Datasets:
vgainullin
/
xciting_data

Dataset card Data Studio Files
xet
 Community
1
paragraph_index
int64
sec
string
p_has_citation
int64
cites
string
citeids
list
pmid
int64
cited_id
string
sentences
string
all_sent_cites
list
sent_len
int64
sentence_batch_index
int64
sent_has_citation
float64
qc_fail
bool
cited_sentence
string
cites_in_sentence
list
cln_sentence
string
is_cap
bool
is_alpha
bool
ends_wp
bool
cit_qc
bool
lgtm
bool
__index_level_0__
int64
2
DISCUSSION
1
26
[ "bib26", "bib41", "bib46", "bib47", "bib48" ]
18,362,172
pmid-16497973|pmid-15585887|pmid-10809739|pmid-10952975|pmid-12645574
Clearly, in the liver unlike other organs, endothelial CD44 may be dispensable due to the presence of HARE and possibly other unidentified HA receptors.
[ "26", "41", "46", "47", "48" ]
152
37,216
0
false
Clearly, in the liver unlike other organs, endothelial CD44 may be dispensable due to the presence of HARE and possibly other unidentified HA receptors.
[]
Clearly, in the liver unlike other organs, endothelial CD44 may be dispensable due to the presence of HARE and possibly other unidentified HA receptors.
true
true
true
true
true
6,381
3
DISCUSSION
1
49
[ "bib49", "bib50" ]
18,362,172
pmid-9550421|pmid-11325633
If HA is constitutively expressed on sinusoidal endothelium and CD44 is constitutively expressed on neutrophils, modification of either HA or CD44 is necessary for active binding in response to LPS.
[ "49", "50" ]
198
37,217
0
false
If HA is constitutively expressed on sinusoidal endothelium and CD44 is constitutively expressed on neutrophils, modification of either HA or CD44 is necessary for active binding in response to LPS.
[]
If HA is constitutively expressed on sinusoidal endothelium and CD44 is constitutively expressed on neutrophils, modification of either HA or CD44 is necessary for active binding in response to LPS.
true
true
true
true
true
6,382
3
DISCUSSION
1
49
[ "bib49", "bib50" ]
18,362,172
pmid-9550421|pmid-11325633
Although CD44 is constitutively expressed on circulating lymphocytes, neutrophils, and other leukocytes, it is normally present in an inactive conformation that does not bind to HA (49).
[ "49", "50" ]
186
37,218
1
false
Although CD44 is constitutively expressed on circulating lymphocytes, neutrophils, and other leukocytes, it is normally present in an inactive conformation that does not bind to HA.
[ "49" ]
Although CD44 is constitutively expressed on circulating lymphocytes, neutrophils, and other leukocytes, it is normally present in an inactive conformation that does not bind to HA.
true
true
true
true
true
6,382
3
DISCUSSION
1
50
[ "bib49", "bib50" ]
18,362,172
pmid-9550421|pmid-11325633
Indeed, many mechanisms for increased affinity and/or avidity of leukocyte CD44 for HA have been identified, including increased CD44 expression, receptor clustering, altered glycosylation, phosphorylation, and sulfation (50).
[ "49", "50" ]
226
37,219
1
false
Indeed, many mechanisms for increased affinity and/or avidity of leukocyte CD44 for HA have been identified, including increased CD44 expression, receptor clustering, altered glycosylation, phosphorylation, and sulfation.
[ "50" ]
Indeed, many mechanisms for increased affinity and/or avidity of leukocyte CD44 for HA have been identified, including increased CD44 expression, receptor clustering, altered glycosylation, phosphorylation, and sulfation.
true
true
true
true
true
6,382
3
DISCUSSION
1
49
[ "bib49", "bib50" ]
18,362,172
pmid-9550421|pmid-11325633
However, many of these findings were derived from studies of lymphocytes and not neutrophils.
[ "49", "50" ]
93
37,220
0
false
However, many of these findings were derived from studies of lymphocytes and not neutrophils.
[]
However, many of these findings were derived from studies of lymphocytes and not neutrophils.
true
true
true
true
true
6,382
3
DISCUSSION
1
49
[ "bib49", "bib50" ]
18,362,172
pmid-9550421|pmid-11325633
We found that treatment of neutrophils with LPS, chemokines, TNF-α, plasma from LPS-treated mice, or freshly isolated neutrophils from endotoxemic mice was sufficient for CD18 activation and L-selectin shedding (unpublished data), but not sufficient to induce neutrophil CD44 to adhere to HA.
[ "49", "50" ]
292
37,221
0
false
We found that treatment of neutrophils with LPS, chemokines, TNF-α, plasma from LPS-treated mice, or freshly isolated neutrophils from endotoxemic mice was sufficient for CD18 activation and L-selectin shedding (unpublished data), but not sufficient to induce neutrophil CD44 to adhere to HA.
[]
We found that treatment of neutrophils with LPS, chemokines, TNF-α, plasma from LPS-treated mice, or freshly isolated neutrophils from endotoxemic mice was sufficient for CD18 activation and L-selectin shedding (unpublished data), but not sufficient to induce neutrophil CD44 to adhere to HA.
true
true
true
true
true
6,382
3
DISCUSSION
1
49
[ "bib49", "bib50" ]
18,362,172
pmid-9550421|pmid-11325633
Although a slight shift in the population of neutrophils binding to FL-HA was observed after treatment with LPS, this did not translate into cells adhering to immobilized HA under flow conditions.
[ "49", "50" ]
196
37,222
0
false
Although a slight shift in the population of neutrophils binding to FL-HA was observed after treatment with LPS, this did not translate into cells adhering to immobilized HA under flow conditions.
[]
Although a slight shift in the population of neutrophils binding to FL-HA was observed after treatment with LPS, this did not translate into cells adhering to immobilized HA under flow conditions.
true
true
true
true
true
6,382
3
DISCUSSION
1
49
[ "bib49", "bib50" ]
18,362,172
pmid-9550421|pmid-11325633
Thus, LPS-induced activation of neutrophil CD44 is not sufficient for neutrophil recruitment in the sinusoids.
[ "49", "50" ]
110
37,223
0
false
Thus, LPS-induced activation of neutrophil CD44 is not sufficient for neutrophil recruitment in the sinusoids.
[]
Thus, LPS-induced activation of neutrophil CD44 is not sufficient for neutrophil recruitment in the sinusoids.
true
true
true
true
true
6,382
4
DISCUSSION
1
51
[ "bib51", "bib27", "bib52", "bib27", "bib27" ]
18,362,172
pmid-10871609|pmid-16702221|pmid-14977887|pmid-16702221|pmid-16702221
Alternatively, there is new evidence that CD44–HA interactions can be regulated by qualitative changes in HA.
[ "51", "27", "52", "27", "27" ]
109
37,224
0
false
Alternatively, there is new evidence that CD44–HA interactions can be regulated by qualitative changes in HA.
[]
Alternatively, there is new evidence that CD44–HA interactions can be regulated by qualitative changes in HA.
true
true
true
true
true
6,383
4
DISCUSSION
1
51
[ "bib51", "bib27", "bib52", "bib27", "bib27" ]
18,362,172
pmid-10871609|pmid-16702221|pmid-14977887|pmid-16702221|pmid-16702221
For example, alterations of HA polymer length by enzymes or reactive oxygen species liberated during inflammation can modulate the binding of HA to CD44 (51).
[ "51", "27", "52", "27", "27" ]
158
37,225
1
false
For example, alterations of HA polymer length by enzymes or reactive oxygen species liberated during inflammation can modulate the binding of HA to CD44.
[ "51" ]
For example, alterations of HA polymer length by enzymes or reactive oxygen species liberated during inflammation can modulate the binding of HA to CD44.
true
true
true
true
true
6,383
4
DISCUSSION
1
51
[ "bib51", "bib27", "bib52", "bib27", "bib27" ]
18,362,172
pmid-10871609|pmid-16702221|pmid-14977887|pmid-16702221|pmid-16702221
Additionally, covalent modifications of HA by multiple circulating factors such as SHAP (IαI heavy chains) and extracellular matrix components including versican/PG-M can alter HA matrix organization, leading to increased avidity for leukocyte CD44 (27, 52).
[ "51", "27", "52", "27", "27" ]
258
37,226
0
false
Additionally, covalent modifications of HA by multiple circulating factors such as SHAP (IαI heavy chains) and extracellular matrix components including versican/PG-M can alter HA matrix organization, leading to increased avidity for leukocyte CD44.
