Datasets:
vgainullin
/
xciting_data

Dataset card Data Studio Files
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INTRODUCTION
1
2
[ "R1", "R2" ]
20,556,200
NA|pmid-17624822|NA|NA|NA|pmid-16055883
Staining of slides by Ziehl-Neelsen (ZN) methods for AFB diagnosis remain the main procedure utilized in these countries, while fluorescent microscopy has been used in developed countries for decades in the identification of M. tuberculosis in clinical specimens [2].
[ "1", "2" ]
267
39,816
1
false
Staining of slides by Ziehl-Neelsen (ZN) methods for AFB diagnosis remain the main procedure utilized in these countries, while fluorescent microscopy has been used in developed countries for decades in the identification of M. tuberculosis in clinical specimens.
[ "2" ]
Staining of slides by Ziehl-Neelsen (ZN) methods for AFB diagnosis remain the main procedure utilized in these countries, while fluorescent microscopy has been used in developed countries for decades in the identification of M. tuberculosis in clinical specimens.
true
true
true
true
true
6,882
0
INTRODUCTION
1
1
[ "R1", "R2" ]
20,556,200
NA|pmid-17624822|NA|NA|NA|pmid-16055883
Acid fast staining and microscopy is technically challenging and labor intensive.
[ "1", "2" ]
81
39,817
0
false
Acid fast staining and microscopy is technically challenging and labor intensive.
[]
Acid fast staining and microscopy is technically challenging and labor intensive.
true
true
true
true
true
6,882
0
INTRODUCTION
1
1
[ "R1", "R2" ]
20,556,200
NA|pmid-17624822|NA|NA|NA|pmid-16055883
Culture techniques, the gold standard for tuberculosis diagnosis, are also expensive, technically difficult and generally not available in developing countries.
[ "1", "2" ]
160
39,818
0
false
Culture techniques, the gold standard for tuberculosis diagnosis, are also expensive, technically difficult and generally not available in developing countries.
[]
Culture techniques, the gold standard for tuberculosis diagnosis, are also expensive, technically difficult and generally not available in developing countries.
true
true
true
true
true
6,882
0
INTRODUCTION
1
1
[ "R1", "R2" ]
20,556,200
NA|pmid-17624822|NA|NA|NA|pmid-16055883
Fluorescent microscopy of sputum smears is an alternative to traditional AFB (acid fast bacilli) staining and light microscopy.
[ "1", "2" ]
127
39,819
0
false
Fluorescent microscopy of sputum smears is an alternative to traditional AFB (acid fast bacilli) staining and light microscopy.
[]
Fluorescent microscopy of sputum smears is an alternative to traditional AFB (acid fast bacilli) staining and light microscopy.
true
true
true
true
true
6,882
0
INTRODUCTION
1
1
[ "R1", "R2" ]
20,556,200
NA|pmid-17624822|NA|NA|NA|pmid-16055883
A portable LED (light-emitting diode) fluorescent adaptor, called ParaLens™ (QBC Diagnostic Inc., Port Matilda, PA), allows a traditional light microscope to utilize fluorescent technology.
[ "1", "2" ]
189
39,820
0
false
A portable LED (light-emitting diode) fluorescent adaptor, called ParaLens™ (QBC Diagnostic Inc., Port Matilda, PA), allows a traditional light microscope to utilize fluorescent technology.
[]
A portable LED (light-emitting diode) fluorescent adaptor, called ParaLens™ (QBC Diagnostic Inc., Port Matilda, PA), allows a traditional light microscope to utilize fluorescent technology.
true
true
true
true
true
6,882
0
INTRODUCTION
1
1
[ "R1", "R2" ]
20,556,200
NA|pmid-17624822|NA|NA|NA|pmid-16055883
However, little is known about the functionality of LED-based systems for AFB fluorescent microscopy in the developing world.
[ "1", "2" ]
125
39,821
0
false
However, little is known about the functionality of LED-based systems for AFB fluorescent microscopy in the developing world.
[]
However, little is known about the functionality of LED-based systems for AFB fluorescent microscopy in the developing world.
true
true
true
true
true
6,882
0
INTRODUCTION
1
1
[ "R1", "R2" ]
20,556,200
NA|pmid-17624822|NA|NA|NA|pmid-16055883
Therefore the purpose of this study was to test this ParaLens system (an updated version from a previous non-QBC based attachment) and thus fluorescent microscopy in various urban and rural resource poor settings lacking conventional laboratory facilities to determine its usefulness in these environments.
[ "1", "2" ]
306
39,822
0
false
Therefore the purpose of this study was to test this ParaLens system (an updated version from a previous non-QBC based attachment) and thus fluorescent microscopy in various urban and rural resource poor settings lacking conventional laboratory facilities to determine its usefulness in these environments.
[]
Therefore the purpose of this study was to test this ParaLens system (an updated version from a previous non-QBC based attachment) and thus fluorescent microscopy in various urban and rural resource poor settings lacking conventional laboratory facilities to determine its usefulness in these environments.
true
true
true
true
true
6,882
0
INTRODUCTION
1
1
[ "R1", "R2" ]
20,556,200
NA|pmid-17624822|NA|NA|NA|pmid-16055883
The authors also compared the accuracy of the ParaLens versus a traditional fluorescent microscope in a controlled setting for the diagnosis of mycobacterial disease in a public health laboratory in the United States.
[ "1", "2" ]
217
39,823
0
false
The authors also compared the accuracy of the ParaLens versus a traditional fluorescent microscope in a controlled setting for the diagnosis of mycobacterial disease in a public health laboratory in the United States.
[]
The authors also compared the accuracy of the ParaLens versus a traditional fluorescent microscope in a controlled setting for the diagnosis of mycobacterial disease in a public health laboratory in the United States.
true
true
true
true
true
6,882
0
DISCUSSION
1
1
[ "R1", "R5", "R5", "R6" ]
20,556,200
NA|pmid-17624822|NA|NA|NA|pmid-16055883
Tuberculosis is a leading cause of morbidity and mortality worldwide, especially in resource-limited settings [1, 5].
[ "1", " 5", "5", "6" ]
117
39,824
0
false
Tuberculosis is a leading cause of morbidity and mortality worldwide, especially in resource-limited settings.
[ "1, 5" ]
Tuberculosis is a leading cause of morbidity and mortality worldwide, especially in resource-limited settings.
true
true
true
true
true
6,883
0
DISCUSSION
1
1
[ "R1", "R5", "R5", "R6" ]
20,556,200
NA|pmid-17624822|NA|NA|NA|pmid-16055883
The WHO has made the recognition and treatment of patients with tuberculosis one of its highest priorities.
[ "1", " 5", "5", "6" ]
107
39,825
0
false
The WHO has made the recognition and treatment of patients with tuberculosis one of its highest priorities.
[]
The WHO has made the recognition and treatment of patients with tuberculosis one of its highest priorities.
true
true
true
true
true
6,883
0
DISCUSSION
1
1
[ "R1", "R5", "R5", "R6" ]
20,556,200
NA|pmid-17624822|NA|NA|NA|pmid-16055883
Research and development of improved diagnostics is one of the main goals set in The Global Plan to Stop TB 2006-2015 (WHO)
[ "1", " 5", "5", "6" ]
123
39,826
0
false
Research and development of improved diagnostics is one of the main goals set in The Global Plan to Stop TB 2006-2015 (WHO)
[]
Research and development of improved diagnostics is one of the main goals set in The Global Plan to Stop TB 2006-2015 (WHO)
true
true
false
true
false
6,883
0
DISCUSSION
1
6
[ "R1", "R5", "R5", "R6" ]
20,556,200
NA|pmid-17624822|NA|NA|NA|pmid-16055883
To meet these needs, diagnostic tools must be made more adequate than currently utilized methods and must also be safe, affordable and easy to use [6].
[ "1", " 5", "5", "6" ]
151
39,827
1
false
To meet these needs, diagnostic tools must be made more adequate than currently utilized methods and must also be safe, affordable and easy to use.
