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INTRODUCTION
1
6
[ "B1", "B2", "B3", "B4", "B5", "B6", "B7", "B8" ]
17,439,965
pmid-15372042|pmid-17011485|pmid-16814728|pmid-16557279|pmid-16141076|pmid-16736018|pmid-16258535|pmid-16459310
Reverse-complement 2′-O-methyl sugar modified RNA is frequently being used to block miRNA function in cell-based systems (6).
[ "1", "2", "3", "4", "5", "6", "7", "8" ]
125
4,300
1
false
Reverse-complement 2′-O-methyl sugar modified RNA is frequently being used to block miRNA function in cell-based systems.
[ "6" ]
Reverse-complement 2′-O-methyl sugar modified RNA is frequently being used to block miRNA function in cell-based systems.
true
true
true
true
true
734
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5", "B6", "B7", "B8" ]
17,439,965
pmid-15372042|pmid-17011485|pmid-16814728|pmid-16557279|pmid-16141076|pmid-16736018|pmid-16258535|pmid-16459310
The use of miRNA inhibitors in mice, however, remains challenging.
[ "1", "2", "3", "4", "5", "6", "7", "8" ]
66
4,301
0
false
The use of miRNA inhibitors in mice, however, remains challenging.
[]
The use of miRNA inhibitors in mice, however, remains challenging.
true
true
true
true
true
734
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5", "B6", "B7", "B8" ]
17,439,965
pmid-15372042|pmid-17011485|pmid-16814728|pmid-16557279|pmid-16141076|pmid-16736018|pmid-16258535|pmid-16459310
Recently, two independent approaches to silence miRNAs in vivo have been reported.
[ "1", "2", "3", "4", "5", "6", "7", "8" ]
82
4,302
0
false
Recently, two independent approaches to silence miRNAs in vivo have been reported.
[]
Recently, two independent approaches to silence miRNAs in vivo have been reported.
true
true
true
true
true
734
0
INTRODUCTION
1
7
[ "B1", "B2", "B3", "B4", "B5", "B6", "B7", "B8" ]
17,439,965
pmid-15372042|pmid-17011485|pmid-16814728|pmid-16557279|pmid-16141076|pmid-16736018|pmid-16258535|pmid-16459310
Our group demonstrated silencing of miRNAs in mice based on RNA analogs termed ‘antagomirs’ (7).
[ "1", "2", "3", "4", "5", "6", "7", "8" ]
96
4,303
1
false
Our group demonstrated silencing of miRNAs in mice based on RNA analogs termed ‘antagomirs’.
[ "7" ]
Our group demonstrated silencing of miRNAs in mice based on RNA analogs termed ‘antagomirs’.
true
true
true
true
true
734
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5", "B6", "B7", "B8" ]
17,439,965
pmid-15372042|pmid-17011485|pmid-16814728|pmid-16557279|pmid-16141076|pmid-16736018|pmid-16258535|pmid-16459310
Antagomirs are RNA-like oligonucleotides that harbor various modifications for RNAse protection and pharmacologic properties such as enhanced tissue and cellular uptake.
[ "1", "2", "3", "4", "5", "6", "7", "8" ]
169
4,304
0
false
Antagomirs are RNA-like oligonucleotides that harbor various modifications for RNAse protection and pharmacologic properties such as enhanced tissue and cellular uptake.
[]
Antagomirs are RNA-like oligonucleotides that harbor various modifications for RNAse protection and pharmacologic properties such as enhanced tissue and cellular uptake.
true
true
true
true
true
734
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5", "B6", "B7", "B8" ]
17,439,965
pmid-15372042|pmid-17011485|pmid-16814728|pmid-16557279|pmid-16141076|pmid-16736018|pmid-16258535|pmid-16459310
They differ from normal RNA by complete 2′-O-methylation of sugar, phosphorothioate backbone and a cholesterol-moiety at 3′-end.
[ "1", "2", "3", "4", "5", "6", "7", "8" ]
128
4,305
0
false
They differ from normal RNA by complete 2′-O-methylation of sugar, phosphorothioate backbone and a cholesterol-moiety at 3′-end.
[]
They differ from normal RNA by complete 2′-O-methylation of sugar, phosphorothioate backbone and a cholesterol-moiety at 3′-end.
true
true
true
true
true
734
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5", "B6", "B7", "B8" ]
17,439,965
pmid-15372042|pmid-17011485|pmid-16814728|pmid-16557279|pmid-16141076|pmid-16736018|pmid-16258535|pmid-16459310
Antagomirs efficiently silence miRNAs in most tissues after three injections at 80 mg/kg bodyweight (bw) on consecutive days.
[ "1", "2", "3", "4", "5", "6", "7", "8" ]
125
4,306
0
false
Antagomirs efficiently silence miRNAs in most tissues after three injections at 80 mg/kg bodyweight (bw) on consecutive days.
[]
Antagomirs efficiently silence miRNAs in most tissues after three injections at 80 mg/kg bodyweight (bw) on consecutive days.
true
true
true
true
true
734
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5", "B6", "B7", "B8" ]
17,439,965
pmid-15372042|pmid-17011485|pmid-16814728|pmid-16557279|pmid-16141076|pmid-16736018|pmid-16258535|pmid-16459310
Esau et al.
[ "1", "2", "3", "4", "5", "6", "7", "8" ]
11
4,307
0
false
Esau et al.
[]
Esau et al.
true
true
true
true
true
734
0
INTRODUCTION
1
8
[ "B1", "B2", "B3", "B4", "B5", "B6", "B7", "B8" ]
17,439,965
pmid-15372042|pmid-17011485|pmid-16814728|pmid-16557279|pmid-16141076|pmid-16736018|pmid-16258535|pmid-16459310
recently demonstrated a different strategy to silence miRNA(miR)-122 in mouse liver (8).
[ "1", "2", "3", "4", "5", "6", "7", "8" ]
88
4,308
1
false
recently demonstrated a different strategy to silence miRNA(miR)-122 in mouse liver.
[ "8" ]
recently demonstrated a different strategy to silence miRNA(miR)-122 in mouse liver.
false
true
true
true
false
734
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5", "B6", "B7", "B8" ]
17,439,965
pmid-15372042|pmid-17011485|pmid-16814728|pmid-16557279|pmid-16141076|pmid-16736018|pmid-16258535|pmid-16459310
They inhibited miR-122 following a four-week treatment protocol with two injections per week of 12.5–75 mg/kg bw of an antisense oligonucleotide (ASO) harboring a complete 2′-O-methoxyethyl and phosphorothioate modification.
[ "1", "2", "3", "4", "5", "6", "7", "8" ]
224
4,309
0
false
They inhibited miR-122 following a four-week treatment protocol with two injections per week of 12.5–75 mg/kg bw of an antisense oligonucleotide (ASO) harboring a complete 2′-O-methoxyethyl and phosphorothioate modification.
[]
They inhibited miR-122 following a four-week treatment protocol with two injections per week of 12.5–75 mg/kg bw of an antisense oligonucleotide (ASO) harboring a complete 2′-O-methoxyethyl and phosphorothioate modification.
true
true
true
true
true
734
1
INTRODUCTION
0
null
null
17,439,965
pmid-16369549|pmid-16690972|pmid-16690972
Ultimately the efficient use of oligonucleotides to target miRNAs for functional studies and therapeutic use will be dependent on characterizations based on miRNA targets in vivo.
null
179
4,310
0
false
null
null
Ultimately the efficient use of oligonucleotides to target miRNAs for functional studies and therapeutic use will be dependent on characterizations based on miRNA targets in vivo.
true
true
true
true
true
735
1
INTRODUCTION
0
null
null
17,439,965
pmid-16369549|pmid-16690972|pmid-16690972
Moreover, more efficient strategies could be developed through a more detailed understanding of the mechanisms of miRNA silencing.
null
130
4,311
0
false
null
null
Moreover, more efficient strategies could be developed through a more detailed understanding of the mechanisms of miRNA silencing.
true
true
true
true
true
735
1
INTRODUCTION
0
null
null
17,439,965
pmid-16369549|pmid-16690972|pmid-16690972
In this study, we begin to address these questions using regulation of endogenous miR-122 targets and fluorophore-tagged antagomirs.
null
132
4,312
0
false
null
null
In this study, we begin to address these questions using regulation of endogenous miR-122 targets and fluorophore-tagged antagomirs.
true
true
true
true
true
735
0
DISCUSSION
0
null
null
17,439,965
pmid-15372042|pmid-17011485|pmid-16814728|pmid-16557279|pmid-16141076|pmid-16736018|pmid-16258535|pmid-16459310
In this study, we characterized the inhibition of miRNAs with antagomirs in vivo.
