Datasets:
vgainullin
/
xciting_data

Dataset card Data Studio Files
xet
 Community
1
paragraph_index
int64
sec
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2
DISCUSSION
1
1
[ "r1", "r41", "r42", "r22", "r5", "r6", "r35", "r20", "r21", "r3", "r20", "r21", "r43", "r44" ]
18,443,205
pmid-16186396|pmid-9832430|pmid-17141630|pmid-17227768|pmid-16823477|pmid-12606524|pmid-16505240|pmid-12021247|pmid-11489937|pmid-11533494|pmid-12021247|pmid-11489937|pmid-17959861|pmid-17317777
Although the role of TNF-α in the development of skeletal muscle insulin resistance in type 2 diabetic patients remains unresolved, current evidence suggests that IKKβ may be an intermediate kinase through which TNF-α and other inflammatory processes induce skeletal muscle insulin resistance (5,6,35).
[ "1", "41", "42", "22", "5", "6", "35", "20", "21", "3", "20", "21", "43", "44" ]
302
42,719
0
false
Although the role of TNF-α in the development of skeletal muscle insulin resistance in type 2 diabetic patients remains unresolved, current evidence suggests that IKKβ may be an intermediate kinase through which TNF-α and other inflammatory processes induce skeletal muscle insulin resistance.
[ "5,6,35" ]
Although the role of TNF-α in the development of skeletal muscle insulin resistance in type 2 diabetic patients remains unresolved, current evidence suggests that IKKβ may be an intermediate kinase through which TNF-α and other inflammatory processes induce skeletal muscle insulin resistance.
true
true
true
true
true
7,403
2
DISCUSSION
1
1
[ "r1", "r41", "r42", "r22", "r5", "r6", "r35", "r20", "r21", "r3", "r20", "r21", "r43", "r44" ]
18,443,205
pmid-16186396|pmid-9832430|pmid-17141630|pmid-17227768|pmid-16823477|pmid-12606524|pmid-16505240|pmid-12021247|pmid-11489937|pmid-11533494|pmid-12021247|pmid-11489937|pmid-17959861|pmid-17317777
IKKβ activation has been closely linked to the development and pathogenesis of insulin resistance (20,21).
[ "1", "41", "42", "22", "5", "6", "35", "20", "21", "3", "20", "21", "43", "44" ]
106
42,720
0
false
IKKβ activation has been closely linked to the development and pathogenesis of insulin resistance.
[ "20,21" ]
IKKβ activation has been closely linked to the development and pathogenesis of insulin resistance.
true
true
true
true
true
7,403
2
DISCUSSION
1
43
[ "r1", "r41", "r42", "r22", "r5", "r6", "r35", "r20", "r21", "r3", "r20", "r21", "r43", "r44" ]
18,443,205
pmid-16186396|pmid-9832430|pmid-17141630|pmid-17227768|pmid-16823477|pmid-12606524|pmid-16505240|pmid-12021247|pmid-11489937|pmid-11533494|pmid-12021247|pmid-11489937|pmid-17959861|pmid-17317777
Pharmacological inhibition of IKKβ activity improves insulin-mediated glucose metabolism (3,20,21), even in insulin-resistant obese, nondiabetic individuals (43).
[ "1", "41", "42", "22", "5", "6", "35", "20", "21", "3", "20", "21", "43", "44" ]
162
42,721
1
false
Pharmacological inhibition of IKKβ activity improves insulin-mediated glucose metabolism, even in insulin-resistant obese, nondiabetic individuals.
[ "3,20,21", "43" ]
Pharmacological inhibition of IKKβ activity improves insulin-mediated glucose metabolism, even in insulin-resistant obese, nondiabetic individuals.
true
true
true
true
true
7,403
2
DISCUSSION
1
44
[ "r1", "r41", "r42", "r22", "r5", "r6", "r35", "r20", "r21", "r3", "r20", "r21", "r43", "r44" ]
18,443,205
pmid-16186396|pmid-9832430|pmid-17141630|pmid-17227768|pmid-16823477|pmid-12606524|pmid-16505240|pmid-12021247|pmid-11489937|pmid-11533494|pmid-12021247|pmid-11489937|pmid-17959861|pmid-17317777
Increased expression of IKKβ has been noted in omental fat from obese humans, potentially contributing to differential roles of omental and subcutaneous fat in the pathophysiology of obesity (44).
[ "1", "41", "42", "22", "5", "6", "35", "20", "21", "3", "20", "21", "43", "44" ]
196
42,722
1
false
Increased expression of IKKβ has been noted in omental fat from obese humans, potentially contributing to differential roles of omental and subcutaneous fat in the pathophysiology of obesity.
[ "44" ]
Increased expression of IKKβ has been noted in omental fat from obese humans, potentially contributing to differential roles of omental and subcutaneous fat in the pathophysiology of obesity.
true
true
true
true
true
7,403
3
DISCUSSION
1
45
[ "r45", "r3", "r46" ]
18,443,205
pmid-15351728|pmid-11533494|pmid-14755344
Studies linking IKKβ and skeletal muscle insulin resistance in rodents have yielded conflicting results.
[ "45", "3", "46" ]
104
42,723
0
false
Studies linking IKKβ and skeletal muscle insulin resistance in rodents have yielded conflicting results.
[]
Studies linking IKKβ and skeletal muscle insulin resistance in rodents have yielded conflicting results.
true
true
true
true
true
7,404
3
DISCUSSION
1
45
[ "r45", "r3", "r46" ]
18,443,205
pmid-15351728|pmid-11533494|pmid-14755344
Pharmacological IKKβ inhibition ameliorated insulin resistance and upregulated plasma levels of adiponectin in KKAy mice fed a high-fat diet (45).
[ "45", "3", "46" ]
146
42,724
1
false
Pharmacological IKKβ inhibition ameliorated insulin resistance and upregulated plasma levels of adiponectin in KKAy mice fed a high-fat diet.
[ "45" ]
Pharmacological IKKβ inhibition ameliorated insulin resistance and upregulated plasma levels of adiponectin in KKAy mice fed a high-fat diet.
true
true
true
true
true
7,404
3
DISCUSSION
1
3
[ "r45", "r3", "r46" ]
18,443,205
pmid-15351728|pmid-11533494|pmid-14755344
Heterozygous IKKβ+/− mice fed a high-fat diet or intergressed on an obese ob/ob mice background were protected against the development of insulin resistance (3).
[ "45", "3", "46" ]
161
42,725
1
false
Heterozygous IKKβ+/− mice fed a high-fat diet or intergressed on an obese ob/ob mice background were protected against the development of insulin resistance.
[ "3" ]
Heterozygous IKKβ+/− mice fed a high-fat diet or intergressed on an obese ob/ob mice background were protected against the development of insulin resistance.
true
true
true
true
true
7,404
3
DISCUSSION
1
46
[ "r45", "r3", "r46" ]
18,443,205
pmid-15351728|pmid-11533494|pmid-14755344
Conversely, mice with either skeletal muscle–specific IKKβ knockout or a separate cohort of heterozygous IKKβ+/− were not protected against gold thioglucose–induced obesity or dietary-induced metabolic abnormalities (46).
[ "45", "3", "46" ]
221
42,726
1
false
Conversely, mice with either skeletal muscle–specific IKKβ knockout or a separate cohort of heterozygous IKKβ+/− were not protected against gold thioglucose–induced obesity or dietary-induced metabolic abnormalities.
[ "46" ]
Conversely, mice with either skeletal muscle–specific IKKβ knockout or a separate cohort of heterozygous IKKβ+/− were not protected against gold thioglucose–induced obesity or dietary-induced metabolic abnormalities.
true
true
true
true
true
7,404
3
DISCUSSION
1
45
[ "r45", "r3", "r46" ]
18,443,205
pmid-15351728|pmid-11533494|pmid-14755344
The reason for the differences noted between these animal models is unknown, but the differences could be strain specific or related to undefined experimental differences.
[ "45", "3", "46" ]
171
42,727
0
false
The reason for the differences noted between these animal models is unknown, but the differences could be strain specific or related to undefined experimental differences.
[]
The reason for the differences noted between these animal models is unknown, but the differences could be strain specific or related to undefined experimental differences.
true
true
true
true
true
7,404
4
DISCUSSION
1
47
[ "r47", "r25", "r26", "r48" ]
18,443,205
pmid-17498510|pmid-12714600|pmid-12409308|pmid-14764603
TNF-α exposure leads to activation of two separate transcription factor–signaling pathways, namely the IKKβ and JNK pathways, which are linked to proinflammatory responses associated with obesity and insulin resistance (47).
[ "47", "25", "26", "48" ]
224
42,728
1
false
TNF-α exposure leads to activation of two separate transcription factor–signaling pathways, namely the IKKβ and JNK pathways, which are linked to proinflammatory responses associated with obesity and insulin resistance.
