Datasets:
vgainullin
/
xciting_data

Dataset card Data Studio Files
xet
 Community
1
paragraph_index
int64
sec
string
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int64
cites
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pmid
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cit_qc
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__index_level_0__
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0
DISCUSSION
1
1
[ "B1", "B1", "B2", "B2", "B1" ]
17,066,524
pmid-4020086|pmid-1778144|pmid-2919305|pmid-4020086|pmid-4020086|pmid-11693342|pmid-11693342|pmid-4020086
In the present case, the hamartoma occurred in a middle-aged man who had normal colonic mucosa.
[ "1", "1", "2", "2", "1" ]
95
38,116
0
false
In the present case, the hamartoma occurred in a middle-aged man who had normal colonic mucosa.
[]
In the present case, the hamartoma occurred in a middle-aged man who had normal colonic mucosa.
true
true
true
true
true
6,538
0
DISCUSSION
1
1
[ "B1", "B1", "B2", "B2", "B1" ]
17,066,524
pmid-4020086|pmid-1778144|pmid-2919305|pmid-4020086|pmid-4020086|pmid-11693342|pmid-11693342|pmid-4020086
Additional multiple hamartomatous polyps were later found to be distributed along the entire colon.
[ "1", "1", "2", "2", "1" ]
99
38,117
0
false
Additional multiple hamartomatous polyps were later found to be distributed along the entire colon.
[]
Additional multiple hamartomatous polyps were later found to be distributed along the entire colon.
true
true
true
true
true
6,538
0
DISCUSSION
1
1
[ "B1", "B1", "B2", "B2", "B1" ]
17,066,524
pmid-4020086|pmid-1778144|pmid-2919305|pmid-4020086|pmid-4020086|pmid-11693342|pmid-11693342|pmid-4020086
This case was not associated with hereditary or familial polyposis syndromes.
[ "1", "1", "2", "2", "1" ]
77
38,118
0
false
This case was not associated with hereditary or familial polyposis syndromes.
[]
This case was not associated with hereditary or familial polyposis syndromes.
true
true
true
true
true
6,538
0
DISCUSSION
1
1
[ "B1", "B1", "B2", "B2", "B1" ]
17,066,524
pmid-4020086|pmid-1778144|pmid-2919305|pmid-4020086|pmid-4020086|pmid-11693342|pmid-11693342|pmid-4020086
Preoperatively, we diagnosed the case as multiple colonic carcinomas based on the endoscopic observation, and because cancer could not be diagnostically excluded due to the patient's age.
[ "1", "1", "2", "2", "1" ]
187
38,119
0
false
Preoperatively, we diagnosed the case as multiple colonic carcinomas based on the endoscopic observation, and because cancer could not be diagnostically excluded due to the patient's age.
[]
Preoperatively, we diagnosed the case as multiple colonic carcinomas based on the endoscopic observation, and because cancer could not be diagnostically excluded due to the patient's age.
true
true
true
true
true
6,538
0
DISCUSSION
1
1
[ "B1", "B1", "B2", "B2", "B1" ]
17,066,524
pmid-4020086|pmid-1778144|pmid-2919305|pmid-4020086|pmid-4020086|pmid-11693342|pmid-11693342|pmid-4020086
In addition, resection was required because of luminal obstruction.
[ "1", "1", "2", "2", "1" ]
67
38,120
0
false
In addition, resection was required because of luminal obstruction.
[]
In addition, resection was required because of luminal obstruction.
true
true
true
true
true
6,538
1
DISCUSSION
1
5
[ "B5" ]
17,066,524
pmid-4317531
Colonic hamartomas are non-neoplastic lesions composed of localized, disorganized overgrowths of normal mature tissues.
[ "5" ]
119
38,121
0
false
Colonic hamartomas are non-neoplastic lesions composed of localized, disorganized overgrowths of normal mature tissues.
[]
Colonic hamartomas are non-neoplastic lesions composed of localized, disorganized overgrowths of normal mature tissues.
true
true
true
true
true
6,539
1
DISCUSSION
1
5
[ "B5" ]
17,066,524
pmid-4317531
In one rare case, an adenocarcinoma was reported to have arisen from a hamartomatous polyp.5 Although the lesion is rarely associated with cancer, endoscopic or surgical removal seems prudent, particularly if the lesion grossly resembles a villous polyp, which is associated with a high incidence of cancer.
[ "5" ]
307
38,122
0
false
In one rare case, an adenocarcinoma was reported to have arisen from a hamartomatous polyp.5 Although the lesion is rarely associated with cancer, endoscopic or surgical removal seems prudent, particularly if the lesion grossly resembles a villous polyp, which is associated with a high incidence of cancer.
[]
In one rare case, an adenocarcinoma was reported to have arisen from a hamartomatous polyp.5 Although the lesion is rarely associated with cancer, endoscopic or surgical removal seems prudent, particularly if the lesion grossly resembles a villous polyp, which is associated with a high incidence of cancer.
true
true
true
true
true
6,539
1
DISCUSSION
1
5
[ "B5" ]
17,066,524
pmid-4317531
Another argument for lesion removal is the impossibility of differentiating between an adenoma and a hamartoma in small biopsy specimens.
[ "5" ]
137
38,123
0
false
Another argument for lesion removal is the impossibility of differentiating between an adenoma and a hamartoma in small biopsy specimens.
[]
Another argument for lesion removal is the impossibility of differentiating between an adenoma and a hamartoma in small biopsy specimens.
true
true
true
true
true
6,539
2
DISCUSSION
0
null
null
17,066,524
null
In summary, multiple giant hamartomas of the colon that are not associated with hereditary or familial polyposis syndromes are rarely encountered in adults.
null
156
38,124
0
false
null
null
In summary, multiple giant hamartomas of the colon that are not associated with hereditary or familial polyposis syndromes are rarely encountered in adults.
true
true
true
true
true
6,540
2
DISCUSSION
0
null
null
17,066,524
null
Only two previous cases have been reported in the medical literature.
null
69
38,125
0
false
null
null
Only two previous cases have been reported in the medical literature.
true
true
true
true
true
6,540
2
DISCUSSION
0
null
null
17,066,524
null
Hamartomas can be large in size and may simulate a malignant lesion.
null
68
38,126
0
false
null
null
Hamartomas can be large in size and may simulate a malignant lesion.
true
true
true
true
true
6,540
2
DISCUSSION
0
null
null
17,066,524
null
As in the present case, endoscopic biopsies may not be definitive in the diagnosis of hamartoma, and resection may be required for an accurate diagnosis and for the relief of obstruction.
null
187
38,127
0
false
null
null
As in the present case, endoscopic biopsies may not be definitive in the diagnosis of hamartoma, and resection may be required for an accurate diagnosis and for the relief of obstruction.
true
true
true
true
true
6,540
2
DISCUSSION
0
null
null
17,066,524
null
For this case, continuous follow-up is required to monitor the symptom that has not been appeared.
null
98
38,128
0
false
null
null
For this case, continuous follow-up is required to monitor the symptom that has not been appeared.
true
true
true
true
true
6,540
0
DISCUSSION
1
37
[ "bib37", "bib38", "bib39", "bib40", "bib41" ]
15,824,085
NA|pmid-12529460|pmid-12951585|pmid-11742494|pmid-12527945
A long-term clinical follow-up of more than 300 patients with prostate adenocarcinomas (PCa) showed a significant correlation between the TIL density and prognosis (37).
[ "37", "38", "39", "40", "41" ]
169
38,129
1
false
A long-term clinical follow-up of more than 300 patients with prostate adenocarcinomas (PCa) showed a significant correlation between the TIL density and prognosis.
[ "37" ]
A long-term clinical follow-up of more than 300 patients with prostate adenocarcinomas (PCa) showed a significant correlation between the TIL density and prognosis.
true
true
true
true
true
6,541
0
DISCUSSION
1
37
[ "bib37", "bib38", "bib39", "bib40", "bib41" ]
15,824,085
NA|pmid-12529460|pmid-12951585|pmid-11742494|pmid-12527945
Absent or weak TIL were found to be signs of increased tumor progression risk and poor prognosis.
[ "37", "38", "39", "40", "41" ]
97
38,130
0
false
Absent or weak TIL were found to be signs of increased tumor progression risk and poor prognosis.
[]
Absent or weak TIL were found to be signs of increased tumor progression risk and poor prognosis.
true
true
true
true
true
6,541
0
DISCUSSION
1
38
[ "bib37", "bib38", "bib39", "bib40", "bib41" ]
15,824,085
NA|pmid-12529460|pmid-12951585|pmid-11742494|pmid-12527945
However, a major limit of similar epidemiological studies (38) is that lymphocytic infiltration is present in benign hyperplasia as well, leaving unanswered the question whether TIL represent a lymphocytic nonspecific inflammation or a true, evolving tumor-specific immune response.
[ "37", "38", "39", "40", "41" ]
282
38,131
1
false
However, a major limit of similar epidemiological studies is that lymphocytic infiltration is present in benign hyperplasia as well, leaving unanswered the question whether TIL represent a lymphocytic nonspecific inflammation or a true, evolving tumor-specific immune response.
[ "38" ]
However, a major limit of similar epidemiological studies is that lymphocytic infiltration is present in benign hyperplasia as well, leaving unanswered the question whether TIL represent a lymphocytic nonspecific inflammation or a true, evolving tumor-specific immune response.
true
true
true
true
true
6,541
0
DISCUSSION
1
39
[ "bib37", "bib38", "bib39", "bib40", "bib41" ]
15,824,085
NA|pmid-12529460|pmid-12951585|pmid-11742494|pmid-12527945
In many melanomas, it has been conclusively shown that TIL are directed against either melanocyte differentiation antigens or mutated proteins, and they can be expanded ex vivo to exert antitumor activity after adoptive transfer to the patient (39).
[ "37", "38", "39", "40", "41" ]
249
38,132
1
false
In many melanomas, it has been conclusively shown that TIL are directed against either melanocyte differentiation antigens or mutated proteins, and they can be expanded ex vivo to exert antitumor activity after adoptive transfer to the patient.
[ "39" ]
In many melanomas, it has been conclusively shown that TIL are directed against either melanocyte differentiation antigens or mutated proteins, and they can be expanded ex vivo to exert antitumor activity after adoptive transfer to the patient.
true
true
true
true
true
6,541
0
DISCUSSION
1
37
[ "bib37", "bib38", "bib39", "bib40", "bib41" ]
15,824,085
NA|pmid-12529460|pmid-12951585|pmid-11742494|pmid-12527945
In the case of prostate cancer, there are few reports.
[ "37", "38", "39", "40", "41" ]
54
38,133
0
false
In the case of prostate cancer, there are few reports.