null
81
4,313
0
false
null
null
In this study, we characterized the inhibition of miRNAs with antagomirs in vivo.
true
true
true
true
true
736
0
DISCUSSION
0
null
null
17,439,965
pmid-15372042|pmid-17011485|pmid-16814728|pmid-16557279|pmid-16141076|pmid-16736018|pmid-16258535|pmid-16459310
A detailed understanding of this process is needed to investigate miRNA function in mice and exploit their therapeutic potential.
null
129
4,314
0
false
null
null
A detailed understanding of this process is needed to investigate miRNA function in mice and exploit their therapeutic potential.
true
true
true
true
true
736
0
DISCUSSION
0
null
null
17,439,965
pmid-15372042|pmid-17011485|pmid-16814728|pmid-16557279|pmid-16141076|pmid-16736018|pmid-16258535|pmid-16459310
Our study provides a unique platform since its major read-out is based on the dose-and time-dependent regulation of several endogenous and validated targets of miR-122.
null
168
4,315
0
false
null
null
Our study provides a unique platform since its major read-out is based on the dose-and time-dependent regulation of several endogenous and validated targets of miR-122.
true
true
true
true
true
736
1
DISCUSSION
1
11
[ "B11", "B12", "B12" ]
17,439,965
pmid-16369549|pmid-16690972|pmid-16690972
Specificity of drug-like oligonucleotides is important to minimize off-target effects and to discriminate between related miRNAs that sometimes differ by only a single nucleotide.
[ "11", "12", "12" ]
179
4,316
0
false
Specificity of drug-like oligonucleotides is important to minimize off-target effects and to discriminate between related miRNAs that sometimes differ by only a single nucleotide.
[]
Specificity of drug-like oligonucleotides is important to minimize off-target effects and to discriminate between related miRNAs that sometimes differ by only a single nucleotide.
true
true
true
true
true
737
1
DISCUSSION
1
11
[ "B11", "B12", "B12" ]
17,439,965
pmid-16369549|pmid-16690972|pmid-16690972
Previous studies have demonstrated that locked nucleic acid (LNA) are sensitive to single mismatch in in-situ staining protocols of zebrafish embryos (11).
[ "11", "12", "12" ]
155
4,317
1
false
Previous studies have demonstrated that locked nucleic acid (LNA) are sensitive to single mismatch in in-situ staining protocols of zebrafish embryos.
[ "11" ]
Previous studies have demonstrated that locked nucleic acid (LNA) are sensitive to single mismatch in in-situ staining protocols of zebrafish embryos.
true
true
true
true
true
737
1
DISCUSSION
1
12
[ "B11", "B12", "B12" ]
17,439,965
pmid-16369549|pmid-16690972|pmid-16690972
Tissue-culture-based luciferase assays indicated that 2′-O-methoxyethyl oligonucleotides might have a similar specificity (12).
[ "11", "12", "12" ]
127
4,318
1
false
Tissue-culture-based luciferase assays indicated that 2′-O-methoxyethyl oligonucleotides might have a similar specificity.
[ "12" ]
Tissue-culture-based luciferase assays indicated that 2′-O-methoxyethyl oligonucleotides might have a similar specificity.
true
true
true
true
true
737
1
DISCUSSION
1
11
[ "B11", "B12", "B12" ]
17,439,965
pmid-16369549|pmid-16690972|pmid-16690972
In line with these data we show that the antagomir chemistry enables discrimination of a single nucleotide.
[ "11", "12", "12" ]
107
4,319
0
false
In line with these data we show that the antagomir chemistry enables discrimination of a single nucleotide.
[]
In line with these data we show that the antagomir chemistry enables discrimination of a single nucleotide.
true
true
true
true
true
737
1
DISCUSSION
1
11
[ "B11", "B12", "B12" ]
17,439,965
pmid-16369549|pmid-16690972|pmid-16690972
Intriguingly, this effect depends on the position of the mismatch within the antagomir sequence.
[ "11", "12", "12" ]
96
4,320
0
false
Intriguingly, this effect depends on the position of the mismatch within the antagomir sequence.
[]
Intriguingly, this effect depends on the position of the mismatch within the antagomir sequence.
true
true
true
true
true
737
1
DISCUSSION
1
11
[ "B11", "B12", "B12" ]
17,439,965
pmid-16369549|pmid-16690972|pmid-16690972
Nucleotide exchanges at the very 5′-end of the antagomir or in the center did not prevent downregulation of miR-122 levels in northern blots and upregulation of miR-122 targets.
[ "11", "12", "12" ]
177
4,321
0
false
Nucleotide exchanges at the very 5′-end of the antagomir or in the center did not prevent downregulation of miR-122 levels in northern blots and upregulation of miR-122 targets.
[]
Nucleotide exchanges at the very 5′-end of the antagomir or in the center did not prevent downregulation of miR-122 levels in northern blots and upregulation of miR-122 targets.
true
true
true
true
true
737
1
DISCUSSION
1
12
[ "B11", "B12", "B12" ]
17,439,965
pmid-16369549|pmid-16690972|pmid-16690972
This observation is in agreement with the work published by Davis et al., who reported a similar result in luciferase-based assays (12).
[ "11", "12", "12" ]
136
4,322
1
false
This observation is in agreement with the work published by Davis et al., who reported a similar result in luciferase-based assays.
[ "12" ]
This observation is in agreement with the work published by Davis et al., who reported a similar result in luciferase-based assays.
true
true
true
true
true
737
1
DISCUSSION
1
11
[ "B11", "B12", "B12" ]
17,439,965
pmid-16369549|pmid-16690972|pmid-16690972
Asymmetry of a single nucleotide mismatch may therefore be more detrimental for targeting miRNAs than symmetric changes.
[ "11", "12", "12" ]
120
4,323
0
false
Asymmetry of a single nucleotide mismatch may therefore be more detrimental for targeting miRNAs than symmetric changes.
[]
Asymmetry of a single nucleotide mismatch may therefore be more detrimental for targeting miRNAs than symmetric changes.
true
true
true
true
true
737
1
DISCUSSION
1
11
[ "B11", "B12", "B12" ]
17,439,965
pmid-16369549|pmid-16690972|pmid-16690972
These data are important for the design of antagomirs that target specific members of miRNA families or when off-target effects have to be considered.
[ "11", "12", "12" ]
150
4,324
0
false
These data are important for the design of antagomirs that target specific members of miRNA families or when off-target effects have to be considered.
[]
These data are important for the design of antagomirs that target specific members of miRNA families or when off-target effects have to be considered.
true
true
true
true
true
737
2
DISCUSSION
1
12
[ "B12", "B7", "B8", "B7", "B13", "B14", "B13" ]
17,439,965
pmid-16690972|pmid-16258535|pmid-16459310|pmid-16258535|pmid-16271385|pmid-16271386|pmid-16271385
The mechanism of oligonucleotide-mediated miRNA silencing is still unknown.
[ "12", "7", "8", "7", "13", "14", "13" ]
75
4,325
0
false
The mechanism of oligonucleotide-mediated miRNA silencing is still unknown.
[]
The mechanism of oligonucleotide-mediated miRNA silencing is still unknown.
true
true
true
true
true
738
2
DISCUSSION
1
12
[ "B12", "B7", "B8", "B7", "B13", "B14", "B13" ]
17,439,965
pmid-16690972|pmid-16258535|pmid-16459310|pmid-16258535|pmid-16271385|pmid-16271386|pmid-16271385
Previous data from our group and others suggested that this process involves degradation of the miRNA in vitro (12) and in vivo (7,8).
[ "12", "7", "8", "7", "13", "14", "13" ]
134
4,326
1
false
Previous data from our group and others suggested that this process involves degradation of the miRNA in vitro and in vivo.
[ "12", "7,8" ]
Previous data from our group and others suggested that this process involves degradation of the miRNA in vitro and in vivo.
true
true
true
true
true
738
2
DISCUSSION
1
12
[ "B12", "B7", "B8", "B7", "B13", "B14", "B13" ]
17,439,965
pmid-16690972|pmid-16258535|pmid-16459310|pmid-16258535|pmid-16271385|pmid-16271386|pmid-16271385
Northern blots of tissue samples treated with antagomirs fail to detect fragments of the targeted miRNA.
[ "12", "7", "8", "7", "13", "14", "13" ]
104
4,327
0
false
Northern blots of tissue samples treated with antagomirs fail to detect fragments of the targeted miRNA.
