Datasets:
vgainullin
/
xciting_data

Dataset card Data Studio Files
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 Community
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14
DISCUSSION
0
null
null
12,743,167
null
The next section argues for the selectivity filter as a target for protonation, but, as demonstrated in the accompanying paper, the binding of protons to the EEDD pore locus is not related to the proton-induced modification of channel activation.
null
246
40,818
0
false
null
null
The next section argues for the selectivity filter as a target for protonation, but, as demonstrated in the accompanying paper, the binding of protons to the EEDD pore locus is not related to the proton-induced modification of channel activation.
true
true
true
true
true
7,031
15
DISCUSSION
1
Tytgat et al. (1990)
[ "bib33", "bib8", "bib21", "bib18", "bib24" ]
12,743,167
NA|NA|NA|NA|NA
Tytgat et al.
[ "Tytgat et al. (1990)", "Delisle and Satin (2000)", "Polo-Parada and Korn, 1997", "Lee et al., 1999", "Serrano et al., 1999" ]
14
40,819
0
false
Tytgat et al.
[]
Tytgat et al.
true
true
true
true
true
7,032
15
DISCUSSION
1
Tytgat et al. (1990)
[ "bib33", "bib8", "bib21", "bib18", "bib24" ]
12,743,167
NA|NA|NA|NA|NA
(1990) reported that extracellular acidification reduces the conductance of single cardiac T-type channels in the guinea pig.
[ "Tytgat et al. (1990)", "Delisle and Satin (2000)", "Polo-Parada and Korn, 1997", "Lee et al., 1999", "Serrano et al., 1999" ]
125
40,820
0
false
(1990) reported that extracellular acidification reduces the conductance of single cardiac T-type channels in the guinea pig.
[]
reported that extracellular acidification reduces the conductance of single cardiac T-type channels in the guinea pig.
false
true
true
true
false
7,032
15
DISCUSSION
1
Tytgat et al. (1990)
[ "bib33", "bib8", "bib21", "bib18", "bib24" ]
12,743,167
NA|NA|NA|NA|NA
However, Delisle and Satin (2000) concluded that protons do not block the α1H channel, but actually increase the whole-cell conductance and decrease the Ca2+/monovalent cation selectivity.
[ "Tytgat et al. (1990)", "Delisle and Satin (2000)", "Polo-Parada and Korn, 1997", "Lee et al., 1999", "Serrano et al., 1999" ]
188
40,821
0
false
However, Delisle and Satin (2000) concluded that protons do not block the α1H channel, but actually increase the whole-cell conductance and decrease the Ca2+/monovalent cation selectivity.
[]
However, Delisle and Satin concluded that protons do not block the α1H channel, but actually increase the whole-cell conductance and decrease the Ca2+/monovalent cation selectivity.
true
true
true
true
true
7,032
15
DISCUSSION
1
Tytgat et al. (1990)
[ "bib33", "bib8", "bib21", "bib18", "bib24" ]
12,743,167
NA|NA|NA|NA|NA
These discrepant results might be reconciled by the different extracellular Ca2+ and Na+ concentrations that were used in these reports.
[ "Tytgat et al. (1990)", "Delisle and Satin (2000)", "Polo-Parada and Korn, 1997", "Lee et al., 1999", "Serrano et al., 1999" ]
136
40,822
0
false
These discrepant results might be reconciled by the different extracellular Ca2+ and Na+ concentrations that were used in these reports.
[]
These discrepant results might be reconciled by the different extracellular Ca2+ and Na+ concentrations that were used in these reports.
true
true
true
true
true
7,032
15
DISCUSSION
1
Polo-Parada and Korn, 1997
[ "bib33", "bib8", "bib21", "bib18", "bib24" ]
12,743,167
NA|NA|NA|NA|NA
In fact, it has been shown that ion conduction through Ca2+ channels depends on both Ca2+ and Na+ concentrations (Polo-Parada and Korn, 1997) and that Na+ can contribute significantly to the current through T-type channels (Lee et al., 1999; Serrano et al., 1999).
[ "Tytgat et al. (1990)", "Delisle and Satin (2000)", "Polo-Parada and Korn, 1997", "Lee et al., 1999", "Serrano et al., 1999" ]
264
40,823
1
false
In fact, it has been shown that ion conduction through Ca2+ channels depends on both Ca2+ and Na+ concentrations and that Na+ can contribute significantly to the current through T-type channels.
[ "Polo-Parada and Korn, 1997", "Lee et al., 1999; Serrano et al., 1999" ]
In fact, it has been shown that ion conduction through Ca2+ channels depends on both Ca2+ and Na+ concentrations and that Na+ can contribute significantly to the current through T-type channels.
true
true
true
true
true
7,032
15
DISCUSSION
1
Tytgat et al. (1990)
[ "bib33", "bib8", "bib21", "bib18", "bib24" ]
12,743,167
NA|NA|NA|NA|NA
Our data about the effects of extracellular Ca2+ and Na+ on the open pore block and the changes in ion selectivity induced by protons in α1G and the EEED pore mutant support this contention.
[ "Tytgat et al. (1990)", "Delisle and Satin (2000)", "Polo-Parada and Korn, 1997", "Lee et al., 1999", "Serrano et al., 1999" ]
190
40,824
0
false
Our data about the effects of extracellular Ca2+ and Na+ on the open pore block and the changes in ion selectivity induced by protons in α1G and the EEED pore mutant support this contention.
[]
Our data about the effects of extracellular Ca2+ and Na+ on the open pore block and the changes in ion selectivity induced by protons in α1G and the EEED pore mutant support this contention.
true
true
true
true
true
7,032
16
DISCUSSION
0
null
null
12,743,167
null
We have found that in α1G, extracellular acidification from pH 9.1 to 6.2 decreased the amplitude of inward tail currents by ∼33% in the presence of 2 mM Ca2+ (150 NMDG+), whereas the block was maximal 10% in 20 mM Ca2+, indicating that open-pore proton block is larger at low [Ca2+]e.
null
285
40,825
0
false
null
null
We have found that in α1G, extracellular acidification from pH 9.1 to 6.2 decreased the amplitude of inward tail currents by ∼33% in the presence of 2 mM Ca2+ (150 NMDG+), whereas the block was maximal 10% in 20 mM Ca2+, indicating that open-pore proton block is larger at low [Ca2+]e.
true
true
true
true
true
7,033
16
DISCUSSION
0
null
null
12,743,167
null
Analogue experiments with the EEED pore mutant confirmed that open-pore proton block is Ca2+ dependent and showed that proton block of Ca2+ conduction (20 mM Ca2+) was stronger than in the wild-type channel.
null
207
40,826
0
false
null
null
Analogue experiments with the EEED pore mutant confirmed that open-pore proton block is Ca2+ dependent and showed that proton block of Ca2+ conduction (20 mM Ca2+) was stronger than in the wild-type channel.
true
true
true
true
true
7,033
17
DISCUSSION
1
Talavera et al., 2001
[ "bib30", "bib10", "bib7", "bib30", "bib4" ]
12,743,167
NA|NA|NA|NA|NA
The reversal potentials were less positive in the EEED mutant than in the wild-type channel under all conditions, in agreement with our previous findings (Talavera et al., 2001).
[ "Talavera et al., 2001", "Ellinor et al., 1995", "Chen and Tsien, 1997", "Talavera et al., 2001", "Cataldi et al., 2002" ]
178
40,827
1
false
The reversal potentials were less positive in the EEED mutant than in the wild-type channel under all conditions, in agreement with our previous findings.
[ "Talavera et al., 2001" ]
The reversal potentials were less positive in the EEED mutant than in the wild-type channel under all conditions, in agreement with our previous findings.
true
true
true
true
true
7,034
17
DISCUSSION
1
Talavera et al., 2001
[ "bib30", "bib10", "bib7", "bib30", "bib4" ]
12,743,167
NA|NA|NA|NA|NA
The fact that this was observed at pHe 9.1 may indicate that the EEED mutant has a decreased Ca2+ selectivity respect to α1G, independently from the channel protonation.
[ "Talavera et al., 2001", "Ellinor et al., 1995", "Chen and Tsien, 1997", "Talavera et al., 2001", "Cataldi et al., 2002" ]
169
40,828
0
false
The fact that this was observed at pHe 9.1 may indicate that the EEED mutant has a decreased Ca2+ selectivity respect to α1G, independently from the channel protonation.
[]
The fact that this was observed at pHe 9.1 may indicate that the EEED mutant has a decreased Ca2+ selectivity respect to α1G, independently from the channel protonation.
true
true
true
true
true
7,034
17
DISCUSSION
1
Ellinor et al., 1995
[ "bib30", "bib10", "bib7", "bib30", "bib4" ]
12,743,167
NA|NA|NA|NA|NA
This hypothesis would mean that the exchange of the aspartate residue D1487 for glutamate disrupts the coordination of Ca2+ binding to the selectivity filter in contrast to the results in L-type Ca2+ channels (Ellinor et al., 1995).
[ "Talavera et al., 2001", "Ellinor et al., 1995", "Chen and Tsien, 1997", "Talavera et al., 2001", "Cataldi et al., 2002" ]
232
40,829
1
false
This hypothesis would mean that the exchange of the aspartate residue D1487 for glutamate disrupts the coordination of Ca2+ binding to the selectivity filter in contrast to the results in L-type Ca2+ channels.
[ "Ellinor et al., 1995" ]
This hypothesis would mean that the exchange of the aspartate residue D1487 for glutamate disrupts the coordination of Ca2+ binding to the selectivity filter in contrast to the results in L-type Ca2+ channels.
true
true
true
true
true
7,034
17
DISCUSSION
1
Chen and Tsien, 1997
[ "bib30", "bib10", "bib7", "bib30", "bib4" ]
12,743,167
NA|NA|NA|NA|NA
A second possibility is that some protonation occurs at nanomolar extracellular proton concentrations, implying a much higher proton affinity of the EEED arrangement in the α1G template than in that of the L-type channel (Chen and Tsien, 1997).
[ "Talavera et al., 2001", "Ellinor et al., 1995", "Chen and Tsien, 1997", "Talavera et al., 2001", "Cataldi et al., 2002" ]
244
40,830
1
false
A second possibility is that some protonation occurs at nanomolar extracellular proton concentrations, implying a much higher proton affinity of the EEED arrangement in the α1G template than in that of the L-type channel.
[ "Chen and Tsien, 1997" ]
A second possibility is that some protonation occurs at nanomolar extracellular proton concentrations, implying a much higher proton affinity of the EEED arrangement in the α1G template than in that of the L-type channel.
true
true
true
true
true
7,034
17
DISCUSSION
1
Talavera et al., 2001
[ "bib30", "bib10", "bib7", "bib30", "bib4" ]
12,743,167
NA|NA|NA|NA|NA
This hypothesis fits nicely with previous evidence suggesting that an EEEE selectivity filter in the α1G channel impose a narrower ionic pathway than in HVA channels (Talavera et al., 2001), which is in turn in agreement with the fact that the pore of the wild-type T-type channels is narrower than that of HVA Ca2+ chan...