[]
In the case of prostate cancer, there are few reports.
true
true
true
true
true
6,541
0
DISCUSSION
1
40
[ "bib37", "bib38", "bib39", "bib40", "bib41" ]
15,824,085
NA|pmid-12529460|pmid-12951585|pmid-11742494|pmid-12527945
However, peptide-pulsed autologous DC were able to stimulate prostate TIL and induce recognition of an HLA-A2-restricted epitope of the antigen parathyroid hormone-related protein, suggesting that TIL separated from their surrounding environment possess full antigen responsiveness (40).
[ "37", "38", "39", "40", "41" ]
287
38,134
1
false
However, peptide-pulsed autologous DC were able to stimulate prostate TIL and induce recognition of an HLA-A2-restricted epitope of the antigen parathyroid hormone-related protein, suggesting that TIL separated from their surrounding environment possess full antigen responsiveness.
[ "40" ]
However, peptide-pulsed autologous DC were able to stimulate prostate TIL and induce recognition of an HLA-A2-restricted epitope of the antigen parathyroid hormone-related protein, suggesting that TIL separated from their surrounding environment possess full antigen responsiveness.
true
true
true
true
true
6,541
0
DISCUSSION
1
41
[ "bib37", "bib38", "bib39", "bib40", "bib41" ]
15,824,085
NA|pmid-12529460|pmid-12951585|pmid-11742494|pmid-12527945
In some cases TIL from PCa, isolated and kept in culture in the presence of IL-2 for at least 14 d, were capable of killing tumor cells via perforin-dependent and -independent pathways only when tumor cells were previously treated with chemotherapeutic drugs (41).
[ "37", "38", "39", "40", "41" ]
264
38,135
1
false
In some cases TIL from PCa, isolated and kept in culture in the presence of IL-2 for at least 14 d, were capable of killing tumor cells via perforin-dependent and -independent pathways only when tumor cells were previously treated with chemotherapeutic drugs.
[ "41" ]
In some cases TIL from PCa, isolated and kept in culture in the presence of IL-2 for at least 14 d, were capable of killing tumor cells via perforin-dependent and -independent pathways only when tumor cells were previously treated with chemotherapeutic drugs.
true
true
true
true
true
6,541
1
DISCUSSION
1
26
[ "bib26", "bib27", "bib42", "bib43" ]
15,824,085
pmid-10972084|pmid-11590434|pmid-10026868|pmid-15087405
Many of these studies, however, suffer from the limitation that T lymphocytes are activated after repeated in vitro stimulations in a disrupted tumor environment.
[ "26", "27", "42", "43" ]
162
38,136
0
false
Many of these studies, however, suffer from the limitation that T lymphocytes are activated after repeated in vitro stimulations in a disrupted tumor environment.
[]
Many of these studies, however, suffer from the limitation that T lymphocytes are activated after repeated in vitro stimulations in a disrupted tumor environment.
true
true
true
true
true
6,542
1
DISCUSSION
1
26
[ "bib26", "bib27", "bib42", "bib43" ]
15,824,085
pmid-10972084|pmid-11590434|pmid-10026868|pmid-15087405
Within the tumor site, tumor-specific lymphocytes are sensitive to any changes in the microenvironment, and these changes can condition their function and activation state.
[ "26", "27", "42", "43" ]
172
38,137
0
false
Within the tumor site, tumor-specific lymphocytes are sensitive to any changes in the microenvironment, and these changes can condition their function and activation state.
[]
Within the tumor site, tumor-specific lymphocytes are sensitive to any changes in the microenvironment, and these changes can condition their function and activation state.
true
true
true
true
true
6,542
1
DISCUSSION
1
26
[ "bib26", "bib27", "bib42", "bib43" ]
15,824,085
pmid-10972084|pmid-11590434|pmid-10026868|pmid-15087405
Most solid tumors are characterized by lymphocyte infiltration, but TIL frequently are unable to kill autologous tumor cells, indicating that they are in an anergic/tolerant state (26, 27, 42, 43).
[ "26", "27", "42", "43" ]
197
38,138
0
false
Most solid tumors are characterized by lymphocyte infiltration, but TIL frequently are unable to kill autologous tumor cells, indicating that they are in an anergic/tolerant state.
[ "26, 27, 42, 43" ]
Most solid tumors are characterized by lymphocyte infiltration, but TIL frequently are unable to kill autologous tumor cells, indicating that they are in an anergic/tolerant state.
true
true
true
true
true
6,542
1
DISCUSSION
1
26
[ "bib26", "bib27", "bib42", "bib43" ]
15,824,085
pmid-10972084|pmid-11590434|pmid-10026868|pmid-15087405
The data presented here provide new insight into the biology of T lymphocytes infiltrating human PCa.
[ "26", "27", "42", "43" ]
101
38,139
0
false
The data presented here provide new insight into the biology of T lymphocytes infiltrating human PCa.
[]
The data presented here provide new insight into the biology of T lymphocytes infiltrating human PCa.
true
true
true
true
true
6,542
1
DISCUSSION
1
26
[ "bib26", "bib27", "bib42", "bib43" ]
15,824,085
pmid-10972084|pmid-11590434|pmid-10026868|pmid-15087405
TIL within PCa are mainly CD8+ T lymphocytes with an antigen-experienced, terminally differentiated phenotype.
[ "26", "27", "42", "43" ]
110
38,140
0
false
TIL within PCa are mainly CD8+ T lymphocytes with an antigen-experienced, terminally differentiated phenotype.
[]
TIL within PCa are mainly CD8+ T lymphocytes with an antigen-experienced, terminally differentiated phenotype.
true
true
true
true
true
6,542
1
DISCUSSION
1
26
[ "bib26", "bib27", "bib42", "bib43" ]
15,824,085
pmid-10972084|pmid-11590434|pmid-10026868|pmid-15087405
However, they remain in a dormant state that is not altered by cytokines affecting T lymphocyte proliferation such as IL-2.
[ "26", "27", "42", "43" ]
123
38,141
0
false
However, they remain in a dormant state that is not altered by cytokines affecting T lymphocyte proliferation such as IL-2.
[]
However, they remain in a dormant state that is not altered by cytokines affecting T lymphocyte proliferation such as IL-2.
true
true
true
true
true
6,542
1
DISCUSSION
1
26
[ "bib26", "bib27", "bib42", "bib43" ]
15,824,085
pmid-10972084|pmid-11590434|pmid-10026868|pmid-15087405
Unlike normally responsive lymphocytes in tumor-free prostates and peripheral blood, TIL are not activated locally by powerful signals acting either on TCR or downstream signaling pathways.
[ "26", "27", "42", "43" ]
189
38,142
0
false
Unlike normally responsive lymphocytes in tumor-free prostates and peripheral blood, TIL are not activated locally by powerful signals acting either on TCR or downstream signaling pathways.
[]
Unlike normally responsive lymphocytes in tumor-free prostates and peripheral blood, TIL are not activated locally by powerful signals acting either on TCR or downstream signaling pathways.
true
true
true
true
true
6,542
1
DISCUSSION
1
26
[ "bib26", "bib27", "bib42", "bib43" ]
15,824,085
pmid-10972084|pmid-11590434|pmid-10026868|pmid-15087405
The steady-state regulation of the dormant state is dependent on the enhanced intratumoral metabolism of the amino acid L-Arg, because the simple addition of ARG- and NOS-specific inhibitors was sufficient to rouse these CTL, activate them, and start a number of events leading to cytolytic granule polarization and kill...
[ "26", "27", "42", "43" ]
343
38,143
0
false
The steady-state regulation of the dormant state is dependent on the enhanced intratumoral metabolism of the amino acid L-Arg, because the simple addition of ARG- and NOS-specific inhibitors was sufficient to rouse these CTL, activate them, and start a number of events leading to cytolytic granule polarization and kill...
[]
The steady-state regulation of the dormant state is dependent on the enhanced intratumoral metabolism of the amino acid L-Arg, because the simple addition of ARG- and NOS-specific inhibitors was sufficient to rouse these CTL, activate them, and start a number of events leading to cytolytic granule polarization and kill...
true
true
true
true
true
6,542
1
DISCUSSION
1
26
[ "bib26", "bib27", "bib42", "bib43" ]
15,824,085
pmid-10972084|pmid-11590434|pmid-10026868|pmid-15087405
These data were confirmed and extended in TRAMP mice, allowing us to evaluate the tumor-specific reactivity of TIL rescued from the dormant state by the ARG and NOS inhibitor and expanded by low doses of IL-2.
[ "26", "27", "42", "43" ]
209
38,144
0
false
These data were confirmed and extended in TRAMP mice, allowing us to evaluate the tumor-specific reactivity of TIL rescued from the dormant state by the ARG and NOS inhibitor and expanded by low doses of IL-2.
[]
These data were confirmed and extended in TRAMP mice, allowing us to evaluate the tumor-specific reactivity of TIL rescued from the dormant state by the ARG and NOS inhibitor and expanded by low doses of IL-2.
true
true
true
true
true
6,542
2
DISCUSSION
1
15
[ "bib15" ]
15,824,085
pmid-15050972
Our findings suggest that the L-Arg–metabolizing enzymes are up-regulated in prostate cancer cells rather than in tumor-infiltrating myeloid cells such as macrophages, although we cannot rule out the contribution of these latter cells.
[ "15" ]
235
38,145
0
false
Our findings suggest that the L-Arg–metabolizing enzymes are up-regulated in prostate cancer cells rather than in tumor-infiltrating myeloid cells such as macrophages, although we cannot rule out the contribution of these latter cells.
[]
Our findings suggest that the L-Arg–metabolizing enzymes are up-regulated in prostate cancer cells rather than in tumor-infiltrating myeloid cells such as macrophages, although we cannot rule out the contribution of these latter cells.
true
true
true
true
true
6,543
2
DISCUSSION
1
15
[ "bib15" ]
15,824,085
pmid-15050972
In line with our results, it is known that several tumor cell lines express high levels of ARG and that inhibition of arginase activity often abolishes in vitro cell growth (15).
[ "15" ]
178
38,146
1
false
In line with our results, it is known that several tumor cell lines express high levels of ARG and that inhibition of arginase activity often abolishes in vitro cell growth.
[ "15" ]
In line with our results, it is known that several tumor cell lines express high levels of ARG and that inhibition of arginase activity often abolishes in vitro cell growth.
true
true
true
true
true
6,543
2
DISCUSSION
1
15
[ "bib15" ]
15,824,085
pmid-15050972
Our data, together with the recent literature, suggest that intratumoral arginase induction might be beneficial for the tumor through different pathways, i.e., supporting tumor growth and development by providing polyamines and suppressing antitumor immune response by negatively affecting TIL.