[ "6" ]
To meet these needs, diagnostic tools must be made more adequate than currently utilized methods and must also be safe, affordable and easy to use.
true
true
true
true
true
6,883
1
DISCUSSION
1
7
[ "R7" ]
20,556,200
pmid-9542935
Fluorescent microscopy methods for the identification of acid-fast organisms have become the mainstay of many mycobacteriological laboratories in the United States and around the world [7].
[ "7" ]
189
39,828
1
false
Fluorescent microscopy methods for the identification of acid-fast organisms have become the mainstay of many mycobacteriological laboratories in the United States and around the world.
[ "7" ]
Fluorescent microscopy methods for the identification of acid-fast organisms have become the mainstay of many mycobacteriological laboratories in the United States and around the world.
true
true
true
true
true
6,884
1
DISCUSSION
1
7
[ "R7" ]
20,556,200
pmid-9542935
In standard acid-fast microscopy, the oil immersion lens is used to scan the slide (1000x magnification) while in fluorescent microscopy, lesser magnification is used, thus saving a significant amount of time on each negative slide.
[ "7" ]
232
39,829
0
false
In standard acid-fast microscopy, the oil immersion lens is used to scan the slide (1000x magnification) while in fluorescent microscopy, lesser magnification is used, thus saving a significant amount of time on each negative slide.
[]
In standard acid-fast microscopy, the oil immersion lens is used to scan the slide (1000x magnification) while in fluorescent microscopy, lesser magnification is used, thus saving a significant amount of time on each negative slide.
true
true
true
true
true
6,884
1
DISCUSSION
1
7
[ "R7" ]
20,556,200
pmid-9542935
Fluorescent microscopy is preferred in healthcare settings with large numbers of specimens submitted for suspected mycobacterial disease.
[ "7" ]
137
39,830
0
false
Fluorescent microscopy is preferred in healthcare settings with large numbers of specimens submitted for suspected mycobacterial disease.
[]
Fluorescent microscopy is preferred in healthcare settings with large numbers of specimens submitted for suspected mycobacterial disease.
true
true
true
true
true
6,884
2
DISCUSSION
1
8
[ "R8", "R9", "R6", "R10", "R12" ]
20,556,200
pmid-17620757|pmid-18405928|pmid-16055883|pmid-16931408|pmid-18532893
The use of improved diagnostics including fluorescent microscopy (such as the ParaLens system) in developing nations has been limited by lack of infrastructure, trained laboratory staff and lack of funding [8, 9].
[ "8", " 9", "6", " 10", "12" ]
213
39,831
0
false
The use of improved diagnostics including fluorescent microscopy (such as the ParaLens system) in developing nations has been limited by lack of infrastructure, trained laboratory staff and lack of funding.
[ "8, 9" ]
The use of improved diagnostics including fluorescent microscopy (such as the ParaLens system) in developing nations has been limited by lack of infrastructure, trained laboratory staff and lack of funding.
true
true
true
true
true
6,885
2
DISCUSSION
1
8
[ "R8", "R9", "R6", "R10", "R12" ]
20,556,200
pmid-17620757|pmid-18405928|pmid-16055883|pmid-16931408|pmid-18532893
However, fluorescent microscopy is potentially more sensitive and less labor intensive than traditional light microscopy using the Ziehl-Neelsen or Kinyoun method for the identification of acid-fast bacilli
[ "8", " 9", "6", " 10", "12" ]
206
39,832
0
false
However, fluorescent microscopy is potentially more sensitive and less labor intensive than traditional light microscopy using the Ziehl-Neelsen or Kinyoun method for the identification of acid-fast bacilli
[]
However, fluorescent microscopy is potentially more sensitive and less labor intensive than traditional light microscopy using the Ziehl-Neelsen or Kinyoun method for the identification of acid-fast bacilli
true
true
false
true
false
6,885
2
DISCUSSION
1
8
[ "R8", "R9", "R6", "R10", "R12" ]
20,556,200
pmid-17620757|pmid-18405928|pmid-16055883|pmid-16931408|pmid-18532893
[6, 10-12].
[ "8", " 9", "6", " 10", "12" ]
11
39,833
0
false
.
[ "6, 10-12" ]
.
false
false
true
true
false
6,885
2
DISCUSSION
1
8
[ "R8", "R9", "R6", "R10", "R12" ]
20,556,200
pmid-17620757|pmid-18405928|pmid-16055883|pmid-16931408|pmid-18532893
Thus microscopists trained using conventional fluorescent staining and dark-field microscopy will have no problem reading slides with the ParaLens, as the technology is virtually the same.
[ "8", " 9", "6", " 10", "12" ]
188
39,834
0
false
Thus microscopists trained using conventional fluorescent staining and dark-field microscopy will have no problem reading slides with the ParaLens, as the technology is virtually the same.
[]
Thus microscopists trained using conventional fluorescent staining and dark-field microscopy will have no problem reading slides with the ParaLens, as the technology is virtually the same.
true
true
true
true
true
6,885
3
DISCUSSION
1
13
[ "R13", "R14", "R12", "R15" ]
20,556,200
pmid-7535314|pmid-8458971|pmid-18532893|pmid-16546544
Therefore the ParaLens system is uniquely suited for application in developing countries.
[ "13", " 14", "12", "15" ]
89
39,835
0
false
Therefore the ParaLens system is uniquely suited for application in developing countries.
[]
Therefore the ParaLens system is uniquely suited for application in developing countries.
true
true
true
true
true
6,886
3
DISCUSSION
1
13
[ "R13", "R14", "R12", "R15" ]
20,556,200
pmid-7535314|pmid-8458971|pmid-18532893|pmid-16546544
Lower costs than traditional fluorescent scopes provides affordability, and as demonstrated in this study, it is functional, durable, accurate and easy to use in rural, resource poor field environments and with various power options.
[ "13", " 14", "12", "15" ]
233
39,836
0
false
Lower costs than traditional fluorescent scopes provides affordability, and as demonstrated in this study, it is functional, durable, accurate and easy to use in rural, resource poor field environments and with various power options.
[]
Lower costs than traditional fluorescent scopes provides affordability, and as demonstrated in this study, it is functional, durable, accurate and easy to use in rural, resource poor field environments and with various power options.
true
true
true
true
true
6,886
3
DISCUSSION
1
13
[ "R13", "R14", "R12", "R15" ]
20,556,200
pmid-7535314|pmid-8458971|pmid-18532893|pmid-16546544
The attachment avoids the purchase of a second microscope, since it utilizes an already existing compound microscope.
[ "13", " 14", "12", "15" ]
117
39,837
0
false
The attachment avoids the purchase of a second microscope, since it utilizes an already existing compound microscope.
[]
The attachment avoids the purchase of a second microscope, since it utilizes an already existing compound microscope.
true
true
true
true
true
6,886
3
DISCUSSION
1
13
[ "R13", "R14", "R12", "R15" ]
20,556,200
pmid-7535314|pmid-8458971|pmid-18532893|pmid-16546544
Previous studies have tested a non-QBC ParaLens system utilizing a halogen bulb and fiber-optic cable, which limited the bulb life and luminosity [13, 14].
[ "13", " 14", "12", "15" ]
155
39,838
0
false
Previous studies have tested a non-QBC ParaLens system utilizing a halogen bulb and fiber-optic cable, which limited the bulb life and luminosity.
[ "13, 14" ]
Previous studies have tested a non-QBC ParaLens system utilizing a halogen bulb and fiber-optic cable, which limited the bulb life and luminosity.
true
true
true
true
true
6,886
3
DISCUSSION
1
13
[ "R13", "R14", "R12", "R15" ]
20,556,200
pmid-7535314|pmid-8458971|pmid-18532893|pmid-16546544
The use of LED bulbs in place of standard fluorescent bulbs provides extended life (estimated to be 15-30,000 hours), much longer compared to the life of a standard bulb (estimated 800 hours).