[ "Talavera et al., 2001", "Ellinor et al., 1995", "Chen and Tsien, 1997", "Talavera et al., 2001", "Cataldi et al., 2002" ]
348
40,831
1
false
This hypothesis fits nicely with previous evidence suggesting that an EEEE selectivity filter in the α1G channel impose a narrower ionic pathway than in HVA channels, which is in turn in agreement with the fact that the pore of the wild-type T-type channels is narrower than that of HVA Ca2+ channels.
[ "Talavera et al., 2001", "Cataldi et al., 2002" ]
This hypothesis fits nicely with previous evidence suggesting that an EEEE selectivity filter in the α1G channel impose a narrower ionic pathway than in HVA channels, which is in turn in agreement with the fact that the pore of the wild-type T-type channels is narrower than that of HVA Ca2+ channels.
true
true
true
true
true
7,034
17
DISCUSSION
1
Talavera et al., 2001
[ "bib30", "bib10", "bib7", "bib30", "bib4" ]
12,743,167
NA|NA|NA|NA|NA
In both α1G and the EEED mutant, the proton-induced decrease of the Ca2+/monovalent cation selectivity (judged by the negative shift of the reversal potential) was observed in 2 but not in 20 mM Ca2+.
[ "Talavera et al., 2001", "Ellinor et al., 1995", "Chen and Tsien, 1997", "Talavera et al., 2001", "Cataldi et al., 2002" ]
200
40,832
0
false
In both α1G and the EEED mutant, the proton-induced decrease of the Ca2+/monovalent cation selectivity (judged by the negative shift of the reversal potential) was observed in 2 but not in 20 mM Ca2+.
[]
In both α1G and the EEED mutant, the proton-induced decrease of the Ca2+/monovalent cation selectivity was observed in 2 but not in 20 mM Ca2+.
true
true
true
true
true
7,034
17
DISCUSSION
1
Talavera et al., 2001
[ "bib30", "bib10", "bib7", "bib30", "bib4" ]
12,743,167
NA|NA|NA|NA|NA
For the EEED mutant, the negative shift of the reversal potential in 2 mM Ca2+ was not observed in the presence of Na+, probably because in this condition the channel selectivity for monovalent cations is so high that extracellular acidification does not further increase it, in contrast with the observations in the wil...
[ "Talavera et al., 2001", "Ellinor et al., 1995", "Chen and Tsien, 1997", "Talavera et al., 2001", "Cataldi et al., 2002" ]
340
40,833
0
false
For the EEED mutant, the negative shift of the reversal potential in 2 mM Ca2+ was not observed in the presence of Na+, probably because in this condition the channel selectivity for monovalent cations is so high that extracellular acidification does not further increase it, in contrast with the observations in the wil...
[]
For the EEED mutant, the negative shift of the reversal potential in 2 mM Ca2+ was not observed in the presence of Na+, probably because in this condition the channel selectivity for monovalent cations is so high that extracellular acidification does not further increase it, in contrast with the observations in the wil...
true
true
true
true
true
7,034
18
DISCUSSION
1
Delisle and Satin (2000)
[ "bib8", "bib1" ]
12,743,167
NA|NA
Intriguingly, Delisle and Satin (2000) found that extracellular acidification increased the macroscopic conductance of the T-type channel α1H.
[ "Delisle and Satin (2000)", "Alvarez et al., 2000" ]
142
40,834
0
false
Intriguingly, Delisle and Satin (2000) found that extracellular acidification increased the macroscopic conductance of the T-type channel α1H.
[]
Intriguingly, Delisle and Satin found that extracellular acidification increased the macroscopic conductance of the T-type channel α1H.
true
true
true
true
true
7,035
18
DISCUSSION
1
Delisle and Satin (2000)
[ "bib8", "bib1" ]
12,743,167
NA|NA
Suspecting that this was due to the presence of extracellular Na+, we also addressed the effects of sodium ions on proton block and permeation through α1G.
[ "Delisle and Satin (2000)", "Alvarez et al., 2000" ]
155
40,835
0
false
Suspecting that this was due to the presence of extracellular Na+, we also addressed the effects of sodium ions on proton block and permeation through α1G.
[]
Suspecting that this was due to the presence of extracellular Na+, we also addressed the effects of sodium ions on proton block and permeation through α1G.
true
true
true
true
true
7,035
18
DISCUSSION
1
Delisle and Satin (2000)
[ "bib8", "bib1" ]
12,743,167
NA|NA
We found that the proton block in the presence of 150 mM Na+ and 2 mM Ca2+ was significantly reduced at negative potentials compared with that in 150 mM NMDG+, suggesting that channel protonation increased the Na+ permeation through the channel (Fig.
[ "Delisle and Satin (2000)", "Alvarez et al., 2000" ]
250
40,836
0
false
We found that the proton block in the presence of 150 mM Na+ and 2 mM Ca2+ was significantly reduced at negative potentials compared with that in 150 mM NMDG+, suggesting that channel protonation increased the Na+ permeation through the channel (Fig.
[]
We found that the proton block in the presence of 150 mM Na+ and 2 mM Ca2+ was significantly reduced at negative potentials compared with that in 150 mM NMDG+, suggesting that channel protonation increased the Na+ permeation through the channel (Fig.
true
true
true
true
true
7,035
18
DISCUSSION
1
Delisle and Satin (2000)
[ "bib8", "bib1" ]
12,743,167
NA|NA
Interestingly, the substitution of NMDG+ by Na+ did not significantly change the reversal potential of α1G, in contrast with the significant shift to positive potentials of V r in the EEED mutant at pHe 9.1 and 6.2 (Fig.
[ "Delisle and Satin (2000)", "Alvarez et al., 2000" ]
220
40,837
0
false
Interestingly, the substitution of NMDG+ by Na+ did not significantly change the reversal potential of α1G, in contrast with the significant shift to positive potentials of V r in the EEED mutant at pHe 9.1 and 6.2 (Fig.
[]
Interestingly, the substitution of NMDG+ by Na+ did not significantly change the reversal potential of α1G, in contrast with the significant shift to positive potentials of V r in the EEED mutant at pHe 9.1 and 6.2 (Fig.
true
true
true
true
true
7,035
18
DISCUSSION
1
Delisle and Satin (2000)
[ "bib8", "bib1" ]
12,743,167
NA|NA
On the other hand, the comparison of the amplitude of the tail currents recorded in the presence of NMDG+ or Na+ (Fig.
[ "Delisle and Satin (2000)", "Alvarez et al., 2000" ]
118
40,838
0
false
On the other hand, the comparison of the amplitude of the tail currents recorded in the presence of NMDG+ or Na+ (Fig.
[]
On the other hand, the comparison of the amplitude of the tail currents recorded in the presence of NMDG+ or Na+ (Fig.
true
true
true
true
true
7,035
18
DISCUSSION
1
Delisle and Satin (2000)
[ "bib8", "bib1" ]
12,743,167
NA|NA
11) indicates that under alkaline conditions extracellular Na+ blocks inward current through a1G, whereas Na+ appears to contribute to the inward current in acid extracellular medium.
[ "Delisle and Satin (2000)", "Alvarez et al., 2000" ]
183
40,839
0
false
11) indicates that under alkaline conditions extracellular Na+ blocks inward current through a1G, whereas Na+ appears to contribute to the inward current in acid extracellular medium.
[]
11) indicates that under alkaline conditions extracellular Na+ blocks inward current through a1G, whereas Na+ appears to contribute to the inward current in acid extracellular medium.
false
false
true
true
false
7,035
18
DISCUSSION
1
Alvarez et al., 2000
[ "bib8", "bib1" ]
12,743,167
NA|NA
These observations are in agreement with the previous finding that variations of extracellular Na+ do not change the basal T-type current in cardiac cells at pHe 7.4 (Alvarez et al., 2000).
[ "Delisle and Satin (2000)", "Alvarez et al., 2000" ]
189
40,840
1
false
These observations are in agreement with the previous finding that variations of extracellular Na+ do not change the basal T-type current in cardiac cells at pHe 7.4.
[ "Alvarez et al., 2000" ]
These observations are in agreement with the previous finding that variations of extracellular Na+ do not change the basal T-type current in cardiac cells at pHe 7.4.
true
true
true
true
true
7,035
18
DISCUSSION
1
Delisle and Satin (2000)
[ "bib8", "bib1" ]
12,743,167
NA|NA
In the EEED mutant, substitution of NMDG+ by Na+ increased inward currents, in accord with the significant enhancement of Na+ selectivity deduced from the changes in reversal potentials.
[ "Delisle and Satin (2000)", "Alvarez et al., 2000" ]
186
40,841
0
false
In the EEED mutant, substitution of NMDG+ by Na+ increased inward currents, in accord with the significant enhancement of Na+ selectivity deduced from the changes in reversal potentials.
[]
In the EEED mutant, substitution of NMDG+ by Na+ increased inward currents, in accord with the significant enhancement of Na+ selectivity deduced from the changes in reversal potentials.
true
true
true
true
true
7,035
19
DISCUSSION
0
null
null
12,743,167
null
Notably, the proton block of the Ca2+ permeation through α1G did not show voltage dependence and the same was the case for the effects of the substitution of NMDG+ by Na+ for both α1G and the EEED mutant.
null
204
40,842
0
false
null
null
Notably, the proton block of the Ca2+ permeation through α1G did not show voltage dependence and the same was the case for the effects of the substitution of NMDG+ by Na+ for both α1G and the EEED mutant.
true
true
true
true
true
7,036
19
DISCUSSION
0
null
null
12,743,167
null
These results suggest that the site of protonation and Na+ binding senses very little of the membrane electric field.
null
117
40,843
0
false
null
null
These results suggest that the site of protonation and Na+ binding senses very little of the membrane electric field.
true
true
true
true
true
7,036
19
DISCUSSION
0
null
null
12,743,167
null
The voltage dependence of the proton block in the wild-type channel in the presence of extracellular Na+ and in the EEED mutant are likely to be related to the proton-induced increase of the monovalent conduction at very negative potentials.
null
241
40,844
0
false
null
null
The voltage dependence of the proton block in the wild-type channel in the presence of extracellular Na+ and in the EEED mutant are likely to be related to the proton-induced increase of the monovalent conduction at very negative potentials.
true
true
true
true
true
7,036
20
DISCUSSION
1
Chen et al., 1996
[ "bib6", "bib13", "bib7", "bib34", "bib22", "bib15" ]
12,743,167
NA|NA|NA|NA|NA|NA
The evidence gathered from the L-type Ca2+ channel indicate that channel protonation controlling permeation properties occurs at the selectivity filter of this channel, i.e., the carboxilates of the EEEE pore locus (Chen et al., 1996; Klockner et al., 1996; Chen and Tsien, 1997; Varadi et al., 1999), rather than at a s...