[ "27, 52" ]
Additionally, covalent modifications of HA by multiple circulating factors such as SHAP (IαI heavy chains) and extracellular matrix components including versican/PG-M can alter HA matrix organization, leading to increased avidity for leukocyte CD44.
true
true
true
true
true
6,383
4
DISCUSSION
1
51
[ "bib51", "bib27", "bib52", "bib27", "bib27" ]
18,362,172
pmid-10871609|pmid-16702221|pmid-14977887|pmid-16702221|pmid-16702221
Zhuo et al.
[ "51", "27", "52", "27", "27" ]
11
37,227
0
false
Zhuo et al.
[]
Zhuo et al.
true
true
true
true
true
6,383
4
DISCUSSION
1
27
[ "bib51", "bib27", "bib52", "bib27", "bib27" ]
18,362,172
pmid-10871609|pmid-16702221|pmid-14977887|pmid-16702221|pmid-16702221
(27) recently demonstrated that HA–SHAP complexes isolated from arthritic joints increase HA binding avidity for CD44.
[ "51", "27", "52", "27", "27" ]
118
37,228
1
false
recently demonstrated that HA–SHAP complexes isolated from arthritic joints increase HA binding avidity for CD44.
[ "27" ]
recently demonstrated that HA–SHAP complexes isolated from arthritic joints increase HA binding avidity for CD44.
false
true
true
true
false
6,383
4
DISCUSSION
1
51
[ "bib51", "bib27", "bib52", "bib27", "bib27" ]
18,362,172
pmid-10871609|pmid-16702221|pmid-14977887|pmid-16702221|pmid-16702221
Interestingly, SHAP was not directly required for cell adhesion, suggesting that it may function to alter HA structure, resulting in increased avidity for CD44.
[ "51", "27", "52", "27", "27" ]
160
37,229
0
false
Interestingly, SHAP was not directly required for cell adhesion, suggesting that it may function to alter HA structure, resulting in increased avidity for CD44.
[]
Interestingly, SHAP was not directly required for cell adhesion, suggesting that it may function to alter HA structure, resulting in increased avidity for CD44.
true
true
true
true
true
6,383
4
DISCUSSION
1
27
[ "bib51", "bib27", "bib52", "bib27", "bib27" ]
18,362,172
pmid-10871609|pmid-16702221|pmid-14977887|pmid-16702221|pmid-16702221
Most relevant to our study was that HA–SHAP complexes were shown to increase lymphocyte binding under flow conditions in vitro at shear stresses <1 dyn/cm2 (27), which is the physiological shear stress within sinusoids but not postcapillary venules.
[ "51", "27", "52", "27", "27" ]
249
37,230
1
false
Most relevant to our study was that HA–SHAP complexes were shown to increase lymphocyte binding under flow conditions in vitro at shear stresses <1 dyn/cm2, which is the physiological shear stress within sinusoids but not postcapillary venules.
[ "27" ]
Most relevant to our study was that HA–SHAP complexes were shown to increase lymphocyte binding under flow conditions in vitro at shear stresses <1 dyn/cm2, which is the physiological shear stress within sinusoids but not postcapillary venules.
true
true
true
true
true
6,383
4
DISCUSSION
1
51
[ "bib51", "bib27", "bib52", "bib27", "bib27" ]
18,362,172
pmid-10871609|pmid-16702221|pmid-14977887|pmid-16702221|pmid-16702221
A striking increase in SHAP deposition on the luminal surface of the hepatic sinusoids only after LPS stimulation but not under basal conditions suggests that endothelial HA is biologically altered through interactions with proteins that may potentiate CD44–HA binding.
[ "51", "27", "52", "27", "27" ]
269
37,231
0
false
A striking increase in SHAP deposition on the luminal surface of the hepatic sinusoids only after LPS stimulation but not under basal conditions suggests that endothelial HA is biologically altered through interactions with proteins that may potentiate CD44–HA binding.
[]
A striking increase in SHAP deposition on the luminal surface of the hepatic sinusoids only after LPS stimulation but not under basal conditions suggests that endothelial HA is biologically altered through interactions with proteins that may potentiate CD44–HA binding.
true
true
true
true
true
6,383
4
DISCUSSION
1
51
[ "bib51", "bib27", "bib52", "bib27", "bib27" ]
18,362,172
pmid-10871609|pmid-16702221|pmid-14977887|pmid-16702221|pmid-16702221
This supports the hypothesis that LPS may activate CD44–HA engagement in the sinusoids by activating the formation of complexes between endothelial HA and modifying factors such as SHAP in a TLR4-dependent manner, thereby enhancing the avidity of HA for neutrophil CD44.
[ "51", "27", "52", "27", "27" ]
270
37,232
0
false
This supports the hypothesis that LPS may activate CD44–HA engagement in the sinusoids by activating the formation of complexes between endothelial HA and modifying factors such as SHAP in a TLR4-dependent manner, thereby enhancing the avidity of HA for neutrophil CD44.
[]
This supports the hypothesis that LPS may activate CD44–HA engagement in the sinusoids by activating the formation of complexes between endothelial HA and modifying factors such as SHAP in a TLR4-dependent manner, thereby enhancing the avidity of HA for neutrophil CD44.
true
true
true
true
true
6,383
4
DISCUSSION
1
51
[ "bib51", "bib27", "bib52", "bib27", "bib27" ]
18,362,172
pmid-10871609|pmid-16702221|pmid-14977887|pmid-16702221|pmid-16702221
Indeed, our preliminary data suggest that endothelial but not neutrophil TLR4 is necessary for neutrophil adhesion in the sinusoids (unpublished data).
[ "51", "27", "52", "27", "27" ]
151
37,233
0
false
Indeed, our preliminary data suggest that endothelial but not neutrophil TLR4 is necessary for neutrophil adhesion in the sinusoids (unpublished data).
[]
Indeed, our preliminary data suggest that endothelial but not neutrophil TLR4 is necessary for neutrophil adhesion in the sinusoids (unpublished data).
true
true
true
true
true
6,383
5
DISCUSSION
1
53
[ "bib53" ]
18,362,172
pmid-17116736
The most clinically relevant finding reported in this study was the observation that sinusoidal neutrophil sequestration and impaired perfusion resulting from 4 h of endotoxemia was rapidly ameliorated by acute administration of an anti-CD44 mAb.
[ "53" ]
246
37,234
0
false
The most clinically relevant finding reported in this study was the observation that sinusoidal neutrophil sequestration and impaired perfusion resulting from 4 h of endotoxemia was rapidly ameliorated by acute administration of an anti-CD44 mAb.
[]
The most clinically relevant finding reported in this study was the observation that sinusoidal neutrophil sequestration and impaired perfusion resulting from 4 h of endotoxemia was rapidly ameliorated by acute administration of an anti-CD44 mAb.
true
true
true
true
true
6,384
5
DISCUSSION
1
53
[ "bib53" ]
18,362,172
pmid-17116736
Within 1 h of administration, antibody treatment effectively reversed the neutrophil adhesion in sinusoids and significantly improved perfusion through these conduits.
[ "53" ]
167
37,235
0
false
Within 1 h of administration, antibody treatment effectively reversed the neutrophil adhesion in sinusoids and significantly improved perfusion through these conduits.
[]
Within 1 h of administration, antibody treatment effectively reversed the neutrophil adhesion in sinusoids and significantly improved perfusion through these conduits.
true
true
true
true
true
6,384
5
DISCUSSION
1
53
[ "bib53" ]
18,362,172
pmid-17116736
Although it was thought that neutrophils that adhere firmly to substratum form a subjacent space that is impenetrable to proteins including proteases and antibodies, we now know that at least in the cremaster and brain vasculature, neutrophil adhesion is dynamic and includes some crawling under flow conditions in vivo ...
[ "53" ]
401
37,236
1
false
Although it was thought that neutrophils that adhere firmly to substratum form a subjacent space that is impenetrable to proteins including proteases and antibodies, we now know that at least in the cremaster and brain vasculature, neutrophil adhesion is dynamic and includes some crawling under flow conditions in vivo,...
[ "53" ]
Although it was thought that neutrophils that adhere firmly to substratum form a subjacent space that is impenetrable to proteins including proteases and antibodies, we now know that at least in the cremaster and brain vasculature, neutrophil adhesion is dynamic and includes some crawling under flow conditions in vivo,...
true
true
true
true
true
6,384
6
DISCUSSION
1
54
[ "bib54" ]
18,362,172
pmid-17384648
The reasons for the disproportionate neutrophil sequestration in the liver and lung in response to bacterial endotoxin are not fully understood, but recent evidence suggests that neutrophils home to liver and lung capillaries during endotoxemia and sepsis as an antibacterial mechanism whereby neutrophils enhance the ca...