[]
Northern blots of tissue samples treated with antagomirs fail to detect fragments of the targeted miRNA.
true
true
true
true
true
738
2
DISCUSSION
1
12
[ "B12", "B7", "B8", "B7", "B13", "B14", "B13" ]
17,439,965
pmid-16690972|pmid-16258535|pmid-16459310|pmid-16258535|pmid-16271385|pmid-16271386|pmid-16271385
This could be explained by cellular RNase activity that readily degrades them.
[ "12", "7", "8", "7", "13", "14", "13" ]
78
4,328
0
false
This could be explained by cellular RNase activity that readily degrades them.
[]
This could be explained by cellular RNase activity that readily degrades them.
true
true
true
true
true
738
2
DISCUSSION
1
7
[ "B12", "B7", "B8", "B7", "B13", "B14", "B13" ]
17,439,965
pmid-16690972|pmid-16258535|pmid-16459310|pmid-16258535|pmid-16271385|pmid-16271386|pmid-16271385
We have previously demonstrated that increasing the cellular amount of endogenous miRNA by introducing duplexes of miRNA/antagomir leads to detectable degradation products (7).
[ "12", "7", "8", "7", "13", "14", "13" ]
176
4,329
1
false
We have previously demonstrated that increasing the cellular amount of endogenous miRNA by introducing duplexes of miRNA/antagomir leads to detectable degradation products.
[ "7" ]
We have previously demonstrated that increasing the cellular amount of endogenous miRNA by introducing duplexes of miRNA/antagomir leads to detectable degradation products.
true
true
true
true
true
738
2
DISCUSSION
1
12
[ "B12", "B7", "B8", "B7", "B13", "B14", "B13" ]
17,439,965
pmid-16690972|pmid-16258535|pmid-16459310|pmid-16258535|pmid-16271385|pmid-16271386|pmid-16271385
In this study, we used this approach to ask whether antagomir-mediated silencing of miRNA involves a RNA-induced silencing complex (RISC)-dependent cleavage mechanism.
[ "12", "7", "8", "7", "13", "14", "13" ]
167
4,330
0
false
In this study, we used this approach to ask whether antagomir-mediated silencing of miRNA involves a RNA-induced silencing complex (RISC)-dependent cleavage mechanism.
[]
In this study, we used this approach to ask whether antagomir-mediated silencing of miRNA involves a RNA-induced silencing complex (RISC)-dependent cleavage mechanism.
true
true
true
true
true
738
2
DISCUSSION
1
12
[ "B12", "B7", "B8", "B7", "B13", "B14", "B13" ]
17,439,965
pmid-16690972|pmid-16258535|pmid-16459310|pmid-16258535|pmid-16271385|pmid-16271386|pmid-16271385
In the RNAi pathway, the siRNA duplex of passenger strand and guide strand is integrated into the RISC complex and the argonaute-2 (Ago2) protein subsequently cleaves the passenger strand across from the guide strand's phosphate bond between position 10 and 11 (13,14).
[ "12", "7", "8", "7", "13", "14", "13" ]
269
4,331
0
false
In the RNAi pathway, the siRNA duplex of passenger strand and guide strand is integrated into the RISC complex and the argonaute-2 (Ago2) protein subsequently cleaves the passenger strand across from the guide strand's phosphate bond between position 10 and 11.
[ "13,14" ]
In the RNAi pathway, the siRNA duplex of passenger strand and guide strand is integrated into the RISC complex and the argonaute-2 protein subsequently cleaves the passenger strand across from the guide strand's phosphate bond between position 10 and 11.
true
true
true
true
true
738
2
DISCUSSION
1
13
[ "B12", "B7", "B8", "B7", "B13", "B14", "B13" ]
17,439,965
pmid-16690972|pmid-16258535|pmid-16459310|pmid-16258535|pmid-16271385|pmid-16271386|pmid-16271385
This cleavage was inhibited by a single 2′-O-methylation of the passenger strand corresponding to nucleotide 11 of the guide strand (13).
[ "12", "7", "8", "7", "13", "14", "13" ]
137
4,332
1
false
This cleavage was inhibited by a single 2′-O-methylation of the passenger strand corresponding to nucleotide 11 of the guide strand.
[ "13" ]
This cleavage was inhibited by a single 2′-O-methylation of the passenger strand corresponding to nucleotide 11 of the guide strand.
true
true
true
true
true
738
2
DISCUSSION
1
12
[ "B12", "B7", "B8", "B7", "B13", "B14", "B13" ]
17,439,965
pmid-16690972|pmid-16258535|pmid-16459310|pmid-16258535|pmid-16271385|pmid-16271386|pmid-16271385
Hypothetically, antagomirs could cleave miRNAs within RISC with the antagomir acting as the guide strand.
[ "12", "7", "8", "7", "13", "14", "13" ]
105
4,333
0
false
Hypothetically, antagomirs could cleave miRNAs within RISC with the antagomir acting as the guide strand.
[]
Hypothetically, antagomirs could cleave miRNAs within RISC with the antagomir acting as the guide strand.
true
true
true
true
true
738
2
DISCUSSION
1
12
[ "B12", "B7", "B8", "B7", "B13", "B14", "B13" ]
17,439,965
pmid-16690972|pmid-16258535|pmid-16459310|pmid-16258535|pmid-16271385|pmid-16271386|pmid-16271385
To test this, we injected miRNA/antagomir-duplexes into mice that harbored a 2′-O-methyl endonuclease protection of the microRNA corresponding to nucleotide 10 and 11 of the antagomir.
[ "12", "7", "8", "7", "13", "14", "13" ]
184
4,334
0
false
To test this, we injected miRNA/antagomir-duplexes into mice that harbored a 2′-O-methyl endonuclease protection of the microRNA corresponding to nucleotide 10 and 11 of the antagomir.
[]
To test this, we injected miRNA/antagomir-duplexes into mice that harbored a 2′-O-methyl endonuclease protection of the microRNA corresponding to nucleotide 10 and 11 of the antagomir.
true
true
true
true
true
738
2
DISCUSSION
1
12
[ "B12", "B7", "B8", "B7", "B13", "B14", "B13" ]
17,439,965
pmid-16690972|pmid-16258535|pmid-16459310|pmid-16258535|pmid-16271385|pmid-16271386|pmid-16271385
However, endonuclease protection between nucleotides 10 and 11 did not prevent the degradation of the miRNA as demonstrated by abundant miRNA fragments in northern analysis, nor did it prevent the upregulation of miR-122 targets.
[ "12", "7", "8", "7", "13", "14", "13" ]
229
4,335
0
false
However, endonuclease protection between nucleotides 10 and 11 did not prevent the degradation of the miRNA as demonstrated by abundant miRNA fragments in northern analysis, nor did it prevent the upregulation of miR-122 targets.
[]
However, endonuclease protection between nucleotides 10 and 11 did not prevent the degradation of the miRNA as demonstrated by abundant miRNA fragments in northern analysis, nor did it prevent the upregulation of miR-122 targets.
true
true
true
true
true
738
2
DISCUSSION
1
12
[ "B12", "B7", "B8", "B7", "B13", "B14", "B13" ]
17,439,965
pmid-16690972|pmid-16258535|pmid-16459310|pmid-16258535|pmid-16271385|pmid-16271386|pmid-16271385
Thus Ago2-mediated cleavage is unlikely to mediate this process.
[ "12", "7", "8", "7", "13", "14", "13" ]
64
4,336
0
false
Thus Ago2-mediated cleavage is unlikely to mediate this process.
[]
Thus Ago2-mediated cleavage is unlikely to mediate this process.
true
true
true
true
true
738
2
DISCUSSION
1
12
[ "B12", "B7", "B8", "B7", "B13", "B14", "B13" ]
17,439,965
pmid-16690972|pmid-16258535|pmid-16459310|pmid-16258535|pmid-16271385|pmid-16271386|pmid-16271385
Similar results were obtained when the miRNA was protected at the outside positions using phosphorothioates, indicating that the miRNA targeting does not dependent on exonuclease activity either.
[ "12", "7", "8", "7", "13", "14", "13" ]
195
4,337
0
false
Similar results were obtained when the miRNA was protected at the outside positions using phosphorothioates, indicating that the miRNA targeting does not dependent on exonuclease activity either.
[]
Similar results were obtained when the miRNA was protected at the outside positions using phosphorothioates, indicating that the miRNA targeting does not dependent on exonuclease activity either.
true
true
true
true
true
738
2
DISCUSSION
1
12
[ "B12", "B7", "B8", "B7", "B13", "B14", "B13" ]
17,439,965
pmid-16690972|pmid-16258535|pmid-16459310|pmid-16258535|pmid-16271385|pmid-16271386|pmid-16271385
However, the fact that miRNA/antagomir-duplexes regulate miRNA targets suggests antagomir recycling.