[ "47" ]
TNF-α exposure leads to activation of two separate transcription factor–signaling pathways, namely the IKKβ and JNK pathways, which are linked to proinflammatory responses associated with obesity and insulin resistance.
true
true
true
true
true
7,405
4
DISCUSSION
1
47
[ "r47", "r25", "r26", "r48" ]
18,443,205
pmid-17498510|pmid-12714600|pmid-12409308|pmid-14764603
Here, we show that siRNA-mediated gene silencing of IKKβ prevented TNF-α–induced insulin resistance on glucose uptake and metabolism in cultured myotubes, with a concomitant increase in phosphorylation of Akt (at Ser473, Thr308), and AS160.
[ "47", "25", "26", "48" ]
240
42,729
0
false
Here, we show that siRNA-mediated gene silencing of IKKβ prevented TNF-α–induced insulin resistance on glucose uptake and metabolism in cultured myotubes, with a concomitant increase in phosphorylation of Akt, and AS160.
[ "at Ser473, Thr308" ]
Here, we show that siRNA-mediated gene silencing of IKKβ prevented TNF-α–induced insulin resistance on glucose uptake and metabolism in cultured myotubes, with a concomitant increase in phosphorylation of Akt, and AS160.
true
true
true
true
true
7,405
4
DISCUSSION
1
47
[ "r47", "r25", "r26", "r48" ]
18,443,205
pmid-17498510|pmid-12714600|pmid-12409308|pmid-14764603
Inhibition of ERK signaling using pharmacological inhibitor PD98059 did not alter TNF-α–mediated reduction in insulin-stimulated glycogen synthesis.
[ "47", "25", "26", "48" ]
148
42,730
0
false
Inhibition of ERK signaling using pharmacological inhibitor PD98059 did not alter TNF-α–mediated reduction in insulin-stimulated glycogen synthesis.
[]
Inhibition of ERK signaling using pharmacological inhibitor PD98059 did not alter TNF-α–mediated reduction in insulin-stimulated glycogen synthesis.
true
true
true
true
true
7,405
4
DISCUSSION
1
47
[ "r47", "r25", "r26", "r48" ]
18,443,205
pmid-17498510|pmid-12714600|pmid-12409308|pmid-14764603
Furthermore, the TNF-α–mediated activation of ERK and JNK was unaffected by the siRNA-mediated reduction of IKKβ.
[ "47", "25", "26", "48" ]
113
42,731
0
false
Furthermore, the TNF-α–mediated activation of ERK and JNK was unaffected by the siRNA-mediated reduction of IKKβ.
[]
Furthermore, the TNF-α–mediated activation of ERK and JNK was unaffected by the siRNA-mediated reduction of IKKβ.
true
true
true
true
true
7,405
4
DISCUSSION
1
47
[ "r47", "r25", "r26", "r48" ]
18,443,205
pmid-17498510|pmid-12714600|pmid-12409308|pmid-14764603
Additionally, the siRNA-mediated reduction of IKKβ did not prevent TNF-α–induced IRS-1 serine phosphorylation on Ser312 or the IRS-1 mobility shift as determined by SDS-PAGE.
[ "47", "25", "26", "48" ]
174
42,732
0
false
Additionally, the siRNA-mediated reduction of IKKβ did not prevent TNF-α–induced IRS-1 serine phosphorylation on Ser312 or the IRS-1 mobility shift as determined by SDS-PAGE.
[]
Additionally, the siRNA-mediated reduction of IKKβ did not prevent TNF-α–induced IRS-1 serine phosphorylation on Ser312 or the IRS-1 mobility shift as determined by SDS-PAGE.
true
true
true
true
true
7,405
4
DISCUSSION
1
47
[ "r47", "r25", "r26", "r48" ]
18,443,205
pmid-17498510|pmid-12714600|pmid-12409308|pmid-14764603
This is in contrast to some reports indicating that inhibition of IKKβ prevents IRS-1 Ser307 (equivalent to human IRS-1 Ser312) phosphorylation in cultured HEPG2, 3T3-L1 adipocytes, or embryonic kidney cells (25,26,48) but is consistent with other observations that IKKβ is disassociated from IRS-1 phosphorylation (Stev...
[ "47", "25", "26", "48" ]
396
42,733
0
false
This is in contrast to some reports indicating that inhibition of IKKβ prevents IRS-1 Ser307 (equivalent to human IRS-1 Ser312) phosphorylation in cultured HEPG2, 3T3-L1 adipocytes, or embryonic kidney cells but is consistent with other observations that IKKβ is disassociated from IRS-1 phosphorylation (Steven E. Shoel...
[ "25,26,48" ]
This is in contrast to some reports indicating that inhibition of IKKβ prevents IRS-1 Ser307 (equivalent to human IRS-1 Ser312) phosphorylation in cultured HEPG2, 3T3-L1 adipocytes, or embryonic kidney cells but is consistent with other observations that IKKβ is disassociated from IRS-1 phosphorylation (Steven E. Shoel...
true
true
true
true
true
7,405
4
DISCUSSION
1
47
[ "r47", "r25", "r26", "r48" ]
18,443,205
pmid-17498510|pmid-12714600|pmid-12409308|pmid-14764603
Our results indicate that the TNF-α effect on IRS-1 serine phosphorylation is primarily mediated via parallel IKKβ independent pathways, such as JNK.
[ "47", "25", "26", "48" ]
149
42,734
0
false
Our results indicate that the TNF-α effect on IRS-1 serine phosphorylation is primarily mediated via parallel IKKβ independent pathways, such as JNK.
[]
Our results indicate that the TNF-α effect on IRS-1 serine phosphorylation is primarily mediated via parallel IKKβ independent pathways, such as JNK.
true
true
true
true
true
7,405
5
DISCUSSION
0
null
null
18,443,205
null
IKKβ silencing fully restored the TNF-α–mediated reduction of insulin-stimulated glucose metabolism, despite modest impairments in insulin signaling at the level of Akt.
null
169
42,735
0
false
null
null
IKKβ silencing fully restored the TNF-α–mediated reduction of insulin-stimulated glucose metabolism, despite modest impairments in insulin signaling at the level of Akt.
true
true
true
true
true
7,406
5
DISCUSSION
0
null
null
18,443,205
null
However, TNF-α exposure was associated with a profound impairment in insulin-stimulated AS160 phosphorylation, which was restored following IKKβ silencing.
null
155
42,736
0
false
null
null
However, TNF-α exposure was associated with a profound impairment in insulin-stimulated AS160 phosphorylation, which was restored following IKKβ silencing.
true
true
true
true
true
7,406
5
DISCUSSION
0
null
null
18,443,205
null
Since AS160 is a critical step in the processes involved from insulin signaling to glucose transport, this may explain the enhanced glucose metabolism in IKKβ-depleted myotubes.
null
177
42,737
0
false
null
null
Since AS160 is a critical step in the processes involved from insulin signaling to glucose transport, this may explain the enhanced glucose metabolism in IKKβ-depleted myotubes.
true
true
true
true
true
7,406
5
DISCUSSION
0
null
null
18,443,205
null
Our results may also indicate that a relatively small pool of total Akt is critical for signaling to AS160, and this pool may be highly sensitive to TNF-α, possibly due to cellular localization.
null
194
42,738
0
false
null
null
Our results may also indicate that a relatively small pool of total Akt is critical for signaling to AS160, and this pool may be highly sensitive to TNF-α, possibly due to cellular localization.
true
true
true
true
true
7,406
6
DISCUSSION
1
49
[ "r49", "r50", "r51" ]
18,443,205
pmid-12584189|pmid-16960890|pmid-16007092
In primary cultures of human muscle, TNF-α exposure enhanced phosphorylation of GSK3β.
[ "49", "50", "51" ]
86
42,739
0
false
In primary cultures of human muscle, TNF-α exposure enhanced phosphorylation of GSK3β.
[]
In primary cultures of human muscle, TNF-α exposure enhanced phosphorylation of GSK3β.
true
true
true
true
true
7,407
6
DISCUSSION
1
49
[ "r49", "r50", "r51" ]
18,443,205
pmid-12584189|pmid-16960890|pmid-16007092
This finding is consistent with a finding of a previous study in HEK293 cells and mouse embryonic fibroblasts (49), where TNF-α–mediated activation of ERK was partly dependent on GSK3β phosphorylation.
[ "49", "50", "51" ]
201
42,740
1
false
This finding is consistent with a finding of a previous study in HEK293 cells and mouse embryonic fibroblasts, where TNF-α–mediated activation of ERK was partly dependent on GSK3β phosphorylation.
[ "49" ]
This finding is consistent with a finding of a previous study in HEK293 cells and mouse embryonic fibroblasts, where TNF-α–mediated activation of ERK was partly dependent on GSK3β phosphorylation.
true
true
true
true
true
7,407
6
DISCUSSION
1
50
[ "r49", "r50", "r51" ]
18,443,205
pmid-12584189|pmid-16960890|pmid-16007092
Conversely, TNF-α exposure has also been shown to prevent insulin-stimulated phosphorylation of GSK3β in HEPG2 cells (50).
