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
INTRODUCTION
1
17
[ "B10", "B15", "B16", "B17", "B18", "B19", "B20", "B21", "B22", "B23", "B24", "B25" ]
19,321,500
pmid-7665619|pmid-9857202|pmid-9003792|pmid-10394359|pmid-14675538|pmid-9372926|pmid-11172724|pmid-16698552|pmid-16156639|pmid-11943866|pmid-18451872|pmid-18450493
This domain is initially unfolded, and partially folds upon binding to eIF4E in the human complex (17).
[ "10", "15", "16", "17", "18", "19", "20", "21", "22", "23", "24", "25" ]
103
39,116
1
false
This domain is initially unfolded, and partially folds upon binding to eIF4E in the human complex.
[ "17" ]
This domain is initially unfolded, and partially folds upon binding to eIF4E in the human complex.
true
true
true
true
true
6,736
2
INTRODUCTION
1
18
[ "B10", "B15", "B16", "B17", "B18", "B19", "B20", "B21", "B22", "B23", "B24", "B25" ]
19,321,500
pmid-7665619|pmid-9857202|pmid-9003792|pmid-10394359|pmid-14675538|pmid-9372926|pmid-11172724|pmid-16698552|pmid-16156639|pmid-11943866|pmid-18451872|pmid-18450493
In yeast it folds to a larger extent wrapping around eIF4E's N-terminus (18).
[ "10", "15", "16", "17", "18", "19", "20", "21", "22", "23", "24", "25" ]
77
39,117
1
false
In yeast it folds to a larger extent wrapping around eIF4E's N-terminus.
[ "18" ]
In yeast it folds to a larger extent wrapping around eIF4E's N-terminus.
true
true
true
true
true
6,736
2
INTRODUCTION
1
10
[ "B10", "B15", "B16", "B17", "B18", "B19", "B20", "B21", "B22", "B23", "B24", "B25" ]
19,321,500
pmid-7665619|pmid-9857202|pmid-9003792|pmid-10394359|pmid-14675538|pmid-9372926|pmid-11172724|pmid-16698552|pmid-16156639|pmid-11943866|pmid-18451872|pmid-18450493
The middle domain of eIF4G (MIF4G) is critical for assembly of the translation machinery, since it harbors the binding site for eIF3 and eIF4A (19,20).
[ "10", "15", "16", "17", "18", "19", "20", "21", "22", "23", "24", "25" ]
151
39,118
0
false
The middle domain of eIF4G (MIF4G) is critical for assembly of the translation machinery, since it harbors the binding site for eIF3 and eIF4A.
[ "19,20" ]
The middle domain of eIF4G (MIF4G) is critical for assembly of the translation machinery, since it harbors the binding site for eIF3 and eIF4A.
true
true
true
true
true
6,736
2
INTRODUCTION
1
21
[ "B10", "B15", "B16", "B17", "B18", "B19", "B20", "B21", "B22", "B23", "B24", "B25" ]
19,321,500
pmid-7665619|pmid-9857202|pmid-9003792|pmid-10394359|pmid-14675538|pmid-9372926|pmid-11172724|pmid-16698552|pmid-16156639|pmid-11943866|pmid-18451872|pmid-18450493
The MIF4G contains a single HEAT domain, whereas the human C-terminus of eIF4G contains two additional HEAT domains, which include the binding site for Mnk1, a kinase that phosphorylates eIF4E, and a second binding site for eIF4A (21).
[ "10", "15", "16", "17", "18", "19", "20", "21", "22", "23", "24", "25" ]
235
39,119
1
false
The MIF4G contains a single HEAT domain, whereas the human C-terminus of eIF4G contains two additional HEAT domains, which include the binding site for Mnk1, a kinase that phosphorylates eIF4E, and a second binding site for eIF4A.
[ "21" ]
The MIF4G contains a single HEAT domain, whereas the human C-terminus of eIF4G contains two additional HEAT domains, which include the binding site for Mnk1, a kinase that phosphorylates eIF4E, and a second binding site for eIF4A.
true
true
true
true
true
6,736
2
INTRODUCTION
1
22
[ "B10", "B15", "B16", "B17", "B18", "B19", "B20", "B21", "B22", "B23", "B24", "B25" ]
19,321,500
pmid-7665619|pmid-9857202|pmid-9003792|pmid-10394359|pmid-14675538|pmid-9372926|pmid-11172724|pmid-16698552|pmid-16156639|pmid-11943866|pmid-18451872|pmid-18450493
The large subunit of the nuclear cap-binding complex, CBP80, shares a common origin and domain structure with the eIF4G (22).
[ "10", "15", "16", "17", "18", "19", "20", "21", "22", "23", "24", "25" ]
125
39,120
1
false
The large subunit of the nuclear cap-binding complex, CBP80, shares a common origin and domain structure with the eIF4G.
[ "22" ]
The large subunit of the nuclear cap-binding complex, CBP80, shares a common origin and domain structure with the eIF4G.
true
true
true
true
true
6,736
2
INTRODUCTION
1
23
[ "B10", "B15", "B16", "B17", "B18", "B19", "B20", "B21", "B22", "B23", "B24", "B25" ]
19,321,500
pmid-7665619|pmid-9857202|pmid-9003792|pmid-10394359|pmid-14675538|pmid-9372926|pmid-11172724|pmid-16698552|pmid-16156639|pmid-11943866|pmid-18451872|pmid-18450493
Other eIF4G isoforms include the MIF4G domain but lack the N-terminal domain, such as the human 97 kDa protein DAP5 (23) or the 130 kDa splice-variant of the Caenorhabditis elegans eIF4G.
[ "10", "15", "16", "17", "18", "19", "20", "21", "22", "23", "24", "25" ]
187
39,121
1
false
Other eIF4G isoforms include the MIF4G domain but lack the N-terminal domain, such as the human 97 kDa protein DAP5 or the 130 kDa splice-variant of the Caenorhabditis elegans eIF4G.
[ "23" ]
Other eIF4G isoforms include the MIF4G domain but lack the N-terminal domain, such as the human 97 kDa protein DAP5 or the 130 kDa splice-variant of the Caenorhabditis elegans eIF4G.
true
true
true
true
true
6,736
2
INTRODUCTION
1
24
[ "B10", "B15", "B16", "B17", "B18", "B19", "B20", "B21", "B22", "B23", "B24", "B25" ]
19,321,500
pmid-7665619|pmid-9857202|pmid-9003792|pmid-10394359|pmid-14675538|pmid-9372926|pmid-11172724|pmid-16698552|pmid-16156639|pmid-11943866|pmid-18451872|pmid-18450493
They were shown to participate in cap-independent translation of transcripts encoding pro-apoptotic genes under stress conditions (24).
[ "10", "15", "16", "17", "18", "19", "20", "21", "22", "23", "24", "25" ]
135
39,122
1
false
They were shown to participate in cap-independent translation of transcripts encoding pro-apoptotic genes under stress conditions.
[ "24" ]
They were shown to participate in cap-independent translation of transcripts encoding pro-apoptotic genes under stress conditions.
true
true
true
true
true
6,736
2
INTRODUCTION
1
25
[ "B10", "B15", "B16", "B17", "B18", "B19", "B20", "B21", "B22", "B23", "B24", "B25" ]
19,321,500
pmid-7665619|pmid-9857202|pmid-9003792|pmid-10394359|pmid-14675538|pmid-9372926|pmid-11172724|pmid-16698552|pmid-16156639|pmid-11943866|pmid-18451872|pmid-18450493
DAP5 is also necessary for maintaining cell survival during mitosis by promoting cap-independent translation of at least two prosurvival proteins represented by Bcl2 and CDK1 (25).
[ "10", "15", "16", "17", "18", "19", "20", "21", "22", "23", "24", "25" ]
180
39,123
1
false
DAP5 is also necessary for maintaining cell survival during mitosis by promoting cap-independent translation of at least two prosurvival proteins represented by Bcl2 and CDK1.
[ "25" ]
DAP5 is also necessary for maintaining cell survival during mitosis by promoting cap-independent translation of at least two prosurvival proteins represented by Bcl2 and CDK1.
true
true
true
true
true
6,736
3
INTRODUCTION
1
26
[ "B26", "B17", "B27", "B28", "B17", "B29" ]
19,321,500
pmid-15690031|pmid-10394359|pmid-7651417|pmid-9118949|pmid-10394359|pmid-8521827|pmid-14675538|pmid-10409688
The eIF4E–eIF4G interaction is a key target for translation control (26).
[ "26", "17", "27", "28", "17", "29" ]
73
39,124
1
false
The eIF4E–eIF4G interaction is a key target for translation control.
