Datasets:
vgainullin
/
xciting_data

Dataset card Data Studio Files
xet
 Community
1
paragraph_index
int64
sec
string
p_has_citation
int64
cites
string
citeids
list
pmid
int64
cited_id
string
sentences
string
all_sent_cites
list
sent_len
int64
sentence_batch_index
int64
sent_has_citation
float64
qc_fail
bool
cited_sentence
string
cites_in_sentence
list
cln_sentence
string
is_cap
bool
is_alpha
bool
ends_wp
bool
cit_qc
bool
lgtm
bool
__index_level_0__
int64
0
DISCUSSION
1
Rocheleau et al., 2006
[ "bib23", "bib45", "bib6", "bib23" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
Thus, at 0 mV the activation gate machinery of the channel is predicted to be undergoing large movements while equilibrating between open and closed states.
[ "Rocheleau et al., 2006", "Xu et al., 2008", "Chung et al., 2009", "Rocheleau et al., 2006" ]
156
38,216
0
false
Thus, at 0 mV the activation gate machinery of the channel is predicted to be undergoing large movements while equilibrating between open and closed states.
[]
Thus, at 0 mV the activation gate machinery of the channel is predicted to be undergoing large movements while equilibrating between open and closed states.
true
true
true
true
true
6,555
0
DISCUSSION
1
Rocheleau et al., 2006
[ "bib23", "bib45", "bib6", "bib23" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
Moreover, there is evidence that the E1 TM domain rotates during gating (Xu et al., 2008; Chung et al., 2009), which if propagated to the C terminus would also promote widespread cross-linking.
[ "Rocheleau et al., 2006", "Xu et al., 2008", "Chung et al., 2009", "Rocheleau et al., 2006" ]
193
38,217
0
false
Moreover, there is evidence that the E1 TM domain rotates during gating, which if propagated to the C terminus would also promote widespread cross-linking.
[ "Xu et al., 2008; Chung et al., 2009" ]
Moreover, there is evidence that the E1 TM domain rotates during gating, which if propagated to the C terminus would also promote widespread cross-linking.
true
true
true
true
true
6,555
0
DISCUSSION
1
Rocheleau et al., 2006
[ "bib23", "bib45", "bib6", "bib23" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
Accordingly, the reactive Q1 cysteine mutants identified here form cross-links with most of the E1 cysteine mutants studied.
[ "Rocheleau et al., 2006", "Xu et al., 2008", "Chung et al., 2009", "Rocheleau et al., 2006" ]
124
38,218
0
false
Accordingly, the reactive Q1 cysteine mutants identified here form cross-links with most of the E1 cysteine mutants studied.
[]
Accordingly, the reactive Q1 cysteine mutants identified here form cross-links with most of the E1 cysteine mutants studied.
true
true
true
true
true
6,555
0
DISCUSSION
1
Rocheleau et al., 2006
[ "bib23", "bib45", "bib6", "bib23" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
In spite of this caveat, we were able to identify three residues in Q1 (H363C, P369C, and I257C) that readily formed disulfide bonds with cysteine residues in the E1 C-terminal domain (Figs.
[ "Rocheleau et al., 2006", "Xu et al., 2008", "Chung et al., 2009", "Rocheleau et al., 2006" ]
190
38,219
0
false
In spite of this caveat, we were able to identify three residues in Q1 (H363C, P369C, and I257C) that readily formed disulfide bonds with cysteine residues in the E1 C-terminal domain (Figs.
[]
In spite of this caveat, we were able to identify three residues in Q1 that readily formed disulfide bonds with cysteine residues in the E1 C-terminal domain (Figs.
true
true
true
true
true
6,555
0
DISCUSSION
1
Rocheleau et al., 2006
[ "bib23", "bib45", "bib6", "bib23" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
Statistical analysis demonstrated that there was some selectivity for certain E1 residues: H363C with H73C, S74C, and D76C;
[ "Rocheleau et al., 2006", "Xu et al., 2008", "Chung et al., 2009", "Rocheleau et al., 2006" ]
123
38,220
0
false
Statistical analysis demonstrated that there was some selectivity for certain E1 residues: H363C with H73C, S74C, and D76C;
[]
Statistical analysis demonstrated that there was some selectivity for certain E1 residues: H363C with H73C, S74C, and D76C;
true
true
false
true
false
6,555
0
DISCUSSION
1
Rocheleau et al., 2006
[ "bib23", "bib45", "bib6", "bib23" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
P369C with D76C.
[ "Rocheleau et al., 2006", "Xu et al., 2008", "Chung et al., 2009", "Rocheleau et al., 2006" ]
16
38,221
0
false
P369C with D76C.
[]
P369C with D76C.
true
true
true
true
true
6,555
0
DISCUSSION
1
Rocheleau et al., 2006
[ "bib23", "bib45", "bib6", "bib23" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
Based on a previous periodicity analysis of mutation-induced perturbations of Q1–E1 complex function (Rocheleau et al., 2006), these three residues are predicted to face the Q1 channel.
[ "Rocheleau et al., 2006", "Xu et al., 2008", "Chung et al., 2009", "Rocheleau et al., 2006" ]
185
38,222
1
false
Based on a previous periodicity analysis of mutation-induced perturbations of Q1–E1 complex function, these three residues are predicted to face the Q1 channel.
[ "Rocheleau et al., 2006" ]
Based on a previous periodicity analysis of mutation-induced perturbations of Q1–E1 complex function, these three residues are predicted to face the Q1 channel.
true
true
true
true
true
6,555
0
DISCUSSION
1
Rocheleau et al., 2006
[ "bib23", "bib45", "bib6", "bib23" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
Although not statistically significant, visual inspection of the biochemical reactivity of the E1 cysteine mutants uncannily mirrors the previously studied functionally disruptive alanine mutants: 73, 74, 76, 78, 81, and 82.
[ "Rocheleau et al., 2006", "Xu et al., 2008", "Chung et al., 2009", "Rocheleau et al., 2006" ]
224
38,223
0
false
Although not statistically significant, visual inspection of the biochemical reactivity of the E1 cysteine mutants uncannily mirrors the previously studied functionally disruptive alanine mutants: 73, 74, 76, 78, 81, and 82.
[]
Although not statistically significant, visual inspection of the biochemical reactivity of the E1 cysteine mutants uncannily mirrors the previously studied functionally disruptive alanine mutants: 73, 74, 76, 78, 81, and 82.
true
true
true
true
true
6,555
0
DISCUSSION
1
Rocheleau et al., 2006
[ "bib23", "bib45", "bib6", "bib23" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
Given that the cross-linked Q1–E1 subunits arose from Q1–E1 complexes that were properly folded (presence of mature glycosylation; Figs.
[ "Rocheleau et al., 2006", "Xu et al., 2008", "Chung et al., 2009", "Rocheleau et al., 2006" ]
136
38,224
0
false
Given that the cross-linked Q1–E1 subunits arose from Q1–E1 complexes that were properly folded (presence of mature glycosylation; Figs.
[]
Given that the cross-linked Q1–E1 subunits arose from Q1–E1 complexes that were properly folded (presence of mature glycosylation; Figs.
true
true
true
true
true
6,555
0
DISCUSSION
1
Rocheleau et al., 2006
[ "bib23", "bib45", "bib6", "bib23" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
2–4) with IKs kinetics (Fig.
[ "Rocheleau et al., 2006", "Xu et al., 2008", "Chung et al., 2009", "Rocheleau et al., 2006" ]
28
38,225
0
false
2–4) with IKs kinetics (Fig.
[]
2–4) with IKs kinetics (Fig.
false
false
true
true
false
6,555
0
DISCUSSION
1
Rocheleau et al., 2006
[ "bib23", "bib45", "bib6", "bib23" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
5 A and Fig.
[ "Rocheleau et al., 2006", "Xu et al., 2008", "Chung et al., 2009", "Rocheleau et al., 2006" ]
12
38,226
0
false
5 A and Fig.
[]
5 A and Fig.
false
false
true
true
false
6,555
0
DISCUSSION
1
Rocheleau et al., 2006
[ "bib23", "bib45", "bib6", "bib23" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
S2), and at the cell surface (Fig.