[ "49", "50", "51" ]
122
42,741
1
false
Conversely, TNF-α exposure has also been shown to prevent insulin-stimulated phosphorylation of GSK3β in HEPG2 cells.
[ "50" ]
Conversely, TNF-α exposure has also been shown to prevent insulin-stimulated phosphorylation of GSK3β in HEPG2 cells.
true
true
true
true
true
7,407
6
DISCUSSION
1
49
[ "r49", "r50", "r51" ]
18,443,205
pmid-12584189|pmid-16960890|pmid-16007092
Here, we report that IKKβ silencing prevents the TNF-α–mediated increase in GSK3β phosphorylation; however, the functional consequence requires further investigation.
[ "49", "50", "51" ]
166
42,742
0
false
Here, we report that IKKβ silencing prevents the TNF-α–mediated increase in GSK3β phosphorylation; however, the functional consequence requires further investigation.
[]
Here, we report that IKKβ silencing prevents the TNF-α–mediated increase in GSK3β phosphorylation; however, the functional consequence requires further investigation.
true
true
true
true
true
7,407
6
DISCUSSION
1
51
[ "r49", "r50", "r51" ]
18,443,205
pmid-12584189|pmid-16960890|pmid-16007092
Although GSK3β Ser9 phosphorylation has been linked to a reduction in the constitutive ability of GSK3 to phosphorylate Ser641 of glycogen synthase, it does not completely abolish the ability of GSK3 to phosphorylate glycogen synthase (51).
[ "49", "50", "51" ]
240
42,743
1
false
Although GSK3β Ser9 phosphorylation has been linked to a reduction in the constitutive ability of GSK3 to phosphorylate Ser641 of glycogen synthase, it does not completely abolish the ability of GSK3 to phosphorylate glycogen synthase.
[ "51" ]
Although GSK3β Ser9 phosphorylation has been linked to a reduction in the constitutive ability of GSK3 to phosphorylate Ser641 of glycogen synthase, it does not completely abolish the ability of GSK3 to phosphorylate glycogen synthase.
true
true
true
true
true
7,407
6
DISCUSSION
1
49
[ "r49", "r50", "r51" ]
18,443,205
pmid-12584189|pmid-16960890|pmid-16007092
Thus, further studies are warranted to establish whether GSK3 activity is modulated.
[ "49", "50", "51" ]
84
42,744
0
false
Thus, further studies are warranted to establish whether GSK3 activity is modulated.
[]
Thus, further studies are warranted to establish whether GSK3 activity is modulated.
true
true
true
true
true
7,407
7
DISCUSSION
1
23
[ "r23", "r34", "r22" ]
18,443,205
pmid-16461467|pmid-15951441|pmid-17227768
MAP4K4 is a member of the NCK interacting kinase family (23).
[ "23", "34", "22" ]
61
42,745
1
false
MAP4K4 is a member of the NCK interacting kinase family.
[ "23" ]
MAP4K4 is a member of the NCK interacting kinase family.
true
true
true
true
true
7,408
7
DISCUSSION
1
34
[ "r23", "r34", "r22" ]
18,443,205
pmid-16461467|pmid-15951441|pmid-17227768
NCK interacting kinase family kinases are potent activators of the IKK complex and activators of ERK and JNK (34), which suggests that MAP4K4 is likely to be an upstream regulator of IKKβ.
[ "23", "34", "22" ]
188
42,746
1
false
NCK interacting kinase family kinases are potent activators of the IKK complex and activators of ERK and JNK, which suggests that MAP4K4 is likely to be an upstream regulator of IKKβ.
[ "34" ]
NCK interacting kinase family kinases are potent activators of the IKK complex and activators of ERK and JNK, which suggests that MAP4K4 is likely to be an upstream regulator of IKKβ.
true
true
true
true
true
7,408
7
DISCUSSION
1
23
[ "r23", "r34", "r22" ]
18,443,205
pmid-16461467|pmid-15951441|pmid-17227768
Here, we show that siRNA-mediated silencing of IKKβ had no effect on expression of MAP4K4, excluding a negative feedback on this upstream kinase.
[ "23", "34", "22" ]
145
42,747
0
false
Here, we show that siRNA-mediated silencing of IKKβ had no effect on expression of MAP4K4, excluding a negative feedback on this upstream kinase.
[]
Here, we show that siRNA-mediated silencing of IKKβ had no effect on expression of MAP4K4, excluding a negative feedback on this upstream kinase.
true
true
true
true
true
7,408
7
DISCUSSION
1
22
[ "r23", "r34", "r22" ]
18,443,205
pmid-16461467|pmid-15951441|pmid-17227768
We have previously reported that the siRNA-mediated reduction of MAP4K4 rescues TNF-α–mediated insulin resistance in primary human skeletal muscle cultures (22), consistent with our present findings for IKKβ.
[ "23", "34", "22" ]
208
42,748
1
false
We have previously reported that the siRNA-mediated reduction of MAP4K4 rescues TNF-α–mediated insulin resistance in primary human skeletal muscle cultures, consistent with our present findings for IKKβ.
[ "22" ]
We have previously reported that the siRNA-mediated reduction of MAP4K4 rescues TNF-α–mediated insulin resistance in primary human skeletal muscle cultures, consistent with our present findings for IKKβ.
true
true
true
true
true
7,408
7
DISCUSSION
1
23
[ "r23", "r34", "r22" ]
18,443,205
pmid-16461467|pmid-15951441|pmid-17227768
Although a reduction of either MAP4K4 or IKKβ prevents the effect of TNF-α on insulin-mediated glucose uptake and metabolism, the reduction of MAP4K4 also prevented IRS-1 serine phosphorylation and signaling to ERK 1/2 and JNK.
[ "23", "34", "22" ]
227
42,749
0
false
Although a reduction of either MAP4K4 or IKKβ prevents the effect of TNF-α on insulin-mediated glucose uptake and metabolism, the reduction of MAP4K4 also prevented IRS-1 serine phosphorylation and signaling to ERK 1/2 and JNK.
[]
Although a reduction of either MAP4K4 or IKKβ prevents the effect of TNF-α on insulin-mediated glucose uptake and metabolism, the reduction of MAP4K4 also prevented IRS-1 serine phosphorylation and signaling to ERK 1/2 and JNK.
true
true
true
true
true
7,408
7
DISCUSSION
1
23
[ "r23", "r34", "r22" ]
18,443,205
pmid-16461467|pmid-15951441|pmid-17227768
In contrast, siRNA silencing of IKKβ did not alter TNF-α signaling to either IRS-1 Ser312, JNK, or ERK phosphorylation.
[ "23", "34", "22" ]
119
42,750
0
false
In contrast, siRNA silencing of IKKβ did not alter TNF-α signaling to either IRS-1 Ser312, JNK, or ERK phosphorylation.
[]
In contrast, siRNA silencing of IKKβ did not alter TNF-α signaling to either IRS-1 Ser312, JNK, or ERK phosphorylation.
true
true
true
true
true
7,408
7
DISCUSSION
1
23
[ "r23", "r34", "r22" ]
18,443,205
pmid-16461467|pmid-15951441|pmid-17227768
These results are consistent with the hypothesis that downstream signals from MAP4K4 diverge toward an ERK/JNK pathway that mediates effects on IRS-1 serine phosphorylation and an IKKβ pathway that mediates effects on glucose uptake and metabolism.
[ "23", "34", "22" ]
248
42,751
0
false
These results are consistent with the hypothesis that downstream signals from MAP4K4 diverge toward an ERK/JNK pathway that mediates effects on IRS-1 serine phosphorylation and an IKKβ pathway that mediates effects on glucose uptake and metabolism.
[]
These results are consistent with the hypothesis that downstream signals from MAP4K4 diverge toward an ERK/JNK pathway that mediates effects on IRS-1 serine phosphorylation and an IKKβ pathway that mediates effects on glucose uptake and metabolism.
true
true
true
true
true
7,408
8
DISCUSSION
0
null
null
18,443,205
null
In summary, targeted deletion of IKKβ using siRNA prevents TNF-α–mediated insulin resistance on Akt and AS160 phosphorylation and glucose uptake and metabolism in human skeletal muscle.
null
185
42,752
0
false
null
null
In summary, targeted deletion of IKKβ using siRNA prevents TNF-α–mediated insulin resistance on Akt and AS160 phosphorylation and glucose uptake and metabolism in human skeletal muscle.
true
true
true
true
true
7,409
8
DISCUSSION
0
null
null
18,443,205
null
These results underscore IKKβ as a potential therapeutic target to prevent peripheral insulin resistance.
null
105
42,753
0
false
null
null
These results underscore IKKβ as a potential therapeutic target to prevent peripheral insulin resistance.
true
true
true
true
true
7,409
0
DISCUSSION
1
12
[ "bib12", "bib13", "bib15" ]
19,965,595
pmid-16862216|pmid-16484451|pmid-18769635
During the past few years, Yang et al.
