Datasets:
vgainullin
/
xciting_data

Dataset card Data Studio Files
xet
 Community
1
paragraph_index
int64
sec
string
p_has_citation
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cites
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sentences
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int64
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__index_level_0__
int64
5
DISCUSSION
1
8
[ "B8", "B35", "B35", "B36" ]
19,465,384
pmid-2840206|pmid-15989962|pmid-15989962|pmid-11994740
One of the main arguments against considering long-range pre-RNA interactions is that they will not likely occur kinetically during transcription, which is believed to promote local RNA structure formation in the wake of the RNA polymerase (8).
[ "8", "35", "35", "36" ]
244
42,919
1
false
One of the main arguments against considering long-range pre-RNA interactions is that they will not likely occur kinetically during transcription, which is believed to promote local RNA structure formation in the wake of the RNA polymerase.
[ "8" ]
One of the main arguments against considering long-range pre-RNA interactions is that they will not likely occur kinetically during transcription, which is believed to promote local RNA structure formation in the wake of the RNA polymerase.
true
true
true
true
true
7,437
5
DISCUSSION
1
35
[ "B8", "B35", "B35", "B36" ]
19,465,384
pmid-2840206|pmid-15989962|pmid-15989962|pmid-11994740
However, a study in yeast analyzing the ability of a sequence to base-pair with and disrupt the formation of a ribozyme revealed that the competitor sequence was more effective when it was transcribed before the ribozyme rather than after it in vitro, whereas there was no positional effect in vivo (e.g., the competitor...
[ "8", "35", "35", "36" ]
434
42,920
1
false
However, a study in yeast analyzing the ability of a sequence to base-pair with and disrupt the formation of a ribozyme revealed that the competitor sequence was more effective when it was transcribed before the ribozyme rather than after it in vitro, whereas there was no positional effect in vivo (e.g., the competitor...
[ "35" ]
However, a study in yeast analyzing the ability of a sequence to base-pair with and disrupt the formation of a ribozyme revealed that the competitor sequence was more effective when it was transcribed before the ribozyme rather than after it in vitro, whereas there was no positional effect in vivo (e.g., the competitor...
true
true
true
true
true
7,437
5
DISCUSSION
1
8
[ "B8", "B35", "B35", "B36" ]
19,465,384
pmid-2840206|pmid-15989962|pmid-15989962|pmid-11994740
This suggests that the formation of RNA secondary structure is more dependent on other factors, such as transiently binding proteins, which could allow a ‘delayed folding’ of the RNA (35,36).
[ "8", "35", "35", "36" ]
191
42,921
0
false
This suggests that the formation of RNA secondary structure is more dependent on other factors, such as transiently binding proteins, which could allow a ‘delayed folding’ of the RNA.
[ "35,36" ]
This suggests that the formation of RNA secondary structure is more dependent on other factors, such as transiently binding proteins, which could allow a ‘delayed folding’ of the RNA.
true
true
true
true
true
7,437
5
DISCUSSION
1
8
[ "B8", "B35", "B35", "B36" ]
19,465,384
pmid-2840206|pmid-15989962|pmid-15989962|pmid-11994740
Since our set of stem structures are predicted to be thermodynamically highly stable, we propose that the kinetics of the stem formation is the main regulatory mechanism.
[ "8", "35", "35", "36" ]
170
42,922
0
false
Since our set of stem structures are predicted to be thermodynamically highly stable, we propose that the kinetics of the stem formation is the main regulatory mechanism.
[]
Since our set of stem structures are predicted to be thermodynamically highly stable, we propose that the kinetics of the stem formation is the main regulatory mechanism.
true
true
true
true
true
7,437
6
DISCUSSION
1
15
[ "B15", "B37" ]
19,465,384
pmid-16213213|pmid-16287842
What is the probable frequency of secondary structures that influence splicing?
[ "15", "37" ]
79
42,923
0
false
What is the probable frequency of secondary structures that influence splicing?
[]
What is the probable frequency of secondary structures that influence splicing?
true
true
true
true
true
7,438
6
DISCUSSION
1
15
[ "B15", "B37" ]
19,465,384
pmid-16213213|pmid-16287842
Our search conditions were deliberately overly restrictive, to generate a smaller data set with a high potential for being relevant for splicing modulation.
[ "15", "37" ]
156
42,924
0
false
Our search conditions were deliberately overly restrictive, to generate a smaller data set with a high potential for being relevant for splicing modulation.
[]
Our search conditions were deliberately overly restrictive, to generate a smaller data set with a high potential for being relevant for splicing modulation.
true
true
true
true
true
7,438
6
DISCUSSION
1
15
[ "B15", "B37" ]
19,465,384
pmid-16213213|pmid-16287842
In fact, we did not find the few RNA structures known to influence alternative splicing in Drosophila, such as those involved in Dscam splicing (15,37), because these did not meet our search criteria (such as distance to splice sites, or phylogenetic conservation).
[ "15", "37" ]
265
42,925
0
false
In fact, we did not find the few RNA structures known to influence alternative splicing in Drosophila, such as those involved in Dscam splicing, because these did not meet our search criteria (such as distance to splice sites, or phylogenetic conservation).
[ "15,37" ]
In fact, we did not find the few RNA structures known to influence alternative splicing in Drosophila, such as those involved in Dscam splicing, because these did not meet our search criteria (such as distance to splice sites, or phylogenetic conservation).
true
true
true
true
true
7,438
6
DISCUSSION
1
15
[ "B15", "B37" ]
19,465,384
pmid-16213213|pmid-16287842
Note that these structures can still be found by relaxing the search constraints, but with an unacceptable increase of the false discovery rate.
[ "15", "37" ]
144
42,926
0
false
Note that these structures can still be found by relaxing the search constraints, but with an unacceptable increase of the false discovery rate.
[]
Note that these structures can still be found by relaxing the search constraints, but with an unacceptable increase of the false discovery rate.
true
true
true
true
true
7,438
6
DISCUSSION
1
15
[ "B15", "B37" ]
19,465,384
pmid-16213213|pmid-16287842
Additionally, several of our restrictions do not reflect necessary conditions for secondary structures to influence splicing.
[ "15", "37" ]
125
42,927
0
false
Additionally, several of our restrictions do not reflect necessary conditions for secondary structures to influence splicing.
[]
Additionally, several of our restrictions do not reflect necessary conditions for secondary structures to influence splicing.
true
true
true
true
true
7,438
6
DISCUSSION
1
15
[ "B15", "B37" ]
19,465,384
pmid-16213213|pmid-16287842
For example, the extremely high phylogenetic conservation of secondary structures in our set is a strong indicator that these play an important role, for instance, in splicing regulation.
[ "15", "37" ]
187
42,928
0
false
For example, the extremely high phylogenetic conservation of secondary structures in our set is a strong indicator that these play an important role, for instance, in splicing regulation.
[]
For example, the extremely high phylogenetic conservation of secondary structures in our set is a strong indicator that these play an important role, for instance, in splicing regulation.
true
true
true
true
true
7,438
6
DISCUSSION
1
15
[ "B15", "B37" ]
19,465,384
pmid-16213213|pmid-16287842
However, structures that are not conserved could also be involved in splicing modulation and could be important for species-specific alternative splicing.
[ "15", "37" ]
154
42,929
0
false
However, structures that are not conserved could also be involved in splicing modulation and could be important for species-specific alternative splicing.
[]
However, structures that are not conserved could also be involved in splicing modulation and could be important for species-specific alternative splicing.
true
true
true
true
true
7,438
6
DISCUSSION
1
15
[ "B15", "B37" ]
19,465,384
pmid-16213213|pmid-16287842
Likewise, restricting the stem structures to introns allowed us to visualize the ‘islands’ of conservation of these sequences in the low-conservation intronic regions (as compared to the relatively high conservation of the exons).
[ "15", "37" ]
230
42,930
0
false
Likewise, restricting the stem structures to introns allowed us to visualize the ‘islands’ of conservation of these sequences in the low-conservation intronic regions (as compared to the relatively high conservation of the exons).
[]
Likewise, restricting the stem structures to introns allowed us to visualize the ‘islands’ of conservation of these sequences in the low-conservation intronic regions (as compared to the relatively high conservation of the exons).
true
true
true
true
true
7,438
6
DISCUSSION
1
15
[ "B15", "B37" ]
19,465,384
pmid-16213213|pmid-16287842
Nonetheless, stem structures that are partially or entirely present in exonic regions would also be able to efficiently modulate splicing.
[ "15", "37" ]
138
42,931
0
false
Nonetheless, stem structures that are partially or entirely present in exonic regions would also be able to efficiently modulate splicing.
[]
Nonetheless, stem structures that are partially or entirely present in exonic regions would also be able to efficiently modulate splicing.
true
true
true
true
true
7,438
7
DISCUSSION
0
null
null
19,465,384
null
Therefore, we propose that the modulation of alternative splicing by RNA stem structures in Drosophila is more common than it is currently believed.
null
148
42,932
0
false
null
null
Therefore, we propose that the modulation of alternative splicing by RNA stem structures in Drosophila is more common than it is currently believed.
true
true
true
true
true
7,439
7
DISCUSSION
0
null
null
19,465,384
null
We predict that this type of modulation plays an important role in alternative splicing in other eukaryotic species as well.
null
124
42,933
0
false
null
null
We predict that this type of modulation plays an important role in alternative splicing in other eukaryotic species as well.
true
true
true
true
true
7,439
0
DISCUSSION
1
1
[ "B1" ]
11,752,971
pmid-6604429
For a variety of reasons, including immobilization hypercalciuria, urinary stasis, infection, and the introduction of a Foley catheter, patients with spinal cord injury are predisposed to calculi (1).