[ "Chen et al., 1996", "Klockner et al., 1996", "Chen and Tsien, 1997", "Varadi et al., 1999", "Prod'hom et al., 1989", "Kuo and Hess, 1993" ]
427
40,845
0
false
The evidence gathered from the L-type Ca2+ channel indicate that channel protonation controlling permeation properties occurs at the selectivity filter of this channel, i.e., the carboxilates of the EEEE pore locus, rather than at a site modulating channel conductance via an allosteric mechanism.
[ "Chen et al., 1996; Klockner et al., 1996; Chen and Tsien, 1997; Varadi et al., 1999", "Prod'hom et al., 1989; Kuo and Hess, 1993" ]
The evidence gathered from the L-type Ca2+ channel indicate that channel protonation controlling permeation properties occurs at the selectivity filter of this channel, i.e., the carboxilates of the EEEE pore locus, rather than at a site modulating channel conductance via an allosteric mechanism.
true
true
true
true
true
7,037
20
DISCUSSION
1
Chen et al., 1996
[ "bib6", "bib13", "bib7", "bib34", "bib22", "bib15" ]
12,743,167
NA|NA|NA|NA|NA|NA
Taken together, we can conclude that in T-type Ca2+ channels, (a) the open pore block of the Ca2+ conduction and the decrease of the Ca2+/monovalent cations selectivity induced by protons depend on the [Ca2+]e, (b) at low pHe monovalent cations contribute significantly to the conduction, (c) protonation leading to a mo...
[ "Chen et al., 1996", "Klockner et al., 1996", "Chen and Tsien, 1997", "Varadi et al., 1999", "Prod'hom et al., 1989", "Kuo and Hess, 1993" ]
462
40,846
0
false
Taken together, we can conclude that in T-type Ca2+ channels, (a) the open pore block of the Ca2+ conduction and the decrease of the Ca2+/monovalent cations selectivity induced by protons depend on the [Ca2+]e, (b) at low pHe monovalent cations contribute significantly to the conduction, (c) protonation leading to a mo...
[]
Taken together, we can conclude that in T-type Ca2+ channels, the open pore block of the Ca2+ conduction and the decrease of the Ca2+/monovalent cations selectivity induced by protons depend on the e, (b) at low pHe monovalent cations contribute significantly to the conduction, (c) protonation leading to a modification...
true
true
true
true
true
7,037
20
DISCUSSION
1
Chen et al., 1996
[ "bib6", "bib13", "bib7", "bib34", "bib22", "bib15" ]
12,743,167
NA|NA|NA|NA|NA|NA
We propose that protonation of glutamate and/or aspartate residues neutralizes part of the negative charge of the selectivity filter and reduces the affinity for Ca2+, decreasing Ca2+/monovalent cation selectivity.
[ "Chen et al., 1996", "Klockner et al., 1996", "Chen and Tsien, 1997", "Varadi et al., 1999", "Prod'hom et al., 1989", "Kuo and Hess, 1993" ]
214
40,847
0
false
We propose that protonation of glutamate and/or aspartate residues neutralizes part of the negative charge of the selectivity filter and reduces the affinity for Ca2+, decreasing Ca2+/monovalent cation selectivity.
[]
We propose that protonation of glutamate and/or aspartate residues neutralizes part of the negative charge of the selectivity filter and reduces the affinity for Ca2+, decreasing Ca2+/monovalent cation selectivity.
true
true
true
true
true
7,037
20
DISCUSSION
1
Chen et al., 1996
[ "bib6", "bib13", "bib7", "bib34", "bib22", "bib15" ]
12,743,167
NA|NA|NA|NA|NA|NA
It is reasonable to think that protonation of the selectivity filter of Ca2+ channels might mimic the structure of the selectivity filter of sodium channels, which is built by a far less electronegative DEKA locus.
[ "Chen et al., 1996", "Klockner et al., 1996", "Chen and Tsien, 1997", "Varadi et al., 1999", "Prod'hom et al., 1989", "Kuo and Hess, 1993" ]
214
40,848
0
false
It is reasonable to think that protonation of the selectivity filter of Ca2+ channels might mimic the structure of the selectivity filter of sodium channels, which is built by a far less electronegative DEKA locus.
[]
It is reasonable to think that protonation of the selectivity filter of Ca2+ channels might mimic the structure of the selectivity filter of sodium channels, which is built by a far less electronegative DEKA locus.
true
true
true
true
true
7,037
21
DISCUSSION
1
Shah et al., 2001
[ "bib25", "bib33", "bib8" ]
12,743,167
NA|NA|NA
We propose that protons and Ca2+ modulate T-type channel gating by two mechanisms.
[ "Shah et al., 2001", "Tytgat et al., 1990", "Delisle and Satin, 2000" ]
82
40,849
0
false
We propose that protons and Ca2+ modulate T-type channel gating by two mechanisms.
[]
We propose that protons and Ca2+ modulate T-type channel gating by two mechanisms.
true
true
true
true
true
7,038
21
DISCUSSION
1
Shah et al., 2001
[ "bib25", "bib33", "bib8" ]
12,743,167
NA|NA|NA
First, both ions shift the voltage-dependent kinetics by neutralizing negative surface charges; and second, Ca2+ prevents the proton-induced inhibition of channel activation.
[ "Shah et al., 2001", "Tytgat et al., 1990", "Delisle and Satin, 2000" ]
174
40,850
0
false
First, both ions shift the voltage-dependent kinetics by neutralizing negative surface charges; and second, Ca2+ prevents the proton-induced inhibition of channel activation.
[]
First, both ions shift the voltage-dependent kinetics by neutralizing negative surface charges; and second, Ca2+ prevents the proton-induced inhibition of channel activation.
true
true
true
true
true
7,038
21
DISCUSSION
1
Shah et al., 2001
[ "bib25", "bib33", "bib8" ]
12,743,167
NA|NA|NA
The potential patho-physiological implications of the proton modulation of T-type channels has been associated with the activity of the thalamocortical network (Shah et al., 2001), the pacemaker function (Tytgat et al., 1990), and the generation of arrhythmias (Delisle and Satin, 2000) in cardiac tissue.
[ "Shah et al., 2001", "Tytgat et al., 1990", "Delisle and Satin, 2000" ]
305
40,851
1
false
The potential patho-physiological implications of the proton modulation of T-type channels has been associated with the activity of the thalamocortical network, the pacemaker function, and the generation of arrhythmias in cardiac tissue.
[ "Shah et al., 2001", "Tytgat et al., 1990", "Delisle and Satin, 2000" ]
The potential patho-physiological implications of the proton modulation of T-type channels has been associated with the activity of the thalamocortical network, the pacemaker function, and the generation of arrhythmias in cardiac tissue.
true
true
true
true
true
7,038
21
DISCUSSION
1
Shah et al., 2001
[ "bib25", "bib33", "bib8" ]
12,743,167
NA|NA|NA
In this context the consequences of the interrelated modifications of the activation and the inactivation of T-type channels by extracellular protons are particularly interesting.
[ "Shah et al., 2001", "Tytgat et al., 1990", "Delisle and Satin, 2000" ]
179
40,852
0
false
In this context the consequences of the interrelated modifications of the activation and the inactivation of T-type channels by extracellular protons are particularly interesting.
[]
In this context the consequences of the interrelated modifications of the activation and the inactivation of T-type channels by extracellular protons are particularly interesting.
true
true
true
true
true
7,038
21
DISCUSSION
1
Shah et al., 2001
[ "bib25", "bib33", "bib8" ]
12,743,167
NA|NA|NA
Ischemic and hypoxic conditions induce both extracellular acidification and cell depolarization in cardiac and nervous tissues.
[ "Shah et al., 2001", "Tytgat et al., 1990", "Delisle and Satin, 2000" ]
127
40,853
0
false
Ischemic and hypoxic conditions induce both extracellular acidification and cell depolarization in cardiac and nervous tissues.
[]
Ischemic and hypoxic conditions induce both extracellular acidification and cell depolarization in cardiac and nervous tissues.
true
true
true
true
true
7,038
21
DISCUSSION
1
Shah et al., 2001
[ "bib25", "bib33", "bib8" ]
12,743,167
NA|NA|NA
Thus, the coupled shift of steady-state activation and inactivation in extracellular acidification results in a concomitant shift of the T-type window current along the voltage axis in the direction of the change of the basal membrane potential.
[ "Shah et al., 2001", "Tytgat et al., 1990", "Delisle and Satin, 2000" ]
245
40,854
0
false
Thus, the coupled shift of steady-state activation and inactivation in extracellular acidification results in a concomitant shift of the T-type window current along the voltage axis in the direction of the change of the basal membrane potential.
[]
Thus, the coupled shift of steady-state activation and inactivation in extracellular acidification results in a concomitant shift of the T-type window current along the voltage axis in the direction of the change of the basal membrane potential.
true
true
true
true
true
7,038
21
DISCUSSION
1
Shah et al., 2001
[ "bib25", "bib33", "bib8" ]
12,743,167
NA|NA|NA
This means that, although protons reduce channel activation, the Ca2+ entry through T-type channels could be preserved during extracellular acidification, which in turn might regulate cellular functions by constant injection of inward current and the increase in intracellular Ca2+ concentration.
[ "Shah et al., 2001", "Tytgat et al., 1990", "Delisle and Satin, 2000" ]
296
40,855
0
false
This means that, although protons reduce channel activation, the Ca2+ entry through T-type channels could be preserved during extracellular acidification, which in turn might regulate cellular functions by constant injection of inward current and the increase in intracellular Ca2+ concentration.
[]
This means that, although protons reduce channel activation, the Ca2+ entry through T-type channels could be preserved during extracellular acidification, which in turn might regulate cellular functions by constant injection of inward current and the increase in intracellular Ca2+ concentration.
true
true
true
true
true
7,038
21
DISCUSSION
1
Shah et al., 2001
[ "bib25", "bib33", "bib8" ]
12,743,167
NA|NA|NA
On the other hand, we can speculate that the uneven proton effects on activation and inactivation properties, as well as the proton-induced change in channel selectivity toward monovalent ions and the block of Ca2+ permeation could protect against harmful Ca2+ overload.
[ "Shah et al., 2001", "Tytgat et al., 1990", "Delisle and Satin, 2000" ]
270
40,856
0
false
On the other hand, we can speculate that the uneven proton effects on activation and inactivation properties, as well as the proton-induced change in channel selectivity toward monovalent ions and the block of Ca2+ permeation could protect against harmful Ca2+ overload.
[]
On the other hand, we can speculate that the uneven proton effects on activation and inactivation properties, as well as the proton-induced change in channel selectivity toward monovalent ions and the block of Ca2+ permeation could protect against harmful Ca2+ overload.
true
true
true
true
true
7,038
0
DISCUSSION
1
Chen et al., 2003
[ "bib15", "bib23" ]
20,008,522
NA|NA
In this paper, we demonstrate a novel function for PD-L1 in promoting the development and sustaining the function of iT reg cells.