[ "26" ]
The eIF4E–eIF4G interaction is a key target for translation control.
true
true
true
true
true
6,737
3
INTRODUCTION
1
26
[ "B26", "B17", "B27", "B28", "B17", "B29" ]
19,321,500
pmid-15690031|pmid-10394359|pmid-7651417|pmid-9118949|pmid-10394359|pmid-8521827|pmid-14675538|pmid-10409688
This interaction relies on a short sequence of about 15 amino acids in the N-terminus of eIF4G, which contains a conserved motif Y(X4)LΦ, where X is any amino acid and Φ is a hydrophobic residue (17,27,28).
[ "26", "17", "27", "28", "17", "29" ]
206
39,125
0
false
This interaction relies on a short sequence of about 15 amino acids in the N-terminus of eIF4G, which contains a conserved motif Y(X4)LΦ, where X is any amino acid and Φ is a hydrophobic residue.
[ "17,27,28" ]
This interaction relies on a short sequence of about 15 amino acids in the N-terminus of eIF4G, which contains a conserved motif Y(X4)LΦ, where X is any amino acid and Φ is a hydrophobic residue.
true
true
true
true
true
6,737
3
INTRODUCTION
1
17
[ "B26", "B17", "B27", "B28", "B17", "B29" ]
19,321,500
pmid-15690031|pmid-10394359|pmid-7651417|pmid-9118949|pmid-10394359|pmid-8521827|pmid-14675538|pmid-10409688
This motif forms a short helical structure that binds conserved amino acids on the dorsal side of eIF4E (17).
[ "26", "17", "27", "28", "17", "29" ]
109
39,126
1
false
This motif forms a short helical structure that binds conserved amino acids on the dorsal side of eIF4E.
[ "17" ]
This motif forms a short helical structure that binds conserved amino acids on the dorsal side of eIF4E.
true
true
true
true
true
6,737
3
INTRODUCTION
1
26
[ "B26", "B17", "B27", "B28", "B17", "B29" ]
19,321,500
pmid-15690031|pmid-10394359|pmid-7651417|pmid-9118949|pmid-10394359|pmid-8521827|pmid-14675538|pmid-10409688
Several other proteins, such as the eIF4E-binding proteins (4E-BPs), contain this consensus sequence and thus compete with eIF4G for binding to eIF4E, depending upon its phosphorylation state.
[ "26", "17", "27", "28", "17", "29" ]
192
39,127
0
false
Several other proteins, such as the eIF4E-binding proteins (4E-BPs), contain this consensus sequence and thus compete with eIF4G for binding to eIF4E, depending upon its phosphorylation state.
[]
Several other proteins, such as the eIF4E-binding proteins (4E-BPs), contain this consensus sequence and thus compete with eIF4G for binding to eIF4E, depending upon its phosphorylation state.
true
true
true
true
true
6,737
3
INTRODUCTION
1
29
[ "B26", "B17", "B27", "B28", "B17", "B29" ]
19,321,500
pmid-15690031|pmid-10394359|pmid-7651417|pmid-9118949|pmid-10394359|pmid-8521827|pmid-14675538|pmid-10409688
This regulates translation by affecting the 48S preinitiation complex formation (29).
[ "26", "17", "27", "28", "17", "29" ]
85
39,128
1
false
This regulates translation by affecting the 48S preinitiation complex formation.
[ "29" ]
This regulates translation by affecting the 48S preinitiation complex formation.
true
true
true
true
true
6,737
4
INTRODUCTION
1
30–32
[ "B30 B31 B32", "B31", "B32" ]
19,321,500
pmid-15388875|pmid-17041189|pmid-15694484|pmid-17041189|pmid-15694484|pmid-7651417|pmid-7651417
Cap-binding proteins in trypanosomatids are expected to have gone through structural adaptations that enable them to interact with the unusual cap-4 structure.
[ "30–32", "31", "32" ]
159
39,129
0
false
Cap-binding proteins in trypanosomatids are expected to have gone through structural adaptations that enable them to interact with the unusual cap-4 structure.
[]
Cap-binding proteins in trypanosomatids are expected to have gone through structural adaptations that enable them to interact with the unusual cap-4 structure.
true
true
true
true
true
6,738
4
INTRODUCTION
1
30–32
[ "B30 B31 B32", "B31", "B32" ]
19,321,500
pmid-15388875|pmid-17041189|pmid-15694484|pmid-17041189|pmid-15694484|pmid-7651417|pmid-7651417
The biochemical and cellular features of four eIF4E isoforms in Leishmania major which were denoted LeishIF4E-1 through LeishIF4E-4, have been previously described (30–32).
[ "30–32", "31", "32" ]
172
39,130
1
false
The biochemical and cellular features of four eIF4E isoforms in Leishmania major which were denoted LeishIF4E-1 through LeishIF4E-4, have been previously described.
[ "30–32" ]
The biochemical and cellular features of four eIF4E isoforms in Leishmania major which were denoted LeishIF4E-1 through LeishIF4E-4, have been previously described.
true
true
true
true
true
6,738
4
INTRODUCTION
1
30–32
[ "B30 B31 B32", "B31", "B32" ]
19,321,500
pmid-15388875|pmid-17041189|pmid-15694484|pmid-17041189|pmid-15694484|pmid-7651417|pmid-7651417
None of these isoforms could functionally complement a yeast eIF4E knockout strain, strongly supporting that they have a structurally diverged eIF4E/eIF4G interface.
[ "30–32", "31", "32" ]
165
39,131
0
false
None of these isoforms could functionally complement a yeast eIF4E knockout strain, strongly supporting that they have a structurally diverged eIF4E/eIF4G interface.
[]
None of these isoforms could functionally complement a yeast eIF4E knockout strain, strongly supporting that they have a structurally diverged eIF4E/eIF4G interface.
true
true
true
true
true
6,738
4
INTRODUCTION
1
30–32
[ "B30 B31 B32", "B31", "B32" ]
19,321,500
pmid-15388875|pmid-17041189|pmid-15694484|pmid-17041189|pmid-15694484|pmid-7651417|pmid-7651417
Furthermore, since there is yet no in vitro system for translation initiation for any of the trypanosomatids, the specific role of the different candidates was evaluated indirectly by biochemical and biophysical assays.
[ "30–32", "31", "32" ]
219
39,132
0
false
Furthermore, since there is yet no in vitro system for translation initiation for any of the trypanosomatids, the specific role of the different candidates was evaluated indirectly by biochemical and biophysical assays.
[]
Furthermore, since there is yet no in vitro system for translation initiation for any of the trypanosomatids, the specific role of the different candidates was evaluated indirectly by biochemical and biophysical assays.
true
true
true
true
true
6,738
4
INTRODUCTION
1
30–32
[ "B30 B31 B32", "B31", "B32" ]
19,321,500
pmid-15388875|pmid-17041189|pmid-15694484|pmid-17041189|pmid-15694484|pmid-7651417|pmid-7651417
Fluorescence titration assays showed that LeishIF4E-1 and LeishIF4E-4 bind m7GTP and cap-4 comparably well whereas LeishIF4E-2 binds mainly to the cap-4.
[ "30–32", "31", "32" ]
153
39,133
0
false
Fluorescence titration assays showed that LeishIF4E-1 and LeishIF4E-4 bind m7GTP and cap-4 comparably well whereas LeishIF4E-2 binds mainly to the cap-4.
[]
Fluorescence titration assays showed that LeishIF4E-1 and LeishIF4E-4 bind m7GTP and cap-4 comparably well whereas LeishIF4E-2 binds mainly to the cap-4.
true
true
true
true
true
6,738
4
INTRODUCTION
1
31
[ "B30 B31 B32", "B31", "B32" ]
19,321,500
pmid-15388875|pmid-17041189|pmid-15694484|pmid-17041189|pmid-15694484|pmid-7651417|pmid-7651417
LeishIF4E-3 was found to bind mainly to m7GTP, excluding its involvement in translation of cap-4 protected mRNAs (31).
[ "30–32", "31", "32" ]
118
39,134
1
false
LeishIF4E-3 was found to bind mainly to m7GTP, excluding its involvement in translation of cap-4 protected mRNAs.
[ "31" ]
LeishIF4E-3 was found to bind mainly to m7GTP, excluding its involvement in translation of cap-4 protected mRNAs.
true
true
true
true
true
6,738
4
INTRODUCTION
1
32
[ "B30 B31 B32", "B31", "B32" ]
19,321,500
pmid-15388875|pmid-17041189|pmid-15694484|pmid-17041189|pmid-15694484|pmid-7651417|pmid-7651417
A bioinformatics search for eIF4G revealed five isoforms that contain the HEAT repeats of the MIF4G (32).
[ "30–32", "31", "32" ]
105
39,135
1
false
A bioinformatics search for eIF4G revealed five isoforms that contain the HEAT repeats of the MIF4G.
[ "32" ]
A bioinformatics search for eIF4G revealed five isoforms that contain the HEAT repeats of the MIF4G.
true
true
true
true
true
6,738
4
INTRODUCTION
1
30–32
[ "B30 B31 B32", "B31", "B32" ]
19,321,500
pmid-15388875|pmid-17041189|pmid-15694484|pmid-17041189|pmid-15694484|pmid-7651417|pmid-7651417
Here we describe LeishIF4G-3, the most probable candidate for functioning as the Leishmania eIF4G, based on its ability to interact with the LeishIF4Es.