[ "1" ]
200
42,934
1
false
For a variety of reasons, including immobilization hypercalciuria, urinary stasis, infection, and the introduction of a Foley catheter, patients with spinal cord injury are predisposed to calculi.
[ "1" ]
For a variety of reasons, including immobilization hypercalciuria, urinary stasis, infection, and the introduction of a Foley catheter, patients with spinal cord injury are predisposed to calculi.
true
true
true
true
true
7,440
1
DISCUSSION
1
2
[ "B2", "B3" ]
11,752,971
pmid-7411703|pmid-9439426
Calculus formation over a hair introduced into the bladder is a preventable complication (2).
[ "2", "3" ]
93
42,935
1
false
Calculus formation over a hair introduced into the bladder is a preventable complication.
[ "2" ]
Calculus formation over a hair introduced into the bladder is a preventable complication.
true
true
true
true
true
7,441
1
DISCUSSION
1
3
[ "B2", "B3" ]
11,752,971
pmid-7411703|pmid-9439426
Being a foreign material, hair in this location is an ideal site for crystalline precipitation, which may then be perpetuated by the reaction of urothelium with the extraneous material (3).
[ "2", "3" ]
189
42,936
1
false
Being a foreign material, hair in this location is an ideal site for crystalline precipitation, which may then be perpetuated by the reaction of urothelium with the extraneous material.
[ "3" ]
Being a foreign material, hair in this location is an ideal site for crystalline precipitation, which may then be perpetuated by the reaction of urothelium with the extraneous material.
true
true
true
true
true
7,441
2
DISCUSSION
1
4
[ "B4" ]
11,752,971
pmid-9267926
The absence of normal micturition in spinal cord injury patients exacerbates the problem because it prevents spontaneous passage of small stone fragments.
[ "4" ]
154
42,937
0
false
The absence of normal micturition in spinal cord injury patients exacerbates the problem because it prevents spontaneous passage of small stone fragments.
[]
The absence of normal micturition in spinal cord injury patients exacerbates the problem because it prevents spontaneous passage of small stone fragments.
true
true
true
true
true
7,442
2
DISCUSSION
1
4
[ "B4" ]
11,752,971
pmid-9267926
Some therefore undergo intermittent urethral catherization, and in some care centers it is routine practice to recommend periodic shaving of pubic hair in such patients (4).
[ "4" ]
173
42,938
1
false
Some therefore undergo intermittent urethral catherization, and in some care centers it is routine practice to recommend periodic shaving of pubic hair in such patients.
[ "4" ]
Some therefore undergo intermittent urethral catherization, and in some care centers it is routine practice to recommend periodic shaving of pubic hair in such patients.
true
true
true
true
true
7,442
3
DISCUSSION
1
1
[ "B1" ]
11,752,971
pmid-6604429
In 1983, Amendola et al.
[ "1" ]
24
42,939
0
false
In 1983, Amendola et al.
[]
In 1983, Amendola et al.
true
true
true
true
true
7,443
3
DISCUSSION
1
1
[ "B1" ]
11,752,971
pmid-6604429
reported that during a 12 - year period, plain radiographs of three of eight patients with bladder calculi formed over a hair nidus showed characteristic serpiginous, linear calculi (1).
[ "1" ]
186
42,940
1
false
reported that during a 12 - year period, plain radiographs of three of eight patients with bladder calculi formed over a hair nidus showed characteristic serpiginous, linear calculi.
[ "1" ]
reported that during a 12 - year period, plain radiographs of three of eight patients with bladder calculi formed over a hair nidus showed characteristic serpiginous, linear calculi.
false
true
true
true
false
7,443
3
DISCUSSION
1
1
[ "B1" ]
11,752,971
pmid-6604429
To the best of our knowledge, however, the IVU findings in patients with bladder calculi over a hair nidus have not been previously reported.
[ "1" ]
141
42,941
0
false
To the best of our knowledge, however, the IVU findings in patients with bladder calculi over a hair nidus have not been previously reported.
[]
To the best of our knowledge, however, the IVU findings in patients with bladder calculi over a hair nidus have not been previously reported.
true
true
true
true
true
7,443
4
DISCUSSION
0
null
null
11,752,971
null
In our case, IVU revealed serpiginous radiopacity within the filling defect.
null
76
42,942
0
false
null
null
In our case, IVU revealed serpiginous radiopacity within the filling defect.
true
true
true
true
true
7,444
4
DISCUSSION
0
null
null
11,752,971
null
Compared with the pathologic specimen, the serpiginous dense radiopacity seen at plain radiography and IVU revealed a calculus formed over a hair.
null
146
42,943
0
false
null
null
Compared with the pathologic specimen, the serpiginous dense radiopacity seen at plain radiography and IVU revealed a calculus formed over a hair.
true
true
true
true
true
7,444
5
DISCUSSION
0
null
null
11,752,971
null
When plain radiographs or IVU in patients with a neurogenic bladder show serpiginous radiopacity, the presence of bladder calculi formed over hair introduced into the bladder during catheterization may be suspected.
null
215
42,944
0
false
null
null
When plain radiographs or IVU in patients with a neurogenic bladder show serpiginous radiopacity, the presence of bladder calculi formed over hair introduced into the bladder during catheterization may be suspected.
true
true
true
true
true
7,445
5
DISCUSSION
0
null
null
11,752,971
null
An understanding of this etiology may help prevent bladder calculus.
null
68
42,945
0
false
null
null
An understanding of this etiology may help prevent bladder calculus.
true
true
true
true
true
7,445
0
DISCUSSION
0
null
null
19,651,810
null
Our goal is to understand the molecular basis that links insulin resistance to abnormal production of proinflammatory cytokine IL-1β in macrophages.
null
148
42,946
0
false
null
null
Our goal is to understand the molecular basis that links insulin resistance to abnormal production of proinflammatory cytokine IL-1β in macrophages.
true
true
true
true
true
7,446
0
DISCUSSION
0
null
null
19,651,810
null
We show that FoxO1 stimulated IL-1β production in activated macrophages.
null
72
42,947
0
false
null
null
We show that FoxO1 stimulated IL-1β production in activated macrophages.
true
true
true
true
true
7,446
0
DISCUSSION
0
null
null
19,651,810
null
This effect was inhibited by insulin, which is correlated with the ability of FoxO1 to undergo insulin-dependent phosphorylation and nuclear exclusion.
null
151
42,948
0
false
null
null
This effect was inhibited by insulin, which is correlated with the ability of FoxO1 to undergo insulin-dependent phosphorylation and nuclear exclusion.
true
true
true
true
true
7,446
0
DISCUSSION
0
null
null
19,651,810
null
FoxO1 was shown to bind to the IL-1β promoter and enhance IL-1β promoter activity.
null
82
42,949
0
false
null
null
FoxO1 was shown to bind to the IL-1β promoter and enhance IL-1β promoter activity.
true
true
true
true
true
7,446
0
DISCUSSION
0
null
null
19,651,810
null
In accordance with these observations, there is a highly conserved FoxO1 binding site within the IL-1β promoter of humans, rats, and mice.
null
138
42,950
0
false
null
null
In accordance with these observations, there is a highly conserved FoxO1 binding site within the IL-1β promoter of humans, rats, and mice.
true
true
true
true
true
7,446
0
DISCUSSION
0
null
null
19,651,810
null
Mutations of the FoxO1 consensus site abrogated FoxO1-mediated induction of IL-1β promoter activity.
null
100
42,951
0
false
null
null
Mutations of the FoxO1 consensus site abrogated FoxO1-mediated induction of IL-1β promoter activity.
true
true
true
true
true
7,446
0
DISCUSSION
0
null
null
19,651,810
null
In LPS- or palmitate-treated macrophages, FoxO1 expression along with its nuclear localization was increased, contributing to augmented FoxO1 activity and elevated IL-1β production.
null
181
42,952
0
false
null
null
In LPS- or palmitate-treated macrophages, FoxO1 expression along with its nuclear localization was increased, contributing to augmented FoxO1 activity and elevated IL-1β production.
true
true
true
true
true
7,446
0
DISCUSSION
0
null
null
19,651,810
null
LPS or palmitate treatment also impaired the ability of insulin to promote IRS2 and FoxO1 phosphorylation in cultured macrophages.
null
130
42,953
0
false
null
null
LPS or palmitate treatment also impaired the ability of insulin to promote IRS2 and FoxO1 phosphorylation in cultured macrophages.
true
true
true
true
true
7,446
0
DISCUSSION
0
null
null
19,651,810
null
These data characterize FoxO1 at the interface between abnormal production of proinflammatory cytokine IL-1β and the pathogenesis of insulin resistance in macrophages.
null
167
42,954
0
false
null
null
These data characterize FoxO1 at the interface between abnormal production of proinflammatory cytokine IL-1β and the pathogenesis of insulin resistance in macrophages.
true
true
true
true
true
7,446
1
DISCUSSION
1
11
[ "B11", "B38", "B38", "B39", "B40", "B41", "B25", "B26", "B27", "B30", "B42", "B43", "B44", "B45", "B46" ]
19,651,810
pmid-16823477|pmid-11937262|pmid-11937262|pmid-12052830|pmid-17182583|pmid-18250410|pmid-15137936|pmid-15860415|pmid-18927507|pmid-18497885|pmid-14633847|pmid-15364812|pmid-11238525|pmid-15181049|pmid-16804037
Macrophage production of IL-1β is governed by NF-κB, a master regulator that integrates inflammatory signals to cytokine gene expression (11,38).