[ "12", "7", "8", "7", "13", "14", "13" ]
100
4,338
0
false
However, the fact that miRNA/antagomir-duplexes regulate miRNA targets suggests antagomir recycling.
[]
However, the fact that miRNA/antagomir-duplexes regulate miRNA targets suggests antagomir recycling.
true
true
true
true
true
738
2
DISCUSSION
1
12
[ "B12", "B7", "B8", "B7", "B13", "B14", "B13" ]
17,439,965
pmid-16690972|pmid-16258535|pmid-16459310|pmid-16258535|pmid-16271385|pmid-16271386|pmid-16271385
The appearance of miRNA fragments of decreased length suggests that degradation is involved in this recycling process.
[ "12", "7", "8", "7", "13", "14", "13" ]
118
4,339
0
false
The appearance of miRNA fragments of decreased length suggests that degradation is involved in this recycling process.
[]
The appearance of miRNA fragments of decreased length suggests that degradation is involved in this recycling process.
true
true
true
true
true
738
2
DISCUSSION
1
12
[ "B12", "B7", "B8", "B7", "B13", "B14", "B13" ]
17,439,965
pmid-16690972|pmid-16258535|pmid-16459310|pmid-16258535|pmid-16271385|pmid-16271386|pmid-16271385
Further elucidation of the mechanism of degradation will be important for optimizing miRNA silencing.
[ "12", "7", "8", "7", "13", "14", "13" ]
101
4,340
0
false
Further elucidation of the mechanism of degradation will be important for optimizing miRNA silencing.
[]
Further elucidation of the mechanism of degradation will be important for optimizing miRNA silencing.
true
true
true
true
true
738
3
DISCUSSION
1
15
[ "B15", "B16", "B17", "B7" ]
17,439,965
pmid-15000825|pmid-15659426|pmid-15538359|pmid-16258535
To address the subcellular compartment where interaction of miRNA and antagomir occurs we engineered flurophore-labeled antagomirs.
[ "15", "16", "17", "7" ]
131
4,341
0
false
To address the subcellular compartment where interaction of miRNA and antagomir occurs we engineered flurophore-labeled antagomirs.
[]
To address the subcellular compartment where interaction of miRNA and antagomir occurs we engineered flurophore-labeled antagomirs.
true
true
true
true
true
739
3
DISCUSSION
1
15
[ "B15", "B16", "B17", "B7" ]
17,439,965
pmid-15000825|pmid-15659426|pmid-15538359|pmid-16258535
Flurophore labeling of siRNA has previously been used to evaluate cellular uptake of siRNA (15,16).
[ "15", "16", "17", "7" ]
99
4,342
0
false
Flurophore labeling of siRNA has previously been used to evaluate cellular uptake of siRNA.
[ "15,16" ]
Flurophore labeling of siRNA has previously been used to evaluate cellular uptake of siRNA.
true
true
true
true
true
739
3
DISCUSSION
1
17
[ "B15", "B16", "B17", "B7" ]
17,439,965
pmid-15000825|pmid-15659426|pmid-15538359|pmid-16258535
Q570-labeled antagomirs were cleared from the plasma at a t1/2 of ∼30 min (data not shown), which is considerably faster than the plasma-clearance of cholesterol-conjugated siRNA of ∼90 min (17).
[ "15", "16", "17", "7" ]
195
4,343
1
false
Q570-labeled antagomirs were cleared from the plasma at a t1/2 of ∼30 min (data not shown), which is considerably faster than the plasma-clearance of cholesterol-conjugated siRNA of ∼90 min.
[ "17" ]
Q570-labeled antagomirs were cleared from the plasma at a t1/2 of ∼30 min (data not shown), which is considerably faster than the plasma-clearance of cholesterol-conjugated siRNA of ∼90 min.
true
true
true
true
true
739
3
DISCUSSION
1
15
[ "B15", "B16", "B17", "B7" ]
17,439,965
pmid-15000825|pmid-15659426|pmid-15538359|pmid-16258535
A striking overlap of the subcellular localization profiles of antagomirs and miRNAs by sucrose gradient ultracentrifugation analysis of liver homogenates indicates that they might share subcellular compartments.
[ "15", "16", "17", "7" ]
212
4,344
0
false
A striking overlap of the subcellular localization profiles of antagomirs and miRNAs by sucrose gradient ultracentrifugation analysis of liver homogenates indicates that they might share subcellular compartments.
[]
A striking overlap of the subcellular localization profiles of antagomirs and miRNAs by sucrose gradient ultracentrifugation analysis of liver homogenates indicates that they might share subcellular compartments.
true
true
true
true
true
739
3
DISCUSSION
1
15
[ "B15", "B16", "B17", "B7" ]
17,439,965
pmid-15000825|pmid-15659426|pmid-15538359|pmid-16258535
Antagomir localization within hepatocytes was strictly limited to the cytosol.
[ "15", "16", "17", "7" ]
78
4,345
0
false
Antagomir localization within hepatocytes was strictly limited to the cytosol.
[]
Antagomir localization within hepatocytes was strictly limited to the cytosol.
true
true
true
true
true
739
3
DISCUSSION
1
7
[ "B15", "B16", "B17", "B7" ]
17,439,965
pmid-15000825|pmid-15659426|pmid-15538359|pmid-16258535
This could explain why antagomirs did not influence steady-state levels of the nuclear precursors of miRNAs (7).
[ "15", "16", "17", "7" ]
112
4,346
1
false
This could explain why antagomirs did not influence steady-state levels of the nuclear precursors of miRNAs.
[ "7" ]
This could explain why antagomirs did not influence steady-state levels of the nuclear precursors of miRNAs.
true
true
true
true
true
739
3
DISCUSSION
1
15
[ "B15", "B16", "B17", "B7" ]
17,439,965
pmid-15000825|pmid-15659426|pmid-15538359|pmid-16258535
We asked whether antagomirs could localize to P-bodies, since this compartment has been linked to the miRNA pathway.
[ "15", "16", "17", "7" ]
116
4,347
0
false
We asked whether antagomirs could localize to P-bodies, since this compartment has been linked to the miRNA pathway.
[]
We asked whether antagomirs could localize to P-bodies, since this compartment has been linked to the miRNA pathway.
true
true
true
true
true
739
3
DISCUSSION
1
15
[ "B15", "B16", "B17", "B7" ]
17,439,965
pmid-15000825|pmid-15659426|pmid-15538359|pmid-16258535
P-bodies are enriched in Ago 2 as well as mRNA that is targeted by miRNAs.
[ "15", "16", "17", "7" ]
74
4,348
0
false
P-bodies are enriched in Ago 2 as well as mRNA that is targeted by miRNAs.
[]
P-bodies are enriched in Ago 2 as well as mRNA that is targeted by miRNAs.
true
true
true
true
true
739
3
DISCUSSION
1
15
[ "B15", "B16", "B17", "B7" ]
17,439,965
pmid-15000825|pmid-15659426|pmid-15538359|pmid-16258535
It is, however, still unknown to which degree endogenous miRNAs localize to P-bodies.
[ "15", "16", "17", "7" ]
85
4,349
0
false
It is, however, still unknown to which degree endogenous miRNAs localize to P-bodies.
[]
It is, however, still unknown to which degree endogenous miRNAs localize to P-bodies.
true
true
true
true
true
739
3
DISCUSSION
1
15
[ "B15", "B16", "B17", "B7" ]
17,439,965
pmid-15000825|pmid-15659426|pmid-15538359|pmid-16258535
In any case, we did not observe any co-localization of antagomirs and P-bodies and conclude that the interaction of antagomirs and miRNAs occurs upstream of this compartment.
[ "15", "16", "17", "7" ]
174
4,350
0
false
In any case, we did not observe any co-localization of antagomirs and P-bodies and conclude that the interaction of antagomirs and miRNAs occurs upstream of this compartment.
[]
In any case, we did not observe any co-localization of antagomirs and P-bodies and conclude that the interaction of antagomirs and miRNAs occurs upstream of this compartment.
true
true
true
true
true
739
4
DISCUSSION
1
12
[ "B12", "B18" ]
17,439,965
pmid-16690972|pmid-10604941
In this study, we also extended our previous analysis of the influence of different chemical modifications on antagomirs.
[ "12", "18" ]
121
4,351
0
false
In this study, we also extended our previous analysis of the influence of different chemical modifications on antagomirs.
[]
In this study, we also extended our previous analysis of the influence of different chemical modifications on antagomirs.
true
true
true
true
true
740
4
DISCUSSION
1
12
[ "B12", "B18" ]
17,439,965
pmid-16690972|pmid-10604941
Phosphorothioate modifications provide protection against RNase activity and their lipophilicity contributes to enhanced tissue uptake.