[ "Rocheleau et al., 2006", "Xu et al., 2008", "Chung et al., 2009", "Rocheleau et al., 2006" ]
34
38,227
0
false
S2), and at the cell surface (Fig.
[]
S2), and at the cell surface (Fig.
true
true
true
true
true
6,555
0
DISCUSSION
1
Rocheleau et al., 2006
[ "bib23", "bib45", "bib6", "bib23" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
S3 B), we conclude that these mutant Q1–E1 complexes have maintained their wild-type structure.
[ "Rocheleau et al., 2006", "Xu et al., 2008", "Chung et al., 2009", "Rocheleau et al., 2006" ]
95
38,228
0
false
S3 B), we conclude that these mutant Q1–E1 complexes have maintained their wild-type structure.
[]
S3 B), we conclude that these mutant Q1–E1 complexes have maintained their wild-type structure.
true
true
true
true
true
6,555
0
DISCUSSION
1
Rocheleau et al., 2006
[ "bib23", "bib45", "bib6", "bib23" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
Thus, our data show that the E1 C-terminal domain forms a protein–protein interaction with Q1 residues below the S6 activation gate and in the S4–S5 linker.
[ "Rocheleau et al., 2006", "Xu et al., 2008", "Chung et al., 2009", "Rocheleau et al., 2006" ]
156
38,229
0
false
Thus, our data show that the E1 C-terminal domain forms a protein–protein interaction with Q1 residues below the S6 activation gate and in the S4–S5 linker.
[]
Thus, our data show that the E1 C-terminal domain forms a protein–protein interaction with Q1 residues below the S6 activation gate and in the S4–S5 linker.
true
true
true
true
true
6,555
1
DISCUSSION
1
Chung et al., 2009
[ "bib6" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
Surprisingly, oxidation of two of the biochemically reactive Q1 cysteine residues (P369C and I257C) in whole cell recordings had no measurable effect on Q1–E1 complex function when paired with a reactive E1 cysteine mutant (Fig.
[ "Chung et al., 2009" ]
228
38,230
0
false
Surprisingly, oxidation of two of the biochemically reactive Q1 cysteine residues (P369C and I257C) in whole cell recordings had no measurable effect on Q1–E1 complex function when paired with a reactive E1 cysteine mutant (Fig.
[]
Surprisingly, oxidation of two of the biochemically reactive Q1 cysteine residues in whole cell recordings had no measurable effect on Q1–E1 complex function when paired with a reactive E1 cysteine mutant (Fig.
true
true
true
true
true
6,556
1
DISCUSSION
1
Chung et al., 2009
[ "bib6" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
Lack of functional phenotype for these two Q1 mutants may be due to diminished reactivity of peroxide in the reducing environment of the cell, even though we increased the concentration 10-fold for these intact cell experiments.
[ "Chung et al., 2009" ]
228
38,231
0
false
Lack of functional phenotype for these two Q1 mutants may be due to diminished reactivity of peroxide in the reducing environment of the cell, even though we increased the concentration 10-fold for these intact cell experiments.
[]
Lack of functional phenotype for these two Q1 mutants may be due to diminished reactivity of peroxide in the reducing environment of the cell, even though we increased the concentration 10-fold for these intact cell experiments.
true
true
true
true
true
6,556
1
DISCUSSION
1
Chung et al., 2009
[ "bib6" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
It is also possible that these two Q1 residues are indeed forming a cross-link with the E1 subunit, but the disulfide bond does not hinder the voltage gating of the complex, and thus function is unaffected.
[ "Chung et al., 2009" ]
206
38,232
0
false
It is also possible that these two Q1 residues are indeed forming a cross-link with the E1 subunit, but the disulfide bond does not hinder the voltage gating of the complex, and thus function is unaffected.
[]
It is also possible that these two Q1 residues are indeed forming a cross-link with the E1 subunit, but the disulfide bond does not hinder the voltage gating of the complex, and thus function is unaffected.
true
true
true
true
true
6,556
1
DISCUSSION
1
Chung et al., 2009
[ "bib6" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
A similar functionally non-disruptive cross-link hypothesis has been proposed for extracellular biochemical cross-links that do not perturb Q1–E1 function (Chung et al., 2009).
[ "Chung et al., 2009" ]
176
38,233
1
false
A similar functionally non-disruptive cross-link hypothesis has been proposed for extracellular biochemical cross-links that do not perturb Q1–E1 function.
[ "Chung et al., 2009" ]
A similar functionally non-disruptive cross-link hypothesis has been proposed for extracellular biochemical cross-links that do not perturb Q1–E1 function.
true
true
true
true
true
6,556
2
DISCUSSION
0
null
null
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA
In contrast to P369C and I257C, we observed rapid loss of function when H363C was in the Q1–E1 complex.
null
103
38,234
0
false
null
null
In contrast to P369C and I257C, we observed rapid loss of function when H363C was in the Q1–E1 complex.
true
true
true
true
true
6,557
2
DISCUSSION
0
null
null
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA
However, the extent of oxidant-induced current inhibition for H363C was similar for all of the E1 cysteine mutants—even for residues that showed minimal reactivity in biochemical experiments (Fig.
null
196
38,235
0
false
null
null
However, the extent of oxidant-induced current inhibition for H363C was similar for all of the E1 cysteine mutants—even for residues that showed minimal reactivity in biochemical experiments (Fig.
true
true
true
true
true
6,557
2
DISCUSSION
0
null
null
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA
This across the board loss of function suggested that H363C was forming an inter Q1 subunit cross-link, which we confirmed with the H363C–E1-cys complex in electrical recordings and nonreducing SDS-PAGE (Fig.
null
208
38,236
0
false
null
null
This across the board loss of function suggested that H363C was forming an inter Q1 subunit cross-link, which we confirmed with the H363C–E1-cys complex in electrical recordings and nonreducing SDS-PAGE (Fig.
true
true
true
true
true
6,557
2
DISCUSSION
0
null
null
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA
Although the Q1–Q1 cross-link accounted for most of the current inhibition observed with H363C, inclusion of certain E1 cysteine mutants in the complex increased the amount of oxidized-induced current inhibition (Fig.
null
217
38,237
0
false
null
null
Although the Q1–Q1 cross-link accounted for most of the current inhibition observed with H363C, inclusion of certain E1 cysteine mutants in the complex increased the amount of oxidized-induced current inhibition (Fig.
true
true
true
true
true
6,557
2
DISCUSSION
0
null
null
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA
Whether this additional reduction of current is due to a direct Q1–E1 cross-link (as was observed in biochemical experiments) or an E1 cysteine–mediated acceleration of Q1–Q1 cross-link formation is uncertain.
null
209
38,238
0
false
null
null
Whether this additional reduction of current is due to a direct Q1–E1 cross-link (as was observed in biochemical experiments) or an E1 cysteine–mediated acceleration of Q1–Q1 cross-link formation is uncertain.
true
true
true
true
true
6,557
2
DISCUSSION
0
null
null
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA
Nonetheless, either mechanism requires the E1 cysteine residue to be spatially close to the H363C residue.
null
106
38,239
0
false
null
null
Nonetheless, either mechanism requires the E1 cysteine residue to be spatially close to the H363C residue.
true
true
true
true
true
6,557
3
DISCUSSION
0
null
null
20,479,109
NA|NA
Because oxidation-induced inhibition of H363C could be monitored in whole cell recordings, we compared the rates of inhibition using two different voltage pulse protocols to determine whether cross-link formation was occurring in a state-dependent manner (Fig.
null
260
38,240
0
false
null
null
Because oxidation-induced inhibition of H363C could be monitored in whole cell recordings, we compared the rates of inhibition using two different voltage pulse protocols to determine whether cross-link formation was occurring in a state-dependent manner (Fig.
true
true
true
true
true
6,558
3
DISCUSSION
0
null
null
20,479,109
NA|NA
By exploiting the unusual gating kinetics of the Q1–E1 complex (slow activation and lack of inactivation at depolarizing potentials), we showed in intact cells that H363C predominately formed a cross-link in the closed state.
null
225
38,241
0
false
null
null
By exploiting the unusual gating kinetics of the Q1–E1 complex (slow activation and lack of inactivation at depolarizing potentials), we showed in intact cells that H363C predominately formed a cross-link in the closed state.
true
true
true
true
true
6,558
3
DISCUSSION
0
null
null
20,479,109
NA|NA
Inclusion of a cross-linkable cysteine in E1 (D76C) into the complex did not change the state dependency of oxidant-induced inhibition of H363C.
null
144
38,242
0
false
null
null
Inclusion of a cross-linkable cysteine in E1 (D76C) into the complex did not change the state dependency of oxidant-induced inhibition of H363C.
true
true
true
true
true
6,558
3
DISCUSSION
0
null
null
20,479,109
NA|NA
Thus, from these state-dependent experiments, we conclude that the H363C residues are adjacent to each other when the Q1 activation gate is closed, and D76 in E1 is also near the cytoplasmic gate in the closed state.
null
216
38,243
0
false
null
null
Thus, from these state-dependent experiments, we conclude that the H363C residues are adjacent to each other when the Q1 activation gate is closed, and D76 in E1 is also near the cytoplasmic gate in the closed state.
true
true
true
true
true
6,558
4
DISCUSSION
1
Smith et al., 2007
[ "bib32", "bib10", "bib23", "bib45", "bib6", "bib3", "bib18" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA
Using these experimental results, we generated a closed-state model of the Q1–E1 cytoplasmic region (Fig.