[ "13", " 14", "12", "15" ]
192
39,839
0
false
The use of LED bulbs in place of standard fluorescent bulbs provides extended life, much longer compared to the life of a standard bulb (estimated 800 hours).
[ "estimated to be 15-30,000 hours" ]
The use of LED bulbs in place of standard fluorescent bulbs provides extended life, much longer compared to the life of a standard bulb (estimated 800 hours).
true
true
true
true
true
6,886
3
DISCUSSION
1
13
[ "R13", "R14", "R12", "R15" ]
20,556,200
pmid-7535314|pmid-8458971|pmid-18532893|pmid-16546544
The attachment can be used with standard 110V electricity, 220V electricity and with a battery for locations without electricity.
[ "13", " 14", "12", "15" ]
129
39,840
0
false
The attachment can be used with standard 110V electricity, 220V electricity and with a battery for locations without electricity.
[]
The attachment can be used with standard 110V electricity, 220V electricity and with a battery for locations without electricity.
true
true
true
true
true
6,886
3
DISCUSSION
1
13
[ "R13", "R14", "R12", "R15" ]
20,556,200
pmid-7535314|pmid-8458971|pmid-18532893|pmid-16546544
The attachment compared favorably with more expensive conventional fluorescent microscopes in brightness, clarity and ease of viewing (see Figs.
[ "13", " 14", "12", "15" ]
144
39,841
0
false
The attachment compared favorably with more expensive conventional fluorescent microscopes in brightness, clarity and ease of viewing (see Figs.
[]
The attachment compared favorably with more expensive conventional fluorescent microscopes in brightness, clarity and ease of viewing (see Figs.
true
true
true
true
true
6,886
3
DISCUSSION
1
13
[ "R13", "R14", "R12", "R15" ]
20,556,200
pmid-7535314|pmid-8458971|pmid-18532893|pmid-16546544
Other authors have also found that the use of such equipment can indeed provide an excellent tool for identification of mycobacteria and can be a useful alternative to conventional fluorescent microscopy
[ "13", " 14", "12", "15" ]
203
39,842
0
false
Other authors have also found that the use of such equipment can indeed provide an excellent tool for identification of mycobacteria and can be a useful alternative to conventional fluorescent microscopy
[]
Other authors have also found that the use of such equipment can indeed provide an excellent tool for identification of mycobacteria and can be a useful alternative to conventional fluorescent microscopy
true
true
false
true
false
6,886
4
DISCUSSION
0
null
null
20,556,200
null
One limitation of this study was that the results were based on known positive and negative control slides prepared in the United States.
null
137
39,843
0
false
null
null
One limitation of this study was that the results were based on known positive and negative control slides prepared in the United States.
true
true
true
true
true
6,887
4
DISCUSSION
0
null
null
20,556,200
null
While this does not affect the durability portion of the study, it is possible that sputum samples collected from patients outside the controlled setting of a public health laboratory in the United States under field conditions in the developing world may stain differently.
null
274
39,844
0
false
null
null
While this does not affect the durability portion of the study, it is possible that sputum samples collected from patients outside the controlled setting of a public health laboratory in the United States under field conditions in the developing world may stain differently.
true
true
true
true
true
6,887
0
DISCUSSION
1
52
[ "bib52", "bib53" ]
17,646,409
pmid-10221902|pmid-17168741
The early successes of molecularly targeted therapy, such as imatinib mesylate directed against the BCR-ABL fusion protein in chronic myelogenous leukemia, stimulated enormous interest in subverting abnormal signaling pathways in cancer cells.
[ "52", "53" ]
243
39,845
0
false
The early successes of molecularly targeted therapy, such as imatinib mesylate directed against the BCR-ABL fusion protein in chronic myelogenous leukemia, stimulated enormous interest in subverting abnormal signaling pathways in cancer cells.
[]
The early successes of molecularly targeted therapy, such as imatinib mesylate directed against the BCR-ABL fusion protein in chronic myelogenous leukemia, stimulated enormous interest in subverting abnormal signaling pathways in cancer cells.
true
true
true
true
true
6,888
0
DISCUSSION
1
52
[ "bib52", "bib53" ]
17,646,409
pmid-10221902|pmid-17168741
The NOTCH signaling cascade influences normal development by regulating differentiation, proliferation, and apoptosis (52).
[ "52", "53" ]
123
39,846
1
false
The NOTCH signaling cascade influences normal development by regulating differentiation, proliferation, and apoptosis.
[ "52" ]
The NOTCH signaling cascade influences normal development by regulating differentiation, proliferation, and apoptosis.
true
true
true
true
true
6,888
0
DISCUSSION
1
53
[ "bib52", "bib53" ]
17,646,409
pmid-10221902|pmid-17168741
Activation of the NOTCH signaling pathway is firmly established in T-ALL and is likely involved in the genesis of many other tumor types (53).
[ "52", "53" ]
142
39,847
1
false
Activation of the NOTCH signaling pathway is firmly established in T-ALL and is likely involved in the genesis of many other tumor types.
[ "53" ]
Activation of the NOTCH signaling pathway is firmly established in T-ALL and is likely involved in the genesis of many other tumor types.
true
true
true
true
true
6,888
0
DISCUSSION
1
52
[ "bib52", "bib53" ]
17,646,409
pmid-10221902|pmid-17168741
Thus, it is not surprising that efforts to block NOTCH signaling as a novel therapeutic strategy are under way in T-ALL as well as in solid tumors.
[ "52", "53" ]
147
39,848
0
false
Thus, it is not surprising that efforts to block NOTCH signaling as a novel therapeutic strategy are under way in T-ALL as well as in solid tumors.
[]
Thus, it is not surprising that efforts to block NOTCH signaling as a novel therapeutic strategy are under way in T-ALL as well as in solid tumors.
true
true
true
true
true
6,888
0
DISCUSSION
1
52
[ "bib52", "bib53" ]
17,646,409
pmid-10221902|pmid-17168741
One of the most promising approaches has been to inhibit NOTCH receptor signaling using GSIs.
[ "52", "53" ]
93
39,849
0
false
One of the most promising approaches has been to inhibit NOTCH receptor signaling using GSIs.
[]
One of the most promising approaches has been to inhibit NOTCH receptor signaling using GSIs.
true
true
true
true
true
6,888
0
DISCUSSION
1
52
[ "bib52", "bib53" ]
17,646,409
pmid-10221902|pmid-17168741
This strategy suppresses the generation of NICD and thus, in principle, should inhibit the downstream transcriptional events normally induced by this key signaling component after it traverses to the nucleus.
[ "52", "53" ]
208
39,850
0
false
This strategy suppresses the generation of NICD and thus, in principle, should inhibit the downstream transcriptional events normally induced by this key signaling component after it traverses to the nucleus.
[]
This strategy suppresses the generation of NICD and thus, in principle, should inhibit the downstream transcriptional events normally induced by this key signaling component after it traverses to the nucleus.
true
true
true
true
true
6,888
0
DISCUSSION
1
52
[ "bib52", "bib53" ]
17,646,409
pmid-10221902|pmid-17168741
Although effective against some T-ALL cell lines, GSIs do not uniformly eliminate leukemic cells with activated NOTCH signaling.
[ "52", "53" ]
128
39,851
0
false
Although effective against some T-ALL cell lines, GSIs do not uniformly eliminate leukemic cells with activated NOTCH signaling.
[]
Although effective against some T-ALL cell lines, GSIs do not uniformly eliminate leukemic cells with activated NOTCH signaling.
true
true
true
true
true
6,888
0
DISCUSSION
1
52
[ "bib52", "bib53" ]
17,646,409
pmid-10221902|pmid-17168741
Understanding the mechanisms of GSI resistance may lead to better treatments for T-ALL.
[ "52", "53" ]
87
39,852
0
false
Understanding the mechanisms of GSI resistance may lead to better treatments for T-ALL.