[ "30–32", "31", "32" ]
152
39,136
0
false
Here we describe LeishIF4G-3, the most probable candidate for functioning as the Leishmania eIF4G, based on its ability to interact with the LeishIF4Es.
[]
Here we describe LeishIF4G-3, the most probable candidate for functioning as the Leishmania eIF4G, based on its ability to interact with the LeishIF4Es.
true
true
true
true
true
6,738
4
INTRODUCTION
1
30–32
[ "B30 B31 B32", "B31", "B32" ]
19,321,500
pmid-15388875|pmid-17041189|pmid-15694484|pmid-17041189|pmid-15694484|pmid-7651417|pmid-7651417
Using yeast two-hybrid, site-directed mutagenesis and nuclear magnetic resonance (NMR) spectroscopy techniques, we further characterize the consensus peptide of LeishIF4G-3 (20-YPGFSLDE-27) that is responsible for this interaction and highlight variations between the Leishmania cap-binding complex and its counterpart f...
[ "30–32", "31", "32" ]
348
39,137
0
false
Using yeast two-hybrid, site-directed mutagenesis and nuclear magnetic resonance (NMR) spectroscopy techniques, we further characterize the consensus peptide of LeishIF4G-3 (20-YPGFSLDE-27) that is responsible for this interaction and highlight variations between the Leishmania cap-binding complex and its counterpart f...
[]
Using yeast two-hybrid, site-directed mutagenesis and nuclear magnetic resonance (NMR) spectroscopy techniques, we further characterize the consensus peptide of LeishIF4G-3 that is responsible for this interaction and highlight variations between the Leishmania cap-binding complex and its counterpart from higher eukary...
true
true
true
true
true
6,738
0
DISCUSSION
1
31
[ "B31" ]
19,321,500
pmid-3181145|pmid-7826014|pmid-15463739|pmid-15811531|pmid-14555465|pmid-17765983|pmid-1349605|pmid-17041189
The cap-binding complex in Leishmania and trypanosomatids is of special interest in view of the unusual cap-4 structure, which is found at the 5′-end of all mRNAs.
[ "31" ]
163
39,138
0
false
The cap-binding complex in Leishmania and trypanosomatids is of special interest in view of the unusual cap-4 structure, which is found at the 5′-end of all mRNAs.
[]
The cap-binding complex in Leishmania and trypanosomatids is of special interest in view of the unusual cap-4 structure, which is found at the 5′-end of all mRNAs.
true
true
true
true
true
6,739
0
DISCUSSION
1
31
[ "B31" ]
19,321,500
pmid-3181145|pmid-7826014|pmid-15463739|pmid-15811531|pmid-14555465|pmid-17765983|pmid-1349605|pmid-17041189
Components of the cap-binding complex, particularly LeishIF4E, must have gone through changes that enable efficient binding to, and assembly on this highly modified structure.
[ "31" ]
175
39,139
0
false
Components of the cap-binding complex, particularly LeishIF4E, must have gone through changes that enable efficient binding to, and assembly on this highly modified structure.
[]
Components of the cap-binding complex, particularly LeishIF4E, must have gone through changes that enable efficient binding to, and assembly on this highly modified structure.
true
true
true
true
true
6,739
0
DISCUSSION
1
31
[ "B31" ]
19,321,500
pmid-3181145|pmid-7826014|pmid-15463739|pmid-15811531|pmid-14555465|pmid-17765983|pmid-1349605|pmid-17041189
This is reflected by the inability of the different LeishIF4Es to replace eIF4E from higher eukaryotes (31).
[ "31" ]
108
39,140
1
false
This is reflected by the inability of the different LeishIF4Es to replace eIF4E from higher eukaryotes.
[ "31" ]
This is reflected by the inability of the different LeishIF4Es to replace eIF4E from higher eukaryotes.
true
true
true
true
true
6,739
0
DISCUSSION
1
31
[ "B31" ]
19,321,500
pmid-3181145|pmid-7826014|pmid-15463739|pmid-15811531|pmid-14555465|pmid-17765983|pmid-1349605|pmid-17041189
A bioinformatics analysis highlighted the presence of several putative eIF4G homologs in Leishmania; in this study, we showed that one of these candidates, LeishIF4G-3 was eluted from an m7GTP-Sepharose column, along with LeishIF4E-1, LeishIF4E-4 and LeishIF4A-1, which are part of the eIF4F complex.
[ "31" ]
300
39,141
0
false
A bioinformatics analysis highlighted the presence of several putative eIF4G homologs in Leishmania; in this study, we showed that one of these candidates, LeishIF4G-3 was eluted from an m7GTP-Sepharose column, along with LeishIF4E-1, LeishIF4E-4 and LeishIF4A-1, which are part of the eIF4F complex.
[]
A bioinformatics analysis highlighted the presence of several putative eIF4G homologs in Leishmania; in this study, we showed that one of these candidates, LeishIF4G-3 was eluted from an m7GTP-Sepharose column, along with LeishIF4E-1, LeishIF4E-4 and LeishIF4A-1, which are part of the eIF4F complex.
true
true
true
true
true
6,739
0
DISCUSSION
1
31
[ "B31" ]
19,321,500
pmid-3181145|pmid-7826014|pmid-15463739|pmid-15811531|pmid-14555465|pmid-17765983|pmid-1349605|pmid-17041189
This strongly suggests that LeishIF4G-3 is the general translation factor of trypanosomatids.
[ "31" ]
93
39,142
0
false
This strongly suggests that LeishIF4G-3 is the general translation factor of trypanosomatids.
[]
This strongly suggests that LeishIF4G-3 is the general translation factor of trypanosomatids.
true
true
true
true
true
6,739
0
DISCUSSION
1
31
[ "B31" ]
19,321,500
pmid-3181145|pmid-7826014|pmid-15463739|pmid-15811531|pmid-14555465|pmid-17765983|pmid-1349605|pmid-17041189
However, proteins which were eluted from an m7GTP column are not restricted to translation, and could be associated with other RNA metabolism and transport processes between the nucleus and the cytoplasm.
[ "31" ]
204
39,143
0
false
However, proteins which were eluted from an m7GTP column are not restricted to translation, and could be associated with other RNA metabolism and transport processes between the nucleus and the cytoplasm.
[]
However, proteins which were eluted from an m7GTP column are not restricted to translation, and could be associated with other RNA metabolism and transport processes between the nucleus and the cytoplasm.
true
true
true
true
true
6,739
0
DISCUSSION
1
31
[ "B31" ]
19,321,500
pmid-3181145|pmid-7826014|pmid-15463739|pmid-15811531|pmid-14555465|pmid-17765983|pmid-1349605|pmid-17041189
Thus, a more direct approach for monitoring the interactions between the putative LeishIF4G-3 and the Leishmania cap-binding translation initiation factors is required.
[ "31" ]
168
39,144
0
false
Thus, a more direct approach for monitoring the interactions between the putative LeishIF4G-3 and the Leishmania cap-binding translation initiation factors is required.
[]
Thus, a more direct approach for monitoring the interactions between the putative LeishIF4G-3 and the Leishmania cap-binding translation initiation factors is required.
true
true
true
true
true
6,739
0
DISCUSSION
1
31
[ "B31" ]
19,321,500
pmid-3181145|pmid-7826014|pmid-15463739|pmid-15811531|pmid-14555465|pmid-17765983|pmid-1349605|pmid-17041189
We therefore characterized the interaction between LeishIF4G-3 and the different LeishIF4E homologs by pull-down assays.
[ "31" ]
120
39,145
0
false
We therefore characterized the interaction between LeishIF4G-3 and the different LeishIF4E homologs by pull-down assays.
[]
We therefore characterized the interaction between LeishIF4G-3 and the different LeishIF4E homologs by pull-down assays.
true
true
true
true
true
6,739
0
DISCUSSION
1
31
[ "B31" ]
19,321,500
pmid-3181145|pmid-7826014|pmid-15463739|pmid-15811531|pmid-14555465|pmid-17765983|pmid-1349605|pmid-17041189
Only LeishIF4E-1 and LeishIF4E-4 were coprecipitated in vitro with the recombinant GST-LeishIF4G-3 fusion protein from Glutathione-Agarose beads, in agreement with our previous report on their ability to bind the human 4E-BP1.
[ "31" ]
226
39,146
0
false
Only LeishIF4E-1 and LeishIF4E-4 were coprecipitated in vitro with the recombinant GST-LeishIF4G-3 fusion protein from Glutathione-Agarose beads, in agreement with our previous report on their ability to bind the human 4E-BP1.