[ "Smith et al., 2007", "Kang et al., 2008", "Rocheleau et al., 2006", "Xu et al., 2008", "Chung et al., 2009", "H. Chen et al., 2003", "Morin and Kobertz, 2008" ]
105
38,244
0
false
Using these experimental results, we generated a closed-state model of the Q1–E1 cytoplasmic region (Fig.
[]
Using these experimental results, we generated a closed-state model of the Q1–E1 cytoplasmic region (Fig.
true
true
true
true
true
6,559
4
DISCUSSION
1
Smith et al., 2007
[ "bib32", "bib10", "bib23", "bib45", "bib6", "bib3", "bib18" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA
We fashioned our model from the predicted three-dimensional structural model of the human Q1 channel in the closed conformation (Smith et al., 2007) and the NMR structure of E1 TM domain reconstituted in lyso-myristoylphosphatidylglycerol micelles (Kang et al., 2008).
[ "Smith et al., 2007", "Kang et al., 2008", "Rocheleau et al., 2006", "Xu et al., 2008", "Chung et al., 2009", "H. Chen et al., 2003", "Morin and Kobertz, 2008" ]
268
38,245
1
false
We fashioned our model from the predicted three-dimensional structural model of the human Q1 channel in the closed conformation and the NMR structure of E1 TM domain reconstituted in lyso-myristoylphosphatidylglycerol micelles.
[ "Smith et al., 2007", "Kang et al., 2008" ]
We fashioned our model from the predicted three-dimensional structural model of the human Q1 channel in the closed conformation and the NMR structure of E1 TM domain reconstituted in lyso-myristoylphosphatidylglycerol micelles.
true
true
true
true
true
6,559
4
DISCUSSION
1
Smith et al., 2007
[ "bib32", "bib10", "bib23", "bib45", "bib6", "bib3", "bib18" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA
Unfortunately, neither structure possesses the data to model the Q1 and E1 cytoplasmic domains in their native conformation.
[ "Smith et al., 2007", "Kang et al., 2008", "Rocheleau et al., 2006", "Xu et al., 2008", "Chung et al., 2009", "H. Chen et al., 2003", "Morin and Kobertz, 2008" ]
124
38,246
0
false
Unfortunately, neither structure possesses the data to model the Q1 and E1 cytoplasmic domains in their native conformation.
[]
Unfortunately, neither structure possesses the data to model the Q1 and E1 cytoplasmic domains in their native conformation.
true
true
true
true
true
6,559
4
DISCUSSION
1
Smith et al., 2007
[ "bib32", "bib10", "bib23", "bib45", "bib6", "bib3", "bib18" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA
Therefore, we propagated the TM helices of Q1 and E1 until we reached beyond the regions of interest.
[ "Smith et al., 2007", "Kang et al., 2008", "Rocheleau et al., 2006", "Xu et al., 2008", "Chung et al., 2009", "H. Chen et al., 2003", "Morin and Kobertz, 2008" ]
101
38,247
0
false
Therefore, we propagated the TM helices of Q1 and E1 until we reached beyond the regions of interest.
[]
Therefore, we propagated the TM helices of Q1 and E1 until we reached beyond the regions of interest.
true
true
true
true
true
6,559
4
DISCUSSION
1
Rocheleau et al., 2006
[ "bib32", "bib10", "bib23", "bib45", "bib6", "bib3", "bib18" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA
For the juxtamembranous part of the E1 C terminus, we chose to introduce a kink at E1 residue P77 because we have previously shown that this domain is either a proline-kinked helix or a helix that experiences two different protein–protein interactions (Rocheleau et al., 2006).
[ "Smith et al., 2007", "Kang et al., 2008", "Rocheleau et al., 2006", "Xu et al., 2008", "Chung et al., 2009", "H. Chen et al., 2003", "Morin and Kobertz, 2008" ]
277
38,248
1
false
For the juxtamembranous part of the E1 C terminus, we chose to introduce a kink at E1 residue P77 because we have previously shown that this domain is either a proline-kinked helix or a helix that experiences two different protein–protein interactions.
[ "Rocheleau et al., 2006" ]
For the juxtamembranous part of the E1 C terminus, we chose to introduce a kink at E1 residue P77 because we have previously shown that this domain is either a proline-kinked helix or a helix that experiences two different protein–protein interactions.
true
true
true
true
true
6,559
4
DISCUSSION
1
Smith et al., 2007
[ "bib32", "bib10", "bib23", "bib45", "bib6", "bib3", "bib18" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA
To create the model of the Q1–E1 cytoplasmic region, we positioned the E1 C-terminal domain adjacent to the Q1 activation gate machinery, such that D76C, the most reactive E1 residue, was centrally located while keeping the E1 TM domain close to the S6, S1, and S4 helices of Q1 (Xu et al., 2008; Chung et al., 2009).
[ "Smith et al., 2007", "Kang et al., 2008", "Rocheleau et al., 2006", "Xu et al., 2008", "Chung et al., 2009", "H. Chen et al., 2003", "Morin and Kobertz, 2008" ]
317
38,249
0
false
To create the model of the Q1–E1 cytoplasmic region, we positioned the E1 C-terminal domain adjacent to the Q1 activation gate machinery, such that D76C, the most reactive E1 residue, was centrally located while keeping the E1 TM domain close to the S6, S1, and S4 helices of Q1.
[ "Xu et al., 2008; Chung et al., 2009" ]
To create the model of the Q1–E1 cytoplasmic region, we positioned the E1 C-terminal domain adjacent to the Q1 activation gate machinery, such that D76C, the most reactive E1 residue, was centrally located while keeping the E1 TM domain close to the S6, S1, and S4 helices of Q1.
true
true
true
true
true
6,559
4
DISCUSSION
1
Smith et al., 2007
[ "bib32", "bib10", "bib23", "bib45", "bib6", "bib3", "bib18" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA
Because the cytoplasmic domains are not based on crystallographic data or NMR restraints, no computer simulations or docking were used; however, a visual inspection of the superimposed structures was performed to exclude any imposition of van der Waals volumes.
[ "Smith et al., 2007", "Kang et al., 2008", "Rocheleau et al., 2006", "Xu et al., 2008", "Chung et al., 2009", "H. Chen et al., 2003", "Morin and Kobertz, 2008" ]
261
38,250
0
false
Because the cytoplasmic domains are not based on crystallographic data or NMR restraints, no computer simulations or docking were used; however, a visual inspection of the superimposed structures was performed to exclude any imposition of van der Waals volumes.
[]
Because the cytoplasmic domains are not based on crystallographic data or NMR restraints, no computer simulations or docking were used; however, a visual inspection of the superimposed structures was performed to exclude any imposition of van der Waals volumes.
true
true
true
true
true
6,559
4
DISCUSSION
1
Smith et al., 2007
[ "bib32", "bib10", "bib23", "bib45", "bib6", "bib3", "bib18" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA
Only one of the two E1 subunits is shown in Fig.