[]
Understanding the mechanisms of GSI resistance may lead to better treatments for T-ALL.
true
true
true
true
true
6,888
1
DISCUSSION
0
null
null
17,646,409
null
We found missense FBW7 mutations or homozygous FBW7 deletion in GSI-resistant T-ALL cell lines and in primary T-ALL samples.
null
124
39,853
0
false
null
null
We found missense FBW7 mutations or homozygous FBW7 deletion in GSI-resistant T-ALL cell lines and in primary T-ALL samples.
true
true
true
true
true
6,889
1
DISCUSSION
0
null
null
17,646,409
null
Moreover, we have defined the NOTCH phosphodegron and demonstrated that the mutant forms of FBW7 found in T-ALL cannot bind to the NICD.
null
136
39,854
0
false
null
null
Moreover, we have defined the NOTCH phosphodegron and demonstrated that the mutant forms of FBW7 found in T-ALL cannot bind to the NICD.
true
true
true
true
true
6,889
1
DISCUSSION
0
null
null
17,646,409
null
Each T-ALL cell line with constitutive NICD expression harbored either NOTCH1 PEST domain or FBW7 mutations, suggesting that these two classes of mutations provide a mutually exclusive means of prolonging the NICD half-life.
null
224
39,855
0
false
null
null
Each T-ALL cell line with constitutive NICD expression harbored either NOTCH1 PEST domain or FBW7 mutations, suggesting that these two classes of mutations provide a mutually exclusive means of prolonging the NICD half-life.
true
true
true
true
true
6,889
1
DISCUSSION
0
null
null
17,646,409
null
We also show that the expression of NOTCH target genes including DELTEX1 and MYC are not affected by GSI treatment in five resistant T-ALL cell lines with mutations in FBW7 (CEM, BE13, PEER, DU528, and HSB2), demonstrating that the mechanism of resistance in these leukemias lies upstream of MYC and DELTEX1 transcriptio...
null
322
39,856
0
false
null
null
We also show that the expression of NOTCH target genes including DELTEX1 and MYC are not affected by GSI treatment in five resistant T-ALL cell lines with mutations in FBW7 (CEM, BE13, PEER, DU528, and HSB2), demonstrating that the mechanism of resistance in these leukemias lies upstream of MYC and DELTEX1 transcriptio...
true
true
true
true
true
6,889
1
DISCUSSION
0
null
null
17,646,409
null
It appears that in these T-ALL lines, one consequence of FBW7 mutation is stabilization of the NICD resulting in sustained NOTCH signaling, and thus promoting resistance to GSIs.
null
178
39,857
0
false
null
null
It appears that in these T-ALL lines, one consequence of FBW7 mutation is stabilization of the NICD resulting in sustained NOTCH signaling, and thus promoting resistance to GSIs.
true
true
true
true
true
6,889
1
DISCUSSION
0
null
null
17,646,409
null
However, other FBW7 substrates, such as MYC, may also account for selection for FBW7 mutations and for GSI resistance in T-ALL, as suggested by our finding that ALL-associated FBW7 mutations can dominantly inhibit MYC degradation.
null
230
39,858
0
false
null
null
However, other FBW7 substrates, such as MYC, may also account for selection for FBW7 mutations and for GSI resistance in T-ALL, as suggested by our finding that ALL-associated FBW7 mutations can dominantly inhibit MYC degradation.
true
true
true
true
true
6,889
2
DISCUSSION
0
null
null
17,646,409
null
An important question is why FBW7 mutation confers GSI resistance, whereas NOTCH PEST domain truncations that remove the FBW7 interaction domain do not.
null
152
39,859
0
false
null
null
An important question is why FBW7 mutation confers GSI resistance, whereas NOTCH PEST domain truncations that remove the FBW7 interaction domain do not.
true
true
true
true
true
6,890
2
DISCUSSION
0
null
null
17,646,409
null
In each cell line with PEST mutations, only one allele is affected by these heterozygous mutations, leaving the remaining normal allele, which encodes an NICD that is stabilized in the presence of mutant FBW7.
null
209
39,860
0
false
null
null
In each cell line with PEST mutations, only one allele is affected by these heterozygous mutations, leaving the remaining normal allele, which encodes an NICD that is stabilized in the presence of mutant FBW7.
true
true
true
true
true
6,890
2
DISCUSSION
0
null
null
17,646,409
null
Thus, although the amount of increased NOTCH activity resulting from the single allele PEST mutations may be sufficient to underlie the primary selection for these mutations, disruption of FBW7 function may be more active in sustaining NOTCH signaling and also may prolong the half-life of MYC (as well as other substrat...
null
360
39,861
0
false
null
null
Thus, although the amount of increased NOTCH activity resulting from the single allele PEST mutations may be sufficient to underlie the primary selection for these mutations, disruption of FBW7 function may be more active in sustaining NOTCH signaling and also may prolong the half-life of MYC (as well as other substrat...
true
true
true
true
true
6,890
3
DISCUSSION
1
5
[ "bib5", "bib54" ]
17,646,409
pmid-16751266|pmid-12479216
The association between FBW7 mutations and resistance to GSIs has implications for clinical testing of these agents in patients whose cancers show deregulation of the NOTCH pathway.
[ "5", "54" ]
181
39,862
0
false
The association between FBW7 mutations and resistance to GSIs has implications for clinical testing of these agents in patients whose cancers show deregulation of the NOTCH pathway.
[]
The association between FBW7 mutations and resistance to GSIs has implications for clinical testing of these agents in patients whose cancers show deregulation of the NOTCH pathway.
true
true
true
true
true
6,891
3
DISCUSSION
1
5
[ "bib5", "bib54" ]
17,646,409
pmid-16751266|pmid-12479216
Molecular analysis of the FBW7 gene, as well as genes encoding the relevant NOTCH receptors and other key components of the NOTCH signaling pathway, such as NUMB, may contribute to identification of patients likely to be most responsive to GSI therapy.
[ "5", "54" ]
252
39,863
0
false
Molecular analysis of the FBW7 gene, as well as genes encoding the relevant NOTCH receptors and other key components of the NOTCH signaling pathway, such as NUMB, may contribute to identification of patients likely to be most responsive to GSI therapy.
[]
Molecular analysis of the FBW7 gene, as well as genes encoding the relevant NOTCH receptors and other key components of the NOTCH signaling pathway, such as NUMB, may contribute to identification of patients likely to be most responsive to GSI therapy.
true
true
true
true
true
6,891
3
DISCUSSION
1
5
[ "bib5", "bib54" ]
17,646,409
pmid-16751266|pmid-12479216
Because Myc has recently been shown to be an important target of Notch in mammary tumorigenesis as well as in T-ALL (5), it might also be possible to overcome GSI resistance by combining GSIs with other drugs that block the MYC pathway to synergistically reduce MYC levels and block tumor cell growth.
[ "5", "54" ]
301
39,864
1
false
Because Myc has recently been shown to be an important target of Notch in mammary tumorigenesis as well as in T-ALL, it might also be possible to overcome GSI resistance by combining GSIs with other drugs that block the MYC pathway to synergistically reduce MYC levels and block tumor cell growth.
[ "5" ]
Because Myc has recently been shown to be an important target of Notch in mammary tumorigenesis as well as in T-ALL, it might also be possible to overcome GSI resistance by combining GSIs with other drugs that block the MYC pathway to synergistically reduce MYC levels and block tumor cell growth.
true
true
true
true
true
6,891
3
DISCUSSION
1
5
[ "bib5", "bib54" ]
17,646,409
pmid-16751266|pmid-12479216
One attractive candidate is TMPyP4, a cationic porphyrin that binds to and stabilizes guanine quadruplexes in DNA.
[ "5", "54" ]
114
39,865
0
false
One attractive candidate is TMPyP4, a cationic porphyrin that binds to and stabilizes guanine quadruplexes in DNA.
[]
One attractive candidate is TMPyP4, a cationic porphyrin that binds to and stabilizes guanine quadruplexes in DNA.
true
true
true
true
true
6,891
3
DISCUSSION
1
54
[ "bib5", "bib54" ]
17,646,409
pmid-16751266|pmid-12479216
MYC contains a sequence in its promoter that forms a guanine quadruplex, and TMPyP4 has been shown to inhibit MYC transcription and the growth of tumor cells in vivo (54).