[ "15" ]
294
38,147
0
false
Our data, together with the recent literature, suggest that intratumoral arginase induction might be beneficial for the tumor through different pathways, i.e., supporting tumor growth and development by providing polyamines and suppressing antitumor immune response by negatively affecting TIL.
[]
Our data, together with the recent literature, suggest that intratumoral arginase induction might be beneficial for the tumor through different pathways, i.e., supporting tumor growth and development by providing polyamines and suppressing antitumor immune response by negatively affecting TIL.
true
true
true
true
true
6,543
3
DISCUSSION
1
18
[ "bib18", "bib23", "bib44", "bib45" ]
15,824,085
pmid-12528889|pmid-12856639|pmid-7538668|pmid-10854324
NOS activity has been detected in many human tumors, including prostate cancer, although its function is unclear (18, 23).
[ "18", "23", "44", "45" ]
122
38,148
0
false
NOS activity has been detected in many human tumors, including prostate cancer, although its function is unclear.
[ "18, 23" ]
NOS activity has been detected in many human tumors, including prostate cancer, although its function is unclear.
true
true
true
true
true
6,544
3
DISCUSSION
1
44
[ "bib18", "bib23", "bib44", "bib45" ]
15,824,085
pmid-12528889|pmid-12856639|pmid-7538668|pmid-10854324
NO stimulates angiogenesis, thus enhancing tumor growth and invasiveness (44).
[ "18", "23", "44", "45" ]
78
38,149
1
false
NO stimulates angiogenesis, thus enhancing tumor growth and invasiveness.
[ "44" ]
NO stimulates angiogenesis, thus enhancing tumor growth and invasiveness.
true
true
true
true
true
6,544
3
DISCUSSION
1
45
[ "bib18", "bib23", "bib44", "bib45" ]
15,824,085
pmid-12528889|pmid-12856639|pmid-7538668|pmid-10854324
Moreover, NO induced an enhanced expression of the DNA-dependent protein-kinase catalytic subunit, DNA-PKcs, that should protect tumor cells from the damaging activity of NO and other DNA-damaging agents, such as X-ray radiation, Adriamycin, bleomycin, and cisplatin (45).
[ "18", "23", "44", "45" ]
272
38,150
1
false
Moreover, NO induced an enhanced expression of the DNA-dependent protein-kinase catalytic subunit, DNA-PKcs, that should protect tumor cells from the damaging activity of NO and other DNA-damaging agents, such as X-ray radiation, Adriamycin, bleomycin, and cisplatin.
[ "45" ]
Moreover, NO induced an enhanced expression of the DNA-dependent protein-kinase catalytic subunit, DNA-PKcs, that should protect tumor cells from the damaging activity of NO and other DNA-damaging agents, such as X-ray radiation, Adriamycin, bleomycin, and cisplatin.
true
true
true
true
true
6,544
4
DISCUSSION
1
46
[ "bib46", "bib47", "bib48", "bib49" ]
15,824,085
pmid-9192673|pmid-9712892|pmid-10226050|pmid-9405597
Depletion of cytosolic L-Arg content by ARG might trigger the generation of superoxide (O2 -) from the NOS2 reductase domain (46, 47).
[ "46", "47", "48", "49" ]
134
38,151
0
false
Depletion of cytosolic L-Arg content by ARG might trigger the generation of superoxide (O2 -) from the NOS2 reductase domain.
[ "46, 47" ]
Depletion of cytosolic L-Arg content by ARG might trigger the generation of superoxide (O2 -) from the NOS2 reductase domain.
true
true
true
true
true
6,545
4
DISCUSSION
1
46
[ "bib46", "bib47", "bib48", "bib49" ]
15,824,085
pmid-9192673|pmid-9712892|pmid-10226050|pmid-9405597
The reductase domain of NOS2 generates O2 − that reacts immediately with NO generated by the oxygenase domain.
[ "46", "47", "48", "49" ]
110
38,152
0
false
The reductase domain of NOS2 generates O2 − that reacts immediately with NO generated by the oxygenase domain.
[]
The reductase domain of NOS2 generates O2 − that reacts immediately with NO generated by the oxygenase domain.
true
true
true
true
true
6,545
4
DISCUSSION
1
48
[ "bib46", "bib47", "bib48", "bib49" ]
15,824,085
pmid-9192673|pmid-9712892|pmid-10226050|pmid-9405597
The chemical byproducts of this reaction are ONOO−, highly reactive oxidizing agents that nitrate protein-associate tyrosines and damage different biological targets (48).
[ "46", "47", "48", "49" ]
171
38,153
1
false
The chemical byproducts of this reaction are ONOO−, highly reactive oxidizing agents that nitrate protein-associate tyrosines and damage different biological targets.
[ "48" ]
The chemical byproducts of this reaction are ONOO−, highly reactive oxidizing agents that nitrate protein-associate tyrosines and damage different biological targets.
true
true
true
true
true
6,545
4
DISCUSSION
1
49
[ "bib46", "bib47", "bib48", "bib49" ]
15,824,085
pmid-9192673|pmid-9712892|pmid-10226050|pmid-9405597
Cell membranes offer no significant barrier to diffusion of peroxynitrites from different compartments, within or between cells, at a rate that is faster than the known decomposition pathways of these moieties (49).
[ "46", "47", "48", "49" ]
215
38,154
1
false
Cell membranes offer no significant barrier to diffusion of peroxynitrites from different compartments, within or between cells, at a rate that is faster than the known decomposition pathways of these moieties.
[ "49" ]
Cell membranes offer no significant barrier to diffusion of peroxynitrites from different compartments, within or between cells, at a rate that is faster than the known decomposition pathways of these moieties.
true
true
true
true
true
6,545
4
DISCUSSION
1
46
[ "bib46", "bib47", "bib48", "bib49" ]
15,824,085
pmid-9192673|pmid-9712892|pmid-10226050|pmid-9405597
This lack of a barrier indicates that, whenever O2 − and NO are generated from the same or different cells in a microenvironment, they will immediately associate, and the resulting ONOO− will diffuse freely through cell membranes.
[ "46", "47", "48", "49" ]
230
38,155
0
false
This lack of a barrier indicates that, whenever O2 − and NO are generated from the same or different cells in a microenvironment, they will immediately associate, and the resulting ONOO− will diffuse freely through cell membranes.
[]
This lack of a barrier indicates that, whenever O2 − and NO are generated from the same or different cells in a microenvironment, they will immediately associate, and the resulting ONOO− will diffuse freely through cell membranes.
true
true
true
true
true
6,545
5
DISCUSSION
1
50
[ "bib29", "bib30", "bib50", "bib29", "bib51", "bib53" ]
15,824,085
pmid-11369646|pmid-10092790|pmid-11593016|pmid-11369646|pmid-12763060|pmid-10630617
A number of lines of evidence indicate that peroxynitrites are quite toxic for lymphocytes: they can prime T lymphocytes to undergo apoptotic cell death through different pathways involving inhibition of protein tyrosine phosphorylation via nitration of tyrosine residues (29, 30) or by nitration of the protein voltage-...
[ "29", "30", "50", "29", "51", "53" ]
408
38,156
1
false
A number of lines of evidence indicate that peroxynitrites are quite toxic for lymphocytes: they can prime T lymphocytes to undergo apoptotic cell death through different pathways involving inhibition of protein tyrosine phosphorylation via nitration of tyrosine residues or by nitration of the protein voltage-dependent...
[ "29, 30", "50" ]
A number of lines of evidence indicate that peroxynitrites are quite toxic for lymphocytes: they can prime T lymphocytes to undergo apoptotic cell death through different pathways involving inhibition of protein tyrosine phosphorylation via nitration of tyrosine residues or by nitration of the protein voltage-dependent...
true
true
true
true
true
6,546
5
DISCUSSION
1
29
[ "bib29", "bib30", "bib50", "bib29", "bib51", "bib53" ]
15,824,085
pmid-11369646|pmid-10092790|pmid-11593016|pmid-11369646|pmid-12763060|pmid-10630617
Nitrotyrosine, a marker of peroxynitrite activity in tissues, is found in thymic extracts and thymic sections colocalized with apoptotic cells, suggesting that peroxynitrites are also involved in thymic apoptosis in vivo (29).
[ "29", "30", "50", "29", "51", "53" ]
226
38,157
1
false
Nitrotyrosine, a marker of peroxynitrite activity in tissues, is found in thymic extracts and thymic sections colocalized with apoptotic cells, suggesting that peroxynitrites are also involved in thymic apoptosis in vivo.
[ "29" ]
Nitrotyrosine, a marker of peroxynitrite activity in tissues, is found in thymic extracts and thymic sections colocalized with apoptotic cells, suggesting that peroxynitrites are also involved in thymic apoptosis in vivo.
true
true
true
true
true
6,546
5
DISCUSSION
1
29
[ "bib29", "bib30", "bib50", "bib29", "bib51", "bib53" ]
15,824,085
pmid-11369646|pmid-10092790|pmid-11593016|pmid-11369646|pmid-12763060|pmid-10630617
Staining for nitrotyrosine in PCa tissue sections gave a diffuse pattern with some hot spots in the TIL.
[ "29", "30", "50", "29", "51", "53" ]
104
38,158
0
false
Staining for nitrotyrosine in PCa tissue sections gave a diffuse pattern with some hot spots in the TIL.
[]
Staining for nitrotyrosine in PCa tissue sections gave a diffuse pattern with some hot spots in the TIL.
true
true
true
true
true
6,546
5
DISCUSSION
1
29
[ "bib29", "bib30", "bib50", "bib29", "bib51", "bib53" ]
15,824,085
pmid-11369646|pmid-10092790|pmid-11593016|pmid-11369646|pmid-12763060|pmid-10630617
Whether T lymphocytes are more prone to the effect of ONOO− and their decomposition by-products or instead activate additional intracellular pathways for nitrotyrosine generation is not known.
[ "29", "30", "50", "29", "51", "53" ]
192
38,159
0
false
Whether T lymphocytes are more prone to the effect of ONOO− and their decomposition by-products or instead activate additional intracellular pathways for nitrotyrosine generation is not known.
[]
Whether T lymphocytes are more prone to the effect of ONOO− and their decomposition by-products or instead activate additional intracellular pathways for nitrotyrosine generation is not known.
true
true
true
true
true
6,546
5
DISCUSSION
1
29
[ "bib29", "bib30", "bib50", "bib29", "bib51", "bib53" ]
15,824,085
pmid-11369646|pmid-10092790|pmid-11593016|pmid-11369646|pmid-12763060|pmid-10630617
Indeed, recent data suggest that protein nitration can be considered a cellular signaling mechanism, because it is specific and reversible (51–53).