[ "Smith et al., 2007", "Kang et al., 2008", "Rocheleau et al., 2006", "Xu et al., 2008", "Chung et al., 2009", "H. Chen et al., 2003", "Morin and Kobertz, 2008" ]
48
38,251
0
false
Only one of the two E1 subunits is shown in Fig.
[]
Only one of the two E1 subunits is shown in Fig.
true
true
true
true
true
6,559
4
DISCUSSION
1
Smith et al., 2007
[ "bib32", "bib10", "bib23", "bib45", "bib6", "bib3", "bib18" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA
7 (H. Chen et al., 2003; Morin and Kobertz, 2008).
[ "Smith et al., 2007", "Kang et al., 2008", "Rocheleau et al., 2006", "Xu et al., 2008", "Chung et al., 2009", "H. Chen et al., 2003", "Morin and Kobertz, 2008" ]
50
38,252
0
false
7.
[ "H. Chen et al., 2003; Morin and Kobertz, 2008" ]
7.
false
false
true
true
false
6,559
4
DISCUSSION
1
Smith et al., 2007
[ "bib32", "bib10", "bib23", "bib45", "bib6", "bib3", "bib18" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA
The model provocatively intimates that the E1 C-terminal domains may encumber the Q1 activation gate machinery, slowing down the transition from closed to open and leading to the generation of the cardiac IKs current.
[ "Smith et al., 2007", "Kang et al., 2008", "Rocheleau et al., 2006", "Xu et al., 2008", "Chung et al., 2009", "H. Chen et al., 2003", "Morin and Kobertz, 2008" ]
217
38,253
0
false
The model provocatively intimates that the E1 C-terminal domains may encumber the Q1 activation gate machinery, slowing down the transition from closed to open and leading to the generation of the cardiac IKs current.
[]
The model provocatively intimates that the E1 C-terminal domains may encumber the Q1 activation gate machinery, slowing down the transition from closed to open and leading to the generation of the cardiac IKs current.
true
true
true
true
true
6,559
4
DISCUSSION
1
Smith et al., 2007
[ "bib32", "bib10", "bib23", "bib45", "bib6", "bib3", "bib18" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA
If our model is operational, the slowed activation of Q1–E1 complexes could arise from either the specific Q1–E1 interactions identified here, or by nonspecific obstruction of activation gate opening by the E1 C terminus.
[ "Smith et al., 2007", "Kang et al., 2008", "Rocheleau et al., 2006", "Xu et al., 2008", "Chung et al., 2009", "H. Chen et al., 2003", "Morin and Kobertz, 2008" ]
221
38,254
0
false
If our model is operational, the slowed activation of Q1–E1 complexes could arise from either the specific Q1–E1 interactions identified here, or by nonspecific obstruction of activation gate opening by the E1 C terminus.
[]
If our model is operational, the slowed activation of Q1–E1 complexes could arise from either the specific Q1–E1 interactions identified here, or by nonspecific obstruction of activation gate opening by the E1 C terminus.
true
true
true
true
true
6,559
5
DISCUSSION
0
null
null
20,479,109
null
Cartoon model depicting the cytoplasmic interactions of the E1 C-terminal domain and the Q1 activation gate machinery.
null
118
38,255
0
false
null
null
Cartoon model depicting the cytoplasmic interactions of the E1 C-terminal domain and the Q1 activation gate machinery.
true
true
true
true
true
6,560
5
DISCUSSION
0
null
null
20,479,109
null
(Inset) Magnification of the region of interest depicting the residues identified by cysteine cross-linking.
null
108
38,256
0
false
null
null
(Inset) Magnification of the region of interest depicting the residues identified by cysteine cross-linking.
false
false
true
true
false
6,560
5
DISCUSSION
0
null
null
20,479,109
null
Q1 subunits are gray, E1 subunit is blue, and the indentified residues are red and rendered as space-fill.
null
106
38,257
0
false
null
null
Q1 subunits are gray, E1 subunit is blue, and the indentified residues are red and rendered as space-fill.
true
true
true
true
true
6,560
0
DISCUSSION
0
null
null
19,651,816
null
The major novel finding of this study was that in a subset of VADT participants, the benefit of intensive glycemic control on CVD outcomes was greater for those with lower CAC.
null
176
38,258
0
false
null
null
The major novel finding of this study was that in a subset of VADT participants, the benefit of intensive glycemic control on CVD outcomes was greater for those with lower CAC.
true
true
true
true
true
6,561
0
DISCUSSION
0
null
null
19,651,816
null
Models with CAC parameterized either as a continuous variable [log(CAC + 1)] or by categories of CAC, whether or not adjustment was made for multiple covariates, provided consistent evidence for the presence of a significant treatment-calcium interaction.
null
255
38,259
0
false
null
null
Models with CAC parameterized either as a continuous variable [log(CAC + 1)] or by categories of CAC, whether or not adjustment was made for multiple covariates, provided consistent evidence for the presence of a significant treatment-calcium interaction.
true
true
true
true
true
6,561
0
DISCUSSION
0
null
null
19,651,816
null
These results were also observed when the analysis was limited to RACED subjects without a baseline history of CVD.
null
115
38,260
0
false
null
null
These results were also observed when the analysis was limited to RACED subjects without a baseline history of CVD.
true
true
true
true
true
6,561
0
DISCUSSION
0
null
null
19,651,816
null
Both the continuous model and the model based on the categories of CAC indicated that intensive glucose therapy reduced future CVD events predominantly in participants with less extensive atherosclerotic disease.
null
212
38,261
0
false
null
null
Both the continuous model and the model based on the categories of CAC indicated that intensive glucose therapy reduced future CVD events predominantly in participants with less extensive atherosclerotic disease.
true
true
true
true
true
6,561
0
DISCUSSION
0
null
null
19,651,816
null
This translated to a nearly 90% reduction in incidence of CVD events in those with very low CAC (subgroup with CAC ≤100 where the median CAC was <5 or with CAC ≤10 in the log model).
null
182
38,262
0
false
null
null
This translated to a nearly 90% reduction in incidence of CVD events in those with very low CAC (subgroup with CAC ≤100 where the median CAC was <5 or with CAC ≤10 in the log model).
true
true
true
true
true
6,561
0
DISCUSSION
0
null
null
19,651,816
null
In this low-CAC group, the estimated number needed to treat with intensive glucose lowering to prevent one CVD event was 29.
null
124
38,263
0
false
null
null
In this low-CAC group, the estimated number needed to treat with intensive glucose lowering to prevent one CVD event was 29.
true
true
true
true
true
6,561
0
DISCUSSION
0
null
null
19,651,816
null
Less benefit was observed at higher levels of CAC.
null
50
38,264
0
false
null
null
Less benefit was observed at higher levels of CAC.
true
true
true
true
true
6,561
1
DISCUSSION
1
11
[ "B11", "B12" ]
19,651,816
pmid-18539917|pmid-18539916
These RACED substudy results suggest that intensive glycemic control may not be effective in those with more advanced vascular disease.
[ "11", "12" ]
135
38,265
0
false
These RACED substudy results suggest that intensive glycemic control may not be effective in those with more advanced vascular disease.
[]
These RACED substudy results suggest that intensive glycemic control may not be effective in those with more advanced vascular disease.
true
true
true
true
true
6,562
1
DISCUSSION
1
11
[ "B11", "B12" ]
19,651,816
pmid-18539917|pmid-18539916
Based on the CAC distribution in this VADT subset, nearly 40% of the full VADT cohort presumably would have had extensive atherosclerosis (with CAC >400) at baseline and >60% would have CAC >100 at study entry.
[ "11", "12" ]
210
38,266
0
false
Based on the CAC distribution in this VADT subset, nearly 40% of the full VADT cohort presumably would have had extensive atherosclerosis (with CAC >400) at baseline and >60% would have CAC >100 at study entry.
[]
Based on the CAC distribution in this VADT subset, nearly 40% of the full VADT cohort presumably would have had extensive atherosclerosis (with CAC >400) at baseline and >60% would have CAC >100 at study entry.
true
true
true
true
true
6,562
1
DISCUSSION
1
11
[ "B11", "B12" ]
19,651,816
pmid-18539917|pmid-18539916
Thus, intensive glycemic control would not be expected to be beneficial in that large portion of the VADT cohort which had more extensive atherosclerosis.