[ "Chen et al., 2003", "Fantini et al., 2004" ]
130
40,857
0
false
In this paper, we demonstrate a novel function for PD-L1 in promoting the development and sustaining the function of iT reg cells.
[]
In this paper, we demonstrate a novel function for PD-L1 in promoting the development and sustaining the function of iT reg cells.
true
true
true
true
true
7,039
0
DISCUSSION
1
Chen et al., 2003
[ "bib15", "bib23" ]
20,008,522
NA|NA
There was a profound defect in conversion of naive CD4 T cells into Foxp3+ iT reg cells in the absence of PD-L1.
[ "Chen et al., 2003", "Fantini et al., 2004" ]
112
40,858
0
false
There was a profound defect in conversion of naive CD4 T cells into Foxp3+ iT reg cells in the absence of PD-L1.
[]
There was a profound defect in conversion of naive CD4 T cells into Foxp3+ iT reg cells in the absence of PD-L1.
true
true
true
true
true
7,039
0
DISCUSSION
1
Chen et al., 2003
[ "bib15", "bib23" ]
20,008,522
NA|NA
Consistent with this observation, PD-L1 presented on beads (along with anti-CD3 and anti-CD28) could induce the development of functional Foxp3+ iT reg cells, demonstrating that PD-L1 is responsible for promoting iT reg cell development.
[ "Chen et al., 2003", "Fantini et al., 2004" ]
237
40,859
0
false
Consistent with this observation, PD-L1 presented on beads (along with anti-CD3 and anti-CD28) could induce the development of functional Foxp3+ iT reg cells, demonstrating that PD-L1 is responsible for promoting iT reg cell development.
[]
Consistent with this observation, PD-L1 presented on beads could induce the development of functional Foxp3+ iT reg cells, demonstrating that PD-L1 is responsible for promoting iT reg cell development.
true
true
true
true
true
7,039
0
DISCUSSION
1
Chen et al., 2003
[ "bib15", "bib23" ]
20,008,522
NA|NA
Although TGF-β signaling is important for the conversion of naive CD4+ T cells toward Foxp3-expressing cells with suppressive capacity (Chen et al., 2003; Fantini et al., 2004), PD-L1 could induce T reg cells in the absence of exogenous TGF-β, suggesting that PD-L1 signaling alone can serve to promote iT reg cell devel...
[ "Chen et al., 2003", "Fantini et al., 2004" ]
327
40,860
0
false
Although TGF-β signaling is important for the conversion of naive CD4+ T cells toward Foxp3-expressing cells with suppressive capacity, PD-L1 could induce T reg cells in the absence of exogenous TGF-β, suggesting that PD-L1 signaling alone can serve to promote iT reg cell development.
[ "Chen et al., 2003; Fantini et al., 2004" ]
Although TGF-β signaling is important for the conversion of naive CD4+ T cells toward Foxp3-expressing cells with suppressive capacity, PD-L1 could induce T reg cells in the absence of exogenous TGF-β, suggesting that PD-L1 signaling alone can serve to promote iT reg cell development.
true
true
true
true
true
7,039
0
DISCUSSION
1
Chen et al., 2003
[ "bib15", "bib23" ]
20,008,522
NA|NA
Our signaling studies support the conclusion that PD-L1 reduces signaling of the Akt–mTOR pathway in naive T cells, which is critical for their conversion into iT reg cells.
[ "Chen et al., 2003", "Fantini et al., 2004" ]
173
40,861
0
false
Our signaling studies support the conclusion that PD-L1 reduces signaling of the Akt–mTOR pathway in naive T cells, which is critical for their conversion into iT reg cells.
[]
Our signaling studies support the conclusion that PD-L1 reduces signaling of the Akt–mTOR pathway in naive T cells, which is critical for their conversion into iT reg cells.
true
true
true
true
true
7,039
0
DISCUSSION
1
Chen et al., 2003
[ "bib15", "bib23" ]
20,008,522
NA|NA
Furthermore, we show that PD-L1 has a novel role in sustaining expression of Foxp3 in iT reg cells and in enhancing iT reg cell suppressive function.
[ "Chen et al., 2003", "Fantini et al., 2004" ]
149
40,862
0
false
Furthermore, we show that PD-L1 has a novel role in sustaining expression of Foxp3 in iT reg cells and in enhancing iT reg cell suppressive function.
[]
Furthermore, we show that PD-L1 has a novel role in sustaining expression of Foxp3 in iT reg cells and in enhancing iT reg cell suppressive function.
true
true
true
true
true
7,039
0
DISCUSSION
1
Chen et al., 2003
[ "bib15", "bib23" ]
20,008,522
NA|NA
Thus, these studies reveal a new mechanism by which PD-L1 mediates T cell tolerance.
[ "Chen et al., 2003", "Fantini et al., 2004" ]
84
40,863
0
false
Thus, these studies reveal a new mechanism by which PD-L1 mediates T cell tolerance.
[]
Thus, these studies reveal a new mechanism by which PD-L1 mediates T cell tolerance.
true
true
true
true
true
7,039
0
DISCUSSION
1
Chen et al., 2003
[ "bib15", "bib23" ]
20,008,522
NA|NA
PD-L1 can inhibit self-reactive T cell responses by promoting iT reg cell development and maintaining iT reg cell function.
[ "Chen et al., 2003", "Fantini et al., 2004" ]
123
40,864
0
false
PD-L1 can inhibit self-reactive T cell responses by promoting iT reg cell development and maintaining iT reg cell function.
[]
PD-L1 can inhibit self-reactive T cell responses by promoting iT reg cell development and maintaining iT reg cell function.
true
true
true
true
true
7,039
1
DISCUSSION
1
Keir et al., 2008
[ "bib39", "bib12" ]
20,008,522
NA|NA
Where does PD-L1 exert its critical effects on iT reg cell development and function?
[ "Keir et al., 2008", "Brown et al., 2003" ]
84
40,865
0
false
Where does PD-L1 exert its critical effects on iT reg cell development and function?
[]
Where does PD-L1 exert its critical effects on iT reg cell development and function?
true
true
true
true
true
7,040
1
DISCUSSION
1
Keir et al., 2008
[ "bib39", "bib12" ]
20,008,522
NA|NA
PD-L1 is widely expressed on hematopoietic and nonhematopoietic cells (Keir et al., 2008).
[ "Keir et al., 2008", "Brown et al., 2003" ]
90
40,866
1
false
PD-L1 is widely expressed on hematopoietic and nonhematopoietic cells.
[ "Keir et al., 2008" ]
PD-L1 is widely expressed on hematopoietic and nonhematopoietic cells.
true
true
true
true
true
7,040
1
DISCUSSION
1
Brown et al., 2003
[ "bib39", "bib12" ]
20,008,522
NA|NA
There may be a critical interaction between PD-L1 expressing DC and T cells during the induction of T reg cell development from naive T cells (Brown et al., 2003).
[ "Keir et al., 2008", "Brown et al., 2003" ]
163
40,867
1
false
There may be a critical interaction between PD-L1 expressing DC and T cells during the induction of T reg cell development from naive T cells.
[ "Brown et al., 2003" ]
There may be a critical interaction between PD-L1 expressing DC and T cells during the induction of T reg cell development from naive T cells.
true
true
true
true
true
7,040
1
DISCUSSION
1
Keir et al., 2008
[ "bib39", "bib12" ]
20,008,522
NA|NA
PD-L1 is also expressed on T cells; however, WT T cells transferred into PD-L1−/−PD-L2−/−
[ "Keir et al., 2008", "Brown et al., 2003" ]
89
40,868
0
false
PD-L1 is also expressed on T cells; however, WT T cells transferred into PD-L1−/−PD-L2−/−
[]
PD-L1 is also expressed on T cells; however, WT T cells transferred into PD-L1−/−PD-L2−/−
true
true
false
true
false
7,040
1
DISCUSSION
1
Keir et al., 2008
[ "bib39", "bib12" ]
20,008,522
NA|NA
Rag−/− recipients could not convert to iT reg cells, suggesting that T cell–T cell interaction via PD-L1 is not sufficient to drive naive T cell conversion.
[ "Keir et al., 2008", "Brown et al., 2003" ]
156
40,869
0
false
Rag−/− recipients could not convert to iT reg cells, suggesting that T cell–T cell interaction via PD-L1 is not sufficient to drive naive T cell conversion.
[]
Rag−/− recipients could not convert to iT reg cells, suggesting that T cell–T cell interaction via PD-L1 is not sufficient to drive naive T cell conversion.
true
true
true
true
true
7,040
1
DISCUSSION
1
Keir et al., 2008
[ "bib39", "bib12" ]
20,008,522
NA|NA
Instead an interaction with the host environment is crucial for T reg cell conversion.
[ "Keir et al., 2008", "Brown et al., 2003" ]
86
40,870
0
false
Instead an interaction with the host environment is crucial for T reg cell conversion.
[]
Instead an interaction with the host environment is crucial for T reg cell conversion.
true
true
true
true
true
7,040
2
DISCUSSION
1
Keir et al., 2006
[ "bib36" ]
20,008,522
NA
Our bone marrow chimera studies have demonstrated an important role for PD-L1 on nonhematopoietic cells in mediating tissue tolerance (Keir et al., 2006).
[ "Keir et al., 2006" ]
154
40,871
1
false
Our bone marrow chimera studies have demonstrated an important role for PD-L1 on nonhematopoietic cells in mediating tissue tolerance.
[ "Keir et al., 2006" ]
Our bone marrow chimera studies have demonstrated an important role for PD-L1 on nonhematopoietic cells in mediating tissue tolerance.
true
true
true
true
true
7,041
2
DISCUSSION
1
Keir et al., 2006
[ "bib36" ]
20,008,522
NA
Our findings of critical roles for PD-L1 in the development and maintenance of iT reg cell function suggest that PD-L1 may protect tissues from the potentially pathogenic self-reactive T eff cells not only by inhibiting the function of T eff cells but also by increasing the frequency and function of T reg cells in the ...
[ "Keir et al., 2006" ]
334
40,872
0
false
Our findings of critical roles for PD-L1 in the development and maintenance of iT reg cell function suggest that PD-L1 may protect tissues from the potentially pathogenic self-reactive T eff cells not only by inhibiting the function of T eff cells but also by increasing the frequency and function of T reg cells in the ...
[]
Our findings of critical roles for PD-L1 in the development and maintenance of iT reg cell function suggest that PD-L1 may protect tissues from the potentially pathogenic self-reactive T eff cells not only by inhibiting the function of T eff cells but also by increasing the frequency and function of T reg cells in the ...
true
true
true
true
true
7,041
2
DISCUSSION
1
Keir et al., 2006
[ "bib36" ]
20,008,522
NA
By promoting de novo generation of iT reg cells in situ, PD-L1 may play a role in mediating immune privilege, especially in environments where TGF-β is present (e.g., placenta and eye).