[ "5", "54" ]
171
39,866
1
false
MYC contains a sequence in its promoter that forms a guanine quadruplex, and TMPyP4 has been shown to inhibit MYC transcription and the growth of tumor cells in vivo.
[ "54" ]
MYC contains a sequence in its promoter that forms a guanine quadruplex, and TMPyP4 has been shown to inhibit MYC transcription and the growth of tumor cells in vivo.
true
true
true
true
true
6,891
3
DISCUSSION
1
5
[ "bib5", "bib54" ]
17,646,409
pmid-16751266|pmid-12479216
Thus, TMPyP4 or other agents that inhibit MYC transcription may be useful in combination with GSIs to overcome resistance in patients harboring FBW7 mutations.
[ "5", "54" ]
159
39,867
0
false
Thus, TMPyP4 or other agents that inhibit MYC transcription may be useful in combination with GSIs to overcome resistance in patients harboring FBW7 mutations.
[]
Thus, TMPyP4 or other agents that inhibit MYC transcription may be useful in combination with GSIs to overcome resistance in patients harboring FBW7 mutations.
true
true
true
true
true
6,891
3
DISCUSSION
1
5
[ "bib5", "bib54" ]
17,646,409
pmid-16751266|pmid-12479216
Pharmacologic or genetic strategies that restore the normal function of FBW7 in tumor cells could also be therapeutically useful.
[ "5", "54" ]
129
39,868
0
false
Pharmacologic or genetic strategies that restore the normal function of FBW7 in tumor cells could also be therapeutically useful.
[]
Pharmacologic or genetic strategies that restore the normal function of FBW7 in tumor cells could also be therapeutically useful.
true
true
true
true
true
6,891
0
DISCUSSION
1
21
[ "ref21", "ref43", "ref42", "ref44", "ref45" ]
19,117,953
pmid-16682620|NA|pmid-8035875|pmid-12912912|pmid-12399450
The crystal structure of p35 C285A depicts one possible arrangement of the intact polypeptide chains in procaspase-1 dimers at very high concentrations.
[ "21", "43", "42", "44", "45" ]
153
39,869
0
false
The crystal structure of p35 C285A depicts one possible arrangement of the intact polypeptide chains in procaspase-1 dimers at very high concentrations.
[]
The crystal structure of p35 C285A depicts one possible arrangement of the intact polypeptide chains in procaspase-1 dimers at very high concentrations.
true
true
true
true
true
6,892
0
DISCUSSION
1
21
[ "ref21", "ref43", "ref42", "ref44", "ref45" ]
19,117,953
pmid-16682620|NA|pmid-8035875|pmid-12912912|pmid-12399450
This arrangement is likely similar to what occurs during oligomerization on inflammasomes and lends support for a mechanism of activation that occurs through intradimer cleavage.
[ "21", "43", "42", "44", "45" ]
180
39,870
0
false
This arrangement is likely similar to what occurs during oligomerization on inflammasomes and lends support for a mechanism of activation that occurs through intradimer cleavage.
[]
This arrangement is likely similar to what occurs during oligomerization on inflammasomes and lends support for a mechanism of activation that occurs through intradimer cleavage.
true
true
true
true
true
6,892
0
DISCUSSION
1
21
[ "ref21", "ref43", "ref42", "ref44", "ref45" ]
19,117,953
pmid-16682620|NA|pmid-8035875|pmid-12912912|pmid-12399450
This is observed in the C-terminal region of the large subunit, which is positioned along the dimer interface in a cavity that is normally unoccupied in the ligand-free form of the enzyme (Fig.
[ "21", "43", "42", "44", "45" ]
196
39,871
0
false
This is observed in the C-terminal region of the large subunit, which is positioned along the dimer interface in a cavity that is normally unoccupied in the ligand-free form of the enzyme (Fig.
[]
This is observed in the C-terminal region of the large subunit, which is positioned along the dimer interface in a cavity that is normally unoccupied in the ligand-free form of the enzyme (Fig.
true
true
true
true
true
6,892
0
DISCUSSION
1
21
[ "ref21", "ref43", "ref42", "ref44", "ref45" ]
19,117,953
pmid-16682620|NA|pmid-8035875|pmid-12912912|pmid-12399450
3, A and B) (21, 43).
[ "21", "43", "42", "44", "45" ]
23
39,872
0
false
3, A and B).
[ "21,\n 43" ]
3, A and B).
false
false
true
true
false
6,892
0
DISCUSSION
1
21
[ "ref21", "ref43", "ref42", "ref44", "ref45" ]
19,117,953
pmid-16682620|NA|pmid-8035875|pmid-12912912|pmid-12399450
The peptide chain undergoes a sharp turn at Gly287, continues for 10 amino acids down the dimer interface, and ends with Asp297 positioned very close to the catalytic residue of the neighboring enzyme (Fig.
[ "21", "43", "42", "44", "45" ]
210
39,873
0
false
The peptide chain undergoes a sharp turn at Gly287, continues for 10 amino acids down the dimer interface, and ends with Asp297 positioned very close to the catalytic residue of the neighboring enzyme (Fig.
[]
The peptide chain undergoes a sharp turn at Gly287, continues for 10 amino acids down the dimer interface, and ends with Asp297 positioned very close to the catalytic residue of the neighboring enzyme (Fig.
true
true
true
true
true
6,892
0
DISCUSSION
1
21
[ "ref21", "ref43", "ref42", "ref44", "ref45" ]
19,117,953
pmid-16682620|NA|pmid-8035875|pmid-12912912|pmid-12399450
This position is close enough to the catalytic site to allow cleavage of the peptide bond following Asp297.
[ "21", "43", "42", "44", "45" ]
109
39,874
0
false
This position is close enough to the catalytic site to allow cleavage of the peptide bond following Asp297.
[]
This position is close enough to the catalytic site to allow cleavage of the peptide bond following Asp297.
true
true
true
true
true
6,892
0
DISCUSSION
1
21
[ "ref21", "ref43", "ref42", "ref44", "ref45" ]
19,117,953
pmid-16682620|NA|pmid-8035875|pmid-12912912|pmid-12399450
Normally, the aspartic acid side chain of substrate is bound in a positively charged pocket containing Arg179 and Arg341, but this pocket is not formed in the zymogen structure because the putative substrate is positioned on the opposite side of the catalytic cysteine.
[ "21", "43", "42", "44", "45" ]
273
39,875
0
false
Normally, the aspartic acid side chain of substrate is bound in a positively charged pocket containing Arg179 and Arg341, but this pocket is not formed in the zymogen structure because the putative substrate is positioned on the opposite side of the catalytic cysteine.
[]
Normally, the aspartic acid side chain of substrate is bound in a positively charged pocket containing Arg179 and Arg341, but this pocket is not formed in the zymogen structure because the putative substrate is positioned on the opposite side of the catalytic cysteine.
true
true
true
true
true
6,892
0
DISCUSSION
1
42
[ "ref21", "ref43", "ref42", "ref44", "ref45" ]
19,117,953
pmid-16682620|NA|pmid-8035875|pmid-12912912|pmid-12399450
For proteolysis to occur here, only the catalytic cysteine needs to reposition for hydrolysis because activity is not absolutely dependent on the other member of the catalytic dyad, His237 (42).
[ "21", "43", "42", "44", "45" ]
197
39,876
1
false
For proteolysis to occur here, only the catalytic cysteine needs to reposition for hydrolysis because activity is not absolutely dependent on the other member of the catalytic dyad, His237.