[ "12", "18" ]
135
4,352
0
false
Phosphorothioate modifications provide protection against RNase activity and their lipophilicity contributes to enhanced tissue uptake.
[]
Phosphorothioate modifications provide protection against RNase activity and their lipophilicity contributes to enhanced tissue uptake.
true
true
true
true
true
740
4
DISCUSSION
1
12
[ "B12", "B18" ]
17,439,965
pmid-16690972|pmid-10604941
On the other hand, phosphorothioates decrease the melting temperature of RNA duplexes (12) and have been shown to be general inhibitors of cellular RNAse activity (18).
[ "12", "18" ]
168
4,353
1
false
On the other hand, phosphorothioates decrease the melting temperature of RNA duplexes and have been shown to be general inhibitors of cellular RNAse activity.
[ "12", "18" ]
On the other hand, phosphorothioates decrease the melting temperature of RNA duplexes and have been shown to be general inhibitors of cellular RNAse activity.
true
true
true
true
true
740
4
DISCUSSION
1
12
[ "B12", "B18" ]
17,439,965
pmid-16690972|pmid-10604941
Indeed our results indicate a critical balance of the number of phosphorothioates within the antagomir chemistry.
[ "12", "18" ]
113
4,354
0
false
Indeed our results indicate a critical balance of the number of phosphorothioates within the antagomir chemistry.
[]
Indeed our results indicate a critical balance of the number of phosphorothioates within the antagomir chemistry.
true
true
true
true
true
740
4
DISCUSSION
1
12
[ "B12", "B18" ]
17,439,965
pmid-16690972|pmid-10604941
While a significant number of phosphorothioates increases efficiency, complete phosphorothioate modification decreased efficiency.
[ "12", "18" ]
130
4,355
0
false
While a significant number of phosphorothioates increases efficiency, complete phosphorothioate modification decreased efficiency.
[]
While a significant number of phosphorothioates increases efficiency, complete phosphorothioate modification decreased efficiency.
true
true
true
true
true
740
4
DISCUSSION
1
12
[ "B12", "B18" ]
17,439,965
pmid-16690972|pmid-10604941
Our data also demonstrate that antagomirs require >19-nt length for optimal function.
[ "12", "18" ]
85
4,356
0
false
Our data also demonstrate that antagomirs require >19-nt length for optimal function.
[]
Our data also demonstrate that antagomirs require >19-nt length for optimal function.
true
true
true
true
true
740
5
DISCUSSION
1
7
[ "B7" ]
17,439,965
pmid-16258535
Lastly, we demonstrate that antagomirs can efficiently decrease miR-16 levels in mouse brain when injected locally.
[ "7" ]
115
4,357
0
false
Lastly, we demonstrate that antagomirs can efficiently decrease miR-16 levels in mouse brain when injected locally.
[]
Lastly, we demonstrate that antagomirs can efficiently decrease miR-16 levels in mouse brain when injected locally.
true
true
true
true
true
741
5
DISCUSSION
1
7
[ "B7" ]
17,439,965
pmid-16258535
Systemic infusions of antagomir-16 do not change brain levels of miR-16, most likely because of an inability to cross the blood-brain barrier (7).
[ "7" ]
146
4,358
1
false
Systemic infusions of antagomir-16 do not change brain levels of miR-16, most likely because of an inability to cross the blood-brain barrier.
[ "7" ]
Systemic infusions of antagomir-16 do not change brain levels of miR-16, most likely because of an inability to cross the blood-brain barrier.
true
true
true
true
true
741
5
DISCUSSION
1
7
[ "B7" ]
17,439,965
pmid-16258535
Local injections of small amounts of antagomir-16 efficiently reduced expression of this miR-16 in the cortex.
[ "7" ]
110
4,359
0
false
Local injections of small amounts of antagomir-16 efficiently reduced expression of this miR-16 in the cortex.
[]
Local injections of small amounts of antagomir-16 efficiently reduced expression of this miR-16 in the cortex.
true
true
true
true
true
741
5
DISCUSSION
1
7
[ "B7" ]
17,439,965
pmid-16258535
This inhibition was specific since the expression of other miRNAs was not affected and no alteration in miR-16 levels were measured in the contralateral hemisphere that was injected with PBS.
[ "7" ]
191
4,360
0
false
This inhibition was specific since the expression of other miRNAs was not affected and no alteration in miR-16 levels were measured in the contralateral hemisphere that was injected with PBS.
[]
This inhibition was specific since the expression of other miRNAs was not affected and no alteration in miR-16 levels were measured in the contralateral hemisphere that was injected with PBS.
true
true
true
true
true
741
5
DISCUSSION
1
7
[ "B7" ]
17,439,965
pmid-16258535
These results suggest that miRNA-inhibitors could facilitate the elucidation of miRNA function in the CNS.
[ "7" ]
106
4,361
0
false
These results suggest that miRNA-inhibitors could facilitate the elucidation of miRNA function in the CNS.
[]
These results suggest that miRNA-inhibitors could facilitate the elucidation of miRNA function in the CNS.
true
true
true
true
true
741
6
DISCUSSION
1
6
[ "B6", "B12", "B7", "B8", "B12" ]
17,439,965
pmid-16736018|pmid-16690972|pmid-16258535|pmid-16459310|pmid-16690972
Different chemical modifications have been described to block miRNA function in vitro (6,12) or in vivo (7,8).
[ "6", "12", "7", "8", "12" ]
110
4,362
0
false
Different chemical modifications have been described to block miRNA function in vitro or in vivo.
[ "6,12", "7,8" ]
Different chemical modifications have been described to block miRNA function in vitro or in vivo.
true
true
true
true
true
742
6
DISCUSSION
1
12
[ "B6", "B12", "B7", "B8", "B12" ]
17,439,965
pmid-16736018|pmid-16690972|pmid-16258535|pmid-16459310|pmid-16690972
However, detailed characterizations of these inhibitors are either lacking or based on heterologous miRNA target reporter assays (12).
[ "6", "12", "7", "8", "12" ]
134
4,363
1
false
However, detailed characterizations of these inhibitors are either lacking or based on heterologous miRNA target reporter assays.
[ "12" ]
However, detailed characterizations of these inhibitors are either lacking or based on heterologous miRNA target reporter assays.
true
true
true
true
true
742
6
DISCUSSION
1
6
[ "B6", "B12", "B7", "B8", "B12" ]
17,439,965
pmid-16736018|pmid-16690972|pmid-16258535|pmid-16459310|pmid-16690972
In this study, we used the expression levels of endogenous miR-122 targets as a read-out.
[ "6", "12", "7", "8", "12" ]
89
4,364
0
false
In this study, we used the expression levels of endogenous miR-122 targets as a read-out.
[]
In this study, we used the expression levels of endogenous miR-122 targets as a read-out.
true
true
true
true
true
742
6
DISCUSSION
1
6
[ "B6", "B12", "B7", "B8", "B12" ]
17,439,965
pmid-16736018|pmid-16690972|pmid-16258535|pmid-16459310|pmid-16690972
We show that antagomirs can be used in a time- and dose-dependent fashion to study miRNA targets.
[ "6", "12", "7", "8", "12" ]
97
4,365
0
false
We show that antagomirs can be used in a time- and dose-dependent fashion to study miRNA targets.
[]
We show that antagomirs can be used in a time- and dose-dependent fashion to study miRNA targets.
true
true
true
true
true
742
6
DISCUSSION
1
6
[ "B6", "B12", "B7", "B8", "B12" ]
17,439,965
pmid-16736018|pmid-16690972|pmid-16258535|pmid-16459310|pmid-16690972
Furthermore, we characterized antagomirs with regard to specificity, functional minimal-length requirements and effectiveness in the CNS following direct application.
[ "6", "12", "7", "8", "12" ]
166
4,366
0
false
Furthermore, we characterized antagomirs with regard to specificity, functional minimal-length requirements and effectiveness in the CNS following direct application.
[]
Furthermore, we characterized antagomirs with regard to specificity, functional minimal-length requirements and effectiveness in the CNS following direct application.
true
true
true
true
true
742
6
DISCUSSION
1
6
[ "B6", "B12", "B7", "B8", "B12" ]
17,439,965
pmid-16736018|pmid-16690972|pmid-16258535|pmid-16459310|pmid-16690972
Our data support the conclusion that antagomirs will be powerful tools for further studies on miRNA function in mice and possibly non-rodent models and enhance the validation of miRNA inhibitors as potential therapeutics.