[ "12", "13", "15" ]
38
42,754
0
false
During the past few years, Yang et al.
[]
During the past few years, Yang et al.
true
true
true
true
true
7,410
0
DISCUSSION
1
12
[ "bib12", "bib13", "bib15" ]
19,965,595
pmid-16862216|pmid-16484451|pmid-18769635
(12, 13) showed that an FTI ameliorates disease phenotypes in a mouse model of HGPS.
[ "12", "13", "15" ]
84
42,755
0
false
showed that an FTI ameliorates disease phenotypes in a mouse model of HGPS.
[ "12, 13" ]
showed that an FTI ameliorates disease phenotypes in a mouse model of HGPS.
false
true
true
true
false
7,410
0
DISCUSSION
1
15
[ "bib12", "bib13", "bib15" ]
19,965,595
pmid-16862216|pmid-16484451|pmid-18769635
Although the results were significant and reproducible, putting the findings into perspective is challenging, particularly with the discovery that LmnanHG/+ mice develop disease (15).
[ "12", "13", "15" ]
183
42,756
1
false
Although the results were significant and reproducible, putting the findings into perspective is challenging, particularly with the discovery that LmnanHG/+ mice develop disease.
[ "15" ]
Although the results were significant and reproducible, putting the findings into perspective is challenging, particularly with the discovery that LmnanHG/+ mice develop disease.
true
true
true
true
true
7,410
0
DISCUSSION
1
12
[ "bib12", "bib13", "bib15" ]
19,965,595
pmid-16862216|pmid-16484451|pmid-18769635
LmnanHG/+ have all of the same progeria-like disease phenotypes as LmnaHG/+ mice, albeit somewhat milder, and they invariably succumb to the disease.
[ "12", "13", "15" ]
149
42,757
0
false
LmnanHG/+ have all of the same progeria-like disease phenotypes as LmnaHG/+ mice, albeit somewhat milder, and they invariably succumb to the disease.
[]
LmnanHG/+ have all of the same progeria-like disease phenotypes as LmnaHG/+ mice, albeit somewhat milder, and they invariably succumb to the disease.
true
true
true
true
true
7,410
0
DISCUSSION
1
12
[ "bib12", "bib13", "bib15" ]
19,965,595
pmid-16862216|pmid-16484451|pmid-18769635
The discovery that nonfarnesylated progerin elicits disease prompted us to consider the possibility that the beneficial effects of the FTI in LmnaHG/+ mice might have little to do with a direct effect on the farnesylation of progerin.
[ "12", "13", "15" ]
234
42,758
0
false
The discovery that nonfarnesylated progerin elicits disease prompted us to consider the possibility that the beneficial effects of the FTI in LmnaHG/+ mice might have little to do with a direct effect on the farnesylation of progerin.
[]
The discovery that nonfarnesylated progerin elicits disease prompted us to consider the possibility that the beneficial effects of the FTI in LmnaHG/+ mice might have little to do with a direct effect on the farnesylation of progerin.
true
true
true
true
true
7,410
0
DISCUSSION
1
12
[ "bib12", "bib13", "bib15" ]
19,965,595
pmid-16862216|pmid-16484451|pmid-18769635
Instead, we wondered whether the effect of the FTI might be more indirect, perhaps secondary to inhibiting the farnesylation of other cellular proteins.
[ "12", "13", "15" ]
152
42,759
0
false
Instead, we wondered whether the effect of the FTI might be more indirect, perhaps secondary to inhibiting the farnesylation of other cellular proteins.
[]
Instead, we wondered whether the effect of the FTI might be more indirect, perhaps secondary to inhibiting the farnesylation of other cellular proteins.
true
true
true
true
true
7,410
0
DISCUSSION
1
12
[ "bib12", "bib13", "bib15" ]
19,965,595
pmid-16862216|pmid-16484451|pmid-18769635
If the effects of the FTI were indirect, one would predict the FTI might be equally efficacious in LmnaHG/+ and LmnanHG/+ mice.
[ "12", "13", "15" ]
127
42,760
0
false
If the effects of the FTI were indirect, one would predict the FTI might be equally efficacious in LmnaHG/+ and LmnanHG/+ mice.
[]
If the effects of the FTI were indirect, one would predict the FTI might be equally efficacious in LmnaHG/+ and LmnanHG/+ mice.
true
true
true
true
true
7,410
0
DISCUSSION
1
12
[ "bib12", "bib13", "bib15" ]
19,965,595
pmid-16862216|pmid-16484451|pmid-18769635
This prediction was not borne out.
[ "12", "13", "15" ]
34
42,761
0
false
This prediction was not borne out.
[]
This prediction was not borne out.
true
true
true
true
true
7,410
0
DISCUSSION
1
12
[ "bib12", "bib13", "bib15" ]
19,965,595
pmid-16862216|pmid-16484451|pmid-18769635
FTI treatment had no effect on body weight, survival, the number of rib fractures, fat stores, bone cortical thickness, or bone density of LmnanHG/+ mice.
[ "12", "13", "15" ]
154
42,762
0
false
FTI treatment had no effect on body weight, survival, the number of rib fractures, fat stores, bone cortical thickness, or bone density of LmnanHG/+ mice.
[]
FTI treatment had no effect on body weight, survival, the number of rib fractures, fat stores, bone cortical thickness, or bone density of LmnanHG/+ mice.
true
true
true
true
true
7,410
0
DISCUSSION
1
12
[ "bib12", "bib13", "bib15" ]
19,965,595
pmid-16862216|pmid-16484451|pmid-18769635
In contrast, the FTI improved all of these phenotypes in LmnaHG/+ mice, and did so in a highly significant fashion.
[ "12", "13", "15" ]
115
42,763
0
false
In contrast, the FTI improved all of these phenotypes in LmnaHG/+ mice, and did so in a highly significant fashion.
[]
In contrast, the FTI improved all of these phenotypes in LmnaHG/+ mice, and did so in a highly significant fashion.
true
true
true
true
true
7,410
0
DISCUSSION
1
12
[ "bib12", "bib13", "bib15" ]
19,965,595
pmid-16862216|pmid-16484451|pmid-18769635
The fact that the FTI improved disease in LmnaHG/+ but not LmnanHG/+ mice suggests that the beneficial effect of the FTI in LmnaHG/+ mice is likely a consequence of inhibiting the prenylation of progerin, rather than an indirect effect of the drug on other cellular proteins.
[ "12", "13", "15" ]
275
42,764
0
false
The fact that the FTI improved disease in LmnaHG/+ but not LmnanHG/+ mice suggests that the beneficial effect of the FTI in LmnaHG/+ mice is likely a consequence of inhibiting the prenylation of progerin, rather than an indirect effect of the drug on other cellular proteins.
[]
The fact that the FTI improved disease in LmnaHG/+ but not LmnanHG/+ mice suggests that the beneficial effect of the FTI in LmnaHG/+ mice is likely a consequence of inhibiting the prenylation of progerin, rather than an indirect effect of the drug on other cellular proteins.
true
true
true
true
true
7,410
1
DISCUSSION
1
20
[ "bib20", "bib8", "bib14", "bib15" ]
19,965,595
pmid-18178963|pmid-16129834|pmid-18082640|pmid-18769635
The beneficial effects of the FTI on disease phenotypes in LmnaHG/+ mice were very apparent, and most of the differences were significant at a P < 0.0001 level.
[ "20", "8", "14", "15" ]
160
42,765
0
false
The beneficial effects of the FTI on disease phenotypes in LmnaHG/+ mice were very apparent, and most of the differences were significant at a P < 0.0001 level.
[]
The beneficial effects of the FTI on disease phenotypes in LmnaHG/+ mice were very apparent, and most of the differences were significant at a P < 0.0001 level.
true
true
true
true
true
7,411
1
DISCUSSION
1
20
[ "bib20", "bib8", "bib14", "bib15" ]
19,965,595
pmid-18178963|pmid-16129834|pmid-18082640|pmid-18769635
In contrast, the FTI had no significant effects in LmnanHG/+ mice.
[ "20", "8", "14", "15" ]
66
42,766
0
false
In contrast, the FTI had no significant effects in LmnanHG/+ mice.
[]
In contrast, the FTI had no significant effects in LmnanHG/+ mice.
true
true
true
true
true
7,411
1
DISCUSSION
1
20
[ "bib20", "bib8", "bib14", "bib15" ]
19,965,595
pmid-18178963|pmid-16129834|pmid-18082640|pmid-18769635
One could argue that there may have been a slight trend toward improved body weights and lower numbers of rib fractures in FTI-treated LmnanHG/+ mice, but these differences did not achieve statistical significance.
[ "20", "8", "14", "15" ]
214
42,767
0
false
One could argue that there may have been a slight trend toward improved body weights and lower numbers of rib fractures in FTI-treated LmnanHG/+ mice, but these differences did not achieve statistical significance.