[ "42" ]
For proteolysis to occur here, only the catalytic cysteine needs to reposition for hydrolysis because activity is not absolutely dependent on the other member of the catalytic dyad, His237.
true
true
true
true
true
6,892
0
DISCUSSION
1
21
[ "ref21", "ref43", "ref42", "ref44", "ref45" ]
19,117,953
pmid-16682620|NA|pmid-8035875|pmid-12912912|pmid-12399450
The carbonyl oxygen of Asp297, however, is within 3.5 Å of the amide nitrogen of Arg240 and near the side chains of Arg240 and Arg286, which could stabilize a negatively charged transition state and behave like an oxyanion hole.
[ "21", "43", "42", "44", "45" ]
232
39,877
0
false
The carbonyl oxygen of Asp297, however, is within 3.5 Å of the amide nitrogen of Arg240 and near the side chains of Arg240 and Arg286, which could stabilize a negatively charged transition state and behave like an oxyanion hole.
[]
The carbonyl oxygen of Asp297, however, is within 3.5 Å of the amide nitrogen of Arg240 and near the side chains of Arg240 and Arg286, which could stabilize a negatively charged transition state and behave like an oxyanion hole.
true
true
true
true
true
6,892
0
DISCUSSION
1
21
[ "ref21", "ref43", "ref42", "ref44", "ref45" ]
19,117,953
pmid-16682620|NA|pmid-8035875|pmid-12912912|pmid-12399450
After initial cleavage at Asp297 the peptide chain may be less constrained and thus free to exit the cavity at the dimer interface, which would allow space for the adjacent, unprocessed chain to position the second Asp297 near the opposite catalytic cysteine.
[ "21", "43", "42", "44", "45" ]
263
39,878
0
false
After initial cleavage at Asp297 the peptide chain may be less constrained and thus free to exit the cavity at the dimer interface, which would allow space for the adjacent, unprocessed chain to position the second Asp297 near the opposite catalytic cysteine.
[]
After initial cleavage at Asp297 the peptide chain may be less constrained and thus free to exit the cavity at the dimer interface, which would allow space for the adjacent, unprocessed chain to position the second Asp297 near the opposite catalytic cysteine.
true
true
true
true
true
6,892
0
DISCUSSION
1
21
[ "ref21", "ref43", "ref42", "ref44", "ref45" ]
19,117,953
pmid-16682620|NA|pmid-8035875|pmid-12912912|pmid-12399450
The higher degree of flexibility observed in the active-site and Asp297 region (Fig.
[ "21", "43", "42", "44", "45" ]
86
39,879
0
false
The higher degree of flexibility observed in the active-site and Asp297 region (Fig.
[]
The higher degree of flexibility observed in the active-site and Asp297 region (Fig.
true
true
true
true
true
6,892
0
DISCUSSION
1
21
[ "ref21", "ref43", "ref42", "ref44", "ref45" ]
19,117,953
pmid-16682620|NA|pmid-8035875|pmid-12912912|pmid-12399450
3D) also suggests flexibility that could accommodate nucleophilic attack of Asp297 by Cys285 in this region.
[ "21", "43", "42", "44", "45" ]
110
39,880
0
false
3D) also suggests flexibility that could accommodate nucleophilic attack of Asp297 by Cys285 in this region.
[]
3D) also suggests flexibility that could accommodate nucleophilic attack of Asp297 by Cys285 in this region.
false
false
true
true
false
6,892
0
DISCUSSION
1
21
[ "ref21", "ref43", "ref42", "ref44", "ref45" ]
19,117,953
pmid-16682620|NA|pmid-8035875|pmid-12912912|pmid-12399450
Alternatively, it could be the exclusion of one linker region from the core of the protein that allows the excluded Asp297 to be processed by yet another zymogen neighbor by interdimer cleavage.
[ "21", "43", "42", "44", "45" ]
197
39,881
0
false
Alternatively, it could be the exclusion of one linker region from the core of the protein that allows the excluded Asp297 to be processed by yet another zymogen neighbor by interdimer cleavage.
[]
Alternatively, it could be the exclusion of one linker region from the core of the protein that allows the excluded Asp297 to be processed by yet another zymogen neighbor by interdimer cleavage.
true
true
true
true
true
6,892
0
DISCUSSION
1
21
[ "ref21", "ref43", "ref42", "ref44", "ref45" ]
19,117,953
pmid-16682620|NA|pmid-8035875|pmid-12912912|pmid-12399450
Arguments have been made for both intradimer and interdimer processing (44, 45), and either scenario would explain how forced dimerization with an inflammasome could activate the caspase-1 auto-proteolytic pathway.
[ "21", "43", "42", "44", "45" ]
218
39,882
0
false
Arguments have been made for both intradimer and interdimer processing, and either scenario would explain how forced dimerization with an inflammasome could activate the caspase-1 auto-proteolytic pathway.
[ "44,\n 45" ]
Arguments have been made for both intradimer and interdimer processing, and either scenario would explain how forced dimerization with an inflammasome could activate the caspase-1 auto-proteolytic pathway.
true
true
true
true
true
6,892
1
DISCUSSION
1
25
[ "ref25" ]
19,117,953
pmid-11752425
FIGURE 4.Structural comparison of initiator and effector caspase zymogens.
[ "25" ]
74
39,883
0
false
FIGURE 4.Structural comparison of initiator and effector caspase zymogens.
[]
FIGURE 4.Structural comparison of initiator and effector caspase zymogens.
true
true
true
true
true
6,893
1
DISCUSSION
1
25
[ "ref25" ]
19,117,953
pmid-11752425
A, procaspase-1 (PDB code 3E4C) shown as a schematic with the linker region shown as a thick ribbon.
[ "25" ]
101
39,884
0
false
A, procaspase-1 (PDB code 3E4C) shown as a schematic with the linker region shown as a thick ribbon.
[]
A, procaspase-1 (PDB code 3E4C) shown as a schematic with the linker region shown as a thick ribbon.
true
true
true
true
true
6,893
1
DISCUSSION
1
25
[ "ref25" ]
19,117,953
pmid-11752425
Both aspartic acid cleavage sites between the p20 and p10 in one monomer are shown as spheres.
[ "25" ]
95
39,885
0
false
Both aspartic acid cleavage sites between the p20 and p10 in one monomer are shown as spheres.
[]
Both aspartic acid cleavage sites between the p20 and p10 in one monomer are shown as spheres.
true
true
true
true
true
6,893
1
DISCUSSION
1
25
[ "ref25" ]
19,117,953
pmid-11752425
The dotted line represents unresolved residues not seen in the electron density maps.
[ "25" ]
87
39,886
0
false
The dotted line represents unresolved residues not seen in the electron density maps.
[]
The dotted line represents unresolved residues not seen in the electron density maps.
true
true
true
true
true
6,893
1
DISCUSSION
1
25
[ "ref25" ]
19,117,953
pmid-11752425
B, schematic representation of procaspase-7 (PDB code 1GQF (25)), an effector caspase, with the interdomain linker shown as a thick ribbon.
[ "25" ]
141
39,887
0
false
B, schematic representation of procaspase-7 ), an effector caspase, with the interdomain linker shown as a thick ribbon.
[ "PDB code\n 1GQF (25" ]
B, schematic representation of procaspase-7 ), an effector caspase, with the interdomain linker shown as a thick ribbon.
true
true
true
true
true
6,893
1
DISCUSSION
1
25
[ "ref25" ]
19,117,953
pmid-11752425
Only the first site of processing in effector caspases is required for activation.
[ "25" ]
83
39,888
0
false
Only the first site of processing in effector caspases is required for activation.
[]
Only the first site of processing in effector caspases is required for activation.
true
true
true
true
true
6,893
1
DISCUSSION
1
25
[ "ref25" ]
19,117,953
pmid-11752425
It is noticeable that the first cleavage site is up and away from the dimer interface in caspase-7.
[ "25" ]
100
39,889
0
false
It is noticeable that the first cleavage site is up and away from the dimer interface in caspase-7.
[]
It is noticeable that the first cleavage site is up and away from the dimer interface in caspase-7.
true
true
true
true
true
6,893
2
DISCUSSION
1
25
[ "ref25" ]
19,117,953
pmid-11752425
Structural comparison of initiator and effector caspase zymogens.