[ "29", "30", "50", "29", "51", "53" ]
147
38,160
0
false
Indeed, recent data suggest that protein nitration can be considered a cellular signaling mechanism, because it is specific and reversible.
[ "51–53" ]
Indeed, recent data suggest that protein nitration can be considered a cellular signaling mechanism, because it is specific and reversible.
true
true
true
true
true
6,546
5
DISCUSSION
1
29
[ "bib29", "bib30", "bib50", "bib29", "bib51", "bib53" ]
15,824,085
pmid-11369646|pmid-10092790|pmid-11593016|pmid-11369646|pmid-12763060|pmid-10630617
Although the biochemical pathway responsible for tyrosine denitration is not known, our results indicate that CTL posses a mechanism capable of eliminating nitrotyrosines and rescuing T cell functions.
[ "29", "30", "50", "29", "51", "53" ]
201
38,161
0
false
Although the biochemical pathway responsible for tyrosine denitration is not known, our results indicate that CTL posses a mechanism capable of eliminating nitrotyrosines and rescuing T cell functions.
[]
Although the biochemical pathway responsible for tyrosine denitration is not known, our results indicate that CTL posses a mechanism capable of eliminating nitrotyrosines and rescuing T cell functions.
true
true
true
true
true
6,546
6
DISCUSSION
1
17
[ "bib17", "bib20" ]
15,824,085
pmid-15313928|pmid-12810105
As in previous mouse studies, inhibition of both ARG and NOS was crucial to rescue T cell functions.
[ "17", "20" ]
100
38,162
0
false
As in previous mouse studies, inhibition of both ARG and NOS was crucial to rescue T cell functions.
[]
As in previous mouse studies, inhibition of both ARG and NOS was crucial to rescue T cell functions.
true
true
true
true
true
6,547
6
DISCUSSION
1
17
[ "bib17", "bib20" ]
15,824,085
pmid-15313928|pmid-12810105
We are currently investigating the mechanism for such synergy.
[ "17", "20" ]
62
38,163
0
false
We are currently investigating the mechanism for such synergy.
[]
We are currently investigating the mechanism for such synergy.
true
true
true
true
true
6,547
6
DISCUSSION
1
17
[ "bib17", "bib20" ]
15,824,085
pmid-15313928|pmid-12810105
However, in addition to having a synergistic activity in peroxynitrite generation, ARG and NOS can exert independent inhibitory activities on T lymphocytes, as shown in different tumor models.
[ "17", "20" ]
192
38,164
0
false
However, in addition to having a synergistic activity in peroxynitrite generation, ARG and NOS can exert independent inhibitory activities on T lymphocytes, as shown in different tumor models.
[]
However, in addition to having a synergistic activity in peroxynitrite generation, ARG and NOS can exert independent inhibitory activities on T lymphocytes, as shown in different tumor models.
true
true
true
true
true
6,547
6
DISCUSSION
1
17
[ "bib17", "bib20" ]
15,824,085
pmid-15313928|pmid-12810105
ARG depletes L-Arg in local microenvironments, leading to loss of the CD3 ζ chain in T lymphocytes and their functional paralysis after antigen recognition (17), whereas NO blocks the signaling through the IL-2 receptors of T lymphocytes by impeding phosphorylation of the intracellular signaling proteins STAT5, Akt, an...
[ "17", "20" ]
331
38,165
1
false
ARG depletes L-Arg in local microenvironments, leading to loss of the CD3 ζ chain in T lymphocytes and their functional paralysis after antigen recognition, whereas NO blocks the signaling through the IL-2 receptors of T lymphocytes by impeding phosphorylation of the intracellular signaling proteins STAT5, Akt, and Erk...
[ "17", "20" ]
ARG depletes L-Arg in local microenvironments, leading to loss of the CD3 ζ chain in T lymphocytes and their functional paralysis after antigen recognition, whereas NO blocks the signaling through the IL-2 receptors of T lymphocytes by impeding phosphorylation of the intracellular signaling proteins STAT5, Akt, and Erk...
true
true
true
true
true
6,547
7
DISCUSSION
1
54
[ "bib54" ]
15,824,085
pmid-15343367
A number of studies have proposed that cancers induce immunosuppression by inhibiting CD3 ζ chain expression in T lymphocytes (for review see reference 54).
[ "54" ]
156
38,166
0
false
A number of studies have proposed that cancers induce immunosuppression by inhibiting CD3 ζ chain expression in T lymphocytes.
[ "for review see reference 54" ]
A number of studies have proposed that cancers induce immunosuppression by inhibiting CD3 ζ chain expression in T lymphocytes.
true
true
true
true
true
6,548
7
DISCUSSION
1
54
[ "bib54" ]
15,824,085
pmid-15343367
We analyzed the expression of CD3 ζ chain in both PBL and TIL from PCa patients, but we were unable to demonstrate its down-regulation (unpublished data).
[ "54" ]
154
38,167
0
false
We analyzed the expression of CD3 ζ chain in both PBL and TIL from PCa patients, but we were unable to demonstrate its down-regulation (unpublished data).
[]
We analyzed the expression of CD3 ζ chain in both PBL and TIL from PCa patients, but we were unable to demonstrate its down-regulation (unpublished data).
true
true
true
true
true
6,548
7
DISCUSSION
1
54
[ "bib54" ]
15,824,085
pmid-15343367
Moreover, PBL from PCa patients responded normally to all the stimuli we provided, indicating that no evident signaling defects were present.
[ "54" ]
141
38,168
0
false
Moreover, PBL from PCa patients responded normally to all the stimuli we provided, indicating that no evident signaling defects were present.
[]
Moreover, PBL from PCa patients responded normally to all the stimuli we provided, indicating that no evident signaling defects were present.
true
true
true
true
true
6,548
7
DISCUSSION
1
54
[ "bib54" ]
15,824,085
pmid-15343367
In contrast, TIL from PCa patients were unresponsive even when stimulated with PMA plus ionomycin, stimuli that by-pass TCR signaling.
[ "54" ]
134
38,169
0
false
In contrast, TIL from PCa patients were unresponsive even when stimulated with PMA plus ionomycin, stimuli that by-pass TCR signaling.
[]
In contrast, TIL from PCa patients were unresponsive even when stimulated with PMA plus ionomycin, stimuli that by-pass TCR signaling.
true
true
true
true
true
6,548
7
DISCUSSION
1
54
[ "bib54" ]
15,824,085
pmid-15343367
Altogether, these data indicate that in PCa the ARG2 activity does not induce immunosuppression through CD3 ζ down-regulation.
[ "54" ]
126
38,170
0
false
Altogether, these data indicate that in PCa the ARG2 activity does not induce immunosuppression through CD3 ζ down-regulation.
[]
Altogether, these data indicate that in PCa the ARG2 activity does not induce immunosuppression through CD3 ζ down-regulation.
true
true
true
true
true
6,548
8
DISCUSSION
1
37
[ "bib37", "bib38", "bib55", "bib33", "bib56", "bib57", "bib58", "bib59", "bib60" ]
15,824,085
NA|pmid-12529460|pmid-15240536|pmid-11673513|pmid-8621219|pmid-11342625|pmid-12766758|pmid-12719728|pmid-2442289
Although it seems that the number of TIL in the tumor might correlate with prognosis (37, 38, 55), it is suggested that TIL are functionally deficient and that this deficiency is transient and attributable to the tumor environment because, on purification from tumor cells, tumor-specific killing can be detected (33, 56...
[ "37", "38", "55", "33", "56", "57", "58", "59", "60" ]
326
38,171
0
false
Although it seems that the number of TIL in the tumor might correlate with prognosis, it is suggested that TIL are functionally deficient and that this deficiency is transient and attributable to the tumor environment because, on purification from tumor cells, tumor-specific killing can be detected.
[ "37, 38, 55", "33, 56, 57" ]
Although it seems that the number of TIL in the tumor might correlate with prognosis, it is suggested that TIL are functionally deficient and that this deficiency is transient and attributable to the tumor environment because, on purification from tumor cells, tumor-specific killing can be detected.
true
true
true
true
true
6,549
8
DISCUSSION
1
37
[ "bib37", "bib38", "bib55", "bib33", "bib56", "bib57", "bib58", "bib59", "bib60" ]
15,824,085
NA|pmid-12529460|pmid-15240536|pmid-11673513|pmid-8621219|pmid-11342625|pmid-12766758|pmid-12719728|pmid-2442289
CTL kill their target cell by polarized secretion of their lytic granules at the immunological synapse (58, 59).
[ "37", "38", "55", "33", "56", "57", "58", "59", "60" ]
112
38,172
0
false
CTL kill their target cell by polarized secretion of their lytic granules at the immunological synapse.
[ "58, 59" ]
CTL kill their target cell by polarized secretion of their lytic granules at the immunological synapse.
true
true
true
true
true
6,549
8
DISCUSSION
1
60
[ "bib37", "bib38", "bib55", "bib33", "bib56", "bib57", "bib58", "bib59", "bib60" ]
15,824,085
NA|pmid-12529460|pmid-15240536|pmid-11673513|pmid-8621219|pmid-11342625|pmid-12766758|pmid-12719728|pmid-2442289
Polarization and secretion of lytic granules are triggered by recognition of MHC class I–peptide complexes on the target cell through the T cell receptor (60).
[ "37", "38", "55", "33", "56", "57", "58", "59", "60" ]
159
38,173
1
false
Polarization and secretion of lytic granules are triggered by recognition of MHC class I–peptide complexes on the target cell through the T cell receptor.
[ "60" ]
Polarization and secretion of lytic granules are triggered by recognition of MHC class I–peptide complexes on the target cell through the T cell receptor.
true
true
true
true
true
6,549
8
DISCUSSION
1
37
[ "bib37", "bib38", "bib55", "bib33", "bib56", "bib57", "bib58", "bib59", "bib60" ]
15,824,085
NA|pmid-12529460|pmid-15240536|pmid-11673513|pmid-8621219|pmid-11342625|pmid-12766758|pmid-12719728|pmid-2442289
Therefore, our results showing that inhibition of ARG and NOS activities in the tumor results in spontaneous polarization of cytotoxic granules in TIL indicate that CD8+ T cells infiltrating prostate cancer are terminally differentiated cytotoxic T cells that are in contact with the target cell but are unable to kill b...
[ "37", "38", "55", "33", "56", "57", "58", "59", "60" ]
372
38,174
0
false
Therefore, our results showing that inhibition of ARG and NOS activities in the tumor results in spontaneous polarization of cytotoxic granules in TIL indicate that CD8+ T cells infiltrating prostate cancer are terminally differentiated cytotoxic T cells that are in contact with the target cell but are unable to kill b...
