INT9953

Context Info Confidence 0.34 First Reported 1992 Last Reported 2009 Negated 0 Speculated 0 Reported most in Body Documents 10 Total Number 10 Disease Relevance 3.21 Pain Relevance 1.51

cytosol (Gnas) endosome (Gnas) signal transduction (Gnas) extracellular region (Gnas) plasma membrane (Gnas) GTPase activity (Gnas)

Anatomy Link Frequency lymphocytes 1 cleavage 1 Gnas (Mus musculus)

Pain Link Frequency Relevance Heat Clonidine 5 98.76 Morphine 3 98.16 analgesia 2 96.08 Opioid 3 95.44 Antinociceptive 2 87.20 Intracerebroventricular 2 75.00 antinociception 1 75.00 Inflammation 65 72.64 tail-flick 1 70.76 agonist 3 68.68

Disease Link Frequency Relevance Heat Muscular Dystrophy 86 98.92 Repression 164 97.32 Age-related Macular Degeneration 245 92.72 Disease 33 88.36 Bordatella Infection 1 86.16 Colon Cancer 2 83.20 Hypoxia 1 82.32 Lung Cancer 2 81.12 Vibrio Infection 1 75.44 Duchenne Muscular Dystrophy 8 74.04

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

It is concluded that opioids and clonidine promote analgesia after binding to receptors functionally coupled to Gi/G(o) proteins, moreover, the activity of morphine, beta-endorphin and clonidine in this test seems to be counteracted by a process involving activation of Gs alpha transducer proteins.

Positive_regulation (activation) of Gs alpha associated with opioid, morphine, analgesia and clonidine

1) Confidence 0.34 Published 1992 Journal Life Sci. Section Abstract Doc Link 1447947 Disease Relevance 0.16 Pain Relevance 1.42

This suggests that there is a lower threshold effect, and the low dose did not seem to be sufficient to induce exon skipping in patients with Duchenne muscular dystrophy; therefore, we proceeded straight to the high dose.

Positive_regulation (induce) of exon associated with muscular dystrophy

2) Confidence 0.01 Published 2009 Journal Lancet Neurol Section Body Doc Link PMC2755039 Disease Relevance 0.29 Pain Relevance 0.07

Antisense oligonucleotides have been used for experimental gene silencing and recently as splice-switching oligonucleotides to modify splicing and induce exon skipping,13 particularly in myoblasts from patients with DMD in vitro,14,15 and in mouse and dog models of DMD.16–18 One patient with DMD who had a deletion of exon 20 received an intravenous infusion of a splice-switching oligonucleotide with a phosphorothioate backbone, which induced skipping of exon 19 and restored the DMD open reading frame in lymphocytes but had no effect in skeletal muscle.19 A recent phase 1 clinical study reported encouraging results in four boys with DMD who received a single intramuscular injection of a 2L'O-methyl-ribooligonucleoside-phoshophorothioate splice-switching oligonucleotide that was targeted to skip exon 51.

Positive_regulation (induce) of exon in lymphocytes associated with muscular dystrophy

3) Confidence 0.01 Published 2009 Journal Lancet Neurol Section Body Doc Link PMC2755039 Disease Relevance 0.95 Pain Relevance 0

When co-expressed with CaMK IV dCT, exon skipping was sharply increased, indicating that CaRRE 2 is also sufficient for CaMK IV–dependent repression (Figure 4B, lanes 1 and 2).

Positive_regulation (increased) of exon associated with repression

4) Confidence 0.01 Published 2007 Journal PLoS Biology Section Body Doc Link PMC1790950 Disease Relevance 0.30 Pain Relevance 0

CaRRE 2 was inserted at the +3 position of the Dup175 exon, the same position relative to the 3?

Positive_regulation (position) of exon

5) Confidence 0.01 Published 2007 Journal PLoS Biology Section Body Doc Link PMC1790950 Disease Relevance 0.20 Pain Relevance 0

After the original duplication event, subsequent accumulation of mutations, presumably in both exon 5a and 5b, have resulted in the two similar but distinct SNAP-25 proteins present in all higher vertebrates.

Positive_regulation (accumulation) of exon

6) Confidence 0.01 Published 2008 Journal PLoS Genetics Section Body Doc Link PMC2581893 Disease Relevance 0.11 Pain Relevance 0.03

Western blot analysis using the C-terminal specific c/ebp Beta antibody showed that the levels of both the LAP and LIP isoforms of c/ebp Beta were increased after treatment with LPS, in accordance with a previous report (14) (Figure 3).

Positive_regulation (increased) of isoforms

7) Confidence 0.01 Published 2009 Journal Nucleic Acids Research Section Body Doc Link PMC2761263 Disease Relevance 0.25 Pain Relevance 0

The c/ebp Beta transcript encodes three isoforms, designated as LAP*, LAP and LIP, that are generated by differential translational initiation (Figure 2A).

Positive_regulation (generated) of isoforms

8) Confidence 0.01 Published 2009 Journal Nucleic Acids Research Section Body Doc Link PMC2761263 Disease Relevance 0 Pain Relevance 0

The expression of the three isoforms is regulated in a complex manner, and even differential activation of the c/ebp Beta isoforms upon LPS stimulation has been reported (25).

Positive_regulation (activation) of isoforms

9) Confidence 0.01 Published 2009 Journal Nucleic Acids Research Section Body Doc Link PMC2761263 Disease Relevance 0.12 Pain Relevance 0

Currently available anti-VEGF agents include an aptamer (pegaptanib sodium), which targets the VEGF165 isoform of VEGF-A, and the monoclonal antibody fragment ranibizumab, which targets all VEGF-A isoforms and cleavage products.

Positive_regulation (targets) of isoforms in cleavage

10) Confidence 0.00 Published 2007 Journal Core Evidence Section Body Doc Link PMC3012443 Disease Relevance 0.82 Pain Relevance 0

General Comments

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