[ "25" ]
65
39,890
0
false
Structural comparison of initiator and effector caspase zymogens.
[]
Structural comparison of initiator and effector caspase zymogens.
true
true
true
true
true
6,894
2
DISCUSSION
1
25
[ "ref25" ]
19,117,953
pmid-11752425
A, procaspase-1 (PDB code 3E4C) shown as a schematic with the linker region shown as a thick ribbon.
[ "25" ]
101
39,891
0
false
A, procaspase-1 (PDB code 3E4C) shown as a schematic with the linker region shown as a thick ribbon.
[]
A, procaspase-1 (PDB code 3E4C) shown as a schematic with the linker region shown as a thick ribbon.
true
true
true
true
true
6,894
2
DISCUSSION
1
25
[ "ref25" ]
19,117,953
pmid-11752425
Both aspartic acid cleavage sites between the p20 and p10 in one monomer are shown as spheres.
[ "25" ]
95
39,892
0
false
Both aspartic acid cleavage sites between the p20 and p10 in one monomer are shown as spheres.
[]
Both aspartic acid cleavage sites between the p20 and p10 in one monomer are shown as spheres.
true
true
true
true
true
6,894
2
DISCUSSION
1
25
[ "ref25" ]
19,117,953
pmid-11752425
The dotted line represents unresolved residues not seen in the electron density maps.
[ "25" ]
87
39,893
0
false
The dotted line represents unresolved residues not seen in the electron density maps.
[]
The dotted line represents unresolved residues not seen in the electron density maps.
true
true
true
true
true
6,894
2
DISCUSSION
1
25
[ "ref25" ]
19,117,953
pmid-11752425
B, schematic representation of procaspase-7 (PDB code 1GQF (25)), an effector caspase, with the interdomain linker shown as a thick ribbon.
[ "25" ]
141
39,894
0
false
B, schematic representation of procaspase-7 ), an effector caspase, with the interdomain linker shown as a thick ribbon.
[ "PDB code\n 1GQF (25" ]
B, schematic representation of procaspase-7 ), an effector caspase, with the interdomain linker shown as a thick ribbon.
true
true
true
true
true
6,894
2
DISCUSSION
1
25
[ "ref25" ]
19,117,953
pmid-11752425
Only the first site of processing in effector caspases is required for activation.
[ "25" ]
83
39,895
0
false
Only the first site of processing in effector caspases is required for activation.
[]
Only the first site of processing in effector caspases is required for activation.
true
true
true
true
true
6,894
2
DISCUSSION
1
25
[ "ref25" ]
19,117,953
pmid-11752425
It is noticeable that the first cleavage site is up and away from the dimer interface in caspase-7.
[ "25" ]
100
39,896
0
false
It is noticeable that the first cleavage site is up and away from the dimer interface in caspase-7.
[]
It is noticeable that the first cleavage site is up and away from the dimer interface in caspase-7.
true
true
true
true
true
6,894
3
DISCUSSION
1
24
[ "ref24", "ref25", "ref39", "ref40", "ref46", "ref47" ]
19,117,953
pmid-11701129|pmid-11752425|pmid-15941357|pmid-18309328|pmid-16977332|pmid-18084239
Comparing caspase-1 and caspase-7 zymogens reveals an intriguing difference, the linkers between the large and small subunits start their association with the dimer interface at different points (Fig.
[ "24", "25", "39", "40", "46", "47" ]
203
39,897
0
false
Comparing caspase-1 and caspase-7 zymogens reveals an intriguing difference, the linkers between the large and small subunits start their association with the dimer interface at different points (Fig.
[]
Comparing caspase-1 and caspase-7 zymogens reveals an intriguing difference, the linkers between the large and small subunits start their association with the dimer interface at different points (Fig.
true
true
true
true
true
6,895
3
DISCUSSION
1
24
[ "ref24", "ref25", "ref39", "ref40", "ref46", "ref47" ]
19,117,953
pmid-11701129|pmid-11752425|pmid-15941357|pmid-18309328|pmid-16977332|pmid-18084239
4, A and B) (24, 25).
[ "24", "25", "39", "40", "46", "47" ]
23
39,898
0
false
4, A and B).
[ "24,\n 25" ]
4, A and B).
false
false
true
true
false
6,895
3
DISCUSSION
1
24
[ "ref24", "ref25", "ref39", "ref40", "ref46", "ref47" ]
19,117,953
pmid-11701129|pmid-11752425|pmid-15941357|pmid-18309328|pmid-16977332|pmid-18084239
This altered orientation impacts the location of the first cleavage point in the zymogens.
[ "24", "25", "39", "40", "46", "47" ]
91
39,899
0
false
This altered orientation impacts the location of the first cleavage point in the zymogens.
[]
This altered orientation impacts the location of the first cleavage point in the zymogens.
true
true
true
true
true
6,895
3
DISCUSSION
1
24
[ "ref24", "ref25", "ref39", "ref40", "ref46", "ref47" ]
19,117,953
pmid-11701129|pmid-11752425|pmid-15941357|pmid-18309328|pmid-16977332|pmid-18084239
In caspase-1, the first cleavage site of one monomer is buried in the dimer interface near the adjacent catalytic cysteine, whereas in caspase-7 this region is absent from the protein core leaving the first cleavage site exposed.
[ "24", "25", "39", "40", "46", "47" ]
233
39,900
0
false
In caspase-1, the first cleavage site of one monomer is buried in the dimer interface near the adjacent catalytic cysteine, whereas in caspase-7 this region is absent from the protein core leaving the first cleavage site exposed.
[]
In caspase-1, the first cleavage site of one monomer is buried in the dimer interface near the adjacent catalytic cysteine, whereas in caspase-7 this region is absent from the protein core leaving the first cleavage site exposed.
true
true
true
true
true
6,895
3
DISCUSSION
1
24
[ "ref24", "ref25", "ref39", "ref40", "ref46", "ref47" ]
19,117,953
pmid-11701129|pmid-11752425|pmid-15941357|pmid-18309328|pmid-16977332|pmid-18084239
This major difference between an initiator (caspase-1) and an effector caspase (caspase-7) explains the need for oligomerization to start the activation process in caspase-1.
[ "24", "25", "39", "40", "46", "47" ]
176
39,901
0
false
This major difference between an initiator (caspase-1) and an effector caspase (caspase-7) explains the need for oligomerization to start the activation process in caspase-1.
[]
This major difference between an initiator (caspase-1) and an effector caspase (caspase-7) explains the need for oligomerization to start the activation process in caspase-1.
true
true
true
true
true
6,895
3
DISCUSSION
1
24
[ "ref24", "ref25", "ref39", "ref40", "ref46", "ref47" ]
19,117,953
pmid-11701129|pmid-11752425|pmid-15941357|pmid-18309328|pmid-16977332|pmid-18084239
Effector enzymes, like caspase-7 and caspase-3, function as downstream components in the proteolytic cascade and do not contain oligomerization or recruitment domains at the N termini.
[ "24", "25", "39", "40", "46", "47" ]
186
39,902
0
false
Effector enzymes, like caspase-7 and caspase-3, function as downstream components in the proteolytic cascade and do not contain oligomerization or recruitment domains at the N termini.
[]
Effector enzymes, like caspase-7 and caspase-3, function as downstream components in the proteolytic cascade and do not contain oligomerization or recruitment domains at the N termini.
true
true
true
true
true
6,895
3
DISCUSSION
1
24
[ "ref24", "ref25", "ref39", "ref40", "ref46", "ref47" ]
19,117,953
pmid-11701129|pmid-11752425|pmid-15941357|pmid-18309328|pmid-16977332|pmid-18084239
Their zymogens are found dimeric in solution without catalytic activity and are readily activated by cleavage of the interdomain site by upstream initiators (such as caspase-8 and caspase-9).
[ "24", "25", "39", "40", "46", "47" ]
194
39,903
0
false
Their zymogens are found dimeric in solution without catalytic activity and are readily activated by cleavage of the interdomain site by upstream initiators (such as caspase-8 and caspase-9).
