30 B31 B32" ]
17,586,814
pmid-15870264|pmid-15831785|pmid-16676321
The HPRT and the Rosa26 locus are frequently used for the genomic integration of expression vectors and have also been used for shRNA vectors (30–32).
[ "30–32" ]
150
1,317
1
false
The HPRT and the Rosa26 locus are frequently used for the genomic integration of expression vectors and have also been used for shRNA vectors.
[ "30–32" ]
The HPRT and the Rosa26 locus are frequently used for the genomic integration of expression vectors and have also been used for shRNA vectors.
true
true
true
true
true
230
2
DISCUSSION
1
30–32
[ "B30 B31 B32" ]
17,586,814
pmid-15870264|pmid-15831785|pmid-16676321
Since the HPRT locus is affected by X-inactivation in female mice, we chose the Rosa26 locus for integration of our shRNA vectors.
[ "30–32" ]
130
1,318
0
false
Since the HPRT locus is affected by X-inactivation in female mice, we chose the Rosa26 locus for integration of our shRNA vectors.
[]
Since the HPRT locus is affected by X-inactivation in female mice, we chose the Rosa26 locus for integration of our shRNA vectors.
true
true
true
true
true
230
2
DISCUSSION
1
30–32
[ "B30 B31 B32" ]
17,586,814
pmid-15870264|pmid-15831785|pmid-16676321
Using a reporter gene, we showed in homologous recombinant ES cells that our conditional shRNA expressed from one vector copy in the Rosa26 locus gives rise to highly efficient gene knockdown after Cre mediated recombination, comparable to transient transfections of multiple vector copies.
[ "30–32" ]
290
1,319
0
false
Using a reporter gene, we showed in homologous recombinant ES cells that our conditional shRNA expressed from one vector copy in the Rosa26 locus gives rise to highly efficient gene knockdown after Cre mediated recombination, comparable to transient transfections of multiple vector copies.
[]
Using a reporter gene, we showed in homologous recombinant ES cells that our conditional shRNA expressed from one vector copy in the Rosa26 locus gives rise to highly efficient gene knockdown after Cre mediated recombination, comparable to transient transfections of multiple vector copies.
true
true
true
true
true
230
2
DISCUSSION
1
30–32
[ "B30 B31 B32" ]
17,586,814
pmid-15870264|pmid-15831785|pmid-16676321
Thus, the Rosa26 locus allows effective and reproducible U6 promoter driven transcription of shRNA and the amount of shRNA transcribed from one single vector integrant is sufficient for efficient gene knockdown.
[ "30–32" ]
211
1,320
0
false
Thus, the Rosa26 locus allows effective and reproducible U6 promoter driven transcription of shRNA and the amount of shRNA transcribed from one single vector integrant is sufficient for efficient gene knockdown.
[]
Thus, the Rosa26 locus allows effective and reproducible U6 promoter driven transcription of shRNA and the amount of shRNA transcribed from one single vector integrant is sufficient for efficient gene knockdown.
true
true
true
true
true
230
2
DISCUSSION
1
30–32
[ "B30 B31 B32" ]
17,586,814
pmid-15870264|pmid-15831785|pmid-16676321
The functionality of the U6 promoter within a defined chromosomal locus, like Rosa26, lays the basis for conditional RNAi in mice using a single vector copy that is recombined by Cre recombinase into a single, predictable product.
[ "30–32" ]
230
1,321
0
false
The functionality of the U6 promoter within a defined chromosomal locus, like Rosa26, lays the basis for conditional RNAi in mice using a single vector copy that is recombined by Cre recombinase into a single, predictable product.
[]
The functionality of the U6 promoter within a defined chromosomal locus, like Rosa26, lays the basis for conditional RNAi in mice using a single vector copy that is recombined by Cre recombinase into a single, predictable product.
true
true
true
true
true
230
3
DISCUSSION
0
null
null
17,586,814
null
To circumvent the laborious and inefficient homologous recombination step for mouse generation, we further used RMCE to produce ES cells harboring one copy of the shRNA expression vector in the Rosa26 locus.
null
207
1,322
0
false
null
null
To circumvent the laborious and inefficient homologous recombination step for mouse generation, we further used RMCE to produce ES cells harboring one copy of the shRNA expression vector in the Rosa26 locus.
true
true
true
true
true
231
3
DISCUSSION
0
null
null
17,586,814
null
With this approach, the frequency of properly recombined ES cell clones among selection positive clones rises from ∼1% with homologous recombination at Rosa26 to 40–60% with RMCE.
null
179
1,323
0
false
null
null
With this approach, the frequency of properly recombined ES cell clones among selection positive clones rises from ∼1% with homologous recombination at Rosa26 to 40–60% with RMCE.
true
true
true
true
true
231
4
DISCUSSION
1
20
[ "B20", "B21" ]
17,586,814
pmid-10571233|pmid-10471508
Our RNAi mice generated with these techniques harbor a conditional shRNA vector either against Braf or Mek1 and Mek2 at once.
[ "20", "21" ]
125
1,324
0
false
Our RNAi mice generated with these techniques harbor a conditional shRNA vector either against Braf or Mek1 and Mek2 at once.
[]
Our RNAi mice generated with these techniques harbor a conditional shRNA vector either against Braf or Mek1 and Mek2 at once.
true
true
true
true
true
232
4
DISCUSSION
1
20
[ "B20", "B21" ]
17,586,814
pmid-10571233|pmid-10471508
These mice are viable, fertile, show no overt phenotype, and do not express the specific shRNA before Cre mediated recombination.
[ "20", "21" ]
129
1,325
0
false
These mice are viable, fertile, show no overt phenotype, and do not express the specific shRNA before Cre mediated recombination.
[]
These mice are viable, fertile, show no overt phenotype, and do not express the specific shRNA before Cre mediated recombination.
true
true
true
true
true
232
4
DISCUSSION
1
20
[ "B20", "B21" ]
17,586,814
pmid-10571233|pmid-10471508
We used two different Cre expressing mouse lines—both expressing Cre recombinase in a brain-specific manner—to activate shRNA transcription.
[ "20", "21" ]
140
1,326
0
false
We used two different Cre expressing mouse lines—both expressing Cre recombinase in a brain-specific manner—to activate shRNA transcription.
[]
We used two different Cre expressing mouse lines—both expressing Cre recombinase in a brain-specific manner—to activate shRNA transcription.
true
true
true
true
true
232
4
DISCUSSION
1
20
[ "B20", "B21" ]
17,586,814
pmid-10571233|pmid-10471508
We showed that in shBraf+/flox/CamKII-cre mice Cre mediated recombination occurs only in neurons of forebrain regions of the adult brain and in shMek+/flox/Nestin-cre mice in all cells of the adult brain, as described previously (20,21).
[ "20", "21" ]
237
1,327
0
false
We showed that in shBraf+/flox/CamKII-cre mice Cre mediated recombination occurs only in neurons of forebrain regions of the adult brain and in shMek+/flox/Nestin-cre mice in all cells of the adult brain, as described previously.