[ "11", "12" ]
154
38,267
0
false
Thus, intensive glycemic control would not be expected to be beneficial in that large portion of the VADT cohort which had more extensive atherosclerosis.
[]
Thus, intensive glycemic control would not be expected to be beneficial in that large portion of the VADT cohort which had more extensive atherosclerosis.
true
true
true
true
true
6,562
1
DISCUSSION
1
11
[ "B11", "B12" ]
19,651,816
pmid-18539917|pmid-18539916
Consistent with this, the reduction in CVD observed in the intensive treatment group in the overall VADT (unadjusted HR 0.88
[ "11", "12" ]
124
38,268
0
false
Consistent with this, the reduction in CVD observed in the intensive treatment group in the overall VADT (unadjusted HR 0.88
[]
Consistent with this, the reduction in CVD observed in the intensive treatment group in the overall VADT (unadjusted HR 0.88
true
true
false
true
false
6,562
1
DISCUSSION
1
11
[ "B11", "B12" ]
19,651,816
pmid-18539917|pmid-18539916
[95% CI 0.74–1.05]; P = 0.14) was not significant and was comparable with that found for all subjects in this substudy (0.72 [0.47–1.10]; P = 0.13).
[ "11", "12" ]
148
38,269
0
false
[95% CI 0.74–1.05]; P = 0.14) was not significant and was comparable with that found for all subjects in this substudy (0.72 [0.47–1.10]; P = 0.13).
[]
; P = 0.14) was not significant and was comparable with that found for all subjects in this substudy.
false
false
true
true
false
6,562
1
DISCUSSION
1
11
[ "B11", "B12" ]
19,651,816
pmid-18539917|pmid-18539916
The modestly better outcome in the RACED cohort (compared with that in the overall VADT study) may reflect a different composition of participants or more intensive glucose lowering, but this is not apparent from the baseline clinical characteristics (Table 1) or
[ "11", "12" ]
263
38,270
0
false
The modestly better outcome in the RACED cohort (compared with that in the overall VADT study) may reflect a different composition of participants or more intensive glucose lowering, but this is not apparent from the baseline clinical characteristics (Table 1) or
[]
The modestly better outcome in the RACED cohort (compared with that in the overall VADT study) may reflect a different composition of participants or more intensive glucose lowering, but this is not apparent from the baseline clinical characteristics or
true
true
false
true
false
6,562
1
DISCUSSION
1
11
[ "B11", "B12" ]
19,651,816
pmid-18539917|pmid-18539916
A1C values observed during the study (Fig.
[ "11", "12" ]
42
38,271
0
false
A1C values observed during the study (Fig.
[]
A1C values observed during the study (Fig.
true
true
true
true
true
6,562
1
DISCUSSION
1
11
[ "B11", "B12" ]
19,651,816
pmid-18539917|pmid-18539916
Moreover, despite the slight trend for a more favorable outcome in response to intensive glucose reduction in the RACED cohort, those with higher levels of CAC received substantially less benefit from intensive therapy than did those with lower CAC.
[ "11", "12" ]
249
38,272
0
false
Moreover, despite the slight trend for a more favorable outcome in response to intensive glucose reduction in the RACED cohort, those with higher levels of CAC received substantially less benefit from intensive therapy than did those with lower CAC.
[]
Moreover, despite the slight trend for a more favorable outcome in response to intensive glucose reduction in the RACED cohort, those with higher levels of CAC received substantially less benefit from intensive therapy than did those with lower CAC.
true
true
true
true
true
6,562
1
DISCUSSION
1
11
[ "B11", "B12" ]
19,651,816
pmid-18539917|pmid-18539916
This conclusion seems to provide a plausible interpretation of the results from the ACCORD and ADVANCE trials (11,12).
[ "11", "12" ]
118
38,273
0
false
This conclusion seems to provide a plausible interpretation of the results from the ACCORD and ADVANCE trials.
[ "11,12" ]
This conclusion seems to provide a plausible interpretation of the results from the ACCORD and ADVANCE trials.
true
true
true
true
true
6,562
1
DISCUSSION
1
11
[ "B11", "B12" ]
19,651,816
pmid-18539917|pmid-18539916
Both of those studied populations were older and included participants with established diabetes and one or more CVD risk factors, suggesting that most of the participants in these studies may also have had relatively advanced atherosclerosis.
[ "11", "12" ]
243
38,274
0
false
Both of those studied populations were older and included participants with established diabetes and one or more CVD risk factors, suggesting that most of the participants in these studies may also have had relatively advanced atherosclerosis.
[]
Both of those studied populations were older and included participants with established diabetes and one or more CVD risk factors, suggesting that most of the participants in these studies may also have had relatively advanced atherosclerosis.
true
true
true
true
true
6,562
1
DISCUSSION
1
11
[ "B11", "B12" ]
19,651,816
pmid-18539917|pmid-18539916
This is supported by the fact that nearly one-third of both cohorts had a history of CVD at study entry.
[ "11", "12" ]
104
38,275
0
false
This is supported by the fact that nearly one-third of both cohorts had a history of CVD at study entry.
[]
This is supported by the fact that nearly one-third of both cohorts had a history of CVD at study entry.
true
true
true
true
true
6,562
1
DISCUSSION
1
11
[ "B11", "B12" ]
19,651,816
pmid-18539917|pmid-18539916
Therefore, inferring from the current results, both the ACCORD and ADVANCE cohorts may also have had such extensive atherosclerosis that no benefit from intensive glucose lowering was observed.
[ "11", "12" ]
193
38,276
0
false
Therefore, inferring from the current results, both the ACCORD and ADVANCE cohorts may also have had such extensive atherosclerosis that no benefit from intensive glucose lowering was observed.
[]
Therefore, inferring from the current results, both the ACCORD and ADVANCE cohorts may also have had such extensive atherosclerosis that no benefit from intensive glucose lowering was observed.
true
true
true
true
true
6,562
2
DISCUSSION
1
11
[ "B11", "B6", "B20" ]
19,651,816
pmid-18539917|pmid-9742977|pmid-18784090
The current RACED study does, however, indicate that intensive glycemic therapy may be effective in those with less extensive coronary atherosclerosis.
[ "11", "6", "20" ]
151
38,277
0
false
The current RACED study does, however, indicate that intensive glycemic therapy may be effective in those with less extensive coronary atherosclerosis.
[]
The current RACED study does, however, indicate that intensive glycemic therapy may be effective in those with less extensive coronary atherosclerosis.
true
true
true
true
true
6,563
2
DISCUSSION
1
11
[ "B11", "B6", "B20" ]
19,651,816
pmid-18539917|pmid-9742977|pmid-18784090
Consistent with these results, two subgroups of subjects in the ACCORD study that could reasonably be expected to have reduced atherosclerosis—those with lower baseline A1C
[ "11", "6", "20" ]
172
38,278
0
false
Consistent with these results, two subgroups of subjects in the ACCORD study that could reasonably be expected to have reduced atherosclerosis—those with lower baseline A1C
[]
Consistent with these results, two subgroups of subjects in the ACCORD study that could reasonably be expected to have reduced atherosclerosis—those with lower baseline A1C
true
true
false
true
false
6,563
2
DISCUSSION
1
11
[ "B11", "B6", "B20" ]
19,651,816
pmid-18539917|pmid-9742977|pmid-18784090
values (<8%) and those with no prior history of CVD—demonstrated significant reductions in the primary composite CVD end point in response to intensive glycemic control (11).
[ "11", "6", "20" ]
174
38,279
1
false
values (<8%) and those with no prior history of CVD—demonstrated significant reductions in the primary composite CVD end point in response to intensive glycemic control.
[ "11" ]
values (<8%) and those with no prior history of CVD—demonstrated significant reductions in the primary composite CVD end point in response to intensive glycemic control.
false
true
true
true
false
6,563
2
DISCUSSION
1
11
[ "B11", "B6", "B20" ]
19,651,816
pmid-18539917|pmid-9742977|pmid-18784090
This may also explain the more favorable results in the UK Prospective Diabetes Study, which evaluated improved glucose control in patients with newly diagnosed diabetes (6,20).
[ "11", "6", "20" ]
177
38,280
0
false
This may also explain the more favorable results in the UK Prospective Diabetes Study, which evaluated improved glucose control in patients with newly diagnosed diabetes.
