I was going to incorporate these changes directly into my 3D animatic, but I find it has been difficult to conceptualize in Maya... so did some brainstorming...
A very horrible attempt at visualizing MC's suggestion (pull back to show bigger picture):
A very horrible attempt at visualizing MC's suggestion (pull back to show bigger picture):
This interaction causes TrkA to dimerize and auto-phosphorylate...
...forming binding sites for adaptor proteins coupled to several intracellular signalling cascades. In one of these pathways, TRPV1 cation channels that open in response to noxious heat and acidity, become phosphorylated.
-----Once there, the complex acts on transcription factors to induce changes in gene expression. This leads to an increased production of pronociceptive molecules.
The expression of a number of ion channels is also increased...
...including voltage-gated sodium channels, acid-sensing ion channels, and TRPV1...
These ion channels are transported to both the peripheral and central ends of the nociceptor.
...including voltage-gated sodium channels, acid-sensing ion channels, and TRPV1...
These ion channels are transported to both the peripheral and central ends of the nociceptor.
Would I have the same sequence for the pronociceptive molecules? But that would be rather repetitive...
Concluding section
I received a lot of mixed feedback for my original ending, some love the concept, some hate it... Personally, I've been staring at this thing for so many months, it's become difficult to stay objective (to the point I have no opinion on this matter anymore...)
So I thought I would do some brainstorming for this section. It'd be nice to end with a 2D still frame/slightly animated sequence (see Hotel Dusk example from last post) in the same style as the opening to create greater unity.
My ideas are pretty cheesy/clichéd though... :(
Concluding section
I received a lot of mixed feedback for my original ending, some love the concept, some hate it... Personally, I've been staring at this thing for so many months, it's become difficult to stay objective (to the point I have no opinion on this matter anymore...)
So I thought I would do some brainstorming for this section. It'd be nice to end with a 2D still frame/slightly animated sequence (see Hotel Dusk example from last post) in the same style as the opening to create greater unity.
My ideas are pretty cheesy/clichéd though... :(
Currently, researchers at McGill University are working towards an understanding of the maturation and degradation pathways of NGF in inflamed joints.
By manipulating the enzymes responsible for NGF production, they hope to develop pharmacological interventions to reduce endogeous levels of NGF...
...a research area with great therapeutic potential that remains largely unexplored.
^ I'm really not sure what's going on in this bit because unfortunately, only a very small network/cascade is available so it wouldn't look nearly as impressive visually as what I had in mind in the original animatic. I would also like to somehow bring back the old woman to tie it all together. How? I have no idea yet...Technical visual challenges
When ion channels are manufactured in and transported from the cell body, would all the different ion channel types be transported represented in different vesicles? Or is it possible to have a vesicle carrying multiple types of channels? (Probably depends on trafficking signals... will need to read up)
Also - simplify to show a sort of diffusion? Otherwise would need motor proteins, the cytoskeleton, etc.
Transitions
EX's suggestion:
NGF also increases pain sensation...
...by acting directly on nociceptive endings
Orientation of nociceptor membrane in molecular view
I tried rotating the membrane 90 degrees (or just slightly less) to better match the orientation of the nociceptor in cellular view. I'm really not a fan because I think it creates a bit of visual confusion... but I do wonder if viewers will get disoriented because the pain signals travel downwards at the molecular view, but up/right in the cellular view...
I also considered reorienting the nociceptor, but I think it makes more sense for it to fire upwards towards the CNS.
Depiction of TrkA
I'm still rather concerned with my depiction of TrkA - only the extracellular binding domain of TrkA is available on the PDB. This also raises the issue that in the following image, NGF (pink/turquoise) looks quite large when in complex with TrkA (blue/purple), but TrkA is much larger in its entirety. David Goodsell simplifies it with schematic representations (wouldn't be too attractive in an animation though?! Unless... have some sort of schematic like this at first before I fade out the extracellular parts to focus on the intracellular part)
I tried rotating the membrane 90 degrees (or just slightly less) to better match the orientation of the nociceptor in cellular view. I'm really not a fan because I think it creates a bit of visual confusion... but I do wonder if viewers will get disoriented because the pain signals travel downwards at the molecular view, but up/right in the cellular view...
I also considered reorienting the nociceptor, but I think it makes more sense for it to fire upwards towards the CNS.
Depiction of TrkA
I'm still rather concerned with my depiction of TrkA - only the extracellular binding domain of TrkA is available on the PDB. This also raises the issue that in the following image, NGF (pink/turquoise) looks quite large when in complex with TrkA (blue/purple), but TrkA is much larger in its entirety. David Goodsell simplifies it with schematic representations (wouldn't be too attractive in an animation though?! Unless... have some sort of schematic like this at first before I fade out the extracellular parts to focus on the intracellular part)
surface model based on 2IFG (extracellular segment of human TrkA in complex with nerve growth factor)TrkA structure is described as:
"The extracellular domain of TrkA is composed of two cysteine-rich motifs that are separated by three leucine-rich motifs; these are followed by two Ig-like motifs... There is a single short transmemrbrane spanning region that is followed by the juxtamembrane region. Beyond the juxtamembrane region is the catalytic domain that contains the conserved tyrosine residues..."
- Nicol and Vasko 2007. Molecular Interventions 7: 26-41.
"The extracellular domain of TrkA is composed of two cysteine-rich motifs that are separated by three leucine-rich motifs; these are followed by two Ig-like motifs... There is a single short transmemrbrane spanning region that is followed by the juxtamembrane region. Beyond the juxtamembrane region is the catalytic domain that contains the conserved tyrosine residues..."
- Nicol and Vasko 2007. Molecular Interventions 7: 26-41.
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