[]
Only LeishIF4E-1 and LeishIF4E-4 were coprecipitated in vitro with the recombinant GST-LeishIF4G-3 fusion protein from Glutathione-Agarose beads, in agreement with our previous report on their ability to bind the human 4E-BP1.
true
true
true
true
true
6,739
0
DISCUSSION
1
31
[ "B31" ]
19,321,500
pmid-3181145|pmid-7826014|pmid-15463739|pmid-15811531|pmid-14555465|pmid-17765983|pmid-1349605|pmid-17041189
LeishIF4G-3 comigrates with LeishIF4E-1 and LeishIF4E-4 in sucrose gradients, supporting that these proteins can share the same sub-cellular particles.
[ "31" ]
151
39,147
0
false
LeishIF4G-3 comigrates with LeishIF4E-1 and LeishIF4E-4 in sucrose gradients, supporting that these proteins can share the same sub-cellular particles.
[]
LeishIF4G-3 comigrates with LeishIF4E-1 and LeishIF4E-4 in sucrose gradients, supporting that these proteins can share the same sub-cellular particles.
true
true
true
true
true
6,739
1
DISCUSSION
1
38
[ "B38", "B31" ]
19,321,500
pmid-9019810|pmid-11909525|pmid-7665619|pmid-11022043|pmid-9702200|pmid-10364159|pmid-11909525|pmid-16194295|pmid-18713834|pmid-17041189
The effect of heat shock on the migration profile of polysomes in Leishmania is in agreement with other reports in Trypanosoma brucei, showing that the relative amount of polysomes decreases whereas the 80S fraction is enlarged (38).
[ "38", "31" ]
233
39,148
1
false
The effect of heat shock on the migration profile of polysomes in Leishmania is in agreement with other reports in Trypanosoma brucei, showing that the relative amount of polysomes decreases whereas the 80S fraction is enlarged.
[ "38" ]
The effect of heat shock on the migration profile of polysomes in Leishmania is in agreement with other reports in Trypanosoma brucei, showing that the relative amount of polysomes decreases whereas the 80S fraction is enlarged.
true
true
true
true
true
6,740
1
DISCUSSION
1
38
[ "B38", "B31" ]
19,321,500
pmid-9019810|pmid-11909525|pmid-7665619|pmid-11022043|pmid-9702200|pmid-10364159|pmid-11909525|pmid-16194295|pmid-18713834|pmid-17041189
In response to temperature elevation of Leishmania parasites, LeishIF4E-4 disintegrates from heavier complexes, and is found only at the top of the gradient, as free RNPs.
[ "38", "31" ]
171
39,149
0
false
In response to temperature elevation of Leishmania parasites, LeishIF4E-4 disintegrates from heavier complexes, and is found only at the top of the gradient, as free RNPs.
[]
In response to temperature elevation of Leishmania parasites, LeishIF4E-4 disintegrates from heavier complexes, and is found only at the top of the gradient, as free RNPs.
true
true
true
true
true
6,740
1
DISCUSSION
1
31
[ "B38", "B31" ]
19,321,500
pmid-9019810|pmid-11909525|pmid-7665619|pmid-11022043|pmid-9702200|pmid-10364159|pmid-11909525|pmid-16194295|pmid-18713834|pmid-17041189
However, LeishIF4E-1 which goes up in amastigotes (31), and LeishIF4G-3 continues to comigrate with the 80S particles, even when the general translation activity is low.
[ "38", "31" ]
169
39,150
1
false
However, LeishIF4E-1 which goes up in amastigotes, and LeishIF4G-3 continues to comigrate with the 80S particles, even when the general translation activity is low.
[ "31" ]
However, LeishIF4E-1 which goes up in amastigotes, and LeishIF4G-3 continues to comigrate with the 80S particles, even when the general translation activity is low.
true
true
true
true
true
6,740
1
DISCUSSION
1
38
[ "B38", "B31" ]
19,321,500
pmid-9019810|pmid-11909525|pmid-7665619|pmid-11022043|pmid-9702200|pmid-10364159|pmid-11909525|pmid-16194295|pmid-18713834|pmid-17041189
This is in-line with the requirement that amastigotes resume their protein synthesis activity at elevated temperatures following differentiation to the life form that resides in mammals.
[ "38", "31" ]
186
39,151
0
false
This is in-line with the requirement that amastigotes resume their protein synthesis activity at elevated temperatures following differentiation to the life form that resides in mammals.
[]
This is in-line with the requirement that amastigotes resume their protein synthesis activity at elevated temperatures following differentiation to the life form that resides in mammals.
true
true
true
true
true
6,740
2
DISCUSSION
0
null
null
19,321,500
pmid-7665619|pmid-9857202|pmid-9003792|pmid-10394359|pmid-14675538|pmid-9372926|pmid-11172724|pmid-16698552|pmid-16156639|pmid-11943866|pmid-18451872|pmid-18450493
The interactions between recombinant proteins in vitro do not always provide a faithful reflection of the parallel in vivo processes, because they do not involve the complete subunit repertoire of their complexes.
null
213
39,152
0
false
null
null
The interactions between recombinant proteins in vitro do not always provide a faithful reflection of the parallel in vivo processes, because they do not involve the complete subunit repertoire of their complexes.
true
true
true
true
true
6,741
2
DISCUSSION
0
null
null
19,321,500
pmid-7665619|pmid-9857202|pmid-9003792|pmid-10394359|pmid-14675538|pmid-9372926|pmid-11172724|pmid-16698552|pmid-16156639|pmid-11943866|pmid-18451872|pmid-18450493
The interaction between LeishIF4G-3 and LeishIF4Es were therefore monitored in vivo.
null
84
39,153
0
false
null
null
The interaction between LeishIF4G-3 and LeishIF4Es were therefore monitored in vivo.
true
true
true
true
true
6,741
2
DISCUSSION
0
null
null
19,321,500
pmid-7665619|pmid-9857202|pmid-9003792|pmid-10394359|pmid-14675538|pmid-9372926|pmid-11172724|pmid-16698552|pmid-16156639|pmid-11943866|pmid-18451872|pmid-18450493
FLAG-tagged LeishIF4G-3 was able to pull-down only LeishIF4E-4.
null
63
39,154
0
false
null
null
FLAG-tagged LeishIF4G-3 was able to pull-down only LeishIF4E-4.
true
true
true
true
true
6,741
2
DISCUSSION
0
null
null
19,321,500
pmid-7665619|pmid-9857202|pmid-9003792|pmid-10394359|pmid-14675538|pmid-9372926|pmid-11172724|pmid-16698552|pmid-16156639|pmid-11943866|pmid-18451872|pmid-18450493
However, the reciprocal approach, where both LeishIF4E-1 and LeishIF4E-4 were TAP-tagged in vivo, verified the interaction between LeishIF4G-3 and LeishIF4E-1, as well as with LeishIF4E-4, in agreement with the results obtained from the in vitro pull-down assays.
null
263
39,155
0
false
null
null
However, the reciprocal approach, where both LeishIF4E-1 and LeishIF4E-4 were TAP-tagged in vivo, verified the interaction between LeishIF4G-3 and LeishIF4E-1, as well as with LeishIF4E-4, in agreement with the results obtained from the in vitro pull-down assays.
true
true
true
true
true
6,741
2
DISCUSSION
0
null
null
19,321,500
pmid-7665619|pmid-9857202|pmid-9003792|pmid-10394359|pmid-14675538|pmid-9372926|pmid-11172724|pmid-16698552|pmid-16156639|pmid-11943866|pmid-18451872|pmid-18450493
In the case of TAP-tagged LeishIF4E-1, the anti-LeishIF4G-3 antibodies identified a band that migrates slightly faster, suggesting perhaps that LeishIF4E-1 and LeishIF4E-4 interact with different phosphorylated forms of LeishIF4G-3 (Figure 5).
null
243
39,156
0
false
null
null
In the case of TAP-tagged LeishIF4E-1, the anti-LeishIF4G-3 antibodies identified a band that migrates slightly faster, suggesting perhaps that LeishIF4E-1 and LeishIF4E-4 interact with different phosphorylated forms of LeishIF4G-3 (Figure 5).
true
true
true
true
true
6,741
2
DISCUSSION
0
null
null
19,321,500
pmid-7665619|pmid-9857202|pmid-9003792|pmid-10394359|pmid-14675538|pmid-9372926|pmid-11172724|pmid-16698552|pmid-16156639|pmid-11943866|pmid-18451872|pmid-18450493
This faster migrating band also cosediments with LeishIF4E-1 and LeishIF4E-4 in sucrose gradients (Figure 2).
null
109
39,157
0
false
null
null
This faster migrating band also cosediments with LeishIF4E-1 and LeishIF4E-4 in sucrose gradients (Figure 2).
true
true
true
true
true
6,741
3
DISCUSSION
1
18
[ "B18", "B39" ]
19,321,500
pmid-15690031|pmid-10394359|pmid-7651417|pmid-9118949|pmid-10394359|pmid-8521827|pmid-14675538|pmid-10409688
In yeast eIF4G, the amino terminus is unfolded, and binding to eIF4E induces the folding of a region that encompasses 100 amino acids (positions 393–490) into a ‘molecular bracelet’ of α-helices that encircles the unstructured amino terminus of the eIF4E (18,39).