[]
Their zymogens are found dimeric in solution without catalytic activity and are readily activated by cleavage of the interdomain site by upstream initiators (such as caspase-8 and caspase-9).
true
true
true
true
true
6,895
3
DISCUSSION
1
24
[ "ref24", "ref25", "ref39", "ref40", "ref46", "ref47" ]
19,117,953
pmid-11701129|pmid-11752425|pmid-15941357|pmid-18309328|pmid-16977332|pmid-18084239
This is in contrast to caspase-1, and other initiator caspase zymogens such as caspase-9 and DRONC, which require some activity as zymogens to autoprocess themselves.
[ "24", "25", "39", "40", "46", "47" ]
168
39,904
0
false
This is in contrast to caspase-1, and other initiator caspase zymogens such as caspase-9 and DRONC, which require some activity as zymogens to autoprocess themselves.
[]
This is in contrast to caspase-1, and other initiator caspase zymogens such as caspase-9 and DRONC, which require some activity as zymogens to autoprocess themselves.
true
true
true
true
true
6,895
3
DISCUSSION
1
24
[ "ref24", "ref25", "ref39", "ref40", "ref46", "ref47" ]
19,117,953
pmid-11701129|pmid-11752425|pmid-15941357|pmid-18309328|pmid-16977332|pmid-18084239
Caspase-1, however, apparently differs from these two initiator caspases as cleavage of the enzyme leads to large increases in enzyme activity and dimerization.
[ "24", "25", "39", "40", "46", "47" ]
162
39,905
0
false
Caspase-1, however, apparently differs from these two initiator caspases as cleavage of the enzyme leads to large increases in enzyme activity and dimerization.
[]
Caspase-1, however, apparently differs from these two initiator caspases as cleavage of the enzyme leads to large increases in enzyme activity and dimerization.
true
true
true
true
true
6,895
3
DISCUSSION
1
24
[ "ref24", "ref25", "ref39", "ref40", "ref46", "ref47" ]
19,117,953
pmid-11701129|pmid-11752425|pmid-15941357|pmid-18309328|pmid-16977332|pmid-18084239
Caspase-9 and DRONC activation have been shown to be enhanced much more by oligomerization than by proteolysis (39, 40, 46, 47).
[ "24", "25", "39", "40", "46", "47" ]
133
39,906
0
false
Caspase-9 and DRONC activation have been shown to be enhanced much more by oligomerization than by proteolysis.
[ "39,\n 40,\n 46,\n 47" ]
Caspase-9 and DRONC activation have been shown to be enhanced much more by oligomerization than by proteolysis.
true
true
true
true
true
6,895
3
DISCUSSION
1
24
[ "ref24", "ref25", "ref39", "ref40", "ref46", "ref47" ]
19,117,953
pmid-11701129|pmid-11752425|pmid-15941357|pmid-18309328|pmid-16977332|pmid-18084239
An interpretation of our combined structural, kinetic, and biochemical data can help explain what is different about caspase-1 and why both dimerization and proteolysis are important for activity.
[ "24", "25", "39", "40", "46", "47" ]
199
39,907
0
false
An interpretation of our combined structural, kinetic, and biochemical data can help explain what is different about caspase-1 and why both dimerization and proteolysis are important for activity.
[]
An interpretation of our combined structural, kinetic, and biochemical data can help explain what is different about caspase-1 and why both dimerization and proteolysis are important for activity.
true
true
true
true
true
6,895
4
DISCUSSION
1
35
[ "ref35", "ref21", "ref23" ]
19,117,953
pmid-8662843|pmid-16682620|pmid-15314233
The low level activity of procaspase-1 has previously been recognized in cell lysates and is characterized kinetically in our report (Table 1) (35).
[ "35", "21", "23" ]
151
39,908
1
false
The low level activity of procaspase-1 has previously been recognized in cell lysates and is characterized kinetically in our report (Table 1).
[ "35" ]
The low level activity of procaspase-1 has previously been recognized in cell lysates and is characterized kinetically in our report (Table 1).
true
true
true
true
true
6,896
4
DISCUSSION
1
35
[ "ref35", "ref21", "ref23" ]
19,117,953
pmid-8662843|pmid-16682620|pmid-15314233
One possibility for the reduced activity of the zymogen could be negative allosteric regulation by the location of the p20 C terminus.
[ "35", "21", "23" ]
136
39,909
0
false
One possibility for the reduced activity of the zymogen could be negative allosteric regulation by the location of the p20 C terminus.
[]
One possibility for the reduced activity of the zymogen could be negative allosteric regulation by the location of the p20 C terminus.
true
true
true
true
true
6,896
4
DISCUSSION
1
35
[ "ref35", "ref21", "ref23" ]
19,117,953
pmid-8662843|pmid-16682620|pmid-15314233
An allosteric regulatory site in this region has previously been characterized in both caspase-1 and caspase-7 (21, 23).
[ "35", "21", "23" ]
123
39,910
0
false
An allosteric regulatory site in this region has previously been characterized in both caspase-1 and caspase-7.
[ "21,\n 23" ]
An allosteric regulatory site in this region has previously been characterized in both caspase-1 and caspase-7.
true
true
true
true
true
6,896
4
DISCUSSION
1
35
[ "ref35", "ref21", "ref23" ]
19,117,953
pmid-8662843|pmid-16682620|pmid-15314233
The tryptophan and phenylalanine that bind in this region occupy a position similar to small molecule-allosteric inhibitors (Fig.
[ "35", "21", "23" ]
131
39,911
0
false
The tryptophan and phenylalanine that bind in this region occupy a position similar to small molecule-allosteric inhibitors (Fig.
[]
The tryptophan and phenylalanine that bind in this region occupy a position similar to small molecule-allosteric inhibitors (Fig.
true
true
true
true
true
6,896
4
DISCUSSION
1
35
[ "ref35", "ref21", "ref23" ]
19,117,953
pmid-8662843|pmid-16682620|pmid-15314233
However, despite the conserved positioning, the small molecules are more potent because they completely inactivate the enzyme.
[ "35", "21", "23" ]
127
39,912
0
false
However, despite the conserved positioning, the small molecules are more potent because they completely inactivate the enzyme.
[]
However, despite the conserved positioning, the small molecules are more potent because they completely inactivate the enzyme.
true
true
true
true
true
6,896
4
DISCUSSION
1
35
[ "ref35", "ref21", "ref23" ]
19,117,953
pmid-8662843|pmid-16682620|pmid-15314233
This may be due to the covalent bond between the small molecules and Cys331.
[ "35", "21", "23" ]
77
39,913
0
false
This may be due to the covalent bond between the small molecules and Cys331.
[]
This may be due to the covalent bond between the small molecules and Cys331.
true
true
true
true
true
6,896
4
DISCUSSION
1
35
[ "ref35", "ref21", "ref23" ]
19,117,953
pmid-8662843|pmid-16682620|pmid-15314233
The added effect of this bond could be to completely block protein rearrangement in this region that occurs during substrate binding (see substrate-bound state in Fig.
[ "35", "21", "23" ]
169
39,914
0
false
The added effect of this bond could be to completely block protein rearrangement in this region that occurs during substrate binding (see substrate-bound state in Fig.
[]
The added effect of this bond could be to completely block protein rearrangement in this region that occurs during substrate binding (see substrate-bound state in Fig.
true
true
true
true
true
6,896
4
DISCUSSION
1
35
[ "ref35", "ref21", "ref23" ]
19,117,953
pmid-8662843|pmid-16682620|pmid-15314233
The p20 C terminus, when bound at this site, is likely to be more flexible during active-site binding.
[ "35", "21", "23" ]
103
39,915
0
false
The p20 C terminus, when bound at this site, is likely to be more flexible during active-site binding.
[]
The p20 C terminus, when bound at this site, is likely to be more flexible during active-site binding.
true
true
true
true
true
6,896