[ "Keir et al., 2006" ]
185
40,873
0
false
By promoting de novo generation of iT reg cells in situ, PD-L1 may play a role in mediating immune privilege, especially in environments where TGF-β is present (e.g., placenta and eye).
[]
By promoting de novo generation of iT reg cells in situ, PD-L1 may play a role in mediating immune privilege, especially in environments where TGF-β is present.
true
true
true
true
true
7,041
3
DISCUSSION
1
Dong et al., 2002
[ "bib21", "bib34", "bib67", "bib41", "bib70", "bib9", "bib30", "bib53", "bib22", "bib74", "bib33", "bib51", "bib52", "bib76" ]
20,008,522
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
PD-L1 may also exert its inhibitory effects on anti-tumor and anti-microbial immunity, at least in part by inducing T reg cell development and sustaining iT reg cell function.
[ "Dong et al., 2002", "Iwai et al., 2002", "Strome et al., 2003", "Konishi et al., 2004", "Thompson et al., 2004", "Blank et al., 2005", "Hirano et al., 2005", "Ohigashi et al., 2005", "Dorfman et al., 2006", "Wu et al., 2006", "Inman et al., 2007", "Nakanishi et al., 2007", "Nomi et al., 200...
175
40,874
0
false
PD-L1 may also exert its inhibitory effects on anti-tumor and anti-microbial immunity, at least in part by inducing T reg cell development and sustaining iT reg cell function.
[]
PD-L1 may also exert its inhibitory effects on anti-tumor and anti-microbial immunity, at least in part by inducing T reg cell development and sustaining iT reg cell function.
true
true
true
true
true
7,042
3
DISCUSSION
1
Dong et al., 2002
[ "bib21", "bib34", "bib67", "bib41", "bib70", "bib9", "bib30", "bib53", "bib22", "bib74", "bib33", "bib51", "bib52", "bib76" ]
20,008,522
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
PD-L1 is expressed on a wide variety of tumors, and high levels of PD-L1 expression strongly correlate with unfavorable prognosis in several cancers (Dong et al., 2002; Iwai et al., 2002; Strome et al., 2003; Konishi et al., 2004; Thompson et al., 2004; Blank et al., 2005; Hirano et al., 2005; Ohigashi et al., 2005; Do...
[ "Dong et al., 2002", "Iwai et al., 2002", "Strome et al., 2003", "Konishi et al., 2004", "Thompson et al., 2004", "Blank et al., 2005", "Hirano et al., 2005", "Ohigashi et al., 2005", "Dorfman et al., 2006", "Wu et al., 2006", "Inman et al., 2007", "Nakanishi et al., 2007", "Nomi et al., 200...
440
40,875
0
false
PD-L1 is expressed on a wide variety of tumors, and high levels of PD-L1 expression strongly correlate with unfavorable prognosis in several cancers.
[ "Dong et al., 2002; Iwai et al., 2002; Strome et al., 2003; Konishi et al., 2004; Thompson et al., 2004; Blank et al., 2005; Hirano et al., 2005; Ohigashi et al., 2005; Dorfman et al., 2006; Wu et al., 2006; Inman et al., 2007; Nakanishi et al., 2007; Nomi et al., 2007; Zhang et al., 2008" ]
PD-L1 is expressed on a wide variety of tumors, and high levels of PD-L1 expression strongly correlate with unfavorable prognosis in several cancers.
true
true
true
true
true
7,042
3
DISCUSSION
1
Dong et al., 2002
[ "bib21", "bib34", "bib67", "bib41", "bib70", "bib9", "bib30", "bib53", "bib22", "bib74", "bib33", "bib51", "bib52", "bib76" ]
20,008,522
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
The numbers of Foxp3+ T cells within tumors also correlates with a poor prognosis.
[ "Dong et al., 2002", "Iwai et al., 2002", "Strome et al., 2003", "Konishi et al., 2004", "Thompson et al., 2004", "Blank et al., 2005", "Hirano et al., 2005", "Ohigashi et al., 2005", "Dorfman et al., 2006", "Wu et al., 2006", "Inman et al., 2007", "Nakanishi et al., 2007", "Nomi et al., 200...
82
40,876
0
false
The numbers of Foxp3+ T cells within tumors also correlates with a poor prognosis.
[]
The numbers of Foxp3+ T cells within tumors also correlates with a poor prognosis.
true
true
true
true
true
7,042
3
DISCUSSION
1
Dong et al., 2002
[ "bib21", "bib34", "bib67", "bib41", "bib70", "bib9", "bib30", "bib53", "bib22", "bib74", "bib33", "bib51", "bib52", "bib76" ]
20,008,522
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
Our work provides a mechanism by which high PD-L1 expression can lead to increased numbers of Foxp3+ T reg cells and thus, poor prognosis.
[ "Dong et al., 2002", "Iwai et al., 2002", "Strome et al., 2003", "Konishi et al., 2004", "Thompson et al., 2004", "Blank et al., 2005", "Hirano et al., 2005", "Ohigashi et al., 2005", "Dorfman et al., 2006", "Wu et al., 2006", "Inman et al., 2007", "Nakanishi et al., 2007", "Nomi et al., 200...
138
40,877
0
false
Our work provides a mechanism by which high PD-L1 expression can lead to increased numbers of Foxp3+ T reg cells and thus, poor prognosis.
[]
Our work provides a mechanism by which high PD-L1 expression can lead to increased numbers of Foxp3+ T reg cells and thus, poor prognosis.
true
true
true
true
true
7,042
3
DISCUSSION
1
Dong et al., 2002
[ "bib21", "bib34", "bib67", "bib41", "bib70", "bib9", "bib30", "bib53", "bib22", "bib74", "bib33", "bib51", "bib52", "bib76" ]
20,008,522
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
Increased PD-L1 expression by tumor cells may induce and maintain iT reg cells in the periphery, thereby augmenting the suppression of anti-tumor T cell responses and allowing tumor progression.
[ "Dong et al., 2002", "Iwai et al., 2002", "Strome et al., 2003", "Konishi et al., 2004", "Thompson et al., 2004", "Blank et al., 2005", "Hirano et al., 2005", "Ohigashi et al., 2005", "Dorfman et al., 2006", "Wu et al., 2006", "Inman et al., 2007", "Nakanishi et al., 2007", "Nomi et al., 200...
194
40,878
0
false
Increased PD-L1 expression by tumor cells may induce and maintain iT reg cells in the periphery, thereby augmenting the suppression of anti-tumor T cell responses and allowing tumor progression.
[]
Increased PD-L1 expression by tumor cells may induce and maintain iT reg cells in the periphery, thereby augmenting the suppression of anti-tumor T cell responses and allowing tumor progression.
true
true
true
true
true
7,042
4
DISCUSSION
1
Belkaid, 2008
[ "bib5", "bib20", "bib6", "bib3", "bib65" ]
20,008,522
NA|NA|NA|NA|NA
Increased T reg cells are also seen during chronic infections (Belkaid, 2008), correlating with a lack of sterilizing immunity.
[ "Belkaid, 2008", "Das et al., 2006", "Beswick et al., 2007", "Barber et al., 2006", "Sharpe et al., 2007" ]
127
40,879
1
false
Increased T reg cells are also seen during chronic infections, correlating with a lack of sterilizing immunity.
[ "Belkaid, 2008" ]
Increased T reg cells are also seen during chronic infections, correlating with a lack of sterilizing immunity.
true
true
true
true
true
7,043
4
DISCUSSION
1
Das et al., 2006
[ "bib5", "bib20", "bib6", "bib3", "bib65" ]
20,008,522
NA|NA|NA|NA|NA
During persistent infection by Helicobacter pylori, PD-L1 is up-regulated on gastric epithelial cells (Das et al., 2006).
[ "Belkaid, 2008", "Das et al., 2006", "Beswick et al., 2007", "Barber et al., 2006", "Sharpe et al., 2007" ]
121
40,880
1
false
During persistent infection by Helicobacter pylori, PD-L1 is up-regulated on gastric epithelial cells.
[ "Das et al., 2006" ]
During persistent infection by Helicobacter pylori, PD-L1 is up-regulated on gastric epithelial cells.
true
true
true
true
true
7,043
4
DISCUSSION
1
Beswick et al., 2007
[ "bib5", "bib20", "bib6", "bib3", "bib65" ]
20,008,522
NA|NA|NA|NA|NA
Blocking PD-L1 on gastric epithelial cells enhances CD4 T eff cell function and prevents the generation of CD4+CD25hiFoxp3+ T reg cells in vitro (Beswick et al., 2007).
[ "Belkaid, 2008", "Das et al., 2006", "Beswick et al., 2007", "Barber et al., 2006", "Sharpe et al., 2007" ]
168
40,881
1
false
Blocking PD-L1 on gastric epithelial cells enhances CD4 T eff cell function and prevents the generation of CD4+CD25hiFoxp3+ T reg cells in vitro.
[ "Beswick et al., 2007" ]
Blocking PD-L1 on gastric epithelial cells enhances CD4 T eff cell function and prevents the generation of CD4+CD25hiFoxp3+ T reg cells in vitro.
true
true
true
true
true
7,043
4
DISCUSSION
1
Belkaid, 2008
[ "bib5", "bib20", "bib6", "bib3", "bib65" ]
20,008,522
NA|NA|NA|NA|NA
During chronic viral infections, PD-L1 has a key role in limiting the function of exhausted CD8 T cells (Barber et al., 2006; Sharpe et al., 2007).
[ "Belkaid, 2008", "Das et al., 2006", "Beswick et al., 2007", "Barber et al., 2006", "Sharpe et al., 2007" ]
147
40,882
0
false
During chronic viral infections, PD-L1 has a key role in limiting the function of exhausted CD8 T cells.
[ "Barber et al., 2006; Sharpe et al., 2007" ]
During chronic viral infections, PD-L1 has a key role in limiting the function of exhausted CD8 T cells.
true
true
true
true
true
7,043
4
DISCUSSION
1
Belkaid, 2008
[ "bib5", "bib20", "bib6", "bib3", "bib65" ]
20,008,522
NA|NA|NA|NA|NA
PD-L1 blockade reinvigorates the function of these T cells and enhances viral clearance.
[ "Belkaid, 2008", "Das et al., 2006", "Beswick et al., 2007", "Barber et al., 2006", "Sharpe et al., 2007" ]
88
40,883
0
false
PD-L1 blockade reinvigorates the function of these T cells and enhances viral clearance.
[]
PD-L1 blockade reinvigorates the function of these T cells and enhances viral clearance.
true
true
true
true
true
7,043
4
DISCUSSION
1
Belkaid, 2008
[ "bib5", "bib20", "bib6", "bib3", "bib65" ]
20,008,522
NA|NA|NA|NA|NA
Thus, PD-L1 may exert inhibitory effects in chronic infections by promoting iT reg cell development and maintaining iT reg cell function, as well as by inhibiting anti-microbial T eff cell function.