[ "6", "12", "7", "8", "12" ]
221
4,367
0
false
Our data support the conclusion that antagomirs will be powerful tools for further studies on miRNA function in mice and possibly non-rodent models and enhance the validation of miRNA inhibitors as potential therapeutics.
[]
Our data support the conclusion that antagomirs will be powerful tools for further studies on miRNA function in mice and possibly non-rodent models and enhance the validation of miRNA inhibitors as potential therapeutics.
true
true
true
true
true
742
0
INTRODUCTION
1
1–14
[ "B1 B2 B3 B4 B5 B6 B7 B8 B9 B10 B11 B12 B13 B14", "B6", "B3", "B10", "B11", "B15", "B16", "B4" ]
17,526,524
pmid-12691757|pmid-12773376|pmid-14583191|pmid-12596263|pmid-15581897|pmid-16292304|pmid-14517984|pmid-14517985|pmid-16021622|pmid-15731101|pmid-16322583|pmid-15531586|pmid-16537382|pmid-14967023|pmid-16292304|pmid-14583191|pmid-15731101|pmid-16322583|pmid-10972297|pmid-15713490|pmid-12596263
Knotted proteins have become more common in recent years (1–14) due to the enormously growing number of structures deposited in the Protein Data Bank (PDB).
[ "1–14", "6", "3", "10", "11", "15", "16", "4" ]
156
4,368
1
false
Knotted proteins have become more common in recent years due to the enormously growing number of structures deposited in the Protein Data Bank (PDB).
[ "1–14" ]
Knotted proteins have become more common in recent years due to the enormously growing number of structures deposited in the Protein Data Bank (PDB).
true
true
true
true
true
743
0
INTRODUCTION
1
1–14
[ "B1 B2 B3 B4 B5 B6 B7 B8 B9 B10 B11 B12 B13 B14", "B6", "B3", "B10", "B11", "B15", "B16", "B4" ]
17,526,524
pmid-12691757|pmid-12773376|pmid-14583191|pmid-12596263|pmid-15581897|pmid-16292304|pmid-14517984|pmid-14517985|pmid-16021622|pmid-15731101|pmid-16322583|pmid-15531586|pmid-16537382|pmid-14967023|pmid-16292304|pmid-14583191|pmid-15731101|pmid-16322583|pmid-10972297|pmid-15713490|pmid-12596263
The knots in proteins are more than just topological novelties.
[ "1–14", "6", "3", "10", "11", "15", "16", "4" ]
63
4,369
0
false
The knots in proteins are more than just topological novelties.
[]
The knots in proteins are more than just topological novelties.
true
true
true
true
true
743
0
INTRODUCTION
1
1–14
[ "B1 B2 B3 B4 B5 B6 B7 B8 B9 B10 B11 B12 B13 B14", "B6", "B3", "B10", "B11", "B15", "B16", "B4" ]
17,526,524
pmid-12691757|pmid-12773376|pmid-14583191|pmid-12596263|pmid-15581897|pmid-16292304|pmid-14517984|pmid-14517985|pmid-16021622|pmid-15731101|pmid-16322583|pmid-15531586|pmid-16537382|pmid-14967023|pmid-16292304|pmid-14583191|pmid-15731101|pmid-16322583|pmid-10972297|pmid-15713490|pmid-12596263
The knotted regions have been shown to be important in both ligand binding and enzyme activity.
[ "1–14", "6", "3", "10", "11", "15", "16", "4" ]
95
4,370
0
false
The knotted regions have been shown to be important in both ligand binding and enzyme activity.
[]
The knotted regions have been shown to be important in both ligand binding and enzyme activity.
true
true
true
true
true
743
0
INTRODUCTION
1
6
[ "B1 B2 B3 B4 B5 B6 B7 B8 B9 B10 B11 B12 B13 B14", "B6", "B3", "B10", "B11", "B15", "B16", "B4" ]
17,526,524
pmid-12691757|pmid-12773376|pmid-14583191|pmid-12596263|pmid-15581897|pmid-16292304|pmid-14517984|pmid-14517985|pmid-16021622|pmid-15731101|pmid-16322583|pmid-15531586|pmid-16537382|pmid-14967023|pmid-16292304|pmid-14583191|pmid-15731101|pmid-16322583|pmid-10972297|pmid-15713490|pmid-12596263
For example, the unique knot topology in bacterial phytochrome (6) is common to all red/far-red photochromic phytochrome and is important in stabilizing the chromophore-binding region.
[ "1–14", "6", "3", "10", "11", "15", "16", "4" ]
184
4,371
1
false
For example, the unique knot topology in bacterial phytochrome is common to all red/far-red photochromic phytochrome and is important in stabilizing the chromophore-binding region.
[ "6" ]
For example, the unique knot topology in bacterial phytochrome is common to all red/far-red photochromic phytochrome and is important in stabilizing the chromophore-binding region.
true
true
true
true
true
743
0
INTRODUCTION
1
3
[ "B1 B2 B3 B4 B5 B6 B7 B8 B9 B10 B11 B12 B13 B14", "B6", "B3", "B10", "B11", "B15", "B16", "B4" ]
17,526,524
pmid-12691757|pmid-12773376|pmid-14583191|pmid-12596263|pmid-15581897|pmid-16292304|pmid-14517984|pmid-14517985|pmid-16021622|pmid-15731101|pmid-16322583|pmid-15531586|pmid-16537382|pmid-14967023|pmid-16292304|pmid-14583191|pmid-15731101|pmid-16322583|pmid-10972297|pmid-15713490|pmid-12596263
The knot regions in TrmD tRNA methyltransferase (MTase) have been shown to be important for S-adenosyl-L-methionine (AdoMet) binding and catalytic activity (3).
[ "1–14", "6", "3", "10", "11", "15", "16", "4" ]
160
4,372
1
false
The knot regions in TrmD tRNA methyltransferase (MTase) have been shown to be important for S-adenosyl-L-methionine (AdoMet) binding and catalytic activity.
[ "3" ]
The knot regions in TrmD tRNA methyltransferase (MTase) have been shown to be important for S-adenosyl-L-methionine (AdoMet) binding and catalytic activity.
true
true
true
true
true
743
0
INTRODUCTION
1
10
[ "B1 B2 B3 B4 B5 B6 B7 B8 B9 B10 B11 B12 B13 B14", "B6", "B3", "B10", "B11", "B15", "B16", "B4" ]
17,526,524
pmid-12691757|pmid-12773376|pmid-14583191|pmid-12596263|pmid-15581897|pmid-16292304|pmid-14517984|pmid-14517985|pmid-16021622|pmid-15731101|pmid-16322583|pmid-15531586|pmid-16537382|pmid-14967023|pmid-16292304|pmid-14583191|pmid-15731101|pmid-16322583|pmid-10972297|pmid-15713490|pmid-12596263
The deep trefoil knot region in N-acetylornithine transcarbamylase forms part of the active site (10).
[ "1–14", "6", "3", "10", "11", "15", "16", "4" ]
102
4,373
1
false
The deep trefoil knot region in N-acetylornithine transcarbamylase forms part of the active site.
[ "10" ]
The deep trefoil knot region in N-acetylornithine transcarbamylase forms part of the active site.
true
true
true
true
true
743
0
INTRODUCTION
1
11
[ "B1 B2 B3 B4 B5 B6 B7 B8 B9 B10 B11 B12 B13 B14", "B6", "B3", "B10", "B11", "B15", "B16", "B4" ]
17,526,524
pmid-12691757|pmid-12773376|pmid-14583191|pmid-12596263|pmid-15581897|pmid-16292304|pmid-14517984|pmid-14517985|pmid-16021622|pmid-15731101|pmid-16322583|pmid-15531586|pmid-16537382|pmid-14967023|pmid-16292304|pmid-14583191|pmid-15731101|pmid-16322583|pmid-10972297|pmid-15713490|pmid-12596263
The figure-eight knot in the mainly α-helical domain of ketol–acid reductoisomerase (KARI) forms most of the keto–acid substrate-binding site (11).
[ "1–14", "6", "3", "10", "11", "15", "16", "4" ]
147
4,374
1
false
The figure-eight knot in the mainly α-helical domain of ketol–acid reductoisomerase (KARI) forms most of the keto–acid substrate-binding site.