[ "18", "39" ]
263
39,158
0
false
In yeast eIF4G, the amino terminus is unfolded, and binding to eIF4E induces the folding of a region that encompasses 100 amino acids into a ‘molecular bracelet’ of α-helices that encircles the unstructured amino terminus of the eIF4E.
[ "positions 393–490", "18,39" ]
In yeast eIF4G, the amino terminus is unfolded, and binding to eIF4E induces the folding of a region that encompasses 100 amino acids into a ‘molecular bracelet’ of α-helices that encircles the unstructured amino terminus of the eIF4E.
true
true
true
true
true
6,742
3
DISCUSSION
1
18
[ "B18", "B39" ]
19,321,500
pmid-15690031|pmid-10394359|pmid-7651417|pmid-9118949|pmid-10394359|pmid-8521827|pmid-14675538|pmid-10409688
In LeishIF4G-3 the amino terminus is much shorter, and consists of only 49 amino acids upstream of the first HEAT repeat.
[ "18", "39" ]
121
39,159
0
false
In LeishIF4G-3 the amino terminus is much shorter, and consists of only 49 amino acids upstream of the first HEAT repeat.
[]
In LeishIF4G-3 the amino terminus is much shorter, and consists of only 49 amino acids upstream of the first HEAT repeat.
true
true
true
true
true
6,742
3
DISCUSSION
1
18
[ "B18", "B39" ]
19,321,500
pmid-15690031|pmid-10394359|pmid-7651417|pmid-9118949|pmid-10394359|pmid-8521827|pmid-14675538|pmid-10409688
This region was found to be sufficient to promote the binding of LeishIF4G-3 to LeishIF4E-4, as indicated by the yeast two-hybrid assay.
[ "18", "39" ]
136
39,160
0
false
This region was found to be sufficient to promote the binding of LeishIF4G-3 to LeishIF4E-4, as indicated by the yeast two-hybrid assay.
[]
This region was found to be sufficient to promote the binding of LeishIF4G-3 to LeishIF4E-4, as indicated by the yeast two-hybrid assay.
true
true
true
true
true
6,742
4
DISCUSSION
1
27
[ "B27", "B27" ]
19,321,500
pmid-15388875|pmid-17041189|pmid-15694484|pmid-17041189|pmid-15694484|pmid-7651417|pmid-7651417
An oligo-peptide in the N-terminal region of LeishIF4G-3 that shows partial conservation with the consensus signature peptide Y(X4)L of higher eukaryotes was verified by specific point mutations (Figure 7).
[ "27", "27" ]
206
39,161
0
false
An oligo-peptide in the N-terminal region of LeishIF4G-3 that shows partial conservation with the consensus signature peptide Y(X4)L of higher eukaryotes was verified by specific point mutations (Figure 7).
[]
An oligo-peptide in the N-terminal region of LeishIF4G-3 that shows partial conservation with the consensus signature peptide Y(X4)L of higher eukaryotes was verified by specific point mutations.
true
true
true
true
true
6,743
4
DISCUSSION
1
27
[ "B27", "B27" ]
19,321,500
pmid-15388875|pmid-17041189|pmid-15694484|pmid-17041189|pmid-15694484|pmid-7651417|pmid-7651417
The first tyrosine of the LeishIF4G-3 peptide is essential for binding to LeishIF4E-4.
[ "27", "27" ]
86
39,162
0
false
The first tyrosine of the LeishIF4G-3 peptide is essential for binding to LeishIF4E-4.
[]
The first tyrosine of the LeishIF4G-3 peptide is essential for binding to LeishIF4E-4.
true
true
true
true
true
6,743
4
DISCUSSION
1
27
[ "B27", "B27" ]
19,321,500
pmid-15388875|pmid-17041189|pmid-15694484|pmid-17041189|pmid-15694484|pmid-7651417|pmid-7651417
Its replacement by alanine abrogates the binding completely, whereas replacement by a phenylalanine residue indicates that the peptide is still functional, although growth of the yeast expressing the Y20F mutant is slower.
[ "27", "27" ]
222
39,163
0
false
Its replacement by alanine abrogates the binding completely, whereas replacement by a phenylalanine residue indicates that the peptide is still functional, although growth of the yeast expressing the Y20F mutant is slower.
[]
Its replacement by alanine abrogates the binding completely, whereas replacement by a phenylalanine residue indicates that the peptide is still functional, although growth of the yeast expressing the Y20F mutant is slower.
true
true
true
true
true
6,743
4
DISCUSSION
1
27
[ "B27", "B27" ]
19,321,500
pmid-15388875|pmid-17041189|pmid-15694484|pmid-17041189|pmid-15694484|pmid-7651417|pmid-7651417
A similar exchange in the human eIF4G peptide where tyrosine was replaced by phenylalanine had little, or no effect on its binding to eIF4E (27).
[ "27", "27" ]
145
39,164
1
false
A similar exchange in the human eIF4G peptide where tyrosine was replaced by phenylalanine had little, or no effect on its binding to eIF4E.
[ "27" ]
A similar exchange in the human eIF4G peptide where tyrosine was replaced by phenylalanine had little, or no effect on its binding to eIF4E.
true
true
true
true
true
6,743
4
DISCUSSION
1
27
[ "B27", "B27" ]
19,321,500
pmid-15388875|pmid-17041189|pmid-15694484|pmid-17041189|pmid-15694484|pmid-7651417|pmid-7651417
Both amino acids are aromatic and a phenylalanine residue also occupies the parallel position in the consensus peptide of eIF4G from C. elegans (386-FGRDFMV-392).
[ "27", "27" ]
162
39,165
0
false
Both amino acids are aromatic and a phenylalanine residue also occupies the parallel position in the consensus peptide of eIF4G from C. elegans (386-FGRDFMV-392).
[]
Both amino acids are aromatic and a phenylalanine residue also occupies the parallel position in the consensus peptide of eIF4G from C. elegans.
true
true
true
true
true
6,743
4
DISCUSSION
1
27
[ "B27", "B27" ]
19,321,500
pmid-15388875|pmid-17041189|pmid-15694484|pmid-17041189|pmid-15694484|pmid-7651417|pmid-7651417
As expected, the leucine residue (L25) in the peptide is conserved and essential, and its replacement by alanine eliminates binding to LeishIF4E-4 completely.
[ "27", "27" ]
158
39,166
0
false
As expected, the leucine residue (L25) in the peptide is conserved and essential, and its replacement by alanine eliminates binding to LeishIF4E-4 completely.
[]
As expected, the leucine residue in the peptide is conserved and essential, and its replacement by alanine eliminates binding to LeishIF4E-4 completely.
true
true
true
true
true
6,743
4
DISCUSSION
1
27
[ "B27", "B27" ]
19,321,500
pmid-15388875|pmid-17041189|pmid-15694484|pmid-17041189|pmid-15694484|pmid-7651417|pmid-7651417
However, the subsequent residue in trypanosomatids is not hydrophobic, as in higher eukaryotes, and is replaced by an acidic residue, aspartic acid in L. major and L. infantum, or glutamic acid in T. brucei and T. cruzi (Figure 7A).
[ "27", "27" ]
232
39,167
0
false
However, the subsequent residue in trypanosomatids is not hydrophobic, as in higher eukaryotes, and is replaced by an acidic residue, aspartic acid in L. major and L. infantum, or glutamic acid in T. brucei and T. cruzi (Figure 7A).
[]
However, the subsequent residue in trypanosomatids is not hydrophobic, as in higher eukaryotes, and is replaced by an acidic residue, aspartic acid in L. major and L. infantum, or glutamic acid in T. brucei and T. cruzi.
true
true
true
true
true
6,743
4
DISCUSSION
1
27
[ "B27", "B27" ]
19,321,500
pmid-15388875|pmid-17041189|pmid-15694484|pmid-17041189|pmid-15694484|pmid-7651417|pmid-7651417
This acidic residue is nonessential in Leishmania, and can be replaced by alanine without affecting the binding between LeishIF4G-3 and LeishIF4E-4.
[ "27", "27" ]
148
39,168
0
false
This acidic residue is nonessential in Leishmania, and can be replaced by alanine without affecting the binding between LeishIF4G-3 and LeishIF4E-4.
[]
This acidic residue is nonessential in Leishmania, and can be replaced by alanine without affecting the binding between LeishIF4G-3 and LeishIF4E-4.
true
true
true
true
true
6,743
4
DISCUSSION
1
27
[ "B27", "B27" ]
19,321,500
pmid-15388875|pmid-17041189|pmid-15694484|pmid-17041189|pmid-15694484|pmid-7651417|pmid-7651417
Another example where the hydrophobic residue is not conserved is the eIF4E-binding peptide (YERAFMK) of 4E-BP from Drosophila melanogaster (NP_477295), where the sixth position following the tyrosine in that peptide is occupied by a basic lysine residue, marked in bold.