[ "Belkaid, 2008", "Das et al., 2006", "Beswick et al., 2007", "Barber et al., 2006", "Sharpe et al., 2007" ]
198
40,884
0
false
Thus, PD-L1 may exert inhibitory effects in chronic infections by promoting iT reg cell development and maintaining iT reg cell function, as well as by inhibiting anti-microbial T eff cell function.
[]
Thus, PD-L1 may exert inhibitory effects in chronic infections by promoting iT reg cell development and maintaining iT reg cell function, as well as by inhibiting anti-microbial T eff cell function.
true
true
true
true
true
7,043
5
DISCUSSION
1
Clark et al., 1999
[ "bib16", "bib13", "bib63" ]
20,008,522
NA|NA|NA
PD-L1−/−PD-L2−/−Rag−/− recipients of Foxp3− naive T cells resemble scurfy mice, which have a deficit in Foxp3 and die by 3 wk of age as a result of multiorgan infiltration of CD4+CD8− T cells (Clark et al., 1999; Brunkow et al., 2001; Schubert et al., 2001).
[ "Clark et al., 1999", "Brunkow et al., 2001", "Schubert et al., 2001" ]
258
40,885
0
false
PD-L1−/−PD-L2−/−Rag−/− recipients of Foxp3− naive T cells resemble scurfy mice, which have a deficit in Foxp3 and die by 3 wk of age as a result of multiorgan infiltration of CD4+CD8− T cells.
[ "Clark et al., 1999; Brunkow et al., 2001; Schubert et al., 2001" ]
PD-L1−/−PD-L2−/−Rag−/− recipients of Foxp3− naive T cells resemble scurfy mice, which have a deficit in Foxp3 and die by 3 wk of age as a result of multiorgan infiltration of CD4+CD8− T cells.
true
true
true
true
true
7,044
5
DISCUSSION
1
Clark et al., 1999
[ "bib16", "bib13", "bib63" ]
20,008,522
NA|NA|NA
PD-L1−/−PD-L2−/−Rag−/− recipients had a marked deficit in Foxp3+ T reg cell development, altering the T reg/T eff cell ratio.
[ "Clark et al., 1999", "Brunkow et al., 2001", "Schubert et al., 2001" ]
125
40,886
0
false
PD-L1−/−PD-L2−/−Rag−/− recipients had a marked deficit in Foxp3+ T reg cell development, altering the T reg/T eff cell ratio.
[]
PD-L1−/−PD-L2−/−Rag−/− recipients had a marked deficit in Foxp3+ T reg cell development, altering the T reg/T eff cell ratio.
true
true
true
true
true
7,044
5
DISCUSSION
1
Clark et al., 1999
[ "bib16", "bib13", "bib63" ]
20,008,522
NA|NA|NA
These findings illustrate the important role of PD-L1 in regulating the dynamic balance between T eff and T reg cells in vivo.
[ "Clark et al., 1999", "Brunkow et al., 2001", "Schubert et al., 2001" ]
126
40,887
0
false
These findings illustrate the important role of PD-L1 in regulating the dynamic balance between T eff and T reg cells in vivo.
[]
These findings illustrate the important role of PD-L1 in regulating the dynamic balance between T eff and T reg cells in vivo.
true
true
true
true
true
7,044
5
DISCUSSION
1
Clark et al., 1999
[ "bib16", "bib13", "bib63" ]
20,008,522
NA|NA|NA
PD-L1 may do the following: (a) control T reg cell development in lymphoid organs, which is important for immune homeostasis; (b) promote T reg cell development at target tissues, protecting against immune-mediated tissue damage, and (c) sustain and enhance T reg cell function within an inflammatory microenvironment, e...
[ "Clark et al., 1999", "Brunkow et al., 2001", "Schubert et al., 2001" ]
375
40,888
0
false
PD-L1 may do the following: (a) control T reg cell development in lymphoid organs, which is important for immune homeostasis; (b) promote T reg cell development at target tissues, protecting against immune-mediated tissue damage, and (c) sustain and enhance T reg cell function within an inflammatory microenvironment, e...
[]
PD-L1 may do the following: control T reg cell development in lymphoid organs, which is important for immune homeostasis; (b) promote T reg cell development at target tissues, protecting against immune-mediated tissue damage, and (c) sustain and enhance T reg cell function within an inflammatory microenvironment, effec...
true
true
true
true
true
7,044
6
DISCUSSION
1
Fontenot et al., 2003
[ "bib24", "bib31", "bib71", "bib63", "bib24", "bib25", "bib31", "bib27", "bib29", "bib50", "bib55", "bib57", "bib18", "bib29", "bib57", "bib64", "bib46" ]
20,008,522
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
Foxp3 is a transcription factor only expressed in the T reg cell lineage (Fontenot et al., 2003; Hori et al., 2003; Vignali et al., 2008).
[ "Fontenot et al., 2003", "Hori et al., 2003", "Vignali et al., 2008", "Schubert et al., 2001", "Fontenot et al. 2003", "2005", "Hori et al., 2003", "Gavin et al., 2007", "Hill et al., 2007", "Marie et al., 2005", "Pyzik and Piccirillo, 2007", "Ramsdell, 2003", "Collison et al., 2007", "Hil...
138
40,889
0
false
Foxp3 is a transcription factor only expressed in the T reg cell lineage.
[ "Fontenot et al., 2003; Hori et al., 2003; Vignali et al., 2008" ]
Foxp3 is a transcription factor only expressed in the T reg cell lineage.
true
true
true
true
true
7,045
6
DISCUSSION
1
Fontenot et al., 2003
[ "bib24", "bib31", "bib71", "bib63", "bib24", "bib25", "bib31", "bib27", "bib29", "bib50", "bib55", "bib57", "bib18", "bib29", "bib57", "bib64", "bib46" ]
20,008,522
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
Along with contributing a distinct genetic signature to T reg cells, Foxp3 conveys regulatory activity to nT reg cells, iT reg cells, and, upon ectopic expression, in conventional T cells (Schubert et al., 2001; Fontenot et al.
[ "Fontenot et al., 2003", "Hori et al., 2003", "Vignali et al., 2008", "Schubert et al., 2001", "Fontenot et al. 2003", "2005", "Hori et al., 2003", "Gavin et al., 2007", "Hill et al., 2007", "Marie et al., 2005", "Pyzik and Piccirillo, 2007", "Ramsdell, 2003", "Collison et al., 2007", "Hil...
227
40,890
0
false
Along with contributing a distinct genetic signature to T reg cells, Foxp3 conveys regulatory activity to nT reg cells, iT reg cells, and, upon ectopic expression, in conventional T cells (Schubert et al., 2001; Fontenot et al.
[]
Along with contributing a distinct genetic signature to T reg cells, Foxp3 conveys regulatory activity to nT reg cells, iT reg cells, and, upon ectopic expression, in conventional T cells (Schubert et al., 2001; Fontenot et al.
true
true
true
true
true
7,045
6
DISCUSSION
1
Fontenot et al., 2003
[ "bib24", "bib31", "bib71", "bib63", "bib24", "bib25", "bib31", "bib27", "bib29", "bib50", "bib55", "bib57", "bib18", "bib29", "bib57", "bib64", "bib46" ]
20,008,522
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
2003, 2005; Hori et al., 2003; Gavin et al., 2007; Hill et al., 2007).
[ "Fontenot et al., 2003", "Hori et al., 2003", "Vignali et al., 2008", "Schubert et al., 2001", "Fontenot et al. 2003", "2005", "Hori et al., 2003", "Gavin et al., 2007", "Hill et al., 2007", "Marie et al., 2005", "Pyzik and Piccirillo, 2007", "Ramsdell, 2003", "Collison et al., 2007", "Hil...
70
40,891
0
false
2003, 2005; Hori et al., 2003; Gavin et al., 2007; Hill et al., 2007).
[]
2003, 2005; Hori et al., 2003; Gavin et al., 2007; Hill et al., 2007).
false
false
true
true
false
7,045
6
DISCUSSION
1
Fontenot et al., 2003
[ "bib24", "bib31", "bib71", "bib63", "bib24", "bib25", "bib31", "bib27", "bib29", "bib50", "bib55", "bib57", "bib18", "bib29", "bib57", "bib64", "bib46" ]
20,008,522
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
PD-L1 can induce and maintain the expression of Foxp3 in iT reg cells, suggesting that PD-L1 may function to stabilize and sustain T reg cell function in the periphery, similar to effects reported for TGF-β (Marie et al., 2005;
[ "Fontenot et al., 2003", "Hori et al., 2003", "Vignali et al., 2008", "Schubert et al., 2001", "Fontenot et al. 2003", "2005", "Hori et al., 2003", "Gavin et al., 2007", "Hill et al., 2007", "Marie et al., 2005", "Pyzik and Piccirillo, 2007", "Ramsdell, 2003", "Collison et al., 2007", "Hil...
227
40,892
0
false
PD-L1 can induce and maintain the expression of Foxp3 in iT reg cells, suggesting that PD-L1 may function to stabilize and sustain T reg cell function in the periphery, similar to effects reported for TGF-β (Marie et al., 2005;
[]
PD-L1 can induce and maintain the expression of Foxp3 in iT reg cells, suggesting that PD-L1 may function to stabilize and sustain T reg cell function in the periphery, similar to effects reported for TGF-β (Marie et al., 2005;
true
true
false
true
false
7,045
6
DISCUSSION
1
Fontenot et al., 2003
[ "bib24", "bib31", "bib71", "bib63", "bib24", "bib25", "bib31", "bib27", "bib29", "bib50", "bib55", "bib57", "bib18", "bib29", "bib57", "bib64", "bib46" ]
20,008,522
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
Pyzik and Piccirillo, 2007).
[ "Fontenot et al., 2003", "Hori et al., 2003", "Vignali et al., 2008", "Schubert et al., 2001", "Fontenot et al. 2003", "2005", "Hori et al., 2003", "Gavin et al., 2007", "Hill et al., 2007", "Marie et al., 2005", "Pyzik and Piccirillo, 2007", "Ramsdell, 2003", "Collison et al., 2007", "Hil...
28
40,893
0
false
Pyzik and Piccirillo, 2007).
[]
Pyzik and Piccirillo, 2007).
true
true
true
true
true
7,045
6
DISCUSSION
1
Fontenot et al., 2003
[ "bib24", "bib31", "bib71", "bib63", "bib24", "bib25", "bib31", "bib27", "bib29", "bib50", "bib55", "bib57", "bib18", "bib29", "bib57", "bib64", "bib46" ]
20,008,522
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
This maintenance of Foxp3 expression may explain both the increased efficiency of suppression seen for T reg cells cultured with PD-L1 and the lack of T reg cell conversion in the PD-L1−/−PD-L2−/−Rag−/− adoptive transfer recipients.
