INT312933

Context Info Confidence 0.63 First Reported 2010 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 1 Total Number 19 Disease Relevance 7.94 Pain Relevance 0.53

nucleus (Hes3) DNA binding (Hes3) transcription factor binding (Hes3)

Anatomy Link Frequency nucleus 6 stem cells 4 precursor cell 1 Hes3 (Mus musculus)

Pain Link Frequency Relevance Heat withdrawal 95 100.00 Perioperative pain 38 57.04 cytokine 19 53.52 Central nervous system 19 42.88 imagery 38 5.00 anesthesia 19 5.00 isoflurane 19 5.00 Hippocampus 19 5.00

Disease Link Frequency Relevance Heat Glioblastoma 19 99.96 Vibrio Infection 437 99.28 Brain Tumor 19 98.68 Malignant Neoplastic Disease 19 98.16 Cancer 57 98.08 Neurological Disease 57 91.68 Stress 38 86.16 Disease 57 85.20 Stroke 57 78.96 Bordatella Infection 19 70.44

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Protein

Mutation

Event

Anatomy

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Speculation

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A key finding is that the localization of Hes3 correlates strongly with the proliferative state of stem cells: Quiescent endogenous stem cells throughout the adult brain exclude Hes3 from the nucleus but express it in the cytoplasm; when placed in culture under mitogenic support that promotes proliferation, Hes3 is found in both the cytoplasm and nucleus.

Localization (found) of Hes3 in stem cells

1) Confidence 0.63 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2877108 Disease Relevance 0.69 Pain Relevance 0

Similarly, in human biopsies from Grade IV Glioblastoma multiforme, Hes3 is found in both the cytoplasm and nucleus.

Localization (found) of Hes3 in nucleus associated with glioblastoma

2) Confidence 0.63 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2877108 Disease Relevance 0.70 Pain Relevance 0

When fetal NSCs were treated with CholAB for 2 days (following 4 days in FGF2), the nuclear localization of Hes3 markedly increased.

Localization (localization) of Hes3

3) Confidence 0.63 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2877108 Disease Relevance 0.06 Pain Relevance 0.08

A key finding is that the localization of Hes3 correlates strongly with the proliferative state of stem cells: Quiescent endogenous stem cells throughout the adult brain exclude Hes3 from the nucleus but express it in the cytoplasm; when placed in culture under mitogenic support that promotes proliferation, Hes3 is found in both the cytoplasm and nucleus.

Localization (localization) of Hes3 in stem cells

4) Confidence 0.63 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2877108 Disease Relevance 0.69 Pain Relevance 0

In culture conditions that support the self-renewal of mouse fetal NSCs in vitro (in the presence of FGF2), Hes3 is localized both in the nucleus and the cytoplasm of fetal NSCs (Figure 3a,b; Figure S2; Figure S3), whereas when differentiation is induced (by a 2-day FGF2 withdrawal), Hes3 is only found in the cytoplasm.

Localization (localized) of Hes3 in nucleus associated with withdrawal

5) Confidence 0.63 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2877108 Disease Relevance 0.13 Pain Relevance 0.05

Here we show that a cell biology mechanism that is activated by cholera toxin converges into this pathway (at the levels of receptor trafficking and Hes3 localization) to regulate stem cell and precursor cell numbers.

Localization (localization) of Hes3 in stem cell associated with vibrio infection

6) Confidence 0.63 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2877108 Disease Relevance 0.39 Pain Relevance 0

Cholera toxin increases immunoreactivity for the Tie2 receptor and rapidly induces the nuclear localization of Hes3.

Localization (localization) of Hes3 associated with vibrio infection

7) Confidence 0.55 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC2877108 Disease Relevance 0.35 Pain Relevance 0

A key finding is that the localization of Hes3 correlates strongly with the proliferative state of stem cells: Quiescent endogenous stem cells throughout the adult brain exclude Hes3 from the nucleus but express it in the cytoplasm; when placed in culture under mitogenic support that promotes proliferation, Hes3 is found in both the cytoplasm and nucleus.