[ "11" ]
The figure-eight knot in the mainly α-helical domain of ketol–acid reductoisomerase (KARI) forms most of the keto–acid substrate-binding site.
true
true
true
true
true
743
0
INTRODUCTION
1
15
[ "B1 B2 B3 B4 B5 B6 B7 B8 B9 B10 B11 B12 B13 B14", "B6", "B3", "B10", "B11", "B15", "B16", "B4" ]
17,526,524
pmid-12691757|pmid-12773376|pmid-14583191|pmid-12596263|pmid-15581897|pmid-16292304|pmid-14517984|pmid-14517985|pmid-16021622|pmid-15731101|pmid-16322583|pmid-15531586|pmid-16537382|pmid-14967023|pmid-16292304|pmid-14583191|pmid-15731101|pmid-16322583|pmid-10972297|pmid-15713490|pmid-12596263
In addition, knots in proteins present a challenge in the study of protein folding, for it is hard to image a peptide chain to thread through a hoop to form a knot in a reproducible way (15).
[ "1–14", "6", "3", "10", "11", "15", "16", "4" ]
191
4,375
1
false
In addition, knots in proteins present a challenge in the study of protein folding, for it is hard to image a peptide chain to thread through a hoop to form a knot in a reproducible way.
[ "15" ]
In addition, knots in proteins present a challenge in the study of protein folding, for it is hard to image a peptide chain to thread through a hoop to form a knot in a reproducible way.
true
true
true
true
true
743
0
INTRODUCTION
1
16
[ "B1 B2 B3 B4 B5 B6 B7 B8 B9 B10 B11 B12 B13 B14", "B6", "B3", "B10", "B11", "B15", "B16", "B4" ]
17,526,524
pmid-12691757|pmid-12773376|pmid-14583191|pmid-12596263|pmid-15581897|pmid-16292304|pmid-14517984|pmid-14517985|pmid-16021622|pmid-15731101|pmid-16322583|pmid-15531586|pmid-16537382|pmid-14967023|pmid-16292304|pmid-14583191|pmid-15731101|pmid-16322583|pmid-10972297|pmid-15713490|pmid-12596263
Interestingly, a recent study (16) showed that YibK (4), a SpoU MTase containing a deep trefoil knot, is able to fold efficiently and behaves remarkably similar to other proteins.
[ "1–14", "6", "3", "10", "11", "15", "16", "4" ]
179
4,376
1
false
Interestingly, a recent study showed that YibK, a SpoU MTase containing a deep trefoil knot, is able to fold efficiently and behaves remarkably similar to other proteins.
[ "16", "4" ]
Interestingly, a recent study showed that YibK, a SpoU MTase containing a deep trefoil knot, is able to fold efficiently and behaves remarkably similar to other proteins.
true
true
true
true
true
743
1
INTRODUCTION
1
17
[ "B17", "B18", "B17", "B19", "B15", "B19", "B6" ]
17,526,524
pmid-12798035|pmid-12389038|pmid-12798035|pmid-16710448|pmid-10972297|pmid-16710448|pmid-16292304
Though the identification of a general knot is a topologically difficult problem, it is relatively easy to identify knots in proteins.
[ "17", "18", "17", "19", "15", "19", "6" ]
134
4,377
0
false
Though the identification of a general knot is a topologically difficult problem, it is relatively easy to identify knots in proteins.
[]
Though the identification of a general knot is a topologically difficult problem, it is relatively easy to identify knots in proteins.
true
true
true
true
true
744
1
INTRODUCTION
1
17
[ "B17", "B18", "B17", "B19", "B15", "B19", "B6" ]
17,526,524
pmid-12798035|pmid-12389038|pmid-12798035|pmid-16710448|pmid-10972297|pmid-16710448|pmid-16292304
However, there were still many cases of misidentified knots in proteins (17,18) due to the lack of a convenient tool available to general biologists.
[ "17", "18", "17", "19", "15", "19", "6" ]
149
4,378
0
false
However, there were still many cases of misidentified knots in proteins due to the lack of a convenient tool available to general biologists.
[ "17,18" ]
However, there were still many cases of misidentified knots in proteins due to the lack of a convenient tool available to general biologists.
true
true
true
true
true
744
1
INTRODUCTION
1
17
[ "B17", "B18", "B17", "B19", "B15", "B19", "B6" ]
17,526,524
pmid-12798035|pmid-12389038|pmid-12798035|pmid-16710448|pmid-10972297|pmid-16710448|pmid-16292304
The causes of the misidentification of knots in proteins may be due to the presence of mobile loops, missing residues or just visual error in tracing out the entangled protein chains.
[ "17", "18", "17", "19", "15", "19", "6" ]
183
4,379
0
false
The causes of the misidentification of knots in proteins may be due to the presence of mobile loops, missing residues or just visual error in tracing out the entangled protein chains.
[]
The causes of the misidentification of knots in proteins may be due to the presence of mobile loops, missing residues or just visual error in tracing out the entangled protein chains.
true
true
true
true
true
744
1
INTRODUCTION
1
17
[ "B17", "B18", "B17", "B19", "B15", "B19", "B6" ]
17,526,524
pmid-12798035|pmid-12389038|pmid-12798035|pmid-16710448|pmid-10972297|pmid-16710448|pmid-16292304
For example, the SET domain was originally identified to have a knot, but later it was pointed out that part of the loop relevant to the formation of the knot is in fact connected through hydrogen bonds (17).
[ "17", "18", "17", "19", "15", "19", "6" ]
208
4,380
1
false
For example, the SET domain was originally identified to have a knot, but later it was pointed out that part of the loop relevant to the formation of the knot is in fact connected through hydrogen bonds.
[ "17" ]
For example, the SET domain was originally identified to have a knot, but later it was pointed out that part of the loop relevant to the formation of the knot is in fact connected through hydrogen bonds.
true
true
true
true
true
744
1
INTRODUCTION
1
17
[ "B17", "B18", "B17", "B19", "B15", "B19", "B6" ]
17,526,524
pmid-12798035|pmid-12389038|pmid-12798035|pmid-16710448|pmid-10972297|pmid-16710448|pmid-16292304
As a result, the knot in the SET domain turns out not to be an authentic one.
[ "17", "18", "17", "19", "15", "19", "6" ]
77
4,381
0
false
As a result, the knot in the SET domain turns out not to be an authentic one.
[]
As a result, the knot in the SET domain turns out not to be an authentic one.
true
true
true
true
true
744
1
INTRODUCTION
1
19
[ "B17", "B18", "B17", "B19", "B15", "B19", "B6" ]
17,526,524
pmid-12798035|pmid-12389038|pmid-12798035|pmid-16710448|pmid-10972297|pmid-16710448|pmid-16292304
Other examples of misidentified knots are the trefoil knot in clathrin D6 coat protein (19), the left-handed trefoil knot in ubiquitin hydrolase (15) and the figure-eight knot in histone K79 methyltransferase (19).
[ "17", "18", "17", "19", "15", "19", "6" ]
214
4,382
2
true
Other examples of misidentified knots are the trefoil knot in clathrin D6 coat protein, the left-handed trefoil knot in ubiquitin hydrolase and the figure-eight knot in histone K79 methyltransferase.
[ "19", "15", "19" ]
Other examples of misidentified knots are the trefoil knot in clathrin D6 coat protein, the left-handed trefoil knot in ubiquitin hydrolase and the figure-eight knot in histone K79 methyltransferase.
true
true
true
true
true
744
1
INTRODUCTION
1
17
[ "B17", "B18", "B17", "B19", "B15", "B19", "B6" ]
17,526,524
pmid-12798035|pmid-12389038|pmid-12798035|pmid-16710448|pmid-10972297|pmid-16710448|pmid-16292304
These knots are in fact caused by breaks in the chain and are therefore not authentic knots.
[ "17", "18", "17", "19", "15", "19", "6" ]
92
4,383
0
false
These knots are in fact caused by breaks in the chain and are therefore not authentic knots.
[]
These knots are in fact caused by breaks in the chain and are therefore not authentic knots.
true
true
true
true
true
744
1
INTRODUCTION
1
6
[ "B17", "B18", "B17", "B19", "B15", "B19", "B6" ]
17,526,524
pmid-12798035|pmid-12389038|pmid-12798035|pmid-16710448|pmid-10972297|pmid-16710448|pmid-16292304
A more recent example is the misidentified trefoil knot in the chromophore-binding domain of phytochrome (6), which in fact contains a figure-eight knot.
[ "17", "18", "17", "19", "15", "19", "6" ]
153
4,384
1
false
A more recent example is the misidentified trefoil knot in the chromophore-binding domain of phytochrome, which in fact contains a figure-eight knot.
[ "6" ]
A more recent example is the misidentified trefoil knot in the chromophore-binding domain of phytochrome, which in fact contains a figure-eight knot.
true
true
true
true
true
744
0
INTRODUCTION
1
1
[ "b1" ]
17,130,147
pmid-11753382
Alternative splicing (AS) is a phenomenon in which various combinations of exons are integrated into different types of transcripts.