[ "20,21" ]
We showed that in shBraf+/flox/CamKII-cre mice Cre mediated recombination occurs only in neurons of forebrain regions of the adult brain and in shMek+/flox/Nestin-cre mice in all cells of the adult brain, as described previously.
true
true
true
true
true
232
4
DISCUSSION
1
20
[ "B20", "B21" ]
17,586,814
pmid-10571233|pmid-10471508
Consequently, shRNA expression and reduction of mRNA and protein is detectable in these tissues from mice expressing Cre recombinase.
[ "20", "21" ]
133
1,328
0
false
Consequently, shRNA expression and reduction of mRNA and protein is detectable in these tissues from mice expressing Cre recombinase.
[]
Consequently, shRNA expression and reduction of mRNA and protein is detectable in these tissues from mice expressing Cre recombinase.
true
true
true
true
true
232
4
DISCUSSION
1
20
[ "B20", "B21" ]
17,586,814
pmid-10571233|pmid-10471508
The extent of specific mRNA and protein knockdown reaches ∼70% in case of Braf and Mek1 and ∼50% for Mek2.
[ "20", "21" ]
106
1,329
0
false
The extent of specific mRNA and protein knockdown reaches ∼70% in case of Braf and Mek1 and ∼50% for Mek2.
[]
The extent of specific mRNA and protein knockdown reaches ∼70% in case of Braf and Mek1 and ∼50% for Mek2.
true
true
true
true
true
232
4
DISCUSSION
1
20
[ "B20", "B21" ]
17,586,814
pmid-10571233|pmid-10471508
Important to mention here is, that shMek+/flox/Nestin-cre mice produce one shRNA targeting Mek1 and Mek2 at once.
[ "20", "21" ]
113
1,330
0
false
Important to mention here is, that shMek+/flox/Nestin-cre mice produce one shRNA targeting Mek1 and Mek2 at once.
[]
Important to mention here is, that shMek+/flox/Nestin-cre mice produce one shRNA targeting Mek1 and Mek2 at once.
true
true
true
true
true
232
4
DISCUSSION
1
20
[ "B20", "B21" ]
17,586,814
pmid-10571233|pmid-10471508
Although the efficiency of RNAi is not identical for both genes, we show that it is feasible to knockdown several related genes simultaneously.
[ "20", "21" ]
143
1,331
0
false
Although the efficiency of RNAi is not identical for both genes, we show that it is feasible to knockdown several related genes simultaneously.
[]
Although the efficiency of RNAi is not identical for both genes, we show that it is feasible to knockdown several related genes simultaneously.
true
true
true
true
true
232
5
DISCUSSION
1
33
[ "B33", "B34" ]
17,586,814
pmid-16706848|pmid-9288752
So, this technique will facilitate functional studies of gene families where the loss of one gene may be compensated by other family members (33,34).
[ "33", "34" ]
149
1,332
0
false
So, this technique will facilitate functional studies of gene families where the loss of one gene may be compensated by other family members.
[ "33,34" ]
So, this technique will facilitate functional studies of gene families where the loss of one gene may be compensated by other family members.
true
true
true
true
true
233
5
DISCUSSION
1
33
[ "B33", "B34" ]
17,586,814
pmid-16706848|pmid-9288752
Addressing such questions with conventional knockout strategies implies an enormous effort of breeding and genotyping to obtain double or even triple knockout animals.
[ "33", "34" ]
167
1,333
0
false
Addressing such questions with conventional knockout strategies implies an enormous effort of breeding and genotyping to obtain double or even triple knockout animals.
[]
Addressing such questions with conventional knockout strategies implies an enormous effort of breeding and genotyping to obtain double or even triple knockout animals.
true
true
true
true
true
233
5
DISCUSSION
1
33
[ "B33", "B34" ]
17,586,814
pmid-16706848|pmid-9288752
With RNAi, generating multiple knockdown mice is not more effort as compared to single knockdown mice.
[ "33", "34" ]
102
1,334
0
false
With RNAi, generating multiple knockdown mice is not more effort as compared to single knockdown mice.
[]
With RNAi, generating multiple knockdown mice is not more effort as compared to single knockdown mice.
true
true
true
true
true
233
5
DISCUSSION
1
33
[ "B33", "B34" ]
17,586,814
pmid-16706848|pmid-9288752
Furthermore, the production of shRNA expressing mice is much faster and easier than that of knockout mice, especially with the use of RMCE.
[ "33", "34" ]
139
1,335
0
false
Furthermore, the production of shRNA expressing mice is much faster and easier than that of knockout mice, especially with the use of RMCE.
[]
Furthermore, the production of shRNA expressing mice is much faster and easier than that of knockout mice, especially with the use of RMCE.
true
true
true
true
true
233
5
DISCUSSION
1
33
[ "B33", "B34" ]
17,586,814
pmid-16706848|pmid-9288752
Thus, in 3–4 months even conditional knockdown mice can be generated whereas at least 12 months are required for the production of a classical unconditional knockout strain.
[ "33", "34" ]
173
1,336
0
false
Thus, in 3–4 months even conditional knockdown mice can be generated whereas at least 12 months are required for the production of a classical unconditional knockout strain.
[]
Thus, in 3–4 months even conditional knockdown mice can be generated whereas at least 12 months are required for the production of a classical unconditional knockout strain.
true
true
true
true
true
233
5
DISCUSSION
1
33
[ "B33", "B34" ]
17,586,814
pmid-16706848|pmid-9288752
Moreover, the effort of breeding shRNA mice is significantly decreased since only one shRNA allele is required to exert the knockdown of the targeted gene and breeding for homozygosity (as for knockout mice) is not required.
[ "33", "34" ]
224
1,337
0
false
Moreover, the effort of breeding shRNA mice is significantly decreased since only one shRNA allele is required to exert the knockdown of the targeted gene and breeding for homozygosity (as for knockout mice) is not required.
[]
Moreover, the effort of breeding shRNA mice is significantly decreased since only one shRNA allele is required to exert the knockdown of the targeted gene and breeding for homozygosity (as for knockout mice) is not required.
true
true
true
true
true
233
6
DISCUSSION
1
35
[ "B35", "B36", "B37" ]
17,586,814
pmid-14994337|pmid-10209122|pmid-12567186
In the conditional shRNA mice against MAPKs reported here, we reached knockdown levels of up to 70% after Cre mediated recombination.
[ "35", "36", "37" ]
133
1,338
0
false
In the conditional shRNA mice against MAPKs reported here, we reached knockdown levels of up to 70% after Cre mediated recombination.
[]
In the conditional shRNA mice against MAPKs reported here, we reached knockdown levels of up to 70% after Cre mediated recombination.
true
true
true
true
true
234
6
DISCUSSION
1
35
[ "B35", "B36", "B37" ]
17,586,814
pmid-14994337|pmid-10209122|pmid-12567186
In the reporter gene experiments, we showed that in ES cells a higher knockdown level of up to 90% is possible with the single-copy approach in the Rosa26 locus.