[]
One could argue that there may have been a slight trend toward improved body weights and lower numbers of rib fractures in FTI-treated LmnanHG/+ mice, but these differences did not achieve statistical significance.
true
true
true
true
true
7,411
1
DISCUSSION
1
20
[ "bib20", "bib8", "bib14", "bib15" ]
19,965,595
pmid-18178963|pmid-16129834|pmid-18082640|pmid-18769635
We suspect that the trend simply reflected the play of chance.
[ "20", "8", "14", "15" ]
62
42,768
0
false
We suspect that the trend simply reflected the play of chance.
[]
We suspect that the trend simply reflected the play of chance.
true
true
true
true
true
7,411
1
DISCUSSION
1
20
[ "bib20", "bib8", "bib14", "bib15" ]
19,965,595
pmid-18178963|pmid-16129834|pmid-18082640|pmid-18769635
However, if one were forced to suggest a potential explanation for the trend, one could point to the lower levels of mature lamin A in the setting of FTI treatment.
[ "20", "8", "14", "15" ]
164
42,769
0
false
However, if one were forced to suggest a potential explanation for the trend, one could point to the lower levels of mature lamin A in the setting of FTI treatment.
[]
However, if one were forced to suggest a potential explanation for the trend, one could point to the lower levels of mature lamin A in the setting of FTI treatment.
true
true
true
true
true
7,411
1
DISCUSSION
1
20
[ "bib20", "bib8", "bib14", "bib15" ]
19,965,595
pmid-18178963|pmid-16129834|pmid-18082640|pmid-18769635
Genetic studies have suggested that lower levels of lamin A synthesis reduce the disease phenotypes elicited by a LmnaHG allele (20).
[ "20", "8", "14", "15" ]
133
42,770
1
false
Genetic studies have suggested that lower levels of lamin A synthesis reduce the disease phenotypes elicited by a LmnaHG allele.
[ "20" ]
Genetic studies have suggested that lower levels of lamin A synthesis reduce the disease phenotypes elicited by a LmnaHG allele.
true
true
true
true
true
7,411
1
DISCUSSION
1
20
[ "bib20", "bib8", "bib14", "bib15" ]
19,965,595
pmid-18178963|pmid-16129834|pmid-18082640|pmid-18769635
The finding of lower lamin A levels in association with FTI treatment was also observed in earlier studies (8, 14, 15).
[ "20", "8", "14", "15" ]
119
42,771
0
false
The finding of lower lamin A levels in association with FTI treatment was also observed in earlier studies.
[ "8, 14, 15" ]
The finding of lower lamin A levels in association with FTI treatment was also observed in earlier studies.
true
true
true
true
true
7,411
1
DISCUSSION
1
20
[ "bib20", "bib8", "bib14", "bib15" ]
19,965,595
pmid-18178963|pmid-16129834|pmid-18082640|pmid-18769635
The mechanism for the fall in lamin A levels is unclear but we suspect that sustained blockade of prelamin A farnesylation leads to the eventual turnover of nonfarnesylated prelamin A, reducing the production of mature lamin A.
[ "20", "8", "14", "15" ]
227
42,772
0
false
The mechanism for the fall in lamin A levels is unclear but we suspect that sustained blockade of prelamin A farnesylation leads to the eventual turnover of nonfarnesylated prelamin A, reducing the production of mature lamin A.
[]
The mechanism for the fall in lamin A levels is unclear but we suspect that sustained blockade of prelamin A farnesylation leads to the eventual turnover of nonfarnesylated prelamin A, reducing the production of mature lamin A.
true
true
true
true
true
7,411
2
DISCUSSION
1
21
[ "bib21", "bib21" ]
19,965,595
pmid-18587406|pmid-18587406
The current study reinforces the idea that an FTI can ameliorate disease in LmnaHG/+ mice, but important questions remain about the utility of FTIs in the treatment of humans with HGPS.
[ "21", "21" ]
185
42,773
0
false
The current study reinforces the idea that an FTI can ameliorate disease in LmnaHG/+ mice, but important questions remain about the utility of FTIs in the treatment of humans with HGPS.
[]
The current study reinforces the idea that an FTI can ameliorate disease in LmnaHG/+ mice, but important questions remain about the utility of FTIs in the treatment of humans with HGPS.
true
true
true
true
true
7,412
2
DISCUSSION
1
21
[ "bib21", "bib21" ]
19,965,595
pmid-18587406|pmid-18587406
Indeed, questions were raised about whether an FTI is the most appropriate drug for inhibiting the prenylation of progerin (21).
[ "21", "21" ]
128
42,774
1
false
Indeed, questions were raised about whether an FTI is the most appropriate drug for inhibiting the prenylation of progerin.
[ "21" ]
Indeed, questions were raised about whether an FTI is the most appropriate drug for inhibiting the prenylation of progerin.
true
true
true
true
true
7,412
2
DISCUSSION
1
21
[ "bib21", "bib21" ]
19,965,595
pmid-18587406|pmid-18587406
Varela et al.
[ "21", "21" ]
13
42,775
0
false
Varela et al.
[]
Varela et al.
true
true
true
true
true
7,412
2
DISCUSSION
1
21
[ "bib21", "bib21" ]
19,965,595
pmid-18587406|pmid-18587406
(21) reported data suggesting that progerin can be geranylgeranylated in the setting of an FTI, and they proposed that a combination of a statin and a bisphosphonate (which would theoretically inhibit both farnesylation and geranylgeranylation) might be more useful for treating HGPS.
[ "21", "21" ]
284
42,776
1
false
reported data suggesting that progerin can be geranylgeranylated in the setting of an FTI, and they proposed that a combination of a statin and a bisphosphonate (which would theoretically inhibit both farnesylation and geranylgeranylation) might be more useful for treating HGPS.
[ "21" ]
reported data suggesting that progerin can be geranylgeranylated in the setting of an FTI, and they proposed that a combination of a statin and a bisphosphonate (which would theoretically inhibit both farnesylation and geranylgeranylation) might be more useful for treating HGPS.
false
true
true
true
false
7,412
2
DISCUSSION
1
21
[ "bib21", "bib21" ]
19,965,595
pmid-18587406|pmid-18587406
They went on to show that a statin/bisphosphonate combination improved progeria-like disease phenotypes in ZMPSTE24-deficient mice; however, they provided no evidence that the combination actually inhibited the prenylation of prelamin A (or any other protein) in mice.
[ "21", "21" ]
268
42,777
0
false
They went on to show that a statin/bisphosphonate combination improved progeria-like disease phenotypes in ZMPSTE24-deficient mice; however, they provided no evidence that the combination actually inhibited the prenylation of prelamin A (or any other protein) in mice.
[]
They went on to show that a statin/bisphosphonate combination improved progeria-like disease phenotypes in ZMPSTE24-deficient mice; however, they provided no evidence that the combination actually inhibited the prenylation of prelamin A (or any other protein) in mice.
true
true
true
true
true
7,412
2
DISCUSSION
1
21
[ "bib21", "bib21" ]
19,965,595
pmid-18587406|pmid-18587406
Until such evidence is in hand, doubts will remain about the rationale for the statin/bisphosphonate combination, and in particular, whether the combination ameliorates disease indirectly (perhaps secondary to the bone-strengthening properties of bisphosphonates) or more directly by inhibiting the prenylation of prelam...
[ "21", "21" ]
325
42,778
0
false
Until such evidence is in hand, doubts will remain about the rationale for the statin/bisphosphonate combination, and in particular, whether the combination ameliorates disease indirectly (perhaps secondary to the bone-strengthening properties of bisphosphonates) or more directly by inhibiting the prenylation of prelam...
[]
Until such evidence is in hand, doubts will remain about the rationale for the statin/bisphosphonate combination, and in particular, whether the combination ameliorates disease indirectly (perhaps secondary to the bone-strengthening properties of bisphosphonates) or more directly by inhibiting the prenylation of prelam...
true
true
true
true
true
7,412
2
DISCUSSION
1
21
[ "bib21", "bib21" ]
19,965,595
pmid-18587406|pmid-18587406
For those interested in investigating the utility of a bisphosphonate/statin combination, the approach outlined in the current study should be of interest.
[ "21", "21" ]
155
42,779
0
false
For those interested in investigating the utility of a bisphosphonate/statin combination, the approach outlined in the current study should be of interest.
[]
For those interested in investigating the utility of a bisphosphonate/statin combination, the approach outlined in the current study should be of interest.
true
true
true
true
true
7,412
2
DISCUSSION
1
21
[ "bib21", "bib21" ]
19,965,595
pmid-18587406|pmid-18587406
If a statin/bisphosphonate combination were to improve disease phenotypes in LmnanHG/+ mice, that would suggest that the mechanism for the combination was likely indirect, perhaps due to the bone-strengthening properties of the bisphosphonates, and not to a specific effect on the prenylation of prelamin A.
[ "21", "21" ]
307
42,780
0
false
If a statin/bisphosphonate combination were to improve disease phenotypes in LmnanHG/+ mice, that would suggest that the mechanism for the combination was likely indirect, perhaps due to the bone-strengthening properties of the bisphosphonates, and not to a specific effect on the prenylation of prelamin A.