[ "54" ]
359
37,237
0
false
The reasons for the disproportionate neutrophil sequestration in the liver and lung in response to bacterial endotoxin are not fully understood, but recent evidence suggests that neutrophils home to liver and lung capillaries during endotoxemia and sepsis as an antibacterial mechanism whereby neutrophils enhance the ca...
[]
The reasons for the disproportionate neutrophil sequestration in the liver and lung in response to bacterial endotoxin are not fully understood, but recent evidence suggests that neutrophils home to liver and lung capillaries during endotoxemia and sepsis as an antibacterial mechanism whereby neutrophils enhance the ca...
true
true
true
true
true
6,385
6
DISCUSSION
1
54
[ "bib54" ]
18,362,172
pmid-17384648
Neutrophil arrest within the liver sinusoids allows for the release of webs of DNA called neutrophil extracellular traps (NETS) that ensnare blood-borne bacteria during sepsis (54).
[ "54" ]
181
37,238
1
false
Neutrophil arrest within the liver sinusoids allows for the release of webs of DNA called neutrophil extracellular traps (NETS) that ensnare blood-borne bacteria during sepsis.
[ "54" ]
Neutrophil arrest within the liver sinusoids allows for the release of webs of DNA called neutrophil extracellular traps (NETS) that ensnare blood-borne bacteria during sepsis.
true
true
true
true
true
6,385
6
DISCUSSION
1
54
[ "bib54" ]
18,362,172
pmid-17384648
However, NETS are covered with bactericidal proteases that may inadvertently cause hepatotoxicity.
[ "54" ]
98
37,239
0
false
However, NETS are covered with bactericidal proteases that may inadvertently cause hepatotoxicity.
[]
However, NETS are covered with bactericidal proteases that may inadvertently cause hepatotoxicity.
true
true
true
true
true
6,385
6
DISCUSSION
1
54
[ "bib54" ]
18,362,172
pmid-17384648
We therefore hypothesize that neutrophil sequestration within liver sinusoids is a well-coordinated, programmed, innate immune survival mechanism during sepsis that occurs at the expense of damage to the liver.
[ "54" ]
210
37,240
0
false
We therefore hypothesize that neutrophil sequestration within liver sinusoids is a well-coordinated, programmed, innate immune survival mechanism during sepsis that occurs at the expense of damage to the liver.
[]
We therefore hypothesize that neutrophil sequestration within liver sinusoids is a well-coordinated, programmed, innate immune survival mechanism during sepsis that occurs at the expense of damage to the liver.
true
true
true
true
true
6,385
6
DISCUSSION
1
54
[ "bib54" ]
18,362,172
pmid-17384648
Thus, although blockade of CD44–HA interactions diminished neutrophil-mediated damage to the liver during endotoxemia, this treatment may also affect various aspects of the physiological antibacterial response in the liver.
[ "54" ]
223
37,241
0
false
Thus, although blockade of CD44–HA interactions diminished neutrophil-mediated damage to the liver during endotoxemia, this treatment may also affect various aspects of the physiological antibacterial response in the liver.
[]
Thus, although blockade of CD44–HA interactions diminished neutrophil-mediated damage to the liver during endotoxemia, this treatment may also affect various aspects of the physiological antibacterial response in the liver.
true
true
true
true
true
6,385
6
DISCUSSION
1
54
[ "bib54" ]
18,362,172
pmid-17384648
With the advent of antibiotics, tissue injury associated with this mechanism of bacterial trapping via NETS may be therapeutically preventable without increasing susceptibility of the host to infection.
[ "54" ]
202
37,242
0
false
With the advent of antibiotics, tissue injury associated with this mechanism of bacterial trapping via NETS may be therapeutically preventable without increasing susceptibility of the host to infection.
[]
With the advent of antibiotics, tissue injury associated with this mechanism of bacterial trapping via NETS may be therapeutically preventable without increasing susceptibility of the host to infection.
true
true
true
true
true
6,385
6
DISCUSSION
1
54
[ "bib54" ]
18,362,172
pmid-17384648
Our findings help further the understanding of neutrophil recruitment within the microvasculature of the liver, and suggest potentially useful approaches for the development of therapeutic strategies to combat pathological hepatic inflammation.
[ "54" ]
244
37,243
0
false
Our findings help further the understanding of neutrophil recruitment within the microvasculature of the liver, and suggest potentially useful approaches for the development of therapeutic strategies to combat pathological hepatic inflammation.
[]
Our findings help further the understanding of neutrophil recruitment within the microvasculature of the liver, and suggest potentially useful approaches for the development of therapeutic strategies to combat pathological hepatic inflammation.
true
true
true
true
true
6,385
0
DISCUSSION
1
10
[ "bib10", "bib21" ]
17,389,239
pmid-15539565|pmid-14684827
The selection of Vα14 NKT cells in the thymus is dependent on the expression of iGb3–CD1d complexes by cortical thymocytes.
[ "10", "21" ]
123
37,244
0
false
The selection of Vα14 NKT cells in the thymus is dependent on the expression of iGb3–CD1d complexes by cortical thymocytes.
[]
The selection of Vα14 NKT cells in the thymus is dependent on the expression of iGb3–CD1d complexes by cortical thymocytes.
true
true
true
true
true
6,386
0
DISCUSSION
1
10
[ "bib10", "bib21" ]
17,389,239
pmid-15539565|pmid-14684827
Presentation of the endogenous iGb3 by CD1d molecules requires the presence of iGb3 in the lysosomes and its assisted loading into CD1d by LTPs.
[ "10", "21" ]
144
37,245
0
false
Presentation of the endogenous iGb3 by CD1d molecules requires the presence of iGb3 in the lysosomes and its assisted loading into CD1d by LTPs.
[]
Presentation of the endogenous iGb3 by CD1d molecules requires the presence of iGb3 in the lysosomes and its assisted loading into CD1d by LTPs.
true
true
true
true
true
6,386
0
DISCUSSION
1
10
[ "bib10", "bib21" ]
17,389,239
pmid-15539565|pmid-14684827
We previously showed that the impaired production of iGb3 or the lack of saposins resulted in the severe deficiency or lack of Vα14 NKT cells (10, 21).
[ "10", "21" ]
151
37,246
0
false
We previously showed that the impaired production of iGb3 or the lack of saposins resulted in the severe deficiency or lack of Vα14 NKT cells.
[ "10, 21" ]
We previously showed that the impaired production of iGb3 or the lack of saposins resulted in the severe deficiency or lack of Vα14 NKT cells.
true
true
true
true
true
6,386
0
DISCUSSION
1
10
[ "bib10", "bib21" ]
17,389,239
pmid-15539565|pmid-14684827
In an attempt to find other lysosomal LTPs involved in the loading of lipid antigens into CD1d, we investigated whether NPC2 could play a role in Vα14 NKT cell selection and lipid antigen presentation.
[ "10", "21" ]
201
37,247
0
false
In an attempt to find other lysosomal LTPs involved in the loading of lipid antigens into CD1d, we investigated whether NPC2 could play a role in Vα14 NKT cell selection and lipid antigen presentation.
[]
In an attempt to find other lysosomal LTPs involved in the loading of lipid antigens into CD1d, we investigated whether NPC2 could play a role in Vα14 NKT cell selection and lipid antigen presentation.
true
true
true
true
true
6,386
1
DISCUSSION
1
27
[ "bib27" ]
17,389,239
pmid-15071184
Our study establishes that a deficiency in NPC2 profoundly affects the numbers of Vα14 NKT cells in the thymus and peripheral tissues.
[ "27" ]
134
37,248
0
false
Our study establishes that a deficiency in NPC2 profoundly affects the numbers of Vα14 NKT cells in the thymus and peripheral tissues.
[]
Our study establishes that a deficiency in NPC2 profoundly affects the numbers of Vα14 NKT cells in the thymus and peripheral tissues.
true
true
true
true
true
6,387
1
DISCUSSION
1
27
[ "bib27" ]
17,389,239
pmid-15071184
It is important to notice that this phenotype was observed in mice and cells that have some residual NPC2 activity (27) and that a complete knockout of expression would likely reinforce the traits that we observed.