[ "35", "36", "37" ]
161
1,339
0
false
In the reporter gene experiments, we showed that in ES cells a higher knockdown level of up to 90% is possible with the single-copy approach in the Rosa26 locus.
[]
In the reporter gene experiments, we showed that in ES cells a higher knockdown level of up to 90% is possible with the single-copy approach in the Rosa26 locus.
true
true
true
true
true
234
6
DISCUSSION
1
35
[ "B35", "B36", "B37" ]
17,586,814
pmid-14994337|pmid-10209122|pmid-12567186
Using shRNAs against the CRHR1 (corticotropin releasing hormone receptor 1) and LRRK2 (leucine-rich repeat kinase 2) genes we indeed obtained knockdown efficiencies of 80 and 90%, respectively, in the adult brain (R. Kühn, unpublished data).
[ "35", "36", "37" ]
241
1,340
0
false
Using shRNAs against the CRHR1 (corticotropin releasing hormone receptor 1) and LRRK2 (leucine-rich repeat kinase 2) genes we indeed obtained knockdown efficiencies of 80 and 90%, respectively, in the adult brain (R. Kühn, unpublished data).
[]
Using shRNAs against the CRHR1 (corticotropin releasing hormone receptor 1) and LRRK2 (leucine-rich repeat kinase 2) genes we indeed obtained knockdown efficiencies of 80 and 90%, respectively, in the adult brain (R. Kühn, unpublished data).
true
true
true
true
true
234
6
DISCUSSION
1
35
[ "B35", "B36", "B37" ]
17,586,814
pmid-14994337|pmid-10209122|pmid-12567186
Therefore, the level of knockdown that can be reached in vivo with the Rosa26-shRNA approach is not limited to 70% but rather depends on the intrinsic efficacy of the specific target sequence of an individual shRNA, able to elicit either higher or lower levels of gene silencing.
[ "35", "36", "37" ]
279
1,341
0
false
Therefore, the level of knockdown that can be reached in vivo with the Rosa26-shRNA approach is not limited to 70% but rather depends on the intrinsic efficacy of the specific target sequence of an individual shRNA, able to elicit either higher or lower levels of gene silencing.
[]
Therefore, the level of knockdown that can be reached in vivo with the Rosa26-shRNA approach is not limited to 70% but rather depends on the intrinsic efficacy of the specific target sequence of an individual shRNA, able to elicit either higher or lower levels of gene silencing.
true
true
true
true
true
234
6
DISCUSSION
1
35
[ "B35", "B36", "B37" ]
17,586,814
pmid-14994337|pmid-10209122|pmid-12567186
Using public available siRNA prediction programs as paradigm for the design of five shRNA vectors for each gene, we usually find one vector that induces in vitro a knockdown of 90%.
[ "35", "36", "37" ]
181
1,342
0
false
Using public available siRNA prediction programs as paradigm for the design of five shRNA vectors for each gene, we usually find one vector that induces in vitro a knockdown of 90%.
[]
Using public available siRNA prediction programs as paradigm for the design of five shRNA vectors for each gene, we usually find one vector that induces in vitro a knockdown of 90%.
true
true
true
true
true
234
6
DISCUSSION
1
35
[ "B35", "B36", "B37" ]
17,586,814
pmid-14994337|pmid-10209122|pmid-12567186
This average efficiency should improve in future with the further development of siRNA and shRNA prediction algorithms.
[ "35", "36", "37" ]
119
1,343
0
false
This average efficiency should improve in future with the further development of siRNA and shRNA prediction algorithms.
[]
This average efficiency should improve in future with the further development of siRNA and shRNA prediction algorithms.
true
true
true
true
true
234
6
DISCUSSION
1
35
[ "B35", "B36", "B37" ]
17,586,814
pmid-14994337|pmid-10209122|pmid-12567186
To obtain higher knockdown levels for Braf and Mek1/2 the selection of new, more efficient shRNA sequences would be necessary.
[ "35", "36", "37" ]
126
1,344
0
false
To obtain higher knockdown levels for Braf and Mek1/2 the selection of new, more efficient shRNA sequences would be necessary.
[]
To obtain higher knockdown levels for Braf and Mek1/2 the selection of new, more efficient shRNA sequences would be necessary.
true
true
true
true
true
234
6
DISCUSSION
1
35
[ "B35", "B36", "B37" ]
17,586,814
pmid-14994337|pmid-10209122|pmid-12567186
Another possibility to enhance the efficiency of less potent shRNA sequences may be to increase the number of active siRNAs in the cell.
[ "35", "36", "37" ]
136
1,345
0
false
Another possibility to enhance the efficiency of less potent shRNA sequences may be to increase the number of active siRNAs in the cell.
[]
Another possibility to enhance the efficiency of less potent shRNA sequences may be to increase the number of active siRNAs in the cell.
true
true
true
true
true
234
6
DISCUSSION
1
35
[ "B35", "B36", "B37" ]
17,586,814
pmid-14994337|pmid-10209122|pmid-12567186
To test whether increased shRNA levels result in improved knockdown, we compared the residual target gene expression in single copy heterozygous and double copy homozygous shRNA mice.
[ "35", "36", "37" ]
183
1,346
0
false
To test whether increased shRNA levels result in improved knockdown, we compared the residual target gene expression in single copy heterozygous and double copy homozygous shRNA mice.
[]
To test whether increased shRNA levels result in improved knockdown, we compared the residual target gene expression in single copy heterozygous and double copy homozygous shRNA mice.
true
true
true
true
true
234
6
DISCUSSION
1
35
[ "B35", "B36", "B37" ]
17,586,814
pmid-14994337|pmid-10209122|pmid-12567186
In the three tested mouse lines we found in homozygous shRNA mice a moderate (∼5–10%) but not dramatic increase of knockdown efficiency (C. Hitz, P. Steuber-Buchberger, unpublished data).
[ "35", "36", "37" ]
187
1,347
0
false
In the three tested mouse lines we found in homozygous shRNA mice a moderate (∼5–10%) but not dramatic increase of knockdown efficiency (C. Hitz, P. Steuber-Buchberger, unpublished data).
[]
In the three tested mouse lines we found in homozygous shRNA mice a moderate but not dramatic increase of knockdown efficiency (C. Hitz, P. Steuber-Buchberger, unpublished data).
true
true
true
true
true
234
6
DISCUSSION
1
35
[ "B35", "B36", "B37" ]
17,586,814
pmid-14994337|pmid-10209122|pmid-12567186
But even a less potent protein knockdown can result in a phenotype giving interesting insights to the mode of function of the gene.
[ "35", "36", "37" ]
131
1,348
0
false
But even a less potent protein knockdown can result in a phenotype giving interesting insights to the mode of function of the gene.