[ "11", "38", "38", "39", null, "41", "25", null, "27", "30", "42", "43", "44", null, "46" ]
145
42,955
0
false
Macrophage production of IL-1β is governed by NF-κB, a master regulator that integrates inflammatory signals to cytokine gene expression.
[ "11,38" ]
Macrophage production of IL-1β is governed by NF-κB, a master regulator that integrates inflammatory signals to cytokine gene expression.
true
true
true
true
true
7,447
1
DISCUSSION
1
11
[ "B11", "B38", "B38", "B39", "B40", "B41", "B25", "B26", "B27", "B30", "B42", "B43", "B44", "B45", "B46" ]
19,651,810
pmid-16823477|pmid-11937262|pmid-11937262|pmid-12052830|pmid-17182583|pmid-18250410|pmid-15137936|pmid-15860415|pmid-18927507|pmid-18497885|pmid-14633847|pmid-15364812|pmid-11238525|pmid-15181049|pmid-16804037
In unstimulated cells, NF-κB is bound by IκB and is sequestered in the cytoplasm.
[ "11", "38", "38", "39", null, "41", "25", null, "27", "30", "42", "43", "44", null, "46" ]
81
42,956
0
false
In unstimulated cells, NF-κB is bound by IκB and is sequestered in the cytoplasm.
[]
In unstimulated cells, NF-κB is bound by IκB and is sequestered in the cytoplasm.
true
true
true
true
true
7,447
1
DISCUSSION
1
11
[ "B11", "B38", "B38", "B39", "B40", "B41", "B25", "B26", "B27", "B30", "B42", "B43", "B44", "B45", "B46" ]
19,651,810
pmid-16823477|pmid-11937262|pmid-11937262|pmid-12052830|pmid-17182583|pmid-18250410|pmid-15137936|pmid-15860415|pmid-18927507|pmid-18497885|pmid-14633847|pmid-15364812|pmid-11238525|pmid-15181049|pmid-16804037
In the presence of inflammatory stimuli, IκB is phosphorylated by IκB kinase and is destined for proteasome-mediated degradation.
[ "11", "38", "38", "39", null, "41", "25", null, "27", "30", "42", "43", "44", null, "46" ]
129
42,957
0
false
In the presence of inflammatory stimuli, IκB is phosphorylated by IκB kinase and is destined for proteasome-mediated degradation.
[]
In the presence of inflammatory stimuli, IκB is phosphorylated by IκB kinase and is destined for proteasome-mediated degradation.
true
true
true
true
true
7,447
1
DISCUSSION
1
38
[ "B11", "B38", "B38", "B39", "B40", "B41", "B25", "B26", "B27", "B30", "B42", "B43", "B44", "B45", "B46" ]
19,651,810
pmid-16823477|pmid-11937262|pmid-11937262|pmid-12052830|pmid-17182583|pmid-18250410|pmid-15137936|pmid-15860415|pmid-18927507|pmid-18497885|pmid-14633847|pmid-15364812|pmid-11238525|pmid-15181049|pmid-16804037
As a result, NF-κB is dissociated from IκB and is translocated to the nucleus for promoting target gene expression (38).
[ "11", "38", "38", "39", null, "41", "25", null, "27", "30", "42", "43", "44", null, "46" ]
120
42,958
1
false
As a result, NF-κB is dissociated from IκB and is translocated to the nucleus for promoting target gene expression.
[ "38" ]
As a result, NF-κB is dissociated from IκB and is translocated to the nucleus for promoting target gene expression.
true
true
true
true
true
7,447
1
DISCUSSION
1
11
[ "B11", "B38", "B38", "B39", "B40", "B41", "B25", "B26", "B27", "B30", "B42", "B43", "B44", "B45", "B46" ]
19,651,810
pmid-16823477|pmid-11937262|pmid-11937262|pmid-12052830|pmid-17182583|pmid-18250410|pmid-15137936|pmid-15860415|pmid-18927507|pmid-18497885|pmid-14633847|pmid-15364812|pmid-11238525|pmid-15181049|pmid-16804037
Consistent with this notion is the conservation of a consensus NF-κB target site within the IL-1β promoter among different species (supplemental Fig.
[ "11", "38", "38", "39", null, "41", "25", null, "27", "30", "42", "43", "44", null, "46" ]
149
42,959
0
false
Consistent with this notion is the conservation of a consensus NF-κB target site within the IL-1β promoter among different species (supplemental Fig.
[]
Consistent with this notion is the conservation of a consensus NF-κB target site within the IL-1β promoter among different species (supplemental Fig.
true
true
true
true
true
7,447
1
DISCUSSION
1
11
[ "B11", "B38", "B38", "B39", "B40", "B41", "B25", "B26", "B27", "B30", "B42", "B43", "B44", "B45", "B46" ]
19,651,810
pmid-16823477|pmid-11937262|pmid-11937262|pmid-12052830|pmid-17182583|pmid-18250410|pmid-15137936|pmid-15860415|pmid-18927507|pmid-18497885|pmid-14633847|pmid-15364812|pmid-11238525|pmid-15181049|pmid-16804037
However, this mechanism falls short of explaining why insulin resistance provokes the induction of IL-1β production in activated macrophages.
[ "11", "38", "38", "39", null, "41", "25", null, "27", "30", "42", "43", "44", null, "46" ]
141
42,960
0
false
However, this mechanism falls short of explaining why insulin resistance provokes the induction of IL-1β production in activated macrophages.
[]
However, this mechanism falls short of explaining why insulin resistance provokes the induction of IL-1β production in activated macrophages.
true
true
true
true
true
7,447
1
DISCUSSION
1
11
[ "B11", "B38", "B38", "B39", "B40", "B41", "B25", "B26", "B27", "B30", "B42", "B43", "B44", "B45", "B46" ]
19,651,810
pmid-16823477|pmid-11937262|pmid-11937262|pmid-12052830|pmid-17182583|pmid-18250410|pmid-15137936|pmid-15860415|pmid-18927507|pmid-18497885|pmid-14633847|pmid-15364812|pmid-11238525|pmid-15181049|pmid-16804037
To address this fundamental issue, several independent studies show that activation of the PI3 kinase-Akt pathway is effective in limiting LPS-stimulated inflammatory cytokine production with uncharacterized mechanisms (39–41).
[ "11", "38", "38", "39", null, "41", "25", null, "27", "30", "42", "43", "44", null, "46" ]
227
42,961
0
false
To address this fundamental issue, several independent studies show that activation of the PI3 kinase-Akt pathway is effective in limiting LPS-stimulated inflammatory cytokine production with uncharacterized mechanisms.
[ "39–41" ]
To address this fundamental issue, several independent studies show that activation of the PI3 kinase-Akt pathway is effective in limiting LPS-stimulated inflammatory cytokine production with uncharacterized mechanisms.
true
true
true
true
true
7,447
1
DISCUSSION
1
11
[ "B11", "B38", "B38", "B39", "B40", "B41", "B25", "B26", "B27", "B30", "B42", "B43", "B44", "B45", "B46" ]
19,651,810
pmid-16823477|pmid-11937262|pmid-11937262|pmid-12052830|pmid-17182583|pmid-18250410|pmid-15137936|pmid-15860415|pmid-18927507|pmid-18497885|pmid-14633847|pmid-15364812|pmid-11238525|pmid-15181049|pmid-16804037
Here we show that macrophage IL-1β expression is regulated by FoxO1, a key nuclear transcriptional factor that mediates the inhibitory effect of insulin on target gene expression.
[ "11", "38", "38", "39", null, "41", "25", null, "27", "30", "42", "43", "44", null, "46" ]
179
42,962
0
false
Here we show that macrophage IL-1β expression is regulated by FoxO1, a key nuclear transcriptional factor that mediates the inhibitory effect of insulin on target gene expression.
[]
Here we show that macrophage IL-1β expression is regulated by FoxO1, a key nuclear transcriptional factor that mediates the inhibitory effect of insulin on target gene expression.
true
true
true
true
true
7,447
1
DISCUSSION
1
11
[ "B11", "B38", "B38", "B39", "B40", "B41", "B25", "B26", "B27", "B30", "B42", "B43", "B44", "B45", "B46" ]
19,651,810
pmid-16823477|pmid-11937262|pmid-11937262|pmid-12052830|pmid-17182583|pmid-18250410|pmid-15137936|pmid-15860415|pmid-18927507|pmid-18497885|pmid-14633847|pmid-15364812|pmid-11238525|pmid-15181049|pmid-16804037
In the absence of insulin, FoxO1 acts in the nucleus as an enhancer for promoting target gene expression, whereas in the presence of insulin, FoxO1 is phosphorylated by Akt/PKB, resulting in its nuclear exclusion and contributing to the inhibition of target gene expression.
[ "11", "38", "38", "39", null, "41", "25", null, "27", "30", "42", "43", "44", null, "46" ]
274
42,963
0
false
In the absence of insulin, FoxO1 acts in the nucleus as an enhancer for promoting target gene expression, whereas in the presence of insulin, FoxO1 is phosphorylated by Akt/PKB, resulting in its nuclear exclusion and contributing to the inhibition of target gene expression.