[ "27" ]
214
37,249
1
false
It is important to notice that this phenotype was observed in mice and cells that have some residual NPC2 activity and that a complete knockout of expression would likely reinforce the traits that we observed.
[ "27" ]
It is important to notice that this phenotype was observed in mice and cells that have some residual NPC2 activity and that a complete knockout of expression would likely reinforce the traits that we observed.
true
true
true
true
true
6,387
1
DISCUSSION
1
27
[ "bib27" ]
17,389,239
pmid-15071184
The thymic phenotype reveals two pieces of information: (a) NPC2 is required for the normal selection of Vα14 NKT cells, and (b) the resident thymic population is similarly affected, suggesting similar selecting ligands, but has the capacity to accumulate over time, indicating that it behaves differently from periphera...
[ "27" ]
332
37,250
0
false
The thymic phenotype reveals two pieces of information: (a) NPC2 is required for the normal selection of Vα14 NKT cells, and (b) the resident thymic population is similarly affected, suggesting similar selecting ligands, but has the capacity to accumulate over time, indicating that it behaves differently from periphera...
[]
The thymic phenotype reveals two pieces of information: (a) NPC2 is required for the normal selection of Vα14 NKT cells, and (b) the resident thymic population is similarly affected, suggesting similar selecting ligands, but has the capacity to accumulate over time, indicating that it behaves differently from periphera...
true
true
true
true
true
6,387
1
DISCUSSION
1
27
[ "bib27" ]
17,389,239
pmid-15071184
NPC2 is not involved in the egress of NKT cells from the thymus as they are found in the periphery.
[ "27" ]
99
37,251
0
false
NPC2 is not involved in the egress of NKT cells from the thymus as they are found in the periphery.
[]
NPC2 is not involved in the egress of NKT cells from the thymus as they are found in the periphery.
true
true
true
true
true
6,387
1
DISCUSSION
1
27
[ "bib27" ]
17,389,239
pmid-15071184
However, the small number of exported immature NKT cells does not lead to a normal peripheral compartment through expansion, as the deficit remains severe throughout the life of these animals.
[ "27" ]
192
37,252
0
false
However, the small number of exported immature NKT cells does not lead to a normal peripheral compartment through expansion, as the deficit remains severe throughout the life of these animals.
[]
However, the small number of exported immature NKT cells does not lead to a normal peripheral compartment through expansion, as the deficit remains severe throughout the life of these animals.
true
true
true
true
true
6,387
2
DISCUSSION
1
43
[ "bib43" ]
17,389,239
pmid-12154358
The delay observed in the expansion of peripheral NKT cells in NPC2−/− animals suggests that in these mice, mainly DCs present αGalCer to Vα14 NKT cells, as it is known that the injection of αGalCer-pulsed DCs induces a delayed expansion of Vα14 NKT cells and cytokine production as compared with the injection of αGalCe...
[ "43" ]
333
37,253
1
false
The delay observed in the expansion of peripheral NKT cells in NPC2−/− animals suggests that in these mice, mainly DCs present αGalCer to Vα14 NKT cells, as it is known that the injection of αGalCer-pulsed DCs induces a delayed expansion of Vα14 NKT cells and cytokine production as compared with the injection of αGalCe...
[ "43" ]
The delay observed in the expansion of peripheral NKT cells in NPC2−/− animals suggests that in these mice, mainly DCs present αGalCer to Vα14 NKT cells, as it is known that the injection of αGalCer-pulsed DCs induces a delayed expansion of Vα14 NKT cells and cytokine production as compared with the injection of αGalCe...
true
true
true
true
true
6,388
2
DISCUSSION
1
43
[ "bib43" ]
17,389,239
pmid-12154358
In addition, the normal degree of expansion of Vα14 NKT cells in NPC2−/− mice suggests that NPC2 deficiency does not affect the function of Vα14 NKT cells but only antigen presentation.
[ "43" ]
185
37,254
0
false
In addition, the normal degree of expansion of Vα14 NKT cells in NPC2−/− mice suggests that NPC2 deficiency does not affect the function of Vα14 NKT cells but only antigen presentation.
[]
In addition, the normal degree of expansion of Vα14 NKT cells in NPC2−/− mice suggests that NPC2 deficiency does not affect the function of Vα14 NKT cells but only antigen presentation.
true
true
true
true
true
6,388
3
DISCUSSION
1
10
[ "bib10", "bib21" ]
17,389,239
pmid-15539565|pmid-14684827
The defect of the presentation of exogenous glycosphingolipid such as αGalCer and Galα1-2αGalCer by NPC2- deficient splenocytes and thymocytes, whereas the presentation of these same lipids by BMDCs was only slightly affected, indicates that the LTP requirements for exogenous lipid uptake and presentation are different...
[ "10", "21" ]
348
37,255
0
false
The defect of the presentation of exogenous glycosphingolipid such as αGalCer and Galα1-2αGalCer by NPC2- deficient splenocytes and thymocytes, whereas the presentation of these same lipids by BMDCs was only slightly affected, indicates that the LTP requirements for exogenous lipid uptake and presentation are different...
[]
The defect of the presentation of exogenous glycosphingolipid such as αGalCer and Galα1-2αGalCer by NPC2- deficient splenocytes and thymocytes, whereas the presentation of these same lipids by BMDCs was only slightly affected, indicates that the LTP requirements for exogenous lipid uptake and presentation are different...
true
true
true
true
true
6,389
3
DISCUSSION
1
10
[ "bib10", "bib21" ]
17,389,239
pmid-15539565|pmid-14684827
It also strongly suggests a model in which multiple LTPs shape the repertoire of lipid presented by CD1d molecules.
[ "10", "21" ]
115
37,256
0
false
It also strongly suggests a model in which multiple LTPs shape the repertoire of lipid presented by CD1d molecules.
[]
It also strongly suggests a model in which multiple LTPs shape the repertoire of lipid presented by CD1d molecules.
true
true
true
true
true
6,389
3
DISCUSSION
1
10
[ "bib10", "bib21" ]
17,389,239
pmid-15539565|pmid-14684827
This hypothesis is also supported by the profile of stimulation of non-Vα14 NKT cells by NPC2−/− cells.
[ "10", "21" ]
103
37,257
0
false
This hypothesis is also supported by the profile of stimulation of non-Vα14 NKT cells by NPC2−/− cells.
[]
This hypothesis is also supported by the profile of stimulation of non-Vα14 NKT cells by NPC2−/− cells.
true
true
true
true
true
6,389
3
DISCUSSION
1
10
[ "bib10", "bib21" ]
17,389,239
pmid-15539565|pmid-14684827
Although TCB11 stimulation was normal, TBD7 stimulation was partially affected.
[ "10", "21" ]
79
37,258
0
false
Although TCB11 stimulation was normal, TBD7 stimulation was partially affected.
[]
Although TCB11 stimulation was normal, TBD7 stimulation was partially affected.
true
true
true
true
true
6,389
3
DISCUSSION
1
10
[ "bib10", "bib21" ]
17,389,239
pmid-15539565|pmid-14684827
We have not encountered this discrepant phenotype in prosaposin-deficient animals and GM2a−/− mice in which both stimulations were normal (references 10, 21; unpublished data).
[ "10", "21" ]
176
37,259
0
false
We have not encountered this discrepant phenotype in prosaposin-deficient animals and GM2a−/− mice in which both stimulations were normal.
[ "references 10, 21; unpublished data" ]
We have not encountered this discrepant phenotype in prosaposin-deficient animals and GM2a−/− mice in which both stimulations were normal.
true
true
true
true
true
6,389
3
DISCUSSION
1
10
[ "bib10", "bib21" ]
17,389,239
pmid-15539565|pmid-14684827
The almost normal presentation of lipids by DCs derived from NPC2−/− mice also suggests that in vitro matured DCs do not faithfully represent some of the DC subsets present (for example, in the spleen).
[ "10", "21" ]
202
37,260
0
false
The almost normal presentation of lipids by DCs derived from NPC2−/− mice also suggests that in vitro matured DCs do not faithfully represent some of the DC subsets present (for example, in the spleen).
[]
The almost normal presentation of lipids by DCs derived from NPC2−/− mice also suggests that in vitro matured DCs do not faithfully represent some of the DC subsets present (for example, in the spleen).
true
true
true
true
true
6,389
3
DISCUSSION
1
10
[ "bib10", "bib21" ]
17,389,239
pmid-15539565|pmid-14684827
This situation will compel us to examine the presentation capacity of NPC2−/− DCs directly isolated and purified from spleen and lymph nodes to understand these discrepancies.