[]
But even a less potent protein knockdown can result in a phenotype giving interesting insights to the mode of function of the gene.
true
true
true
true
true
234
6
DISCUSSION
1
35
[ "B35", "B36", "B37" ]
17,586,814
pmid-14994337|pmid-10209122|pmid-12567186
For example Shalin et al.
[ "35", "36", "37" ]
25
1,349
0
false
For example Shalin et al.
[]
For example Shalin et al.
true
true
true
true
true
234
6
DISCUSSION
1
35
[ "B35", "B36", "B37" ]
17,586,814
pmid-14994337|pmid-10209122|pmid-12567186
(35) showed impaired fear conditioning in mice with a 40% reduction in ERK1/2 activation.
[ "35", "36", "37" ]
89
1,350
1
false
showed impaired fear conditioning in mice with a 40% reduction in ERK1/2 activation.
[ "35" ]
showed impaired fear conditioning in mice with a 40% reduction in ERK1/2 activation.
false
true
true
true
false
234
6
DISCUSSION
1
36
[ "B35", "B36", "B37" ]
17,586,814
pmid-14994337|pmid-10209122|pmid-12567186
Furthermore, constitutive knockdown with our shRNA against Mek1/2, indeed, does not lead to a placental defect as described for the constitutive knockout of Mek1 (36), but it leads to dwarfism and death at the age of 6 weeks (data not shown).
[ "35", "36", "37" ]
242
1,351
1
false
Furthermore, constitutive knockdown with our shRNA against Mek1/2, indeed, does not lead to a placental defect as described for the constitutive knockout of Mek1, but it leads to dwarfism and death at the age of 6 weeks (data not shown).
[ "36" ]
Furthermore, constitutive knockdown with our shRNA against Mek1/2, indeed, does not lead to a placental defect as described for the constitutive knockout of Mek1, but it leads to dwarfism and death at the age of 6 weeks (data not shown).
true
true
true
true
true
234
6
DISCUSSION
1
37
[ "B35", "B36", "B37" ]
17,586,814
pmid-14994337|pmid-10209122|pmid-12567186
All in all, the doubling of the shRNA copy number and the use of different shRNA target sequences offer the option to exploit differences in efficiency of shRNA sequences to produce allelic series as refined models of genetic diseases beyond the ‘all or nothing’ principle of knockout mice (37).
[ "35", "36", "37" ]
295
1,352
1
false
All in all, the doubling of the shRNA copy number and the use of different shRNA target sequences offer the option to exploit differences in efficiency of shRNA sequences to produce allelic series as refined models of genetic diseases beyond the ‘all or nothing’ principle of knockout mice.
[ "37" ]
All in all, the doubling of the shRNA copy number and the use of different shRNA target sequences offer the option to exploit differences in efficiency of shRNA sequences to produce allelic series as refined models of genetic diseases beyond the ‘all or nothing’ principle of knockout mice.
true
true
true
true
true
234
7
DISCUSSION
1
38
[ "B38", "B10" ]
17,586,814
pmid-17376804|pmid-12718851
We demonstrate that RNAi is a powerful tool for the generation of conditional mouse mutants to study the function of single or related genes in vivo.
[ "38", "10" ]
149
1,353
0
false
We demonstrate that RNAi is a powerful tool for the generation of conditional mouse mutants to study the function of single or related genes in vivo.
[]
We demonstrate that RNAi is a powerful tool for the generation of conditional mouse mutants to study the function of single or related genes in vivo.
true
true
true
true
true
235
7
DISCUSSION
1
38
[ "B38", "B10" ]
17,586,814
pmid-17376804|pmid-12718851
Recently, Seibler et al.
[ "38", "10" ]
24
1,354
0
false
Recently, Seibler et al.
[]
Recently, Seibler et al.
true
true
true
true
true
235
7
DISCUSSION
1
38
[ "B38", "B10" ]
17,586,814
pmid-17376804|pmid-12718851
(38) described a new approach for conditional RNAi using the tetO/tetR system.
[ "38", "10" ]
78
1,355
1
false
described a new approach for conditional RNAi using the tetO/tetR system.
[ "38" ]
described a new approach for conditional RNAi using the tetO/tetR system.
false
true
true
true
false
235
7
DISCUSSION
1
38
[ "B38", "B10" ]
17,586,814
pmid-17376804|pmid-12718851
In contrast to our cell type-specific Cre/loxP regulated system the tetR regulated system is reversible and can be switched on and off optionally.
[ "38", "10" ]
146
1,356
0
false
In contrast to our cell type-specific Cre/loxP regulated system the tetR regulated system is reversible and can be switched on and off optionally.
[]
In contrast to our cell type-specific Cre/loxP regulated system the tetR regulated system is reversible and can be switched on and off optionally.
true
true
true
true
true
235
7
DISCUSSION
1
38
[ "B38", "B10" ]
17,586,814
pmid-17376804|pmid-12718851
However, the tetO/tetR system is not cell type specific and acts simultaneously in all organs and cell types.
[ "38", "10" ]
109
1,357
0
false
However, the tetO/tetR system is not cell type specific and acts simultaneously in all organs and cell types.
[]
However, the tetO/tetR system is not cell type specific and acts simultaneously in all organs and cell types.
true
true
true
true
true
235
7
DISCUSSION
1
38
[ "B38", "B10" ]
17,586,814
pmid-17376804|pmid-12718851
Since more than 150 strains of tissue specific Cre transgenic mice are available, we expect that our conditional shRNA approach can be applied to a wide range of biological questions in a variety of tissues.
[ "38", "10" ]
207
1,358
0
false
Since more than 150 strains of tissue specific Cre transgenic mice are available, we expect that our conditional shRNA approach can be applied to a wide range of biological questions in a variety of tissues.
[]
Since more than 150 strains of tissue specific Cre transgenic mice are available, we expect that our conditional shRNA approach can be applied to a wide range of biological questions in a variety of tissues.
true
true
true
true
true
235
7
DISCUSSION
1
10
[ "B38", "B10" ]
17,586,814
pmid-17376804|pmid-12718851
Here, we used this approach to generate brain-specific knockdown mice for members of the MAPK pathway to gain insight into the function of this signaling cascade that has been proposed to play a role in mood disorders (10).
[ "38", "10" ]
223
1,359
1
false
Here, we used this approach to generate brain-specific knockdown mice for members of the MAPK pathway to gain insight into the function of this signaling cascade that has been proposed to play a role in mood disorders.
[ "10" ]
Here, we used this approach to generate brain-specific knockdown mice for members of the MAPK pathway to gain insight into the function of this signaling cascade that has been proposed to play a role in mood disorders.
true
true
true
true
true
235
7
DISCUSSION
1
38
[ "B38", "B10" ]
17,586,814
pmid-17376804|pmid-12718851
In a first behavioral characterization of Mek1/2 knockdown mice, we observed a contribution of these kinases to the expression of exploratory and anxiety related behavior (data not shown).