[]
In the absence of insulin, FoxO1 acts in the nucleus as an enhancer for promoting target gene expression, whereas in the presence of insulin, FoxO1 is phosphorylated by Akt/PKB, resulting in its nuclear exclusion and contributing to the inhibition of target gene expression.
true
true
true
true
true
7,447
1
DISCUSSION
1
11
[ "B11", "B38", "B38", "B39", "B40", "B41", "B25", "B26", "B27", "B30", "B42", "B43", "B44", "B45", "B46" ]
19,651,810
pmid-16823477|pmid-11937262|pmid-11937262|pmid-12052830|pmid-17182583|pmid-18250410|pmid-15137936|pmid-15860415|pmid-18927507|pmid-18497885|pmid-14633847|pmid-15364812|pmid-11238525|pmid-15181049|pmid-16804037
This phosphorylation-dependent protein trafficking mechanism is critical for insulin to regulate FoxO1 transcriptional activity in cells (25–27,30).
[ "11", "38", "38", "39", null, "41", "25", null, "27", "30", "42", "43", "44", null, "46" ]
148
42,964
0
false
This phosphorylation-dependent protein trafficking mechanism is critical for insulin to regulate FoxO1 transcriptional activity in cells.
[ "25–27,30" ]
This phosphorylation-dependent protein trafficking mechanism is critical for insulin to regulate FoxO1 transcriptional activity in cells.
true
true
true
true
true
7,447
1
DISCUSSION
1
11
[ "B11", "B38", "B38", "B39", "B40", "B41", "B25", "B26", "B27", "B30", "B42", "B43", "B44", "B45", "B46" ]
19,651,810
pmid-16823477|pmid-11937262|pmid-11937262|pmid-12052830|pmid-17182583|pmid-18250410|pmid-15137936|pmid-15860415|pmid-18927507|pmid-18497885|pmid-14633847|pmid-15364812|pmid-11238525|pmid-15181049|pmid-16804037
Our present studies shed light on the molecular basis that couples insulin resistance to the induction of proinflammatory cytokines.
[ "11", "38", "38", "39", null, "41", "25", null, "27", "30", "42", "43", "44", null, "46" ]
132
42,965
0
false
Our present studies shed light on the molecular basis that couples insulin resistance to the induction of proinflammatory cytokines.
[]
Our present studies shed light on the molecular basis that couples insulin resistance to the induction of proinflammatory cytokines.
true
true
true
true
true
7,447
1
DISCUSSION
1
11
[ "B11", "B38", "B38", "B39", "B40", "B41", "B25", "B26", "B27", "B30", "B42", "B43", "B44", "B45", "B46" ]
19,651,810
pmid-16823477|pmid-11937262|pmid-11937262|pmid-12052830|pmid-17182583|pmid-18250410|pmid-15137936|pmid-15860415|pmid-18927507|pmid-18497885|pmid-14633847|pmid-15364812|pmid-11238525|pmid-15181049|pmid-16804037
It follows that in insulin-resistant states, loss of insulin inhibition of FoxO1 activity consequently results in unrestrained IL-1β expression in activated macrophages (Fig.
[ "11", "38", "38", "39", null, "41", "25", null, "27", "30", "42", "43", "44", null, "46" ]
174
42,966
0
false
It follows that in insulin-resistant states, loss of insulin inhibition of FoxO1 activity consequently results in unrestrained IL-1β expression in activated macrophages (Fig.
[]
It follows that in insulin-resistant states, loss of insulin inhibition of FoxO1 activity consequently results in unrestrained IL-1β expression in activated macrophages (Fig.
true
true
true
true
true
7,447
1
DISCUSSION
1
11
[ "B11", "B38", "B38", "B39", "B40", "B41", "B25", "B26", "B27", "B30", "B42", "B43", "B44", "B45", "B46" ]
19,651,810
pmid-16823477|pmid-11937262|pmid-11937262|pmid-12052830|pmid-17182583|pmid-18250410|pmid-15137936|pmid-15860415|pmid-18927507|pmid-18497885|pmid-14633847|pmid-15364812|pmid-11238525|pmid-15181049|pmid-16804037
Consistent with this interpretation, we show that FoxO1 activity was significantly increased, correlating with impaired insulin action and elevated IL-1β production in LPS- and palmitate-stimulated macrophages.
[ "11", "38", "38", "39", null, "41", "25", null, "27", "30", "42", "43", "44", null, "46" ]
210
42,967
0
false
Consistent with this interpretation, we show that FoxO1 activity was significantly increased, correlating with impaired insulin action and elevated IL-1β production in LPS- and palmitate-stimulated macrophages.
[]
Consistent with this interpretation, we show that FoxO1 activity was significantly increased, correlating with impaired insulin action and elevated IL-1β production in LPS- and palmitate-stimulated macrophages.
true
true
true
true
true
7,447
1
DISCUSSION
1
11
[ "B11", "B38", "B38", "B39", "B40", "B41", "B25", "B26", "B27", "B30", "B42", "B43", "B44", "B45", "B46" ]
19,651,810
pmid-16823477|pmid-11937262|pmid-11937262|pmid-12052830|pmid-17182583|pmid-18250410|pmid-15137936|pmid-15860415|pmid-18927507|pmid-18497885|pmid-14633847|pmid-15364812|pmid-11238525|pmid-15181049|pmid-16804037
Furthermore, addition of insulin resulted in only partial suppression of IL-1β promoter activity, which is indicative of insulin resistance in LPS-stimulated RAW264.7 cells (Fig.
[ "11", "38", "38", "39", null, "41", "25", null, "27", "30", "42", "43", "44", null, "46" ]
178
42,968
0
false
Furthermore, addition of insulin resulted in only partial suppression of IL-1β promoter activity, which is indicative of insulin resistance in LPS-stimulated RAW264.7 cells (Fig.
[]
Furthermore, addition of insulin resulted in only partial suppression of IL-1β promoter activity, which is indicative of insulin resistance in LPS-stimulated RAW264.7 cells (Fig.
true
true
true
true
true
7,447
1
DISCUSSION
1
11
[ "B11", "B38", "B38", "B39", "B40", "B41", "B25", "B26", "B27", "B30", "B42", "B43", "B44", "B45", "B46" ]
19,651,810
pmid-16823477|pmid-11937262|pmid-11937262|pmid-12052830|pmid-17182583|pmid-18250410|pmid-15137936|pmid-15860415|pmid-18927507|pmid-18497885|pmid-14633847|pmid-15364812|pmid-11238525|pmid-15181049|pmid-16804037
Likewise, primary peritoneal macrophages retrieved from LPS-treated mice and insulin-resistant db/db mice were invariably associated with increased FoxO1 activity, accompanied by elevated IL-1β levels in plasma.
[ "11", "38", "38", "39", null, "41", "25", null, "27", "30", "42", "43", "44", null, "46" ]
211
42,969
0
false
Likewise, primary peritoneal macrophages retrieved from LPS-treated mice and insulin-resistant db/db mice were invariably associated with increased FoxO1 activity, accompanied by elevated IL-1β levels in plasma.
[]
Likewise, primary peritoneal macrophages retrieved from LPS-treated mice and insulin-resistant db/db mice were invariably associated with increased FoxO1 activity, accompanied by elevated IL-1β levels in plasma.
true
true
true
true
true
7,447
1
DISCUSSION
1
11
[ "B11", "B38", "B38", "B39", "B40", "B41", "B25", "B26", "B27", "B30", "B42", "B43", "B44", "B45", "B46" ]
19,651,810
pmid-16823477|pmid-11937262|pmid-11937262|pmid-12052830|pmid-17182583|pmid-18250410|pmid-15137936|pmid-15860415|pmid-18927507|pmid-18497885|pmid-14633847|pmid-15364812|pmid-11238525|pmid-15181049|pmid-16804037
Tripathy et al.
[ "11", "38", "38", "39", null, "41", "25", null, "27", "30", "42", "43", "44", null, "46" ]
15
42,970
0
false
Tripathy et al.
[]
Tripathy et al.
true
true
true
true
true
7,447
1
DISCUSSION
1
42
[ "B11", "B38", "B38", "B39", "B40", "B41", "B25", "B26", "B27", "B30", "B42", "B43", "B44", "B45", "B46" ]
19,651,810
pmid-16823477|pmid-11937262|pmid-11937262|pmid-12052830|pmid-17182583|pmid-18250410|pmid-15137936|pmid-15860415|pmid-18927507|pmid-18497885|pmid-14633847|pmid-15364812|pmid-11238525|pmid-15181049|pmid-16804037
(42) show that acute elevation of free fatty acid directly provokes inflammation, culminating in enhanced NF-κB activity and increased proinflammatory cytokine expression in mononuclear cells in healthy individuals.
[ "11", "38", "38", "39", null, "41", "25", null, "27", "30", "42", "43", "44", null, "46" ]
215
42,971
1
false
show that acute elevation of free fatty acid directly provokes inflammation, culminating in enhanced NF-κB activity and increased proinflammatory cytokine expression in mononuclear cells in healthy individuals.
[ "42" ]
show that acute elevation of free fatty acid directly provokes inflammation, culminating in enhanced NF-κB activity and increased proinflammatory cytokine expression in mononuclear cells in healthy individuals.
false
true
true
true
false
7,447
1
DISCUSSION
1
43
[ "B11", "B38", "B38", "B39", "B40", "B41", "B25", "B26", "B27", "B30", "B42", "B43", "B44", "B45", "B46" ]
19,651,810
pmid-16823477|pmid-11937262|pmid-11937262|pmid-12052830|pmid-17182583|pmid-18250410|pmid-15137936|pmid-15860415|pmid-18927507|pmid-18497885|pmid-14633847|pmid-15364812|pmid-11238525|pmid-15181049|pmid-16804037
These findings together with our data support the notion that circulating mononuclear cells in insulinresistant obese subjects are in a proinflammatory state (43).