[ "10", "21" ]
175
37,261
0
false
This situation will compel us to examine the presentation capacity of NPC2−/− DCs directly isolated and purified from spleen and lymph nodes to understand these discrepancies.
[]
This situation will compel us to examine the presentation capacity of NPC2−/− DCs directly isolated and purified from spleen and lymph nodes to understand these discrepancies.
true
true
true
true
true
6,389
4
DISCUSSION
1
27
[ "bib27", "bib38", "bib29", "bib37", "bib38", "bib44", "bib45", "bib45", "bib46", "bib47" ]
17,389,239
pmid-15071184|pmid-15972801|pmid-16785493|pmid-3865225|pmid-15972801|pmid-12554680|pmid-14989468|pmid-14989468|pmid-10092649|pmid-11296289
With respect to lipid trafficking, cholesterol and gangliosides, including GM2 and GM3, have been shown to accumulate in mice deficient in NPC1 (27, 38).
[ "27", "38", "29", "37", "38", "44", "45", "45", "46", "47" ]
153
37,262
0
false
With respect to lipid trafficking, cholesterol and gangliosides, including GM2 and GM3, have been shown to accumulate in mice deficient in NPC1.
[ "27, 38" ]
With respect to lipid trafficking, cholesterol and gangliosides, including GM2 and GM3, have been shown to accumulate in mice deficient in NPC1.
true
true
true
true
true
6,390
4
DISCUSSION
1
27
[ "bib27", "bib38", "bib29", "bib37", "bib38", "bib44", "bib45", "bib45", "bib46", "bib47" ]
17,389,239
pmid-15071184|pmid-15972801|pmid-16785493|pmid-3865225|pmid-15972801|pmid-12554680|pmid-14989468|pmid-14989468|pmid-10092649|pmid-11296289
In addition, the transport of BODIPY-LacCer to the Golgi and of fluorescent αGalCer to the lysosome in NPC1−/− cells has been shown to be heavily perturbed with the presence of a late endosomal block (29, 37, 38).
[ "27", "38", "29", "37", "38", "44", "45", "45", "46", "47" ]
213
37,263
0
false
In addition, the transport of BODIPY-LacCer to the Golgi and of fluorescent αGalCer to the lysosome in NPC1−/− cells has been shown to be heavily perturbed with the presence of a late endosomal block.
[ "29, 37, 38" ]
In addition, the transport of BODIPY-LacCer to the Golgi and of fluorescent αGalCer to the lysosome in NPC1−/− cells has been shown to be heavily perturbed with the presence of a late endosomal block.
true
true
true
true
true
6,390
4
DISCUSSION
1
44
[ "bib27", "bib38", "bib29", "bib37", "bib38", "bib44", "bib45", "bib45", "bib46", "bib47" ]
17,389,239
pmid-15071184|pmid-15972801|pmid-16785493|pmid-3865225|pmid-15972801|pmid-12554680|pmid-14989468|pmid-14989468|pmid-10092649|pmid-11296289
A similar study in NPC2−/− cells has been very limited besides establishing that some cell types were accumulating cholesterol in the absence of NPC2 (44).
[ "27", "38", "29", "37", "38", "44", "45", "45", "46", "47" ]
155
37,264
1
false
A similar study in NPC2−/− cells has been very limited besides establishing that some cell types were accumulating cholesterol in the absence of NPC2.
[ "44" ]
A similar study in NPC2−/− cells has been very limited besides establishing that some cell types were accumulating cholesterol in the absence of NPC2.
true
true
true
true
true
6,390
4
DISCUSSION
1
45
[ "bib27", "bib38", "bib29", "bib37", "bib38", "bib44", "bib45", "bib45", "bib46", "bib47" ]
17,389,239
pmid-15071184|pmid-15972801|pmid-16785493|pmid-3865225|pmid-15972801|pmid-12554680|pmid-14989468|pmid-14989468|pmid-10092649|pmid-11296289
Moreover, important differences between NPC1−/− and NPC2−/− cells have been documented for the transport of GM2 ganglioside to the lysosome (45).
[ "27", "38", "29", "37", "38", "44", "45", "45", "46", "47" ]
145
37,265
1
false
Moreover, important differences between NPC1−/− and NPC2−/− cells have been documented for the transport of GM2 ganglioside to the lysosome.
[ "45" ]
Moreover, important differences between NPC1−/− and NPC2−/− cells have been documented for the transport of GM2 ganglioside to the lysosome.
true
true
true
true
true
6,390
4
DISCUSSION
1
45
[ "bib27", "bib38", "bib29", "bib37", "bib38", "bib44", "bib45", "bib45", "bib46", "bib47" ]
17,389,239
pmid-15071184|pmid-15972801|pmid-16785493|pmid-3865225|pmid-15972801|pmid-12554680|pmid-14989468|pmid-14989468|pmid-10092649|pmid-11296289
Whereas NPC1−/− cells could not deliver GM2 to the lysosome, NPC2−/− cells could internalize GM2 into endocytic vesicles and deliver it to the lysosome (45).
[ "27", "38", "29", "37", "38", "44", "45", "45", "46", "47" ]
157
37,266
1
false
Whereas NPC1−/− cells could not deliver GM2 to the lysosome, NPC2−/− cells could internalize GM2 into endocytic vesicles and deliver it to the lysosome.
[ "45" ]
Whereas NPC1−/− cells could not deliver GM2 to the lysosome, NPC2−/− cells could internalize GM2 into endocytic vesicles and deliver it to the lysosome.
true
true
true
true
true
6,390
4
DISCUSSION
1
27
[ "bib27", "bib38", "bib29", "bib37", "bib38", "bib44", "bib45", "bib45", "bib46", "bib47" ]
17,389,239
pmid-15071184|pmid-15972801|pmid-16785493|pmid-3865225|pmid-15972801|pmid-12554680|pmid-14989468|pmid-14989468|pmid-10092649|pmid-11296289
Our evaluation of the transport of LacCer and PBS-81 in NPC2−/− fibroblasts and splenocytes is very much in agreement with this observation.
[ "27", "38", "29", "37", "38", "44", "45", "45", "46", "47" ]
140
37,267
0
false
Our evaluation of the transport of LacCer and PBS-81 in NPC2−/− fibroblasts and splenocytes is very much in agreement with this observation.
[]
Our evaluation of the transport of LacCer and PBS-81 in NPC2−/− fibroblasts and splenocytes is very much in agreement with this observation.
true
true
true
true
true
6,390
4
DISCUSSION
1
27
[ "bib27", "bib38", "bib29", "bib37", "bib38", "bib44", "bib45", "bib45", "bib46", "bib47" ]
17,389,239
pmid-15071184|pmid-15972801|pmid-16785493|pmid-3865225|pmid-15972801|pmid-12554680|pmid-14989468|pmid-14989468|pmid-10092649|pmid-11296289
The transport of these two glycolipids through the endocytic pathway appeared close to normal in most cells.
[ "27", "38", "29", "37", "38", "44", "45", "45", "46", "47" ]
108
37,268
0
false
The transport of these two glycolipids through the endocytic pathway appeared close to normal in most cells.
[]
The transport of these two glycolipids through the endocytic pathway appeared close to normal in most cells.
true
true
true
true
true
6,390
4
DISCUSSION
1
27
[ "bib27", "bib38", "bib29", "bib37", "bib38", "bib44", "bib45", "bib45", "bib46", "bib47" ]
17,389,239
pmid-15071184|pmid-15972801|pmid-16785493|pmid-3865225|pmid-15972801|pmid-12554680|pmid-14989468|pmid-14989468|pmid-10092649|pmid-11296289
A morphometric quantification of these results will allow us to appreciate the precise numbers of vesicles in which lysosomal markers and PBS-81 colocalize in WT and mutant cells and also to compare the impact of NPC2 deficiency in different cell types.
[ "27", "38", "29", "37", "38", "44", "45", "45", "46", "47" ]
253
37,269
0
false
A morphometric quantification of these results will allow us to appreciate the precise numbers of vesicles in which lysosomal markers and PBS-81 colocalize in WT and mutant cells and also to compare the impact of NPC2 deficiency in different cell types.