[]
Therefore, our results showing that inhibition of ARG and NOS activities in the tumor results in spontaneous polarization of cytotoxic granules in TIL indicate that CD8+ T cells infiltrating prostate cancer are terminally differentiated cytotoxic T cells that are in contact with the target cell but are unable to kill b...
true
true
true
true
true
6,549
8
DISCUSSION
1
37
[ "bib37", "bib38", "bib55", "bib33", "bib56", "bib57", "bib58", "bib59", "bib60" ]
15,824,085
NA|pmid-12529460|pmid-15240536|pmid-11673513|pmid-8621219|pmid-11342625|pmid-12766758|pmid-12719728|pmid-2442289
However, even inside the tumor, CTL activity can be restored pharmaceutically.
[ "37", "38", "55", "33", "56", "57", "58", "59", "60" ]
78
38,175
0
false
However, even inside the tumor, CTL activity can be restored pharmaceutically.
[]
However, even inside the tumor, CTL activity can be restored pharmaceutically.
true
true
true
true
true
6,549
9
DISCUSSION
1
61
[ "bib61", "bib62", "bib63" ]
15,824,085
pmid-12461516|pmid-11478904|pmid-12530480
Based on our findings, drugs controlling ARG and NOS might be useful in aiding immunotherapeutic approaches for the treatment of cancer by creating a favorable tumor environment for the T lymphocyte effector program.
[ "61", "62", "63" ]
216
38,176
0
false
Based on our findings, drugs controlling ARG and NOS might be useful in aiding immunotherapeutic approaches for the treatment of cancer by creating a favorable tumor environment for the T lymphocyte effector program.
[]
Based on our findings, drugs controlling ARG and NOS might be useful in aiding immunotherapeutic approaches for the treatment of cancer by creating a favorable tumor environment for the T lymphocyte effector program.
true
true
true
true
true
6,550
9
DISCUSSION
1
61
[ "bib61", "bib62", "bib63" ]
15,824,085
pmid-12461516|pmid-11478904|pmid-12530480
Molecules are being developed to create novel isozyme-specific inhibitors for both NO synthases and arginases (61, 62), but more must be done to enhance selectivity.
[ "61", "62", "63" ]
165
38,177
0
false
Molecules are being developed to create novel isozyme-specific inhibitors for both NO synthases and arginases, but more must be done to enhance selectivity.
[ "61, 62" ]
Molecules are being developed to create novel isozyme-specific inhibitors for both NO synthases and arginases, but more must be done to enhance selectivity.
true
true
true
true
true
6,550
9
DISCUSSION
1
61
[ "bib61", "bib62", "bib63" ]
15,824,085
pmid-12461516|pmid-11478904|pmid-12530480
ARG1 is found at highest concentrations in the mammalian liver where it carries out the final cytosolic step of the urea cycle, a process that allows the disposal of nitrogenous waste.
[ "61", "62", "63" ]
184
38,178
0
false
ARG1 is found at highest concentrations in the mammalian liver where it carries out the final cytosolic step of the urea cycle, a process that allows the disposal of nitrogenous waste.
[]
ARG1 is found at highest concentrations in the mammalian liver where it carries out the final cytosolic step of the urea cycle, a process that allows the disposal of nitrogenous waste.
true
true
true
true
true
6,550
9
DISCUSSION
1
61
[ "bib61", "bib62", "bib63" ]
15,824,085
pmid-12461516|pmid-11478904|pmid-12530480
Arginase inhibitors might thus cause hyperammonemia and interfere with hepatic urea cycle.
[ "61", "62", "63" ]
90
38,179
0
false
Arginase inhibitors might thus cause hyperammonemia and interfere with hepatic urea cycle.
[]
Arginase inhibitors might thus cause hyperammonemia and interfere with hepatic urea cycle.
true
true
true
true
true
6,550
9
DISCUSSION
1
61
[ "bib61", "bib62", "bib63" ]
15,824,085
pmid-12461516|pmid-11478904|pmid-12530480
Moreover, some activities of inhibitors are not predictable.
[ "61", "62", "63" ]
60
38,180
0
false
Moreover, some activities of inhibitors are not predictable.
[]
Moreover, some activities of inhibitors are not predictable.
true
true
true
true
true
6,550
9
DISCUSSION
1
63
[ "bib61", "bib62", "bib63" ]
15,824,085
pmid-12461516|pmid-11478904|pmid-12530480
For example, the effect of Nω-nitro-l-arginine methyl ester, considered a selective NOS2 antagonist, requires reconsideration, because it can also inhibit arginase both in vivo and in vitro (63).
[ "61", "62", "63" ]
195
38,181
1
false
For example, the effect of Nω-nitro-l-arginine methyl ester, considered a selective NOS2 antagonist, requires reconsideration, because it can also inhibit arginase both in vivo and in vitro.
[ "63" ]
For example, the effect of Nω-nitro-l-arginine methyl ester, considered a selective NOS2 antagonist, requires reconsideration, because it can also inhibit arginase both in vivo and in vitro.
true
true
true
true
true
6,550
9
DISCUSSION
1
61
[ "bib61", "bib62", "bib63" ]
15,824,085
pmid-12461516|pmid-11478904|pmid-12530480
Thus, the identification of the specific biochemical pathways responsible for immunosuppression, such as the protein nitration described here, may allow the development of more specific and less toxic immunoprotective molecules.
[ "61", "62", "63" ]
228
38,182
0
false
Thus, the identification of the specific biochemical pathways responsible for immunosuppression, such as the protein nitration described here, may allow the development of more specific and less toxic immunoprotective molecules.
[]
Thus, the identification of the specific biochemical pathways responsible for immunosuppression, such as the protein nitration described here, may allow the development of more specific and less toxic immunoprotective molecules.
true
true
true
true
true
6,550
0
INTRODUCTION
1
Barhanin et al., 1996
[ "bib1", "bib26", "bib16", "bib1", "bib26", "bib15", "bib27", "bib21", "bib24", "bib34", "bib42", "bib40", "bib25", "bib1", "bib26", "bib5", "bib19", "bib34", "bib35", "bib5", "bib20", "bib33" ]
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
KCNQ1 (Q1 or Kv7.1) voltage-gated K+ channels are composed of archetypical six transmembrane (TM) subunits that tetramerize to form an ion-conducting pore domain (S5–S6) surrounded by four voltage-sensing domains (S1–S4).
[ "Barhanin et al., 1996", "Sanguinetti et al., 1996", "McCrossan and Abbott, 2004", "Barhanin et al., 1996", "Sanguinetti et al., 1996", "Mall et al., 2000", "Schroeder et al., 2000", "Nicolas et al., 2001", "Roepke et al., 2006", "Splawski et al., 1997b", "Vetter et al., 1996", "Tyson et al., ...
221
38,183
0
false
KCNQ1 (Q1 or Kv7.1) voltage-gated K+ channels are composed of archetypical six transmembrane (TM) subunits that tetramerize to form an ion-conducting pore domain (S5–S6) surrounded by four voltage-sensing domains (S1–S4).
[]
KCNQ1 voltage-gated K+ channels are composed of archetypical six transmembrane (TM) subunits that tetramerize to form an ion-conducting pore domain surrounded by four voltage-sensing domains.
true
true
true
true
true
6,551
0
INTRODUCTION
1
Barhanin et al., 1996
[ "bib1", "bib26", "bib16", "bib1", "bib26", "bib15", "bib27", "bib21", "bib24", "bib34", "bib42", "bib40", "bib25", "bib1", "bib26", "bib5", "bib19", "bib34", "bib35", "bib5", "bib20", "bib33" ]
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
The cytoplasmic S4–S5 linker between these two functionally distinct domains mechanically couples voltage sensing to activation gate opening and closing.
[ "Barhanin et al., 1996", "Sanguinetti et al., 1996", "McCrossan and Abbott, 2004", "Barhanin et al., 1996", "Sanguinetti et al., 1996", "Mall et al., 2000", "Schroeder et al., 2000", "Nicolas et al., 2001", "Roepke et al., 2006", "Splawski et al., 1997b", "Vetter et al., 1996", "Tyson et al., ...
153
38,184
0
false
The cytoplasmic S4–S5 linker between these two functionally distinct domains mechanically couples voltage sensing to activation gate opening and closing.
[]
The cytoplasmic S4–S5 linker between these two functionally distinct domains mechanically couples voltage sensing to activation gate opening and closing.
true
true
true
true
true
6,551
0
INTRODUCTION
1
McCrossan and Abbott, 2004
[ "bib1", "bib26", "bib16", "bib1", "bib26", "bib15", "bib27", "bib21", "bib24", "bib34", "bib42", "bib40", "bib25", "bib1", "bib26", "bib5", "bib19", "bib34", "bib35", "bib5", "bib20", "bib33" ]
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 homotetrameric Q1 channels generate a fast activating delayed rectifier K+ current when expressed in standard expression systems (Barhanin et al., 1996; Sanguinetti et al., 1996), in native tissues the channel is obligatorily coassembled with one of the five members of the KCNE family of regulatory subunits (K...
[ "Barhanin et al., 1996", "Sanguinetti et al., 1996", "McCrossan and Abbott, 2004", "Barhanin et al., 1996", "Sanguinetti et al., 1996", "Mall et al., 2000", "Schroeder et al., 2000", "Nicolas et al., 2001", "Roepke et al., 2006", "Splawski et al., 1997b", "Vetter et al., 1996", "Tyson et al., ...
410
38,185
1
false
Although homotetrameric Q1 channels generate a fast activating delayed rectifier K+ current when expressed in standard expression systems, in native tissues the channel is obligatorily coassembled with one of the five members of the KCNE family of regulatory subunits (KCNE1-5; encoded proteins are MinK and MiRP1-4, res...
[ "Barhanin et al., 1996; Sanguinetti et al., 1996", "McCrossan and Abbott, 2004" ]
Although homotetrameric Q1 channels generate a fast activating delayed rectifier K+ current when expressed in standard expression systems, in native tissues the channel is obligatorily coassembled with one of the five members of the KCNE family of regulatory subunits.
true
true
true
true
true
6,551
0
INTRODUCTION
1
Barhanin et al., 1996
[ "bib1", "bib26", "bib16", "bib1", "bib26", "bib15", "bib27", "bib21", "bib24", "bib34", "bib42", "bib40", "bib25", "bib1", "bib26", "bib5", "bib19", "bib34", "bib35", "bib5", "bib20", "bib33" ]
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
Coassembly with these type I TM peptides markedly changes the voltage gating of the Q1 channel, allowing it to properly function in different tissues, including cardiac myocytes, cochlea, renal, gastrointestinal, and pulmonary epithelia (Barhanin et al., 1996; Sanguinetti et al., 1996; Mall et al., 2000; Schroeder et a...