[ "11", "38", "38", "39", null, "41", "25", null, "27", "30", "42", "43", "44", null, "46" ]
163
42,972
1
false
These findings together with our data support the notion that circulating mononuclear cells in insulinresistant obese subjects are in a proinflammatory state.
[ "43" ]
These findings together with our data support the notion that circulating mononuclear cells in insulinresistant obese subjects are in a proinflammatory state.
true
true
true
true
true
7,447
1
DISCUSSION
1
11
[ "B11", "B38", "B38", "B39", "B40", "B41", "B25", "B26", "B27", "B30", "B42", "B43", "B44", "B45", "B46" ]
19,651,810
pmid-16823477|pmid-11937262|pmid-11937262|pmid-12052830|pmid-17182583|pmid-18250410|pmid-15137936|pmid-15860415|pmid-18927507|pmid-18497885|pmid-14633847|pmid-15364812|pmid-11238525|pmid-15181049|pmid-16804037
Indeed, treatment with thiazolidenediones, a class of insulin sensitizers for improving peripheral insulin resistance, reduces mononuclear NF-κB activity and ameliorates inflammation in obese subjects (44–46).
[ "11", "38", "38", "39", null, "41", "25", null, "27", "30", "42", "43", "44", null, "46" ]
209
42,973
0
false
Indeed, treatment with thiazolidenediones, a class of insulin sensitizers for improving peripheral insulin resistance, reduces mononuclear NF-κB activity and ameliorates inflammation in obese subjects.
[ "44–46" ]
Indeed, treatment with thiazolidenediones, a class of insulin sensitizers for improving peripheral insulin resistance, reduces mononuclear NF-κB activity and ameliorates inflammation in obese subjects.
true
true
true
true
true
7,447
2
DISCUSSION
0
null
null
19,651,810
null
Convergence of the FoxO1 and NF-κB pathways in IL-1β gene expression.
null
69
42,974
0
false
null
null
Convergence of the FoxO1 and NF-κB pathways in IL-1β gene expression.
true
true
true
true
true
7,448
2
DISCUSSION
0
null
null
19,651,810
null
FoxO1 targets at the IRE DNA motif of the IL-1β promoter for trans-activation.
null
78
42,975
0
false
null
null
FoxO1 targets at the IRE DNA motif of the IL-1β promoter for trans-activation.
true
true
true
true
true
7,448
2
DISCUSSION
0
null
null
19,651,810
null
Under insulin-resistant or inflammatory conditions, FoxO1 activity is increased because of impaired abilities of insulin to phosphorylate and translocate FoxO1 from the nucleus to cytoplasm.
null
190
42,976
0
false
null
null
Under insulin-resistant or inflammatory conditions, FoxO1 activity is increased because of impaired abilities of insulin to phosphorylate and translocate FoxO1 from the nucleus to cytoplasm.
true
true
true
true
true
7,448
2
DISCUSSION
0
null
null
19,651,810
null
This effect along with the activation of the NF-κB pathway synergistically promotes macrophage production of proinflammatory cytokine IL-1β.
null
140
42,977
0
false
null
null
This effect along with the activation of the NF-κB pathway synergistically promotes macrophage production of proinflammatory cytokine IL-1β.
true
true
true
true
true
7,448
2
DISCUSSION
0
null
null
19,651,810
null
The evolutionally conserved IRE DNA motif and NF-κB binding site are indicated within the promoter-proximal region.
null
115
42,978
0
false
null
null
The evolutionally conserved IRE DNA motif and NF-κB binding site are indicated within the promoter-proximal region.
true
true
true
true
true
7,448
3
DISCUSSION
0
null
null
19,651,810
null
Although FoxO1 targeted IL-1β promoter for trans-activation, FoxO1 did not elicit a significant induction of IL-1β expression in cultured RAW264.7 cells in the absence of inflammatory stimuli.
null
192
42,979
0
false
null
null
Although FoxO1 targeted IL-1β promoter for trans-activation, FoxO1 did not elicit a significant induction of IL-1β expression in cultured RAW264.7 cells in the absence of inflammatory stimuli.
true
true
true
true
true
7,449
3
DISCUSSION
0
null
null
19,651,810
null
In response to inflammatory signals such as LPS or palmitate treatment, FoxO1 protein levels were markedly upregulated, contributing to enhanced FoxO1 activity.
null
160
42,980
0
false
null
null
In response to inflammatory signals such as LPS or palmitate treatment, FoxO1 protein levels were markedly upregulated, contributing to enhanced FoxO1 activity.
true
true
true
true
true
7,449
3
DISCUSSION
0
null
null
19,651,810
null
This effect was mirrored by the activation of NF-κB in LPS- or palmitate-activated macrophages.
null
95
42,981
0
false
null
null
This effect was mirrored by the activation of NF-κB in LPS- or palmitate-activated macrophages.
true
true
true
true
true
7,449
3
DISCUSSION
0
null
null
19,651,810
null
Interestingly, we show that FoxO1 in concert with activated NF-κB produced a synergistic effect on the induction of IL-1β overproduction in the presence of inflammation.
null
169
42,982
0
false
null
null
Interestingly, we show that FoxO1 in concert with activated NF-κB produced a synergistic effect on the induction of IL-1β overproduction in the presence of inflammation.
true
true
true
true
true
7,449
3
DISCUSSION
0
null
null
19,651,810
null
Together these results suggest that augmented FoxO1 activity serves to amplify the action of NF-κB in stimulating macrophage IL-1β production under inflammatory conditions (Fig.
null
177
42,983
0
false
null
null
Together these results suggest that augmented FoxO1 activity serves to amplify the action of NF-κB in stimulating macrophage IL-1β production under inflammatory conditions (Fig.
true
true
true
true
true
7,449
3
DISCUSSION
0
null
null
19,651,810
null
This interpretation is underpinned by three lines of evidence.
null
62
42,984
0
false
null
null
This interpretation is underpinned by three lines of evidence.
true
true
true
true
true
7,449
3
DISCUSSION
0
null
null
19,651,810
null
First, the productive interaction between FoxO1 and IL-1β promoter DNA was significantly enhanced in the presence of P50 production, correlating with the costimulatory effect of FoxO1 and P50 on IL-1β promoter activity in cultured macrophages.
null
243
42,985
0
false
null
null
First, the productive interaction between FoxO1 and IL-1β promoter DNA was significantly enhanced in the presence of P50 production, correlating with the costimulatory effect of FoxO1 and P50 on IL-1β promoter activity in cultured macrophages.
true
true
true
true
true
7,449
3
DISCUSSION
0
null
null
19,651,810
null
Second, siRNA-mediated knockdown of P50 significantly attenuated the ability of FoxO1 to stimulate IL-1β expression in LPS-stimulated macrophages.
null
146
42,986
0
false
null
null
Second, siRNA-mediated knockdown of P50 significantly attenuated the ability of FoxO1 to stimulate IL-1β expression in LPS-stimulated macrophages.
true
true
true
true
true
7,449
3
DISCUSSION
0
null
null
19,651,810
null
Third, the IL-1β promoter contains both FoxO1 and NF-κB target sites that are juxtaposed within the promoter-proximal region of the Il1b gene in mice, rats, and humans (supplemental Fig.
null
186
42,987
0
false
null
null
Third, the IL-1β promoter contains both FoxO1 and NF-κB target sites that are juxtaposed within the promoter-proximal region of the Il1b gene in mice, rats, and humans (supplemental Fig.
true
true
true
true
true
7,449
3
DISCUSSION
0
null
null
19,651,810
null
S2), implying an evolutionally conserved mechanism for FoxO1 signaling through the NF-κB pathway in regulating proinflammatory cytokine IL-1β production in macrophages in response to insulin resistance.
null
202
42,988
0
false
null
null
S2), implying an evolutionally conserved mechanism for FoxO1 signaling through the NF-κB pathway in regulating proinflammatory cytokine IL-1β production in macrophages in response to insulin resistance.
true
true
true
true
true
7,449
4
DISCUSSION
0
null
null
19,651,810
null
In conclusion, we characterized the Il1b gene as a FoxO1 target, demonstrating that macrophage production of IL-1β was stimulated by FoxO1 and inhibited by insulin.
null
164
42,989
0
false
null
null
In conclusion, we characterized the Il1b gene as a FoxO1 target, demonstrating that macrophage production of IL-1β was stimulated by FoxO1 and inhibited by insulin.
true
true
true
true
true
7,450
4
DISCUSSION
0
null
null
19,651,810
null
Under insulin-resistant or inflammatory conditions, FoxO1 activity was augmented, because of an impaired ability of insulin to phosphorylate FoxO1 and promote its nuclear exclusion.
null
181
42,990
0
false
null
null
Under insulin-resistant or inflammatory conditions, FoxO1 activity was augmented, because of an impaired ability of insulin to phosphorylate FoxO1 and promote its nuclear exclusion.
true
true
true
true
true
7,450
4
DISCUSSION
0
null
null
19,651,810
null
This effect along with active NF-κB contributed to macrophage overproduction of IL-1β.
null
86
42,991
0
false
null
null
This effect along with active NF-κB contributed to macrophage overproduction of IL-1β.
true
true
true
true
true
7,450
4
DISCUSSION
0
null
null
19,651,810
null
Although insulin resistance is associated with low-grade inflammation in obesity and type 2 diabetes, the underlying mechanism remains obscure.
null
143
42,992
0
false
null
null
Although insulin resistance is associated with low-grade inflammation in obesity and type 2 diabetes, the underlying mechanism remains obscure.
true
true
true
true
true
7,450
4
DISCUSSION
0
null
null
19,651,810
null
Our data suggest that FoxO1 signaling through NF-κB plays a significant role in coupling insulin resistance to proinflammatory cytokine IL-1β production in obesity and type 2 diabetes.
null
184
42,993
0
false
null
null
Our data suggest that FoxO1 signaling through NF-κB plays a significant role in coupling insulin resistance to proinflammatory cytokine IL-1β production in obesity and type 2 diabetes.
true
true
true
true
true
7,450
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5" ]
20,507,904
pmid-19483709|pmid-19302050|pmid-16485027|pmid-18267068|pmid-17047224|pmid-15128824|pmid-17707233|pmid-14527995
Cells recognize intruding microorganisms with the help of specific membrane-bound or intracellular receptors and respond with the synthesis of proinflammatory mediators such as tumor necrosis factor (TNF) and interleukin 1 (IL-1).