[]
A morphometric quantification of these results will allow us to appreciate the precise numbers of vesicles in which lysosomal markers and PBS-81 colocalize in WT and mutant cells and also to compare the impact of NPC2 deficiency in different cell types.
true
true
true
true
true
6,390
4
DISCUSSION
1
27
[ "bib27", "bib38", "bib29", "bib37", "bib38", "bib44", "bib45", "bib45", "bib46", "bib47" ]
17,389,239
pmid-15071184|pmid-15972801|pmid-16785493|pmid-3865225|pmid-15972801|pmid-12554680|pmid-14989468|pmid-14989468|pmid-10092649|pmid-11296289
These major differences between NPC1−/− and NPC2−/− cells with respect to lipid endocytosis and transport reinforce the idea that the two molecules are present in different compartments: late endosomes for NPC1 and lysosomes for NPC2 (46, 47).
[ "27", "38", "29", "37", "38", "44", "45", "45", "46", "47" ]
243
37,270
0
false
These major differences between NPC1−/− and NPC2−/− cells with respect to lipid endocytosis and transport reinforce the idea that the two molecules are present in different compartments: late endosomes for NPC1 and lysosomes for NPC2.
[ "46, 47" ]
These major differences between NPC1−/− and NPC2−/− cells with respect to lipid endocytosis and transport reinforce the idea that the two molecules are present in different compartments: late endosomes for NPC1 and lysosomes for NPC2.
true
true
true
true
true
6,390
4
DISCUSSION
1
27
[ "bib27", "bib38", "bib29", "bib37", "bib38", "bib44", "bib45", "bib45", "bib46", "bib47" ]
17,389,239
pmid-15071184|pmid-15972801|pmid-16785493|pmid-3865225|pmid-15972801|pmid-12554680|pmid-14989468|pmid-14989468|pmid-10092649|pmid-11296289
This dichotomy could explain why NPC2 did not grossly perturb endocytosis and transport to the lysosome.
[ "27", "38", "29", "37", "38", "44", "45", "45", "46", "47" ]
104
37,271
0
false
This dichotomy could explain why NPC2 did not grossly perturb endocytosis and transport to the lysosome.
[]
This dichotomy could explain why NPC2 did not grossly perturb endocytosis and transport to the lysosome.
true
true
true
true
true
6,390
4
DISCUSSION
1
27
[ "bib27", "bib38", "bib29", "bib37", "bib38", "bib44", "bib45", "bib45", "bib46", "bib47" ]
17,389,239
pmid-15071184|pmid-15972801|pmid-16785493|pmid-3865225|pmid-15972801|pmid-12554680|pmid-14989468|pmid-14989468|pmid-10092649|pmid-11296289
However, the absence of NPC2 in the lysosome could affect the egress of lipids from this compartment; this issue will need further inquiry.
[ "27", "38", "29", "37", "38", "44", "45", "45", "46", "47" ]
139
37,272
0
false
However, the absence of NPC2 in the lysosome could affect the egress of lipids from this compartment; this issue will need further inquiry.
[]
However, the absence of NPC2 in the lysosome could affect the egress of lipids from this compartment; this issue will need further inquiry.
true
true
true
true
true
6,390
5
DISCUSSION
0
null
null
17,389,239
null
Our initial assessment of the degree of lipid storage in various cell types by using lysosomal dyes showed that NPC2 deficiency affected mostly splenocytes and BMDCs, whereas thymocytes were only marginally perturbed.
null
217
37,273
0
false
null
null
Our initial assessment of the degree of lipid storage in various cell types by using lysosomal dyes showed that NPC2 deficiency affected mostly splenocytes and BMDCs, whereas thymocytes were only marginally perturbed.
true
true
true
true
true
6,391
5
DISCUSSION
0
null
null
17,389,239
null
We can conclude from this observation that lipid accumulation and presentation phenotypes are not correlated.
null
109
37,274
0
false
null
null
We can conclude from this observation that lipid accumulation and presentation phenotypes are not correlated.
true
true
true
true
true
6,391
5
DISCUSSION
0
null
null
17,389,239
null
This dissociation is one additional argument against a nonspecific effect of lipid storage as the cause for the observed phenotype resulting from the absence of NPC2.
null
166
37,275
0
false
null
null
This dissociation is one additional argument against a nonspecific effect of lipid storage as the cause for the observed phenotype resulting from the absence of NPC2.
true
true
true
true
true
6,391
6
DISCUSSION
0
null
null
17,389,239
null
Collectively, these observations suggest a direct role of NPC2 in the transport and loading of glycolipids into CD1d.
null
117
37,276
0
false
null
null
Collectively, these observations suggest a direct role of NPC2 in the transport and loading of glycolipids into CD1d.
true
true
true
true
true
6,392
6
DISCUSSION
0
null
null
17,389,239
null
The poor presentation of exogenous lipids and the almost complete absence of endogenous ligand presentation in NPC2−/− mice support this role, as does the in vitro loading of iGb3 into CD1d.
null
190
37,277
0
false
null
null
The poor presentation of exogenous lipids and the almost complete absence of endogenous ligand presentation in NPC2−/− mice support this role, as does the in vitro loading of iGb3 into CD1d.
true
true
true
true
true
6,392
6
DISCUSSION
0
null
null
17,389,239
null
However, the ability of recombinant NPC2 to complement the deficient phenotype is the most compelling argument supporting this hypothesis.
null
138
37,278
0
false
null
null
However, the ability of recombinant NPC2 to complement the deficient phenotype is the most compelling argument supporting this hypothesis.
true
true
true
true
true
6,392
6
DISCUSSION
0
null
null
17,389,239
null
In addition, the observation that only dimers of NPC2 are capable of transferring glycosphingolipids, whereas both dimers and monomers can bind cholesterol, suggests that the binding of cholesterol and the transfer of glycosphingolipids by NPC2 are mechanistically different.
null
275
37,279
0
false
null
null
In addition, the observation that only dimers of NPC2 are capable of transferring glycosphingolipids, whereas both dimers and monomers can bind cholesterol, suggests that the binding of cholesterol and the transfer of glycosphingolipids by NPC2 are mechanistically different.
true
true
true
true
true
6,392
6
DISCUSSION
0
null
null
17,389,239
null
The engineering of mutants of NPC2, which cannot form dimers, will help clarify this point further.
null
99
37,280
0
false
null
null
The engineering of mutants of NPC2, which cannot form dimers, will help clarify this point further.
true
true
true
true
true
6,392
7
DISCUSSION
1
17
[ "bib17", "bib18" ]
17,389,239
pmid-15789345|pmid-16145712
In summary, this study establishes that NPC2 is critical for the loading of iGb3 and exogenous lipids into CD1d.
[ "17", "18" ]
112
37,281
0
false
In summary, this study establishes that NPC2 is critical for the loading of iGb3 and exogenous lipids into CD1d.
[]
In summary, this study establishes that NPC2 is critical for the loading of iGb3 and exogenous lipids into CD1d.
true
true
true
true
true
6,393
7
DISCUSSION
1
17
[ "bib17", "bib18" ]
17,389,239
pmid-15789345|pmid-16145712
This observation suggests a model in which multiple LTPs present in the CD1d-containing compartments, such as saposin and NPC2, select the repertoire of CD1d-presented lipids and glycosphingolipids (17, 18).
[ "17", "18" ]
207
37,282
0
false
This observation suggests a model in which multiple LTPs present in the CD1d-containing compartments, such as saposin and NPC2, select the repertoire of CD1d-presented lipids and glycosphingolipids.
[ "17, 18" ]
This observation suggests a model in which multiple LTPs present in the CD1d-containing compartments, such as saposin and NPC2, select the repertoire of CD1d-presented lipids and glycosphingolipids.
true
true
true
true
true
6,393
7
DISCUSSION
1
17
[ "bib17", "bib18" ]
17,389,239
pmid-15789345|pmid-16145712
The polymorphism of NPC2 will have to be studied in the context of NKT cells to determine whether pathological conditions are associated with variants of NPC2 that might affect immune functions.
[ "17", "18" ]
194
37,283
0
false
The polymorphism of NPC2 will have to be studied in the context of NKT cells to determine whether pathological conditions are associated with variants of NPC2 that might affect immune functions.