[ "Fontenot et al., 2003", "Hori et al., 2003", "Vignali et al., 2008", "Schubert et al., 2001", "Fontenot et al. 2003", "2005", "Hori et al., 2003", "Gavin et al., 2007", "Hill et al., 2007", "Marie et al., 2005", "Pyzik and Piccirillo, 2007", "Ramsdell, 2003", "Collison et al., 2007", "Hil...
232
40,894
0
false
This maintenance of Foxp3 expression may explain both the increased efficiency of suppression seen for T reg cells cultured with PD-L1 and the lack of T reg cell conversion in the PD-L1−/−PD-L2−/−Rag−/− adoptive transfer recipients.
[]
This maintenance of Foxp3 expression may explain both the increased efficiency of suppression seen for T reg cells cultured with PD-L1 and the lack of T reg cell conversion in the PD-L1−/−PD-L2−/−Rag−/− adoptive transfer recipients.
true
true
true
true
true
7,045
6
DISCUSSION
1
Fontenot et al., 2003
[ "bib24", "bib31", "bib71", "bib63", "bib24", "bib25", "bib31", "bib27", "bib29", "bib50", "bib55", "bib57", "bib18", "bib29", "bib57", "bib64", "bib46" ]
20,008,522
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
It has been suggested that although Foxp3 expression is a salient feature of the regulatory cell signature, it is not the master regulator of T reg cell development (Ramsdell, 2003; Collison et al., 2007; Hill et al., 2007).
[ "Fontenot et al., 2003", "Hori et al., 2003", "Vignali et al., 2008", "Schubert et al., 2001", "Fontenot et al. 2003", "2005", "Hori et al., 2003", "Gavin et al., 2007", "Hill et al., 2007", "Marie et al., 2005", "Pyzik and Piccirillo, 2007", "Ramsdell, 2003", "Collison et al., 2007", "Hil...
224
40,895
0
false
It has been suggested that although Foxp3 expression is a salient feature of the regulatory cell signature, it is not the master regulator of T reg cell development.
[ "Ramsdell, 2003; Collison et al., 2007; Hill et al., 2007" ]
It has been suggested that although Foxp3 expression is a salient feature of the regulatory cell signature, it is not the master regulator of T reg cell development.
true
true
true
true
true
7,045
6
DISCUSSION
1
Lin et al., 2007
[ "bib24", "bib31", "bib71", "bib63", "bib24", "bib25", "bib31", "bib27", "bib29", "bib50", "bib55", "bib57", "bib18", "bib29", "bib57", "bib64", "bib46" ]
20,008,522
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
In fact, it is increasingly clear that other factors (such as TGF-β and IL-2; Ramsdell, 2003; Setoguchi et al., 2005) induce key changes within the regulatory cell transcriptome that contribute to the identity of T reg cells separate from, and in addition to, the effects attributed to Foxp3 (Lin et al., 2007).
[ "Fontenot et al., 2003", "Hori et al., 2003", "Vignali et al., 2008", "Schubert et al., 2001", "Fontenot et al. 2003", "2005", "Hori et al., 2003", "Gavin et al., 2007", "Hill et al., 2007", "Marie et al., 2005", "Pyzik and Piccirillo, 2007", "Ramsdell, 2003", "Collison et al., 2007", "Hil...
311
40,896
1
false
In fact, it is increasingly clear that other factors induce key changes within the regulatory cell transcriptome that contribute to the identity of T reg cells separate from, and in addition to, the effects attributed to Foxp3.
[ "such as TGF-β and IL-2; Ramsdell, 2003; Setoguchi et al., 2005", "Lin et al., 2007" ]
In fact, it is increasingly clear that other factors induce key changes within the regulatory cell transcriptome that contribute to the identity of T reg cells separate from, and in addition to, the effects attributed to Foxp3.
true
true
true
true
true
7,045
6
DISCUSSION
1
Fontenot et al., 2003
[ "bib24", "bib31", "bib71", "bib63", "bib24", "bib25", "bib31", "bib27", "bib29", "bib50", "bib55", "bib57", "bib18", "bib29", "bib57", "bib64", "bib46" ]
20,008,522
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
In vivo, TGF-β production is maintained at a basal level and up-regulated with inflammation.
[ "Fontenot et al., 2003", "Hori et al., 2003", "Vignali et al., 2008", "Schubert et al., 2001", "Fontenot et al. 2003", "2005", "Hori et al., 2003", "Gavin et al., 2007", "Hill et al., 2007", "Marie et al., 2005", "Pyzik and Piccirillo, 2007", "Ramsdell, 2003", "Collison et al., 2007", "Hil...
92
40,897
0
false
In vivo, TGF-β production is maintained at a basal level and up-regulated with inflammation.
[]
In vivo, TGF-β production is maintained at a basal level and up-regulated with inflammation.
true
true
true
true
true
7,045
6
DISCUSSION
1
Fontenot et al., 2003
[ "bib24", "bib31", "bib71", "bib63", "bib24", "bib25", "bib31", "bib27", "bib29", "bib50", "bib55", "bib57", "bib18", "bib29", "bib57", "bib64", "bib46" ]
20,008,522
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
Interestingly, endogenous TGF-β was not sufficient to induce and/or maintain Foxp3+ iT reg cells in PD-L1−/−PD-L2−/−
[ "Fontenot et al., 2003", "Hori et al., 2003", "Vignali et al., 2008", "Schubert et al., 2001", "Fontenot et al. 2003", "2005", "Hori et al., 2003", "Gavin et al., 2007", "Hill et al., 2007", "Marie et al., 2005", "Pyzik and Piccirillo, 2007", "Ramsdell, 2003", "Collison et al., 2007", "Hil...
116
40,898
0
false
Interestingly, endogenous TGF-β was not sufficient to induce and/or maintain Foxp3+ iT reg cells in PD-L1−/−PD-L2−/−
[]
Interestingly, endogenous TGF-β was not sufficient to induce and/or maintain Foxp3+ iT reg cells in PD-L1−/−PD-L2−/−
true
true
false
true
false
7,045
6
DISCUSSION
1
Fontenot et al., 2003
[ "bib24", "bib31", "bib71", "bib63", "bib24", "bib25", "bib31", "bib27", "bib29", "bib50", "bib55", "bib57", "bib18", "bib29", "bib57", "bib64", "bib46" ]
20,008,522
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
Rag−/− recipients.
[ "Fontenot et al., 2003", "Hori et al., 2003", "Vignali et al., 2008", "Schubert et al., 2001", "Fontenot et al. 2003", "2005", "Hori et al., 2003", "Gavin et al., 2007", "Hill et al., 2007", "Marie et al., 2005", "Pyzik and Piccirillo, 2007", "Ramsdell, 2003", "Collison et al., 2007", "Hil...
18
40,899
0
false
Rag−/− recipients.
[]
Rag−/− recipients.
true
true
true
true
true
7,045
6
DISCUSSION
1
Fontenot et al., 2003
[ "bib24", "bib31", "bib71", "bib63", "bib24", "bib25", "bib31", "bib27", "bib29", "bib50", "bib55", "bib57", "bib18", "bib29", "bib57", "bib64", "bib46" ]
20,008,522
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
In complementary studies, PD-L1 blockade similarly impaired iT reg cell development in vivo, showing that loss of PD-L1 can diminish the effect of TGF-β, which is critical for iT reg cell identity and function.
[ "Fontenot et al., 2003", "Hori et al., 2003", "Vignali et al., 2008", "Schubert et al., 2001", "Fontenot et al. 2003", "2005", "Hori et al., 2003", "Gavin et al., 2007", "Hill et al., 2007", "Marie et al., 2005", "Pyzik and Piccirillo, 2007", "Ramsdell, 2003", "Collison et al., 2007", "Hil...
210
40,900
0
false
In complementary studies, PD-L1 blockade similarly impaired iT reg cell development in vivo, showing that loss of PD-L1 can diminish the effect of TGF-β, which is critical for iT reg cell identity and function.
[]
In complementary studies, PD-L1 blockade similarly impaired iT reg cell development in vivo, showing that loss of PD-L1 can diminish the effect of TGF-β, which is critical for iT reg cell identity and function.
true
true
true
true
true
7,045
6
DISCUSSION
1
Fontenot et al., 2003
[ "bib24", "bib31", "bib71", "bib63", "bib24", "bib25", "bib31", "bib27", "bib29", "bib50", "bib55", "bib57", "bib18", "bib29", "bib57", "bib64", "bib46" ]
20,008,522
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
This indicates that PD-L1 contributes unique and essential signals that drive iT reg cell development and function.
[ "Fontenot et al., 2003", "Hori et al., 2003", "Vignali et al., 2008", "Schubert et al., 2001", "Fontenot et al. 2003", "2005", "Hori et al., 2003", "Gavin et al., 2007", "Hill et al., 2007", "Marie et al., 2005", "Pyzik and Piccirillo, 2007", "Ramsdell, 2003", "Collison et al., 2007", "Hil...
115
40,901
0
false
This indicates that PD-L1 contributes unique and essential signals that drive iT reg cell development and function.
[]
This indicates that PD-L1 contributes unique and essential signals that drive iT reg cell development and function.
true
true
true
true
true
7,045
7
DISCUSSION
1
Qu et al., 2007
[ "bib56", "bib66", "bib28", "bib48", "bib62" ]
20,008,522
NA|NA|NA|NA|NA
We find that PD-L1 attenuates the Akt signaling pathway during the conversion of naive T cells to T reg cells by reducing the phosphorylation of Akt and its downstream substrates mTOR and S6 while simultaneously augmenting PTEN.
[ "Qu et al., 2007", "Strauss et al., 2007", "Haxhinasto et al., 2008", "Long and Buckner, 2008", "Sauer et al., 2008" ]
228
40,902
0
false
We find that PD-L1 attenuates the Akt signaling pathway during the conversion of naive T cells to T reg cells by reducing the phosphorylation of Akt and its downstream substrates mTOR and S6 while simultaneously augmenting PTEN.
[]
We find that PD-L1 attenuates the Akt signaling pathway during the conversion of naive T cells to T reg cells by reducing the phosphorylation of Akt and its downstream substrates mTOR and S6 while simultaneously augmenting PTEN.
true
true
true
true
true
7,046
7
DISCUSSION
1
Qu et al., 2007
[ "bib56", "bib66", "bib28", "bib48", "bib62" ]
20,008,522
NA|NA|NA|NA|NA
Previous work has shown that truncation of TCR signaling and inhibition of the Akt–mTOR signaling axis is critical for T reg cell development (Qu et al., 2007; Strauss et al., 2007;
[ "Qu et al., 2007", "Strauss et al., 2007", "Haxhinasto et al., 2008", "Long and Buckner, 2008", "Sauer et al., 2008" ]
181
40,903
0
false
Previous work has shown that truncation of TCR signaling and inhibition of the Akt–mTOR signaling axis is critical for T reg cell development (Qu et al., 2007; Strauss et al., 2007;
[]
Previous work has shown that truncation of TCR signaling and inhibition of the Akt–mTOR signaling axis is critical for T reg cell development (Qu et al., 2007; Strauss et al., 2007;
true
true
false
true
false
7,046
7
DISCUSSION
1
Qu et al., 2007
[ "bib56", "bib66", "bib28", "bib48", "bib62" ]
20,008,522
NA|NA|NA|NA|NA
Haxhinasto et al., 2008; Long and Buckner, 2008; Sauer et al., 2008).