[ "1", "2", "3", "4", "5" ]
230
42,994
0
false
Cells recognize intruding microorganisms with the help of specific membrane-bound or intracellular receptors and respond with the synthesis of proinflammatory mediators such as tumor necrosis factor (TNF) and interleukin 1.
[ "IL-1" ]
Cells recognize intruding microorganisms with the help of specific membrane-bound or intracellular receptors and respond with the synthesis of proinflammatory mediators such as tumor necrosis factor (TNF) and interleukin 1.
true
true
true
true
true
7,451
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5" ]
20,507,904
pmid-19483709|pmid-19302050|pmid-16485027|pmid-18267068|pmid-17047224|pmid-15128824|pmid-17707233|pmid-14527995
Once secreted, these cytokines in turn trigger their cognate receptors and thus help to rapidly amplify the inflammatory response (1).
[ "1", "2", "3", "4", "5" ]
134
42,995
1
false
Once secreted, these cytokines in turn trigger their cognate receptors and thus help to rapidly amplify the inflammatory response.
[ "1" ]
Once secreted, these cytokines in turn trigger their cognate receptors and thus help to rapidly amplify the inflammatory response.
true
true
true
true
true
7,451
0
INTRODUCTION
1
2
[ "B1", "B2", "B3", "B4", "B5" ]
20,507,904
pmid-19483709|pmid-19302050|pmid-16485027|pmid-18267068|pmid-17047224|pmid-15128824|pmid-17707233|pmid-14527995
The NF-κB transcription factor is a key component for the production of many cytokines and also acts as a central mediator of cytokine-triggered effects (2).
[ "1", "2", "3", "4", "5" ]
157
42,996
1
false
The NF-κB transcription factor is a key component for the production of many cytokines and also acts as a central mediator of cytokine-triggered effects.
[ "2" ]
The NF-κB transcription factor is a key component for the production of many cytokines and also acts as a central mediator of cytokine-triggered effects.
true
true
true
true
true
7,451
0
INTRODUCTION
1
3
[ "B1", "B2", "B3", "B4", "B5" ]
20,507,904
pmid-19483709|pmid-19302050|pmid-16485027|pmid-18267068|pmid-17047224|pmid-15128824|pmid-17707233|pmid-14527995
The five members of the NF-κB family of transcription factors can form different dimer combinations, but a heterodimer between p50 and the strongly transactivating p65 subunit is the most frequently detected form (3).
[ "1", "2", "3", "4", "5" ]
217
42,997
1
false
The five members of the NF-κB family of transcription factors can form different dimer combinations, but a heterodimer between p50 and the strongly transactivating p65 subunit is the most frequently detected form.
[ "3" ]
The five members of the NF-κB family of transcription factors can form different dimer combinations, but a heterodimer between p50 and the strongly transactivating p65 subunit is the most frequently detected form.
true
true
true
true
true
7,451
0
INTRODUCTION
1
4
[ "B1", "B2", "B3", "B4", "B5" ]
20,507,904
pmid-19483709|pmid-19302050|pmid-16485027|pmid-18267068|pmid-17047224|pmid-15128824|pmid-17707233|pmid-14527995
All inducers of the canonical NF-κB activation pathway lead to the proteasomal elimination of inhibitory IκB proteins and thus release the DNA-binding subunits (4).
[ "1", "2", "3", "4", "5" ]
164
42,998
1
false
All inducers of the canonical NF-κB activation pathway lead to the proteasomal elimination of inhibitory IκB proteins and thus release the DNA-binding subunits.
[ "4" ]
All inducers of the canonical NF-κB activation pathway lead to the proteasomal elimination of inhibitory IκB proteins and thus release the DNA-binding subunits.
true
true
true
true
true
7,451
0
INTRODUCTION
1
5
[ "B1", "B2", "B3", "B4", "B5" ]
20,507,904
pmid-19483709|pmid-19302050|pmid-16485027|pmid-18267068|pmid-17047224|pmid-15128824|pmid-17707233|pmid-14527995
IκB degradation depends on its prior phosphorylation by the IκB kinase complex that consists of the IκB kinases (IKK) IKKα, IKKβ and the regulatory subunit IKKγ/NEMO (5).
[ "1", "2", "3", "4", "5" ]
170
42,999
1
false
IκB degradation depends on its prior phosphorylation by the IκB kinase complex that consists of the IκB kinases (IKK) IKKα, IKKβ and the regulatory subunit IKKγ/NEMO.
[ "5" ]
IκB degradation depends on its prior phosphorylation by the IκB kinase complex that consists of the IκB kinases (IKK) IKKα, IKKβ and the regulatory subunit IKKγ/NEMO.
true
true
true
true
true
7,451
1
INTRODUCTION
1
6
[ "B6" ]
20,507,904
pmid-19859064|pmid-18267068|pmid-16485027|pmid-16934762|pmid-18408078|pmid-18025230|pmid-18362169|pmid-19038492|pmid-18408078|pmid-15516339|pmid-20001970|pmid-19864627|pmid-18263619
After release from IκB and nuclear translocation, the dimeric DNA-binding subunits can bind to their cognate DNA sequences and trigger expression of hundreds of target genes (6).
[ "6" ]
178
43,000
1
false
After release from IκB and nuclear translocation, the dimeric DNA-binding subunits can bind to their cognate DNA sequences and trigger expression of hundreds of target genes.
[ "6" ]
After release from IκB and nuclear translocation, the dimeric DNA-binding subunits can bind to their cognate DNA sequences and trigger expression of hundreds of target genes.
true
true
true
true
true
7,452
1
INTRODUCTION
1
6
[ "B6" ]
20,507,904
pmid-19859064|pmid-18267068|pmid-16485027|pmid-16934762|pmid-18408078|pmid-18025230|pmid-18362169|pmid-19038492|pmid-18408078|pmid-15516339|pmid-20001970|pmid-19864627|pmid-18263619
Some NF-κB-dependent genes are important for the immune response, while others regulate cell survival and proliferation.
[ "6" ]
120
43,001
0
false
Some NF-κB-dependent genes are important for the immune response, while others regulate cell survival and proliferation.
[]
Some NF-κB-dependent genes are important for the immune response, while others regulate cell survival and proliferation.
true
true
true
true
true
7,452
2
INTRODUCTION
1
7
[ "B7", "B3", "B8", "B9", "B9", "B10", "B7" ]
20,507,904
pmid-18927578|pmid-16485027|pmid-14532125|pmid-17707233|pmid-17707233|pmid-14527995|pmid-18927578|pmid-19595715|pmid-16888014|pmid-15879144|pmid-17332413|NA|pmid-12702806|pmid-17081985|pmid-17545995|pmid-20188669
It is currently unclear how the free NF-κB dimers control key parameters of the target gene-specific response.
[ "7", "3", "8", "9", "9", "10", "7" ]
110
43,002
0
false
It is currently unclear how the free NF-κB dimers control key parameters of the target gene-specific response.
[]
It is currently unclear how the free NF-κB dimers control key parameters of the target gene-specific response.
true
true
true
true
true
7,453
2
INTRODUCTION
1
7
[ "B7", "B3", "B8", "B9", "B9", "B10", "B7" ]
20,507,904
pmid-18927578|pmid-16485027|pmid-14532125|pmid-17707233|pmid-17707233|pmid-14527995|pmid-18927578|pmid-19595715|pmid-16888014|pmid-15879144|pmid-17332413|NA|pmid-12702806|pmid-17081985|pmid-17545995|pmid-20188669
Each individual NF-κB activating stimulus leads to the induction of a specific overlapping and distinct subset of genes (7).
[ "7", "3", "8", "9", "9", "10", "7" ]
124
43,003
1
false
Each individual NF-κB activating stimulus leads to the induction of a specific overlapping and distinct subset of genes.
[ "7" ]
Each individual NF-κB activating stimulus leads to the induction of a specific overlapping and distinct subset of genes.
true
true
true
true
true
7,453
2
INTRODUCTION
1
3
[ "B7", "B3", "B8", "B9", "B9", "B10", "B7" ]
20,507,904
pmid-18927578|pmid-16485027|pmid-14532125|pmid-17707233|pmid-17707233|pmid-14527995|pmid-18927578|pmid-19595715|pmid-16888014|pmid-15879144|pmid-17332413|NA|pmid-12702806|pmid-17081985|pmid-17545995|pmid-20188669
All parameters (induction, kinetics, cofactor recruitment, amplitude and termination) are specifically tailored for each gene in order to suit the specific requirements of the inducing stimulus (3).