[ "27", "27" ]
271
39,169
0
false
Another example where the hydrophobic residue is not conserved is the eIF4E-binding peptide (YERAFMK) of 4E-BP from Drosophila melanogaster (NP_477295), where the sixth position following the tyrosine in that peptide is occupied by a basic lysine residue, marked in bold.
[]
Another example where the hydrophobic residue is not conserved is the eIF4E-binding peptide (YERAFMK) of 4E-BP from Drosophila melanogaster, where the sixth position following the tyrosine in that peptide is occupied by a basic lysine residue, marked in bold.
true
true
true
true
true
6,743
4
DISCUSSION
1
27
[ "B27", "B27" ]
19,321,500
pmid-15388875|pmid-17041189|pmid-15694484|pmid-17041189|pmid-15694484|pmid-7651417|pmid-7651417
In contrast, the neighboring glutamic acid at position 27 from LeishIF4G-3 participates in the binding activity to LeishIF4E.
[ "27", "27" ]
125
39,170
0
false
In contrast, the neighboring glutamic acid at position 27 from LeishIF4G-3 participates in the binding activity to LeishIF4E.
[]
In contrast, the neighboring glutamic acid at position 27 from LeishIF4G-3 participates in the binding activity to LeishIF4E.
true
true
true
true
true
6,743
4
DISCUSSION
1
27
[ "B27", "B27" ]
19,321,500
pmid-15388875|pmid-17041189|pmid-15694484|pmid-17041189|pmid-15694484|pmid-7651417|pmid-7651417
We further highlighted additional deviations of the LeishIF4G-3 signature peptide as compared with its higher eukaryotic counterpart.
[ "27", "27" ]
133
39,171
0
false
We further highlighted additional deviations of the LeishIF4G-3 signature peptide as compared with its higher eukaryotic counterpart.
[]
We further highlighted additional deviations of the LeishIF4G-3 signature peptide as compared with its higher eukaryotic counterpart.
true
true
true
true
true
6,743
4
DISCUSSION
1
27
[ "B27", "B27" ]
19,321,500
pmid-15388875|pmid-17041189|pmid-15694484|pmid-17041189|pmid-15694484|pmid-7651417|pmid-7651417
The four amino acids that follow the essential tyrosine residue (Y20) are conserved among trypanosomatids, and our mutational analysis shows that the phenylalanine (F23) is essential, whereas the proline and glycine residues (P21 and G22) have a partial effect on the binding.
[ "27", "27" ]
276
39,172
0
false
The four amino acids that follow the essential tyrosine residue (Y20) are conserved among trypanosomatids, and our mutational analysis shows that the phenylalanine (F23) is essential, whereas the proline and glycine residues (P21 and G22) have a partial effect on the binding.
[]
The four amino acids that follow the essential tyrosine residue are conserved among trypanosomatids, and our mutational analysis shows that the phenylalanine is essential, whereas the proline and glycine residues have a partial effect on the binding.
true
true
true
true
true
6,743
4
DISCUSSION
1
27
[ "B27", "B27" ]
19,321,500
pmid-15388875|pmid-17041189|pmid-15694484|pmid-17041189|pmid-15694484|pmid-7651417|pmid-7651417
In higher eukaryotes, replacement of amino acids at these positions has no effect on the binding to eIF4E (27).
[ "27", "27" ]
111
39,173
1
false
In higher eukaryotes, replacement of amino acids at these positions has no effect on the binding to eIF4E.
[ "27" ]
In higher eukaryotes, replacement of amino acids at these positions has no effect on the binding to eIF4E.
true
true
true
true
true
6,743
4
DISCUSSION
1
27
[ "B27", "B27" ]
19,321,500
pmid-15388875|pmid-17041189|pmid-15694484|pmid-17041189|pmid-15694484|pmid-7651417|pmid-7651417
The different structural requirements in the peptide of LeishIF4G-3 are most probably required to promote assembly of the parasite eIF4F subunits on the highly modified cap-4 structure.
[ "27", "27" ]
185
39,174
0
false
The different structural requirements in the peptide of LeishIF4G-3 are most probably required to promote assembly of the parasite eIF4F subunits on the highly modified cap-4 structure.
[]
The different structural requirements in the peptide of LeishIF4G-3 are most probably required to promote assembly of the parasite eIF4F subunits on the highly modified cap-4 structure.
true
true
true
true
true
6,743
4
DISCUSSION
1
27
[ "B27", "B27" ]
19,321,500
pmid-15388875|pmid-17041189|pmid-15694484|pmid-17041189|pmid-15694484|pmid-7651417|pmid-7651417
The binding of the LeishIF4G-3 peptide to LeishIF4E-1 was also investigated by NMR spectroscopy.
[ "27", "27" ]
96
39,175
0
false
The binding of the LeishIF4G-3 peptide to LeishIF4E-1 was also investigated by NMR spectroscopy.
[]
The binding of the LeishIF4G-3 peptide to LeishIF4E-1 was also investigated by NMR spectroscopy.
true
true
true
true
true
6,743
4
DISCUSSION
1
27
[ "B27", "B27" ]
19,321,500
pmid-15388875|pmid-17041189|pmid-15694484|pmid-17041189|pmid-15694484|pmid-7651417|pmid-7651417
Following the addition of an 18 amino acids LeishIF4G-3 peptide to LeishIF4E-1, chemical shifts were observed, when compared with the LeishIF4E-1 NMR spectra recorded in the absence of the same peptide (Figure 8).
[ "27", "27" ]
213
39,176
0
false
Following the addition of an 18 amino acids LeishIF4G-3 peptide to LeishIF4E-1, chemical shifts were observed, when compared with the LeishIF4E-1 NMR spectra recorded in the absence of the same peptide (Figure 8).
[]
Following the addition of an 18 amino acids LeishIF4G-3 peptide to LeishIF4E-1, chemical shifts were observed, when compared with the LeishIF4E-1 NMR spectra recorded in the absence of the same peptide (Figure 8).
true
true
true
true
true
6,743
4
DISCUSSION
1
27
[ "B27", "B27" ]
19,321,500
pmid-15388875|pmid-17041189|pmid-15694484|pmid-17041189|pmid-15694484|pmid-7651417|pmid-7651417
The resonances that were most strongly affected mapped to amino acids in LeishIF4E-1 that are homologous (by sequence alignment) to the binding site in the mouse and yeast eIF4Es.
[ "27", "27" ]
179
39,177
0
false
The resonances that were most strongly affected mapped to amino acids in LeishIF4E-1 that are homologous (by sequence alignment) to the binding site in the mouse and yeast eIF4Es.
[]
The resonances that were most strongly affected mapped to amino acids in LeishIF4E-1 that are homologous (by sequence alignment) to the binding site in the mouse and yeast eIF4Es.
true
true
true
true
true
6,743
5
DISCUSSION
1
40
[ "B40" ]
19,321,500
pmid-10666465
The deviations of the cap-4 binding complex of Leishmania from its higher eukaryote counterpart are further emphasized by the inability of LeishIF4G-3 to bind the murine eIF4E (Figure 3).
[ "40" ]
187
39,178
0
false
The deviations of the cap-4 binding complex of Leishmania from its higher eukaryote counterpart are further emphasized by the inability of LeishIF4G-3 to bind the murine eIF4E (Figure 3).
[]
The deviations of the cap-4 binding complex of Leishmania from its higher eukaryote counterpart are further emphasized by the inability of LeishIF4G-3 to bind the murine eIF4E (Figure 3).
true
true
true
true
true
6,744
5
DISCUSSION
1
40
[ "B40" ]
19,321,500
pmid-10666465
This can be partly due to changes in the eIF4E binding peptide that are described above, and to the fact that the amino terminus of LeishIF4G-3 is rather short, questioning its ability to create the ‘molecular bracelet’ that has been shown for the yeast eIF4G.
[ "40" ]
260
39,179
0
false
This can be partly due to changes in the eIF4E binding peptide that are described above, and to the fact that the amino terminus of LeishIF4G-3 is rather short, questioning its ability to create the ‘molecular bracelet’ that has been shown for the yeast eIF4G.
[]
This can be partly due to changes in the eIF4E binding peptide that are described above, and to the fact that the amino terminus of LeishIF4G-3 is rather short, questioning its ability to create the ‘molecular bracelet’ that has been shown for the yeast eIF4G.
true
true
true
true
true
6,744
5
DISCUSSION
1
40
[ "B40" ]
19,321,500
pmid-10666465
In higher eukaryotes, the amino terminus is also responsible for interacting with the PABP at the 3′-end of the mRNA.
[ "40" ]
117
39,180
0
false
In higher eukaryotes, the amino terminus is also responsible for interacting with the PABP at the 3′-end of the mRNA.