[ "38", "10" ]
188
1,360
0
false
In a first behavioral characterization of Mek1/2 knockdown mice, we observed a contribution of these kinases to the expression of exploratory and anxiety related behavior (data not shown).
[]
In a first behavioral characterization of Mek1/2 knockdown mice, we observed a contribution of these kinases to the expression of exploratory and anxiety related behavior (data not shown).
true
true
true
true
true
235
7
DISCUSSION
1
38
[ "B38", "B10" ]
17,586,814
pmid-17376804|pmid-12718851
Further, more detailed studies using conditional knockdown mice are in progress to establish the relation of this phenotype to human anxiety disorders.
[ "38", "10" ]
151
1,361
0
false
Further, more detailed studies using conditional knockdown mice are in progress to establish the relation of this phenotype to human anxiety disorders.
[]
Further, more detailed studies using conditional knockdown mice are in progress to establish the relation of this phenotype to human anxiety disorders.
true
true
true
true
true
235
0
INTRODUCTION
1
1
[ "b1", "b5" ]
17,090,601
pmid-12634793|pmid-10404161
The availability of genome sequences, in conjunction with spectacular advances in mass spectrometric (MS) technology for protein identification have now made it possible to quickly determine large numbers of proteins in complex mixtures (1–5).
[ "1", "5" ]
243
1,362
0
false
The availability of genome sequences, in conjunction with spectacular advances in mass spectrometric (MS) technology for protein identification have now made it possible to quickly determine large numbers of proteins in complex mixtures.
[ "1–5" ]
The availability of genome sequences, in conjunction with spectacular advances in mass spectrometric (MS) technology for protein identification have now made it possible to quickly determine large numbers of proteins in complex mixtures.
true
true
true
true
true
236
0
INTRODUCTION
1
1
[ "b1", "b5" ]
17,090,601
pmid-12634793|pmid-10404161
One early application of MS-based proteomics has been the mapping of various proteomes—that is, the identification of their constituent proteins.
[ "1", "5" ]
145
1,363
0
false
One early application of MS-based proteomics has been the mapping of various proteomes—that is, the identification of their constituent proteins.
[]
One early application of MS-based proteomics has been the mapping of various proteomes—that is, the identification of their constituent proteins.
true
true
true
true
true
236
1
INTRODUCTION
1
6
[ "b6", "b7", "b8", "b9" ]
17,090,601
pmid-12368866|pmid-12368870|pmid-16231421|pmid-16953200
Partial proteomes of microorganisms have been reported, for instance the malaria parasite proteome in various stages of its life cycle (6,7) and international consortia are studying the liver and brain proteome in mice and men.
[ "6", "7", "8", "9" ]
227
1,364
0
false
Partial proteomes of microorganisms have been reported, for instance the malaria parasite proteome in various stages of its life cycle and international consortia are studying the liver and brain proteome in mice and men.
[ "6,7" ]
Partial proteomes of microorganisms have been reported, for instance the malaria parasite proteome in various stages of its life cycle and international consortia are studying the liver and brain proteome in mice and men.
true
true
true
true
true
237
1
INTRODUCTION
1
6
[ "b6", "b7", "b8", "b9" ]
17,090,601
pmid-12368866|pmid-12368870|pmid-16231421|pmid-16953200
The proteomes of body fluids, such as the plasma proteome, the urinary proteome and many others may have potential diagnostic utility.
[ "6", "7", "8", "9" ]
134
1,365
0
false
The proteomes of body fluids, such as the plasma proteome, the urinary proteome and many others may have potential diagnostic utility.
[]
The proteomes of body fluids, such as the plasma proteome, the urinary proteome and many others may have potential diagnostic utility.
true
true
true
true
true
237
1
INTRODUCTION
1
6
[ "b6", "b7", "b8", "b9" ]
17,090,601
pmid-12368866|pmid-12368870|pmid-16231421|pmid-16953200
The proteins expressed in specific cell types and cell lines provide clues to functions of these cells and are useful resource for researchers employing them as models.
[ "6", "7", "8", "9" ]
168
1,366
0
false
The proteins expressed in specific cell types and cell lines provide clues to functions of these cells and are useful resource for researchers employing them as models.
[]
The proteins expressed in specific cell types and cell lines provide clues to functions of these cells and are useful resource for researchers employing them as models.
true
true
true
true
true
237
1
INTRODUCTION
1
6
[ "b6", "b7", "b8", "b9" ]
17,090,601
pmid-12368866|pmid-12368870|pmid-16231421|pmid-16953200
Finally, ‘organellar proteomes’ are the proteins constituting sub-cellular structures such as mitochondria or non-membrane enclosed structures such as the nucleolus (8,9).
[ "6", "7", "8", "9" ]
171
1,367
0
false
Finally, ‘organellar proteomes’ are the proteins constituting sub-cellular structures such as mitochondria or non-membrane enclosed structures such as the nucleolus.
[ "8,9" ]
Finally, ‘organellar proteomes’ are the proteins constituting sub-cellular structures such as mitochondria or non-membrane enclosed structures such as the nucleolus.
true
true
true
true
true
237
2
INTRODUCTION
1
10
[ "b10", "b11", "b12", "b2", "b13" ]
17,090,601
pmid-16784548|pmid-14651853|pmid-15635413|pmid-15340378|pmid-14718574
Despite its obvious utility, proteome mapping faces several technological and some conceptual challenges.
[ "10", "11", "12", "2", "13" ]
105
1,368
0
false
Despite its obvious utility, proteome mapping faces several technological and some conceptual challenges.
[]
Despite its obvious utility, proteome mapping faces several technological and some conceptual challenges.
true
true
true
true
true
238
2
INTRODUCTION
1
10
[ "b10", "b11", "b12", "b2", "b13" ]
17,090,601
pmid-16784548|pmid-14651853|pmid-15635413|pmid-15340378|pmid-14718574
Because of the finite dynamic range and sequencing speed of MS, it is difficult to exhaustively map proteomes with the current state of technology (10).
[ "10", "11", "12", "2", "13" ]
152
1,369
1
false
Because of the finite dynamic range and sequencing speed of MS, it is difficult to exhaustively map proteomes with the current state of technology.
[ "10" ]
Because of the finite dynamic range and sequencing speed of MS, it is difficult to exhaustively map proteomes with the current state of technology.
true
true
true
true
true
238
2
INTRODUCTION
1
10
[ "b10", "b11", "b12", "b2", "b13" ]
17,090,601
pmid-16784548|pmid-14651853|pmid-15635413|pmid-15340378|pmid-14718574
Therefore, proteomes will remain ‘in progress’ for some time.
[ "10", "11", "12", "2", "13" ]
61
1,370
0
false
Therefore, proteomes will remain ‘in progress’ for some time.
[]
Therefore, proteomes will remain ‘in progress’ for some time.
true
true
true
true
true
238
2
INTRODUCTION
1
10
[ "b10", "b11", "b12", "b2", "b13" ]
17,090,601
pmid-16784548|pmid-14651853|pmid-15635413|pmid-15340378|pmid-14718574
Proteomes are not static (i.e.