[]
If a statin/bisphosphonate combination were to improve disease phenotypes in LmnanHG/+ mice, that would suggest that the mechanism for the combination was likely indirect, perhaps due to the bone-strengthening properties of the bisphosphonates, and not to a specific effect on the prenylation of prelamin A.
true
true
true
true
true
7,412
3
DISCUSSION
0
null
null
19,965,595
null
In summary, an FTI ameliorates disease phenotypes in LmnaHG/+ mice, but not LmnanHG/+ mice.
null
91
42,781
0
false
null
null
In summary, an FTI ameliorates disease phenotypes in LmnaHG/+ mice, but not LmnanHG/+ mice.
true
true
true
true
true
7,413
3
DISCUSSION
0
null
null
19,965,595
null
The failure of the FTI to improve disease in LmnanHG/+ mice suggests that the beneficial effects of the drug in LmnaHG/+ mice are likely due to blocking the farnesylation of progerin.
null
183
42,782
0
false
null
null
The failure of the FTI to improve disease in LmnanHG/+ mice suggests that the beneficial effects of the drug in LmnaHG/+ mice are likely due to blocking the farnesylation of progerin.
true
true
true
true
true
7,413
0
INTRODUCTION
0
null
null
20,466,808
null
Small non-coding RNAs, in particular microRNAs (miRNAs), have been identified to regulate global gene expression patterns.
null
122
42,783
0
false
null
null
Small non-coding RNAs, in particular microRNAs (miRNAs), have been identified to regulate global gene expression patterns.
true
true
true
true
true
7,414
0
INTRODUCTION
0
null
null
20,466,808
null
MiRNAs are transcribed as long precursors and then cleaved to pre-miRNAs of characteristic hairpin structure.
null
109
42,784
0
false
null
null
MiRNAs are transcribed as long precursors and then cleaved to pre-miRNAs of characteristic hairpin structure.
true
true
true
true
true
7,414
0
INTRODUCTION
0
null
null
20,466,808
null
Pre-miRNAs are further processed to generate mature miRNAs.
null
59
42,785
0
false
null
null
Pre-miRNAs are further processed to generate mature miRNAs.
true
true
true
true
true
7,414
0
INTRODUCTION
0
null
null
20,466,808
null
For several pre-miRNAs, both strands are processed and give rise to a functional miRNA.
null
87
42,786
0
false
null
null
For several pre-miRNAs, both strands are processed and give rise to a functional miRNA.
true
true
true
true
true
7,414
0
INTRODUCTION
0
null
null
20,466,808
null
If either one is known to be expressed at <15% of the other form, it is designated as miRNA* (star form).
null
105
42,787
0
false
null
null
If either one is known to be expressed at <15% of the other form, it is designated as miRNA* (star form).
true
true
true
true
true
7,414
0
INTRODUCTION
0
null
null
20,466,808
null
If the expression ratio is not known, a mature miRNA is designated with suffix ‘-3p’ or ‘-5p’, depending on the originating strand.
null
131
42,788
0
false
null
null
If the expression ratio is not known, a mature miRNA is designated with suffix ‘-3p’ or ‘-5p’, depending on the originating strand.
true
true
true
true
true
7,414
1
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4" ]
20,466,808
pmid-19255566|pmid-14744438|pmid-16557279|pmid-19630570
Functional miRNAs regulate the translation and cleavage of mRNAs by sequence-specific interaction with the 3′-UTR [reviewed in (1)].
[ "1", "2", "3", "4" ]
132
42,789
0
false
Functional miRNAs regulate the translation and cleavage of mRNAs by sequence-specific interaction with the 3′-UTR.
[ "reviewed in (1)" ]
Functional miRNAs regulate the translation and cleavage of mRNAs by sequence-specific interaction with the 3′-UTR.
true
true
true
true
true
7,415
1
INTRODUCTION
1
2
[ "B1", "B2", "B3", "B4" ]
20,466,808
pmid-19255566|pmid-14744438|pmid-16557279|pmid-19630570
MiRNAs are involved in the regulation of most physiological processes, including differentiation, development and apoptosis (2).
[ "1", "2", "3", "4" ]
128
42,790
1
false
MiRNAs are involved in the regulation of most physiological processes, including differentiation, development and apoptosis.
[ "2" ]
MiRNAs are involved in the regulation of most physiological processes, including differentiation, development and apoptosis.
true
true
true
true
true
7,415
1
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4" ]
20,466,808
pmid-19255566|pmid-14744438|pmid-16557279|pmid-19630570
In cancer, miRNAs may exert oncogenic function by inhibiting tumor suppressor genes or may act as tumor suppressors by inhibiting oncogenes (3,4).
[ "1", "2", "3", "4" ]
146
42,791
0
false
In cancer, miRNAs may exert oncogenic function by inhibiting tumor suppressor genes or may act as tumor suppressors by inhibiting oncogenes.
[ "3,4" ]
In cancer, miRNAs may exert oncogenic function by inhibiting tumor suppressor genes or may act as tumor suppressors by inhibiting oncogenes.
true
true
true
true
true
7,415
2
INTRODUCTION
1
5–7
[ "B5 B6 B7", "B8 B9 B10 B11 B12 B13 B14 B15 B16 B17 B18 B19 B20 B21", "B22", "B23" ]
20,466,808
pmid-12612655|pmid-17586306|pmid-12901961|pmid-18230126|pmid-17283129|pmid-18505919|pmid-19713529|pmid-18493594|pmid-17604727|pmid-18940866|pmid-19531210|pmid-17943719|pmid-19706822|pmid-18504438|pmid-17297439|pmid-19924232|pmid-19946337|pmid-18639376|pmid-19199973
Neuroblastoma (NB) is the most common extracranial, solid tumor of childhood, comprising 15% of childhood cancer deaths [reviewed in (5–7)].
[ "5–7", "8–21", "22", "23" ]
140
42,792
0
false
Neuroblastoma (NB) is the most common extracranial, solid tumor of childhood, comprising 15% of childhood cancer deaths.
[ "reviewed in (5–7)" ]
Neuroblastoma (NB) is the most common extracranial, solid tumor of childhood, comprising 15% of childhood cancer deaths.
true
true
true
true
true
7,416
2
INTRODUCTION
1
5–7
[ "B5 B6 B7", "B8 B9 B10 B11 B12 B13 B14 B15 B16 B17 B18 B19 B20 B21", "B22", "B23" ]
20,466,808
pmid-12612655|pmid-17586306|pmid-12901961|pmid-18230126|pmid-17283129|pmid-18505919|pmid-19713529|pmid-18493594|pmid-17604727|pmid-18940866|pmid-19531210|pmid-17943719|pmid-19706822|pmid-18504438|pmid-17297439|pmid-19924232|pmid-19946337|pmid-18639376|pmid-19199973
NB is characterized by a broad clinical and biological heterogeneity.
[ "5–7", "8–21", "22", "23" ]
69
42,793
0
false
NB is characterized by a broad clinical and biological heterogeneity.
[]
NB is characterized by a broad clinical and biological heterogeneity.
true
true
true
true
true
7,416
2
INTRODUCTION
1
5–7
[ "B5 B6 B7", "B8 B9 B10 B11 B12 B13 B14 B15 B16 B17 B18 B19 B20 B21", "B22", "B23" ]
20,466,808
pmid-12612655|pmid-17586306|pmid-12901961|pmid-18230126|pmid-17283129|pmid-18505919|pmid-19713529|pmid-18493594|pmid-17604727|pmid-18940866|pmid-19531210|pmid-17943719|pmid-19706822|pmid-18504438|pmid-17297439|pmid-19924232|pmid-19946337|pmid-18639376|pmid-19199973
Patients with favorable NB have a very good prognosis as tumor regression or differentiation is often observed even in the absence of specific treatment.
[ "5–7", "8–21", "22", "23" ]
153
42,794
0
false
Patients with favorable NB have a very good prognosis as tumor regression or differentiation is often observed even in the absence of specific treatment.
[]
Patients with favorable NB have a very good prognosis as tumor regression or differentiation is often observed even in the absence of specific treatment.
true
true
true
true
true
7,416
2
INTRODUCTION
1
5–7
[ "B5 B6 B7", "B8 B9 B10 B11 B12 B13 B14 B15 B16 B17 B18 B19 B20 B21", "B22", "B23" ]
20,466,808
pmid-12612655|pmid-17586306|pmid-12901961|pmid-18230126|pmid-17283129|pmid-18505919|pmid-19713529|pmid-18493594|pmid-17604727|pmid-18940866|pmid-19531210|pmid-17943719|pmid-19706822|pmid-18504438|pmid-17297439|pmid-19924232|pmid-19946337|pmid-18639376|pmid-19199973
In contrast, most patients with highly aggressive NB, often characterized by amplification of the MYCN oncogene, die despite intensive therapy.