[ "6,20" ]
This may also explain the more favorable results in the UK Prospective Diabetes Study, which evaluated improved glucose control in patients with newly diagnosed diabetes.
true
true
true
true
true
6,563
2
DISCUSSION
1
11
[ "B11", "B6", "B20" ]
19,651,816
pmid-18539917|pmid-9742977|pmid-18784090
An important implication of these findings is that it may be possible to identify patients who may obtain greater CVD benefit from intensive glucose-lowering therapy while preserving quality of life and avoiding unnecessary expenditure of resources and risk of adverse side effects of intensive treatment in those less l...
[ "11", "6", "20" ]
337
38,281
0
false
An important implication of these findings is that it may be possible to identify patients who may obtain greater CVD benefit from intensive glucose-lowering therapy while preserving quality of life and avoiding unnecessary expenditure of resources and risk of adverse side effects of intensive treatment in those less l...
[]
An important implication of these findings is that it may be possible to identify patients who may obtain greater CVD benefit from intensive glucose-lowering therapy while preserving quality of life and avoiding unnecessary expenditure of resources and risk of adverse side effects of intensive treatment in those less l...
true
true
true
true
true
6,563
3
DISCUSSION
1
21
[ "B21", "B21", "B22" ]
19,651,816
pmid-14670831|pmid-14670831|pmid-19373446
An important, but unanswered, question is why glucose lowering is less effective in reducing CVD events in individuals with more advanced atherosclerosis.
[ "21", "21", "22" ]
154
38,282
0
false
An important, but unanswered, question is why glucose lowering is less effective in reducing CVD events in individuals with more advanced atherosclerosis.
[]
An important, but unanswered, question is why glucose lowering is less effective in reducing CVD events in individuals with more advanced atherosclerosis.
true
true
true
true
true
6,564
3
DISCUSSION
1
21
[ "B21", "B21", "B22" ]
19,651,816
pmid-14670831|pmid-14670831|pmid-19373446
Although numerous mechanisms have been implicated in the initiation and development of atherosclerosis in diabetes, there is less information about which processes may be responsive to lowered glucose.
[ "21", "21", "22" ]
201
38,283
0
false
Although numerous mechanisms have been implicated in the initiation and development of atherosclerosis in diabetes, there is less information about which processes may be responsive to lowered glucose.
[]
Although numerous mechanisms have been implicated in the initiation and development of atherosclerosis in diabetes, there is less information about which processes may be responsive to lowered glucose.
true
true
true
true
true
6,564
3
DISCUSSION
1
21
[ "B21", "B21", "B22" ]
19,651,816
pmid-14670831|pmid-14670831|pmid-19373446
One may speculate that when sufficient plaque development has occurred, the presence of modified lipoproteins, activated vascular cells, and altered immune cell signaling may generate a self-propagating process that maintains atherogenesis even in the face of improved glucose control.
[ "21", "21", "22" ]
285
38,284
0
false
One may speculate that when sufficient plaque development has occurred, the presence of modified lipoproteins, activated vascular cells, and altered immune cell signaling may generate a self-propagating process that maintains atherogenesis even in the face of improved glucose control.
[]
One may speculate that when sufficient plaque development has occurred, the presence of modified lipoproteins, activated vascular cells, and altered immune cell signaling may generate a self-propagating process that maintains atherogenesis even in the face of improved glucose control.
true
true
true
true
true
6,564
3
DISCUSSION
1
21
[ "B21", "B21", "B22" ]
19,651,816
pmid-14670831|pmid-14670831|pmid-19373446
Alternatively, chronic hyperglycemia leads to advanced glycation end product formation and extensive protein cross-linking—a process that is not readily reversible, increases with age, and is enhanced by oxidative stress (21).
[ "21", "21", "22" ]
226
38,285
1
false
Alternatively, chronic hyperglycemia leads to advanced glycation end product formation and extensive protein cross-linking—a process that is not readily reversible, increases with age, and is enhanced by oxidative stress.
[ "21" ]
Alternatively, chronic hyperglycemia leads to advanced glycation end product formation and extensive protein cross-linking—a process that is not readily reversible, increases with age, and is enhanced by oxidative stress.
true
true
true
true
true
6,564
3
DISCUSSION
1
21
[ "B21", "B21", "B22" ]
19,651,816
pmid-14670831|pmid-14670831|pmid-19373446
For older individuals with a long history of diabetes, the past burden of hyperglycemia and advanced glycation end product formation is presumably extensive and may have long-term negative “legacy” effects (21,22).
[ "21", "21", "22" ]
214
38,286
0
false
For older individuals with a long history of diabetes, the past burden of hyperglycemia and advanced glycation end product formation is presumably extensive and may have long-term negative “legacy” effects.
[ "21,22" ]
For older individuals with a long history of diabetes, the past burden of hyperglycemia and advanced glycation end product formation is presumably extensive and may have long-term negative “legacy” effects.
true
true
true
true
true
6,564
3
DISCUSSION
1
21
[ "B21", "B21", "B22" ]
19,651,816
pmid-14670831|pmid-14670831|pmid-19373446
Although glucose lowering may prevent new advanced glycation end product formation and limit new vascular injury, 3–5 years of intensive glycemic control as occurs during clinical trials is presumably insufficient to reverse the accumulated vascular damage from decades of hyperglycemia or other metabolic abnormalities.
[ "21", "21", "22" ]
320
38,287
0
false
Although glucose lowering may prevent new advanced glycation end product formation and limit new vascular injury, 3–5 years of intensive glycemic control as occurs during clinical trials is presumably insufficient to reverse the accumulated vascular damage from decades of hyperglycemia or other metabolic abnormalities.
[]
Although glucose lowering may prevent new advanced glycation end product formation and limit new vascular injury, 3–5 years of intensive glycemic control as occurs during clinical trials is presumably insufficient to reverse the accumulated vascular damage from decades of hyperglycemia or other metabolic abnormalities.
true
true
true
true
true
6,564
4
DISCUSSION
1
18
[ "B18", "B19" ]
19,651,816
pmid-17239724|pmid-18564546
Several limitations of this study deserve mention.
[ "18", "19" ]
50
38,288
0
false
Several limitations of this study deserve mention.
[]
Several limitations of this study deserve mention.
true
true
true
true
true
6,565
4
DISCUSSION
1
18
[ "B18", "B19" ]
19,651,816
pmid-17239724|pmid-18564546
The number of incident CVD events in this substudy of the VADT is relatively modest.
[ "18", "19" ]
84
38,289
0
false
The number of incident CVD events in this substudy of the VADT is relatively modest.
[]
The number of incident CVD events in this substudy of the VADT is relatively modest.
true
true
true
true
true
6,565
4
DISCUSSION
1
18
[ "B18", "B19" ]
19,651,816
pmid-17239724|pmid-18564546
Although we accounted for the available cardiovascular risk factors that appeared to be relevant determinants of CVD events in this cohort, it is possible that other useful predictors may exist and were not examined.
[ "18", "19" ]
216
38,290
0
false
Although we accounted for the available cardiovascular risk factors that appeared to be relevant determinants of CVD events in this cohort, it is possible that other useful predictors may exist and were not examined.
[]
Although we accounted for the available cardiovascular risk factors that appeared to be relevant determinants of CVD events in this cohort, it is possible that other useful predictors may exist and were not examined.
true
true
true
true
true
6,565
4
DISCUSSION
1
18
[ "B18", "B19" ]
19,651,816
pmid-17239724|pmid-18564546
However, comparison of risk factors and relevant medication use between standard and intensive groups in RACED participants with lower CAC at baseline revealed similar levels of risk factors (Table 3), and treatment effects persisted in multivariable (i.e., adjusted) models.
[ "18", "19" ]
275
38,291
0
false
However, comparison of risk factors and relevant medication use between standard and intensive groups in RACED participants with lower CAC at baseline revealed similar levels of risk factors (Table 3), and treatment effects persisted in multivariable (i.e., adjusted) models.
