INT193037

Context Info Confidence 0.19 First Reported 2006 Last Reported 2010 Negated 0 Speculated 4 Reported most in Body Documents 7 Total Number 14 Disease Relevance 8.82 Pain Relevance 0.64

signal transduction (Chrm2) plasma membrane (Chrm2) signal transducer activity (Chrm2)

Anatomy Link Frequency plasma 1 nerves 1 brain 1 Chrm2 (Mus musculus)

Pain Link Frequency Relevance Heat Central nervous system 6 98.88 dopamine receptor 24 98.36 Dopamine 66 97.52 Inflammation 62 91.84 agonist 68 89.48 antagonist 28 81.44 Inflammatory mediators 8 79.92 Potency 18 75.00 bradykinin 6 72.08 opiate 9 46.36

Disease Link Frequency Relevance Heat Targeted Disruption 217 99.80 Influenza Virus Infection 162 98.12 Sprains And Strains 141 97.24 Pulmonary Disease 102 96.96 Apoptosis 6 95.40 Hypersensitivity 8 93.12 Infection 156 92.40 Cognitive Disorder 12 92.08 INFLAMMATION 72 91.84 Viral Infection 8 90.96

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

This trend continued until the end of the time-course, with a higher frequency of live cells found in the M2-transduced population versus the M2.Stop retrovirus control (Figure 2B).

Regulation (control) of M2

1) Confidence 0.19 Published 2008 Journal PLoS Pathogens Section Body Doc Link PMC2270344 Disease Relevance 0.08 Pain Relevance 0

At day 2 post-transduction, the M2-transduced cells have equal frequencies of live cells as the control M2.Stop retrovirus transduced cells (Figure 2B).

Regulation (control) of M2

2) Confidence 0.19 Published 2008 Journal PLoS Pathogens Section Body Doc Link PMC2270344 Disease Relevance 0.10 Pain Relevance 0

To examine the roles of M2, M4 and D2 receptors in male-female interactions, we measured USVs of M2 and M4 KO mice.

Spec (examine) Regulation (roles) of M2 associated with targeted disruption

3) Confidence 0.16 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2268741 Disease Relevance 1.12 Pain Relevance 0.13

Furthermore, given the effects of M2, M4, M5 muscarinic receptors and the D2 dopamine receptor in dopamine release [23]–[25], [66], and their varied and wide distribution in the brain [28], [29], we postulate that, these receptors are more likely to contribute to the regulation of emotion and motivation.

Spec (postulate) Regulation (effects) of M2 in brain associated with dopamine and dopamine receptor

4) Confidence 0.14 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2268741 Disease Relevance 0.33 Pain Relevance 0.13

By studying knockout mice, we further found that: 1) USVs were lost in about 75% of M2 KO mice, associated with a loss of sexual interaction. 2) In M5 KO mice, frequency-modulated USVs from male mice were reduced by almost 80%. 3) USVs were not altered reliably in M4 KO mice. 4) M2, M5 and D2 receptors played a role in either duration or peak or bandwidth of USVs.

Regulation (played) of M2 associated with targeted disruption

5) Confidence 0.06 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2268741 Disease Relevance 0.57 Pain Relevance 0

While we continued to evaluate the protective efficacy of NP and M2 in the mouse model, we extended our investigation into the ferret model in this study.

Regulation (efficacy) of M2

6) Confidence 0.06 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2843722 Disease Relevance 1.21 Pain Relevance 0

Significant anti-M2 humoral responses were detected in animals immunized with NP+M2 post-rAd boost (p?

Regulation (responses) of M2

7) Confidence 0.06 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2843722 Disease Relevance 0.23 Pain Relevance 0

M2 is responsible for protein translocation, and is expressed at a high density in the plasma membrane of infected cells in tetramer forms.

Regulation (responsible) of M2 in plasma

8) Confidence 0.06 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2843722 Disease Relevance 0.92 Pain Relevance 0

The corresponding Emax values in wild-type and M2 receptor knockout mice were approximately the same, but that in the M3 receptor knockout mouse was only 36% of wild type.

Regulation (values) of M2 associated with targeted disruption

9) Confidence 0.05 Published 2009 Journal Naunyn Schmiedebergs Arch Pharmacol Section Abstract Doc Link PMC2749929 Disease Relevance 0.68 Pain Relevance 0.12

Ferrets were immunized with HA alone, NP alone, M2 alone, NP+M2, HA+NP+M2, and control using gene-based vaccines delivered in DNA/rAd5 vectors.

Regulation (control) of M2

10) Confidence 0.03 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2843722 Disease Relevance 0.71 Pain Relevance 0

Here, we investigate the relative efficacy of NP and M2 compared to HA in protecting against HPAI H5N1 virus.

Spec (investigate) Regulation (efficacy) of M2

11) Confidence 0.03 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC2843722 Disease Relevance 0.52 Pain Relevance 0

Distinct mechanisms underlie the M2 autoreceptor dysfunction.

Regulation (underlie) of M2

12) Confidence 0.03 Published 2006 Journal Respir Res Section Body Doc Link PMC1479816 Disease Relevance 0.96 Pain Relevance 0.07

Cholinergic neurotransmission in the parasympathetic ganglia is regulated by nicotinic receptors in conjunction with muscarinic M1 receptors, whereas ganglionic release of acetylcholine from preganglionic nerves is under regulation of M2 autoreceptors [61,62] (Figure 2).

Regulation (regulation) of M2 in nerves

13) Confidence 0.02 Published 2006 Journal Respir Res Section Body Doc Link PMC1479816 Disease Relevance 0.92 Pain Relevance 0.19

However, we find that the protective efficacy of NP and M2 diminishes as the virulence and dose of the challenge virus are increased.

Spec (investigate) Regulation (efficacy) of M2

14) Confidence 0.01 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC2843722 Disease Relevance 0.49 Pain Relevance 0

General Comments

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