[ "7", "3", "8", "9", "9", "10", "7" ]
198
43,004
1
false
All parameters (induction, kinetics, cofactor recruitment, amplitude and termination) are specifically tailored for each gene in order to suit the specific requirements of the inducing stimulus.
[ "3" ]
All parameters (induction, kinetics, cofactor recruitment, amplitude and termination) are specifically tailored for each gene in order to suit the specific requirements of the inducing stimulus.
true
true
true
true
true
7,453
2
INTRODUCTION
1
8
[ "B7", "B3", "B8", "B9", "B9", "B10", "B7" ]
20,507,904
pmid-18927578|pmid-16485027|pmid-14532125|pmid-17707233|pmid-17707233|pmid-14527995|pmid-18927578|pmid-19595715|pmid-16888014|pmid-15879144|pmid-17332413|NA|pmid-12702806|pmid-17081985|pmid-17545995|pmid-20188669
The individual contribution of the respective NF-κB subunits to cytokine-induced gene expression patterns was revealed by gene array experiments (8).
[ "7", "3", "8", "9", "9", "10", "7" ]
149
43,005
1
false
The individual contribution of the respective NF-κB subunits to cytokine-induced gene expression patterns was revealed by gene array experiments.
[ "8" ]
The individual contribution of the respective NF-κB subunits to cytokine-induced gene expression patterns was revealed by gene array experiments.
true
true
true
true
true
7,453
2
INTRODUCTION
1
9
[ "B7", "B3", "B8", "B9", "B9", "B10", "B7" ]
20,507,904
pmid-18927578|pmid-16485027|pmid-14532125|pmid-17707233|pmid-17707233|pmid-14527995|pmid-18927578|pmid-19595715|pmid-16888014|pmid-15879144|pmid-17332413|NA|pmid-12702806|pmid-17081985|pmid-17545995|pmid-20188669
In addition, a systematic analysis of binding sites for the p65 subunit by chromatin immunoprecipitation (ChIP) assays revealed thousands of binding sites in the genome of monocytes (9).
[ "7", "3", "8", "9", "9", "10", "7" ]
186
43,006
1
false
In addition, a systematic analysis of binding sites for the p65 subunit by chromatin immunoprecipitation (ChIP) assays revealed thousands of binding sites in the genome of monocytes.
[ "9" ]
In addition, a systematic analysis of binding sites for the p65 subunit by chromatin immunoprecipitation (ChIP) assays revealed thousands of binding sites in the genome of monocytes.
true
true
true
true
true
7,453
2
INTRODUCTION
1
7
[ "B7", "B3", "B8", "B9", "B9", "B10", "B7" ]
20,507,904
pmid-18927578|pmid-16485027|pmid-14532125|pmid-17707233|pmid-17707233|pmid-14527995|pmid-18927578|pmid-19595715|pmid-16888014|pmid-15879144|pmid-17332413|NA|pmid-12702806|pmid-17081985|pmid-17545995|pmid-20188669
Although ‘-omics’ approaches identified many genes containing NF-κB binding sites in their regulatory regions (9,10), each inflammatory gene must be expressed and turned off with peculiar kinetics that fit to its specific function.
[ "7", "3", "8", "9", "9", "10", "7" ]
231
43,007
0
false
Although ‘-omics’ approaches identified many genes containing NF-κB binding sites in their regulatory regions, each inflammatory gene must be expressed and turned off with peculiar kinetics that fit to its specific function.
[ "9,10" ]
Although ‘-omics’ approaches identified many genes containing NF-κB binding sites in their regulatory regions, each inflammatory gene must be expressed and turned off with peculiar kinetics that fit to its specific function.
true
true
true
true
true
7,453
2
INTRODUCTION
1
7
[ "B7", "B3", "B8", "B9", "B9", "B10", "B7" ]
20,507,904
pmid-18927578|pmid-16485027|pmid-14532125|pmid-17707233|pmid-17707233|pmid-14527995|pmid-18927578|pmid-19595715|pmid-16888014|pmid-15879144|pmid-17332413|NA|pmid-12702806|pmid-17081985|pmid-17545995|pmid-20188669
The mechanisms that specify these transcriptional programs are still not well understood and include dimer exchange, differential chromatin organization and modification of the DNA-binding subunits by post-translational modifications (7).
[ "7", "3", "8", "9", "9", "10", "7" ]
238
43,008
1
false
The mechanisms that specify these transcriptional programs are still not well understood and include dimer exchange, differential chromatin organization and modification of the DNA-binding subunits by post-translational modifications.
[ "7" ]
The mechanisms that specify these transcriptional programs are still not well understood and include dimer exchange, differential chromatin organization and modification of the DNA-binding subunits by post-translational modifications.
true
true
true
true
true
7,453
3
INTRODUCTION
1
11–16
[ "B11 B12 B13 B14 B15 B16", "B17", "B18", "B19", "B20", "B21", "B22", "B19", "B23", "B24", "B25", "B26", "B27" ]
20,507,904
pmid-15226358|pmid-8710491|pmid-11533489|pmid-14690596|pmid-19864627|pmid-7925300|pmid-12419806|pmid-12456660|pmid-9660950|pmid-15457532|pmid-17431096|pmid-18408078|pmid-9660950|pmid-15489227|pmid-19339690|pmid-19270718|pmid-17468759|pmid-17928811|pmid-19595715|pmid-18927578|pmid-19648011|pmid-12789343|pmid-12789342|pm...
These modifications occur for all NF-κB DNA-binding subunits, but are most extensively characterized for p65 which can be regulated by ubiquitination, nitrosylation, acetylation, prolyl isomerization, monomethylation and phosphorylation (11–16).
[ "11–16", "17", "18", "19", "20", "21", "22", "19", "23", "24", "25", "26", "27" ]
245
43,009
1
false
These modifications occur for all NF-κB DNA-binding subunits, but are most extensively characterized for p65 which can be regulated by ubiquitination, nitrosylation, acetylation, prolyl isomerization, monomethylation and phosphorylation.
[ "11–16" ]
These modifications occur for all NF-κB DNA-binding subunits, but are most extensively characterized for p65 which can be regulated by ubiquitination, nitrosylation, acetylation, prolyl isomerization, monomethylation and phosphorylation.
true
true
true
true
true
7,454
3
INTRODUCTION
1
11–16
[ "B11 B12 B13 B14 B15 B16", "B17", "B18", "B19", "B20", "B21", "B22", "B19", "B23", "B24", "B25", "B26", "B27" ]
20,507,904
pmid-15226358|pmid-8710491|pmid-11533489|pmid-14690596|pmid-19864627|pmid-7925300|pmid-12419806|pmid-12456660|pmid-9660950|pmid-15457532|pmid-17431096|pmid-18408078|pmid-9660950|pmid-15489227|pmid-19339690|pmid-19270718|pmid-17468759|pmid-17928811|pmid-19595715|pmid-18927578|pmid-19648011|pmid-12789343|pmid-12789342|pm...
The functional consequences of these modifications are quite distinct, as exemplified by regulatory acetylation.
[ "11–16", "17", "18", "19", "20", "21", "22", "19", "23", "24", "25", "26", "27" ]
112
43,010
0
false
The functional consequences of these modifications are quite distinct, as exemplified by regulatory acetylation.
[]
The functional consequences of these modifications are quite distinct, as exemplified by regulatory acetylation.
true
true
true
true
true
7,454
3
INTRODUCTION
1
11–16
[ "B11 B12 B13 B14 B15 B16", "B17", "B18", "B19", "B20", "B21", "B22", "B19", "B23", "B24", "B25", "B26", "B27" ]
20,507,904
pmid-15226358|pmid-8710491|pmid-11533489|pmid-14690596|pmid-19864627|pmid-7925300|pmid-12419806|pmid-12456660|pmid-9660950|pmid-15457532|pmid-17431096|pmid-18408078|pmid-9660950|pmid-15489227|pmid-19339690|pmid-19270718|pmid-17468759|pmid-17928811|pmid-19595715|pmid-18927578|pmid-19648011|pmid-12789343|pmid-12789342|pm...
Acetylation of p65 at lysines 122 and 123 impairs p65 transactivation, while acetylation at lysines 218 and 221 inhibits IκBα binding and increases p65-dependent transcription (17,18).
[ "11–16", "17", "18", "19", "20", "21", "22", "19", "23", "24", "25", "26", "27" ]
184
43,011
0
false
Acetylation of p65 at lysines 122 and 123 impairs p65 transactivation, while acetylation at lysines 218 and 221 inhibits IκBα binding and increases p65-dependent transcription.
[ "17,18" ]
Acetylation of p65 at lysines 122 and 123 impairs p65 transactivation, while acetylation at lysines 218 and 221 inhibits IκBα binding and increases p65-dependent transcription.
true
true
true
true
true
7,454
3
INTRODUCTION
1
19
[ "B11 B12 B13 B14 B15 B16", "B17", "B18", "B19", "B20", "B21", "B22", "B19", "B23", "B24", "B25", "B26", "B27" ]
20,507,904
pmid-15226358|pmid-8710491|pmid-11533489|pmid-14690596|pmid-19864627|pmid-7925300|pmid-12419806|pmid-12456660|pmid-9660950|pmid-15457532|pmid-17431096|pmid-18408078|pmid-9660950|pmid-15489227|pmid-19339690|pmid-19270718|pmid-17468759|pmid-17928811|pmid-19595715|pmid-18927578|pmid-19648011|pmid-12789343|pmid-12789342|pm...