[ "Barhanin et al., 1996", "Sanguinetti et al., 1996", "McCrossan and Abbott, 2004", "Barhanin et al., 1996", "Sanguinetti et al., 1996", "Mall et al., 2000", "Schroeder et al., 2000", "Nicolas et al., 2001", "Roepke et al., 2006", "Splawski et al., 1997b", "Vetter et al., 1996", "Tyson et al., ...
373
38,186
0
false
Coassembly with these type I TM peptides markedly changes the voltage gating of the Q1 channel, allowing it to properly function in different tissues, including cardiac myocytes, cochlea, renal, gastrointestinal, and pulmonary epithelia.
[ "Barhanin et al., 1996; Sanguinetti et al., 1996; Mall et al., 2000; Schroeder et al., 2000; Nicolas et al., 2001; Roepke et al., 2006" ]
Coassembly with these type I TM peptides markedly changes the voltage gating of the Q1 channel, allowing it to properly function in different tissues, including cardiac myocytes, cochlea, renal, gastrointestinal, and pulmonary epithelia.
true
true
true
true
true
6,551
0
INTRODUCTION
1
Splawski et al., 1997b
[ "bib1", "bib26", "bib16", "bib1", "bib26", "bib15", "bib27", "bib21", "bib24", "bib34", "bib42", "bib40", "bib25", "bib1", "bib26", "bib5", "bib19", "bib34", "bib35", "bib5", "bib20", "bib33" ]
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
Modulation of Q1 channel function by all five KCNE proteins has been observed; however, Q1’s association with KCNE1 (E1) has been studied more thoroughly due to the involvement of this complex in several pathophysiological conditions ranging from inherited ventricular arrhythmias (Splawski et al., 1997b) to deafness (V...
[ "Barhanin et al., 1996", "Sanguinetti et al., 1996", "McCrossan and Abbott, 2004", "Barhanin et al., 1996", "Sanguinetti et al., 1996", "Mall et al., 2000", "Schroeder et al., 2000", "Nicolas et al., 2001", "Roepke et al., 2006", "Splawski et al., 1997b", "Vetter et al., 1996", "Tyson et al., ...
360
38,187
1
false
Modulation of Q1 channel function by all five KCNE proteins has been observed; however, Q1’s association with KCNE1 (E1) has been studied more thoroughly due to the involvement of this complex in several pathophysiological conditions ranging from inherited ventricular arrhythmias to deafness.
[ "Splawski et al., 1997b", "Vetter et al., 1996; Tyson et al., 2000" ]
Modulation of Q1 channel function by all five KCNE proteins has been observed; however, Q1’s association with KCNE1 has been studied more thoroughly due to the involvement of this complex in several pathophysiological conditions ranging from inherited ventricular arrhythmias to deafness.
true
true
true
true
true
6,551
0
INTRODUCTION
1
Barhanin et al., 1996
[ "bib1", "bib26", "bib16", "bib1", "bib26", "bib15", "bib27", "bib21", "bib24", "bib34", "bib42", "bib40", "bib25", "bib1", "bib26", "bib5", "bib19", "bib34", "bib35", "bib5", "bib20", "bib33" ]
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 cardiomyocytes, the Q1–E1 complex conducts the slowly activating and deactivating, yet apparently non-inactivating, IKs current (Sanguinetti and Jurkiewicz, 1990; Barhanin et al., 1996; Sanguinetti et al., 1996), which is involved in the repolarization phase of cardiac action potential.
[ "Barhanin et al., 1996", "Sanguinetti et al., 1996", "McCrossan and Abbott, 2004", "Barhanin et al., 1996", "Sanguinetti et al., 1996", "Mall et al., 2000", "Schroeder et al., 2000", "Nicolas et al., 2001", "Roepke et al., 2006", "Splawski et al., 1997b", "Vetter et al., 1996", "Tyson et al., ...
290
38,188
0
false
In cardiomyocytes, the Q1–E1 complex conducts the slowly activating and deactivating, yet apparently non-inactivating, IKs current, which is involved in the repolarization phase of cardiac action potential.
[ "Sanguinetti and Jurkiewicz, 1990; Barhanin et al., 1996; Sanguinetti et al., 1996" ]
In cardiomyocytes, the Q1–E1 complex conducts the slowly activating and deactivating, yet apparently non-inactivating, IKs current, which is involved in the repolarization phase of cardiac action potential.
true
true
true
true
true
6,551
0
INTRODUCTION
1
Barhanin et al., 1996
[ "bib1", "bib26", "bib16", "bib1", "bib26", "bib15", "bib27", "bib21", "bib24", "bib34", "bib42", "bib40", "bib25", "bib1", "bib26", "bib5", "bib19", "bib34", "bib35", "bib5", "bib20", "bib33" ]
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
Mutations in either Q1 (Chouabe et al., 1997; Napolitano et al., 2005) or E1 (Splawski et al., 1997b, 2000) that decrease the conductance of the complex prolong the cardiac action potential and cause arrhythmias, including long QT syndrome.
[ "Barhanin et al., 1996", "Sanguinetti et al., 1996", "McCrossan and Abbott, 2004", "Barhanin et al., 1996", "Sanguinetti et al., 1996", "Mall et al., 2000", "Schroeder et al., 2000", "Nicolas et al., 2001", "Roepke et al., 2006", "Splawski et al., 1997b", "Vetter et al., 1996", "Tyson et al., ...
240
38,189
0
false
Mutations in either Q1 or E1 that decrease the conductance of the complex prolong the cardiac action potential and cause arrhythmias, including long QT syndrome.
[ "Chouabe et al., 1997; Napolitano et al., 2005", "Splawski et al., 1997b, 2000" ]
Mutations in either Q1 or E1 that decrease the conductance of the complex prolong the cardiac action potential and cause arrhythmias, including long QT syndrome.
true
true
true
true
true
6,551
0
INTRODUCTION
1
Barhanin et al., 1996
[ "bib1", "bib26", "bib16", "bib1", "bib26", "bib15", "bib27", "bib21", "bib24", "bib34", "bib42", "bib40", "bib25", "bib1", "bib26", "bib5", "bib19", "bib34", "bib35", "bib5", "bib20", "bib33" ]
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 the inner ear, where Q1–E1 complex provides a passage for K+ to the endolymph in the cavities of the cochlear labyrinth, these detrimental mutations can cause congenital deafness (Chouabe et al., 1997; Neyroud et al., 1997; Splawski et al., 1997a).
[ "Barhanin et al., 1996", "Sanguinetti et al., 1996", "McCrossan and Abbott, 2004", "Barhanin et al., 1996", "Sanguinetti et al., 1996", "Mall et al., 2000", "Schroeder et al., 2000", "Nicolas et al., 2001", "Roepke et al., 2006", "Splawski et al., 1997b", "Vetter et al., 1996", "Tyson et al., ...
251
38,190
0
false
In the inner ear, where Q1–E1 complex provides a passage for K+ to the endolymph in the cavities of the cochlear labyrinth, these detrimental mutations can cause congenital deafness.
[ "Chouabe et al., 1997; Neyroud et al., 1997; Splawski et al., 1997a" ]
In the inner ear, where Q1–E1 complex provides a passage for K+ to the endolymph in the cavities of the cochlear labyrinth, these detrimental mutations can cause congenital deafness.
true
true
true
true
true
6,551
1
INTRODUCTION
1
Wang et al., 1996
[ "bib44", "bib36", "bib39", "bib17", "bib22", "bib4", "bib9", "bib13", "bib45", "bib6", "bib8" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
In contrast to K+ channel interactions with strictly cytoplasmic modulators, such as G proteins, KChIPs, or Kvβ subunits, the site of action of E1, a single-pass membrane protein, has been sought in the extracellular, cytoplasmic, and membrane-embedded regions of Q1.
[ "Wang et al., 1996", "Tai and Goldstein, 1998", "Tapper and George, 2001", "Melman et al., 2004", "Panaghie et al., 2006", "Y.H. Chen et al., 2003", "Hong et al., 2005", "Lundby et al., 2007", "Xu et al., 2008", "Chung et al., 2009", "Haitin et al., 2009" ]
267
38,191
0
false
In contrast to K+ channel interactions with strictly cytoplasmic modulators, such as G proteins, KChIPs, or Kvβ subunits, the site of action of E1, a single-pass membrane protein, has been sought in the extracellular, cytoplasmic, and membrane-embedded regions of Q1.
[]
In contrast to K+ channel interactions with strictly cytoplasmic modulators, such as G proteins, KChIPs, or Kvβ subunits, the site of action of E1, a single-pass membrane protein, has been sought in the extracellular, cytoplasmic, and membrane-embedded regions of Q1.
true
true
true
true
true
6,552
1
INTRODUCTION
1
Wang et al., 1996
[ "bib44", "bib36", "bib39", "bib17", "bib22", "bib4", "bib9", "bib13", "bib45", "bib6", "bib8" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
Initial electrophysiological studies focused on the membrane-embedded portion of the Q1–E1 complex, and it was proposed that the E1 TM segment lined the conductivity pathway (Wang et al., 1996; Tai and Goldstein, 1998) of the complex.
[ "Wang et al., 1996", "Tai and Goldstein, 1998", "Tapper and George, 2001", "Melman et al., 2004", "Panaghie et al., 2006", "Y.H. Chen et al., 2003", "Hong et al., 2005", "Lundby et al., 2007", "Xu et al., 2008", "Chung et al., 2009", "Haitin et al., 2009" ]
234
38,192
0
false
Initial electrophysiological studies focused on the membrane-embedded portion of the Q1–E1 complex, and it was proposed that the E1 TM segment lined the conductivity pathway of the complex.
[ "Wang et al., 1996; Tai and Goldstein, 1998" ]
Initial electrophysiological studies focused on the membrane-embedded portion of the Q1–E1 complex, and it was proposed that the E1 TM segment lined the conductivity pathway of the complex.
true
true
true
true
true
6,552
1
INTRODUCTION
1
Wang et al., 1996
[ "bib44", "bib36", "bib39", "bib17", "bib22", "bib4", "bib9", "bib13", "bib45", "bib6", "bib8" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
However, the many high resolution structures of the tightly packed helices of the K+ channel pore domain have made this location infeasible.
[ "Wang et al., 1996", "Tai and Goldstein, 1998", "Tapper and George, 2001", "Melman et al., 2004", "Panaghie et al., 2006", "Y.H. Chen et al., 2003", "Hong et al., 2005", "Lundby et al., 2007", "Xu et al., 2008", "Chung et al., 2009", "Haitin et al., 2009" ]
140
38,193
0
false
However, the many high resolution structures of the tightly packed helices of the K+ channel pore domain have made this location infeasible.