[]
In higher eukaryotes, the amino terminus is also responsible for interacting with the PABP at the 3′-end of the mRNA.
true
true
true
true
true
6,744
5
DISCUSSION
1
40
[ "B40" ]
19,321,500
pmid-10666465
This is in agreement with our inability to show direct binding of LeishIF4G-3 to the Leishmania PABP (40) in the yeast two-hybrid assay (data not shown).
[ "40" ]
153
39,181
1
false
This is in agreement with our inability to show direct binding of LeishIF4G-3 to the Leishmania PABP in the yeast two-hybrid assay (data not shown).
[ "40" ]
This is in agreement with our inability to show direct binding of LeishIF4G-3 to the Leishmania PABP in the yeast two-hybrid assay (data not shown).
true
true
true
true
true
6,744
5
DISCUSSION
1
40
[ "B40" ]
19,321,500
pmid-10666465
At this stage we cannot exclude the possibility that the translation initiation complex in Leishmania may contain additional components that complement the function of the LeishIF4G-3 amino terminus in stabilizing the LeishIF4F complex.
[ "40" ]
236
39,182
0
false
At this stage we cannot exclude the possibility that the translation initiation complex in Leishmania may contain additional components that complement the function of the LeishIF4G-3 amino terminus in stabilizing the LeishIF4F complex.
[]
At this stage we cannot exclude the possibility that the translation initiation complex in Leishmania may contain additional components that complement the function of the LeishIF4G-3 amino terminus in stabilizing the LeishIF4F complex.
true
true
true
true
true
6,744
6
DISCUSSION
1
31
[ "B31" ]
19,321,500
pmid-17041189
Unlike most eIF4E homologs from higher eukaryotes, LeishIF4E-4 has a relatively long amino terminus of about 100 amino acids, and overall shows a low degree of conservation with eIF4E from higher eukaryotes.
[ "31" ]
207
39,183
0
false
Unlike most eIF4E homologs from higher eukaryotes, LeishIF4E-4 has a relatively long amino terminus of about 100 amino acids, and overall shows a low degree of conservation with eIF4E from higher eukaryotes.
[]
Unlike most eIF4E homologs from higher eukaryotes, LeishIF4E-4 has a relatively long amino terminus of about 100 amino acids, and overall shows a low degree of conservation with eIF4E from higher eukaryotes.
true
true
true
true
true
6,745
6
DISCUSSION
1
31
[ "B31" ]
19,321,500
pmid-17041189
Furthermore, part of the residues that occupy positions which are expected to interact with eIF4G are not conserved (31).
[ "31" ]
121
39,184
1
false
Furthermore, part of the residues that occupy positions which are expected to interact with eIF4G are not conserved.
[ "31" ]
Furthermore, part of the residues that occupy positions which are expected to interact with eIF4G are not conserved.
true
true
true
true
true
6,745
6
DISCUSSION
1
31
[ "B31" ]
19,321,500
pmid-17041189
This includes exchange of the murine histidine 37 and proline 38 by methionine residues at both positions in LeishIF4E-4.
[ "31" ]
121
39,185
0
false
This includes exchange of the murine histidine 37 and proline 38 by methionine residues at both positions in LeishIF4E-4.
[]
This includes exchange of the murine histidine 37 and proline 38 by methionine residues at both positions in LeishIF4E-4.
true
true
true
true
true
6,745
7
DISCUSSION
1
41
[ "B41" ]
19,321,500
pmid-17254965
In conclusion, the variability in the amino termini of LeishIF4G-3 and LeishIF4E-4, as well as the specific changes of conserved amino acids that are expected to promote the interaction between them, could represent adaptations that occurred during evolution to enable the eIF4F assembly on the unique cap-4 moiety in tr...
[ "41" ]
334
39,186
0
false
In conclusion, the variability in the amino termini of LeishIF4G-3 and LeishIF4E-4, as well as the specific changes of conserved amino acids that are expected to promote the interaction between them, could represent adaptations that occurred during evolution to enable the eIF4F assembly on the unique cap-4 moiety in tr...
[]
In conclusion, the variability in the amino termini of LeishIF4G-3 and LeishIF4E-4, as well as the specific changes of conserved amino acids that are expected to promote the interaction between them, could represent adaptations that occurred during evolution to enable the eIF4F assembly on the unique cap-4 moiety in tr...
true
true
true
true
true
6,746
7
DISCUSSION
1
41
[ "B41" ]
19,321,500
pmid-17254965
In view of the above, we further speculate that the cap-4 binding complex could possibly serve as an intriguing target for the development of novel drugs, as shown for eukaryotes, where inhibitors of the interaction between eIF4E and eIF4G affect the growth of malignant cells in culture (41).
[ "41" ]
293
39,187
1
false
In view of the above, we further speculate that the cap-4 binding complex could possibly serve as an intriguing target for the development of novel drugs, as shown for eukaryotes, where inhibitors of the interaction between eIF4E and eIF4G affect the growth of malignant cells in culture.
[ "41" ]
In view of the above, we further speculate that the cap-4 binding complex could possibly serve as an intriguing target for the development of novel drugs, as shown for eukaryotes, where inhibitors of the interaction between eIF4E and eIF4G affect the growth of malignant cells in culture.
true
true
true
true
true
6,746
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B7" ]
20,157,602
pmid-371790|pmid-15035904|pmid-279931|pmid-10963459|pmid-3965937
The role of ascorbate (vitamin C) in cancer treatment is a subject with a controversial history (1,2).
[ "1", "2", "3", "4", "7" ]
102
39,188
0
false
The role of ascorbate (vitamin C) in cancer treatment is a subject with a controversial history.
[ "1,2" ]
The role of ascorbate (vitamin C) in cancer treatment is a subject with a controversial history.
true
true
true
true
true
6,747
0
INTRODUCTION
1
3
[ "B1", "B2", "B3", "B4", "B7" ]
20,157,602
pmid-371790|pmid-15035904|pmid-279931|pmid-10963459|pmid-3965937
The core of this controversy is the lack of reproducibility of the therapeutic effects of ascorbate on cancer patients (3), a problem compounded by uncertainties associated with deficiencies of independent pathologic confirmation and failure to include appropriate placebo groups in clinical studies (4-7).
[ "1", "2", "3", "4", "7" ]
306
39,189
1
false
The core of this controversy is the lack of reproducibility of the therapeutic effects of ascorbate on cancer patients, a problem compounded by uncertainties associated with deficiencies of independent pathologic confirmation and failure to include appropriate placebo groups in clinical studies.
[ "3", "4-7" ]
The core of this controversy is the lack of reproducibility of the therapeutic effects of ascorbate on cancer patients, a problem compounded by uncertainties associated with deficiencies of independent pathologic confirmation and failure to include appropriate placebo groups in clinical studies.
true
true
true
true
true
6,747
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B7" ]
20,157,602
pmid-371790|pmid-15035904|pmid-279931|pmid-10963459|pmid-3965937
However, more recent studies on the therapeutic effects of ascorbate have provided a clearer understanding of its effect in cancer treatment.
[ "1", "2", "3", "4", "7" ]
141
39,190
0
false
However, more recent studies on the therapeutic effects of ascorbate have provided a clearer understanding of its effect in cancer treatment.
[]
However, more recent studies on the therapeutic effects of ascorbate have provided a clearer understanding of its effect in cancer treatment.
true
true
true
true
true
6,747
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B7" ]
20,157,602
pmid-371790|pmid-15035904|pmid-279931|pmid-10963459|pmid-3965937
The action of ascorbate in cancer cells has also been more clearly defined by in vitro studies.
[ "1", "2", "3", "4", "7" ]
95
39,191
0
false
The action of ascorbate in cancer cells has also been more clearly defined by in vitro studies.
[]
The action of ascorbate in cancer cells has also been more clearly defined by in vitro studies.
true
true
true
true
true
6,747
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B7" ]
20,157,602
pmid-371790|pmid-15035904|pmid-279931|pmid-10963459|pmid-3965937
In this review, we summarize these new findings and discuss the biological mechanism of action of ascorbate in cancer therapy.
[ "1", "2", "3", "4", "7" ]
126
39,192
0
false
In this review, we summarize these new findings and discuss the biological mechanism of action of ascorbate in cancer therapy.
[]
In this review, we summarize these new findings and discuss the biological mechanism of action of ascorbate in cancer therapy.
true
true
true
true
true
6,747
0
DISCUSSION
1
13
[ "bib13", "bib14" ]
19,153,216
pmid-16371515|pmid-16528796
If the effect of treatment varies with the propensity score, different approaches to estimating it will give different results.
[ "13", "14" ]
127
39,193
0
false
If the effect of treatment varies with the propensity score, different approaches to estimating it will give different results.
[]
If the effect of treatment varies with the propensity score, different approaches to estimating it will give different results.
true
true
true
true
true
6,748
0
DISCUSSION
1
13
[ "bib13", "bib14" ]
19,153,216
pmid-16371515|pmid-16528796
This phenomenon has been observed by Kurth et al.