[ "10", "11", "12", "2", "13" ]
30
1,371
0
false
Proteomes are not static (i.e.
[]
Proteomes are not static (i.e.
true
true
true
true
true
238
2
INTRODUCTION
1
11
[ "b10", "b11", "b12", "b2", "b13" ]
17,090,601
pmid-16784548|pmid-14651853|pmid-15635413|pmid-15340378|pmid-14718574
body fluid proteomes change with the state of the organism), organellar proteomes vary between cell types (11) and generally as a function of cell state (12).
[ "10", "11", "12", "2", "13" ]
158
1,372
1
false
body fluid proteomes change with the state of the organism), organellar proteomes vary between cell types and generally as a function of cell state.
[ "11", "12" ]
body fluid proteomes change with the state of the organism), organellar proteomes vary between cell types and generally as a function of cell state.
false
true
true
true
false
238
2
INTRODUCTION
1
10
[ "b10", "b11", "b12", "b2", "b13" ]
17,090,601
pmid-16784548|pmid-14651853|pmid-15635413|pmid-15340378|pmid-14718574
Biochemical purification of an organelle is never 100% successful, and additional steps need to be incorporated into the proteomic analysis to distinguish genuine members of the proteome from co-purifying ones.
[ "10", "11", "12", "2", "13" ]
210
1,373
0
false
Biochemical purification of an organelle is never 100% successful, and additional steps need to be incorporated into the proteomic analysis to distinguish genuine members of the proteome from co-purifying ones.
[]
Biochemical purification of an organelle is never 100% successful, and additional steps need to be incorporated into the proteomic analysis to distinguish genuine members of the proteome from co-purifying ones.
true
true
true
true
true
238
2
INTRODUCTION
1
10
[ "b10", "b11", "b12", "b2", "b13" ]
17,090,601
pmid-16784548|pmid-14651853|pmid-15635413|pmid-15340378|pmid-14718574
For these and other reasons, constructing databases of proteomes is not as straightforward as constructing sequence databases and proteome databases have to include much additional information concerning the technology employed in mapping and the state of the proteome.
[ "10", "11", "12", "2", "13" ]
269
1,374
0
false
For these and other reasons, constructing databases of proteomes is not as straightforward as constructing sequence databases and proteome databases have to include much additional information concerning the technology employed in mapping and the state of the proteome.
[]
For these and other reasons, constructing databases of proteomes is not as straightforward as constructing sequence databases and proteome databases have to include much additional information concerning the technology employed in mapping and the state of the proteome.
true
true
true
true
true
238
2
INTRODUCTION
1
2
[ "b10", "b11", "b12", "b2", "b13" ]
17,090,601
pmid-16784548|pmid-14651853|pmid-15635413|pmid-15340378|pmid-14718574
Of more immediate concern for proteome database construction is the fact that MS technology can mis-identify proteins, particularly when low-resolution technology is employed (2).
[ "10", "11", "12", "2", "13" ]
179
1,375
1
false
Of more immediate concern for proteome database construction is the fact that MS technology can mis-identify proteins, particularly when low-resolution technology is employed.
[ "2" ]
Of more immediate concern for proteome database construction is the fact that MS technology can mis-identify proteins, particularly when low-resolution technology is employed.
true
true
true
true
true
238
2
INTRODUCTION
1
10
[ "b10", "b11", "b12", "b2", "b13" ]
17,090,601
pmid-16784548|pmid-14651853|pmid-15635413|pmid-15340378|pmid-14718574
Anderson et al.
[ "10", "11", "12", "2", "13" ]
15
1,376
0
false
Anderson et al.
[]
Anderson et al.
true
true
true
true
true
238
2
INTRODUCTION
1
13
[ "b10", "b11", "b12", "b2", "b13" ]
17,090,601
pmid-16784548|pmid-14651853|pmid-15635413|pmid-15340378|pmid-14718574
(13) have noted that four studies of the blood plasma proteome identified together 1175 proteins but only had an overlap of 4% between them.
[ "10", "11", "12", "2", "13" ]
140
1,377
1
false
have noted that four studies of the blood plasma proteome identified together 1175 proteins but only had an overlap of 4% between them.
[ "13" ]
have noted that four studies of the blood plasma proteome identified together 1175 proteins but only had an overlap of 4% between them.
false
true
true
true
false
238
3
INTRODUCTION
1
14
[ "b14", "b15" ]
17,090,601
pmid-15347803|pmid-16118637
We have embarked on the mapping of a large number of different proteomes.
[ "14", "15" ]
73
1,378
0
false
We have embarked on the mapping of a large number of different proteomes.
[]
We have embarked on the mapping of a large number of different proteomes.
true
true
true
true
true
239
3
INTRODUCTION
1
14
[ "b14", "b15" ]
17,090,601
pmid-15347803|pmid-16118637
We employ high resolution mass spectrometry and peptide masses are typically measured within a few p.p.m.
[ "14", "15" ]
105
1,379
0
false
We employ high resolution mass spectrometry and peptide masses are typically measured within a few p.p.m.
[]
We employ high resolution mass spectrometry and peptide masses are typically measured within a few p.p.m.
true
true
true
true
true
239
3
INTRODUCTION
1
14
[ "b14", "b15" ]
17,090,601
pmid-15347803|pmid-16118637
Typically, proteins have to be identified with at least two peptides, or peptides have to have been sequenced by MS3 [two subsequent stages of mass spectrometry, (14)].
[ "14", "15" ]
168
1,380
0
false
Typically, proteins have to be identified with at least two peptides, or peptides have to have been sequenced by MS3.
[ "two subsequent stages of mass spectrometry, (14)" ]
Typically, proteins have to be identified with at least two peptides, or peptides have to have been sequenced by MS3.
true
true
true
true
true
239
3
INTRODUCTION
1
14
[ "b14", "b15" ]
17,090,601
pmid-15347803|pmid-16118637
Identified peptides generated by enzymatic cleavage have to obey strict enzyme specificity.
[ "14", "15" ]
91
1,381
0
false
Identified peptides generated by enzymatic cleavage have to obey strict enzyme specificity.
[]
Identified peptides generated by enzymatic cleavage have to obey strict enzyme specificity.
true
true
true
true
true
239
3
INTRODUCTION
1
15
[ "b14", "b15" ]
17,090,601
pmid-15347803|pmid-16118637
For our reference proteomes, criteria are chosen such that a search against a nonsense database consisting of reversed sequence entries (15) indicates error rates of less than one in a thousand.
[ "14", "15" ]
194
1,382
1
false
For our reference proteomes, criteria are chosen such that a search against a nonsense database consisting of reversed sequence entries indicates error rates of less than one in a thousand.