[]
The polymorphism of NPC2 will have to be studied in the context of NKT cells to determine whether pathological conditions are associated with variants of NPC2 that might affect immune functions.
true
true
true
true
true
6,393
0
DISCUSSION
0
null
null
20,562,439
null
The interactions between histones and DNA create a hindrance to recognition and access to DNA lesions by DNA repair proteins.
null
125
37,284
0
false
null
null
The interactions between histones and DNA create a hindrance to recognition and access to DNA lesions by DNA repair proteins.
true
true
true
true
true
6,394
0
DISCUSSION
0
null
null
20,562,439
null
This barrier may be overcome, however, if DNA lesions change the structural and/or dynamic properties of nucleosomes to promote the accessibility of repair factors, including ancillary proteins such as chromatin remodeling complexes.
null
233
37,285
0
false
null
null
This barrier may be overcome, however, if DNA lesions change the structural and/or dynamic properties of nucleosomes to promote the accessibility of repair factors, including ancillary proteins such as chromatin remodeling complexes.
true
true
true
true
true
6,394
0
DISCUSSION
0
null
null
20,562,439
null
In this study, the unwrapping dynamics of nucleosomes containing UV lesions, either by UV irradiation or incorporation of a single UV photoproduct, was monitored in reconstituted NCPs consisting of the model 601 DNA sequence and recombinant histone octamers.
null
258
37,286
0
false
null
null
In this study, the unwrapping dynamics of nucleosomes containing UV lesions, either by UV irradiation or incorporation of a single UV photoproduct, was monitored in reconstituted NCPs consisting of the model 601 DNA sequence and recombinant histone octamers.
true
true
true
true
true
6,394
0
DISCUSSION
0
null
null
20,562,439
null
The presence of UV lesions did not hinder the reconstitution of NCPs, allowing for measurement of their dynamic properties.
null
123
37,287
0
false
null
null
The presence of UV lesions did not hinder the reconstitution of NCPs, allowing for measurement of their dynamic properties.
true
true
true
true
true
6,394
0
DISCUSSION
0
null
null
20,562,439
null
Results from two experimental strategies, FRET and REA, indicate that the equilibrium of dynamic unwrapping-rewrapping fluctuations shifts toward the unwrapped states with increased DNA damage.
null
193
37,288
0
false
null
null
Results from two experimental strategies, FRET and REA, indicate that the equilibrium of dynamic unwrapping-rewrapping fluctuations shifts toward the unwrapped states with increased DNA damage.
true
true
true
true
true
6,394
0
DISCUSSION
0
null
null
20,562,439
null
Furthermore, we found that a single UV photoproduct (either CPD or 6-4PP) in NCPs is sufficient to drive nucleosomes toward the more open state.
null
144
37,289
0
false
null
null
Furthermore, we found that a single UV photoproduct (either CPD or 6-4PP) in NCPs is sufficient to drive nucleosomes toward the more open state.
true
true
true
true
true
6,394
0
DISCUSSION
0
null
null
20,562,439
null
Thus, UV damaged nucleosomes spend more time in unwrapped states.
null
65
37,290
0
false
null
null
Thus, UV damaged nucleosomes spend more time in unwrapped states.
true
true
true
true
true
6,394
1
DISCUSSION
0
null
null
20,562,439
null
The fact that UV lesions do not prevent bulk nucleosome assembly (Fig.
null
70
37,291
0
false
null
null
The fact that UV lesions do not prevent bulk nucleosome assembly (Fig.
true
true
true
true
true
6,395
1
DISCUSSION
0
null
null
20,562,439
null
2) but do affect salt stability (Fig.
null
37
37,292
0
false
null
null
2) but do affect salt stability (Fig.
false
false
true
true
false
6,395
1
DISCUSSION
0
null
null
20,562,439
null
4) may seem conflicting.
null
24
37,293
0
false
null
null
4) may seem conflicting.
false
false
true
true
false
6,395
1
DISCUSSION
0
null
null
20,562,439
null
However, as UV lesions cause local distortion in DNA structure that is not necessarily propagated along the DNA (e.g.
null
117
37,294
0
false
null
null
However, as UV lesions cause local distortion in DNA structure that is not necessarily propagated along the DNA (e.g.
true
true
true
true
true
6,395
1
DISCUSSION
0
null
null
20,562,439
null
blocked by the strong positioning ability of the 601 sequence), the local distortion may not be able to disrupt the overall interaction between histones and DNA, translating into successful nucleosome reconstitution with different UV damaged DNA fragments (Fig.
null
261
37,295
0
false
null
null
blocked by the strong positioning ability of the 601 sequence), the local distortion may not be able to disrupt the overall interaction between histones and DNA, translating into successful nucleosome reconstitution with different UV damaged DNA fragments (Fig.
false
true
true
true
false
6,395
1
DISCUSSION
0
null
null
20,562,439
null
In addition, UV lesions may change the local “sequence adjustment” of the DNA, which may affect the salt stability and intrinsic site exposure of individual bases, yielding an increased sensitivity to salt (Fig.
null
211
37,296
0
false
null
null
In addition, UV lesions may change the local “sequence adjustment” of the DNA, which may affect the salt stability and intrinsic site exposure of individual bases, yielding an increased sensitivity to salt (Fig.
true
true
true
true
true
6,395
1
DISCUSSION
0
null
null
20,562,439
null
Finally, UV photoproducts may destabilize histone-DNA interactions at specific damaged sites, which could promote DNA peeling off the histone core and partial unwrapping from the end (Fig.
null
188
37,297
0
false
null
null
Finally, UV photoproducts may destabilize histone-DNA interactions at specific damaged sites, which could promote DNA peeling off the histone core and partial unwrapping from the end (Fig.
true
true
true
true
true
6,395
2
DISCUSSION
1
2
[ "B2", "B2", "B9" ]
20,562,439
pmid-9305837|pmid-9305837|pmid-7737185
Interestingly, a CPD at position 58 (15 bp from the dyad center; or SHL1.5 (2)) appears to be more efficient in driving unwrapping of NCPs than a 6-4PP at this position (Fig.
[ "2", "2", "9" ]
174
37,298
0
false
Interestingly, a CPD at position 58 ) appears to be more efficient in driving unwrapping of NCPs than a 6-4PP at this position (Fig.
[ "15 bp from the dyad center; or SHL1.5 (2" ]
Interestingly, a CPD at position 58 ) appears to be more efficient in driving unwrapping of NCPs than a 6-4PP at this position (Fig.
true
true
true
true
true
6,396
2
DISCUSSION
1
2
[ "B2", "B2", "B9" ]
20,562,439
pmid-9305837|pmid-9305837|pmid-7737185
6, B and C).
[ "2", "2", "9" ]
12
37,299
0
false
6, B and C).
[]
6, B and C).
false
false
true
true
false
6,396
2
DISCUSSION
1
2
[ "B2", "B2", "B9" ]
20,562,439
pmid-9305837|pmid-9305837|pmid-7737185
The histone DNA binding surface at this location causes an outward bulge in the DNA and shows significant bending (2).
[ "2", "2", "9" ]
118
37,300
1
false
The histone DNA binding surface at this location causes an outward bulge in the DNA and shows significant bending.
[ "2" ]
The histone DNA binding surface at this location causes an outward bulge in the DNA and shows significant bending.
true
true
true
true
true
6,396
2
DISCUSSION
1
2
[ "B2", "B2", "B9" ]
20,562,439
pmid-9305837|pmid-9305837|pmid-7737185
The solution structure of duplexes containing a 6-4PP shows a greater extent of helix distortion than identical duplexes containing a CPD (supplemental Fig.
[ "2", "2", "9" ]
156
37,301
0
false
The solution structure of duplexes containing a 6-4PP shows a greater extent of helix distortion than identical duplexes containing a CPD (supplemental Fig.
[]
The solution structure of duplexes containing a 6-4PP shows a greater extent of helix distortion than identical duplexes containing a CPD (supplemental Fig.
true
true
true
true
true
6,396
2
DISCUSSION
1
2
[ "B2", "B2", "B9" ]
20,562,439
pmid-9305837|pmid-9305837|pmid-7737185
S4, naked DNA).
[ "2", "2", "9" ]
15
37,302
0
false
S4, naked DNA).
[]
S4, naked DNA).
true
true
true
true
true
6,396
2
DISCUSSION
1
9
[ "B2", "B2", "B9" ]
20,562,439
pmid-9305837|pmid-9305837|pmid-7737185
The ∼44° kinking angle (9) around the 6-4PP at site 58 is expected to alter the DNA curvature at this position, which could moderate the increase in rate of nucleosome unwrapping and/or change the average distance (R) between the dyes.
[ "2", "2", "9" ]
235
37,303
1
false
The ∼44° kinking angle around the 6-4PP at site 58 is expected to alter the DNA curvature at this position, which could moderate the increase in rate of nucleosome unwrapping and/or change the average distance (R) between the dyes.