Phosphorylation of p65 is found at many sites, but the most extensively studied are serine 276 (19) as well as serine 468 and 536 which are both contained in the C-terminal transactivation domain (20,21).
[ "11–16", "17", "18", "19", "20", "21", "22", "19", "23", "24", "25", "26", "27" ]
204
43,012
1
false
Phosphorylation of p65 is found at many sites, but the most extensively studied are serine 276 as well as serine 468 and 536 which are both contained in the C-terminal transactivation domain.
[ "19", "20,21" ]
Phosphorylation of p65 is found at many sites, but the most extensively studied are serine 276 as well as serine 468 and 536 which are both contained in the C-terminal transactivation domain.
true
true
true
true
true
7,454
3
INTRODUCTION
1
11–16
[ "B11 B12 B13 B14 B15 B16", "B17", "B18", "B19", "B20", "B21", "B22", "B19", "B23", "B24", "B25", "B26", "B27" ]
20,507,904
pmid-15226358|pmid-8710491|pmid-11533489|pmid-14690596|pmid-19864627|pmid-7925300|pmid-12419806|pmid-12456660|pmid-9660950|pmid-15457532|pmid-17431096|pmid-18408078|pmid-9660950|pmid-15489227|pmid-19339690|pmid-19270718|pmid-17468759|pmid-17928811|pmid-19595715|pmid-18927578|pmid-19648011|pmid-12789343|pmid-12789342|pm...
The physiological relevance of p65 phosphorylation was revealed in a knock-in mouse model expressing a p65 protein with a serine 276 to alanine mutation.
[ "11–16", "17", "18", "19", "20", "21", "22", "19", "23", "24", "25", "26", "27" ]
153
43,013
0
false
The physiological relevance of p65 phosphorylation was revealed in a knock-in mouse model expressing a p65 protein with a serine 276 to alanine mutation.
[]
The physiological relevance of p65 phosphorylation was revealed in a knock-in mouse model expressing a p65 protein with a serine 276 to alanine mutation.
true
true
true
true
true
7,454
3
INTRODUCTION
1
22
[ "B11 B12 B13 B14 B15 B16", "B17", "B18", "B19", "B20", "B21", "B22", "B19", "B23", "B24", "B25", "B26", "B27" ]
20,507,904
pmid-15226358|pmid-8710491|pmid-11533489|pmid-14690596|pmid-19864627|pmid-7925300|pmid-12419806|pmid-12456660|pmid-9660950|pmid-15457532|pmid-17431096|pmid-18408078|pmid-9660950|pmid-15489227|pmid-19339690|pmid-19270718|pmid-17468759|pmid-17928811|pmid-19595715|pmid-18927578|pmid-19648011|pmid-12789343|pmid-12789342|pm...
These animals showed aberrant gene expression which caused embryonic lethality at different time points (22).
[ "11–16", "17", "18", "19", "20", "21", "22", "19", "23", "24", "25", "26", "27" ]
109
43,014
1
false
These animals showed aberrant gene expression which caused embryonic lethality at different time points.
[ "22" ]
These animals showed aberrant gene expression which caused embryonic lethality at different time points.
true
true
true
true
true
7,454
3
INTRODUCTION
1
11–16
[ "B11 B12 B13 B14 B15 B16", "B17", "B18", "B19", "B20", "B21", "B22", "B19", "B23", "B24", "B25", "B26", "B27" ]
20,507,904
pmid-15226358|pmid-8710491|pmid-11533489|pmid-14690596|pmid-19864627|pmid-7925300|pmid-12419806|pmid-12456660|pmid-9660950|pmid-15457532|pmid-17431096|pmid-18408078|pmid-9660950|pmid-15489227|pmid-19339690|pmid-19270718|pmid-17468759|pmid-17928811|pmid-19595715|pmid-18927578|pmid-19648011|pmid-12789343|pmid-12789342|pm...
Mechanistic work has shown that phosphorylation can control several parameters such as protein/protein interactions and p65 ubiquitination.
[ "11–16", "17", "18", "19", "20", "21", "22", "19", "23", "24", "25", "26", "27" ]
139
43,015
0
false
Mechanistic work has shown that phosphorylation can control several parameters such as protein/protein interactions and p65 ubiquitination.
[]
Mechanistic work has shown that phosphorylation can control several parameters such as protein/protein interactions and p65 ubiquitination.
true
true
true
true
true
7,454
3
INTRODUCTION
1
19
[ "B11 B12 B13 B14 B15 B16", "B17", "B18", "B19", "B20", "B21", "B22", "B19", "B23", "B24", "B25", "B26", "B27" ]
20,507,904
pmid-15226358|pmid-8710491|pmid-11533489|pmid-14690596|pmid-19864627|pmid-7925300|pmid-12419806|pmid-12456660|pmid-9660950|pmid-15457532|pmid-17431096|pmid-18408078|pmid-9660950|pmid-15489227|pmid-19339690|pmid-19270718|pmid-17468759|pmid-17928811|pmid-19595715|pmid-18927578|pmid-19648011|pmid-12789343|pmid-12789342|pm...
Phosphorylation at serine 276 results in conformational changes that allow binding of CREB-binding protein (CBP)/p300 (19), while phosphorylation of serine 536 favors binding of TATA-binding protein-associated factor II31, a component of TFIID (23).
[ "11–16", "17", "18", "19", "20", "21", "22", "19", "23", "24", "25", "26", "27" ]
249
43,016
1
false
Phosphorylation at serine 276 results in conformational changes that allow binding of CREB-binding protein (CBP)/p300, while phosphorylation of serine 536 favors binding of TATA-binding protein-associated factor II31, a component of TFIID.
[ "19", "23" ]
Phosphorylation at serine 276 results in conformational changes that allow binding of CREB-binding protein (CBP)/p300, while phosphorylation of serine 536 favors binding of TATA-binding protein-associated factor II31, a component of TFIID.
true
true
true
true
true
7,454
3
INTRODUCTION
1
11–16
[ "B11 B12 B13 B14 B15 B16", "B17", "B18", "B19", "B20", "B21", "B22", "B19", "B23", "B24", "B25", "B26", "B27" ]
20,507,904
pmid-15226358|pmid-8710491|pmid-11533489|pmid-14690596|pmid-19864627|pmid-7925300|pmid-12419806|pmid-12456660|pmid-9660950|pmid-15457532|pmid-17431096|pmid-18408078|pmid-9660950|pmid-15489227|pmid-19339690|pmid-19270718|pmid-17468759|pmid-17928811|pmid-19595715|pmid-18927578|pmid-19648011|pmid-12789343|pmid-12789342|pm...
TNF-induced p65 ser 468 phosphorylation is a prerequisite for its association with a protein complex consisting of the acetyltransferase GCN5 and the ubiquitin E3 ligase components COMMD1 and Cullin-2, which lead to target gene specific p65 ubiquitination and degradation (24,25).
[ "11–16", "17", "18", "19", "20", "21", "22", "19", "23", "24", "25", "26", "27" ]
280
43,017
0
false
TNF-induced p65 ser 468 phosphorylation is a prerequisite for its association with a protein complex consisting of the acetyltransferase GCN5 and the ubiquitin E3 ligase components COMMD1 and Cullin-2, which lead to target gene specific p65 ubiquitination and degradation.
[ "24,25" ]
TNF-induced p65 ser 468 phosphorylation is a prerequisite for its association with a protein complex consisting of the acetyltransferase GCN5 and the ubiquitin E3 ligase components COMMD1 and Cullin-2, which lead to target gene specific p65 ubiquitination and degradation.
true
true
true
true
true
7,454
3
INTRODUCTION
1
26
[ "B11 B12 B13 B14 B15 B16", "B17", "B18", "B19", "B20", "B21", "B22", "B19", "B23", "B24", "B25", "B26", "B27" ]
20,507,904
pmid-15226358|pmid-8710491|pmid-11533489|pmid-14690596|pmid-19864627|pmid-7925300|pmid-12419806|pmid-12456660|pmid-9660950|pmid-15457532|pmid-17431096|pmid-18408078|pmid-9660950|pmid-15489227|pmid-19339690|pmid-19270718|pmid-17468759|pmid-17928811|pmid-19595715|pmid-18927578|pmid-19648011|pmid-12789343|pmid-12789342|pm...
Another ubiquitin E3 ligase regulating p65 stability is PDLIM2, which mediates LPS-induced p65 polyubiquitination and sequesters the transcription factor in promyelocytic leukemia nuclear bodies (PML-NBs) (26).
[ "11–16", "17", "18", "19", "20", "21", "22", "19", "23", "24", "25", "26", "27" ]
210
43,018
1
false
Another ubiquitin E3 ligase regulating p65 stability is PDLIM2, which mediates LPS-induced p65 polyubiquitination and sequesters the transcription factor in promyelocytic leukemia nuclear bodies (PML-NBs).
[ "26" ]
Another ubiquitin E3 ligase regulating p65 stability is PDLIM2, which mediates LPS-induced p65 polyubiquitination and sequesters the transcription factor in promyelocytic leukemia nuclear bodies (PML-NBs).
true
true
true
true
true
7,454