[]
However, the many high resolution structures of the tightly packed helices of the K+ channel pore domain have made this location infeasible.
true
true
true
true
true
6,552
1
INTRODUCTION
1
Wang et al., 1996
[ "bib44", "bib36", "bib39", "bib17", "bib22", "bib4", "bib9", "bib13", "bib45", "bib6", "bib8" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
More recent electrophysiological investigations have relocated the E1 TM on the backside of the Q1 pore domain (Tapper and George, 2001; Melman et al., 2004; Panaghie et al., 2006).
[ "Wang et al., 1996", "Tai and Goldstein, 1998", "Tapper and George, 2001", "Melman et al., 2004", "Panaghie et al., 2006", "Y.H. Chen et al., 2003", "Hong et al., 2005", "Lundby et al., 2007", "Xu et al., 2008", "Chung et al., 2009", "Haitin et al., 2009" ]
181
38,194
0
false
More recent electrophysiological investigations have relocated the E1 TM on the backside of the Q1 pore domain.
[ "Tapper and George, 2001; Melman et al., 2004; Panaghie et al., 2006" ]
More recent electrophysiological investigations have relocated the E1 TM on the backside of the Q1 pore domain.
true
true
true
true
true
6,552
1
INTRODUCTION
1
Wang et al., 1996
[ "bib44", "bib36", "bib39", "bib17", "bib22", "bib4", "bib9", "bib13", "bib45", "bib6", "bib8" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
The discovery of atrial fibrillation mutations in the extracellular S1–S2 loop of Q1 (Y.H.
[ "Wang et al., 1996", "Tai and Goldstein, 1998", "Tapper and George, 2001", "Melman et al., 2004", "Panaghie et al., 2006", "Y.H. Chen et al., 2003", "Hong et al., 2005", "Lundby et al., 2007", "Xu et al., 2008", "Chung et al., 2009", "Haitin et al., 2009" ]
90
38,195
0
false
The discovery of atrial fibrillation mutations in the extracellular S1–S2 loop of Q1 (Y.H.
[]
The discovery of atrial fibrillation mutations in the extracellular S1–S2 loop of Q1 (Y.H.
true
true
true
true
true
6,552
1
INTRODUCTION
1
Wang et al., 1996
[ "bib44", "bib36", "bib39", "bib17", "bib22", "bib4", "bib9", "bib13", "bib45", "bib6", "bib8" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
Chen et al., 2003; Hong et al., 2005; Lundby et al., 2007) has shifted attention toward the extracellular domains of the Q1–E1 complex.
[ "Wang et al., 1996", "Tai and Goldstein, 1998", "Tapper and George, 2001", "Melman et al., 2004", "Panaghie et al., 2006", "Y.H. Chen et al., 2003", "Hong et al., 2005", "Lundby et al., 2007", "Xu et al., 2008", "Chung et al., 2009", "Haitin et al., 2009" ]
135
38,196
0
false
Chen et al., 2003; Hong et al., 2005; Lundby et al., 2007) has shifted attention toward the extracellular domains of the Q1–E1 complex.
[]
Chen et al., 2003; Hong et al., 2005; Lundby et al., 2007) has shifted attention toward the extracellular domains of the Q1–E1 complex.
true
true
true
true
true
6,552
1
INTRODUCTION
1
Wang et al., 1996
[ "bib44", "bib36", "bib39", "bib17", "bib22", "bib4", "bib9", "bib13", "bib45", "bib6", "bib8" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
Two different studies using cysteine cross-linking have identified protein–protein interactions between the E1 N terminus and the extracellular tops of the S1 and S4 segments, and the pore domain of Q1 (Xu et al., 2008; Chung et al., 2009).
[ "Wang et al., 1996", "Tai and Goldstein, 1998", "Tapper and George, 2001", "Melman et al., 2004", "Panaghie et al., 2006", "Y.H. Chen et al., 2003", "Hong et al., 2005", "Lundby et al., 2007", "Xu et al., 2008", "Chung et al., 2009", "Haitin et al., 2009" ]
240
38,197
0
false
Two different studies using cysteine cross-linking have identified protein–protein interactions between the E1 N terminus and the extracellular tops of the S1 and S4 segments, and the pore domain of Q1.
[ "Xu et al., 2008; Chung et al., 2009" ]
Two different studies using cysteine cross-linking have identified protein–protein interactions between the E1 N terminus and the extracellular tops of the S1 and S4 segments, and the pore domain of Q1.
true
true
true
true
true
6,552
1
INTRODUCTION
1
Wang et al., 1996
[ "bib44", "bib36", "bib39", "bib17", "bib22", "bib4", "bib9", "bib13", "bib45", "bib6", "bib8" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
In total, these studies position the E1 TM segment in a cleft between the pore and voltage-sensing domains of the Q1 channel.
[ "Wang et al., 1996", "Tai and Goldstein, 1998", "Tapper and George, 2001", "Melman et al., 2004", "Panaghie et al., 2006", "Y.H. Chen et al., 2003", "Hong et al., 2005", "Lundby et al., 2007", "Xu et al., 2008", "Chung et al., 2009", "Haitin et al., 2009" ]
125
38,198
0
false
In total, these studies position the E1 TM segment in a cleft between the pore and voltage-sensing domains of the Q1 channel.
[]
In total, these studies position the E1 TM segment in a cleft between the pore and voltage-sensing domains of the Q1 channel.
true
true
true
true
true
6,552
1
INTRODUCTION
1
Haitin et al., 2009
[ "bib44", "bib36", "bib39", "bib17", "bib22", "bib4", "bib9", "bib13", "bib45", "bib6", "bib8" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA|NA
A recent coimmunoprecipitation study of the cytoplasmic parts of the Q1–E1 complex has identified a large stretch of residues at the E1 C terminus that binds to the subunit identification (“tetramerization”) domain of the Q1 channel, providing an anchoring point at the C terminus (Haitin et al., 2009).
[ "Wang et al., 1996", "Tai and Goldstein, 1998", "Tapper and George, 2001", "Melman et al., 2004", "Panaghie et al., 2006", "Y.H. Chen et al., 2003", "Hong et al., 2005", "Lundby et al., 2007", "Xu et al., 2008", "Chung et al., 2009", "Haitin et al., 2009" ]
303
38,199
1
false
A recent coimmunoprecipitation study of the cytoplasmic parts of the Q1–E1 complex has identified a large stretch of residues at the E1 C terminus that binds to the subunit identification (“tetramerization”) domain of the Q1 channel, providing an anchoring point at the C terminus.
[ "Haitin et al., 2009" ]
A recent coimmunoprecipitation study of the cytoplasmic parts of the Q1–E1 complex has identified a large stretch of residues at the E1 C terminus that binds to the subunit identification domain of the Q1 channel, providing an anchoring point at the C terminus.
true
true
true
true
true
6,552
2
INTRODUCTION
1
Takumi et al., 1991
[ "bib37", "bib38", "bib7", "bib35", "bib29", "bib14", "bib12", "bib19", "bib23" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA
A cytoplasmic domain of E1 that has been of continual interest comprises the ∼20 residues that abut the membrane, which are seemingly ideally located near the cytoplasmic machinery of Q1 responsible for voltage-dependent gating.
[ "Takumi et al., 1991", "Tapper and George, 2000", "Gage and Kobertz, 2004", "Splawski et al., 2000", "Schulze-Bahr et al., 2001", "Ma et al., 2003", "Lai et al., 2005", "Napolitano et al., 2005", "Rocheleau et al., 2006" ]
228
38,200
0
false
A cytoplasmic domain of E1 that has been of continual interest comprises the ∼20 residues that abut the membrane, which are seemingly ideally located near the cytoplasmic machinery of Q1 responsible for voltage-dependent gating.
[]
A cytoplasmic domain of E1 that has been of continual interest comprises the ∼20 residues that abut the membrane, which are seemingly ideally located near the cytoplasmic machinery of Q1 responsible for voltage-dependent gating.
true
true
true
true
true
6,553
2
INTRODUCTION
1
Takumi et al., 1991
[ "bib37", "bib38", "bib7", "bib35", "bib29", "bib14", "bib12", "bib19", "bib23" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA
One of the first mutagenesis investigations of E1 (then IKs) showed that point mutations in this C-terminal domain greatly affect channel activity (Takumi et al., 1991).
[ "Takumi et al., 1991", "Tapper and George, 2000", "Gage and Kobertz, 2004", "Splawski et al., 2000", "Schulze-Bahr et al., 2001", "Ma et al., 2003", "Lai et al., 2005", "Napolitano et al., 2005", "Rocheleau et al., 2006" ]
169
38,201
1
false
One of the first mutagenesis investigations of E1 (then IKs) showed that point mutations in this C-terminal domain greatly affect channel activity.
[ "Takumi et al., 1991" ]
One of the first mutagenesis investigations of E1 showed that point mutations in this C-terminal domain greatly affect channel activity.
true
true
true
true
true
6,553
2
INTRODUCTION
1
Takumi et al., 1991
[ "bib37", "bib38", "bib7", "bib35", "bib29", "bib14", "bib12", "bib19", "bib23" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA
Subsequent deletion and chimera studies have indicated that this domain is critical for the characteristic slow activation kinetics of the Q1–E1 complex (Tapper and George, 2000; Gage and Kobertz, 2004).
[ "Takumi et al., 1991", "Tapper and George, 2000", "Gage and Kobertz, 2004", "Splawski et al., 2000", "Schulze-Bahr et al., 2001", "Ma et al., 2003", "Lai et al., 2005", "Napolitano et al., 2005", "Rocheleau et al., 2006" ]
203
38,202
0
false
Subsequent deletion and chimera studies have indicated that this domain is critical for the characteristic slow activation kinetics of the Q1–E1 complex.
[ "Tapper and George, 2000; Gage and Kobertz, 2004" ]
Subsequent deletion and chimera studies have indicated that this domain is critical for the characteristic slow activation kinetics of the Q1–E1 complex.
true
true
true
true
true
6,553
2
INTRODUCTION
1
Takumi et al., 1991
[ "bib37", "bib38", "bib7", "bib35", "bib29", "bib14", "bib12", "bib19", "bib23" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA
Moreover, several missense point mutants that cause long QT syndrome cluster to this C-terminal domain in E1 (Splawski et al., 2000; Schulze-Bahr et al., 2001; Ma et al., 2003; Lai et al., 2005; Napolitano et al., 2005).
[ "Takumi et al., 1991", "Tapper and George, 2000", "Gage and Kobertz, 2004", "Splawski et al., 2000", "Schulze-Bahr et al., 2001", "Ma et al., 2003", "Lai et al., 2005", "Napolitano et al., 2005", "Rocheleau et al., 2006" ]
220
38,203
0
false
Moreover, several missense point mutants that cause long QT syndrome cluster to this C-terminal domain in E1.