[ "9" ]
The ∼44° kinking angle around the 6-4PP at site 58 is expected to alter the DNA curvature at this position, which could moderate the increase in rate of nucleosome unwrapping and/or change the average distance (R) between the dyes.
true
true
true
true
true
6,396
2
DISCUSSION
1
2
[ "B2", "B2", "B9" ]
20,562,439
pmid-9305837|pmid-9305837|pmid-7737185
At the same time, CPDs should cause less structural deformity at this site, and the enhanced nucleosome unwrapping dynamics caused by this lesion may be less affected by changes in DNA curvature.
[ "2", "2", "9" ]
195
37,304
0
false
At the same time, CPDs should cause less structural deformity at this site, and the enhanced nucleosome unwrapping dynamics caused by this lesion may be less affected by changes in DNA curvature.
[]
At the same time, CPDs should cause less structural deformity at this site, and the enhanced nucleosome unwrapping dynamics caused by this lesion may be less affected by changes in DNA curvature.
true
true
true
true
true
6,396
2
DISCUSSION
1
2
[ "B2", "B2", "B9" ]
20,562,439
pmid-9305837|pmid-9305837|pmid-7737185
Clearly, a definitive answer only may be obtained with crystal structures of NCPs containing either of these two DNA lesions at this specific location.
[ "2", "2", "9" ]
151
37,305
0
false
Clearly, a definitive answer only may be obtained with crystal structures of NCPs containing either of these two DNA lesions at this specific location.
[]
Clearly, a definitive answer only may be obtained with crystal structures of NCPs containing either of these two DNA lesions at this specific location.
true
true
true
true
true
6,396
2
DISCUSSION
1
2
[ "B2", "B2", "B9" ]
20,562,439
pmid-9305837|pmid-9305837|pmid-7737185
Furthermore, it will be interesting to examine the effects of these DNA photoproducts at other locations in NCPs on nucleosome-unwrapping dynamics.
[ "2", "2", "9" ]
147
37,306
0
false
Furthermore, it will be interesting to examine the effects of these DNA photoproducts at other locations in NCPs on nucleosome-unwrapping dynamics.
[]
Furthermore, it will be interesting to examine the effects of these DNA photoproducts at other locations in NCPs on nucleosome-unwrapping dynamics.
true
true
true
true
true
6,396
3
DISCUSSION
1
25
[ "B25", "B41" ]
20,562,439
pmid-12242292|pmid-18702521
The REA results indicate that unwrapped states of the UV-damaged NCPs occur primarily in the terminal regions of the DNA (Fig.
[ "25", "41" ]
126
37,307
0
false
The REA results indicate that unwrapped states of the UV-damaged NCPs occur primarily in the terminal regions of the DNA (Fig.
[]
The REA results indicate that unwrapped states of the UV-damaged NCPs occur primarily in the terminal regions of the DNA (Fig.
true
true
true
true
true
6,397
3
DISCUSSION
1
25
[ "B25", "B41" ]
20,562,439
pmid-12242292|pmid-18702521
Previous work on undamaged nucleosomes by FRET and REA has shown that DNA unwraps as far into NCPs as the dyad axis (25, 41).
[ "25", "41" ]
125
37,308
0
false
Previous work on undamaged nucleosomes by FRET and REA has shown that DNA unwraps as far into NCPs as the dyad axis.
[ "25, 41" ]
Previous work on undamaged nucleosomes by FRET and REA has shown that DNA unwraps as far into NCPs as the dyad axis.
true
true
true
true
true
6,397
3
DISCUSSION
1
25
[ "B25", "B41" ]
20,562,439
pmid-12242292|pmid-18702521
Our results suggest that the presence of UV lesions mainly drive the unwrapping (or breathing) of DNA near the edges of nucleosomes, as UV lesions did not enhance the REA of RsaI near the dyad center of NCPs.
[ "25", "41" ]
208
37,309
0
false
Our results suggest that the presence of UV lesions mainly drive the unwrapping (or breathing) of DNA near the edges of nucleosomes, as UV lesions did not enhance the REA of RsaI near the dyad center of NCPs.
[]
Our results suggest that the presence of UV lesions mainly drive the unwrapping (or breathing) of DNA near the edges of nucleosomes, as UV lesions did not enhance the REA of RsaI near the dyad center of NCPs.
true
true
true
true
true
6,397
3
DISCUSSION
1
25
[ "B25", "B41" ]
20,562,439
pmid-12242292|pmid-18702521
As the change in conformational equilibrium and enhanced accessibility of damaged nucleosomes does not require the involvement of other factors, the UV damage-induced unwrapping is an intrinsic property of NCPs.
[ "25", "41" ]
211
37,310
0
false
As the change in conformational equilibrium and enhanced accessibility of damaged nucleosomes does not require the involvement of other factors, the UV damage-induced unwrapping is an intrinsic property of NCPs.
[]
As the change in conformational equilibrium and enhanced accessibility of damaged nucleosomes does not require the involvement of other factors, the UV damage-induced unwrapping is an intrinsic property of NCPs.
true
true
true
true
true
6,397
4
DISCUSSION
1
40
[ "B40", "B51", "B52", "B53", "B37" ]
20,562,439
pmid-15020582|pmid-11425866|pmid-14690611|pmid-15525516|pmid-17597150
In the context of damaged nucleosomes, lesions must be exposed and accessed by the repair machinery to remove the damaged bases.
[ "40", "51", "52", "53", "37" ]
128
37,311
0
false
In the context of damaged nucleosomes, lesions must be exposed and accessed by the repair machinery to remove the damaged bases.
[]
In the context of damaged nucleosomes, lesions must be exposed and accessed by the repair machinery to remove the damaged bases.
true
true
true
true
true
6,398
4
DISCUSSION
1
40
[ "B40", "B51", "B52", "B53", "B37" ]
20,562,439
pmid-15020582|pmid-11425866|pmid-14690611|pmid-15525516|pmid-17597150
The breathing of nucleosomal DNA ends, which exist in equilibrium between associated and dissociated from the histone octamer, may serve to allow this accession to take place.
[ "40", "51", "52", "53", "37" ]
175
37,312
0
false
The breathing of nucleosomal DNA ends, which exist in equilibrium between associated and dissociated from the histone octamer, may serve to allow this accession to take place.
[]
The breathing of nucleosomal DNA ends, which exist in equilibrium between associated and dissociated from the histone octamer, may serve to allow this accession to take place.
true
true
true
true
true
6,398
4
DISCUSSION
1
40
[ "B40", "B51", "B52", "B53", "B37" ]
20,562,439
pmid-15020582|pmid-11425866|pmid-14690611|pmid-15525516|pmid-17597150
Partial dissociation of the DNA ends from histone octamers has been demonstrated by monitoring the salt-dependent changes in FRET (40).
[ "40", "51", "52", "53", "37" ]
135
37,313
1
false
Partial dissociation of the DNA ends from histone octamers has been demonstrated by monitoring the salt-dependent changes in FRET.
[ "40" ]
Partial dissociation of the DNA ends from histone octamers has been demonstrated by monitoring the salt-dependent changes in FRET.
true
true
true
true
true
6,398
4
DISCUSSION
1
40
[ "B40", "B51", "B52", "B53", "B37" ]
20,562,439
pmid-15020582|pmid-11425866|pmid-14690611|pmid-15525516|pmid-17597150
Furthermore, NCPs are assembled with DNA that binds tightly to the (H3-H4)2 tetramer and position about the dyad center.
[ "40", "51", "52", "53", "37" ]
120
37,314
0
false
Furthermore, NCPs are assembled with DNA that binds tightly to the (H3-H4)2 tetramer and position about the dyad center.
[]
Furthermore, NCPs are assembled with DNA that binds tightly to the 2 tetramer and position about the dyad center.
true
true
true
true
true
6,398
4
DISCUSSION
1
51
[ "B40", "B51", "B52", "B53", "B37" ]
20,562,439
pmid-15020582|pmid-11425866|pmid-14690611|pmid-15525516|pmid-17597150
The (H2A-H2B) dimers can exchange dynamically in vivo (51) and this may play an important role in ATP-dependent nucleosome remodeling (52, 53).
[ "40", "51", "52", "53", "37" ]
143
37,315
1
false
The (H2A-H2B) dimers can exchange dynamically in vivo and this may play an important role in ATP-dependent nucleosome remodeling.
[ "51", "52, 53" ]
The (H2A-H2B) dimers can exchange dynamically in vivo and this may play an important role in ATP-dependent nucleosome remodeling.
true
true
true
true
true
6,398