[ "1" ]
132
4,385
0
false
Alternative splicing (AS) is a phenomenon in which various combinations of exons are integrated into different types of transcripts.
[]
Alternative splicing (AS) is a phenomenon in which various combinations of exons are integrated into different types of transcripts.
true
true
true
true
true
745
0
INTRODUCTION
1
1
[ "b1" ]
17,130,147
pmid-11753382
By utilizing AS, diverse transcripts can be produced.
[ "1" ]
53
4,386
0
false
By utilizing AS, diverse transcripts can be produced.
[]
By utilizing AS, diverse transcripts can be produced.
true
true
true
true
true
745
0
INTRODUCTION
1
1
[ "b1" ]
17,130,147
pmid-11753382
Although it might not be always true that all the variants are translated, this mechanism at least enables a single locus to encode functionally divergent proteins.
[ "1" ]
164
4,387
0
false
Although it might not be always true that all the variants are translated, this mechanism at least enables a single locus to encode functionally divergent proteins.
[]
Although it might not be always true that all the variants are translated, this mechanism at least enables a single locus to encode functionally divergent proteins.
true
true
true
true
true
745
0
INTRODUCTION
1
1
[ "b1" ]
17,130,147
pmid-11753382
Actual abundant cases have been reported for such diversification of the gene functions mediated by AS, in which the binding site of a growth factor receptor or an activation site of transcription factor are modified.
[ "1" ]
217
4,388
0
false
Actual abundant cases have been reported for such diversification of the gene functions mediated by AS, in which the binding site of a growth factor receptor or an activation site of transcription factor are modified.
[]
Actual abundant cases have been reported for such diversification of the gene functions mediated by AS, in which the binding site of a growth factor receptor or an activation site of transcription factor are modified.
true
true
true
true
true
745
0
INTRODUCTION
1
1
[ "b1" ]
17,130,147
pmid-11753382
Especially in mammals, use of AS is widespread
[ "1" ]
46
4,389
0
false
Especially in mammals, use of AS is widespread
[]
Especially in mammals, use of AS is widespread
true
true
false
true
false
745
0
INTRODUCTION
1
1
[ "b1" ]
17,130,147
pmid-11753382
[it is reported that 40–60% of entire human genes have AS variants (1)] and is supposed to provide a molecular basis for highly fabricated systems, such as immune systems and neural networks.
[ "1" ]
191
4,390
0
false
and is supposed to provide a molecular basis for highly fabricated systems, such as immune systems and neural networks.
[ "it is reported that 40–60% of entire human genes have AS variants (1)" ]
and is supposed to provide a molecular basis for highly fabricated systems, such as immune systems and neural networks.
false
true
true
true
false
745
1
INTRODUCTION
1
2
[ "b2", "b3", "b4" ]
17,130,147
pmid-16381912|pmid-12519958|pmid-16914452
Because of the growing interests in AS, a number of databases were launched, such as ASD [; (2)] and ASAP [; (3)].
[ "2", "3", "4" ]
114
4,391
0
false
Because of the growing interests in AS, a number of databases were launched, such as ASD and ASAP.
[ "; (2)", "; (3)" ]
Because of the growing interests in AS, a number of databases were launched, such as ASD and ASAP.
true
true
true
true
true
746
1
INTRODUCTION
1
2
[ "b2", "b3", "b4" ]
17,130,147
pmid-16381912|pmid-12519958|pmid-16914452
However, most of these preexisting AS databases are still incomplete in a sense that they are mainly based on the fragmented information of partially and imprecisely sequenced cDNAs (ESTs) or computationally divided information of the exons.
[ "2", "3", "4" ]
241
4,392
0
false
However, most of these preexisting AS databases are still incomplete in a sense that they are mainly based on the fragmented information of partially and imprecisely sequenced cDNAs (ESTs) or computationally divided information of the exons.
[]
However, most of these preexisting AS databases are still incomplete in a sense that they are mainly based on the fragmented information of partially and imprecisely sequenced cDNAs (ESTs) or computationally divided information of the exons.
true
true
true
true
true
746
1
INTRODUCTION
1
2
[ "b2", "b3", "b4" ]
17,130,147
pmid-16381912|pmid-12519958|pmid-16914452
In order to elucidate the functional relevance of the alternative variants to the protein functions, comprehensive information about the cDNA sequences is indispensable because sometimes protein motifs are embedded over a wide region of the protein sequences, and all of the combinations of the AS exons may not be allow...
[ "2", "3", "4" ]
323
4,393
0
false
In order to elucidate the functional relevance of the alternative variants to the protein functions, comprehensive information about the cDNA sequences is indispensable because sometimes protein motifs are embedded over a wide region of the protein sequences, and all of the combinations of the AS exons may not be allow...
[]
In order to elucidate the functional relevance of the alternative variants to the protein functions, comprehensive information about the cDNA sequences is indispensable because sometimes protein motifs are embedded over a wide region of the protein sequences, and all of the combinations of the AS exons may not be allow...
true
true
true
true
true
746
1
INTRODUCTION
1
2
[ "b2", "b3", "b4" ]
17,130,147
pmid-16381912|pmid-12519958|pmid-16914452
Besides, for certain types of subcellular targeting signals, such as signal peptides, the position within the protein sequence is critical.
[ "2", "3", "4" ]
139
4,394
0
false
Besides, for certain types of subcellular targeting signals, such as signal peptides, the position within the protein sequence is critical.
[]
Besides, for certain types of subcellular targeting signals, such as signal peptides, the position within the protein sequence is critical.
true
true
true
true
true
746
1
INTRODUCTION
1
4
[ "b2", "b3", "b4" ]
17,130,147
pmid-16381912|pmid-12519958|pmid-16914452
Also, very recent reports, including ours (4), have demonstrated that many loci are subjected to complex patterns of AS in which two distinct genes seemed to be bridged (in which a variant uses exons from two adjacent loci), nested (in which a variant is located inside long intron of another locus) or degenerated (in w...
[ "2", "3", "4" ]
387
4,395
1
false
Also, very recent reports, including ours, have demonstrated that many loci are subjected to complex patterns of AS in which two distinct genes seemed to be bridged (in which a variant uses exons from two adjacent loci), nested (in which a variant is located inside long intron of another locus) or degenerated (in which...
[ "4" ]
Also, very recent reports, including ours, have demonstrated that many loci are subjected to complex patterns of AS in which two distinct genes seemed to be bridged (in which a variant uses exons from two adjacent loci), nested (in which a variant is located inside long intron of another locus) or degenerated (in which...
true
true
true
true
true
746
1
INTRODUCTION
1
2
[ "b2", "b3", "b4" ]
17,130,147
pmid-16381912|pmid-12519958|pmid-16914452
Its another name is multiple CDS): in all three cases, completely unrelated proteins are encoded by a single locus.
[ "2", "3", "4" ]
115
4,396
0
false
Its another name is multiple CDS): in all three cases, completely unrelated proteins are encoded by a single locus.
[]
Its another name is multiple CDS): in all three cases, completely unrelated proteins are encoded by a single locus.
true
true
true
true
true
746
1
INTRODUCTION
1
2
[ "b2", "b3", "b4" ]
17,130,147
pmid-16381912|pmid-12519958|pmid-16914452
These cases might not be regarded as alterative splicing in a strict sense.
[ "2", "3", "4" ]
75
4,397
0
false
These cases might not be regarded as alterative splicing in a strict sense.
[]
These cases might not be regarded as alterative splicing in a strict sense.
true
true
true
true
true
746
1
INTRODUCTION
1
2
[ "b2", "b3", "b4" ]
17,130,147
pmid-16381912|pmid-12519958|pmid-16914452
However, when those cases are also considered as extreme cases of functional diversification of a single locus and are subjected to be functional annotations, it is impossible to precisely characterize the combination of the exon usages.
[ "2", "3", "4" ]
237
4,398
0
false
However, when those cases are also considered as extreme cases of functional diversification of a single locus and are subjected to be functional annotations, it is impossible to precisely characterize the combination of the exon usages.
[]
However, when those cases are also considered as extreme cases of functional diversification of a single locus and are subjected to be functional annotations, it is impossible to precisely characterize the combination of the exon usages.
true
true
true
true
true
746
2
INTRODUCTION
1
5
[ "b5", "b6", "b7", "b4", "b8" ]
17,130,147
pmid-15103394|pmid-15860772|pmid-9521921|pmid-16914452|pmid-15273986
Here, we introduce our new database of AS database, H-DBAS.
[ "5", "6", "7", "4", "8" ]
59
4,399
0
false
Here, we introduce our new database of AS database, H-DBAS.
[]
Here, we introduce our new database of AS database, H-DBAS.
true
true
true
true
true
747