[ "15" ]
For our reference proteomes, criteria are chosen such that a search against a nonsense database consisting of reversed sequence entries indicates error rates of less than one in a thousand.
true
true
true
true
true
239
3
INTRODUCTION
1
14
[ "b14", "b15" ]
17,090,601
pmid-15347803|pmid-16118637
Our goal is to eventually cover most important organelles, cell types and tissues as well as body fluids in MAPU, accompanied by a set of unified analysis tools.
[ "14", "15" ]
161
1,383
0
false
Our goal is to eventually cover most important organelles, cell types and tissues as well as body fluids in MAPU, accompanied by a set of unified analysis tools.
[]
Our goal is to eventually cover most important organelles, cell types and tissues as well as body fluids in MAPU, accompanied by a set of unified analysis tools.
true
true
true
true
true
239
0
INTRODUCTION
0
null
null
17,071,714
pmid-15121902|pmid-9767141|pmid-16713953
Maturation of eukaryotic cytoplasmic tRNAs is a multistage process that includes the processing of 5′ and 3′ ends, intron splicing in the case of intron-containing pre-tRNAs, transport from the nucleus to the cytoplasm and numerous nucleoside modifications that take place both in the nucleus and in the cytoplasm.
null
314
1,384
0
false
null
null
Maturation of eukaryotic cytoplasmic tRNAs is a multistage process that includes the processing of 5′ and 3′ ends, intron splicing in the case of intron-containing pre-tRNAs, transport from the nucleus to the cytoplasm and numerous nucleoside modifications that take place both in the nucleus and in the cytoplasm.
true
true
true
true
true
240
0
INTRODUCTION
0
null
null
17,071,714
pmid-15121902|pmid-9767141|pmid-16713953
Three classes of intron-containing tRNA genes are present in the human nuclear genome: tRNA(GΨA)Tyr (8 genes with intron lengths ranging from 16 to 21 bp), tRNA(m5CAA)Leu (5 genes with intron lengths ranging from 22 to 25 bp) and tRNA(UCU)Arg (1 gene containing a 15 bp intron) (Genomic tRNA database, ).
null
304
1,385
0
false
null
null
Three classes of intron-containing tRNA genes are present in the human nuclear genome: tRNA(GΨA)Tyr (8 genes with intron lengths ranging from 16 to 21 bp), tRNA(m5CAA)Leu (5 genes with intron lengths ranging from 22 to 25 bp) and tRNA(UCU)Arg (1 gene containing a 15 bp intron) (Genomic tRNA database, ).
true
true
true
true
true
240
0
INTRODUCTION
0
null
null
17,071,714
pmid-15121902|pmid-9767141|pmid-16713953
In all cases, introns are located one nucleotide downstream from the anticodon, which is a typical feature of nuclear intron-containing tRNA genes.
null
147
1,386
0
false
null
null
In all cases, introns are located one nucleotide downstream from the anticodon, which is a typical feature of nuclear intron-containing tRNA genes.
true
true
true
true
true
240
1
INTRODUCTION
1
1
[ "b1", "b3", "b4", "b5", "b6", "b7", "b5" ]
17,071,714
pmid-6339954|pmid-3357766|pmid-1582418|pmid-3537724|NA|pmid-9869432|pmid-3537724|pmid-6514577|pmid-6514577|pmid-6773543|pmid-3537724|pmid-10445884
In the case of tRNA(GΨA)Tyr genes, it has been shown that the introduction of pseudouridine in the middle position of the anticodon (Ψ35) is intron dependent in yeast, plants, animals and humans (1–3).
[ "1", "3", "4", "5", "6", "7", "5" ]
201
1,387
0
false
In the case of tRNA(GΨA)Tyr genes, it has been shown that the introduction of pseudouridine in the middle position of the anticodon is intron dependent in yeast, plants, animals and humans.
[ "Ψ35", "1–3" ]
In the case of tRNA(GΨA)Tyr genes, it has been shown that the introduction of pseudouridine in the middle position of the anticodon is intron dependent in yeast, plants, animals and humans.
true
true
true
true
true
241
1
INTRODUCTION
1
4
[ "b1", "b3", "b4", "b5", "b6", "b7", "b5" ]
17,071,714
pmid-6339954|pmid-3357766|pmid-1582418|pmid-3537724|NA|pmid-9869432|pmid-3537724|pmid-6514577|pmid-6514577|pmid-6773543|pmid-3537724|pmid-10445884
Moreover, it has been demonstrated that the introduction of Ψ35 strictly depends on the nucleotide sequence surrounding the U35 to be modified and depends rather on the length of the intron than on its structure (4).
[ "1", "3", "4", "5", "6", "7", "5" ]
216
1,388
1
false
Moreover, it has been demonstrated that the introduction of Ψ35 strictly depends on the nucleotide sequence surrounding the U35 to be modified and depends rather on the length of the intron than on its structure.
[ "4" ]
Moreover, it has been demonstrated that the introduction of Ψ35 strictly depends on the nucleotide sequence surrounding the U35 to be modified and depends rather on the length of the intron than on its structure.
true
true
true
true
true
241
1
INTRODUCTION
1
1
[ "b1", "b3", "b4", "b5", "b6", "b7", "b5" ]
17,071,714
pmid-6339954|pmid-3357766|pmid-1582418|pmid-3537724|NA|pmid-9869432|pmid-3537724|pmid-6514577|pmid-6514577|pmid-6773543|pmid-3537724|pmid-10445884
Transfer RNA(CAA)Leu genes contain introns in yeast and vertebrates (5,6).
[ "1", "3", "4", "5", "6", "7", "5" ]
74
1,389
0
false
Transfer RNA(CAA)Leu genes contain introns in yeast and vertebrates.
[ "5,6" ]
Transfer RNA(CAA)Leu genes contain introns in yeast and vertebrates.
true
true
true
true
true
241
1
INTRODUCTION
1
7
[ "b1", "b3", "b4", "b5", "b6", "b7", "b5" ]
17,071,714
pmid-6339954|pmid-3357766|pmid-1582418|pmid-3537724|NA|pmid-9869432|pmid-3537724|pmid-6514577|pmid-6514577|pmid-6773543|pmid-3537724|pmid-10445884
However, in plants, there are no introns in these genes (7).
[ "1", "3", "4", "5", "6", "7", "5" ]
60
1,390
1
false
However, in plants, there are no introns in these genes.
[ "7" ]
However, in plants, there are no introns in these genes.
true
true
true
true
true
241
1
INTRODUCTION
1
1
[ "b1", "b3", "b4", "b5", "b6", "b7", "b5" ]
17,071,714
pmid-6339954|pmid-3357766|pmid-1582418|pmid-3537724|NA|pmid-9869432|pmid-3537724|pmid-6514577|pmid-6514577|pmid-6773543|pmid-3537724|pmid-10445884
The first position of the yeast anticodon sequence—cytosine—in tRNA(CAA)Leu is methylated to 5-methylcytosine (m5C)34.
[ "1", "3", "4", "5", "6", "7", "5" ]
118
1,391
0
false
The first position of the yeast anticodon sequence—cytosine—in tRNA(CAA)Leu is methylated to 5-methylcytosine 34.