[ "Splawski et al., 2000; Schulze-Bahr et al., 2001; Ma et al., 2003; Lai et al., 2005; Napolitano et al., 2005" ]
Moreover, several missense point mutants that cause long QT syndrome cluster to this C-terminal domain in E1.
true
true
true
true
true
6,553
2
INTRODUCTION
1
Rocheleau et al., 2006
[ "bib37", "bib38", "bib7", "bib35", "bib29", "bib14", "bib12", "bib19", "bib23" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA
Periodicity analysis of mutagenic perturbation experiments have shown that this membrane-abutting domain of E1 adopts an α-helical structure when split in half at a conserved proline residue (Rocheleau et al., 2006).
[ "Takumi et al., 1991", "Tapper and George, 2000", "Gage and Kobertz, 2004", "Splawski et al., 2000", "Schulze-Bahr et al., 2001", "Ma et al., 2003", "Lai et al., 2005", "Napolitano et al., 2005", "Rocheleau et al., 2006" ]
216
38,204
1
false
Periodicity analysis of mutagenic perturbation experiments have shown that this membrane-abutting domain of E1 adopts an α-helical structure when split in half at a conserved proline residue.
[ "Rocheleau et al., 2006" ]
Periodicity analysis of mutagenic perturbation experiments have shown that this membrane-abutting domain of E1 adopts an α-helical structure when split in half at a conserved proline residue.
true
true
true
true
true
6,553
2
INTRODUCTION
1
Takumi et al., 1991
[ "bib37", "bib38", "bib7", "bib35", "bib29", "bib14", "bib12", "bib19", "bib23" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA
This secondary structure predicts that all of the known long QT mutations in this domain will face the Q1 channel.
[ "Takumi et al., 1991", "Tapper and George, 2000", "Gage and Kobertz, 2004", "Splawski et al., 2000", "Schulze-Bahr et al., 2001", "Ma et al., 2003", "Lai et al., 2005", "Napolitano et al., 2005", "Rocheleau et al., 2006" ]
114
38,205
0
false
This secondary structure predicts that all of the known long QT mutations in this domain will face the Q1 channel.
[]
This secondary structure predicts that all of the known long QT mutations in this domain will face the Q1 channel.
true
true
true
true
true
6,553
2
INTRODUCTION
1
Takumi et al., 1991
[ "bib37", "bib38", "bib7", "bib35", "bib29", "bib14", "bib12", "bib19", "bib23" ]
20,479,109
NA|NA|NA|NA|NA|NA|NA|NA|NA
Despite the extensive study by several laboratories, the protein–protein interactions between the E1 C-terminal domain and Q1 have remained uninvestigated.
[ "Takumi et al., 1991", "Tapper and George, 2000", "Gage and Kobertz, 2004", "Splawski et al., 2000", "Schulze-Bahr et al., 2001", "Ma et al., 2003", "Lai et al., 2005", "Napolitano et al., 2005", "Rocheleau et al., 2006" ]
155
38,206
0
false
Despite the extensive study by several laboratories, the protein–protein interactions between the E1 C-terminal domain and Q1 have remained uninvestigated.
[]
Despite the extensive study by several laboratories, the protein–protein interactions between the E1 C-terminal domain and Q1 have remained uninvestigated.
true
true
true
true
true
6,553
3
INTRODUCTION
1
Schulteis et al., 1996
[ "bib28", "bib11" ]
20,479,109
NA|NA
To identify the Q1 cytoplasmic surfaces that interact with the E1 C-terminal domain, we used oxidant-mediated disulfide bond formation between exogenous cysteine point mutations in a cysteine-null background (Schulteis et al., 1996; Kobertz et al., 2000).
[ "Schulteis et al., 1996", "Kobertz et al., 2000" ]
255
38,207
0
false
To identify the Q1 cytoplasmic surfaces that interact with the E1 C-terminal domain, we used oxidant-mediated disulfide bond formation between exogenous cysteine point mutations in a cysteine-null background.
[ "Schulteis et al., 1996; Kobertz et al., 2000" ]
To identify the Q1 cytoplasmic surfaces that interact with the E1 C-terminal domain, we used oxidant-mediated disulfide bond formation between exogenous cysteine point mutations in a cysteine-null background.
true
true
true
true
true
6,554
3
INTRODUCTION
1
Schulteis et al., 1996
[ "bib28", "bib11" ]
20,479,109
NA|NA
We found two residues below the S6 bundle crossing (H363C and P369C) and only one residue in the S4–S5 linker (I257C) that formed disulfide bonds with the panel of KCNE1 cysteine mutants.
[ "Schulteis et al., 1996", "Kobertz et al., 2000" ]
187
38,208
0
false
We found two residues below the S6 bundle crossing (H363C and P369C) and only one residue in the S4–S5 linker (I257C) that formed disulfide bonds with the panel of KCNE1 cysteine mutants.
[]
We found two residues below the S6 bundle crossing and only one residue in the S4–S5 linker (I257C) that formed disulfide bonds with the panel of KCNE1 cysteine mutants.
true
true
true
true
true
6,554
3
INTRODUCTION
1
Schulteis et al., 1996
[ "bib28", "bib11" ]
20,479,109
NA|NA
Statistical analysis of cross-link efficiency demonstrated that H363C preferentially reacted with H73C, S74C, and D76C; P369C reacted with D76C only; and I257C was the only residue that had widespread reactivity with the KCNE1 cysteine panel.
[ "Schulteis et al., 1996", "Kobertz et al., 2000" ]
242
38,209
0
false
Statistical analysis of cross-link efficiency demonstrated that H363C preferentially reacted with H73C, S74C, and D76C; P369C reacted with D76C only; and I257C was the only residue that had widespread reactivity with the KCNE1 cysteine panel.
[]
Statistical analysis of cross-link efficiency demonstrated that H363C preferentially reacted with H73C, S74C, and D76C; P369C reacted with D76C only; and I257C was the only residue that had widespread reactivity with the KCNE1 cysteine panel.
true
true
true
true
true
6,554
3
INTRODUCTION
1
Schulteis et al., 1996
[ "bib28", "bib11" ]
20,479,109
NA|NA
Functional examination of H363C showed that disulfide bond formation was voltage dependent, occurring predominately when the channel was closed, which was due to two factors: formation of a disulfide bond with E1 and also with a neighboring H363C subunit within the channel complex.
[ "Schulteis et al., 1996", "Kobertz et al., 2000" ]
282
38,210
0
false
Functional examination of H363C showed that disulfide bond formation was voltage dependent, occurring predominately when the channel was closed, which was due to two factors: formation of a disulfide bond with E1 and also with a neighboring H363C subunit within the channel complex.
[]
Functional examination of H363C showed that disulfide bond formation was voltage dependent, occurring predominately when the channel was closed, which was due to two factors: formation of a disulfide bond with E1 and also with a neighboring H363C subunit within the channel complex.
true
true
true
true
true
6,554
3
INTRODUCTION
1
Schulteis et al., 1996
[ "bib28", "bib11" ]
20,479,109
NA|NA
Using these experimental constraints, we built a closed-state model of the Q1–E1 cytoplasmic region that positions the E1 C-terminal domain adjacent to the activation gate machinery, which suggests that these protein–protein interactions may slow the opening of the Q1–E1 complex.
[ "Schulteis et al., 1996", "Kobertz et al., 2000" ]
280
38,211
0
false
Using these experimental constraints, we built a closed-state model of the Q1–E1 cytoplasmic region that positions the E1 C-terminal domain adjacent to the activation gate machinery, which suggests that these protein–protein interactions may slow the opening of the Q1–E1 complex.
[]
Using these experimental constraints, we built a closed-state model of the Q1–E1 cytoplasmic region that positions the E1 C-terminal domain adjacent to the activation gate machinery, which suggests that these protein–protein interactions may slow the opening of the Q1–E1 complex.
true
true
true
true
true
6,554
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
Previous Q1–E1 cysteine cross-linking studies have focused on extracellular protein–protein interactions in intact cells, where the environment is oxidizing and the membrane potential of the cell provides control of complex conformation.
[ "Rocheleau et al., 2006", "Xu et al., 2008", "Chung et al., 2009", "Rocheleau et al., 2006" ]
237
38,212
0
false
Previous Q1–E1 cysteine cross-linking studies have focused on extracellular protein–protein interactions in intact cells, where the environment is oxidizing and the membrane potential of the cell provides control of complex conformation.
[]
Previous Q1–E1 cysteine cross-linking studies have focused on extracellular protein–protein interactions in intact cells, where the environment is oxidizing and the membrane potential of the cell provides control of complex conformation.
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 the present work, we focused on the juxtamembranous part of the E1 C terminus because this domain adopts a helical structure, where both laboratory-made and long QT mutations cluster to one face of the helix predicted to face the cytoplasmic side of the Q1 channel (Rocheleau et al., 2006).
[ "Rocheleau et al., 2006", "Xu et al., 2008", "Chung et al., 2009", "Rocheleau et al., 2006" ]
293
38,213
1
false
In the present work, we focused on the juxtamembranous part of the E1 C terminus because this domain adopts a helical structure, where both laboratory-made and long QT mutations cluster to one face of the helix predicted to face the cytoplasmic side of the Q1 channel.
[ "Rocheleau et al., 2006" ]
In the present work, we focused on the juxtamembranous part of the E1 C terminus because this domain adopts a helical structure, where both laboratory-made and long QT mutations cluster to one face of the helix predicted to face the cytoplasmic side of 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
To identify these Q1–E1 protein interactions, we oxidized hypotonically lysed cells, which provided cytoplasmic access to the complex in a membranous environment.
[ "Rocheleau et al., 2006", "Xu et al., 2008", "Chung et al., 2009", "Rocheleau et al., 2006" ]
162
38,214
0
false
To identify these Q1–E1 protein interactions, we oxidized hypotonically lysed cells, which provided cytoplasmic access to the complex in a membranous environment.
[]
To identify these Q1–E1 protein interactions, we oxidized hypotonically lysed cells, which provided cytoplasmic access to the complex in a membranous environment.
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 these conditions enabled us to screen hundreds of pairs of Q1–E1 residues, our approach comes with a caveat: hypotonic lysis destroys the electrochemical gradient and TM potential.
[ "Rocheleau et al., 2006", "Xu et al., 2008", "Chung et al., 2009", "Rocheleau et al., 2006" ]
189
38,215
0
false
Although these conditions enabled us to screen hundreds of pairs of Q1–E1 residues, our approach comes with a caveat: hypotonic lysis destroys the electrochemical gradient and TM potential.
[]
Although these conditions enabled us to screen hundreds of pairs of Q1–E1 residues, our approach comes with a caveat: hypotonic lysis destroys the electrochemical gradient and TM potential.
true
true
true
true
true
6,555