[ "5–7", "8–21", "22", "23" ]
143
42,795
0
false
In contrast, most patients with highly aggressive NB, often characterized by amplification of the MYCN oncogene, die despite intensive therapy.
[]
In contrast, most patients with highly aggressive NB, often characterized by amplification of the MYCN oncogene, die despite intensive therapy.
true
true
true
true
true
7,416
2
INTRODUCTION
1
8–21
[ "B5 B6 B7", "B8 B9 B10 B11 B12 B13 B14 B15 B16 B17 B18 B19 B20 B21", "B22", "B23" ]
20,466,808
pmid-12612655|pmid-17586306|pmid-12901961|pmid-18230126|pmid-17283129|pmid-18505919|pmid-19713529|pmid-18493594|pmid-17604727|pmid-18940866|pmid-19531210|pmid-17943719|pmid-19706822|pmid-18504438|pmid-17297439|pmid-19924232|pmid-19946337|pmid-18639376|pmid-19199973
Most recently, attempts were made to analyze the contribution of miRNAs to NB tumor biology (8–21), reviewed in (22,23).
[ "5–7", "8–21", "22", "23" ]
120
42,796
1
false
Most recently, attempts were made to analyze the contribution of miRNAs to NB tumor biology, reviewed in.
[ "8–21", "22,23" ]
Most recently, attempts were made to analyze the contribution of miRNAs to NB tumor biology, reviewed in.
true
true
true
true
true
7,416
3
INTRODUCTION
1
9
[ "B9", "B15", "B16", "B19", "B12", "B17", "B10", "B18", "B19", "B8" ]
20,466,808
pmid-17283129|pmid-19531210|pmid-17943719|pmid-17297439|pmid-18493594|pmid-19706822|pmid-18505919|pmid-18504438|pmid-17297439|pmid-18230126
Several groups analyzed miRNA expression in primary NBs using miRNA microarrays or high-throughput RT-qPCR.
[ "9", "15", "16", "19", "12", "17", "10", "18", "19", "8" ]
107
42,797
0
false
Several groups analyzed miRNA expression in primary NBs using miRNA microarrays or high-throughput RT-qPCR.
[]
Several groups analyzed miRNA expression in primary NBs using miRNA microarrays or high-throughput RT-qPCR.
true
true
true
true
true
7,417
3
INTRODUCTION
1
9
[ "B9", "B15", "B16", "B19", "B12", "B17", "B10", "B18", "B19", "B8" ]
20,466,808
pmid-17283129|pmid-19531210|pmid-17943719|pmid-17297439|pmid-18493594|pmid-19706822|pmid-18505919|pmid-18504438|pmid-17297439|pmid-18230126
They reported broad deregulation of miRNA patterns correlated with MYCN amplification, 11q deletion and prognosis (9,15,16,19).
[ "9", "15", "16", "19", "12", "17", "10", "18", "19", "8" ]
127
42,798
0
false
They reported broad deregulation of miRNA patterns correlated with MYCN amplification, 11q deletion and prognosis.
[ "9,15,16,19" ]
They reported broad deregulation of miRNA patterns correlated with MYCN amplification, 11q deletion and prognosis.
true
true
true
true
true
7,417
3
INTRODUCTION
1
9
[ "B9", "B15", "B16", "B19", "B12", "B17", "B10", "B18", "B19", "B8" ]
20,466,808
pmid-17283129|pmid-19531210|pmid-17943719|pmid-17297439|pmid-18493594|pmid-19706822|pmid-18505919|pmid-18504438|pmid-17297439|pmid-18230126
Further functional analysis identified miRNAs of the MYCN-regulated miR-17-92 cluster to be important for proliferation and migration as well as invasive growth of NB cells (12, 17).
[ "9", "15", "16", "19", "12", "17", "10", "18", "19", "8" ]
182
42,799
0
false
Further functional analysis identified miRNAs of the MYCN-regulated miR-17-92 cluster to be important for proliferation and migration as well as invasive growth of NB cells.
[ "12, 17" ]
Further functional analysis identified miRNAs of the MYCN-regulated miR-17-92 cluster to be important for proliferation and migration as well as invasive growth of NB cells.
true
true
true
true
true
7,417
3
INTRODUCTION
1
9
[ "B9", "B15", "B16", "B19", "B12", "B17", "B10", "B18", "B19", "B8" ]
20,466,808
pmid-17283129|pmid-19531210|pmid-17943719|pmid-17297439|pmid-18493594|pmid-19706822|pmid-18505919|pmid-18504438|pmid-17297439|pmid-18230126
Furthermore, miR-34a, located in a region of frequent chromosomal loss, appears to directly downregulate expression of the MYCN oncogene (10,18,19).
[ "9", "15", "16", "19", "12", "17", "10", "18", "19", "8" ]
148
42,800
0
false
Furthermore, miR-34a, located in a region of frequent chromosomal loss, appears to directly downregulate expression of the MYCN oncogene.
[ "10,18,19" ]
Furthermore, miR-34a, located in a region of frequent chromosomal loss, appears to directly downregulate expression of the MYCN oncogene.
true
true
true
true
true
7,417
3
INTRODUCTION
1
8
[ "B9", "B15", "B16", "B19", "B12", "B17", "B10", "B18", "B19", "B8" ]
20,466,808
pmid-17283129|pmid-19531210|pmid-17943719|pmid-17297439|pmid-18493594|pmid-19706822|pmid-18505919|pmid-18504438|pmid-17297439|pmid-18230126
The only attempt to clone NB-specific miRNAs from primary tumors was compromised by the low coverage of the generated libraries (8).
[ "9", "15", "16", "19", "12", "17", "10", "18", "19", "8" ]
132
42,801
1
false
The only attempt to clone NB-specific miRNAs from primary tumors was compromised by the low coverage of the generated libraries.
[ "8" ]
The only attempt to clone NB-specific miRNAs from primary tumors was compromised by the low coverage of the generated libraries.
true
true
true
true
true
7,417
4
INTRODUCTION
1
24–28
[ "B24 B25 B26 B27 B28", "B13", "B26", "B29", "B26", "B30" ]
20,466,808
pmid-18849523|pmid-19564845|pmid-18285502|pmid-19508715|pmid-19390579|pmid-17604727|pmid-18285502|pmid-17599088|pmid-18285502|pmid-15035981
With the availability of high-throughput next-generation sequencing (NGS) (24–28), the technical drawbacks of probe-based methodologies, especially restriction to detection of only previously known sequences, can be overcome.
[ "24–28", "13", "26", "29", "26", "30" ]
225
42,802
1
false
With the availability of high-throughput next-generation sequencing (NGS), the technical drawbacks of probe-based methodologies, especially restriction to detection of only previously known sequences, can be overcome.
[ "24–28" ]
With the availability of high-throughput next-generation sequencing (NGS), the technical drawbacks of probe-based methodologies, especially restriction to detection of only previously known sequences, can be overcome.
true
true
true
true
true
7,418
4
INTRODUCTION
1
24–28
[ "B24 B25 B26 B27 B28", "B13", "B26", "B29", "B26", "B30" ]
20,466,808
pmid-18849523|pmid-19564845|pmid-18285502|pmid-19508715|pmid-19390579|pmid-17604727|pmid-18285502|pmid-17599088|pmid-18285502|pmid-15035981
As miRNAs are sequenced directly, information about SNPs as well as post-transcriptional RNA editing, 3′-terminal addition of single nucleotides and variation in miRNA length becomes available for further analysis (13,26,29).
[ "24–28", "13", "26", "29", "26", "30" ]
225
42,803
0
false
As miRNAs are sequenced directly, information about SNPs as well as post-transcriptional RNA editing, 3′-terminal addition of single nucleotides and variation in miRNA length becomes available for further analysis.
[ "13,26,29" ]
As miRNAs are sequenced directly, information about SNPs as well as post-transcriptional RNA editing, 3′-terminal addition of single nucleotides and variation in miRNA length becomes available for further analysis.
true
true
true
true
true
7,418
4
INTRODUCTION
1
26
[ "B24 B25 B26 B27 B28", "B13", "B26", "B29", "B26", "B30" ]
20,466,808
pmid-18849523|pmid-19564845|pmid-18285502|pmid-19508715|pmid-19390579|pmid-17604727|pmid-18285502|pmid-17599088|pmid-18285502|pmid-15035981
It has become evident that post-transcriptional modifications of miRNAs produce multiple mature variants, which are referred to as isomiRs (26).
[ "24–28", "13", "26", "29", "26", "30" ]
144
42,804
1
false
It has become evident that post-transcriptional modifications of miRNAs produce multiple mature variants, which are referred to as isomiRs.
[ "26" ]
It has become evident that post-transcriptional modifications of miRNAs produce multiple mature variants, which are referred to as isomiRs.
true
true
true
true
true
7,418
4
INTRODUCTION
1
30
[ "B24 B25 B26 B27 B28", "B13", "B26", "B29", "B26", "B30" ]
20,466,808
pmid-18849523|pmid-19564845|pmid-18285502|pmid-19508715|pmid-19390579|pmid-17604727|pmid-18285502|pmid-17599088|pmid-18285502|pmid-15035981
NGS of the small RNA transcriptome also provides data on the expression of other small RNAs, such as piRNAs, snoRNAs and other less well characterized short, regulatory RNAs that do not meet the criteria of miRNAs (30).