[ "m5C" ]
The first position of the yeast anticodon sequence—cytosine—in tRNA(CAA)Leu is methylated to 5-methylcytosine 34.
true
true
true
true
true
241
1
INTRODUCTION
1
5
[ "b1", "b3", "b4", "b5", "b6", "b7", "b5" ]
17,071,714
pmid-6339954|pmid-3357766|pmid-1582418|pmid-3537724|NA|pmid-9869432|pmid-3537724|pmid-6514577|pmid-6514577|pmid-6773543|pmid-3537724|pmid-10445884
In yeast, this methylation is intron dependent and its introduction strictly depends on the intron structure (5).
[ "1", "3", "4", "5", "6", "7", "5" ]
113
1,392
1
false
In yeast, this methylation is intron dependent and its introduction strictly depends on the intron structure.
[ "5" ]
In yeast, this methylation is intron dependent and its introduction strictly depends on the intron structure.
true
true
true
true
true
241
2
INTRODUCTION
1
1
[ "b1", "b5", "b8" ]
17,071,714
pmid-6339954|pmid-3537724|pmid-1461724|pmid-10445884|pmid-15121902
The first functional evidence of the importance of Ψ35 in tRNATyr and m5C34 in tRNALeu came from the Abelson laboratory (1,5).
[ "1", "5", "8" ]
126
1,393
0
false
The first functional evidence of the importance of Ψ35 in tRNATyr and m5C34 in tRNALeu came from the Abelson laboratory.
[ "1,5" ]
The first functional evidence of the importance of Ψ35 in tRNATyr and m5C34 in tRNALeu came from the Abelson laboratory.
true
true
true
true
true
242
2
INTRODUCTION
1
1
[ "b1", "b5", "b8" ]
17,071,714
pmid-6339954|pmid-3537724|pmid-1461724|pmid-10445884|pmid-15121902
The construction of mutant yeast tRNATyr and tRNALeu genes without introns resulted in the production of mature tRNA molecules without appropriate modified bases.
[ "1", "5", "8" ]
162
1,394
0
false
The construction of mutant yeast tRNATyr and tRNALeu genes without introns resulted in the production of mature tRNA molecules without appropriate modified bases.
[]
The construction of mutant yeast tRNATyr and tRNALeu genes without introns resulted in the production of mature tRNA molecules without appropriate modified bases.
true
true
true
true
true
242
2
INTRODUCTION
1
1
[ "b1", "b5", "b8" ]
17,071,714
pmid-6339954|pmid-3537724|pmid-1461724|pmid-10445884|pmid-15121902
When the suppressor activity of a tRNATyr product derived from intron-containing tRNA (SUP 6 coding for ochre suppressor tRNA) with the ochre suppressor tRNA transcribed from the gene without intron was compared, it turned out that tRNATyr derived from the mutated gene without intron exhibited a strong reduction in the suppressor activity.
[ "1", "5", "8" ]
341
1,395
0
false
When the suppressor activity of a tRNATyr product derived from intron-containing tRNA (SUP 6 coding for ochre suppressor tRNA) with the ochre suppressor tRNA transcribed from the gene without intron was compared, it turned out that tRNATyr derived from the mutated gene without intron exhibited a strong reduction in the suppressor activity.
[]
When the suppressor activity of a tRNATyr product derived from intron-containing tRNA (SUP 6 coding for ochre suppressor tRNA) with the ochre suppressor tRNA transcribed from the gene without intron was compared, it turned out that tRNATyr derived from the mutated gene without intron exhibited a strong reduction in the suppressor activity.
true
true
true
true
true
242
2
INTRODUCTION
1
1
[ "b1", "b5", "b8" ]
17,071,714
pmid-6339954|pmid-3537724|pmid-1461724|pmid-10445884|pmid-15121902
In an analogous experiment, a mutant, intron-less yeast tRNALeu gene encoding amber suppressor tRNA (SUP 53) also gave a product with a weak suppressor activity when compared with the intron-containing amber tRNALeu suppressor gene product.
[ "1", "5", "8" ]
240
1,396
0
false
In an analogous experiment, a mutant, intron-less yeast tRNALeu gene encoding amber suppressor tRNA also gave a product with a weak suppressor activity when compared with the intron-containing amber tRNALeu suppressor gene product.
[ "SUP 53" ]
In an analogous experiment, a mutant, intron-less yeast tRNALeu gene encoding amber suppressor tRNA also gave a product with a weak suppressor activity when compared with the intron-containing amber tRNALeu suppressor gene product.
true
true
true
true
true
242
2
INTRODUCTION
1
1
[ "b1", "b5", "b8" ]
17,071,714
pmid-6339954|pmid-3537724|pmid-1461724|pmid-10445884|pmid-15121902
In both cases, the decreased suppressor activity correlated with the absence of Ψ35 and m5C34, respectively.
[ "1", "5", "8" ]
108
1,397
0
false
In both cases, the decreased suppressor activity correlated with the absence of Ψ35 and m5C34, respectively.
[]
In both cases, the decreased suppressor activity correlated with the absence of Ψ35 and m5C34, respectively.
true
true
true
true
true
242
2
INTRODUCTION
1
8
[ "b1", "b5", "b8" ]
17,071,714
pmid-6339954|pmid-3537724|pmid-1461724|pmid-10445884|pmid-15121902
Similarly, Ψ35 is required in the anticodon (GΨA) of cytoplasmic tRNATyr from Nicotiana rustica for UAG and UAA suppression in the translation of the tobacco mosaic virus (TMV) RNA (8).
[ "1", "5", "8" ]
185
1,398
1
false
Similarly, Ψ35 is required in the anticodon (GΨA) of cytoplasmic tRNATyr from Nicotiana rustica for UAG and UAA suppression in the translation of the tobacco mosaic virus (TMV) RNA.
[ "8" ]
Similarly, Ψ35 is required in the anticodon (GΨA) of cytoplasmic tRNATyr from Nicotiana rustica for UAG and UAA suppression in the translation of the tobacco mosaic virus (TMV) RNA.
true
true
true
true
true
242
2
INTRODUCTION
1
1
[ "b1", "b5", "b8" ]
17,071,714
pmid-6339954|pmid-3537724|pmid-1461724|pmid-10445884|pmid-15121902
Summarizing the afore-mentioned experiments, it is clear that both Ψ35 and m5C34 are necessary to stabilize anticodon–codon pairing leading to the correct decoding of mRNA.
[ "1", "5", "8" ]
172
1,399
0
false
Summarizing the afore-mentioned experiments, it is clear that both Ψ35 and m5C34 are necessary to stabilize anticodon–codon pairing leading to the correct decoding of mRNA.
[]
Summarizing the afore-mentioned experiments, it is clear that both Ψ35 and m5C34 are necessary to stabilize anticodon–codon pairing leading to the correct decoding of mRNA.
true
true
true
true
true
242