Localization (found) of Hes3 in stem cells

8) Confidence 0.55 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2877108 Disease Relevance 0.69 Pain Relevance 0

In culture conditions that support the self-renewal of mouse fetal NSCs in vitro (in the presence of FGF2), Hes3 is localized both in the nucleus and the cytoplasm of fetal NSCs (Figure 3a,b; Figure S2; Figure S3), whereas when differentiation is induced (by a 2-day FGF2 withdrawal), Hes3 is only found in the cytoplasm.

Localization (found) of Hes3 in nucleus associated with withdrawal

9) Confidence 0.55 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2877108 Disease Relevance 0.13 Pain Relevance 0.08

This is supported by our mechanistic data showing that treatment with the full (active) cholera toxin protein increases immunostaining for the Tie2 receptor and induces the nuclear localization of the transcription factor Hes3, two processes characteristic of self renewing NSCs [22], [23], [24], [25].

Localization (localization) of Hes3 associated with vibrio infection

10) Confidence 0.55 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2877108 Disease Relevance 0.49 Pain Relevance 0

Uncovering novel treatments that will affect Hes3 expression and localization will be a new set of tools in regenerative and cancer medicine.

Localization (localization) of Hes3 associated with cancer

11) Confidence 0.55 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2877108 Disease Relevance 0.76 Pain Relevance 0.06

Cholera toxin increases immunoreactivity for the Tie2 receptor and rapidly induces the nuclear localization of Hes3.

Localization (localization) of Hes3 associated with vibrio infection

12) Confidence 0.55 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC2877108 Disease Relevance 0.35 Pain Relevance 0

Similarly, in human biopsies from Grade IV Glioblastoma multiforme, Hes3 is found in both the cytoplasm and nucleus.

Localization (found) of Hes3 in nucleus associated with glioblastoma

13) Confidence 0.55 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2877108 Disease Relevance 0.70 Pain Relevance 0

This is supported by our mechanistic data showing that treatment with the full (active) cholera toxin protein increases immunostaining for the Tie2 receptor and induces the nuclear localization of the transcription factor Hes3, two processes characteristic of self renewing NSCs [22], [23], [24], [25].

Localization (localization) of Hes3 associated with vibrio infection

14) Confidence 0.55 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2877108 Disease Relevance 0.49 Pain Relevance 0

In culture conditions that support the self-renewal of mouse fetal NSCs in vitro (in the presence of FGF2), Hes3 is localized both in the nucleus and the cytoplasm of fetal NSCs (Figure 3a,b; Figure S2; Figure S3), whereas when differentiation is induced (by a 2-day FGF2 withdrawal), Hes3 is only found in the cytoplasm.

Localization (found) of Hes3 in nucleus associated with withdrawal

15) Confidence 0.55 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2877108 Disease Relevance 0.07 Pain Relevance 0.08

In culture conditions that support the self-renewal of mouse fetal NSCs in vitro (in the presence of FGF2), Hes3 is localized both in the nucleus and the cytoplasm of fetal NSCs (Figure 3a,b; Figure S2; Figure S3), whereas when differentiation is induced (by a 2-day FGF2 withdrawal), Hes3 is only found in the cytoplasm.

Localization (localized) of Hes3 in nucleus associated with withdrawal

16) Confidence 0.55 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2877108 Disease Relevance 0.13 Pain Relevance 0.08

When fetal NSCs were treated with CholAB for 2 days (following 4 days in FGF2), the nuclear localization of Hes3 markedly increased.

Localization (localization) of Hes3

17) Confidence 0.55 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2877108 Disease Relevance 0.06 Pain Relevance 0.08

Our findings show that cholera toxin regulates the expression and localization of Tie2 and Hes3 and induces powerful expansion of cultured NSCs.

Localization (localization) of Hes3 associated with vibrio infection

18) Confidence 0.55 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2877108 Disease Relevance 0.66 Pain Relevance 0.03

Here we show that a cell biology mechanism that is activated by cholera toxin converges into this pathway (at the levels of receptor trafficking and Hes3 localization) to regulate stem cell and precursor cell numbers.

Localization (localization) of Hes3 in precursor cell associated with vibrio infection

19) Confidence 0.21 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2877108 Disease Relevance 0.39 Pain Relevance 0

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