[ "24–28", "13", "26", "29", "26", "30" ]
219
42,805
1
false
NGS of the small RNA transcriptome also provides data on the expression of other small RNAs, such as piRNAs, snoRNAs and other less well characterized short, regulatory RNAs that do not meet the criteria of miRNAs.
[ "30" ]
NGS of the small RNA transcriptome also provides data on the expression of other small RNAs, such as piRNAs, snoRNAs and other less well characterized short, regulatory RNAs that do not meet the criteria of miRNAs.
true
true
true
true
true
7,418
5
INTRODUCTION
1
14
[ "B14" ]
20,466,808
pmid-18940866
We compared the small RNA transcriptomes of five favorable and five unfavorable, MYCN-amplified NBs by means of ultra-deep NGS using the SOLiD system (Applied Biosystems).
[ "14" ]
171
42,806
0
false
We compared the small RNA transcriptomes of five favorable and five unfavorable, MYCN-amplified NBs by means of ultra-deep NGS using the SOLiD system (Applied Biosystems).
[]
We compared the small RNA transcriptomes of five favorable and five unfavorable, MYCN-amplified NBs by means of ultra-deep NGS using the SOLiD system (Applied Biosystems).
true
true
true
true
true
7,419
5
INTRODUCTION
1
14
[ "B14" ]
20,466,808
pmid-18940866
NGS results were compared with miRNA expression patterns generated for the same samples by high-throughput RT-qPCR to correlate results from both systems and validate miRNA expression patterns (14).
[ "14" ]
198
42,807
1
false
NGS results were compared with miRNA expression patterns generated for the same samples by high-throughput RT-qPCR to correlate results from both systems and validate miRNA expression patterns.
[ "14" ]
NGS results were compared with miRNA expression patterns generated for the same samples by high-throughput RT-qPCR to correlate results from both systems and validate miRNA expression patterns.
true
true
true
true
true
7,419
5
INTRODUCTION
1
14
[ "B14" ]
20,466,808
pmid-18940866
Favorable and unfavorable NBs were distinguishable by hierarchical clustering of miRNA patterns.
[ "14" ]
96
42,808
0
false
Favorable and unfavorable NBs were distinguishable by hierarchical clustering of miRNA patterns.
[]
Favorable and unfavorable NBs were distinguishable by hierarchical clustering of miRNA patterns.
true
true
true
true
true
7,419
5
INTRODUCTION
1
14
[ "B14" ]
20,466,808
pmid-18940866
Expression of single miRNAs also differed significantly between the two groups.
[ "14" ]
79
42,809
0
false
Expression of single miRNAs also differed significantly between the two groups.
[]
Expression of single miRNAs also differed significantly between the two groups.
true
true
true
true
true
7,419
5
INTRODUCTION
1
14
[ "B14" ]
20,466,808
pmid-18940866
We subsequently analyzed RNA editing as well as occurrence and frequency of isomiR expression, and identified 13 candidates for novel miRNAs of which three were further validated in 70 primary NBs using RT-qPCR.
[ "14" ]
211
42,810
0
false
We subsequently analyzed RNA editing as well as occurrence and frequency of isomiR expression, and identified 13 candidates for novel miRNAs of which three were further validated in 70 primary NBs using RT-qPCR.
[]
We subsequently analyzed RNA editing as well as occurrence and frequency of isomiR expression, and identified 13 candidates for novel miRNAs of which three were further validated in 70 primary NBs using RT-qPCR.
true
true
true
true
true
7,419
5
INTRODUCTION
1
14
[ "B14" ]
20,466,808
pmid-18940866
To our knowledge, this is the first comprehensive presentation of the composition of the small RNA transcriptome of a primary tumor, using NB as a model system.
[ "14" ]
160
42,811
0
false
To our knowledge, this is the first comprehensive presentation of the composition of the small RNA transcriptome of a primary tumor, using NB as a model system.
[]
To our knowledge, this is the first comprehensive presentation of the composition of the small RNA transcriptome of a primary tumor, using NB as a model system.
true
true
true
true
true
7,419
5
INTRODUCTION
1
14
[ "B14" ]
20,466,808
pmid-18940866
By comparing tumors of divergent biology and clinical outcome, we also provide insights into the heterogeneity of the small RNA transcriptomes in cancer.
[ "14" ]
153
42,812
0
false
By comparing tumors of divergent biology and clinical outcome, we also provide insights into the heterogeneity of the small RNA transcriptomes in cancer.
[]
By comparing tumors of divergent biology and clinical outcome, we also provide insights into the heterogeneity of the small RNA transcriptomes in cancer.
true
true
true
true
true
7,419
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B5" ]
18,162,713
pmid-7996359|pmid-8032367|pmid-8219187|pmid-11238097|pmid-7996359|pmid-7795648|pmid-8961624|pmid-14612666|pmid-11242115
Wiskott-Aldrich syndrome (WAS) (Online Mendelian Inheritance in Man [OMIM] 301000) is an X-linked recessive disorder characterized by thrombocytopenia, eczema, and immunodeficiency.
[ "1", "2", "3", "5" ]
181
42,813
0
false
Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder characterized by thrombocytopenia, eczema, and immunodeficiency.
[ "Online Mendelian Inheritance in Man [OMIM] 301000" ]
Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder characterized by thrombocytopenia, eczema, and immunodeficiency.
true
true
true
true
true
7,420
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B5" ]
18,162,713
pmid-7996359|pmid-8032367|pmid-8219187|pmid-11238097|pmid-7996359|pmid-7795648|pmid-8961624|pmid-14612666|pmid-11242115
Clinical symptoms include petechiae, bloody diarrhea, inability to generate antibodies against polysaccharide antigens, and in some cases, autoimmune manifestations.
[ "1", "2", "3", "5" ]
165
42,814
0
false
Clinical symptoms include petechiae, bloody diarrhea, inability to generate antibodies against polysaccharide antigens, and in some cases, autoimmune manifestations.
[]
Clinical symptoms include petechiae, bloody diarrhea, inability to generate antibodies against polysaccharide antigens, and in some cases, autoimmune manifestations.
true
true
true
true
true
7,420
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B5" ]
18,162,713
pmid-7996359|pmid-8032367|pmid-8219187|pmid-11238097|pmid-7996359|pmid-7795648|pmid-8961624|pmid-14612666|pmid-11242115
Affected boys often die because of malignant tumors, particularly lymphoma (1, 2).
[ "1", "2", "3", "5" ]
82
42,815
0
false
Affected boys often die because of malignant tumors, particularly lymphoma.
[ "1, 2" ]
Affected boys often die because of malignant tumors, particularly lymphoma.
true
true
true
true
true
7,420
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B5" ]
18,162,713
pmid-7996359|pmid-8032367|pmid-8219187|pmid-11238097|pmid-7996359|pmid-7795648|pmid-8961624|pmid-14612666|pmid-11242115
Treatments for WAS include antimicrobial therapy for infections, intravenous immune globulin, splenectomy for thrombocytopenia, and allogeneic bone marrow transplantation (3-5).
[ "1", "2", "3", "5" ]
177
42,816
0
false
Treatments for WAS include antimicrobial therapy for infections, intravenous immune globulin, splenectomy for thrombocytopenia, and allogeneic bone marrow transplantation.
[ "3-5" ]
Treatments for WAS include antimicrobial therapy for infections, intravenous immune globulin, splenectomy for thrombocytopenia, and allogeneic bone marrow transplantation.
true
true
true
true
true
7,420
1
INTRODUCTION
1
6
[ "B6", "B7", "B8", "B9", "B10", "B11" ]
18,162,713
pmid-8069912|pmid-8647957|pmid-7795648|pmid-8961624|pmid-14612666|pmid-11242115|NA|pmid-14612666|NA
The gene responsible for WAS was isolated, and designated the WAS gene (6).
[ "6", "7", "8", "9", "10", "11" ]
75
42,817
1
false
The gene responsible for WAS was isolated, and designated the WAS gene.
[ "6" ]
The gene responsible for WAS was isolated, and designated the WAS gene.
true
true
true
true
true
7,421
1
INTRODUCTION
1
6
[ "B6", "B7", "B8", "B9", "B10", "B11" ]
18,162,713
pmid-8069912|pmid-8647957|pmid-7795648|pmid-8961624|pmid-14612666|pmid-11242115|NA|pmid-14612666|NA
The gene is composed of 12 exons spanning approximately 9 kilobases.
[ "6", "7", "8", "9", "10", "11" ]
68
42,818
0
false
The gene is composed of 12 exons spanning approximately 9 kilobases.
[]
The gene is composed of 12 exons spanning approximately 9 kilobases.
true
true
true
true
true
7,421