[]
However, comparison of risk factors and relevant medication use between standard and intensive groups in RACED participants with lower CAC at baseline revealed similar levels of risk factors (Table 3), and treatment effects persisted in multivariable (i.e., adjusted) models.
true
true
true
true
true
6,565
4
DISCUSSION
1
18
[ "B18", "B19" ]
19,651,816
pmid-17239724|pmid-18564546
Although examination of baseline CAC (using either log CAC or clinical CAC categories) as an effect modifier of glycemic control was a prespecified aim of this study, the decision to dichotomize CAC at 100 was determined post hoc to facilitate analysis in the context of the very low number of events in those with low C...
[ "18", "19" ]
323
38,292
0
false
Although examination of baseline CAC (using either log CAC or clinical CAC categories) as an effect modifier of glycemic control was a prespecified aim of this study, the decision to dichotomize CAC at 100 was determined post hoc to facilitate analysis in the context of the very low number of events in those with low C...
[]
Although examination of baseline CAC (using either log CAC or clinical CAC categories) as an effect modifier of glycemic control was a prespecified aim of this study, the decision to dichotomize CAC at 100 was determined post hoc to facilitate analysis in the context of the very low number of events in those with low C...
true
true
true
true
true
6,565
4
DISCUSSION
1
18
[ "B18", "B19" ]
19,651,816
pmid-17239724|pmid-18564546
The cut point of 100 Agatston units for CAC is clinically used to stratify CVD risk and reflected expected differences in incidence of CVD between the low and high CAC categories within the RACED cohort (18,19).
[ "18", "19" ]
211
38,293
0
false
The cut point of 100 Agatston units for CAC is clinically used to stratify CVD risk and reflected expected differences in incidence of CVD between the low and high CAC categories within the RACED cohort.
[ "18,19" ]
The cut point of 100 Agatston units for CAC is clinically used to stratify CVD risk and reflected expected differences in incidence of CVD between the low and high CAC categories within the RACED cohort.
true
true
true
true
true
6,565
4
DISCUSSION
1
18
[ "B18", "B19" ]
19,651,816
pmid-17239724|pmid-18564546
Moreover, when CAC was considered as a continuous variable, which fit the data somewhat better than the CAC dichotomization approach, there was a progressive increase in benefit of intensive treatment with decreasing values of CAC, and again, no treatment benefit was seen in those at the highest CAC scores.
[ "18", "19" ]
308
38,294
0
false
Moreover, when CAC was considered as a continuous variable, which fit the data somewhat better than the CAC dichotomization approach, there was a progressive increase in benefit of intensive treatment with decreasing values of CAC, and again, no treatment benefit was seen in those at the highest CAC scores.
[]
Moreover, when CAC was considered as a continuous variable, which fit the data somewhat better than the CAC dichotomization approach, there was a progressive increase in benefit of intensive treatment with decreasing values of CAC, and again, no treatment benefit was seen in those at the highest CAC scores.
true
true
true
true
true
6,565
4
DISCUSSION
1
18
[ "B18", "B19" ]
19,651,816
pmid-17239724|pmid-18564546
Additional sensitivity analyses, using CAC expressed either as tertiles or as three clinical categories (0–100, 101–400, and >400) also demonstrated that the benefit of intensive glycemic control for CVD was present only for individuals within the lowest CAC category.
[ "18", "19" ]
268
38,295
0
false
Additional sensitivity analyses, using CAC expressed either as tertiles or as three clinical categories (0–100, 101–400, and >400) also demonstrated that the benefit of intensive glycemic control for CVD was present only for individuals within the lowest CAC category.
[]
Additional sensitivity analyses, using CAC expressed either as tertiles or as three clinical categories also demonstrated that the benefit of intensive glycemic control for CVD was present only for individuals within the lowest CAC category.
true
true
true
true
true
6,565
4
DISCUSSION
1
18
[ "B18", "B19" ]
19,651,816
pmid-17239724|pmid-18564546
Despite these consistent results, it is important that these novel findings be confirmed in larger diabetes cohorts and in studies with a greater proportion of female participants.
[ "18", "19" ]
180
38,296
0
false
Despite these consistent results, it is important that these novel findings be confirmed in larger diabetes cohorts and in studies with a greater proportion of female participants.
[]
Despite these consistent results, it is important that these novel findings be confirmed in larger diabetes cohorts and in studies with a greater proportion of female participants.
true
true
true
true
true
6,565
4
DISCUSSION
1
18
[ "B18", "B19" ]
19,651,816
pmid-17239724|pmid-18564546
In summary, these data provide support for the concept that intensive glucose-lowering therapy may be most effective in reducing CVD in those with less extensive coronary atherosclerosis.
[ "18", "19" ]
187
38,297
0
false
In summary, these data provide support for the concept that intensive glucose-lowering therapy may be most effective in reducing CVD in those with less extensive coronary atherosclerosis.
[]
In summary, these data provide support for the concept that intensive glucose-lowering therapy may be most effective in reducing CVD in those with less extensive coronary atherosclerosis.
true
true
true
true
true
6,565
0
DISCUSSION
1
25
[ "B25" ]
20,713,682
pmid-1716521
Although a relationship between obesity and inflammation in fat has been previously observed, in most cases these inflammatory changes have been viewed as being secondary to obesity.
[ "25" ]
182
38,298
0
false
Although a relationship between obesity and inflammation in fat has been previously observed, in most cases these inflammatory changes have been viewed as being secondary to obesity.
[]
Although a relationship between obesity and inflammation in fat has been previously observed, in most cases these inflammatory changes have been viewed as being secondary to obesity.
true
true
true
true
true
6,566
0
DISCUSSION
1
25
[ "B25" ]
20,713,682
pmid-1716521
Our data, comparing diabetes-prone B6 mouse and diabetes-resistant 129 mouse at 6 weeks of age, show alterations in the inflammatory process in adipose tissue even before differences in metabolic parameters can be detected.
[ "25" ]
223
38,299
0
false
Our data, comparing diabetes-prone B6 mouse and diabetes-resistant 129 mouse at 6 weeks of age, show alterations in the inflammatory process in adipose tissue even before differences in metabolic parameters can be detected.
[]
Our data, comparing diabetes-prone B6 mouse and diabetes-resistant 129 mouse at 6 weeks of age, show alterations in the inflammatory process in adipose tissue even before differences in metabolic parameters can be detected.
true
true
true
true
true
6,566
0
DISCUSSION
1
25
[ "B25" ]
20,713,682
pmid-1716521
Thus, B6 mice exhibit increased expression of the T-cell chemokines SDF1α and CCL5/RANTES and an increased number of T-cells in the fat tissue.
[ "25" ]
143
38,300
0
false
Thus, B6 mice exhibit increased expression of the T-cell chemokines SDF1α and CCL5/RANTES and an increased number of T-cells in the fat tissue.
[]
Thus, B6 mice exhibit increased expression of the T-cell chemokines SDF1α and CCL5/RANTES and an increased number of T-cells in the fat tissue.
true
true
true
true
true
6,566
0
DISCUSSION
1
25
[ "B25" ]
20,713,682
pmid-1716521
These differences are associated with higher IFNγ and CD80 levels in the B6 mice—both molecules are known to participate in T-cell function and activation (25) (summarized in the model shown in Fig.
[ "25" ]
198
38,301
1
false
These differences are associated with higher IFNγ and CD80 levels in the B6 mice—both molecules are known to participate in T-cell function and activation (summarized in the model shown in Fig.
[ "25" ]
These differences are associated with higher IFNγ and CD80 levels in the B6 mice—both molecules are known to participate in T-cell function and activation (summarized in the model shown in Fig.
true
true
true
true
true
6,566
1
DISCUSSION
0
null
null
20,713,682
null
Schematic model illustrating the potential causes and consequences related to the different repertoire of immune cells in adipose tissue of B6 and 129 mice.
null
156
38,302
0
false
null
null
Schematic model illustrating the potential causes and consequences related to the different repertoire of immune cells in adipose tissue of B6 and 129 mice.
true
true
true
true
true
6,567
1
DISCUSSION
0
null
null
20,713,682
null
Solid arrows, secretion; dashed arrows, migration; dotted arrows, migration/differentiation.
null
92
38,303
0
false
null
null
Solid arrows, secretion; dashed arrows, migration; dotted arrows, migration/differentiation.
true
true
true
true
true
6,567
2
DISCUSSION
1
26
[ "B26", "B27", "B28", "B29", "B29", "B29" ]
20,713,682
pmid-19633656|pmid-19633657|pmid-19633658|pmid-18420999|pmid-18420999|pmid-18420999
Recent work has shown that T-cells infiltrate into the visceral adipose tissue of obese animals and humans with type 2 diabetes, and this is followed by recruitment of macrophages and development of insulin resistance (26–29).