[ "Qu et al., 2007", "Strauss et al., 2007", "Haxhinasto et al., 2008", "Long and Buckner, 2008", "Sauer et al., 2008" ]
69
40,904
0
false
Haxhinasto et al., 2008; Long and Buckner, 2008; Sauer et al., 2008).
[]
Haxhinasto et al., 2008; Long and Buckner, 2008; Sauer et al., 2008).
true
true
true
true
true
7,046
7
DISCUSSION
1
Qu et al., 2007
[ "bib56", "bib66", "bib28", "bib48", "bib62" ]
20,008,522
NA|NA|NA|NA|NA
In these studies, drug inhibitors (FK506, rapamycin) or retrovirally modified Akt were used to demonstrate the role of Akt and mTOR in T reg cell development.
[ "Qu et al., 2007", "Strauss et al., 2007", "Haxhinasto et al., 2008", "Long and Buckner, 2008", "Sauer et al., 2008" ]
158
40,905
0
false
In these studies, drug inhibitors (FK506, rapamycin) or retrovirally modified Akt were used to demonstrate the role of Akt and mTOR in T reg cell development.
[]
In these studies, drug inhibitors or retrovirally modified Akt were used to demonstrate the role of Akt and mTOR in T reg cell development.
true
true
true
true
true
7,046
7
DISCUSSION
1
Qu et al., 2007
[ "bib56", "bib66", "bib28", "bib48", "bib62" ]
20,008,522
NA|NA|NA|NA|NA
We provide the first demonstration of a naturally occurring protein that can inhibit the Akt–mTOR cascade and regulate the development of T reg cells.
[ "Qu et al., 2007", "Strauss et al., 2007", "Haxhinasto et al., 2008", "Long and Buckner, 2008", "Sauer et al., 2008" ]
150
40,906
0
false
We provide the first demonstration of a naturally occurring protein that can inhibit the Akt–mTOR cascade and regulate the development of T reg cells.
[]
We provide the first demonstration of a naturally occurring protein that can inhibit the Akt–mTOR cascade and regulate the development of T reg cells.
true
true
true
true
true
7,046
8
DISCUSSION
1
Adler et al., 2007
[ "bib1", "bib32", "bib49" ]
20,008,522
NA|NA|NA
Similar to the Akt–mTOR pathway, recent data indicate an important role for the MAP kinase cascade in iT reg cell development (Adler et al., 2007; Huber et al., 2008; Luo et al., 2008).
[ "Adler et al., 2007", "Huber et al., 2008", "Luo et al., 2008" ]
185
40,907
0
false
Similar to the Akt–mTOR pathway, recent data indicate an important role for the MAP kinase cascade in iT reg cell development.
[ "Adler et al., 2007; Huber et al., 2008; Luo et al., 2008" ]
Similar to the Akt–mTOR pathway, recent data indicate an important role for the MAP kinase cascade in iT reg cell development.
true
true
true
true
true
7,047
8
DISCUSSION
1
Adler et al., 2007
[ "bib1", "bib32", "bib49" ]
20,008,522
NA|NA|NA
We found that PD-L1 attenuated the phosphorylation of p42/ERK2, suggesting that PD-L1 may mediate the induction of T reg cells by modulating ERK2 activity and, hence, the MAP kinase signaling cascade.
[ "Adler et al., 2007", "Huber et al., 2008", "Luo et al., 2008" ]
200
40,908
0
false
We found that PD-L1 attenuated the phosphorylation of p42/ERK2, suggesting that PD-L1 may mediate the induction of T reg cells by modulating ERK2 activity and, hence, the MAP kinase signaling cascade.
[]
We found that PD-L1 attenuated the phosphorylation of p42/ERK2, suggesting that PD-L1 may mediate the induction of T reg cells by modulating ERK2 activity and, hence, the MAP kinase signaling cascade.
true
true
true
true
true
7,047
8
DISCUSSION
1
Adler et al., 2007
[ "bib1", "bib32", "bib49" ]
20,008,522
NA|NA|NA
No discernable effects of PD-L1–Ig on p38 were detected (unpublished data).
[ "Adler et al., 2007", "Huber et al., 2008", "Luo et al., 2008" ]
75
40,909
0
false
No discernable effects of PD-L1–Ig on p38 were detected (unpublished data).
[]
No discernable effects of PD-L1–Ig on p38 were detected.
true
true
true
true
true
7,047
9
DISCUSSION
1
Roncarolo and Battaglia, 2007
[ "bib59", "bib35", "bib75" ]
20,008,522
NA|NA|NA
There is great interest in generating T reg cells ex vivo as a therapy for autoimmune diseases and transplant rejection (Roncarolo and Battaglia, 2007).
[ "Roncarolo and Battaglia, 2007", "Joetham et al., 2008", "Yang et al., 2008" ]
152
40,910
1
false
There is great interest in generating T reg cells ex vivo as a therapy for autoimmune diseases and transplant rejection.
[ "Roncarolo and Battaglia, 2007" ]
There is great interest in generating T reg cells ex vivo as a therapy for autoimmune diseases and transplant rejection.
true
true
true
true
true
7,048
9
DISCUSSION
1
Roncarolo and Battaglia, 2007
[ "bib59", "bib35", "bib75" ]
20,008,522
NA|NA|NA
However, recent studies indicate that T reg cells exhibit functional plasticity and can produce proinflammatory cytokines at the site of inflammation (Joetham et al., 2008; Yang et al., 2008).
[ "Roncarolo and Battaglia, 2007", "Joetham et al., 2008", "Yang et al., 2008" ]
192
40,911
0
false
However, recent studies indicate that T reg cells exhibit functional plasticity and can produce proinflammatory cytokines at the site of inflammation.
[ "Joetham et al., 2008; Yang et al., 2008" ]
However, recent studies indicate that T reg cells exhibit functional plasticity and can produce proinflammatory cytokines at the site of inflammation.
true
true
true
true
true
7,048
9
DISCUSSION
1
Roncarolo and Battaglia, 2007
[ "bib59", "bib35", "bib75" ]
20,008,522
NA|NA|NA
Thus, in order for T reg cell therapy to be a viable approach, it is critical to find ways to maintain and enhance the suppressive function of T reg cells.
[ "Roncarolo and Battaglia, 2007", "Joetham et al., 2008", "Yang et al., 2008" ]
155
40,912
0
false
Thus, in order for T reg cell therapy to be a viable approach, it is critical to find ways to maintain and enhance the suppressive function of T reg cells.
[]
Thus, in order for T reg cell therapy to be a viable approach, it is critical to find ways to maintain and enhance the suppressive function of T reg cells.
true
true
true
true
true
7,048
9
DISCUSSION
1
Roncarolo and Battaglia, 2007
[ "bib59", "bib35", "bib75" ]
20,008,522
NA|NA|NA
Our work suggests that administration of PD-L1–Ig or PD-1 agonists may harness the therapeutic potential of iT reg cells by providing a novel means of sustaining and enhancing their function in vivo while concomitantly suppressing the expansion and functions of activated T eff cells.
[ "Roncarolo and Battaglia, 2007", "Joetham et al., 2008", "Yang et al., 2008" ]
284
40,913
0
false
Our work suggests that administration of PD-L1–Ig or PD-1 agonists may harness the therapeutic potential of iT reg cells by providing a novel means of sustaining and enhancing their function in vivo while concomitantly suppressing the expansion and functions of activated T eff cells.
[]
Our work suggests that administration of PD-L1–Ig or PD-1 agonists may harness the therapeutic potential of iT reg cells by providing a novel means of sustaining and enhancing their function in vivo while concomitantly suppressing the expansion and functions of activated T eff cells.
true
true
true
true
true
7,048
0
INTRODUCTION
1
1
[ "B1", "B2", "B3 B4 B5" ]
19,465,379
pmid-16262681|pmid-12634793|pmid-11752321|pmid-16381927|pmid-17145710
Recent technological advances, such as yeast two-hybrid screens (1) and co-immunoprecipitation (coIP) assays (2), enable the systematic characterization of protein–protein interaction (PPI) networks across multiple species.
[ "1", "2", "3–5" ]
223
40,914
1
false
Recent technological advances, such as yeast two-hybrid screens and co-immunoprecipitation (coIP) assays, enable the systematic characterization of protein–protein interaction (PPI) networks across multiple species.
[ "1", "2" ]
Recent technological advances, such as yeast two-hybrid screens and co-immunoprecipitation (coIP) assays, enable the systematic characterization of protein–protein interaction (PPI) networks across multiple species.
true
true
true
true
true
7,049
0
INTRODUCTION
1
3–5
[ "B1", "B2", "B3 B4 B5" ]
19,465,379
pmid-16262681|pmid-12634793|pmid-11752321|pmid-16381927|pmid-17145710
Large-scale PPI networks are currently available for human and most model species (3–5).
[ "1", "2", "3–5" ]
88
40,915
1
false
Large-scale PPI networks are currently available for human and most model species.
[ "3–5" ]
Large-scale PPI networks are currently available for human and most model species.
true
true
true
true
true
7,049
1
INTRODUCTION
1
6
[ "B6", "B7", "B8", "B9", "B10", "B11 B12 B13", "B14", "B15" ]
19,465,379
pmid-11731503|pmid-16601728|pmid-15687504|pmid-16899655|pmid-16449501|pmid-10200254|pmid-11525815|pmid-14759257|pmid-14557537|pmid-14993205
To date, evolutionary analysis of protein network data has been mostly limited to comparison of single interactions (6), or whole networks (7).
[ "6", "7", "8", "9", "10", "11–13", "14", "15" ]
143
40,916
1
false
To date, evolutionary analysis of protein network data has been mostly limited to comparison of single interactions, or whole networks.
[ "6", "7" ]
To date, evolutionary analysis of protein network data has been mostly limited to comparison of single interactions, or whole networks.
true
true
true
true
true
7,050
1
INTRODUCTION
1
6
[ "B6", "B7", "B8", "B9", "B10", "B11 B12 B13", "B14", "B15" ]
19,465,379
pmid-11731503|pmid-16601728|pmid-15687504|pmid-16899655|pmid-16449501|pmid-10200254|pmid-11525815|pmid-14759257|pmid-14557537|pmid-14993205
In the context of the latter, methods were developed to identify protein complexes that are conserved across species (8,9).
[ "6", "7", "8", "9", "10", "11–13", "14", "15" ]
123
40,917
0
false
In the context of the latter, methods were developed to identify protein complexes that are conserved across species.
[ "8,9" ]
In the context of the latter, methods were developed to identify protein complexes that are conserved across species.
true
true
true
true
true
7,050