[ "13", "14" ]
49
39,194
0
false
This phenomenon has been observed by Kurth et al.
[]
This phenomenon has been observed by Kurth et al.
true
true
true
true
true
6,748
0
DISCUSSION
1
13
[ "bib13", "bib14" ]
19,153,216
pmid-16371515|pmid-16528796
and was commented on by Stürmer et al.
[ "13", "14" ]
38
39,195
0
false
and was commented on by Stürmer et al.
[]
and was commented on by Stürmer et al.
false
true
true
true
false
6,748
0
DISCUSSION
1
13
[ "bib13", "bib14" ]
19,153,216
pmid-16371515|pmid-16528796
The reason is that the different methods are effectively estimating the effect in different populations, with different distributions of covariates.
[ "13", "14" ]
148
39,196
0
false
The reason is that the different methods are effectively estimating the effect in different populations, with different distributions of covariates.
[]
The reason is that the different methods are effectively estimating the effect in different populations, with different distributions of covariates.
true
true
true
true
true
6,748
0
DISCUSSION
1
13
[ "bib13", "bib14" ]
19,153,216
pmid-16371515|pmid-16528796
So, which is the best estimate to use?
[ "13", "14" ]
38
39,197
0
false
So, which is the best estimate to use?
[]
So, which is the best estimate to use?
true
true
true
true
true
6,748
1
DISCUSSION
0
null
null
19,153,216
null
In fact, every estimate has the drawback that it applies to only one particular distribution of covariates.
null
107
39,198
0
false
null
null
In fact, every estimate has the drawback that it applies to only one particular distribution of covariates.
true
true
true
true
true
6,749
1
DISCUSSION
0
null
null
19,153,216
null
A population with a different distribution of covariates will have a different treatment effect.
null
96
39,199
0
false
null
null
A population with a different distribution of covariates will have a different treatment effect.
true
true
true
true
true
6,749
1
DISCUSSION
0
null
null
19,153,216
null
This property implies that no single estimate could be guaranteed to apply to any subsequent population.
null
104
39,200
0
false
null
null
This property implies that no single estimate could be guaranteed to apply to any subsequent population.
true
true
true
true
true
6,749
1
DISCUSSION
0
null
null
19,153,216
null
In the presence of effect modification, however, the same would be true of the effect estimate from a randomized trial: if the treatment were subsequently used in a population with a different distribution of covariates, the expected treatment effect would differ from that seen in the trial.
null
292
39,201
0
false
null
null
In the presence of effect modification, however, the same would be true of the effect estimate from a randomized trial: if the treatment were subsequently used in a population with a different distribution of covariates, the expected treatment effect would differ from that seen in the trial.
true
true
true
true
true
6,749
2
DISCUSSION
0
null
null
19,153,216
null
Our analysis shows how a specific treatment effect varies across propensity quintiles.
null
86
39,202
0
false
null
null
Our analysis shows how a specific treatment effect varies across propensity quintiles.
true
true
true
true
true
6,750
2
DISCUSSION
0
null
null
19,153,216
null
In practice, it would be important to show how the treatment effect differed according to the variables that made up the propensity score: doing so would enable clinicians to judge the likely effect of that treatment in a given patient.
null
236
39,203
0
false
null
null
In practice, it would be important to show how the treatment effect differed according to the variables that made up the propensity score: doing so would enable clinicians to judge the likely effect of that treatment in a given patient.
true
true
true
true
true
6,750
3
DISCUSSION
0
null
null
19,153,216
null
There are drawbacks to presenting an overall effect of treatment when the effect in fact varies between different types of individuals.
null
135
39,204
0
false
null
null
There are drawbacks to presenting an overall effect of treatment when the effect in fact varies between different types of individuals.
true
true
true
true
true
6,751
3
DISCUSSION
0
null
null
19,153,216
null
Still, each overall effect estimate can be interpreted as the effect of treatment on a particular population.
null
109
39,205
0
false
null
null
Still, each overall effect estimate can be interpreted as the effect of treatment on a particular population.
true
true
true
true
true
6,751
3
DISCUSSION
0
null
null
19,153,216
null
Both the standardized mortality ratio–weighted estimator and that derived from matching with replacement measure the average effect of treatment in those who are treated, that isThis causal parameter may be of interest as a measure of how the exposure affected the subjects who were exposed.
null
291
39,206
0
false
null
null
Both the standardized mortality ratio–weighted estimator and that derived from matching with replacement measure the average effect of treatment in those who are treated, that isThis causal parameter may be of interest as a measure of how the exposure affected the subjects who were exposed.
true
true
true
true
true
6,751
4
DISCUSSION
0
null
null
19,153,216
null
The inverse probability of treatment–weighting estimator measureswhich may again be of some interest in a particular population.
null
128
39,207
0
false
null
null
The inverse probability of treatment–weighting estimator measureswhich may again be of some interest in a particular population.
true
true
true
true
true
6,752
5
DISCUSSION
1
14
[ "bib14" ]
19,153,216
pmid-16528796
In contrast, the matching without replacement estimator gives a measure of the average effect of treatment in those exposed subjects for whom a match can be found, which is a subpopulation of the exposed unlikely to be of any interest.
[ "14" ]
235
39,208
0
false
In contrast, the matching without replacement estimator gives a measure of the average effect of treatment in those exposed subjects for whom a match can be found, which is a subpopulation of the exposed unlikely to be of any interest.
[]
In contrast, the matching without replacement estimator gives a measure of the average effect of treatment in those exposed subjects for whom a match can be found, which is a subpopulation of the exposed unlikely to be of any interest.
true
true
true
true
true
6,753
5
DISCUSSION
1
14
[ "bib14" ]
19,153,216
pmid-16528796
Equally, the weights used in the maximum likelihood stratified estimator are chosen to maximize the precision of the estimate, assuming that the effect is constant across strata, and there is no reason why the average effect of treatment in this particular population would be of interest.
[ "14" ]
289
39,209
0
false
Equally, the weights used in the maximum likelihood stratified estimator are chosen to maximize the precision of the estimate, assuming that the effect is constant across strata, and there is no reason why the average effect of treatment in this particular population would be of interest.
[]
Equally, the weights used in the maximum likelihood stratified estimator are chosen to maximize the precision of the estimate, assuming that the effect is constant across strata, and there is no reason why the average effect of treatment in this particular population would be of interest.
true
true
true
true
true
6,753
5
DISCUSSION
1
14
[ "bib14" ]
19,153,216
pmid-16528796
An alternative would be to standardize the stratum-specific estimates to a specified distribution of propensity scores.
[ "14" ]
119
39,210
0
false
An alternative would be to standardize the stratum-specific estimates to a specified distribution of propensity scores.
[]
An alternative would be to standardize the stratum-specific estimates to a specified distribution of propensity scores.
true
true
true
true
true
6,753
5
DISCUSSION
1
14
[ "bib14" ]
19,153,216
pmid-16528796
For example, one could calculate a standardized mortality ratio from the stratum-specific estimates (14).
[ "14" ]
105
39,211
1
false
For example, one could calculate a standardized mortality ratio from the stratum-specific estimates.
[ "14" ]
For example, one could calculate a standardized mortality ratio from the stratum-specific estimates.
true
true
true
true
true
6,753
6
DISCUSSION
0
null
null
19,153,216
null
All of the estimates have a valid interpretation as the overall benefit of treatment in a given population.
null
107
39,212
0
false
null
null
All of the estimates have a valid interpretation as the overall benefit of treatment in a given population.
true
true
true
true
true
6,754
6
DISCUSSION
0
null
null
19,153,216
null
However, they are valid only if the assumptions of the propensity score methodology are satisfied, that is, if there are no unmeasured confounders, the propensity score model is correctly specified, the study size is sufficiently large to make the asymptotically unbiased estimator in fact unbiased, and the standard err...
null
337
39,213
0
false
null
null
However, they are valid only if the assumptions of the propensity score methodology are satisfied, that is, if there are no unmeasured confounders, the propensity score model is correctly specified, the study size is sufficiently large to make the asymptotically unbiased estimator in fact unbiased, and the standard err...
true
true
true
true
true
6,754
7
DISCUSSION
0
null
null
19,153,216
null
The increasing mortality rate among the unexposed subjects is extremely unusual.
null
80
39,214
0
false
null
null
The increasing mortality rate among the unexposed subjects is extremely unusual.
true
true
true
true
true
6,755
7
DISCUSSION
0
null
null
19,153,216
null
Although it is theoretically possible that increasing disease severity is associated with increased mortality in the unexposed but not in the exposed, a more likely explanation of this almost-10-fold increase in rate is unmeasured confounding in the upper quintiles.
null
266
39,215
0
false
null
null
Although it is theoretically possible that increasing disease severity is associated with increased mortality in the unexposed but not in the exposed, a more likely explanation of this almost-10-fold increase in rate is unmeasured confounding in the upper quintiles.
true
true
true
true
true
6,755