[ "26", null, null, "29", "29", "29" ]
226
38,304
0
false
Recent work has shown that T-cells infiltrate into the visceral adipose tissue of obese animals and humans with type 2 diabetes, and this is followed by recruitment of macrophages and development of insulin resistance.
[ "26–29" ]
Recent work has shown that T-cells infiltrate into the visceral adipose tissue of obese animals and humans with type 2 diabetes, and this is followed by recruitment of macrophages and development of insulin resistance.
true
true
true
true
true
6,568
2
DISCUSSION
1
29
[ "B26", "B27", "B28", "B29", "B29", "B29" ]
20,713,682
pmid-19633656|pmid-19633657|pmid-19633658|pmid-18420999|pmid-18420999|pmid-18420999
Based on these findings, a model for the role of T-cells in the pathogenesis of obesity and insulin resistance has been proposed in which increases in SDF1α and CCL5/RANTES levels in adipose tissue occur in response to an obesogenic environment and promote infiltration with T lymphocytes (29).
[ "26", null, null, "29", "29", "29" ]
294
38,305
1
false
Based on these findings, a model for the role of T-cells in the pathogenesis of obesity and insulin resistance has been proposed in which increases in SDF1α and CCL5/RANTES levels in adipose tissue occur in response to an obesogenic environment and promote infiltration with T lymphocytes.
[ "29" ]
Based on these findings, a model for the role of T-cells in the pathogenesis of obesity and insulin resistance has been proposed in which increases in SDF1α and CCL5/RANTES levels in adipose tissue occur in response to an obesogenic environment and promote infiltration with T lymphocytes.
true
true
true
true
true
6,568
2
DISCUSSION
1
29
[ "B26", "B27", "B28", "B29", "B29", "B29" ]
20,713,682
pmid-19633656|pmid-19633657|pmid-19633658|pmid-18420999|pmid-18420999|pmid-18420999
IFNγ derived from these T-cells then promotes MCP1 secretion by preadipocytes (and possibly other cell types), resulting in recruitment of macrophages that further contribute to insulin resistance by production of proinflammatory cytokines (29).
[ "26", null, null, "29", "29", "29" ]
245
38,306
1
false
IFNγ derived from these T-cells then promotes MCP1 secretion by preadipocytes (and possibly other cell types), resulting in recruitment of macrophages that further contribute to insulin resistance by production of proinflammatory cytokines.
[ "29" ]
IFNγ derived from these T-cells then promotes MCP1 secretion by preadipocytes (and possibly other cell types), resulting in recruitment of macrophages that further contribute to insulin resistance by production of proinflammatory cytokines.
true
true
true
true
true
6,568
3
DISCUSSION
1
27
[ "B27", "B28" ]
20,713,682
pmid-19633657|pmid-19633658
Our study provides evidence to support a major impact of the genetic background of different mouse strains in the migration of T-cells to the adipose tissue, both in the basal state and in response to weight gain.
[ "27", "28" ]
213
38,307
0
false
Our study provides evidence to support a major impact of the genetic background of different mouse strains in the migration of T-cells to the adipose tissue, both in the basal state and in response to weight gain.
[]
Our study provides evidence to support a major impact of the genetic background of different mouse strains in the migration of T-cells to the adipose tissue, both in the basal state and in response to weight gain.
true
true
true
true
true
6,569
3
DISCUSSION
1
27
[ "B27", "B28" ]
20,713,682
pmid-19633657|pmid-19633658
In B6 mice, the number of T-cells in the adipose tissue correlates positively with the increase in adipose mass as a consequence of aging or HFD.
[ "27", "28" ]
145
38,308
0
false
In B6 mice, the number of T-cells in the adipose tissue correlates positively with the increase in adipose mass as a consequence of aging or HFD.
[]
In B6 mice, the number of T-cells in the adipose tissue correlates positively with the increase in adipose mass as a consequence of aging or HFD.
true
true
true
true
true
6,569
3
DISCUSSION
1
27
[ "B27", "B28" ]
20,713,682
pmid-19633657|pmid-19633658
By contrast, this response is practically absent in 129 mice despite a significant increase in adiposity in response to age or HFD.
[ "27", "28" ]
131
38,309
0
false
By contrast, this response is practically absent in 129 mice despite a significant increase in adiposity in response to age or HFD.
[]
By contrast, this response is practically absent in 129 mice despite a significant increase in adiposity in response to age or HFD.
true
true
true
true
true
6,569
3
DISCUSSION
1
27
[ "B27", "B28" ]
20,713,682
pmid-19633657|pmid-19633658
Thus, similar to mice with ablation of T-cells (27,28), 129 mice develop only mild insulin resistance in response to obesity.
[ "27", "28" ]
125
38,310
0
false
Thus, similar to mice with ablation of T-cells, 129 mice develop only mild insulin resistance in response to obesity.
[ "27,28" ]
Thus, similar to mice with ablation of T-cells, 129 mice develop only mild insulin resistance in response to obesity.
true
true
true
true
true
6,569
3
DISCUSSION
1
27
[ "B27", "B28" ]
20,713,682
pmid-19633657|pmid-19633658
To what extent aging and the composition of the diet impact the infiltration of T-cells into adipose tissue, in addition to the effects of weight gain, remain to be determined.
[ "27", "28" ]
176
38,311
0
false
To what extent aging and the composition of the diet impact the infiltration of T-cells into adipose tissue, in addition to the effects of weight gain, remain to be determined.
[]
To what extent aging and the composition of the diet impact the infiltration of T-cells into adipose tissue, in addition to the effects of weight gain, remain to be determined.
true
true
true
true
true
6,569
3
DISCUSSION
1
27
[ "B27", "B28" ]
20,713,682
pmid-19633657|pmid-19633658
It is clear though that insulin resistance in response to increased adiposity differ substantially between mouse strains, and this phenomenon is correlated with the migration of T-cell to the adipose tissue.
[ "27", "28" ]
207
38,312
0
false
It is clear though that insulin resistance in response to increased adiposity differ substantially between mouse strains, and this phenomenon is correlated with the migration of T-cell to the adipose tissue.
[]
It is clear though that insulin resistance in response to increased adiposity differ substantially between mouse strains, and this phenomenon is correlated with the migration of T-cell to the adipose tissue.
true
true
true
true
true
6,569
3
DISCUSSION
1
27
[ "B27", "B28" ]
20,713,682
pmid-19633657|pmid-19633658
Thus, inflammation in the adipose tissue does not always correlate with weight gain and is strongly dependent on the genetic background of the host.
[ "27", "28" ]
148
38,313
0
false
Thus, inflammation in the adipose tissue does not always correlate with weight gain and is strongly dependent on the genetic background of the host.
[]
Thus, inflammation in the adipose tissue does not always correlate with weight gain and is strongly dependent on the genetic background of the host.
true
true
true
true
true
6,569
3
DISCUSSION
1
27
[ "B27", "B28" ]
20,713,682
pmid-19633657|pmid-19633658
Similar differences dependent on genetic background are likely to occur in humans and contribute to differences in obesity-induced diabetes risk in different ethnic groups or even different individuals, allowing for some of the “fat-fit” phenotype.
[ "27", "28" ]
248
38,314
0
false
Similar differences dependent on genetic background are likely to occur in humans and contribute to differences in obesity-induced diabetes risk in different ethnic groups or even different individuals, allowing for some of the “fat-fit” phenotype.
[]
Similar differences dependent on genetic background are likely to occur in humans and contribute to differences in obesity-induced diabetes risk in different ethnic groups or even different individuals, allowing for some of the “fat-fit” phenotype.
true
true
true
true
true
6,569
4
DISCUSSION
0
null
null
20,713,682
null
Among other implications, these observations clearly impact the choice of models for metabolic studies, in particular when knockout mice are used.
null
146
38,315
0
false
null
null
Among other implications, these observations clearly impact the choice of models for metabolic studies, in particular when knockout mice are used.
true
true
true
true
true
6,570